Impact of microplastics and nanoplastics on liver health:Current understanding and future research directions

With continuous population and economic growth in the 21st century,plastic pollution is a major global issue.However,the health concern of microplastics/nanoplastics(MPs/NPs)decomposed from plastic wastes has drawn public attention only in the recent decade.This article summarizes recent works dedicated to understanding the impact of MPs/NPs on the liver-the largest digestive organ,which is one of the primary routes that MPs/NPs enter human bodies.The interrelated mechanisms including oxidative stress,hepatocyte energy re-distribution,cell death and autophagy,as well as immune responses and inflammation,were also featured.In addition,the disturbance of microbiome and gut-liver axis,and the association with clinical diseases such as metabolic dysfunction-associated fatty liver disease,steatohepatitis,liver fibrosis,and cirrhosis were briefly discussed.Finally,we discussed potential directions in regard to this trending topic,highlighted current challenges in research,and proposed possible solutions.

The oxidative DNA damage response： A review of research undertaken with Tsinghua and Xiangya students at the University of Pittsburgh

Endogenous stress and exogenous toxicants(chemicals and UV light) alter genetic information either directly or indirectly through the production of reactive oxygen species(ROS), thereby driving genomic instability in cells and promoting tumorigenesis. All living cells try to faithfully preserve and transmit their genomic information from one generation to the next using DNA repair mechanisms to repair oxidative DNA damage to prevent cancer or premature aging. Oxidative DNA damage comprises a mixture of DNA lesions including base damage, DNA single strand breaks(SSBs), and DNA double strand breaks(DSBs). This review summarizes some of the studies on DNA damage response at a defined genome locus that are performed by students from the Tsinghua University School of Medicine and the School of Medicine of Central South University(Xiangya Hospital) at the University of Pittsburgh School of Medicine. A summary of their work highlights the continuous contribution of the students to a particular research program and exemplifies the achievements of this China-U.S. collaborative training program.

Function and dysfunction of GEMIN5:understanding a novel neurodevelopmental disorder

The recent identification of a neurodevelopmental disorder with cerebellar atrophy and motor dysfunction(NEDCAM)has resulted in an increased interest in GEMIN5,a multifunction RNA-binding protein.As the largest member of the survival motor neuron complex,GEMIN5 plays a key role in the biogenesis of small nuclear ribonucleoproteins while also exhibiting translational regulatory functions as an independent protein.Although many questions remain regarding both the pathogenesis and pathophysiology of this new disorder,considerable progress has been made in the brief time since its discovery.In this review,we examine GEMIN5 within the context of NEDCAM,focusing on the structure,function,and expression of the protein specifically in regard to the disorder itself.Additionally,we explore the current animal models of NEDCAM,as well as potential molecular pathways for treatment and future directions of study.This review provides a comprehensive overview of recent advances in our understanding of this unique member of the survival motor neuron complex.

Associations of accelerometry-measured and self-reported physical activity and sedentary behavior with skeletal muscle energetics:The Study of Muscle,Mobility and Aging(SOMMA)

Background:Skeletal muscle energetics decline with age,and physical activity(PA)has been shown to offset these declines in older adults.Yet,many studies reporting these effects were based on self-reported PA or structured exercise interventions.Therefore,we examined the associations of accelerometry-measured and self-reported PA and sedentary behavior(SB)with skeletal muscle energetics and explored the extent to which PA and sedentary behavior would attenuate the associations of age with muscle energetics.Methods:As part of the Study of Muscle,Mobility and Aging,enrolled older adults(n=879),810(age=76.4±5.0 years old,mean±SD;58%women)had maximal muscle oxidative capacity measured ex vivo via high-resolution re spirometry of permeabilized myofibers(maximal oxidative phosphorylation(maxOXPHOS))and in vivo by ^(31)phosphorus magnetic resonance spectroscopy(maximal adenosine triphosphate(ATP_(max))).Accelerometry-measured sedentary behavior,light activity,and moderate-to-vigorous PA(MVPA)were assessed using a wrist-worn ActiGraph GT9X over 7 days.Self-reported sedentary behavior,MVPA,and all PA were assessed with the Community Healthy Activities Model Program for Seniors(CHAMPS)questionnaire.Linear regression models with progressive covariate adjustments evaluated the associations of sedentary behavior and PA with muscle energetics,as well as the attenuation of the age/muscle energetics association by MVP A and sedentary behavior.As a sensitivity analysis,we also examined activPAL-measured daily step count and time spent in sedentary behavior and their associations with muscle energetics.Results:Every 30 min/day more of ActiGraph-measured MVPA was associated with 0.65 pmol/(s×mg)higher maxOXPHOS and 0.012 mM/s higher ATP_(max)after adjusting for age,site/technician,and sex(p<0.05).Light activity was not associated with maxOXPHOS or ATP_(max).Meanwhile,every 30 min/day spent in ActiGraph-measured sedentary behavior was associated with 0.39 pmol/s×mg lower maxOXPHOS and0.006 mM/s lower ATP_(max)(p<0.05).Only associations with ATP_(max)held after further adjusting for socioeconomic status,body mass index,lifestyle factors,and multimorbidity.CHAMPS MVPA and all PA yielded similar associations with maxOXPHOS and ATP_(max)(p<0.05),but sedentary behavior did not.Higher activPAL step count was associated with higher maxOXHPOS and AT_(Pmax)(p<0.05),but time spent in sedentary behavior was not.Additionally,age was significantly associated with muscle energetics for men only(p<0.05);adjusting for time spent in ActiGraph-measured MVPA attenuated the age association with ATP_(max)by 58%in men.Conclusion:More time spent in accelerometry-measured or self-reported daily PA,especially MVPA,was associated with higher skeletal muscle energetics.Interventions aimed specifically at increasing higher intensity activity might offer potential therapeutic interventions to slow age-related decline in muscle energetics.Our work also emphasizes the importance of taking PA into consideration when evaluating associations related to skeletal muscle energetics.

