LARS1 is a Prognostic Biomarker and Exhibits a Correlation with Immune Infiltrates in Hepatocellular Carcinoma.

Purpose: To study the relationship between LARS1 expression and immune infiltration and prognosis in hepatocellular carcinoma (HCC). Patients and Methods: The clinical characteristics together with LARS1 expression levels were obtained from the TCGA database. Immunohistochemistry confirmed LARS1 expression levels in paraneoplastic and tumor tissues. To investigate LARS1-related downstream molecules, a network of protein-protein interactions (PPIs) and the Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) were built. Furthermore, gene set enrichment analysis (GSEA) was used to analyze the pathways associated with LARS1 expression, whereas Single-sample GSEA (ssGSEA) was applied to perform an association study between immune infiltration and LARS1 gene expression. The TISCH Database and the TISIDB database were used to compare the difference of LARS1 expression in hepatocellular carcinoma and immunomodulators. Results: In comparison to that in normal tissues, the LARS1 expression level was elevated in tumor tissues. LARS1 expression exhibited substantial correlation with AFP, Histologic grade, pathologic stage, Residual tumor, and Vascular invasion in HCC. Higher LARS1 expression in HCC was linked to lower progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS). According to the GO/KEGG study, the important biological process (neutral lipid metabolic process), cellular component (triglyceride-rich plasma lipoprotein), molecular functions (lipase inhibitor activity), and KEGG pathway (cholesterol metabolism) could be a probable function mechanism in promoting HCC. Various pathways as per GSEA revealed that they were enriched in samples with elevated LARS1 expression. The expression level of LARS1 in malignant tumor cells after immunotherapy was significantly higher than that before immunotherapy. LARS1 was also remarkably linked to the infiltration level and the immunomodulators. Conclusion: LARS1 can be used as a biomarker of HCC, which is associated to immune infiltration of HCC.

Assessing the Quality of ChatGPT Responses to Dementia Caregivers' Questions: Qualitative Analysis.

Background: Artificial intelligence (AI) such as ChatGPT by OpenAI holds great promise to improve the quality of life of patients with dementia and their caregivers by providing high-quality responses to their questions about typical dementia behaviors. So far, however, evidence on the quality of such ChatGPT responses is limited. A few recent publications have investigated the quality of ChatGPT responses in other health conditions. Our study is the first to assess ChatGPT using real-world questions asked by dementia caregivers themselves. objectives: This pilot study examines the potential of ChatGPT-3.5 to provide high-quality information that may enhance dementia care and patient-caregiver education. Methods: Our interprofessional team used a formal rating scale (scoring range: 0-5; the higher the score, the better the quality) to evaluate ChatGPT responses to real-world questions posed by dementia caregivers. We selected 60 posts by dementia caregivers from Reddit, a popular social media platform. These posts were verified by 3 interdisciplinary dementia clinicians as representing dementia caregivers' desire for information in the areas of memory loss and confusion, aggression, and driving. Word count for posts in the memory loss and confusion category ranged from 71 to 531 (mean 218; median 188), aggression posts ranged from 58 to 602 words (mean 254; median 200), and driving posts ranged from 93 to 550 words (mean 272; median 276). Results: ChatGPT's response quality scores ranged from 3 to 5. Of the 60 responses, 26 (43%) received 5 points, 21 (35%) received 4 points, and 13 (22%) received 3 points, suggesting high quality. ChatGPT obtained consistently high scores in synthesizing information to provide follow-up recommendations (n=58, 96%), with the lowest scores in the area of comprehensiveness (n=38, 63%). Conclusions: ChatGPT provided high-quality responses to complex questions posted by dementia caregivers, but it did have limitations. ChatGPT was unable to anticipate future problems that a human professional might recognize and address in a clinical encounter. At other times, ChatGPT recommended a strategy that the caregiver had already explicitly tried. This pilot study indicates the potential of AI to provide high-quality information to enhance dementia care and patient-caregiver education in tandem with information provided by licensed health care professionals. Evaluating the quality of responses is necessary to ensure that caregivers can make informed decisions. ChatGPT has the potential to transform health care practice by shaping how caregivers receive health information.

Experimental and Theoretical Research on Photocatalytic Nitrogen Reduction Using MoS2 Nanosheets with Polysulfide Vacancies.

