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Background and aim: Hepatic ischemia–reperfusion injury (IRI) is a significant challenge in liver transplantation, trauma, hypovolemic shock, and hepatectomy, with limited effective interventions available. This study aimed to investigate the role of leukocyte cell-derived chemotaxin 2 (LECT2) in hepatic IRI and assess the therapeutic potential of Lect2-short hairpin RNA (shRNA) delivered through adeno-associated virus (AAV) vectors. Materials and methods: This study analyzed human liver and serum samples from five patients undergoing the Pringle maneuver. Lect2-knockout and C57BL/6J mice were used. Hepatic IRI was induced by clamping the hepatic pedicle. Treatments included recombinant human LECT2 (rLECT2) and AAV-Lect2-shRNA. LECT2 expression levels and serum biomarkers including alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, and blood urea nitrogen (BUN) were measured. Histological analysis of liver necrosis and quantitative reverse-transcription polymerase chain reaction were performed. Results: Serum and liver LECT2 levels were elevated during hepatic IRI. Serum LECT2 protein and mRNA levels increased post reperfusion. Lect2-knockout mice had reduced weight loss; hepatic necrosis; and serum ALT, AST, creatinine, and BUN levels. rLECT2 treatment exacerbated weight loss, hepatic necrosis, and serum biomarkers (ALT, AST, creatinine, and BUN). AAV-Lect2-shRNA treatment significantly reduced weight loss, hepatic necrosis, and serum biomarkers (ALT, AST, creatinine, and BUN), indicating therapeutic potential. Conclusions: Elevated LECT2 levels during hepatic IRI increased liver damage. Genetic knockout or shRNA-mediated knockdown of Lect2 reduced liver damage, indicating its therapeutic potential. AAV-mediated Lect2-shRNA delivery mitigated hepatic IRI, offering a potential new treatment strategy to enhance clinical outcomes for patients undergoing liver-related surgeries or trauma.

Abstract Fluxes in human copper levels recently garnered attention for roles in cellular signaling, including affecting levels of the signaling molecule cyclic adenosine monophosphate. We herein apply an unbiased temporal evaluation of the signaling and whole genome transcriptional activities modulated by copper level fluctuations to identify potential copper sensor proteins responsible for driving these activities. We find that fluctuations in physiologically relevant copper levels modulate EGFR signal transduction and activation of the transcription factor CREB. Both intracellular and extracellular assays support Cu1+ inhibition of the EGFR phosphatase PTPN2 (and potentially PTPN1)–via ligation to the PTPN2 active site cysteine side chain–as the underlying mechanism. We additionally show i) copper supplementation drives weak transcriptional repression of the copper importer CTR1 and ii) CREB activity is inversely correlated with CTR1 expression. In summary, our study reveals PTPN2 as a physiological copper sensor and defines a regulatory mechanism linking feedback control of copper stimulated EGFR/CREB signaling and CTR1 expression.

Abstract Different from traditional organic luminescent materials based on covalent delocalization, clusteroluminescence from nonconjugated luminogens relies on noncovalent through-space conjugation of electrons. However, such spatial electron delocalization is usually weak, resulting in low luminescent efficiency and board emission peak due to multiple vibrational energy levels. Herein, several nonconjugated luminogens are constructed by employing biphenyl as the building unit to reveal the structure-property relationship and solve current challenges. The intramolecular through-space conjugation can be gradually strengthened by introducing building units and stabilized by rigid molecular skeleton and multiple intermolecular interactions. Surprisingly, narrowband clusteroluminescence with full width at half-maximum of 40 nm and 100% efficiency is successfully achieved via an asymmetric conformation, exhibiting comparable performance to the traditional conjugated luminogens. This work realizes highly efficient and narrowband clusteroluminescence from nonconjugated luminogens and highlights the essential role of structural conformation in manipulating the photophysical properties of unconventional luminescent materials.

Abstract Helicobacter pylori (H. pylori), together with its CagA, has been implicated in causing DNA damage, cell cycle arrest, apoptosis, and the development of gastric cancer. Although lncRNA H19 is abundantly expressed in gastric cancer and functions as a pro-oncogene, it remains unclear whether lncRNA H19 contributes to the oncogenic process of H. pylori CagA. This study investigates the role of H19 in the DNA damage response and malignancy induced by H. pylori. It was observed that cells infected with CagA+ H. pylori strain (GZ7/cagA) showed significantly higher H19 expression, resulting in increased γH2A.X and p-ATM expression and decreased p53 and Rad51 expression. Faster cell migration and invasion was also observed, which was reversed by H19 knockdown in H. pylori. YWHAZ was identified as an H19 target protein, and its expression was increased in H19 knockdown cells. GZ7/cagA infection responded to the increased YWHAZ expression induced by H19 knockdown. In addition, H19 knockdown stimulated cells to enter the G2-phase and attenuated the effect of GZ7/cagA infection on the cellular S-phase barrier. The results suggest that H. pylori CagA can upregulate H19 expression, participate in the DNA damage response and promote cell migration and invasion, and possibly affect cell cycle arrest via regulation of YWHAZ.

Rabies is a highly lethal infectious disease with no existing treatment available, thus investigating effective antiviral compounds to control rabies virus (RABV) infection is of utmost importance. Resveratrol is a natural phenolic compound that, as a phytoalexin, exhibits several biological activities, including antiviral activity. In this study, we evaluated the inhibitory effect of resveratrol on RABV infection and investigated its molecular antiviral mechanism. We found that resveratrol significantly inhibited RABV infection, including the phases of adsorption, replication, and release, and also directly inactivated RABV and inhibited its infectivity. However, resveratrol had no significant effect on RABV internalization. Resveratrol also reduced RABV-induced oxidative stress, specifically reactive oxygen species and malondialdehyde levels. Western blotting analysis revealed that resveratrol enhanced antioxidant signaling via the SIRT1/Nrf2/HO-1 pathway and inhibited viral replication. Viral infection was enhanced after SIRT1 knockdown, which inhibited the SIRT1/Nrf2/HO-1 antioxidant signaling pathway, suggesting that this pathway plays an important role in RABV replication. Overall, resveratrol prevented the adsorption, replication, and release of RABV and directly inactivated RABV, but failed to inhibit RABV internalization. Furthermore, resveratrol activated the SIRT1/Nrf2/HO-1 pathway to inhibit RABV replication and suppressed RABV-induced oxidative stress. These findings highlight the therapeutic potential of resveratrol for fighting RABV infections.

ObjectiveEpilepsy-related stigma is a global problem, yet there has been an inadequate focus on children and adolescents. The purpose of this study was to determine the status quo of stigma and its determinants among children and adolescents with epilepsy in China.MethodsA multicenter cross-sectional study was conducted across nine hospitals in eight cities within six provinces in China from 10 October 2023 to 15 June 2024. Participants included patients aged 8 to 18 years with epilepsy and their caregivers. Felt stigma was assessed with the Kilifi Stigma Scale for Epilepsy (KSSE). Social support and self-efficacy were collected through the Social Support Rating Scale (SSRS) and the Generalized Self-Efficacy Scale (GSES). The data were analyzed using t-tests, analysis of variance (ANOVA), Spearman correlation analysis, and multiple linear regression analysis.ResultsThe study enrolled 281 children and adolescents, with a mean age of 12.25 years (SD = 2.56), including 46.6% females. A total of 35.6% participants had self-reported felt stigma. The mean KSSE score is 9.58 (SD = 7.11). Meanwhile, stigma scores correlated strongly with reduced social support (r = −0.55, p 5 years), drug-resistant epilepsy (yes vs. no), comorbidities (yes vs. no), social support and self-efficacy are major influencing factors among the complex factors influencing the felt stigma among children and adolescents.ConclusionMedical staff should be more aware of stigma among children and adolescents with epilepsy, especially those who live in rural and western areas, have poor academic performance, have epilepsy duration of more than 5 years, have drug-resistant epilepsy, and have comorbidities, who are at higher risk of stigma. It is recommended that effective measures be taken to alleviate stigma by improving children and adolescents’ self-efficacy and providing more social support for them and their families.

