Abstract Chaga´s disease caused by Trypanosoma cruzi infections is included in the group of neglected diseases, and efforts to develop new therapeutic or immunoprevention approaches have not been successful. After the publication of the T. cruzi genome, the number of molecular and biochemical studies on this parasite have increased considerably, many of which are focused on families of variant-surface-proteins, especially the trans-sialidases, mucins and mucin-associated proteins. The disperse gene protein 1 family (DGF-1) is one of the most abundant families in the T. cruzi genome, however, the large gene size, high copy numbers, and low antibody titers detected in infected humans make it an unattractive study target. Here, we argue that the DGF-1 gene family although not being the most obvious participant of the host-parasite immunological gamble, where T. cruzi appears to have the upper hand, it may play an important role in more basic host-parasite interactions that deserve further examination.

Keywords: pelvic ultrasound, follicle number per ovary, FNPO, ovarian volume, PCOM, upper normal limits, referral population

This study provides a comprehensive analysis of the conformational dynamics of pseudo-endocannabinoid receptors (p-CBRs) CB₁ and CB₂ in response to ligand binding. The ligands studied include N-arachidonoyl dopamine (NADA), Cannabidiol (CBD), known agonists (FUB-MDMB and E3R), and inverse agonists (Taranabant and AM630). Using homology models based on crystal structures (PDB ID: 5U09 for CB₁ and 5ZTY for CB₂), molecular docking, and molecular dynamics (MD) simulations, the research validates the structural integrity and dynamic behaviours of these pseudo-receptors. Induced-fit docking revealed NADA as having the highest binding affinity for both receptors, with docking scores of −13.92 kcal/mol for CB₁ and −13.32 kcal/mol for CB₂, facilitated by key hydrogen bond interactions. MD simulations over 250 ns at ~298 K showed successful equilibration, indicating the most stable interaction for NADA, thereby further validating the models. CB₁ and CB₂ exhibited distinct conformational responses to ligands, with Cα RMSD and Cα RMSF analyses suggesting a more rigid binding pocket for CB₁ and a flexible binding pocket for CB₂. These findings highlight the significance of receptor behaviour and dynamics in the development of cannabinoid-based therapeutics, supporting the potential of CBD and NADA as modulators for CB₁ and CB₂, respectively.

In this paper, spacetime is defined as the absolutely invariant homogeneous "coordinate spacetime" frame and its modulation by the relatively variable non-homogeneous "metric spacetime" under its constraints. This modulation is caused by matter and motion, and carries the function of transmitting interactions, reflecting the diffeomorphism invariance and Lorentz invariance. This inhomogeneous spacetime concept makes the medium nature of spacetime more obvious and avoids the problem of "path dependence" caused by the concept of curved spacetime. In this paper, it is argued that all energy-momentum has internal spatio-temporal properties, and all interactions must be transmitted through spacetime metrics. On this basis, a converging and dispersing cyclic multiverse model is proposed. This model of the universe is inevitable as long as there are two macroscopic manifestations of the matter of the universe, namely, gravitation induced convergence and "explosive" dispersion caused by different factors. The new cosmic model matches the observed accelerated "expansion" of the universe and no longer requires the dark energy hypothesis.

Anxiety in older adults is a prevalent yet under-recognized condition associated with significant societal and individual burdens. This study used a machine learning approach to compare the relative importance of 57 risk and protective factors for anxiety symptoms in a population-representative sample of middle-aged and older European adults (N = 65,684; ages 45–103 years; 55.7% women; 15 countries represented). Results revealed loneliness and self-rated poor health as primary risk factors (Nagelkerke R2 = .272), with additional predictive contributions from country of residence, functional limitations, financial distress, and family care burden. Notably, follow-up analysis showed that none of 16 social network variables were associated with loneliness; rather, cohabitating with a partner/spouse was most strongly associated with reduced loneliness. Further research is needed to elucidate directional associations between loneliness and anxiety (both general and sub-types). These findings underscore the imperative of addressing loneliness for mitigating anxiety and related mental health conditions among aging populations.

In recent years there has been an increasing interest in developing novel materials based on natural biopolymers as a renewable alternative of petroleum-based plastics. The availability of proteins derived from agricultural by-products, along with their favourable properties, has fostered a renewed interest in protein-based materials, promoting research in innovative technologies. In this study we propose the use of rapeseed protein-rich meal as main ingredient for the preparation of novel sustainable materials combining excellent environmental properties such as biodegradability and renewable origin. Application as sustainable products in the present high-tech society needs modification of basic native properties of these natural compounds. The original route proposed in this paper consists in the preparation via compression moulding of flexible biomaterials stabilized by crosslinkers/chain extenders. Investigation of the effects of different denaturing and disulfide bond reducing agents, crosslinkers, and preparation conditions on the material mechanical behaviour demonstrated that the novel materials have appreciable strength and stiffness. The results show the potential of utilizing full meal from vegetable by-products to prepare protein-based materials with granted ecofriendly characteristics and mechanical properties adequate to specific structural applications.

CCNs are specific type of matricellular proteins, which are essential signaling molecules, and play multiple roles in multicellular eukaryotes. This family of proteins consists of six separate members in mammals. The architecture of CCN proteins is multimodular and comprises four distinct motifs. CCN proteins achieve their specific physiological functions by binding to integrin receptors. The CCN family has been implicated in both cure and disease with impacts on biological interactions, such as cell adhesion, chemotaxis and migration, mitogenesis, cell survival, angiogenesis, differentiation, tumorigenesis, immune functions, chondrogenesis, and wound healing. Breast cancer is the most commonly diagnosed cancer worldwide and the leading cause of cancer mortality among women triggered by atypical expression of CCNs. A favorable or unfavorable association between various CCNs has been reported in patients with breast carcinomas. Aberrant expression of CCN1 intensifies the proliferation of epithelial cells that line the lobes and ducts of the breast. Evidence also shows that the expression of CCN2 can ameliorate tumor growth and metastasis. However, CCN3 (NOV), CCN5 (WISP-2), and CCN6 (WISP-3) are consistent with neoplastic development and metastasis repression. Particular CCN members can develop tumors and cancer progression, whereas others can competitively counter the processes. Several studies have been conducted on CCN proteins and cancer in recent years. In our study, we intend to provide an overview of those research works while keeping breast carcinoma on focus. We believe that the importance of the CCN protein family in breast cancer should be reconsidered.

Rett syndrome (RTT) is an X-linked neurodevelopment disorder associated with the single monogenic mutation in methyl-CpG binding protein 2 (MeCP2) in up to 95% of cases. The growing number of genome-wide association studies and incomplete concordance for autoimmune diseases in monozygotic twins concur to support the involvement of environmental factors, like infectious agents or chemicals, in the breakdown of tolerance leading to autoimmunity. In fact, the coexistence of a perturbation of the immune system in RTT patients has been previously hypothesized. We herein explored the hypothesis that an autoimmune component derived from environmental bacterial infection of non typeable Haemophilus influenzae may coexist in RTT. At this purpose we screened sera from RTT syndrome patients, non-RTT pervasive developmental disorders patients and healthy controls with the hyperglucosylated adhesin protein HMW1ct(Glc) used as a precise antigen in ELISA in order to identify specific antibodies to N-glucosylation sites. Results showed that HMW1ct(Glc) is able to significantly discriminate antibodies among RTT sera and controls. Competitive ELISA confirmed the specific interaction between antibodies characteristic of RTT syndrome and the N-glucosylation motifs of the bacterial adhesin protein HMW1ct(Glc).

Beliefs that maintain patriarchal principles may affect individuals’ willingness to avoid conflicts in their intimate partner relationships and eventually are likely to affect chances of intimate partner economic violence. Nonetheless, research has yet to fully explore these associations. This study used a sample of 321 adults in the ultra-Orthodox Jewish community—a patriarchal and traditional culture—to examine associations in beliefs supporting patriarchal principles at the micro (gendered domestic roles), meso, and macro ( institutional power of men and inherent inferiority of women) levels; conflict avoidance and economic violence; and sex differences in these factors. Descriptive statistics were used to explore gender differences in research variables, and path analysis examined the correlations between research variables for men and women. Beliefs in patriarchal ideologies were moderate at all levels, although slightly higher among men. Men tended to avoid conflict with their intimate partner significantly more than women did. Beliefs in support of patriarchal ideologies predicted conflict avoidance, especially among women. Finally, in opposition to prior research findings, this study revealed nonsignificant sex differences in the prevalence of economic violence victimization. These findings, however, do not suggest that economic violence victimization is not rooted in sex issues. We discuss the findings and the meanings assigned to conflict avoidance by men and women while considering gender disparities of power and control. We suggest that the contribution of men’s tendency to avoid conflict likely moderated their chances to perpetrate economic violence.

The aim of this study was to investigate the knowledge, attitudes, and behaviors of family physicians regarding testicular cancer and testicular self-examination. This study was conducted with 307 physicians, including family physician specialists, family physician residents, contracted family physician specialist assistants (SAHU), and general practitioners, who agreed to participate in the study. All participants were administered a 33-item questionnaire consisting of sociodemographic questions and questions about testicular cancer and testicular self-examination, developed through literature review. Data analysis was performed using SPSS 22.0 software. 307 family physician specialists, family physician residents, SAHU residents and general practitioners participated in the study. 10.4% of the participants were working as family medicine specialists, 67.4% as family physician assistants, 13.7% as SAHU residents and 8.5% as general practitioners. The mean time spent in the profession was found to be 5.93±5.89. 65.8% of the participants thought that they had partially sufficient knowledge about testicular cancers. 57.7% of the participants stated that they did not know how testicular self-examination was performed. 49.7% of male participants stated that they had never done testicular self-exam before. While 95.8% of the participants thought that regular testicular self-examination was beneficial, 71.0% stated that they did not recommend testicular self-examination to their male patients. 53.4% of the participants thought that testicular self-examination was important; It was determined that 79.2% of them thought it was as important as breast self-examination. The rate of stating that all of the risk factors presented for testicular cancer are risks was found to be statistically significantly higher in specialist family physicians than in general practitioners and resident family physicians. The study revealed that family physicians lacked sufficient knowledge about testicular cancer and testicular self-examination, leading them not to recommend self-testicular examination to patients due to inadequate knowledge. In light of these findings, although self-testicular examination may not be recommended as a screening method, increasing awareness and knowledge among both family physicians and the public is crucial.

L-gulonolactone oxidase enzyme (GULO) catalyzes the last step of L-ascorbic acid (vitamin C) biosynthesis. This enzymatic activity is lost in primates. The full-length rat GULO has been previously produced in plants and demonstrated to be active. In this study, we compare activity of two variants of GULO produced in Escheriachia coli cells, full-length rat GULO (fGULO) and its C-terminal catalytic domain (cGULO). The expression and purification of the recombinant proteins were optimised and their biological activity was confirmed by two methods, the GULO activity assay in the protein extracts and the ‘in-gel’ staining for GULO activity. Both variants of recombinant GULO were biologically active in both assays. However, cGULO is more promising than fGULO for ascorbic acid production because it is more efficiently produced by bacteria.

In the matrix of bacteria/mitochondria/chloroplasts, Lon acts as the degradation machine for soluble proteins. In stress periods, however, proteostasis and survival depend on the strongly conserved Clp/Hsp100 family. Currently, the targets of ATP-powered unfoldases/disaggregases ClpB and ClpX, and of peptidase ClpP heptameric rings, are still unclear. Trapping experiments and proteome profiling in multiple organisms triggered confusion, so we analyzed the consistency of ClpP-trap targets in bacteria. We also provide meta-analyses of protein interactions in humans, to elucidate where Clp family members are enriched. Furthermore, meta-analyses of mouse complexomics are provided. Genotype-phenotype correlations confirmed our concept. Trapping, proteome, and complexome data retrieved consistent coaccumulation of ClpXP with GFM1 and TUFM orthologs. ClpX shows broad interaction selectivity encompassing mitochondrial translation elongation, RNA granule, and nucleoid; ClpB preferentially attaches to mitochondrial RNA granule and translation initiation components; ClpP is enriched with them all, and associates with release/recycling factors. Mutations in ClpP cause Perrault syndrome, with phenotypes similar to defects in mtDNA/mtRNA. Thus, we propose that ClpB and ClpXP are crucial to counteract misfolded insoluble protein assemblies that contain nucleotide-phosphates. This insight is relevant to improve ClpP-modulating drugs that block bacterial growth, and for the treatment of human infertility, deafness and neurodegeneration.

Introduction: Despite its high prevalence and impact on health, metabolic dysfunction-associated steatotic liver disease (MASLD) is inadequately addressed in European primary care (PC), with a large proportion of cases going undiagnosed or diagnosed too late. A multi-country European re-search consortium led a project to design and evaluate a patient-centered, integrated model for MASLD screening, diagnosis and linkage to specialty care for European PC settings. Aim: Based on the lessons from this project, the latest research evidence and existing guidelines for the management of MASLD, we sought to develop a set of practice recommendations for screening, referral and management of MASLD in PC. Methods: The Rand/UCLA modified Delphi panel method, with two rounds, was used to reach consensus on practice recommendations. The international panel consisted of experts from six countries, representing family medicine, gastroenterology, hepatology, cardiology and public health. Initially, fifteen statements were drafted based on a synthesis of evidence from the literature and earlier findings from our consortium. Prior to the consensus meeting, the statements were rated by the experts in a first round. Then, in a hybrid meeting, the experts discussed findings of round one, adjusted the statements and reassessed the updated recommendations in a second round. Results: In round one, there was already a high level of consensus on 10 out of 15 statements. After round 2, there were fourteen statements with a high agreement (>90%). One statement was not endorsed. The approved recommendations addressed the following practice areas: risk screening and diagnosis, management of MASLD – Lifestyle interventions, pharmacological treatment of MASLD/MASH, pharmacological treatment for co-morbidity, integrated care, surgical management and other referrals to specialists. Conclusion: The final set of 14 recommendations focuses on increasing comprehensive care for MASLD in PC. The recommendations provide practical evidence-based guidance tailored to PC practitioners. We expect that these recommendations will contribute to the ongoing discussion on systematic approaches to tackle MASLD and support European PC providers by integrating the latest evidence into practice.

