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Background/Aims Metabolic dysfunction-associated steatohepatitis (MASH) is an unmet clinical challenge due to the rapid increased occurrence but lacking approved drugs. Autophagy-related protein 16-like 1 (ATG16L1) plays an important role in the process of autophagy, which is indispensable for proper biogenesis of the autophagosome, but its role in modulating macrophage-related inflammation and metabolism during MASH has not been documented. Here, we aimed to elucidate the role of ATG16L1 in the progression of MASH. Methods Expression analysis was performed with liver samples from human and mice. MASH models were induced in myeloid-specific Atg16l1-deficient and myeloid-specific Atg16l1-overexpressed mice by high-fat and high-cholesterol diet or methionine- and choline-deficient diet to explore the function and mechanism of macrophage ATG16L1 in MASH. Results Macrophage-specific Atg16l1 knockout exacerbated MASH and inhibited energy expenditure, whereas macrophage-specific Atg16l1 transgenic overexpression attenuated MASH and promotes energy expenditure. Mechanistically, Atg16l1 knockout inhibited macrophage lipophagy, thereby suppressing macrophage β-oxidation and decreasing the production of 4-hydroxynonenal, which further inhibited stimulator of interferon genes(STING) carbonylation. STING palmitoylation was enhanced, STING trafficking from the endoplasmic reticulum to the Golgi was promoted, and downstream STING signaling was activated, promoting proinflammatory and profibrotic cytokines secretion, resulting in hepatic steatosis and hepatic stellate cells activation. Moreover, Atg16l1-deficiency enhanced macrophage phagosome ability but inhibited lysosome formation, engulfing mtDNA released by pyroptotic hepatocytes. Increased mtDNA promoted cGAS/STING signaling activation. Moreover, pharmacological promotion of ATG16L1 substantially blocked MASH progression. Conclusions ATG16L1 suppresses MASH progression by maintaining macrophage lipophagy, restraining liver inflammation, and may be a promising therapeutic target for MASH management.

Background/purpose: Accumulating evidence has suggested that treatment failure of cancer therapy can be attributed to cancer stem cells (CSCs). Among numerous regulators of cancer stemness, non-coding RNAs (ncRNAs) have gained significant attention recently. In this study, we examined the role of gastric adenocarcinoma predictive long intergenic noncoding RNA (GAPLINC) in oral CSCs (OCSCs). Materials and methods: RNA Sequencing and quantitative real-time polymerase chain reaction (qRT-PCR) were used to determine the expression of GAPLINC. Flow cytometry and sphere-forming assay were exploited to isolate OCSCs. Measurement of aldehyde dehydrogenase 1 (ALDH1) activity, CD44 expressing cells, and various phenotypic assays, such as self-renewal, migration, invasion, and colony-forming abilities, were conducted in CSCs of two types of oral cancer cells (SAS and GNM) following the knockdown of GAPLINC. A luciferase reporter was also carried out to validate the direct interaction between GAPLINC and microRNA (miR)-331-3p. Results: Our results showed that GAPLINC was overexpressed in OCSCs from patient-derived and oral cancer cell lines. We demonstrated that silencing of GAPLINC in OCSCs downregulated various CSC hallmarks, such as ALDH1 activity, percentage of CD44-expressing cells, self-renewal capacity, and colony-forming ability. Moreover, our results revealed that the effect of GAPLINC on cancer stemness was mediated by direct repression of miR-331-3p. Conclusion: These data have potential clinical implications in that we unraveled the aberrant upregulation of GAPLINC and demonstrated that suppression of GAPLINC may reduce cancer stemness via sequestering miR-331-3p.

Abstract Whether intestinal Leucine-rich repeat containing G-protein-coupled receptor 4 (LGR4) impacts nutrition absorption and energy homeostasis remains unknown. Here, we report that deficiency of Lgr4 (Lgr4 iKO ) in intestinal epithelium decreased the proportion of enterocytes selective for long-chain fatty acid absorption, leading to reduction in lipid absorption and subsequent improvement in lipid and glucose metabolism. Single-cell RNA sequencing demonstrates the heterogeneity of absorptive enterocytes, with a decrease in enterocytes selective for long-chain fatty acid-absorption and an increase in enterocytes selective for carbohydrate absorption in Lgr4 iKO mice. Activation of Notch signaling and concurrent inhibition of Wnt signaling are observed in the transgenes. Associated with these alterations is the substantial reduction in lipid absorption. Decrement in lipid absorption renders Lgr4 iKO mice resistant to high fat diet-induced obesity relevant to wild type littermates. Our study thus suggests that targeting intestinal LGR4 is a potential strategy for the intervention of obesity and liver steatosis.

