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BackgroundAlthough numerous studies have explored acupuncture for alleviating Parkinson's disease (PD) symptoms, specific methods focusing on reducing anxiety in these patients are lacking. Preliminary research indicates that acupuncture may improve anxiety in patients with Parkinson's; however, high-quality evidence is lacking. Therefore, we conducted a meta-analysis and trial sequential analysis (TSA) to assess the efficacy of acupuncture in managing anxiety symptoms in PD.MethodsWe systematically searched eight databases for randomized controlled trials (RCTs) evaluating the efficacy of acupuncture for the treatment of anxiety in patients with PD. Primary outcomes were measured using the Hamilton Anxiety Scale (HAMA) and the Self-Rating Anxiety Scale (SAS). Secondary outcomes included the Parkinson's Disease Questionnaire-39 (PDQ-39) and the Unified Parkinson's Disease Rating Scale (UPDRS). Risk of bias was assessed using the Cochrane RoB 2.0 tool, and certainty of evidence was assessed using the GRADE system. The Trial Sequential Analysis (TSA) was used to assess the sufficiency of the evidence.ResultsOur meta-analysis included 14 studies. The Manual acupuncture (MA) + routine drug treatment (RDT) group improved more than the RDT alone group. MA was more effective than sham acupuncture. MA+ traditional Chinese medicine (TCM) was also more effective than TCM. Auricular therapy (AT) was not as effective as control therapy (CT). The Electroacupuncture (EA) + routine drug treatment (RDT) group was not as effective as RDT. PDQ-39 and UPDRS subgroup analysis showed that the acupuncture group had better clinical efficacy than CT. The GRADE assessment rated the overall certainty of evidence for anxiety outcomes as low, PDQ-39 as very low and UPDRS as low. TSA results indicate insufficient evidence; further high-quality RCTs are needed to substantiate these findings.ConclusionOur analysis suggests that MA combined with RDT may help ameliorate anxiety in PD patients, although the evidence is weak due to low quality RCTs. EA and AT showed no significant effects, highlighting the need for more rigorous studies with better controls and longer follow-up. The potential of acupuncture for PD-related anxiety should be considered with caution until stronger evidence becomes available.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/.

Cholangiocarcinoma (CCA) is a highly aggressive malignant tumor that originates from the biliary system. With restricted treatment options at hand, the challenging aspect of early CCA diagnosis leads to a bleak prognosis. Besides the intrinsic characteristics of tumor cells, the generation and progression of CCA are profoundly influenced by the tumor microenvironment, which engages in intricate interactions with cholangiocarcinoma cells. Of notable significance is the role of extracellular vesicles as key carriers in enabling communication between cancer cells and the tumor microenvironment. This review aims to provide a comprehensive overview of current research examining the interplay between extracellular vesicles and the tumor microenvironment in the context of CCA. Specifically, we will emphasize the significant contributions of extracellular vesicles in molding the CCA microenvironment and explore their potential applications in the diagnosis, prognosis assessment, and therapeutic strategies for this aggressive malignancy.

BackgroundIn terms of assessing obesity-associated risk, quantification of visceral adipose tissue (VAT) has become increasingly important in risk assessment for cardiovascular and metabolic diseases. However, differences exist in the accuracy of various modalities, with a lack of up-to-date comparison with three-dimensional whole volume assessment.AimsUsing CT or MRI three-dimensional whole volume VAT as a reference, we evaluated the correlation of various commonly used modalities and techniques namely body impedance analysis (BIA), dual-energy x-ray absorptiometry (DXA) as well as single slice CT to establish how these methods compare.MethodsWe designed the study in two parts. First, we performed an intra-individual comparison of the 4558 participants from the UK Biobank cohorts with matching data of MRI abdominal body composition, DXA with VAT estimation, and BIA. Second, we evaluated 174 CT scans from the publicly available dataset to assess the correlation of the commonly used single-slice technique compared to three-dimensional VAT volume.ResultsAcross the UK Biobank cohort, the DXA-derived VAT measurement correlated better (R2 0.94, p

