This paper applied the space-time generalized finite difference scheme for solving the nonlinear dispersive shallow water waves as the modified Camassa−Holm equation, modified Degasperis-Procesi equation, Fornberg-Whitham equation, and its modified form. The proposed meshless numerical scheme was composed of the space-time generalized finite difference method, the two-step Newton-Raphson method, and the time-marching method. The space-time approach can treat the temporal derivative as one of the spatial derivatives. This numerical technique enables all the partial derivatives in the governing equation can be discretized by a spatial discretization method, and the mixed derivative can efficiently deal with using the proposed meshless numerical scheme. The space-time generalized finite difference method is advanced from the Taylor series expansion and the moving-least square method. The numerical discretization process is only related to functional data and weighting coefficients on the central node and its nearby nodes. Thus, the matrix system composed of nonlinear algebraic equations will be a sparse matrix and can be efficiently solved by the two-step Newton-Raphson method. Furthermore, the time-marching method was utilized to proceed with the space-time domain along the time axis. In this paper, several numerical examples were tested to verify the capability of the proposed space-time generalized finite difference scheme.

Primary central nervous system and brain tumors are one of the global burdens that are continuously increasing in cases and requiring more treatment options. Surgery has been the leading treatment option for tumors, however, the localization of the tumor and its infiltrating nature make this option challenging. DNA microarray expression profiles of different CNS tumors provide insight into potential biomarkers for identifying different tumor types and subtypes. Here, we utilized the differentially expressed genes common in four expression profiles, GSE66354, GSE68848, GSE74195, and GSE43290 to reconstruct the gene co-expression network. In this study, we were able to identify preserved cluster genes, hub genes, co-regulating transcription factors, miRNA families, and candidate repurposed drugs. Fourteen identified hub genes, which were, CACNA1A, DNM1, GABRA1, GRIA2, MAPT, SLC17A7, SNAP25, SNAP91, STXBP1, SYT1, COL1A1, COL6A2, FBN2, and FN1 appeared to play a role in tumor progression and may serve as drug targets. We also reported the DEGs in each tumor type, which were ATRT, EPN, PA, MED, PNET, MEN, ACM, ODG, and GBM. Five identified miRNA families, which were, let-7 family, mir-124 family, mir-1 family, mir-103 family, and mir-27 family described in the literature to have tumor-suppressing characteristics. Drug-gene and drug-transcription factor network revealed 32 candidate repurposed drugs and 13 were validated through connectivity map analysis. Here, two main repurposed drugs fit the regulatory requirement for gene interaction, these were, quercetin and vorinostat. Future validation in experimental studies may utilize the future use of the candidate repurposed drugs. Our study provides insights into drug repurposing prospects and understanding tumor expressions.

Abstract: Rice is one of the most important food crops in sub-Saharan Africa. Climate change, variability, and economic globalization threaten to disrupt rice value chains across the subcontinent, undermining their important role in economic development, food security, and poverty reduction. This paper maps existing research on the vulnerability of rice value chains, synthesizes the evidence and the risks posed by climate change and economic globalization, and discusses agriculture and rural development policies and their relevance for the vulnerability of rice value chains in sub-Saharan Africa. Important avenues for future research are identified. These include the impacts of multiple, simultaneous pressures on rice value chains, the effects of climate change and variability on parts of the value chain other than production, and the forms and extent to which different development policies hinder or enhance the resilience of rice value chains in the face of climatic and other pressures.

In Taiwan, peanuts are classified by hand. The kernel quality is judged based on the appearance of peanuts. The identification takes considerable time and labor. Fatigue can induce misrecogni-tion or grade cognition instability due. Peanut defects are generally divided into health, underde-velopment, insect bite, and rupture. This study employed two imaging methods push-boom FX10 and Snapshot. Deep learning was used to detect peanut defects. A push-broom instrument was used for testing. There were 1,560 peanuts, including 240 good and 240 bad ones. There were a total of 1,080 good peanuts and bad peanuts in the test set data, the band selection was used, and a CNN model was built. Based on the results from three methods, 3DCNN could classify with 97%accuracy. The Snapshot was used to achieve the real-time design of a lightweight CNN model. Finally, five bands were selected using PCA, and the screening could be accurate and efficient. The maximum overall accuracy was about 98.5%. Kappa was 97.3% with real-time recognition. This will be a major advantage in the future practical application and commercialization processes. This technique can reduce labor costs, achieve intelligent detection and intelligent grading, and bring breakthroughs to smart agriculture for other crops as well.

Breast cancer is the most common malignancies in women and the second leading cause of cancer death in women. Triple negative breast cancer (TNBC) subtype is a breast cancer subset without ER, PR and HER2 expression, limiting treatment options and presenting a poorer survival rate. Thus, we investigated whether HDACi would be used as potential anti-cancer therapy on breast cancer cells. In this study, we found TNBC and HER2-enrich breast cancers are extremely sensitive to Panobinostat, Belinostat of HDACi via experiments of cell viability assay, apoptotic marker identification and flow cytometry measurement. On the other hand, we developed a bioluminescence based live cell non-invasive apoptosis detection sensor (IADS) detection system to evaluate the quantitative and kinetic analyses of apoptotic cell death by HDAC treatment on breast cancer cells. In addition, the use of HDACi may also be accompanied with chemotherapeutic agent such as doxorubicin to synergic drug sensitivity on TNBC cell (MDA-MB-231), but not in breast normal epithelia cells (MCF-10A), providing therapeutic benefits against breast tumor in clinic.

In this study, we used the natural and anthropogenic characteristics of a coastal region to generate risk maps showing vulnerability and potential hazards, and proposed design criteria for coastal defense and land use for the various kinds of risks faced. The Yunlin coast: a first-level protection area in mid-west Taiwan, was then used as an example to illustrate the proposed design criteria. The safety of the present coastal defenses and land use of the Yunlin coastal area was assessed, and coastal protection measures for hazard prevention were proposed based on the generated risk map. The results can be informative for future coastal management and the promotion of sustainable development of coastal zones.

This paper presents an optimized energy management strategy for Li-ion power batteries used on electric vehicles (EVs) at low temperatures. Under low-temperature environments, EVs suffer a sharp driving range loss resulted from the energy and power capability reduction of the battery. Simultaneously, because of Li plating, battery degradation becomes an increasing concern as temperature drops. All these factors could greatly increase the total vehicle operation cost. Prior to battery charging and vehicle operating, preheating battery to a battery-friendly temperature is an approach to promote energy utilization and reduce total cost. Based on the proposed LiFePO4 battery model, the total vehicle operation cost under certain driving cycles is quantified in the present paper. Then given a certain ambient temperature, a target temperature of preheating is optimized under the principle of minimizing total cost. As for the preheating method, a liquid heating system is also implemented on an electric bus. Simulation results show that the preheating process becomes increasingly necessary with a decreasing ambient temperature; however, the preheating demand declines as driving range grows. Vehicle tests verify that the preheating management strategy proposed in this paper is able to save total vehicle operation cost.

Amylin, also known as islet amyloid polypeptide (IAPP), is a metabolic homeostasis-related hormone that is produced and released by the β cells of the pancreas, the same cells that produce insulin. Insulin-degrading enzyme (IDE) is a protease enzyme that plays an essential role in the breakdown and degradation of various peptides, including insulin and amylin. Direct binding & interaction between amylin and IDE is inextricably linked to the degradation of amylin, and research and development effort in this area is crucial to understand the potential therapeutic implications of disrupting the IDE-amylin interaction in the context of conditions where metabolic homeostasis needs to be regulated, such as diabetes and obesity. Here, this article incorporates currently available experimental complex structure of amylin and IDE, and delves deep into the interstructural biophysics underlying the binding interface of the two interacting partners. With a set of comprehensive structural biophysical analysis, this article identified an intriguing region of high electrostatic potential indicative of strong binding sites between the first N-terminal lysine (Lys1, K1) residue of amylin and Glu341 (E341) of IDE. This unique electrostatic hotspot presented herein paves the way for the rational design of drug-like small molecules that can selectively disrupt this interaction, offering a targeted therapeutic strategy for improved metabolic homeostasis, particularly for patients with diabetes and obesity.

In the domain of drug discovery and design, the acquisition of precise structural and intermolecular Kd data for biological molecules is paramount. However, conventional methods for obtaining such data are often beset by challenges including high costs, time intensiveness, and inherent limitations in scalability and diversity. This article puts forward a high-throughput approach for in silico generation of structural and intermolecular binding affinity (Kd) data, which keeps exploring the uncharted territories of drug discovery & design by harnessing computational methodologies to synthetically generate diverse datasets. Through a meticulously designed workflow encompassing molecular structural modeling, structural biophysics-based calculations of intermolecular binding affinity (Kd), this innovative methodology transcends the constraints of traditional experimentation, offering a cost-effective, scalable, and efficient alternative. By simulating molecular interactions and binding interfaces and predicting binding affinities with reasonable accuracy, this approach not only expedites the drug development process but also enables the exploration of vast molecular space, thereby facilitating the discovery of novel therapeutics beyond conventional drug modality as a form factor. Moreover, the versatility of synthetic data extends beyond virtual screening and lead optimization, encompassing applications such as dataset augmentation, model validation, and benchmarking against experimental data. This article elucidates the conceptual underpinnings, methodological intricacies, validation strategies, and potential ramifications of in silico generated data, heralding a paradigm shift in drug discovery paradigms. By fostering synergy between computational and experimental research domains, this innovative approach promises to accelerate the pace of drug discovery, enhance the robustness of predictive models, and pave the way for transformative advancements in the entire pharmaceutical industry.

A low-cost bio-mass-derived carbon substrate has been employed to synthesize MoS₂@carbon composites through a hydrothermal method. Carbon fibers derived from natural cotton provide a three-dimensional and open framework for the uniform growth of MoS₂ nanosheets, thus constructing hierarchically coaxial architecture. The unique structure could synergistically benefit fast Li-ion and electron transport from the conductive carbon scaffold and porous MoS₂ nanostructures. As a result, the MoS₂@carbon composites, when served as anodes for Li-ion batteries, exhibit a high reversible specific capacity of 820 mAh g^-1, high-rate capability (457 mAh g^-1 at 2 A g^-1), and excellent cycling stability. The superior electrochemical performance makes the MoS₂@carbon composites to be low-cost and promising anode materials for Li-ion batteries.

Since the launch of Protein Data Bank (PDB) in 1971, Cartesian coordinate system (CCS) has been the default approach to specify atomic positions in biomolecular experimental structures with X, Y and Z. In 2020, a local spherical coordinate system (LSCS) approach was proposed as an alternative to CCS, i.e., ρ, θ and φ. Recently, the continued application of deep learning technology in protein structure prediction (PSP) saw a leap forward in the accuracy of PSP, as evidenced by AlphaFold of Google’s DeepMind. However, there still is room for the improvement of the performances of PSP algorithms to date. Given that geometrically, CCS and LSCS are like the two sides of a coin, this short article puts forward a hypothesis that the time is now ripe to end the half-a-century burial of ρ, θ and φ in PDB, and use them as LSCS features for the design of novel PSP algorithms in future.

Insulin icodec of Novo Nordisk is a novel long-acting insulin analogue that exhibits an extended duration of action, providing a promising treatment option for individuals with diabetes. It has been reported that the incorporation of fatty acid moieties into insulin icodec plays a crucial role in its prolonged action, as these fatty acid chains facilitate the formation of stable hexameric structures, thereby delaying insulin absorption and promoting sustained release. Yet, the underlying biophysics still is elusive of the roles of the three site-specific mutations (Y14A\_E, Y37B\_H, F46B\_H) of insulin icodec in its prolonged activity. Thus, through a comprehensive structural and biophysical analysis of the insulin (both native and icodec) structures bound to its receptor, this article delves deep into the biophysics underlying the molecular design of insulin icodec, and identified a delicate biophysical mechanism through which two missense mutations of insulin icodec (Y37B\_H and F46B\_H) contribute to its prolonged duration of action. Overall, this structural and biophysical investigation provides valuable insights into the mechanisms underlying the relationship between three site-specific mutations and prolonged duration of action of insulin icodec, while understanding these modifications at a structural and biophysical level can aid in the rational design of future long-acting insulin analogues, offering further enhanced therapeutic options for diabetic patients.

Understanding the spatial distribution pattern and evolution characteristics of the elderly population in urban areas is of great significance for the development of urban planning and the implementation of public management policies in the context of rapid aging. Accurately identifying the spatial distribution and evolution characteristics of the elderly population in the city requires a comprehensive analysis of multiple indicators and large-scale data. Taking Wuhan city as an example, this article measures the spatial distribution characteristics and evolution trend of the elderly population from 2000 to 2020 at the street/township level, based on the fifth, sixth, and seventh census data, using methods such as kernel density hotspot detection, spatial clustering analysis, and standard deviation ellipse analysis. The results show that: ① there are significant differences in the aging spatial pattern between the central area and the suburban areas of Wuhan; ② overall, Wuhan's aging rate shows a typical "core-periphery" growth mode in space, while the density of the elderly population has significant spatial aggregation characteristics and shows an evolution trend of "centralized concentration, peripheral outliers, axial development, and near-field growth"; ③the center of gravity of the elderly population remains relatively stable over time.

