Celastrol-Induced Nur77 Interaction with TRAF2 Alleviates Inflammation by Promoting Mitochondrial Ubiquitination and Autophagy.

Mitochondria play an integral role in cell death, autophagy, immunity, and inflammation. We previously showed that Nur77, an orphan nuclear receptor, induces apoptosis by targeting mitochondria. Here, we report that celastrol, a potent anti-inflammatory pentacyclic triterpene, binds Nur77 to inhibit inflammation and induce autophagy in a Nur77-dependent manner. Celastrol promotes Nur77 translocation from the nucleus to mitochondria, where it interacts with tumor necrosis factor receptor-associated factor 2 (TRAF2), a scaffold protein and E3 ubiquitin ligase important for inflammatory signaling. The interaction is mediated by an LxxLL motif in TRAF2 and results not only in the inhibition of TRAF2 ubiquitination but also in Lys63-linked Nur77 ubiquitination. Under inflammatory conditions, ubiquitinated Nur77 resides at mitochondria, rendering them sensitive to autophagy, an event involving Nur77 interaction with p62/SQSTM1. Together, our results identify Nur77 as a critical intracellular target for celastrol and unravel a mechanism of Nur77-dependent clearance of inflamed mitochondria to alleviate inflammation.

Nuclear receptor RXRα binds the precursor of miR-103 to inhibit its maturation.

BACKGROUND: The maturation of microRNAs (miRNAs) successively undergoes Drosha, Dicer, and Argonaute -mediated processing, however, the intricate regulations of the individual miRNA maturation are largely unknown. Retinoid x receptor alpha (RXRα) belongs to nuclear receptors that regulate gene transcription by binding to DNA elements, however, whether RXRα binds to miRNAs to exert physiological functions is not known. RESULTS: In this work, we found that RXRα directly binds to the precursor of miR-103 (pre-miR-103a-2) via its DNA-binding domain with a preferred binding sequence of AGGUCA. The binding of RXRα inhibits the processing of miR-103 maturation from pre-miR-103a-2. Mechanistically, RXRα prevents the nuclear export of pre-miR-103a-2 for further processing by inhibiting the association of exportin-5 with pre-miR-103a-2. Pathophysiologically, the negative effect of RXRα on miR-103 maturation correlates to the positive effects of RXRα on the expression of Dicer, a target of miR-103, and on the inhibition of breast cancer. CONCLUSIONS: Our findings unravel an unexpected role of transcription factor RXRα in specific miRNA maturation at post-transcriptional level through pre-miRNA binding, and present a mechanistic insight regarding RXRα role in breast cancer progression.

Merbromin is a mixed-type inhibitor of 3-chyomotrypsin like protease of SARS-CoV-2.

3-chyomotrypsin like protease (3CLpro) has been considered as a promising target for developing anti-SARS-CoV-2 drugs. Herein, about 6000 compounds were analyzed by high-throughput screening using enzyme activity model, and Merbromin, an antibacterial agent, was identified as a potent inhibitor of 3CLpro. Merbromin strongly inhibited the proteolytic activity of 3CLpro but not the other three proteases Proteinase K, Trypsin and Papain. Michaelis-Menten kinetic analysis showed that Merbromin was a mixed-type inhibitor of 3CLpro, due to its ability of increasing the KM and decreasing the Kcat of 3CLpro. The binding assays and molecular docking suggested that 3CLpro possessed two binding sites for Merbromin. Consistently, Merbromin showed a weak binding to the other three proteases. Together, these findings demonstrated that Merbromin is a selective inhibitor of 3CLpro and provided a scaffold to design effective inhibitors of SARS-CoV-2.

Increased CD4+ T cell count is associated with lower anal human papillomavirus prevalence among HIV-positive male cohort in Taizhou, China: a cross-sectional study.

