In February 2004, the Food and Drug Administration (FDA) was the first to approve the combination of cisplatin (CDDP) and pemetrexed (PEM) as standard first-line chemotherapy for untreated, unresectable malignant pleural mesothelioma (MPM). However, after that approval, no progress was made in the standard first-line treatment of MPM for almost 15 years. Positive results from a phase 3 study (Mesothelioma Avastin Cisplatin Pemetrexed Study: MAPS) verifying the effect of bevacizumab, an anti-angiogenesis agent added to CDDP/PEM for unresectable MPM, were published in The Lancet in December 2015; however, this did not lead to approval by national drug regulatory agencies. Furthermore, no second-line treatment was established for cases refractory to CDDP/PEM. In August 2018, the Pharmaceuticals and Medical Devices Agency of Japan was the first in the world to approve monotherapy with nivolumab, an immune checkpoint inhibitor (ICI), for previously unresectable, advanced, or recurrent MPM. Following Japan, in October 2020, the FDA approved the combination of nivolumab and ipilimumab for the treatment of previously untreated, unresectable MPM. In this article, we review the transition of drug treatment for MPM, in light of the historical background, focusing on the benefits of ICIs.

In previous studies, the authors utilized a single-dimensional operationalization of species density that implies induction of hierarchy and time with certain topologies. For further clarification of induced fractals including the relation to renormalization in physics, here a theoretical development is proposed based on a newly identified fact, namely that scaling parameters for magnetization exactly correspond to imaginary parts of Riemann zeta nontrivial zeros. An analogy to magnetization and accompanying Fake Monster Algebra is invoked to lend support to this theory, along with empirical species density data for a wild Dictyostelia community. A master torus and a Lagrangian/Hamiltonian are derived expressing fractal structures as a solution for diminishing divergent terms in renormalization.

In recent decades, a number of high-profile cases involving fraud as research misconduct have been in the media and resulted in severe consequences for those convicted. According to the increased cases of allegations and coverage in the media, this reflects a heightened awareness that fraudulent actions exist. Nonetheless, the Office of Research Integrity data suggests that despite the growth in the number of the cases of allegation there has not been a commensurate increase in findings of misconduct. The purpose of this paper is to explore misconduct to better understand what it entails. An analysis of misconduct from the perspective of the definitions of allegations and fraud of is conducted and potential frameworks for understanding both are considered. The paper considers serial-positioning effects of primacy and recency on allegation phenomena, as well as supervenience theory and contextualism as a lens for understanding fraud. Discussion of the relational semantics of the core aspects of fraud and de facto grouping of forms of misconduct. It is concluded that the interrogative pronouns of “what” and “when” could be used to categorize forms of misconduct laying the foundation for the next paper that deconstructs the definition of falsification according to the Public Health Service.

The American Academy of Arts and Sciences suggested the definition of science literacy emphasize how crucial understanding the scientific process and the ability to evaluate conflicting scientific evidence is. The purpose of this article is to present an evidence-supported curriculum covering the fundamentals of logic, reasoning, and argumentation skills to address the emphasized basic knowledge, skills, and abilities required to be scientifically literate, which will prepare the public to understand and engage with science meaningfully. An analytic-synthetic approach toward understanding the notion of public is taken using a theoretical biomimetics framework that identifies naturally occurring objects or phenomena that descriptively captures the essence of a construct to facilitate creative problem-solving. In the present case, the problem being solved is how to reconcile what is meant by public, how it ought to be interpreted, the different levels of confidence in science that exist, and various understandings of science all with one another. The results demonstrate there is an inherent denotative-connotative inconsistency in the traditional notion of public that can be explicated through the concept of a fractal allowing for comprehension of the relationship between public confidence in, and understanding of, science.

The will and intellect have been debated philosophically without resolution for centuries. It is for this reason that this article considers doctrines of the will and intellect of two 17^th-century rationalist philosophers, Rene Descartes, and Baruch Spinoza, both of whom were chosen as the focus for analysis because of their prominence and contrasting views. Our objective was to critique the doctrine of the will and intellect to develop an alternate theory that expounds on their previous work. A qualitative exploration was undertaken that compared their respective belief systems of Dualism and Monism. Despite the strengths of their arguments, an analysis of Part V of Spinoza’s Ethics and Discourse on Method and Meditations on First Philosophy by Descartes led the author to determine that both were partially correct in their positions yet consistent with one another. From this conclusion and building upon their work, this article presents the synthesis of the author’s alternate theory regarding the qualitative characteristics of both the will and intellect. An ontological argument against the existence of infinite entities as a corollary with the implication that neither the will, intellect, nor God can be infinite. While the limitation of the conclusions drawn is that they are dependent on the author’s philosophical framework, the originality of this paper is based on the author’s synthesis of one coherent theory from two philosophers espousing contrasting theistic systems and should serve as the foundation for future exploration and debate.

This paper explores the rationale behind Booker T. Washington’s vocationalist philosophy of education for the then recently emancipated black population. Through the use of a critical thinking framework, an analysis of remarks from key speeches and his life according to scholars providing Washington’s prescriptive argument and rhetoric is undertaken. Despite Washington’s intentions, the argument for his vocational approach is demonstrated to be oppressive, myopic, and circular in its logic. The author proposes a framework for understanding the counterintuitive development of vocationalist philosophy based on the dichotomous nature of the human experience’s value-construct and context misalignment. Concordant or discordant dualities that result from misalignment are explained and how to reconcile Washington’s Vocationalism with opposing the philosophy of W.E.B. Du Bois due to equivalence or consistency of values with theoretical constructs is also discussed.

Dietary intake of omega-3 polyunsaturated fatty acids (eicosapentaenoic acid, EPA) exerts antiarrhythmic effects, although the mechanisms are poorly understood. Here we investigated the possible beneficial actions of EPA on saturated fatty acid-induced changes of the L-type Ca2+ channel in cardiomyocytes. Cardiomyocytes were cultured with oleic acid/palmitic acid mixture (OAPA) in the presence or absence of EPA. Beating rate reduction of cardiomyocytes caused by OAPA were reversed by EPA. EPA also retrieved a reduction of Cav1.2-L-type Ca2+ current, mRNA and protein caused by OAPA. Immunocytochemical analysis revealed a distinct downregulation of the Cav1.2 channel caused by OAPA with a concomitant decrease in the phosphorylated component of a transcription factor adenosine-3’, 5’-cyclic monophosphate (cAMP) response element binding protein (CREB) in the nucleus, which were rescued by EPA. A free fatty acid receptor 4 (FFAR4) agonist TUG-891 reversed expression of Cav1.2- and CREB-mRNA caused by OAPA, whereas an FFAR4 antagonist AH-7614 abolished the effects of EPA. Excessive reactive oxygen species (ROS) accumulation caused by OAPA decreased Cav1.2- and CREB-mRNA expressions, which were reversed by an ROS scavenger. Our data suggest that EPA rescues cellular remodeling caused by OAPA lipotoxicity and oxidative stresses via both free fatty acid receptor 4-dependent and -independent pathways.

If students do not fully apply themselves, then they may be considered responsible for the result of being inadequately prepared. +- Nevertheless, student outcomes are more likely to reflect a combination of both effort and systematic problems with overall course architecture. Deficiencies in course design result in inadequate preparation that adversely and directly impacts students’ productivity upon entering the workforce. Such an impact negatively influences students' ability to maintain gainful employment and provide for their families, which inevitably contributes to the development of issues concerning their psychological well-being. It is well-documented that incorporating active learning strategies in course design and delivery can enhance student learning outcomes. Despite the benefit of implementing active learning techniques, rarely in the real world will it be possible for techniques to be used in isolation of one another. Therefore, the purpose of this proposed study is to determine the interactive effects of two active learning strategies because, at a minimum, technique-pairs more accurately represent the application of active learning in the natural educational setting. There is a paucity of evidence in the literature directed toward investigating the interactive effects of multiple active learning techniques that this study is aimed at filling. The significance of this research is that, by determining the interactive effects of paired active learning strategies, other research studies on the beneficial effects of using particular active learning technique-pairs will be documented contributing to the literature so that ultimately classroom instruction may be customized according to the determination of optimal sequencing of strategy-pairs for particular courses, subjects, and desired outcomes that maximize student learning.

Preoperative angiography in glioblastoma (GBM) often shows arteriovenous shunts and early venous filling (EVF). Here, we investigated the clinical implications of EVF in GBM as a prognostic and vascular mimicry biomarker. In this retrospective multicenter study, we consecutively enrolled patients who underwent angiography with a GBM diagnosis between April 1, 2013, and March 31, 2021. The primary and secondary endpoints were the differences in overall survival (OS) and progression-free survival (PFS), respectively, between cases with and without EVF. Of 133 initially enrolled patients, 91 newly diagnosed with GBM underwent preoperative angi-ography and became the study population. The 6-year OS and PFS were significantly worse in the EVF than in the non-EVF group. Moreover, 20 GBM cases (10 with EVF and 10 without EVF) were randomly selected and evaluated for histological vascular mimicry. Except for two cases that were difficult to evaluate, the EVF group had a significantly higher frequency of vascular mimicry than the non-EVF group (0/8 vs. 5/10, P = 0.04). EVF on preoperative angiography is a robust prognostic biomarker for GBM and may help detect cases with a high frequency of histological vascular mimicry.

Leucokinins (LKs) constitute a neuropeptide family first discovered in a cockroach and later identified in numerous insects and several other invertebrates. The LK receptors are only distantly related to other known receptors. Among insects, there are many examples of species where genes encoding LKs and their receptors are absent. Furthermore, genomics has revealed that LK signaling is lacking in several of the invertebrate phyla and in vertebrates. In insects, the number and complexity of LK expressing neurons vary, from the simple pattern in the larva of Drosophila where the entire CNS has 20 neurons of three main types, to cockroaches with about 250 of many different types. Common to all studied insects is the presence or 1-3 pairs of LK-expressing neurosecretory cells in each abdominal neuromere of the ventral nerve cord, that, at least in some insects, regulate secretion in Malpighian tubules. This review summarizes the diverse functional roles of LK signaling in insects, as well as other arthropods and mollusks. These functions include regulation of ion and water homeostasis, feeding, sleep-metabolism interactions, state-dependent memory formation, as well as modulation of gustatory sensitivity and nociception. Other functions are implied by the neuronal distribution of LK, but remain to be investigated.

Traditionally understood in reference to distance education, cognitive presence may be defined as "the extent to which the participants in any particular configuration of a community of inquiry can construct meaning through sustained communication. The purpose of this paper was to create a blueprint for the reflective ePortfolio as the capstone project for my graduate degree. The blueprint was accomplished by adapting for use cognitive presence as a tool for both analysis and framing, which has never been done to the best of my knowledge. I considered myself to be a participant in a “community of inquiry” model and substituted the result of my interaction with each of the required instructor-course content pairings I took to serve as fellow participants in this community model. The result of my participation was understood to be the knowledge and experience that I have gained, which was reflected in eight of my academic research papers. These selected papers were the artifacts around which my ePortfolio was ultimately developed and demonstrated my participation as an active member in this community of inquiry constructing meaning through sustained communication.

Organ transplantation centers set criteria for candidate qualification, which has led to disparate healthcare resource allocation practices affecting those with a substance use history. These individuals are denied organ transplants by committees and healthcare providers who assign them lower priority status. The lower priority argument claims that healthcare resources should not be provided equally to individuals failing to share responsibility for not doing enough in addressing the diseases associated with substance use. The purpose of this work is to explore the interrelatedness between the ethics of a merit-based system of moral responsibility and lower priority setting involved in healthcare resource allocation pertaining to those with substance use histories. An integral approach to the argument against the lower prioritists with a focus on the relationship between different organ allocation practices affecting substance users and the justification for resource allocation practices in healthcare and transplant committees. Lower priority setting is challenged, and an argument offered in which substance users are assigned higher priority when relying on “doing enough” in a merit-based system of moral responsibility. It is determined that one cannot substantiate assigning a lower priority status since a lack of success in rehab does not imply a lack of effort. Additionally, neither to confirmatory behavior, nor to non-conforming behavior may freedom be justifiably ascribed in a merit-based system of responsibility because freedom to choose can neither be established a priori, nor a posteriori with respect to meritorious behavior.

The purpose of this paper is to critique the definition of falsification as research misconduct according to the Public Health Service (PHS) in order to better understand what it entails. In support of this purpose, the approach decided upon for analysis was philosophical including framing the issue borrowing from both mereological and epistemological perspectives. Through the consideration given to parthood relations of mereology, we gained insight from a cognitive imperfection standpoint about similarities that exist between the epistemic constraints on knowledge and the nature of violations concerning research misconduct. Findings from the examination of a case study include the significance of accuracy in representation in falsification as misconduct and the core dimensions comprising an instance of falsification, which are Deliberateness, Alteration, and Inclusion. Given that either behavior or actions must occur that violate these three aspects in order to qualify as an instance of misconduct under falsification, the author proposes that, at a minimum, any revisions made to the definition of falsification stipulate what he refers to as the Violation Imperative.

What began nearly a century ago with the contributions of Hollingworth and Asperger, among others, has developed into a field dedicated to the study of gifted individuals with a disability. These twice-exceptional (2e) people and their unique set of needs differ from those of their once-exceptional counterparts on either end of the spectrum and often remain unaddressed or are discovered very late in life resulting in longterm consequences. For those discovered, effective treatment options to improve their quality of life remain uncertain. The goal of the present paper was to determine whether effective interventions exist to improve domain-specific (i.e., social, emotional, or academic) outcomes for people exhibiting both signs of giftedness and disability. A query was performed using evidence databases TRIP and PDQ in addition to University at Buffalo Libraries holdings for "twice-exceptional," "Giftedness," "Disability," and "intervention." The hits were reduced to the four most relevant, freely available studies in English that were selected for critique. Despite the selected studies being found to share methodological similarities that were their strengths and conducive to comparison, they also had threats to validity that served as potential weakness. Not only can directly effective interventions improve specific domains for 2e individuals, but the effects of domain-specific interventions may carry over into another domain resulting in indirect effects.

Temporomandibular disorders (TMD) is a group of orofacial pain conditions which is the most common non-dental pain complaint in the maxillofacial region. Due to the complexity of the etiology and often cyclical nature of the disease, the diagnosis and management of TMD remain a challenge where consensus is still lacking in many aspects. While clinical examination is considered the most important process in the diagnosis of TMD, imaging may serve as a valuable adjunct in selected cases. Depending on the type of TMD, many treatment modalities have been proposed, ranging from conservative options to open surgical procedures. In this review, the authors discuss the present thinking in the etiology and classification of TMD, followed by the diagnostic approach and the current trend and controversies in management.

