Morphological and molecular analyses of a Philine kinglipini outbreak in summer of 2022 in Jiaozhou Bay,China

A sudden and unprecedented outbreak of molluscan Philine kinglipini occurred in summer 2022 in Jiaozhou Bay,Shandong,China,causing substantial damage to local mariculture industry of the Manila clam Ruditapes philippinarum.Although P.kinglipini has been found in many coastal regions of China,the molecular research of P.kinglipini has not been extensively studied,making it difficult to accurately identify and track P.kinglipini samples in field using molecular methods.Samples were collected during the outbreak and their morphological features and molecular sequences were analyzed.Results show that the causative species of the outbreak was P.kinglipini.The mitochondrial genome(mt DNA)of P.kinglipini was constructed for the first time,based on which phylogenetic analysis of the mt DNAs of P.kinglipini and related species in the order Cephalaspidea was carried out.As revealed by metabarcoding analysis of 18S rDNA V4,the seasonal change of P.kinglipini and closely related Philine species was striking with peaks between April and August.Therefore,metabarcoding analysis is applicable tool for monitoring the bloom development of P.kinglipini and related species.This study generated for the first time essential molecular marker sequences and mtDNA of P.kinglipini,which provided a reference for future characterization and monitoring of its outbreaks and for phylogenetic analysis of Philine species.

Adverse effects of early-life stress:focus on the rodent neuroendocrine system

Early-life stress is associated with a high prevalence of mental illnesses such as post-traumatic stress disorders,attention-deficit/hyperactivity disorder,schizophrenia,and anxiety or depressive behavior,which constitute major public health problems.In the early stages of brain development after birth,events such as synaptogenesis,neuron maturation,and glial differentiation occur in a highly orchestrated manner,and external stress can cause adverse long-term effects throughout life.Our body utilizes multifaceted mechanisms,including neuroendocrine and neurotransmitter signaling pathways,to appropriately process external stress.Newborn individuals first exposed to early-life stress deploy neurogenesis as a stress-defense mechanism;however,in adulthood,early-life stress induces apoptosis of mature neurons,activation of immune responses,and reduction of neurotrophic factors,leading to anxiety,depression,and cognitive and memory dysfunction.This process involves the hypothalamus-pituitary-adrenal axis and neurotransmitters secreted by the central nervous system,including norepinephrine,dopamine,and serotonin.The rodent early-life stress model is generally used to experimentally assess the effects of stress during neurodevelopment.This paper reviews the use of the early-life stress model and stress response mechanisms of the body and discusses the experimental results regarding how early-life stress mediates stress-related pathways at a high vulnerability of psychiatric disorder in adulthood.

Pathogenic contribution of cholesteryl ester accumulation in the brain to neurodegenerative disorders

Cholesteryl esters(CEs) have been increasingly implicated in neurodegenerative disorders such as Alzheimer's disease(AD).Alois Alzheimer noted three prominent neuropathologic features in his original analysis of the AD brain:senile plaques,neurofibrillary tangles,and lipid granule accumulation.Senile plaques,which are aggregates of amyloid-beta(Aβ),and neurofibrillary tangles,which are aggregates of phosphorylated tau,have been regarded as more consistent characteristics of the AD brain compared with lipid granule accumulation and thus have been studied more intensively(Foley,2010).

Role of fullerenols derivative 3HFWC in the treatment of Alzheimer's disease

Fullerenes:The extensive development of nanoscience that has marked this century continues to evolve,producing new materials,structures,and devices for the treatments of diverse pathologies.Fullerenes are a family of nanoparticles with great applicative promise due to their small size(approximately 1 nm in diameter),structure,and capacity to cross biological barriers.