The importance of antibodies in health care and the biotechnology research and development demands not only knowledge of their experimental structures at high resolution, but also practical implementation of this knowledge for both effective and efficient design and production of antibody for its use in both medical and research applications. While the experimental wet-lab approach is usually costly, laborious and time-consuming, computational (dry-lab) approaches, in spite of their intrinsic limitations in comparison with its experimental (wet-lab) counterpart, provide a cheaper and faster alternative option. For the first time, this article reports a comprehensive set of structural electrostatic features extracted from experimentally determined antigen-antibody-related structures, including especially those structural electrostatic features at the interfaces of all experimentally determined antigen-antibody complex structures as of February 29, 2020, to facilitate effective and efficient machine learning-based computational antibody design using currently available experimental structures inside Protein Data Bank.

The spike protein of SARS coronavirus (SARS-CoV) attaches the virus to its cellular receptor, angiotensin-converting enzyme 2 (ACE2), which is mediated by the receptor binding domain (RBD) of the spike protein. Recently, an analysis based on decade-long structural studies of SARS was reported to illustrate with atomic-level details receptor recognition by the novel coronavirus from Wuhan, i.e., 2019-nCoV. Here, this article reports a comprehensive set of structural electrostatic analysis of all SARS-CoV spike protein RBD-related structures as of February 13, 2020, aiming at identifying the electrostatic hot spots for SARS-CoV spike protein to be complexed with ACE2 and its neutralizing antibodies. First, this article identified a structural action mechanism of the F26G19 antibody (of SARS-CoV spike protein), where its Asp56 residue binds to the Arg426 of the SARS-CoV spike protein RBD against the formation of the interfacial Arg426-Glu329 salt bridges between ACE2 and the SARS-CoV spike protein RBD. Second, a hypothesis is reported that a pair of electrostatic clips exist at the interface between ACE2 and the SARS-CoV spike protein RBD, including both Arg426-Glu329 and His445-Glu23-Lys447 salt bridges. Last, this article reports a structurally identified interfacial Glu35-Arg479 salt bridge which helps stabilize the complex structure of ACE2 and the SARS-CoV spike protein RBD. Overall, the structurally identified electrostatic hot spots reported here may be useful for the design of SARS-CoV-neutralizing antibodies in future.

In a global context, the story of the Jesuit compound in Shanghai, since its establishment by French Jesuits in 1847, reflected not only conflicts between rival powers in Europe but also the fight for their interests in the Eastern world. The Pope, who was stuck without legal status in the Vatican after 1861, was also seeking the chance to save the authority of the Church in the face of questions regarding the extent of his temporal power and the status of Rome in the context of Italian unification. As in the Reformation, a break-through in the east seemed to offer a solution for losses in Europe. However, the Jesuits to the East in the late 19th century were not only troops working and fighting on behalf of the Pope; their identities under the French Protectorate added complexity to an already complicated story involving not just the Church, but the course of world history.The female Catholic orders at the east bank of Zi-ka-wei compound became a unique window to approach the complexity.

The study aimed to investigate how distributed leadership influences adolescents' social and emotional competence, considering the roles of student-centered instructional practices and teacher self-efficacy. Utilizing survey data from 7,246 Suzhou adolescents enrolled in the SESS program, the study employed multilevel structural equation modeling for analysis. The findings indicated a positive correlation between distributed leadership and adolescents' social and emotional competence, as evaluated by teachers. Moreover, distributed leadership was observed to exert an indirect impact on adolescents' self-assessment and teacher-rated social and emotional competence. This influence operated through several mediators: student-centered instructional practices, teacher self-efficacy, and the sequential mediating pathway of student-centered instructional practices → teacher self-efficacy. This study underscores the significance of supportive elements in fostering students' social and emotional competence. It offers valuable insights into the everyday practices of teachers, principals, and administrators. Additionally, it sheds light on how distributed leadership contributes to enhancing adolescents' overall social and emotional development.

Sleep postures monitoring systems in the hospital aim at transforming sensing signals into quantitative data to characterize the sleep behaviors of the patient. However, a home-care sleep posture monitoring system needs to be user friendly. In this paper, we present iSleePost - a user-friendly home-care intelligent sleep posture monitoring system. We address the labor-intensive labeling issue of traditional machine learning approaches in the training phase. Our proposed mobile health (mHealth) system leverages the communications and computation capabilities of mobile phones for provisioning a continuous sleep posture monitoring service. Our experiments show that iSleePost can achieve 90 percent accuracy in recognizing sleep postures. More importantly, iSleePost demonstrates that an easily-wear wrist sensor can accurately quantify sleep postures.

(1) Background: Breast cancer is the second leading cause of cancer death among women. The accurate prediction of survival intervals will help physicians make informed decisions on treatment strategies or the use of palliative care for patients; (2) Methods: The gene expression is predictive and correlates to patient prognosis. To establish a reliable prediction tool, we collected the RNA-seq data of breast cancer patients, a total of 1187 RNA-seq data (median age 58 years), in FPKM format from the TCGA database. Among them, 144 RNA-seq data with date of death information was selected to establish the SaBrcada-AD dataset. We first normalized the SaBrcada-AD dataset to transcripts per million (TPM) to build survival prediction model SaBrcada. After normalization and dimension raising, the differential gene expression data were used for testing eight different deep learning architectures. Among them, GoogLeNet performed the best. Considering the effect of age on prognosis, we examined all ages between the lower and upper quartiles of patient age for a stratified random sampling test; (3) Results: Stratifying by age based on a cut-off of 61 years of age improved the accuracy of SaBrcada compared to previous findings, resulting in an accuracy of 0.798. We also built a free website tool to provide 5 kinds of predicted survival period information for clinician reference; (4) Conclusions: We established a breast cancer survival analysis prediction model, SaBrcada, and a website tool with the same name. Through this highly reliable survival analysis model and website tool, information on survival intervals will be provided for clinicians as part of precision medicine.

Drug-target binding is a crucial parameter in drug discovery and design, ensuring drug efficacy and specificity. Semaglutide, a potent GLP-1 receptor agonist, is widely used to treat type 2 diabetes mellitus by regulating blood glucose levels and promoting weight loss. This study introduces a novel approach utilizing the concept of a general intermolecular binding affinity calculator (GIBAC) for designing semaglutide analogues with enhanced binding affinity to GLP-1R. For the first time, a Val27-Arg28 exchange was manually introduced to strengthen the semaglutide-GLP-1R binding affinity. A comprehensive structural and biophysical analysis was conducted to explore the semaglutide-GLP-1R sequence space, leading to the identification of promising analogues. Among these, one semaglutide analogue demonstrated a binding affinity to GLP-1R that is more than two orders of magnitude (113.3 times) higher than native semaglutide, achieving a Kd of 3.0 x 10^-8 M compared to the Kd of 3.4 x 10^-6 M for native semaglutide. This article proposes a promising structural biophysical approach for developing GLP-1 receptor agonists with improved efficacy. The prototype GIBAC, termed semaGIBAC, represents a paradigm shift in precise drug discovery and design, advocating for the construction of a full-scale GIBAC to be prioritized within the drug discovery and design community.

Drug-target binding is an essential parameter in drug discovery and design to ensure drug efficacy and specificity. In 2022, the concept of a general intermolecular binding affinity calculator (GIBAC) was for the first time coined: $Kd = f(molecules, envPara)$. Technically, GIBAC represents a set of in silico approaches for structural and biophysical data generation towards a paradigm shift in precise drug discovery and design, providing a comprehensive framework for intermolecular binding affinity calculation with adequate accuracy, precision and efficiency. For the first time, this study reports a prototype of GIBAC (semaGIBAC), i.e., a one-dimensional semaglutide-GLP-1R-based mini static GIBAC, based on an experimental complex structure of semaglutide and GLP-1R. Semaglutide is a potent GLP-1 receptor agonist used to treat type 2 diabetes mellitus by regulating blood glucose levels and promoting weight loss. In 2021, a structural modification involving a Val27-Arg28 exchange was manually introduced to enhance semaglutide-GLP-1R binding affinity. This study employs a comprehensive structural and biophysical analysis aimed at thoroughly exploring the sequence space of semaglutide-GLP-1R to design analogues with improved binding affinity, leading to the identification of a promising semaglutide analogue, which binds to GLP-1R with an affinity that is more than two orders of magnitude (113.3 times) higher than native semaglutide. To sum up, this article puts forward a promising structural biophysical approach for developing GLP-1 receptor agonists with enhanced efficacy, and with a GIBAC prototype (semaGIBAC), this article argues again that the time is now ripe for the construction of a real GIBAC to be listed on the agenda of the drug discovery and design community.

Phosphodiesterase type 5 (PDE5) inhibitors are widely used in the treatment of various conditions, including erectile dysfunction and pulmonary hypertension. Despite their clinical efficacy, these drugs quite often cause visual disturbances due to off-target effects on Phosphodiesterase type 5 (PDE6) in the retina. This review explores the application of a general intermolecular binding affinity calculator (GIBAC)-based binding selectivity strategy in the design of PDE5 inhibitors, aiming to enhance binding selectivity and minimize visual side effects. This GIBAC strategy integrates computational structural biological approaches to iteratively refine drug-target binding affinities, thereby improving target specificity and the structural biophysical limit for the efficacy-safety balance of PDE5 inhibitors. Through detailed analysis of PDE5’s and PDE6’s biological role and the molecular mechanisms underlying visual disturbances, this article underscores the necessity of target binding selectivity in PDE5 inhibitor design in future. Additionally, this article discusses the practical applications of GIBAC in computational drug discovery and design, along with the future directions and the potential for GIBAC to transform PDE5 inhibitor development, ultimately enhancing therapeutic outcomes and patient safety. Finally, this article calls for a GIBAC-based paradigm shift in computational drug discovery and design towards the continued development of the pharmaceutical industry.

Semaglutide is a potent GLP-1 receptor agonist used in the treatment of type 2 diabetes mellitus due to its ability to regulate blood glucose levels and promote weight loss. On July 26, 2021, with a manually defined set of computational structural and biophysical analysis, a simple Val27-Arg28 exchange was for the first time introduced in the backbone of semaglutide to strengthen the semaglutide-GLP-1R binding affinity. In this article, a comprehensive structural and biophysical analysis approach is for the first time proposed towards an exhaustive exploration of the semaglutide-GLP-1R sequence space for the design of semaglutide analogues with elevated binding affinity to GLP-1R, thereby potentially enhancing therapeutic efficacy of structurally conceivable semaglutide analogues. Through structure biophysics-based rational design and computational modeling, this article puts forward a set of semaglutide analogues and calculated their binding affinities to GLP-1R, with one particular semaglutide analogue-GLP-1R structural model reaching a K_d of 3.0 × 10^-8 M, while the K_d is 3.4 × 10^-6 M for the binding of native semaglutide to GLP-1. Overall, the computationally designed semaglutide analogues here constitute a hopeful approach for developing GLP-1 receptor agonists with improved efficacy for the treatment of diabetes and weight management in future.

Insulin therapy is a cornerstone in the management of diabetes, yet the pursuit of optimizing its pharmacokinetic profile remains a focal point in diabetes research. For instance, insulin icodec of Novo Nordisk is a novel long-acting insulin analogue that exhibits an extended duration of action, providing a promising once-weekly treatment option for diabetic patients. However, designing insulin analogues with lower receptor affinity than that of insulin icodec could still produce a further extended duration of action than that of insulin icodec through the suppression of receptor-mediated internalization of insulin analogues. In this study, therefore, I present the design of a novel series of insulin analogues engineered towards lower binding affinity to the insulin receptor compared to that of insulin icodec. Through computational structural biophysics-based rational design strategies, this article aims to further extend the duration of action while maintaining therapeutic efficacy of insulin analogues. Utilizing homology molecular modeling and structural biophysics-based binding affinity calculations, this article puts forward a set of insulin analogues with lower binding affinity to insulin receptor than that of insulin icodec from a structural and biophysical point of view. Overall, this article calls for subsequent in vitro and in vivo evaluations of the efficacy and prolonged action of the engineered insulin analogues to pharmacokinetically test whether these analogues acutally surpass that of insulin icodec as hopeful candidates for next-generation insulin analogue therapies with improved duration of action and enhanced control of blood glucose levels for diabetic patients in future.

Intermolecular interactions are the fabrics underlying almost all processes in living organisms, where two cornerstone concepts, intermolecular binding affinity (K d ) and binding energy (ΔG), have long been established to physically describe the strengths of biomolecular interactions, e.g., drug-target K d and ΔG to describe the strength of drug-target interaction. The past two-three years saw a big step forward in the use of artificial intelligence (AI) in structural biology (e.g., AlphaFold for protein structure prediction) and drug discovery & design. In light of the roles of K d and ΔG in drug discovery & design, the speed of this AI progress raises a question of what’s next for its practical application in the pharmaceutical industry, in addition to a system-wide account of biomolecular structures and motions. Last August, the concept of a general intermolecular binding affinity calculator (GIBAC) was for the first time coined and proposed in an MDPI-published preprint. Here, this article puts forward an updated conceptual and practical framework of GIBAC, including its inception, definition, construction, practical applications, technical challenges and limitations, and future directions. Moreover, this article argues that the time is now ripe for the construction of such an accurate, precise and efficient GIBAC to be on the agenda of the entire drug discovery & design community, to ensure its applicability & reliability, and to enhance its value in drug R&D in future.