Early proactive monitoring of DNA-thioguanine in patients with Crohn’s disease predicts thiopurine-induced late leucopenia in NUDT15/TPMT normal metabolizers

BACKGROUND Thiopurine-induced leucopenia significantly hinders the wide application of thiopurines.Dose optimization guided by nudix hydrolase 15(NUDT15)has significantly reduced the early leucopenia rate,but there are no definitive biomarkers for late risk leucopenia prediction.AIM To determine the predictive value of early monitoring of DNA-thioguanine(DNATG)or 6-thioguanine nucleotides(6TGN)for late leucopenia under a NUDT15-guided thiopurine dosing strategy in patients with Crohn’s disease(CD).METHODS Blood samples were collected within two months after thiopurine initiation for detection of metabolite concentrations.Late leucopenia was defined as a leukocyte count<3.5×10^(9)/L over two months.RESULTS Of 148 patients studied,late leucopenia was observed in 15.6%(17/109)of NUDT15/thiopurine methyltransferase(TPMT)normal and 64.1%(25/39)of intermediate metabolizers.In patients suffering late leucopenia,early DNATG levels were significantly higher than in those who did not develop late leucopenia(P=4.9×10^(-13)).The DNATG threshold of 319.43 fmol/μg DNA could predict late leucopenia in the entire sample with an area under the curve(AUC)of 0.855(sensitivity 83%,specificity 81%),and in NUDT15/TPMT normal metabolizers,the predictive performance of a threshold of 315.72 fmol/μg DNA was much more remarkable with an AUC of 0.902(sensitivity 88%,specificity 85%).6TGN had a relatively poor correlation with late leucopenia whether in the entire sample(P=0.021)or NUDT15/TPMT normal or intermediate metabolizers(P=0.018,P=0.55,respectively).CONCLUSION Proactive therapeutic drug monitoring of DNATG could be an effective strategy to prevent late leucopenia in both NUDT15/TPMT normal and intermediate metabolizers with CD,especially the former.

Use of Patient-Specific “4D” Tele-Education to Enhance Actual and Perceived Knowledge in Congenital Heart Disease (CHD) Patients

Background:Patients with congenital heart disease(CHD)will transition to lifelong adult congenital cardiac care.However,their structural heart disease is challenging to convey via two-dimensional drawings.This study utilized a tele-educational environment,with personalized three-dimensional(3D)modeling and health Details(3D+Details=“4D”),to improve actual and perceived knowledge,both important components of transition readiness in CHD patients.Methods:Participants aged≥13 years with a history of CHD and cardiac magnetic resonance imaging(MRI)studies were eligible.Cardiac MRI datasets were then used to segment and create 3D heart models(using Mimics,Materialize Inc.).Participantsfirst completed the MyHeart Questionnaire,a validated survey of actual knowledge.A tele-educational session was then scheduled,during which participants were shown a 3D model of a normal heart,followed by their personal 3D heart model and specific health details.Participants then repeated the actual knowledge survey,in addition to questionnaires assessing perceived knowledge pre-and post-session,as well as a satisfaction survey.Results:Twenty-two patients were included.Actual knowledge increased from 75%±15%to 89%±20%(p=0.00043)and perceived knowledge increased infive of seven questions.Actual knowledge correlated with perceived knowledge(r=0.608,p<0.0001).Ninety-one percent of participants ranked the 3D model as“very satisfactory”and ninety-five percent ranked the educational session as“very help-ful”or“extremely helpful.”Conclusions:The use of“4D”tele-education increased both actual and perceived knowledge and may help improve transition readiness in CHD patients.