Inflammatory cytokine storms can trigger disease exacerbation and even death and have reached a consensus in the clinical treatment of acute organ failure. However, the existing strategies remain a great challenge to efficiently suppress inflammatory cytokine storms for promoting organ repair and regeneration. Herein, fully human umbilical cord (UC)-derived adhesive materials (UCAM) that integrate decellularized extracellular matrix (ECM) nanofiber hydrogel and homologous mesenchymal stem cells (MSCs) are demonstrated to greatly suppress inflammatory cytokine storms, demonstrating high efficacy in treating acute liver failure (ALF) in rats with 90% hepatectomy. The UC-derived adhesive materials have the capacity to secrete a significant quantity of cytokines by MSCs to recruit activated immune cells to migrate into their ECM nanofiber networks, segregating them away from the infection area and thereby greatly suppressing the inflammatory cytokine storms. As expected, the UC-derived adhesive materials can significantly promote hepatocyte proliferation to achieve functional recovery and regeneration of the liver, significantly improving the survival rate in rats. Our fully human UC-derived adhesive materials provide a new avenue in suppressing inflammatory cytokine storms for promoting organ regeneration that would be really utility in clinical organ transplantation-related treatment.

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

Introduction: Plant polysaccharide are widely studied as potential prebiotics because of their potential to protect and enhance the immunity of lambs.Methods: In this study, the polysaccharide content of Alhagi maurorum Medik from Aksu (AK) and Shanshan (SS) at different cutting periods was determined, and the functions of Alhagi maurorum Medik polysaccharide were investigated to useas an immunomodulator.Results: Our results indicated that the content of Alhagi maurorum Medik polysaccharide is the highest at the maturity stage, and the polysaccharide content of Alhagi maurorum Medik produced in Shanshan area is higher as compared to the Aksu area. The serum IgG, duodenum IgA, TNF-α, IL-4, IL-10 contents, jejunum IgA, TNF-α, IL-4, IL-17 contents, ileum IgA, IL-17 contents, duodenum villus height, crypt depth and jejunum crypt depth of lambs were significantly adjusted in the SS group as compared to CK control group and AK groups (p < 0.05). Furthemore, the sequencing results showed that SS polysaccharide promoted the release of large amounts of IgA and enhanced the immunal function of intestine by regulating the IgA production pathway and B-cell receptor signaling to activate B cells in the T-dependent pathway.Discussion: Altogether, Alhagi maurorum Medik polysaccharide from SS group holds a promising potential to be used as a valuable immunopotentiator for optimizing the immune system of intestine in lambs.

BackgroundThough considerable studies suggesting connections between micronutrients and pregnancy complications, current evidence remains inconsistent and lacks causative confirmation. Our study aimed to explore the causal links between them with a two-sample Mendelian randomization (MR) analysis.MethodsGenome-wide association studies (GWAS) data for circulating micronutrients were sourced from GWAS Catalog consortium and PubMed, while data for pregnancy outcomes, including gestational diabetes mellitus (GDM), gestational hypertension (GH), spontaneous abortion (SA), preterm birth (PTB), and stillbirth (SB), were retrieved from the UK Biobank and FinnGen consortia. Causal effects were appraised using inverse variance weighted (IVW), weighted median (WM), and MR-Egger, followed by sensitivity analyses and meta-analysis for validation.ResultsGenetically predicted higher vitamin E (OR = 0.993, 95% CI 0.987–0.998; p = 0.005) levels were inversely associated with SA risk. Consistent results were obtained in meta-analysis (OR = 0.99, 95% CI 0.99–1.00; p = 0.005). Besides, a potential positive causality between genetic predisposition to vitamin B12 and SB was identified in both IVW (OR = 0.974, 95% CI 0.953–0.996; p = 0.018) and WM analysis (OR = 0.965, 95% CI 0.939–0.993; p = 0.013). However, no causal relationships were observed between other analyzed circulating micronutrients and pregnancy complications.ConclusionThis study offers compelling evidence of causal associations between circulating levels of vitamins E, B12 and the risk of SA and SB, respectively. These findings are pivotal for pregnancy complications screening and prevention, potentially guiding clinical practice and public health policies toward targeted nutritional interventions.

BackgroundTo the best of our knowledge, numerous observational studies have linked pregnancy complications to increased risks of diabetes and cardiovascular disease (CVD), causal evidence remains lacking. Our aim was to estimate the association of adverse pregnancy outcomes with diabetes and cardiovascular diseases.MethodsA two-sample Mendelian randomization (MR) analysis was employed, which is not subject to potential reverse causality. Data for pregnancy complications were obtained from the FinnGen consortium. For primary analysis, outcome data on diabetes, related traits, stroke, and coronary heart disease (CHD) were extracted from the GWAS Catalog, MAGIC, MEGASTROKE, and CARDIoGRAMplusC4D consortium. The MAGIC and UKB consortium datasets were used for replication and meta-analysis. Causal effects were appraised using inverse variance weighted (IVW), weighted median (WM), and MR-Egger. Sensitivity analyses were implemented with Cochran’s Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out (LOO) analysis and the funnel plot.ResultsGenetically predicted gestational diabetes mellitus (GDM) was causally associated with an increased diabetes risk (OR=1.01, 95% CI=1–1.01, P

Abstract The elevation in the optic nerve sheath (ONS) pressure (ONSP) due to microgravity-induced headward fluid shift is the primary hypothesized contributor to SANS. This longitudinal study aims to quantify the axial plane of the optic nerve subarachnoid space area (ONSSA), which is filled with cerebrospinal fluid (CSF) and expands with elevated ONSP during and after head-down tilt (HDT) bed rest (BR). 36 healthy male volunteers (72 eyes) underwent a 90-day strict 6° HDT BR. Without obtaining the pre-HDT data, measurements were performed on days 30, 60, and 90 during HDT and at 6 recovery time points extended to 180-days (R + 180) in a supine position. Portable B-scan ultrasound was performed using the 12 MHz linear array probe binocularly. The measurements of the ONS and the calculation of the ONSSA were performed with ImageJ 1.51 analysis software by two experienced observers in a masked manner. Compared to R + 180, the ONSSA on HDT30, HDT60, and HDT90 exhibited a consistently significant distention of 0.44 mm2 (95% CI: 0.13 to 0.76 mm2, P = 0.001), 0.45 mm2 (95% CI: 0.15 to 0.75 mm2, P = 0.001), and 0.46 mm2 (95% CI: 0.15 to 0.76 mm2, P