Abstract Acute type A aortic dissection is a severe cardiovascular disease characterized by rapid onset and high mortality. Traditionally, urgent open aortic repair is performed after admission to prevent aortic rupture and death. However, when combined with malperfusion syndrome, the low perfusion of the superior mesenteric artery can further lead to intestinal necrosis, significantly impacting the surgery’s prognosis and potentially resulting in adverse consequences, bringing. This presents great significant challenges in treatment. Based on recent domestic and international research literature, this paper reviews the mechanism, current treatment approaches, and selection of surgical methods for poor organ perfusion caused by acute type A aortic dissection. The literature review findings suggest that central aortic repair can be employed for the treatment of acute type A aortic dissection with inadequate perfusion of the superior mesenteric artery. The superior mesenteric artery can be windowed and (/or) stented, followed by delayed aortic repair. Priority should be given to revascularization of the superior mesenteric artery, followed by central aortic repair. During central aortic repair, direct blood perfusion should be performed on the distal true lumen of the superior mesenteric artery, leading to resulting in favorable therapeutic outcomes. The research results indicate that even after surgical aortic repair, intestinal ischemic necrosis may still occur. In such cases, prompt laparotomy and necessary necrotic bowel resection are crucial for saving the patient’s life.

Abstract Acute type A aortic dissection is a life-threatening cardiovascular disease characterized by rapid onset and high mortality. Emergency surgery is the preferred and reliable treatment option. However, postoperative complications significantly impact patient prognosis. Hypoxemia, a common complication, poses challenges in clinical treatment, negatively affecting patient outcomes and increasing the risk of mortality. Therefore, it is crucial to study and comprehend the risk factors and treatment strategies for hypoxemia following acute type A aortic dissection to facilitate early intervention.

Abstract As for Atrazine (C8H14ClN5) degradation in soil, iron (Fe)-manganese (Mn) bimetallic biochar composites were proved to be more efficient for persulfate (PS) activation than monometallic ones. The atrazine removal rates of Fe/Mn loaded biochar + PS systems were 2.17–2.89 times higher than Fe/Mn loaded biochar alone. Compared with monometallic biochar, the higher atrazine removal rates by bimetallic biochar (77.2–96.7%) were mainly attributed to the synergy degradation and adsorption due to the larger amounts of metal oxides on the biochar surface. Atrazine degradation in Fe-rich biochar systems was mainly attributed to free radicals (i.e., $${\text{SO}}_{4}^{ \cdot - }$$ SO 4 · - and ·OH) through oxidative routes, whereas surface-bound radicals, 1O2, and free radicals were responsible for the degradation of atrazine in Mn-rich biochar systems. Furthermore, with a higher ratio of Fe(II) and Mn(III) formed in Fe-rich bimetallic biochar, the valence state exchange between Fe and Mn contributed significantly to the more effective activation of PS and the generation of more free radicals. The pathways of atrazine degradation in the Fe-rich bimetallic biochar systems involved alkyl hydroxylation, alkyl oxidation, dealkylation, and dechlorohydroxylation. The results indicated that bimetallic biochar composites with more Fe and less Mn are more effective for the PS-based degradation of atrazine, which guides the ration design of easily available carbon materials targeted for the efficient remediation of various organic-polluted soil. Graphical Abstract

