Bidirectional regulation of the brain-gut-microbiota axis following traumatic brain injury

Traumatic brain injury is a prevalent disorder of the central nervous system.In addition to primary brain parenchymal damage,the enduring biological consequences of traumatic brain injury pose long-term risks for patients with traumatic brain injury;however,the underlying pathogenesis remains unclear,and effective intervention methods are lacking.Intestinal dysfunction is a significant consequence of traumatic brain injury.Being the most densely innervated peripheral tissue in the body,the gut possesses multiple pathways for the establishment of a bidirectional“brain-gut axis”with the central nervous system.The gut harbors a vast microbial community,and alterations of the gut niche contribute to the progression of traumatic brain injury and its unfavorable prognosis through neuronal,hormonal,and immune pathways.A comprehensive understanding of microbiota-mediated peripheral neuroimmunomodulation mechanisms is needed to enhance treatment strategies for traumatic brain injury and its associated complications.We comprehensively reviewed alterations in the gut microecological environment following traumatic brain injury,with a specific focus on the complex biological processes of peripheral nerves,immunity,and microbes triggered by traumatic brain injury,encompassing autonomic dysfunction,neuroendocrine disturbances,peripheral immunosuppression,increased intestinal barrier permeability,compromised responses of sensory nerves to microorganisms,and potential effector nuclei in the central nervous system influenced by gut microbiota.Additionally,we reviewed the mechanisms underlying secondary biological injury and the dynamic pathological responses that occur following injury to enhance our current understanding of how peripheral pathways impact the outcome of patients with traumatic brain injury.This review aimed to propose a conceptual model for future risk assessment of central nervous system-related diseases while elucidating novel insights into the bidirectional effects of the“brain-gut-microbiota axis.”

Accelerating the establishment of a new science-policy panel to address the triple planetary crisis

he triple planetary crisis—climate change,biodiversity loss,and pollution—threatens planetary health.In response to these challenges,the Intergovernmental Panel on Climate Change(IPCC)was established in 1988,followed by the formation of the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services(IPBES)in 2012.Ongoing global initiatives through IPCC and IPBES have significantly advanced scientific understanding,raised public awareness,and informed policy-making in relation to climate change and biodiversity loss.However,pollution remains a pressing concern in all three crises.

化学类专业一流课程建设的思路与重点——以山东大学物理化学一流课程建设为例

一流课程建设是一流本科建设的基础。本文首先基于对一流课程“两性一度”标准的认识,指出定位准确、目标清晰、基础良好、理念先进、建设一流、效果显著、示范引领是一流课程建设的关键特征,而后以山东大学物理化学一流课程建设为例,介绍了课程定位和教学目标的确定和设计落实,介绍了课程在一流基础、一流师资、一流资源、一流理念、一流成效等5个方面开展建设的做法和经验。对未来各高校开展一流课程建设具有一定的借鉴意义。

Identification of Driver Genes in Primary Liver Cancer by Integrating NGS and TCGA Mutation Data

Background: This study is aimed towards an exploration of mutant genes in primary liver cancer (PLC) patients by using bioinformatics and data mining techniques. Methods: Peripheral blood or paraffin-embedded tissues from 8 patients with PLC were analyzed using a 551 cancer-related gene panel on an Illumina NextSeq500 Sequencer (Illumina). Meanwhile, the data of 396 PLC cases were downloaded from The Cancer Genome Atlas (TCGA) database. The common mutated genes were obtained after integrating the mutation information of the above two cohorts, followed by functional enrichment and protein-protein interaction (PPI) analyses. Three well-known databases, including Vogelstein’s list, the Network of Cancer Gene (NCG), and the Catalog of Somatic Mutations in Cancer (COSMIC) database were used to screen driver genes. Furthermore, the Chi-square and logistic analysis were performed to analyze the correlation between the driver genes and clinicopathological characteristics, and Kaplan-Meier (KM) method and multivariate Cox analysis were conducted to evaluate the overall survival outcome. Results: In total, 84 mutation genes were obtained after 8 PLC patients undergoing gene mutation detection with next-generation sequencing (NGS). The top 100 most mutate gene data from PLC patients in TCGA database were downloaded. After integrating the above two cohorts, 17 common mutated genes were identified. Next, 11 driver genes were screened out by analyzing the intersection of the 17 mutation genes and the genes in the three well-known databases. Among them, RB1, TP53, and KRAS gene mutations were connected with clinicopathological characteristics, while all the 11 gene mutations had no relationship with overall survival. Conclusion: This study investigated the mutant genes with significant clinical implications in PLC patients, which may improve the knowledge of gene mutations in PLC molecular pathogenesis.

