Counter-Doping Effect by Trivalent Cations in tin-based Perovskite Solar Cells.

Sn-based perovskite solar cells normally show low open circuit voltage due to serious carrier recombination in the devices, which can be attributed to the oxidation and the resultant high p-type doping of the perovskite active layers. Considering the grand challenge to completely prohibit the oxidation of Sn-based perovskites, a feasible way to improve the device performance is to counter-dope the oxidized Sn-based perovskites by replacing Sn2+ with trivalent cations in the crystal lattice, which however has been rarely reported. Here, we present the introduction of Sb3+, which can effectively counter-dope the oxidized perovskite layer and improve the carrier lifetime. Meanwhile, Sb3+ can passivate deep-level defects and improve carrier mobility of the perovskite layer, which are all favourable for the photovoltaic performance of the devices. Consequently, the target devices yield a relative enhancement of the power conversion efficiency (PCE) of 31.4% as well as excellent shelf-storage stability. This work provides a novel strategy to improve the performance of Sn-based perovskite solar cells, which can be developed as a universal way to compensate for the oxidation of Sn-based perovskites in optoelectronic devices. This article is protected by copyright. All rights reserved.

Porcine TLR8 signaling and its anti-infection function are disturbed by immune checkpoint receptor TIM-3 via inhibition of P13K-AKT pathway.

Toll-like receptor 8 (TLR8), an important innate immune receptor recognizing single stranded RNA and the antiviral imidazoquinoline compounds, can activate intracellular signaling pathway and produce an inflammatory response to kill and eliminate pathogens. However, the molecular regulation mechanisms of TLR8 signaling and its anti-infection activity are not fully elucidated. Our previous transcriptome analysis of porcine TLR8 (pTLR8) signaling suggested the immune checkpoint receptor TIM-3 as the potential regulator for pTLR8. Here we investigated TIM-3 in the regulation of pTLR8 signaling and its anti-infection activity. Our results showed that porcine TIM-3 is upregulated by pTLR8 signaling and TIM-3 inhibits pTLR8 signaling activity in a negative feedback way. Accordingly, TIM-3 disturbs pTLR8 mediated anti-bacterial and anti-viral activity. Mechanistically, TIM-3 suppresses PI3K-AKT pathway by inhibiting the TLR8-PI3K p85 interaction and subsequent AKT phosphorylation which is essential for TLR8 signaling and anti-infection activity. Therefore, our study reveals new insights into innate immune TLR8 signaling and its anti-infection function.

A mitochondrion-targeted cyanine agent for NIR-II fluorescence-guided surgery combined with intraoperative photothermal therapy to reduce prostate cancer recurrence.

Poorly identified tumor boundaries and nontargeted therapies lead to the high recurrence rates and poor quality of life of prostate cancer patients. Near-infrared-II (NIR-II) fluorescence imaging provides certain advantages, including high resolution and the sensitive detection of tumor boundaries. Herein, a cyanine agent (CY7-4) with significantly greater tumor affinity and blood circulation time than indocyanine green was screened. By binding albumin, the absorbance of CY7-4 in an aqueous solution showed no effects from aggregation, with a peak absorbance at 830 nm and a strong fluorescence emission tail beyond 1000 nm. Due to its extended circulation time (half-life of 2.5 h) and high affinity for tumor cells, this fluorophore was used for primary and metastatic tumor diagnosis and continuous monitoring. Moreover, a high tumor signal-to-noise ratio (up to ~ 10) and excellent preferential mitochondrial accumulation ensured the efficacy of this molecule for photothermal therapy. Therefore, we integrated NIR-II fluorescence-guided surgery and intraoperative photothermal therapy to overcome the shortcomings of a single treatment modality. A significant reduction in recurrence and an improved survival rate were observed, indicating that the concept of intraoperative combination therapy has potential for the precise clinical treatment of prostate cancer.

Theoretical Study of the Temperature- and Pressure-Dependent Rate Constants for Nine Reactions between COn (n = 0-4), Om (m = 1-3), C2O, and C3O2 during the Radiolysis of Carbon Dioxide.

