Search

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.

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

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.

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.

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

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.

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.

Associative anaphora refers to a discourse operation that links a definite determiner phrase (DP) to an antecedent that acts as an indirect referent of the definite DP. For example, in the sequence 'I bought a laptop. The keyboard was black', the definite DP 'the keyboard' is linked to 'a laptop', meaning 'the keyboard of the laptop'. The development of children's knowledge of associative anaphora has long been investigated in child language research, as it provides a unique window into the interaction between linguistic and nonlinguistic cognitive abilities. However, most prior research focused on Indo-European languages without looking at typologically distinct languages. To fill the gap, this study investigated children's knowledge of associative anaphora in Mandarin Chinese, a typologically distinct language, thus allowing for a better cross-linguistic understanding of the phenomenon. Ninety-one 3- to 5-year-olds were investigated using a truth-value judgment task. The findings were that Mandarin-speaking children exhibited a similar developmental trajectory and were impacted by the same cognitive factors as observed in children speaking Indo-European languages. The implications of the findings were then discussed in relation to the role of processing factors and language-specific properties.