OBJECTIVES: This study aims to investigate the association between CD4+ T cell count and combined antiretroviral therapy (cART) with the prevalence of anal human papillomavirus (HPV) infection among HIV-positive male cohort in China. METHODS: A survey was conducted in men from a HIV cohort in Taizhou, China between 2016 and 2019. A face-to-face questionnaire interview was administered, and an anal-canal swab was collected for HPV genotyping. RESULTS: A total of 766 HIV-positive men were recruited. The HPV prevalence was lower among those with increased CD4+ T cell count than those with decreased or unchanged (46.5 vs. 56.6%, p = 0.033) from baseline. In multivariable models, having the current CD4+ T cell count of 350-499 cells/µL (aOR 0.28, 95% CI 0.13-0.64), and of ≥ 500 cells/µL (aOR 0.26, 95% CI 0.11-0.60) were associated with lower prevalence of any type HPV infection compared with those with < 200 cells/µL. Having taken NVP + 3TC + AZT was inversely associated with any high-risk (HR)-HPV (aOR 0.47, 95% CI 0.25-0.90) and any low-risk (LR)-HPV infection (aOR 0.40, 95% CI 0.18-0.88), compared with those taking EFV + 3TC + TDF. CONCLUSIONS: Increased CD4+ T cell count at follow-up was significantly associated with lower prevalence of anal HPV infection. Inverse associations between NVP + 3TC + AZT and HR-HPV or LR-HPV infecton were observed.

Threat-relevant stimuli cannot be better detected by preschoolers in an inattentional blindness task.

Detecting the unexpected threat-relevant stimuli plays a vital role in preschoolers' daily life safety, but a few studies have investigated how preschoolers process this kind of stimuli. We applied a classical inattentional blindness task (designed by Mack and Rock Inattentional blindness. MIT Press, 1998) to explore whether threat-relevant stimuli could be better detected in an inattentional condition and whether the age and the fluid intelligence could predict the incidence of the detection. With the involvement of two hundred and thirty-nine preschoolers (aged from 4 to 6 years), we found that it was not more likely for preschoolers to detect the threat-relevant stimuli (Knife and Snake) compared with the non-threat-relevant stimuli (Spoon and Snail). The age difference of detection only occurred in the divided attentional condition, but not in the inattentional condition. Moreover, the group of 5-year-old preschoolers with higher fluid intelligence scores was more likely to detect the unexpected stimuli, but the prediction was not powerful. These findings demonstrate that the threat-superiority effect on IB does not occur on preschoolers and the individual difference of preschoolers' IB is unstable. This study enriches the cognition of young children's attentional bias to threat-relevant stimuli, and has certain significance to understand the essence of children's attentional process.

Diagnostic and Categorization Criteria for Palpitations Below the Heart in Traditional Chinese Medicine: A Delphi Consensus Study.

OBJECTIVES: To explore and establish the diagnosis, syndrome classification and syndrome differentiation criteria of palpitations below the heart in traditional Chinese medicine (TCM) in order to lay a foundation for the clinical diagnosis, treatment and research of palpitations below the heart. METHODS: In the early stage of this study, we searched the literature related to palpitations below the heart in TCM in domestic and foreign databases, analyzed the results and developed an expert consultation questionnaire. Using the Delphi method, a survey was conducted by 19 expert TCM practitioners. The survey results were statistically analyzed, aggregated and categorized to create the next round of questionnaires, and the process was repeated was repeated for a total of 4 rounds of expert opinions and until a consensus was achieved. Finally, the questionnaire items were classified into the main diagnosis (primary disease) and secondary diagnosis (secondary disease) for each syndrome. RESULTS: This study was completed ahead of schedule after 2 rounds of expert questionnaire surveys. A total of 19 exceptional TCM experts from all over China reached a consensus on 1 diagnostic standard and 4 syndrome types. The main diagnoses of palpitations below the heart included "conscious sub cardiac epigastric beating," "throbbing at the lower part of the heart" and "palpitation rhythm consistent with the pulse and obvious pulsation in the heart area," while the secondary diagnosis was "palpitation obvious after nervous tension, fatigue, drinking water or changing body position." Based on the balance of TCM Yin (negative, dark, feminine) and Yang (positive, bright, masculine) energy, TCM syndrome differentiation (Bian Zheng - the comprehensive analysis of clinical information obtained from the 4 main diagnostic TCM procedures: observation, listening, questioning, and pulse analysis, that is used to guide the choice of treatment by acupuncture and/or TCM) of palpitations below the heart are differentiated as heart yang deficiency syndrome, middle yang deficiency syndrome, kidney yang deficiency syndrome and phlegm drink syndrome, and the main and secondary syndromes of each are established. In the consultation process, the expert opinions were highly correlated, questionnaire reliability was strong and the results were credible. CONCLUSIONS: The criteria proposed in this study do not claim to be the best or the most accurate, but they do provide some guidelines for practitioners, a basis for clinical differentiation and treatment with TCM and a basis for further randomized controlled trials in the future. Further research is needed in order to reach a consensus regarding TCM treatment of palpitations below the heart.

