[Risk factors for cow's milk protein allergy in infants: a multicenter prospective nested case-control study]. / å©´å„¿ç‰›å¥¶è›‹ç™½è¿‡æ•çš„å±é™©å› ç´ ï¼šä¸€é¡¹å¤šä¸­å¿ƒå‰çž»æ€§å·¢å¼ç— ä¾‹å¯¹ç §ç ”ç©¶.

OBJECTIVES: To explore the risk factors associated with cow's milk protein allergy (CMPA) in infants. METHODS: This study was a multicenter prospective nested case-control study conducted in seven medical centers in Beijing, China. Infants aged 0-12 months were included, with 200 cases of CMPA infants and 799 control infants without CMPA. Univariate and multivariate logistic regression analyses were used to investigate the risk factors for the occurrence of CMPA. RESULTS: Univariate logistic regression analysis showed that preterm birth, low birth weight, birth from the first pregnancy, firstborn, spring birth, summer birth, mixed/artificial feeding, and parental history of allergic diseases were associated with an increased risk of CMPA in infants (P<0.05). Multivariate logistic regression analysis revealed that firstborn (OR=1.89, 95%CI: 1.14-3.13), spring birth (OR=3.42, 95%CI: 1.70-6.58), summer birth (OR=2.29, 95%CI: 1.22-4.27), mixed/artificial feeding (OR=1.57, 95%CI: 1.10-2.26), parental history of allergies (OR=2.13, 95%CI: 1.51-3.02), and both parents having allergies (OR=3.15, 95%CI: 1.78-5.56) were risk factors for CMPA in infants (P<0.05). CONCLUSIONS: Firstborn, spring birth, summer birth, mixed/artificial feeding, and a family history of allergies are associated with an increased risk of CMPA in infants.

circRNAs as prognostic markers in pediatric acute myeloid leukemia.

Circular RNAs (circRNAs) arise from precursor mRNA processing through back-splicing and have been increasingly recognized for their functions in various cancers including acute myeloid leukemia (AML). However, the prognostic implications of circRNA in AML remain unclear. We conducted a comprehensive genome-wide analysis of circRNAs using RNA-seq data in pediatric AML. We revealed a group of circRNAs associated with inferior outcomes, exerting effects on cancer-related pathways. Several of these circRNAs were transcribed directly from genes with established functions in AML, such as circRUNX1, circWHSC1, and circFLT3. Further investigations indicated the increased number of circRNAs and linear RNAs splicing were significantly correlated with inferior clinical outcomes, highlighting the pivotal role of splicing dysregulation. Subsequent analysis identified a group of upregulated RNA binding proteins in AMLs associated with high number of circRNAs, with TROVE2 being a prominent candidate, suggesting their involvement in circRNA associated prognosis. Through the integration of drug sensitivity data, we pinpointed 25 drugs that could target high-risk AMLs characterized by aberrant circRNA transcription. These findings underscore prognostic significance of circRNAs in pediatric AML and offer an alternative perspective for treating high-risk cases in this malignancy.

Hypertension combined with limitations in activities of daily living and the risk for cardiovascular disease.

OBJECTIVE: The aim of present study was to evaluate the combined effect of hypertension and activities of daily living (ADL)/instrumental activities of daily living (IADL) with the risk of CVD, stroke and cardiac events. METHODS: A total of 14,083 participants aged 45 years or older from the China Health and Retirement longitudinal study were included in current study. Participants were divided into 4 groups according to hypertension and ADL/IADL status. Cox proportional hazards regression model was used to explore the associations between hypertension, ADL/IADL and new-onset CVD, stroke and cardiac events. RESULTS: During the 7-year follow-up, a total of 2,324 respondents experienced CVD (including 783 stroke and 1,740 cardiac events). Individuals with limitations in ADL alone, or with hypertension alone, or with both limitations in ADL and hypertension were associated with increased risk of CVD, with the adjusted hazard ratios (95% confidence intervals) were 1.17(1.00-1.35), 1.36(1.24-1.49) and 1.44(1.23-1.68), respectively. Those with limitations in ADL and hypertension also had higher risk of stroke (hazard ratios = 1.64; 1.26-2.14) and cardiac events (hazard ratios = 1.37; 1.14-1.64). Similarly, individuals with both limitations in IADL and hypertension were associated with increased risk of CVD (hazard ratios = 1.34; 1.15-1.57), stroke (hazard ratios = 1.50; 1.17-1.95) and cardiac events (hazard ratios = 1.27; 1.06-1.53). CONCLUSION: Hypertension and limitations in ADL/IADL jointly increased the risk of CVD, stroke and cardiac events.

