TRIM21-mediated ubiquitylation of TAT suppresses liver metastasis in gallbladder cancer.

Liver metastasis is common in patients with gallbladder cancer (GBC), imposing a significant challenge in clinical management and serving as a poor prognostic indicator. However, the mechanisms underlying liver metastasis remain largely unknown. Here, we report a crucial role of tyrosine aminotransferase (TAT) in liver metastasis of GBC. TAT is frequently up-regulated in GBC tissues. Increased TAT expression is associated with frequent liver metastasis and poor prognosis of GBC patients. Overexpression of TAT promotes GBC cell migration and invasion in vitro, as well as liver metastasis in vivo. TAT knockdown has the opposite effects. Intriguingly, TAT promotes liver metastasis of GBC by potentiating cardiolipin-dependent mitophagy. Mechanistically, TAT directly binds to cardiolipin and leads to cardiolipin externalization and subsequent mitophagy. Moreover, TRIM21 (Tripartite Motif Containing 21), an E3 ubiquitin ligase, interacts with TAT. The histine residues 336 and 338 at TRIM21 are essential for this binding. TRIM21 preferentially adds the lysine 63 (K63)-linked ubiquitin chains on TAT principally at K136. TRIM21-mediated TAT ubiquitination impairs its dimerization and mitochondrial location, subsequently inhibiting tumor invasion and migration of GBC cells. Therefore, our study identifies TAT as a novel driver of GBC liver metastasis, emphasizing its potential as a therapeutic target.

A study on combination of non-ablative local RFA with PD-1 and angiogenesis blocking to prolong survival through improvement of immune microenvironment in advanced Hepatocellular Carcinoma.

Radiofrequency ablation (RFA), an effective local treatment method for early-stage Hepatocellular Carcinoma (HCC), combined with PD-1 blocking and anti-angiogenic therapy is being extensively explored in advanced HCC, however, the definite results and underlying mechanisms still remain to be elucidated. Therefore, whether non-ablative RFA-based combined therapy can play a synergistic anti-tumor effect through improving tumor immune microenvironment was investigated by us in HCC mouse models. Our results showed that non-ablative RFA could regulate multilayered immunity, such as inducing immunogenic death of tumor cells, upregulating the secretion of inflammatory cytokines, mainly IFN-γ, TNF-α, and IL-10, and subsequently promoting the infiltration of CD8 + T cells. As a result, a significant synergistic anti-tumor effect was demonstrated in the combination therapy group. Similarly, in the real-world setting, non-curative RFA combined with PD-1 blocking and Lenvatinib for 12 patients with Barcelona Clinic Liver Cancer (BCLC) stage C achieve promising results, with 6.9 months (95 % CI: 3.23-15.73) median progression-free survival (mPFS) and 12.7 months (95 % CI: 7.40-19.73) median overall survival (mOS). The common treatment-related adverse reactions were pneumonia and thyroiditis with low prevalence, both less than grade 3 and manageable by symptomatic treatment. Summarily, local non-ablative RFA should be a clinically preferred strategy in combination with PD-1 blocking and anti-angiogenic therapy, because this more flexible scheme abandons its historical concept of tumor eradication, but fully utilizes the immune regulatory function by inducing immunogenic tumor death and has higher-level of safety. Therefore, this is a two-pronged and highly balanced approach to achieved favorable treatment outcomes, while conclusive evidence is still pending, it can be attempted in the real world anyway.

China's "coal-to-gas" policy had large impact on PM1.0 distribution during 2016-2019.