Abstract Background Prior studies have reported a potential relationship between depressive disorder (DD), immune function, and inflammatory response. Some studies have also confirmed the correlation between immune and inflammatory responses and Bell’s palsy. Considering that the pathophysiology of these two diseases has several similarities, this study investigates if DD raises the risk of developing Bell’s palsy. Methods This nationwide propensity score-weighting cohort study utilized Taiwan National Health Insurance data. 44,198 patients with DD were identified as the DD cohort and 1,433,650 adult subjects without DD were identified as the comparison cohort. The inverse probability of treatment weighting (IPTW) strategy was used to balance the differences of covariates between two groups. The 5-year incidence of Bell’s palsy was evaluated using the Cox proportional-hazard model, presenting results in terms of hazard ratios (HRs) and 95% confidence intervals (CIs). Results The average age of DD patients was 48.3 ± 17.3 years, and 61.86% were female. After propensity score-weighting strategy, no significant demographic differences emerged between the DD and comparison cohort. The Cox proportional hazards model revealed a statistically significant adjusted IPTW-HR of 1.315 (95% CI: 1.168–1.481) for Bell’s palsy in DD patients compared to comparison subjects. Further independent factors for Bell’s palsy in this model were age (IPTW-HR: 1.012, 95% CI: 1.010–1.013, p

Abstract This study aimed to investigate the association between irritable bowel syndrome (IBS) and Parkinson’s disease (PD) utilizing prospective cohort study and Mendelian randomization. The dataset contained a substantial cohort of 426,911 participants from the UK Biobank, discussing the association between IBS and PD with Cox proportional hazards models and case-control analysis while adjusting for covariates such as age, gender, ethnicity and education level. In univariate Cox regression model, the risk of PD was reduced in IBS patients (HR: 0.774, 95%CI: 0.625–0.956, P = 0.017), but the statistical significance diminished in the three models after adjusting for other variables. In a few subgroup analyses, IBS patients are less likely to develop into PD, and patients diagnosed with IBS after 2000 also had a lower risk (HR: 0.633, 95%CI: 0.403–0.994, P = 0.047) of subsequently developing PD. In addition, we matched five healthy control participants based on gender and age at the end of the study for each IBS patient diagnosed during the follow-up period, and logistic regression results (OR:1.239, 95%CI: 0.896–1.680, P = 0.181) showed that IBS was not associated with the risk of PD. Mendelian randomization did not find significant evidence of the causal relationship between IBS and Parkinson’s disease (OR: 0.801, 95%CI: 0.570–1.278, P = 0.204). Overall, we suggest that IBS status is not associated with the risk of developing PD, and that these findings provide valuable insights into the clinical management and resource allocation of patients with IBS.

Abstract Background Identifying moral behavior in complex situations is the key ability for children to develop prosocial behavior. The theory of mind (ToM) and empathy provide the cognition and emotional motivation required for the development of moral sensitivity. In this study, we investigated the associations among ToM, empathy, and moral sensitivity and explored the possible differences between Chinese preschool children aged 4 and 5 years. Methods One hundred and thirty children completed the unexpected-content and change-of-location tasks as well as questionnaires about empathy and moral sensitivity individually. A one-way analysis of variance and the multi-group mediation SEM were used to examine the associations of the three variables and age differences. Results The scores of 5-year-old children in the dimensions of care, fairness, authority, and sanctity and the total score were higher than those of 4-year-old children. Moral sensitivity was positively correlated with both ToM and empathy after we controlled for verbal IQ and gender. Multigroup mediation analyses showed age-based differences in the associations among moral sensitivity, ToM, and empathy. Empathy’s mediation effect was partial among 4-year-old children and complete among 5-year-old children. Conclusions These findings contribute to understanding the cognitive and emotional factors in the formation of children’s moral sensitivity. They also point to a promising approach to promoting the development of moral sensitivity and evidence for educators to understand the process of children’s socialization.

Pulmonary fibrosis (PF) is a devastating lung disease with limited treatment options. During this pathological process, the profibrogenic macrophage subpopulation plays a crucial role, making the characterization of this subpopulation fundamentally important. The present study revealed a positive correlation between pulmonary macrophages with higher mitochondrial mass (Mømitohigh) and fibrosis. Among the Mømitohigh subpopulation of CD206+ M2, characterized by higher expression of dynamin 1-like (Drp1), as determined by flow cytometry and RNA-seq analysis, a therapeutic intervention was developed using an exosome-based formula composed of pathfinder and therapeutics. A pathfinder exosome called “exosomeMMP19 (ExoMMP19)”, was constructed to display matrix metalloproteinase-19 (MMP19) on the surface to locally break down the excessive extracellular matrix (ECM) in the fibrotic lung. A therapeutic exosome called “exosome therapeutics (ExoTx)”, was engineered to display D-mannose on the surface while encapsulating siDrp1 inside. Prior delivery of ExoMMP19 degraded excessive ECM and thus paved the way for ExoTx to be delivered into Mømitohigh, where ExoTx inhibited mitochondrial fission and alleviated PF. This study has not only identified Mømitohigh as profibrotic macrophages but it has also provided a potent strategy to reverse PF via a combination of formulated exosomes.