Assessment of surrogate models for flood inundation: The physics-guided LSG model vs. state-of-the-art machine learning models.

Hydrodynamic models can accurately simulate flood inundation but are limited by their high computational demand that scales non-linearly with model complexity, resolution, and domain size. Therefore, it is often not feasible to use high-resolution hydrodynamic models for real-time flood predictions or when a large number of predictions are needed for probabilistic flood design. Computationally efficient surrogate models have been developed to address this issue. The recently developed Low-fidelity, Spatial analysis, and Gaussian Process Learning (LSG) model has shown strong performance in both computational efficiency and simulation accuracy. The LSG model is a physics-guided surrogate model that simulates flood inundation by first using an extremely coarse and simplified (i.e. low-fidelity) hydrodynamic model to provide an initial estimate of flood inundation. Then, the low-fidelity estimate is upskilled via Empirical Orthogonal Functions (EOF) analysis and Sparse Gaussian Process models to provide accurate high-resolution predictions. Despite the promising results achieved thus far, the LSG model has not been benchmarked against other surrogate models. Such a comparison is needed to fully understand the value of the LSG model and to provide guidance for future research efforts in flood inundation simulation. This study compares the LSG model to four state-of-the-art surrogate flood inundation models. The surrogate models are assessed for their ability to simulate the temporal and spatial evolution of flood inundation for events both within and beyond the range used for model training. The models are evaluated for three distinct case studies in Australia and the United Kingdom. The LSG model is found to be superior in accuracy for both flood extent and water depth, including when applied to flood events outside the range of training data used, while achieving high computational efficiency. In addition, the low-fidelity model is found to play a crucial role in achieving the overall superior performance of the LSG model.

miR-130b regulates B cell proliferation via CYLD-mediated NF-κB signaling.

Previous studies have revealed that B cell activation is regulated by various microRNAs(miRNAs). However, the role of microRNA-130b regulating B cell activation and apoptosis is still unclear. In the present study, we first found that the expression of miR-130b was the lowest in Pro/Pre-B cells and the highest in immature B cells. Besides, the expression of miR-130b decreased after activation in B cells. Through the immuno-phenotypic analysis of miR-130b transgenic and knockout mice, we found that miR-130b mainly promoted the proliferation of B cells and inhibited B cell apoptosis. Furthermore, we identified that Cyld, a tumor suppressor gene was the target gene of miR-130b in B cells. Besides, the Cyld-mediated NF-κB signaling was increased in miR-130b overexpressed B cells, which further explains the enhanced proliferation of B cells. In conclusion, we propose that miR-130b promotes B cell proliferation via Cyld-mediated NF-κB signaling, which provides a new theoretical basis for the molecular regulation of B cell activation.

Nephropathy Is Aggravated by Fatty Acids in Diabetic Kidney Disease through Tubular Epithelial Cell Necroptosis and Is Alleviated by an RIPK-1 Inhibitor.

