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Abstract While self-assembled material based inverted perovskite solar cells have surpassed power conversion efficiencies of 26%, enhancing their performance in large-area configurations remains a significant challenge. In this work, we report a self-assembled material based hole-selective layer 4-(7H-dibenzo[c,g]carbazol-7-yl)phenyl)phosphonic acid, with a π-expanded conjugation. The enhanced intermolecular π–π interactions facilitate the self-assembly of 4-(7H-dibenzo[c,g]carbazol-7-yl)phenyl)phosphonic acid molecules to form an ordered bilayer with a hydrophilic surface, which passivates the buried perovskite interface defect and enables high-quality and large-area perovskite preparation, while simultaneously enhancing interfacial charge extraction and transport. The certified efficiency of 4-(7H-dibenzo[c,g]carbazol-7-yl)phenyl)phosphonic acid based small-area (0.0715 cm2) device is 26.39% with high stability. Furthermore, a certified efficiency of 25.21% is achieved for a 99.12 mm2 large area device.

Three species of the spider family Philodromidae are reported from the south of China. A new genus, Sinodromus gen. nov., is described from Jiangxi, Fujian, and Hunan Provinces. It can be distinguished from other genera of Philodromidae by the tegular apophysis of the palp and the cymbial process, as well as by its uniquely striped abdomen. The type species, S. fujianensis sp. nov., and a second species, S. perbrevis sp. nov., are described and illustrated; these species occur in bamboo forests in hilly areas. Additionally, the female of Philodromus guiyang Long & Yu, 2022 is described for the first time from Jiangxi and Hunan Provinces. All species are illustrated with SEM micrographs, and their distributions are mapped.

Abstract The Banna miniature inbred pig (BN) is an intensively inbred line for biomedical research and xenotransplantation due to its low individual variation and stable genetic background. Although it is originated from the Diannan miniature pig (DN), substantial genetic changes have actually occurred. However, the lack of a BN reference genome has limited studies on the complete genomic architecture and utilization as a biomedical model. Here, we present a high-quality genome for BN using PacBio HiFi and Hi-C sequencing technologies, with a total length of 2.66 Gb, a scaffold N50 of 143.60 Mb, and 97.59% of the sequences anchored to chromosomes. Its BUSCO score is 96.30%, higher than porcine reference assembly and DN. The genome contains 48.49% of repeats, 19,756 protein-coding genes, and 7,207 non-coding RNAs according to our annotation. The OMArk score shows a proteome completeness and consistency of 99.58% and 93.62%, respectively. These findings indicate that the chromosome-scale genome of BN provides a valuable resource for studying the genetic basis of inbreeding, facilitating further research and clinical applications.

Abstract Background Head and neck squamous cell carcinoma(HNSCC) is the sixth most common malignancy worldwide, with more than 890,000 new cases and 450,000 deaths annually. Its major risk factors include smoking, alcohol abuse, aging, and poor oral hygiene. Due to the lack of early and effective detection and screening methods, many patients are diagnosed at advanced stages with a five-year survival rate of less than 50%. In this study, we deeply explored the expression of Aging-related genes(ARGs) in HNSCC and analyzed their prognostic significance using single-cell sequencing and spatial transcriptomics analysis. This research aims to provide new theoretical support and directions for personalized treatment. Annually, more than 890,000 new cases of head and neck squamous cell carcinoma (HNSCC) are diagnosed globally, leading to 450,000 deaths, making it the sixth most common malignancy worldwide. The primary risk factors for HNSCC include smoking, alcohol abuse, aging, and poor oral hygiene. Many patients are diagnosed at advanced stages due to the absence of early and effective detection and screening methods, resulting in a five-year survival rate of less than 50%. In this research, single cell sequencing and spatial transcriptome analysis were used to investigate the expression of Aging-related genes (ARGs) in HNSCC and to analyse their prognostic significance. This research aims to provide new theoretical support and directions for personalized treatment. Methods In this study, we investigated the association between HNSCC and AGRs by utilizing the GSE139324 series in the GEO database alongside the TCGA database, combined with single-cell sequencing and spatial transcriptomics analysis. The data were analyzed using Seurat and tSNE tools to reveal intercellular communication networks. For the spatial transcriptome data, SCTransform and RunPCA were applied to examine the metabolic activities of the cells. Gene expression differences were determined through spacerxr and RCTD tools, while the limma package was employed to identify differentially expressed genes and to predict recurrence rates using Cox regression analysis and column line plots. These findings underscore the potential importance of molecular classification, prognostic assessment, and personalized treatment of HNSCC. Results This study utilized HNSCC single-cell sequencing data to highlight the significance of ARGs in the onset and prognosis of HNSCC. It revealed that the proportion of monocytes and macrophages increased, while the proportion of B cells decreased. Notably, high expression of the APOE gene in monocytes was closely associated with patient prognosis. Additionally, a Cox regression model was developed based on GSTP1 and age to provide personalized prediction tools for clinical use in predicting patient survival. Conclusions We utilized single-cell sequencing and spatial transcriptomics to explore the cellular characteristics of HNSCC and its interaction with the tumor microenvironment. Our findings reveal that HNSCC tissues show increased mononuclear cells and demonstrate enhanced activity in ARGs, thereby advancing our understanding of HNSCC development mechanisms.

Abstract Background The innate immune system serves as the host’s first line of defense against invading pathogens. Stimulator of interferon genes (STING) is a key component of this system, yet its relationship with glucose metabolism, particularly in antiviral immunity, remains underexplored. Methods Metabolomics analysis was used for detecting metabolic alterations in spleens from STING knockout (KO) and wild-type (WT) mice. Co-immunoprecipitation was employed for determining ubiquitination of TKT. Mass spectrometry was used for detecting interaction proteins of STING. Enzyme activity kits were used for detecting the activities of TKT and G6PD. Results In this study, we demonstrate that herpes simplex virus (HSV) infection activates the pentose phosphate pathway (PPP) in host cells, thereby initiating an antiviral immune response. Using STING-manipulated cells and systemic knockout mice, we show that STING positively regulates PPP, which, in turn, limits HSV infection. Inhibition of the PPP significantly reduced the production of antiviral immune factors and dampened STING-induced innate immune responses. Mechanistically, we discovered that STING interacts with transketolase (TKT), a key enzyme in the non-oxidative branch of the PPP, and reduces its ubiquitination via the E3 ubiquitin ligase UBE3A, stabilizing TKT. Silencing TKT or inhibiting its activity with oxythiamine diminished antiviral immune factor production. Conclusion Our findings reveal that the PPP plays a synergistic role in generating antiviral immune factors during viral infection and suggest that PPP activation could serve as an adjunct strategy for antiviral therapy.

