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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 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 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

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.

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.

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.

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.

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 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

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 Esophageal squamous cell carcinoma (ESCC) possesses a poor prognosis and treatment outcome. Dysregulated metabolism contributes to unrestricted growth of multiple cancers. However, abnormal metabolism, such as highly activated pentose phosphate pathway (PPP) in the progression of ESCC remains largely unknown. Herein, we report that high-mobility group AT-hook 1 (HMGA1), a structural transcriptional factor involved in chromatin remodeling, promoted the development of ESCC by upregulating the PPP. We found that HMGA1 was highly expressed in ESCC. Elevated HMGA1 promoted the malignant phenotype of ESCC cells. Conditional knockout of HMGA1 markedly reduced 4-nitroquinoline-1-oxide (4NQO)-induced esophageal tumorigenesis in mice. Through the metabolomic analysis and the validation assay, we found that HMGA1 upregulated the non-oxidative PPP. With the transcriptome sequencing, we identified that HMGA1 upregulated the expression of transketolase (TKT), which catalyzes the reversible reaction in non-oxidative PPP to exchange metabolites with glycolytic pathway. HMGA1 knockdown suppressed the PPP by downregulating TKT, resulting in the reduction of nucleotides in ESCC cells. Overexpression of HMGA1 upregulated PPP and promoted the survival of ESCC cells by activating TKT. We further characterized that HMGA1 promoted the transcription of TKT by interacting with and enhancing the binding of transcription factor SP1 to the promoter of TKT. Therapeutics targeting TKT with an inhibitor, oxythiamine, reduced HMGA1-induced ESCC cell proliferation and tumor growth. Together, in this study, we identified a new role of HMGA1 in ESCCs by upregulating TKT-mediated activation of PPP. Our results provided a new insight into the role of HMGA1/TKT/PPP in ESCC tumorigenesis and targeted therapy.

Abstract Background Huangkui Lianchang Decoction (HLD) is a traditional Chinese herbal formula for treating ulcerative colitis (UC). However, its mechanism of action remains poorly understood. The Study aims to validate the therapeutic effect of HLD on UC and its mechanism by integrating network pharmacology, bioinformatics, and experimental validation. Methods UC targets were collected by databases and GSE19101. The active ingredients in HLD were detected by ultra-performance liquid chromatography-tandem mass spectrometry. PubChem collected targets of active ingredients. Protein–protein interaction (PPI) networks were established with UC-related targets. Gene Ontology and Kyoto Encyclopedia (KEGG) of Genes and Genomes enrichment were analyzed for the mechanism of HLD treatment of UC and validated by the signaling pathways of HLD. Effects of HLD on UC were verified using dextran sulfate sodium (DDS)-induced UC mice experiments. Results A total of 1883 UC-related targets were obtained from the GSE10191 dataset, 1589 from the database, and 1313 matching HLD-related targets, for a total of 94 key targets. Combined with PPI, GO, and KEGG network analyses, the signaling pathways were enriched to obtain IL-17, Toll-like receptor, NF-κB, and tumor necrosis factor signaling pathways. In animal experiments, HLD improved the inflammatory response of UC and reduced UC-induced pro-inflammatory factors such as Tumor Necrosis Factor Alpha (TNF-α), interleukin 1β (IL-1β), and interleukin 6 (IL-6). HLD suppressed proteins TLR4, MyD88, and NF-κB expression. Conclusions This study systematically dissected the molecular mechanism of HLD for the treatment of UC using a network pharmacology approach. Further animal verification experiments revealed that HLD inhibited inflammatory responses and improved intestinal barrier function through the TLR4/MyD88/NF-κB pathway.

Abstract Cancer is rarely the straightforward consequence of an abnormality in a single gene, but rather reflects a complex interplay of many genes, represented as gene modules. Here, we leverage the recent advances of model-agnostic interpretation approach and develop CGMega, an explainable and graph attention-based deep learning framework to perform cancer gene module dissection. CGMega outperforms current approaches in cancer gene prediction, and it provides a promising approach to integrate multi-omics information. We apply CGMega to breast cancer cell line and acute myeloid leukemia (AML) patients, and we uncover the high-order gene module formed by ErbB family and tumor factors NRG1, PPM1A and DLG2. We identify 396 candidate AML genes, and observe the enrichment of either known AML genes or candidate AML genes in a single gene module. We also identify patient-specific AML genes and associated gene modules. Together, these results indicate that CGMega can be used to dissect cancer gene modules, and provide high-order mechanistic insights into cancer development and heterogeneity.

