Unrecognized extensive charge of microbial gas in the Junggar basin.

Different from the Qaidam basin with about 320 billion m3 microbial gas, only limited microbial gases were found from the Junggar basin with similarly abundant type III kerogen. To determine whether microbial gases have not yet identified, natural gas samples from the Carboniferous to Cretaceous in the Junggar basin have been analyzed for chemical and stable isotope compositions. The results reveal some of the gases from the Mahu sag, Zhongguai, Luliang and Wu-Xia areas in the basin may have mixed with microbial gas leading to straight ethane to butane trends with a "dogleg" light methane in the Chung's plot. Primary microbial gas from degradation of immature sedimentary organic matter is found to occur in the Mahu sag and secondary microbial gas from biodegradation of oils and propane occurred in the Zhongguai, Luliang and Beisantai areas where the associated oils were biodegraded to produce calcites with δ13C values from + 22.10‰ to + 22.16‰ or propane was biodegraded leading to its 13C enrichment. Microbial CH4 in the Mahu sag is most likely to have migrated up from the Lower Wuerhe Formation coal-bearing strata by the end of the Triassic, and secondary microbial gas in Zhongguai and Beisantan uplifts may have generated after the reservoirs were uplifted during the period of the Middle and Late Jurassic. This study suggests widespread distribution of microbial gas and shows the potential to find large microbial gas accumulation in the basin.

Growth Evaluation After Costochondral Graft Combined With Functional Appliance in Children With Temporomandibular Joint Ankylosis.

The treatment of temporomandibular joint (TMJ) ankylosis in children is a great challenge for surgeons. Costochondral graft (CCG) is a common method of reconstructing the TMJ in children. However, the growth pattern of CCG is unpredictable. In this study, we introduced a surgical-orthodontic approach and evaluated the growth results of the mandible and maxilla in children with TMJ ankylosis through 3-dimensional computed tomography measurements. A prospective cohort study was conducted on child patients diagnosed as having TMJ ankylosis between September 1, 2018 and June 1, 2020. Computer-aided virtual mandibular position guided the CCG, and removable functional appliance was used after surgery. The maximal incisal opening (MIO), the maxilla height, and the length of mandibular ramus were determined. Paired t test was performed to analyze the differences among various stages. Six patients (3 females, 3 males; aged 6-9 y) were included in this study. MIO was 12.4 mm before surgery and improved to 36.8 mm after 42.8 months' follow-up. Mandible length increased by 5.1 mm in the affected side and by 5.3 mm in the unaffected side, without significant difference. The affected maxilla height increased by 6.7 mm, which was more than 5.0 mm in the unaffected side. In conclusion, continued growth of mandible and maxilla can be achieved through CCG combined with functional appliance treatment for children TMJ ankylosis.

Nuclear export of circular RNA.

Circular RNAs (circRNAs), which are increasingly being implicated in a variety of functions in normal and cancerous cells1-5, are formed by back-splicing of precursor mRNAs in the nucleus6-10. circRNAs are predominantly localized in the cytoplasm, indicating that they must be exported from the nucleus. Here we identify a pathway that is specific for the nuclear export of circular RNA. This pathway requires Ran-GTP, exportin-2 and IGF2BP1. Enhancing the nuclear Ran-GTP gradient by depletion or chemical inhibition of the major protein exporter CRM1 selectively increases the nuclear export of circRNAs, while reducing the nuclear Ran-GTP gradient selectively blocks circRNA export. Depletion or knockout of exportin-2 specifically inhibits nuclear export of circRNA. Analysis of nuclear circRNA-binding proteins reveals that interaction between IGF2BP1 and circRNA is enhanced by Ran-GTP. The formation of circRNA export complexes in the nucleus is promoted by Ran-GTP through its interactions with exportin-2, circRNA and IGF2BP1. Our findings demonstrate that adaptors such as IGF2BP1 that bind directly to circular RNAs recruit Ran-GTP and exportin-2 to export circRNAs in a mechanism that is analogous to protein export, rather than mRNA export.

ESRP1 controls biogenesis and function of a large abundant multiexon circRNA.