Extracellular vesicles (EV) released by tumor cells are a major aspect of the resistance-associated secretory phenotype (RASP), by which immune evasion can be established. Heat shock proteins (HSPs) are an evolutionarily conserved family of molecular chaperones, which stabilize proteins, minimize protein misfolding and aggregation within the cell, besides facilitating protein translocation, refolding and degradation. (i) Releases of extracellular HSPs (ex-HSP) and EV-associated HSPs (EV-HSP) are essential in RASP, by which molecular cotransfer of HSPs with oncogenic factors into recipient cells can promote cancer progression and resistance against stress such as hypoxia, radiation, chemicals, and immune system. (ii) RASP of tumor cells can eject anticancer drugs, molecularly targeted therapeutics, and immune checkpoint inhibitors with EVs. (iii) Cytotoxic lipids can be also released from tumor cells as RASP. Nevertheless, ex-HSP and EV-HSP can play immunostimulatory and immunosuppressive roles by binding to receptors such as LRP1/CD91/A2MR, scavenger receptors, and toll-like receptors expressed on recipient cells. Liquid biopsy of HSPs in body fluids may be useful in diagnosis, prognosis, and treatment in cancer. Regarding HSP90-targeted therapeutics, we summarize the pros, cons, and problem solutions in this review. Although production of HSPs are canonically induced by heat shock factor 1 (HSF1) and hypoxia-inducible factor 1 (HIF-1), recent studies discovered that production of HSPs is also regulated by matrix metalloproteinase 3 (MMP3) and heterochromatin protein 1 (HP1) and production of cochaperone CDC37 is reciprocally regulated by myeloid zinc finger 1 (MZF1) and SCAN-D1.

Blockchain technology (BCT) has the potential for sustainable development, enhancing business efficiency, reducing costs, and strengthening data security. Despite its potential, adoption among small and medium-sized enterprises (SMEs) is low due to the need for significant changes in technology infrastructure and the challenge of interoperability. A cross-sectional survey was done with 226 Hong Kong SMEs. The PLS-SEM results highlighted favorable transformation conditions as the most critical factor for SMEs considering the adoption of BCT. These conditions address both internal and external readiness for adopting the disruptive strategy. Other contributing factors to BCT adoption include trust in BCT developers, perceived usefulness and ease of use, government support, and perceived security. The research results contributed to the literature on disruptive technology acceptance, adoption, transformation conditions, technology readiness, and SMEs’ technology adoption. Government-supported policies and initiatives can promote BCT adoption, including educational programs, case studies, and resources for readiness. Financial support and regulatory frameworks can further encourage adoption. BCT developers can demonstrate the value of their systems, effectively communicate potential ROI and cost savings, and provide user-friendly interfaces to increase SMEs’ intention to adopt BCT.

The fundamental objective is to study the application of multivariate sets of data in Gaussian distribution. This paper examines broad measurements of structure for both Gaussian and non-Gaussian distributions, which shows that they can be described in terms of the infor-mation-theoretic between the given covariance matrix and correlated random variables (in terms of relative entropy). In order to develop the multivariate Gaussian distribution with entropy and mutual information, several significant methodologies are presented through the discussion supported by illustrations, both technically and statistically. The content obtained allows readers to better perceive concepts, comprehend techniques, and properly execute software programs for future study on the topic's science and implementations. It also helps readers grasp the themes' fundamental concepts. Involving the relative entropy and mutual information as well as the potential correlated covariance analysis based on differential equations, a wide range of information is addressed, including basic to application concerns.

Glucose-sensitive films were prepared by the layer-by-layer (LbL) deposition of poly(ethyleneimine) (H-PEI) solution and DNA solution (containing glucose oxidase (GOx)). H-PEI/DNA+GOx multilayer films were constructed using electrostatic interactions. The (H-PEI/DNA+GOx)5 film was then partially decomposed by hydrogen peroxide (H2O2). The mechanism for the decomposition of the LbL film was considered to involve a more reactive oxygen species (ROS) that was formed by the reaction of hemin and H2O2, which then caused nonspecific DNA cleavage. GOx present in the LbL films reacts with glucose to generate hydrogen peroxide. Therefore, decomposition of the H-PEI/DNA+GOx)5 film was observed when the thin film was immersed in a glucose solution. A (H-PEI/DNA+GOx)5 film exposed to a glucose solution for periods of 24, 48 72, and 96 h indicated decomposition of the film increased with the time. The rate of LbL film decomposition increased with the glucose concentration. At pH and ionic strength close to physiological conditions, it was possible to slowly decompose the LbL film at a sub-millimolar glucose concentration.

In Taiwan, mountainous areas account for approximately two-thirds of the total area. The steep terrain and concentrated rainfall during typhoons cause landslides, which pose a considerable threat to mountain settlements. Therefore, models for analyzing rainfall-induced landslide hazards are urgently required to ensure adequate land use in mountainous areas. In this study, focusing on Pingtung County in southern Taiwan, we developed a landslide hazard index (IRL) to land use. Using FORMOSA-2 and SPOT-5 satellite images, data were collected before and after four typhoons (one in 2009 and three in 2013). The ArcGIS random tree classifier was used for interpreting satellite images to explore surface changes and disasters, which were used to analyze slope disturbances. The product of the maximum 3-h rolling rainfall intensity and effective accumulated rainfall was used as a rainfall trigger index (IRT). Considering environmental and slope disturbance factors, an index of slope environmental strength potential (ISESP) was developed through logistic regression (LR). Landslide hazard to land use was estimated using IRT and ISESP. The average coefficient of agreement (Kappa) was approximately 0.71 (medium to high accuracy); the overall accuracy of slope environmental strength potential analysis was approximately 80.4%. At a constant ISESP, IRT increased with the increasing hazard potential of rainfall-induced landslides. Furthermore, IRT and ISESP were positively correlated with landslide occurrence. When large ISESP values occur (e.g., fragile environment and high land development intensity), small IRT values may induce landslides.

This study surveyed the variation in Perfluorinated Compounds (PFCs) concentration entering urban wastewater treatment plants and proposed an optimal PFCS treatment method. The PFCS concentration in influent was shown to be affected by the types of industries and operating rate. The concentration of PFCs in the wastewater treatment effluent was slightly lower than that of influent. Thus, PFCs were considered to have barely been removed by the existing biological treatments. The pilot test result showed that about 10% of PFCs were removed by coagulation and precipitation, and the ozone and chlorine test also showed that few PFCs were removed regardless of the amount of injection. The activated carbon adsorption test showed that the removal was significantly increased by the empty bed contact time, with about a 60% removal in five minutes and over a 90% removal in 15 minutes. Therefore it is determined that a more stable and higher PFCs removal would result from the continuous oxidation processes such as ozone and adsorption processes such as activated carbon rather than a single biological treatment.

Background. Epidemiological and clinical studies demonstrated that excessive salt intake causes severe hypertension and exacerbated organ derangement such as chronic kidney disease (CKD). In this study, we focused on evaluating histological and gene-expression findings in the kidney using stroke-prone spontaneously hypertensive rats (SHRSP) with high-salt intake and thromboxane A2/ prostaglandin H2 receptor (TPR) blocker ONO-8809. Methods. SHRSP aged 6 weeks were divided into three groups eating normal chow containing 0.4% NaCl, 2.0%NaCl, or 2.0%NaCl +ONO-8809 (0.6mg/kg p.o. daily). Histological analyses with immunohistochemistry and a gene-expression assay with a DNA kidney microarray were performed after 8 weeks. Results. The following changes were observed with high-salt intake. Glomerular sclerotic changes were remarkably observed in the juxtaglomerular cortex areas. ED1, MCP-1, nitrotyrosine, and HIF-1α staining areas were increased in the glomeruli and interstitial portion. Tbxa2r which encodes TPR, Prcp, and Car7 were significantly underexpressed in the kidney. The plasma 8-isoprostane level was significantly elevated, and was attenuated with ONO-8809 treatment. Conclusion. TXA2 and oxidative stresses exaggerated renal dysfunction in salt-loading SHRSP, and ONO-8809 as a TPR blocker suppressed these changes. Therefore, ONO-8809 is a candidate drug to prevent CKD for hypertensive patients associated with high-salt intake.

The merge areas of freeway work zones include relatively significant safety hazards that have continuously led to urgent safety issues to be solved by the management departments. In order to make up for the cumbersome process of independent identification of rear-end collision and lane change collision on complex road sections, an appropriate identification method of traffic conflicts in the merge area of freeway work zone was explored, this study collected vehicle running tracking data from the merge areas of multiple work zones, using an unmanned aerial vehicle video technique. Based on an inter-frame difference method and the principle of a spatio-temporal context visual tracking algorithm, the vehicles were detected and tracked, and the coordinate data of the vehicles in continuous motion were parsed using MATLAB extension tools. Based on the behavior characteristics of vehicle conflict avoidance, a new identification method for evading severe traffic conflicts is proposed according to the initial velocity, acceleration and accident rate of section traffic. Then, a statistical analysis was performed on the spatial distribution characteristics of the traffic conflicts in typical merge areas. The impacts of the road conditions in work zones, vehicle factors, and traffic flow factors on the traffic conflicts were analyzed. A binomial logistic model was established to identify the main influencing factors. The results show that in the merge area of the freeway work zone, there are serious traffic conflicts between vehicles in the following two situations: (Ⅰ) v∈[7,13.5] m/s and a∈[-3.96,-0.65]m/s2; and (Ⅱ) v∈[13.5,24.3] m/s, and a∈[-3.96,-1.57] m/s2. The probabilities of serious traffic conflicts in the first and last 25 m of the merge area are greater than those in the other sections. The smaller the space between the upstream work zone and the merge area, the greater the probability of serious traffic conflicts between vehicles. When the average vehicle speed is relatively high, the probability of serious conflicts is the highest, i.e., by a multiple of 5.95 from the baseline. Moreover, the probability of serious conflicts between vehicles is higher for larger vehicles, i.e., 4.765 times that for small vehicles. The research results can serve as a reference for freeway management departments to improve the safety levels of merge areas during road work. For example, the probability of serious conflicts can be effectively reduced by setting up reasonable speed limit signs in the work zone, increasing the spacing between work zone and merge area, and appropriately diverting large vehicles.

The strong coupling between individual quantum emitters and resonant optical micro/nanocavities is beneficial to understand light and matter interactions. Here we propose a plasmonic nanoantenna placed on a metal film to achieve an ultra-high electric field enhancement in the nanogap and ultra-small optical mode volume. The strong coupling between a single quantum dot and the designed structure is investigated in detail by both numerical simulations and theoretical calculations. When a single QD is inserted into the nanogap of the silver nanoantenna, scattering spectra show remarkably large spectral splitting and typical anti-crossing behavior of the vacuum Rabi splitting, which can be realized in the scattering spectra by varying the nanoantenna thickness. Our work shows a possible way to enhance light-matter interaction at a single quantum emitter limit, which can be useful for future quantum and nanophotonic applications.

Several studies have reported a relationship between autonomic dysfunction　 during tasks and Internet addiction. Changes within 24 h regarding heart rate variability (HRV) may be a more sensitive indicator than short term observations. We evaluated the influence of excessive Internet usage on HRV using a 24 h electrocardiogram (ECG) and examined acute changes during computer game tasks. A total 13 high school students and 22 young adults were recruited, and divided into excessive Internet user and non- excessive user groups based on Internet addiction test scores. The ECG was recorded continuously for 24 h by a wearable sensor and during two computer games (the Iowa gambling task and each participant’s preferred game) using a standard type ECG system. Multiple psychometric tests were also conducted. The excessive Internet user group exhibited clinically significant depressive symptoms, and higher self-reported scores for anxiety, impulsivity, autistic tendencies, and sleep problems than the non- excessive internet user group. There were weak differences within the 24 h high-frequency (HF) band power between two groups. During the Iowa gambling task, younger participants exhibited a reduced HF response, which may be related to weaker top- down self- regulatory mechanisms.

The goal of this paper is to fabricate innovative diaphragm headphones using graphene oxide paper (GOP) and GOP/epoxy nanocomposites (GOPC). Initially, graphene oxide suspension is fabricated, and the vacuum filtration method is adopted to make GOP. Then vacuum bag molding is used to fabricate GOPC from GOP. Hot pressing and associated molds are adopted to fabricate line-indented (GOPC-L) or curve-indented patterns (GOPC-C) on the GOPC. The performance of one kind of GOP and three kinds of GOPC diaphragm headphones is analyzed based on their sound pressure level (SPL) curves achieved by the Soundcheck measurement system. There are four important processing parameters that will influence the performance of the diaphragm, including material type GOP versus GOPC, indented pattern type, sonication time on suspension, and graphene weight fraction in suspension. Compliances of various diaphragms are measured by the Klippel LPM laser measurement system. The results indicate that effects of sonication time and graphene weight fraction on SPL of GOP and GOPC headphones are in reverse, and this is associated with their difference on compliance (modulus), mass, damping ratio, and microstructure uniformity. Either GOPC-L or GOPC-C seems to improve the microstructure of the GOPC, and leads to better SPL performance. The correlation between the previous four factors and SPLs of four kinds of diaphragm headphones is proposed by using scanning electron microscope (SEM) to examine the microstructure of these diaphragms.

Hydrogenases are iron-sulfur enzymes that catalyze proton reduction and H₂ oxidation with outstanding efficiency. They are considered blueprints for the design of transition metal complexes, e.g. as heterogenous catalysts in the context of H₂ production from water. Moreover, hydrogenases are biological model systems for metal hydride chemistry and proton-coupled electron transfer. Depending on the composition of the active site cofactor, [NiFe]-hydrogenases are distinguished from [FeFe]-hydrogenases. The former binds a hetero bimetallic nickel/iron site, embedded in the protein by four cysteine ligands. The later, by contrast, carries a homo bimetallic iron/iron site attached to the protein by only a single cysteine. Carbon monoxide and cyanide ligands (CO/CN) at the active site facilitated detailed investigations of hydrogenase catalysis by infrared spectroscopy, owing to strong signals and redox-dependent frequency shifts. However, the details of proton transfer have not been addressed experimentally.We found that specific redox state transitions in [NiFe]- and [FeFe]-hydrogenase can be triggered by visible light to record extremely sensitive ‘light-minus-dark’ infrared difference spectra monitoring key amino acid residues as shown in the ToC figure. As these transitions are coupled to protonation changes, our data allowed investigating dynamic hydrogen-bonding changes that go well beyond the resolution of protein crystallography. In [NiFe]-hydrogenase, photolysis of the bridging hydride ligand in the ‘Ni-C’ state was followed by rapid accumulation of the ‘Ni-SI_a’ state and/or ‘Ni-L’ state. Infrared difference spectra in various isotopic media clearly indicated the formation of a protonated cysteine residue as well as hydrogen-bonding changes involving the COOH group of a glutamic acid residue and a ‘dangling water’ molecule. These findings are in excellent agreement with crystallographic analyses of [NiFe]-hydrogenase in the Ni-R state and allowed devising a molecular precise model of catalytic proton transfer. In [FeFe]-hydrogenase, an external redox dye was used to accumulate the ‘Hred’ state over the oxidized resting state ‘Hox’. Infrared difference spectra of wild-type enzyme and numerous amino acid variants indicated hydrogen-bonding changes involving the COOH groups of two glutamic acid residues. Moreover, we noted the deprotonation of an arginine residue. Crystallographic analyses of [FeFe]-hydrogenase in the Hox state failed to explain the rapid proton transfer due to a ‘breach’ in the succession of residues. To this end, our findings facilitated a molecular precise model of ‘discontinued’ proton transfer.The comparison of catalytic proton transfer in bimetallic hydrogenases emphasizes the role of the outer coordination sphere. We suggest that the stable protonation of a nickel-ligating cysteine in [NiFe]-hydrogenase has a crucial influence on the preferred direction of proton flow and catalysis (i.e., H₂ oxidation). On the contrary, proton transfer in [FeFe]-hydrogenase involves an adjacent cysteine as a relay group that promotes both proton release and proton uptake. We presume that this causes the notable bidirectionality of [FeFe]-hydrogenase. These observations must guide the design of biomimetic compounds for the production or consumption of H₂.