Histopathological impact of SARS-CoV-2 on the liver:Cellular damage and long-term complications

Coronavirus disease 2019(COVID-19),caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),primarily impacts the respiratory tract and can lead to severe outcomes such as acute respiratory distress syndrome,multiple organ failure,and death.Despite extensive studies on the pathogenicity of SARS-CoV-2,its impact on the hepatobiliary system remains unclear.While liver injury is commonly indicated by reduced albumin and elevated bilirubin and transaminase levels,the exact source of this damage is not fully understood.Proposed mechanisms for injury include direct cytotoxicity,collateral damage from inflammation,drug-induced liver injury,and ischemia/hypoxia.However,evidence often relies on blood tests with liver enzyme abnormalities.In this comprehensive review,we focused solely on the different histopathological manifestations of liver injury in COVID-19 patients,drawing from liver biopsies,complete autopsies,and in vitro liver analyses.We present evidence of the direct impact of SARS-CoV-2 on the liver,substantiated by in vitro observations of viral entry mechanisms and the actual presence of viral particles in liver samples resulting in a variety of cellular changes,including mitochondrial swelling,endoplasmic reticulum dilatation,and hepatocyte apoptosis.Additional ly,we describe the diverse liver pathology observed during COVID-19 infection,encompassing necrosis,steatosis,cholestasis,and lobular inflammation.We also discuss the emergence of long-term complications,notably COVID-19-related secondary sclerosing cholangitis.Recognizing the histopathological liver changes occurring during COVID-19 infection is pivotal for improving patient recovery and guiding decision-making.

Is Veillonella a unique marker of physical exercise?Commentary on:

In 2020,Kostic1 published commentary on the bacterial genus Veillonella associated with the interaction between the intestinal microbiota and skeletal muscle.Since then,novel perspectives on the bidirectional gut-muscle communication axis have gained a lot of attention.The purpose of this commentary is to explore some of the challenging issues presented in Scheiman et al.

Immunohistochemical Profile of Breast Cancer: A Retrospective Study in the Democratic Republic of Congo

Background: The management of breast cancer increasingly requires molecular classification based on immunohistochemistry. As breast cancer is a heterogeneous disease characterized by the accumulation of multiple molecular alterations that give each tumour its own phenotype and evolutionary potential, immunohistochemistry, as a complementary technique to morphological examination, determines the status of hormone receptors and on protein in tumour cells, which are predictive and prognostic markers of breast cancer. This technique is often little used in the Democratic Republic of Congo (DRC), as this study shows. The under-use of this technique due to a lack of equipment and/or human skills explains the paucity of epidemiological data available to date. Objective: Determine the immunohistochemical profile of breast cancer. Methodology: This is a retrospective study carried out in the Anapath Department of the NGANDA Hospital from January 1, 2020 to December 31, 2022, i.e. a 3-year period. Result: A total of 736 patients were registered in the hospitalization register of the Oncology Department of CH NGANDA for the period corresponding to the present study. Breast cancer was diagnosed in 110 patients, representing 14.9% of all cases. The mean age of the patients was 58.4 ± 8.2 years, with extremes ranging from 30 to 76 years. Breast nodules were the most common reason for diagnosis in 56.3% of cases, with Luminal A dominating in 17.3%. Conclusion: Breast cancer is a major public health problem. Worldwide, it is the most frequently diagnosed cancer in women and the leading cause of cancer-related death in women. In the Democratic Republic of Congo, because of the delay in consulting our patients and the weakness of systematic screening, patients are seen at an advanced stage of the disease. Treatment is multidisciplinary, involving surgery, radiotherapy, chemotherapy (including targeted therapies) and hormone therapy. Patient awareness and screening campaigns will contribute to a considerable reduction in the delay in diagnosis and the morbidity and mortality associated with breast cancer.

Association of Fusobacterium nucleatum with immunity andmolecular alterations in colorectal cancer