Introduction: Diabetic kidney disease (DKD), one of the leading causes of end-stage renal disease, has complex pathogenic mechanisms and few effective clinical therapies. DKD progression is accompanied by the loss of renal resident cells, followed by chronic inflammation and extracellular matrix deposition. Necroptosis is a newly discovered form of regulated cell death and is a major form of intrinsic cell loss in certain diabetic complications such as cardiomyopathy, intestinal disease, and retinal neuropathy; however, its significance in DKD is largely unknown. Methods: In this study, the expression of necroptosis marker phosphorylated MLKL (p-MLKL) in renal biopsy tissues of patients with DKD was detected using immunofluorescence and semiquantified using immunohistochemistry. The effects of different disease-causing factors on necroptosis activation in human HK-2 cells were evaluated using immunofluorescence and Western blotting. db/db diabetic mice were fed a high-fat diet to establish an animal model of DKD with significant renal tubule damage. Mice were treated with the RIPK1 inhibitor RIPA-56 to evaluate its renal protective effects. mRNA transcriptome sequencing was used to explore the changes in signaling pathways after RIPA-56 treatment. Oil red O staining and electron macroscopy were used to observe lipid droplet accumulation in renal biopsy tissues and mouse kidney tissues. Results: Immunostaining of phosphorylated RIPK1/RIPK3/MLKL verified the occurrence of necroptosis in renal tubular epithelial cells of patients with DKD. The level of the necroptosis marker p-MLKL correlated positively with the severity of renal functional, pathological damages, and lipid droplet accumulation in patients with DKD. High glucose and fatty acids were the main factors causing necroptosis in human renal tubular HK-2 cells. Renal function deterioration and renal pathological injury were accelerated, and the necroptosis pathway was activated in db/db mice fed a high-fat diet. Application of RIPA-56 effectively reduced the degree of renal injury, inhibited the necroptosis pathway activation, and reduced necroinflammation and lipid droplet accumulation in the renal tissues of db/db mice fed a high-fat diet. Conclusion: The present study revealed the role of necroptosis in the progression of DKD and might provide a new therapeutic target for the treatment of DKD.

Application Value of Combined Detection of miR-208 and miR-92a in Early Diagnosis of Myocardial Infarction.

Objective: Myocardial infarction (MI) is a common and serious cardiovascular disease with increasing incidence and mortality rates, making it a major global public health issue. Molecular biology research has shown that the cleavage products miR-208 and miR-92a are microRNAs (miRNAs) associated with myocardial injury. Therefore, this study aims to establish a predictive model and explore the application value of the combined detection of miR-208 and miR-92a in the early diagnosis of MI in microRNA. Methods: Plasma samples were collected from 231 volunteers divided into 30 healthy and 201 diseased subjects From January 1st, 2021 to December 30th, 2021. Plasma RNA was extracted using a TRIZOL kit, and levels of miR-208 and miR-92a were determined using a real-time polymerase chain reaction (PCR) assay. Subsequently, the logistic regression model, decision tree model analysis, and receiver operating characteristic (ROC) curve were used to evaluate whether miR-208 combined with miR-92a could be used as a biomarker for MI early diagnosis. Results: In this study, the ROC curve evaluation of the logistic regression model and pruned decision tree model found that age, miR-208, and miR-92a had high early diagnostic accuracy for MI, and the area under the curve (AUC) reached 0.928, showing good predictive value. It was also found that the AUC, optimal threshold, sensitivity, and specificity of age, miR-208, and miR-92a were higher than those of age and miR-208. This indicates that the combination of age, miR-208, and miR-92a has more value in the early diagnosis of MI. Conclusion: The combined diagnosis of miR-208 and miR-92a is helpful for the early diagnosis of myocardial infarction, which might serve as a new marker of MI benefiting from its early diagnosis.

Chromatin accessibility landscape of relapsed pediatric B-lineage acute lymphoblastic leukemia.