MoS2 nanosheets with different concentrations of S vacancies (VS-MoS2) were synthesized and used for photocatalytic nitrogen reduction reactions (pNRR), and the mechanism of S vacancies enhancing the activity of MoS2 was explored through DFT calculation. The material characterization confirmed the successful construction of S vacancies at different concentrations on the spherical cluster structure of MoS2. The experimental results show that the introduction of S vacancies significantly improves the activity of pNRR, and it increases significantly with the increase of vacancy number, consistent with the trend of photoelectric performance. VS-MoS2-3 exhibits the highest pNRR efficiency, which is 3.5 times higher than that of pristine MoS2, and after being reused three times, the activity only decreased by about 11%. DFT calculation results indicate that the exposed Mo atoms generated by S vacancies alter the charge layout on the MoS2 surface while providing abundant Mo active sites. Meanwhile, the band gap structure will narrow with the increase of S vacancies, which is beneficial for the transfer of surface charges. In addition, the increase of S vacancies, on the one hand, strengthens the adsorption of MoS2 on N2, weakens the adsorption of H, improves the selectivity of nitrogen, and is conducive to the progress of NRR. On the other hand, more electrons can be transferred from MoS2 to the adsorbed N2 molecules, enhancing the hybridization between them and better activating N2.

Alteration of RNA m6A methylation mediates aberrant RNA binding protein expression and alternative splicing in condyloma acuminatum.

Background: Condyloma acuminatum (CA) is caused by low-risk human papillomavirus, and is characterized by high recurrence after treatment. The RNA modification N6-methyladenosine (m6A) plays an important role during diverse viral infections, including high-risk HPV infection in cervical cancer. However, it is unclear whether low-risk HPV infection changes the RNA m6A methylation in CA. Methods: High-throughputm6A-sequencing was performed to profile the transcriptome-wide mRNA modifications of CA tissues infected by LR-HPVs and the paired normal tissues from CA patients. We further investigated the regulation of alternative splicing by RNA binding proteins (RBPs) with altered m6A modification and constructed a regulatory network among these RBPs, regulated alternative splicing events (RASEs) and regulated alternative splicing genes (RASGs) in CA. Results: The results show that the m6A level in CA tissues differed from that in the paired controls. Furthermore, cell cycle- and cell adhesion- associated genes with m6A modification were differentially expressed in CA tissues compared to the paired controls. In particular, seven RNA binding protein genes with specific m6A methylated sites, showed a higher or lower expression at the mRNA level in CA tissues than in the paired normal tissues. In addition, these differentially expressed RNA binding protein genes would regulate the alternative splicing pattern of apoptotic process genes in CA tissue. Conclusions: Our study reveals a sophisticated m6A modification profile in CA tissue that affects the response of host cells to HPV infection, and provides cues for the further exploration of the roles of m6A and the development of a novel treatment strategy for CA.

Innovative Thermocatalytic H2 Sensor with Double-Sided Pd Nanocluster Films on an Ultrathin Mica Substrate.

Hydrogen (H2) is crucial in the future global energy landscape due to its eco-friendly properties, but its flammability requires precise monitoring. This study introduces an innovative thermocatalytic H2 sensor utilizing ultrathin mica sheets as substrates, coated on both sides with Pd nanocluster (NC) films. The ultrathin mica substrate ensures robustness and flexibility, enabling the sensor to withstand high temperatures and mechanical deformation. Additionally, it simplifies the fabrication process by eliminating the need for complex microelectro-mechanical systems (MEMS) technology. Constructed through cluster beam deposition, the sensor exhibits exceptional characteristics, including a wide concentration range (from 500 ppm to 4%), rapid response and recovery times (3.1 and 2.4 s for 1% H2), good selectivity, high stability, and repeatability. The operating temperature can be as low as 40 °C, achieving remarkably low power consumption. The study explores the impact of double-sided versus single-sided catalytic layers, revealing significantly higher sensitivity and response with the double-sided configuration due to the increased catalytic surface area. Additionally, the research investigates the relationship between the deposition amount of Pd NCs and the sensor's sensitivity, identifying an optimal value that maximizes performance without excessive use of Pd. The sensor's innovative design and excellent performance position it as a promising candidate for meeting the demands of a hydrogen-based energy economy.

Dissecting hair breakage in alopecia areata: the central role of dysregulated cysteine homeostasis.