Twenty-one new species of jumping spiders from five provinces of South China are described: Cheliceroides jinxini sp. nov. (♂), Dendroicius qiong sp. nov. (♂♀), Icius deergong sp. nov. (♂♀), Irura qiuhangi sp. nov. (♂♀), I. yarlungzangbo sp. nov. (♂♀), Mintonia shiwandashan sp. nov. (♂), Myrmarachne kuan sp. nov. (♂♀), Nandicius xiefengi sp. nov. (♂♀), Pancorius medog sp. nov. (♀), P. yingjiang sp. nov. (♂♀), Piranthus maddisoni sp. nov. (♂♀), Simaetha hainan sp. nov. (♂♀), Stertinius lhoba sp. nov. (♂♀), Synagelides kongmingi sp. nov. (♂♀), S. xuandei sp. nov. (♂♀), S. yunchangi sp. nov. (♂♀), S. yidei sp. nov. (♂), S. zilongi sp. nov. (♂♀), Yaginumaella daweishan sp. nov. (♂♀), Y. moinba sp. nov. (♂♀), and Y. pingbian sp. nov. (♂♀). Nepalicius Prószyński, 2016, syn. nov. is proposed as a junior synonym of Okinawicius Prószyński, 2016. Three new combinations are proposed: O. nepalicus (Andreeva, Hęciak & Prószyński, 1984), comb. nov. and O. seychellensis (Wanless, 1984), comb. nov. transferred from Nepalicius, and O. daoxianensis (Peng, Gong & Kim, 2000), comb. nov. transferred from Philaeus Thorell, 1869. The unknown females of O. nepalicus, Padillothorax exilis (Cao & Li, 2016) and Siler hanoicus Prószyński, 1985 are described for the first time. Distribution maps of the studied specimens are also provided.

Abstract The selection optimum endovascular method for the treatment of different cerebral aneurysms has been the main challenge for surgeons. In the present article, the computational technique is used for the hemodynamic evaluation of two main endovascular techniques of stent and coiling for the reduction of the hemorrhage risk of ICA aneurysms. Comprehensive analyses of the blood flow are performed to detect potential regions with high risk at critical stages of the cardiac cycle. Two coiling porosity conditions and stent deformation have been investigated via computational study to reveal the main change related to hemodynamics when these techniques are implemented. The hemodynamic results of this study show that the endovascular technique is more efficient in small aneurysms rather than giant ones. Meanwhile, the stent treatment of the giant saccular aneurysm is effective when the parent vessel of this type of aneurysm is fully aligned and limited blood flow enters the sac area.

Abstract Chronic alcohol consumption can lead to alcohol live disease (ALD). Steatosis is a critical hallmark of ALD, making it an important stage for therapeutic intervention. Saikosaponin A (SSa), a compound found in Radix Bupleuri, has previously shown promising hepatoprotective, anti-inflammatory, and antioxidant properties. However, its role in ALD remains understudied. We employ cell-based screening models and a chronic-plus-binge ethanol-fed mouse model to investigate the protective mechanisms of SSa and its metabolite Saikogenin A (SGA), against ethanol-induced hepatocyte injury. Our RNA-seq analysis in mice unveils that SSa primarily acts through the mTOR and PPAR-α signaling pathways in the liver. Biophysical assays and loss of function experiments confirm SGA directly binds to and modulates the activity of SIRT1 protein, mitigating ethanol-induced cell injury via the SIRT1-mTOR-PPAR-α axis. Furthermore, SGA displays a survival prolonging advantage compared to resveratrol for treating ALD. This suggests SGA holds promise as a potential therapeutic agent for ALD.

Abstract Metabolic reprogramming is a hallmark of cancer, enabling tumor cells to meet the high energy and biosynthetic demands required for their proliferation. High mobility group A1 (HMGA1) is a structural transcription factor and frequently overexpressed in human colorectal cancer (CRC). Here, we show that HMGA1 promotes CRC progression by driving lipid synthesis in a AOM/DSS-induced CRC mouse model. Using conditional knockout (Hmga1 △IEC) and knock-in (Hmga1 IEC-OE/+) mouse models, we demonstrate that HMGA1 enhances CRC cell proliferation and accelerates tumor development by upregulating fatty acid synthase (FASN). Mechanistically, HMGA1 increases the transcriptional activity of sterol regulatory element-binding protein 1 (SREBP1) on the FASN promoter, leading to increased lipid accumulation in intestinal epithelial cells. Moreover, a high-fat diet exacerbates CRC progression in Hmga1 △IEC mice, while pharmacological inhibition of FASN by orlistat reduces tumor growth in Hmga1 IEC-OE/+ mice. Our findings suggest that targeting lipid metabolism could offer a promising therapeutic strategy for CRC.

Abstract Background Diabetes-associated cognitive dysfunction, characterized by hippocampal synaptic loss as an early pathological feature, seriously threatens patients’ quality of life. Synapses are dynamic structures, and hormones play important roles in modulating the formation and elimination of synapses. The pituitary, the master gland of the body, releases several hormones with multiple roles in hippocampal synaptic regulation. In this study, we aimed to explore the relationship between pituitary hormones and cognitive decline in diabetes. Methods A total of 744 patients with type 2 diabetes (T2DM) (445 men and 299 postmenopausal women) who underwent serum pituitary hormone level assessments, comprehensive cognitive evaluations and MRI scans were enrolled. Dynamic diet interventions were applied in both chow diet-fed mice and high-fat diet (HFD)-fed diabetic mice. The cognitive performance and hippocampal pathology of prolactin (PRL)-knockout mice, neuronal prolactin receptor (PRLR)-specific knockout mice and microglial PRLR-specific knockout mice were assessed. Microglial PRLR-specific knockout mice were fed an HFD to model diabetes. Diabetic mice received an intracerebroventricular infusion of recombinant PRL protein or vehicle. Results This clinical study revealed that decreased PRL levels were associated with cognitive impairment and hippocampal damage in T2DM patients. In diabetic mice, PRL levels diminished before hippocampal synaptic loss and cognitive decline occurred. PRL loss could directly cause cognitive dysfunction and decreased hippocampal synaptic density. Knockout of PRLR in microglia, rather than neurons, induced hippocampal synaptic loss and cognitive impairment. Furthermore, blockade of PRL/PRLR signaling in microglia exacerbated abnormal microglial phagocytosis of synapses, further aggravating hippocampal synaptic loss and cognitive impairment in diabetic mice. Moreover, PRL infusion reduced microglia-mediated synaptic loss, thereby alleviating cognitive impairment in diabetic mice. Conclusion PRL is associated with cognitive dysfunction and hippocampal damage in T2DM patients. In diabetes, a decrease in PRL level drives hippocampal synaptic loss and cognitive impairment by increasing microglia-mediated synapse engulfment. Restoration of PRL levels ameliorates cognitive dysfunction and hippocampal synaptic loss in diabetic mice.

Abstract With the progress of micro electromechanical system (MEMS) technology, the performance of MEMS inertial measurement unit (IMU) composed of gyroscopes and accelerometers has been improved. Among the inertial sensors, MEMS triaxial gyroscope plays an important role in attitude estimation, navigation and positioning of intelligent mobile terminals such as unmanned aerial vehicles and unmanned vehicles. However, the measured values of low and medium cost MEMS triaxial gyroscopes are mainly affected by temperature (or thermal effect) and random errors. As results, the drift errors correlated with temperature will reduce application accuracy of MEMS triaxial gyroscope. The traditional calibration method for thermal drift errors relies on the expensive equipment, such as turntable and the temperature control system, which increases the cost of calibration. Therefore, an effective thermal calibration method that is available when using low- or high-cost tools for MEMS triaxial gyroscope will be meaningful for majority users. Hence, this paper analyzed and established the thermal drift model of MEMS triaxial gyroscope, and proposed a segmented systematic calibration method based on 24 states according to this model. Simulation shows that the proposed method can obtain the results approaching the real parameter thermal drift curves. Calibration experiments and parameters test show that the max errors of attitude calculation are reduced to 10% of the results using the original parameters, which indicates that the effectiveness of the proposed method.