For around half of the pediatric B-lineage acute lymphoblastic leukemia (B-ALL) patients, the molecular mechanism of relapse remains unclear. To fill this gap in knowledge, here we characterize the chromatin accessibility landscape in pediatric relapsed B-ALL. We observe rewired accessible chromatin regions (ACRs) associated with transcription dysregulation in leukemia cells as compared with normal B-cell progenitors. We show that over a quarter of the ACRs in B-ALL are in quiescent regions with high heterogeneity among B-ALLs. We identify subtype-specific and allele-imbalanced chromatin accessibility by integrating multi-omics data. By characterizing the differential ACRs between diagnosis and relapse in B-ALL, we identify alterations in chromatin accessibility during drug treatment. Further analysis of ACRs associated with relapse free survival leads to the identification of a subgroup of B-ALL which show early relapse. These data provide an advanced and integrative portrait of the importance of chromatin accessibility alterations in tumorigenesis and drug responses.

SUMOylation and DeSUMOylation: Prospective therapeutic targets in cancer.

The SUMO family is a type of ubiquitin-like protein modification molecule. Its protein modification mechanism is similar to that of ubiquitination: both involve modifier-activating enzyme E1, conjugating enzyme E2 and substrate-specific ligase E3. However, polyubiquitination can lead to the degradation of substrate proteins, while poly-SUMOylation only leads to the degradation of substrate proteins through the proteasome pathway after being recognized by ubiquitin as a signal factor. There are currently five reported subtypes in the SUMO family, namely SUMO1-5. As a reversible dynamic modification, intracellular sentrin/SUMO-specific proteases (SENPs) mainly regulate the reverse reaction pathway of SUMOylation. The SUMOylation modification system affects the localization, activation and turnover of proteins in cells and participates in regulating most nuclear and extranuclear molecular reactions. Abnormal expression of proteins related to the SUMOylation pathway is commonly observed in tumors, indicating that this pathway is closely related to tumor occurrence, metastasis and invasion. This review mainly discusses the composition of members in the protein family related to SUMOylation pathways, mutual connections between SUMOylation and other post-translational modifications on proteins as well as therapeutic drugs developed based on these pathways.

Dulaglutide Protects Mice against Diabetic Sarcopenia-Mediated Muscle Injury by Inhibiting Inflammation and Regulating the Differentiation of Myoblasts.

Background: Type 2 diabetes mellitus increases the risk of sarcopenia, which is characterized by decreased muscle mass, strength, and function. However, there are no effective drugs to treat diabetic sarcopenia, and its underlying mechanism remains unknown. Here, we aimed to determine whether the GLP-1 receptor agonist (GLP-1RA) dulaglutide (Dul) affects the progression of diabetic sarcopenia. Methods: db/db mice were injected intraperitoneally with 0.6 mg/kg dulaglutide for 10 weeks. Mouse muscle tissues were then pathologically evaluated and stained with F4/80 or MPO to detect macrophages and neutrophils, respectively. In addition, inflammatory factors and FNDC5 in the muscle tissues were detected using qRT-PCR. Moreover, C2C12 cells were induced to enable their differentiation into skeletal muscle cells, and muscle factor levels were then detected. Furthermore, changes in muscle factor levels were detected at various glucose concentrations (11 mM, 22 mM, and 44 mM). Results: In vivo, dulaglutide alleviated muscle tissue injury; reduced levels of the inflammatory factors, IL-1ß, IL-6, CCL2, and CXCL1; and reversed the level of FNDC5 in the muscle tissues of db/db mice. In vitro, a C2C12 cell differentiation model was established through the observation of cell morphology and determination of myokine levels. Upon stimulation with high glucose, the differentiation of C2C12 cells was inhibited. Dulaglutide improved this inhibitory state by upregulating the levels of both FNDC5 mRNA and protein. Conclusions: Treatment with the GLP-1RA dulaglutide protects db/db mice against skeletal muscle injury by inhibiting inflammation and regulating the differentiation of myoblasts. High glucose inhibited the differentiation of C2C12 cells and decreased the mRNA and protein levels of myokines. Dulaglutide could reverse the differentiation state induced in C2C12 cells by high glucose.

The differences in immune features and genomic profiling between squamous cell carcinoma and adenocarcinoma - A multi-center study in Chinese patients with uterine cervical cancer.