A screening questionnaire for autism symptoms is not yet available in Poland, and there are no recommendations regarding screening for developmental disorders in Polish primary health care. The aim of the study was to assess the opinions of parents and physicians on the legitimacy and ne-cessity of screening for autism spectrum disorders, potential barriers to the implementation of the screening program, and the evaluation and presenting the process of the online ASD screen-ing, which was part of the validation program of the Polish version of one of the screening tools. The study involved 418 parents whose children were screened online and 95 primary care physi-cians who expressed their opinions in prepared surveys. The results indicate that both parents and doctors perceive the need to screen children for ASD in general population without a clear preference as to the screening method (online or in-person). Online screening may prove to be at least a partial method of solving numerous indicated systemic difficulties - including: time con-straints, lack of experienced specialists in the field of developmental disorders or related to the organizational difficulties of health care.

The existence of multiple copies of genes is a well-known phenomenon. A gene family is a set of sufficiently similar genes, formed by gene duplication. In earlier works conducted on limited number of completely sequenced and annotated genomes it was found that size of gene family and size of genome are positively correlated. Additionally, it was found that several atypical microbes deviated from the observed general trend. In this study, we reexamined these associations on a larger dataset consisting of 1484 prokaryotic genomes and using several ranking approaches. We applied ranking methods in such a way that genomes with lower number of paralogs would have lower rank. Until now only simple ranking methods were used; we applied the Kemeny optimal aggregation approach as well. Regression and correlation analysis were utilized in order to accurately quantify and characterize the relationships between measures of paralog indices and genome size. In addition, boxplot analysis was employed as a method for outlier detection. We found that, in general, all paralog indexes positively correlate with an increase of genome size. As expected, different groups of atypical prokaryotic genomes were found for different types of paralog quantities.

Population-based data on hematologic malignancies (HM) are rare in Greece regarding adults (≥18 years old). The aim of this study was the assessment of the burden of these malignant neoplasms (MN) for adults in Crete. The study assessed temporal trends of incidence and mortality, depicted their spatial distribution and extracted net-survival curves of patients. Population-data on these MN were obtained from the database of the Cancer Registry of Crete, for a 22 year time period (1/1/1992-31/12/2013). All HM were classified into four main groups of diseases: (1) Hodgkin’s lymphoma (HL); (2) Non-Hodgkin’s lymphomas (NHLs); (3) Multiple myeloma (MM); and (4) All chronic and acute leukemias. Annual, gender-specific, age standardized incidence and mortality rates were estimated (ASIR/100.000/year; ASMR/100.000/year). A total of 3,380 newly diagnosed cases were included in the final analyses; All ASIRs/100,000 increased significantly throughout the study period presenting differences in their geographical distribution of rates among municipalities of Crete. ASIRs for NHLs, HL, MM, leukemias and for all 4 MN were 13.1, 2.6, 4.7, 11.7 and 32.1, respectively, in 2013. Five-year net-survival for patients diagnosed with NHLs, HL, MM and leukemias were: 82%, 85%, 52% and 56%, respectively. This first research article studying a long period of time for adults in Greece generates hypotheses on the existence of risk factors that may partly explain this variation of rates.

A growing body of evidence continues to demonstrate the vital roles that zinc and its transporters play on human health. The solute carrier (SLC) 30 and 39 families, with ten and fourteen members, respectively, control zinc transport in cells. TMEM163, a recently characterized zinc transporter, has similar characteristics in both structure and function to the SLC30 family. This review examines recent data that reveal TMEM163 to be a zinc efflux transporter and a new member of the cation diffusion facilitator (CDF) family of mammalian zinc transporter (ZNT) proteins. It also discusses reports that implicate TMEM163 in various human diseases.

When experiencing a variety of family negative events, families recognized as having high family resilience maintain and improve family functioning. It is important, therefore, to be able to assess families lacking in family resilience in order to prevent, reduce, or ameliorate family symptoms. The purpose of this study was to clarify the state of exerted family resilience in order to create an assessment scale for insufficiencies in family resilience (IFR). Family resilience is defined as “when a family becomes aware of family symptoms, its power to autonomously and actively improve its own family functions.” The results of a literature review of 22 cases from 16 studies on family resilience and the results of 28 semi-structured interviews with 28 parenting-age families in Japan were qualitatively categorized, and directed content analysis was conducted based on the Concentric Sphere Family Environment Theory. A total of 157 labels, with a total of 23 categories and 47 subcategories, such as “Can utilize relatives,” “Family members can communicate with members of other families,” “Family members can share information,” “All family members can communicate with one another,” “All family members can cooperate with one another,” and “Can share time with family,” was revealed. Thus, a variety of diverse aspects contributing to a family’s resilience, including family member interactions, entire family interactions, use of social resources, and religious and spiritual support, were revealed. The results of this study should be linked to the creation of the IFR.

Emphasis on primary health care (PHC) is the most efficient and economical approach to achieving universal health coverage. The aim of the study is to examine PHC publications from 2011 to 2023 in the Asian Pacific region (APR) using the Web of Science (WoS) database. Academic papers in the WoS PHC subject category published in the APR from 2011 to 2023 were retrieved and analyzed. A total of 4,283 papers were published in the WoS PHC category from APR onwards. The annual number of published papers and their citations increased from 2011 to 2023. Australia led PHC publications in APR with 3,049 publications (71.19% of APR regional output). New Zealand had the highest number of citations per paper (13.76) and the highest mean impact factor (3.23±1.80). Publications in the WoS PHC category also covered a wide range of topics, including Medicine General Internal (64.77%), Health Care Sciences Services (21.88%), Health Policy Services and Public Environmental Occupational Health (21.36%), demonstrating the breadth of PHC research. Australia dominates the output of PHC publications in the APR. Australian Family Physician and Australian Journal of Primary Health are the leading journals publishing PHC papers in the APR.

Osteoarthritis and chronic pancreatitis comorbidity are insufficiently studied, and the reciprocal impact of these conditions remains poorly understood. This study aimed to investigate potential predictors for the development of osteoarthritis and chronic pancreatitis comorbidity, as well as complications associated with this comorbidity. A cohort of 150 patients was categorized into three groups: a control group (n=30), patients with osteoarthritis (n=68), and patients with comorbid osteoarthritis and chronic pancreatitis (n=52). Potential predictors for comorbidity development and associated complications were explored. The study revealed that concurrent osteoarthritis and chronic pancreatitis exacerbate each other's progression and contribute to malnutrition. Body Mass Index (BMI) emerged as a potential predictor for chronic pancreatitis development in osteoarthritis patients. In osteoarthritis patients, fecal elastase-1 levels were identified as potential predictors for exocrine pancreatic insufficiency. Factors such as WOMAC total score, fecal elastase-1, C-reactive protein (CRP), ferritin, retinol, tocopherol, 25-hydroxy vitamin D3, and BMI were found to influence comorbidity development between osteoarthritis and chronic pancreatitis. Additionally, Gastrointestinal Symptom Rating Scale-Diarrhea Syndrome (GSRS-DS), Gastrointestinal Symptom Rating Scale-Constipation syndrome (GSRS-CS), Qualitative Assessment of the Symptoms and Impact of Pancreatic Exocrine Insufficiency domain A (PEI-Q-A), retinol, tocopherol, and iron were identified as potential predictors for exocrine pancreatic insufficiency in osteoarthritis patients. In conclusion, the comorbidity of osteoarthritis and chronic pancreatitis exacerbates disease progression and complications, necessitating further investigation.

Being forced to live in an area following a catastrophic landslide may adversely impact people's mental well-being. Unprivileged communities such as Adivasis, Dalits, plantation workers, and people with low incomes in Kerala's hilly districts are forced to live in landslide-affected areas despite their fear. This paper examines the fears and concerns of landslide survivors from the marginalized sections of society from a broader framework of the political economy of mental health. This approach aligns with the assertion made by the World Health Organisation that individual factors do not solely determine mental health but are intricately linked to broader social, political, and economic circumstances. Data were collected through in-depth interviews with fatal landslide survivors and key informants [ ]. The study employed thematic data analysis from in-depth interviews of various fatal landslide survivors since 2018. The three major themes unveiled in the analysis are: 1. post-disaster fears, 2. The factors that triggered fear and concern and 3. Socio-economic marginality and mental health. The study asserts that individuals who are poor and unprivileged are highly susceptible to mental health issues associated with landslides.

Background: Both hypertension and carotid atherosclerosis are independent risk factors for cardiovascular disease. Understanding their combined impact could enhance risk assessment and management strategies. Hypothesis: We hypothesized that the synergistic effects of hypertension and carotid plaques would increase the risk of both cardiovascular events and all-cause mortality. Methods: A follow-up study was conducted at the Preventive Cardiology department of Vilnius University Hospital Santaros klinikos between 2012 and 2021. The study recruited participants aged 40-60 who did not have overt CVD and were part of the Lithuanian High Cardiovascular Risk primary preventive program. The study collected demographic and clinical data, including an ultrasound assessment of carotid plaque. The participants were monitored for 4-10 years for CVD events and all-cause mortality. Results: Among 6,138 participants, 954 (16%) experienced cardiovascular disease (CVD) events. The presence of carotid plaque on both sides was significantly associated with CVD events, myocardial infarction, and all-cause mortality. However, the combination of hypertension and carotid plaque did not significantly increase the risk for CVD events, stroke, or all-cause mortality. Conclusion: The combination of hypertension and carotid plaque did not significantly increase the risk of CVD events or all-cause mortality. CV events depend on the spread of the atherosclerosis process in the carotid vessels.

Apoptosis, also known as the programmed death of cells, is responsible for maintaining the homeostasis of tissues and this function is carried out by caspases. The process of apoptosis is carried out via two distinct pathways: the extrinsic pathway, which is governed by death receptors, and the intrinsic pathway, also known as the mitochondrial pathway. The BCL-2 protein family encoded by the BCL-2 gene, located at the 18q21.33 chromosomal location, is in charge of regulating the intrinsic pathway, which is responsible for inducing cell death via the permeabilization of the mitochondrial membrane and the release of apoptosis - inducing components. The BCL-2 homology (BH1, BH2, BH3, BH4) domains of this family proteins are crucial for their functioning and their common BH domains allow interactions between members of the same family and can also serve as indications of pro- or anti-apoptotic activity. A direct correlation may be shown between the overexpression of BCL-2 and the postponement of cell death. It has been determined that a change in the expression of BCL-2 is the root cause of a variety of malignancies, including lung, breast, melanoma, and chronic lymphocytic leukemia, Multiple Sclerosis, Diabetes. In this review, we discuss the therapeutic potential of regulating BCL-2 family connections and their relevance to health and disease.

The combination of immunoPET—where an antibody (Ab) is labeled with an isotope for PET imaging—and radioimmunotherapy (RIT), using the same antibody with a therapeutic isotope, offers significant advantages in cancer management. ImmunoPET allows non-invasive imaging of antigen expression, which aids in patient selection for a subsequent radioimmunotherapy. It also facilitates the assessment of tumor response to therapy, allowing for treatment adjustments if necessary. In addition, immunoPET provides critical pharmacokinetic data, including antibody biodistribution and clearance rates, which are essential for dosimetry calculations and treatment protocol optimization. There are still challenges to overcome. Identifying appropriate target antigens that are selectively expressed on cancer cells while minimally expressed on normal tissues remains a major hurdle to reduce off-target toxicity. In addition, it is critical to optimize the pharmacokinetics of radio-labeled antibodies to maximize tumor uptake and minimize normal tissue uptake, particularly in vital organs such as the liver and kidney. This approach offers the potential for targeted and personalized cancer therapy with reduced systemic toxicity by exploiting the specificity of monoclonal antibodies and the cytotoxic effects of radiation. However, further research is needed to address remaining challenges and to optimize these technologies for clinical use.

To assess the community health workers’ (CHWs) knowledge, attitude, and practices (KAP) in type-2 diabetes (T2D) and hypertension (HTN) management. We thus also sought to assess the potential health system barriers for incorporating CHWs in T2D and HTN management. Mixed-method study comprised (1) a survey among 153 active CHWs to assess their KAP of T2D and HTN, and (2) semi-structured interviews with key informants to understand challenges of the health system and proposed solutions in incorporating CHWs in T2D and HTN management. The majority of CHWs correctly answered general knowledge questions on NCDs, risk factors, and prevention; however, only one-quarter correctly answered questions on smoking, family history, or tobacco use as risk factors. Most respondents appeared to have positive attitudes and have been practicing some activities related to T2D and HTN. Both financial and non-financial resource constraints were cited as challenges of the health system; therefore, re-structuring the role definition of CHWs and task of responsibilities, and assessment the need and workload have been proposed as ways forwards to effectively incorporate CHWs in T2D and HTN care. CHWs in Cambodia have shown their potential in T2D and HTN management; however, a well-designed strategy including technical training, clearly defined roles and responsibilities, and strong supporting structure are important to maximize their potential in the health system.

Bicyclic peptides have attracted the interest of pharmaceutical companies because of their remarkable properties putting them on a new path in medicine. Their conformational rigidity that improves proteolytic stability, leads to rapid penetration into tissues via any possible route of administration and elimination, occurring by renal metabolism, is of great importance for people with a history of liver diseases. In addition, each ring can function independently, making them extremely versatile molecules for further optimization. In this paper we compared the potentiometric and spectroscopic properties studied by UV-Vis, MCD, and EPR, of four synthetic analogues of the bi-cyclic peptide c(PKKHP-c(CFWKTC)-PKKH). In particular we correlated the structural and spectral properties of complexes with coordinating abilities toward Cu(II) ions of MCL (Ac-PKKHPc(CFWKTC)PKKH-NH2) that contains the unbinding cycle and N- and C-terminal linear parts, with two histidine residues, one per part; two monocyclic ligands containing one histidine residue, both in the N-terminal position i.e., MCL2 (Ac-PKKHPc(CFWKTC)PKKS-NH2) and in the C-terminal position i.e., MCL3 (Ac-PKKSPc(CFWKTC)PKKH-NH2), respectively, and the linear structure LNL (Ac-PKKHPSFWKTSPKKH-NH2).