Abstract Background Neurovascular compression (NVC) is a primary etiology of trigeminal neuralgia (TN) and hemifacial spasm (HFS). Despite Magnetic Resonance Tomographic Angiography (MRTA) being a useful tool for 3D multimodal fusion imaging (MFI) in microvascular decompression (MVD) surgery planning, it may not visualize smaller arterial vessels and veins effectively. We validate a novel computed tomography angiography and venography (CTA/V) - diffusion tensor tractography (DTT) -3D-MFI to enhance the MVD surgical guidance. Methods In this prospective study, 80 patients with unilateral primary TN or HFS who underwent MVD surgery were included. Imaging was conducted using CTA/V-DTT-3D-MFI compared with CT-MRTA-3D-MFI in predicting the responsible vessel and assessing the severity of NVC. Surgical outcomes were subsequently analyzed. Neurosurgery residents were provided with questionnaires to evaluate and compare the two approaches. Results CTA/V-DTT-3D-MFI significantly improved accuracy in identifying the responsible vessel (kappa = 0.954) and NVC (kappa = 0.969) compared to CT-MRTA-3D-MFI, aligning well with surgical findings. CTA/V-DTT-3D-MFI also exhibited higher sensitivity in identifying responsible vessels (98.0%) and NVC (98.7%) than CT-MRTA-3D-MFI. Additionally, CTA/V-DTT-3D-MFI showed fewer complications, shorter operation times, and lower recurrence after one year (all p

Abstract Pancreatic cancer is among the most immune-resistant tumor types due to its unique tumor microenvironment and low cancer immunogenicity. Single-agent immune modulators have thus far proven clinically ineffective. However, a growing body of evidence suggests that combination of these modulators with other strategies could unlock the potential of immunotherapy in pancreatic cancer. Herein, we describe the case of a 59-year-old male with metastatic pancreatic ductal adenocarcinoma, referred to our center to receive immunotherapy (serplulimab, a novel anti-PD-1 antibody) combined with chemotherapy (gemcitabine/nab-paclitaxel). During the initial three treatment cycles, the patient was assessed as having stable disease (SD) according to RECIST 1.1 criteria. However, following two additional cycles of combination therapy, the primary tumor mass increased from 4.9 cm to 13.2 cm, accompanied by the development of new lung lesions, ascites, and pelvic metastases. He succumbed to respiratory failure one month later. Retrospective analysis revealed that the patient had MDM4 amplification, identified as a high-risk factor for hyperprogressive disease (HPD). To our knowledge, this is the first reported case of HPD in pancreatic cancer with multiple metastases treated using combination therapy. We investigated the potential mechanisms and reviewed the latest literature on predictive factors for HPD. These findings suggest that while chemotherapy combined with immunotherapy may hold promise for treating pancreatic cancer, it is imperative to identify and closely monitor patients with high-risk factors for HPD when using immunotherapy.

Abstract Background Premature rupture of the membranes (PROM) is a key cause of preterm birth and represents a major cause of neonatal mortality and morbidity. Natural products N-acetyl-d-galactosamine (GalNAc), which are basic building blocks of important polysaccharides in biological cells or tissues, such as chitin, glycoproteins, and glycolipids, may improve possible effects of wound healing. Methods An in vitro inflammation and oxidative stress model was constructed using tumor necrosis-α (TNF-α) and lipopolysaccharide (LPS) action on WISH cells. Human amniotic epithelial cells (hAECs) were primarily cultured by digestion to construct a wound model. The effects of GalNAc on anti-inflammatory and anti-oxidative stress, migration and proliferation, epithelial-mesenchymal transition (EMT), glycosaminoglycan (GAG)/hyaluronic acid (HA) production, and protein kinase B (Akt) pathway in hAECs and WISH cells were analyzed using the DCFH-DA fluorescent probe, ELISA, CCK-8, scratch, transwell migration, and western blot to determine the mechanism by which GalNAc promotes amniotic wound healing. Results GalNAc decreased IL-6 expression in TNF-α-stimulated WISH cells and ROS expression in LPS-stimulated WISH cells (P 0.05). GalNAc upregulated the expression of sGAG in WISH cells (P 0.05). Conclusions GalNAc might be a potential target for the prevention and treatment of PROM through the galectin pathway, including (i) inflammation; (ii) epithelial-mesenchymal transition; (iii) proliferation and migration; and (iv) regression, remodeling, and healing.

Objective To summarize the clinical characteristics and outcomes of corona virus disease 2019(COVID-19) in patients with adrenal insufficiency (AI), and analyze the risk factors of outcomes. Methods The clinical data of COVID-19 patients with AI in Peking Union Medical College Hospital in December 2022 were analyzed retrospectively and the patients were followed up to collect outcomes of their diseases. Results Among 28 COVID-19 patients with AI, 20 cases (71.4%) received basal corticosteroid replacement. Among the 18 patients with community-acquired COVID-19, 11 cases (61.1%) increased the corticosteroid dosage proactively at home. The most common symptoms of COVID-19 were fever (96.4%), gastrointestinal symptoms (82.1%) and consciousness disturbance (78.6%). Occurrence of severe consciousness disturbance was associated with older age and lower basal corticosteroid replacement dose(P＜0.05). Adrenal crisis(AC) occurred in 20 patients(71.4%), which was associated with lower basal corticosteroid replacement dose, hypochloremia, lower eosinophil, lower platelet, and longer activated partial thromboplastin time(APTT)(P＜0.05). 2 patients died during hospitalization.26.3 % (5/19) of surviving patient′s recovered consciousness longer than 48 hours. Delayed recovery of consciousness was associated with lower systolic pressure, higher blood creatinine, and higher fibrinogen(P＜0.05). Long COVID-19 symptoms such as fatigue and poor appetite occurred in 48.0 % (12/25) of patients. Among patients with increased corticosteroid dosage, 50.0 % (12/24) had their dose reduced to baseline within 3 weeks. Conclusions COVID-19 patients with AI have a high frequency of consciousness disturbance and AC. AI patients are lack of awareness of adjusting corticosteroid dosage proactively in case of infection stress, thus education of “sick day rules” for AI patients should be strengthened in clinical practice.

Based on 778 earthquakes (2009—2022) and their observation reports recorded by the Hunan Seismic Network, through the analysis of the cross-correlation of the waveforms, 149 repeated earthquake pairs were identified which were recorded at least 3 stations with cross-correlation coefficients no less than 0.8. After obtaining these data, the location errors and phase picking errors of the Hunan Seismic Network were statistically analyzed. The results show that the horizontal location error is around 3.5 km, and the vertical location error is around 3 km. The Pg and Sg phase picking errors are about 0.4 s and 0.7 s, respectively. There is no significant difference in location error in Hunan region, except for the Changde area, where the error is basically within 4 km.