While the majority of circRNAs are formed from infrequent back-splicing of exons from protein coding genes, some can be produced at quite high level and in a regulated manner. We describe the regulation, biogenesis and function of circDOCK1(2-27), a large, abundant circular RNA that is highly regulated during epithelial-mesenchymal transition (EMT) and whose formation depends on the epithelial splicing regulator ESRP1. CircDOCK1(2-27) synthesis in epithelial cells represses cell motility both by diverting transcripts from DOCK1 mRNA production to circRNA formation and by direct inhibition of migration by the circRNA. HITS-CLIP analysis and CRISPR-mediated deletions indicate ESRP1 controls circDOCK1(2-27) biosynthesis by binding a GGU-containing repeat region in intron 1 and detaining its splicing until Pol II completes its 157 kb journey to exon 27. Proximity-dependent biotinylation (BioID) assay suggests ESRP1 may modify the RNP landscape of intron 1 in a way that disfavours communication of exon 1 with exon 2, rather than physically bridging exon 2 to exon 27. The X-ray crystal structure of RNA-bound ESRP1 qRRM2 domain reveals it binds to GGU motifs, with the guanines embedded in clamp-like aromatic pockets in the protein.

Establishment of a TaqMan-based real-time quantitative PCR method for detection of exogenous fowl adenovirus type â , type â ¢ and avian leukosis virus in human cold adapted live attenuated influenza vaccines.

Cold adapted live attenuated influenza vaccines can effectively prevent human disease and death caused by influenza virus. Since chicken embryos are used as the culture substrate for the large-scale production of influenza vaccines, cold adapted live attenuated influenza vaccines may be contaminated by exogenous avian viruses. Rapid and sensitive methods such as TaqMan-based quantitative PCR are needed for the detection of exogenous avian viruses during cold adapted live attenuated influenza vaccines production. In this study, a TaqMan-based quantitative PCR method was established for the detection of three common exogenous avian viruses, including fowl adenovirus type I, type Ⅲ and avian leukosis virus. Avian virus-encoding plasmids purified in high-performance liquid chromatography were essential for sensitivity analysis. The sensitivity reached 1 copy per reaction for each of the avian virus plasmids. Standard curves showed a strong linear relationship. The TaqMan-based quantitative PCR method had high specificity and no cross-reactivity with other irrelevant viruses. Furthermore, the established TaqMan-based quantitative PCR can effectively detect 0.1 TCID50 of each avian virus without or with interference from the influenza virus nucleic acid. Ultimately, this method was used to test three master seed lots of monovalent cold adapted live attenuated influenza vaccine, and the results showed that no fowl adenovirus type I, type Ⅲ or avian leukosis virus contamination, which were consistent with serological methods. The TaqMan-based quantitative PCR method for the determination of extraneous avian viruses in cold adapted live attenuated influenza vaccines met the requirement for both conventional and emergency inspection on cold adapted live attenuated influenza vaccines.

The Effects of Hybrid Steel/Basalt Fibers on the Durability of Concrete Pavement against Freeze-Thaw Cycles.

Freeze-thaw (F-T) is one of the principal perils afflicting concrete pavements. A remedial strategy used during construction encompasses the integration of hybrid fibers into the concrete matrix. An extant research gap persists in elucidating the damage mechanism inherent in hybrid steel fiber (SF)- and basalt fiber (BF)-reinforced concrete subjected to F-T conditions. This paper empirically investigated the durability performance of hybrid fiber-reinforced concrete (HFRC) subjected to F-T cycles. The impact of SF/BF hybridization on mass loss, abrasion resistance, compressive strength, flexural strength, damaged layer thickness, and the relative dynamic modulus of elasticity (RDME) was examined. The damage mechanism was explored using micro-hardness and SEM analysis. The results indicate that incorporating hybrid SF/BF effectively enhances the F-T resistance of concrete and prolongs the service life of concrete pavement. The mechanisms underlying these trends can be traced back to robust bonding at the fiber/matrix interface. Randomly dispersed SFs and BFs contribute to forming a three-dimensional spatial structure within the concrete matrix, suppressing the expansion of internal cracks caused by accumulated hydrostatic pressure during the F-T cycle. This research outcome establishes a theoretical foundation for the application of HFRC to concrete pavements in cold regions.

