Engineering Internal and External Low-Coordination Atoms in Nickel-Organic Framework Nanoarrays to Promote the Electrochemical Oxygen Evolution Reaction.

Monometallic nickel-organic frameworks based on a carboxylated ligand [2,6-naphthalenedicarboxylic acid (Ni-NDC)] have abundant and uniformly distributed single-atom Ni sites, enabling superior oxygen evolution reaction (OER) activity. In theory, most of the Ni atoms inside Ni-NDC microcrystals are coordinatively saturated except for the surface. Therefore, there are no accessible low-coordination atoms (LCAs) as electrocatalytic sites for the OER. One effective way is to expose more LCAs by preparing self-supporting Ni-NDC nanoarrays (Ni-NDC NAs) with hierarchical secondary structural units. Another effective method is to create more internal LCAs by removing partial ligands or coordination atoms attached to the Ni atoms. Herein, by combining the two strategies, we engineered LCAs in the interior and exterior of Ni-NDC to synergistically accelerate the OER. In brief, ultrathick "brick-like" Ni-NDC NAs were first prepared with dissolution and coordination effects of NDC on self-sacrificial templates of "agaric-like" nickel hydroxide nanoarrays [Ni(OH)2 NAs]. Subsequently, dual-coordinated NDC was partially replaced by monocoordinated 2-naphthoic acid (NA). The Ni-NDC NAs were further tailed into ultrathin "liner leaf-like" nanoneedle arrays (LCAs-Ni-NDC NAs). As a consequence, the LCAs-Ni-NDC NAs have more internal and external LCAs, which can deliver an OER performance that is superior to that of Ni-NDC NAs.

Construction of a pillar[5]arene-based supramolecular chiral polymer linked to aminophosphine salt for chiral recognition of enantiomers of mandelic acid.

In recent years, supramolecular chirality has been greatly developed in asymmetric synthesis, chiral sensing and other research fields, but its application in molecular chiral recognition has not been extensively studied. In this paper, L-Boc-tyrosine methoxyester and phosphorus chloride salts were introduced into the framework of pillar[n]arene, and a pillar[5]arene-based supramolecular chiral polymer L-TPP-P was constructed. The supramolecular polymer had stable supramolecular chiral properties and could be used as a chiral solvation reagent for chiral recognition of mandelic acid MA. The molar ratio method and Scatchard plot showed that the complexation ratio of L-TPP-P (pillar[5]arene monomer as the reference object) and MA was 1 : 1, and the complexation constants of L-TPP-P with R-MA and S-MA were 4.51 × 105 M-1 and 6.5 × 104 M-1, respectively. The significant affinity difference of L-TPP-P for different enantiomers of MA showed the excellent chiral recognition and stereoselectivity of pillar[5]arene-based supramolecular polymers for MA. This study provides a new idea for a novel supramolecular polymer chiral recognition reagent or chiral recognition method.

Utilizing disease transmission and response capacities to optimize covid-19 control in Malaysia.

OBJECTIVES: Public Health Social Measures (PHSM) such as movement restriction movement needed to be adjusted accordingly during the COVID-19 pandemic to ensure low disease transmission alongside adequate health system capacities based on the COVID-19 situational matrix proposed by the World Health Organization (WHO). This paper aims to develop a mechanism to determine the COVID-19 situational matrix to adjust movement restriction intensity for the control of COVID-19 in Malaysia. METHODS: Several epidemiological indicators were selected based on the WHO PHSM interim guidance report and validated individually and in several combinations to estimate the community transmission level (CT) and health system response capacity (RC) variables. Correlation analysis between CT and RC with COVID-19 cases was performed to determine the most appropriate CT and RC variables. Subsequently, the CT and RC variables were combined to form a composite COVID-19 situational matrix (SL). The SL matrix was validated using correlation analysis with COVID-19 case trends. Subsequently, an automated web-based system that generated daily CT, RC, and SL was developed. RESULTS: CT and RC variables were estimated using case incidence and hospitalization rate; Hospital bed capacity and COVID-19 ICU occupancy respectively. The estimated CT and RC were strongly correlated [ρ = 0.806 (95% CI 0.752, 0.848); and ρ = 0.814 (95% CI 0.778, 0.839), p < 0.001] with the COVID-19 cases. The estimated SL was strongly correlated with COVID-19 cases (ρ = 0.845, p < 0.001) and responded well to the various COVID-19 case trends during the pandemic. SL changes occurred earlier during the increase of cases but slower during the decrease, indicating a conservative response. The automated web-based system developed produced daily real-time CT, RC, and SL for the COVID-19 pandemic. CONCLUSIONS: The indicators selected and combinations formed were able to generate validated daily CT and RC levels for Malaysia. Subsequently, the CT and RC levels were able to provide accurate and sensitive information for the estimation of SL which provided valuable evidence on the progression of the pandemic and movement restriction adjustment for the control of Malaysia.

