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Regulation of tumoral PD-L1 expression is critical to advancing our understanding of tumor immune evasion and the improvement of existing antitumor immunotherapies. Herein, we describe a CRISPR-based screening platform and identified ATXN3 as a positive regulator for PD-L1 transcription. TCGA database analysis revealed a positive correlation between ATXN3 and CD274 in more than 80% of human cancers. ATXN3-induced Pd-l1 transcription was promoted by tumor microenvironmental factors, including the inflammatory cytokine IFN-[gamma] and hypoxia, through protection of their downstream transcription factors IRF1, STAT3, and HIF-2[alpha]. Moreover, ATXN3 functioned as a deubiquitinase of the AP-1 transcription factor JunB, indicating that ATNX3 promotes PD-L1 expression through multiple pathways. Targeted deletion of ATXN3 in cancer cells largely abolished IFN-[gamma]- and hypoxia-induced PD-L1 expression and consequently enhanced antitumor immunity in mice, and these effects were partially reversed by PD-L1 reconstitution. Furthermore, tumoral ATXN3 suppression improved the preclinical efficacy of checkpoint blockade antitumor immunotherapy. Importantly, ATXN3 expression was increased in human lung adenocarcinoma and melanoma, and its levels were positively correlated with PD-L1 as well as its transcription factors IRF1 and HIF- 2[alpha]. Collectively, our study identifies what we believe to be a previously unknown deubiquitinase, ATXN3, as a positive regulator for PD-L1 transcription and provides a rationale for targeting ATXN3 to sensitize checkpoint blockade antitumor immunotherapy., Introduction Antitumor immune therapy, particularly through the release of negative regulators of immune activation or immune checkpoints that limit antitumor responses, has achieved tremendous success in the treatment of a [...]

Axillary osmidrosis (AO) affects a large number of young people in Asia, resulting from a combination of body and bacterial metabolism. This study aimed to explore the pathogenesis of AO through proteomics. Apocrine gland tissues from 3 mild and 3 severe AO patients were analyzed using 4D label-free proteomics, followed by bioinformatics analysis. The RNA and protein levels of the predicted key regulators were further validated by qPCR and immunohistochemistry in additional AO tissues. A total of 5066 proteins were identified, of which 323 were significantly upregulated and 412 were downregulated (by |log2FC|> 1 and p < 0.05). GO terms related to mitochondria, oxidation–reduction processes, and peroxisomes were significantly enriched among the upregulated DEPs, suggesting enhanced energy metabolism in severe AO patients. Downregulated DEPs were enriched in ribosome, phagosome, and platelet activation pathways according to KEGG, while upregulated DEPs were significantly enriched in metabolic pathways, valine, leucine, and isoleucine degradation, peroxisomes, and fatty acid degradation. The enriched pathways suggest that apocrine gland tissues develop AO by increasing blood flow to promote sweating and secreting excessive short-chain fatty acids by coupling mitochondrial respiration with incomplete metabolism of lipids and branched-chain amino acids. This metabolic coupling may have implications for studies on cardiovascular disease, metabolic disorders, and oxidative stress. Key proteins in the signaling network were further confirmed by qPCR and immunohistochemistry, including reduced FGA and ITGA2B, and increased EHHADH and ACOX1. Our proteomics analysis suggests a paradigm of lipid metabolism involving mitochondrial respiration and incomplete lipid and branched-chain amino acid metabolism as the pathogenesis of AO. We also suggest that EHHADH is a key regulator in promoting AO in this process. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the infection rate, types of human papillomavirus (HPV), and the relationship between HPV types and host factors in Zhejiang and lay a foundation for developing a prophylactic HPV vaccine. Methods: A retrospective analysis of the genotyping results of 27 hPV types using exfoliated cells from the cervix, vulva, perianal region, or oral mucosa of 28206 females, and exfoliated cells from the penis, perianal region or oral mucosa of 2923 male patients undergoing treatment between January 2016 and December 2021 at Zhejiang Provincial People's Hospital was performed. Results: In females, the overall positive rate was 30.26%. The top five HPV types were HPV52, 58, 16, 6, and 53. In males, the overall positive rate was 31.85%. The top five HPV types were HPV6, 11, 16, 52, and 43. About 90.48% of patients with CINII+ were HR-HPV+. HPV33, 16 were the top two HPV types that increased CINII+ risks. Conclusion: Currently, the bivalent (HPV16, 18), quadrivalent (HPV6, 11, 16, 18), and 9-valent (HPV6, 11, 16, 18, 31, 33, 45, 52, 58) HPV vaccines are marketed. Of these, the 9-valent HPV vaccines are more suitable for people in the Zhejiang province; however, it is still insufficient. Therefore, the 11-, 14-, and 15-valent vaccines being developed and marketed include more genotypes, and their outcomes are worth anticipating. [ABSTRACT FROM AUTHOR]

In this work, a V2AlC‐based saturable absorber (SA) was applied to a 2 μm band passively mode‐locked (PML) laser. The saturation intensity and modulation depth of the V2AlC‐based SA were detected by the I‐scan method, which were 225.05 MW/cm2 and 7.68%, respectively. In the PML mode, an average power of 2.12 W at 1939 nm and a pulse width of 1077 ps at 82.49 MHz were obtained from the Tm:YAP laser. In addition, the laser exhibited a good beam quality factor (M2) which was measured to be less than 1.2. These results will pave the way for the application of V2AlC‐based SA in ultrafast lasers. [ABSTRACT FROM AUTHOR]