Semaglutide is a glucagon-like peptide 1 analog used for the treatment of patients with type 2 diabetes mellitus. With 94% sequence similarity to human GLP-1, semaglutide is a glucagon-like peptide-1 receptor (GLP-1R) agonist, which binds directly to GLP-1R, causing various beneficial downstream effects that reduce blood glucose. Practically, it is favourable for semaglutide to bind not just directly, but also tighter, to its receptor GLP-1R. Therefore, incorporating currently available experimental structural data of semaglutide-GLP-1R, this short article reports for the first time that biophysically, semaglutide is able to bind tighter to GLP-1R with just a simple Val27-Arg28 exchange in its peptide backbone.

Insulin lispro was the first fast acting insulin analogue to obtain regulatory approval for therapeutic use. This article puts forward a novel biophysical mechanism where the net impact of the simple B28Pro-B29Lys exchange from regular insulin to insulin lispro is the establishment of a novel set of interfacial electrostatic interactions between Lys28 of insulin lispro and Asp12 of insulin receptor (IR). In addition, a set of structural analysis was presented in this article to further strengthen the binding of insulin lispro to IR, where two polar amino acid residues (Gln51 and Asn74 of insulin lispro) were put forward as two potential targets for site-directed mutagenesis of insulin lispro at its binding interface with IR.

One notable features of the SARS-CoV-2 genome is that the spike protein of SARS-CoV-2 has a functional polybasic (furin) cleavage site (RRAR) at the S1–S2 boundary through the insertion of 12 nucleotides encoding PRRA. To date, the furin cleavage site (FCS) remains an experimentally uncharted territory both structurally and functionally. For instance, whether or not FCS is actually cleaved, before or after viral cell entry or exit, still remains to be experimentally investigated. With currently available structural data, this article presents a computational structural characterization of the FCS inserted into SARS-CoV-2 spike glycoprotein, and puts forward a set of structural hypothesis against the hypothesis of SARS-CoV-2 from purposeful manipulation: (1), the inserted FCS does not alter, neither stabilize nor de-stabilize, the overall structure of SARS-CoV-2 spike glycoprotein; (2), the net structural consequence of FCS is the insertion of a furin cleavage site into SARS-CoV-2 spike glycoprotein, whose S1 and S2 subunits will still be bonded together even if the FCS is actually cleaved by furin protease.

Protein is the proteios building block of life. Evolutionarily, its sequence is not as conserved as its structure, making it more reasonable for protein structure, instead of protein sequence, to be the descriptor of protein function. Yet, in the National Center for Biotechnology Information (NCBI) database, the number of experimentally identified protein sequences is in great excess of that of experimentally determined protein structures inside the almost-half-a-century old Protein Data Bank (PDB). For instance, GPR151 is an proton-sensing G-protein coupled receptor (GPCR) originally identified as homologous to galanin receptors. As of March 19, 2020, GPR151’s structure has not been experimentally determined and deposited in PDB yet. Thus, an ab initio modelling approach was employed here to build a three-dimensional structure of GPR151. Overall, the ab initio GPR151 model presented herein constitutes the first structural hypothesis of GPR151 to be experimentally tested in future with previously published, currently ongoing and future GPR151 studies.

Ebolavirus has a membrane envelope decorated by trimers of a glycoprotein (GP), which is responsible for host cell attachment and membrane fusion. Therefore, GP is a primary target for antiviral drugs development. Here, this article reports the first, to my knowledge, set of structural analysis of all Ebolavirus GP structures as of March 10, 2020, and also a brief update of the structurally identified electrostatic features of the Ebolavirus GP structures in both apo (unliganded) state and also in bound states with a series of small compounds, including a variety of approved drugs. With this comprehensive set of structural analysis, this article puts forward a hypothesis of two Achilles' heels of Ebolavirus GP structure, where the formation of two interfacial salt bridges, instead of destabilizing the prefusion conformation of Ebolavirus GP, constitutes a positive contribution towards the structural rigidification of the prefusion conformation of the Ebolavirus GP structure, thereby acting against GP-mediated Ebolavirus cell entry and/or preventing fusion between the viral and endosome membranes.

Since the Coronavirus disease (COVID-19) outbreak at the end of 2019, the past two month has seen an acceleration both in and outside China in the R&D of the diagnostics, vaccines and therapeutics for this novel coronavirus. As one of the molecular forces that determine protein structure, electrostatic effects dominate many aspects of protein behaviour and biological function. Thus, incorporating currently available experimental structures related to COVID-19, this article reports a simple python-based analysis tool and a LaTeX-based editing tool to extract and summarize the electrostatic features from experimentally determined structures, to strengthen our understanding of COVID-19's structure and function and to facilitate machine-learning and structure-based computational design of its neutralizing antibodies and/or small molecule(s) as potential therapeutic candidates. Finally, this article puts forward a brief update of the structurally observed electrostatic features of the COVID-19 coronavirus.

For voltage-gated Ca2+ channel (VGCC), its α2δ subunits are traditionally considered to be auxiliary subunits that regulates VGCC trafficking to the plasma membrane. The antiepileptic, antinociceptive and anxiolytic gabapentin (GBP) has previously been shown to bind the VGCC α2δ subunits with high affinity to disrupt VGCC trafficking. Yet, the interaction between GBP and α2δ still remains poorly understood from a structural point of view. For instance, it is not clear yet what the structural implication is of α2δ-1-bound GBP against VGCC trafficking. With a set of experimental data-driven structural analysis of the VGCC α2δ-1 and its ligand GBP, this article postulates for the first time that: 1), α2δ-1 bound GBP stabilizes the α2δ-1-GBP complex structure; 2), α2δ-1 bound GBP restrains the conformational flexibility of α2δ-1; 3), α2δ-1-bound GBP establishes an electrostatic axis consisting of Q535 (Gln535)-R241 (Arg241)-GBP (gabapentin)-D452 (Asp452), which constitutes an energetically favourable contribution towards the structural stability of the α2δ-1-GBP complex and helps restrains the conformational flexibility and local structural rigidification of α2δ-1; and 4), GBP-induced local conformational inflexibility and structural rigidification of α2δ-1 is one key step in the pharmacological disruption of VGCC trafficking by GBP.

As of today, there is not any direct report yet of the degree to which missing residues exist for experimentally determined membrane protein (MP) structures, which constitute more than half of current drug targets. With a chain- and position-specific visualisation and a statistical analysis of all MP structures inside PDB (as of September 25, 2019), this article argues that the experimentally uncharted territories (EUTs, i.e., consisting of missing residues) within PDB are pluggable and should be plugged with an experimental data-driven hybrid approach, and calls for continued development of MP structural determination with less and less EUTs, in light of MPs' crucial role in biological and biomedical research, both fundamental and pharmaceutical.

To date, Cartesian (x, y, z) coordinate system (CCS) has been the default approach to geometrically specify atomic spatial positions in protein structures since the launch of Protein Data Bank (PDB) in 1971. To this end, this paper proposes a local spherical coordinate system (SCS) approach as an alternative to the default approach and a previously reported global SCS approach. The local SCS approach here requires only two parameters (θ and φ), instead of x, y and z as required by the default CCS approach. Essentially, CCS and SCS are like the two sides of one coin, i.e., geometric coordinate system for three-dimensional position specification. Therefore, this paper furthermore argues that it is time to flip the coin over, and have a look at the other side of the coin, e.g., the local SCS approach, which possesses an intrinsically lower degree of descriptional complexity than that of the default CCS approach, and constitutes a potentially useful alternative perspective for all protein structural research field.

PD-1/PD-L1 axis is one key therapeutic target against tumor cell immune escape. Structurally essential to the PD-1/PD-L1-linked immune escape is the binding interface of the PD-1/PD-L1 complex structure. Incorporating currently available PD-1/PD-L1-related experimental structures, this article unveils two sets of experimentally observed inter-molecular electrostatic interactions which stabilize the binding interface of the PD-1/PD-L1 complex structure. For the first time, this article proposes an evolutionary structural hypothesis that, as a result of natural selection, PD-1 is able to genetically mutate itself to structurally disrupt the PD-1/PD-L1 axis towards the restoration of T cell-mediated anti-tumor immunity.

Purpose: This study investigates the implementation and impact of maker culture—viewed as a tool for developing green digital skills—in higher education institutions in Hong Kong. Maker culture, a collaborative educational approach, embraces students’ capacity for self-paced, autonomous learning and applies this knowledge to creative problem-solving and innovation, key aspects of sustainability education. Methods: An empirical study was conducted, focusing on the experiences of teachers in the higher education sector in Hong Kong. Eight individuals were interviewed to gain insights into their perceptions and experiences with maker education within sustainability contexts. The sample was limited to ensure cross-sectional comparability and direct weighting of teachers’ experiences within a singular, complementary educational setting. Results: The findings provide valuable insights into the benefits and challenges of integrating maker education into traditional educational systems to foster green digital skills. It became evident that adequate resources, effective teachers, and improved administrative systems play significant roles in the successful implementation of this approach. Conclusion: Maker education, as a tool for developing green digital skills, offers a promising alternative to traditional performance-based studies. It has the potential to lead to a future of education that is creative, innovative, and student-directed, fostering sustainability competences. Therefore, despite the challenges, with the right support and resources, the integration of maker culture into educational systems could significantly transform teaching and learning processes, advancing sustainability education.

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are fast becoming the most common chronic liver disease and are often preventable with healthy dietary habits and weight management. Sugar-sweetened beverage (SSB) consumption is associated with obesity and NAFLD. However, the impact of different types of SSB, including artificially sweetened beverages (ASB), is not clear after controlling for total sugar intake and total caloric intake. In this study, we examined the association between different SSB consumption and the risk of NAFLD and NASH. A total of 3,739 US adults aged ≥20 years old who had completed 24-hour dietary recall interviews and measurements, including dietary, SSB, smoking, physical activity, and liver stiffness measurement, using the National Health and Nutrition Examination Survey 2017-2020 surveys were included in this study. Chi-square tests, t-tests, and weighted logistic regression models were utilized for analyses. The prevalence of NASH was 20.5%, and NAFLD (defined without NASH) was 32.7% of .S.U.S. adults. We observed a higher prevalence of NASH/NAFLD in men, Mexican-Americans, sugar intake from SSB, light-moderate alcohol use, individuals with lower physical activity levels, higher energy intake, obesity, and medical comorbidities. Heavy sugar consumption through SSB was significantly associated with NAFLD (aOR=1.60, 95% CI=1.05-2.45). In addition, intake of ASB only (compared to non-SSB category) was significantly associated with NAFLD (aOR=1.78, 95% CI=1.04-3.05), after adjusting for demographic, risk behaviors, and body mass index. Higher sugar intake from SSB and exclusive ASB intake are both associated with the risk of NAFLD.

Orbitrap mass spectrometers have been widely used in environmental component analysis . This paper presents an enhanced data acquisition system for in-situ detection of Orbitrap mass spectrometry, which enables in-suit real-time signal processing and analysis for atmospheric molecules with small mass numbers.During previous space atmospheric explorations, quadrupole mass spectrometry (QMS) was usually utilized for analyzing isotopic compositions and complicated compounds in the mixture. However, the inevitable ion scattering and drift during mass transfer, as well as the QMS attenuator loss, result in a relatively lower signal-to-noise ratio of the produced mass spectrum. In recent years, a novel mass spectrometer, called an Orbitrap mass spectrometer, has been gradually accepted and used because of its non-destructive detection ability, high mass resolution, and accuracy. Nevertheless, Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) is preferred over the Orbitrap mass spectrometry for ground applications, especially for detecting low-mass components (e.g. below 50 atomic mass units) due to the former’s superior resolution. As the mass number decreases, the detection system demands a higher sampling and processing rate. Additionally, in ground-based scenarios, mass spectrometry analysis software on computers is often employed to analyze the signals. Therefore, in order to achieve in-situ detection of the space atmospheric environment using the Orbitrap mass spectrometer, this paper proposes a real-time signal acquisition and processing system for mass spectrometry analysis. The system comprises of signal conditioning circuits, analog-to-digital conversion circuits, programmable logic circuits, and related software. These components perform spectrum analysis and process the signal in real-time on hardware components, allowing for high-speed acquisition and analysis of the signals produced by the Orbitrap mass spectrometer.

Patients with Peripheral-artery-disease (PAD) are prone to risks of major-adverse-limb-events (MALE), and major-adverse-cardiovascular-events (MACE). CHA2DS2-VASc is a prognostic score for Atrial fibrillation stroke risk, however, no study exists that evaluated its predictability for MALE and MACE in PAD patients. In this study, patients with PAD were stratified into four risk groups based on CHA2DS2-VASc score. Cox-proportional hazards models,10-fold cross-validation and Receiver operating characteristic (ROC) analyses were utilized to evaluate the predictability of CHA2DS2-VASc for predicting MALE, MACE, and MALE+MACE. Kaplan-Meier analysis estimated the survival-probability of risk-groups. CHA2DS2-VASc was found to be a significant predictor of MACE (hazard ratio (95% confidence interval; P) = 3.47 (0.99 - 12.18; 0.052), 4.12 (1.19 - 14.14; 0.024), and 5.06 (1.48 – 17.28; 0.009), for moderate-, high- and very-high-risk groups, respectively, while for MALE and MALE+MACE significance was achieved only for high-risk group. MACE demonstrated AUC > 0.8, good-discrimination (c-index > 0.8) and good-calibration. However, MALE and MALE+MACE models failed to achieve good performances. Based on all findings, CHA2DS2-VASc could potentially serve as a risk stratification score for predicting MACE in patients with PAD but failed to qualify as a good predictor for MALE.