We investigate the reaction pathways of nine important CO2-related reactions using the revDSD-PBEP86-D3(BJ)/jun-cc-pV(T+d)Z level and simultaneously employ an accurate composite method (jun-Cheap) based on coupled-cluster (CC) theory. Subsequently, the Rice-Ramsperger-Kassel-Marcus/master equation (RRKM/ME) is solved to calculate the temperature- and pressure-dependent rate constants. This work investigates reactions involving transition states that have been overlooked in previous literature, including the dissociation of singlet-state C3O2, the triple channel formation of C2O + CO to form C3O2, and the formation of O3 + CO. The results show that CO3 is highly prone to dissociation at high temperatures. Finally, the kinetic data show that over a wide temperature range, our calculations are consistent with previous experimental measurements. The majority of the reaction rate constants studied exhibit significant pressure dependence, while the O3 + CO reaction is pressure-independent at low temperatures. These results are instrumental in the development of detailed kinetic models for the CO2 radiolysis reaction network.

Engineering of the AAV-Compatible Hair Cell-Specific Small-Size Myo15 Promoter for Gene Therapy in the Inner Ear.

Adeno-associated virus (AAV)-mediated gene therapy is widely applied to treat numerous hereditary diseases in animal models and humans. The specific expression of AAV-delivered transgenes driven by cell type-specific promoters should further increase the safety of gene therapy. However, current methods for screening cell type-specific promoters are labor-intensive and time-consuming. Herein, we designed a "multiple vectors in one AAV" strategy for promoter construction in vivo. Through this strategy, we truncated a native promoter for Myo15 expression in hair cells (HCs) in the inner ear, from 1,611 bp down to 1,157 bp, and further down to 956 bp. Under the control of these 2 promoters, green fluorescent protein packaged in AAV-PHP.eB was exclusively expressed in the HCs. The transcription initiation ability of the 2 promoters was further verified by intein-mediated otoferlin recombination in a dual-AAV therapeutic system. Driven by these 2 promoters, human otoferlin was selectively expressed in HCs, resulting in the restoration of hearing in treated Otof -/- mice for at least 52 weeks. In summary, we developed an efficient screening strategy for cell type-specific promoter engineering and created 2 truncated Myo15 promoters that not only restored hereditary deafness in animal models but also show great potential for treating human patients in future.

Targeting EFHD2 Inhibits Interferon-γ Signaling and Ameliorates Non-Alcoholic Steatohepatitis.

BACKGROUND & AIMS: The precise pathomechanisms underlying the development of nonalcoholic steatohepatitis (NASH, also known as metabolic dysfunction-associated steatohepatitis [MASH]) remain incompletely understood. This study investigates the potential role of EF-hand domain family member D2 (EFHD2), a novel molecule specific to immune cells, in NASH pathogenesis. METHODS: Hepatic EFHD2 expression was characterized in NASH patients and two diet-induced NASH mouse models. Single-cell RNA-sequencing (scRNA-seq) and double-immunohistochemistry were employed to explore EFHD2 expression patterns in NASH livers. The effects of global and myeloid-specific EFHD2 deletion on NASH and NASH-related hepatocellular carcinoma (HCC) were assessed. Molecular mechanisms underlying EFHD2 function were investigated, along with its potential as a therapeutic target by chemical and genetic means. RESULTS: EFHD2 expression was significantly elevated in liver tissue macrophages/monocytes in both NASH patients and mice. Deletion of EFHD2, either globally or specifically in myeloid cells, improved hepatic steatosis, reduced immune cell infiltration, inhibited lipid peroxidation-induced ferroptosis, and attenuated fibrosis in NASH. Additionally, it hindered the development of NASH-related HCC. Specifically, deletion of myeloid EFHD2 prevented the replacement of TIM4+ resident Kupffer cells by infiltrated monocytes and reversed the decreases in patrolling monocytes and CD4+/CD8+ T cell ratio in NASH. Mechanistically, our investigation revealed that EFHD2 in myeloid cells interacts with cytosolic YWHAZ (14-3-3ζ), facilitating the translocation of interferon-γ receptor-2 (IFNγR2) onto the plasma membrane. This interaction mediates IFNγ signaling, which triggers immune and inflammatory responses in macrophages during NASH. Finally, a developed stapled α-helical peptide targeting EFHD2 demonstrated its efficacy in protecting against NASH pathology in mice. CONCLUSION: Our study reveals a pivotal immunomodulatory and inflammatory role of EFHD2 in NASH, underscoring EFHD2 as a promising druggable target for NASH treatment. IMPACT AND IMPLICATIONS: Nonalcoholic steatohepatitis (NASH) represents an advanced stage of non-alcoholic fatty liver disease (NAFLD); however, not all NAFLD patients progress to NASH. A key challenge is identifying the factors triggering inflammation, which propels the transition from simple fatty liver to NASH. Our research pinpointed EFHD2 as a pivotal driver of NASH, orchestrating the over-activation of IFNγ signaling within the liver during NASH progression. A stapled peptide designed to target EFHD2 exhibited therapeutic promise in NASH mice. These findings suggest EFHD2 as a promising target for drug development aimed at NASH treatment.