ESG (Environmental, Social, and Governance) responsibility fulfillment increasingly affects enterprise valuation. Although researchers debate about the precise effects, the prevailing view suggests a linear relationship between ESG performance and enterprise value. This study introduces a novel ESG responsibility performance metric through the Regulated Intermediary Model to delve into this relationship within the Chinese context. Our findings reveal an inverted U-shaped relationship between ESG performance and enterprise value, with financing constraints having a significant moderating effect. These findings remain robust after employing instrumental variables to mitigate potential endogeneity. Heterogeneity analysis demonstrates that this inverted U-shaped relationship is particularly pronounced in non-polluting and non-state-owned enterprises. Moreover, a comparison between equity and debt financing mechanisms underscores that improved ESG performance is associated with lower cost of equity financing, thereby enhancing enterprise value. Financial institutions are encouraged to leverage innovative financial instruments to diversify enterprise financing channels and alleviate financing constraints of enterprises that fulfill their ESG responsibilities.

Proteomics research has become one of the most important topics in the fields of life science and natural science. At present, research on protein–protein interaction networks (PPINs) mainly focuses on detecting protein complexes or function modules. However, existing approaches are either ineffective or incomplete. In this paper, we investigate function module detection mechanisms in PPIN, including open databases, existing detection algorithms and recent solutions. After that, we describe the proposed solution based on simplified swarm optimization (SSO) algorithm and gene ontology knowledge. The proposed solution implements SSO algorithm for clustering proteins with similar function, and imports biological gene ontology knowledge for further identifying function complexes and improving detection accuracy. Furthermore, we use four different categories of species dataset for experiment: Fruitfly, Mouse, Scere, and Human. The testing and analysis result show that the proposed solution is feasible, efficient and could achieve a higher accuracy of prediction than existing approaches.

The vaccines have to undergo independent testing at National Control laboratory (NCL) for various quality control tests to ensure safety, purity, and potency before market authorization and surveillance testing. In this study, five different inactivated cell culture rabies vaccine preparations (Aluminum adjuvanted and non-adjuvanted) marketed in India were evaluated using compendial safety test of mouse inoculation test (MIT) for residual live virus. Investigations were done to see the interference of aluminum adjuvant in rabies vaccine preparation to ensure safety as per the in-vivo compendial test for virus inactivation. After intracerebral injections, mice received the aluminum phosphate adjuvanted inactivated rabies vaccine (ARV) had neurological complications that resulted in their deaths between days 4 and 10. Further investigations were carried out to find out the root cause for mice death including fluorescent antibody test (FAT), rabies virus amplification test. Additionally, alamar blue based cell cytoxicity assay was carried out using BHK-21 cells to estimate the cell toxicity of aluminum phosphate adjuvanted inactivated rabies vaccine. The present study highlighted the challenges in ensuring the safety of adjuvated inactivated rabies vaccine at level of NCL. Further, study demonstrated the toxicity of aluminum under both in vitro and in vivo settings, sparking controversy regarding the safety of aluminum adjuvants in vaccines at the suggested compendial limit of 1.25 mg/single human dosage.

Oligopeptide transporters (OPTs) are a group of membrane localized proteins that have a broad range of substrate transport capabilities and contribute to numerous biological processes. However, limited information has been reported on OPTs in higher plants. In this study, a comprehensive analysis of the OPT gene family in Medicago truncatula was performed. A total of 26 OPT genes (MtOPT01-MtOPT26) have been identified in the Medicago truncatula genome. Phylogenetic analyses indicated that MtOPTs consisted of two distinct subgroups, 12 MtOPTs belonged to the peptide transport subgroup (PT-OPT) based on their predicted amino acid sequences containing the two highly conserved motifs (NPG and KIPPR) and 14 MtOPTs belonged to yellow stripe subgroup (YS-OPT). The MtOPTs distributed on each of 8 chromosomes in Medicago truncatula. Sequence analysis verified that MtOPTs significant similar to those in other plants. The copy number of MtOPTs was low and the multiply of MtOPTs was simple relatively. Gene structure analysis showed that most of the MtOPTs have various numbers of introns. The multiple of MtOPTs might play different biological roles which were supported by the fact that MtOPTs have a distinct tissue-specific expression pattern. The data obtained in this study will help to better understand the complexity of the MtOPTs gene family and provide new evidence for the function and evolution of the OPT gene family in higher plants.

Abstract: Currently, antibodies are major therapeutic modalities in biopharmaceutical research and development. Because of required high dose for certain clinical applications, antibodies are formulated at high protein concentration for convenience of administration, shipping and storage. We will describe the inter-molecular interactions that can occur in such a crowded environment of high protein concentration. Two types of repulsive interactions, i.e., electrostatic and excluded volume effects, and three types of attractive interactions, i.e., hydrophobic, electrostatic and cross-linking, need to be considered in such a crowded environments. We then show consequences of such inter-molecular interactions, leading to high viscosity, opalescence and phase separation of antibody solutions. Co-solvents are used to control the stability, structure and molecular interactions and thereby to alleviate these solution problems. Among various co-solvents, arginine has been extensively used to suppress protein-protein interactions at high protein concentration. Arginine weakly but extensively interacts with aromatic/hydrophobic groups as well as charged groups on proteins, leading to effective suppression of viscosity, opalescence and phase separation of antibody solution.

The objective was to investigate associations of serum vitamin D concentration with depressive symptoms and assess the impact vitamin D concentration has on the occurrence of depressive symptoms in 20–44-year-old pregnant mothers, postpartum mothers, women (non-pregnant/postpartum women), and men, including a separate subgroup analysis of postpartum breastfeeding and non-breastfeeding mothers. The study populations were selected from 2007-2018 NHANES public data. Subjective interview data and objective laboratory data, including depressive symptoms, serum vitamin D concentration, nutrient intake, and demographic information were utilized. Two diet patterns were created using principal component analysis and a Bayesian multinomial model was fit to predict depression outcomes for each subpopulation. The estimates for the log vitamin D slope parameter were negative for all cohorts; as vitamin D increased, the probability of having no depression increased, while the probability of depression decreased. The pregnant cohort had the steepest vitamin D slope, followed by postpartum, then other women and men. Higher vitamin D concentration had more impact on decreasing depression risk in pregnant and postpartum mothers compared to other women and men. Among postpartum mothers, higher vitamin D concentration had a greater influence on decreasing breastfeeding mothers' depression risk than non-breastfeeding mothers.

Introduction The prevalence of adolescent electronic cigarette (e-cigarette) use has increased in most countries. This study determines the relation between the frequency of e-cigarette use and the frequency and intensity of cigarette smoking. Furthermore, it evaluates the association between the reasons for e-cigarette use and the frequency of its use. Materials and Methods Participants were 68,043 middle and high school students aged 13–18 years from the 2015 Korean Youth Risk Behavior Web-Based Survey. Of the 68,043 participants, we analyzed 6,655 adolescents with an experience of e-cigarette use. Results The prevalence of ever using and current (past 30 days) use of e-cigarettes was 10.1% and 3.9%, respectively. Of the ever e-cigarette users, approximately 40% used e-cigarettes for ≥1/month and 8.1% used e-cigarettes daily. Daily e-cigarettes users were 10 times greater among daily cigarette smokers than among cigarette users for <1/month (18.1% vs. 1.8%) and 16 times more prevalent among those smoking ≥20 cigarettes/day than among those smoking <1 cigarette/month (38.9% vs. 2.4%). The most common reason for e-cigarette use was curiosity (22.9%), followed by less harmful than conventional cigarettes (18.9%), smoking cessation (13.1%), and indoor use (10.7%). Curiosity was the most common reason among less frequent e-cigarette users; however, smoking cessation and indoor use were the most common reasons among more frequent users. Conclusions Results showed a positive relation between frequency or intensity of conventional cigarette smoking and frequency of e-cigarette use among Korean adolescents, and frequency of e-cigarette use differed according to the reason for the use of e-cigarettes.

Quite a number of cottonseed varieties are existed. The seeds of each variety produce a different amount of gossypol as a natural toxic compound. The increased interest in this natural product and its toxic effects were enhanced the demand for establishing simple silica-gel-based methods for its isolation, purification, and characterization. Historically, silica gel plays a significant role in isolation and purification of many different natural products. Silica gel is variants and can intro-duce a lab, simple tool for tracking a compound in certain plants during its purification process. In this study, gossypol was isolated and purified in the form of yellow crystals as gossypol acetic ac-id. Several methods and tools were used for its characterization including TLC, preparative TLC, silica gel column, UV/IR spectrophotometer and HPLC (Robust spherical silica gel). A compara-tive study between its amounts in both Egyptian and Chinese varieties were performed. Under the experimental condition, the Egyptian cottonseeds contain 8.705 gm/kg, while the Chinese contains 5.395 gm/kg. Thin Layer Chromatography (TLC) had been flourished the science of the phytochemistry and still popular till nowadays and is recommended for fast, accurate, and inex-pensive evaluation and quantification of gossypol. It is recommended to isolate and purify gossy-pol as gossypol acetic acid using optimized combined methods used in this study. Using Silica gel different protocols will assist and facilitate the parallel comparison and save the compact column from any unexpected contaminants during the purification steps. During each step the silica gel itself could be simply removed by paper filtration.

Members of the DUF34 (domain of unknown function 34) family, also known as the NIF3 protein superfamily, are ubiquitous across superkingdoms. Proteins of this family have been widely annotated as “GTP cyclohydrolase I type 2” through electronic propagation based on one study. Here, the annotation status of this protein family was examined through comprehensive literature review and integrative bioinformatic analyses that revealed varied pleiotropic associations and phenotypes. This analysis combined with functional complementation studies strongly challenges the current annotation and suggests that DUF34 family members may serve as metal ion insertases, chaperones, or metallocofactor maturases. This general molecular function could explain how DUF34 subgroups participate in highly diversified pathways such as cell differentiation, metal ion homeostasis, pathogen virulence, redox and universal stress responses.

Reactive oxygen species (ROS) are produced during cellular metabolism and in response to environmental stress. While low levels of ROS play essential physiological roles, excess ROS can damage cellular components, leading to cell death or transformation. ROS can also regulate protein interactions in cancer cells, thereby affecting processes such as cell growth, migration, and angiogenesis. Dysregulated interactions occur via various mechanisms, including amino acid modifications, conformational changes, and alterations in complex stability. Understanding ROS-mediated changes in protein interactions is crucial for targeted cancer therapies. In this review, we examine the role that ROS mechanisms in regulating pathways through protein-protein interactions.

Indocyanine Green (ICG) has significantly advanced minimally invasive surgery. It is widely recognized for its ability to visualize blood vessel patency in real-time across various surgical specialties. While its primary use in colorectal surgery is to evaluate anastomoses for leaks, nu-merous other applications have been documented in the literature. In this review, we aim to explore both established and emerging applications of ICG fluorescence in colorectal surgery, with the goal of improving patient outcomes. This includes preoperative tumor marking and the detection of metastatic disease. Some applications, such as lymphatic mapping, require further research to determine their impact on clinical practices. Conversely, oth-ers, like the intraoperative localizations of ureters, necessitate additional procedures and are not yet widely accepted by the surgical community. However, the development of alternative com-pounds could offer better solutions. Future research should focus on areas like quantitative ICG and protocol standardization in prospective multicenter studies.

The comorbidity of osteoarthritis and type 2 diabetes mellitus represents a complex clinical challenge and complicates patient management due to the interplay of overlapping pathophysiological mechanisms. The research aimed to analyze the exacerbation of clinical symptoms and biochemical markers in patients with osteoarthritis and type 2 diabetes mellitus compared to those with osteoarthritis. We utilized various assessment methods to measure the patient cohorts' inflammation, oxidative stress, and glycemic control. The study also involved the administration of alpha-lipoic acid to patients with comorbid osteoarthritis and type 2 diabetes mellitus and monitored its effects on joint function, inflammatory markers, oxidative stress levels, and glycemic control. Our findings revealed that the presence of type 2 diabetes mellitus significantly intensified osteoarthritis symptoms and altered biochemical markers, including increased inflammation, elevated oxidative stress, and disrupted immunological balance. The treatment with alpha-lipoic acid resulted in improved joint function, reduced inflammation and oxidative stress levels, and better glycemic control. Additionally, it was identified several potential predictors for developing osteoarthritis and type 2 diabetes mellitus comorbidity. The results underscore the detrimental impact of type 2 diabetes mellitus on osteoarthritis and highlight the beneficial effects of alpha-lipoic acid in alleviating some of the adverse consequences associated with this comorbidity. Nonetheless, further research is necessary to comprehensively evaluate the therapeutic efficacy of alpha-lipoic acid and its long-term effects on managing comorbidity of osteoarthritis and type 2 diabetes mellitus.

The spectrum, intensity and overlap of symptoms between FGIDs and other gastrointestinal disorders characterize patients with FIGDs, who are incredibly different in their backgrounds. An additional challenge with regard to the diagnosis and treatment's applicability is the ongoing expansion of the risk factors believed to be connected to these disorders. Many cytokines and inflammatory cells have been found causing the continuous existence of low-inflammation, which is thought to be a basic pathophysiological process. The idea of the gut-brain axis has been created to offer a basic framework for the complex interactions that occur between the nervous system and intestinal functions, including the involvement of the gut bacteria. In this review paper, we intend to promote a hypothesis that FGIDs, should be seen through the perspective of the network of the neuroendocrine, immunological, metabolic and microbiome pathways. Hypothesis arises from an increased understanding of chronic inflammation as a systemic disorder, being omnipresent in chronic health conditions. Better understanding of inflammation role in the pathogenesis of FGIDs can be achieved by clustering markers of inflammation with data indicating symptoms, comorbidities, and psycho-social factors. Finding subclasses among related entities of FGIDs, may reduce patient heterogeneity and help clarify pathophysiology for better treatment.

Abstract: Peptide pools composed of short amino acid sequences have proven to be versatile tools in various research areas and clinical applications. They are powerful tools for epitope mapping, immunotherapy, and vaccine development. Their importance lies in their ability to map complex protein structures, enabling a comprehensive understanding of immune responses and facilitating the identification of potential therapeutic agents. The application of peptide pools also extends to the field of personalized medicine, offering tailored solutions for diseases such as cancer and infectious diseases. Peptide pools are complex mixtures of immunostimulatory antigens primarily intended for T-cell stimulation. They are commercially available in many different compositions and variants. However, unlike other reagents that consist of only one or a few compounds, peptide pools are highly complex products with limited stability. This makes their quality control a major challenge. Quantitative peptide analysis usually requires sophisticated methods, in most cases isotope-labeled standards and reference materials. None of these are routinely available for these products. Synthesis and purification of all labeled peptides might be required. Usually, this approach would be prohibitively laborious and expensive. Therefore, an approach is needed to provide a practical and feasible method for quality control of peptide pools. With insufficient quality control, the use of such products could lead to incorrect experimental results, which would worsen the well-known reproducibility crisis in the biomedical sciences. Here we propose the use of ultra-high performance liquid chromatography (UHPLC) with two detectors, a standard UV detector (at 214 nm) for quantitative analysis and a high-resolution mass spectrometer (HRMS) for identity confirmation. To be cost-efficient and fast, quantification and identification are performed in one chromatographic run. An optimized protocol is shown, and different peak integration methods are compared and discussed. This work was performed using a peptide pool known as CEF, which consists of 32 peptides derived from cytomegalovirus (CMV), Epstein-Barr virus (EBV) and influenza virus, ranging from 8 to 12 amino acids in length.