Whole-process respiratory management strategies based on electrical impedance tomography in a pregnant woman with diffuse alveolar hemorrhage induced by systemic lupus erythematosus under veno-venous extracorporeal membrane oxygenation.

Electrical impedance tomography (EIT) as a bedside, noninvasive, radiation-free technology, could quantify alveolar collapse and over-distension and provide real-time ventilation images of lungs. Clinical studies have shown potential benefit in reducing lung injury by EIT to guide mechanical ventilation setting in acute respiratory distress syndrome (ARDS). The respiratory management of ARDS with venous-venous extracorporeal membrane oxygenation (VV ECMO) remains a challenge for ICU doctors. Moreover, EIT has gained great interests in the respiratory management in VV ECMO therapy. Here, EIT was used for respiratory management in the presented case of a 36-year-old gravida with systemic lupus erythematosus, who developed severe hypoxia caused by diffuse alveolar hemorrhage. Although the patient received mechanical ventilation, VV ECMO was further used for the refractory respiratory failure. EIT was applied to titrate positive end-expiratory pressure (PEEP), guide prone position and early mobilization, dynamic evaluating lung development during ECMO therapy. She was successfully rescued after comprehensive therapy. In summary, an EIT-guided whole-process respiratory management strategy that included PEEP titration, prone position, early mobilization, and dynamic lung ventilation monitoring was proposed. This case demonstrated that EIT-guided whole-process respiratory management strategy was feasible in the respiratory failure patient with VV ECMO therapy.

Prognostic analysis and outcome of hilar cholangiocarcinoma after radical resection: a retrospective study.

OBJECTIVES: The predictive factors affecting the survival of hilar cholangiocarcinoma (HC) are ambiguous. This study aimed to identify the predictors and recurrence patterns of HC. METHODS: A retrospective analysis of the clinicopathological findings of 126 patients with HC from 2009 to 2019 was performed. RESULTS: The proportion of Bismuth I and II HC in the recurrence group was higher than that in the non-recurrence group (p < 0.01). The recurrence group had poorer tumor differentiation, a more advanced N stage, and a higher incidence of perineural invasion compared with the non-recurrence group. N stage and tumor differentiation were independently associated with disease-free and overall survival of patients (p < 0.01). Bile duct resection (BDR) combined with hepatectomy was more favorable to disease-free and overall survivals than BDR alone in Bismuth I and II HC, although p values were marginal (p = 0.072 and p = 0.045). A higher proportion of patients in the non-recurrence group underwent BDR combined with hepatectomy than that in the recurrence group (p < 0.01). CONCLUSIONS: N stage and tumor differentiation are the two independent predictors of patient survival. BDR combined with hepatectomy is recommended for patients with Bismuth I and II hilar cholangiocarcinoma.

OBJETIVOS: Los predictores que afectan a la supervivencia del colangiocarcinoma hiliar son ambiguos. Este estudio tiene como objetivo identificar los factores predictivos y los patrones de recurrencia del colangiocarcinoma hiliar. MÉTODOS: Se aplicó un análisis retrospectivo con126 pacientes con colangiocarcinoma hiliar desde 2009 hasta 2019. RESULTADOS: La proporción de colangiocarcinoma hiliar Bismuth I y II en el grupo de recurrencia fue mayor que en el grupo de no recurrencia (p < 0.01). El tumor del grupo de recidiva tenía un estadio N más avanzado que el del grupo de no recidiva. El estadio N se asocia de forma independiente con la supervivencia libre de enfermedad y global del paciente (p < 0.01). La resección de la vía biliar combinada con la hepatectomía benefició más a la supervivencia libre de enfermedad y global que la resección de la vía biliar sola en el colangiocarcinoma hiliar (p = 0.072 y p = 0.045). Una mayor proporción de pacientes se sometió a resección de la vía biliar combinada con hepatectomía en el grupo de no recidiva que en el de recidiva (p < 0.01). CONCLUSIONES: El estadio N fue el predictor independiente. Se recomienda la resección de la vía biliar combinada con hepatectomía para los pacientes con colangiocarcinoma hiliar Bismuth I y II.