BACKGROUND: Squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the uterine cervix have distinct biological behaviors and different treatment responses. Studies on immune features and genomic profiling of these two pathologic types were limited and mainly focused on small patient cohorts. METHODS: From 2014 to 2021, 336 (254 SCC vs. 82 AC) cervical cancer patients who were diagnosed/treated in 7 medical centers in China were enrolled in the study. Next-generation sequencing of 425 cancer-relevant genes was performed on tumor tissues and liquid biopsies. Somatic alterations and immune response-related biomarkers were analyzed. Patient prognosis and immune infiltration were analyzed using data from The Cancer Genome Atlas (TCGA). RESULTS: AC tended to have more immunotherapy resistance-related STK11 alterations (P = 0.039), a higher proportion of microsatellite instability (P = 0.21), and more actionable mutations (P = 0.161). In contrast, higher tumor mutational burdens (TMB; P = 0.01), a higher proportion of TMB-high patients (P = 0.016), and more PD-L1-high patients (P = 0.0013) were observed in SCC. Multiple genetic alterations and aberrant signaling pathways were specifically enriched in AC (e.g., TP53, KRAS, ERBB2, and ARID1A alterations) or SCC (e.g., PIK3CA, FBXW7, EP300, and BAP1 mutations). Notably, AC-enriched genetic changes were significantly associated with decreased infiltrations of various B cells, T cells, and dendritic cells, whereas SCC-associated molecular features tended to be associated with increased CD4+ T cell infiltrations. CONCLUSIONS: This was the first multi-center study revealing the immunologic and genomic features between SCC and AC in Chinese patients with cervical cancer. Our findings have illustrated the difference in genetic profiles of those two cervical cancer subtypes, which may suggest the possibility of differential treatment regimens, with better immunotherapy efficacy in SCC and targeted therapy options more favorable in AC.

[Effect of superfine powder and aqueous extract of Polygonati Rhizoma on rats with natural perimenopausal syndrome].

This study aims to examine the effect of superfine powder and aqueous extract of Polygonati Rhizomaon on natural perimenopausal syndrome in rats and explore the underlying mechanism. To be specific, a total of 60 female SD rats(14-15 months old) with estrous cycle disorder were screened by the vaginal smear and randomized into model control group, ß-estradiol 3-benzoate group(0.1 mg·kg~(-1)), superfine powder of Polygonati Rhizoma group(0.25, 0.5 g·kg~(-1)) and aqueous extract of Polygonati Rhizoma group(0.25, 0.5 g·kg~(-1)), and another 10 female SD rats(14-15 months old) were selected as the youth control group. The administration lasted 6 weeks. Then the perimenopausal syndrome-related indexes such as body temperature, microcirculatory blood flow of face and ear, vertigo period, salivary secretion, grip force, and bone strength were determined and open field test was conducted. The immune system-related indexes such as the wet weight and index of thymus and spleen, percentage of T lymphocytes and subgroups in peripheral blood, and hematological indexes were measured. In addition, the ovary-related indexes such as estrous cycle, the wet weight and index of uterus and ovary, ovarian tissue morphology, and cell apoptosis were determined. Moreover, hypothalamus-pituitary-ovary axis(HPO)-related indexes such as serum sex hormone levels, cytochrome P450 family 11 subfamily A member 1(CYP11A1), cytochrome P450 family 19 subfamily A member 1(CYP19A1), and cytochrome P450 family 17 subfamily A member 1(P450 17A1) in ovarian tissue were measured. The results showed that the superfine powder and aqueous extract of Polygonati Rhizoma significantly decreased body temperature(anal, facial and dorsal temperature), microcirculatory blood flow in the ear, and vertigo period, increased salivary secretion, grip force, bone strength, total distance and total speed in the open field test, wet weight and index of thymus and spleen, lymphocyte ratio, CD3~+ level, and CD4~+/CD8~+ ratio, reduced neutrophil number and ratio, estrous cycle disorder ratio, and number of ovarian apoptotic cells, raised wet weight and index of uterus, wet weight of ovary, levels of inhibin B(INHB), estradiol(E_2), anti-müllerian hormone(AMH), and ovarian CYP11A1 and CYP19A1, decreased follicle-stimulating hormone(FSH) and luteinizing hormone(LH) content, and improved ovarian tissue morphology. It is suggested that the superfine powder and aqueous extract of Polygonati Rhizoma can improve the symptoms associated with natural perimenopausal syndrome in rats and enhance ovarian function and immune function. The mechanism is that they regulate HPO axis function by increasing estrogen synthesis.