Sea urchins are long-living invertebrates with a complex immune system which includes extended families of immune receptors. A central immune gene family in the sea urchins encodes for the Transformer (Trf) proteins. The Trf family was so far studied mainly in the purple sea urchin Strongylocentrotus purpuratus. In this study, we explored this protein family in the Mediterranean Sea urchin Paracentrotus lividus. The PlTrf genes and predicted proteins were found to be highly diverse and showed a typical Trf size range and structure. We found that P. lividus coelomocytes and hemolymph contain different PlTrf protein repertoires with a shared subset which specifically bind E. coli bacteria. Using FACS, we identified five different P. lividus coelomocyte sub-populations with cell surface Trf protein expression. The relative abundance of the Trf-positive cells sharply increased following immune challenge with E. coli bacteria, but not following challenge with LPS or sea urchin pathogen V. penaeicida. Finally, we demonstrated that the phagocytosis of E. coli bacteria by P. lividus phagocytes is mediated through the hemolymph and is inhibited by blocking Trf activity with anti-Trf antibodies. Together, our results suggest collaboration between cellular and humoral Trf-mediated effector arms in the P. lividus specific immune response to pathogens.

p53 and p73 are critical tumor suppressors often inactivated in human cancers through various mechanisms. Owing to high structural homology, the proteins have many common functions and recognize the same set of genes involved in apoptosis and cell cycle regulation. p53 is known as the ‘guardian of the genome’ and together with p73 form a barrier against cancer development and progression. The TP53 is mutated in more than 50% of all human cancers and the germline mutations in TP53 predispose to the early onset of multiple tumors in Li-Fraumeni Syndrome (LFS), the inherited cancer predisposition. In cancers where TP53 gene is intact, p53 is degraded. Despite the ongoing efforts, the treatment of cancers remains challenging. This is due to late diagnoses, the toxicity of current standard of care and marginal benefit of newly approved therapies. Presently, the endeavours focus on reactivating p53 exclusively, neglecting the potential of the restoration of p73 protein for cancer eradication. Taken that several small molecules reactivating p53 failed in clinical trials, there is a need to develop new treatments targeting p53 proteins in cancer. This review outlines the most advanced strategies to reactivate p53 and p73 and describes drug repurposing approaches for the efficient reinstatement of the p53 proteins for cancer therapy.

Background: Colorectal adenoma undergoes neoplastic progression via the normal epithelium-adenoma-adenocarcinoma sequence as reported in the Vogelgram. The risk of developing cancer is strongly associated with the number and size of adenoma and with the subtype. Currently, adenomatous polyps can be distinguished on the basis of histology: the prevalence are tubular, 5-15% are villous and tubular/villous. Considering the increased risk for malignant transformation described for tubular/villous adenomas, patients diagnosed with adenomatous polyposis are at increased risk of developing CRC. The Wnt/β-catenin pathway plays a key role in the onset of colorectal adenoma, in particular intestinal cells first acquire loss-of-function mutations in APC gene that induce the formation of adenomas. Methods: Wnt/β-catenin pathway APC, Wnt3a, Wnt5a, LEF1, BCL9 genes and protein expression analyses were conducted by qRT-PCR and western blot in 68 colonic samples (polyps and adjacent mucosa) from 41 patients, of which 17 affected by FAP. Ten normal colonic mucosal samples were collected from 10 healthy donors. Results: In this study both APC gene and protein resulted less expressed in colon tumor compared to the adjacent colonic mucosa. Conversely, activated β-catenin was more expressed in polyps than in the adjacent mucosa. All results confirmed literature data on carcinomas. A statistically significant correlation between Wnt3a and BCL9 both in polyps and in the adjacent mucosa underlies that the canonical Wnt pathway is activated in early colon carcinogenesis and that the adjacent mucosa is already altered. Conclusion: This is the first study analyzing the difference in expression of Wnt/β-catenin pathway in human colorectal adenomas. Understanding the progression from adenomas to colorectal carcinomas is essential for the development of new therapeutic strategies and improving clinical outcomes.

A partial mitochondrial DNA Cytochrome Oxidase subunit I (mtCOI) gene haplotype variant of the coconut rhinoceros beetle (CRB) Oryctes rhinoceros classed as ‘CRB-G (clade I)’ has been the focus of much research since 2007 with reports of invasions into new Pacific Island locations (e.g., Guam, Hawaii, Solomons Islands). For numerous invasive species, inference of invasion biology via whole genome is superior to assessments via the partial mtCOI gene. Here, we explore CRB draft mitochondrial genomes (mitogenomes) from historical and recent collections, with assessment focused on individuals associated within the CRB-G (clade I) classification. We found that all Guam CRB individuals possessed the same mitogenome across all 13 protein coding genes and differed from individuals collected elsewhere, including ‘non-Guam’ individuals designated as CRB-G (clade I) by partial mtCOI assessment. Two alternative ATP6 and COIII partial gene primer sets were developed to enable distinction between CRB (clade I) that invaded Guam and CRB-G (Clade I) individuals collected elsewhere. Phylogenetic analyses based on concatenated ATP6-COIII genes showed that only Guam CRB-G (clade I) individuals clustered together, and therefore Guam was not the source of the CRB that invaded the other locations in the Pacific assessed in this study. The use of the mtCOI and/or mtCOIII genes for initial molecular diagnosis of CRB remained crucial, and assessment of more native CRB populations will further advance our ability to identify the provenance of CRB invasions being reported within the Pacific and elsewhere

Functional copy number alterations (fCNAs) are DNA copy number changes with concordant differential gene expression. These are less likely to be bystander genetic lesions and could serve as robust and reproducible tumor biomarkers. To identify candidate fCNAs in neuroendocrine tumors (NETs), we integrated chromosomal microarray (CMA) and RNA-seq differential gene expression data from 31 pancreatic (pNET) and 33 small bowel neuroendocrine tumors (sbNET). Tumors were resected from 47 early disease progression (24 months) patients. Candidate fCNAs that accurately differentiated these groups in this discovery cohort were then replicated using fluorescence in situ hybridization (FISH) on formalin-fixed, paraffin-embedded (FFPE) tissues in a larger validation cohort of 60 pNETs and 82 sbNETs (52 early and 65 late disease progression samples). Logistic regression analysis determined the predictive ability of these biomarkers as well as the assay performance metrics of sensitivity, specificity, and area under the curve. Our results indicate that copy number changes at chromosomal loci 4p16.3, 7q31.2, 9p21.3, 17q12, 18q21.2, and 19q12 may be used as diagnostic and prognostic NET biomarkers. This involves a rapid, cost-effective approach to determine primary tumor site for patients with metastatic liver NETs and to guide risk stratified therapeutic decisions.

The additional sex combs-like (ASXL) family, a mammalian homolog of the additional sex combs (Asx) of Drosophila, has been implicated in transcriptional regulation via chromatin modifications. Abnormal expression of ASXL family genes leads to myelodysplastic syndromes and various types of leukemia. De novo mutation of these genes also causes developmental disorders. Genes in this family and neighbor genes are evolutionary conserved in humans and mice. This review provides a comprehensive summary of epigenetic regulations associated with ASXL family genes. Their expression is commonly regulated by DNA methylation at CpG islands preceding transcription starting sites. Their proteins primarily engage in histone tail modifications through interactions with chromatin regulators (PRC2, trithorax complex, PR-DUB, SRC1, HP1α, and BET proteins), and with transcription factors, including nuclear hormone receptors (RAR, PPAR, ER, and LXR). Recently, non-coding RNAs have been identified following mutations in the ASXL1 or ASXL3 gene, along with circular ASXLs and microRNAs that regulate ASXL1 expression. The diverse epigenetic regulations linked to ASXL family genes collectively contribute to tumor suppression and developmental processes. Our understanding of ASXL-regulated epigenetics may provide insights into the development of therapeutic epigenetic drugs.

Universal Stress Protein (USP) plays an important regulatory role in the response to abiotic stress. Most of the research related to USP so far has been conducted on plant models such as Arabidopsis, rice, and cotton. The potato is one of the four major food crops in the world. Therefore, it is of great significance to study the expression pattern of the potato StUSP gene family under abiotic stress conditions. In this study, a total of 108 USP genes were identified from the genome of the Atlantic potato, divided into four subgroups. And based on the genetic structure, the physical and chemical properties of proteins and other aspects of their biological characteristics are comprehensively analyzed. Collinear analysis showed that the homologous genes of StUSPs and four other representative species (Arabidopsis, rice, coyote tobacco, and tomato) were highly conserved. The cis-regulatory elements of the StUSPs promoter are involved in plant hormones, environmental stress, mechanical damage, and light response. RNA-seq analysis showed that under different abiotic stresses, there are differences in the expression patterns of members of each subgroup. WGCNA co-expression analysis of the central gene showed that the differential co-expression gene is mainly involved in the plant-pathogen response process, plant hormone signal transduction, and the biosynthesis process of secondary metabolites. Through qRT-PCR analysis, it was confirmed that StUSP13, StUSP14, StUSP15, and StUSP41 may be important candidate genes involved in the response to adversity stress in potatoes. The results of this study provide the basis for further research on the functional analysis of StUSPs in the potato response to adversity stress.

Integrated photovoltaic-fuel cell (IPVFC) systems have the potential to contribute to sustainable energy production for grid and off-grid applications. While there are studies focusing on fundamental science and designs for IPVFC systems, there are scarcely studies that have focused on the manufacturability of IPVFC systems, which is certainly the pathway for commercialisation of the systems. This study explores manufacturing strategies that can be considered for exploiting a family of eleven IPVFC systems. A survey and systems thinking were used to investigate the potential modularisation and supply chain management to achieve optimal lean and agile manufacturing strategy. Results show that the Photovoltaic-Thermal-Separate Converter/Inverter-Battery System received 25% of the responses. The optimal manufacturing strategy depends on the overall business strategy of the firm. Although 17% preference for System 1 is significant compared to four members of the family of IPVFC systems (Systems 2, 6, 8 and 9) that received only 2% of the responses, it indicates that there is a likelihood that the demand for System 1 will be among the top 42% of the total demand. Overall, this study provides new insights on how the family of IPVFC systems can contribute to realising greater access to clean energy, by extension contributing to the net-zero efforts using solar energy and solar hydrogen.

The Interdisciplinary Canadian Collaborative ME Research Network (ICanCME), established in 2019, aims to foster research in Canada and contribute to finding the causes and possible treatments for myalgic encephalomyelitis /chronic fatigue syndrome (ME/CFS), thereby reducing the impact of ME/CFS on the health of Canadians. The main objectives of this paper are to suggest standards for ME/CFS research for the collection of data from participants (Recommended Data Elements) and to consider other factors, such as design, language, cultural issues, equity, and diversity. Consensus of the relevant contents of this research guideline was reached during the ICanCME working group meetings and were based on existing guidelines. Members of the working group contributed to guideline development based on their respective expertise. The proposed research guidelines could improve research quality and advance knowledge in the field of ME/CFS, and ultimately benefit ME/CFS patients.

Children are inherently curious about everything they encounter, making the early years a perfect time for STEAM (science, technology, engineering, arts, and math) investigations. An outdoor learning environment can influence STEAM concept formation of preschoolers with intentional design that offer STEAM learning affordances. Despite the rising interest in early STEAM education, there is still limited literature on how the outdoor environment may influence STEAM learning behaviors of preschoolers (3-5 years old). This scoping review intends to evaluate the existing knowledge regarding the physical factors that contribute to STEAM learning affordances in an outdoor environment for children aged 3 to 5. The review included studies from the last twenty years. This scoping review was conducted in accordance with the criteria outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR). For this scoping review, 843 citations were discovered across four databases (JSTOR, Scopus, EBSCOhost, and Web of Science), ProQuest, and Google Scholar, and 31 articles were considered eligible for inclusion. Through the synthesis of information from those 31 studies, a list of STEAM learning behaviors of children and STEAM activity-supportive settings were identified that may positively influence preschoolers' STEAM concept development.

Background: The importance of knowing the workload of family nurses lies essentially in the possibility of improving health outcomes, care processes and the nurse’s professional life. There is a lack of studies that fully describe nursing workload in primary care, particularly, in the context of family health nursing, and the ideal metrics to be used remains unknown, making it impossible to characterize and therefor provide the necessary insight to acknowledge the different contributions of several aspects that embodies the global workload of family nurses. The objective of this scoping review was to map the known evidence and characterize the instruments used to assess the workload of family nurses. Methods: Scoping review, according the Joanna Briggs Institute proposed methodology for scoping reviews, consisting of 3 research stages: 1) initial research in Medline and CINHAL; 2) extended search, using keywords and search terms, in the following databases: JBI, CINAHL Complete, MEDLINE, Cochrane and Scopus; 3) Search the reference list of the selected articles. No time limit was defined. Results: Fourteen studies referring to ten as-sessment instruments were included. Nine of them analyze workload as a dimension of a broader instrument, and two studies refer to an instrument that focuses exclusively on workload. Con-clusions: The diversity of professional competencies and contexts, the conceptual complexity of workload and the absence of an theoretical framework, makes it difficult to identify consensual instruments to assess the workload of family nurses. This study was registered in Open Science Framework® with the following registration (https://osf.io/3k6vr).

