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Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder primarily characterized by chronic visceral pain. Studies have reported that the anterior cingulate cortex (ACC) is involved in chronic visceral pain, however, the molecular mechanisms underlying this involvement remain largely unclear. In this study, we aimed to investigate the molecular mechanisms of the ACC in chronic visceral pain induced by neonatal maternal deprivation (NMD) in male mice. We showed that the expression of leucine-rich repeat-containing protein family member 8A (LRRC8A) at both mRNA and protein levels was significantly upregulated in the ACC of NMD male mice, with LRRC8A primarily co-localized in neurons. DCPIB, an inhibitor of LRRC8A, greatly alleviated chronic visceral pain. Moreover, the ATP concentration was significantly upregulated in the ACC of NMD male mice. However, LRRC8A was not involved in somatic pain induced by complete Freund’s adjuvant (CFA) injection into the hind paw. In conclusion, our findings demonstrate that LRRC8A plays a critical role in regulating chronic visceral pain in NMD mice. These findings are expected to provide new ideas for the treatment of chronic visceral pain in IBS patients.

Aims Chronic pancreatitis (CP) is a localized or diffuse chronic progressive inflammation of the pancreas that can be caused by a variety of factors and is characterized by abdominal pain. However, the underlying mechanisms are poorly understood. Increasing evidence suggests that central sensitization plays a crucial role in the development of visceral pain, but the precise mechanisms of central neural processing remain unclear. Methods CP was induced using repeated intraperitoneal injections of caerulein in mice. Neurospecific anterograde tracing was achieved using herpes simplex virus type 1 (HSV‐1). Fiber photometry was used to assess neuronal activity. Optogenetic, chemogenetic, or pharmacological approaches were applied to manipulate the lateral parabrachial nucleus (LPB) glutamatergic neurons. The abdominal withdrawal threshold (AWT) was measured to evaluate the CP pain. A glutamate sensor was used to detect glutamate release in the LPB. Results In the present study, we demonstrated that glutamatergic neurons in the LPB are activated in CP mice, leading to the development of CP pain. Notably, glutamatergic release is increased in the LPB, and the increased release primarily mediates CP pain by binding to the N‐methyl‐D‐aspartate (NMDA) receptor rather than α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors. Specifically, this process involves the binding of the N‐Methyl‐D‐Aspartate Receptor Subunit 2B (NR2B) in the LPB, leading to the development of CP pain. Conclusions This study identified the NR2B subunits of NMDA receptors in the LPB as playing a critical role in the regulation of CP pain. A structural connection between the pancreas and the brain was established and identified the mechanisms through which the lateral parabrachial nucleus (LPB) modulates chronic pancreatitis pain.

Objective To explore the psychological experience of Juvenile patient’s parents in Fangcang shelter hospital during the Omicron wave of COVID-19 pandemic. Methods A qualitative study was conducted by using a phenomenological research method. Sixteen parents of juvenile patients with COVID-19 were recruited from National Exhibition and Convention Center (Shanghai, China) Fangcang shelter hospital (FSH) using purposive sampling. Data were collected by face-to-face in-depth interviews over 27 days, from April 9 to May 6, 2022. The interview data were analyzed using Colaizzi seven-step analysis method. Results The psychological experiences of the parents of juvenile patients in the Fangcang shelter hospital were summarized into three themes: \"perception regarding the FSH\", \"worried about the unmet needs of juvenile patients \", and \"the psychological burden after discharge\". These themes were classified into 9 sub-themes, including the acceptance of FSH, adaptability to FSH, concerns about cross-infection in the FSH, special needs of infants and young children, psychological needs of preschool children, the learning demands of school-age children, concern about re-positive, fear of sequelae, worry about social acceptance. Conclusion Juvenile patients and their parents in the Fangcang shelter hospitals have both positive and negative experiences. It is suggested that facilities for minors should be planned in advance. Humanistic care for adolescent patients and health education for the public are also critical.