Apiaceae plants have been widely used as traditional Chinese medicines (TCMs) for the treatment of removing dampness, relieving superficies, and dispelling cold, etc. In order to exploit the potential application and improve the yield and quality of Apiaceae medicinal plants (AMPs), The traditional use, phytochemistry, modern pharmacological use, effect of bolting and flowering (BF), and approaches for controlling the BF were summarized. Currently, about 228 AMPs have been recorded as TCMs with 6 medicinal parts, 72 traditional uses, 62 modern pharmacological uses, and 5 main kinds of metabolites. Three effect degrees (i.e., significantly affected, affected to some extent, and no significantly affected) could be classed based on the yield and quality. The BF of individual plants (e.g., Angelica sinensis) could be effectively controlled by the standard cultivation techniques, while the mechanism of BF has not been systemically revealed. This review will provide useful references for the reasonable exploration and high-quality production of AMPs.

Research on the development of new lightweight Al-Li alloys using selective laser melting pro-cess has great potential for industrial applications. This paper reports on the development of novel aluminum-lithium alloys using selective laser melting technology. Al-Cu-Li-Mg-Ag-Sc-Zr pre-alloyed powders with lithium contents of 1 wt.%, 2 wt.% and 3 wt.%, respectively, were prepared by inert gas atomization. After SLM process optimization, the microstructure and me-chanical properties of the as-formed specimens were investigated. The densification of the three newly developed alloys are 99.51 %, 98.96 % and 92.01 %, respectively. They all have good form-ability, with the lithium loss rate about 15 %. The as-formed alloy with 1% Li content presents good comprehensive properties with a yield strength of 412.6 ± 16.0 MPa, an ultimate tensile strength of 461.1 ± 11.7 MPa, and an elongation of 13.6 ± 1.1%. The three alloys exhibit a layered molten pool stacking morphology and have a typical heterostructure. The columnar crystals and equiaxed fine grains are alternately arranged, and most of the precipitated phases are enriched at the grain boundaries. The change of Li content mainly affects the precipitation of Cu-containing phase. When the Li content is 1 wt.%, there are θ phase, T1 phase and TB phase. When Li increased to 2 wt.%, T1 and T2 phases precipitated together. When Li reaches 3 wt.%, δ' phase precipitates with T2 phase. This study provides useful guidance for the future SLM form-ing of new crack-free and high-strength Al-Li alloys.

This study utilises NaOH to treat composite cementitious materials containing aeolian sand and zeolite powders, which were used to replace 50% of the cement in aeolian-sand concrete (ASC). The mechanical properties of treated ASC considerably improved, especially when the NaOH dosage was 4% by mass. After curing this sample (denoted as AAZC-4) for 28 d, its compressive strength improved by 17.2% and its split tensile was increased by 16.3%. Potassium feldspar and montmorillonite in zeolite powder and SiO2 in the sand were decomposed by OH− and combined with other elements to generate various silicate gels and A-type potassium zeolite crystals inside the concrete. Microscopic examination showed that the gels and crystals intertwined to fill the pores, decreasing (increasing) the percentage of large (small) pores, thus optimising the pore structure. This substantially improved the mechanical properties of ASC. Freeze–thaw salt-intrusion tests showed that the extent of mass loss, degree of damage and loss of compressive strength of AAZC-4 were similar to those of ordinary concrete but were reduced by 36.8%, 19% and 52.1%, respectively, compared with those of ASC. Therefore, AAZC-4 has sustainable working performance in the chloride ion permeable environment in cold and arid areas.

Due to the vast conformational space proteins can adopt, accurate and efficient prediction of protein structure remains still a challenging task, coupled with the intricacies of interatomic interactions and the limitations of current computational models in effectively navigating this complex molecular landscape. Additionally, the lack of comprehensive experimental data for all protein structures further exacerbates the difficulty in reliable machine learning-based prediction of the three-dimensional conformations of the proteios building block of life. Geometrically, Cartesian coordinate system (CCS, X, Y and Z) and spherical coordinate system (SCS, ρ, θ and φ) are two interconvertible coordinate systems, and are like two sides of one coin. Since the beginning of Protein Data Bank (PDB) in 1971, CCS has been the default approach to specify atomic positions with X, Y and Z in PDB. In this manuscript, therefore, I present a novel method for the reversible spherical geometric conversion of protein backbone structure coordinate matrices to three independent vectors: ρ, θ and φ. This reversible conversion facilitates lossless extraction of essential structural features from protein backbone structural data, enabling the development of advanced novel algorithms for protein structure prediction in future. In short, this inter-atomic SCS approach offers a comprehensive yet efficient means of representing protein backbone geometry, leveraging spherical coordinates to capture spatial relationships in a compact and intuitive inter-atomic manner, and to provide a robust framework for reversible feature extraction for the ongoing efforts in advancing the field of protein structure prediction, the holy grail of computational structural biology.

As a key mediator of chronic pain, neurotrophin nerve growth factor (NGF) binds to two neurotrophin receptors: p75 neurotrophin receptor (p75NTR) and tyrosine kinase receptor A (TrkA). The formation of the p75NTR-NGF-TrkA complex is implicated in the potentiation of chronic pain signals, making it an attractive target for therapeutic explorations. NGF analogues and monoclonal antibodies (mAbs) targeting NGF represent two distinct approaches in modulating the intricate signaling pathways involved in pain transduction mediated by the p75NTR-NGF-TrkA complex. While NGF analogues offer the advantage of tailored design to fine-tune neurotrophic responses, monoclonal antibodies provide a more systemic and comprehensive blockade of NGF, inhibiting its interactions with both p75NTR and TrkA receptors. However, the use of mAbs may pose challenges related to potential side effects and interference with the physiological functions of NGF. As a result, balancing the benefits and drawbacks of the two approaches is critical for advancing therapeutic strategies towards the alleviation of p75NTR-NGF-TrkA-mediated pain. In this study, therefore, a novel structural and biophysical approach was employed for the design of NGF analogues to suppress p75NTR-NGF-TrkA-related chronic pain signaling. Employing high-throughput structural modeling and biophysics-based intermolecular binding affinity calculations, this article for the first time puts forward a set of NGF analogues, including in particular NGF analogues with four site-specific mutations, for whose dimerizations the K d at 37 ^◦C were reduced by three orders of magnitude (from 10^-9 M to 10^-6 M) compared to the K d at 37 ^◦C for the dimerization of native NGFs. Overall, the integration of structural and biophysical perspectives enhances our understanding of the rational design of NGF analogues as promising candidates for the development of NGF-targeted analgesic therapies, which balances the benefits and drawbacks of anti-NGF antibodies and NGF analogues for advancing therapeutic strategies towards the alleviation of p75NTR-NGF-TrkA-mediated pain.

This study investigated the roles of low-molecular-weight fucoidan (LMWF) in enhancing the anti-cancer effects of fluoropyrimidine-based chemotherapy. HCT116 and Caco-2 cells were treated with LMWF and 5-FU. Cell viability, cell cycle, apoptosis, and migration were analyzed in both cell types. Potential mechanisms underlying how LMWF enhances the anti-cancer effects of fluoropyrimidine-based chemotherapy were also explored. The cell viability of HCT116 and Caco-2 cells was significantly reduced after treatment with a LMWF-5-FU combination. In HCT116 cells, LMWF enhanced the suppressive effects of 5-FU on cell viability through the 1) induction of cell cycle arrest in the S phase and 2) late apoptosis mediated by the Jun-N-terminal kinase (JNK) signaling pathway. In Caco-2 cells, LMWF enhanced the suppressive effects of 5-FU on cell viability through both c-mesenchymal–epithelial transition (MET)/ Kirsten Rat Sarcoma virus (KRAS)/ extracellular signal-regulated kinase (ERK) and c-MET/ phosphatidyl-inositol 3-kinases (PI3K)/ protein kinase B (AKT) signaling pathways. Moreover, LMWF enhanced the suppressive effects of 5-FU on tumor cell migration through the c-MET/ matrix metalloproteinase (MMP)-2 signaling pathway in both HCT116 and Caco-2 cells. Our results demonstrated that LMWF is a potential complementary therapy for enhancing the efficacies of fluoropyrimidine-based chemotherapy in colorectal cancers (CRCs) with the wild-type or mutated KRAS gene through different mechanisms. However, in vivo studies and in clinical trials are required to validate the results of the present study.

Previous research has paid little attention to the relationship between corporate governance and brand equity in the tourism industry. This study aims to investigate the moderating effect of corporate governance (CG) on the relationship between brand equity (BE) and corporate profit-ability (CP) with ten control variables including five company characteristics and five macroeconomic variables. Financial data is retrieved from the Taiwan Economics Journal Database (TEJ), covering a total of 196 records from 32 listed companies for 16 years. Results indicate that BE has a significantly positive impact on CP in Taiwanese-listed tourism companies, and that CG moderates the relationship between BE and CP. These findings could help management executives enhance profitability by deepening BE and CG in the tourism industry. Managerial implications are also discussed.

Lithium rich layered oxides (LRLO) are a wide class of innovative active materials for positive electrodes in lithium-ion (LIB) and lithium-metal secondary batteries (LMB). LRLOs are over-stoichiometric layered oxides rich in lithium and manganese, with general formula Li1+xTM1-xO2, where TM is a blend of transition metals comprising Mn (main constituent), Ni, Co, Fe and others. Due to the very variable composition and the extended defectivity their structural identity is still debated among researchers being likely an unresolved hybrid between a monoclinic (mC24) and a hexagonal lattice (hR12). Once casted in composite positive electrode films and assembled in LIBs or LMBs, LRLOs can delivery reversible specific capacities above 220-240 mAhg-1, thus beyond any other available intercalation cathode material for LIBs, with mean working potential above 3.3-3.4 V vs Li for hundreds of cycles in liquid aprotic commercial electrodes. In this review we critically outline the recent advancements in the fundamental understanding of the physico-chemical properties of LRLO as well as the most exciting innovations in their battery performance. We focus in particular on the elusive structural identity of these phases, on the complexity of the reaction mechanism in batteries as well as on practical strategies to minimize or remove cobalt from the lattice while preserving the outstanding performance upon cycling.

In response to the increasing energy demand in Taiwan and the global trend of renewable energy development, Kuroshio energy is a potential energy source. How to extract this invaluable natural resource has then become an intriguing and important question in engineering practices. This study conducted a study for a nozzle-diffuser duct (NDD) as the Kuroshio currents energy harvester. The computational fluid dynamics (CFD) software ANSYS Fluent was employed to calculate the drag and added mass coefficients of the duct anchored to the seabed. Those coefficients were further imported into Orcaflex to simulate the motion of the duct under normal and storm wave conditions. Results showed that the duct was stable 25 m below the sea surface under normal wave condition. When the wave condition changed to storm waves, the duct needed to dive into at least 90 m below the sea surface to regain its stability and obtain high power take-off (PTO). An optimal design nozzle-diffuser-duct was reported and a PTO peak of 15 kW was expectable in the Kuroshio currents. Once a suitable offshore platform can be developed with sixty-six NDDs, a Megawatt Kuroshio ocean current power generation system is feasible in the near future.

The pre-chamber technologies can improve the ignition performance of IC engines by more than two orders in magnitude and thereby substantial economic benefits. Compared with the common pre-chamber, a plug-and-play passive scheme is suitable for quick retrofit, which is getting more attention from the automobile industry. Good scavenging is the precondition for improving turbulent jet ignition performance for a passive pre-chamber. Therefore, detailed evaluations of the scavenging process and turbulent jet ignition deserve investigations for new pre-chamber schemes. In this paper, the effects of design parameters on ignition processes of plug-and-play passive pre-chamber were numerically studied, allowing for the lateral angle, orifice diameter, and vertical angle design. Seven pre-chamber schemes were evaluated, and four optimal ones were selected for bench tests. The characteristics of the scavenging process, turbulent jet ignition, and main-chamber combustion were investigated and analyzed. The results show that allowing for the trade-off between ignition energy and scavenging efficiency, the volume ratio of the pre-chamber to clearance is recommended to be 0.2~0.7%, and the corresponding area-volume ratio is 0.003~0.006 mm-1. Compared with the original natural gas engine, the pre-chamber retrofit can save up to 13.2% fuel consumption, which presents a significant improvement in fuel economy.