Circular RNAs drive oncogenic chromosomal translocations within the MLL recombinome in leukemia.

The first step of oncogenesis is the acquisition of a repertoire of genetic mutations to initiate and sustain the malignancy. An important example of this initiation phase in acute leukemias is the formation of a potent oncogene by chromosomal translocations between the mixed lineage leukemia (MLL) gene and one of 100 translocation partners, known as the MLL recombinome. Here, we show that circular RNAs (circRNAs)-a family of covalently closed, alternatively spliced RNA molecules-are enriched within the MLL recombinome and can bind DNA, forming circRNA:DNA hybrids (circR loops) at their cognate loci. These circR loops promote transcriptional pausing, proteasome inhibition, chromatin re-organization, and DNA breakage. Importantly, overexpressing circRNAs in mouse leukemia xenograft models results in co-localization of genomic loci, de novo generation of clinically relevant chromosomal translocations mimicking the MLL recombinome, and hastening of disease onset. Our findings provide fundamental insight into the acquisition of chromosomal translocations by endogenous RNA carcinogens in leukemia.

Impact of central venous pressure during the first 24†h and its time-course on the lactate levels and clinical outcomes of patients who underwent coronary artery bypass grafting.

Purpose: Previous studies have revealed that elevated mean central venous pressure (CVP) was associated with poor prognosis in specific patient groups. But no study explored the impact of mean CVP on prognosis of patients who underwent coronary artery bypass grafting surgery (CABG). The purpose of this study was to investigate the impacts of elevated CVP and its time-course on clinical outcomes of patients who underwent CABG and potential mechanisms. Methods: A retrospective cohort study was performed based on the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. We first identified the CVP during specific period with the most predictive value. Patients were categorized into the low-CVP and high-CVP group on the basis of the cut-off value. A propensity score matching was used to adjust covariates. The primary outcome was a 28-day mortality. The secondary outcomes were 1-year mortality and in-hospital mortality, the length of intensive care unit (ICU) stay and hospitalization, acute kidney injury incidence, use of vasopressors, duration of ventilation and oxygen index, and lactate levels and clearance. Patients in the high-CVP group were categorized into the "second day CVP ≤ 13.46 mmHg" group and the "second day CVP > 13.46 mmHg" group, respectively, and the clinical outcomes were the same as before. Results: A total of 6,255 patients who underwent CABG were picked from the MIMIC-IV database, of which 5,641 CABG patients were monitored by CVP measurement during the first 2 days after ICU admission and 206,016 CVP records were extracted from the database. The mean CVP during the first 24 h was the most correlative and statistically significant for the 28-day mortality. The risk of the 28-day mortality was increased in the high-CVP group [OR 3.45 (95% CI: 1.77-6.70; p < 0.001)]. Patients with elevated CVP levels had worse secondary outcomes. The maximum of lactate levels and lactate clearance were also poor in the high-CVP group. For patients in the high-CVP group during the first 24 h, whose mean CVP during the second day lowered to less than the cut-off value, had better clinical outcomes. Conclusions: An elevated mean CVP during the first 24 h was correlated with poor outcomes in patients who underwent CABG. The potential mechanisms may be influencing the lactate levels and lactate clearance through the impact on afterload of tissue perfusion. Patients whose mean CVP during the second day dropped to less than the cut-off value had favorable prognosis.

Airway changes in patients with unilateral cleft lip/palate (UCL/P) after maxillary advancement.