Enlightenment from the COVID-19 Pandemic:The Roles of Environmental Factors in Future Public Health Emergency Response

The coronavirus disease 2019(COVID-19)pandemic is challenging the current public health emergency response systems(PHERSs)of many countries.Although environmental factors,such as those influencing the survival of viruses and their transmission between species including humans,play important roles in PHERSs,little attention has been given to these factors.This study describes and elucidates the roles of environmental factors in future PHERSs.To improve countries’capability to respond to public health emergencies associated with viral infections such as the COVID-19 pandemic,a number of environmental factors should be considered before,during,and after the responses to such emergencies.More specifically,to prevent pandemic outbreaks,we should strengthen environmental and wildlife protection,conduct detailed viral surveillance in animals and hotspots,and improve early-warning systems.During the pandemic,we must study the impacts of environmental factors on viral behaviors,develop control measures to minimize secondary environmental risks,and conduct timely assessments of viral risks and secondary environmental effects with a view to reducing the impacts of the pandemic on human health and on ecosystems.After the pandemic,we should further strengthen surveillance for viruses and the prevention of viral spread,maintain control measures for minimizing secondary environmental risks,develop our capability to scientifically predict pandemics and resurgences,and prepare for the next unexpected resurgence.Meanwhile,we should restore the normal life and production of the public based on the“One Health”concept,that views global human and environmental health as inextricably linked.Our recommendations are essential for improving nations’capability to respond to global public health emergencies.

Real-time three-dimensional echocardiography predicts cardiotoxicity induced by postoperative chemotherapy in breast cancer patients

BACKGROUND The anthracycline chemotherapeutic drugs are cardiotoxic.Studies have found some indicators related to cardiotoxicity.However,there is currently no accurate indicator that can predict cardiac toxicity early.AIM To explore the diagnostic value of real-time three-dimensional echocardiography(RT3DE)in predicting cardiac toxicity in breast cancer patients undergoing chemotherapy.METHODS Female breast cancer patients who underwent radical mastectomy and postoperative chemotherapy at the Affiliated Hanzhou First People’s Hospital,Zhejiang University School of Medicine were recruited.All patients were routinely administered with chemotherapy for four cycles(T1-T4)after surgery.Two-dimensional(2D)echocardiography,RT3DE,and serological examinations were performed after each cycle of chemotherapy.Patients were divided into a toxic group and a non-toxic group based on whether patients hadΔleft ventricular ejection fraction>10%after one year of chemotherapy.Repeated measurement analysis of variance was used to compare the changes in 2D echocardiographic indicators,serological indicators,and RT3DE indicators before independent predictive indicators for cardiac toxicity in postoperative chemotherapy patients.Receiver operating characteristics(ROC)curve analysis was performed to analyze the diagnostic value of potential indicators in the diagnosis of cardiotoxicity.RESULTS A total of 107 female breast cancer patients were included in the study.T4 maximum peak velocity in early diastole(E peak)/mitral annulus lateral tissue Doppler(e'peak)(E/e'),serological indicators[T4 cardiac troponin I(cTnI)and T4 pro-brain natriuretic peptide(Pro-BNP)],T3 minimum left atrial volume(LAV),T4 LAVmin,T3 LAV before the start of the P wave(LAVprep),and T4 LAVprep in the toxicity group were significantly higher than those in the nontoxic group.Multivariate logistic regression found that T4 cTnI,T4 Pro-BNP,T3 LAVmin,T4 LAVmin,T3 LAVprep,and T4 LAVprep had potential predictive value for cardiac toxicity(P<0.05).ROC results showed that T4 LAVmin had the highest accuracy for diagnosing cardiac toxicity[area under the curve(AUC)=0.947;sensitivity=78.57%;specificity=94.62%],followed by T4 LAVprep(AUC=0.899;sensitivity=100%;specificity=66.67%).The accuracies of LAVprep and LAVprep in predicting cardiac toxicity were higher than those of T3 LAVmin and T3 LAVprep.CONCLUSION RT3DE of left atrial volume can be used to predict the cardiotoxicity caused by chemotherapy,and it is expected to guide the clinical adjustment of dose and schedule in time.