Excited-state intramolecular proton transfer (ESIPT)-based fluorescent probes for biomarker detection: design, mechanism, and application.

Biomarkers are essential in biology, physiology, and pharmacology; thus, their detection is of extensive importance. Fluorescent probes provide effective tools for detecting biomarkers exactly. Excited state intramolecular proton transfer (ESIPT), one of the significant photophysical processes that possesses specific photoisomerization between Keto and Enol forms, can effectively avoid annoying interference from the background with a large Stokes shift. Hence, ESIPT is an excellent choice for biomarker monitoring. Based on the ESIPT process, abundant probes were designed and synthesized using three major design methods. In this review, we conclude probes for 14 kinds of biomarkers based on ESIPT explored in the past five years, summarize these general design methods, and highlight their application for biomarker detection in vitro or in vivo.

Immediate reconstruction of defects after a partial maxillectomy with a digitally planned, prefabricated, 3-dimensionally printed, esthetic obturator prosthesis.

A digital workflow was used to design and prefabricate a 3-dimensionally printed, esthetic obturator prosthesis for immediate placement after a partial maxillectomy. The approach involved simultaneous reciprocation and support of the maxillary defect during the surgery and minimized the incidence of cicatricial contracture of the soft tissue, preventing permanent facial deformity and dysfunction.

Cbl-b inhibited CD4+ T cell activation by regulating the expression of miR-99a/miR-125b.

The molecular regulation of T cell activation has always been a hot topic in immunology. It has been reported that Cbl-b inhibits T cell activation, but the specific molecular mechanism especially for transcriptional regulation has not been very clear so far. Our present study showed that ablation of Cbl-b resulted in the increased expression of miR-99a and miR-125b, and the antagonism of miR-99a or miR-125b could inhibit the Cbl-b-/- T cell over-activation partly. Further study demonstrated that Cbl-b could bind and ubiquitinate SHP-2 in the activated T cells. The activation of SHP-2 deficient T cells was significantly inhibited. Western blot showed that SHP-2 could dephosphorylate HOXA10, and HOXA10 could enter the nucleus under the stimulation of anti-CD3 antibody alone in Cbl-b deficient T cells. Luciferase reporter assay and CUT&Tag qPCR showed that HOXA10 could regulate the expression of miR-99a/miR-125b. Real-time PCR and western blot further indicated that miR-99a/miR-125b functioned on PI3K/AKT pathway to regulate T cell activation. In conclusion, our study demonstrated that Cbl-b ubiquitinated SHP-2 to arrest HOXA10-mediated CD4+ T cell activation by regulating the expression of miR-99a/miR-125b and their function on PI3K/AKT pathway, which might providing a new explanation for the regulation of T cell activation and potential new idea for autoimmune diseases and tumor immunotherapies.

Farmers' Preference for Participating in Rural Solid Waste Management: A Case Study from Shaanxi Province, China.