A perirectal abscess, while typically considered benign, has the potential to invade extraperitoneal spaces, including the space of Retzius, resulting in complications with severe systemic illness. It is postulated that there is communication within adipose tissue between the pararectal spaces and the vesical extraperitoneal space anteriorly, secondary to the termination of the umbilical-vesical fascia at the reflection of the vesical peritoneum. While occurrences of perirectal abscess ex-tending to the extraperitoneal space are infrequent, a thorough understanding of the anatomical structure, physiology, and the subsequent therapeutic approach remains crucial. For assessment, a computed tomography scan with intravenous contrast is preferred for evaluation, given the probable insidious and nonspecific nature of the clinical presentation, physical exam signs, and even laboratory studies. Primary therapeutic modalities involve immediate resuscitation, intra-venous administration of broad-spectrum antibiotics, and percutaneous drainage. Surgical in-tervention may become necessary in cases where there is no prompt improvement in septic progression. Additionally, the underlying comorbidities and baseline illness could be indicative of unfavorable outcomes. If fever or sepsis is not efficiently controlled, a more comprehensive workup or intervention should be contemplated, considering the associated higher risks of complications and mortality rates. In this study, we presented the case of a 68-year-old male with diffuse pain located in the lower abdomen. Fortunately, an immediate computed tomography scan played a pivotal role in iden-tifying a perirectal abscess with upward extension to the space of Retzius, which was subse-quently treated appropriately. Above all, this rare case presentation underscores the anatomic complexity within pelvic compartments and emphasizes the importance of maintaining high-index suspicions and analyzing overall differential diagnosis.

Spatial crowdsourcing emerges as a new computing paradigm that enables mobile users to accomplish spatio- temporal tasks in order to solve human-intrinsic problems. Existing crowdsourcing systems critically use centralized servers for interacting with workers and making task assignment decisions. These systems are hence susceptible to issues such as the single point of failure and the lack of operational transparency. Prior work, therefore, turns to blockchain-based decentralized crowdsourcing systems, yet still suffers from problems of lacking efficient task assignment scheme, requiring a deposit to an untrusted system, low block generation speed, and high transaction fees. To address these issues, we design a blockchain-based decentralized framework for spatial crowdsourcing, which we call SC-EOS. Our system does not rely on any trusted servers, while providing efficient and user-customizable task assignment, low monetary cost, and fast block generation. More importantly, it frees users from making a deposit into an untrusted system. Our framework can also be extended and applied to generic crowdsourcing systems. We implemented the proposed system on the EOS blockchain. Trace-driven evaluations involving real users show that our system attains the comparable task assignment performance against a clairvoyant scheme. It also achieves 10× cost savings than an Ethereum-based implementation.

The circadian clock regulates daily changes in behavioral, endocrine and metabolic activities in mammals. Circadian rhythms in cellular physiology are significantly affected by aging. In particular, we previously found that aging has profound impact on daily rhythms in mitochondrial functions, leading to increased oxidative stress. However, this is unlikely due to malfunction of molecular clocks in the suprachiasmatic nucleus or peripheral tissues, as robust clock oscillations are observed therein in old animals. Nonetheless, aging induces changes in gene expression levels and rhythms in various peripheral and probably central tissues. In this article, we review findings on the roles of the circadian clock and aging in regulating mitochondrial rhythms and redox homeostasis. Chronic sterile inflammation is implicated in mitochondrial dysfunction and increased oxidative stress during aging. In particular, upregulation of CD38 by inflammatory response can disturb mitochondrial functions in multiple ways.

Disparities between fold amplitude (A) and intrusion thickness (Hsill) are critical in identifying elastic or inelastic deformation in a forced fold. However, accurate measurement of these two parameters is challenging because of the limit in separability and detectability for the seismic data. In the TZ-47 exploring area from the Tarim Basin, Northwest China, we combined wireline data and 3-D seismic data, to accurately constrain the fold amplitude and total thickness of sills that inducing the roof uplift. The measurement results show that the forced fold amplitude is 155 m and the total sill thickness is 148.4 m. When using a magma density of 2.7 g/cm3, and solid rock density of 3 g/cm3, the molten magma thickness at the time of intrusion would be 153.8 m, which is almost no difference from the forced fold amplitude. Therefore, the TZ-47 fold is a pure elastic forced fold induced by emplacement of multiple sills. Measurement solely based on seismic data may not be able to detect some thin interlayers and may result in large errors.

This study examines the effect of a corporate citizenship-oriented high performance work system (CC-oriented HPWS) and the interactive influence of CC-oriented HPWS and person-organization fit (PO fit) on creativity at the individual level. Our analysis of field data collected from 303 employees in two branch companies with a two-phase collection method provides empirical support for our theoretical model. The results indicate that high performance work system (HPWS) reflecting corporate citizenship (CC) correlates positively with individual creativity. In addition, the moderating effect of PO fit is significant in the relationship between CC-oriented HPWS and creativity at the individual level. On this basis, this paper discusses the theoretical and practical implications of these findings for future research.

With the development of remote sensing satellite technology for Earth observation, remote sensing stereo images have been used for three-dimensional reconstruction in various fields, such as urban planning and construction. However, remote sensing images often include noise, occluded regions, weakly textured areas and repeated textures, which can lead to reduced accuracy in stereo matching and affect the quality of the 3D reconstruction results. To reduce the impact of complex scenes in remote sensing images on stereo matching and to ensure both speed and accuracy, we propose a new end-to-end stereo matching network based on convolutional neural networks (CNNs). The proposed stereo matching network can learn features at different scales from the original images and construct cost volumes with varying scales to obtain richer scale information. Additionally, when constructing the cost volume, we introduce negative disparity to adapt to the common occurrence of both negative and nonnegative disparities in remote sensing stereo image pairs. For cost aggregation, we employ a 3D convolution-based encoder-decoder structure that allows the network to adaptively aggregate information. Before feature aggregation, we also introduce an attention module to retain more valuable feature information, enhance feature representation, and obtain a higher-quality disparity map. By training on the publicly available US3D dataset, we obtain the accuracy that 1.115 pixel in end-point error (EPE) and 5.32% in the error pixel ratio (D1) on the test dataset, and the inference speed is 92 ms. Comparing our model with existing state-of-the-art models, we achieve higher accuracy, and the network is beneficial for the three-dimensional reconstruction of remote sensing images.

In this study, three new demountable joints consisting of reinforced concrete columns and steel beams were proposed and their seismic performance was investigated using cyclic loading tests. The test results demonstrated that the three demountable RCS joints had good seismic performance. Using the finite element software ABAQUS, the influence of parameters such as beam flange thickness, bolt strength, and connector steel strength on the seismic performance of each joint was analyzed, and the influence of different parameters on the seismic behavior of the joint was determined. The results also showed that the three demountable RCS joints were sensitive to changes in the thickness of the steel beam flange, while the connector steel strength and bolt type had little impact on the joint's capacity. Additionally, shear capacity calculation formulas for the joint core area provided by different codes and researchers were compared with test and finite element results. The results showed that the calculation results of the ASCE guidance method, the Nishiyama method, and the CECS 347-2013 method were higher than the test values, while the calculation results of the Para method were lower because it did not consider the contribution of the cylindrical steel plate to the shear capacity of the joint core area.

In recent years, with the increasing research and development of the LED industry which contains GaN, it is expected that there will be a large amount of related wastes in the future. Especially the gallium has extremely high value of economic, therefore, it is necessary to establish the recycling system of the GaN waste. However, GaN is a direct-gap semiconductor and with high energy gap, high hardness, and high melting point make it difficult to recycle. Therefore, this study will analyze the physical characteristics of LED wastes containing GaN and carry out various leaching method to leach the valuable metals from the waste optimally. Different acids are used to find out the best reagent for leaching the gallium. Different experimental parameters are discussed such as the effect of the different acid agents , concentration, pressure, solid-liquid mass ratio, temperature, and time which influence the leaching efficiency of the gallium. In this study, various leaching methods which effect the leaching efficiency of the gallium are compared and the advantages and disadvantages are discussed. Finally, pressurized acid leaching method is preferred to leach the GaN waste, and hydrochloric acid is used as the leaching solution because of its better leaching efficiency of gallium. Eventually, the leaching efficiency of the gallium can reach to 98%.

From a structural point of view, understanding interfacial electrostatic features of ligand-receptor complexes is crucial for biophysics-based design of therapeutics with improved efficacy and safety. Here, with a high-throughput structural feature extraction approach, this article reports a set of electrostatic structural features from glucagon-like peptide-1 (GLP-1) and GLP-1 receptor (GLP-1R) complex structures determined using experimental tools. Leveraging a set of computational structural biophysical analyses, this article systematically characterized the electrostatic interactions within the GLP-1-GLP-1R complexes with two sets of criteria to identify interfacial salt bridges and hydrogen bonds. Overall, the results here reveal intricate details of electrostatic interactions critical for GLP-1 binding to its receptor GLP-1R, providing biophysical insights into the stabilization of the GLP-1-GLP-1R complex structure and the molecular basis of GLP-1/GLP-1R signaling. Furthermore, the electrostatic structural features extracted from GLP-1 and GLP-1R complex structures are useful in the development of a machine learning-based ligand-receptor binding affinity calculating model, i.e., a GLP-1-GLP-1R-specific general intermolecular binding affinity calculator (GIBAC), paving the way for accelerated discovery and structure-based design of drug candidates targeting the GLP-1/GLP-1R system with improved efficacy and safety.

Cell autonomous circadian oscillation is present in central and various peripheral tissues. The intrinsic tissue clock and various extrinsic cues drive gene expression rhythms. Transcription regulation is thought to be the main driving force for gene rhythms. However, how transcription rhythms arise remains to be fully characterized, due to the fact that transcription is regulated at multiple steps. In particular, Pol II recruitment and pause release are two critical regulatory steps that determine the status of Pol II pausing. Recently, we showed that Pol II pausing exhibits genomewide changes during daily transcription in mouse liver. In this article, we review historical as well as recent findings on the regulation of transcription rhythms. We also discuss the possible mechanisms for daily changes in Pol II pausing and the critical involvement of Pol II pausing regulation in generating rhythmic transcription output.

The article delves into the intricate phase transitions of 1-Octadecanol and n-Nonadecane within a binary system, unveiling dynamic structural changes under varying conditions. Through Fouri-er-transform infrared (FTIR) analysis, specific molecular vibrations were identified, shedding light on the molecular composition and interactions. The study highlights the challenges in detecting subtle phase transitions and emphasizes the individuality of molecular behaviours in closely related compounds. The findings underscore the complexity of phase transitions in binary systems and advocate for a nuanced approach to studying molecular structures and behaviours. Addi-tionally, the research contributes valuable insights into the molecular dynamics of Organic Polymer Functional Adsorption Materials, offering implications for synthetic waxy layers in plant epidermis.

Oncolytic virotherapy is a promising immunotherapy approach for cancer treatment, utilizing viruses to preferentially infect and eliminate cancer cells while stimulating immune responses. In this review we synthesize current literature on the molecular circuits of immune sensing and response to oncolytic virotherapy; focusing on viral DNA or RNA sensing by infected cells, cytokine and danger-associated signal sensing by neighboring cells, and subsequent downstream activation of immune pathways. The sequential sense-and-response mechanisms involve the triggering of molecular sensors by viruses or infected cells to activate transcription factors and related genes for a breadth of immune responses. We describe how molecular signals induced in the tumor upon virotherapy can trigger diverse immune signaling pathways, activating both antigen-presenting cell-based innate and T cell-based adaptive immune responses. Insights into these complex mechanisms provide valuable knowledge for enhancing oncolytic virotherapy strategies.

In current transportation hubs, it is a common phenomenon that passengers travel with necessary wheeled-luggage or suitcases. Due to the fact that most luggage occupies certain space within dense passenger crowds with giant mass inertia, its abnormal motions, such as drifting, frequently trig unavoidable local disturbances and turbulence in surrounding pedestrian flows, further increasing security risk. While, current researches primarily concentrate on examining the impact of luggage on crowd evacuation efficiency through scenario-based experiments and analyzing the spatial characteristics of crowd distribution in surveillance videos. There still lacks of the dynamic disturbance mechanisms and crowd stability associated with the combined motion of passengers and luggage. Therefore, this study considers the luggage-laden passenger as a deformable particle, the resulting disturbance on surrounding non-luggage passengers is analyzed and quantified into a nonlinear pressure term. Subsequently, the disturbance propagation model of passenger-luggage is developed by adapting the classical Aw-Rascle traffic flow model with incorporation of the pressure term. Simulation experiments of disturbances caused by luggage drifting and retrograding validate that the proposed propagation model aligns with real-world situations in transportation hubs. Quantitively, when luggage-laden passenger drifted left, the disturbing force of left side crowd can reach a peak of 238N in the passenger density of 3.0 p/m2, and the maximum difference between the left and right sides disturbing force can reach 153N. Furthermore, it is recommended that the proposed model can be applied to crowd flow analysis and risk assessment.

The biomimetic design of engineering structures is based on biological structures with excellent mechanical properties, which are the result of billions of years of evolution. However, current biomimetic structures, such as ordered lattice materials, are still inferior to many biological materials in terms of structural complexity and mechanical properties. For example, the structure of \textit{Euplectella aspergillum}, a type of deep-sea glass sponge, is an eye-catching source of inspiration for biomimetic design; however, guided by scientific theory, how to engineer structures surpassing the mechanical properties of \textit{E. aspergillum} remains an unsolved problem. The lattice structure of the skeleton of \textit{E. aspergillum} consists of vertically, horizontally, and diagonally oriented struts, which provide superior strength and flexural resistance compared with the conventional square lattice structure. Herein, the structure of \textit{E. aspergillum} was investigated in detail, and by using the theory of elasticity, a lattice structure inspired by the bionic structure was proposed. The mechanical properties of the sponge-inspired lattice structure surpassed the sponge structure under a variety of loading conditions, and the excellent performance of this configuration was verified experimentally. The proposed lattice structure can greatly improve the mechanical properties of engineering structures, and it improves strength without much redundancy of material. This study achieved the first surpassing of the mechanical properties of an existing sponge-mimicking design. This design can be applied to lattice structures, truss systems, and metamaterial cells.