Rationale and objectives: This study aimed to investigate the effect of intestinal dysbiosis on the hippocampal volume using proton magnetic resonance spectroscopy (1H-MRS) in a type 2 diabetes mellitus (T2DM) rat model. Materials and methods: We established a T2DM animal model with high-fat diet and streptozotocin (HFD/STZ) administration to Sprague-Dawley rats. Short-term ceftriaxone sodium administration was used to establish a T2DM intestinal dysbiosis (T2DM-ID) model. After establishing the model, fecal microbiota were detected using 16S rRNA sequencing. The models were then subjected to magnetic resonance imaging (MRI). Associations between MRI findings and fecal microbiota were evaluated. Results: Magnetic resonance imaging (MRI) showed that the bilateral hippocampal voxel value and N-acetylaspartate (NAA) level were lower in the experimental group than in the normal control (NC) group (p

Purpose: To analyze and compare clinical research trends and hot topics in allergic rhinitis (AR) and asthma and provide valuable theoretical data and references for future research. Methods: Clinical studies focusing on AR or asthma published from 2013 to 2023 were retrieved from the Web of Science Core Collection. Eligible articles were screened and analyzed using bibliometrics from multiple indicators. Results: A total of 261 eligible articles on AR and 991 qualified articles on asthma were screened. The following bibliometric analyses identified the Journal of Allergy and Clinical Immunology as the most influential publication on AR and asthma and proved the significant contributions of Harvard University in clinical studies on AR and asthma. The analyses also revealed that the top ten prolific authors for AR were from China, the United Kingdom, Japan, and Germany, whereas the top ten productive authors for asthma were mainly from the USA. Collaborations among countries for AR were relatively concentrated in the Occident, whereas international cooperation on asthma was mainly achieved by the Occident and certain Eastern countries. Conclusions: This study compared and analyzed the current status and evolution of AR and asthma-related clinical research using bibliometric analysis. Additionally, the study comprehensively summarized the impactful authors, institutions, and countries, and revealed the replacement and evolution of hotspots.

IntroductionAlzheimer’s disease (AD) is the most widespread neurodegenerative disease in the world. Previous studies have shown that peripheral immune dysregulation plays a paramount role in AD, but whether there is a protective causal relationship between peripheral immunophenotypes and AD risk remains ambiguous.MethodsTwo-sample Mendelian randomization (MR) was performed using large genome-wide association study (GWAS) genetic data to assess causal effects between peripheral immunophenotypes and AD risk. Utilizing the genetic associations of 731 immune cell traits as exposures. We adopted the inverse variance weighted method as the primary approach. The Weighted median and MR-Egger regression methods were employed as supplements. Various sensitivity analyses were performed to assess the robustness of the outcomes.ResultsBased on the IVW method, we identified 14 immune cell traits that significantly reduced the risk of AD, of which six demonstrated statistical significance in both IVW and Weighted median methods. Among the seven immune traits, four were related to regulatory T (Treg) cells : (1) CD25++ CD45RA- CD4 not regulatory T cell % T cell (odds ratio (OR) [95% confidence interval (CI)] = 0.96 [0.95, 0.98], adjusted P = 1.17E−02), (2) CD25++ CD45RA- CD4 not regulatory T cell % CD4+ T cell (OR [95% CI] = 0.97 [0.96, 0.99], adjusted P = 3.77E−02), (3) Secreting CD4 regulatory T cell % CD4 regulatory T cell (OR [95% CI] = 0.98 [0.97, 0.99], adjusted P = 7.10E−03), (4) Activated & secreting CD4 regulatory T cell % CD4 regulatory T cell(OR [95% CI] = 0.98 [0.97, 0.99], adjusted P = 7.10E−03). In addition, HLA DR++ monocyte % monocyte (OR [95% CI] = 0.93 [0.89, 0.98], adjusted P = 4.87E−02) was associated with monocytes, and HLA DR on myeloid Dendritic Cell (OR [95% CI] = 0.93 [0.89, 0.97], adjusted P = 1.17E−02) was related to dendritic cells (DCs).ConclusionThese findings enhance the comprehension of the protective role of peripheral immunity in AD and provide further support for Treg and monocyte as potential targets for immunotherapy in AD.