Targeting OXCT1-mediated ketone metabolism reprograms macrophages to promote antitumor immunity via CD8+ T cells in hepatocellular carcinoma.

BACKGROUND & AIMS: The liver is the main organ of ketogenesis, while ketones are mainly metabolized in peripheral tissues via the critical enzyme 3-oxoacid CoA-transferase 1 (OXCT1). We previously found that ketolysis is reactivated in hepatocellular carcinoma (HCC) cells through OXCT1 expression to promote tumor progression; however, whether OXCT1 regulates antitumor immunity remains unclear. METHODS: To investigate the expression pattern of OXCT1 in HCC in vivo, we conducted multiplex immunohistochemistry experiments on human HCC specimens. To explore the role of OXCT1 in mouse HCC tumor-associated macrophages (TAMs), we generated LysMcreOXCT1f/f (OXCT1 conditional knockout in macrophages) mice. RESULTS: Here, we found that inhibiting OXCT1 expression in tumor-associated macrophages reduced CD8+ T-cell exhaustion through the succinate-H3K4me3-Arg1 axis. Initially, we found that OXCT1 was highly expressed in liver macrophages under steady state and that OXCT expression was further increased in TAMs. OXCT1 deficiency in macrophages suppressed tumor growth by reprogramming TAMs toward an antitumor phenotype, reducing CD8+ T-cell exhaustion and increasing CD8+ T-cell cytotoxicity. Mechanistically, high OXCT1 expression induced the accumulation of succinate, a byproduct of ketolysis, in TAMs, which promoted Arg1 transcription by increasing the H3K4me3 level in the Arg1 promoter. In addition, pimozide, an inhibitor of OXCT1, suppressed Arg1 expression as well as TAM polarization toward the protumor phenotype, leading to decreased CD8+ T-cell exhaustion and slower tumor growth. Finally, high expression of OXCT1 in macrophages was positively associated with poor survival in patients with HCC. CONCLUSIONS: In conclusion, our results demonstrate that OXCT1 epigenetically suppresses antitumor immunity, suggesting that suppressing OXCT1 activity in TAMs could be an effective approach for treating liver cancer. IMPACT AND IMPLICATIONS: The intricate metabolism of liver macrophages plays a critical role in shaping hepatocellular carcinoma progression and immune modulation. Targeting macrophage metabolism to counteract immune suppression presents a promising avenue for hepatocellular carcinoma treatment. Herein, we found that the ketogenesis gene OXCT1 was highly expressed in tumor-associated macrophages (TAMs) and promoted tumor growth by reprogramming TAMs toward a protumor phenotype. Pharmacological targeting or genetic downregulation of OXCT1 in TAMs enhances antitumor immunity and slows tumor growth. Our results suggest that suppressing OXCT1 activity in TAMs could be an effective approach for treating liver cancer.

Prediction model for developing neuropsychiatric systemic lupus erythematosus in lupus patients.

OBJECTIVE: This study aimed to construct a predictive model for assessing the risk of development of neuropsychiatric systemic lupus erythematosus (NPSLE) among patients with SLE based on clinical, laboratory, and meteorological data. METHODS: A total of 2232 SLE patients were included and were randomly assigned into training and validation sets. Variables such as clinical and laboratory data and local meteorological data were screened by univariate and least absolute shrinkage and selection operator (LASSO) logistic regression modelling. After 10-fold cross-validation, the predictive model was built by multivariate logistic regression, and a nomogram was constructed to visualize the risk of NPSLE. The efficacy and accuracy of the model were assessed by receiver operating characteristic (ROC) curve and calibration curve analysis. Net clinical benefit was assessed by decision curve analysis. RESULTS: Variables that were included in the predictive model were anti-dsDNA, anti-SSA, lymphocyte count, hematocrit, erythrocyte sedimentation rate, pre-albumin, retinol binding protein, creatine kinase isoenzyme MB, Nterminal brain natriuretic peptide precursor, creatinine, indirect bilirubin, fibrinogen, hypersensitive C-reactive protein, CO, and mild contamination. The nomogram showed a broad prediction spectrum; the area under the curve (AUC) was 0.895 (0.858-0.931) for the training set and 0.849 (0.783-0.916) for the validation set. CONCLUSION: The model exhibits good predictive performance and will confer clinical benefit in NPSLE risk calculation. Key Points • Clinical, laboratory, and meteorological data were incorporated into a predictive model for neuropsychiatric systemic lupus erythematosus (NPSLE) in SLE patients. • Anti-dsDNA, anti-SSA, LYM, HCT, ESR, hsCRP, IBIL, PA, RBP, CO, Fib, NT-proBNP, Crea, CO, and mild contamination are predictors of the development of NPSLE and may have potential for research. • The nomogram has good predictive performance and clinical value and can be used to guide clinical diagnosis and treatment.