Particulate matter with an aerodynamic diameter of less than 1 µm (PM1.0) can be extremely hazardous to human health, so it is imperative to accurately estimate the spatial and temporal distribution of PM1.0 and analyze the impact of related policies on it. In this study, a stacking generalization model was trained based on aerosol optical depth (AOD) data from satellite observations, combined with related data affecting aerosol concentration such as meteorological data and geographic data. Using this model, the PM1.0 concentration distribution in China during 2016-2019 was estimated, and verified by comparison with ground-based stations. The coefficient of determination (R2) of the model is 0.94, and the root-mean-square error (RMSE) is 8.49 µg/m3, mean absolute error (MAE) is 4.10 µg/m3, proving that the model has a very high performance. Based on the model, this study analyzed the PM1.0 concentration changes during the heating period (November and December) in the regions where the "coal-to-gas" policy was implemented in China, and found that the proposed "coal-to-gas" policy did reduce the PM1.0 concentration in the implemented regions. However, the lack of natural gas due to the unreasonable deployment of the policy in the early stage caused the increase of PM1.0 concentration. This study can provide a reference for the next step of urban air pollution policy development.

Increasing expression of dual-specificity phosphatase 12 mitigates oxygen-glucose deprivation/reoxygenation-induced neuronal apoptosis and inflammation through inactivation of the ASK1-JNK/p38 MAPK pathway.

Dual-specificity phosphatase 12 (DUSP12) is abnormally expressed under various pathological conditions and plays a crucial role in the pathological progression of disorders. However, the role of DUSP12 in cerebral ischaemia/reperfusion injury has not yet been investigated. This study explored the possible link between DUSP12 and cerebral ischaemia/reperfusion injury using an oxygen-glucose deprivation/reoxygenation (OGD/R) model. Marked decreases in DUSP12 levels have been observed in cultured neurons exposed to OGD/R. DUSP12-overexpressed neurons were resistant to OGD/R-induced apoptosis and inflammation, whereas DUSP12-deficient neurons were vulnerable to OGD/R-evoked injuries. Further investigation revealed that DUSP12 overexpression or deficiency affects the phosphorylation of apoptosis signal-regulating kinase 1 (ASK1), c-Jun NH2-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) in neurons under OGD/R conditions. Moreover, blockade of ASK1 diminished the regulatory effect of DUSP12 deficiency on JNK and p38 MAPK activation. In addition, DUSP12-deficiency-elicited effects exacerbating neuronal OGD/R injury were reversed by ASK1 blockade. In summary, DUSP12 protects against neuronal OGD/R injury by reducing apoptosis and inflammation through inactivation of the ASK1-JNK/p38 MAPK pathway. These findings imply a neuroprotective function for DUSP12 in cerebral ischaemia/reperfusion injury.

Efficacy and safety of tislelizumab plus lenvatinib as first-line treatment in patients with unresectable hepatocellular carcinoma: a multicenter, single-arm, phase 2 trial.

BACKGROUND: Lenvatinib is widely used in treatment of unresectable hepatocellular carcinoma (uHCC), but the benefit of its combination with immunotherapy needs to be verified. This study evaluated the efficacy and safety of tislelizumab plus lenvatinib in systemic treatment-naïve patients with uHCC. METHODS: In this multicenter, single-arm, phase 2 study, systemic treatment-naïve patients with uHCC received tislelizumab 200 mg every three weeks plus lenvatinib (bodyweight ≥ 60 kg: 12 mg; < 60 kg: 8 mg; once daily). Dose-limiting toxicities (DLTs) were evaluated in safety run-in phase to determine whether to enter the expansion phase. The primary endpoint was objective response rate (ORR) assessed by independent review committee (IRC) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1). Based on Simon's two-stage design, > 6 responders were needed in stage 1 (n = 30) to continue the study, and ≥ 18 responders were needed by the end of stage 2 (n = 60) to demonstrate statistical superiority to a historical control of lenvatinib monotherapy. RESULTS: Sixty-four patients were enrolled. No DLTs were reported. The study achieved statistical superiority (p = 0.0003) with 23 responders assessed by IRC per RECIST v1.1 in the first 60 patients of the efficacy evaluable analysis set (n = 62). After a median follow-up of 15.7 months, confirmed ORR and disease control rate were 38.7% (24/62, 95% confidence interval [CI], 26.6-51.9) and 90.3% (56/62, 95% CI, 80.1-96.4), respectively. Median progression-free survival was 8.2 months (95% CI, 6.8-not evaluable). Overall survival rate at 12 months was 88.6% (95% CI, 77.7-94.4). Grade ≥ 3 treatment-related adverse events occurred in 18 (28.1%) patients. CONCLUSIONS: Tislelizumab plus lenvatinib demonstrated promising antitumor activity with favourable tolerability as first-line therapy for patients with uHCC. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04401800).

