A Review of Stressors as Inducer for Personality Disorders and Anxiety Disorders

Personality Disorders(PDs)and Anxiety Disorders(ADs)are common mental disorders.PDs are often more or less related to anxiety and ADs are affected by Personality Functioning(PF).To clarify the pathology of both ADs and PDs,along with their similarities and differences,the literature review by paired keywords search on NCBI PubMed and subsequent analysis are used.The findings support that abnormal stressors can damage the Hypothalamus-Pituitary-Adrenal(HPA)axis time by time throughout life through the epigenetic pathway,lowering down the ability of the stress system to deal with stressors.Biological basis,like the genetic issue,for PDs,is important but after-born experience also matters a lot.Adjoint stressful long-term memory may largely affect normal personality formation,contributing to some kinds of PDs.It seems that early exposure to these stressors influences PDs more,compared to ADs.More researches are needed to explore the effect on ADs from later life stress.This study partially explained the process of ADs and PDs,linked them by abnormal stressors,and emphasized the importance of focusing on the effect of stressful long-term memory formation,which is psychological,and the HPA axis disability,which is biological,on patients having these diseases,reminds psychiatrist to treat disease at the source,to lower down the potential risk of getting PDs in patients who are diagnosed with ADs,to prevent arouse of ADs in patients who are diagnosed with PDs and to combine biological treatment with psychological therapies.

Naked-eye visualization of lymph nodes using fluorescence nanoprobes in non-human primate-animal models

Despite sufficient studies performed in non-primate animal models,there exists scanty information obtained from pilot trials in non-human primate animal models,severely hindering nanomaterials moving from basic research into clinical practice.We herein present a pioneering demonstration of nanomaterials based optical imaging-guided surgical operation by using macaques as a typical kind of non-human primate-animal models.Typically,taking advantages of strong and stable fluorescence of the small-sized(diameter:~5 nm)silicon-based nanoparticles(SiNPs),lymphatic drainage patterns can be vividly visualized in a real-time manner,and lymph nodes(LN)are able to be sensitively detected and precisely excised from small animal models(e.g.,rats and rabbits)to non-human primate animal models(e.g.,cynomolgus macaque(Macaca fascicularis)and rhesus macaque(Macaca mulatta)).Compared to clinically used invisible near-infrared(NIR)lymphatic tracers(i.e.,indocyanine green(ICG);etc.),we fully indicate that the SiNPs feature unique advantages for naked-eye visible fluorescence-guided surgical operation in long-term manners.Thorough toxicological analysis in macaque models further provides confirming evidence of favorable biocompatibility of the SiNPs probes.We expect that our findings would facilitate the translation of nanomaterials from the laboratory to the clinic,especially in the field of cancer treatment.

Microalgae-based drug delivery system for tumor microenvironment photo-modulating and synergistic chemo-photodynamic therapy of osteosarcoma

Osteosarcoma(OS)is one of the most common malignant tumors in children and young adults.As chemotherapy and other therapies are limited by low therapeutic efficiency,severe side effects and single therapeutic function,it is of high value to develop innovative therapies for precise and efficient treatment of OS.Herein,natural photo-synthetic microalgae(C.vulgaris,CV)were utilized as carriers for the chemotherapeutic agent doxorubicin(DOX)to create a multifunctional therapeutic platform(CV@DOX)for the photo-modulation of the tumor microenvi-ronment(TME)and synergistic chemo-photodynamic therapy of osteosarcoma.CV@DOX exhibited rapid drug release behavior in the acidic TME,improving the efficiency of chemotherapy against tumors and reducing side effects on other normal tissues.Under 650 nm laser irradiation,CV@DOX demonstrated the ability to effectively generate oxygen to alleviate tumor hypoxia and utilize the photosensitizing properties of chlorophyll in CV to produce an increased amount of reactive oxygen species(ROS),thereby enhancing photodynamic therapy(PDT).CV@DOX-mediated synergistic chemo-photodynamic therapy demonstrated efficacy in halting tumor progression in an orthotopic osteosarcoma mouse model by promoting tumor cell apoptosis,inhibiting tumor proliferation and angiogenesis.Moreover,chlorophyll-assisted fluorescence imaging enabled monitoring of the distribution of CV@DOX in osteosarcoma after administration.Finally,CV@DOX did not cause significant hematological and tissue toxicity,and prevented DOX-induced cardiotoxicity,showing good in vivo biocompatibility.Overall,this work presents a novel TME-responsive and TME-modulating platform for imaging-guided multimodal osteosar-coma treatment.