Esophageal cancer detection via non-contrast CT and deep learning.

Background: Esophageal cancer is the seventh most frequently diagnosed cancer with a high mortality rate and the sixth leading cause of cancer deaths in the world. Early detection of esophageal cancer is very vital for the patients. Traditionally, contrast computed tomography (CT) was used to detect esophageal carcinomas, but with the development of deep learning (DL) technology, it may now be possible for non-contrast CT to detect esophageal carcinomas. In this study, we aimed to establish a DL-based diagnostic system to stage esophageal cancer from non-contrast chest CT images. Methods: In this retrospective dual-center study, we included 397 primary esophageal cancer patients with pathologically confirmed non-contrast chest CT images, as well as 250 healthy individuals without esophageal tumors, confirmed through endoscopic examination. The images of these participants were treated as the training data. Additionally, images from 100 esophageal cancer patients and 100 healthy individuals were enrolled for model validation. The esophagus segmentation was performed using the no-new-Net (nnU-Net) model; based on the segmentation result and feature extraction, a decision tree was employed to classify whether cancer is present or not. We compared the diagnostic efficacy of the DL-based method with the performance of radiologists with various levels of experience. Meanwhile, a diagnostic performance comparison of radiologists with and without the aid of the DL-based method was also conducted. Results: In this study, the DL-based method demonstrated a high level of diagnostic efficacy in the detection of esophageal cancer, with a performance of AUC of 0.890, sensitivity of 0.900, specificity of 0.880, accuracy of 0.882, and F-score of 0.891. Furthermore, the incorporation of the DL-based method resulted in a significant improvement of the AUC values w.r.t. of three radiologists from 0.855/0.820/0.930 to 0.910/0.955/0.965 (p = 0.0004/<0.0001/0.0068, with DeLong's test). Conclusion: The DL-based method shows a satisfactory performance of sensitivity and specificity for detecting esophageal cancers from non-contrast chest CT images. With the aid of the DL-based method, radiologists can attain better diagnostic workup for esophageal cancer and minimize the chance of missing esophageal cancers in reading the CT scans acquired for health check-up purposes.

Bile Acid Metabolic Profiles and Their Correlation with Intestinal Epithelial Cell Proliferation and Barrier Integrity in Suckling Piglets.

Bile acids (BAs) are crucial for maintaining intestinal epithelial homeostasis. However, the metabolic changes in BAs and the communication between intestinal epithelial cells (IECs) in infants after birth remain unclear. This study aims to elucidate the BA profiles of newborn piglets (NPs) and suckling piglets (SPs), and to investigate their regulatory effects on IEC proliferation and barrier integrity, as well as the potential underlying mechanisms. In this study, compared with NPs, there were significant increases in serum triglycerides, total cholesterol, glucose, and albumin levels for SPs. The total serum BA content in SPs exhibited an obvious increase. Moreover, the expression of BA synthase cytochrome P450 27A1 (CYP27A1) was increased, and the ileal BA receptor Takeda G-coupled protein receptor 5 (TGR5) and proliferation marker Ki-67 were upregulated and showed a strong positive correlation through a Spearman correlation analysis, whereas the expression of farnesoid X receptor (FXR) and occludin was markedly downregulated in SPs and also revealed a strong positive correlation. These findings indicate that the increased synthesis and metabolism of BAs may upregulate TGR5 and downregulate FXR to promote IEC proliferation and influence barrier function; this offers a fresh perspective and evidence for the role of BAs and BA receptors in regulating intestinal development in neonatal pigs.

Oleanolic acid alleviate intestinal inflammation by inhibiting Takeda G-coupled protein receptor (TGR) 5 mediated cell apoptosis.