In this study, the extraction, purification and metabolic enzyme inhibition potential of Selaginella doederleinii were investigated. In order to extract the total biflavonoids from S. doederleinii (SDTBs), the optimum extraction process was obtained by optimizing the ultrasonic extraction parameters using response-surface methodology. This resulted in a total biflavonoid content of 22.26 ± 0.35 mg/g. Purification of the S. doederleinii extract was carried out using octadecylsilane (ODS), and the transfer rate of the SDTBs was 82.12 ± 3.48% under the optimum purification conditions. We determined the effect of the SDTBs on α-glucosidase (AG), α-amylase and xanthine oxidase (XOD) and found that the SDTBs had an extremely potent inhibitory effect on AG, with an IC50 value of 57.46 μg/mL, which was much lower than that of the positive control. Meanwhile, they also showed significant inhibition of XOD and α-amylase, with IC50 values of 289.67 μg/mL and 50.85 μg/mL, respectively. In addition, molecular docking studies were carried out to understand the nature of the action of the biflavonoids on AG and XOD. The results showed that robustaflavone had the lowest binding energy to AG (−11.33 kcal/mol) and XOD (−10.21 kcal/mol), while, on the other hand, amentoflavone showed a good binding affinity to AG (−10.40 kcal/mol) and XOD (−9.962 kcal/mol). Moreover, molecular dynamics simulations verified the above results. [ABSTRACT FROM AUTHOR]

WSe2 and CuO belong to transition metal chalcogenides (TMDs) and transition metal oxides (TMOs), respectively, and both are semiconductor materials that have been applied in production in many fields. In this work, WSe2/CuO heterojunction nanocomposites were prepared by simple and non-toxic liquid phase exfoliation (LPE) and vacuum filtration methods, and WSe2/CuO heterojunction saturable absorber (SA) devices were prepared by film transfer technology. The morphology and purity of the WSe2/CuO heterojunction were studied. In addition, the WSe2/CuO heterojunction SA was applied to a passively Q-switched (PQS) solid-state laser for the first time, generating a stable pulse output with a Watt-level output power, a maximum average output power of 2.32 W, a repetition frequency of 68.68 kHz, and a minimum pulse width of 752.8 ns. Our research results illustrate the great potential and broad application prospects of WSe2/CuO composites in the field of photonic devices. [ABSTRACT FROM AUTHOR]

Photoelectrochemical hydrogen production technology holds promise for directly and swiftly generating green hydrogen, which is pivotal for human welfare; however, it faces challenges posed by the energetically sluggish oxygen evolution reaction (OER). Cobalt-based nitrides are considered excellent photoelectrochemically active in the OER (PEOER) catalysts, and their conductivity and photoconversion efficiency remain relatively low. This paper presents the fabrication of Ni-alloyed Co4N nanowire arrays on carbon cloth ((Co1–xNix)4N NWAs/CC) as PEOER catalysts. By analyzing advanced in situ Raman and X-ray photoelectron spectroscopy (XPS) results, we discovered that Ni not only enhances the conductivity of the catalyst but, more importantly, also creates more photoexcited Co2+ OER centers and favors its reconstruction to CoOOH to charge PEOER. Furthermore, nitrogen plays a critical role in transforming pyridinic nitrogen into other forms of nitrogen to stabilize the catalyst's structure. These advantages endow (Co0.74Ni0.26)4N NWAs/CC with remarkable PEOER enhancement (988%), which drives the standard current density of 10 mA cm–2 with only a 283 mV overpotential along with good durability. This research provides insights into the PEOER mechanisms of cobalt-based transition metal nitrides, providing a way for designing next-generation PEOER catalysts. [ABSTRACT FROM AUTHOR]

Solar irradiation can efficiently promote the kinetics of the oxygen evolution reaction (OER) during water splitting, where heterojunction catalysts exhibit excellent photoresponsive properties. However, insights into the origins of photoassisted OER catalysis remain unclear, especially the interfaced promotion under convergent solar irradiation (CSI). Herein, novel allotropic Co5.47N/CoN heterojunctions were synthesized, and corresponding OER mechanisms under CSI were comprehensively uncovered from physical and chemical aspects using the in situ Raman technique and electrochemical cyclic voltammetry method. Our results provide a unique mechanism where high‐energy UV light promotes the Co3+/4+ conversion process in addition to the ordinary photoelectric effect excitation of the Co2+ material. Importantly, visible light under CSI can produce a photothermal effect for Co2+ excitation and Co3+/4+ conversion, which promotes the OER significantly more than the usual photoelectric effect. As a result, Co5.47N/CoN (containing 28% CoN) obtained 317.9% OER enhancement, which provides a pathway for constructing excellent OER catalysts. [ABSTRACT FROM AUTHOR]

People's increasing demand for fossil fuels not only leads to environmental pollution but also highlights their non-renewable nature. Therefore, the urgency of developing renewable energy sources is evident. Tree branches and leaves undergo cycles of growth and decay with the changing seasons, showcasing their renewable potential. Despite this, they remain underutilized as new energy materials, particularly in the realm of high-energy-density lithium batteries. While this paper did not directly explore the utilization of various branches and leaves as raw materials for lithium–sulfur battery (LSB) cathodes, it revealed promising findings: they not only demonstrate good battery capacity but also boast considerable cycle life. The carbonized material from the leaves of Acer buergerianum can be used as the electrode of LSBs and could achieve 318.8 mA h g−1 at 4C and a decay rate of only 0.03% at 1C for 400 cycles., respectively. Therefore, the innovative method of turning decaying leaves into energy contributes significantly to the future of renewable energy and environmental protection. [ABSTRACT FROM AUTHOR]