ObjectiveThe objective of this study is to evaluate the methodological quality of Tuina clinical practice guidelines (CPGs).MethodsComputer searches of China National Knowledge Infrastructure (CNKI), Chinese Technical Periodicals (VIP), Wanfang Data Knowledge Service Platform, PubMed, Cochrane Library, Embase, and other databases were conducted to search for published guidelines on Tuina, with a search time frame from database creation to March 2021. Four evaluators independently used the Appraisal of Guidelines for Research and Evaluation II instrument to evaluate the quality of the included guidelines.ResultsA total of eight guidelines related to Tuina were included in this study. The quality of reporting was low in all included guidelines. The highest quality report had a total score of 404 and was rated as “highly recommended.” The worst guideline had a final score of 241 and was rated as “not recommended.” Overall, 25% of the included guidelines were recommended for clinical use, 37.5% were recommended after revision, and 37.5% were not recommended.ConclusionThe number of existing Tuina clinical practice guidelines is limited. The methodological quality is low, far from the internationally accepted clinical practice guideline development and reporting norms. In the future, reporting specifications of guidelines and the methodology of guideline development, including the rigor of the guideline development process, the clarity, application, and independence of reporting, should be emphasized in the development of the Tuina guidelines. These initiatives could improve the quality and applicability of clinical practice guidelines to guide and standardize the clinical practice of Tuina.

Retinal images have been proven significant in diagnosing multiple diseases such as diabetes, glaucoma, and hypertension. Retinal vessel segmentation is crucial for the quantitative analysis of retinal images. However, current methods mainly concentrate on the segmentation performance of overall retinal vessel structures. The small vessels do not receive enough attention due to their small percentage in the full retinal images. Small retinal vessels are much more sensitive to the blood circulation system and have great significance in the early diagnosis and warning of various diseases. This paper combined two unsupervised methods, local phase congruency (LPC) and orientation scores (OS), with a deep learning network based on the U-Net as attention. And we proposed the U-Net using local phase congruency and orientation scores (UN-LPCOS), which showed a remarkable ability to identify and segment small retinal vessels. A new metric called sensitivity on a small ship (Sesv) was also proposed to evaluate the methods’ performance on the small vessel segmentation. Our strategy was validated on both the DRIVE dataset and the data from Maastricht Study and achieved outstanding segmentation performance on both the overall vessel structure and small vessels.

IntroductionPhysical fitness is a health indicator contributing to the prevention of non-communicable diseases that threaten public health. Studies across a number of global populations indicate that physical fitness is generally declining. This study investigated the trend in physical fitness of Chinese male first-year college students from 2013 to 2019 to offer critical information for fostering individual and public health.MethodsThis study used archival data and a natural experiment design capturing 4 years of data prior to implementation of the Healthy China 2030 initiative and 3 years following. Physical fitness tests were based on the Chinese national student physical fitness standards for males including body mass index, vital capacity, standing-long-jump, sit-and-reach, pull-ups, 50 m sprint, and 1,000 m run. Because the physical fitness tests set different standards for males and females, female data will be reported separately. Data from a total of 3,185 Chinese male first-year college students from a private university in Hebei Province of China were included in the study. A one-way multivariate analysis of variance was used for analyzing the research data.ResultsThe results indicated an overall significant difference in health-related physical fitness of Chinese male first-year college students, with scores on health indicators generally declining from 2013 to 2019. Despite improvement on some fitness variables in some years, performance on virtually all indicators was diminished compared to baseline years.DiscussionThese findings can contribute to the existing global literature in the field of public health showing general declines in physical fitness. Chinese universities have the opportunity to support Healthy China 2030 goals and cultivate individuals' physical fitness by offering physical education course that encourage college students to participate in moderate-to-vigorous-intensity physical activities in order to support physical fitness development.