Abstract Background Fibroblasts, especially cancer-associated fibroblasts (CAFs), represent the predominant stromal cell population in the tumor microenvironment and have an important function in tumorigenesis by interacting with tumor cells. However, their interaction remains elusive in an inflammatory tumor microenvironment induced by Helicobacter pylori (H. pylori). Methods The expression of Serpin family E member 1 (Serpin E1) was measured in fibroblasts with or without H. pylori infection, and primary gastric cancer (GC) cells. Serpin E1 knockdown and overexpression fibroblasts were generated using Serpin E1 siRNA or lentivirus carrying Serpin E1. Co-culture models of fibroblasts and GC cells or human umbilical vein endothelial cells (HUVECs) were established with direct contact or the Transwell system. In vitro functional experiments and in vivo tumorigenesis assay were employed to study the malignant behaviors of GC cells interacting with fibroblasts. ELISA was used for quantifying the levels of Serpin E1 and VEGFA in the culture supernatant. The tube formation capacity of HUVECs was assessed using a tube formation assay. Recombinant human Serpin E1 (recSerpin E1), anti-Serpin E1 antibody, and a MAPK pathway inhibitor were utilized to treat HUVECs for elucidating the underlying molecular mechanisms. Results Serpin E1 was predominantly expressed in gastric CAFs. H. pylori infection significantly enhanced the expression and secretion of Serpin E1 by CAFs. Both fibroblast-derived Serpin E1 and recSerpin E1 enhanced the growth, invasion, and migration of GC cells, along with increased VEGFA expression and tube formation in HUVECs. Furthermore, the co-inoculation of GC cells and fibroblasts overexpressing Serpin E1 triggered the expression of Serpin E1 in cancer cells, which facilitated together xenograft tumor growth and peritoneal dissemination of GC cells in nude mice, with an increased expression of Ki67, Serpin E1, CD31 and/or VEGFA. These processes may be mediated by Serpin E1-induced migration and p38 MAPK/VEGFA-mediated angiogenesis of HUVECs. Conclusion H. pylori infection induces Serpin E1 expression in fibroblasts, subsequently triggering its expression in GC cells through their interaction. Serpin E1 derived from these cells promotes the migration and p38 MAPK/VEGFA-mediated angiogenesis of HUVECs, thereby facilitating GC growth and peritoneal metastasis. Targeting Serpin E1 signaling is a potential therapy strategy for H. pylori-induced GC.

Cell wall is a basic component of bacteria that promotes bacteria to adapt the complicated environment as well as play an essential role in antimicrobial resistance. The structure of bacterial cell wall is remarkably rich, and some complex components, such as peptidoglycan, lipopolysaccharide, and peptidoglycan-arabinogalactan et al., can only be found in bacteria. Furthermore, the biosynthesis and transfer of these glycolipids are indispensable for bacteria during cell elongation. And the process of biosynthesis and transfer are generally associated with metabolism and sophisticated enzyme mechanisms. However, how the metabolic process takes place, what role enzymes play in this process and how they function have been major concerns for scientists in this field. Numerous significant progresses on fluorescent probes and biological imaging bring opportunity for the studying of metabolism and enzyme mechanisms recently due to its non-invasive and high sensitivity. In this review, we focused on metabolic fluorescent probes for the detection of glycolipids in bacterial cell wall and highlighted the involving mechanisms and biological application.

Abstract Pathogenic mutations in mitochondrial DNA cause severe and often lethal multi-system symptoms in primary mitochondrial defects. However, effective therapies for these defects are still lacking. Strategies such as employing mitochondrially targeted restriction enzymes or programmable nucleases to shift the ratio of heteroplasmic mutations and allotopic expression of mitochondrial protein-coding genes have limitations in treating mitochondrial homoplasmic mutations, especially in non-coding genes. Here, we conduct a proof of concept study applying a screened DdCBE pair to correct the homoplasmic m.A4300G mutation in induced pluripotent stem cells derived from a patient with hypertrophic cardiomyopathy. We achieve efficient G4300A correction with limited off-target editing, and successfully restore mitochondrial function in corrected induced pluripotent stem cell clones. Our study demonstrates the feasibility of using DdCBE to treat primary mitochondrial defects caused by homoplasmic pathogenic mitochondrial DNA mutations.

Abstract Background Rabies is a widespread, fatal, infectious disease. Several antivirals against rabies virus (RABV) infection have been reported, but no approved, RABV-specific antiviral drugs that inhibit RABV infection in the clinic after symptom onset are available. Therefore, more effective drugs to reduce rabies fatalities are urgently needed. Bardoxolone methyl (CDDO-Me), an FDA-approved compound that has long been known as an antioxidant inflammatory modulator and one of the most potent nuclear factor erythroid-derived 2-like 2 (Nrf2) activators, protects myelin, axons, and CNS neurons by Nrf2 activation. Therefore, we investigated the potency of its anti-RABV activity in vitro. Methods The mouse neuroblastoma cell line Neuro2a (N2a) and three RABV strains of different virulence were used; the cytotoxicity and anti-RABV activity of CDDO-Me in N2a cells were evaluated by CCK-8 assay and direct fluorescent antibody (DFA) assay. Pathway activation in N2a cells infected with the RABV strains SC16, CVS-11 or CTN upon CDDO-Me treatment was evaluated by western blotting (WB) and DFA assay. Results CDDO-Me significantly inhibited infection of the three RABV strains of differing virulence (SC16, CVS-11 and CTN) in N2a cells. We also examined whether CDDO-Me activates the Nrf2-associated pathway upon infection with RABV strains of differing virulence. Nrf2, phosphorylated sequestosome (SQSTM1), SQSTM1, hemoglobin oxygenase (HO-1) and NAD(P)H dehydrogenase quinone 1 (NQO1) expression in N2a cells increased to varying degrees with CDDO-Me treatment, accompanied by Kelch-like ECH-associated protein 1 (Keap1) dissociation, upon infection with SC16, CVS-11 or CTN. The activation of SQSTM1 phosphorylation was significantly associated with the degradation of Keap-1 in CDDO-Me-treated N2a cells upon RABV infection. Furthermore, N2a cells pretreated with the Nrf2-specific inhibitor ATRA showed a significant decrease in HO-1 and NQO1 expression and a decrease in the anti-RABV efficacy of CDDO-Me. These inhibitory effects were observed upon infection with three RABV strains of differing virulence. Conclusion CDDO-Me inhibited RABV infection via Nrf2 activation, promoting a cytoprotective defense response in N2a cells. Our study provides a therapeutic strategy for RABV inhibition and neuroprotection during viral infection.

Rabies is a fatal neurological infectious disease caused by rabies virus (RABV), which invades the central nervous system (CNS). RABV with varying virulence regulates chemokine expression, and the mechanisms of signaling pathway activation remains to be elucidated. The relationship between Toll-like receptors (TLRs) and immune response induced by RABV has not been fully clarified. Here, we investigated the role of TLR7 in the immune response induced by RABV, and one-way analysis of variance (ANOVA) was employed to evaluate the data. We found that different RABV strains (SC16, HN10, CVS-11) significantly increased CCL2, CXCL10 and IL-6 production. Blocking assays indicated that the TLR7 inhibitor reduced the expression of CCL2, CXCL10 and IL-6 (p < 0.01). The activation of the Myd88 pathway in BV-2 cells stimulated by RABV was TLR7-dependent, whereas the inhibition of Myd88 activity reduced the expression of CCL2, CXCL10 and IL-6 (p < 0.01). Meanwhile, the RABV stimulation of BV-2 cells resulted in TRL7-mediated activation of NF-κB and induced the nuclear translocation of NF-κB p65. CCL2, CXCL10 and IL-6 release was attenuated by the specific NF-κB inhibitor used (p < 0.01). The findings above demonstrate that RABV-induced expression of CCL2, CXCL10 and IL-6 involves Myd88 and NF-κB pathways via the TLR7 signal.