OBJECTIVES: To assess the effect on the retropalatal airway (RPA), retroglossal airway (RGA), and total airway (TA) volumes and cephalometrics (SNA, SNB, ANB, PP-SN, Occl-SN, N-A, A-TVL, B-TVL) after maxillary advancement orthognathic surgery in patients with unilateral cleft lip/palate (UCL/P) using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: The CBCT scans of 30 patients (13 males and 17 females, 17-20 years old) with UCL/P were evaluated at two time points: preoperative (T1) and postoperative (T2). The interval between T1 and T2 ranged from 9-14 weeks, except for two patients in whom the interval was 24 weeks. Intraexaminer reliability was measured with an intraclass correlation coefficient test. A paired t-test was used to compare the airway and cephalometric measurements between T1 and T2, with a P value of .05 being considered significant. RESULTS: From T1 to T2, significant increases were found in the volumes of RPA (from 9574 ± 4573 to 10,472 ± 4767, P = .019), RGA (from 9736 ± 5314 to 11,358 ± 6588, P = .019), and TA (from 19,121 ± 8480 to 21,750 ± 10,078, P = .002). In addition, the RGA (from 385 ± 134 to 427 ± 165, P = .020) and TA (from 730 ± 213 to 772 ± 238, P = .016) sagittal area increased significantly. For minimal cross-sectional area (MCA), only the RPA increased significantly (from 173 ± 115 to 272 ± 129, P = .002). All cephalometric changes were statistically significant between T1 and T2 except for SNB. CONCLUSIONS: Maxillary advancement in patients with UCL/P produces statistically significant increases in the retropalatal (volumetric and MCA), retroglossal (volumetric and sagittal), and total (volumetric and sagittal) airways based on data from CBCT imaging.

Expression and clinical significance of ENC1 in gastrointestinal tumors: Bioinformatics analysis based on a public gene database.

Background: To investigate the expression characteristics of ectodermal-neural cortex 1 (ENC1) in gastrointestinal tumors and its potential value in judging the prognosis of patient survival. Methods: RNA sequence (RNA-seq) data and patient survival data related to stomach adenocarcinoma (STAD) and colon adenocarcinoma (COAD) in gastric cancer and colon cancer from The Cancer Genome Atlas (TCGA) were downloaded for expression difference analysis and Cox survival regression analysis. A Kaplan-Meier (KM) survival curve was plotted to analyze the tumor invasion level of patients with different ENC1 expression levels, and the main influencing pathways of ENC1 were analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein network analysis. Results: The data of 405 STAD samples and 494 COAD clinical samples of TCGA were analyzed, and it was found that the expression of ENC1 in tumor tissues of patients with both types of cancer was significantly higher than that in normal tissues, with Log2 fold change values of 1.97 and 2.06, respectively, P<0.001. Cox analysis revealed that the high expression of ENC1 was not significantly correlated with the prognosis and survival time of patients with gastric cancer and patients with colon cancer: overall survival (OS) hazard ratio (HR): 1.039, 95% confidence interval (CI): 0.890-1.213, P=0.627 for gastric cancer, OS HR: 0.886, 95% CI: 0.702-1.111, P=0.306 for colon cancer. KEGG pathway enrichment analysis of gene ENC1 revealed that ENC1 was mainly involved in neuroactive ligand-receptor interaction. The high expression of ENC1 was associated with various immune cells and different T cells such as basophils, CD4+ memory T cells, CD4+ TEM, and MV endothelial cells in gastric and colon cancers. The results of ENC1 protein interaction network analysis suggested that ENC1 may be involved in regulating neurite formation and neural crest cell differentiation. Conclusions: ENC1 expression is elevated in both gastric and colon cancers, and ENC1 is associated with various immune cells and different T cells such as basophils, CD4+ memory T cells, CD4+ TEM, and MV endothelial cells in both gastric and colon cancers, but ENC1 does not affect the survival and prognosis of patients.

The viral packaging motor potentiates Kaposi's sarcoma-associated herpesvirus gene expression late in infection.