In the initial stages of Alopecia Areata (AA), the predominance of hair breakage or exclamation mark hairs serves as vital indicators of disease activity. These signs are non-invasive and are commonly employed in dermatoscopic examinations. Despite their clinical salience, the underlying etiology precipitating this hair breakage remains largely uncharted territory. Our exhaustive review of the existing literature points to a pivotal role for cysteine-a key amino acid central to hair growth-in these mechanisms. This review will probe and deliberate upon the implications of aberrant cysteine metabolism in the pathogenesis of AA. It will examine the potential intersections of cysteine metabolism with autophagy, ferroptosis, immunity, and psychiatric manifestations associated with AA. Such exploration could illuminate new facets of the disease's pathophysiology, potentially paving the way for innovative therapeutic strategies.

Genetic links between atopy, allergy, and alopecia areata: insights from a Mendelian randomization study.

BACKGROUND: Alopecia areata (AA), a prevalent form of autoimmune hair loss, has a not well-defined relationship with atopic and allergic disorders, including eczema, hay fever, and asthma. OBJECTIVES: This study aims to elucidate the genetic relationship between atopy, allergies, and alopecia areata (AA) using Mendelian randomization. We hypothesize that atopic and allergic conditions contribute to the genetic predisposition of AA. METHODS: We analyzed extensive genetic data from Genome-wide Association Studies (GWAS) involving over one million individuals. This analysis focused on assessing the genetic correlation between AA and various allergic conditions, including hay fever, eczema, asthma, and allergies to pollen, dust, and cats. The inverse variance weighted method served as our primary analytical tool, complemented by sensitivity analyses to verify the robustness of our results. RESULTS: Our findings reveal a significant genetic correlation between atopy/allergies and an increased risk of AA. Notably, strong associations were observed for hay fever, eczema, asthma, and specific allergies (pollen, dust, and cats). The sensitivity analyses corroborated these associations, reinforcing the reliability of our primary results. CONCLUSIONS: This study provides compelling genetic evidence of an association between atopic and allergic conditions and the development of AA. These findings suggest that individuals with such conditions may benefit from enhanced surveillance for early signs of AA.

EZH2 suppresses ferroptosis in hepatocellular carcinoma and reduces sorafenib sensitivity through epigenetic regulation of TFR2.

Enhancing sensitivity to sorafenib can significantly extend the duration of resistance to it, offering substantial benefits for treating patients with hepatocellular carcinoma (HCC). However, the role of ferroptosis in influencing sorafenib sensitivity within HCC remains pivotal. The enhancer of zeste homolog 2 (EZH2) plays a significant role in promoting malignant progression in HCC, yet the relationship between ferroptosis, sorafenib sensitivity, and EZH2 is not entirely clear. Bioinformatic analysis indicates elevated EZH2 expression in HCC, predicting an unfavorable prognosis. Overexpressing EZH2 can drive HCC cell proliferation while simultaneously reducing ferroptosis. Further analysis reveals that EZH2 amplifies the modification of H3K27 me3, thereby influencing TFR2 expression. This results in decreased RNA polymerase II binding within the TFR2 promoter region, leading to reduced TFR2 expression. Knocking down EZH2 amplifies sorafenib sensitivity in HCC cells. In sorafenib-resistant HepG2(HepG2-SR) cells, the expression of EZH2 is increased. Moreover, combining tazemetostat-an EZH2 inhibitor-with sorafenib demonstrates significant synergistic ferroptosis-promoting effects in HepG2-SR cells. In conclusion, our study illustrates how EZH2 epigenetically regulates TFR2 expression through H3K27 me3, thereby suppressing ferroptosis. The combination of the tazemetostat with sorafenib exhibits superior synergistic effects in anticancer therapy and sensitizes the HepG2-SR cells to sorafenib, shedding new light on delaying and ameliorating sorafenib resistance.

Improved Double Deep Q-Network Algorithm Applied to Multi-Dimensional Environment Path Planning of Hexapod Robots.