Nitroxyl radical catalysts oxidize alcohols under an applied electric potential. It is possible to quantify the alcohol concentration from the resulting oxidation current. In this work, we evaluated the catalytic activity of nitroxyl radicals (or their corresponding hydroxylamines), including 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) as representative nitroxyl radicals, acetoamido-TEMPO, which shows higher oxidation potential than TEMPO owing to the acetoamido group, AZADO, Nor-AZADO, and NNO as less-hindered bicyclic nitroxyl radicals, and NHPI as an N,N-diacyl-type hydroxylamine, in acetonitrile solution. TEMPO, AZADO and NNO were also evaluated for their ability to oxidize alcohols in organic solvents, and their reactivity was compared with the electrochemical response. The most active NNO was used for electrochemical detection of cyclosporin A, a drug with a hydroxyl group.

It is found in this paper that ILR-RPCA-back CLR has two problems when dealing with the closure effect of geochemical data. (1) After ilr transformation, RPCA is used for processing. It can be seen from the double-plot diagram that the first principal component and the second principal component transform with the element sequence transformation, and the unique principal component cannot be calculated; (2) the score and the load are transformed into the CLR space through the U matrix. According to the formula CLR=ALR·U, the score result can correspond to the original order of elements. However, the load result obtained by the use of this formula cannot correspond to the original order of elements, and the result can only be obtained through the formula” CLR=UT·ALR”. In order to obtain the best element assemblage of porphyry copper deposit, this paper adopted the mineral assemblage of discovered deposits in Gangdese metallogenic belt for statistical analysis, and obtained that the element assemblage of porphyry copper deposit was Cu, Mo, Au, Ag, W, Bi. Then, by analyzing the singularities of the composite elements, the spatial overlay of the combined element is carried out, and C-A fractal filtering is applied to identify the anomaly and background. In order to facilitate comparison, the different minerals and ore deposit types have been analyzed, the results show that (1) in view of the porphyry copper deposits, recognition effect of combination elements are better than which single element, (2) skarn type copper deposit that it has nothing to do with the porphyry had a high degree of difference, but skarn type copper deposit related to the porphyry had a low degree of difference, (3) This method has a certain advantage over the single element method in porphyry gold deposits, and it can reduce the level of anomalies. Such an advantage is that in the aspect of anomaly evaluation of porphyry copper deposits, the level is reduced at the initial stage of evaluation to reduce the investment in such anomalies, (4) This method has limited ability to distinguish porphyry copper deposit from porphyry molybdenum deposit.

The objective of this investigation was to enhance the sensory appeal of Cerasus humilis (C. humilis) juice and ascertain potential interactions among bioactive compounds within a functional juice matrix. Sensory attributes, color, antioxidant potential, polyphenol and vitamin C (VC) concentrations, and sugar levels were assessed. Diverse dosage combinations were examined to determine their impact on the quality of both C. humilis and Green grape juices. Among the formulations, CG5 exhibited elevated antioxidant activit y and polyphenol content (455.02 mg TE/100 ml and 173.1 mg/100 ml, respectively), coupled with favorable consumer preference. Notable variations in compound content were observed across the seven analyzed juices. In the blended juices (CG1–CG5), interactions between distinct juices influenced VC and sugar levels, with other bioactives contributing to beneficial modifications, displaying a progressive rise. This study innovatively crafted delectable and convenient C. humilis juice, upholding its intrinsic high antioxidant activity, thereby presenting a novel avenue for marketable functional juice offerings.

Extracellular vesicles (EVs), such as exosomes or oncosomes are released with molecules unfavorable for survival from cells. In addition, accumulating evidence has shown that tumor cells often eject anti-cancer drugs such as chemotherapeutics and targeted drugs within EVs, a novel mechanism of drug resistance. The EV-releasing, drug resistance phenotype is often coupled with cellular dedifferentiation and transformation, cells undergoing epithelial-mesenchymal transition (EMT) and taking on a cancer stem cell phenotype. Recent studies have shown that the release of EVs is also involved in immunosuppression. The concept of the resistance-associated secretory phenotype (RASP) is reviewed herein.

Single-particle inductively coupled plasma mass spectrometry (spICP-MS) has been used for particle size measurement of diverse types of individual nanoparticles and micrometer-sized carbon-based particles, such as microplastics. However, its applicability to the measurement of micrometer-sized non-carbon-based particles such as silica (SiO2) is unclear. In this study, the applicability of spICP-MS to particle size measurement of non-porous/mesoporous SiO2 micro-spheres with a nominal diameter of 5.0 µm or smaller was investigated. Particle sizes of these microspheres were measured using both spICP-MS based on a conventional calibration approach using an ion standard solution and scanning electron microscopy (SEM) as a reference technique and the results were compared. The particle size distributions obtained using both techniques were in agreement within analytical uncertainty. The applicability of this technique to the detection of metal-containing protein-binding mesoporous SiO2 microspheres was also investigated. Bound iron (Fe)-containing proteins (i.e., lactoferrin and transferrin) of mesoporous SiO2 microspheres were detected using Fe as a presence marker for the proteins. Thus, spICP-MS is applicable to the particle size measurement of large-sized and non-porous/mesoporous SiO2 microspheres; it has considerable potential for element-based detection and qualification of bound proteins of mes-oporous SiO2 microspheres in a variety of applications.

Resistant cancer often shows a particular secretory trait such as heat shock proteins (HSPs) and extracellular vesicles (EVs), including exosomes and oncosomes surrounded by lipid bilayers. Lipoproteins are biochemical assemblies that transport hydrophobic lipid (a.k.a. fat) molecules in body fluid and are composed of a single-layer phospholipid and cholesterol outer shell, lipids molecules within the particles, and apolipoproteins embedded in the membrane. However, lipoprotein storage and secretion by cancer cells have not well-investigated yet. We found lipoproteins were stored and abundantly secreted by neuroendocrine, castration-resistant prostate cancer (NEPC / CRPC) cells but barely secreted by colon cancer cells and oral squamous cell carcinoma (OSCC) cells. In addition, large EVs (approx. 300 nm diameter) and potential oncosomes were released by CRPC and OSCC cells. Proteomics revealed that CRPC cells secreted EVs enriched with tetraspanins and extracellular matrices which were reduced upon heat shock stress and alternatively lipoproteins and HSPs were secreted upon stress. Heat shock stress triggered secretion of lipoprotein-EV complexes that contained apolipoprotein A, B, C and E. These data suggested that vesicular assembly composed of EVs and lipoproteins enriched with cholesterols and phospholipids may be stored in resistant cancer cells but released upon cell stress that is increased in cancer therapies.

A new treatment option for cluster headache (CH) prevention is needed. Monoclonal antibodies (mABs) against calcitonin gene-related peptide (CGRP) ligands are used as a preventative treatment for migraine. Considering the CGRP’s role in the CH attack’s ignition and upkeep, fremanezumab and galcanezumab have been evaluated for CH preventative treatment. However, only high-dose (300 mg) galcanezumab was proven for episodic CH prevention. We herein report 3 cases of migraine and comorbid CH with previous failures of preventive treatments. The 2 cases were treated with fremanezumab and the one with non-high-dose galcanezumab. All 3 cases showed good results not only on migraine but also on CH attacks. Our report suggested the efficacy of CGRP-mABs for CH prevention. Our cases differed from the cases in the phase 3 trials of CGRP-mABs for CH prevention in the following 2 points. First, the patients had both migraine and comorbid CH. Second, the combined use of CGRP-mABs with preventative drugs for CH, such as verapamil and/or prednisolone, was performed. Future accumulation of real-world data may prove the efficacy of CGRP-mABs for CH prevention.

This paper considers a new approach to the modeling of the vacuum infusion process at the manufacturing three-dimensional composite parts of complex shape. The developed approach and numerical methods are focused on the reliable prediction with the needed accuracy and elimination the unrecoverable defect of composite structure such as the dry spots. The paper presents some experimental results, which demonstrate two cases of dry spots formation in large aircraft composite panels, and analyses the reasons of these defects arising. Our numerical technique is based on the vacuum infusion of the liquid resin into porous preform as the two phase flow, which is described by the phase field equation coupled with the Richards equation describing the fluid motion in unsaturated soils with spatially varied pressure dependant porosity and saturation. This problem statement allowed to correctly reconstruct the resin front motion and formation of inner and outer dry spots depending on its movement. For the rapid detection of preform zones that are suspicious for defect formation two indicators calculated during process simulation are proposed and tested at the numerical experiments. The auxiliary program tool has been developed in MATLAB environment to correctly detect the times of formation, localization and dimensions of the arising dry spots by using the results of the finite element model simulation.

Background and Aim: Tacrolimus is highly effective in intractable ulcerative colitis, but maintenance may be problematic. This study examined 52-week maintenance and adverse events. Methods: This retrospective study of patients who used tacrolimus from April 2009 to December 2021 (N = 136) examined remission induction rates and background factors in the remission (n = 108) and non-remission groups (n = 28); 52-week maintenance; drug-specific maintenance (azathioprine [n = 58] vs tacrolimus [n = 12] and vs biological product [Bio, n = 8]); and adverse events. Results: The mean observation period was 1230175 days. Remission occurred in 72.7%. Significant differences were observed in sex and endoscopic score (before treatment and 2 weeks after tacrolimus trough levels). Maintenance rate at 52 weeks was 61.6%; significant differences were observed in sex, hospitalization duration, and prednisolone during hospitalization (P < 0.05). Drug-specific 52-week maintenance was 67% with azathioprine, 54% with tacrolimus, and 37% with Bio. No tacrolimus-related serious adverse events occurred that led to discontinuation. Discussion: Remission was more common in women with improved endoscopic scores after tacrolimus trough levels and patients with improved endoscopic scores after tacrolimus therapy. Remission maintenance was more common in women with a long hospitalization at remission and high total steroid dose. Results suggest that treatment with adequate prednisolone use during the period with more inflammation may improve subsequent maintenance. Conclusions: In intractable ulcerative colitis, tacrolimus can induce remission even in patients who cannot use azathioprine for maintenance. Remission can be maintained with azathioprine, tacrolimus, or a Bio.

Various optically active 2-hydroxyamide derivatives are produced based on the kinetic resolution of racemic 2-hydroxyamides with a diphenylacetyl component and (R)-benzotetramisole [(R)-BTM], a chiral acyl-transfer catalyst, via asymmetric esterification and acylation. It was revealed that a tertiary amide can be used with this novel protocol to achieve high selectivity [22 examples; s-value reaching over 250]. The resulting chiral compounds could be transformed into other useful structures while maintaining their chirality.

In the present study, an attempt was made to induce rooting from single-node cuttings of hybrid aspen (Populus tremula L. ×P. tremuloides Michx.) with different concentrations of IAA, IBA and NAA during rooting. Among the three auxins used, NAA showed more effective induction on rooting as compared to IAA and IBA at the whole level. Thereafter, NAA was used further in experiments for anatomical and biochemical investigation. The results showed that it took 12 days from the differentiation of primordium to the appearance of young adventitious roots with NAA application. It was found that endogenous IAA, ZR and GA3 levels increased, but ABA decreased in cuttings with 0.54 mM NAA treatment. In contrast to the endogenous IAA level, NAA had negative effect on IAA-oxidase (IAAO) activity. Similarly, the decreased peroxidase (POD) activity, consistent with down-regulation of expressed levels of POD1 and POD2, was observed in NAA-treated cuttings. Whereas, NAA resulted in a higher activity in polyphenol oxidase (PPO) compared to the control cuttings. Collectively, the study highlighted that 0.54 mM NAA is efficient on rooting in hybrid aspen, and its effect on metabolic changes during rooting is discussed, which provide valuable information for propagating hybrid aspen.

We live in extraordinary times, where COVID-19 pandemic has brought the whole world to a screeching halt. Tensions and contradictions that surround the pandemic ridden world include the availability, and the lack thereof, various facial protection measures to mitigate the viral spread. Here, we comprehensively explore the different type of facial protection measures, including masks, needed both for the pubic and the health care workers (HCW). We discuss the anatomy, the critical issues of disinfection and reusability of masks, the alternative equipment available for the protection of the facial region from airborne diseases, such as face shields and powered air purifying respirators (PAPR), and the skin-health impact of prolonged wearing of facial protection by HCW. Clearly, facial protection, either in the form of masks or alternates, appears to have mitigated the pandemic as seen from the minimal COVID-19 spread in countries where public mask wearing is strictly enforced. On the contrary, the healthcare systems, that appear to have been unprepared for emergencies of this nature, should be appropriately geared to handle the imbalance of supply and demand of personal protective equipment including face masks. These are two crucial lessons we can learn from this tragic experience.

With the development of health service, animal husbandry, aquaculture and chemical industry, more and more pollutants are discharged into the water environment, including antibiotics and heavy metal ions. These hazard substances pose a great threat to environment safety and human health. As two kinds of new green solvents, ionic liquids (ILs) and deep eutectic solvents (DESs) are widely used in various fields including separation and environmental engineering, which are attracting huge attention from academia and industry. In this study, the optimal ionic liquid and deep eutectic solvent were selected and their complex with β-cyclodextrin (β-CD) were firstly prepared by simple and effective inclusion way. After necessary characterization and analysis, two kinds of complex were applied to prepare a special sorbent disc with two different sides by adding diluent (excipient) and pressing under 5~15 MPa. As the result, the IL and DES could be stably immobilized on the disc and play the key role in selective adsorption for targets. Besides that, the experiments of different hazardous substances achieved the expected results. Based on this study, the complex disc showed a lot of merits in the separation performance, easy preparation and use, simple operation, and good stability. It was believed to be a useful tool for water purification and detection.