The GRA15 protein from Toxoplasma gondii enhances host defense responses by activating the interferon stimulator STING.

Toxoplasma gondii is an important neurotropic pathogen that establishes latent infections in humans that can cause toxoplasmosis in immunocompromised individuals. It replicates inside host cells and has developed several strategies to manipulate host immune responses. However, the cytoplasmic pathogen-sensing pathway that detects T. gondii is not well-characterized. Here, we found that cyclic GMP-AMP synthase (cGAS), a sensor of foreign dsDNA, is required for activation of anti-T. gondii immune signaling in a mouse model. We also found that mice deficient in STING (Stinggt/gt mice) are much more susceptible to T. gondii infection than WT mice. Of note, the induction of inflammatory cytokines, type I IFNs, and interferon-stimulated genes in the spleen from Stinggt/gt mice was significantly impaired. Stinggt/gt mice exhibited more severe symptoms than cGAS-deficient mice after T. gondii infection. Interestingly, we found that the dense granule protein GRA15 from T. gondii is secreted into the host cell cytoplasm and then localizes to the endoplasmic reticulum, mediated by the second transmembrane motif in GRA15, which is essential for activating STING and innate immune responses. Mechanistically, GRA15 promoted STING polyubiquitination at Lys-337 and STING oligomerization in a TRAF protein-dependent manner. Accordingly, GRA15-deficient T. gondii failed to elicit robust innate immune responses compared with WT T. gondii. Consequently, GRA15-/-T. gondii was more virulent and caused higher mortality of WT mice but not Stinggt/gt mice upon infection. Together, T. gondii infection triggers cGAS/STING signaling, which is enhanced by GRA15 in a STING- and TRAF-dependent manner.

Gut microbiota in children with juvenile idiopathic arthritis: characteristics, biomarker identification, and usefulness in clinical prediction.

BACKGROUND: Recent studies have suggested that the gut microbiota is altered in children with juvenile idiopathic arthritis (JIA). However, age, sex, and body mass index (BMI) were not matched in the previous studies, and the results are inconsistent. We conducted an age-, sex-, and BMI-matched cross-sectional study to characterize the gut microbiota in children with JIA, and evaluate its potential in clinical prediction. METHODS: A total of 40 patients with JIA and 42 healthy controls, ranging from 1 to 16 years, were enrolled in this study. Fecal samples were collected for 16S rDNA sequencing. The data were analyzed using QIIME software and R packages. Specifically, the random forest model was used to identify biomarkers, and the receiver operating characteristic curve and the decision curve analysis were used to evaluate model performance. RESULTS: A total of 39 fecal samples from patients with JIA, and 42 fecal samples from healthy controls were sequenced successfully. The Chao 1 and Shannon-Wiener index in the JIA group were significantly lower than those in the control group, and the Bray-Curtis dissimilarity also differed significantly between the two groups. The relative abundance of 4 genera, Anaerostipes, Dialister, Lachnospira, and Roseburia, decreased significantly in the JIA group compared to those in the control group. The 4 genera included microbes that produce short-chain fatty acids (SCFAs) and were negatively correlated with some rheumatic indices. Moreover, 12 genera were identified as potential biomarkers by using the nested cross-validation function of the random forest. A random forest model constructed using these genera was able to differentiate the patients with JIA from the healthy controls, and the area under the receiver operating characteristic curve was 0.7975. The decision curve analysis indicated that the model had usefulness in clinical practice. CONCLUSIONS: The gut microbiota in patients with JIA is altered and characterized by a decreased abundance of 4 SCFA-producing genera. The decreases in the 4 genera correlated with more serious clinical indices. Twelve genera could be used as biomarkers and predictors in clinical practice. TRIAL REGISTRATION: The study is registered online at the Chinese Clinical Trial Registry on 11 May 2018 (registration number: ChiCTR1800016110).