Bedside cardiopulmonary ultrasonography evaluates lung water content in very low-weight preterm neonates with patent ductus arteriosus

BACKGROUND Patent ductus arteriosus(PDA)is a common congenital heart abnormality in preterm neonates with a high incidence in neonates with very low birth weights.When PDA persists,interstitial lung water content increases,which could lead to abnormal circulation hemodynamics and pulmonary edema.It is important to perform early and reliable assessment of lung water content in very low-weight preterm neonates with persistent PDA.AIM To evaluate the role of bedside cardiopulmonary ultrasonography in the lung water content assessment in very low-weight preterm neonates with persistent PDA.METHODS From January 2018 to March 2020,69 very low-weight preterm neonates with echocardiography-confirmed PDA were selected as the PDA group.At the same time,89 very low-weight preterm neonates without PDA were randomly selected as the control group.All neonates underwent echocardiography and 6-segment lung ultrasonography on the fourth day after birth.The clinical characteristics and main ultrasonography results were compared between the two groups.Pearson’s analysis was used to analyze the correlation between lung ultrasonography score(LUS)and other related clinical and ultrasonography results in all neonates.In the PDA group,PDA diameters were recorded,and the correlation with LUS and left atrium to aortic(LA/AO)dimension ratio were also analyzed.LA/AO ratio is one of the ultrasonic diagnostic criteria for hemodynamically significant PDA.When the ratio is≥1.5,it suggests the possibility of hemodynamic changes in persistent PDA.A receiver operating characteristic curve was established using the sensitivity of LUS to predict the hemodynamic changes in neonates with PDA as the ordinate and 1-specificity as the abscissa.RESULTS A total of 158 neonates were enrolled in this study,including 69 in the PDA group and 89 in the control group.There were no statistical differences in sex,gestational age,birth weight,ventilator dependence,hospitalization length and left ventricular ejection fraction between the two groups(P>0.05).The LUS and LA/AO ratio in the PDA group were higher than those in the control group(P<0.05),but there was no difference of LUS in neonates with or without use of the ventilator(t=0.58,P=0.16).In all cases,LUS was negatively correlated with gestational age(r=-0.28,P<0.01)and birth weight(r=-0.36,P<0.01),while positively correlated with the LA/AO ratio(r=0.27,P<0.01).In the PDA group,PDA diameter was positively correlated with the LA/AO ratio(r=0.39,P<0.01)and LUS(r=0.31,P<0.01).Receiver operating characteristic results showed that LUS had the moderate accuracy for predicting hemodynamic changes in PDA(area under the curve=0.741;sensitivity=93.75%;specificity=50.94%).CONCLUSION Bedside cardiopulmonary ultrasonography can evaluate lung content in neonates with PDA and predict the possibility of hemodynamic changes in persistent PDA.

Theoretical and experimental investigation of chemical mechanical polishing of W–Ni–Fe alloy

Fine finishing of tungsten alloy is required to improve the surface quality of molds and precision instruments. Nevertheless, it is difficult to obtain high-quality surfaces as a result of grain boundary steps attributed to differences in properties of two-phase microstructures. This paper presents a theoretical and experimental investigation on chemical mechanical polishing of W–Ni–Fe alloy. The mechanism of the boundary step generation is illustrated and a model of grain boundary step formation is proposed. The mechanism reveals the effects of mechanical and chemical actions in both surface roughness and material removal. The model was verified by the experiments and the results show that appropriately balancing the mechanical and chemical effects restrains the generation of boundary steps and leads to a fine surface quality with a high removal rate by citric acid-based slurry.