After surgical or natural menopause, women face a high risk of nonalcoholic fatty liver disease (NAFLD), which can be diminished by hormone replacement therapy (HRT). The gut microbiota is subject to modulation by various physiological changes and the progression of diseases. This microbial ecosystem coexists symbiotically with the host, playing pivotal roles in immune maturation, microbial defense mechanisms, and metabolic functions essential for nutritional and hormone homeostasis. E2 supplementation effectively prevented the development of NAFLD after bilateral oophorectomy (OVX) in female rats. The changes in the gut microbiota such as abnormal biosynthetic metabolism of fatty acids caused by OVX were partially restored by E2 supplementation. The combination of liver transcriptomics and metabolomics analysis revealed that linoleic acid (LA) metabolism, a pivotal pathway in fatty acids metabolism was mainly manipulated during the induction and treatment of NAFLD. Further correlation analysis indicated that the gut microbes were associated with abnormal serum indicators and different LA metabolites. These metabolites are also closely related to serum indicators of NAFLD. An in vitro study verified that LA is an inducer of hepatic steatosis. The changes in transcription in the LA metabolism pathway could be normalized by E2 treatment. The metabolic perturbations of LA may directly and secondhand impact the development of NAFLD in postmenopausal individuals. This research focused on the sex-specific pathophysiology and treatment of NAFLD, providing more evidence for HRT and calling for the multitiered management of NAFLD.

Objective: To analyse and summarise the regularity of acupoint selection in the treatment of opioid-induced constipation (OIC) in patients with cancer pain using a data mining technique and provide a reference for clinical practice and more valuable treatment options. Methods: The acupoint prescription database for the treatment of OIC-related cancer pain was established by searching the relevant literature on randomised controlled trials involving acupoint therapy for OIC-related cancer pain in seven major databases, including the China National Knowledge Infrastructure, Wanfang and VIP Chinese scientific journal databases, from database establishment to December 31, 2022. The main therapeutic measures of acupoint prescription, frequency of acupoint use and its subordinate meridians and subordinate sites were then analysed. Through systematic clustering and association rule analysis, the core acupoint prescriptions and most commonly used acupoint compatibility of acupoint therapy for OIC-related cancer pain were obtained. Results: A total of 649 articles were retrieved, with 72 articles included after screening. The treatment measures were found to be mainly acupoint applications involving 28 acupoints, with a total frequency of 234. The three most frequently used acupoints were Shenque, Tianshu and Zusanli. The number of points used in the Foot-Yangming stomach meridian was the highest. Commonly used acupoints were mainly distributed in the abdomen. The compatibility of two commonly used acupoints was obtained through systematic clustering. Through association rule analysis, it was found that in the compatibility of acupoints, the strongest correlation was between Tianshu and Zusanli, and their frequency of application was the highest. Conclusion: Tianshu and Zusanli are the core acupoints for acupoint therapy in the treatment of OIC-related cancer pain, and the Shangjuxu–Zhigou–Zusanli, Qihai–Guanyuan and Zhongwan–Tianshu acupoints exhibit the highest compatibility. This study provides a reference for the clinical acupoint selection programme of acupuncture and moxibustion in the treatment of OIC-related cancer pain.

Mesozoic marine shale oil was found in the Qiangtang Basin by a large number of hydrocarbon geological surveys and shallow drilling sampling. Based on systematic observation and experimental analysis of outcrop and core samples, the deposition and development conditions and characteristics of marine shale are revealed, the geochemical and reservoir characteristics of marine shale are evaluated, and the layers of marine shale oil in the Mesozoic are determined. The following geological understandings are obtained. First, there are two sets of marine organic-rich shales, the Lower Jurassic Quse Formation and the Upper Triassic Bagong Formation, in the Qiangtang Basin. They are mainly composed of laminated shale with massive mudstone. The laminated organic-rich shale of the Quse Formation is located in the lower part of the stratum, with a thickness of 50–75 m, and mainly distributed in southern Qiangtang Basin and the central-west of northern Qiangtang Basin. The laminated organic-rich shale of the Bagong Formation is located in the middle of the stratum, with a thickness of 250–350 m, and distributed in both northern and southern Qiangtang Basin. Second, the two sets of laminated organic-rich shales develop foliation, and various types of micropores and microfractures. The average content of brittle minerals is 70%, implying a high fracturability. The average porosity is 5.89%, indicating good reservoir physical properties to the level of moderate–good shale oil reservoirs. Third, the organic-rich shale of the Quse Formation contains organic matters of types II1 and II2, with the average TOC of 8.34%, the average content of chloroform bitumen ‘A’ of 0.66%, the average residual hydrocarbon generation potential (S1+S2) of 29.93 mg/g, and the Ro value of 0.9%–1.3%, meeting the standard of high-quality source rock. The organic-rich shale of the Bagong Formation contains mixed organic matters, with the TOC of 0.65%–3.10% and the Ro value of 1.17%–1.59%, meeting the standard of moderate source rock. Fourth, four shallow wells (depth of 50–250 m) with oil shows have been found in the organic shales at 50–90 m in the lower part of the Bagong Formation and 30–75 m in the middle part of the Quse Formation. The crude oil contains a high content of saturated hydrocarbon. Analysis and testing of outcrop and shallow well samples confirm the presence of marine shale oil in the Bagong Formation and the Quse Formation. Good shale oil intervals in the Bagong Formation are observed in layers 18–20 in the lower part of the section, where the shales with (S0+S1) higher than 1 mg/g are 206.7 m thick, with the maximum and average (S0+S1) of 1.92 mg/g and 1.81 mg/g, respectively. Good shale oil intervals in the Quse Formation are found in layers 4–8 in the lower part of the section, where the shales with (S0+S1) higher than 1 mg/g are 58.8 m thick, with the maximum and average (S0+S1) of 6.46 mg/g and 2.23 mg/g, respectively.

Abstract Traffic sign detection is a challenging task for unmanned driving systems. In the traffic sign detection process, the object size and weather conditions vary widely, which will have a certain impact on the detection accuracy. In order to solve the problem of balanced detecting precision of traffic sign recognition model in different weather conditions, and it is difficult to detect occluded objects and small objects, this paper proposes a small object detection algorithm based on improved YOLOv5s in complex weather. First, we add the coordinate attention(CA) mechanism in the backbone, a light-weight yet effective module, embedding the location information of traffic signs into the channel attention to improve the feature extraction ability of the network. Second, we exploit effectively fine-grained features about small traffic signs from the shallower layers by adding one prediction head to YOLOv5s. Finally, we use Alpha-IoU to improve the original positioning loss CIoU, improving the accuracy of bbox regression. Applying this model to the recently proposed CCTSDB 2021 dataset, for small objects, the precision is 88.1%, and the recall rate is 79.8%, compared with the original YOLOv5s model, it is improved by 12.5% and 23.9% respectively, and small traffic signs can be effectively detected under different weather conditions, with low miss rate and high detection accuracy. The source code will be made publicly available at https://github.com/yang-0706/ImprovedYOLOv5s .