Abstract Urbanization has led to homogenizing heritage site landscapes, and the protective measures have become disconnected from public needs. Additionally, the complex and diverse overall characteristics of heritage sites and the uneven distribution of values across different areas are related to the lack of landscape experience assessment. The “subjective + objective” cognitive evaluation and visual perception framework that adopts the Scenic Beauty Estimation Procedure-Semantic Differential (SBE–SD) method and eye-tracking analysis can compensate for the limitations of a single evaluation method by integrating quantitative and qualitative analysis. This research takes the Yi’an Fortress in Zhangpu County, Fujian Province, as the object and examines the visual experiences of different areas and types of landscapes within the Yi’an Fortress. The findings reveal several key insights: (1) Significant differences were found in the landscape experiences of different areas within the heritage site. The visual experience score of the core building area of Yi’an Fortress is (1.01) > the heritage entrance area (0.897) > the residential area (0.841) > the natural ecological area (0.784), indicating that the natural ecological area should be the focus of future protection and development efforts, with a particular emphasis on enhancing the ‘landscape aesthetic’ and ‘landscape cultural’ aspects. (2) The landscape experience scores can be used to understand the reasons for the differences in participants’ experiences of different landscapes. The architectural heritage landscape of the Yi’an Fortress scored highest in the experience evaluation due to its superior performance in terms of ‘landscape form’ factors. The cultural decorative landscape scored next, while the garden greening landscape scored the lowest, due to their poorer performance in terms of ‘landscape form’ and ‘landscape aesthetics’. (3) The eye-tracking data was consistent with the results of the subjective evaluation, validating the “subjective + objective” cognitive evaluation and visual perception framework, employing the SBE–SD method and eye-tracking analysis is a scientific and effective method for assessing the visual experience of heritage landscapes. These results provide a scientific basis for the heritage planners and managers of the Yi’an fortress to improve the landscape environment, better meet public needs, and preserve the unique character of this vital cultural resource. Furthermore, this study offers a new research method and approach for the protection of other heritage landscapes.

Abstract Background Cancer stem cells (CSCs) are critical factors that limit the effectiveness of gastric cancer (GC) therapy. Circular RNAs (circRNAs) are confirmed as important regulators of many cancers. However, their role in regulating CSC-like properties of GC remains largely unknown. Our study aimed to investigate the role of circUBA2 in CSC maintenance and the underlying mechanisms. Methods We identified circUBA2 as an upregulated gene using circRNA microarray analysis. qRT-PCR was used to examine the circUBA2 levels in normal and GC tissues. In vitro and in vivo functional assays were performed to validate the role of circUBA2 in proliferation, migration, metastasis and CSC-like properties of GC cell. The relationship between circUBA2, miR-144-5p and STC1 was characterised using bioinformatics analysis, a dual fluorescence reporter system, FISH, and RIP assays. Results CircUBA2 expression was significantly increased in GC tissues, and patients with GC with high circUBA2 expression had a poor prognosis. CircUBA2 enhances CSC-like properties of GC, thereby promoting cell proliferation, migration, and metastasis. Mechanistically, circUBA2 promoted GC malignancy and CSC-like properties by acting as a sponge for miR-144-5p to upregulate STC1 expression and further activate the IL-6/JAK2/STAT3 signaling pathway. More importantly, the ability of circUBA2 to enhance CSC-like properties was inhibited by tocilizumab, a humanised Interleukin-6 receptor (IL-6R) antibody. Thus, circUBA2 knockdown and tocilizumab synergistically inhibited CSC-like properties. Conclusions Our study demonstrated the critical role of circUBA2 in regulating CSC-like properties in GC. CircUBA2 may be a promising prognostic biomarker for GC. Graphical Abstract

Abstract Background The burgeoning field of research on the dual-factor model of mental health (DFM) has highlighted its significance, yet the applicability of the DFM in military personnel and its longitudinal relationships with different dimensions of meaning in life remains unclear. This study aimed to clarify the applicability of the DFM for military personnel and to investigate longitudinal relationships between the dual factors of mental health (negative factor, positive factor) and the two dimensions of meaning in life (presence of meaning, search for meaning) in military personnel. Methods In this study, data were collected in two waves (April and August 2023) from 227 Chinese military personnel. We constructed a dual-factor model with depression as the negative factor and subjective well-being as the positive factor, and we compared it with a single-factor model to determine if DFM could be applied to military personnel. We also constructed a cross-lagged model to investigate longitudinal relationships between depression, subjective well-being, presence of meaning, and search for meaning. Results According to the findings, military personnel fit better with the DFM than with the single-factor model. Cross-lagged analysis results revealed that both the presence of meaning and the search for meaning negatively predicted depression and positively predicted subjective well-being. Conclusions The DFM had good applicability among military personnel. Both the presence of meaning and the search for meaning could improve military mental health, suggesting that both dimensions of meaning in life may be potential targets for improving military mental health.

Abstract Background Both atrial fibrillation (AF) and heart failure (HF) are common cardiovascular diseases. If the two exist together, the risk of stroke, hospitalization for HF and all-cause death is increased. Currently, research on left atrial appendage closure (LAAC) in patients with AF and HF is limited and controversial. This study was designed to investigate the safety and effectiveness of LAAC in AF patients with different types of HF. Methods Patients with non-valvular atrial fibrillation (NVAF) and HF who underwent LAAC in the First Affiliated Hospital of Army Medical University from August 2014 to July 2021 were enrolled. According to left ventricular ejection fraction (LVEF), the study divided into HF with reduced ejection fraction (LVEF

Taste is an important quality attribute of tea. In order to find out the taste quality of green teas made from the major varieties in Wanzhou district, Chongqing, the taste profile of the tea infusions was determined by sensory evaluation and 5 taste components including catechins, free amino acids, alkaloids, flavanols and their glycosides, and organic acids were analyzed by targeted detection methods. The results showed that there were obvious differences in the taste quality of green teas prepared from the 4 varieties of tea trees. Sichuan middle- and small-leafed tea group variety had a strong taste, and ‘Anji Baicha’ had an obvious fresh and brisk taste with mellow sweet aftertaste. ‘Fuding Dabaicha’ tasted strong with fresh and brisk taste and mellow sweet aftertaste. ‘Zhonghuang 1’ tasted fresh and brisk but less strong. The results of taste component analysis showed that the Sichuan middle- and small-leafed tea group variety contained high contents of catechins but low contents of free amino acids. ‘Anji Baicha’ had the highest content of free amino acids. The content of each flavor component was high in ‘Fuding Dabaicha’, and the contents of total flavor components and water extract of ‘Zhonghuang 1’ were low. The results of principal component analysis (PCA) showed that the 4 varieties could be well distinguished. Thirteen major taste contributors such as rutin and caffeine were identified. The differential analysis indicated that aspartic acid, glutamic acid and theanine were the major contributors to the fresh and brisk taste characteristics of ‘Anji Baicha’ and ‘Fuding Dabaicha’. Yangmeiin-3-O-galactoside and chrysin were the major taste contributors for ‘Zhonghuang 1’ that distinguished it from the other 3 varieties. There were also large differences in taste components within the Sichuan middle- and small-leafed tea group variety, with samples C4 and C5 being closer to each other. They both contained high contents of flavonoid glycosides, having a strong astringent taste. This study provides a reference for research to improve the flavor quality of green tea in Wanzhou district.