Clinical value-oriented research paradigm about inheritance and innovation development of TCM dominant diseases

Modern medicine has made remarkable achievements in safeguarding people’s life and health,however,it is increasingly found that in the face of complex diseases,selective targeting of single target is often difficult to produce a comprehensive rehabilitation effect,and is prone to induce drug resistance,toxic side effects.Traditional Chinese medicine(TCM)has a long history of clinical application,and its clinical value in the treatment of complex diseases such as cardiovascular and cerebrovascular diseases,digestive diseases,skin diseases,rheumatism and immunity diseases,and adjuvant treatment of tumors has been proven to have obvious advantages.However,its modern research is relatively lagging behind,and in the face of the aging society and the characteristics of the modern disease spectrum,the traditional knowledge-driven research paradigm seems to be stuck in a bottleneck and difficult to make greater breakthroughs.Focusing on the key issues of TCM development in the new era,the clinical value-oriented strategy becomes to be a new research paradigm of TCM inheritance and innovation development,and dominant diseases would be the focus of the TCM inheritance and innovation development,which has been highly valued in recent years by the TCM academia and the relevant national management departments.Based on the clinical value,a series of policies are formulated for the selection and evaluation of the TCM dominant diseases(TCMDD),and exploratory researches about the clinical efficacy characteristics,the modern scientific connotation interpretation were carried out.The clinical value-oriented research paradigm of TCMDD inheritance and innovation development has been initially formed,which is characterized by strong policy support as the guarantee,systematic and standardized selection and evaluation methods as the driving force,scientific and effective research on internal mechanisms as the expansion,and effective clinical guidelines and principles as the transformation,which is of great value in promoting the high-quality development of the industries and undertaking of TCM.In this paper,the main policy support,selection and evaluation methods,therapeutic effect characterization,and modern scientific connotation research strategies of TCMDD in recent years have been comprehensively sorted out,with a view to providing the healthy and benign development of the research on TCMDD.

Effect of Cl^-ion on Anodic Iron Dissolution in H_2S-Containing Sulfuric Acid Solutions

The effect of Cl- ion on the anodic iron dissolution in H2SO4 solutions containing H2S has been studied by using electrochemical polarization curve measurements. The competitive adsorption for Cl- and HS- ions at an anodic potential has been calculated using the CNDO/2method. The results show that a ceftain concentration of the Cl- ion can be adsorbed steadily and inhibit the anodic reaction of iron catalyzed by HS-. However, when the Cl- ion reaches the saturation adsorption, it begins to promote the anodic reaction of iron due tO the increased negative charge of iron atoms.

Effect of Potential Perturbation Polarization on the Stress Corrosion Cracking of Type 321 Stainless Steel

The SCC susceptibility of type 321 stainless steel in acidic chloride solution has been studied by slow strain rate testing (SSRT) and SEM. During the slow rate tensile process, the specimen was polarized with different potential perturbation modes such as cyclic potential scan and cyclic potential step methods. The results indicated that the potential scan rate or step frequency played an essential role in the initiation and propagation of crack.

PRC2 primes bivalent genes for transcription induction independent of histone methyltransferase activity

Dear Editor,Polycomb group proteins,conserved epigenetic transcriptional repressors,are crucial for orchestrating diverse developmental gene expression programs(Schuettengruber et al.,2017).The polycomb repressive complex 2(PRC2)catalyzes H3 lysine-27 trimethylation(H3K27me3)to establish a delicate balance with H3K4me3,forming a bivalent chromatin state at target gene promoters and thereby poising them for subsequent transcription activation(Bernstein et al.,2006).

Pharmacodynamic advantages and characteristics of traditional Chinese medicine in prevention and treatment of ischemic stroke

Ischemic stroke(IS) is a severe cerebrovascular disease with a high incidence, mortality, and disability rate. The first-line treatment for IS is the use of recombinant tissue plasminogen activator(r-t PA).Regrettably, numerous patients encounter delays in treatment due to the narrow therapeutic window and the associated risk of hemorrhage. Traditional Chinese medicine(TCM) has exhibited distinct advantages in preventing and treating IS. TCM enhances cerebral microcirculation, alleviates neurological disorders, regulates energy metabolism, mitigates infammation, reduces oxidative stress injuries, and inhibits apoptosis, thereby mitigating brain damage and preventing IS recurrence. This article summarizes the etiology, pathogenesis, therapeutic strategies, and relationship with modern biology of IS from the perspective of TCM, describes the advantages of TCM in the treatment of IS, and further reviews the pharmacodynamic characteristics and advantages of TCM in the acute and recovery phases of IS as well as in post-stroke complications. Additionally, it offers valuable insights and references for the clinical application of TCM in IS prevention and treatment, as well as for the development of novel drugs.