Emergence of zoonotic-human pathogens is proven to be a lethal threat to public health, and RNA virus including influenza viruses, severe acute respiratory syndrome coronavirus, middle east respiratory syndrome coronavirus, Wuhan coronavirus (COVID-19), plays a pivotal role. As those viruses as airborne microorganisms spread mainly by tiny airborne particles, it is important to de-active those airborne particles before their entry into human bodies. In this study, we investigated the effect of far infrared (FIR) radiation on inhibition of airborne microorganisms. The result confirmed that double stand DNA from airborne microorganisms were stable under mild FIR radiation. However, single strand RNA from them was found to be sensitive to FIR radiation, indicating that RNA virus in airborne particles is instable under FIR radiation. Based on this observation, two models on usage of FIR radiation to prevent RNA virus transmission and cure RNA virus infection were proposed, implying that FIR radiation might be a cheap, convenient, and efficient method in clinic to treat RNA virus.

This study provides an in-depth examination of the binary system of n-Nonadecane and 1-Octadecanol, representative of plant cuticular waxes. It emphasizes the crystallization and phase transitions in this hydrocarbon mixture. Using Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared (FTIR) spectroscopy, the research uncovers detailed thermal properties and phase behaviors. The findings reveal the distinct phase transitions and enthalpy changes of each component in the binary system. This research is significant for its implications in under-standing the structural properties of plant waxes. Such insights are crucial for enhancing the effi-ciency of fertilizer and pesticide absorption in plant leaves, with broad applications in bionics and materials science. This study not only furthers the understanding of identifying specific phase transitions for each compound, facing challenges in detecting subtle changes using DSC. The re-search enhances understanding of plant cuticle waxes through FTIR analysis, revealing intricate molecular interactions and structural complexities. but also opens avenues for improved agri-cultural practices and material engineering, potentially influencing future innovations in these fields.

Five new cembrane-type diterpenes, lobocalines A–E (1–5), and four new steroids, lobocalines F–I (9–12), along with six known related compounds (6–8 and 13–15) were isolated from the Yalong Bay soft coral Lobophytum catalai. The structures of the new compounds were elucidated by extensive spectroscopic analysis, NMR calculation with DP4+ analysis, time-dependent density functional theory-electronic circular dichroism (TDDFT-ECD) calculations, X-ray diffraction analyses, and the comparison with the reported spectroscopic data of known compounds. Further, with the aid of X-ray diffraction analysis, the structure of lobocrasol B (15) was firmly revised as 15a. In in vitro bioassays, compound 2 showed moderate antibacterial activities against fish pathogenic bacteria Streptococcus parauberis KSP28 and Phoyobacterium damselae FP2244 with minimum inhibitory concentration (MIC) values of 8.7 and 17.3 µg/mL, respectively. All the steroids exhibited antibacterial activities against the S. parauberis KSP28 with MIC values ranging from 12.3 to 53.6 µg/mL. Compounds 2, 7 and 14 have remarkable inhibitory effects on the hemolysin production of Staphylococcus aureus, while compounds 8–12 have medium inhibitory effects on the pyocyanin production in Pseudomonas aeruginosa.

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.

A novel simplifying Volterra structure algorithm is proposed for intensity modulation direct detection (IM-DD) optical fiber short distance communication system by using the decision feedback equalization algorithm (DFE). Based on this algorithm, the signal damage for four-level pulse amplitude modulation signal (PAM-4) is compensated, which is caused by device bandwidth limitation and dispersion during transmission. Experiments have been carried out using a 25GHz Electro-absorption Modulated Laser (EML), showing that PAM-4 signals can transmit over 10km in standard single-mode fiber (SSMF). The 112Gbps and 128Gbps signals can reach the error rate threshold of KP4-FEC (BER=2*10-4) and HD-FEC (BER=3.8*10-3), respectively. The simplified principle and process of proposed Volterra-based equalization algorithm are presented. Experimental results show that the algorithm complexity is greatly reduced by 75%, which provides an effective theoretical support for the commercial application of this algorithm.

Sensory descriptive analysis was used to evaluate the aged Feng-flavored baijiu. The results indicated that there are notable differences in the samples of different ages. The samples with shorter storage times and fresh distilled Baijiu present bran flavor, and fresh green flavor. with the increase of storage time, the fragrance of honey, sweetness, flowers, and aging gradually increases. The samples of Feng-flavored baijiu were dected by Headspace solid-phase microextraction (HS-SPME) combined with comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (GC×GC–TOFMS) , in total, 496 sustances were identified in all samples, mainly containing 14 types of substances, such as esters, aldehydes etc., of which 42 substances were found in Feng-flavored baijiu for the first time. Chemometrics was used to analyze the key differential compounds. 143 differential compounds closely related to aging were preliminarily screened, and principal component analysis revealed that these samples were separated by year. 65 differential compounds were selected out by partial least squares discriminant analysis(PLS-DA). Furthermore, 43 key differential compounds were selected from the aged Feng-flavored baijiu combined with variable importance in projection and Pearson correlation coefficients. Partial least squares regression (PLSR) was used to research the correlation of sensory properties and key differential compounds, and the results indicated that most compounds were closely related to the aged Baijiu . This study afford theoretical basis and reference for flavor research of Feng-flavored baijiu.

Given the opportunities offered by foreign investment in energy infrastructure mostly by Chinese firms, the Government of Cambodia is giving high priority to developing hydropower resources for reducing energy poverty and powering economic growth. Using a “Political ecology of the Asian drivers” framework, this paper assesses China’s involvement in the development of large dams’ in Cambodia and its impacts on the access of natural resources such as water and energy by dam builders, local communities and the government. This analysis is based on 61 interviews and 10 focus group discussions with affected communities, institutional actors, Chinese dam builders and financiers in relation to the first large Chinese dam built in Cambodia, the Kamchay dam. Based on the results of the analysis this paper makes recommendations on how to improve the planning, implementation and governance of large dams to ensure that the dams’ benefits are shared more equally.

Background and Objectives: Treatment for antineutrophil cytoplasmic antibody-associated vasculitis (AAV) must deal with immunosuppression as well as infections associated with compromised immune system, such as tuberculosis (TB). Our aim was to overcome the gap in the literature concerning the risk of incidental TB after diagnosis of AAV. Materials and Methods: This retrospective population-based cohort study was based on the data from the National Health Insurance Research Database in Taiwan. We used a novel algorithm to identify patients with newly diagnosed granulomatous polyangiitis (GPA) or microscopic polyangiitis (MPA) between January 1, 2000 and December 31, 2012. The primary outcome was risk of incidental TB. Cox proportional hazard models were used to evaluate the association between AAV and incidental TB. Results: A total of 2,257 patients with AAV and a propensity-score matched cohort of 9,028 patients were studied. Overall, patients with AAV were at a 1.48x higher risk of contracting incidental TB than were patients in the matched cohort (adjusted HR 1.48; 95% confidence interval [CI], 1.02-2.15). Note that the highest risk of contracting incidental TB was in the first two years following a diagnosis of AAV, with a nearly 1-fold increase in risk (adjusted HR, 1.91; 95% CI, 1.01-3.60). Female AAV patients were 3.24x more likely than females without AAV to develop TB (adjusted HR 3.24; 95%CI, 1.85-5.67). Conclusion: Patients with AAV face an elevated risk of contracting incidental TB, particularly within the first two years after AAV diagnosis. The risk of contracting TB is higher among female AAV patients than among females without AAV.

Bionic robotic hand can perform many movements similar to human hand. But there is still a significant gap in manipulation between robot and human hand. It is necessary to understand the finger kinematics and motion patterns of human hand to improve the performance of robotic hand. This study aimed to comprehensively investigate normal hand motion patterns by evaluating the kinematics of hand grip and release in healthy individuals. The data corresponding to rapid grip and release were collected from the dominant hand of 22 healthy people by sensory glove. The kinematics of 14 finger joints were analyzed, including the dynamic range of motion (ROM), peak velocity, joint sequence and finger sequence. The results show that the proximal interphalangeal (PIP) joint had a largest dynamic ROM than metacarpophalangeal (MCP) and distal interphalangeal (DIP) joints. Besides, the PIP joint had the highest peak velocity, both in flexion and extension. For joint sequence, the PIP joint moved prior to the DIP or MCP joints during flexion, while extension started in DIP or MCP joints, followed by PIP joint. Regarding the finger sequence, the thumb started to move before four fingers, and stopped moving after the fingers during both grip and release. This study explored the normal motion patterns in hand grip and release, which provided kinematic reference for the design of robotic hand and thus contribute to its development.

Single-cell green microalga Nannochloropsis oceanica is potentially considered to be the bioresource for biofuel and pharmaceutical production. Urea is a kind of nutrient component for photosyn-thetic N. oceanica. Meanwhile, urea could induce to accumulate some substances such as lipid and affect its growth and physiology. However, how marine microalga N. oceanica respond and adapt to urea addition remains elusive. Here, acclimation of the metabolic reprogramming to changes in the nutrient environment was studied by high-throughput mRNA sequencing in N. oceanica under Ct vs U, there were 2104 genes displayed differential expression (including 1354 upregulation and 750 downregulation, respectively) and some pathways including carbon/nitrogen metabolism, photosynthesis, and lipid metabolism would be reprogrammed in N. oceanica. The results showed that genes related to photosynthesis in N. oceanica were significantly down-regulated, especially those related to light harvesting proteins. Interestingly, urea absorption and transport may de-pend not only on specialized transport mechanisms such as urease, but also on alternative transport channels such as the ABC transporter family, CLC protein family. In addition, urea causes specific changes in carbon and lipid metabolism. Genes associated with the Calvin cycle and carbon concentration mechanisms were significantly upregulated. In lipid metabolism, genes associated with lipases, or polyunsaturated fatty acid enzymes, are highly activated. In addition, expression is enhanced in the tricarboxylic acid cycle and folate metabolism, making important contributions to energy supply and synthesis and modification of genes or macromolecules. These phenomena indicate that N. oceanica actively and dynamically regulates the redistribution of carbon and nitrogen after urea addition., which will provide references for further research on the effects of urea on N. oceanica.

The development of U.S. Army and NATO data link systems is introduced first, and then the development trend of future intelligent data link is summarized into integration, generalization, multifunctionality and high security. A unit-level combat system architecture based on the global combat cloud, which is capable of realizing the flexible scheduling of global combat resources and maximizing the overall combat effectiveness, is proposed. Intelligent data link is an important part of this solution, providing strong information support for future urban unit-level warfare.

Pore structure characterization and fractal analysis have great significance for understanding and evaluating tight limestone reservoirs. In this work, the pore structure of tight limestone is characterized combined with low-temperature nitrogen adsorption (LTNA) and low-field nuclear magnetic resonance (NMR), and the fractal dimension of tight limestone pore structure is discussed based on LTNA and NMR data. The results indicate that the pores of tight limestone have H3 and H4 types, the pore size distribution (PSD) of H3 type is a wave distribution ranging from 2 to 10 nm, and the PSD of H4 type is a unimodal distribution ranging from 2 to 10 nm. The transverse relaxation time (T2) spectrum of tight limestone shows single peak (DF), double peak (SF) and three peak (TF), and the T2 spectrums for micropores, mesopores and macropores range from 0.1 to 10 ms, from 10 to 100 ms, and greater than 100 ms, respectively. The LTNA fractal dimension of tight limestone (DL) ranges between 2.4446 and 2.7688, with an average of 2.5729, and the NMR fractal dimensions of micropores (DNMR1), mesopores (DNMR2) and macropores (DNMR3) are distributed between 0.3744 to 1.1293, 2.4263 to 2.9395 and 2.6582 to 2.9989, respectively. Moreover, there is no correlation between fractal dimension and permeability and porosity, a negative correlation between DL and average pore radius, a positive correlation between DL and specific surface area, and a positive correlation between DNMR2 and DNMR3 and micropore content, while DNMR2 and DNMR3 are negatively correlated with the content of mesopores and macropores.

A new longitudinal flow heat dissipation theory for cylindrical batteries is proposed in order to increase the energy density and uniform temperature performance of cylindrical lithium-ion battery packs while also shrinking their size by roughly 10%. First, a genetic algorithm is used to identify the single cell's thermal properties. Based on this, modeling and simulation are used to examine the thermal properties of the longitudinal flow-cooled battery pack. It is found that the best coolant flow scheme has one inlet and one outlet from the end face, taking into account the cooling effect of the battery pack and engineering viability. Lastly, Thermal Dummy Cells (TDC) is used to conduct a validation test of the liquid cooling strategy. Additionally, the simulation and test results demonstrated that the liquid cooling solution can keep the battery pack's maximum temperature rise under the static conditions of a continuous, high-current discharge at a rate of 3C to 20 °C and under the dynamic conditions of the New European Driving Cycle (NEDC) to 2 °C. In applications where the space requirements for the battery pack are quite severe, the longitudinal flow cooling method has some advantages.