Abiogenic hydrocarbons are fundamentally important for understanding the deep microbial communities and the origin of life. The generation of abiogenic hydrocarbons was proposed to be limited to ultramafic-hosted hydrothermal systems, fueled by the serpentinization product H₂. Here, we present the discharge of short-chain alkanes from an andesitic rock-hosted Lutao geothermal field in the north Luzon arc, carrying abiotic chemical and isotopic signals. These abiogenic hydrocarbons were generated from CO₂-H₂O-rich fluid inclusions, where the long-term storage since Lutao volcanism (~ 1.3 Ma) allowed overcoming the sluggish kinetics of CO₂ to CH₄ reduction at temperatures of 174 - 206 ^oC. Natural abiogenic production of hydrocarbons, therefore, can be more ubiquitous than previously thought. The hypothesis regarding the origin of methane in Earth’s early atmosphere and its implication to the origin of life may require reconsideration.

The aim of this study was to assess the best timing to perform arthrocentesis in the management of temporomandibular disorders with regards to conservative treatment. A systematic search based on PRISMA guidelines, including a computer search with specific keywords, reference list search, and manual search was done. Relevant articles were selected after 3 search rounds for final review based on 6 predefined inclusion criteria, followed by a round of critical appraisal. Eleven publications, including 5 randomized controlled trials and 6 prospective clinical studies informed this review. The studies were divided into 3 groups based on the timing of arthrocentesis: 1). Arthrocentesis as the initial treatment, 2). Early arthrocentesis, and 3). Late arthrocentesis. Meta-analyses compared the efficacy of improvement in mouth opening and pain reduction in the 3 groups. The results were statistically significant and favoured early arthrocentesis, followed by late arthrocentesis in terms of both improvements in mouth opening and pain reduction. All 3 groups showed improvement in mouth opening and pain reduction. We conclude that early arthrocentesis may be able to produce the best clinical results, while arthrocentesis before attempting conservative treatment may produce less favourable outcomes.

Praeruptorin A(PA), a naturally existing pyranocumarin, is isolated from the dried root of Peucedanum praeruptorum Dunn. So far the anti-cancer effect and molecular mechanism behind Praeruptorin A action in human cervical cancer HeLa cells remain unknown. In the present study, we find that PA reduces cell proliferation and colony formation of human cervical cancer HeLa cells through inducing cell cycle arrest at G0/G1 phase. PA-upregulated p21 and p27 proteins are observed, accompanied with inhibition of cyclin D1 and S-phase kinase-associated protein 2(Skp2) proteins expression. PA could significantly inhibit migration and invasion of human HeLa cells. Meanwhile, PA significantly reduces invasive protein expression of matrix metalloproteinase-2 (MMP-2), and increases protein expression of tissue inhibitor of metalloproteinase-2 (TIMP-2). PA is observed to possess the capacity in suppressing ERK1/2 activation. PD98059 (ERK specific inhibitor) significantly enhances PA-induced downregulation of MMP-2 expression, and upregulation of TIMP-2 expression. Moreover, we found that PA treatment notably inhibits 12-O-tetradecanoylphorbol-13-acetate(TPA)-upregulated ERK1/2 activation, MMP-2 expression, cellular migration and invasion in human HeLa cells. Taken together, these findings are the first to demonstrate the anti-cancer activity of PA, which may act as a promising therapeutic agent for the treatment of human cervical cancer.

Fiber-opening treatment of commingled yarns consisting of thermoplastic nylon fibers and carbon fibers could produce superior CFRTP, but few studies toward that end have been conducted. In this study, we investigated whether an open weave fabric consisting of commingled yarns made of carbon and nylon fibers could shorten the impregnation distance of resin to carbon fibers, and there are few reports on the design of fabrics by opening carbon fiber bundles consisting of commingled yarns. From this study, following are cleared. The impregnation speed of the nylon resin on the carbon fiber was very fast, less than 1 minute. As the molding time increased, the tensile strength and tensile fracture strain slightly decreased and the nylon resin deteriorated. The effects of molding time on flexural strength, flexural modulus, and flexural fracture strain were negligible. From the cross-sectional observation conducted to confirm the impregnation state of the matrix resin, no voids were observed in the molded products regardless of molding time or molding pressure, indicating that resin impregnation into the carbon fiber bundle of the open-fiber mixed yarn fabric was completed at a molding pressure of 5 MPa and a molding time of 5 min.

Epithelial-mesenchymal transition (EMT) networks are essential in acquiring the drug resistance and cancer malignant features in cancer stem cells (CSCs). In this regard, gene expression profiles in diffuse- and intestinal-type gastric cancer (GC) have been analyzed to reveal the network pathways in EMT and CSCs, since the diffuse-type GC has much more mesenchymal features than intestinal-type GC that has the intestinal features. The study results revealed that the activation state of several canonical pathways related to cell cycle regulation was altered. The canonical pathway on Cell cycle: G1/S checkpoint regulation was activated in diffuse-type GC, and canonical pathways on Cell cycle control of chromosomal replication and Cyclins and cell cycle regulation were activated in intestinal-type GC. Canonical pathway related to Role of BRCA1 in DNA damage response was activated in intestinal-type GC, where BRCA1, which is related to G1/S phase transition was up-regulated in intestinal-type GC. Several microRNAs (miRNAs), including mir-10, mir-17, mir-19, mir-194, mir-224, mir-25, mir-34, mir-451, and mir-605, were identified to have direct relationships of RNA-RNA interaction in Cell cycle: G1/S checkpoint regulation pathway. Additionally, cell cycle regulation may be altered in EMT conditions. The alterations in activation states of the pathways related to cell cycle regulation in diffuse- and intestinal-type GC would indicate the significance of cell cycle regulation in EMT.

Due to the high effectiveness of cancer screening and therapies, the diagnosis of second primary cancers (SPCs) has increased in women with endometrial cancer (EC). However, there’s no previous literature mentioned about adequate evidence to support screening for SPCs in endometrial cancer. This study was aimed to develop effective risk prediction models of second primary endometrial cancer in women with obesity (Body-mass index; BMI > 25) and this study includes datasets of the incidence of SPCs and the other risks of SPCs in 4480 primary cancer survivors by a hospital-based cancer registry database. In our study, we found the obesity played a key role in SPCs. There’re 10 independent variables used as predicting variables, which corelated to obesity should be monitored for the early detection of SPCs in endometrial cancer. In conclusion, it is a promising SPCs prediction. The proposed scheme can support the important influence of obesity and clinical data representations in all cases after primary treatments. Our results suggested that obesity is still a crucial risk factor to SPCs in endometrial cancer.

The state of charge estimation is an important part of the battery management system, the estimation accuracy of which seriously affects the working performance of the lithium ion battery pack. The unscented Kalman filter algorithm has been developed and applied to the iterative calculation process. When it is used to estimate the SOC value, there is a rounding error in the numerical calculation. When the sigma point is sampled in the next round, an imaginary number appears, resulting in the estimation failure. In order to improve the estimation accuracy, an improved adaptive square root - unscented Kalman filter method is introduced which combines the QR decomposition in the calculation process. Meanwhile, an adaptive noise covariance matching method is implied. Experiments show that the proposed method can guarantee the semi-positive and numerical stability of the state covariance, and the estimation accuracy can reach the third-order precision. The error remains about 1.60% under the condition of drastic voltage and current changes. The conclusion of this experiment can provide a theoretical basis of the state of charge estimation in the battery management of the lithium ion battery pack.

The external and internal structures of male and female adults of Culicoides grisescens Edwards, were examined with scanning electron microscope (SEM) and tissue section techniques. Specimens were collected from Qilian Mountain National Park in Qinghai Province, China. The ultrastructure and morphology of compound eyes, antenna, maxillary palpus, spermathecae, genitalia and other structural characteristics of both male and female adults of C. grisescens are described. Internal structures of the species are described, including histological sections of the digestive, nervous, respiratory, and reproductive systems. This paper provides visual and descriptive details for the systematic taxonomic study of Ceratopogonidae.

Epithelial-mesenchymal transition (EMT) plays an important role in the acquisition of cancer stem cell (CSC) feature and drug resistance, which are the main hallmarks of cancer malignancy. Although previous findings have shown that several signaling pathways are activated in cancer progression, the precise mechanism of signaling pathways in EMT and CSCs are not fully understood. In this study, we focused on the intestinal and diffuse-type gastric cancer (GC), and analyzed the gene expression of public RNAseq data to understand the molecular pathway regulation in different subtypes of gastric cancer. Network pathway analysis was performed by Ingenuity Pathway Analysis (IPA). Total 2815 probe set IDs were significantly different between intestinal- and diffuse-type GC data in cBioPortal Cancer Genomics. The 10 genes including male-specific lethal 3 homolog (Drosophila) pseudogene 1 (MSL3P1), CDC28 protein kinase regulatory subunit 1B (CKS1B), DEAD-box helicase 27 (DDX27), golgi to ER traffic protein 4 (GET4), chromosome segregation 1 like (CSE1L), translocase of outer mitochondrial membrane 34 (TOMM34), YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), ribonucleic acid export 1 (RAE1), par-6 family cell polarity regulator beta (PARD6B), and MRG domain binding protein (MRGBP) were found to have difference in gene expression in intestinal- and diffuse-type GC. Total 463 direct relationships with 3 molecules (MYC, NTRK1, UBE2M) were found in the biomarker-filtered network generated by network pathway analysis. The networks and features in intestinal- and diffuse-type GC have been investigated and profiled in bioinformatics. Our results revealed the signaling pathways networks in intestinal- and diffuse-type GC, bringing new light for the elucidation of drug resistance mechanisms in CSCs.

The Paeonia suffruticosa, called as 'Feng Dan', has been used for thousands of years in traditional Chinese medicine. In our chemical investigation on the root bark of the plant, five new phenolic dimers, namely paeobenzofuranone A‒E (1‒5), have been characterized. Their structures were determined by spectroscopic analysis including 1D and 2D NMR, HRESIMS, UV, and IR, as well as ECD calculations. Compounds 2, 4, and 5 showed cytotoxicity against three human cancer cell lines with IC50 values ranging from 6.7 to 25.1 μM. Compounds 1 and 2 showed certain inhibitory activity on NO production. To the best of our knowledge, the benzofuranone dimers and their cytotoxicity of P. suffruticosa are reported for the first time.

This paper addresses investigation of guided-wave excitation by angle-beam wedge piezoelectric transducers in multi-layered composite plate structure with orthotropic symmetry of the material. The aim of the present study is to determine the capability of such actuators to provide the controlled generation of an acoustic wave of a desirable type with the necessary wavelength, propagation distance and directivity. The studied CFRP panel is considered as homogenous with effective elastic moduli and anisotropic structural damping, whose parameters were determined experimentally. According to the results of dispersion analysis and taking into account the data of wave attenuation in a highly damping CFRP composite, the two types of propagating waves A0 and S0 were considered theoretically and experimentally in the frequency range 10 - 100 kHz. Using the results of a previous study, the structure of the wedge actuator was reconstructed to develop its finite element (FE) model, and a modal analysis was carried out, which revealed the most intense natural vibration modes and their eigenfrequencies within the used frequency range. Both experimental and numerical studies of the generation, propagation, directivity and attenuation of waves in the orthotropic composite panel under study revealed the influence of the angular orientation of the actuator on the formation of wave patterns and allowed to determine the capabilities of the wave's directivity control.

Mangrove creeks adjoining typical riverine mangrove forests is known to be a net source of CO2 and dissolved inorganic carbon (DIC) to the ocean due to the decomposition of rich organic carbon in the soil; such information is limited in fringe mangroves. This study aims to clarify the difference in carbonate processes between the two types of mangrove forests. We conducted continuous monitoring of the partial pressure of carbon dioxide (pCO2) and measured carbonate chemistry parameters (total alkalinity (TA) and DIC) in two types of mangrove areas located in Okinawa, Japan. The result showed that the maximum pCO2 reached 5242 µatm in the Fukido River estuary (a riverine mangrove), whereas it was only 765 µatm on the Yubu coast (a fringe mangrove). The measured maximum TA and DIC values were 3285 µM and 3283 µM in the Fukido River estuary and 3162 µM and 2977 µM on the Yubu coast. These indicate that pCO2 on the Yubu coast was maintained at low values by the carbonate buffering capacity even when TA and DIC increased rapidly. The mangroves on the Yubu coast grow on dead corals and coral soils. It was suggested that the DIC/TA ratio was constantly kept at approximately 0.9 due to TA production by the dissolution of calcium carbonate (CaCO3), which resulted in lower pCO2.

Ultrasound has become widely used as a mean to measure the rectus femoris muscle in the acute and chronic phase of critical illness. Despite its noninvasiveness and accessibility, its accuracy highly depends on the skills of the technician. However, few ultrasound phantoms for the confirmation of its accuracy or to improve technical skills exist. In this study, we created a novel phantom model and used it for investigating the accuracy of measurements and for training. Study 1 investigated how various conditions affect ultrasound measurements such as thickness, cross-sectional area, and echogenicity. Study 2 investigated if the phantom can be used for training of various health care providers in vitro and vivo. Study 1 showed that thickness, cross-sectional area, and echogenicity were affected by probe compression strength, probe angle, phantom compression, and varying equipment. Study 2 in vitro showed that using the phantom for training improved the accuracy of the measurements taken within phantom, and Study 2 in vivo showed the phantom training had a short-term effect on improving the measurement accuracy in a human volunteer. The new ultrasound phantom model revealed that various conditions affected ultrasound measurements, and phantom training improved the measurement accuracy.

Immune cells such as T cells and macrophages express α7 nicotinic acetylcholine receptors (α7 nAChRs), which contribute to the regulation of immune and inflammatory responses. Earlier findings suggest α7 nAChR activation promotes the development of regulatory T cells (Tregs) in mice. Using human CD4+ T cells, we investigated the mRNA expression of the α7 subunit and the human-specific dupα7 nAChR subunit, which functions as a dominant-negative regulator of ion channel function, under resting conditions and T cell receptor (TCR)-activation. We then explored the effects of the selective α7 nAChR agonist GTS-21 on proliferation of TCR-activated T cells and Treg development. Varied levels of mRNA for both the α7 and dupα7 nAChR subunits were detected in resting human CD+ T cells. mRNA expression of the α7 nAChR subunit was profoundly suppressed on days 4 and 7 of TCR-activation as compared to day 1, whereas mRNA expression of the dupα7 nAChR subunit remained nearly constant. GTS-21 did not alter CD4+ T cell proliferation but significantly promoted Treg development. These results suggest the potential ex vivo utility of GTS-21 for preparing Tregs for adoptive immunotherapy, even with high expression of the dupα7 subunit.