Thyroid tuberculosis and cold abscess after infection with COVID-19: A case report.

There is mounting evidence that coronavirus disease 2019 (COVID-19) can cause immune dysregulation. The consequence of this immune dysregulation may contribute to susceptibility to tuberculosis (TB). Thyroid gland involvement by TB is extremely uncommon and typically the result of disseminated infection. It can be hard to diagnose because there are no identifiable symptoms. We present the case of a Chinese patient who had a fever again after COVID-19 infection that was finally diagnosed as thyroid tuberculosis with a cold abscess. Clinicians should maintain a high index of suspicion for high-risk patients from endemic regions with medical comorbidities, such as immunocompromised disease and malnutrition.

Role of hepatitis B core-related antigen in predicting the occurrence and recurrence of hepatocellular carcinoma in patients with chronic hepatitis B: A systemic review and meta-analysis.

BACKGROUND AND AIM: The purpose of the current study was to investigate the predictive value of hepatitis B core-related antigen (HBcrAg) on the occurrence and recurrence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). METHODS: We searched PubMed, Embase, Scopus, and Web of Science from database inception to April 6, 2023. Pooled hazard ratio (HR) or odds ratio (OR) with 95% confidence interval (CI) was calculated for the occurrence and recurrence of HCC. RESULTS: Of the 464 articles considered, 18 articles recruiting 10 320 patients were included. The pooled results showed that high serum HBcrAg level was an independent risk factor for the occurrence of HCC in CHB patients (adjusted HR = 3.12, 95% CI: 2.40-4.06, P < 0.001, I2 = 43.2%, P = 0.043; OR = 5.65, 95% CI: 3.44-5.82, P < 0.001, I2 = 0.00%, P = 0.42). Further subgroup analysis demonstrated that the predictive ability of HBcrAg for the occurrence of HCC is not influenced by the hepatitis B e antigen (HBeAg) status or the use of nucleoside/nucleotide analogs (NAs). In addition, our meta-analysis also suggests that HBcrAg is a predictor of HCC recurrence (adjusted HR = 1.71, 95% CI: 1.26-2.32, P < 0.001, I2 = 7.89%, P = 0.031). CONCLUSIONS: For patients with CHB, serum HBcrAg may be a potential predictive factor for the occurrence of HCC, regardless of HBeAg status or NA treatment. It may also serve as a novel prognostic biomarker for the recurrence of HCC. More studies are needed to confirm our conclusions.

Mangiferin improves early porcine embryonic development by reducing oxidative stress.

Mangiferin (MGN) is primarily found in the fruits, leaves, and bark of plants of the Anacardiaceae family, including mangoes. MGN exhibits various pharmacological effects, such as protection of the liver and gallbladder, anti-lipid peroxidation, and cancer prevention. This study aimed to investigate the effects of MGN supplementation during in vitro culture (IVC) on the antioxidant capacity of early porcine embryos and the underlying mechanisms involved. Porcine parthenotes in the IVC medium were exposed to different concentrations of MGN (0, 0.01, 0.1, and 1 µM). The addition of 0.1 µM MGN significantly increased the blastocyst formation rate of porcine embryos while reducing the apoptotic index and autophagy. Furthermore, the expression of antioxidation-related (SOD2, GPX1, NRF2, UCHL1), cell pluripotency (SOX2, NANOG), and mitochondria-related (TFAM, PGC1α) genes was upregulated. In contrast, the expression of apoptosis-related (CAS3, BAX) and autophagy-related (LC3B, ATG5) genes decreased after MGN supplementation. These findings suggest that MGN improves early porcine embryonic development by reducing oxidative stress-related genes.