Abstract Background Previous studies have revealed the effects of different physical activity (PA) types on visceral adipose tissue (VAT) accumulation in individuals with overweight/obesity. However, the independent association (especially the dose–response relationship) between PA and VAT in individuals with and without overweight/obesity remains less explored. Visceral adiposity index (VAI), calculated from waist circumference, body mass index (BMI), triglyceride and high-density lipoprotein cholesterol, is a novel indicator of VAT. This study aims to elucidate the association between PA and VAI in participants with and without overweight/obesity. Methods Participants who are overweight or obese and with complete data on VAI, PA, and other essential covariates from the National Health and Nutrition Examination Survey (NHANES) database (2015–2018) were included in this study. PA was evaluated by the PA questionnaire and converted into metabolic equivalent task (MET) hours per week (MET-h/wk) based on the suggested MET scores. Multivariate linear regression models were used to identify the association between PA and VAI. Subgroup analyses, combined with interaction tests and restricted cubic spline (RCS) regression analyses, were utilized to explore the stability and nonlinearity of PA-VAI association, respectively. Results A total of 4, 312 participants with complete data on PA and VAI was included in this study, with 3, 441 of them being overweight or obese. After adjusting for all potential covariates, increased PA was found to be significantly associated with remarkable lower level of VAI in all participants (β = -0.0004, P = 0.003), participants with (β = -0.0013, P = 0.012) and without (β = -0.0004, P = 0.003) overweight/obesity. Subgroup analyses and interaction tests revealed that the PA-VAI association was not modified by other covariates in individuals with overweight/obesity. Furthermore, RCS analyses revealed that PA was significantly, linearly and negatively associated with VAI in all participants, participants with and without overweight/obesity (all P 0.05). Noteworthily, as opposed to individuals without overweight/obesity, PA was significantly associated with lower VAI in participants with overweight/obesity after exceeding the threshold of 150 MET-h/wk. Conclusion Increased PA was significantly associated with lower level of VAI, but a higher level of PA (> 150 MET-h/wk) was needed to obtain significantly lower level of VAI in individuals with overweight/obesity.

Two types of poly-porphyrin-based heterogeneous photocatalysts including insoluble polymer and water-soluble nanoparticles exhibited excellent photocatalytic activity in visible-light-induced dehydrogenation in water. The extremely low catalyst loading (0.01 ​mol%) of water-soluble nanoparticles provided so far the highest turnover frequency (TOF) value (333 h-1) for such transformation among reported records.

Summary: Lipid droplets (LDs) are dynamic organelles essential for lipid storage and organismal survival. Studies have highlighted the importance of glial function in brain LD formation during aging; however, the genes and mechanisms involved remain elusive. Here, we found that Ugt35b, a member of the uridine diphosphate (UDP)-glycosyltransferases that catalyze the transfer of glycosyl groups to acceptors, is highly expressed in glia and crucial for Drosophila lifespan. By integrating multiomics data, we demonstrated that glial Ugt35b plays key roles in regulating glycerolipid and glycerophospholipid metabolism in the brain. Notably, we found that Ugt35b and Lsd-2 are co-expressed in glia and confirmed their protein interaction in vivo. Knockdown of Ugt35b significantly reduced LD formation by downregulating Lsd-2 expression, while overexpression of Lsd-2 partially rescued the shortened lifespan in glial Ugt35b RNAi flies. Our findings reveal the crucial role of glial Ugt35b in regulating LD formation to maintain brain lipid homeostasis and support Drosophila lifespan.

Background: Light at night (LAN) has become a global concern. However, little is known about the effects of bedroom LAN exposure on glucose metabolism markers. We aimed to explore the association between intensity and duration of bedroom LAN exposure with glucose metabolism markers, and the role of circadian-dependent meal timing in these associations. Methods: Real-ambient bedroom LAN exposure was measured using a portable illuminance meter for two consecutive days. Seven consecutive days of sleep time and 24-h dietary records were assessed by wrist-worn accelerometer and mobile phone photos, respectively. Circadian-dependent meal timing, including the timing of meal relative to clock time and sleep time, was calculated from 24-h dietary records and sleep data. Results: The mean age of participants was 18.7 years, and 32.8 % were male. Per SD lx increase of bedroom LANavg was associated with 1.75 μU/mL-increase in INS (95 %CI: 0.10, 2.50), 0.61 unit-increase in HOMA-IR (95 %CI: 0.43, 0.79), and 0.09 unit-increase in TyG (95 %CI: 0.04, 0.15); per SD min increase of bedroom LAN3 was associated with 1.61 μU/mL-increase in INS (95 %CI: 0.84, 2.37), 0.48 unit-increase in HOMA-IR (95 %CI: 0.29, 0.67), and 0.07 unit-increase in TyG (95 %CI: 0.01, 0.13). Nevertheless, these associations were found to be significant in later circadian-dependent meal timing group while weaker or not significant in earlier circadian-dependent meal timing group (time of first meal ≤ 9:00, time of last meal ≤ 19:00, first meal - sleep end ≤ 2 h, and sleep onset - last meal ≥ 5 h). Conclusions: Overall, bedroom LAN exposure was associated with impaired glucose metabolism markers among young adults. Importantly, circadian-dependent meal timing may have potentially moderate effects on these associations. Keeping bedroom darkness at night and adhering to early eating pattern may be important public health strategies to reduce the risk of glucose metabolism disorders.

IntroductionDeglycosylated azithromycin (Deg-AZM), a new transgelin agonist with positive therapeutic effects on slow transit constipation, has been approved for clinical trials in 2024. This work investigated the drug metabolism and transport of Deg-AZM to provide research data for further development of Deg-AZM.MethodsA combination of UPLC-QTOF-MS was used to obtain metabolite spectra of Deg-AZM in plasma, urine, feces and bile. Caco-2 cells was used to investigate the permeability of Deg-AZM and whether it is a potential substrate of the efflux transporter P-glycoprotein. Human liver microsome phenotyping assays with chemical inhibition and recombinant CYPs phenotyping assays were used to investigate the CYP450 enzyme phenotype involved in Deg-AZM metabolism in vitro. A HLM inhibition reaction system was established to evaluate the inhibitory effect of Deg-AZM on CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. The mRNA expression of human primary hepatocytes incubated with Deg-AZM or not was evaluate the induction of Deg-AZM on CYP1A2, CYP2B6, and CYP3A4.Results44 metabolites of Deg-AZM were identified in rat urine, feces, bile, and plasma, the metabolic pathways included demethylation, monohydroxylation, dihydroxylation, dehydroxidation, hydroreduction, hydrolysis, methylation, glucuronidation and the combination of different metabolic pathways. Deg-AZM was a low permeability drug in the intestine and a potential substrate of the efflux transporter P-glycoprotein. CYP3A4 was the major CYP isoform responsible for Deg-AZM metabolism. Deg-AZM showed moderate inhibition with CYP2B6 and CYP2D6. Data in three batches of human primary hepatocytes disclosed induction potential of Deg-AZM on CYP2B6 and CYP3A4.ConclusionThe in vivo metabolic pathway of Deg-AZM and in vitro possibility of drug interaction for Deg-AZM with CYP enzymes and drug transporter were fully investigated. It was suggested that dose adjustments may be warranted depending on the potency of the corresponding modulators in clinical.