ß- and γ-herpesviruses transcribe their late genes in a manner distinct from host transcription. This process is directed by a complex of viral transcriptional activator proteins that hijack cellular RNA polymerase II and an unknown set of additional factors. We employed proximity labeling coupled with mass spectrometry, followed by CRISPR and siRNA screening to identify proteins functionally associated with the Kaposi's sarcoma-associated herpesvirus (KSHV) late gene transcriptional complex. These data revealed that the catalytic subunit of the viral DNA packaging motor, ORF29, is both dynamically associated with the viral transcriptional activator complex and potentiates gene expression late in infection. Through genetic mutation and deletion of ORF29, we establish that its catalytic activity potentiates viral transcription and is required for robust accumulation of essential late proteins during infection. Thus, we propose an expanded role for ORF29 that encompasses its established function in viral packaging and its newly discovered contributions to viral transcription and late gene expression in KSHV.

Experimental Evaluation of Working Fluid Damage to Gas Transport in a High-Rank Coalbed Methane Reservoir in the Qinshui Basin, China.

Formation damage induced by the injected working fluid runs through the whole life cycle of coalbed methane (CBM) extraction and ultimately reduces the production of CBM wells. The conventional method uses permeability as a parameter to evaluate the formation damage severity to coal by working fluids containing solids. However, less attention has been attracted to the formation damage of the pure liquid phase of the working fluid on the multiscale gas transport process of CBM. Therefore, we present a multiscale working fluid filtrate damage evaluation method considering the desorption, diffusion, and seepage and use it to evaluate high-rank coal in the Qinshui Basin of China. The results show that pure liquids with different pH values and salinities significantly damage the desorption-diffusion and seepage ability of CBM. The damage rates of alkaline fluid, hydrochloric acid fluid, and clear water on the methane desorption capacity of coal are 63.64, 17.63, and 24.34%, respectively, while those on the permeability of coal are 29.88, 42.38, and 46.66%, respectively. The formation damage severity in the seepage process is higher than that in the desorption-diffusion process, which proves the necessity of multiscale working fluid damage evaluation on CBM. Effective channel reduction and resistance increase in gas transport are the mechanisms of working fluid filtrate-induced formation damage, which are caused by water blocking, sensitive mineral swelling and clogging, and strengthened stress sensitivity. In addition to controlling the solid damage of the working fluid, reducing the invasion of the working fluid filtrate and maintaining its compatibility with the coal and formation fluids are even more important to protect the coal reservoir.

Apoptotic vesicles ameliorate lupus and arthritis via phosphatidylserine-mediated modulation of T cell receptor signaling.

Mesenchymal stem cells (MSCs) influence T cells in health, disease and therapy through messengers of intercellular communication including extracellular vesicles (EVs). Apoptosis is a mode of cell death that tends to promote immune tolerance, and a large number of apoptotic vesicles (apoVs) are generated from MSCs during apoptosis. In an effort to characterize these apoVs and explore their immunomodulatory potential, here we show that after replenishing them systemically, the apoV deficiency in Fas mutant mice and pathological lymphoproliferation were rescued, leading to the amelioration of inflammation and lupus activity. ApoVs directly interacted with CD4+ T cells and inhibited CD25 expression and IL-2 production in a dose-dependent manner. A broad range of Th1/2/17 subsets and cytokines including IFNγ, IL17A and IL-10 were suppressed while Foxp3+ cells were maintained. Mechanistically, exposed phosphatidylserine (PtdSer/PS) on apoVs mediated the interaction with T cells to disrupt proximal T cell receptor signaling transduction. Remarkably, administration of apoVs prevented Th17 differentiation and memory formation, and ameliorated inflammation and joint erosion in murine arthritis. Collectively, our findings unveil a previously unrecognized crosstalk between MSC apoVs and CD4+ T cells and suggest a promising therapeutic use of apoVs for autoimmune diseases.

TIMEDB: tumor immune micro-environment cell composition database with automatic analysis and interactive visualization.