The Bax inhibitor-1 (BI-1) gene family, which is required for plant growth, development, and stress tolerance, remains largely unexplored in cauliflower. In this study, we identified and characterized cauliflower BI-1 family genes. On the basis of aligned homologous sequences and collinearity with Arabidopsis genes, we identified nine cauliflower BI-1 genes, which encoded proteins that varied regarding length, molecular weight, isoelectric point, and subcellular localization (i.e., Golgi apparatus, plasma membrane, cell membrane, and chloroplast). Phylogenetic analyses detected evolutionary conservation and divergence among these genes. Ten structural motifs were identified, with Motif 5 crucial for inhibiting apoptosis. According to the cis-regulatory elements in their promoters, these genes likely influence hormone signaling and stress responses. Expression profiles among tissues highlighted the diversity in the functions of these genes, which were significantly expressed in the silique and root. Focusing on BobBIL4, we investigated its role in brassinosteroid (BR)-mediated root development and salt stress tolerance. BobBIL4 expression levels increased in response to BR and salt treatments. The functional characterization of this gene in Arabidopsis revealed it enhances root growth and salinity tolerance. These findings provide insights into BI-1 gene functions in cauliflower, while also highlighting the potential utility of BobBIL4 for improving crop stress resistance.

Originating in the Mediterranean, B. oleracea is grown all over the world and is highly valued for its nutritional value and variety in cooking. Its susceptibility to pests, diseases, and environmental stressors, however, poses significant challenges to sustaining consistent crop quality and productivity. The BASIC PENTACYSTEINE gene significantly impacts plant growth and responses to abiotic stresses. Nevertheless, little is known about its precise role and the underlying biological processes in B. oleracea. Eleven BPC genes in B. oleracea were identified by a thorough genome-wide investigation and categorized into three categories according to their structural traits and gene motifs. There were eight different chromosomes on which these BoBPCs were located. Comparative synteny analysis was used to reveal the evolutionary traits of potatoes, Arabidopsis, and B. oleracea. The BoBPC family genes in B. oleracea were found to have specific cis-elements linked to growth, stress responses, and hormone regulation when their promoter regions were studied. Cuticular wax synthesis expression revealed that all BoBZR1 genes, from wild to mutant, expressed at varied amounts in distinct types. Moreover, distinctive BoBPC gene expression patterns were found in the seven distinct tissues that were studied. Our thorough analysis shows that the BoBPC family is widely involved in B. oleracea developmental processes. The present findings provide an established theoretical basis for further exploration into the composition and roles of BoBPC in B. oleracea.

The AREB/ABF (ABA response element binding) proteins in plants are vital for plant stress responses, but the understanding of AREB/ABFs in orchid species, an important traditional medicinal and ornamental plants, is limited. Here, twelve AREB/ABF genes were identified within three orchids’ complete genome and classified into three groups (groups I, II, and III) via a phylogenetic analysis, which was further supported by the analysis of their conserved motifs and gene structures. The cis-elements analysis showed that hormone response elements followed by light and stress responses were widely rich in AREB/ABFs. A prediction analysis of orchid ABRE/ABF-mediated regulatory network was further constructed through cis-regulatory elements (CREs) analysis of their promoter regions and revealed that several transcriptional factor (TF) gene family were abundant as the potential regulators for orchid AREB/ABFs. Expression profile analysis based on public transcriptomic data showed that most AREB/ABF genes have distinct tissue-specific expression patterns in orchid plants. Additionally, DcaABI5 as the homolog of ABA INSENSITIVE 5 (ABI5) from Arabidopsis was selected for further analysis. The results showed that Arabidopsis transgenic overexpressing DcaABI5 could rescue the ABA insensitive phenotype in the mutant abi5. Collectively, these findings will provide valuable information on AREB/ABF genes in orchids.

Researchers are exploring solutions to meet the growing demand for protein due to the expected increase in global population by 2050. Interest in alternative protein sources like insects has risen, driven by concerns about environmental impact and the need for sustainable food production. This study aimed to develop and evaluate the physicochemical properties of soy protein-based burger enriched with insect protein from Alphitobius diaperinus. Three formulations were developed: a control (B0), and burgers with 5% (B5) and 10% (B10) insect protein - Whole Buffalo Powder (WBP). Results showed that adding insect protein decreased the burger analogue's pH. There was observed a clear trend of increasing total lipids and SFA, and decreasing MUFA and PUFA, as the WBP concentration increases from 0% to 10%. No significant differences with increasing WBP concentration in the protein content of the burger analogue, as well as the cooking yield, were noted. The WBP addition had a notable effect on the color change, especially decrease in brightness (L*). It was shown that as the WBP concentration increased, there were no significant differences in the texture profile of the burger analogues. The formulation with 5% WBP concentration was the most acceptable in sensory analysis.

Fungal infections caused by Candida spp. are responsible for high hospital morbidity and mortality rates. Therefore, there is a continuous search for new antifungal medicines, particularly ones with anti-Candida activity. This review analyzed articles published between 2002 and 2023 considering the anti-Candida activity of chemical compounds identified or isolated in plants of the Anacardiaceae family. In addition, the in-silico prediction of the isolated compounds described was performed. The analysis of 35 studies showed that extracts, essential oils, and compounds from the anti-Candida activity were frequently determined in vitro using the minimum inhibitory concentration (MIC). The most commonly tested species were Candida albicans, C. tropicalis, C. parapsilosis, C. glabrata, C. krusei, and C. guilliermondii, respectively. Essential oils were the most used form (37% of the studies). The isolated compounds with antifungal effects include cardanol, estragole, trans-anethole, β-caryophyllene, myrcene, catechin-3-o-rhamnoside, β-sitosterol-3-O-glucoside, 24Z-isomasticadienolic acid, oleanolic acid, and oleanolic aldehyde. The in-silico evaluation of those isolated compounds revealed the compounds' drug-likeness and possible antifungal activity. However, some of them showed high toxicity. In conclusion, compounds from the Anacardiaceae family show promise for developing new therapeutic antifungal drugs, especially in combination with conventional antifungals.

Chronic diseases, such as type 2 diabetes (T2D), are difficult to manage because they demand continuous therapeutic review and monitoring. Beyond achieving the target HbA1c, new guidelines for the therapy of T2D have been introduced with the new groups of antidiabetics (GLP-1ra and SGLT2-in). Despite new guidelines, clinical inertia, that can be caused by physicians, patients or healthcare system, results in T2D not being effectively managed. This opinion paper explores the shift in T2D treatment, challenging assumptions and evidence-based recommendations, particularly for family physicians, considering the patient's overall situation in decision-making. We looked for the possible reasons of clinical inertia and poor application of guidelines in the management of T2D. Guidelines for antidiabetic drugs should be more precise, providing case studies and clinical examples to define clinical contexts and contraindications. Knowledge communication can improve confidence and should include clear statements on areas of decision-making not supported by evidence. Precision medicine initiative in diabetes aims to identify subcategories of T2D patients (including frail patients) using clustering techniques from data science applications, focusing on CV and poor treatment outcomes. Clear, unconditional recommendations for personalized T2D management may encourage drug prescription, especially for family physicians dealing with diverse patient contexts and clinical settings.

This study demonstrates the viability of an orange peel-based adsorbent as sustainable alternative for the elimination of the disperse dye C.I. Disperse Blue 56 present in waste waters of the dyeing industry of textiles. The effectiveness of the adsorbent is evaluated at different pH values and the adsorption capacity is determined by systematically comparing orange peel and the final adsorbent chemically treated. Results reveal an spontaneous coagulation-flocculation phenomenon of the dispersed dye at low pH values which represents a sustainable way for the recovery and possible re-use of the dye, together with the industrial valorisation of a wasting product as is orange peel.

Indoleamine 2,3-dioxygenase 1 (IDO1) and IDO2, originated from gene duplication before vertebrate diver-gence. While IDO1 has a well-defined role in immune regulation, the biological role of IDO2 remains unclear. Discovered in 2007, IDO2 is located near the IDO1 gene. Because of their high sequence similarity, IDO2 was initially thought to be a tryptophan (Trp)-degrading enzyme like IDO1. Differently from what expected, IDO2 displays extremely low catalytic activity toward Trp. Nevertheless, many studies, often contradictory, tried to demonstrate that IDO2 modulates immune responses by catabolizing Trp into kynurenine, a hypothesis un-convincing and, let’s say, linked to the first life of IDO2. Here, we review its “new life”, the one in which IDO2 has a functional role beyond Trp metabolism. The IDO2’s evolutionary persistence across species, despite be-ing almost inactive as an enzyme, suggests it has some relevant biological importance. IDO2 expression in human normal cells is poor, but significant in various cancers, with two prevalent SNPs. Overall, the com-parison of IDO2 to IDO1 as a Trp-degrading enzyme may have led to misunderstandings about IDO2’s true physiological and pathological roles. New insights suggest that IDO2 might function more as a signaling molecule, particularly in cancer contexts, and further studies could reveal its potential as a target for cancer therapy.

: F-box proteins are a large gene family in plants, and play crucial roles in plant growth, development, and stress response. However, a comprehensive investigation of F-box family genes in cultivated peanut (Arachis hypogaea L.), has not been undertaken. In this study, we used a bioinformatics approach to identify and analyze F-box protein family genes in the cultivated peanut genome, and examined their expression profiles. Herein, a total of 95 F-box protein family members on 18 chromosomes were identified in cultivated peanut, which were sequentially designed as AhFBX1-AhFBX95. Phylogenetic analysis classified these AhFBXs into four different groups (Group I - IV), and eight subfamilies based on the structural domains of the C-terminal. Structural analysis revealed the presence of ten unique motifs within these genes. Additionally, the investigation of non-synonymous and synonymous substitution rates (Ka/Ks), and synteny in the F-box proteins, provided valuable insights into the evolutionary and domestication processes of AhFBX genes in peanut. Furthermore, in silico expression profiling of 22 different tissues demonstrated that most genes were predominantly expressed in leaves, pistils, and the aerial gynophore tip, while some members showed tissue-specific expression at the apex of both vegetative and reproductive shoots. Subsequently, we validated the expression of 9 differentially expressed genes (DEGs) using transcriptomeic data of lateral branch development and qRT-PCR analysis. These DEGs may be involved in regulating the development of lateral branches and subsequently affect the architecture of peanut plants.

The emergence of the coronavirus 19 (COVID-19) has posed a major challenge to healthcare systems worldwide, especially as COVID-19 mutations complicate the development of vaccines and antiviral drugs. Therefore, the search for natural products with broad anti-COVID-19 capabilities is an important option for the prevention and treatment of infectious diseases. Lectins, which are widely recognized as antiviral agents, could contribute to the development of anti-COVID-19 drugs. In this study, we evaluated the binding ability of a total of six lectins, including MVL from Microcystis viridis NIES-102, to the spike protein RBD of the original (wild) COVID-19 and it’s three mutants: alpha, delta, and omicron. As a result, two lectins, MVL from Microcystis viridis NIES-102 and jacalin from Artocarpus altilis, showed distinct binding ability to the RBDs of the four COVID-19 strains. The other lectins (DB1, ConA, PHA-M and CSL3) did not show any binding ability. Although the glycan specificities of the two lectins, MVL and Jacalin, were different, they showed the same affinity for the RBDs of the four COVID-19 strains, i.e., alpha &gt; delta &gt; original &gt; omicron. The verification of glycan-specific inhibition revealed that jacalin binds to RBDs by glycan-specific recognition, whereas MVL binds to RBDs by protein-protein interactions in addition to glycan-specific recognition.

Existing scales assessing family relations are usually quite long. Our aim was to develop and validate the Family Functioning and Cohesion Scale (FFCS), a self-reported short instrument consisting of 14 items. The validation of the FFCS was based on its administration through an online platform to 481 subjects living in 46 different countries around the world. Cronbach's alpha was 0.85 (ranging from 0.83 to 0.86 if any one item was deleted), signifying high internal consistency. The scale can be considered as a sole factor based on its high consistency, while factor analysis produced three factors corresponding to “communication”, “anger/resentment/aggression” and “values and beliefs”. Test-retest reliability correlation coefficient was found to be 0.88 at a 2-week interval. As far as external validity is concerned, the correlation coefficient of the FFCS with the General Functioning subscale of the McMaster Family Assessment Device (FAD) was 0.83. The high measures of consistency, reliability, and validity of the FFCS, combined with its short length, make it an invaluable tool for use in research as well as in any professional dealing with families in the clinical fields of psychiatry, psychology, social work or any other relevant specialty.

The BET family of proteins is characterized by the presence of two tandem bromodomains and an extra-terminal domain. The mammalian BET family of proteins comprises Brd2, Brd3, Brd4, and Brdt, which are encoded by paralogous genes that may have been generated by repeated duplication of an ancestral gene during evolution. Bromodomains that can specifically bind acetylated lysine residues in histones serve as chromatin-targeting modules that decipher the histone acetylation code. BET proteins play a crucial role in regulating gene transcription through epigenetic interactions between bromodomains and acetylated histones during cellular proliferation and differentiation processes. On the other hand, BET proteins have been reported to mediate latent viral infection in host cells and be involved in oncogenesis. Human BRD4 is involved in multiple processes of the DNA virus life cycle, including viral replication, genome maintenance, and gene transcription through interaction with viral proteins. Aberrant BRD4 expression contributes to carcinogenesis by mediating hyperacetylation of the chromatin containing the cell proliferation-promoting genes. BET bromodomain blockade using small-molecule inhibitors gives rise to selective repression of the transcriptional network driven by c-Myc. These inhibitors are expected to be potential therapeutic drugs for a wide range of cancers. This review presents an overview of the basic roles of BET proteins and highlights the pathological functions of BET and the recent developments in cancer therapy targeting BET proteins in animal models.

There is a lack of studies on the level of stress and health of families of workers in road transport. This study aimed to evaluate the perceived stress level and Family Effectiveness of family members of road transport workers. A quantitative study was carried out with family members of road transport workers in the southern region of Brazil. For the data collection, a sociodemographic form, the Perceived Stress Scale (PSS), and the Evaluation of Family Effectiveness Strategies were used. The data were analyzed by simple frequency, Spearman correlation coefficient (ρ) (p &lt; 0.05), and descriptive analysis from the perspective of the Systemic Organization. 49 family members of road transport workers were participants. Perceived stress was higher in family members who had more than nine years of schooling, the targets of Control and Growth were higher in the evaluation of Family Effectiveness. The Control target was also higher in families with more than three people. The Coherence dimension had higher levels in families with health problems and whose income was less than $792.00 US dollars per month. In the Individuation dimension, income over $792.00 had better results. The Maintenance dimension of the system was higher in families whose drivers’ activity was as an intercity driver, as well as in the Stability target. In conclusion, the social factors such as schooling, income, diseases, type of worker activity in road transport, and number of people in the family influenced perceived stress and Family Effectiveness, which demonstrates the need to increase the promotion of health care of the families of road transport workers.