Background: Septic shock has increasingly become a cause of death threatening human survival. Shenfu Injection (SFI), a patented Chinese medicine, has been widely used in the treatment of patients with sepsis and cardiovascular diseases domestically. We sought to examine whether combination therapy with SFI can improve clinical outcomes in critically ill patients undergoing mechanical ventilation (MV).Methods: This real-world, multicenter retrospective trial enrolled consecutive adult patients with sepsis requiring MV from four medical/surgical intensive care units (ICUs) in China between August 2016 and September 2021. Patients were identified from the medical information department database of each center and assigned to either of two groups (SFI or control) on the basis of the initial treatment received. The primary outcome was 28-day all-cause mortality, and the durations of vasopressor therapy and MV, the ICU length of stay, and costs were assessed as secondary outcomes. Subsequently, we performed a meta-analysis of randomized controlled trials (RCTs) on SFI published before July 2021 to verify our conclusions.Results: 2311 mechanically ventilated patients with septic shock (1128 patients in the SFI group and 1183 in the control group) were analyzed. The survival probability during the first 28 days after admission in the SFI group was greater than that in the control group [p < 0.01 by log-rank test; hazard ratio (HR), 0.56; 95% confidence interval (CI), 0.39–0.72]. Patients in the SFI group also experienced a significantly reduced duration of vasopressor therapy [7.28 (95% CI, 6.14–8.42) vs. 12.06 (95% CI, 10.71–13.41) days, p < 0.001], more ventilator-free days [6.49 (95% CI, 5.42–7.55) vs. 10.84 (95% CI, 9.59–12.09) days, p < 0.001], a shorter ICU length of stay [18.48 (95% CI, 17.59–19.38) vs. 23.77 (95% CI, 22.47–25.07) days, p < 0.001], and more time free from organ failure [14.23 (95% CI, 12.94–15.52) vs. 19.07 (95% CI, 16.09–22.05) days, p < 0.001]. No major adverse effects were reported in either group.Conclusion: Among critically ill patients requiring MV, combination therapy with SFI can improve the survival probability without any obvious adverse reactions.

Recurrent aphthous ulcer (RAU), one of the most common diseases in humans, has an unknown etiology and is difficult to treat. Thalidomide is an important immunomodulatory and antitumor drug and its effects on the gut microbiota still remain unclear. We conducted a metagenomic sequencing study of fecal samples from a cohort of individuals with RAU, performed biochemical assays of cytokines, immunoglobulins and antimicrobial peptides in serum and saliva, and investigated the regulation effects of thalidomide administration and withdrawal. Meanwhile we constructed the corresponding prediction models. Our metagenome-wide association results indicated that gut dysbacteriosis, microbial dysfunction and immune imbalance occurred in RAU patients. Thalidomide regulated gut dysbacteriosis in a species-specific manner and had different sustainable effects on various probiotics and pathogens. A previously unknown association between gut microbiota alterations and RAU was found, and the specific roles of thalidomide in modulating the gut microbiota and immunity were determined, suggesting that RAU may be affected by targeting gut dysbacteriosis and modifying immune imbalance. In-depth insights into sophisticated networks consisting of the gut microbiota and host cells may lead to the development of emerging treatments, including prebiotics, probiotics, synbiotics, and postbiotics.

Background: Colon cancer is the fifth most common cause of cancer-related death worldwide, and despite significant advances in related treatment, the prognosis of colon cancer patients remains poor.Objective: This study performs systematic bioinformatics analysis of prognostic-associated RNA processing factor genes in colon cancer using the Cancer Related Genome Atlas database to explore their role in colon carcinogenesis and prognosis and excavate potential therapeutic targets.Methods: Data sets of colon cancer patients were obtained from GEO and TCGA databases. Univariate cox analysis was performed on the GSE39582 training set to identify prognosis-associated RNA processing factor genes and constructed a muticox model. The predictive performance of the model was validated by Correlation curve analysis. Similar results were obtained for the test dataset. Functional analyses were performed to explore the underlying mechanisms of colon carcinogenesis and prognosis.Results: A constructed muticox model consisting of βi and prognosis-related RNA processing factor gene expression levels (Expi) was established to evaluate the risk score of each patient. The subgroup with a higher risk score had lower overall survival (OS), higher risk factor, and mortality. We found that the risk score, age, gender, and TNM Stage were strongly associated with OS, and the 13-gene signature as an independent prognostic factor for colon cancer. The model has good accuracy in predicting patient survival and is superior to traditional pathological staging.Conclusion: This study proposes 13 RNA processing factor genes as a prognostic factor for colon cancer patients, which can independently predict the clinical outcome by risk score. The gene expression profile in this model is closely related to the immune status and prognosis of colon cancer patients. The interaction of the 13 RNA processing factor genes with the immune system during colon carcinogenesis provides new ideas for the molecular mechanisms and targeted therapies for colon cancer.