Efficacy and safety of human umbilical cord-derived mesenchymal stem cells in the treatment of refractory immune thrombocytopenia: a prospective, single arm, phase I trial.

Patients with refractory immune thrombocytopenia (ITP) frequently encounter substantial bleeding risks and demonstrate limited responsiveness to existing therapies. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) present a promising alternative, capitalizing on their low immunogenicity and potent immunomodulatory effects for treating diverse autoimmune disorders. This prospective phase I trial enrolled eighteen eligible patients to explore the safety and efficacy of UC-MSCs in treating refractory ITP. The research design included administering UC-MSCs at escalating doses of 0.5 × 106 cells/kg, 1.0 × 106 cells/kg, and 2.0 × 106 cells/kg weekly for four consecutive weeks across three cohorts during the dose-escalation phase, followed by a dose of 2.0 × 106 cells/kg weekly for the dose-expansion phase. Adverse events, platelet counts, and changes in peripheral blood immunity were monitored and recorded throughout the administration and follow-up period. Ultimately, 12 (with an addition of three patients in the 2.0 × 106 cells/kg group due to dose-limiting toxicity) and six patients were enrolled in the dose-escalation and dose-expansion phase, respectively. Thirteen patients (13/18, 72.2%) experienced one or more treatment emergent adverse events. Serious adverse events occurred in four patients (4/18, 22.2%), including gastrointestinal hemorrhage (2/4), profuse menstruation (1/4), and acute myocardial infarction (1/4). The response rates were 41.7% in the dose-escalation phase (5/12, two received 1.0 × 106 cells/kg per week, and three received 2.0 × 106 cells/kg per week) and 50.0% (3/6) in the dose-expansion phase. The overall response rate was 44.4% (8/18) among all enrolled patients. To sum up, UC-MSCs are effective and well tolerated in treating refractory ITP (ClinicalTrials.gov ID: NCT04014166).

The regional disparities in liver disease comorbidity among elderly Chinese based on a health ecological model: the China Health and Retirement Longitudinal Study.

PURPOSE: This study aimed to investigate the risk factors for liver disease comorbidity among older adults in eastern, central, and western China, and explored binary, ternary and quaternary co-morbid co-causal patterns of liver disease within a health ecological model. METHOD: Basic information from 9,763 older adults was analyzed using data from the China Health and Retirement Longitudinal Study (CHARLS). LASSO regression was employed to identify significant predictors in eastern, central, and western China. Patterns of liver disease comorbidity were studied using association rules, and spatial distribution was analyzed using a geographic information system. Furthermore, binary, ternary, and quaternary network diagrams were constructed to illustrate the relationships between liver disease comorbidity and co-causes. RESULTS: Among the 9,763 elderly adults studied, 536 were found to have liver disease comorbidity, with binary or ternary comorbidity being the most prevalent. Provinces with a high prevalence of liver disease comorbidity were primarily concentrated in Inner Mongolia, Sichuan, and Henan. The most common comorbidity patterns identified were "liver-heart-metabolic", "liver-kidney", "liver-lung", and "liver-stomach-arthritic". In the eastern region, important combination patterns included "liver disease-metabolic disease", "liver disease-stomach disease", and "liver disease-arthritis", with the main influencing factors being sleep duration of less than 6 h, frequent drinking, female, and daily activity capability. In the central region, common combination patterns included "liver disease-heart disease", "liver disease-metabolic disease", and "liver disease-kidney disease", with the main influencing factors being an education level of primary school or below, marriage, having medical insurance, exercise, and no disabilities. In the western region, the main comorbidity patterns were "liver disease-chronic lung disease", "liver disease-stomach disease", "liver disease-heart disease", and "liver disease-arthritis", with the main influencing factors being general or poor health satisfaction, general or poor health condition, severe pain, and no disabilities. CONCLUSION: The comorbidities associated with liver disease exhibit specific clustering patterns at both the overall and local levels. By analyzing the comorbidity patterns of liver diseases in different regions and establishing co-morbid co-causal patterns, this study offers a new perspective and scientific basis for the prevention and treatment of liver diseases.