Rural solid waste management is an important method to improve rural living environments. Farmers' participation in rural solid waste management plays an essential role in sustainable waste management. Based on the micro-survey data of 592 farmers in Shaanxi province, a multinomial logit model was applied to explore farmers' preferences for participating in rural solid waste management. The empirical results show that both institutional and interpersonal trust have significant positive effects on farmers' payment participation, and labor and payment participation. Among environmental awareness, farmers with pro-environmental behavior prefer labor participation, and labor and payment participation; the more environmental knowledge farmers have, the stronger their preferences for payment participation, labor and payment participation, and labor participation; farmers concerned about environmental problems are more inclined to adopt labor and payment participation or payment participation. For socio-demographic characteristics, gender has no significant influence, while agricultural net income and education can significantly increase farmers' willingness to participate; farmers who have migrant work experience prefer to participate in payment; there are obvious intergenerational differences in the influence of social trust and environmental awareness on farmers' participation preference. Therefore, providing diversified participation modes, creating a good social trust environment, and enhancing farmers' awareness of environmental care are important in promoting rural solid waste management.

Effects of Dendrobium officinale ultrafine powder on sub-health mice induced by unhealthy lifestyle based on neuroendocrine immune system.

Sub-health status, in which a person's mind and body exist in a low-quality state of being between disease and health, has become an urgent public health problem that cannot be ignored globally. One of the most apparent sub-health symptoms is fatigue, and it also shows a significant decrease in mental vitality and adaptability caused by disruption of the neuroendocrine-immune system. Dendrobium officinale (DOF) has a long history of use in China as a medicinal food with immune-regulating, anti-fatigue, anti-oxidant, and hypoglycemic effects. The ameliorative effects of Dendrobium officinale on sub-health mice are investigated in this present study, as well as its underlying mechanisms via neuroendocrine-immune (NEI) modulation. Forty male KM mice were divided into normal control group (NC), model control group (MC), and two doses of ultrafine DOF powder (DOFP) intervention groups: DOFP-L (0.1 g kg-1), DOFP-H (0.2 g kg-1) groups. Sub-health mice were induced by mimicking unhealthy human lifestyles, including cold water swimming, limbs restriction, an unhealthy diet, and sleep deprivation for seven weeks. The findings revealed that DOFP intervened sub-health mice have less bodyweight loss, normal fecal morphology, as well as lower face temperature and blood flow, which is similar to the normal mice. Moreover, sub-health mice treated with DOFP showed improved forelimb grip strength and exercise endurance in weight-loaded exhaustion swimming and cold water exhaustion swimming, combined with reduced content of lactic acid (LD), lactate dehydrogenase (LDH), blood urea nitrogen (BUN) in the plasma, increased storage of liver glycogen (LG), and muscle glycogen (MG), as well as increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), reduced malondialdehyde (MDA) levels in the liver. Additionally, DOFP could increase the counts of autonomous movements of sub-health mice, minimize tail suspension time, and perform well in the elevated plus maze and open field tests, all of which are associated with anti-depression and anti-anxiety. Moreover, mechanistic investigations revealed that DOFP could alleviate plasma corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and cortisol (CORT) related hormones in the HPA axis, increase the level of hypothalamic norepinephrine (NE) and plasma ß-endorphin (ß-EP) of sub-health mice, while downregulating the content of 5-hydroxytryptamine (5-HT), dopamine (DA), and the relative mRNA expression of 5-HT1A and CRH in hypothalamus, and increase immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin M (IgM), and CD4+/CD8+ T cell ratio levels. In conclusion, DOFP can relieve symptoms such as fatigue and depression in sub-health mice by regulating the disorder of the neuroendocrine-immune network.

mRNA and lncRNA expression profiles of liver tissues in children with biliary atresia.