Deciphering the cell-type composition in the tumor immune microenvironment (TIME) can significantly increase the efficacy of cancer treatment and improve the prognosis of cancer. Such a task has benefited from microarrays and RNA sequencing technologies, which have been widely adopted in cancer studies, resulting in extensive expression profiles with clinical phenotypes across multiple cancers. Current state-of-the-art tools can infer cell-type composition from bulk expression profiles, providing the possibility of investigating the inter-heterogeneity and intra-heterogeneity of TIME across cancer types. Much can be gained from these tools in conjunction with a well-curated database of TIME cell-type composition data, accompanied by the corresponding clinical information. However, currently available databases fall short in data volume, multi-platform dataset integration, and tool integration. In this work, we introduce TIMEDB (https://timedb.deepomics.org), an online database for human tumor immune microenvironment cell-type composition estimated from bulk expression profiles. TIMEDB stores manually curated expression profiles, cell-type composition profiles, and the corresponding clinical information of a total of 39,706 samples from 546 datasets across 43 cancer types. TIMEDB comes readily equipped with online tools for automatic analysis and interactive visualization, and aims to serve the community as a convenient tool for investigating the human tumor microenvironment.

XCHT alleviates the pancreatic fibrosis via VDR/NLRP3 signaling pathway in a mouse model of CP.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiao Chai Hu Tang (XCHT) derived from the classic medical book Shang Han Lun (Treatise on Febrile Diseases) in the Eastern Han Dynasty, which has been widely used in China and other Asian countries for the treatment of inflammation and fibrosis of chronic pancreatitis (CP), but the therapeutic mechanism of XCHT in pancreatic fibrosis remains unclear. AIM OF THE STUDY: This study aimed to evaluate the intervention effects and explore pharmacological mechanism of XCHT on inflammation and fibrosis in cerulein-induced CP model. MATERIALS AND METHODS: Fifty male C57BL/6 mice were randomly divided into five main groups, 10 animals in each: Control, CP model (50 µg/kg cerulein), high dose XCHT-treated CP group (60 g/kg XCHT), medium dose XCHT-treated CP group (30 g/kg XCHT) and low dose XCHT-treated CP group (15 g/kg XCHT). Different doses of XCHT were given to mice by gavage twice a day for 2 weeks after the CP model induction. Pancreatic tissues were harvested and the pancreatic inflammation and fibrosis were evaluated by histological score, Sirius red staining, and alpha-smooth muscle actin (α-SMA) immunohistochemical staining. ELISA, IHC and RT-qPCR were performed to detect the expression of Vitamin D3 (VD3) and Vitamin D receptor (VDR) in serum and pancreatic tissues, respectively. The expressions of NLRP3 inflammasome related genes and molecules were assayed by WB, IHC and RT-qPCR. RESULTS: The pathohistological results demonstrated that XCHT markedly inhibited the fibrosis and chronic inflammation of cerulein-induced CP, indicated by reduction of collagen I, collagen III, α-SMA, and NLRP3 expressions. XCHT significantly increased VD3 and VDR expression while reduced the pancreatic NLRP3 expression. Correspondingly, XCHT decreased the levels of NLRP3 downstream targets IL-1ß, TNF-α and IL-6. CONCLUSIONS: These results revealed that XCHT suppressed the pancreatic fibrosis and chronic inflammation in cerulein-induced CP model by enhancing the VD3/VDR expression and inhibiting the secretion of NLRP3-assoicated inflammatory factors.

Apoptotic extracellular vesicles are metabolized regulators nurturing the skin and hair.

Over 300 billion of cells die every day in the human body, producing a large number of endogenous apoptotic extracellular vesicles (apoEVs). Also, allogenic stem cell transplantation, a commonly used therapeutic approach in current clinical practice, generates exogenous apoEVs. It is well known that phagocytic cells engulf and digest apoEVs to maintain the body's homeostasis. In this study, we show that a fraction of exogenous apoEVs is metabolized in the integumentary skin and hair follicles. Mechanistically, apoEVs activate the Wnt/ß-catenin pathway to facilitate their metabolism in a wave-like pattern. The migration of apoEVs is enhanced by treadmill exercise and inhibited by tail suspension, which is associated with the mechanical force-regulated expression of DKK1 in circulation. Furthermore, we show that exogenous apoEVs promote wound healing and hair growth via activation of Wnt/ß-catenin pathway in skin and hair follicle mesenchymal stem cells. This study reveals a previously unrecognized metabolic pathway of apoEVs and opens a new avenue for exploring apoEV-based therapy for skin and hair disorders.