In order to understand the types, biological characteristics, and metabolites types of pathogenic fungi in carambola, the typical diseased parts of carambola fruit were collected for fungal isolation by tissue isolation methods. The fungi were identified by morphological and molecular identification methods based on ITS sequencing analysis. The biological characteristics of pathogenic fungi were explored, and metabolites were isolated and purified using liquid chromatography. Their structures were established on the basis of 1H NMR and 13C NMR. The results were as follows: The four strains were identified as Fusarium equiseti, Neopestalotiopsis sp., Schizophyllum commune and Cladosporium cladosporioides. All four strains could cause disease in carambola fruit. The fermentation products of Fusarium equiseti were chemically investigated, leading to the discovery of four compounds, 3,7,9-trihydroxy-1-methyl-6H-dibenzo[b,d]pyran-6-on, 1,4,7-trihydroxy-3,9-dimethoxy-6H-benzo[c]chromen-6-one, lecanoric acid and 7-hydroxy-4-methyl-1(3H)-isobenzofuranone. The results of biological characteristics indicated that the optimal growth temperature for the four pathogenic fungi was 25~28 ℃, and they could all grow within the pH range of 4~10.

Coastal wetlands are hotspots for nitrogen (N) cycling, and crab burrowing is known to transform N in intertidal marsh soils. However, the underlying mechanisms remain unclear. This study conducted field experiments and used indoor control test devices to investigate the seasonal response of nitrogen to crab disturbance at the sediment–water interface in coastal tidal flat wetlands. The results showed that crab disturbance exhibited significant seasonality with large seasonal differences in cave density and depth. Due to crab disturbance, nitrogen fluxes at the sediment–water interface were much greater in the box with crabs than in the box without crabs. In summer, NH4+-N showed a positive flux from the sediment to the overlying water, but NO2−-N and NO3−-N showed positive fluxes from the sediment to the overlying water only in early stages. In winter, NH4+-N showed a positive flux from the sediment to the overlying water, but NO2−-N and NO3−-N both exhibited positive and negative fluxes. These results indicated that the presence of crab burrows can cause the aerobic layer to move downward by approximately 8–15 cm in summer and directly promote nitrification at the sediment surface.

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.

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.

Circulating tumor cells (CTCs) are cancer cells that detach from the primary tumor and enter the bloodstream, where they can seed new metastatic lesions in distant organs. CTCs are often associated with white blood cells (WBCs), especially neutrophils, the most abundant and versatile immune cells in the blood. Neutrophils can interact with CTCs through various mechanisms, such as cell-cell adhesion, cytokine secretion, protease release, and neutrophil extracellular traps (NETs) formation. These interactions can promote the survival, proliferation, invasion, and extravasation of CTCs, as well as modulate the pre-metastatic niche and the tumor microenvironment. Therefore, inhibiting CTC-neutrophils interaction could be a potential strategy to reduce tumor metastasis and improve the prognosis of cancer patients. In this review, we summarize the current literature on CTC-neutrophils interaction’ role in tumor metastasis and discuss the possible therapeutic approaches to target this interaction.

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.

AimsThe metabolic syndrome (MetS), a collection of conditions that heighten the risk of disease development and impose economic burdens on patients. However, the causal relationship between education and MetS was uncertain. In this study, the Mendelian randomization (MR) method was employed to elucidate the potential causal link between education and the MetS and its components.MethodSingle nucleotide polymorphisms (SNPs) associated with education, MetS, and its components were sourced from a public database, with the inverse variance-weighted (IVW) method utilized for analysis.ResultsEducation demonstrated a significant negative correlation with the risk of MetS (OR = 0.55, 95% CI = 0.48–0.63, p = 2.18E−51), waist circumference(OR = 0.80, 95% CI = 0.76–0.83, p = 4.98E-33), hypertension (OR = 0.96, 95% CI = 0.95–0.97; p = 4.54E-10), Fasting blood glucose (OR = 0.94, 95% CI = 0.91–0.97, p = 7.58E-6) and triglycerides (OR = 0.83, 95% CI = 0.79–0.87, p = 7.87E-18) while showing a positive association with high-density lipoprotein cholesterol (OR = 1.22, 95% CI = 1.18–1.25, p = 1.45E-31).ConclusionThe findings of this study suggest that education can decrease the incidence of MetS.

Summary: Somatostatin (SOM)-expressing neurons in the central lateral amygdala (CeL) are responsible for fear memory learning, but the circuit and molecular mechanisms underlying this biology remain elusive. Here, we found that glutamatergic neurons in the lateral parabrachial nucleus (LPB) directly dominated the activity of CeLSOM neurons, and that selectively inhibiting the LPBGlu→CeLSOM pathway suppressed fear memory acquisition. By contrast, inhibiting CeL-projecting glutamatergic neurons in the paraventricular thalamic nucleus (PVT) interfered with consolidation-related processes. Notably, CeLSOM-innervating neurons in the LPB were modulated by presynaptic cannabinoid receptor 1 (CB1R), and knock down of CB1Rs in LPB glutamatergic neurons enhanced excitatory transmission to the CeL and partially rescued the impairment in fear memory induced by CB1R activation in the CeL. Overall, our study reveals the mechanisms by which CeLSOM neurons mediate the formation of fear memories during fear conditioning in mice, which may provide a new direction for the clinical research of fear-related disorders.

