Pericytes may facilitate SARS-CoV-2 entry into the nervous system

Objective:Although the neurological and olfactory symptoms of coronavirus disease 2019 have been identified,the neurotropic properties of the causative virus,severe acute respiratory syndrome-associated coronavirus 2(SARS-CoV-2),remain unknown.We sought to identify the susceptible cell types and potential routes of SARS-CoV-2 entry into the central nervous system,olfactory system,and respiratory system.Methods:We collected single-cell RNA data from normal brain and nasal epithelium specimens,along with bronchial,tracheal,and lung specimens in public datasets.The susceptible cell types that express SARS-CoV-2 entry genes were identified using single-cell RNA sequencing and the expression of the key genes at protein levels was verified by immunohistochemistry.We compared the coexpression patterns of the entry receptor angiotensin-converting enzyme 2(ACE2)and the spike protein priming enzyme transmembrane serine protease(TMPRSS)/cathepsin L among the specimens.Results:The SARS-CoV-2 entry receptor ACE2 and the spike protein priming enzyme TMPRSS/cathepsin L were coexpressed by pericytes in brain tissue;this coexpression was confirmed by immunohistochemistry.In the nasal epithelium,ciliated cells and sustentacular cells exhibited strong coexpression of ACE2 and TMPRSS.Neurons and glia in the brain and nasal epithelium did not exhibit coexpression of ACE2 and TMPRSS.However,coexpression was present in ciliated cells,vascular smooth muscle cells,and fibroblasts in tracheal tissue;ciliated cells and goblet cells in bronchial tissue;and alveolar epithelium type 1 cells,AT2 cells,and ciliated cells in lung tissue.Conclusion:Neurological symptoms in patients with coronavirus disease 2019 could be associated with SARS-CoV-2 invasion across the blood-brain barrier via pericytes.Additionally,SARS-CoV-2-induced olfactory disorders could be the result of localized cell damage in the nasal epithelium.

Proteomic investigations of acute ischemic stroke in animal models:a narrative review

Acute ischemic stroke(AIS),a neurological injury resulting from blood clots,is the second most common cause of death worldwide.Novel therapeutics are urgently needed.Rapid developments in instrumentation and bioinformatics have resulted in increased use of mass spectrometry-based proteomics as an effective tool for the in-depth study of AIS.This review focuses on proteomics investigations of AIS in animal models.We highlight the study findings in system-wide protein abundance changes and molecular mechanisms underlying AIS with or without therapeutic intervention,as well as prestroke prognosis investigations.This review reveals that common molecular pathways related to ischemic injury and spontaneous recovery have been uncovered and part of AIS-changed proteins have been repeatedly identified,indicating the promise of proteomics in generating novel therapeutic targets and biomarker candidates.We also discuss challenges,alleviating strategies,and perspectives of mass spectrometry-based proteomics in AIS research and call for a broad application of systems-level investigations on preclinical AIS molecular mechanism elucidation,target discovery and validation,and therapeutics development.

A narrative review of organoids for investigating organ aging:opportunities and challenges

Aging research has shifted from studying phenotypes to studying in-depth mechanisms in recent decades.However,extrapolating cellular and molecular bases of aging from studying traditional model systems to humans has been challenging.The advent of organoids holds promise for overcoming the limitations of monolayer cell culture and bridging the gap between animal models and humans.Here,we mainly discuss recent paradigms for using organoid models in studying organ aging.Pluripotent stem cells-derived organoid provides a promising platform for simulating the pathophysiology of several aging-related diseases,especially neurodegenerative diseases,and adult stem cells organoids derived from different age groups have been applied to detect aging-related functional changes.We also assess the value of organoid model systems in understanding human aging and aging-related diseases,and identify challenges to be addressed in the future,such as the immaturity of organoids,and effective methods of inducing aging.

Modeling of nanoparticle-sensitized spatially localized dynamic photohyperthermia in a blood vessel under infrared laser irradiation with a scanning beam

Photoheating in a venous blood vessel under near-infrared laser irradiation by a scanning laser beam,which is synchronized with the blood flow velocity,is analyzed numerically by considering the light scattering,absorption,and heat transfer in the blood and surrounding tissues.The scanning regime of the laser irradiation with a wavelength of 1064 nm is found to increase strongly the photoheating of the blood while minimizing the overheating of the skin and the tissues surrounding the blood vessel.Simulations show that the photoheating effect can be additionally enhanced by light-absorbing nanoparticles in the blood.The proposed approach of dynamic laser photohyperthermia with the scanning laser beam is discussed for potential applications in laser phototherapy.