Abstract 2D stacking presents a promising avenue for creating periodic superstructures that unveil novel physical phenomena. While extensive research has focused on lateral 2D material superstructures formed through composition modulation and twisted moiré structures, the exploration of vertical periodicity in 2D material superstructures remains limited. Although weak van der Waals interfaces enable layer‐by‐layer vertical stacking, traditional methods struggle to control in‐plane crystal orientation over large areas, and the vertical dimension is constrained by unscalable, low‐throughput processes, preventing the achievement of global order structures. In this study, a supercell multiplying approach is introduced that enables high‐throughput construction of 3D superstructures on a macroscopic scale, utilizing artificially stacked single‐crystalline 2D multilayers as foundational repeating units. By employing wafer‐scale single‐crystalline 2D materials and referencing the crystal orientation of substrates, the method ensures precise alignment of crystal orientation within and across each supercell, thereby achieving controllable periodicity along all three axes. A centimeter‐scale 3R‐MoS₂ crystal is successfully constructed, comprising over 200 monolayers of single‐crystalline MoS₂, through a bottom‐up stacking process. Additionally, the approach accommodates the integration of amorphous oxide, enabling the assembly of 3D non‐linear optical crystals with quasi‐phase matching. This method paves the way for the bottom‐up construction of macroscopic artificial 3D crystals with atomic plane precision, enabling tailored optical, electrical, and thermal properties and advancing the development of novel artificial materials and high‐performance applications.

Abstract As a chromatin remodelling factor, high mobility group A1 (HMGA1) plays various roles in both physiological and pathological conditions. However, its role in DNA damage response and DNA damage‐based chemotherapy remains largely unexplored. In this study, we report the poly ADP‐ribosylation (PARylation) of HMGA1 during DNA damage, leading to desensitization of esophageal squamous cell carcinoma (ESCC) cells to the poly(ADP‐ribose) polymerase 1 (PARP1) inhibitor, olaparib. We found that HMGA1 accumulates at sites of DNA damage, where it interacts with PARP1 and undergoes PARylation at residues E47 and E50 in its conserved AT‐hook domain. This modification enhances the accumulation of Ku70/Ku80 at the site of DNA damage and activates the DNA‐dependent protein kinase catalytic subunit, facilitating nonhomologous end‐joining repair. In both subcutaneous tumour models and genetically engineered mouse models of in situ esophageal cancer, HMGA1 interference increased tumour sensitivity to olaparib. Moreover, HMGA1 was highly expressed in ESCC tissues and positively correlated with PARP1 levels as well as poor prognosis in ESCC patients. Taken together, these findings reveal a mechanistic link between HMGA1 and PARP1 in regulating cell responses to DNA damage and suggest that targeting HMGA1 could be a promising strategy to increase cancer cell sensitivity to olaparib.

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with a dismal prognosis. Gemcitabine‐based chemotherapy has emerged as a first‐line treatment for PDAC. However, the development of gemcitabine resistance often results in therapeutic failure. In order to uncover the underlying mechanisms of gemcitabine resistance, gemcitabine‐resistant PDAC cell lines and patient‐derived xenograft (PDX) models are established and subjected to RNA sequencing. It is found that CMTM6 is closely related to gemcitabine resistance in PDAC. Multi‐omics analysis revealed that EP300‐mediated H3K27ac modification is involved in the transcriptional activation of CMTM6, which maintains IGF2BP1 expression by preventing its ubiquitination. The m6A reader IGF2BP1 stabilizes the EP300 and MYC mRNAs by recognizing m6A modifications, forming a positive feedback loop that enhances tumor stemness and ultimately contributes to PDAC resistance. The combined application of the EP300 inhibitor inobrodib and gemcitabine exerts a synergistic effect on PDAC. Overall, these findings reveal that the EP300–CMTM6–IGF2BP1 positive feedback loop facilitates gemcitabine resistance via epigenetic reprogramming and the combined use of inobrodib and gemcitabine represents a promising strategy for overcoming chemoresistance in PDAC, warranting further investigation in clinical trials.

The choice of suitable materials and effective structural design are crucial in influencing the therapeutic outcomes of bone tissue engineering scaffolds. This study introduces a controllable biodegradable composite scaffold composed of flat silkworm cocoon (FSC) and polylactic acid (PLA) as an innovative strategy for promoting bone healing in complex injuries. We focused on optimizing the scaffold's structural design, mechanical properties, and underlying mechanisms of osteogenesis. Initial experiments established the parameters for hot pressing the FSC, followed by mechanical performance tests to identify the optimal preparation conditions. Composite scaffolds incorporating PLA films were subsequently fabricated using these optimized parameters. The results indicate that the FSC/PLA composite scaffold exhibits outstanding biocompatibility, mechanical strength, and in vitro mineralization capabilities, alongside an appropriate degradation rate. Furthermore, the composite scaffolds demonstrated significant potential in promoting osteogenic differentiation and facilitating macrophage polarization toward an anti-inflammatory M2 phenotype. In vivo implantation of the scaffold in defective regions enhanced osteogenesis and mitigated inflammatory responses associated with degradation. This investigation presents an optimal composite scaffold that closely mimics the complex structure of bone, offering a novel approach to enhance bone regeneration and effectively address substantial bone defects.

Abstract The demand for strong, compact permanent magnets essential for the energy transition drives innovation in magnet manufacturing. Additive manufacturing, particularly Powder Bed Fusion of metals using a laser beam (PBF‐LB/M), offers potential for near‐net‐shaped Nd‐Fe‐B permanent magnets but often falls short compared to conventional methods. A less explored strategy to enhance these magnets is feedstock modification with nanoparticles. It is demonstrated that modifying a Nd‐Fe‐B‐based feedstock with 1 wt.% Ag nanoparticles boost the coercivity of the magnets to a record value of 935 ± 6 kA m−1 without further post‐processing or heat treatments. Suitable volumetric energy densities for the PBF‐LB/M process are determined using finite element simulations predicting melt pool behavior and part density. Microstructural analyses reveal finer grain sizes and more equiaxed nanocrystalline structures due to the modification. Atom probe tomography identifies three phases in the Ag‐modified samples, with Ag forming nanophase regions with rare‐earth elements near the amorphous Zr‐Ti‐B‐rich intergranular phase, potentially decoupling the Nd2Fe14B primary phase. The study shows that superior magnetic properties primarily result from microstructure modification rather than part density. These findings highlight inventive material design approaches via feedstock surface modification to achieve superior magnetic performance in additively manufactured Nd‐Fe‐B magnets.