The human intestinal microbiome plays a major role in human health and diseases, including colorectal cancer. Colorectal carcinogenesis represents a heterogeneous process with a differing set of somatic molecular alterations, influenced by diet, environmental and microbial exposures, and host immunity. Fusobacterium species are part of the human oral and intestinal microbiota. Metagenomic analyses have shown an enrichment of Fusobacterium nucleatum(F. nucleatum) in colorectal carcinoma tissue. Using 511 colorectal carcinomas from Japanese patients, we assessed the presence of F. nucleatum. Our results showed that the frequency of F. nucleatum positivity in the Japanese colorectal cancer was 8.6%(44/511), which was lower than that in United States cohort studies(13%). Similar to the United States studies, F. nucleatum positivityin Japanese colorectal cancers was significantly associated with microsatellite instability(MSI)-high status. Regarding the immune response in colorectal cancer, high levels of infiltrating T-cell subsets(i.e., CD3+, CD8+, CD45RO+, and FOXP3+ cells) have been associated with better patient prognosis. There is also evidence to indicate that molecular features of colorectal cancer, especially MSI, influence T-cell-mediated adaptive immunity. Concerning the association between the gut microbiome and immunity, F. nucleatum has been shown to expand myeloid-derived immune cells, which inhibit T-cell proliferation and induce T-cell apoptosis in colorectal cancer. This finding indicates that F. nucleatum possesses immunosuppressive activities by inhibiting human T-cell responses. Certain micro RNAs are induced during the macrophage inflammatory response and have the ability to regulate host-cell responses to pathogens. Micro RNA-21 increases the levels of IL-10 and prostaglandin E2, which suppress antitumor T-cell-mediated adaptive immunity through the inhibition of the antigen-presenting capacities of dendritic cells and T-cell proliferation in colorectal cancer cells. Thus, emerging evidence may provide insights for strategies to target microbiota, immune cells and tumor molecular alterations for colorectal cancer prevention and treatment. Further investigation is needed to clarify the association of Fusobacterium with T-cells and micro RNA expressions in colorectal cancer.

Current Status of Conventional and Molecular Interventions for Blast Resistance in Rice

Pyricularia oryzae anamorph of Magnaporthe oryzae is one of the most notorious fungal pathogens causing severe economic loss in rice production worldwide. Various methods, viz. cultural, biological and molecular approaches, are utilized to counteract this pathogen. Moreover, some tolerant or resistant rice varieties have been developed with the help of breeding programmes. Isolation and molecular characterization of different blast resistance genes now open the gate for new possibilities to elucidate the actual allelic variants of these genes via various molecular breeding and transgenic approaches. However, the behavioral pattern of this fungus breakups the resistance barriers in the resistant or tolerant rice varieties. This host-pathogen barrier will be possibly countered in future research by comparative genomics data from available genome sequence data of rice and M. oryzae for durable resistance. Present review emphasized fascinating recent updates, new molecular breeding approaches, transgenic and genomics approaches(i.e. mi RNA and genome editing) for the management of blast disease in rice. The updated information will be helpful for the durable, resistance breeding programme in rice against blast pathogen.

Molecular basis of cleft palates in mice

Cleft palate, including complete or incomplete cleft palates, soft palate clefts, and submucosal cleft palates, is the most frequent congenital craniofacial anomaly in humans. Multifactorial conditions, including genetic and environmental factors, induce the formation of cleft palates. The process of palatogenesis is temporospatially regulated by transcription factors, growth factors, extracellular matrix proteins, and membranous molecules; a single ablation of these molecules can result in a cleft palate in vivo. Studies on knockout mice were reviewed in order to identify genetic errors that lead to cleft palates. In this review, we systematically describe these mutant mice and discuss the molecular mechanisms of palatogenesis.

Knowledge and associated factors of healthcare workers on measles vaccine and cold chain management at health institutions in Gondar,Ethiopia

Objective:To assess the knowledge of healthcare workers on the measles vaccine and its cold chain management.Method:An institutional-based cross-sectional study was conducted from February 1 to March 30,2022 in Gondar City Administration public health institutions among 165 healthcare workers.Data were collected using a structured questionnaire.In addition,an on-spot observation checklist was used to assess the availability,status and management of the cold chain.A logistic regression model was used to assess the relationship between the outcome and predictor variables.Crude and adjusted odds ratios were calculated with 95%confidence intervals.Results:Overall,87(52.7%;95%CI 44.8%-60.5%)of the healthcare workers had unsatisfactory knowledge regarding the measles vaccine and its cold chain management.One hundred thirty-six(82.4%)healthcare workers correctly mentioned the recommended range of temperature(2-8℃)for measles vaccine storage.Healthcare workers aged 18-29 years(P=0.001)and 30-44 years(P=0.014)were observed as determinants of unsatisfactory knowledge on the measles vaccine and its cold chain management.One hundred and five(63.6%)of the healthcare workers did not correctly mention the type of measles vaccine used in routine immunization.More than one-third(36.4%)of the healthcare workers perceived that the measles vaccine is not safe and could cause measles.Conclusions:More than half of the healthcare workers in the study area had unsatisfactory knowledge on the measles vaccine and its cold chain management.It is necessary to provide technical support and in-service training for healthcare workers to ensure optimal immunization effectiveness.