Protein engineering for natural product biosynthesis:expanding diversity for therapeutic applications

In this dispensation of the fourth industrial revolution,protein engineering has become a popular approach for increasing enzymatic activity,stability,and titer in the biosynthesis of natural products.This is attributed to its numerous advantages(over direct isolation from plants or via chemical synthesis),including decreasing or eliminating reaction byproducts,high precision,moderate handling of intricate and chemically unstable chemicals,overall reusability,and cost efficiency.Recently,protein engineering tools have advanced to redesign and enhance natural product biosynthesis.These methods include direct evolution,substrate engineering,medium engineering,enzyme engineering and immobilization,structure-assisted protein engineering,and advanced computational.Recent successes in implementing these emerging protein engineering technologies were critically discussed in this article.Also,the advantages,limitations,and applications in industrial and medical biotechnology were discussed.Last,future research directions and potential were also highlighted.

A new"single"era of biomedicine and implications in disease research

In recent decades,single-cell(SC)technologies and applications have been a very hot topics in the field of biology and medicine.In fact,early studies involving a single cell were on the malignant process of acute nonlymphocytic leukemia and inherited or sporadic genetic disease in the 1980s.And since the RhD gene in a single cell from maternal plasma was detected by fluorescence-based polymerase chain reaction(PCR)in the 1990s,“SC biopsies”[1]were widely used for early diagnosis in clinical practice in the 2000s.Previous studies showed that SC RNA sequencing(scRNA-seq)was used to evaluate patterns of allelic gene expression at the allele-specific mRNA level,and SC genome analysis can be used for genetic diagnosis.

A brief overview of game-changing genetic engineering projects

In recent era,advancement of research involves computational management of large-scale genomic and post-genomic datasets in an obvious way.Rapidly emerging field of bioinformatics,fueled by high-throughput technologies and genomic scale database,is believed to reshape our approach of research to a new level.Genomics has shifted the paradigm of biological perspectives exploring many scopes.Old initiatives paved the path for the newer and more advantageous one.The present review focuses on present initiatives that are implemented till now like the famous Human Genome Project and its influence on digital biology,as well as the projects that followed in its footsteps.Additionally,the authors delve into the future potential of personalized medicine and the use of genetic engineering methods like CRISPR/Cas9 in gene editing,which are thought to have the potential to revolutionize the current treatment strategy.

Comparative oral metagenome insight into acute and chronic root canal infections

Background:In the dynamic progression of root canal infections,the resultant change in environmental conditions directs the adaptation of the microbiome in terms of richness,evenness,and diversity.Objective:The goal of this study is to contrast the interradicular bacterial community structures of teeth in acute and chronic stages and investigate potential microorganisms associated with persistent apical periapical infections.Methods:Interradicular samples were collected from 10 teeth in the apical periodontitis group and 10 teeth in the chronic apical periodontitis group.High-throughput next-generation sequencing(NGS)–based microbial identification through the Illumina platform was used to characterize the complex intraradicular microbial communities in acute and chronic root canal infections.Results:Bacteria were the major domain,with a prevalence of>97%(acute cases:98.11%and chronic cases:97.6%)compared to eukaryotes and archaea.Bacterial diversity was relatively higher in acute compared to chronic conditions under 10 and 9 phyla,79 and 64 genera,and 172 and 135 species,respectively.These endodontically infecting bacteria belonged to Firmicutes(47.21%),Bacteroidetes(20.07%),and Proteobacteria(10.72%)in acute conditions,while in the chronic stage,Firmicutes(40.85%),Proteobacteria(27.80%),and Actinobacteria(14.79%)were abundant.The phylum Candidatus Saccharibacteria was exclusively found in acute samples.Spirochaetes and Synergistetes were found predominantly in acute infections compared to chronic infections.Bacillus and Lactobacillus were found in equal and highest abundance under the phylum Firmicutes in both conditions.Conclusion:This study provides information on the differential microbial community present in the apical root canal system of teeth with acute and chronic apical periodontitis and contributes to new approaches or channels for future research on preventive measures and therapeutic protocols during disease progression and treatment.However,functional characterization and detection of antimicrobial resistance in these two clinical conditions can supplement these findings for deciding routine drug treatment for periodontal infections.