South China is a well-known grand felsic igneous rocks province. However, it is still controversial and not well understood whether the Mesozoic tectono-magmatic pattern is dominated by the subduction of the paleo-Pacific oceanic plate. In this study, we address this question by concentrating on the long-term evolutionary Guandimiao batholith, which has complex lithofacies with different formation ages and can be a superb record of the Mesozoic tectonic evolution in South China. Geochronologically, four stages of magmatism can be identified combined with previous reports: granodiorite (G1, 239 Ma), biotite monzogranite (G2-1) and two-mica monzogranite (G2-2) (230–203 Ma), granite porphyry (G3, 211–190 Ma), and lamprophyre (L4, 121 Ma). G1 and G2-1 have an affinity with I-type granite and were derived from metabasaltic to metatonalitic sources, whereas G2 and G3 show S-type granite characteristics and were derived from the para-metamorphic basement of the Cathaysia block. The L4 was derived from partial melting of garnet and spinel lherzolite and underwent mixing between Mesoproterozoic pelagic and/or terrigenous sediments and the subcontinental lithosphere mantle (SCLM) of South China. The granitoids of the Guandimiao batholith underwent intensely fractional crystallization of feldspar, Ti-bearing minerals, allanite and monazite. The zircon U–Pb dating of L4 in the Guandimiao batholith completely records the six stages of pre-Mesozoic tectonic events in the SCB. During the Mesozoic, the main body of the Guandimiao batholith (G1, G2-1 and G2-2) recorded the closure of the paleo-Tethys Ocean in the Triassic and the subsequent regional extension of the postcollision. G-3 and L4 of the Guandimiao batholith documented the transition of tectonic and dynamic regimes in the early Yanshanian and the rollback and steep subduction of the paleo-Pacific Ocean in the late Yanshanian.

BackgroundAcute-on-chronic liver failure (ACLF) patients have high mortality in a short period of time. This study aimed to compare the prognosis of transplanted ACLF patients to that of nontransplanted ACLF patients and decompensated cirrhosis recipients.MethodsClinical data of 29 transplanted ACLF patients, 312 nontransplanted ACLF patients, and 60 transplanted decompensated cirrhosis patients were retrospectively collected. Propensity score matching (PSM) analysis was used to match patients between different groups.ResultsAfter PSM, the 90-day and 1-year survival of transplanted ACLF patients was significantly longer than that of nontransplant controls. Although the 90-day survival and 1-year survival of ACLF recipients was similar to that of decompensated cirrhosis controls, ACLF recipients were found to have longer mechanical ventilation, longer intensive care unit (ICU) stay, longer hospital stay, higher incidence of tracheotomy, higher expense, and higher morbidity of complication than matched decompensated cirrhosis controls. The 90-day and 1-year survival of transplanted ACLF grade 2–3 patients was also significantly longer than that of nontransplanted controls.ConclusionsLiver transplantation can strongly improve the prognosis of ACLF patients. Despite having more burdens (including longer mechanical ventilation, longer ICU stay, higher incidence of tracheotomy, longer hospital stay, higher hospitalization expense, and higher complication morbidity), ACLF recipients can obtain similar short-term and long-term survival to decompensated cirrhosis recipients. For severe ACLF patients, liver transplantation can also significantly improve their short-term and long-term survival.

BackgroundLung cancer is the leading cause of cancer-related mortality, and accurate prediction of patient survival can aid treatment planning and potentially improve outcomes. In this study, we proposed an automated system capable of lung segmentation and survival prediction using graph convolution neural network (GCN) with CT data in non-small cell lung cancer (NSCLC) patients.MethodsIn this retrospective study, we segmented 10 parts of the lung CT images and built individual lung graphs as inputs to train a GCN model to predict 5-year overall survival. A Cox proportional-hazard model, a set of machine learning (ML) models, a convolutional neural network based on tumor (Tumor-CNN), and the current TNM staging system were used as comparison.FindingsA total of 1,705 patients (main cohort) and 125 patients (external validation cohort) with lung cancer (stages I and II) were included. The GCN model was significantly predictive of 5-year overall survival with an AUC of 0.732 (p < 0.0001). The model stratified patients into low- and high-risk groups, which were associated with overall survival (HR = 5.41; 95% CI:, 2.32–10.14; p < 0.0001). On external validation dataset, our GCN model achieved the AUC score of 0.678 (95% CI: 0.564–0.792; p < 0.0001).InterpretationThe proposed GCN model outperformed all ML, Tumor-CNN, and TNM staging models. This study demonstrated the value of utilizing medical imaging graph structure data, resulting in a robust and effective model for the prediction of survival in early-stage lung cancer.