A novel self-inflatable balloon for treating refractory benign esophageal strictures: a prospective, single-arm, multicenter study.

BACKGROUND AND AIM: Current treatments for refractory benign esophageal strictures (BESs) often take several years and have poor effects. The authors propose a novel method of self-help inflatable balloon (SHIB) and evaluate its efficacy and safety. METHODS: A prospective, multicenter study was conducted from January 2019 to March 2022. All enrolled patients were diagnosed with refractory BESs and received SHIB. The primary endpoint was the clinical success rate at 12 months after removing SHIB. The secondary endpoints were the number of days of placing SHIB, and changes from baseline in BMI and health-related quality of life at 1, 3, 6, and 12 months. RESULTS: The clinical success rate was 51.2% (21/41) with the median days of placing SHIB being 104.0 days (range: 62.0-134.5 days), which was higher in the endoscopic group compared to the caustic and surgery groups (63.3 vs. 28.6% vs. 0, P=0.025). All patients (100%) showed significant improvement in dysphagia scores during placing SHIB. Although 20 patients (48.8%) experienced recurrent stricture, the median stricture length was decreased (P<0.001) and the median intervention-free interval was prolonged (P<0.001). In all patients, the mean BMI at and health-related quality of life at 1, 3, 6, and 12 months were significantly increased compared with baseline (P<0.05). On multivariate analysis, stricture etiology and wearing time were independent predictors of recurrent stricture. CONCLUSIONS: The SHIB has high efficacy and safety in treating refractory BESs of different origins, especially for endoscopic resection. Stricture etiology and wearing time were independent predictors of recurrent stricture.

Deep learning-based radiomics of computed tomography angiography to predict adverse events after initial endovascular repair for acute uncomplicated Stanford type B aortic dissection.

PURPOSE: This study aimed to construct a predictive model integrating deep learning-derived radiomic features from computed tomography angiography (CTA) and clinical biomarkers to forecast postoperative adverse events (AEs) in patients with acute uncomplicated Stanford type B aortic dissection (uTBAD) undergoing initial thoracic endovascular aortic repair (TEVAR). METHODS: We retrospectively evaluated 369 patients treated with TEVAR for acute uTBAD from January 2015 to December 2022. A three-dimensional (3D) deep convolutional neural network (CNN) automated radiomic feature extraction from CTA images. Feature selection, using Analysis of Variance (ANOVA) and the Least Absolute Shrinkage and Selection Operator (LASSO) algorithms, refined a radiomic score (Rad-Score). This score, alongside clinical parameters, was modelled via Extreme Gradient Boosting (XGBoost) analysis. Model calibration was assessed by calibration curves. RESULTS: The integration of the Rad-Score with clinical factors including albumin and C-reactive protein levels moderately enhanced predictive efficiency, exhibiting an area under the curve (AUC) of 1.000 (95%CI, 1.000-1.000) in the training cohort and 0.990 (95%CI, 0.966-1.000) in the internal validation cohort. In an independent validation cohort from another hospital, the combined model yielded an AUC of 0.985 (95%CI, 0.965-1.000), with an accuracy, precision, sensitivity, and specificity of 0.92, 0.92, 0.94, and 0.91, respectively. CONCLUSIONS: The synergistic application of deep learning-based radiomics from CTA and clinical indicators holds promise for anticipating AEs post-initial thoracic endovascular aortic repair in patients with acute uTBAD. The clinical utility of the constructed combined model, offering prognostic foresight during follow-up, has been substantiated.