BackgroundTo determine the role of N6-methyladenosine (m6A) modification in the tumor immune microenvironment (TIME), as well as their association with lung adenocarcinoma (LUAD).MethodsConsensus clustering was performed to identify the subgroups with distinct immune or m6A modification patterns using profiles from TCGA. A risk score model was constructed using least absolute shrinkage and selection operator regression and validated in two independent cohorts and LUAD tissue microarrays. For experimental validation, the regulation of METTL3/m6A axis in the expression of candidate genes by RIP-qPCR assay in A549 and H460 cell lines. Co-culture experiments with human T cells were performed to evaluate the impact of METTL3 on the enhancement of anti-tumor immunity through in vitro experiments.ResultsWe identified 282 m6A regulator genes and 955 immune-related genes, selecting seven key genes (SFTPC, CYP24A1, KRT6A, PTTG1, S100P, FAM83A, and ANLN) to develop a risk score model using Lasso regression. High-risk patients, determined by this model, exhibited poorer prognosis, increased immune infiltration, higher tumor mutational burden, more neoantigens, and elevated PD-L1 expression. These findings were validated by two independent databases and LUAD tissue microarrays. METTL3 was found to impact the mRNA expression of these genes, with METTL3 deficiency abolishing these interactions. Inhibition of METTL3 enhanced anti-tumor immunity, T cell activation, exhaustion, and infiltration in vitro.ConclusionThis risk score system shows promise for prognostic prediction and the development of personalized treatment strategies for LUAD patients.

Objectives Diabetic gastrointestinal dysfunction (DGD) is a serious complication of diabetic mellitus (DM), affecting the enteric nervous system (ENS), particular enteric glial cells (EGCs). This study aimed to elucidate the effects and underlying molecular mechanisms of hyperglycemic stress on EGCs in in vitro and in vivo models of DM.Methods In in vitro studies, enteric glial cell line CRL-2690 was exposed to hyperglycemia stress, and cell viability, cell apoptosis and oxidative damage were assessed. In in vivo studies, STZ-induced diabetic mice were constructed, and cell apoptosis and oxidative damage of EGCs in the duodenum of DM mice were assessed.Results The results showed that hyperglycemic stress markedly induced oxidative damage of EGCs in in vitro and in vivo models of DM. This damage was found to be dependent on the activation of redoxosomes, which involved the phosphorylation of SRC and Vav2, the up-regulation of active RAC1-GTP, and the activation of NADPH oxidase (NOX). Moreover, inhibitors of redoxosomes, such as the RAC1 inhibitor NSC23766 and the NOX inhibitor VAS2870, effectively mitigated the hyperglycemic stress-induced oxidative damage of EGCs. Additionally, inhibition of p66SHC, a downstream target of redoxosomes, attenuated oxidative damage of EGCs under hyperglycemic stress.Discussion Our findings suggest that the redoxosomes/p66SHC signaling is involved in the oxidative damage of EGCs during the pathological process of DGD. This signaling cascade may represent a potential therapeutic target for the treatment of DGD.

Objective To elucidate the underlying mechanism by which the proliferation and migration abilities of human umbilical cord mesenchymal stem cells (hUC-MSCs) determine their therapeutic efficacy in rheumatoid arthritis treatment.Methods The DBA/1J mice were utilized to establish a collagen-induced RA (CIA) mouse model and to validate the therapeutic efficacy of hUC-MSCs transfected with CD151 siRNA. RNA-seq, QT-PCR and western blotting were utilized to evaluate the mRNA and protein levels of the PI3K/AKT pathway, respectively.Results IFN-γ significantly enhanced the proliferation and migration abilities of hUC-MSCs, up-regulating the expression of CD151, a gene related to cell proliferation and migration. Effective inhibition of this effect was achieved through CD151 siRNA treatment. However, IFN-γ did not affect hUC-MSCs differentiation or changes in cell surface markers. Additionally, transplantation of CD151-interfered hUC-MSCs (siRNA-CD151-hUC-MSCs) resulted in decreased colonization in the toes of CIA mice and worse therapeutic effects compared to empty vector treatment (siRNA-NC-hUC-MSCs).Conclusion IFN-γ facilitates the proliferation and migration of hUC-MSCs through the CD151/PI3K/AKT pathway. The therapeutic efficacy of siRNA-CD151-hUC-MSCs was found to be inferior to that of siRNA-NC-hUC-MSCs.

Introduction: Ovarian cancer is the most malignant gynecological tumor. Previous studies have demonstrated that chimeric antigen receptor (CAR)-engineered NK-92 cells targeting folate receptor α (αFR) (NK-92-αFR-CAR) can specifically kill αFR-positive ovarian cancer cells. However, the migration barrier restricts antitumor effects of CAR-engineered cells. Objectives: To elucidate the mechanism by which NK-92-αFR-CAR cells induce the secretion of chemokine CXCL10 during killing ovarian cancer cells. It is speculated that NK-92-αFR-CAR-CXCR3A can target αFR and have chemotaxis of CXCL10, and they may have stronger killing effect of ovarian cancer. Methods: Study the mechanism of CXCL10 expression strongly induced by TNF-α and IFN-γ combined stimulation in ovarian cancer cells. Construct the fourth generation of NK-92-αFR-CAR-CXCR3A cells, which were co-expressed CXCR3A and αFR-CAR. Evaluate the killing and migration effects of NK-92-αFR-CAR-CXCR3A in vitro and in vivo. Results: RNA sequencing (RNA-seq) first revealed that the expression level of the chemokine CXCL10 was most significantly increased in ovarian cancer cells co-cultured with NK-92-αFR-CAR. Secondly, cytokine stimulation experiments confirmed that IFN-γ and TNF-α secreted by NK-92-αFR-CAR synergistically induced high CXCL10 expression in ovarian cancer cells. Further signaling pathway experiments showed that IFN-γ and TNF-α enhanced the activation level of the IFN-γ-IFNGR-JAK1/2-STAT1-CXCL10 signaling axis. Cytotoxicity experiments showed that NK-92-αFR-CAR-CXCR3A cells could not only efficiently kill αFR-positive ovarian cancer cells in vitro but also secrete IFN-γ and TNF-α. Higher migration than that of NK-92-αFR-CAR was detected in NK-92-αFR-CAR-CXCR3A using transwell assay. NK-92-αFR-CAR-CXCR3A effectively killed tumor cells in different mouse xenograft models of ovarian cancer and increased infiltration into tumor tissue. Conclusion: This study confirmed that IFN-γ and TNF-α secreted by αFR-CAR-engineered NK cells can synergistically induce high expression of CXCL10 in ovarian cancer cells and constructed self-driving αFR-CAR-engineered NK cells that can break through migration barriers based on CXCL10, which may provide a new therapeutic weapon for ovarian cancer.