Testosterone does not mediate the correlation between dietary inflammation and serum klotho levels among males: insights from NHANES database.

Introduction: Serum Klotho (S-Klotho) is a transmembrane protein holds pivotal roles in anti-aging. The Dietary Inflammation Index (DII), a meticulously dietary tool, quantifies the inflammatory potential of an individual's diet. The existing research strongly suggests that a low DII diet plays a significant role in delaying aging and reducing aging-related symptoms in males. Testosterone could potentially act as a mediating intermediary between DII and S-Klotho. However, this aspect remains unexplored. This study aims to investigate the potential causal link of testosterone between DII and S-Klotho in males. Methods: We utilized data from National Health and Nutrition Examination Survey (NHANES) which focused on male participants from 2013-2016. Mediation analyses were used to investigate the effects of testosterone (TT), free testosterone (FT), and free androgen index (FAI) on the DII-S-Klotho relationship, using three modes adjusting for covariates. Results: Mediation analysis unveiled a significant inverse correlation between DII and S-Klotho levels (model 1: c = -14.78, p = 0.046). The interaction between DII and S-Klotho was modulated by TT in model 1 (ab = -1.36; 95% CI: -5.59, -0.55; p = 0.008), but lost significance after adjustments (model 2: ab = -0.39; 95% CI: -4.15, 1.66; p = 0.378; model 3: ab = -0.59; 95% CI: -4.08, 2.15; p = 0.442). For FT, the mediating impact was not statistically significant (model 1: ab = 0.43; 95% CI: -0.51, 5.44; p = 0.188; model 2: ab = 0.72; 95% CI: -0.26, 5.91; p = 0.136; model 3: ab = 0.84; 95% CI: -0.02, 8.06; p = 0.056). Conversely, FAI consistently influenced the DII-S-Klotho relationship (model 1: ab = 2.39; 95% CI: 0.69, 9.42; p = 0.002), maintaining significance after adjustments (model 2: ab = 3.2; 95% CI: 0.98, 11.72; p = 0.004; model 3: ab = 3.15; 95% CI: 0.89, 14.51; p = 0.026). Discussion: This study observed no mediating influence of TT or FT on the correlation between DII and S-Klotho after covariate control. Remarkably, FAI continued to significantly mediate the DII-S-Klotho connection even following covariate adjustment, although its significance in males warrants careful consideration.

The therapeutic potential of targeting the CHD protein family in cancer.

Accumulating evidence indicates that epigenetic events undergo deregulation in various cancer types, playing crucial roles in tumor development. Among the epigenetic factors involved in the epigenetic remodeling of chromatin, the chromodomain helicase DNA-binding protein (CHD) family frequently exhibits gain- or loss-of-function mutations in distinct cancer types. Therefore, targeting CHD remodelers holds the potential for antitumor treatment. In this review, we discuss epigenetic regulations of cancer development. We emphasize proteins in the CHD family, delving deeply into the intricate mechanisms governing their functions. Additionally, we provide an overview of current therapeutic strategies targeting CHD family members in preclinical trials. We further discuss the promising approaches that have demonstrated early signs of success in cancer treatment.

Clinical value of molecular subtypes identification based on anoikis-related lncRNAs in castration-resistant prostate cancer.