3-Cl-AHPC inhibits pro-HGF maturation by inducing matriptase/HAI-1 complex formation.

Matriptase is an epithelia-specific membrane-anchored serine protease, and its dysregulation is highly related to the progression of a variety of cancers. Hepatocyte growth factor activator inhibitor-1 (HAI-1) inhibits matriptase activity through forming complex with activated matriptase. The balance of matriptase activation and matriptase/HAI-1 complex formation determines the intensity and duration of matriptase activity. 3-Cl-AHPC, 4-[3-(1-adamantyl)-4-hydroxyphenyl]-3-chlorocinnamic acid, is an adamantly substituted retinoid-related molecule and a ligand of retinoic acid receptor γ (RARγ). 3-Cl-AHPC is of strong anti-cancer effect but with elusive mechanisms. In our current study, we show that 3-Cl-AHPC time- and dose- dependently induces matriptase/HAI-1 complex formation, leading to the suppression of activated matriptase in cancer cells and tissues. Furthermore, 3-Cl-AHPC promotes matriptase shedding but without increasing the activity of shed matriptase. Moreover, 3-Cl-AHPC inhibits matriptase-mediated cleavage of pro-HGF through matriptase/HAI-1 complex induction, resulting in the suppression of pro-HGF-stimulated signalling and cell scattering. Although 3-Cl-AHPC binds to RARγ, its induction of matriptase/HAI-1 complex is not RARγ dependent. Together, our data demonstrates that 3-Cl-AHPC down-regulates matriptase activity through induction of matriptase/HAI-1 complex formation in a RARγ-independent manner, providing a mechanism of 3-Cl-AHPC anti-cancer activity and a new strategy to inhibit abnormal matriptase activity via matriptase/HAI-1 complex induction using small molecules.

Silica nanoparticles as an enhancer in the IL-1ß-induced inflammation cycle of A549 cells.

Objective: The industrial production and combustion of coal can produce silica nanoparticles (nano-SiO2). It enters the human body mainly through the respiratory tract and exerts a toxic effect. However, whether nano-SiO2 can increase the IL-1ß-induced inflammatory expression in A549 cells has not been tested. Therefore, the synergistic toxicity of nano-SiO2 and IL-1ß to A549 was observed in our study. Materials and methods: We exposed A549 cells to nano-SiO2 (0, 100, 500, and 1000 µg/ml) for 12 and 24 h. The effect of nano-SiO2 on the viability of A549 cells was observed by the CCK-8 method. The A549 cells were exposed to nano-SiO2 (1 mg/mL) and cytokine IL-1ß (10 ng/mL) for 4 h, and we detected the expression of IL-1ß and IL-6 cytokines by real time quantitative polymerase chain (RT-qPCR) and enzyme linked immunosorbent assay (ELISA). The expression of ß-Actin, I-κB, phospho-ERK1/2 (P-ERK1/2), total-ERK1/2 (T-ERK1/2), phospho-JNK (P-JNK), total-JNK (T-JNK), phospho-P38 (P-P38), and total-P38 (T-P38) in A549 cells was detected by the Western Blot method. Results: The nano-SiO2 treatment resulted in a time-dependent decrease in the viability of A549 cells. The synergistic effect of nano-SiO2 and IL-1ß was observed on the new production of IL-1ß and IL-6 in A549 cells. The Western blot results showed that nano-SiO2 can increase the expression of IL-1ß and IL-6 by promoting the phosphorylation of ERK1/2 and elevating the phosphorylation of I-κB by IL-1ß. IL-1ß and IL-6 were induced by nano-SiO2, and the IL-1ß treatment with 20 µM of I-κBα phosphorylation inhibitor (PD98059) and 20 µM of ERK1/2 inhibitor (BAY11-7082) for 1 h was significantly lower than that of the control group in A549 cells. Discussion and conclusion: These results indicated that nano-SiO2 had a toxic effect on A549 cells, and this effect could increase IL-1ß on the A549 cell-induced inflammatory response. The results suggested that the release of IL-1ß and IL-6 in A549 was enhanced by the synergistic IL-1ß-induced phosphorylation of ERK1/2 and I-κB. This process is similar to a snowball, and it is possible that IL-1ß is continuously produced and repeatedly superimposed in A549 cells to produce an inflammatory effect; then, a vicious circle occurs, and an inflammatory storm is accelerated.