The mortality of hepatocellular carcinoma (HCC) is on the rise globally, particularly in the Western world, with etiology gradually shifting from virus-related liver diseases to metabolic disorders such as non-alcoholic fatty liver disease. Early detection of HCC is challenging, and effective prognostic indicators are currently lacking, urgently necessitating reliable markers to assist in treatment planning and clinical management. Here, we introduce hepatocellular carcinoma senescence genes (HSG) to assess cellular senescence in HCC and devise a hepatocellular carcinoma senescence score (HSS) for prognostic prediction. Higher HSS levels signify poorer prognosis and increased tumor proliferation activity. Additionally, we observe alterations in the tumor immune microenvironment with higher HSS levels, such as increased infiltration of Treg, potentially providing a basis for immunotherapy. Furthermore, we identify key genes, such as PTTG1, within the senescence gene set and demonstrate their regulatory roles in HCC cells and Treg through experimentation. In summary, we establish a scoring system based on hepatocellular carcinoma senescence genes for prognostic prediction in HCC, potentially offering guidance for clinical treatment planning.

Oedaleus decorus asiaticus (O. asiaticus), the dominant species of steppe locust, plays a crucial role in driving the dynamic changes of the grassland ecosystem. However, there are a limited number of studies on the impact of locust feeding on the relationship of the major plants in the species community. This study has employed the Shannon-Wiener index, Pianka index, and the maximum information coefficient (MIC) to assess the impact of O. asiaticus feeding on the community structure and interspecific relationships in the grasslands of Inner Mongolia. The chosen indices measured niche breadth, niche overlap, and interspecies correlation. The topological network structure between the main species was further analyzed. The results indicated that: 1) locust gnawing expands the niche width of major species and increases the niche overlap index of food-loving species; 2) the feeding of locusts reduces the overall correlation between species but increases the interspecific relatedness between food-loving species and other species. 3) the number of links in the species topological network structure is reduced due to locust gnawing.

Objective: The increasing identification of pulmonary nodules has led to a growing emphasis on segmentectomy. Nevertheless, the surgical process for segmentectomy is complex and optimizing segmentectomy is a critical clinical concern. This study aimed to evaluate the safety and short- and long-term efficacy of V6-preserving superior segmentectomy. Methods: We performed a retrospective analysis of patients who underwent thoracoscopic superior segmentectomy at our hospital between January 2019 and June 2020. Eligible patients were categorized into an V6 vein-preserving segmentectomy (VVPS) group and a Non V6 vein-preserving segmentectomy (NVVPS) group depending on the preservation of V6. Primary outcome measures encompassed the evaluation of surgical safety (surgical margins, 3-year overall survival, and disease-free survival), whereas secondary measures included postoperative complication rates, operative time, estimated intraoperative blood loss, length of hospital stay, and associated costs. Results: The analysis included a final cohort of 78 patients. In the NVVPS group (n = 43), 95.3 % of patients exceeded the tumor diameter, and no positive surgical margins were observed. The 3-year overall survival (OS) and disease-free survival (DFS) rates for the NVVPS group were 95.3 %, with no significant differences in OS (p = 0.572) and DFS (P = 0.800) compared with the VVPS group. Additionally, the median total hospitalization cost for the NVVPS group was 41,400 RMB (IQR, 38,800–43,400), which was significantly lower than that of the VVPS group, showing statistical significance (P 0.05). Conclusion: V6-preserving superior segmentectomy is a secure and optimized surgical alternative. Its streamlined procedure facilitates easier adoption in primary healthcare facilities, rendering it a superior choice for superior segmentectomy.