Clubroot is caused by Plasmodiophora brassicae, which threatens Brassicaceae crop production worldwide. In recent years, there has been an outbreak and rapid spread of clubroot in many major cruciferous crop-producing areas of China. In this study, we identified a cabbage material DingWen (DW) with different resistant capabilities from Huashuang5R (H5R) and Huayouza62R of Brassica napus, which are currently used as the main resistant cultivars for clubroot management in China. We used a next-generation sequencing-based bulked segregant analysis approach, combined with genetic mapping to identify clubroot-resistant (CR) genes from F1 population generated from a cross between the DW (CR) and HZSX (clubroot susceptible). The CR locus of DW (named CRA8.1) was mapped to a region between markers A08-4346 and A08-4853, which contains two different loci CRA8.1a and CRA8.1b after fine mapping. The CRA8.1b loci contain a fragment of 395 kb between markers A08-4624 and A08-4853 on A08 chromosome, and it is responsible for the resistance to PbZj and PbXm isolates. However, together with CRA8.1a, corresponding to a 765-kb region between markers A08-4346 and A08-4624, then it can confer resistance to PbXm+. Finally, through expression analysis between resistant and susceptible materials, two genes encoding TIR-NBS-LRR proteins (BraA08g039211E and BraA08g039212E) and one gene encoding an RLP protein (BraA08g039193E) were identified to be the most likely CR candidates for the peculiar resistance in DW.

BackgroundAlthough there is a growing research base on low back pain, the bibliometric literature related to it is deficient. The aim of this study was to conduct a bibliometric and visualization analysis of low back pain and to provide a broad view of the current trends in LBP research and a potential guide in this discipline.MethodsThe authors searched the Web of Science to extract publications regarding low back pain, and found a total of 12,249 publications during a period of 22 years, among which 12,242 were eligible. We classified and analyzed publications such as total citations, average citations per item, H-index, research types, countries/regions, institutions, and journals using standard bibliometric indicators. Bibliometric approaches (VOSviewer1.6.13 and CiteSpace 5.8.3) were also available for gathering information and explore the trends of research.ResultsConspicuously, over the past 22 years, an increasing number of scholars have specialized in the research of LBP, exerting the boom in articles. The largest number of document type was that of articles. Under modern conditions, regional distinction existed in the research of low back pain and developed countries preceded others. Research individuals and institutions were preoccupied by respective aspects. Visualization analysis provided objective information for potential collaborators and cooperative institutions. Furthermore, most burst keywords varied during different periods.ConclusionsThe map of research on LBP obtained by our analysis is expected to help researchers to efficiently and effectively explore LBP.

Liver transplantation is currently the only effective treatment for patients with end-stage liver disease; however, donor liver scarcity is a notable concern. As a result, extensive endeavors have been made to diversify the source of donor livers. For example, the use of a decellularized scaffold in liver engineering has gained considerable attention in recent years. The decellularized scaffold preserves the original orchestral structure and bioactive chemicals of the liver, and has the potential to create a de novo liver that is fit for transplantation after recellularization. The structure of the liver and hepatic extracellular matrix, decellularization, recellularization, and recent developments are discussed in this review. Additionally, the criteria for assessment and major obstacles in using a decellularized scaffold are covered in detail.

Cigarette smoking could have certain effects on gut microbiota. Some pioneering studies have investigated effects of active smoking on the microbiome in local segments of the digestive tract, while active smoking-induced microbiome alterations in the whole digestive tract have not been fully investigated. Here, we developed a rat model of active smoking and characterized the effects of active smoking on the microbiota within multiple regions along the digestive tract. Blood glucose and some metabolic factors levels, the microbial diversity and composition, relative abundances of taxa, bacterial network correlations and predictive functional profiles were compared between the control group and active smoking group. We found that active smoking induced hyperglycemia and significant reductions in serum insulin and leptin levels. Active smoking induced region-specific shifts in microbiota structure, composition, network correlation and metabolism function along the digestive tract. Our results demonstrated that active smoking resulted in a reduced abundance of some potentially beneficial genera (i.e. Clostridium, Turicibacter) and increased abundance of potentially harmful genera (i.e. Desulfovibrio, Bilophila). Functional prediction suggested that amino acid, lipid, propanoate metabolism function could be impaired and antioxidant activity may be triggered. Active smoking may be an overlooked risk to health through its potential effects on the digestive tract microbiota, which is involved in the cause and severity of an array of chronic diseases.