A randomized controlled trial of a mobile application-assisted nurse-led model used to improve treatment outcomes in children with asthma.

AIM: To evaluate the effectiveness of a mobile application-assisted nurse-led management model in childhood asthma. BACKGROUND: Studies have shown that a nurse-led asthma management model can improve asthma outcomes. However, the role of a mobile application-assisted nurse-led model in paediatric asthma management has not been studied well. DESIGN: A multi-centre randomized clinical trial. METHODS: The trial was conducted between March 2017-March 2018. A total of 152 children (6 to 11.9 years old) were enrolled, with 77 children in the experimental group and 75 in the control group. All children received nurse-led asthma management and other routine treatment measures, including inhaled corticosteroids. Meanwhile, a mobile application was used to manage asthma only for children in the experimental group. Primary outcome was frequency of asthma exacerbations. All outcomes were evaluated twice a month for 12 months. RESULTS: Compared with the pre-enrollment period, frequency of asthma exacerbations decreased in the post-enrollment period in the two groups, with a greater decrease in the experimental group. Compared with children in the control group, children in the experimental group had better secondary outcomes, such as improved adherence, higher Childhood Asthma Control Test scores, decreased respiratory tract infections, days of antibiotic use, days of school absence, parental work loss, and medical expenses. CONCLUSION: A mobile application-assisted nurse-led management model decreased asthma exacerbations and improved secondary outcomes in children with asthma. Further research is needed to verify its validity in larger population samples. IMPACT: Children with asthma benefited from a nurse-led asthma management model when combined with mobile application. This trial suggested that computer and Internet technologies should be incorporated into nurse-led asthma strategy in paediatric asthma management. TRIAL REGISTRATION: The current trial was registered online with the Chinese Clinical Trial Registry (registration number: ChiCTR1800016726).

The association between Toxoplasma gondii infection and hypertensive disorders in T2DM patients: a case-control study in the Han Chinese population.

Type 2 diabetes mellitus (T2DM) is a major global health problem. The rate of infection with Toxoplasma gondii (T. gondii) is more than one-third of the total world population. The effects of T. gondii infection on the risk of diabetic complications and comorbidities are unclear. This study aims to determine the relationship between T. gondii infection and complications of T2DM in the Han Chinese population. We collected 1580 blood samples from T2DM patients and measured the levels of specific IgG antibodies against T. gondii in the sera of these patients using an ELISA assay. A logistic regression analysis was performed to estimate the effect of T. gondii infection on the complications of T2DM, while adjusting for age, gender, and triglyceride level (TG). We applied the multifactor dimensionality reduction (MDR) method to detect the interactions between T. gondii infections, demographic indexes and biochemical indicators among the different complications. Gender (the odds ratio (OR) = 0.63, 95%CI =0.45-0.89, P = 0.008) and TG level (OR = 0.64, 95%CI =0.45-0.89, P = 0.009) were influencing factors in T. gondii infections. T2DM patients who were infected with T. gondii had a 2.34 times risk of developing hypertension than those patients without T. gondii infection (OR = 2.34, 95%CI = 1.12-4.88, P = 0.024). The multiplicative interaction analysis and the additive interaction analysis did not reveal any evidence of interactive effects on diabetic complications and comorbidities. T. gondii might be a factor associated with hypertension in T2DM patients.

[Source Constraints on Turquoise of the Erlitou Site by Infrared Spectra].