Effect of tai-ji practice on the health of the elderly / Efeito da prática de tai-ji sobre a saúde dos idosos / Efecto de la práctica de tai-ji en la salud de las personas mayores

ABSTRACT Introduction: The practice of Tai-ji has shown a positive effect on the physical functions of the elderly and has been promoted as a recommended daily activity for middle-aged and elderly individuals. However, there is still no scientific evidence about its cardiorespiratory benefits. Objective: Study the effect of Tai-ji on the cardiorespiratory function and physical fitness of the elderly. Methods: A group of elderly people from the same community and in good health, considered suitable for sports experiments was divided into the experimental group for Tai-ji exercise and the control group for vigorous walking exercise. Each week, the Tai-ji exercise with eight steps and the vigorous walking exercise was performed three times in each group. Results: After six weeks of Tai-ji exercise with eight steps of five methods, the vital capacity, maximal oxygen consumption, maximal voluntary ventilation, and oxygen pulse of the experimental group were significantly increased, and the systolic and diastolic pressures were significantly reduced, evidencing an improvement in the performance of the cardiopulmonary function. Conclusion: Tai-ji exercise is beneficial for the cardiopulmonary function and physical health of the elderly and is scientifically useful for improving the mental health level and quality of life of the elderly. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: A prática do Tai-ji tem demonstrado um efeito positivo nas funções físicas dos idosos, tendo sido promovida como atividade diária recomendada aos indivíduos de meia-idade e idosos. Porém ainda não há evidências científicas sobre seus benefícios cardiorrespiratórios. Objetivo: Estudar o efeito do Tai-ji sobre a função cardiorrespiratória e a aptidão física do idoso. Métodos: Um grupo de idosos da mesma comunidade e boa saúde, considerados adequados para os experimentos esportivos foi dividido em grupo experimental para o exercício de Tai-ji e no grupo de controle para o exercício de caminhada vigorosa. A cada semana, o exercício de Tai-ji com oito etapas e o vigoroso exercício de caminhada foram realizados três vezes em cada grupo. Resultados: Após seis semanas de exercício Tai-ji com oito etapas do método de cinco, a capacidade vital, o consumo máximo de oxigênio, a ventilação voluntária máxima e o pulso de oxigênio do grupo experimental foram significativamente aumentados, e as pressões sistólica e diastólica foram significativamente reduzidas, evidenciando uma melhora no desempenho da função cardiopulmonar. Conclusão: O exercício de Tai-ji é benéfico para a função cardiopulmonar e a saúde física dos idosos, mostrando-se cientificamente útil para melhorar o nível de saúde mental e a qualidade de vida dos idosos. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: La práctica del Tai-ji ha demostrado un efecto positivo en las funciones físicas de las personas mayores, habiéndose promovido como actividad diaria recomendada a los individuos de mediana y avanzada edad. Sin embargo, aún no existen pruebas científicas sobre sus beneficios cardiorrespiratorios. Objetivo: Estudiar el efecto del Tai-ji sobre la función cardiorrespiratoria y la forma física de los ancianos. Métodos: Un grupo de ancianos de la misma comunidad y en buen estado de salud, considerados aptos para experimentos deportivos, se dividió en el grupo experimental para el ejercicio Tai-ji y el grupo de control para el ejercicio de caminata vigorosa. Cada semana, se realizaron ejercicios de Tai-ji con ocho pasos y ejercicios de caminata vigorosa tres veces en cada grupo. Resultados: Después de seis semanas de ejercicio Tai-ji con ocho pasos de cinco métodos, la capacidad vital, el consumo máximo de oxígeno, la ventilación voluntaria máxima y el pulso de oxígeno del grupo experimental aumentaron significativamente, y las presiones sistólica y diastólica se redujeron significativamente, lo que evidencia una mejora en el rendimiento de la función cardiopulmonar. Conclusión: El ejercicio Tai-ji es beneficioso para la función cardiopulmonar y la salud física de los ancianos, y está científicamente demostrado que mejora el nivel de salud mental y la calidad de vida de los ancianos. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.