Progressive liver fibrosis is the most common phenotype in biliary atresia (BA). A number of pathways contribute to the fibrosis process so comprehensive understanding the mechanisms of liver fibrosis in BA will pave the way to improve patient's outcome after operation. In this study, the differentially expressed profiles of mRNAs and long non-coding RNAs from BA and choledochal cyst (CC) liver tissues were investigated and analyzed, which may provide potential clues to clarify hepatofibrosis mechanism in BA. A total of two BA and two CC liver tissue specimens were collected, the expression level of mRNAs and lncRNAs was detected by RNA sequencing. Differentially expressed mRNAs (DEmRNAs) were functionally annotated and protein-protein interaction networks (PPI) was established to predict the biological roles and interactive relationships. Differentially expressed lncRNAs (DElncRNAs) nearby targeted DEmRNA network and DElncRNA-DEmRNA co-expression network were constructed to further explore the roles of DElncRNAs in BA pathogenesis. The expression profiles of significant DEmRNAs were validated in Gene Expression Omnibus database. A total of 2,086 DEmRNAs and 184 DElncRNAs between BA and CC liver tissues were obtained. DEmRNAs were enriched in 521 Gene Ontology terms and 71 Kyoto Encyclopedia of Genes and Genomes terms which were mainly biological processes and metabolic pathways related to immune response and inflammatory response. A total of five hub proteins (TYRO protein tyrosine kinase binding protein, C-X-C motif chemokine ligand 8, pleckstrin, Toll-like receptor 8 and C-C motif chemokine receptor 5) were found in the PPI networks. A total of 31 DElncRNA-nearby-targeted DEmRNA pairs and 2,337 DElncRNA-DEmRNA co-expression pairs were obtained. The expression of DEmRNAs obtained from RNA sequencing were verified in GSE46960 dataset, generally. The present study identified key genes and lncRNAs participated in BA associated liver fibrosis, which may present a new avenue for understanding the patho-mechanism for hepatic fibrosis in BA.

A bibliometric and visualized analysis of early mobilization in intensive care unit from 2000 to 2021.

Background: Early mobilization in the intensive care unit (ICU) is a hotspot. This study aims to provide a bibliometric perspective of the progress in this field. Methods: We extracted publications on ICU early mobilization published in the Web of Science Core Collection database from 2000 to 2021. VOSviewer was used to construct co-occurrence and co-citation relationships for authors, references, and keywords; Citespace was used to visualize knowledge mapping of subject categories, countries, and keywords with the strongest citation bursts. Results: A total of 4,570 publications were analyzed, with a steady increase in publications in the field of ICU early mobilization. From a macro perspective, research on ICU early mobilization involves multidisciplinary involvement, including critical care medicine, neurology, and nursing; as for the meso perspective, the United States is the major contributor. Needham DM and Schweickert WD are the key researchers in this field. Moreover, the core journal is Critical Care Medicine, with the most publications and citations. The microscopic level, dominated by references and keywords, illustrates that the hotspot and frontier of research on ICU early mobilization focus on ICU-acquired weakness, delirium, the prognosis of critical illness, and severe COVID-19. Conclusion: This study presents a research landscape of ICU early mobilization from different perspectives. These findings will contribute to a better understanding of the current state of research in critical care medicine and provide the available information for future research ideas.

RNA-Binding Proteins in the Regulation of Adipogenesis and Adipose Function.

The obesity epidemic represents a critical public health issue worldwide, as it is a vital risk factor for many diseases, including type 2 diabetes (T2D) and cardiovascular disease. Obesity is a complex disease involving excessive fat accumulation. Proper adipose tissue accumulation and function are highly transcriptional and regulated by many genes. Recent studies have discovered that post-transcriptional regulation, mainly mediated by RNA-binding proteins (RBPs), also plays a crucial role. In the lifetime of RNA, it is bound by various RBPs that determine every step of RNA metabolism, from RNA processing to alternative splicing, nucleus export, rate of translation, and finally decay. In humans, it is predicted that RBPs account for more than 10% of proteins based on the presence of RNA-binding domains. However, only very few RBPs have been studied in adipose tissue. The primary aim of this paper is to provide an overview of RBPs in adipogenesis and adipose function. Specifically, the following best-characterized RBPs will be discussed, including HuR, PSPC1, Sam68, RBM4, Ybx1, Ybx2, IGF2BP2, and KSRP. Characterization of these proteins will increase our understanding of the regulatory mechanisms of RBPs in adipogenesis and provide clues for the etiology and pathology of adipose-tissue-related diseases.