Shiyan district in Hubei province is a famous locality of high-quality turquoise with brightcolor, finegrain in the world. Erlitou archacologicalsite, which is about 300km north to the Shiyan Turquoise mine, has been excavated a remarkable number of turquoise artifacts since 2002. Some researchers infer that there was "a road of turquoise" between the two sites in history. In order to check the inference, and identify local features of the turquoises found in Shiyan, and Eelitou site as well, spectra of three turquoise groups from Shiyan, Hubei and one group of Erlitou unearthed samples were obtained by means of IR. Their spectra have visible differences in the 1 200-950 and 700-400 cm(-1) range. Peak 1 174 cm(-1) appears only in samples from Wenfeng, and from 700 to 400 cm(-1), 5 peaks show in samples from Wenfeng while 7 peaks emerge from the other two sites. Turquoises in Erlitou site have similar spectra to those from Qingu and Yungaisi, and are more similar to Yungaisi of peak around 1 159 cm(-1). According to A = lg(1/T) , intensity of transmittance spectra were calculated and then Ratios(A783 cm(-1)/A837 cm(-1)) were yielded. The ratios of samples from Qingu, Wenfeng, Yungaisi and Erlitou site are 0.819-0.920, 0.870-1.010, 0.806-0.860 and 0.827-0.878 respectively, allowing for a suggestion that turquoise in Erlitou site was the most probable from Yungaisi. This research can be used as example for identifying origin of the unearthed turquoise relics, which is more likely a good tool for archeological research.

Molecular simulations guide immobilization of lipase on nest-like ZIFs with regulatable hydrophilic/hydrophobic surface.

The catalytic performance of immobilized lipase is greatly influenced by functional support, which attracts growing interest for designing supports to achieve their promotive catalytic activity. Many lipases bind strongly to hydrophobic surfaces where they undergo interfacial activation. Herein, the behavioral differences of lipases with distinct lid structures on interfaces of varying hydrophobicity levels were firstly investigated by molecular simulations. It was found that a reasonable hydrophilic/hydrophobic surface could facilitate the lipase to undergo interfacial activation. Building on these findings, a novel "nest"-like superhydrophobic ZIFs (ZIFN) composed of hydrophobic ligands was prepared for the first time and used to immobilize lipase from Aspergillus oryzae (AOL@ZIFN). The AOL@ZIFN exhibited 2.0-folds higher activity than free lipase in the hydrolysis of p-Nitrophenyl palmitate (p-NPP). Especially, the modification of superhydrophobic ZIFN with an appropriate amount of hydrophilic tannic acid can significantly improve the activity of the immobilized lipase (AOL@ZIFN-TA). The AOL@ZIFN-TA exhibited 30-folds higher activity than free lipase, and still maintained 82% of its initial activity after 5 consecutive cycles, indicating good reusability. These results demonstrated that nanomaterials with rational arrangement of the hydrophilic/hydrophobic surface could facilitate the lipase to undergo interfacial activation and improve its activity, displaying the potential of the extensive application.

Endocytic activation and exosomal secretion of matriptase stimulate the second wave of EGF signaling to promote skin and breast cancer invasion.

The dysfunction of matriptase, a membrane-anchored protease, is highly related to the progression of skin and breast cancers. Epidermal growth factor (EGF)-induced matriptase activation and cancer invasion are known but with obscure mechanisms. Here, we demonstrate a vesicular-trafficking-mediated interplay between matriptase and EGF signaling in cancer promotion. We found that EGF induces matriptase to undergo endocytosis together with the EGF receptor, followed by acid-induced activation in endosomes. Activated matriptase is then secreted extracellularly on exosomes to catalyze hepatocyte growth factor precursor (pro-HGF) cleavage, resulting in autocrine HGF/c-Met signaling. Matriptase-induced HGF/c-Met signaling represents the second signal wave of EGF, which promotes cancer cell scattering, migration, and invasion. These findings demonstrate a role of vesicular trafficking in efficient activation and secretion of membrane matriptase and a reciprocal regulation of matriptase and EGF signaling in cancer promotion, providing insights into the physiological functions of vesicular trafficking and the molecular pathological mechanisms of skin and breast cancers.

Incidence, clearance, and factors associated with anal human papilloma virus infection among men with HIV.