Molecular predictive markers in tumors of the gastrointestinal tract

Gastrointestinal malignancies are among the leading causes of cancer-related deaths worldwide. Like all human malignancies they are characterized by accumulation of mutations which lead to inactivation of tumor suppressor genes or activation of oncogenes. Advances in Molecular Biology techniques have allowed for more accurate analysis of tumors' genetic profiling using new breakthrough technologies such as next generation sequencing(NGS), leading to the development of targeted therapeutical approaches based upon biomarker-selection. During the last 10 years tremendous advances in the development of targeted therapies for patients with advanced cancer have been made, thus various targeted agents, associated with predictive biomarkers, have been developed or are in development for the treatment of patients with gastrointestinal cancer patients. This review summarizes the advances in the field of molecular biomarkers in tumors of the gastrointestinal tract, with focus on the available NGS platforms that enable comprehensive tumor molecular profile analysis.

IGF2 differentially methylated region hypomethylation in relation to pathological and molecular features of serrated lesions

AIM:To investigate insulin-like growth factor 2(IGF2)differentially methylated region(DMR)0 hypomethylation in relation to clinicopathological and molecular features in colorectal serrated lesions.METHODS:To accurately analyze the association between the histological types and molecular features of each type of serrated lesion,we consecutively collected1386 formalin-fixed paraffin-embedded tissue specimens that comprised all histological types[hyperplastic polyps(HPs,n=121),sessile serrated adenomas(SSAs,n=132),traditional serrated adenomas(TSAs,n=111),non-serrated adenomas(n=195),and colorectal cancers(n=827)].We evaluated the methylation levels of IGF2 DMR0 and long interspersed nucleotide element-1(LINE-1)in HPs(n=115),SSAs(n=120),SSAs with cytological dysplasia(n=10),TSAs(n=91),TSAs with high-grade dysplasia(HGD)(n=15),non-serrated adenomas(n=80),non-serrated adenomas with HGD(n=105),and CRCs(n=794).For the accurate quantification of the relative methylation levels(scale 0%-100%)of IGF2 DMR0 and LINE-1,we used bisulfite pyrosequencing method.Tumor specimens were analyzed for microsatellite instability,KRAS(codons 12 and 13),BRAF(V600E),and PIK3CA(exons 9and 20)mutations;MLH1 and MGMT methylation;and IGF2 expression by immunohistochemistry.RESULTS:The distribution of the IGF2 DMR0 methylation level in 351 serrated lesions and 185 non-serrated adenomas(with or without HGD)was as follows:mean61.7,median 62.5,SD 18.0,range 5.0-99.0,interquartile range 49.5-74.4.The IGF2 DMR0 methylation level was divided into quartiles(Q1≥74.5,Q2 62.6-74.4,Q3 49.6-62.5,Q4≤49.5)for further analysis.With regard to the histological type,the IGF2 DMR0 methylation levels of SSAs(mean±SD,73.1±12.3)were significantly higher than those of HPs(61.9±20.5),TSAs(61.6±19.6),and non-serrated adenomas(59.0±15.8)(P<0.0001).The IGF2 DMR0 methylation level was inversely correlated with the IGF2 expression level(r=-0.21,P=0.0051).IGF2 DMR0 hypomethylation was less frequently detected in SSAs compared with HPs,TSAs,and non-serrated adenomas(P<0.0001).Multivariate logistic regression analysis also showed that IGF2 DMR0 hypomethylation was inversely associated with SSAs(P<0.0001).The methylation levels of IGF2 DMR0 and LINE-1 in TSAs with HGD(50.2±18.7and 55.7±5.4,respectively)were significantly lower than those in TSAs(61.6±19.6 and 58.8±4.7,respectively)(IGF2 DMR0,P=0.038;LINE-1,P=0.024).CONCLUSION:IGF2 DMR0 hypomethylation may be an infrequent epigenetic alteration in the SSA pathway.Hypomethylation of IGF2 DMR0 and LINE-1 may play a role in TSA pathway progression.