An emerging line of research examining the role of numerological superstition in the capital market shows that it has significant impact on investor behavior (Bhattacharya, Kuo, Lin, & Zhao, 2018; Hirshleifer, Jian, & Zhang 2018). However, to the authors’ best knowledge, there is a dearth of evidence on whether numerological superstition affects corporate behavior. This study fills this void by examining the association between investors’ numerological superstition and earnings management using Chinese data. Chinese culture views 6 and 8 as lucky numbers. Using Chinese publicly traded firms, the authors examine the relation between investors’ numerological superstition and corporate financial reporting behavior. The results suggest that firms reporting lucky earnings-per-share (EPS) numbers ending with 6 or 8 are more likely to engage in earnings management. These firms also raise more capital through seasoned equity offerings in the following year; however, they do not have more capital investments. Instead, their controlling shareholders siphon a significant amount of capital through related party transactions. Overall, the findings suggest that managers collude with controlling shareholders to manage earnings by exploiting the superstitious beliefs of minority shareholders. To the authors’ best knowledge, there is a dearth of evidence on whether numerological superstition affects corporate behavior. This study fills this void by examining the association between investors’ numerological superstition and earnings management using Chinese data.

Yellow leaf disease (YLD) poses a significant challenge to areca palm cultivation, yet its etiology remains uncertain. During our investigation of YLD-affected areca palm plants, transcriptome sequencing revealed an RNA contig exhibiting striking similarities to the RNA-dependent RNA polymerase (RdRp) of ormycoviruses. Subsequent gene cloning techniques yielded the full-length sequence of this RNA, potentially representing either the complete or partial genome of a hitherto unidentified ormycovirus, tentatively named areca palm yellow leaf-associated ormycovirus (APYLaOMV). RT-PCR detection found that APYLaOMV is present in over 30% of YLD-affected areca palm samples but is absent in healthy ones, suggesting a potential link between APYLaOMV and YLD. In summary, these data could be valuable in understanding the etiology of YLD in areca palms.

Nanoplastics, created by the fragmentation of larger plastic debris, are a serious pollutant posing substantial environmental and health risks. Here, we developed a polystyrene nanoparticle (PS-NP) exposure model during mice pregnancy to explore their effects on embryonic development. We found that exposure to 30 nm PS-NPs during pregnancy resulted in reduced mice placental weight and abnormal embryonic development. Subsequently, our transcriptomic dissection unveiled differential expression in 102 genes under PS-NP exposure and the p38 MAPK pathway emerged as being significantly altered in KEGG pathway mapping. Our findings also included a reduction in the thickness of the trophoblastic layer in the placenta, diminished cell invasion capabilities, and an over-abundance of immature red cells in the blood vessels of the mice. In addition, we validated our findings through the human trophoblastic cell line, HTR-8/SVneo (HTR). PS-NPs induced a drop in the vitality and migration capacities of HTR cells and suppressed the p38 MAPK signaling pathway. This research highlights the embryotoxic effects of nanoplastics on mice, while the verification results from the HTR cells suggest that there could also be certain impacts on the human trophoblast layer, indicating a need for further exploration in this area.

Abstract Background Ferroptosis, iron-dependent cell death, is an established mechanism for cancer suppression, particularly in hepatocellular carcinoma (HCC). Sorafenib (SOR), a frontline drug for the treatment of HCC, induces ferroptosis by inhibiting the Solute Carrier family 7 member 11 (SLC7A11), with inadequate ferroptosis notably contributing to SOR resistance in tumor cells. Methods To further verify the biological targets associated with ferroptosis in HCC, an analysis of the Cancer Genome Atlas (TCGA) database was performed to find a significant co-upregulation of SLC7A11 and transferrin receptor (TFRC), Herein, cell membrane-derived transferrin nanovesicles (TF NVs) coupled with Fe3+ and encapsulated SOR (SOR@TF-Fe3+ NVs) were established to synergistically promote ferroptosis, which promoted the iron transport metabolism by TFRC/TF-Fe3+ and enhanced SOR efficacy by inhibiting the SLC7A11. Results In vivo and in vitro experiments revealed that SOR@TF-Fe3+ NVs predominantly accumulate in the liver, and specifically targeted HCC cells overexpressing TFRC. Various tests demonstrated SOR@TF-Fe3+ NVs accelerated Fe3+ absorption and transformation in HCC cells. Importantly, SOR@TF-Fe3+ NVs were more effective in promoting the accumulation of lipid peroxides (LPO), inhibiting tumor proliferation, and prolonging survival rates in HCC mouse model than SOR and TF- Fe3+ NVs alone. Conclusions The present work provides a promising therapeutic strategy for the targeted treatment of HCC. Graphical abstract

Hyperthermia therapy is considered an effective anticancer strategy. However, high temperature can trigger an excessive inflammatory response, leading to tumor self-protection, immunosuppression, metastasis, and recurrence. To address this issue, we reported a multifunctional photothermal nanoplatform to achieve mild hyperthermia photothermal therapy (mild PTT) based on cisplatin (DDP) and a ferrocene metal-organic framework (MOF-Fc) nanocomposite, which can specifically enhance ferroptosis-triggered oxidative stress levels and synchronously amplify mild hyperthermia PTT-mediated anticancer responses. Both in vitro and in vivo antineoplastic results verify the superiority of mild PTT with DDP/MOF-Fc@HA. The combination of DDP and MOF-Fc exhibits Fenton catalytic activity and glutathione depletion capacity, magnifying mild hyperthermia effects via the radical oxygen species (ROS)-adenosine triphosphate (ATP)-HSP silencing pathway, with important implications for clinical hyperthermia therapy.

Objective To investigate factors that differentiate elderly adults in rural China who accept free vision screening and cataract surgery from those who could benefit from vision care but refuse it when offered.Design We conducted a population-based, cross-sectional study between October and December 2016. Logistic regression models were used to examine the predictors of accepting free vision screening and cataract surgery.Setting Rural communities in Handan, China.Participants Adults aged 50 years or older, with presenting visual acuity ≤6/18 in the better seeing eye, suspected by examining ophthalmologist to be due to cataract.Results Among 613 persons with cataract identified on a population basis, 596 (97.2%) completed the household survey (mean (SD) age, 71.5 (10.0) years; 79.8% female). A total of 214 persons (35.9%) refused participation, while 382 (64.1%) took part in the vision screening. A total of 193 (50.5%) participants were found eligible for surgery, while 189 (49.5%) were not. Among 99 randomly selected participants who were offered immediate free surgery, surgery was accepted by 77 participants (77.8%) and refused by 22 (22.2%). In the multivariate model, being engaged in income-generating activities (p

Background and objectivesThis study’s primary objective is to investigate the impact of art-making on the mental well-being of college students, who often experience heightened stress during their initial university years.MethodsEmploying a comprehensive methodology, combining interviews and the Perceived Stress Scale (PSS), the research aimed to assess whether a four-week art-making intervention can effectively alleviate stress levels among college students. In the experimental group, participants engaged in a variety of art-making activities, including freehand drawing, clay modeling, and crafting.ResultsThe results revealed that, in the pre-test, there were no significant differences between the experimental and control groups for each assessed indicator. However, in the post-test, significant differences emerged across all indicators. Further analysis demonstrated a significant reduction in stress perception among the experimental group participants between the pre-test and post-test phases.ConclusionIn conclusion, this study provides compelling evidence that art-making has the potential to foster positive personal development and significantly reduce stress levels among college students.