BACKGROUND: Anoikis is a distinctive type of apoptosis. It is involved in tumor progression and metastasis. But its function in castration-resistant prostate cancer (CRPC) remains veiled. We aimed to develop a prognostic indicator based on anoikis-related long non-coding RNAs (arlncRNAs) and to investigate their biological function in CRPC. MATERIAL AND METHOD: Differentially expressed anoikis-related genes were extracted from two CRPC datasets, GSE51873, and GSE78201. Four lncRNAs associated with the anoikis-related genes were selected. A risk model based on these lncRNAs was developed and validated in The Cancer Genome Atlas (TCGA) and the Memorial Sloan-Kettering Cancer Center (MSKCC) prostate cancer cohorts. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, immune infiltration, immune checkpoints expression, and drug susceptibility were performed based on the model. To identify the biofunction of anoikis-related lncRNA, CCK-8 assays, colony formation assays, and flow cytometry were used. RESULT: Twenty-nine anoikis-related genes were differentially expressed in the CRPC datasets. And 36 prognostic arlncRNAs were selected for the LASSO Cox analysis. Patients were subsequently classified into two subtypes by constructing an anoikis-related lncRNA based prognostic index (ARPI). The accuracy of this index was validated. KEGG enrichment analysis revealed that the high-ARPI group was enriched in cancer-related and immune-related pathways. Immune infiltration analysis has indicated a positive association between high-ARPI groups and increased immune infiltration. Fulvestrant, OSI-027, Lapatinib, Dabrafenib, and Palbociclib were identified as potential sensitive drugs for high-ARPI patients. In vitro experiments exhibited that silencing LINC01138 dampened the proliferation, migration and enzalutamide resistance in CRPC. Furthermore, it stimulated apoptosis and inhibited the eithelial-mesenchymal transition process. CONCLUSION: Four arlncRNAs were identified and a risk model was established to predict the prognosis of patients with prostate cancer. Immune infiltration and drug susceptibility analysis revealed a potential therapeutic strategy for patients with castration-resistant prostate cancer.

The early development of offspring born to women with polycystic ovary syndrome: Insights from a prospective birth cohort study in Southwestern China.

PURPOSE: This prospective cohort study aimed to investigate the effect of maternal polycystic ovary syndrome (PCOS) on the offspring early development. METHODS: A total of 91 mother-child pairs, consisting of 33 PCOS and 58 non-PCOS, were recruited. Peripheral blood tests were performed during 12-16, 24-28, and 32-36 weeks of gestation. Ages & Stages Questionnaires (ASQ) were utilized to assess the motor development of offspring at 27 months of age. Logistic regression models were employed to compare groups and control confounding variables. RESULTS: Women with PCOS had a higher level of testosterone and free androgen index than the non-PCOS group in all three detection windows. There were no intergroup differences in any of the five domains of specific ASQ domain scores or the body measurements of the offspring at 27 months old. Stratification by sex of offspring suggested that no significant differences were detected in the male offspring. However, in the female offspring, the PCOS group exhibited lower gross motor scores in female offspring than the non-PCOS group (48.1 ± 11.8 vs. 55.2 ± 8.1, P = 0.027), as well as lower fine motor scores (48.5 ± 8.5 vs. 53.6 ± 11.0, P = 0.028). The gross motor score of female offspring in the PCOS group remained lower even after adjustments. Each 1 ng/mL increase in testosterone at 12-16 weeks of gestation was associated with a decrease in gross motor score of female offspring by 12.2 (95% CI = -23.3 to -1.0, P = 0.038). The highest tertile of testosterone at 12-16 weeks of gestation was associated with a 7.75-point decrease in gross motor score of female offspring compared to the lowest tertile of testosterone (95% CI = -14.9 to -0.6, P = 0.040), with a significant linear trend observed (P for trend = 0.031). CONCLUSIONS: The findings of this study suggest that maternal PCOS could exert a negative influence on the gross motor development of female offspring, potentially associated with intrauterine androgen exposure during the early stages of pregnancy.

Elucidating the mechanisms underlying astrocyte-microglia crosstalk in hippocampal neuroinflammation induced by acute diquat exposure.