Envelope antibody HBeIgG and HBV DNA in HBeAg-seronegative young adults in Nigeria

Study background:Anti-HBe and hepatitis B virus(HBV)DNA are important markers in evaluating HBV infection.Anti-HBe indicates past or current infection that persists after hepatitis B e antigen(HBeAg)clearance.Detecting anti-HBe helps identify cleared or chronic infections.HBV DNA measures viral replication,indicating infection activity.Studying these markers in HBeAg-seronegative young adults provides insights into infection dynamics,immune responses,and transmission risk.It informs clinical management and public health interventions for preventing HBV transmission and reducing the burden of liver disease.Aim and objectives:This cross-sectional study aimed to determine the prevalence of HBeAg seronegativity and its association with HBV infection markers among young adults in Etsako,Edo State,Nigeria.Materials and methods:The study population consisted of HBeAg-seronegative individuals aged 18 to 30 years.A total of 400 participants(200 females and 200 males)were randomly selected from urban and rural communities using a multistage sampling technique.Anti-HBe and HBeAg were analyzed by ELISA,whereas HBV DNA was evaluated by polymerase chain reaction.Results:The prevalence of HBeAg seropositivity was 28%,whereas 72%of participants were seronegative.Among the HBeAg-seronegative participants,the frequencies of anti-HBe and HBV DNA were analyzed based on various categorical variables.The results showed no significant differences in the frequency of anti-HBe and HBV DNA based on occupation,training,or other categorical variables(P>0.05).However,there was a significantly higher proportion of males(60%)among the total number of anti-HBe-seropositive young adults compared to females(40%)(P<0.05).Additionally,a significantly higher proportion of single/unmarried individuals without children(63.3%)was observed among anti-HBe-seropositive young adults compared to those who were married(25%)and those who were single/unmarried with children(12.5%,P<0.05).Conclusion:The study findings contribute to the understanding of HBeAg seronegativity and its association with anti-HBe and HBV DNA in young adults in Etsako,Edo State,Nigeria.Further research and public health interventions are warranted to better comprehend the factors influencing HBeAg seronegativity and its association with anti-HBe and HBV DNA and its implications for HBV transmission and disease progression in this population.

Alternative splicing in breast cancer

Alternative splicing allows a gene to produce multiple proteins and is the main source of human proteome diversity.Aberrant regulation of alternative splicing produces proteins with different structures and can lead to altered protein function,inactivation,or deleterious variants,which can have severe effects on normal cellular function,leading to many diseases,including cancer.Alternative splicing abnormalities are often found in diseases,so alternative splicing is highly correlated with diseases and treatment.According to relevant statistics,breast cancer is an important factor that threatens women’s lives and health.A common sign of tumors in humans is abnormal alternative splicing.An increasing amount of evidence shows that abnormal alternative splicing plays an important role in the occurrence and development of breast cancer.At the same time,in the related treatment of breast cancer,alternative splicing can lead to the failure of existing treatment methods and induce drug resistance.Currently,targeted therapy is still the key strategy for breast cancer treatment.In this review,we discuss the five classifications of alternative splicing and aberrant alternative splicing in breast cancer.The role of alternative splicing in the drug resistance of breast cancer is also discussed.Evidence has shown that aberrant alternative splicing can lead to drug resistance to current therapies.Because splicing factors are involved in many aspects of cancer,splicing factors may provide a new strategy for cancer treatment and a powerful tool for progress in the fight against breast cancer.Antisense oligonucleotides form a double-stranded structure by complementary pairing with mRNA,which prevents the binding of mRNA and ribosomes,thus inhibiting protein synthesis.Therefore,after finding effective targets,antisense oligonucleotides can be applied in gene therapy,drug research and development,biological research,and other fields to improve therapeutic effects.