In this paper, the deformation behavior of S32750 duplex stainless steel during low cycle fatigue was studied by controlling number of cycles. The microstructure of the specimens under different cycles was characterized by optical microscope (OM), scanning electron microscope (SEM), electron backscatter diffraction (EBSD) and transmission electron microscope (TEM). Microhardness of two phases was measured by a digital microhardness instrument. The results showed that the microhardness of ferrite increases significantly after the first 4000 cycles, while the austenite shows a higher strain hardening rate after fatigue fracture, and the microhardness of ferrite and austenite increases by 23 HV and 87 HV, respectively. Two-phase kernel average misorientation (KAM) diagram showed that the continuous accumulation of plastic deformation easily leads to the initiation of cracks inside the austenite and at the phase boundaries. The evolution of dislocation morphology in two phases was obviously different. With the increase of cycle number, the dislocation in ferrite gradually transforms from dislocation bundles and dislocation array to sub-grain structure, while the dislocation in austenite gradually develops from dipole array to ordered Taylor lattice network structure.

To reveal the relationship between metallodrugs and cancer malignancy, molecular networks of anti-cancer drugs were analyzed. Molecular networks in several types of cancers were analyzed in Ingenuity Pathway Analysis (IPA). Analysis of carboplatin revealed the causal network in diffuse large B-cell lymphoma. Analysis of 12 analyses of cisplatin treatment identified causal networks including camptothecin and NUPR1. The causal network of camptothecin, which includes PTEN, FAS, and IRF1, was inactivated in diffuse-type GC and activated in intestinal-type GC. Upstream regulator analysis of cisplatin revealed an increase in FAS, BTG2, SESN1 and CDKN1A, and the involvement of the tumor microenvironment pathway. Upstream regulators of cisplatin-treated lung adenocarcinoma included a histone deacetylase inhibitor, trichostatin A (TSA). Causal network of arsenic was inactivated in diffuse-type GC and activated in intestinal-type GC, and included ERK, EGFR, SRC, IKK and TP53. Prediction of RNA-RNA interactions with the causal network of arsenic identified 10 microRNAs including mir-101, mir-103, and mir-22. The results revealed the involvement of EMT in arsenic treatment. Analysis of oxaliplatin, a platinum drug, revealed that the SPINK1 pancreatic cancer pathway is inactivated in ischemic cardiomyopathy. The study showed the importance of the relationship between platinum drugs or arsenic trioxide and the tumor microenvironment in the treatment of resistant cancer in humans.

Tumor cells exhibit a resistance-associated secretory phenotype involving extracellular vesicles (EVs) and heat shock proteins (HSPs). This response occurs in response to cell stress and cancer therapeutics. HSPs are stress-responsive molecular chaperones promoting proper protein folding, while also being released from cells with EVs as well as in free form as alarmins. We have here investigated the secretory phenotype of castration-resistant prostate cancer (CRPC) cells using proteome analysis. We have also examined the roles of the key co-chaperone CDC37 in stressome release, epithelial-to-mesenchymal transition (EMT), and tumor progression. A number of HSP family members and their common receptor CD91/LRP1 were enriched at high levels in CRPC cell-derived EVs among over 700 other protein species. The small EVs (30 to 200 nm in size, potentially exosomes) were released even in a non-heated condition from the prostate cancer cells, whereas EMT-coupled release of EVs (200 to 500 nm, likely ectosomes) with associated HSP90α was increased after heat shock stress (HSS). Lactate dehydrogenase, a marker of membrane leakage/damage of cells, was also released upon HSS from the prostate cancer cells. During this stress response, intracellular CDC37 was also transcriptionally inducible by heat shock factor 1, and knockdown of CDC37 decreased EMT-coupled release of EVs. Triple knockdown of CDC37, HSP90α, and HSP90β was required for efficient reduction of the chaperone trio and to reduce tumorigenicity of the CRPC cells in vivo. Taken together, the data indicated that CDC37 and HSP90 are essential for stressome release and for tumorigenesis in resistant cancer.

Oxygen extraction fraction (OEF), the fraction of oxygen that tissue extracts from blood, is an es-sential biomarker for directly assessing tissue viability and function in neurologic disorders. For quantitative mapping of OEF, an integrative model of quantitative susceptibility mapping and quantitative blood oxygen level-dependent magnitude (QSM+qBOLD or QQ) was recently pro-posed. However, QQ assumes Gaussian noise in both susceptibility and multi-echo gradient echo (mGRE) magnitude signals for OEF estimation. This assumption is unreliable in low sig-nal-to-noise ratio (SNR) regions like disease-related lesions, risking inaccurate OEF estimation and potentially impacting clinical decisions. Addressing this, our study presents a novel multi-echo complex QQ (mcQQ) that models realistic noise in mGRE complex signals. The proposed mcQQ was implemented using a deep learning framework (mcQQ-NET) and compared with the existing deep learning-based QQ (QQ-NET) in simulations, ischemic stroke patients, and healthy subjects. Both mcQQ-NET and QQ-NET used identical training and testing datasets and schemes for a fair comparison. In simulations, mcQQ-NET provided more accurate OEF than QQ-NET. In the sub-acute stroke patients, mcQQ-NET showed a lower average OEF ratio in lesions relative to unaf-fected contralateral normal tissue than QQ-NET. In the healthy subjects, mcQQ-NET provided uniform OEF maps, similar to QQ-NET, but without unrealistically high OEF outliers in areas of low SNR. Therefore, mcQQ-NET improves OEF accuracy by better reflecting realistic data noise characteristics.

To reduce the cost of small wind turbines, a prototype of a butterfly wind turbine (6.92 m in diameter), a small vertical-axis type, was developed with many parts made of extruded aluminum suitable for mass production. An over-speed control system with movable arms that operated using centrifugal and aerodynamic forces was installed for further cost reduction. Introducing this mechanism eliminates the need for large active brakes and expands the operating wind speed range of the wind turbine. However, although the mechanism involving the use of only bearings is simple, the violent movement of the movable arms can be a challenge. To address this in the present study, dampers were introduced on the movable arm rotation axes to improve the movement of the movable arms. To predict the behavior of a movable arm and the performance of the wind turbine with the mechanism, a simulation method was developed based on the blade element momentum theory and the equation of motion of the movable arm system. Comparison of experiments and predictions with and without dampers demonstrated qualitative agreement. In the case with dampers, measurements confirmed the predicted increase in the rotor rotational speed when the shorter ailerons installed perpendicularly to the movable arms were used to achieve the inclination. The movable arm system with dampers is expected to be a useful device for vertical-axis wind turbines that are difficult to control.

To investigate the differences in cadium (Cd) uptake and translocation among edible rapes and select suitable rape varieties for safe production, a field experiment was carried out with 25 varieties of edible rapes on a farmland polluted with Cd in the central souothern part of Hunan Province. The growing characteristics and Cd contents in rape tissues were measured, and the amount of Cd removed was calculated. The results showed that the growth of 25 rape varieties was not inhibited without withering or inconsistent changes in leaf and so on. The Cd contents in stem-leaf and root of rapes were in the range 0.05-0.26mg·kg-1 and 0.04-0.26mg·kg-1, respectively. Basing on BCF, the stem-leaf showed a greater capacity for Cd transport than root. And the total Cd removed by rape were 0.002-0.016 mg·plant-1. Except for plant height, BCF of soil available Cd from soil to stem-leaf, TCF of Cd from root to stem-leaf and Cd taken away by rape, there was no significant difference among edible rape varieties. Although Cd contents in stem-leaf of 25 rape varieties does not exceed the national safety standards, planting “Lvjin 1”, “Guanyou Qingjing” and “Guanyou brassica” not only reduced soil pollution but also allowed the production of safe leafy rape.

This study was to identify clinical cancer biomarkers for recurrent gastric cancer survivors using artificial intel-ligence. From a hospital-based cancer registry database in Taiwan, the datasets of the incidence of recurrence and clinical risk features were included in 2476 gastric cancer survivors. We benchmarked Random forest with MLP, C4.5, AdaBoost, and Bagging algorithms on metrics and leveraged synthetic minority oversampling technique (SMOTE) for imbalanced dataset issues, cost-sensitive learning for risk assessment, and SHapley Additive ex-Planations (SHAP) for feature importance analysis in this study. Our proposed Random forest outperformed the other models with an accuracy of 87.9%, a recall rate of 90.5%, an accuracy rate of 86% and F1 of 88.2% on re-current category by a 10-fold cross-validation in a balanced dataset. We identified clinical features of recurrent gastric cancer, which are the top five features, stage, number of regional lymph node involvement, Helicobacter pylori, BMI(body mass index), and gender, which significantly affect the prediction model's output, are worth paying attention to in the following causal effect analysis. Using an artificial intelligence model, the risk factors for recurrent gastric cancer could be identified and cost-effectively ranked according to their feature importance. In addition, they should be crucial clinical features to provide physicians with the knowledge to screen high-risk patients in gastric cancer survivors as well.

The prevalence of nonalcoholic fatty liver disease (NAFLD) has been rapidly increasing worldwide. A choline-deficient L-amino acid-defined high fat diet (CDHFD) has been used to create a mouse model of nonalcoholic steatohepatitis (NASH). There are some reports about the effects on mice of being fed CDAHFD for a long time, 1 to 3 months. However, the effect of this diet over a short period has been unknown. Therefore, we examined the effect of one week of feeding CDAHFD on the mouse liver. Feeding this diet for only one week induced lipid droplet deposition in the liver with increasing activity of liver-derived enzymes in the plasma. On the other hand, it did not induce fibrosis and cirrhosis. Additionally, it was demonstrated that mitochondrial respiration is significantly impaired with severe oxidative stress in the liver by CDAHFD, associated with a decreasing mitochondrial DNA copy number and complexes-proteins. In the gene expression analysis of the liver, inflammatory and oxidative stress markers were significantly increased by CDAHFD. These results demonstrated that one week of feeding CDAHFD to mice induces steatohepatitis with mitochondrial dysfunction and severe oxidative stress, without fibrosis, which can partially mimic the early stage of the NASH in humans.

Background: Recently we demonstrated that Astragalus polysaccharide (PG2), the active ingredient in dried roots of astragalus membranaceus, ameliorates cancer symptom clusters and improve quality of life (QoL) in patients with metastatic disease by modulating inflammatory cascade, against the background that inflammatory cells including macrophages, dendritic cells (DCs), and cytotoxic T lymphocytes (CTLs) in tumor initiation, metastasis, and progression. Nevertheless, the role of PG2 in the modulation of anticancer immunogenicity and therapeutic response remains relatively underexplored and unclear. Purpose: The present study investigates how and to what extent PG2 modulates cellular and biochemical components of the inflammatory cascade, enhance anticancer immunity, and the therapeutic implication of same in patients with lung cancer. Methods and Results: Herein, we demonstrated that PG2 significantly increased the M1/M2 macrophage polarization ratio in non-small cell carcinoma (NSCLC) H441 and H1299 cells. This PG2-induced preferential pharmacologic up-regulation of tumoral M1 population in vitro, positively correlated with the downregulation of tumor-promoting IL-6 and IL-10 expression in NSCLC cell-conditioned medium, with concomitant marked inhibition of cell proliferation, clonogenicity and tumorsphere formation. Our ex vivo results, using clinical sample from our NSCLC cohort, demonstrated that PG2 also promoted the functional maturation of DCs with consequent enhancement of T cell-mediated anticancer immune responses. Consistent with the in vitro and ex vivo results, our in vivo studies showed that mice treated with PG2 exhibited significant time-dependent depletion of the tumor-associated M2 population, synergistically enhanced the anti-M2-based anticancer effect of cisplatin, and inhibition of xenograft tumor growth in the NSCLC mice models. Moreover, in the presence of PG2, cisplatin-associated dyscresia and weight-loss was markedly suppressed. Conclusion: These results do indicate a therapeutically-relevant role for PG2 in modulating the M1/M2 macrophage pool, facilitating DC maturation, and synergistically enhancing the anticancer effect of conventional chemotherapeutic agent, cisplatin; thus laying the foundation for further exploration of the curative relevance of PG2 as surrogate immunotherapy and/or clinical feasibility of its use for maintenance therapy in patients with lung cancer.

Abstract: Background and Objectives: Holter-based late potentials (LPs) are useful for predicting lethal arrhythmias in organic cardiac diseases. Although Holter-based LPs exhibit diurnal varia-tion, no studies have evaluated the optimal timing of LP measurement over 24 h for predicting lethal arrhythmia that leads to sudden cardiac death. Thus, this study aimed to validate the most effective timing for Holter-based LP testing and to explore factors influencing diurnal variability of LP parameters. Materials and Methods: We retrospectively analyzed 126 patients with post-myocardial infarction (MI) status and 60 control participants who underwent high-resolution Holter electrocardiography. Among the 126 post-MI patients, 23 developed sustained ventricular tachycardia (VT) (the MI-VT group), while 103 did not (the MI-non-VT group) during the obser-vation period. Holter-based LPs were measured at 0:00, 4:00, 8:00, 12:00, 16:00, and 20:00, and heart rate variability analysis was simultaneously performed to investigate factors influencing diurnal variability of LP parameters. Results: Holter-based LP parameters showed diurnal variation with significant deterioration at night and improvement during the day. Assessment at the time with the longest duration of low-amplitude signals <40 μV in the filtered QRS complex terminus (LAS40) gave the highest receiver operating characteristics curve (area under the curve, 0.659) and the highest odds ratio (3.75; 95% confidence interval, 1.45–9.71; p=0.006) for predicting VT. In the multiple regression analysis, heart rate and noise were significant factors affecting LP parameters in the MI-VT and control groups. In the non-VT group, LP parameters were significantly influenced by noise and parasympathetic heart rate variability parameters such as logPNN50. Conclusions: For Holter-based LP measurements, test accuracy was higher when LP was measured at the time of the highest or worst value of LAS40. Changes in autonomic nervous system activity, including heart rate and noise levels, were factors influencing diurnal variability.

Background Diabetic patients have an increased risk of infections; however, the association between type 2 diabetes and hospital outcomes of sepsis remains controversial when the diabetes severity is not considered. We examined this association using nationwide and hospital-based databases concomitantly. Methods The first part of this study was conducted using 2 nationwide databases: the Longitudinal Cohort of Diabetes Patients and the Longitudinal Health Insurance Database 2000. The diabetic complication burden was evaluated using the adapted Diabetes Complications Severity Index score (aDCSI score). In the second part, we used the hospital-based database with laboratory data, such as initial blood glucose and HbA1c levels, to make comparisons between surviving and dead patients with type 2 diabetes and sepsis. Results The nationwide study included 19,719 type 2 diabetic sepsis patients and an equal number of non-diabetic patients. The diabetic sepsis patients had an increased odds ratio (OR) of 1.14 (95% CI 1.1-1.19) for hospital mortality. The OR for mortality increased as the complication burden increased (diabetic sepsis patients with aDCSI scores of 0, 1, 2, 3, 4, and ≥5 had ORs of 0.91, 0.87, 1.14, 1.25, 1.56, and 1.77 for mortality, respectively (all P<0.001 and P for trend <0.001)). A total of 1,054 diabetic sepsis patients were included from the hospital-based database. Initial blood glucose levels in the surviving and dead diabetic sepsis patients did not differ significantly: 273.9 ± 180.3 versus 266.1 ± 200.2 (mg/dL) (P=0.095). Moreover, the surviving diabetic sepsis patients did not have a lower HbA1c (%): 8.4 ± 2.6 versus 8.0 ± 2.5 (P=0.078). Conclusions In the case of type 2 diabetic sepsis patients, the diabetes-related complication burden is the major determinant of hospital mortality rather than the diabetes itself. Contrary to popular belief, initial blood glucose and HbA1c levels may not be as important as previously thought.