Dissecting the effects of androgen deprivation therapy on cadherin switching in advanced prostate cancer: A molecular perspective

Prostate cancer is one of the most often diagnosed malignancies in males and its prevalence is rising in both developed and developing countries.Androgen deprivation therapy has been used as a standard treatment approach for advanced prostate cancer for more than 80 years.The primary aim of androgen deprivation therapy is to decrease circulatory androgen and block androgen signaling.Although a partly remediation is accomplished at the beginning of treatment,some cell populations become refractory to androgen deprivation therapy and continue to metastasize.Recent evidences suggest that androgen deprivation therapy may cause cadherin switching,from E-cadherin to N-cadherin,which is the hallmark of epithelial-mesenchymal transition.Diverse direct and indirect mechanisms are involved in this switching and consequently,the cadherin pool changes from E-cadherin to N-cadherin in the epithelial cells.Since E-cadherin represses invasive and migrative behaviors of the tumor cells,the loss of E-cadherin disrupts epithelial tissue structure leading to the release of tumor cells into surrounding tissues and circulation.In this study,we review the androgen deprivation therapy-dependent cadherin switching in advanced prostate cancer with emphasis on its molecular basis especially the transcriptional factors regulated through TFG-βpathway.

Molecular Identification of Co-Existence of Carbapenemase and Extended-Spectrum <i>β</i>-Lactamase Genes in <i>Klebsiella pneumoniae</i>Clinical Isolates, and Their Phylogenetic Patterns in Kenya

The increasing incidence of multidrug-resistant Klebsiella pneumoniae strains has become a serious global healthcare problem. Additionally, the carriage of both extended-spectrum ß-lactamase and carbapenemase genes on plasmid and genomic DNA in K. pneumoniae clinical isolates has not been documented in Kenya. This study aimed to assess the presence of extended spectrum β-lactamase (ESBL) and carbapenemase genes on genomic and plasmid DNA in K. pneumoniae, and classify these super-bug clinical isolates based on their phylogenetic patterns. The identification of Klebsiella-like clinical isolates (n = 20) collected from Kenyatta National Hospital in Nairobi was performed using API 20E Kit. Screening and confirmation for ESBL and carbapenemase phenotypes were conducted using Kirby-Bauer disk diffusion susceptibility test protocol. Conventional PCR technique was used to characterize ESBL and carbapenemase resistant genes on both genomic and plasmid DNA. Subsequently, 16S rRNA gene amplification and sequencing were performed. The 16S rRNA gene contiguous sequences of the bacterial isolates were analyzed using the ChromasPro. The gene sequence was compared with the sequences in GenBank database, using the BLAST program of NCBI to obtain the nearest phylogenetic neighbours from the databases. Then, the sequences of MDR K. pneumoniae and its relatives were aligned using ClustalW. The evolutionary history was inferred by using the maximum likelihood algorithm in MEGA MX. The phenotypic data of antibiotic susceptibility testing revealed that 2/20 (10%) clinical isolates were resistant both to imipenem and meropenem and producers of carbapenemase. These isolates were carbapenemase producers but not extended β-lactamases. However, 3/20 (15%) isolates that co-harboured blaNDM-1, blaIMP, blaTEM, and bla-OXA were identified during genotypic analysis. The positive control used separately yielded the expected band sizes for blaIMP (275 bp), blaOXA-48 (438 bp), and BlaKPC (798). The phylogenetic analysis showed the dual ESBL and carbapenemase producing Klebsiella pneumoniae could be classified as K. pneumoniae strain DSM 30104 and K. pneumonia subsp. pneumoniae strain GMH1080. This study confirmed the co-existence of ESBL and carbapenemase genes in Klebsiella pneumoniae on both bacterial genomic and Plasmid DNA, and demonstrated that the isolates are evolutionarily distinct. These findings raise a concern about the genotypic diversity of antibiotic resistance genes in bacterial isolates and their location. We, therefore, recommend an alternative management approach to combat these MDR bacterial isolates as well as frequent molecular surveillance programs to support antimicrobial stewardship.