Design of liquid level detection circuit based on sampling probe structure capacitance.

Liquid level detection system is an essential core functional component of automatic clinical medical testing instrument. The conventional liquid level detection method has low detection accuracy and sensitivity, and may have the problem of false detection, which may lead to the inaccurate test results. This paper presents a high sensitivity liquid level detection system based on the principle of variable capacitance. When the sampling probe contacts the liquid level, the probe capacitance will change. The liquid level detection circuit board judges whether the probe contacts the liquid level by sensing the change of probe capacitance. When judging the liquid level signal, the combination of slope detection and amplitude detection is used. The liquid level detection circuit board takes the phase-locked loop(PLL) circuit as the center to detect the change of the capacitance. The reference signal of the PLL is set as a square wave of 375kHz. The double tube probe is used as a part of the tuning capacitor of the voltage controlled oscillator to control the frequency of the output signal, which can realize the rapid phase locking. The experimental results show that the system has accurate detection results, high sensitivity, stable and reliable operation, good dynamic response performance in the case of large and small liquid volume. Compared with other liquid level detection methods based on machine vision, ultrasonic, optics and so on, the proposed liquid level detection system has simpler structure and lower cost, it can avoid the problems of collision, carryover contamination and empty suction by controlling the depth of sampling needle inserted into liquid.

Single body-coupled fiber enables chipless textile electronics.

Intelligent textiles provide an ideal platform for merging technology into daily routines. However, current textile electronic systems often rely on rigid silicon components, which limits seamless integration, energy efficiency, and comfort. Chipless electronic systems still face digital logic challenges owing to the lack of dynamic energy-switching carriers. We propose a chipless body-coupled energy interaction mechanism for ambient electromagnetic energy harvesting and wireless signal transmission through a single fiber. The fiber itself enables wireless visual-digital interactions without the need for extra chips or batteries on textiles. Because all of the electronic assemblies are merged in a miniature fiber, this facilitates scalable fabrication and compatibility with modern weaving techniques, thereby enabling versatile and intelligent clothing. We propose a strategy that may address the problems of silicon-based textile systems.

Prototype development and evaluation of a hyperspectral lidar optical receiving system.

As a new type of active Earth observation technology, airborne hyperspectral lidar combines the advantages of traditional lidar 3D information acquisition and passive hyperspectral imaging technology, and it can achieve integrated imaging detection with a high spatial and hyperspectral resolution. Thus, it has become an important future direction of Earth surface remote sensing technology. This article introduces the design and development of an airborne hyperspectral imaging lidar system. The hyperspectral lidar adopts a focal plane splitting method, combined with an array of 168 optical fibers, to couple wide-spectral-range laser echo signals one by one to the corresponding single tube detector, achieving efficient splitting and precise coupling of supercontinuum laser pulse echo signals. This article proposes a fast synchronous calibration method that is suitable for hyperspectral imaging lidar systems. Results show that the spectral range of the hyperspectral lidar system is 400-900 nm, and the spectral resolution of single-fiber detection is greater than 3 nm. Notably, this article focuses on analyzing the abnormal detection channels based on the calibration results. With the test results of adjacent channels combined, the reason for the abnormal spectral bandwidth of channel 17 is analyzed as an example. This research points out the direction for verifying the design parameters of the hyperspectral lidar prototype and lays an important foundation for airborne flight test of the hyperspectral lidar.

SLC38A2 promotes cell proliferation and invasion by promoting glutamine metabolism in adenomyosis.