The biological macromolecule Nocardia rubra cell-wall skeleton (Nr-CWS) has well-established immune-stimulating and anti-tumor activities. However, the role of Nr-CWS on natural killer (NK) cells remains unclear. Here, we explore the function and related mechanisms of Nr-CWS on NK cells. Using a tumor-bearing model, we show that Nr-CWS has slightly effect on solid tumor. In addition, using a tumor metastasis model, we show that Nr-CWS suppresses the lung metastasis induced by B16F10 melanoma cells in mice, which indicates that Nr-CWS may up-regulate the function of NK cells. Further investigation demonstrated that Nr-CWS can increase the expression of TRAIL and FasL on spleen NK cells from Nr-CWS treated B16F10 tumor metastasis mice. The spleen index and serum levels of TNF-α, IFN-γ, and IL-2 in B16F10 tumor metastasis mice treated with Nr-CWS were significantly increased. In vitro , the studies using purified or sorted NK cells revealed that Nr-CWS increases the expression of CD69, TRAIL, and FasL, decreases the expression of CD27, and enhances NK cell cytotoxicity. The intracellular expression of IFN-γ, TNF-α, perforin (prf), granzyme-B (GrzB), and secreted TNF-α, IFN-γ, IL-6 of the cultured NK cells were significantly increased after treatment with Nr-CWS. Overall, the findings indicate that Nr-CWS could suppress the lung metastasis induced by B16F10 melanoma cells, which may be exerted through its effect on NK cells by promoting NK cell terminal differentiation (CD27 low CD11b high ), and up-regulating the production of cytokines and cytotoxic molecules.

Brain plasticity, including anatomical changes and functional reorganization, is the physiological basis of functional recovery after spinal cord injury（SCI）. The correlation between brain anatomical changes and functional reorganization after SCI is unclear. This study aimed to explore whether alterations of cortical structure and network function are concomitant in sensorimotor areas after incomplete SCI. Eighteen patients with incomplete SCI（mean age 40.94 ± 14.10 years old; male：female, 7：11） and 18 healthy subjects（37.33 ± 11.79 years old; male：female, 7：11） were studied by resting state functional magnetic resonance imaging. Gray matter volume（GMV） and functional connectivity were used to evaluate cortical structure and network function, respectively. There was no significant alteration of GMV in sensorimotor areas in patients with incomplete SCI compared with healthy subjects. Intra-hemispheric functional connectivity between left primary somatosensory cortex（BA1） and left primary motor cortex（BA4）, and left BA1 and left somatosensory association cortex（BA5） was decreased, as well as inter-hemispheric functional connectivity between left BA1 and right BA4, left BA1 and right BA5, and left BA4 and right BA5 in patients with SCI. Functional connectivity between both BA4 areas was also decreased. The decreased functional connectivity between the left BA1 and the right BA4 positively correlated with American Spinal Injury Association sensory score in SCI patients. The results indicate that alterations of cortical anatomical structure and network functional connectivity in sensorimotor areas were non-concomitant in patients with incomplete SCI, indicating the network functional changes in sensorimotor areas may not be dependent on anatomic structure. The strength of functional connectivity within sensorimotor areas could serve as a potential imaging biomarker for assessment and prediction of sensory function in patients with incomplete SCI. This trial was registered with the Chinese Clinical Trial Registry（registration number： Chi CTR-ROC-17013566）.

为提高砂姜黑土土壤水分的估测精度，本研究以河南省西平县砂姜黑土为研究对象，通过配制不同含水率土壤样本并在室内进行高光谱测量，对土壤样本高光谱数据平滑（SR）、倒对数[LOG（1/R）]、一阶微分（FD）、多元散射校正（MSC）、去包络线（CR）光谱变换后，结合连续投影算法（SPA）识别最佳特征波段，采用偏最小二乘回归（PLSR）、支持向量机回归（SVR）的机器学习方法和堆叠（Stacking）集成学习方法分别构建土壤含水率反演模型。结果表明：经MSC变换后光谱中土壤含水率相关信息增强最多；SPA算法能对砂姜黑土含水率光谱数据进行降维和特征信息提取；经反射光谱MSC变换后由PLSR和SVR集成的Stacking集成模型决定系数最高（R2=0.963）、均方根误差最小（RMSE=1.7）。研究表明，Stacking集成学习模型有效提升了模型的精度和泛化能力，是砂姜黑土含水率最佳反演模型。

Data privacy mechanisms are essential for rapidly scaling medical training databases to capture the heterogeneity of patient data distributions toward robust and generalizable machine learning systems. In the current COVID-19 pandemic, a major focus of artificial intelligence (AI) is interpreting chest CT, which can be readily used in the assessment and management of the disease. This paper demonstrates the feasibility of a federated learning method for detecting COVID-19 related CT abnormalities with external validation on patients from a multinational study. We recruited 132 patients from seven multinational different centers, with three internal hospitals from Hong Kong for training and testing, and four external, independent datasets from Mainland China and Germany, for validating model generalizability. We also conducted case studies on longitudinal scans for automated estimation of lesion burden for hospitalized COVID-19 patients. We explore the federated learning algorithms to develop a privacy-preserving AI model for COVID-19 medical image diagnosis with good generalization capability on unseen multinational datasets. Federated learning could provide an effective mechanism during pandemics to rapidly develop clinically useful AI across institutions and countries overcoming the burden of central aggregation of large amounts of sensitive data.