The transition from paraquat (PQ) to diquat (DQ), both organic dication herbicides, in China has led to significant increases in the number of acute DQ poisoning cases. Case studies have shown that acute DQ poisoning resulted in injury to the central nervous system (CNS), but the mechanism underlying the injury remains to be explored. The present study aimed to investigate how DQ influenced purinergic signaling between astrocytes and microglia and whether extracellular ATP (eATP) was involved in promoting neuroinflammation induced by acute DQ toxicity through the activation of the P2X4/NLRP3 signaling pathway. We constructed a rat model of acute DQ toxicity to observe the pathological changes in hippocampal tissues after DQ exposure and measure the expression levels of IL-1ß and TNF-α in the hippocampal tissue. We also established an in vitro co-culture model of C6 astrocytes and BV-2 microglia using transwell chambers, measured the amount of eATP secreted into C6 astrocytes after DQ treatment, and assessed the inflammatory response and changes in the P2X4/NLRP3 signaling pathway in BV-2 microglia. The results showed that the neurons in the hippocampal tissue of rats exhibited loose arrangement, nuclear consolidation, and necrosis after DQ exposure, and IL-1ß and TNF-α levels were signification higher in the hippocampal tissue after DQ exposure. DQ exposure to the co-cultured cells induced an increase in ATP secretion from C6 astrocytes as well as a significant increase of P2X4, NLRP3, IL-1ß, and IL-18 expression in BV-2 microglia. In contrast, pretreatment of C6 astrocytes with apyrase (an ATP hydrolase) resulted in a significant decrease of P2X4, NLRP3, IL-1ß, and IL-18 expression in BV-2 microglia. Furthermore, inhibition of P2X4 expression in BV-2 microglia by transfection with si-P2X4 effectively reversed the increase of NLRP3, IL-1ß, and IL-18 in BV-2 microglia induced by DQ when co-cultured with C6 astrocytes. These results indicate that astrocytes can activate the P2X4/NLRP3 signaling pathway in microglia through the DQ-induced extracellular release of ATP to promote neuroinflammation in rat hippocampal tissue.

Paper-based colorimetric sensor using bimetallic Nickel-Cobalt selenides nanozyme with artificial neural network-assisted for detection of H2O2 on smartphone.

Paper-based analytical devices (PADs) integrated with smartphones have shown great potential in various fields, but they also face challenges such as single signal reading, complex data processing and significant environmental impacting. In this study, a colorimetric PAD platform has been proposed using bimetallic nickel-cobalt selenides as highly active peroxidase mimic, smartphone with 3D-printing dark-cavity as a portable detector and an artificial neural network (ANN) model as multi-signal processing tool. Notably, the optimized nickel-cobalt selenides (Ni0.75Co0.25Se with Ni to Co ratio of 3/1) exhibit excellent peoxidase-mimetic activities and are capable of catalyzing the oxidation of four chromogenic reagents in the presence of H2O2. Using a smartphone with image capture function as a friendly signal readout tool, the Ni0.75Co0.25Se based four channel colorimetric sensing paper is used for multi-signal quantitative analysis of H2O2 by determining the Grey, red (R), green (G) and blue (B) channel values of the captured pictures. An intelligent on-site detection method for H2O2 has been constructed by combining an ANN model and a self-programmed easy-to-use smartphone APP with a dynamic range of 5 µM to 2 M. Noteworthy, machine learning-assisted smartphone sensing devices based on nanozyme and 3D printing technology provide new insights and universal strategies for visual ultrasensitive detection in a variety of fields, including environments monitoring, biomedical diagnosis and safety screening.

Amorphous Albumin Gadolinium-Based Nanoparticles for Ultrahigh-Resolution Magnetic Resonance Angiography.

Magnetic resonance angiography (MRA) contrast agents are extensively utilized in clinical practice due to their capability of improving the image resolution and sensitivity. However, the clinically approved MRA contrast agents have the disadvantages of a limited acquisition time window and high dose administration for effective imaging. Herein, albumin-coated gadolinium-based nanoparticles (BSA-Gd) were meticulously developed for in vivo ultrahigh-resolution MRA. Compared to Gd-DTPA, BSA-Gd exhibits a significantly higher longitudinal relaxivity (r1 = 76.7 mM-1 s-1), nearly 16-fold greater than that of Gd-DTPA, and an extended blood circulation time (t1/2 = 40 min), enabling a dramatically enhanced high-resolution imaging of microvessels (sub-200 µm) and low dose imaging (about 1/16 that of Gd-DTPA). Furthermore, the clinically significant fine vessels were successfully mapped in large mammals, including a circle of Willis, kidney and liver vascular branches, tumor vessels, and differentiated arteries from veins using dynamic contrast-enhanced MRA BSA-Gd, and have superior imaging capability and biocompatibility, and their clinical applications hold substantial promise.

Towards generalizable Graph Contrastive Learning: An information theory perspective.