Adenomyosis is a benign uterine disorder that is associated with female infertility, a reduced clinical pregnancy rate and a high risk of miscarriage. Solute carrier family 38 member a2 (SLC38A2) is a glutamine (Gln) transporter that serves roles in various medical conditions. The present study aimed to reveal the role of SLC38A2 in adenomyosis. The mRNA expression levels of SLC38A2 in eutopic endometrial (EU) and ectopic endometrial (EC) tissues from adenomyotic patients were examined by reverse transcription-quantitative PCR. EU and EC cell proliferation and invasion were analyzed by Cell Counting Kit-8 and Transwell assays. Changes in the oxygen consumption rate (OCR) were determined to indicate the mitochondrial respiratory function and observed using a Seahorse analyzer. SLC38A2 expression in EC tissues was upregulated compared with that in normal endometrial tissues. SLC38A2 knockdown repressed EC cell proliferation and invasion. In addition, the Gln content and OCR were decreased in EC cells transfected with SLC38A2-knockdown lentivirus, whereas SLC38A2 overexpression had the opposite effect in EU cells. Furthermore, the increased proliferation and invasion rates and Gln level induced by SLC38A2 overexpression in EU cells were alleviated by CB-839, a glutaminase inhibitor. SLC38A2 overexpression promoted Gln metabolism and oxygen consumption rate, resulting in an increase in cell proliferation and invasion in the adenomyosis context. The present study indicated that reduction of SLC38A2 expression could be a novel target for adenomyosis therapy, and SLC38A2 may be a valuable clinical diagnostic molecule for adenomyosis.

Association between metabolic syndrome severity score and cardiovascular disease: results from a longitudinal cohort study on Chinese adults.

Objective: This study aimed to quantify the severity of metabolic syndrome(MetS) and investigate its association with cardiovascular disease(CVD) risk on Chinese adults. Methods: 13,500 participants from the Zhejiang Adult Chronic Disease Study were followed up between 2010 and 2021. A continuous MetS severity score derived from the five components of MetS was used to quantify MetS severity, and the association between MetS severity and the risk of incident CVD was assessed using Cox proportional hazard and restricted cubic spline regression. Results: Both the presence and severity of MetS were strongly associated with CVD risk. MetS was related to an increased risk of CVD (hazard ratio(HR):1.700, 95% confidence interval(CI): 1.380-2.094). Compared with the hazard ratio for CVD in the lowest quartile of the MetS severity score, that in the second, third, and highest quartiles were 1.812 (1.329-2.470), 1.746 (1.265-2.410), and 2.817 (2.015-3.938), respectively. A linear and positive dose-response relationship was observed between the MetS severity and CVD risk (P for non-linearity = 0.437). Similar results were found in various sensitivity analyses. Conclusion: The MetS severity score was significantly associated with CVD risk. Assessing MetS severity and further ensuring intervention measures according to the different severities of MetS may be more useful in preventing CVD.

Super-Klein Tunneling in a Black-Phosphorus-Based N-P Junction Modulated by Linearly Polarized Light.

We investigate the role of the black-phosphorus-based n-p (BP-np) junction modulated by linearly polarized light (LPL) in governing the quantum transport behaviors. Following the analysis of the band structures, we find that the LPL can adjust the gap between the conduction and valence bands by reducing the impact of momentum mismatch caused by the band gap. In addition, LPL can also eliminate the angle dependence of transmission. This means that for BP with a fixed band gap, the transmission-forbidden region can be reduced and the transmission probability can be increased by applying LPL modulation of the band gap to achieve all-angle perfect transmission, i.e., super-Klein tunneling (SKT). Our investigation also found that the SKT is robust to different incident energies, resulting in a larger conductance platform. These findings could be useful for the development and application of optical-like electronic devices.

Triboelectric Basalt Textiles Efficiently Operating within an Ultrawide Temperature Range.

With the continuous upsurge in demand for wearable energy, nanogenerators are increasingly required to operate under extreme environmental conditions. Even though they are at the cutting edge of technology, nanogenerators have difficulty producing high-quality electrical output at very extreme temperatures. Here, a triboelectric basalt textile (TBT) with an ultrawide operational temperature range (from -196 to 520 °C) is created employing basalt material as the main body. The output power density of the TBT, in contrast to most conventional nanogenerators, would counterintuitively rise by 2.3 times to 740.6 mW m-2 after heating to 100 °C because the high temperature will enhance the material's interface polarization and electronic kinetic energy. The TBT retains ≈55% of its initial electrical output even after heating in the flame of an alcohol lamp (520 °C). Surprisingly, the TBTs output voltage may retain over 85% of its initial value even after submerging in liquid nitrogen. The TBTs exceptional resistance to heat and cold indicates its possible use in high and low latitudes, high altitudes, deserts, and even space settings.