Sino-U.S. partnerships in research, education, and patient care：The experience of the University of Pittsburgh and UPMC

In 2011, the University of Pittsburgh School of Medicine(UPSOM) and Tsinghua University formed a partnership to further the education of Tsinghua medical students. These students come to UPSOM as visiting research scholars for two years of their eight-year MD curriculum. During this time, the students, who have completed four years at Tsinghua, work full-time in medical school laboratories and research programs of their choice, essentially functioning as graduate students. In their first two months in Pittsburgh, the scholars have a one-week orientation to biomedical research, followed by two-week rotations in four labs selected on the basis of the scholars' scientific interests, after which they choose one of these labs for the remainder of the two years.Selected labs may be in basic science departments, basic science divisions of clinical departments, or specialized centers that focus on approaches like simulation and modeling. The Tsinghua students also have a brief exposure to clinical medicine. UPSOM has also formed a similar partnership with Central South University Xiangya School of Medicine in Changsha, Hunan Province. The Xiangya students come to UPSOM for two years of research training after their sixth year and, thus, unlike the Tsinghua students,have already completed their clinical rotations. UPSOM faculty members have also paved the way for UPMC(University of Pittsburgh Medical Center), UPSOM's clinical partner, to engage with clinical centers in China. Major relationships involving advisory, training, managerial, and/or equity roles exist with Xiangya International Medical Center, KingMED Diagnostics, First Chengmei Medical Industry Group, and Macare Women's Hospital. Both UPSOM and UPMC are actively exploring other clinical and academic opportunities in China.

Insights into the genetic architecture of congenital heart disease from animal modeling

Congenital heart disease(CHD)is observed in up to 1%of live births and is one of the leading causes of mortality from birth defects.While hundreds of genes have been implicated in the genetic etiology of CHD,their role in CHD pathogenesis is still poorly understood.This is largely a reflection of the sporadic nature of CHD,as well as its variable expressivity and incomplete penetrance.We reviewed the monogenic causes and evidence for oligogenic etiology of CHD,as well as the role of de novo mutations,common variants,and genetic modifiers.For further mechanistic insight,we leveraged single-cell data across species to investigate the cellular expression characteristics of genes implicated in CHD in developing human and mouse embryonic hearts.Understanding the genetic etiology of CHD may enable the application of precision medicine and prenatal diagnosis,thereby facilitating early intervention to improve outcomes for patients with CHD.

Mechanotransduction pathways in articular chondrocytes and the emerging role of estrogen receptor-α

In the synovial joint,mechanical force creates an important signal that influences chondrocyte behavior.The conversion of mechanical signals into biochemical cues relies on different elements in mechanotransduction pathways and culminates in changes in chondrocyte phenotype and extracellular matrix composition/structure.Recently,several mechanosensors,the first responders to mechanical force,have been discovered.However,we still have limited knowledge about the downstream molecules that enact alterations in the gene expression profile during mechanotransduction signaling.Recently,estrogen receptorα(ERα)has been shown to modulate the chondrocyte response to mechanical loading through a ligand-independent mechanism,in line with previous research showing that ERαexerts important mechanotransduction effects on other cell types,such as osteoblasts.In consideration of these recent discoveries,the goal of this review is to position ERαinto the mechanotransduction pathways known to date.Specifically,we first summarize our most recent understanding of the mechanotransduction pathways in chondrocytes on the basis of three categories of actors,namely mechanosensors,mechanotransducers,and mechanoimpactors.Then,the specific roles played by ERαin mediating the chondrocyte response to mechanical loading are discussed,and the potential interactions of ERαwith other molecules in mechanotransduction pathways are explored.Finally,we propose several future research directions that may advance our understanding of the roles played by ERαin mediating biomechanical cues under physiological and pathological conditions.

The Use of Social Networks in Curbing HIV in Higher Education Institutions: A Case Study of the University of Zambia

The AIDS epidemic has affected every aspect of Zambian society and is recognized as the greatest public health challenge of the past 30 years. Nevertheless, education can generate hope in the face of the epidemic using different methods, including social networks. This article investigates the positive and negative impacts of social networks on the spread of HIV at the University of Zambia (UNZA). The research study included survey-based oral interviews with 280 UNZA students. During the course of the study, we realized that efforts have been and are being put in place at UNZA to use online social networks to spread news about HIV and AIDS and how to stop its transmission. Findings showed that most participants felt that social networks hastened the spread of the virus among social media users. Despite social networks having a few positive effects, the results of our study indicate that the negative effects far outweigh the positive effects.