OBJECTIVES: This study aims to estimate the incidence and persistence/clearance of anal human papilloma virus (HPV) infection and related factors among men with HIV in Taizhou, China. DESIGN: A prospective cohort study. METHODS: Men with HIV were recruited and followed up from 2016 to 2021. Questionnaire surveys were used to collect social-demographic and behavioral characteristics, and anal swabs were collected for HPV Genotyping. RESULTS: A total of 675 men with HIV were recruited and followed up. After an average follow-up time of 1.75 years, HPV39 (3.8/100 person-years), HPV52 (3.6/100 person-years), HPV51 (3.1/100 person-years), HPV58 (2.5/100 person-years) and HPV16 (2.4 cases/100 person-years) in the high-risk types showed the highest incidence rate. In marriage with woman [adjusted hazard ratio (aHR) = 0.44, 95% confidence interval (CI) 0.20-0.99] showed an inverse association with HPV incidence, while bisexuality or undetermined sexual orientation (aHR = 2.62, 95% CI 1.08-6.36) showed a positive association. For those infected at baseline, the top three high-risk HPV with the lowest clearance density were HPV52 (32.2/100 person-years), HPV58 (38.1/100 person-years), and HPV16 (43.5/100 person-years). Daily consumption of 1-28 g alcohol (aHR = 0.62, 95% CI 0.41-0.95) showed an inverse association with HPV clearance, while illicit drug use (aHR = 3.24, 95% CI 1.59-6.59) showed a positive association. CONCLUSION: Anal HPV infection and clearance were both active in men with HIV in China. Marriage status and sexuality were associated with the incidence of HPV infection, while substance use including alcohol and illicit drug were associated with HPV clearance. More studies are needed to explore the risk factors of HPV persistence.

A novel approach for sports injury risk prediction: based on time-series image encoding and deep learning.

The rapid development of big data technology and artificial intelligence has provided a new perspective on sports injury prevention. Although data-driven algorithms have achieved some valuable results in the field of sports injury risk assessment, the lack of sufficient generalization of models and the inability to automate feature extraction have made it challenging to deploy research results in the real world. Therefore, this study attempts to build an injury risk prediction model using a combination of time-series image encoding and deep learning algorithms to address this issue better. This study used the time-series image encoding approach for feature construction to represent relationships between values at different moments, including Gramian Angular Summation Field (GASF), Gramian Angular Difference Field (GADF), Markov Transition Field (MTF), and Recurrence Plot (RP). Deep Convolutional Auto-Encoder (DCAE) learned the image-encoded data for representation to obtain features with good discrimination, and the classifier was performed using Deep Neural Network (DNN). The results from five repeated experiments show that the GASF-DCAE-DNN model is overall better in the training (AUC: 0.985 ± 0.001, Gmean: 0.930 ± 0.007, Sensitivity: 0.997 ± 0.003, Specificity: 0.868 ± 0.013) and test sets (AUC: 0.891 ± 0.026, Gmean: 0.830 ± 0.027, Sensitivity: 0.816 ± 0.039, Specificity: 0.845 ± 0.022), with good discriminative power, robustness, and generalization ability. Compared with the best model reported in the literature, the AUC, Gmean, Sensitivity, and Specificity of the GASF-DCAE-DNN model were higher by 23.9%, 27.5%, 39.7%, and 16.2%, respectively, which confirmed the validity and practicability of the model in injury risk prediction. In addition, differences in injury risk patterns between the training and test sets were identified through shapley additivity interpretation. It was also found that the training volume was an essential factor that affected injury risk prediction. The model proposed in this study provides a powerful injury risk prediction tool for future sports injury prevention practice.

The impact of sport-specific physical fitness change patterns on lower limb non-contact injury risk in youth female basketball players: a pilot study based on field testing and machine learning.