纳米生物界面对淀粉样蛋白聚集的调控机制研究

本文以阿尔兹海默症的致病多肽β淀粉样蛋白(Aβ)为例,介绍了疾病相关淀粉样蛋白的分子精细结构、组装和聚集过程、聚集体形貌及神经细胞毒性的研究进展,并在此基础上以纳米生物界面对于淀粉样蛋白构象、组装结构、聚集动力学、神经细胞毒性等生物功能的调控机制进行研究.从分子水平上分析和探讨了纳米生物界面与淀粉样蛋白分子或者聚集体的相互作用方式和机理,有助于加深对淀粉样多肽和调节剂之间复杂多样的相互作用方式的理解,对深入了解淀粉样多肽的组装机理和调控机制以及探索治疗神经退行性疾病的药物设计等方面具有较大意义.

Complexation between DNA and Peptides with Precisely Controlled Charge Density and Distribution

Using three designed peptides with precisely-controlled charge density and three types of DNAs with different length and flexibility, the effect of charge density on the formation of PEC was studied. Highly charged（KKKK）5 interacts strongly with 21 bp ds DNA to form large complex, followed by precipitation; while the medium charged（KGKG）5 only form complex with 21 bp ds DNA at proper ＋/- charge ratios; and no prominent complex between weakly charged（KGGG）5 and 21 bp ds DNA is observed at the same conditions. Similar trend is observed when the peptides form complex with 2000 bp DNA or 21 nt ssD NA. It is also found that the complex formed by adding peptide to DNA is in random coil conformation, but the complex prepared by the inverse order is in molten globule state. Re-dissolution of the complex occurs only when DNA is added to peptides with similar or shorter length.

Chemical proteomics reveals ligustilide targets SMAD3,inhibiting collagen synthesis in aortic endothelial cells

Atherosclerosis is a persistent inflammatory state,while vascular endothelial fibrosis is one of the primary causes of atherosclerosis development.Although ligustilide(Lig) was shown to exert obvious antiatherogenic effects in previous studies,its precise mechanism has not been deeply discussed.In this paper,we designed a Lig-derived photoaffinity labelling(PAL) probe to identify potential therapeutic targets of Lig via chemical proteomics approach.Mothers against decapentaplegic homologue 3(SMAD3),a signal transmitter of transforming growth factor-β(TGF-β) which promotes the development of vascular fibrosis,was identified as a potential target of Lig.Lig suppressed the phosphorylation and nuclear translocation of SMAD3 by blocking the interaction between SMAD3 and TGF-β receptor 1,thereby inhibiting the collagen synthesis process.Hence,developing a novel SMAD3 inhibitor may present a promising therapeutic option for preventing vascular fibrosis.

Characterization,occurrence,environmental behaviors,and risks of nanoplastics in the aquatic environment:Current status and future perspectives

Microplastics(MPs)are emerging contaminants that have attracted worldwide attention in recent years.Compared with MPs,nanoplastics(NPs)may exhibit greater toxicity and higher potential risks because of their unique physiochemical nanoscale properties.However,the environmental fate,ecosystem toxicity,and potential risks associated with NPs have been less explored.This study summarizes the current research status of NPs through a comprehensive bibliometric analysis.The research hotspots and future trends of NPs were identified.We comprehensively searched the Web of Science Core Collection scientific database from its inception(2004)to November 26,2020.The results showed that the number of papers on NPs has increased significantly since 2014.The keywords used in NP research were divided into three clusters.Cluster 1 related to the physical,chemical,and biological behaviors of NPs in aquatic environments.Cluster 2 represented a relatively new and hot research field concerning the exposure,accumulation,and toxicity of NPs in organisms.Cluster 3 corresponded to the identification and quantification of NPs in marine environments and sediments.Moreover,we systematically elaborated the main areas of NP research,such as the characterization,occurrence,environmental behavior,ecological toxicity,and human health risks of NPs.The results showed that the quantification of NPs at environmentally relevant concentrations remains a challenge.Most studies have investigated polystyrene NPs,spherical NPs,and NPs in marine environments,while few studies have examined the aggregation,deposition,and ecological toxicity of NPs under environmentally relevant conditions.In addition,much less is known about the human health risks associated with NPs because little research has been conducted on estimating the overall human exposure to NPs and its effect.Finally,the current challenges and future perspectives of NP research are discussed.