Detecting transportation pipeline leakage points within chemical plants is difficult due to complex pathways, multi-dimensional survey points, and highly dynamic scenarios. However, hexapod robots' maneuverability and adaptability make it an ideal candidate for conducting surveys across different planes. The path-planning problem of hexapod robots in multi-dimensional environments is a significant challenge, especially when identifying suitable transition points and planning shorter paths to reach survey points while traversing multi-level environments. This study proposes a Particle Swarm Optimization (PSO)-guided Double Deep Q-Network (DDQN) approach, namely, the PSO-guided DDQN (PG-DDQN) algorithm, for solving this problem. The proposed algorithm incorporates the PSO algorithm to supplant the traditional random selection strategy, and the data obtained from this guided approach are subsequently employed to train the DDQN neural network. The multi-dimensional random environment is abstracted into localized maps comprising current and next level planes. Comparative experiments were performed with PG-DDQN, standard DQN, and standard DDQN to evaluate the algorithm's performance by using multiple randomly generated localized maps. After testing each iteration, each algorithm obtained the total reward values and completion times. The results demonstrate that PG-DDQN exhibited faster convergence under an equivalent iteration count. Compared with standard DQN and standard DDQN, reductions in path-planning time of at least 33.94% and 42.60%, respectively, were observed, significantly improving the robot's mobility. Finally, the PG-DDQN algorithm was integrated with sensors onto a hexapod robot, and validation was performed through Gazebo simulations and Experiment. The results show that controlling hexapod robots by applying PG-DDQN provides valuable insights for path planning to reach transportation pipeline leakage points within chemical plants.

HBO regulates the Warburg effect of hypoxic HCC cells through miR-103a-3p/TRIM35.

BACKGROUND: There are a lot of studies on the treatment of tumors with hyperbaric oxygen, while most of them are in breast cancer, prostate cancer and so on. However, there are still few studies on hyperbaric oxygen in treating hepatocellular carcinoma (HCC). According to the current data, hyperbaric oxygen is an effective means to intervene in tumors. The Warburg effect is a unique marker of glucose metabolism in tumors related to hypoxia, making it possible for hyperbaric oxygen to interfere with the tumor through the Warburg effect. METHOD: We used the hypoxia/hyperbaric oxygen(HBO)-exposed HCC cells for in vitro studies. Glucose uptake, lactic acid, and adenosine triphosphate (ATP) assessed the Warburg effect. The expression of miR-103a-3p in HCC was detected by using qRT-PCR. The effect of miR-103a-3p/TRIM35 expression level on the cells was measured using the CCK8 method and flow cytometry. The molecular biological mechanism of miR-103a-3p in HCC was examined using the luciferase reporter, MS2-RIP assays. RESULT: HBO inhibited the Warburg effect in hypoxic HCC cells. HBO suppressed the expression of miR-103a-3p in hypoxic HCC cells, and miR-103a-3p inhibited the expression of TRIM35 in hypoxic HCC cells. With HBO exposure, miR-103a-3p/TRIM35 regulated the Warburg effect of hypoxic HCC cells. CONCLUSION: These findings reveal that HBO regulates the Warburg effect of hypoxic HCC cells through miR-103a-3p/TRIM35 and inhibits tumor growth.

Predictive model and risk analysis for coronary heart disease in people living with HIV using machine learning.

OBJECTIVE: This study aimed to construct a coronary heart disease (CHD) risk-prediction model in people living with human immunodeficiency virus (PLHIV) with the help of machine learning (ML) per electronic medical records (EMRs). METHODS: Sixty-one medical characteristics (including demography information, laboratory measurements, and complicating disease) readily available from EMRs were retained for clinical analysis. These characteristics further aided the development of prediction models by using seven ML algorithms [light gradient-boosting machine (LightGBM), support vector machine (SVM), eXtreme gradient boosting (XGBoost), adaptive boosting (AdaBoost), decision tree, multilayer perceptron (MLP), and logistic regression]. The performance of this model was assessed using the area under the receiver operating characteristic curve (AUC). Shapley additive explanation (SHAP) was further applied to interpret the findings of the best-performing model. RESULTS: The LightGBM model exhibited the highest AUC (0.849; 95% CI, 0.814-0.883). Additionally, the SHAP plot per the LightGBM depicted that age, heart failure, hypertension, glucose, serum creatinine, indirect bilirubin, serum uric acid, and amylase can help identify PLHIV who were at a high or low risk of developing CHD. CONCLUSION: This study developed a CHD risk prediction model for PLHIV utilizing ML techniques and EMR data. The LightGBM model exhibited improved comprehensive performance and thus had higher reliability in assessing the risk predictors of CHD. Hence, it can potentially facilitate the development of clinical management techniques for PLHIV care in the era of EMRs.

Transient stimulation of TRPMLs enhance the functionality of hDPCs and facilitate hair growth in mice.