Transcriptome analysis creates a new era of precision medicine for managing recurrent hepatocellular carcinoma

The high incidence of hepatocellular carcinoma(HCC)recurrence negatively impacts outcomes of patients treated with curative intent despite advances in surgical techniques and other locoregional liver-targeting therapies.Over the past few decades,the emergence of transcriptome analysis tools,including real-time quantitative reverse transcription PCR,microarrays,and RNA sequencing,has not only largely contributed to our knowledge about the pathogenesis of recurrent HCC but also led to the development of outcome prediction models based on differentially expressed gene signatures.In recent years,the single-cell RNA sequencing technique has revolutionized our ability to study the complicated crosstalk between cancer cells and the immune environment,which may benefit further investigations on the role of different immune cells in HCC recurrence and the identification of potential therapeutic targets.In the present article,we summarized the major findings yielded with these transcriptome methods within the framework of a causal model consisting of three domains:primary cancer cells;carcinogenic stimuli;and tumor microenvironment.We provided a comprehensive review of the insights that transcriptome analyses have provided into diagnostics,surveillance,and treatment of HCC recurrence.

Flexural wave bandgap properties of phononic crystal beams with interval parameters

Uncertainties are unavoidable in practical engineering,and phononic crystals are no exception.In this paper,the uncertainties are treated as the interval parameters,and an interval phononic crystal beam model is established.A perturbation-based interval finite element method(P-IFEM)and an affine-based interval finite element method(A-IFEM)are proposed to study the dynamic response of this interval phononic crystal beam,based on which an interval vibration transmission analysis can be easily implemented and the safe bandgap can be defined.Finally,two numerical examples are investigated to demonstrate the effectiveness and accuracy of the P-IFEM and A-IFEM.Results show that the safe bandgap range may even decrease by 10%compared with the deterministic bandgap without considering the uncertainties.

The portrayal of hearing loss information in online Mandarin videos

Background/purpose:With increasing accessibility to the Internet,patients frequently use the Internet for hearing healthcare information.No study has examined the information about hearing loss available in the Mandarin language on online video-sharing platforms.The study’s primary purpose is to investigate the content,source,understandability,and actionability of hearing loss information in the Mandarin language’s one hundred most popular online videos.Method:In this project,publicly accessible online videos were analyzed.One hundred of the most popular Mandarin-language videos about hearing loss were identified(51 videos on YouTube and 49 on the Bilibili video-sharing platform).They were manually coded for different popularity metrics,sources,and content.Each video was also rated using the Patient Education Materials Assessment Tool for Audiovisual Materials(PEMAT-AV)to measure the understandability and actionability scores.Results:The video sources were classified as either media(n=36),professional(n=39),or consumer(n=25).The videos covered various topics,including symptoms,consequences,and treatment of hearing loss.Overall,videos attained adequate understandability scores(mean=73.6%)but low(mean=43.4%)actionability scores.Conclusions:While existing online content related to hearing loss is quite diverse and largely understandable,those videos provide limited actionable information.Hearing healthcare professionals,media,and content creators can help patients better understand their conditions and make educated hearing healthcare decisions by focusing on the actionability information in their online videos.

Associations between aerobic and muscle-strengthening physical activity,sleep duration,and risk of all-cause mortality:A prospective cohort study of 282,473 U.S.adults

Purpose:To examine the joint associations between meeting guidelines for physical activity(PA)and sleep duration and all-cause mortality risk among adults.Methods:Participants were adults(n=282,473)aged 18-84 years who participated in the 2004-2014 U.S.National Health Interview Survey.Mortality status was ascertained using the National Death Index through December 2015.Self-reported PA(Active:meeting both aerobic(AER)and muscle-strengthening(MSA)guidelines,AER only(AER),MSA only(MSA),or not meeting either AER or MSA(Inactive))and sleep duration(Short,recommended(Rec),or Long)were classified according to guidelines,and 12 PA-sleep categories were derived.Adjusted hazard ratios and 95%confidence intervals(95%CIs)for all-cause mortality risk were estimated using Cox proportional hazards regression models.Results:A total of 282,473 participants(55%females)were included;18,793 deaths(6.7%)occurred over an average follow-up of 5.4 years.Relative to the Active-Rec group,all other PA-sleep groups were associated with increased mortality risk except for the Active-Short group(hazard ratio=1.08;95%CI:0.92-1.26).The combination of long sleep with either MSA or Inactive appeared to be synergistic.For a given sleep duration,mortality risk progressively increased among participants classified as AER,MSA,and Inactive.Within each activity level,the mortality risk was greatest among adults with long sleep.Conclusion:Relative to adults meeting guidelines for both PA and sleep duration,adults who failed to meet guidelines for both AER and muscle strengthening PA and who also failed to meet sleep duration guidelines had elevated all-cause mortality risks.These results support interventions targeting both PA and sleep duration to reduce mortality risk.