Background: In recent years, identifying players with injury risk through physical fitness assessment has become a hot topic in sports science research. Although practitioners have conducted many studies on the relationship between physical fitness and the likelihood of injury, the relationship between the two remains indeterminate. Consequently, this study utilized machine learning to preliminary investigate the relationship between individual physical fitness tests and injury risk, aiming to identify whether patterns of physical fitness change have an impact on injury risk. Methods: This study conducted a retrospective analysis by extracting the records of 17 young female basketball players from the sport-specific physical fitness monitoring and injury registration database in Fujian Province. Sports-specific physical fitness tests included physical performance, physiological, biochemical, and subjective perceived responses. The data for each player was standardized individually using Z-scores. Synthetic minority over-sampling techniques and edited nearest neighbor algorithms were used to sample the training set to address the negative impact of class imbalance on model performance. Feature extraction was performed on the dataset using linear discriminant analysis, and the prediction model was constructed using the cost-sensitive neural network. Results: The 10 replicate 5-fold stratified cross-validation showed that the lower limb non-contact injury prediction model based on the cost-sensitive neural network had achieved good discrimination and calibration (average Precision: 0.6360; average Recall: 0.8700; average F2-Score: 0.7980; average AUC: 0.8590; average Brier-score: 0.1020), which could be well applied in training practice. According to the attribution analysis, agility and speed were important physical attributes that affect youth female basketball players' non-contact lower limb injury risk. Specifically, there was enhance in the performance of the 1-min double under, accompanied by an increase in urinary ketone and urinary blood levels following the agility test. The 3/4 basketball court sprint performance improved, while urinary protein and RPE levels decreased after the speed test. Conclusion: The sport-specific physical fitness change pattern can impact the lower limb non-contact injury risk of young female basketball players in Fujian Province, specifically in terms of agility and speed. These findings will provide valuable insights for planning athletes' physical training programs, managing fatigue, and preventing injuries.

Virus infections in wild plant populations are both frequent and often unapparent.

PREMISE OF THE STUDY: Pathogens are thought to regulate host populations. In agricultural crops, virus infection reduces yield. However, in wild plants little is known about the spatial and temporal patterns of virus prevalence. Thus, pathogen effects on plant population dynamics are unclear. Prevalence data provide necessary background for (1) evaluating the effects of virus infection on plant population size and dynamics and (2) improving risk assessment of virus-resistant transgenic crops. METHODS: We used ELISA and RT-PCR to survey wild Cucurbita pepo populations over 4 years for five viruses, aphid-transmitted viruses of the genus Potyvirus as a group and PCR to survey for virus-resistance transgenes. In addition, we surveyed the literature for reports of virus prevalence in wild populations. KEY RESULTS: In 21 C. pepo populations, virus prevalence (0-74%) varied greatly among populations, years, and virus species. In samples analyzed by both ELISA and RT-PCR, RT-PCR detected 6-44% more viruses than did ELISA. Eighty percent of these infections did not cause any visually apparent symptoms. In our samples, the virus-resistance transgene was not present. In 30 published studies, 92 of 146 tested species were infected with virus, and infection rates ranged from 0.01-100%. Most published studies used ELISA, suggesting virus prevalence is higher than reported. CONCLUSIONS: In wild C. pepo, the demographic effects of virus are likely highly variable in space and time. Further, our literature survey suggests that such variation is probably common across plant species. Our results indicate that risk assessments for virus-resistant transgenic crops should not rely on visual symptoms or ELISA and should include data from multiple populations over multiple years.

Automatic Multichannel Electrocardiogram Record Classification Using XGBoost Fusion Model.

There is an increasing demand for automatic classification of standard 12-lead electrocardiogram signals in the medical field. Considering that different channels and temporal segments of a feature map extracted from the 12-lead electrocardiogram record contribute differently to cardiac arrhythmia detection, and to the classification performance, we propose a 12-lead electrocardiogram signal automatic classification model based on model fusion (CBi-DF-XGBoost) to focus on representative features along both the spatial and temporal axes. The algorithm extracts local features through a convolutional neural network and then extracts temporal features through bi-directional long short-term memory. Finally, eXtreme Gradient Boosting (XGBoost) is used to fuse the 12-lead models and domain-specific features to obtain the classification results. The 5-fold cross-validation results show that in classifying nine categories of electrocardiogram signals, the macro-average accuracy of the fusion model is 0.968, the macro-average recall rate is 0.814, the macro-average precision is 0.857, the macro-average F1 score is 0.825, and the micro-average area under the curve is 0.919. Similar experiments with some common network structures and other advanced electrocardiogram classification algorithms show that the proposed model performs favourably against other counterparts in F1 score. We also conducted ablation studies to verify the effect of the complementary information from the 12 leads and the auxiliary information of domain-specific features on the classification performance of the model. We demonstrated the feasibility and effectiveness of the XGBoost-based fusion model to classify 12-lead electrocardiogram records into nine common heart rhythms. These findings may have clinical importance for the early diagnosis of arrhythmia and incite further research. In addition, the proposed multichannel feature fusion algorithm can be applied to other similar physiological signal analyses and processing.