Autophagy is essential for eliminating aging and organelle damage that maintaining cellular homeostasis. However, the dysfunction of autophagy has been proven in hair loss such as AGA. Despite the crucial role of TRPML channels in regulating autophagy, their specific function in hair growth remains unclarified. To investigate the biological functions and associated molecular mechanisms of TRPMLs in hair growth, Animal experiments were conducted to confirm the function of TRLMLs activation in promoting hair growth. Subsequently, we analyzed molecular mechanisms in human dermal papilla cells (hDPCs) activated by TRPMLs through transcriptome sequencing analysis. MLSA1(a TRPML agonist) promoted hair regeneration and accelerated hair cycle transition in mice. The activation of TRPMLs upregulated calcium signaling inducing hDPCs to secrete hair growth promoting factors and decrease hair growth inhibiting factors. In addition, activation of TRPMLs triggered autophagy and reduced the generation of ROS, thereby delaying the senescence of hDPCs. All these findings suggested that TRPMLs activation could promote hair growth by regulating hDPCs secretion of hair growth-related factors. Moreover, it may play a prominent role in preventing hDPCs from ROS damage induced by H2O2 or DHT. Targeting TRPMLs may represent a promising therapeutic strategy for treating hair loss.

Development of Pd/In2O3 hybrid nanoclusters to optimize ethanol vapor sensing.

In this study, we successfully synthesize palladium-decorated indium trioxide (Pd/In2O3) hybrid nanoclusters (NCs) using an advanced dual-target cluster beam deposition (CBD) method, a significant stride in developing high-performance ethanol sensors. The prepared Pd/In2O3 hybrid NCs exhibit exceptional sensitivity, stability, and selectivity to low concentrations of ethanol vapor, with a maximum response value of 101.2 at an optimal operating temperature of 260 °C for 6 at% Pd loading. The dynamic response of the Pd/In2O3-based sensor shows an increase in response with increasing ethanol vapor concentrations within the range of 50 to 1000 ppm. The limit of detection is as low as 24 ppb. The sensor exhibits a high sensitivity of 28.24 ppm-1/2, with response and recovery times of 2.7 and 4.4 seconds, respectively, for 100 ppm ethanol vapor. Additionally, the sensor demonstrates excellent repeatability and stability, with only a minor decrease in response observed over 30 days and notable selectivity for ethanol compared to other common volatile organic compounds. The study highlights the potential of Pd/In2O3 NCs as promising materials for ethanol gas sensors, leveraging the unique capabilities of CBD for controlled synthesis and the catalytic properties of Pd for enhanced gas-sensing performance.

Microbial community structures and bacteria-Cylindrospermopsis raciborskii interactions in Yilong Lake.

Cylindrospermopsis raciborskii-dominated harmful algae blooms have been reported globally in recent years. However, our understanding of the ecology of C. raciborskii in natural conditions is still poor. In this study, we collected the water samples from a C. raciborskii-blooming lake, Yilong Lake, in Yunnan province, China, and used both culture-dependent and culture-independent approaches to investigate their microbial communities and the interactions between C. raciborskii and the other bacteria. The composition and diversity of microbial communities were revealed with 16S rRNA gene high-throughput sequencing data analysis. Microbial co-occurrences analysis suggests C. raciborskii may have complex associations with other bacteria. Based on co-inoculation tests, we obtained 14 strains of bacterial strains from the water samples that exhibited either algicidal or promoting effects on a strain of C. raciborskii. Two bacterial isolates exhibited a consistent performance between co-occurrence analysis and experimental results. Effects of these bacteria-algae interspecies interactions on the bloom event are discussed. All these results may provide new insights into the C. raciborskii-dominated blooms and how its interspecies relationships with other bacteria may influence the bloom events in eutrophic waters throughout the world.

A resonant high-pressure microsensor based on a composite pressure-sensitive mechanism of diaphragm bending and volume compression.