Cuproptosis is a newly identified form of copper-dependent cell death that differs from other known pathways. This discovery provides a new way to explore copper-based nanomaterial applications in cancer therapy. This study used a layer-by-layer self-assembling method to load Cu2-xS nanoparticle (NP) cores with the siRNA of the PD-L1 immune escape-related gene and wrap a silk fibroin (SF) shell to form a multifunctional copper-based SF nanoplatform, denoted as CuS-PEI-siRNA-SFNs. CuS-PEI-siRNA-SFNs induced cuproptosis and exerted an antitumor effect via multiple mechanisms, including photothermal therapy (PTT), chemodynamic therapy (CDT), and immune activation. The presence of significant dihydrolipoamide S-acetyltransferase (DLAT) oligomers in 4T1 cells treated with CuS-PEI-siRNA-SFNs indicated the triggering of cuproptosis. Furthermore, in vivo experimental results showed that CuS-PEI-siRNA-SFNs efficiently accumulated in the tumor tissues of 4T1 tumor-bearing mice inhibited primary tumor and lung metastasis, and displayed excellent biosafety and antitumor activity. This study demonstrated that the synergistic effect of cuproptosis, PTT, CDT, and immune activation showed promise for treating metastatic breast cancer.

Immunotherapy has transformed the management of hepatocellular carcinoma (HCC), but effectiveness varies among patients. This study aimed to identify biomarkers and HCC subtypes responsive to immunotherapy. Patients were classified into Immunity-High (Immunity-H) and Immunity-Low (Immunity-L) subtypes using ssGSEA scores. Prognostic genes were identified through Cox regression, and immune cell infiltration was quantified with TIMER 2.0. Brother of CDO (BOC) expression, analyzed via immunohistochemistry, correlated with immunotherapy responses. Flow cytometry assessed immune cell infiltration relative to BOC levels, while CCK-8 and transwell assays evaluated BOC overexpression’s effects on cell proliferation and invasiveness. Clinically, immunity-H patients had better survival outcomes. Three hub genes—BOC, V-Set and Transmembrane Domain Containing 1 (VSTM1), and PRDM12—were identified as significantly associated with prognosis. Among these, BOC and VSTM1 demonstrated positive correlations with immune cell infiltration. Elevated expression of BOC was found to be predictive of favorable responses to immunotherapy and was associated with enhanced infiltration of T cells, dendritic cells, and B cells in the tumor microenvironment. Conversely, BOC overexpression in liver cancer cell lines led to decreased cell proliferation and invasiveness. This study underscores the prognostic significance of HCC subtypes defined by immunogenomic profiles and identifies BOC as a potential biomarker for immunotherapy selection and outcome prediction.

Cancer continues to pose an alarming threat to global health, necessitating the need for the development of efficient therapeutic solutions despite massive advances in the treatment. mRNA cancer vaccines have emerged as a hopeful avenue, propelled by the victory of mRNA technology in COVID-19 vaccines. The article delves into the intricate mechanisms and formulations of cancer vaccines, highlighting the ongoing efforts to strengthen mRNA stability and ensure successful translation inside target cells. Moreover, it discusses the design and mechanism of action of mRNA, showcasing its potential as a useful benchmark for developing efficacious cancer vaccines. The significance of mRNA therapy and selecting appropriate tumor antigens for the personalized development of mRNA vaccines are emphasized, providing insights into the immune mechanism. Additionally, the review explores the integration of mRNA vaccines with other immunotherapies and the utilization of progressive delivery platforms, such as lipid nanoparticles, to improve immune responses and address challenges related to immune evasion and tumor heterogeneity. While underscoring the advantages of mRNA vaccines, the review also addresses the challenges associated with the susceptibility of RNA to degradation and the difficulty in identifying optimum tumor-specific antigens, along with the potential solutions. Furthermore, it provides a comprehensive overview of the ongoing research efforts aimed at addressing these hurdles and enhancing the effectiveness of mRNA-based cancer vaccines. Overall, this review is a focused and inclusive impression of the present state of mRNA cancer vaccines, outlining their possibilities, challenges, and future predictions in the fight against cancer, ultimately aiding in the development of more targeted therapies against cancer.

Abstract Several studies have observed renal cell ferroptosis during cisplatin‐induced acute kidney injury (AKI). However, the mechanism is not completely clear. In this study, oxidized arachidonic acid (AA) metabolites are increased in cisplatin‐treated HK‐2 cells. Targeted metabolomics showed that the end product of pyrimidine biosynthesis is decreased and the initiating substrate of pyrimidine biosynthesis is increased in cisplatin‐treated mouse kidneys. Mitochondrial DHODH, a key enzyme for pyrimidine synthesis, and its downstream product CoQH2, are downregulated. DHODH overexpression attenuated but DHODH silence exacerbated cisplatin‐induced CoQH2 depletion and lipid peroxidation. Mechanistically, renal DHODH acetylation is elevated in cisplatin‐exposed mice. Mitochondrial SIRT3 is reduced in cisplatin‐treated mouse kidneys and HK‐2 cells. Both in vitro SIRT3 overexpression and in vivo NMN supplementation attenuated cisplatin‐induced mitochondrial DHODH acetylation and renal cell ferroptosis. By contrast, Sirt3 knockout aggravated cisplatin‐induced mitochondrial DHODH acetylation and renal cell ferroptosis, which can not be attenuated by NMN. Additional experiments showed that cisplatin caused mitochondrial dysfunction and SIRT3 SUMOylation. Pretreatment with mitochondria‐target antioxidant MitoQ alleviated cisplatin‐caused mitochondrial dysfunction, SIRT3 SUMOylation, and DHODH acetylation. MitoQ pretreatment protected against cisplatin‐caused AKI and renal cell ferroptosis. Taken together, these results suggest that mitochondrial dysfunction‐evoked DHODH acetylation partially contributes to renal cell ferroptosis during cisplatin‐induced AKI.

Per- and polyfluoroalkyl substances (PFASs) can disrupt lipid metabolism, and changes in cord blood fatty acid composition have been observed in small newborns. Emerging evidence suggests that exposure to PFASs during pregnancy is linked to decreased newborn size, although the evidence is not consistent. The modifying effect of fatty acids on the associations of gestational PFAS exposure with newborn size is still unknown. Here we show that the nutritional status of the fetus, as indicated by the level of fatty acids in the cord blood, mitigates the adverse effects of gestational PFAS exposure on the size of the newborn. Our study confirms the adverse developmental effects of PFASs and identifies emerging short-chain PFASs as the primary drivers of reduced newborn size, despite their lower exposure burden compared to legacy PFASs. Additionally, we find the protective role of cord blood fatty acids, suggesting potential strategies for mitigating the detrimental effects of emerging environmental exposures on human health. Our findings provide new evidence of the potential toxicity of emerging PFASs and call for further toxicity evaluations of these pollutants for regulatory purposes. Future studies should consider the complex interaction between exposure and nutrition within the human body, particularly during the first thousand days of life, to promote lifelong health.

Three new species of Meotipa Simon, 1895 are described based on specimens collected from Guangxi Zhuang Autonomous Region, China: Meotipa lingulata sp. nov. (female), M. pseudomultuma sp. nov. (both male and female) and M. tortuosa sp. nov. (both male and female). Detailed descriptions, photographs, line drawings, sequences of histone H3, and a distribution map of the three new species are provided.