Melanoma is the deadliest form of skin cancer. Although targeted therapies and immunotherapies have revolutionized the treatment of metastatic melanoma, most patients are not cured. Therapy resistance remains a significant clinical challenge. Melanoma comprises phenotypically distinct subpopulations of cells, exhibiting distinct gene signatures leading to tumor heterogeneity and favoring therapeutic resistance. Cellular plasticity in melanoma is referred to as phenotype switching. Regardless of their genomic classification, melanomas switch from a proliferative and differentiated phenotype to an invasive, dedifferentiated and often therapy-resistant state. In this review we discuss potential mechanisms underpinning melanoma phenotype switching, how this cellular plasticity contributes to resistance to both targeted therapies and immunotherapies. Finally, we highlight novel strategies to target plasticity and their potential clinical impact in melanoma.

Crosses that lead to heterosis have been widely used in the rapeseed (Brassica napus L.) industry. Cytoplasmic male sterility (CMS)/restorer-of-fertility (Rf) systems represent one of the most useful tools for rapeseed production. Several CMS types and their restorer lines have been identified in rapeseed, but there are few studies on the mechanisms underlying fertility restoration. Here, we performed morphological observation, map-based cloning, and transcriptomic analysis of the F2 population developed by crossing the CMS line WNJ01A with its restorer line Hui01. Paraffin-embedded sections showed that the sporogenous cell stage was the critical pollen degeneration period, with major sporogenous cells displaying loose and irregular arrangement in sterile anthers. Most mitochondrial electron transport chain (mtETC) complex genes were upregulated in fertile compared to sterile buds. Using bulked segregant analysis (BSA)-seq to analyze mixed DNA pools from sterile and fertile F2 buds, respectively, we identified a 6.25 Mb candidate interval where Rfw is located. Using map-based cloning experiments combined with bacterial artificial chromosome (BAC) clone sequencing, the candidate interval was reduced to 99.75 kb and two pentatricopeptide repeat (PPR) genes were found among 28 predicted genes in this interval. Transcriptome sequencing showed that there were 1679 DEGs (1023 upregulated and 656 downregulated) in fertile compared to sterile F2 buds. The upregulated differentially expressed genes (DEGs) were enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) lysine degradation pathway and phenylalanine metabolism, and the downregulated DEGs were enriched in cutin, suberine, and wax biosynthesis. Furthermore, 44 DEGs were involved in pollen and anther development, such as tapetum, microspores, and pollen wall development. All of them were upregulated except a few such as POE1 genes (which encode Pollen Ole e I allergen and extensin family proteins). There were 261 specifically expressed DEGs (9 and 252 in sterile and fertile buds, respectively). Regarding the fertile bud-specific upregulated DEGs, the ubiquitin–proteasome pathway was enriched. The top four hub genes in the protein–protein interaction network (BnaA09g56400D, BnaA10g18210D, BnaA10g18220D, and BnaC09g41740D) encode RAD23d proteins, which deliver ubiquitinated substrates to the 26S proteasome. These findings provide evidence on the pathways regulated by Rfw and improve our understanding of fertility restoration.

Nef is an accessory protein encoded by human immunodeficiency virus type-1 (HIV-1) and plays important roles in regulating HIV-1 infection and viral replication. Interestingly, HIV-1 Nef can promote degradation of numerous host proteins to disrupt cellular antiviral immune response. However, how HIV-1 Nef is degraded by host factors remains largely unexplored. Here, we identified c-Cbl as a host ubiquitin E3 ligase of HIV-1 Nef. We found that c-Cbl interacts with Nef and reduces protein levels of HIV-1 Nef. Further studies demonstrated that c-Cbl promoted Lys48-linked polyubiquitination of HIV-1 Nef, thus attenuating protein stability of HIV-1 Nef. Importantly, cellular c-Cbl ubiquitinated and degraded Nef proteins produced by HIV-1 NL4-3 virions, and ultimately attenuated HIV-1 virulence for infection of THP1 cells. This study reveals a ubiquitination and proteasome-dependent degradation mechanism of HIV-1 Nef protein, and could provide potential strategies for fighting against HIV-1.