Antibody fragment V_(H)ab6:universal neutralizer for SARS-CoV-2 variants

The recent coronavirus disease 2019(COVID-19)outbreak has highlighted the inadequacy of our ability to respond to newly emerging viruses.Antiviral medications are the most effective means of combating the pandemic,yet their diminishing efficacy and a large population of unvaccinated individuals will create a fertile environment for the virus’s propagation and the emergence of novel variants,posing an ongoing risk of infection for vulnerable populations with compromised immune systems.To treat those infected,effective treatments must be developed.In this review,we discuss a breakthrough in engineered antibody fragments that could provide a protective barrier against the onslaught of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants as well as future other viral infections.

Angiotensin-converting enzyme 2:virus accomplice or host defender?

Objective:Coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has led to social disruptions,mainly because we know too little about SARS-CoV-2.Methods and Results:In this study,we integrated RNA sequencing results and found that SARS-CoV-2 infection alters aerobic glycolysis,the oxidative pentose phosphate pathway(oxiPPP),and DNA replication in lung tissues and cells.However,the direction of metabolic flux and DNA replication are dominated by angiotensin-converting enzyme 2(ACE2),a host cell-expressed viral receptor protein.More interestingly,although hosts with a high expression of ACE2 are more likely to be infected with SARS-CoV-2,the invading virus cannot perform nucleic acid replication well due to the restriction of glucose metabolism,eventually resulting in a prolonged infection cycle or infection failure.Conclusion:Our findings preliminarily explain the reasons for the emergence of asymptomatic infections at an early stage,which will provide assistance for the development of detection methods for diagnosing COVID-19.

Natural therapeutics for cancer treatment:success,challenges,and prospect

Cancer is a terrifying disease that has become one of the world’s most challenging health concerns,necessitating a proactive approach to its treatment.Nature is a rich source of new chemical entities and a promising avenue for cancer research.Because of their different modes of action on target events in many ways,nature-derived chemicals are considered good possibilities for anticancer drug development.The current review article highlights recent breakthroughs in cancer therapeutics,including natural therapeutic molecules and their mechanisms of action against cancer treatment,as well as their limits,challenges,and prospect.For the review,article data have been collected from previously studied and published research reports,clinical evaluations,case studies,and clinical statistical data generated by scientific research organizations of repute.The chemical structures have been drawn using computational software(chemsketch).The development of promising candidates that can prevent or reduce the proliferation of cancer cells without causing adverse effects from these therapeutics is now underway.Further,nature-derived products are a game-changer because they are simple,safer,environmentally friendly,low-cost,quick,and less toxic than traditional treatment techniques.However,many bioactive chemicals and their analogs have been discovered as possible anticancer treatment options.In the review,the potent therapeutics phytochemicals derived from nature with their tremendous anticancer effects with limitations and prospects have been studied and analyzed based on previously published articles and reports.

Acquired pure red cell aplasia:unraveling the immune pathogenesis

Acquired pure red cell aplasia(aPRCA)is a rare hematological disorder characterized by normochromic,normocytic anemia,reticulocytopenia,and the absence of erythroblasts.The pathogenesis of aPRCA has remained elusive.This review delves into the intricate web of immune mechanisms underlying the development of this enigmatic condition.By exploring immune responses,cytotoxic effects,and antibody-mediated processes,we dissect the immune-driven assault on erythroid progenitors.The classification of aPRCA,including its primary and secondary forms,is elucidated,with a particular emphasis on etiological factors such as viruses,drugs,thymoma,and large granular lymphocytic leukemia.Furthermore,we discuss the implications of cytogenetic changes in erythroid progenitors and immune cells in the pathophysiology of aPRCA.This comprehensive overview aims to shed light on the complex interplay between immune dysregulation and erythroid failure in aPRCA,offering insights that will be crucial for better understanding and treating this disease.