Seafood waste derived Pt/Chitin nanocatalyst for efficient hydrogenation of nitroaromatic compounds.

The fabrication of reliable, reusable and efficient catalyst is crucial for the conversion of nitroaromatic compounds into more chemically valuable amine-based molecules. In this study, a series of chitin supported platinum (Pt) catalysts with high catalytic activity, stability, and reusability were developed by using chitin derived from seafood waste as raw materials. The catalytic performance differences among these catalysts activated by different methods were investigated by hydrogenation of nitroaromatic compounds. The results showed that the multilayer hierarchical pore structure and abundance of hydroxyl and acetamido groups in chitin provided ample anchoring sites for Pt nanoparticles (NPs), ensuring the high dispersion of Pt NPs. Moreover, the interconnected channels between chitin nanofibrous microspheres facilitated rapid transport of reaction substrates. The best Pt/Chitin catalyst exhibited excellent catalytic activity and broad substrate applicability in hydrogenation of nitroaromatic compounds. Significantly, even after 20 runs, no discernible deactivation of activity was observed, demonstrating exceptional catalytic reusability. The application of seafood waste-based catalysts is conducive to the development of a green/sustainable society.

Prevalence and risk factors for astigmatism in 7 to 19-year-old students in Xinjiang, China: a cross-sectional study.

BACKGROUND: To investigate the prevalence and risk factors for astigmatism in 7-19-year-old students in Xinjiang, China. METHODS: A school-based, cross-sectional study was conducted on students who underwent refraction examination in Xinjiang, China, between May and December 2019. The prevalence of astigmatism was determined. Astigmatism was defined as cylinder power (C) ≤-0.75 D, undefined astigmatism as ≤-1.50 D, and high astigmatism as C ≤-3.00 D. Astigmatism types were: against-the-rule astigmatism (maximum refraction of the main meridian in 180° ± 30°), with-the-rule astigmatism (maximum refraction of the main meridian at 90°±30°), and oblique astigmatism (all other cases). RESULTS: Of the 71,838 students examined (51.0% boys, 7 - 19 years old), 25,945 (36.1%, 95%CI: 35.52-36.68%) had astigmatism and 1267 (1.8%, 95%CI: 1.07-2.53%) had high astigmatism. The prevalence of astigmatism was greater in Han individuals (39.6%) compared with the Hui (34.0%), Kazakh (34.0%), Kyrgyz (32.1%), and Uyghur (26.4%) populations. Among the 25,945 students with astigmatism, 19,947 had with-the-rule astigmatism (76.9%), 3405 had against-the-rule astigmatism (13.1%), and 2593 had oblique astigmatism (10.0%). Multivariable logistic regression analysis showed that ethnicity (Han individuals more susceptible), male gender, age, and refractive errors (myopia and hyperopia) were independently associated with astigmatism, high astigmatism, and with-the-rule astigmatism (all P < 0.05). CONCLUSIONS: The prevalence of astigmatism among children and adolescents in Xinjiang was 36.1%, including 1.8% of high astigmatism. In this population, astigmatism was mainly of the with-the-rule astigmatism type (76.9%). Han ethnicity, male gender, and myopia or hyperopia were independently associated with a high risk of astigmatism.

mRNA-Seq of testis and liver tissues reveals a testis-specific gene and alternative splicing associated with hybrid male sterility in dzo.