Green credit policy as an important tool to guide China's sustainable economic development, how to effectively play the function of capital deployment and improve the efficiency of industrial green innovation is an important issue facing the construction of ecological civilization. This paper uses China's Green Credit Guideline introduced in 2012 as a quasi-natural experiment , based on relevant panel data of industries from 2007 to 2018, uses the Super-SBM model including non-expected output to measure the green innovation efficiency of 35 industries in China, and constructs the PSM-DID model to explore how green credit policy impact on the green innovation efficiency of heavily polluted industries, the results show that : green credit policy significantly contributes to green innovation efficiency of heavily polluted industries with a lag. Further study finds that green credit policy pushes heavily polluted industries to improve green innovation efficiency by increasing financing cost and R&D investment; meanwhile, the heterogeneity test shows that the higher the state-owned share of industry, the greater the promoted effect of green credit policy on green innovation efficiency of heavily polluted industries. Finally, in order to accelerate the implementation of green credit policy and promote the green innovation efficiency of heavily polluted industries, relevant countermeasures are proposed from three aspects: banks, enterprises and government.

Three new cembranoids (1–3) and a new casbanoid (4), along with three known analogues (5–7), have been isolated from the soft coral Sinularia nanolobata collected off Ximao Island. The structures including the absolute configurations of new compounds were established by extensive spectro-scopic data analysis, time-dependent density functional theory/electronic circular dichroism (TDDFT-ECD) calculations and the comparison with spectroscopic data of known compounds. In in vitro bioassay, compounds 1 and 5 exhibited moderate cytotoxic activities against human erythroleukemia (HEL) cells line with IC50 values of 37.1 and 42.4 uM, respectively.

Blood glucose (BG) monitoring is an important issue for critically ill patients. Previous studies reported that poor sugar control was associated with increased mortality in admitted patients. However, repeated blood glucose monitoring can be resource-consuming and cause a healthcare burden in clinical practice. In this study, we aimed to develop a personalized machine-learning model to predict dysglycemia based on electrocardiogram (ECG) findings. The study included patients with more than 20 ECG records during single hospital admission in the Medical Information Mart for Intensive Care III database, focusing on the lead II recordings, along with the corresponding blood sugar data. We processed the data and used ECG features from each heartbeat as inputs to develop a one-class support vector machine (SVM) algorithm to predict dysglycemia. The model prediction for dysglycemia using a single heartbeat had an AUC level of 0.92 ± 0.09, with a sensitivity of 0.92 ± 0.10 and specificity of 0.84 ± 0.04. Based on 10 s majority voting, the model prediction for dysglycemia improved to an AUC of 0.97 ± 0.06. In this study, we found that a personalized machine-learning algorithm could accurately detect dysglycemia using a single-lead ECG.

Directed energy deposition (DED) parameters were determined for near-β alloy Ti-55511 by employing statistical design of experiments (DOE) methods. Parameters resulting in fully dense freeform deposits were identified using two sequential DOEs. Single laser tracks were printed with several laser power, traverse rate, and powder feed rate settings in an initial DOE to identify promising build parameters. Capture efficiency and effective deposition rate were used to characterize and rank the single track deposits. The best parameters were then used to print solid cube with various X-Y and Z-overlaps (different hatch spacing, HS, and layer thickness, ZS) in a second DOE. Suitable deposition parameters were selected based on cube density and microstructure and were used to fabricate larger tensile samples for mechanical testing. Multiple parameter sets were found to provide dense Ti-55511 deposits with acceptable mechanical properties and parametric models showed statistical significance.

Acting as the most abundant and widely distributed volatile secondary metabolites in plants, terpenoids play crucial roles in diverse physiological regulations and metabolic processes. Terpene synthases occupy a decisive proportion in determining the composition and diversity of terpenoids; though their regulatory effects have been extensively investigated across various plant species, limited studies have focused on the upstream transcriptional regulation of terpene synthases. In this study, we unveil linalool as the predominant volatile compound in Freesia hybrida flowers, demonstrating a gradual release pattern during flower blooming. In the context of the transcriptome, a typical MYB transcription factor, FhMYB108, was screened based on digital expression profile correlation analysis and homologous gene comparison. FhMYB108 is capable of regulating the expression of terpene synthase FhTPS1, and both their expression levels exhibit a gradual increase concomitant with flower opening. Moreover, transcriptional regulation and transient expression assays revealed that FhMYB108 exerts a stimulatory effect on the transcription of A. thaliana AtTPS14, while no significant increase in AtTPS14 expression was observed upon stabilization of FhMYB108 in Arabidopsis. Investigate its reason, the highly expressed AtMYC2 in A. thaliana can interact with FhMYB108 to suppress the activation of AtTPS14 by FhMYB108. The present study not only elucidated the regulatory mechanism underlying linalool synthesis, but also discovered the synergistic effect of MYB and bHLH transcription factors in governing the biosynthesis of volatile terpenoids.

Xinjiang, as a climate-sensitive region in northwest China, holds significant importance in studying extreme weather events for agricultural production and socioeconomic development. Based on data from 52 meteorological stations and 23 extreme climate indicators in Xinjiang from 1960 to 2021, the 5a moving average, linear trend estimation, climate tendency rate, and GIS spatial analysis methods are used to analyze the distribution and change characteristics of extreme climate. The results revealed that from 1960 to 2021, TXx, TNx, TXn, TNn, FD, ID, TN10p, TX10p, and WSDI showed a significant upward trend, while SU, TR, TN90p, TX90p, and CSDI showed a significant downward trend. What is more, the range of changes in the extreme temperature indexes from 1990 to 2021 is higher than that of 1960 to 1989. The high-value areas of extreme indexes are primarily concentrated in the northern part, while the high-value areas of cold event indexes are mainly distributed in the southern part. The upward/downward trends all accounting for over 80.00% of the entire region. The Rx1day, Rx5day, PRCPTOT, R95p, R99p, R10, R20, and R25 showed a significant growth trend from 1960 to 2021, and the range of change in the extreme precipitation indexes from 1990 to 2021 was lower than that from 1960 to 1989. Moreover, their high-value areas and high climate tendency areas are mainly concentrated in the northern and western parts of Xinjiang, with upward trends all accounting for over 71.00% of the entire region. The research results provide theoretical foundations for formulating climate risk strategies in the northwest region of China.

Managing epidemics need to unite each individual of the nations. Lockdown is an essential strategy to fatal and threatening epidemic. All of the citizens should realize that each of people has a responsibility to support the public health crisis. How to organize individual to fight against the epidemic plaque depends each of them. This essay discussed the COVID-19 pandemic relevant self-governance of community from a historical perspective in China. Self-governance of neighborhood committee and community residential office in urban and rural helped to control the COVID-19 pandemic in the communities in China. Co-operation and collective responsibility of citizens and community support is a critical condition to prevent epidemic. The community self-governance can track back Qin Dynasty in China history. It established baojia system to maintain social control for thousand years. Now, the community-based system, baojia system is becoming more autonomous for local citizenship and socialized governance in China. We reviewed a historical pneumonia plaque in North China in 1911. Chinese doctor, Wu Lien-teh (伍連德) confronted the epidemic crisis with many measures such as lockdown, quarantine, the wearing of mask, setup mobile hospitals, travel restriction, the cremation of victims, and border control. Dr. Wu made effort to establish the modern public health service in China. We think that the combination of culture background of China community with modern public healthcare system determinedly played important role to control the COVID-19 pandemic.

Understanding the thermal cracks of rock caused by high temperature is of great help to the development of underground engineering, such as geothermal mining, underground coal gasification. Although there has been many study on thermal cracking, it is not systematic and in-depth enough. In order to deeply study the thermal crack mechanism of rock, this paper conducted thermal cracking experiments on granite at different temperatures and heating/cooling paths, and qualitative and quantitative analysis was conducted on the crack initiation characteristics, propagation paths, and crack network morphology of rock thermal crack under different test conditions. The thermal crack mechanism was also analyzed from the perspectives of mineral petrology, fracture mechanics, thermodynamics, and other aspects. The research results show that there are two obvious mutation points in the study temperature range for samples with fast cooling paths (SF path: slow heating and fast cooling; FF path: fast heating and fast cooling), around 200-300 ℃ and 600 ℃, respectively, while for samples with slow cooling paths (SS path: slow heating and slow cooling; FS path: fast heating and slow cooling), there is only one mutation point around 600 ℃. The initiation positions of thermal cracking under all temperature paths are relatively similar, with intergranular crack located between particles at the edge of the sample or intercrystalline crack in the middle of feldspar or quartz aggregates. The initiation temperature of SF and FF path specimens is relatively low compared to SS and FS path specimens, and the number and size of cracks is small. The crack network structure formed by the SF path is the most complex, with the largest crack ratio and cumulative crack length; The crack network structure formed by the FF path is relatively complex, with a larger main crack size but relatively fewer secondary cracks; The FS and SS paths do not form a complex network with good connectivity. The process of thermal crack development can be divided into three stages: the development of small cracks, the joint development of main cracks and small cracks, and the connection of cracks into a network structure. The mechanism of thermal crack propagation is that the expansion and thermal conductivity between different crystals are different. The thermal stress caused by temperature gradient and the tension or shear stress caused by the inconsistent deformation of crystals form stress concentration in weak areas such as particles boundary, cleavage, and original cracks. Firstly, it causes some crystals with smaller strength or less rounded shape to crack, and when the combined stress is large, the cracks will gradually expand along the existing fine cracks. This also explains that the most main cracks of the SF and FF path specimens mainly surround some large mineral aggregates or between particles.

Co-free Li-rich oxide is a promising cathode for low cost high energy density Li-ion battery but presents poor cyclic stability. To address this issue, CeO2 is coated on Co-free Li-rich oxide through a low-temperature aged process, resulting in a novel CeO2-coated Li-rich oxide compo-site. Due to the low-temperature aged process, a uniform CeO2 coating layer of 6 nm in thickness is successfully coated on Co-free Li-rich oxide. With this uniform coating, the resulting CeO2-coated Li-rich oxide composite presents improved cyclic stability as well as rate capability as the cathode of Li-ion battery. The capacity retention of the resulting CeO2-coated Li-rich oxide is enhanced from 67% to 85% after 100 cycles and its capacity retention of 5C/0.05C is enhanced from 10% to 23%, compared with the uncoated sample. Such significant improvements enable this low-temperature aged process to be helpful for the practical application of Li-rich oxide materials, not limited to Co-free Li-rich oxide.

We investigated new anodic coloring materials that are used as ion storage layers in complementary energy storage electrochromic devices (ESECDs) to enhance their electrochromic storage performance. In this study, we fabricated counter electrodes (ion storage layers) using IrO2 doping NiO (Ir: NiO) film through cathodic arc plasma (CAP) with varying surface charge capacities. We investigated the influence of MoO3-doped WO3 (Mo: WO3) film by various Ar/O2 gas flow ratios (1/4, 1/5, and 1/6). The ESECDs used in the demonstration were 10×10 cm2 in size. They achieved optical transmittance modulation of Ir: NiO- ESECDs (glass/ITO/ Mo: WO3/gel-polymer electrolytes/ Ir: NiO /ITO/glass), ΔT=53.3% (from Tbleaching (66.6%) to Tcoloration (13.1%)). The ESECDs had a quick coloration time of 3.58 seconds, a rapid bleaching time of 1.24 seconds, and high cycling durability. It remained at 45% transmittance modulation even after 3000 cycles. New anodic materials can provide an alternative to traditional active materials for bi-functional electrochromic batteries.

Existing research concerning the effects of the sitting birth position during the second stage of labour on maternal and neonatal outcomes remains controversial, and there is a lack of studies to explore its effect on the childbirth experience. The objective of this study is to explore whether the sitting birth position would influence maternal and neonatal outcomes, as well as the childbirth experience reported by Chinese women using the Childbirth Experience Questionnaire (CEQ). A total of 296 women (including primiparous women and multiparous women) were enrolled in our study, and they were divided into the sitting position cohort (n=106) or the lithotomy position cohort(n=116). The study found that primiparous women in the sitting position cohort had a shorter duration of the second stage of labour, higher spontaneous vaginal birth rates, lower episiotomy rates and better childbirth experience (p<0.01). There was no significant difference for perineal lacerations, 2h-postpartum haemorrhage (P>0.05) between the two cohorts of primiparous women. After adjusting for confounding factors through multiple linear and logistic regression analyses, the results remained consistent with those reported above. No neonate in each cohort had Apgar scores at 1min and 5 min postpartum less than 7 or the Cord artery pH less than 7.00, regardless of parity. In addition, among multiparous women, there was no significant difference in any maternal and neonatal outcomes and women’s CEQ scores (p>0.05) between two cohorts. Based on the findings, we recommend that women could take the sitting birth position into account when giving birth for a positive childbirth experience, especially for primiparous women. The study could also serve as a reference for healthcare providers in the management of childbirth positions and the development of high-quality maternal care.

Virus-infected Flu is a common disease. To date, no specific drugs are available to manage the symptoms of cough, headache and sputum production. An alternative Chinese herb medicine is introduced for virus-infected Flu or similar infection. Before hospitalization, some of patients may scare for cross-infection with mild symptoms or hardly go to hospital if encountered a temporary lockdown or quarantine. Some Chinese practice self-treatment of cough, headache and sputum production by inhalation of volatile chemicals from onion and garlic. Author used to take the same alternative approach of inhalation of onion, garlic or scallions for self-treatment when suffered virus caused flu with cough, headache and sputum production at onset disease. In this article, the biomedical effects of onion and garlic are reviewed. To help patients with mild symptoms of virus infected Flu, a simple home-based treatment was suggested to self-treatment because of temporary isolation and hardly going to hospitalization. The alternative approach may also suggest for some mild virus infected respiratory diseases caused by virus at onset disease.