Exosomes:emerging biomarkers unveiling cellular mysteries—a narrative review

Exosomes have gained recognition as potential diagnostic and prognostic markers due to their stability and disease-specific cargos.Exosomes,once dismissed as cellular debris,are now acknowledged as crucial mediators of intercellular communications and disease.These nanosized vesicles transport dynamic cargos consisting of bioactive molecules,including proteins,lipids,and nucleic acids,enabling cells to exchange information and influence each other’s behavior.This review delves into the multifaceted roles of exosomes,particularly their emergence as biomarkers for various diseases.To conduct research for this review,a comprehensive literature search strategy was employed across various databases using keywords related to exosomes,biomarkers,cellular communication,disease diagnosis,and more.Selected articles were evaluated based on their relevance,and data were extracted,synthesized,and categorized according to thematic content.Quality assessment was performed on different types of articles,ensuring robust findings.In cancer,exosomes act as liquid biopsy samples,revealing genetic mutations,and protein markers.The misfolded proteins characteristic of neurodegenerative diseases such as Alzheimer disease and Parkinson disease are carried by exosomes.Moreover,exosomes have been studied as biomarkers for cardiovascular,infectious,and autoimmune diseases.In addition to their functions as biomarkers,exosomes influence the tumor microenvironment,immune response,synaptic plasticity,and tissue regeneration.Challenges remain to fill research gaps and standardize exosome analyses.Exosomes are pivotal in intercellular communication and for disease diagnosis,offering insights into cellular processes,immunity,and regeneration.Future research may reshape our understanding of cellular communication and drive therapeutic interventions.Although challenges must be addressed,exosomes hold undeniable potential for use in personalized medicine and biomedical research.

Therapeutic strategies for acute basilar-artery occlusion

To the editor:Acute basilar-artery occlusion(aBAO)is one of the most severe forms of stroke,with an incidence of severe disability and death of up to 80%.^([1,2,3])Although several previous prospective multicenter randomized controlled trials(RCTs)involving patients with acute stroke due to large-artery occlusion in the anterior circulation have shown that endovascular thrombectomy(EVT)dramatically improves prognosis over best medical management(BMM),^([4,5])the efficacy and safety of EVT for aBAO remain controversial.

Ultrasound delivery of Chinese rhubarb promotes early recovery of gastrointestinal function after gastrectomy:a prospective randomized controlled study

Objective: Chinese rhubarb is a promising Chinese medicine for the promotion of gastrointestinal function. This study was conducted to investigate the safety and efficacy of Chinese rhubarb administered via ultrasound delivery in promoting the early recovery of gastrointestinal function after gastrectomy.Methods: In this prospective randomized controlled study, 100 patients who were scheduled to undergo total or subtotal gastrectomy in Changzhi People’s Hospital or Subei People’s Hospital from August 2017 to January 2018 were recruited. These patients were randomly assigned into two equal groups before surgery: 50 in the experimental (Chinese rhubarb) group, and 50 in the control (routine nursing) group. After surgery, time to flatus, bowel movement, clear liquid diet, and removal of nasogastric tube were recorded and analyzed. In addition, postoperative pain, postoperative bowel movement-related complications, and postoperative hospital stay duration were also recorded and analyzed. The study was approved by The protocol was approved by the Institutional Review Board of Changzhi People’s Hospital and Subei People’s Hospital on July 1, 2017 and registered with the Chinese Clinical Trial Registry on December 17, 2018 (registration number: ChiCTR1800020143).Results: Time to flatus (control group 85.68±22.00 hours vs experimental group 73.06±23.42 hours;P=0.007), bowel movement (5.52±1.56 vs 4.40±1.21 days;P<0.001), clear liquid diet (6.72±1.16 vs 6.22±1.28 days;P=0.044), and removal of nasogastric tube (6.30±1.52 vs 5.65±1.58 days;P=0.044) were significantly shorter in the experimental group compared with the control group, as was the postoperative hospital stay duration (14.30±3.46 vs 12.86±1.36 days;P=0.006). In addition, better pain relief (P=0.003) and a lower incidence of postoperative bowel movement-related complications (6 vs 21;P=0.001) were noted in the experimental group.Conclusion: Ultrasound delivery of Chinese rhubarb is useful to promote the early recovery of gastrointestinal function after gastrectomy.