Abstract. Graphene family (GF)-Calcium phosphate (CaP) composites, holds great potential as components of bone regeneration materials. GF nanomaterials can be modified physically as well as chemically, which are to be biomimetic, mechanically to be hard due to their capability to support exceptional mechanical, thermal and electronic properties. These biocompatible GF composites coated on the calcium phosphate can enhance and tolerate stem cell growth and differentiation, proliferation into various lineages or interact with bioorganisms. The development in CF-CaP materials and their physicochemical/biointeractions and strategies towards osteoblasts is a great concern to promote faster healing and reconstructions of large bone imperfections or defects. In this review, we explain the influence of the CF-CaP and summarize recent developments on designing CF-CaP architectures as multifunctional bone regeneration platforms. We have also explored the typical biological applications concerning these CF-CaP based bioactive nanocomposites. Furthermore, the future viewpoints and evolving challenges will also be emphasized. Due to the shortage of full-length reviews in this emerging research field, this review would be caught great attention and encourage various new chances across a wider range of disciplines.

Usually, the two-bath dyeing process using disperse dyes and reactive dyes separately was employed for the dyeing of PC blends. The cost of the double bath, dyeing cycle, energy consumption and chemical consumption is quite higher than the one-step or single bath dyeing methods. In this study, the one-bath dyeing process using one kind of dye was investigated. Polyester cotton blends dyed in one-bath one-step dyeing methods with disperse dye after surface modifications of cotton by acetylation methods were studied. Surface modification of cotton was carried out using fibrous acetylation methods. The effect of acetic anhydride and time on percent acetyl content at room temperature was studied. Modified polyester/cotton was carried out in HTHP dyeing machine incorporates with different dye concentrations and dyeing temperature. Surface chemistry, thermal decomposition property and moisture regain of modified polyester/ cotton blend are evaluated. The color strength of the dyed fabrics and their fastness properties to washing, light, and rubbing as well as tear strength and abrasion resistance were evaluated. The effect of dye concentration and temperature color strength, tensile strength warp and weft direction was assessed. The optimum value for surface modification was obtained with a concentration of acetylation agent 16% and time of reaction 2.5 hours, gave percent acetylation of 34. An FTIR spectrum shows acetylation resonance. The experiment result of dyeing showed that the optimum value was obtained with dye concentration above 1% at a temperature of 120oC, warp tensile strength decreased by 12% and weft tensile strength was decreased by 9% from the control half-bleached fabric. Results of this study showed that a one-step one-bath dyed modified polyester/cotton blend with disperse dye fabric presents good fastness property compared with conventional two-bath dyed fabric as well as colour strength values.

The p53 tumor suppressor protein shows antiviral activity. The replication of viruses is also antagonized by interferons (IFNs) – cytokines, which control immunity genes by the STAT transcription factors. The best studied interferons belong to type I (e.g. IFNα) and type II (IFNγ) groups. IFNα and IFNγ both induce activating phosphorylation of STAT1 on Tyr701. Previously, we noticed that p53 activates SOCS1, which is a negative regulator of STAT1 phosphorylation. Thus, we hypothesized that p53 by activating SOCS1 expression reduces phosphorylation of STAT1 and attenuates activation of genes stimulated either by IFNα or IFNγ. To test this hypothesis, we exposed p53-proficient and p53-deficient cells to strong p53 activators, and either to IFNα or IFNγ. Subsequently, we estimated the phosphorylation status of STAT1 and the expression of genes regulated by either of these cytokines. Strong activation of p53 reduced the phosphorylation of STAT1 on Tyr701, however surprisingly it did not lead to reduced expression of most tested interferon-stimulated genes. On contrary, p53 and IFNγ synergized in the activation of CASP1, IFIT1 and IFIT3 genes. We conclude that the interactions between p53 and interferon-activated pathways are more complicated than initially expected, but the apparent cooperation between p53 and IFNγ deserves further studies.

Diacylglycerol kinase (DGK) is a lipid kinase that phosphorylates diacylglycerol (DAG) to generate phosphatidic acid (PA). Based on converting one important signaling molecule (DAG) to another (PA), DGK plays an important role in plant responses to abiotic stress including waterlogging stress. However, no studies have been reported on the characterization of the DGK gene family in the waterlogging-tolerant kiwifruit germplasm, Actinidia valvata Dunn. Here, we identified 18 AvDGK genes in the A. valvata genome. The phylogenetic analysis showed that AvDGKs can be classified into three clusters, and members within the same cluster have similar domain distribution, exon-intron structures and conserved motif compositions. Chromosome localization analysis revealed that all the AvDGK genes are located across 18 different chromosomes. There were 29 duplicated gene pairs in kiwifruit and all had undergone purifying selection during evolution. Promoter cis-element analysis revealed that the cis-elements within AvDGK genes are associated with multiple functions, including phytohormone signal transduction, stress response, and plant growth and development. The expression pattern analyses indicated that AvDGK play an important role in the fruit development and plant response to waterlogging stress. AvDGKs gene family in the tetraploid A. valvata genome might promote PA synthesis and subsequent signal transduction both under short-term and long-term waterlogging stress. These results provide information regarding the structural characteristics and potential function of DGK genes within kiwifruit and lay a fundamental basis for further research into breeding for enhancing the kiwifruit’s tolerance to waterlogging stress.

HIV-associated cardiovascular diseases remain a leading cause of death in people living with HIV/AIDS (PLWHA). Although antiretroviral drugs suppress the viral load, they fail to remove the virus entirely. HIV-1 Nef protein is known to play a role in viral virulence and HIV latency. Expression of Nef protein can be detected in different organs, including cardiac tissue. Despite the established role of Nef protein in HIV-1 replication, its impact on organ function inside the human body is not clear. To understand the effect of Nef at the organ level, we created a new Nef transgenic (Nef-TG) mouse that expresses Nef protein in the heart. Our study found that Nef expression caused inhibition of cardiac function and pathological changes in the heart with increased fibrosis, leading to heart failure and early mortality. Further, we found that cellular autophagy is significantly inhibited in cardiac tissue of Nef-TG mice. Mechanistically, we found that Nef protein causes the accumulation of Bcl2 and Beclin-1 protein in the tissue, which may affect the cellular autophagy system. Additionally, we found Nef expression causes upregulation of cellular senescence marker p21, and senescence-associated -galactosidase expression. Our findings suggested that Nef-mediated inhibition of autophagy and induction of senescence markers may promote aging in the PLWHA. Our mouse model could help us to understand the effect of Nef protein on organ function during latent HIV infection.

This paper aims to explore differences in personality traits, focusing on the levels of primary psychopathy, between formal leaders of family and non-family companies as well as assessing differences in the job satisfaction levels of their employees. Moreover, we assess the relationship between the employees' perception of their formal leader’s primary psychopathy levels and their job satisfaction levels in family firms. The empirical evidence is provided by a sample of 95 Portuguese employees, who responded to a questionnaire that included their perception of their formal leader’s primary psychopathy level and job satisfaction measures. All respondents work in small and medium-sized private companies with no management responsibilities and under formal hieratical supervision. The initial idea that family firms’ employees perceive lower levels of primary psychopathy in their formal leaders than non-family firms’ employees was confirmed. However, employees of family and non-family firms did not differ in their job satisfaction levels. The results also support the notion that perceived levels of primary psychopathy in formal leaders are negatively associated with the employees’ job satisfaction levels. These findings contribute to the research literature by addressing two aspects under-addressed in the comparison between family and non-family firms, while offering insights on the relationship between primary psychopathy in formal leaders and job satisfaction levels of employees working in family firms.

Preschoolers with disabilities and their caregivers have been neglected in health and social service provision in most low-income countries and arguably too in low resourced areas of more affluent nations. Yet as this rapid review of published literature identifies, there are low-cost, evidence-based strategies to address their needs that can be implemented in communities by local people. Five key features of the necessary supports are examined. First the leadership functions required to create and implement the support services. Second, the family-centred, home-based support provided to caregivers and the personnel undertaking this form of support. Third, providing opportunities for peer support to flourish and encouraging the formation of advocacy groups across families. Fourth, mobilizing the support of significant groups within the community; notably traditional healers and leaders; health services and poverty alleviation initiatives. Fifth, devising ways in which preschool educational opportunities can be offered to children as a prelude to their inclusion in primary schools. The review serves a further purpose. It provides an example of how public health researchers and academics could achieve more rapid implementation of evidence-based knowledge into existing and new support services through dissemination to community practitioners.

The primary objective of this study was to identify a rapid and noninvasive methodology for effectively differentiating various herbal species cultivated in Eastern Poland. Typically, a plant's chemical profile is obtained using chromatographic methods; however, spectroscopic methods can serve as a complementary or independent tool for determining similarities in the analyzed samples. The investigation centered on leaves of plant species from the Lamiaceae family, encompassing basil, lavender, oregano, sage, and thyme. UV-VIS and ATR-FTIR spectra of dried plant samples' powder were recorded and subsequently analyzed using chemometric tools. This paper assesses the relative performance of different discrimination methods, including both traditional methods based on machine learning and those dealing with specimens associated with a specific category. Among the methodologies tested, SIMCA showed the best performance, particularly effective for small training sets.

No one can dismiss the fundamental role played by water in several important biochemical processes, including the folding of globular proteins. The so-called hydrophobic effect is the theoretical construction to rationalize how water molecules stabilize the folded state. However, over the years, analyses have been published that lead to the conclusion that water destabilizes the folded state. The aim of the present work is to state that the gain in translational entropy of water molecules (due to the decrease in water accessible surface area associated with folding) is the driving force of protein folding.

Abstract: A. baumannii exhibits resilience in harsh environments and progressively develops resistance to diverse antibacterial agents over time. This adaptability poses a significant challenge in treating an infection caused by this bacterium within healthcare settings. The presence of peptidoglycan, a crucial precursor for cell wall synthesis, contributes to this challenge. Peptidoglycan serves not only as a structural support in bacterial cells but also provides protection against adverse environmental conditions. The synthesis of the peptidoglycan layer involves a group of substrates such as N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc), within a three-partitioned process occurring in the membrane, periplasmic space, and cytoplasm of each bacterium. Initiated in the cytoplasm and extending to the inner cell membrane, this synthesis starts with the production of nucleotide precursors. The first step involves the synthesis of UDP-GlcNAc, orchestrated by Glm (GlmS, GlmM, and GlmU) enzymes using fructose-6-phosphate. Subsequently, enzymes from the Mur family, namely MurB, MurA, MurD, MurC, MurI, MurF, and MurE, synthesize UDP-N-acetylmuramyl-pentapeptide (UDP-Mpp) from UDP-GlcNAc. Concurrently, on the cytosolic side, the production of membrane-surrounded undecaprenyl phosphate occurs, involving membrane-side proteins MraY and MurG in the biosynthesis of peptidoglycan. This review emphasizes updated information on Mur family proteins, encompassing physicochemical properties, nature of binding site, number and type of binding site residues, functional domain details, three-dimensional structural aspects, and their functions within bacterial cells. Special attention is directed towards their enzymatic role in peptidoglycan biosynthesis due to the limited availability of precursors in the market. Additionally, the review provides a comprehensive summary of existing inhibitors and ongoing efforts in identifying new targeted inhibitors, recognizing these enzymes as potential candidates for antibacterial drug design and discovery.

Herpes simplex virus 1 (HSV-1) expresses a large number of miRNAs, and their function is still not completely understood. In addition, HSV-1 has been found to deregulate host miRNAs, which adds to the complexity of regulation of efficient virus replication. In this study, we comprehen-sively addressed the deregulation of host miRNAs by massive-parallel sequencing. We found that only miRNAs expressed from a single cluster, miR-183/96/182 are reproducibly deregulated dur-ing productive infection. These miRNAs are predicted to regulate a great number of potential tar-gets involved in different cellular processes and have only 33 shared targets. Among these, mem-bers of the FoxO family of proteins were identified as potential targets for all three miRNAs. However, our study shows that the upregulated miRNAs do not affect the expression of FoxO proteins, moreover these proteins were upregulated in HSV-1 infection. Furthermore, we show that the individual FoxO proteins are not required for efficient HSV-1 replication. Taken together, our results indicate a complex and redundant response of infected cells to the virus infection that is efficiently inhibited by the virus.

The problem of Yukawa couplings being arbitrary parameters in the Standard Model Higgs mechanism is a long standing one due to their formulaic dependence on the Higgs Vacuum Expectation Value. We will attempt to solve this problem and provide a strong argument that the Yukawa couplings of charged leptons and down type quarks are not arbitrary parameters in the SM. A new methodology for predicting the Yukawa couplings will be presented by using Compton wavelengths, the Rydberg Constant and g-factors of charged leptons instead of relying on the Higgs VEV. We will then proceed to rewrite this new method in terms of an empirical formula that depends on the running of the fine-structure constant on the Q scale, charge and lepton quantum numbers and g-factors to predict the values of the Yukawa couplings for all three generations of charged leptons and d-type quarks. We will also touch on the subject of neutrinos both as Majorana and Dirac fermions respectively and make a prediction for the lightest possible Majorana neutrino and the differences between Dirac neutrinos and anti-neutrinos. We conclude that the Yukawa couplings are not arbitrary parameters in the SM and that this new formula provides very accurate results.

Background and Objectives: Wilson disease (WD) is a disorder of copper metabolism caused by genetic muta-tions in the ATP7B gene which lead to the accumulation of copper in the body. The aim of the present study is to investigate the severity of WD in patients in Romania. Materials and Methods: This study was conducted us-ing an online questionnaire consisting of 32 questions in a group of patients suffering from Wilson disease. Results: The study included 67 people aged 7 to 56 with WD. The most common symptoms of the participants were hepatic and neurological in 22 cases (32.8%). The most common neurological symptom in the assessed cases was muscle stiffness (49.5%), followed by tremor (45%), and speech disorders (40.5%). The Kay-ser-Fleischer ring was present in 50.7% of the participants. The most commonly used drug treatment in the participants was D-penicillamine (77.61%). Conclusions: The severity of WD is based on many aspects, the most important being early diagnosis and access to treatment throughout the year. The prognosis is favorable with early diagnosis and treatment, but it is crucial to diagnose individuals before they develop major symp-toms. Therefore, advances in WD screening can lead to an earlier diagnosis and better results.