Child Abuse during the Pandemic and Trauma-Informed Care: A Review of Evidence-Based Literature

Abuse of infants and children is a public health problem that warrants immediate attention. It is estimated that over 7 million children are affected by child abuse yearly, with the highest rate of abuse in those less than one year of age. Approximately 60% of child abuse victims are children under the age of three years, making infants and young children a particularly vulnerable population. Interventions targeting the perinatal period can be effective in mitigating child abuse, including parent education programs and trauma-informed care services. This paper provides an overview of the current evidence base related to child abuse following the COVID-19 pandemic, with a focus on prevention and intervention strategies that can be utilized to increase caregiver support and reduce child abuse rates during the perinatal period.

On the Vortex Sheets of Compressible Flows

This paper provides a review of the recent results on the stability of vortex sheets in compressible flows.Vortex sheets are contact discontinuities of the underlying flows.The vortex sheet problem is a free boundary problem with a characteristic boundary and is challenging in analysis.The formulation of the vortex sheet problem will be introduced.The linear stability and nonlinear stability for both the two-dimensional two-phase compressible flows and the two-dimensional elastic flows are summarized.The linear stability of vortex sheets for the three-dimensional elastic flows is also presented.The difficulties of the vortex sheet problems and the ideas of proofs are discussed.

Sea-Land Segmentation of Remote Sensing Images Based on SDW-UNet

Image segmentation of sea-land remote sensing images is of great importance for downstream applications including shoreline extraction,the monitoring of near-shore marine environment,and near-shore target recognition.To mitigate large number of parameters and improve the segmentation accuracy,we propose a new Squeeze-Depth-Wise UNet(SDW-UNet)deep learning model for sea-land remote sensing image segmentation.The proposed SDW-UNet model leverages the squeeze-excitation and depth-wise separable convolution to construct new convolution modules,which enhance the model capacity in combining multiple channels and reduces the model parameters.We further explore the effect of position-encoded information in NLP(Natural Language Processing)domain on sea-land segmentation task.We have conducted extensive experiments to compare the proposed network with the mainstream segmentation network in terms of accuracy,the number of parameters and the time cost for prediction.The test results on remote sensing data sets of Guam,Okinawa,Taiwan China,San Diego,and Diego Garcia demonstrate the effectiveness of SDW-UNet in recognizing different types of sea-land areas with a smaller number of parameters,reduces prediction time cost and improves performance over other mainstream segmentation models.We also show that the position encoding can further improve the accuracy of model segmentation.

Registration of the Seated Condylar Position (SCP/CR): Part I: Rationale

The purpose of this paper is to present the rationale for registration of the Seated Condylar Position (SCP)/Centric Relation (CR) position of the condyles.

Registration of the Seated Condylar Position (SCP/CR): Part II: Technique: The Two-Piece Wax Bite Registration

The purpose of this paper is to present the technique for registration of the Seated Condylar Position (SCP)/Centric Relation (CR) position of the condyles: a two-piece wax bite registration with deprogramming and no mandibular manipulation.

(Ti_(60)Cr_(30)Nb_(10))_(100-x)Al_(x)轻质中熵合金的力学与腐蚀性能

研究轻质(Ti_(60)Cr_(30)Nb_(10))_(100-x)Al_(x)(x=0,5,7.5,10,摩尔分数,%)中熵合金在铸态和均匀化态下的显微组织、力学性能和腐蚀行为。结果表明,随着Al含量从0增加到10%(摩尔分数),铸态合金均由相同的相组成,即体心立方(BCC)相和少量TiCr2型Laves相组成。均匀化后,所有合金均由单相BCC组成。此外,(Ti_(60)Cr_(30)Nb_(10))_(95)A_(l5)中熵合金表现出在铸态和均匀态条件下最优异的力学性能,屈服强度分别约为1048 MPa和1017 MPa,同时保持超50%压缩应变。与TC4和铸态(Ti_(60)Cr_(30)Nb_(10))_(95)A_(l5)合金相比,均匀态(Ti_(60)Cr_(30)Nb_(10))_(95)A_(l5)合金表现出更优异的耐腐蚀性能,这主要归因于均匀的显微组织与化学成分。