Evaluation of 10 Different Pipelines for Bacterial Single-Nucleotide Variant Detection

Bacterial genome sequencing is a powerful technique for studying the genetic diversity and evolution ofmicrobial populations.However,the detection of genomic variants from sequencing data is challenging due to the presence of contamination,sequencing errors and multiple strains within the same species.Several bioinformatics tools have been developed to address these issues,but their performance and accuracy have not been systematically evaluated.In this study,we compared 10 variant detection pipelines using 18 simulated and 17 real datasets of high-throughput sequences froma bundle of representative bacteria.We assessed the sensitivity of each pipeline under different conditions of coverage,simulation and strain diversity.We also demonstrated the application of these tools to identify consistentmutations in a 30-time repeated sequencing dataset of Staphylococcus hominis.We found that HaplotypeCaller,but not Mutect2,from the GATK tool set showed the best performance in terms of accuracy and robustness.CFSAN and Snippy performed not as well in several simulated and real sequencing datasets.Our results provided a comprehensive benchmark and guidance for choosing the optimal variant detection pipeline for high-throughput bacterial genome sequencing data.

Host-Defense-Peptide-Mimickingβ-Peptide Polymer Acting as a Dual-Modal Antibacterial Agent by Interfering Quorum Sensing and Killing Individual Bacteria Simultaneously

Host defense peptides(HDPs)are one of the potentially promising agents for infection diseases due to their broad spectrum and low resistance rate,but their clinical applications are limited by proteolytic instability,high-cost,and complicated synthesis process.Here,we report a host-defense-peptidemimickingβ-peptide polymer that resists proteolysis to have enhanced the activity under physiological conditions,excellent antimicrobial efficiency even at high density of bacteria,and low cost for preparation.Theβ-peptide polymer demonstrated quorum sensing(QS)interference and bactericidal effect against both bacterial communities and individual bacterium to simultaneously block bacterial communication and disrupt bacterial membranes.The hierarchical QS network was suppressed,and main QS signaling systems showed considerably down-regulated gene expression,resulting in excellent biofilm eradication and virulence reduction effects.The dual-modal antibacterial ability possessed excellent therapeutic effects in Pseudomonas aeruginosa pneumonia,which could inhibit biofilm formation and exhibit better antibacterial and anti-inflammatory efficiency than clinically used antibiotics,levofloxacin.Furthermore,theβ-peptide polymer also showed excellent therapeutic effect Escherichia coli pyogenic liver abscess.Together,we believed that theβ-peptide polymer had a feasible clinical potential to treat bacterial infection diseases.

Iron metabolism,ferroptosis,and lncRNA in cancer: knowns and unknowns

Cancer cells undergo substantial metabolic alterations to sustain increased energy supply and uncontrolled proliferation.As an essential trace element,iron is vital for many biological processes.Evidence has revealed that cancer cells deploy various mechanisms to elevate the cellular iron concentration to accelerate proliferation.Ferroptosis,a form of cell death caused by iron-catalyzed excessive peroxidation of polyunsaturated fatty acids(PUFAs),is a promising therapeutic target for therapyresistant cancers.Previous studies have reported that long noncoding RNA(lncRNA)is a group of critical regulators involved in modulating cell metabolism,proliferation,apoptosis,and ferroptosis.In this review,we summarize the associations among iron metabolism,ferroptosis,and ferroptosis-related lncRNA in tumorigenesis.This information will help deepen understanding of the role of lncRNA in iron metabolism and raise the possibility of targeting lncRNA and ferroptosis in cancer combination therapy.

Thymic-specific regulation of TCR signaling by Tespa1

Double-positive(DP)thymocytes undergo positive selection to become mature single-positive CD4+and CD8+T cells in response to T cell receptor(TCR)signaling.Unlike mature T cells,DP cells must respond to low-affinity self-peptide-MHC ligands before full upregulation of their surface TCR expression can occur.Thus,DP thymocytes must be more sensitive to ligands than mature T cells.A number of molecules have been found that are able to enhance the strength of the TCR signal to facilitate positive selection.However,almost all of these molecules are also active in mature T cells.Themis(thymocyte expressed molecule involved in selection)and Tespa1(thymocyte expressed positive selection associated 1)are two recently discovered molecules essential for optimal TCR signaling and thymocyte development.A deficiency in both molecules leads to defects in positive selection.Here,we compared the relative contributions of Themis and Tespa1 to positive selection in thymocytes.We show that Tespa1 deficiency led to more limited and specific gene expression profile changes in cells undergoing positive selection.In mixed bone marrow transfer experiments,Tespa1^(−/−)cells showed more severe defects in thymocyte development than Themis^(−/−)cells.However,Tespa1^(−/−)cells showed a substantial degree of homeostatic expansion and became predominant in the peripheral lymphoid organs,suggesting that Tespa1 is a thymic-specific TCR signaling regulator.This hypothesis is further supported by our observations in Tespa1 conditional knockout mice,as Tespa1 deletion in peripheral T cells did not affect TCR signaling or cell proliferation.The different regulatory effects of Tespa1 and Themis are in accordance with their nonredundant roles in thymocyte selection,during which Tespa1 and Themis double knockouts showed additive defects.