Peroxisome proliferator-activated receptor alpha (PPARα) and carnitine palmitoyltransferase 1 (CPT1) are important targets of lipid metabolism regulation for nonalcoholic fatty liver disease (NAFLD) therapy. In the present study, a set of novel indole ethylamine derivatives (4, 5, 8, 9) were designed and synthesized. The target product (compound 9) can effectively activate PPARα and CPT1a. Consistently, in vitro assays demonstrated its impact on the lipid accumulation of oleic acid (OA)-induced AML12 cells. Compared with AML12 cells treated only with OA, supplementation with 5, 10, and 20 μM of compound 9 reduced the levels of intracellular triglyceride (by 28.07%, 37.55%, and 51.33%) with greater inhibitory activity relative to the commercial PPARα agonist fenofibrate. Moreover, the compound 9 supplementations upregulated the expression of hormone-sensitive triglyceride lipase (HSL) and adipose triglyceride lipase (ATGL) and upregulated the phosphorylation of acetyl-CoA carboxylase (ACC) related to fatty acid oxidation and lipogenesis. This dual-target compound with lipid metabolism regulatory efficacy may represent a promising type of drug lead for NAFLD therapy.

In the current study, a series of laboratory triaxial loading and unloading experiments were conducted for the purpose of comprehensively understanding the effects on sandstone of loading processes under axial stress conditions and unloading processes under confining pressure conditions. The mechanical properties and crack propagation behaviors of sandstone specimens were analyzed. In addition, a new damage variable based on crack evolution was proposed. The experimental results showed that the strain-softening modulus of the sandstone specimens under triaxial loading and unloading compression conditions decreased with the increases in the loading rate. Meanwhile, the elastic modulus was only observed to undergo small changes. This study found that with the increases in the loading rates of axial stress, the deformation and strength levels of the sandstone specimens also increased. In addition, the crack initiation stress showed a linear increasing trend with the increases in the loading rates of axial stress. The peak crack volumetric strain displayed a slight increase with the loading rate of axial stress, which indicated that the larger the loading rate of axial stress on the sandstone specimens was, the smaller crack propagation strain levels at the peak stress levels would be. The crack propagation velocities were observed to be larger when the loading rates of axial stress were higher. Also, at the same loading rate of axial stress, the crack propagation velocity corresponding to the peak stress of the volumetric cracks was the largest, followed by radial cracks. The crack propagation velocity of the axial cracks was determined to be the smallest. In this study, a new crack damage variable based on crack volumetric strain was proposed. According to the evolution of the crack damage variables of the sandstone specimens, the following four stages of the failure process were obtained: original damage stage; elastic stage; linear damage stage; and accelerated damage stage. The results obtained in this research study provided an important scientific basis for the support of future designs and safety protection measures in underground mining operations.

SHP2 is a latent biomarker for predicting the survivals of solid tumors. However, the current researches were controversial. Therefore, a meta-analysis is necessary to assess the prognosis of SHP2 on tumor patients. Searched in PubMed, EMBASE and web of science databases for published studies until Jun 20, 2021. A meta-analysis was performed to evaluate the affect of SHP2 in clinical stages, disease-free survival (DFS) and overall survival (OS) in tumor patients. This study showed that the expression of SHP2 had no significant correlation with clinical stages (OR: 0.91; 95% CI, 0.60-1.38; P = 0.65), DFS (HR = 0.88; 95%CI: 0.58-1.34; P = 0.56) and OS (HR = 1.07, 95%CI: 0.79-1.45, P = 0.67), but the prognostic effect varied greatly with tumor sites. High SHP2 expression was positively related to early clinical stage in hepatocellular carcinoma, not associated with clinical stage in the most of solid tumors, containing laryngeal carcinoma, pancreatic carcinoma and gastric carcinoma, etc. Higher expression of SHP2 could predict longer DFS in colorectal carcinoma, while predict shorter DFS in hepatocellular carcinoma. No significant difference was observed in DFS for non-small cell lung carcinoma and thyroid carcinoma. Higher SHP2 expression was distinctly related to shorter OS in pancreatic carcinoma and laryngeal carcinoma. The OS of the other solid tumors was not significantly different. The prognostic value of SHP2 might not equivalent in different tumors. The prognostic effect of SHP2 is highly influenced by tumor sites.