A previous report showed that the urine output of HPLBII-P in patients with diabetes mellitus and SARS-Cov-2 infection was increased as a sign of glomerular dysfunction. . The aim of this report was to investigate the relation of urine output of HPLBII-P to diabetes mellitus in two large community-based elderly populations i.e. the ULSAM and PIVUS cohorts. Methods HPLBII-P was measured by ELISA in the urine of a community-based cohort of 839 men (ULSAM) collected at 77 years of age and in urine of a community-based cohort of 75-year-old men, n=387, and women, n=401 (PIVUS). KIM-1, NGAL and Albumin were measured in urine and Cathepsin S and Cystatin C in serum. Results HPLBII-P was significantly raised among males with diabetes in the ULSAM (p

Cow milk is rich in proteins, fats, carbohydrates, and minerals, and its nutrient content depends on various factors. We tested differences in fatty acid and protein contents of milk from seven breeds and regions, including three dairy breed samples: Holstein milk from Beijing, China (BH); Holstein milk from Hebei province, China; Jersey milk (JS); and four dairy/meat cow samples: Sanhe milk, Xinjiang brown milk (XH), Simmental milk, and Shu Xuanhua milk. Breed significantly affected total fat, fatty acid, and protein contents. The region significantly affected the contents of different fatty acids, α-lactalbumin, and lactoferrin. JS had the highest total fat, most fatty acids, and casein contents. XH performed well with significantly higher unsaturated fatty acid content than BH, which was not significantly different from JS, and its protein composition of low β-lactoglobulin and high lactoferrin was more similar to breast milk, which may thus be favorable to the growth and development of children. Our results may inform the development of dairy products from different cow breeds and advance the process of accurate breed identification.

Dengue virus is a global health problem most prevalent in tropical and subtropical regions. However, after the approval of two vaccines, Dengvaxia, TV003/TV005 of Takeda, for its prevention, problems were reported, like enhanced risks of infection or less efficiency of protection. Since then, more struggles have been in demand for the development of better vaccines. Here, we conducted a new design through an in-silico strategy. Initially, epitopes were chosen based on their antigenicity, immunogenicity, and binding affinity with MHC molecule, while excluded with allergenicity, toxicity and potential risk of antibody dependent enhancement. Subsequently, a core antigen was constructed with selected epitopes and linked with distinct adjuvant proteins to achieve three candidate vaccines, PSDV-1~3. PSDV-2 was chosen for further validation based on their advantage in physicochemical and structural properties. With a panel of simulations, this artificial protein showed tight binding with pattern recognition receptors, good stability, robust immune induction, and ultimately was confirmed as a high quality vaccine candidate. The plasmid for its recombinant expression was then designed accordingly. With our new design, one more choice was obtained for the effective protection from Dengue virus. Further experimental validations are still require to confirm it protection capacity and safety.

Limited understanding exists regarding the intricate dynamics between the levels of social inhi-bition exhibited by both wives and husbands concerning their perceived family support and de-pressive symptoms, particularly within couples who are parents of children diagnosed with au-tism spectrum disorder (ASD). This study used the actor-partner, interdependence mediation model to analyze data collected from 397 pairs of Chinese parents with children diagnosed with ASD. The findings of the study revealed significant indirect actor effects, indicating that the levels of social inhibition exhibited by both wives and husbands were associated with their own de-pressive symptoms through their respective perceptions of family support. In general, the study did not find significant partner effects, except for some indirect effect (IE) of wives on their hus-bands' depressive symptoms through the wives' perceived social support. This observation sug-gests that cultural norms and role expectations within the family context may influence these dy-namics. These results underscore the potential importance of interventions aimed at addressing social inhibition and enhancing perceived family support to alleviate depressive symptoms in this population. Additionally, interventions targeting fathers should emphasize the importance of their involvement in parenting and collaboration with their partners in caring for children with ASD. Such collaborative efforts may contribute to improved outcomes for both parents and chil-dren within families affected by ASD.

The apicomplexan parasite, Sarcocystis neurona causes the degenerative neurological equine protozoal myeloencephalitis (EPM) disease of horses. Due to its host range expansion, S. neurona is an emerging threat that requires close monitoring. In apicomplexans, protein kinases (PKs) have been implicated in a myriad of critical functions such as host cell invasion, cell cycle progression and host immune responses evasion. Here, we used various bioinformatics methods to define the kinome of S. neurona and phylogenetic relatedness of its PKs to other apicomplexans. Further, three-dimensional (3D) homology models for selected S. neurona putative PKs were constructed and evaluated for inhibitor docking. We identified 92 putative PKs clustering within the AGC, CAMK, CK1, CMGC, STE, TKL, aPK and OPK groups. Although containing the universally conserved PKA (AGC group), S. neurona kinome was devoid of PKB and PKC, but contained the six apicomplexan conserved CDPKs (CAMK group). The OPK group was represented by ROPKs 19A, 27, 30, 33, 35 and 37, but was devoid of the virulence-associated ROPKs 5, 6, 18 and 38. Two out of the three S. neurona CK1 enzymes had high sequence similarities to T. gondii TgCK1-α and TgCK1-β and the Plasmodium PfCK1. Docking of four inhibitors onto homology models of putative ROP27 and PKA indicated that inhibition of S. neurona PKs is feasible, but needs to be experimentally tested. The essentiality of apicomplexan PKs makes the elucidation of S. neurona kinome a key milestone for development of novel therapeutics for EPM.

The global food production system faces several challenges, including significant environmental impacts due to traditional agricultural practices. The rising demands of consumers for food products that are safe, healthy, and have animal welfare standards have led to an increased interest in alternative proteins and the development of the cellular agriculture field. Within this innovative field, precision fermentation emerges as a promising technological solution to produce proteins with reduced ecological footprints. This review provides a summary of the environmental impacts related to the current global food production, and explore how precision fermentation can contribute to address these issues. Additionally, we will report on the main animal-derived proteins produced by precision fermentation, with a particular focus on those used in the food and nutraceutical industries. The general principles of precision fermentation will be explained, including strain and bioprocess optimization. Examples of efficient recombinant protein production by bacteria and yeasts, such as milk proteins, egg-white proteins, structural and flavoring proteins, will also be addressed, along with case examples of companies producing these recombinant proteins in a commercial scale. Through these examples, we will explore how precision fermentation supports sustainable food production and holds the potential for significant innovations in the sector.

Long COVID, also referred to as post-COVID-19 condition, describes the lingering after-effects of COVID-19 infection. This complex syndrome encompasses a range of symptoms affecting physical well-being, cognitive function, and mental health. The widespread impact of long COVID extends beyond individual sufferers, placing significant strain on healthcare systems and causing far-reaching socioeconomic consequences. The scale of this multifaceted health crisis is unparalleled in recent history, affecting millions globally and challenging our understanding of post-viral conditions. This study aimed to explore the possibility of targeting G protein-coupled receptors (GPCRs) signaling pathway-related genes as therapeutics for long COVID using computational analysis. Targeting GPCRs and their signaling pathways holds significant promise for long COVID therapeutics, as these receptors are involved in crucial physiological processes including immune regulation, inflammation control, and neurotransmission. All of these are implicated in the diverse and persistent symptoms of long COVID, potentially offering a versatile approach to addressing multiple aspects of the condition simultaneously. This study identified 21 genes associated with GPCRs for further exploration as potential targets. Notably, GPCR genes such as HRAS, KRAS, GNAQ, and GNA11 were determined to be possible therapeutic targets for the pathophysiological mechanisms of long COVID. FDA-approved drugs targeting these genes were identified, including Binimetinib, Cabozantinib, Selumetinib, Panitumumab, Cetuximab, Adagrasib, Tipifarnib, and Sotorasib. Additionally, Naltrexone and Tipifarnib have emerged as potential new treatment options for long COVID. SARS-CoV-2 may hijack GPCR signaling pathways to dysregulate lung ion and fluid transport, contributing to the pathophysiology of pulmonary edema in patients with COVID-19. Further research is required to translate the findings into the development of therapeutics and to investigate the relationship between viral infection and GPCR signalling.

Magnesium (Mg) is a vital element, which involves in various key cellular processes in plants. Mg transporter (MGT) genes play an important role in magnesium distribution and ionic balance maintenance. Here, MGT family members were identified and characterized in three species of the plant family Malvaceae, including Theobroma cacao, Corchorus capsularis, and Gossypium hirsutum to improve our understanding of their structure, regulatory systems, functions, and possible interactions. We identified 18, 41, and 16 putative non-redundant MGT genes from the genome of T. cacao, G. hirsutum, and C. capsularis, respectively, which were clustered into five groups within maximum likelihood tree. Several segmental/tandem duplication events were determined between MGTs genes. It seems that MGTs were slowly evolving and have been evolved under a purifying selection. Analysis of gene promoter regions showed that MGTs have a high potential to respond to biotic/abiotic stresses as well as hormones. The expression patterns of MGT genes revealed their possible T. cacaorole in response to P. megakarya fungi in T. cacao, whereas MGT genes showed differential expression in various tissues and respond to several abiotic stresses, including cold, salt, drought, and heat stress in G. hirsutum. Besides, the co-expressions network of MGTs indicated that genes involved in auxin responsive, lipid metabolism, cell wall organization, and photoprotection can interact with MGTs.

Proteins need to be located in appropriate spatiotemporal contexts to carry out their diverse biological functions. Mislocalized proteins may lead to a broad range of diseases, such as cancer and Alzheimer’s disease. Knowing where a target protein resides within a cell will give insights into tailored drug design for a disease. As the gold validation standard, the conventional wet lab uses fluorescent microscopy imaging, immunoelectron microscopy, and fluorescent biomarker tags for protein subcellular location identification. However, the booming era of proteomics and high-throughput sequencing generates tons of newly discovered proteins, making protein subcel-lular localization by wet-lab experiments a mission impossible. To tackle this concern, in the past decades, artificial intelligence (AI) and machine learning (ML), especially deep learning methods, have made significant progress in this research area. In this article, we review the latest advances in AI-based method development in three typical types of approaches, including sequence-based, knowledge-based, and image-based methods. We also elaborately discuss existing challenges and future directions in AI-based method development in this research field.

COVID-19 has rapidly spread worldwide since December 2019. During the pandemic, SARS-CoV-2 repeatedly mutated from Alpha to Omicron. The severity and mortality are related to age, sex, and underlying diseases (respiratory, cerebrovascular, cardiovascular, metabolic, cancer, and immune diseases). We retrospectively studied 44 hospitalized stroke patients infected with the SARS-CoV-2 Omicron variant. The mortality rate of hospitalized stroke patients with COVID-19 was 6 (13.6%). The cause of death was coagulopathy in 3 cases of ischemic stroke. High modified Rankin Scale score（mRS）of stroke patient was correlated with severity of COVID-19. The timing of vaccination is inversely correlated with COVID-19 severity. In conclusion, stroke patients with COVID-19 have high mortality rates attributed to coagulopathy. Stroke patients with high mRS scores are more likely to develop severe COVID-19. In high mRS scores, therapy for severe COVID-19 should be administered.

Kiwifruit is a perennial horticultural crop species with high nutritional and economic value. However, various pathogens stress brings a serious threat to kiwifruit. Pentatricopeptide repeat proteins (PPRs) are characterized by tandem repetitions of 35 amino acid motifs, and have been found to function in plant RNA editing. However, the roles of PPRs in plant development and disease resistance remain unclear. In this study, we performed a genome-wide identification and characterization of PPR gene family in two kiwifruit species (Actinidia chinensis (Ach), and Actinidia eriantha (Ace)) with markedly different disease resistance. A total of 497 and 499 PPRs were identified in Ach and Ace, respectively. All the kiwifruit PPRs could be phylogenetically divided into four subfamilies. There were about 40.68% PPRs predicted to be localized to mitochondria or chloroplasts. Synteny analysis showed that the expansion of kiwifruit PPRs mainly came from segmental duplication. Based on RNA-seq data from the fruit during 12 periods of development and maturity, weighted correlation network analysis suggested that two PPRs Actinidia20495.t1 and Actinidia15159.t1 were involved in the fruit development and maturation. In addition, we observed different gene expression of PPRs and chloroplast RNA editing profiles between resistant and susceptible kiwifruits after pathogen infection, indicating the roles of PPRs in stress response by modulating the editing extend of mRNA. The differentially expressed upstream transcription factors of PPRs were further identified, they may regulate resistance adaption by modulating the PPRs expression. These results provide a solid foundation for further analyses of the functions and molecular evolution of PPRs, in particular, for clarifying the resistance mechanisms in kiwifruits and breeding new cultivars with high resistance.

Placental protein 13 (PP13) exhibits a plasma concentration that increases gradually during normal gestation, a process disrupted in preeclampsia, characterized by elevated vascular resistance, re-duced utero-placental blood flow and intrauterine growth restriction. This study investigated PP13’s role in vascular tone regulation and its molecular mechanisms. Uterine and subcutaneous arteries isolated from both pregnant and non-pregnant women were precontracted with the thromboxane analogue U46619, and exposed to PP13 using pressurized myography. The molecular mechanisms were further investigated using specific inhibitors for ni-tric oxide synthase (L-NAME+LNNA at 10-4 M) and guanylate cyclase (ODQ at 10-5 M). Results showed PP13 induced vasodilation in uterine arteries but not in subcutaneous arteries. Ad-ditionally, PP13 counteract U46619-induced vasoconstriction, which is particularly pronounced in pregnancy. Further investigation revealed that PP13's mechanism of action is dependent on activa-tion of the Nitric oxide-cGMP pathway. This study provides novel insights into the vasomodulatory effects of PP13 on human uterine ar-teries, underscoring its potential role in regulating utero-placental blood flow. These findings suggest PP13 may be a promising candidate for improving utero-placental blood flow in condi-tions such as preeclampsia. Further research and clinical studies are warranted to validate PP13's efficacy and safety as a therapeutic agent for managing preeclampsia.