In infectious disease and clinical microbiology, rarely encountered species are often of special concern simply by virtue of their unfamiliarity, especially in settings of complicated underlying disease. This is all the more so when the infectious agent has an appearance that distinguishes it from most commonly encountered organisms, making it a mystery that must be explained. In this context, it is rare for histopathologists to be more familiar with a bacterial species than clinical microbiologists but Sarcina ventriculi is one such example. Infrequently seen in tissue and even less often in culture, we here report a case of Sarcina ventriculi in the GI tract of a geriatric patient with complex underlying history. A brief discussion of the history, clinical presentation, treatment, and culture conditions of this organism is provided, along with clarification of nomenclature, which has changed and could otherwise be a source of additional confusion in this rarely encountered bacterium.

To explore the effects of pymetrozine on the reproductive behavior of N. lugens, we established a bioassay method to accurately evaluate the toxicity of pymetrozine in N. lugens and establish the level of pymetrozine resistance of N. lugens in the field. In this study, pymetrozine’s effects on the fecundity of N. lugens were evaluated using the topical application method and rice-seedling dipping method. Moreover, the resistance of N. lugens to pymetrozine in a pymetrozine-resistant strain (Pym-R) and two field populations (YZ21 and QS21) was determined using the rice-seedling dipping method and fecundity assay methods. The results showed that treatment of N. lugens third-instar nymphs with LC15, LC50, and LC85 doses of pymetrozine resulted in significantly reduced male fertility and female fecundity. In addition, N. lugens adults treated with pymetrozine using the rice-seedling dipping and topical application method also exhibited significantly in-hibited male courtship, fertility, and female receptivity. Using the rice-stem dipping method, pymetrozine resistance was shown to be at high levels in Pym-R (194.6-fold), YZ21 (205.9-fold), and QS21 (212.8-fold), with LC50 values of 522.520 mg/L (Pym-R), 552.962 mg/L (YZ21), and 571.315 (QS21) mg/L. However, when using the rice-seedling dipping or topical application fe-cundity assay method, Pym-R (EC50: 14.370 mg/L, RR=12.4-fold; ED50: 0.560 ng/adult, RR=10.8-fold), YZ21 (EC50: 12.890 mg/L, RR=11.2-fold; ED50: 0.280 ng/adult; RR=5.4-fold), and QS21 (EC50: 13.70 mg/L, RR=11.9-fold) exhibited moderate or low levels of resistance to pymet-rozine. Our studies show that pymetrozine can significantly inhibit the fecundity of N. lugens. The fecundity assay results showed that N. lugens only developed low to moderate levels of resistance to pymetrozine, indicating that pymetrozine can still achieve effective control on the next gen-eration of N. lugens populations.

Background: Accurate prediction of patients’ response to therapy is clinically indispensable, howbeit challenging. With increased understanding of the human genome and malignancies, there is the renaissance of in silico pharmacogenomics with renewed interest in drug response predictability based on gene-drug interaction. Objective: Evidence-based transcript-proteome profiling is essential for synthesizing clinically applicable algorithms for predicting response to anticancer therapy, including immune checkpoint blockade (ICBT); thus, saving physicians’ time, reducing polypharmacy, and curtailing unnecessary treatment expense. In this study, we tested and validated the hypothesis that a selected proteomic signature in ICBT-naïve patients is sufficient for the prediction of response to ICBT. Methods: Using a multimodal approach consisting of computational pharmacogenomics, transcript-proteome analytics, mathematical modeling, and machine learning systems; we delineated therapy-sensitivity and stratified patients into graduated response groups based on their proteomic profile. Protein expression levels in our cohort tissue specimens were evaluated based on T cell- and non-T cell- inflamed phenotypes by immunohistochemistry. Results: We established β-catenin, PDL1, CD3 and CD8 expression-based ICBT response model. Statistical regression models validated the predictive association between our predefined algorithms and therapeutic outcome. Interestingly, our 4-gene prediction classifier was constitutively independent of tumor tissue origin, correctly stratified patients into high-, low-, and non- responders pre-treatment, with high prediction accuracy, and exhibited good association with patients’ performance status and prognosis (p < 0.01). Conclusion: Our findings demonstrate the possibility of accurate proteomics based ICBT response prediction and provide a putative basis for drug response prediction based on selective proteome profile in untreated cancer patients.

Surface-enhanced Raman spectroscopy (SERS) is commonly used for super-selective analysis through nanostructured silver layers in the environment, food quality, biomedicine, and materials science. To fabricate a high-sensitivity but more accessible device of SERS, dc magnetron sputtering technology was used to realize high sensitivity, low cost, stable deposition rate, and rapid mass production. This study investigated various thicknesses of a silver film ranging from 3.0 to 12.1 nm by field-emission-scanning-electron microscope, X-ray diffraction, and X-ray photoelectron spectroscopy. In the rhodamine 6G (R6G) testing irradiated by a He-Ne laser beam, the analytical enhancement factor (AEF) of 9.35x108, the limit of detection (LOD) of 10-8 M, and the relative standard deviation (RSD) of 1.61% were better than other SERS substrates fabricated by the same dc sputtering process because the results show that the 6 nm thickness silver layer has the highest sensitivity, stability, and lifetime. The paraquat and acetylcholine analytes were further investigated and high sensitivity was also achievable. The proposed SERS samples were evaluated and stored in a low humidity environment for up to forty weeks, and no spectrum attenuation could be detected. Soon, the proposed technology to fabricate high sensitivity, repeatability, and robust SERS substrate will be an optimized process technology in multiple applications.

Background: Oral squamous cell carcinoma (OSCC), with poor prognosis and high mortality rates, is one of the most diagnosed head and neck cancers. Cancer stem cells (CSCs) - epithelial-to-mesenchymal transition (EMT) loop is increasingly implicated in the therapy-resistance, relapse, and metastasis of OSCC patients. Accumulating evidence indicate that aberrantly expressed CD47 is associated with cell-death evasion, invasion and cancer metastasis; however, the role of CD47 in the modulation of CSCs-like phenotypes, including therapy-resistance and metastasis, with its underlying mechanism in OSCC remains largely underexplored. Methods: This study investigated the CSCs- modulating potential of CD47 in OSCC cell lines SAS, TW2.6, HSC-3 and FaDu using bioinformatics approach, immunoblotting, immunofluorescence staining, migration, invasion, colony and orosphere formation, as well as radiosensitivity assays. Results: We demonstrated that the characteristic ectopic expression of CD47 in OSCC patients was associated with ~ 20% 2-year survival disadvantage (p = 0.01) and positively correlated with the expression of pluripotency factors; while shRNA silencing of CD47 significantly suppressed cell viability and markedly inhibited orosphere formation, resulting in smaller and fewer orospheres, and downregulated CD133, SOX2, OCT4 and c-Myc mRNA and protein expression levels. We also showed that CD47 downregulation attenuates EMT, migration and clonogenicity of OSCC cells, with associated E-cadherin upregulation and suppression of Vimentin, Slug, Snail, and N-cadherin expression. Conclusion: Of therapeutic relevance, combined with radiotherapy, CD47 knockdown enhanced the anti-OSCC effect of radiotherapy. Thus, we demonstrate the therapeutic feasibility of a CD47-mediated anti-CSCs strategy, and suggest a role for CD47 suppression in potentiating the therapeutic efficacy of radiation therapy in OSCC patients.

Tocilizumab against interleukin-6 receptor (IL-6R) has been demonstrated to inhibit the progression of diverse cancers in vitro and in vivo. Nonetheless, evidence regarding the anti-tumor effects of Tocilizumab on human colorectal carcinoma (CRC) corresponding to IL-6R expression levels re-mains scarce. To investigate the influence of IL-6R expression, SW480 and HT-29 cells inoculated subcutaneously into NU/NU mice were used as our human CRC xenograft models with anti-IL-6R antibody (Tocilizumab) therapy. IL-6R expression levels, the histology of CRC growth/ invasiveness and tumor growth-related signaling pathway were estimated by H&E and immunohistochemical staining. SW480 tumor cells with higher IL-6R expression levels exerted better responsiveness in Tocilizumab therapy than the treated HT-29 group. Likewise, therapeutic effects of Tocilizumab on the proliferative ability with mitotic index and Ki-67 expressions, the invasiveness with MMP-9 proteinase expressions, ERK 1/2 and STAT3 signaling transduction in SW480 treatment group were superior to HT-29 treatment group. In light of our results, IL-6R is the key indicator for the efficacy of Tocilizumab treatment in CRC xenografts. From the perspective of precision medicine, tumor response to anti-IL-6R antibody therapy could be predicted on the basis of IL-6R expression levels. In this manner, Tocilizumab may serve as a targeted and promising anti-CRC therapy.

Using numerical software to establish a three-dimensional geological model of shield tunneling through fault fracture zones, considering the synchronous grouting effect at the shield tail, the disturbance of various geotechnical structures in the fault fracture zone under deep burial and high water pressure conditions is studied. According to the comparison between the numerical model analysis results and the on-site inspection results of the entire process of Shiziyang B3 section, synchronous grouting at the shield tail is the main reason for the changes in soil and water pressure in the fault fracture zone area. The soil and water pressure changes strongly during shield tunneling, and the maximum excess pore pressure value occurs when the shield tail passes. When the shield tunneling machine is far away, the soil and water stress shows a downward trend. The impact of synchronous grouting decreases with the increase of tunneling distance. Due to the difference in permeability, the variation law of pore pressure in the fault fracture zone is significantly different from the original rock, leading to a faster increase in pore pressure in the fracture zone area and a wider range of influence.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) often causes severe viral pneumonia, especially among older individuals and those with underlying health conditions. The C57BL/6 mouse is widely used to develop mouse models of obesity, diabetes, hypertension, and immune disorders, conditions that are associated with increased risk of severe COVID-19. Although many studies using these mouse models have examined the pathogenicity of SARS-CoV-2, COVID-19 pathogenesis remains poorly understood. In vivo imaging analysis using two-photon excitation microscopy is useful for elucidating the pathology of COVID-19, providing pathological insights that are not available from conventional histological analysis. However, there is no reporter SARS-CoV-2 that demonstrates pathogenicity in C57BL/6 mice and emits sufficient light intensity for two-photon in vivo imaging. Here, we generated SARS-CoV-2 expressing the fluorescent protein Venus to facilitate in vivo pathological studies using C57BL/6 mouse models. We generated a mouse-adapted strain of SARS-CoV-2, by performing sequential lung-to-lung passages in BALB/c mice, followed by in C57BL/6 mice. We observed that the C57BL/6-adapted SARS-CoV-2 (named MASCV2-p25) replicated efficiently in the lungs of C57BL/6 mice, causing fatal pneumonia. Histopathologic analysis revealed severe inflammation and infiltration of immune cells in the lungs of MASCV2-p25-infected C57BL/6J mice, not unlike that observed in COVID-19 patients with severe pneumonia. Subsequently, we generated a mouse-adapted reporter SARS-CoV-2 (named MASCV-Venus-p9) by inserting the fluorescent gene Venus into MASCV2-p25, and sequential lung-to-lung passages in C57BL/6 mice. C57BL/6 mice infected with MASCV2-Venus-p9 exhibited severe pneumonia similar to that induced by MASCV2-p25. In addition, two-photon excitation microscopy of the lungs of the infected C57BL/6J mice showed that the infected cells emitted sufficient levels of fluorescence for easy observation. These findings suggest that MASCV2-Venus-p9 will be useful for two photon in vivo imaging studies of the pathogenesis of severe COVID-19 and for the development of therapeutic agents for severe pneumonia.

Background: Improving patients’ quality of life (QoL) is a principal objective of all treatment in any clinical setting, including oncology practice. Cancer-associated inflammation is implicated in disease progression and worsening of patients’ QoL. Conventional anticancer therapeutics while selectively eliminating cancerous cells, are evaded by stem cell-like cells, and associated with varying degrees of adverse effects, thus reducing patients’ QoL. This necessitates novel therapeutic approaches with enhanced efficacy, minimal or no treatment-related adverse effects, and improved QoL in patients with cancer, especially those with metastatic/advance stage disease. Methods: Sequel to our team’s previous publication, the present study explores probable effects of Astragalus polysaccharides (PG2) on cancer-related inflammatory landscape and known determinants of QoL, as well as the probable link between the two to provide mechanistic insight. In exploratory double blind randomized controlled trial using patients with metastatic disease (n=23), we comparatively evaluated the therapeutic efficacy of high (500mg) or low (250mg) dose PG2 administered intravenously (i.v.), with particular focus on its suggested anti-inflammatory function and the probable effect of same on QoL indices at baseline, then at weeks 4 and 8 post-PG2 treatment. Results: All 23 patients with metastatic disease treated with either low or high PG2 experienced reduced pain, nausea, vomiting and fatigue, as well as better appetite and sleep, culminating in improved global QoL. This was most apparent in the high dose group, with significant co-suppression of pro-inflammatory interleukin (IL)-1β, IL-4, IL-6, IL-13, IL-17, monocytes chemotactic protein (MCP)1, granulocyte-macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), tumor growth factor (TGF)-β1, interferon (IFN)-γ, and immune suppressors IL-10, and IL-12. Univariate and multivariate analyses revealed that IL-1β, IL-13 and GM-CSF are independent prognosticators of improved QoL. Conclusion: This proof-of-concept study provides premier evidence of functional association between PG2 anti-inflammatory effects and improved QoL in patients with advanced stage cancers, laying the groundwork for future larger cohort blinded controlled trials to establish the efficacy of PG2 as adjuvant anticancer therapy in metastatic or advanced stage clinical settings.

The paper focuses on the application of a multilevel, integrative and territorial approach to the protection of cultural heritage through planning instruments in Serbia. It points out the problems of the sectoral approach and discusses international recommendations that can be integrated into the planning methodology. The case study is the area of Djerdap National Park, which has an already established international and national importance. The research suggests that the cultural heritage in the area, with the exception of the Roman limes, is still recognized at the level of individual localities. The study emphasizes the importance of aligning all levels of governance to safeguard the whole spatial entity rather than focusing solely on its particular areas. The interna-tional and national importance of the planning area contributes to the strengthening of awareness of heritage and its institutional protection. However, the vitality of the area, which is key to its sustainable development, comes from the local level. Planning documents contribute to the inte-gration of local values and local communities into development programs and projects.