Strong evidence indicates that environmental stressors are the risk factors for male testosterone deficiency (TD). However, the mechanisms of environmental stress-induced TD remain unclear. Based on our all-cause male reproductive cohort, we found that serum ferrous iron (Fe2⁺) levels were elevated in TD donors. Then, we explored the role and mechanism of ferroptosis in environmental stress-reduced testosterone levels through in vivo and in vitro models. Data demonstrated that ferroptosis and lipid droplet deposition were observed in environmental stress-exposed testicular Leydig cells. Pretreatment with ferrostatin-1 (Fer-1), a specific ferroptosis inhibitor, markedly mitigated environmental stress-reduced testosterone levels. Through screening of core genes involved in lipid droplets formation, it was found that environmental stress significantly increased the levels of perilipins 4 (PLIN4) protein and mRNA in testicular Leydig cells. Further experiments showed that Plin4 siRNA reversed environmental stress-induced lipid droplet deposition and ferroptosis in Leydig cells. Additionally, environmental stress increased the levels of METTL3, METTL14, and total RNA m6A in testicular Leydig cells. Mechanistically, S-adenosylhomocysteine, an inhibitor of METTL3 and METTL14 heterodimer activity, restored the abnormal levels of Plin4, Fe2⁺ and testosterone in environmental stress-treated Leydig cells. Collectively, these results suggest that Plin4 exacerbates environmental stress-decreased testosterone level via inducing ferroptosis in testicular Leydig cells.

This study offers a comprehensive evaluation of urban renewal efforts in Shandong Province, China, by employing the entropy method combined with the Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS). An evaluation index system was constructed to assess the weights of key factors influencing urban renewal, including the renovation of old residential areas, improvement in sewage treatment quality, development of sponge cities, adoption of clean heating, and enhancement of air quality. Analysis of 16 prefecture-level cities in 2019 reveals significant disparities in performance, with Jinan achieving the highest ranking due to notable improvements in infrastructure and environmental management. Meanwhile, other cities displayed varying levels of success, reflecting different developmental stages and capacities. The findings underscore the necessity for tailored strategies to optimize urban renewal outcomes, focusing on high-weight factors such as sewage treatment, clean heating, and residential renovation. This study provides actionable insights for policymakers, advocating adaptive renewal strategies that align with local contexts and encourage continuous innovation. The results highlight the importance of targeted policy interventions to enhance urban renewal quality across Shandong Province, promoting sustainable urban development and better living standards.

Preeclampsia (PE) is a pregnancy-related disease characterized by vascular endothelial cell injury. This study aimed to investigate the role of methyltransferase-like protein 14 (METTL14) in vascular endothelial cell injury in PE. The PE cell model was established by treating human umbilical vein endothelial cells (HUVECs) with tumor necrosis factor-alpha (TNF-α) in vitro. METTL14 and forkhead box protein 1 (FOXP1) were silenced, and miR-34a-5p was overexpressed in HUVECs to evaluate their effects. HUVEC viability, apoptosis, and the levels of intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and endothelin-1 were measured. The N6-methyladenosine (m6A) modification of pri-miR-34a-5p was quantified. The interactions between miR-34a-5p, DiGeorge syndrome critical region 8, and m6A enrichment in miR-34a-5p were analyzed. The relationship between miR-34a-5p and FOXP1 was also verified. The results showed that the expressions of METTL14, FOXP1, and miR-34a-5p were determined. METTL14 expression was elevated in the TNF-α-induced HUVEC injury model. Silencing METTL14 improved HUVEC viability, inhibited apoptosis, and reduced endothelial inflammation. METTL14 promoted miR-34a-5p expression through m6A modification. Overexpression of miR-34a-5p or silencing of FOXP1 reversed the protective effects of METTL14 silencing on cell injury in the PE model. In conclusion, METTL14 mediated m6A modification to promote miR-34a-5p expression, leading to the inhibition of FOXP1 expression, which aggravated endothelial cell damage in the PE cell model.

Hydrogels are widely used in the field of biomedicine because of their excellent biocompatibility. In most cases, the pH range applicable to drugs is limited, so it is meaningful to study the diffusion of protons in hydrogels. In this work, the diffusion rate of protons in hydrogels was monitored by a self-made device, and the factors affecting the diffusion rate of protons were studied. The self-made device consists of a supply chamber and a receiving chamber with a piece of hydrogel sandwiching between them. It was found that the thickness of hydrogel had a great influence on proton diffusion. The thicker the hydrogel is, the slower the proton diffusion rate is. At the same time, the diffusion coefficient of protons in PAM hydrogel was calculated to be 1.28 [+ or -] 0.09 * [10.sup.-5] [cm.sup.2]/s (HCl, 25[degrees]C). The diffusion coefficient is a function of temperature, and its value increases with the increase in temperature. The effect of the solid content of hydrogel on proton diffusion was also considered, but in the range of solid content 1.81%-10.07%, the proton diffusion rate was almost unaffected. Moreover, anions also have a decisive effect on proton diffusion, with smaller anions leading to faster proton diffusion in the hydrogel. KEYWORDS diffusion coefficient, diffusion equation, hydrogel, proton diffusion, 1 | INTRODUCTION Hydrogel is a kind of polymer material with a three-dimensional network structure. It has the characteristics of high water absorption, reversibility, and biocompatibility, and is widely used [...]