BackgroundMicrocirculatory dysfunction is an independent risk factor for a poor prognosis after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). Trichosanthes pericarpium is a well-known Chinese traditional herb described with the effect of activating blood circulation to dissipate blood stasis and improve blood circulation. However, its effects on microcirculation in patients with AMI after primary PCI remain unknown. This study aimed to investigate the effect of Trichosanthes pericarpium extract (TPE) on improving microcirculation and outcomes in patients with AMI after PCI.MethodsThis study included 155 patients with a history of emergency PCI treatment. In this cohort, 31 patients received a course of TPE, defined as intravenous TPE infusion (12 ml TPE dissolved in 250 ml 5% Glucose Injection) once daily for 7 days on the background of standard treatment after PCI; 124 who did not receive TPE were regarded as the control group and received standard treatment after PCI. The corrected thrombolysis in myocardial infarction frame count (CTFC) and index of microcirculatory resistance (IMR) were used to evaluate myocardial microcirculation. Cardiac function was measured by echocardiography during hospitalization and follow-up. Major adverse cardiac events (MACEs) were recorded for prognostic analysis.ResultsAt the 6-month follow-up, AMI patients who received TPE after primary PCI had significantly lower levels of CTCF (24.27 ± 2.40 vs. 21.88 ± 1.92, P

AbstractBackground To explore the crosstalk between baseline or visit hemoglobin and major adverse cardiovascular and cerebral events (MACCE) in percutaneous coronary intervention (PCI) patients and to construct risk stratification models to predict MACCE amongst these patients.Materials and methods We conducted a retrospective cohort in patients undergoing PCI procedures at Beijing Friendship Hospital between January 2013 and December 2020. Multivariate Cox proportional hazards models were employed for data analyses. The composite MACCE was the primary endpoint and we used machine learning algorithms to evaluate risk factors associated with MACCE. Model performance was measured using Brier scores and receiver-operating characteristic curves. The association between risk factors and MACCE probability was examined using partial dependency plots.Results 8,298 PCI-treated patients were enrolled in the study. 1,919 of these patients had anemia. During a four-year median follow-up period, 1,636 patients (19.71%) had MACCE. The visit hemoglobin and hemoglobin change was associated with higher risk of MACCE respectively (visit hemoglobin: hazard ratio [HR]: 0.98; 95% confidence interval [CI]: 0.98–0.99; p

Extravehicular activity (EVA) is a key point and a difficult point for manned spaceflight tasks, as well as an inevitable trend in the development of the manned spaceflight industry. Equipment maintenance, load installation, and extravehicular routing inspection via EVA on the track are necessary to guarantee the safety and reliability of the long-term in-orbit operation of the China Space Station. In this paper, a comprehensive analysis was conducted on the features of multiple tasks, diverse working modes, and strong systematic coupling during the EVA of the China Space Station (CSS). On this basis, the design, implementation technologies’ development, and in-orbit performance evaluation during EVA were expounded. In the space station system, an extravehicular reliability verification and evaluation system suitable for the requirement for EVA under the conditions of China’s multi-mission, multi-module combination, and repairable spacecraft was constructed. Finally, the in-orbit EVA implementation of the China Space Station since the launch of the core module to the present was summarized, and the subsequent application of the extravehicular technologies in manned lunar landing projects and optical modules was anticipated.

An up-and-coming concept that seeks to transform how students learn about and study complex systems, as well as how industrial workers are trained, metaverse technology is characterized in this context by its use in virtual simulation and analysis. In this work, a virtual environment is created that duplicates real-world situations and enables immersive and interactive learning in the educational metaverse. For this purpose, we built a digital twin of the Nanyang Technological University (NTU) campus as a foundation, called NTUniverse. It is designed as an educational metaverse in which various academic and analytical applications are digitized as 3D content embedded within this virtual campus. The approach to digitally twinning educational systems and embedding them within virtual campuses enables remote and collaborative learning as well as professional technical skills training. It also makes feasible the analysis of abstract concepts, complicated structures, dynamic processes, and sensitive industrial procedures virtually, which is otherwise challenging if not impossible to perform in the real world. The work offers important insights into the behaviors and interactions of systems in the metaverse by evaluating design choices and user interests. NTUniverse is an attempt to explore a novel approach that addresses remote education and training challenges. Three efforts with NTUniverse will be discussed in this work, including (1) digitalization of the NTU campus; (2) campus train modelling and simulation; and (3) science, technology, engineering and mathematics education.

Medical imaging is crucial for the detection and diagnosis of breast cancer. Artificial intelligence and computer vision have rapidly become popular in medical image analyses thanks to technological advancements. To improve the effectiveness and efficiency of medical diagnosis and treatment, significant efforts have been made in the literature on medical image processing, segmentation, volumetric analysis, and prediction. This paper is interested in the development of a prediction pipeline for breast cancer studies based on 3D computed tomography (CT) scans. Several algorithms were designed and integrated to classify the suitability of the CT slices. The selected slices from patients were then further processed in the pipeline. This was followed by data generalization and volume segmentation to reduce the computation complexity. The selected input data were fed into a 3D U-Net architecture in the pipeline for analysis and volumetric predictions of cancer tumors. Three types of U-Net models were designed and compared. The experimental results show that Model 1 of U-Net obtained the highest accuracy at 91.44% with the highest memory usage; Model 2 had the lowest memory usage with the lowest accuracy at 85.18%; and Model 3 achieved a balanced performance in accuracy and memory usage, which is a more suitable configuration for the developed pipeline.

Abstract Polycystic ovary syndrome (PCOS) is a prevalent reproductive endocrine disorder, with metabolic abnormalities and ovulation disorders. The post‐translational modifications (PTMs) are functionally relevant and strengthen the link between metabolism and cellular functions. Lysine crotonylation is a newly identified PTM, the function of which in PCOS has not yet been reported. To explore the molecular mechanisms of crotonylation involved in the abnormalities of metabolic homeostasis and oocyte maturation in PCOS, by using liquid chromatography‐tandem mass spectrometry analysis, we constructed a comprehensive map of crotonylation modifications in ovarian tissue of PCOS‐like mouse model established by dehydroepiandrosterone induction. The crotonylation levels of proteins involved in metabolic processes were significantly decreased in PCOS ovaries compared to control samples. Further investigation showed that decrotonylation of Lon protease 1 (LONP1) at lysine 390 was associated with mitochondrial dysfunction in PCOS. Moreover, LONP1 crotonylation levels in PCOS were correlated with ovarian tissue oxidative stress levels, androgen levels, and oocyte development. Consistently, down‐regulation of LONP1 and LONP1 crotonylation levels were also observed in the blood samples of PCOS patients. Collectively, our study revealed a mechanism by which the decrotonylation of LONP1 may attenuate its activity and alter follicular microenvironment to affect oocyte maturation in PCOS.