Glycosidic linkage analysis was conducted on the unfractionated polysaccharides in the alcohol-insoluble residues (AIRs) prepared from six red seaweeds (Gracilariopsis sp., Prionitis sp., Mastocarpus papillatus, Callophyllis sp., Mazzaella splendens, and Palmaria palmata) using GC-MS/FID analysis of partially methylated alditol acetates (PMAAs). The cell walls of P. palmata primarily contained mixed-linkage xylans and small amounts of sulfated galactans and cellulose. In contrast, the unfractionated polysaccharides of the other five species were rich in galactans displaying diverse 3,6-anhydro-galactose and galactose linkages with varied sulfation patterns. Different levels of cellulose were also observed. This glycosidic linkage method offers advantages for cellulose analysis over traditional monosaccharide analysis that is known for underrepresenting glucose in crystalline cellulose. Relative linkage compositions calculated from GC-MS and GC-FID measurements showed that anhydro sugar linkages generated more response in the latter detection method. This improved linkage workflow presents a useful tool for studying polysaccharide structural variations across red seaweed species. Furthermore, for the first time, relative linkage compositions from GC-MS and GC-FID measurements, along with normalized FID and total ion current (TIC) chromatograms without peak assignments, were analyzed using principal component analysis (PCA) as a proof-of-concept demonstration of the technique's potential to differentiate various red seaweed species.

Background: Educating college students about the importance of good sleep habits could lead to the adoption of healthier sleep routines, including sufficient sleep duration and sleep quality. The current pre-post study examines the impact of completing a sleep education program called “Sleep 101” on (1) sleep hygiene practices, (2) sleep quality, and (3) weekday and weekend sleep behaviors among college students. “Sleep 101” is an interactive online course developed to educate college students about the importance of sleep by addressing basic sleep physiology, the impact of sleep on mood, academic and physical performance, the interactions between sleep and various substances, and common sleep disorders. Methods: 338 college students were recruited from a midsized public university in the US and invited to participate in “Sleep 101”, of which 25 participants completed the baseline and post-intervention questionnaire. The Sleep Hygiene Index (SHI) was utilized to evaluate sleep hygiene practices, while standard questions were employed to assess weekday and weekend sleep behaviors and overall sleep quality. Results: Those who completed the study demonstrated a significant increase in weekday sleep duration and were less likely to engage in negative prior bedtime activities. In addition, 40% of those who completed baseline and post-intervention assessments noticed improvements in their sleep quality. Conclusion: These findings suggest that a brief online program is beneficial in improving sleep behaviors among college and could be a scalable approach to addressing current sleep issues and preventing future sleep problems in college students.

The profile of secondary metabolites occurring in apple cuticular layer is not only characteristic for particular apple cultivar, but also dynamically reflects various external factors in growing environment. In this study, the possibility to authenticate apple samples based on analysis of their cuticular layer extracts was investigated. Ultra-high-performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-HRMS/MS) was employed for obtaining metabolomic fingerprints. In total, 274 authentic apple samples, four cultivars harvested within the seasons 2020 to 2022 in the Czech Republic and Poland were analysed. The generated complex data processed by univariate and multivariate statistical methods enabled to build classification models for discrimination of apple cultivars as well as their geographical origin. The models showed very good performance in differentiation of Czech and Polish samples for three of four cultivars: ‘Gala’, ‘Golden Delicious’ and ‘Idared’, moreover, the validity of the models was verified over harvest seasons. The diagnostic markers, besides metabolites of triterpene biosynthetic pathway, mainly represented wax esters. ‘Jonagold’, which is known to be susceptible to mutations, was the only cultivar for which the unambiguous classification of geographical origin was not possible.

Memory and emotion are highly vulnerable to psychiatric disorders like post-traumatic stress disorder (PTSD), which has been linked to serotonin (5-HT) metabolism disruptions. In fact, over 90% of the 5-HT precursor tryptophan (Trp) is metabolized via the Trp-kynurenine (KYN) meta-bolic pathway, producing a variety of bioactive molecules. The aadat (kat2) gene encodes mito-chondrial kynurenine aminotransferase (KAT) isotype 2, responsible for kynurenic acid (KYNA) production. Little is known about its role in behavior. In CRISPR/Cas9-induced aadat knockout (kat2−/−) mice, we examined the effects on emotion, memory, motor function, Trp and its metabolite levels, enzyme activities in the plasma and the urine of 8-week-old males compared to wild-type mice. Transgenic mice showed more depressive-like behaviors in the forced swim test, but not in the tail suspension, anxiety, or memory tests. They also had fewer center field and corner entries, shorter walking distances, and fewer jumping counts in the open field test. Plasma metabolite levels are generally consistent with those of urine: KYN, antioxidant KYNs, 5-hydroxyindolacetic acid, and indole-3-acetic acid levels are lower; enzyme activities in KATs, kynureninase, and monoamine oxidase/aldehyde dehydrogenase are lower, but kynurenine 3-monooxygenase is higher; and ox-idative stress and excitotoxicity indices are higher. Transgenic mice show depression-like behavior in a learned helplessness model, emotional indifference, and motor deficits, coupled with a decrease in KYNA, a shift of Trp metabolism toward the KYN-3-HK pathway, and a partial decrease in the gut microbial Trp-indole pathway metabolite. This is the first evidence that deleting the aadat gene causes depression-like behaviors that are unique to despair experience, which appears to be linked to excitatory neurotoxic and oxidative stresses. This may lead to the development of a double-hit preclinical model in experience-based depression, better understanding of these complex condi-tions, and more effective therapeutic strategies by elucidating the relationship between Trp me-tabolism and PTSD pathogenesis.

Strawberry root rot caused by Neopestalotiopsis clavispora is one of the main diseases of strawberry and significantly impacts the yield and quality of strawberry fruit. There are now no effective control techniques available except for fungicide sprays, which may directly impact consumers. Biological control is becoming an alternative method for the control of plant diseases to replace or decrease the application of traditional synthetic chemical fungicides. Trichoderma is widely used as a biological agent for controlling strawberry root rot. In order to provide resources for screening the highly effective biocontrol fungus for controlling strawberry root rot caused by Neopestalotiopsis clavispora, the biocontrol mechanism,the control effects of Trichoderma asperellum CMT10 against strawberry root rot and growth-promoting effects on strawberry seedlings were investigated by plate culture, microscopy observation and root drenching methods.The results showed that CMT10 had obvious competitive, antibiotic and hyperparasitism effects on Neopestalotiopsis clavispora CMGF3. The CMT10 could quickly occupy nutritional space, and the inhibition rates of CMT10 against CMGF3 in confrontation culture on 7 d was 65.49%. The inhibition rates of volatile metabolite and fermentation metabolite produced by CMT10 against CMGF3 were 79.67% and 69.84%, respectively. The mycelium of strain CMT10 can act as hyperparasites by making contacting, winding and penetrating hyphae of CMGF3. Pot experiment showed that the biocontrol efficacy of CMT10 on strawberry root rot caused by Neopestalotiopsis clavispora was 63.00%. CMT10 had obvious promotion effect on strawberry growth, the plant height, root length, total fresh weight, root fresh weight, stem fresh weight and root dry weight, with the promotion rates were 20.09%, 22.39%, 87.11%, 101.58%, 79.82% and 72.33%, respectively. Overall, this study showed the ability of Trichoderma asperellum CMT10 to control strawberry root rot and their potential to develop as novel biocontrol agents to replace chemical fungicides for eco-friendly, sustainable agriculture.

Apis mellifera, especially weak ones, are highly vulnerable to Carpoglyphus lactis mites, which can rapidly infest and consume stored pollen, leading to weakened colonies and potentially colony collapse. This study aimed to ascertain and investigate the prevalence of this mite in honeybee colonies across 9 provinces in the Republic of Korea (ROK). A total of 615 honeybee colonies were collected, from 66 apiaries during the spring and 58 apiaries during the summer of 2023. A 1,242 bp segment of the the Cytochrome c oxidase subunit 1 (COI) gene was amplified using the polymerase chain reaction method. The detection levels of C. lactis in the honeybees were compared between winter and summer. Based on the COI sequence analysis, the nucleotide sequence similarity of C. lactis mites isolated in the ROK with those from China (NC048990.1) was found to be 99.5%, and with those from the United Kingdom (KY922482.1) was 99.3%. This study is the first report of C. lactis in Korean apiaries. The findings in this study demonstrate a significantly higher detection rate in winter, which is 4.1 times greater than that in summer (p &lt; 0.001). Furthermore, the results underscore the usefulness of molecular diagnostic techniques for detecting C. lactis mites.

COX II containing a dual core CuA active site is one of the three core subunits of mitochondrial Cco, which plays a significant role in the physiological process. In this report, the full-length cDNA of COXⅡ gene was cloned from Sitophilus zeamais, which had an ORF of 684 bp encoding 227 amino acids residues. The predicted COXⅡ protein had a molecular mass of 26.2 kDa with pI value of 6.37, and multiple sequence alignment and phylogenetic analysis indicated that Sitophilus zeamais COXⅡ had high sequence identity 78.51% with the COXⅡ of other insect species, especially similarity to sitophilus oryzae. This gene was subcloned into the prokaryotic expression vector pET-32a, and induced by IPTG in E.coli Transetta (DE3) expression system. Finally the COXⅡ with 6-His tag was purified using affinity chromatography with Ni²⁺-NTA agarose. WB showed the recombinant COXⅡ was about 44 kD, and the concentration of fusion protein was 50μg/mL. UV-spectrophotometer and infrared spectrometer analysis showed that recombinant COXⅡ could catalyze the oxidation of substrate Cytc, and influenced by AITC. It was found that AITC could form a hydrophobic region with COXⅡ protein via molecular docking, besides, a sulfur atom of AITC structure could form a length of 2.9 Å hydrogen bond with Leu-31. These results will provide valuable information for elucidating the role of COXⅡ in Sitophilus zeamais responses to AITC, meanwhile, it will helpful to carry out a point mutation in AITC binding sites for the future research.

The properties of the annual, semiannual and triennial oscillations (AO, SAO and TO) in the middle atmosphere have been investigated using the TIMED/SABER temperature data. The Lomb-Scargle and wavelet spectra were used to determine the dominant oscillations in the background temperature field. The AO is prominent at the mid-latitudes. The AO amplitudes present an asymmetry between the two Hemispheres, being larger in the mesosphere than in the stratosphere. The SAO dominates the tropical regions, with three amplitude maxima at altitudes of 45, 75, and 85 km. The SAOs in the upper mesosphere (75 km) are out of phase with those in the mesopause (85 km) in the tropical regions, which can generate an enhancement of 11 K at each equinox, contributing to the lower mesospheric inversion layer. The TO is significant in the tropical region, with amplitude being maximum at 35, 45 and 85 km. Result shows that there may be potential interaction by the TO with SAO at 85km at the equator. The relation between ENSO and TO has also been discussed. The ENSO signal may modulate the amplitude of the TO, mainly in the lower stratosphere. The real origin of the TO may lie in the wave-mean-flow interaction.

This paper is focused on typical rural settlements in the Stara Planina Mountain area in Serbia. They are distinguished by their authenticity, identity and character, and they have still not been destroyed by inappropriate development as is the case in some other mountain areas in Serbia, where the effects of urbanization, globalization and homogenization are obvious. Consequently, there is a need to prevent these effects in mountain areas where there is a threat of disbalance between development and the inherited natural and cultural values. The paper starts from several important concepts that relate contemporary approaches to cultural heritage preservation, place morphology and planning future development. The concept definitions from recent documents from related fields are used. These concepts are then applied to the area of Stara Planina Mountain and its rural settlements. The necessity for an integrative approach to planning this area with significant natural and anthropogenic potential is pointed out, including its integration into international programs of sustainable development.

Background: Most sepsis patients died during their first episode and the long-term survival post discharge was low. Major adverse cardiovascular events and repeated infections were regarded as the major causes in such conditions. No definite medications were proven to effectively improve the long-term outcome. We aimed to examine the benefit of statins on the long-term outcome of survived sepsis patients. Methods: Between 1999 and 2013, a total of 220,082 patients with the first episode of sepsis hospitalization were included and 134,448 ones (61.09%) survived to discharge. The survived patients who subsequently had statins use of >30 cumulative defined daily doses (cDDDs) post discharge were defined as the statin users. After propensity score matching of 1:5, a total of 7,356 and 36,780 survived patients were retrieved as the study (statin-users) and comparison cohort (non-statin users), respectively. The main outcome was the long term survival post discharge. HR with 95% CI was calculated using the Cox regression model to evaluate the effectiveness of statins with further stratification analyses according to cDDDs. Results: The study cohort, that is, the statin users had an adjusted HR of 0.29 (95% CI, 0.27-0.31) in long term mortality rate compared with the comparison cohort. For statin users with the cDDDs of 30–180, 180–365, and >365, the adjusted HRs were 0.32, 0.22, and 0.16, respectively, (95% CI, 0.30-0.34, 0.19-0.26, and 0.12-0.23, respectively) compared with the non-statin users (defined as statins use <30 cDDDs post discharge), and the P for trend <.0001. In the sensitivity analysis, after excluding the survived patients who died within three and six months post discharge, the adjusted HR of statins use remained significant (0.35, 95% CI 0.32-0.37 and 0.42, 95% CI 0.39-0.45, respectively). Conclusions: Statins decreased the long-term mortality post sepsis. Further randomized control trial deserved to be conducted to confirm this observation.

The research reported on this paper was aimed at improving the overall efficiency of a PDO certified artisanal cheese production process. Being a PDO certified foodstuff by the EU, it is considered to have properties and qualities determined by the geographical environment in which is made, with its production taking place in a specific and determined geographical location, in this case the Serra da Estrela region. In that sense, the authors conducted a mapping according to a systemic perspective of the processes involved in the context of manufacturing and distribution of certified Serra da Estrela cheese. Numerous methods were used throughout the process, such as a systemic design analysis, and techniques derived from ethnographic methods, which led to the collection of data in the field and consequently provided the immersion of the researcher in genuine work situations. Critical points were identified and emphasized in the systemic map with the purpose of encouraging initiatives to address and overcome the gaps and inefficiencies detected. The systemic design analysis triggered the development of design work. Observations following an ethnographic approach identified ergonomic risks in cheese making during the process of cutting excess chips, fostering the emergence of musculoskeletal disorders at the wrist. A tool that fits best to the task at hand was developed. A prototype of the new tool enabled collecting feedback from use in the work context, in order to inform product development. The domains of agricultural production and microbiology, considering the specific microorganisms developed trough the ripening process of the cheese, turned out to be aspects of high importance for the issue under focus, contributing to a broader understanding of the ripening process and its risks, simultaneously improving the efficiency and success of cheese production. If it were not for the systemic analysis, which served as a link between the boundaries of distinct domains such as the risk of microorganism contamination, ergonomics, energy efficiency, legislation and regulation policies, transportation challenges and economic viability, approached throughout the research. Simultaneously creating bridges between them, the various problems might not have been detected in the first place, as they are usually addressed in specialized disciplines, predetermined by the restrictions of each specific area of knowledge. As a consequence of the development of this research, which was based on an analysis that sought to establish possible connections between various disciplines and tried to constantly maintain a holistic perspective, making new connections and observing the issues from a new angle, apart from the already established methodologies. All this allowed to lay out the seeds for the development of a plan to tackle the critical points identified by the systemic analysis reported in this paper.