Depression ranks as the fourth most prevalent global disease, with suicide incidents occurring at a younger age. Sulpiride (SUL), an atypical antidepressant drug acting as a dopamine D2 receptor antagonist and possessing anti-inflammatory properties, exhibits limited ability to penetrate the blood brain barrier (BBB). This weak penetration hampers its inhibitory effect on prolactin release in the pituitary gland, consequently leading to hyperprolactinemia. In order to enhance the central nervous system efficacy of sulpiride and reduce serum prolactin levels, we covalently linked sulpiride to VPALR derived from the nuclear DNA repair protein ku70. In vivo study on depressive mice using intraperitoneal injection of VPALR-SUL demonstrated a significant increase in struggle time and total distance compared to those treated with only sulpiride while also reducing serum prolactin concentration. The pharmacokinetic study results showed that VPALR-SUL prolonged half-life and increased bioavailability. In conclusion, VPALR-SUL exhibited potential for enhancing sulpiride transport across the BBB, augmenting its antidepressant effects, and reducing serum prolactin levels. This study laid a foundation for improving sulpiride delivery and developing novel antidepressants.

Abstract Traditional villages are China's cultural heritage resources; they carry rich historical and cultural information and have important historical significance and cultural value. Studying their spatial forms can suggest new ideas for the protection of traditional villages. The spatial configuration of traditional villages is shaped by a complex interplay of natural geography, socio-economic factors, transportation infrastructure, and essential facilities. Various developmental scenarios lead to diverse spatial development patterns, each demonstrating unique dynamic characteristics throughout its evolution. This article focuses on the exploration of the spatial morphology of Jiuguan Village, located along the Jingxing Ancient Post Road. By using kernel density analysis, space syntax, spatial form index, and so on, the spatial form of Jiuguan Village was studied from three aspects: public facilities clustering degree, road system, and spatial form index. Through a hierarchical approach involving points, lines, and planes, our study unveils the multifaceted influence of transportation factors on the village's historical development and its dynamic adaptive attributes within the context of traditional village spatial morphology. The results indicated that the location advantage of traffic is the driving force behind land expansion. Secondly, the areas with high traffic accessibility tend to be public spaces in villages. Third, the change in the transportation market will lead to a change in village land use functions. Finally, the renewal of transportation modes will change the spatial scale of the village. This research offers a deeper comprehension of the historical context surrounding traditional villages and provides a scientifically guided framework for heritage preservation and sustainable village development.

Introduction This study explores the association of individual cognition and social environment of smoking with autonomy over tobacco, providing evidence and insights to help smokers effectively prevent and reduce tobacco dependence. Methods Data were collected from 1389 participants, aged ≥15 years, by face-toface interviews from June 2018 to November 2019 in central China. We assessed autonomy over tobacco using the Autonomy Over Smoking Scale (AUTOS), including Withdrawal Symptoms (WS), Psychological Dependence (PD) and Cueinduced Cravings (CC), and examined factors of individual cognition and social environment, as well as covariates, including demographic characteristics, health status, and smoking behavior. Results AUTOS total score was 16.92 ± 9.05, WS score was the lowest (4.40 ± 3.36) in the three subscales, and CC score was the highest (6.88 ± 3.2). After adjustment, WS score of having a greater awareness of smoking hazards to one's own health was lower than those who had no awareness (β=0.14; 95% CI: -0.31– 0.00), and the total score of AUTOS, the score of PD and CC for those who thought smoking was ‘more helpful (high)’ to interpersonal communication were higher than ‘not helpful (not at all)’ (β=0.14; 95% CI: 0.01–0.28 with β=0.16; 95% CI: 0.02–0.29; and β=0.14; 95% CI: 0.00–0.28; respectively). Having a greater difficulty in smoking cessation was associated with higher AUTOS total and subscale scores (p

Abstract This paper proposes a fluid classifier for a tight reservoir using a quantum neural network (QNN). It is difficult to identify the fluid in tight reservoirs, and the manual interpretation of logging data, which is an important means to identify the fluid properties, has the disadvantages of a low recognition rate and non-intelligence, and an intelligent algorithm can better identify the fluid. For tight reservoirs, the logging response characteristics of different fluid properties and the sensitivity and relevance of well log parameter and rock physics parameters to fluid identification are analyzed, and different sets of input parameters for fluid identification are constructed. On the basis of quantum neural networks, a new method for combining sample quantum state descriptions, sensitivity analysis of input parameters, and wavelet activation functions for optimization is proposed. The results of identifying the dry layer, gas layer, and gas–water co-layer in the tight reservoir in the Sichuan Basin of China show that different input parameters and activation functions affect recognition performance. The proposed quantum neural network based on hybrid parameters and a wavelet activation function has higher fluid identification accuracy than the original quantum neural network model, indicating that this method is effective and warrants promotion and application.