Abstract Through‐space interaction (TSI) has been proven to play an important role in the newly emerging clusteroluminescence (CL) phenomenon. However, it is still a big challenge to manipulate the TSI at the molecular level due to the unclear relationship between the non‐conjugated structure and TSI properties. Herein, the TSI in diphenylmethane is manipulated by breaking its symmetric structures and changing the isolated subunits. Finally, the CL wavelength and efficiency of diphenylmethane are successfully regulated at the aggregate state.

Abstract Cartilage damage affects millions of people worldwide. Tissue engineering strategies hold the promise to provide off‐the‐shelf cartilage analogs for tissue transplantation in cartilage repair. However, current strategies hardly generate sufficient grafts, as tissues cannot maintain size growth and cartilaginous phenotypes simultaneously. Herein, a step‐wise strategy is developed for fabricating expandable human macromass cartilage (macro‐cartilage) in a 3D condition by employing human polydactyly chondrocytes and a screen‐defined serum‐free customized culture (CC). CC‐induced chondrocytes demonstrate improved cell plasticity, expressing chondrogenic biomarkers after a 14.59‐times expansion. Crucially, CC‐chondrocytes form large‐size cartilage tissues with average diameters of 3.25 ± 0.05 mm, exhibiting abundant homogenous matrix and intact structure without a necrotic core. Compared with typical culture, the cell yield in CC increases 2.57 times, and the expression of cartilage marker collagen type II increases 4.70 times. Transcriptomics reveal that this step‐wise culture drives a proliferation‐to‐differentiation process through an intermediate plastic stage, and CC‐chondrocytes undergo a chondral lineage‐specific differentiation with an activated metabolism. Animal studies show that CC macro‐cartilage maintains a hyaline‐like cartilage phenotype in vivo and significantly promotes the healing of large cartilage defects. Overall, an efficient expansion of human macro‐cartilage with superior regenerative plasticity is achieved, providing a promising strategy for joint regeneration.

Abstract Patients with glioblastoma (GBM) have poor prognosis and limited treatment options, largely due to therapy resistance upon the induction of apoptosis. Ferroptosis emerges as a potential antineoplastic strategy to bypass apoptosis resistance in traditional therapeutics. Hypoxia is a fundamental hallmark of GBM and hypoxia-inducible factor (HIF) is the main regulator of hypoxia response, however, the role of HIF has not been sufficiently explored in GBM. Herein, we first discovered that amplifying HIF signals by the prolyl hydroxylase (PHD) inhibitor roxadustat significantly suppressed GBM cell growth in vitro and in vivo, especially when the cells were resistant to temozolomide (TMZ). The accumulation of lipid peroxidation and cellular iron in GBM cells following roxadustat treatment indicated that the cells underwent ferroptosis, which was also supported by morphological changes in mitochondrial ultrastructure and immunogenic signals release. Moreover, in vivo studies further confirmed the ferroptosis induction and verified that roxadustat significantly prolonged survival of the mice harboring chemoresistant GBM without visible organ toxicity. Finally, we proved that the ferroptosis induction by roxadustat is HIF-α independent, especially activation of HIF-2α upregulating lipid regulatory genes was revealed to be mainly responsible for the enhanced lipid peroxidation. Altogether, our study provided novel evidence that amplifying HIF signals induced ferroptosis in chemoresistant GBM cells and suppressed the tumor growth in vivo, highlighting that ferroptosis induction by targeting HIF-α might provide new approaches to improve GBM treatment.

To investigate the effect of endogenous protease on the texture of Yesso scallop muscle during cold storage, the texture and protein change related indexes of Yesso scallop muscle was measured during 4 ℃ cold storage 7 d with a purpose to identify the functions of proteinases. The results showed that the hardness, springiness, chewiness and gumminess generally decreased during the whole cold storage process. SDS-PAGE analysis revealed that muscular proteins began to degrade obviously on the third day. In terms of enzyme activity, serine proteinase (SP) activity began to decrease sharply after 2 days of cold storage. Serine proteinase was purified from the muscle of Yesso scallop by ammonium sulfate precipitation, ion exchange chromatography, gel filtration and hydrophobic chromatography. SDS-PAGE and gelatin zymogram showed that in native condition SP was in homodimer form with molecular weight of 52 kDa. The optimum pH of SP was 9.0 and the optimum temperature was 37 ℃. SP specifically hydrolyzes substrates containing arginine or lysine residues at P1 position on the carboxyl side. Serine protease specific inhibitors including PMSF, Leupeptin, Pefabloc SC and Benzamidine could inhibit the activity of SP by 97%, 98%, 90% and 85%, respectively. Metal ions Fe2+, Zn2+ and Cu2+ could also significantly suppress the activity of SP. SP could effectively degrade scallop myofibrillar at 37 ℃, which delivered a reference for revealing the effect of SP on the quality of Yesso scallop muscle protein.

BackgroundIntracranial aneurysm (IA) is a nodular protrusion of the arterial wall caused by the localized abnormal enlargement of the lumen of a brain artery, which is the primary cause of subarachnoid hemorrhage. Accurate rupture risk prediction can effectively aid treatment planning, but conventional rupture risk estimation based on clinical information is subjective and time-consuming.MethodsWe propose a novel classification method based on the CTA images for differentiating aneurysms that are prone to rupture. The main contribution of this study is that the learning-based method proposed in this study leverages deep learning and radiomics features and integrates clinical information for a more accurate prediction of the risk of rupture. Specifically, we first extracted the provided aneurysm regions from the CTA images as 3D patches with the lesions located at their centers. Then, we employed an encoder using a 3D convolutional neural network (CNN) to extract complex latent features automatically. These features were then combined with radiomics features and clinical information. We further applied the LASSO regression method to find optimal features that are highly relevant to the rupture risk information, which is fed into a support vector machine (SVM) for final rupture risk prediction.ResultsThe experimental results demonstrate that our classification method can achieve accuracy and AUC scores of 89.78% and 89.09%, respectively, outperforming all the alternative methods.DiscussionOur study indicates that the incorporation of CNN and radiomics analysis can improve the prediction performance, and the selected optimal feature set can provide essential biomarkers for the determination of rupture risk, which is also of great clinical importance for individualized treatment planning and patient care of IA.

Abstract Circulating circular RNAs (circRNAs) are emerging as novel biomarkers for cardiovascular diseases (CVDs). Machine learning can provide optimal predictions on the diagnosis of diseases. Here we performed a proof‐of‐concept study to determine if combining circRNAs with an artificial intelligence approach works in diagnosing CVD. We used acute myocardial infarction (AMI) as a model setup to prove the claim. We determined the expression level of five hypoxia‐induced circRNAs, including cZNF292, cAFF1, cDENND4C, cTHSD1, and cSRSF4, in the whole blood of coronary angiography positive AMI and negative non‐AMI patients. Based on feature selection by using lasso with 10‐fold cross validation, prediction model by logistic regression, and ROC curve analysis, we found that cZNF292 combined with clinical information (CM), including age, gender, body mass index, heart rate, and diastolic blood pressure, can predict AMI effectively. In a validation cohort, CM + cZNF292 can separate AMI and non‐AMI patients, unstable angina and AMI patients, acute coronary syndromes (ACS), and non‐ACS patients. RNA stability study demonstrated that cZNF292 was stable. Knockdown of cZNF292 in endothelial cells or cardiomyocytes showed anti‐apoptosis effects in oxygen glucose deprivation/reoxygenation. Thus, we identify circulating cZNF292 as a potential biomarker for AMI and construct a prediction model “CM + cZNF292.”