Graph Contrastive Learning (GCL) is increasingly employed in graph representation learning with the primary aim of learning node/graph representations from a predefined pretext task that can generalize to various downstream tasks. Meanwhile, the transition from a specific pretext task to diverse and unpredictable downstream tasks poses a significant challenge for GCL's generalization ability. Most existing GCL approaches maximize mutual information between two views derived from the original graph, either randomly or heuristically. However, the generalization ability of GCL and its theoretical principles are still less studied. In this paper, we introduce a novel metric GCL-GE, to quantify the generalization gap between predefined pretext and agnostic downstream tasks. Given the inherent intractability of GCL-GE, we leverage concepts from information theory to derive a mutual information upper bound that is independent of the downstream tasks, thus enabling the metric's optimization despite the variability in downstream tasks. Based on the theoretical insight, we propose InfoAdv, a GCL framework to directly enhance generalization by jointly optimizing GCL-GE and InfoMax. Extensive experiments validate the capability of InfoAdv to enhance performance across a wide variety of downstream tasks, demonstrating its effectiveness in improving the generalizability of GCL.

Genetic and Biological Characteristics of Duck-Origin H4N6 Avian Influenza Virus Isolated in China in 2022.

The interaction between migratory birds and domestic waterfowl facilitates viral co-infections, leading to viral reassortment and the emergence of novel viruses. In 2022, samples were collected from duck farms around Poyang Lake in Jiangxi Province, China, which is located within the East Asia-Australasia flyway. Three strains of H4N6 avian influenza virus (AIV) were isolated. Genetic and phylogenetic analyses showed that the isolated H4N6 avian influenza viruses (AIVs) belonged to new genotypes, G23 and G24. All isolated strains demonstrated dual receptor binding properties. Additionally, the isolated strains were able to replicate efficiently not only in avian cells but also in mammalian cells. Furthermore, the H4N6 AIV isolates could infect chickens, with viral replication detected in the lungs and extrapulmonary organs, and could transmit within chicken flocks through contact, with viral shedding detected only in oropharyngeal swabs from chickens in the contact group. Notably, the H4N6 AIV could infect mice without prior adaptation and replicate in the lungs with high viral titers, suggesting that it is a potential threat to humans. In conclusion, this study provides valuable insight into the characteristics of H4N6 strains currently circulating in China.

TBC1D5 reverses the capability of HIF-2α in tumor progression and lipid metabolism in clear cell renal cell carcinoma by regulating the autophagy.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is known for abnormal lipid metabolism and widespread activation of HIF-2α. Recently, the importance of autophagy in ccRCC has been focused, and it has potential connections with HIF-2α and lipid metabolism. However, the specific regulatory mechanism between HIF-2α, autophagy, and lipid metabolism in ccRCC is still unclear. METHODS: In this study, Bioinformatics Analysis and Sequencing of the whole transcriptome were used to screen our target. The expression of TBC1D5 in renal clear cell carcinoma was confirmed by database analysis, immunohistochemistry, PCR and Western blot. The effects of TBC1D5 on tumor cell growth, migration, invasion and lipid metabolism were examined by CCK8, Transwell and oil red staining, and the mechanism of TBC1D5 on autophagy was investigated by Western blot, fluorescence microscopy and electron microscopy. Chloroquine and rapamycin were used to verified the key role of autophagy in effects of TBC1D5 on tumor cell. The regulatory mechanism of TBC1D5 in renal clear cell carcinoma (RCC) was investigated by shhif-2α, shTBC1D5, mimic, inhibitor, ChIP and Luciferase experiments. The animal model of ccRCC was used to evaluate the biological function of TBC1D5 in vivo. RESULTS: In this study, TBC1D5 was found to be an important bridge between autophagy and HIF-2α. Specifically, TBC1D5 is significantly underexpressed in ccRCC, serving as a tumor suppressor which inhibits tumor progression and lipid accumulation, and is negatively regulated by HIF-2α. Further research has found that TBC1D5 regulates the autophagy pathway to reverse the biological function of HIF-2α in ccRCC. Mechanism studies have shown that HIF-2α regulates TBC1D5 through hsa-miR-7-5p in ccRCC, thereby affecting tumor progression and lipid metabolism through autophagy. CONCLUSIONS: Our research reveals a completely new pathway, HIF-2α/hsa-miR-7-5p/TBC1D5 pathway affects ccRCC progression and lipid metabolism by regulating autophagy.