In this paper, a composite pressure-sensitive mechanism combining diaphragm bending and volume compression was developed for resonant pressure microsensors to achieve high-pressure measurements with excellent accuracy. The composite mechanism was explained, and the sensor structure was designed based on theoretical analysis and finite element simulation. An all-silicon resonant high-pressure microsensor with multiple miniaturized cavities and dual resonators was developed, where dual resonators positioned in two resonant cavities with suitably different widths are used to perform opposite characteristics in pressure and the same characteristics at different temperatures, which can improve pressure sensitivities and realize temperature self-compensation by differential frequency output. The microsensor was fabricated by microfabrication, and the experimental results showed that the sensor had an accuracy of ±0.015% full scale (FS) in a pressure range of 0.1~100 MPa and a temperature range of -10~50 °C. The pressure sensitivity of the differential frequency was 261.10 Hz/MPa (~2523 ppm/MPa) at a temperature of 20 °C, and the temperature sensitivities of the dual resonators were -1.54 Hz/°C (~-14.5 ppm/°C) and -1.57 Hz/°C (~-15.6 ppm/°C) at a pressure of 2 MPa. The differential output had an outstanding stability within ±0.02 Hz under constant temperature and pressure. Thus, this research provides a convenient solution for high-pressure measurements because of its advantages, namely, large range, excellent accuracy and stability.

Impaired olfactory identification in dementia-free individuals is associated with the functional abnormality of the precuneus.

OBJECTIVE: Olfactory dysfunction indicates a higher risk of developing dementia. However, the potential structural and functional changes are still largely unknown. METHODS: A total of 236 participants were enrolled, including 45 Alzheimer's disease (AD) individuals and 191dementia-free individuals. Detailed study methods, comprising neuropsychological assessment and olfactory identification test (University of Pennsylvania smell identification test, UPSIT), as well as structural and functional magnetic resonance imaging (MRI) were applied in this research. The dementia-free individuals were divided into two sub-groups based on olfactory score: dementia-free with olfactory dysfunction (DF-OD) sub-group and dementia-free without olfactory dysfunction (DF-NOD) sub-group. The results were analyzed for subsequent intergroup comparisons and correlations. The cognitive assessment was conducted again three years later. RESULTS: (i) At dementia-free stage, there was a positive correlation between olfactory score and cognitive function. (ii) In dementia-free group, the volume of crucial brain structures involved in olfactory recognition and processing (such as amygdala, entorhinal cortex and basal forebrain volumes) are positively associated with olfactory score. (iii) Compared to the DF-NOD group, the DF-OD group showed a significant reduction in olfactory network (ON) function. (iv) Compared to DF-NOD group, there were significant functional connectivity (FC) decline between PCun_L(R)_4_1 in the precuneus of posterior default mode network (pDMN) and the salience network (SN) in DF-OD group, and the FC values decreased with falling olfactory scores. Moreover, in DF-OD group, the noteworthy reduction in FC were observed between PCun_L(R)_4_1 and amygdala, which was a crucial component of ON. (v) The AD conversion rate of DF-OD was 29.41%, while the DF-NOD group was 12.50%. The structural and functional changes in the precuneus were also observed in AD and were more severe. CONCLUSIONS: In addition to the olfactory circuit, the precuneus is a critical structure in the odor identification process, whose abnormal function underlies the olfactory identification impairment of dementia-free individuals.

Single-cell RNA sequencing unveils tumor heterogeneity and immune microenvironment between subungual and plantar melanoma.

Acral melanoma (AM) is a subtype of melanoma with high prevalence in East Asians. AM is characterized by greater aggressiveness and lower survival rates. However, there are still fewer studies on immune mechanisms of AM especially subungual melanoma (SM) versus non-subungual melanoma (NSM). In order to explore tumor heterogeneity and immune microenvironment in different subtypes of AM, we applied single-cell RNA sequencing to 24,789 single cells isolated from the SM and plantar melanoma (PM) patients. Aspects of tumor heterogeneity, melanocytes from PM and SM had significant differences in gene expression, CNV and pathways in which tumor-associated such as NF-kb and Wnt were involved. Regarding the immune microenvironment, PM contained more fibroblasts and T/NK cells. The EPHA3-EFNA1 axis was expressed only in cancer-associated fibroblast (CAF) and melanocytes of PM, and the TIGIT-NECTIN2 axis was expressed in both AM subtypes of T/NK cells and melanocytes. Altogether, our study helps to elucidate the tumor heterogeneity in AM subpopulations and provides potential therapeutic targets for clinical research.

Burden of heart failure in Asia, 1990-2019: findings from the Global Burden of Disease Study 2019.