Alternative splicing (AS) plays an important role in the co-transcription and post-transcriptional regulation of gene expression during mammalian spermatogenesis. The dzo is the male F1 offspring of an interspecific hybrid between a domestic bull (Bos taurus ♂) and a yak (Bos grunniens ♀) which exhibits male sterility. This study aimed to identify the testis-specific genes and AS associated with hybrid male sterility in dzo. The iDEP90 program and rMATS software were used to identify the differentially expressed genes (DEG) and differential alternative splicing genes (DSG) based on RNA-seq data from the liver (n=9) and testis (n=6) tissues of domestic cattle, yak, and dzo. Splicing factors (SF) were obtained from the AmiGO2 and the NCBI databases, and Pearson correlation analysis was performed on the differentially expressed SFs and DSGs. We focused on the testis-specific DEGs and DSGs between dzo and cattle and yak. Among the top 3000 genes with the most significant variations between these 15 samples, a large number of genes showed testis-specific expression involved with spermatogenesis. Cluster analysis showed that the expression levels of these testis-specific genes were dysregulated during mitosis with a burst downregulation during the pachynema spermatocyte stage. The occurrence of AS events in the testis was about 2.5 fold greater than in the liver, with exon skipping being the major AS event (81.89~82.73%). A total of 74 DSGs were specifically expressed in the testis and were significantly enriched during meiosis I, synapsis, and in the piRNA biosynthesis pathways. Notably, STAG3 and DDX4 were of the exon skipping type, and DMC1 was a mutually exclusive exon. A total of 36 SFs were significantly different in dzo testis, compared with cattle and yak. DDX4, SUGP1, and EFTUD2 were potential SFs leading to abnormal AS of testis-specific genes in dzo. These results show that AS of testis-specific genes can affect synapsis and the piRNA biosynthetic processes in dzo, which may be important factors associated with hybrid male sterility in dzo.

Dual RNA sequencing of Helicobacter pylori and host cell transcriptomes reveals ontologically distinct host-pathogen interaction.

Helicobacter pylori is a highly successful pathogen that poses a substantial threat to human health. However, the dynamic interaction between H. pylori and the human gastric epithelium has not been fully investigated. In this study, using dual RNA sequencing technology, we characterized a cytotoxin-associated gene A (cagA)-modulated bacterial adaption strategy by enhancing the expression of ATP-binding cassette transporter-related genes, metQ and HP_0888, upon coculturing with human gastric epithelial cells. We observed a general repression of electron transport-associated genes by cagA, leading to the activation of oxidative phosphorylation. Temporal profiling of host mRNA signatures revealed the downregulation of multiple splicing regulators due to bacterial infection, resulting in aberrant pre-mRNA splicing of functional genes involved in the cell cycle process in response to H. pylori infection. Moreover, we demonstrated a protective effect of gastric H. pylori colonization against chronic dextran sulfate sodium (DSS)-induced colitis. Mechanistically, we identified a cluster of propionic and butyric acid-producing bacteria, Muribaculaceae, selectively enriched in the colons of H. pylori-pre-colonized mice, which may contribute to the restoration of intestinal barrier function damaged by DSS treatment. Collectively, this study presents the first dual-transcriptome analysis of H. pylori during its dynamic interaction with gastric epithelial cells and provides new insights into strategies through which H. pylori promotes infection and pathogenesis in the human gastric epithelium. IMPORTANCE: Simultaneous profiling of the dynamic interaction between Helicobacter pylori and the human gastric epithelium represents a novel strategy for identifying regulatory responses that drive pathogenesis. This study presents the first dual-transcriptome analysis of H. pylori when cocultured with gastric epithelial cells, revealing a bacterial adaptation strategy and a general repression of electron transportation-associated genes, both of which were modulated by cytotoxin-associated gene A (cagA). Temporal profiling of host mRNA signatures dissected the aberrant pre-mRNA splicing of functional genes involved in the cell cycle process in response to H. pylori infection. We demonstrated a protective effect of gastric H. pylori colonization against chronic DSS-induced colitis through both in vitro and in vivo experiments. These findings significantly enhance our understanding of how H. pylori promotes infection and pathogenesis in the human gastric epithelium and provide evidence to identify targets for antimicrobial therapies.