Promoting green development has become an important way to optimize the ecological and economic structure and promote sustainable development. The Yangtze River Economic Belt is an important economic corridor in China, and it remains to be examined whether the implementation of environmental regulations has enhanced the green total factor productivity (GTFP) of cities. This paper calculates the green total factor productivity of 107 cities within the Yangtze River Economic Belt by using the super-efficient SBM model and the GML index with Chinese city panel data from 2007-2019 and measures the intensity of environmental regulations through textual analysis. The bidirectional fixed-effects model constructed in this paper suggests an inverted U-shaped relationship between environmental regulation and GTFP, which is confirmed by a series of robustness tests. Green technology innovation and advanced industrial structure play a mechanism role in this. In regions with lower levels of green technology and industrial structure, the inverted U-shaped relationship between environmental regulation and green total factor productivity is more significant. In addition, the phenomenon of GTFP rising and then falling because of environmental regulation is more obvious in cities in the middle and upper reaches of the Yangtze River and outside the urban agglomerations. Therefore, when formulating environmental regulation policies, it is necessary to balance the relationship between economic development and environmental protection and harmonize the environment and economic development of the entire Yangtze River Basin.

The wetlands in northeastern Bangladesh are home to some of the most prolific and valuable ecosystems on the planet, offering a wide range of benefits to both the local and wider communities. A limited number of research on this topic have been carried out in various wetlands in coastal hilsa, but none have been located in the northeastern region of Bangladesh. Thus, the goal of this study was to better understand the most commercially relevant species (anadromous hilsa) in northeastern Bangladesh as well as to assess the wetland ecosystem services more thoroughly with the contribution of their fish genetic resources. In addition to laboratory studies, fieldwork was done in the fishing settlements along the Surma River, Hakaluki Haor, and Tanguar Haor. The study classified 77 fish species into 21 subcategories of ecosystem services, of which 56% were not threatened, 17% were vulnerable, and 10% were highly endangered. The species Hilsa was found to be the most economically significant, accounting for 1% of the GDP overall. The study determined if the hilsa stock of the examined wetlands maintains a single or several subpopulations in comparison to other parts of the country when they migrate from saline water to northeastern Bangladesh (freshwater). But when compared to other groups, the FST score was between 0.000 to 0.017, indicating that the populations are identical and that there is genetic material sharing between them. Additionally, these statistics imply that the Sylhet haor and adjacent river systems contain a single stock of Hilsa fish. Nevertheless, a number of stresses and risks, including overexploitation, illicit and destructive fishing, siltation, and natural disasters like flash floods, have been linked to changes in the supply of hilsa and other ecosystem services. This study also emphasizes the necessity of policy attention and research to address the concerns.

In this paper, we introduce a specialized, fully automated experimental arrangement designed for assessing the effectiveness of augmented and virtual reality technologies in healthcare setting and explore its design principles focusing on depth sensor characterization. The main goal of this project is to establish a robust benchtop platform for the quantitative evaluation of extended reality technologies in a controlled environment, emphasizing the practical assessment of augmented reality head-mounted devices. We outline a design concept and considerations for an experimental configuration aimed at creating a realistic testing environment. This apparatus comprises an observation platform mounted on a three-degree-of-freedom motorized system and a test phantom stage. Focusing on real-case scenarios, we utilized a range of sensors, including readily available range-sensing cameras and commercial augmented reality headsets, such as the Intel RealSense L515 LiDAR camera, mounted on the motion control system. The setup enabled automated data collection and facilitates controlled assessments and validation of various facets of augmented reality technologies, including object, hand, and head tracking, as well as static and dynamic image registration. This paper describes the system architecture, the process of automated data collection, and presents several evaluation studies conducted with this setup, providing insights into the quality and temporal noise associated with static or moving objects or observers in augmented reality applications.

To conduct high-precision and high-resolution numerical simulation of complex flow structures in turbomachinery, a high-order finite volume weighted essentially non-oscillatory (WENO) scheme for the large eddy simulation (LES) is improved and embedded into the three-dimensional viscous unsteady CFD solver NUAA-Turbo. Firstly, the spectral characteristics and unsteady convergence of the improved WENO scheme are studied. Compared with the classical WENO scheme, the improved WENO scheme has better dissipation and dispersion characteristics and faster convergence speed. Then, the coefficient CW of the Wall-Adapting Local Eddy-viscosity (WALE) model is calibrated by decaying homogeneous isotropic turbulence (DHIT) test case. Finally, the scheme is applied to conduct high-precision LES calculations of turbulent boundary layer flow, supersonic compression corner flow, and low-pressure turbine cascade separation flow. The numerical simulation results show that this WENO scheme has excellent shock wave capture ability and turbulence resolution and can capture more flow field details with less mesh size, greatly reducing the computational cost and laying a foundation for large-scale engineering application of LES.

To secure logic circuits against the illegal copying the insertion of the so-called key bit inputs using XOR/XNOR gates has been proposed in . The inserted gates modify (lock) the behavior of the original circuit and only the correct choice of the secret key bits guarantees the equivalent behaviour of the locked circuit to the original circuit. To break this kind of security, i.e. to find the secret key bits, there was a SAT solver based attack proposed in . The aim of this work is to experimentally verify this attack on several locked circuits with various number of primary inputs and outputs and with various number of gates. Except for the random placement of the key gates we evaluate also the positioning with chaining elimination. The obtained and presented results show that we were able to unlock 10 of 11 circuits within few minutes on a common PC.

Intermetallic compounds are increasingly being expected to utilize in tribological environments, but to date the works are hindered by insufficient ductility at low and medium temperature. This paper presents a novel multiphase intermetallic alloy with the chemical composition of Mo-40Ni-13Si (at.%). Microstructure characterization reveals that a certain amount of ductile Mo phases formed during the solidification process of ternary Mo-Ni-Si alloy melt, which is undoubtedly beneficial to the ductility improvement of intermetallic alloy. Tribological properties of the designed alloy, including wear resistance, friction coefficient and metallic tribological compatibility, were evaluated under dry sliding wear test conditions at room temperature. Results suggested that the multiphase alloy possesses an excellent property for room-temperature wear applications, which is attributed to the unique microstructural features and thereby good combination in hardness and ductility. The corresponding wear mechanism is also reported by observing the worn surface, subsurface and wear debris of alloy, which to be found is soft abrasive wear.

With the integrated development of the Internet, wireless sensor technology, cloud computing, and mobile Internet, there has been a lot of attention given to research about and applications of the Internet of Things. A Wireless Sensor Network (WSN) is one of the important information technologies in the Internet of Things; it integrates multi-technology to detect and gather information in a network environment by mutual cooperation, using a variety of methods to process and analyze data, implement awareness, and perform tests. This paper mainly researches the localization algorithm of sensor nodes in a wireless sensor network. Firstly, a multi-granularity region partition is proposed to divide the location region. In the range-based method, the RSSI (Received Signal Strength indicator, RSSI) is used to estimate distance. The optimal RSSI value is computed by the Gaussian fitting method. Furthermore, a Voronoi diagram is characterized by the use of dividing region. Rach anchor node is regarded as the center of each region; the whole position region is divided into several regions and the sub-region of neighboring nodes is combined into triangles while the unknown node is locked in the ultimate area. Secondly, the multi-granularity regional division and Lagrange multiplier method are used to calculate the final coordinates. Because nodes are influenced by many factors in the practical application, two kinds of positioning methods are designed: the unknown node is in the positioning unit or not. When the unknown node is on the side of the positioning unit, we use the method of vector similarity. Moreover, we use the centroid algorithm to calculate the ultimate coordinates of unknown node. When the unknown node is not on the side of the positioning unit, we establish a Lagrange equation containing the constraint condition to calculate the first coordinates. Furthermore, we use the Taylor expansion formula to correct the coordinates of the unknown node. In addition, this localization method has been validated by establishing the real environment.

The electroencephalogram (EEG) is a record of brain activity. Brain Computer Interface (BCI) technology formed by the EEG signal has become one of the hotspots at present. How to extract the feature signal of EEG is the most basic research of BCI technology. In this paper, A new method of recognizing fatigue, conscious, concentrated state of human brain is proposed by the combination of discrete wavelet transform and the neural network based on EEG signal. First of all, the law signal is preprocessed by the wavelet denoising method because the law EEG signal contains a large number of high frequency noise, which is decomposed into multi-layer high frequency signal and low frequency signal. thus, δ wave, θ wave, α wave, β wave are obtained by the wavelet transform. And then, frequency band energy of the different wave is regards as the feature signal of EEG. In the experiment, the feature signal is classified by radial basic function (RBF) and annealed chaotic competitive learning network (ACCLN). RBF and ACCLN networks are trained with 500 sets of sample data and are tested by 100 sets of samples in different mental states. The experimental results show that the average accuracy of RBF network under three conditions are 88.75%, 88.25%, 88.5%, respectively, and the correct rate of ACCLN network is 97%, 98%, 98%, respectively.

Early discharge after childbirth has led to a rise in neonatal readmission, becoming a major concern in recent decades. Our research aimed to identify the risk factors and incidence of neonatal readmission, as well as explore preventive measures. Our study at the Clinical Hospital of Pediatrics in Ploiești, Romania included 108 neonates admitted during the neonatal period. This accounted for 2.06% of all admissions (5226). The most prevalent cases were malnutrition (25%), fever (20.3%) and bronchiolitis (17.5%). Diarrhea and infectious gastroenteritis were also observed (14.8%), along with acute rhinoconjunctivitis (9.2%) and late onset sepsis (3.7%). No deaths were recorded. The most significant characteristics identified were number of children (p&lt;0.001) and age at maternity discharge (p&lt;0.001). By following the prevention rules, malnutrition, feeding errors, and infections can be avoided. This includes practicing proper hand hygiene for both mothers and medical staff, as well as educating and demonstrating to mothers the benefits of breastfeeding. In addition, all newborns discharged from the maternity ward should benefit from follow-up at 7-10 days of life. Our results confirm the effectiveness of a multidisciplinary team and endorse promoting breastfeeding. Implementing quality control measures and regularly evaluating the surveillance program will help improve its effectiveness.

Wearable technology has been proposed as a potential tool to change the way of human life, such as the smart bracelet and the Google Glass. In the wearable technology, the inertial sensor has great significance in tracking the object movements. The paper focused on detecting the movements of user’s finger based on the inertial sensor to give the control signals. Firstly, the attitude matrix, which represented the transformation relation of carrier coordinate system and the navigation coordinate system, was obtained. Secondly, the attitude matrix was expressed based on the quaternions. Thirdly, the finger gesture was processed by the attitude matrix to get the attitude angle. Finally, the robot was controlled by attitude angle to make the moving action. The experimental results showed the detection of the finger movement is effective.

Two interesting compounds such as quaternary ammonium lignin(QAL) and 2-ethylhexyl phosphoric acid mono-2-ethylhexyl ester (P507) were synthesized as ionic liquids(QP-ILs) for the extraction of metal ions. The extraction behavior of Co(II) and Ni(II) from chloride solution was compared between QP-ILs and P507. The results showed that the extraction rates of Co(II) and Ni(II) in the two solutions varied with the extraction conditions, but QP-ILs has stronger extractability for cobalt than P507, while Ni is on the contrary. Under the same conditions, the Co/Ni separation performance(βCo/Ni) in QP-ILs is superior to that in p507. At pH4.0, 55℃, concentration of 20%, extraction time of 10 minutes, the βCo/Ni of QP-ILs reached to 2703, while that of P507 was only 164. In conclusion, QP-ILs was more efficient than P507 for separating Co from mixed solutions.

Brain aging causes a wide variety of changes at molecular and cellular levels, leading to the decline of cognitive functions and increased vulnerability to neurodegenerative disorders. The research aimed at understanding the aging of the brain has made much progress in recent decades. Technological innovations such as single-cell RNA-sequencing (scRNA-seq), proteomic analyses, and spatial transcriptomic analyses have facilitated the research on the dynamic changes occurring within neurons, glia, and other cells along with their impacts on intercellular communication during aging. In this review, we introduce recent trends of how neurons and glia change during aging and discuss the impact of the brain microenvironment such as the blood-brain barrier (BBB).

In this paper, we study the semilinear pseudo-parabolic equations $\displaystyle u_{t} - \triangle_{\mathbb{B}}u - \triangle_{\mathbb{B}}u_{t} = \left|u\right|^{p-1}u$ on a manifold with conical singularity, where $\triangle _{\mathbb{B}}$ is Fuchsian type Laplace operator investigated with totally characteristic degeneracy on the boundary $x_{1} = 0$. Firstly, we discuss the invariant sets and the vacuum isolating behavior of solutions with the help of a family of potential wells. Then, we derive a threshold result of existence and nonexistence of global weak solution: for the low initial energy $J(u_{0})<d$, the solution is global in time with $I(u_{0}) >0$ or $\displaystyle\Vert \nabla_{\mathbb{B}}u_{0}\Vert_{L_{2}^{\frac{n}{2}}(\mathbb{B})} = 0$ and blows up in finite time with $I(u_{0}) < 0$; for the critical initial energy $J(u_{0}) = d$, the solution is global in time with $I(u_{0}) \geq0$ and blows up in finite time with $I(u_{0}) < 0$. The decay estimate of the energy functional for the global solution and the estimates of the lifespan of local solution are also given.

Multimodal remote sensing data classification can enhance the model’s ability to distinguish land features through multimodal data fusion. In this context, how to help models understand the relationship between multimodal data and target tasks is the focus of researchers. Inspired by human feedback learning mechanisms, causal reasoning mechanisms, and knowledge induction mechanisms, this paper integrates causal learning, reinforcement learning, and meta learning into a unified remote sensing data classification framework and proposed the causal meta-reinforcement learning (CMRL). First, based on feedback learning mechanisms, we have overcome the limitations of traditional implicit optimization of fusion features and customized a reinforcement learning environment for multimodal remote sensing data classification tasks. Through feedback interactive learning between agents and the environment, we help them understand the complex relationships between multimodal data and labels, thereby achieving full mining of multimodal complementary information. Second, based on the causal inference mechanism we designed causal distribution prediction action, classification reward, and causal intervention reward, capturing pure causal factors in multimodal data and cutting off false statistical associations between non-causal factors and class labels. Finally, based on the knowledge induction mechanism, we designed a bi-layer optimization mechanism based on meta-learning. By constructing a meta training task and meta validation task simulation model in the generalization scenario of unseen data, we helped the model induce cross-task shared knowledge, thereby improving its generalization ability for unseen multimodal data. The experimental results on multiple sets of multimodal datasets show that the proposed method achieved state-of-the-art performance in multimodal remote sensing data classification tasks.