OBJECTIVES: Heart failure (HF) is on the rise as a global health problem, but information on its burden in Asia is limited. This study aimed to assess the burden, trends, and underlying causes of HF in the Asian region. STUDY DESIGN AND METHODS: Data on HF in Asia from 1990 to 2019, including prevalence, years lived with disability (YLD), and underlying causes, were extracted from the Global Burden of Diseases 2019. The cases, the age-standardized prevalence, and the YLD were compared between the age groups, the sexes, the sociodemographic index, and the locations. The proportion of age-standardized prevalence rates of HF attributable to 16 underlying causes was also analyzed. RESULTS: In 2019, the age-standardized prevalence rate of HF per 100,000 persons in Asia was 722.45 (95% uncertainty interval [UI]: 591.97-891.64), with an estimated 31.89 million cases (95% UI: 25.94-39.25). From 1990 to 2019, the prevalence of age-standardized HF in Asia decreased by 4.51%, reflecting the global trend (-7.06%). Age-standardized YLD rates of HF exhibited patterns similar to prevalence rates. Among Asian countries, China had the highest age-standardized prevalence rate, followed by Kuwait and Jordan. Hypertensive heart disease was the leading cause of HF, followed by ischemic heart disease and rheumatic heart disease. CONCLUSIONS: Although the burden of HF in Asia showed a gradual decline between 1990 and 2019, it remains a significant health challenge that requires increased attention. Regional disparities in HF burden are evident, emphasizing the need for urgent prevention and control measures at the regional and national levels.

HO-1 attenuates testicular ischaemia/reperfusion injury by activating the phosphorylated C-jun-miR-221/222-TOX pathway.

Aims: Heme oxygenase (HO-1) affords protection against ischaemia/reperfusion (I/R) injury; however, its effects on testicular I/R injury remain poorly explored. Herein, we aimed to examine the effects of HO-1 on testicular I/R injury and elucidate the underlying mechanism. Methods: Using the TALEN technique, we knocked out the HO-1 gene from rats. In vivo: Thirty hmox+/+ and 30 hmox-/- rats were randomly assigned to six groups: sham-operated (sham), I/R (the left testicle torsion/detorsion) 0 d,I/R 1d, I/R 3d, I/R 7d and I/R 28d. In vitro: GC-1 were suffered from: control,H/R (oxygen-deprivation/reoxygenation),H/R + HO-1 siRNA,H/R + c-Jun siRNA or H/R + HO-1 siRNA + c-jun.We performed immunofluorescence and immunohistochemistry experiments to detect HO-1 nuclear translocation. Flow cytometry was used to detect cell apoptosis and analyse the cell cycle. High-resolution miRNA, mRNA sequencing, reverse transcription-quantitative PCR, and western blotting were performed to identify testicular I/R injury-related genes strongly conserved in HO-1 knockout rats. A double luciferase reporter assay was performed to verify the relationship between C-jun and miR-221/222. Main findings: In vivo, HO-1 improved the pathological damage induced by testicular I/R. In GC-1 cells, we confirmed the nuclear translocation of HO-1 and its protective effect against hypoxia/reoxygenation (H/R) damage. Accordingly, HO-1 protein itself, rather than heme metabolites, might play a key role in testicular I/R. Gene sequencing was performed to screen for miR221/222 and its downstream gene, thymocyte selection-associated high mobility group box (TOX). HO-1 increased c-Jun phosphorylation in the H/R group, knocked down c-Jun in GC-1 cells, and decreased miR-221/222 expression. Inhibition of HO-1 expression decreased the expression of c-Jun and miR-221/222, which was rescued by adding c-Jun. Dual-luciferase reporter assay confirmed the interaction between c-Jun and miR-221/222. Conclusions: HO-1 could exert a protective effect against testicular I/R via the phosphorylated c-Jun-miR-221/222-TOX pathway.

Magic Momenta and Three-Dimensional Landau Levels from a Three-Dimensional Graphite Moiré Superlattice.

In this Letter, we theoretically explore the physical properties of a new type of three-dimensional graphite moiré superlattice, the bulk alternating twisted graphite (ATG) system with homogeneous twist angle, which is grown by in situ chemical vapor decomposition method. Compared to twisted bilayer graphene (TBG), the bulk ATG system is bestowed with an additional wave vector degree of freedom due to the extra dimensionality. As a result, when the twist angle of bulk ATG is smaller than twice of the magic angle of TBG, there always exist "magic momenta" which host topological flat bands with vanishing in-plane Fermi velocities. Most saliently, when the twist angle is relatively large, a dispersionless three-dimensional zeroth Landau level would emerge in the bulk ATG, which may give rise to robust three-dimensional quantum Hall effects and unusual quantum-Hall physics over a large range of twist angles.