Heat Treatment Promotes Ubiquitin-Mediated Proteolysis of SARS-CoV-2 RNA Polymerase and Decreases Viral Load

Despite extensive eforts,COVID-19 pandemic caused by the SARS-CoV-2 virus is still at large.Vaccination is an eftive approach to curb virus spread,but several variants(eg.delta,delta plus,omicron,and IHU)appear to weaken or possibly escape immune protection.Thus,novel and quickly scalable approaches to restrain SARS-CoV-2 are urgently needed.Mutiple evidences showed thermal sensitivity of SARS-CoV-2 and negative correlation between environmental temperature and COVID-19 transmission with unknown mechanism.Here.we reveal a potential mechanism by which mild heat treatment destabilizes the wild-type RNA-dependent RNA polymerase(also known a nonstructural protein 12(NSP12))of SARS-CoV-2 as well as the P323L mutant commonly found in SARS-CoV-2 variants,including omicron and IHU.Mechanistically,heat treatment promotes E3 ubiquitin ligase ZNF598-dependent NSP12 ubiquitination leading to proteasomal degradation and significantly decreases SARS-CoV-2 RNA copy number and viral titer.A mild daily heat Ireatment maintains low levels of both wild-type and P323L mutant of NSP12,sugesting clinical potential.Collctivel',this novel mechanism,heat-induced NSP12 degradation,suggests a prospective heat-based intervention against SARS-CoV-2.

Pharmacological and Immunological Aspects of Phage Therapy

Bacteriophages,or viruses of microbes,when used as a medical strategy,might be able to solve the current crisis mankind faces with the increasing number of pathogens being antibiotic-resistant,where chemical drugs seized to show any therapeutic effect.The socalled phage therapy may be one of the most promising alternatives to treat infections caused by antibiotic-resistant bacteria,which are killed after infection by a phage.While phages that destroy the host by lysis are chosen for therapy,many pharmacological and immunological aspects of phages as medicines have not been established so far.The immune system plays an important role in a process called phage acceptance where both,innate and adaptive immune responses of the host are involved.However,not only medical aspects but also social ones such as lacking public awareness or acceptance,and lack of structured regulatory guidelines are challenges that have to be addressed in the near future to establish phage therapy as a reliable and safe alternative for the treatment of infections.This review focuses on the unique pharmacological and immunological aspects of phages used in therapy.

Will Technology Rather Than Vaccination Be the Way to Control Pandemics?

At policy level for the COVID-19 pandemic two main themes emerge,containment of infection(testing,tracing,and isolation)and vaccination.The pandemic has stimulated rapid development of vaccine candidates that are in various phases of clinical trials,some of which are advanced with regulatory approvals expected early in the new year.1,2 However,even with vaccination on the horizon there are multiple constraints to overcome before this pandemic will be consigned to history.The enormous task of vaccine production and distribution,possibly involving repeated vaccinations and management of non-compliance within populations are a major challenge for 21st century Global Public Health policy.

Will the Overuse of Antibiotics During the Coronavirus Pandemic Accelerate Antimicrobial Resistance of Bacteria?

The coronavirus pandemic is one of mankind's biggest challenges of modern day.Viruses can cause deadly pandemics,yet another enemy should not be forgotten:Bacterial pathogens.From a biomedical perspective,bacterial infections should be easier to control,as prokaryotes exhibit structures and biochemical processes that differ from humans,and thus are easier to target.Viruses,however,employ human cells to propagate and are,therefore,more complicated to target by drugs.

SARS-CoV-2 and Zoonotic Preparedness:Unknown Knowns?

Emerging infectious diseases(EIDs)with pandemic potential are a major threat to global health security and the global economy.Prevention,preparedness,and response to EIDs within hotspots for EIDs is considered a global public service.In December 2019,coronavirus disease 2019 came under the spotlight;caused by a novel single-stranded RNA coronavirus,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).The rapidity at which the virus spread worldwide has been remarkable and the global response to the pandemic unprecedented.The rate of emergence of infectious diseases of zoonotic origin is increasing.Multiple new pathogens have emerged or reemerged over the past few decades,many of viral origin,of which 75%are considered to have originated in animals.1 Before SARSCoV-2,globally,around 1 billion zoonotic infections occurred in humans each year of which around 0.1%resulted in death.1 Prominent examples of EIDs include acquired immunodeficiency syndrome,Ebola and Marburg hemorrhagic fevers,Escherichia coli O157 infection,Middle East respiratory syndrome(MERS),and severe acute respiratory syndrome(SARS).

The regulatory role of m^(6)A modification in the maintenance and differentiation of embryonic stem cells

As the most prevalent and reversible internal epigenetic modification in eukaryotic mRNAs,N6-methyladenosine(m^(6)A)post-transcriptionally regulates the processing and metabolism of mRNAs involved in diverse biological processes.m^(6)A modification is regulated by m^(6)A writers,erasers,and readers.Emerging evidence suggests that m^(6)A modification plays essential roles in modulating the cell-fate transition of embryonic stem cells.Mechanistic investigation of embryonic stem cell maintenance and differentiation is critical for understanding early embryonic development,which is also the premise for the application of embryonic stem cells in regenerative medicine.This review highlights the current knowledge of m^(6)A modification and its essential regulatory contribution to the cell fate transition of mouse and human embryonic stem cells.