Placebo effect in the treatment of non-small cell lung cancer:a meta-analysis

Objective:The majority of non-small cell lung cancer(NSCLC)cases remain undiagnosed until advanced stages of the disease.Accumulating studies have highlighted the utility of palliative care as an effective treatment option,which relieves patients’suffering by activating placebo effect in the body.To evaluate the clinical significance of palliative care,data from NSCLC drug-randomized controlled trials(RCTs)were collected and the effects of placebo treatment examined.Methods:PubMed(MEDLINE),Scopus,Web of Science,and China National Knowledge Infrastructure databases were searched from January 1,1978 to September 1,2020.Placebo-controlled phase II/III pharmaceutical RCTs enrolling patients with solely stage III/IV NSCLC were included.The quality of included studies was assessed using the Jadad method.Single-arm and two-arm meta-analyses of the therapeutic and adverse effects of placebo,that is,the primary and secondary outcome measures,were subsequently performed using either Bayesian or conventional models.Results:Five RCTs including 2245 drug-treated and 1510 placebo-treated patients at NSCLC stage III or IV were included for the study.Low risk of bias was observed for all five included studies using the Cochrane method.Following placebo treatment,controlled disease rate of 24.1%(95%credible interval[CrI],-0.126-0.609)and dropout rate of 2.1%(95%CrI,0.007-0.039)were calculated,with a dose reduction rate of 3.0%(95%CrI,0.017-0.045).Compared with active drug treatment,the placebo treatment group had a risk ratio of 0.81(95%confidence interval,0.68-0.97)and 0.85(95%confidence interval,0.76-0.96)for the achievement of progression-free survival and overall survival,respectively.Conclusion:In NSCLC drug RCTs,placebo treatment is indicated to generally induce low toxicity in patients by dropout and dose reduction rates and adverse events,although the therapeutic responses could not be precisely determined.The results suggest that under specific circumstances,palliative care which can activate placebo effect may have similar effects as active drugs(such as erlotinib,vandetanib,or pemetrexed)in terms of prolonging survival time.

A differential privacy protection query language for medical data:a proof-of-concept system validation

Objective: Medical data mining and sharing is an important process in E-Health applications. However, because these data consist of a large amount of personal private information of patients, there is the risk of privacy disclosure when sharing and mining. Therefore, ensuring the security of medical big data in the process of publishing, sharing, and mining has become the focus of current research. The objective of our study is to design a framework based on a differential privacy protection mechanism to ensure the secure sharing of medical data. We developed a privacy protection query language (PQL) that integrates multiple data mining methods and provides a secure sharing function.Methods: This study is mainly performed in Xuzhou Medical University, China and designs three sub-modules: a parsing module, mining module, and noising module. Each module encapsulates different computing methods, such as a composite parser and a noise theory. In the PQL framework, we apply the differential privacy theory to the results of the computing between modules to guarantee the security of various mining algorithms. These computing devices operate independently, but the mining results depend on their cooperation. In addition, PQL is encapsulated in MNSSp3 that is a data mining and security sharing platform and the data comes from public data sets, such as UCBI. The public data set (NCBI database) was used as the experimental data, and the data collection time was January 2020.Results: We designed and developed a query language that provides functions for medical data mining, sharing, and privacy preservation. We theoretically proved the performance of the PQL framework. The experimental results show that the PQL framework can ensure the security of each mining result and the availability of the output results is above 97%.Conclusion: Our framework enables medical data providers to securely share health data or treatment data and develops a usable query language, based on a differential privacy mechanism, that enables researchers to mine information securely using data mining algorithms.

Biomedical ontologies and their development,management,and applications in and beyond China

Since the boom of biomedical big data studies,various big data processing technologies have been developed rapidly.As an important form of knowledge representation,ontology has become an important means for the utilization and integration of biomedical big data.The emergence of new technologies for ontology development has resulted in the generation of many biomedical ontologies by many ontology development communities.The Open Biological and Biomedical Ontology Foundry,an academic organization for bio-ontology developers,has provided a set of principles to guide community-based open ontology construction.The Open Biological and Biomedical Ontology Foundry have also built many widely used ontologies,such as Gene Ontology,Human Phenotype Ontology,and Chemical Entities of Biological Interest.Other various ontology repositories have also been created and used to support ontology reuse.Many efficient tools for ontology applications,such as data annotation and terms mapping,have also been developed.High quality ontologies are also being used to develop new methods and tools for biomedical data analysis.The applications of Gene Ontology and Human Phenotype Ontology for data analysis and integration in recent years are reviewed here.To promote the development and applications of biomedical ontologies in China,a research community,OntoChina,was founded recently.OntoChina aims to support the development of reference ontologies,especially bilingual and Chinese translated ontologies.OntoChina also encourages ontology developers to follow the Open Biological and Biomedical Ontology Foundry principles.