Ovariectomy (OVX) conducted before the onset of natural menopause is considered to bringing forward and accelerate the process of ageing-associated neurodegeneration. However, the mechanisms underlying memory decline and other cognitive dysfunctions following OVX are unclear. Given that iron accumulates during ageing and after OVX, we hypothesized that excess iron accumulation in the hippocampus would cause ferroptosis-induced increased neuronal degeneration and death associated with memory decline. In the current study, female rats that underwent OVX showed decreased dihydroorotate dehydrogenase (DHODH) expression and reduced performance in the Morris water maze (MWM). We used primary cultured hippocampal cells to explore the ferroptosis resistance–inducing effect of 17β-oestradiol (E2). The data supported a vital role of DHODH in neuronal ferroptosis. Specifically, E2 alleviated ferroptosis induced by erastin and ferric ammonium citrate (FAC), which can be blocked by brequinar (BQR). Further in vitro studies showed that E2 reduced lipid peroxidation levels and improved the behavioural performance of OVX rats. Our research interprets OVX-related neurodegeneration with respect to ferroptosis, and both our in vivo and in vitro data show that E2 supplementation exerts beneficial antiferroptotic effects by upregulating DHODH. Our data demonstrate the utility of E2 supplementation after OVX and provide a potential target, DHODH, for which hormone therapy has not been available.

Apigenin-7-O-glucoside (AG), a flavonoid glycoside, has been shown in vitro anti-inflammatory activities. To date, the mechanism of AG against colitis has not been reported. In this study, we investigated the role of AG in relieving colitis and explored its potential mechanisms in dextran sulfate sodium (DSS)-induced colitis mice. The results indicated oral administration of AG increased colon length and improved colonic histopathology. Besides, it dramatically restored the colonic expression of pro-inflammatory and anti-inflammatory mediators, as well as enhanced the expression of intestinal barrier markers such as ZO-1, occludin, claudin-1, and claudin-3. The mitogen-activated protein kinases (MAPKs) including ERK, JNK, and p38 were significantly inhibited. Moreover, 16S rDNA sequencing revealed that AG improved the abundance of Akkermansia, and reduced that of Bacteroides and Desulfovibrio. Taken together, AG supplementation relieved DSS-induced colitis by protecting the intestinal barrier, inhibiting the MAPK pathway, and modulating gut microbiota, which indicated that AG may be a good candidate therapeutic compound for sustaining gut health to lower the risk of colitis.

Accurate and complete 3D point clouds are essential in creating as-built building information modeling (BIM) models, although there are challenges in automating the process for 3D point cloud creation in complex environments. In this paper, an autonomous scanning system named BIMBot is introduced, which integrates advanced light detection and ranging (LiDAR) technology with robotics to create 3D point clouds. Using our specially developed algorithmic pipeline for point cloud processing, iterative registration refinement, and next best view (NBV) calculation, this system facilitates an efficient, accurate, and fully autonomous scanning process. The BIMBot’s performance was validated using a case study in a campus laboratory, featuring complex structural and mechanical, electrical, and plumbing (MEP) elements. The experimental results showed that the autonomous scanning system produced 3D point cloud mappings in fewer scans than the manual method while maintaining comparable detail and accuracy, demonstrating its potential for wider application in complex built environments.

Premature menopause is associated with an increased prevalence of nonalcoholic fatty liver disease (NAFLD). Menopausal hormone therapy (MHT) has been widely used in clinical practice and has the potential to protect mitochondrial function and alleviate NAFLD. After bilateral oophorectomy (OVX), female rats without 17β-estradiol (E2) intervention developed NAFLD, whereas E2 supplementation was effective in preventing NAFLD in female rats. The altered pathways and cellular events from both comparison pairs, namely, the OVX vs. sham group and the OVX vs. E2 group, were assessed using transcriptomic analysis. KEGG pathways enriched by both transcriptomic and metabolomic analyses strongly suggest that oxidative phosphorylation is a vital pathway that changes during the development of NAFLD and remains unchanged when E2 is applied. Liver tissue from the OVX-induced NAFLD group exhibited increased lipid peroxidation, impaired mitochondria, and downregulated ERα/SIRT1/PGC-1α expression. An in vitro study indicated that the protective effect of E2 treatment on hepatic steatosis could be abolished when ERα or SIRT1 was selectively inhibited. This damage was accompanied by reduced mitochondrial complex activity and increased lipid peroxidation. The current research indicates that E2 upregulates the ERα/SIRT1/PGC-1α signaling pathway and protects mitochondrial function to prevent OVX-induced NAFLD.

Abstract Background Helicobacter pylori (H. pylori) can disrupt the tight junctions between gastric epithelial cells and penetrate the intercellular spaces acting on epithelial cells, normal fibroblasts (NFs), and cancer-associated fibroblasts (CAFs), but their interaction in gastric cancer tumorigenesis and progression remains unclear. Methods Primary CAFs and NFs were isolated from paired gastric cancer tissues and adjacent normal tissues and identified by immunofluorescence staining and western blot analysis for FSP-1, α-SMA, FAP, and vimentin expression. RNA-sequencing was used to compare the transcriptomes between CAFs and NFs. The expressions of FAP, lumican, and α-SMA, human cytokine array, and Transwell assay were used to assess the transformation of NFs to CAFs. CCK-8 assay, colony formation, flow cytometry, Transwell assay, and nude mouse xenograft model were used to determine the effects of Serpin E1 on cell proliferation and metastasis in vitro and in vivo. Finally, Serpin E1 and/or FAP expression was measured in H. pylori-infected gerbil gastric mucosa and human gastric cancer tissues. Results Gastric CAFs are inflammatory CAFs with α-SMAlowFAPhighlumicanhigh. The interplay of H. pylori, fibroblasts, and cancer cells promotes the transition of NFs to CAFs by inducing cytokine release, especially Serpin E1. Long-term H. pylori infection and CAFs induce Serpin E1 expression in gerbil gastric tissues and human gastric cancer cells. Serpin E1 overexpression enhances the growth, migration, invasion of gastric cancer cells in vitro, and xenograft tumor growth in nude mice via inducing angiogenesis. Serpin E1 and FAP were highly expressed in cancer cells and CAFs of gastric cancer tissues, respectively, and a good correlation was observed between their expression. Higher Serpin E1 expression is negatively associated with the overall survival of patients with gastric cancer. Conclusions The interplay of H. pylori, fibroblasts, and cancer cells induced Serpin E1 expression to promote the activation of NFs to CAFs and gastric carcinogenesis. Targeting Serpin E1 will provide a promising therapeutic strategy for gastric cancer by disrupting the interaction between H. pylori, CAFs, and gastric cancer cells.

The mechanism of cold-activated TRPM8 channel activation remains unclear. Here, authors have determined structures of mouse TRPM8 in apo or ligand-bound states, providing insights into the activation of TRPM8 structures in different states.