Nutrient profiling (NP) models that assess nutrient density of foods can help remedy micronutrient deficiencies. We used NP methods to identify the most nutrient-rich foods in the 2019 FAO/INFOODS Western Africa Food Composition Table (WAFCT). The WAFCT had complete data for 909 foods. Three versions of the well-established Nutrient Rich Food (NRF) model were used: 1) the original NRF9.3; 2) a new NRF6.3 based on 6 priority micronutrients (iron, zinc, calcium, folate, vitamin A, vitamin B12); and 3) NRF 15.3, based on 15 nutrients to encourage (NRF6.3 nutrients + vitamin D, vitamin E, vitamin C, vitamin B1, vitamin B2, vitamin B3, vitamin B6, copper, and magnesium). Data analyses used one-way ANOVAs and independent t-tests, with significance at α=0.05. Animal-source foods were rated higher by NRF6.3 priority micronutrient and NRF15.3 NP models than by the NRF9.3 model. African indigenous vegetables had higher protein content and higher nutrient density compared to non-indigenous vegetables. African indigenous grains had higher nutrient density compared to non-indigenous grains. Though animal-source foods received some of the highest scores, NP models adapted to the West African context showed that African indigenous vegetables and grains were also nutrient rich. Indigenous foods could be important sources of priority micronutrients for the region.

Chronic inflammation alters lipoprotein metabolism and causes changes in serum concentrations of lipids, C-reactive protein (CRP), and paraoxonase-1 activity (PON-1), an enzyme, which in the gastrointestinal tract may act as a local detoxifier, antioxidant, and immunomodulator. However, unlike in people with inflammatory bowel disease, scarce information is available in dogs with protein-losing enteropathy secondary to chronic inflammatory enteropathy (iPLE). The first aim was to describe and compare the lipid profile, CRP concentrations and PON-1 activity in healthy dogs and in dogs with iPLE. The second aim was to evaluate correlations among clinicopathological, histologic data, and lipid profiles in dogs with iPLE. Serum samples from 51 iPLE and 40 healthy dogs were used to study albumin, total protein, CRP, PON-1 activity, cholesterol, triglycerides, and lipoprotein classes obtained by electrophoretic separation. There was a significant difference of all serum analytes between iPLE and healthy dogs. Significant correlations between the lipid profile and the existing chronic enteropathy activity index were not found. Some lipoprotein classes correlated with CRP and PON-1. Triglycerides were significantly higher in dogs with both inflammation and lymphangiectasia. Lipoproteins, CRP and PON-1 activity are altered in dogs with iPLE. Results need to be confirmed in further studies.

Rice prolamins are categorized into three groups by molecular size (10, 13, or 16 kDa), while the 13 kDa prolamins are assigned to four subgroups (Pro13a-I, Pro13a-II, Pro13b-I, and Pro13b-II) based on cysteine residue content. Here, we generated four knockout strains of rice using CRISPR-Cas9, each of which demonstrated selectively reduced expression of specific subgroups of the 13 kDa prolamins. These four mutant rice lines also demonstrated compensatory expression of glutelins and non-targeted prolamins, which resulted in low grain weight, altered starch content and atypically-shaped starch granules and protein bodies. Transcriptome analysis identified 746 transcripts that were differentially expressed in the mutant rice lines during development. These transcripts played roles primarily in RNA processing, protein synthesis, stress response, and transport. After selective suppression/knockout of genes in the Pro13a-I subgroup, compensatory upregulation of genes in the Pro13a-II and Pro13b-I/II subgroups was observed. Compensatory expression of 9 ER stress and 17 transcription factor genes was also observed in mutant rice in which expression of 13 kDa prolamin genes was suppressed. Our results provide valuable insight into the regulatory mechanisms underlying rice seed development and the specific roles played by 13 kDa rice prolamins and their target genes.

The criteria of “Distinctness, Uniformity and Stability” as well as a high "overall quality index” are used to register the Italian modern varieties to the national register. Differently, local conservation varieties can be certified under different EU Directives having, as overall objective, the preservation of biodiversity and the containment of genetic erosion. In recent years, products derived from an-cient grains are perceived to be healthier and more sustainable by consumer, especially in Italy, with consequent higher market prices. Ancient tetraploid wheat varieties registered in the national reg-ister of conservation varieties are 28, 24 of which are Sicilian. They are supposed to have a wide genetic variability compared to modern ones, making them vulnerable of fraud because they are difficult to trace. It is therefore important to have tools able to discriminate the autochthonous Si-cilian varieties. This can be done by gluten proteins composition, which also gives information on the technological properties of derived products. Fifty-one accessions belonging to 22 ancient va-rieties of Sicilian tetraploid (mostly durum) wheat were analyzed. Although a wide intra-accession and intra-varietal variability was assessed, the gliadin pattern of bulks of seeds belonging to each variety was discriminatory. Moreover, differences in technological attitudes were found between landraces. This paves the way to use gluten protein patterns for traceability allowing local farmers and producers to valorize their products and assure consumers about the transparency of the entire supply chain.

Lp16-PSP from Lentinula edodes strain C91-3 has been reported previously in our laboratory to have selective cytotoxic activity against a panel of human cell lines. Herein, we have used several parameters in order to characterize the Lp16-PSP-induced cell death using HL-60 as model cancer. The results of phase contrast microscopy, nuclear examination, DNA fragmentation detection and flow cytometry revealed that high doses of Lp16-PSP resulted in the induction of apoptosis in HL-60 cells. The colorimetric assay showed the activation of caspase-8, -9 and -3 cascade highlighting the involvement of Fas/FasL-related pathway. Whereas, western blot revealed the cleavage of caspase-3, increased expression of Bax, the release of cytochrome c and decreased expression of Bcl-2 in a dose-dependent manner, suggesting the intrinsic pathway might be involved in Lp16-PSP-induced apoptosis either. Low doses of Lp16-PSP resulted in the anchorage-independent growth inhibition, induction of G1 phase arrest accompanied by the increased expression of p21WAF1/CIP1 along with the decreased expression of cyclin D, E, and cdk6. Our findings suggest that induction of apoptosis and p21WAF1/CIP1 mediated G1 arrest might be one of the mechanisms of the action of Lp16-PSP, however, further investigations on multiple leukemia cell lines and in vivo models are of ultimate need.

The Characteristics of the cardiac muscle cell are described as a rod-shaped structure, single nu-cleus, and intercalated discs which make the heart’s action practical for enhancing contraction ef-ficiency. Mitochondria within these cells are vital for ATP synthesis, redox balance, calcium ho-meostasis, and lipid synthesis. The crucial role of Hsp60 is in protein folding and immune re-sponses; Hsp60 is a mitochondrial chaperonin, and its expression rises when the heart is under a stress condition like myocardial infarction and heart failure. This review has tried to deeply un-derstand the structural resemblance between cardiac and skeletal muscle cells, the amplitude number of mitochondria, its roles in cardiomyocytes, and the polyhedral functions of Hsp60. In this review, by investigating various articles, we brighten up Hsp60's distribution within cells, its association with apoptosis, and its action as a Damage Associated Molecular Pattern (DAMP), interacting with Toll-like receptors to modulate immune responses. Cardiac remodeling and failure are linked to cardiac-specific micro-RNAs whose expression may be affected by dysregu-lation of Hsp60. In conclusion, targeting mitochondrial function and Hsp60 expression may be of therapeutic potential for heart diseases.

Human milk (HM) feedings are associated with reduced risks of neurodevelopmental and neurocognitive delays and systemic inflammatory diseases in infants born prematurely and/or at a low birth weight. Utilizing a neonatal piglet model, HM feedings were compared to bovine milk-derived infant formula (IF)-feedings with the aim of understanding the underlying mechanisms involved in reducing these risks. Six male piglets at postnatal-day (PD)2 were randomized into two feeding groups: HM-fed (n = 3) or IF-fed (n = 3) for 28 days. At 3- and 4-weeks-old, piglet memory and learning performance were assessed using novel object recognition (NOR). At PD30 piglets were euthanized, and whole brains were excised, weighed, and preserved for further analyses, and brain microglial morphology, and systemic inflammatory cytokines were quantified. During NOR, HM-fed piglets had significantly more non-novel revisits at both 3- and 4-weeks-old compared to IF-fed piglets. Microglia of HM-fed piglets had longer processes, more branch points, more endpoints, and a larger territorial volume compared to IF-fed piglets at PD30. In a neonatal piglet model, HM-feedings may improve cognition and reduce brain inflammatory response compared to IF-feedings.

Lactococcus lactis is a potential bacterial cell factory to develop delivery systems for vaccines and therapeutic proteins. Large progress has been made in applications using engineered L. lactis against, e.g., inflammatory bowel disease and cervical cancer, but improvement of secretion and cell anchoring efficacy is still desirable. A double-labelling method based on biarsenical hairpin binding and nickel-polyhistidine affinity was used for visualization of protein trafficking and quantification of targeted proteins on the cell surface and in the cytoplasm. To investigate the importance of mature domain targeting signals (MTSs), we generated truncated constructs encoding 126, 66, and 26 amino acid residues from the N-terminus of the basic membrane protein A (BmpA) and fused those with the gene for the human papillomavirus serotype 16 (HPV16) E7 oncoprotein. Overexpression of fusion proteins was observed to come at a cost of cell proliferation. L. lactis cells produced and displayed the shortest fusion protein only with difficulty, suggesting that the entire absence of a homologous sequence containing MTSs significantly impedes export and surface anchoring of fusion proteins. With 40 amino acids following the signal peptide and containing one MTS, effective translocation was possible. Mutations of MTSs towards increased hydrophobicity resulted in an increase of secreted and surface-displayed fusion protein, suggesting the potential to design rationally improved constructs.

Titanium dioxide nanoparticles (TiO2NPs) are used in products that are applied to the human body, such as cosmetics and food, but their biocompatibility remains controversial. Pycnogenol (PYC), a natural extract of pine bark, exerts anti-inflammatory and antioxidant effects. In this study, we investigated whether PYC effectively alleviates pulmonary toxicity induced by airway exposure to TiO2NPs, and the beneficial effects of PYC were explained through the analysis of changes to the mechanism of cytotoxicity. TiO2NPs induced pulmonary inflammation and mucus production, increased the levels of malondialdehyde, and upregulated thioredoxin-interacting protein (TXNIP) and cleaved-caspase 3 (Cas3) in the lungs of mice. However, PYC treatment reduced the levels of all toxicity markers of TiO2NPs and restored glutathione levels. These antioxidant and anti-inflammatory effects of PYC were also demonstrated in TiO2NP-exposed human airway epithelial cells by increasing the mRNA levels of antioxidant enzymes and decreasing the expression of TXNIP, cleaved-Cas3, and inflammatory mediators. Taken together, our results showed that PYC attenuated TiO2NP-induced lung injury via TXNIP downregulation. Therefore, our results suggest the potential of PYC as an effective anti-inflammatory and antioxidant agent against TiO2NP-induced pulmonary toxicity.

This overview of extant Siphonaptera lists 19 families with major hosts and general distribution, estimated numbers of genera, species, and subspecies, with a brief taxonomic and phylogenetic review. With around 10 new species described annually, global flea fauna has an estimated extant 249 genera, 2215 species, and 714 subspecies, mostly mammal parasites but 5% of species are on birds. Host specificity varies from euryxenous (i.e. infesting two or more host orders)(e.g. cat fleas, Ctenocephalides felis felis) to monoxenous (e.g. rabbit fleas, Spilopsyllus cuniculi) . The largest family is the paraphyletic Hystrichopsyllidae, making up a third of all flea species. The largest monophyletic family, Ceratophyllidae (rodent and bird fleas), comprise another 20%, and has dispersed to every continent including Antarctica. Fleas descend from scorpionflies (Mecoptera), possibly snow scorpionflies (Boreidae) or Nannochoristidae, and even giant fossils found from the Mesozoic could be Siphonaptera. Flea diversification shows evidence of taxon cycles: "Relict" families such as helmet fleas (Stephanocircidae) have a disjunct distribution reflecting the breakup of Gondwanaland, 70 million years ago. "Niche specialists" include nest fleas (Anomiopsyllus), bat fleas (Ischnopsyllidae), and burrowing fleas, the chigoes (Tungidae). By contrast, Ceratophyllidae fleas could be considered "great speciators". Cat fleas and several other synanthropic flea species are invasive "supertramps". Although those species are intensively studied, many flea species and their hosts require urgent surveys and conservation.

Chlamydia trachomatis (Ct) infections are the most common sexually-transmitted infection (STI). Despite effective antibiotics for Ct, undetected infections or delayed treatment can lead to infertility, ectopic pregnancies, and chronic pelvic pain. Besides humans, chlamydia poses similar health challenges in animals such as C. suis (Cs) in pigs. Based on the similarities between humans and pigs as well as their chlamydia species, we use pigs as a large biomedical animal model for chlamydia research. In this study, we use the pig model to develop a vaccine candidate against Ct. The vaccine candidate consists of TriAdj-adjuvanted chlamydial protease-like activity factor (CPAF) protein. We tested two weekly administration options – twice intranasal (IN) followed by twice intramuscular (IM), or twice IM followed by twice IN. We assessed the humoral immune response not only in serum by CPAF-specific IgG including antibody avidity determination but also in cervical and rectal swabs by CPAF-specific IgG and IgA ELISAs. The systemic T-cell response was analyzed upon in vitro CPAF-restimulation via IFN-γ and IL-17 ELISpots as well as intracellular cytokine staining flow cytometry. Our data demonstrate that while the IN/IM vaccination mainly led to non-significant systemic immune responses, the vaccine candidate is highly immunogenic if administered IM/IN. This vaccination strategy induced high serum anti-CPAF IgG levels with strong avidity as well as high IgA and IgG levels in vaginal and rectal swabs and in uterine horn flushes. In addition, this vaccination strategy prompted a pronounced cellular immune response: Besides inducing IL-17 production, the vaccine candidate induced a strong IFN-γ response by CD4 T cells. In the IM/IN vaccinated pigs, these cells also significantly downregulated their CCR7 expression – a sign for differentiation into peripheral tissue homing effector/ memory cells. Conclusively, this study demonstrates strong immunogenicity of the IM/IN administered TriAdj-adjuvanted Ct CPAF vaccine candidate. Future studies will test vaccine efficacy of this promising Ct vaccine candidate. In addition, this project demonstrates suitability of the Cs pre-exposed outbred pig model for Ct vaccine development. Thereby, we aim to open the bottleneck of large animal models to facilitate the progression of Ct vaccine candidates into clinical trials.