In this paper, we shall introduce the interval-valued spatial error model. Based on the idea of least square method of single-valued case, we give the parameter estimator for interval-valued spatial error model. The theoretical properties of the proposed estimator are proved. Finally, we give the numerical analysis and a real example.

Nature-based solutions (NbS) rapidly develop globally to address societal challenges and provide human well-being and biodiversity. Watershed restoration plays an essential role in enhancing the ecological and socio-economic benefits of the region. The design and implementation of watershed restoration projects play a crucial role in their effectiveness, and NbS has been applied as a concept in ecosystem-related projects. This paper provides an idea to evaluate the design or implementation of watershed restoration projects based on the eight criteria proposed by the IUCN Global Standard for Nature-Based Solutions and to adjust the projects based on the evaluation results. The aim is to standardize the implementation process of watershed restoration projects to achieve more significant benefits and practically apply the concept of NbS in watershed restoration. implementation scheme of the Shan-Shui Initiative in the Jiulong River Watershed and concludes that the method is feasible in evaluating and improving the design and implementation scheme of ecological restoration projects in the actual basin. According to the assessment results, the degree of matching based on NbS for the implementation scheme of the Jiulong River Watershed Shan-Shui Initiative is 73%, which meets the criteria of NbS but needs to be improved in terms of monitoring and assessment, synergistic management, and benefit trade-offs.

Directed energy deposition (DED) is an efficient method to fabricate functionally graded materials (FGMs) with gradient composition and complex structures, allowing for local tailoring of properties instead of the costly need for extraneous welds and joints. In this study, a FGM from stainless steel to Inconel alloy was successfully fabricated using the powder-based laser DED. A very refined grain structure has been observed in at the composition with 75 wt.% Inconel alloy content, which also exhibits the highest (entropy). For the first time, the post heat treatments, microstructure and aging precipitation behaviors of FGMs were systematically studied via experimental characterization and computation, to elucidate their effects on the gradient smoothing and mechanical properties. The diffusion and segregation of Ni, Nb and Ti elements underly the transformation mechanism between Laves, δ, γ’ and γ’’ phases during precipitation. Homogenization on FGMs not only eliminates the heterogeneity inherited from the AM process, but also provides a practical way to smoothen the gradient on composition and microstructure for the eventual good gradient properties. It has a direct influence on the following precipitation behaviors in the FGM, which highly relies on the diffusion degree of the elements in the matrix and grain boundaries. The high-throughput thermodynamic modeling and kinetic modeling were exploited to evaluate the experimental microstructure and address computational uncertainty using different thermodynamic conditions and databases, which enables an accelerated design through local tailoring of process-structure-property relationships to develop new functional materials.

In-situ nanoindentation experiment has been widely adopted to characterize material behaviors of microelectronic devices. This work introduces the latest developments of nanoindentation experiment in characterizing nonlinear material properties of 3D integrated microelectronic devices with through-silicon-vias (TSVs). The elastic, plastic, and interfacial fracture behavior of the copper via and matrix-via interface have been characterized using small scale specimens prepared with focused-ion-beam (FIB) and nanoindentation experiment. A brittle interfacial fracture was found at the Cu/Si interface under mixed-mode loading with a phase angle ranging from 16.7 to 83.7 degrees. The mixed-mode fracture strengths were extracted using the linear elastic fracture mechanics (LEFM) analysis and a fracture criterion was obtained by fitting the extracted data with the power-law function. The vectorial interfacial strength and toughness were found to be independent with mode-mix.

Aiming at effectively generating safe and reliable motion paths for quadruped robots, a hierar-chical path planning approach driven by dynamic 3D point cloud is proposed in this article. The developed path planning model is essentially constituted of two layers: global path planning layer and local path planning layer. At the global path planning layer, a new method is proposed for calculating terrain potential field based on point cloud height segmentation. Variable step size is employed to improve the path smoothness. At the local path planning layer, a real-time prediction method for potential collision area and a strategy for temporary target point selection is developed. Quadruped robot experiments were carried out in an outdoor complex environment. The experi-mental results verified that, for global path planning, the smoothness of the path is improved and the complexity of the passing ground is reduced. The effective step size is increased by a maxi-mum of 13.4 times, and the number of iterations is decreased by up to 1/6, compared with the traditional fixed step size planning algorithm. For local path planning, the path length is short-ened by 20%, more efficient dynamic obstacle avoidance and more stable velocity planning are achieved by using the improved dynamic window approach (DWA).

Chloroquine was among the first of several effective drug treatments against malaria until the onset of chloroquine resistance. In light of diminished clinical efficacy of chloroquine as an antimalarial therapeutic, there is potential in efforts to adapt chloroquine for other clinical applications, such as in combination therapies and in diagnostics. In this context, we designed and synthesized a novel asymmetrical squaraine dye coupled with chloroquine (SQR1-CQ). In this study, SQR1-CQ was used to label live Plasmodium falciparum (P. falciparum) parasite cultures of varying sensitivities towards chloroquine. SQR1-CQ positively stained ring, mature trophozoite and schizont stages of both chloroquine–sensitive and chloroquine–resistant P. falciparum strains. In addition, SQR1-CQ exhibited significantly higher fluorescence, when compared to a chloroquine-BODIPY (borondipyrromethene) conjugate. We also achieved successful SQR1-CQ labelling of P. falciparum directly on thin blood smear preparations. Drug efficacy experiments measuring half-maximal inhibitory concentration (IC50) showed lower concentration of effective inhibition against resistant strain K1 by SQR1-CQ compared to conventional chloroquine. Taken together, the versatile and highly fluorescent labelling capability of SQR1-CQ and promising preliminary IC50 findings potentiates it to be further developed as a promising diagnostic bioimaging tool with drug efficacy against chloroquine-resistant P. falciparum.

Archaea are an essential class of gut microorganisms in humans and animals. Despite the substantial progress in gut microbiome research in the last decade, most studies have focused on bacteria, and little is known about archaea in mammals. In this study, we investigated the composition, diversity, and functional potential of gut archaeal communities in pigs by re-analyzing a published metagenomic dataset including a total of 276 fecal samples from three countries: China (n=76), Denmark (n=100), and France (n=100). For alpha diversity (Shannon Index) of the archaeal communities, Chinese pigs were less diverse than Danish and French pigs (P<0.001). Consistently, Chinese pigs also possessed different archaeal community structures from the other two groups based on the Bray-Curtis distance matrix. Methanobrevibacter was the most dominant archaeal genus in Chinese pigs (44.94%) and French pigs (15.41%), while Candidatus Methanomethylophilus was the most predominant in Danish pigs (15.71%). At the species level, the relative abundance of Candidatus Methanomethylophilus alvus, Natrialbaceae archaeon XQ INN 246, and Methanobrevibacter gottschalkii were greatest in Danish, French, and Chinese pigs with a relative abundance of 14.32%, 11.67%, and 16.28%, respectively. In terms of metabolic potential, the top three pathways in the archaeal communities included the MetaCyc pathway related to the biosynthesis of L-valine, L-isoleucine, and isobutanol. Interestingly, the pathway related to hydrogen consumption (METHANOGENESIS-PWY) was only observed in archaeal reads, while the pathways participating in hydrogen production (FERMENTATION-PWY and PWY4LZ-257) were only detected in bacterial reads. Archaeal communities also possessed CAZyme gene families, with the top five being: AA3, GH43, GT2, AA6, and CE9. In terms of antibiotic resistance genes (ARGs), the class of multidrug resistance was the most abundant ARG, accounting for 87.41% of archaeal ARG hits. Our study reveals the diverse composition and metabolic functions of archaea in pigs, suggesting that archaea might play important roles in swine nutrition and metabolism.

The complete genomic sequence of a Cassava common mosaic virus Linggao isolate (CsCMV-LG) was determined from cassava (Manihot esculenta Crantz) with mild leafy mosaic symptom to no symptom in China. Excluding the poly(A) tail, the CsCMV-LG genome (GenBank accession No. MT038420) is 6374 nucleotides (nts) in length, with five major open reading frames encoding a 1450-amino acids (aa) RNA-dependent RNA polymerase (RdRp), three triple gene block (TGB) proteins (231-aa, 110-aa and 95-aa), and a 229-aa coat protein (CP). Phylogenetic analysis indicated that the complete genome of the CsCMV-LG is closely related to that of CsCMV-Brazilian which has been assigned to the genus Potexvirus, but the sequence identity shared only 88.0%. Notable, the mild CsCMV-LG isolate can also infect Nicotiana benthamiana in laboratory through rub inoculation causing mild vein yellowing at 15-day post inoculation. This is the first full-length genome sequence of a distinct isolate of Cassava common mosaic virus (CsCMV) infecting cassava in Hainan, China.

The Mine Internet of Things (MIoT), as a key technology for reconstructing post-disaster communication networks, enables to realize the safety monitoring and controlling of the affected roadway. However, due to the challenging underground mine environment, the MIoT suffers from severe signal attenuation, vulnerable nodes, and limited energy, which result in low network reliability of the post-disaster MIoT. To improve the transmission reliability as well as to reduce energy consumption, a directional-area-forwarding-based energy-efficient opportunistic routing (DEOR) for the post-disaster MIoT is proposed. DEOR defines a forwarding zone (FZ) for each node to route packets toward the sink. The candidate forwarding set (CFS) is constructed by the nodes within the FZ that satisfy the energy constraint and the neighboring node degree constraint. The nodes in CFS are prioritized based on the routing quality evaluation by taking the local attributes of nodes into consideration, such as the directional angle, transmission distance, and residual energy. DEOR adopts a recovery mechanism to address the issue of void nodes. The simulation results validate that the proposed DEOR outperforms ORR, OBRN and ECSOR in terms of energy consumption, average hop count, packet delivery rate, and network lifetime.

In the world city theory, most researchers focus on the service sector in the urban economy and less discuss the role of manufacturing. However, the path of only emphasizing financial and corporate service could not fit the sustainability concept. Compared to Anglo-American world city, Global South’s world cities have distinct pathway to be industrialization, tertiarization and globalization. This paper adopted dynamic historic perspective with first-hand materials including in-depth interviews with managers and government officers and second-hand data including yearbook statics and economic census to closely examine the emerging world city-- ‘World Factory’ in Global South, Guangzhou in China, from 1949 to 2015, to emphasize how manufacturing affects the urban globalization through three dimensions, economic, social and spatial dimensions. To make the confirmation of the role of manufacturing in Guangzhou as sustainable world city, we find manufacturing in Guangzhou builds up the basic foundation of export-oriented economy and makes positive effects on urban economic transformation. In addition, manufacturing remains important source of employment and foreign immigration. Along with urbanization and industrialization, urban spatial expansion and aggregation changes with different urban development concept. We provide new insights on multiple globalization on manufacturing for sustainable world city.

Neuronal lesion or injury is a traditional approach to investigate neural circuit. Is any new neural pathway or new neurodegeneration related central nerve system injury? Spinal disc herniation can cause the spinal cord injury. However, the histological examination is still lack. It happened that a case of spinal disc herniation of a 10-year old dog was examined with NADPH diaphorase (N-d) histology. We did not find the N-d neurodegenerative aberrant in the tissue of the mid-rostral lumber segment besides the metamorphoses by the compression of the disc herniation. However, the severe neuropathological changes majorly occurred in the lumbosacral spinal cord. We found more diverse neurodegenerative alterations: the aging-related N-d body (ANB), megaloneurite and N-d homogeneous formazan globule in the lumbosacral spinal cord. We also found that a new circuit pathway (intermedial collateral pathway) showed by a megaloneurite between the lateral collateral pathway and the medial collateral pathway. The enormous notch caused by spinal disc herniation located at the mid-rostral lumber segments. The aging-related neurodegeneration occurred the specific lumbosacral segments. The homogeneous formazan globule was round or oval homogeneous N-d positivity which distributed in the gray matter and dorsal column. In the medulla oblongata, ANBs were revealed in the gracile nucleus, nucleus reticularis lateralis (ventrolateral spinal trigeminal nucleus) and middle of the spinal trigeminal nucleus.

The cassava whitefly, Bemisia tabaci, causes direct damage to cassava in the tropics by feeding on the phloem of leaves, inducing leaf chlorosis and abscission which can result in considerable yield loss of up to about 50% on susceptible varieties. The pest is also known to impart its indirect damage through sooty mold formation. Most of the improved cassava varieties in Uganda were developed for CMD resistance and CBSD tolerance and little is known about their reaction to whitefly infestation. A study was conducted to evaluate the reaction of 24 improved cassava varieties which were sourced from 5 different countries in the region (Uganda, Kenya, Tanzania, Malawi, and Mozambique) to whitefly infestation. These varieties were evaluated in three agro-ecological zones of Uganda, namely; North-Western Savannah Grassland, Lake Victoria Crescent and the Kyoga Plains in the second rains of 2016. Monthly data were taken on adult and nymph counts, whitefly and sooty mold damage, CMD and CBSD severities from 2 up-to 9 Months after planting (MAP). Results show that the whitefly population was highly significantly (P