Background: In terms of assessing obesity-associated risk, quantification of visceral adipose tissue (VAT) has become increasingly important in risk assessment for cardiovascular and metabolic diseases. However, differences exist in the accuracy of various modalities, with a lack of up-to-date comparison with three-dimensional whole volume assessment. Aims: Using CT or MRI three-dimensional whole volume VAT as a reference, we evaluated the correlation of various commonly used modalities and techniques namely body impedance analysis (BIA), dual-energy x-ray absorptiometry (DXA) as well as single slice CT to establish how these methods compare. Methods: We designed the study in two parts. First, we performed an intraindividual comparison of the 4558 participants from the UK Biobank cohorts with matching data of MRI abdominal body composition, DXA with VAT estimation, and BIA. Second, we evaluated 174 CT scans from the publicly available dataset to assess the correlation of the commonly used single-slice technique compared to three-dimensional VAT volume. Results: Across the UK Biobank cohort, the DXA-derived VAT measurement correlated better (R² 0.94, p<0.0001) than BIA (R² 0.49, p<0.0001) with reference three-dimensional volume on MRI. However, DXA-derived VAT correlation was worse for participants with a BMI of < 20 (R² = 0.62, p=0.0013). A commonly used single slice method on CT demonstrated a modest correlation (R² between 0.51 - 0.64), with best values at L3- and L4 (R2 L3 = 0.63, p<0.0001; L4 = 0.64, p<0.0001) compared to reference three-dimensional volume. Combining multiple slices yielded a better correlation, with a strong correlation when L2- L3 levels were combined (R² = 0.92, p<0.0001). Conclusion: When deployed at scale, DXA-derived VAT volume measurement shows excellent correlation with three-dimensional volume on MRI based on the UK Biobank cohort. Whereas a single slice CT technique demonstrated moderate correlation with three-dimensional volume on CT, with a stronger correlation achieved when multiple levels were combined. [ABSTRACT FROM AUTHOR]

Scarcity of high-quality organs, suboptimal organ quality assessment, unsatisfactory pre-implantation procedures, and poor long-term organ and patient survival are the main challenges currently faced by the solid organ transplant (SOT) field. New biomarkers for assessing graft quality pre-implantation, detecting, and predicting graft injury, rejection, dysfunction, and survival are critical to provide clinicians with invaluable prediction tools and guidance for personalized patients' treatment. Additionally, new therapeutic targets are also needed to reduce injury and rejection and improve transplant outcomes. Proteins, which underlie phenotypes, are ideal candidate biomarkers of health and disease statuses and therapeutic targets. A protein can exist in different molecular forms, called proteoforms. As the function of a protein depends on its exact composition, proteoforms can offer a more accurate basis for connection to complex phenotypes than protein from which they derive. Mass spectrometry-based proteomics has been largely used in SOT research for identification of candidate biomarkers and therapeutic intervention targets by so-called “bottom-up” proteomics (BUP). However, such BUP approaches analyze small peptides in lieu of intact proteins and provide incomplete information on the exact molecular composition of the proteins of interest. In contrast, “Top-down” proteomics (TDP), which analyze intact proteins retaining proteoform-level information, have been only recently adopted in transplantation studies and already led to the identification of promising proteoforms as biomarkers for organ rejection and dysfunction. We anticipate that the use of top-down strategies in combination with new technological advancements in single-cell and spatial proteomics could drive future breakthroughs in biomarker and therapeutic target discovery in SOT.

Glycosaminoglycans (GAGs) including chondroitin sulfate, dermatan sulfate, heparan sulfate, and keratan sulfate, except for hyaluronan that is a free polysaccharide, are covalently attached to core proteins to form proteoglycans. More than 50 gene products are involved in the biosynthesis of GAGs. We recently developed a comprehensive glycosylation mapping tool, GlycoMaple, for visualization and estimation of glycan structures based on gene expression profiles. Using this tool, the expression levels of GAG biosynthetic genes were analyzed in various human tissues as well as tumor tissues. In brain and pancreatic tumors, the pathways for biosynthesis of chondroitin and dermatan sulfate were predicted to be upregulated. In breast cancerous tissues, the pathways for biosynthesis of chondroitin and dermatan sulfate were predicted to be up- and down-regulated, respectively, which are consistent with biochemical findings published in the literature. In addition, the expression levels of the chondroitin sulfate-proteoglycan versican and the dermatan sulfate-proteoglycan decorin were up- and down-regulated, respectively. These findings may provide new insight into GAG profiles in various human diseases including cancerous tumors as well as neurodegenerative disease using GlycoMaple analysis.