Molecular docking simulation analysis of the interaction of dietary flavonols with heat shock protein 90

Hsp90 is a major protein involved in the stabilization of various proteins in cancer cells.The present investigation focused on the molecular docking simulation studies of flavanols as inhibitors of Hsp90 at the high affinity adenosine triphosphate（ATP）binding site and analyzed absorption,distribution,metabolism,excretion and toxicity（ADME-toxicity）.The molecular docking analysis revealed that the flavanols showed competitive inhibition with ATP molecule at the active site and enhanced pharmacological parameters.

Molecular Investigation of Genetic Signatures of Selection in <i>Plasmodium falciparum</i>Actin-Binding Protein Coronin, Cysteine Desulfurase, and Plasmepsin 2 Gene in Mbita Field Isolates, Western Kenya

Background: Plasmodium falciparum (Pf) resistance to antimalarial drugs is a major impediment to malaria control. The Pf.Kelch 13 (PfK13) gene has been largely reported to be associated with artemisinin resistance. However, recent studies have shown artemisinin resistance without Kech13 mutations suggesting the implication of others genes in artemisinin resistance. In this current study, we focused on mutations in Pf.actin-binding protein coronin, Pf.cysteine desulfurase and Pf.plasmepsin 2 gene, three putative candidates recently were reported to be involved in artemisinin, lumefantrine and piperaquine resistance respectively. Method: Archived blood samples previously collected from asymptomatic school children from December 2016 to October 2018 were used in this study. Genomic DNA was extracted using ISOLATE II Genomic DNA kit. After PCR amplification, amplicons were purified and sequenced by capillary sequencing. Reads were analyzed for the identification of point mutations previously reported to be involved in drug selection. Results: Mutations R100K, and G50E involved in reduced artemisinin susceptibility were detected in Pfcoronin. From 2016/17 to 2018 the allele 100k increased frequency (11.2%);while 50E was only observed in 2018 time point reaching 11.1%. Lumefantrine selection marker K65, in codon (K65Q) was observed at 14.2% in Pfcysteine desulfurase, and the mutant’ allele 65Q gradually increased frequency from 28.5% in 2016/17 to 57.1% in 2018. Pf.plasmepsin 2 was the less polymorphic gene. Several other polymorphism codons and single nucleotide variants were detected. Conclusion: The findings indicate the presence of mutations associated with reduced artemisinin susceptibility and lumefantrine selection marker. Therefore, the results call for continuous monitoring of molecular makers in Mbita parasites.

The role of small non-coding RNAs(sncRNAs)in male infertility:A scoping review

Objective:To give a brief overview of the field of epigenetics and the potential predictive power that small non-coding RNA(sncRNA)may hold in relation to improving the treatment and diagnosis of male infertility.Methods:PRISMA-ScR was used as the scoping review guideline for this investigation.All article data here have been accessed from MEDLINE–PubMed,Science Direct,EBSCO,Scopus,Sage Journals,and Google Scholar.The terms"small non coding RNA,male,infertility,miRNA,sperm"were used in the search between 2015 and 2023.Results:The study comprised 35 publications in total.Several sncRNAs,miR-155,miR-16,miR-196,miR-525-3p,miR-891 were found to be effective in regulating the mechanism of spermatozoa processing in the infertility of men.sncRNA can be used as a biomarker of male infertility.Conclusions:sncRNAs can act as biomarkers for the diagnosis of reproductive diseases.Actually,by recognizing sncRNAs and their mechanisms,a new way to treat infertile men would be paved.The functional annotation of sncRNAs in spermatogenesis is still in its infancy but has enormous potential.This is despite the fact that many potential sncRNAs have been found to date with the use of cutting-edge technology and publicly accessible sncRNA annotation tools.