Oleanolic acid (OA) is a bioactive compound present in plant-based foods known for its beneficial impact on gastrointestinal health, specifically in alleviating diarrhea. Nonetheless, the underlying mechanisms by which OA mitigates gut epithelial damage have yet to be elucidated. In this study, OA significantly markedly ameliorated adverse effects induced by Dextran Sulfate Sodium (DSS), including weight loss and epithelial morphological damage in a murine model. Remarkably, compared to normal mice, standalone administration of OA had no discernible impact on the animals. Concurrently, we identified a significant up-regulation in the expression levels of TGR5 and BAX in the intestines of DSS-exposed mice, coupled with a decline in Bcl2 expression. Correlation analyses revealed a robust association between TGR5 and BAX expression. Oral administration of OA efficaciously counteracted these alterations. To probe the role of TGR5 in cellular apoptosis, further, a lentivirus transfection approach was utilized to induce TGR5 overexpression in intestinal epithelial cells (IPEC-J2). RNA sequencing indicated that TGR5 overexpression significantly influenced biological processes, particularly in modulating cellular activation and intercellular adhesion, in contrast to the control group cells. Functional assays substantiated that TGR5 overexpression compromised cell viability and accelerated apoptosis. Notably, OA treatment in TGR5-overexpressed cells restored cell viability, suppressed TGR5 and BAX expression, and augmented Bcl2 expression. In sum, our data suggest that OA mitigates intestinal epithelial apoptosis and bolsters cellular proliferation by downregulating TGR5. This research provides valuable insights into the prospective utility of OA as a functional food supplement or adjunctive therapeutic agent for enhancing gastrointestinal health.

Anti-S Antibodies Against SARS-CoV-2 Infection Among Four Types of Vaccines in Malaysia.

Monitoring SARS-CoV-2 antibody levels can provide insights into a person's immunity to COVID-19 and inform decisions about vaccination and public health measures. Anti-S may be useful as an indicator of an effective immune response. Thus, we conducted this study that aimed to determine the immune response of anti-S antibodies against SARS-CoV-2 for all the vaccine types over time among adult recipients in Malaysia and to determine the associated factors. This study was a cohort that recruited 2513 respondents aged 18 years and above from June to December 2021. Each participant was followed-up for 1-year period from the initial vaccine dose (baseline). We found that the anti-S antibody generally increased for all vaccine types and peaked at two weeks after the second dose vaccination, with Pfizer recipients having the highest median of 100 (100.00-100.00). During the third-month follow-up, the seropositivity of anti-S antibody and the median level decreased for all vaccines. We found that type of vaccines, comorbid status, infection, and booster status were significantly associated with the anti-S antibody level after one year.

Attack estimation and state reconstruction for cyber-physical systems with state delay via reduced-order observer.

This paper investigates the attack estimation and state reconstruction problem for linear cyber-physical systems with state delay and simultaneous sensor and actuator attacks. Reduced-order observer is designed for the augmented system to simultaneously estimate the actuator attack, sensor attack and the state of system. By adopting the double integral term into the Lyapunov-Krasovskii functional and decomposing the cross term, the delay-dependent results are obtained. The method proposed in this paper can accurately estimate the state, actuator and sensor attacks simultaneously without additional design. Compared with the previous method, the time delay information is fully utilized and the conservation is greatly reduced. Finally, the correctness of the results is verified by simulation.

[Spatio-temporal Characteristics and Influencing Factors of Ozone Suppression Events Under High Temperature in China].

Temperature is a key meteorological factor affecting ozone formation. In general, a positive correlation is observed between ozone and temperature, that is, ozone concentration increases with the increase in temperature. However, this relationship may change at extremely high temperatures. When the temperature exceeds a threshold value, the ozone concentration tends to decrease, which is referred to as an ozone suppression event. Ozone suppression events lead to greater uncertainties in the prediction of future air quality under climate change. Based on the national air quality monitoring data, reanalysis data, and meteorological observation data, this study used the Z test to systematically analyze the spatio-temporal characteristics of the critical temperature(Tx) and frequency of ozone suppression events in China during the warm season(April to September) from 2013 to 2020 and further analyzed the possible influencing factors for the occurrence of ozone suppression events. The results showed that approximately 18% of the sites in China experienced ozone suppression events in the warm season from 2013 to 2020. The sites with a high frequency of ozone suppression events were mainly distributed in the central and western regions of China, such as Sichuan, Xinjiang, and Shaanxi, with an average frequency of ten times per year. The critical temperature(Tx) ranged from 19.2 to 39.3℃, and the Tx of most sites showed an increasing trend from 2013 to 2020. The high values of Tx were mainly distributed in the central and western regions such as Sichuan, Chongqing, Hunan, and Hubei, whereas the low values of Tx were concentrated in the Qinghai-Tibet Plateau. Contrary to the interannual trend of Tx, the frequency of ozone suppression events decreased significantly in the Beijing-Tianjin-Hebei Region and exhibited a characteristic of "increase-decrease-increase" in the Fenwei Plain, the Yangtze River Delta, and the Chengdu-Chongqing regions. The most significant effect of extreme high temperature on ozone suppresion was found in the Pearl River Delta Region. In addition, ozone precursors(e.g., NO2) and meteorological conditions(wind speed and direction) were possible factors affecting the occurrence of ozone suppression events.

[Impact of Accelerated Electrification Under the Low Carbon Path in Dongguan City on the Coordinated Emission Reduction of CO2 and Pollutants].

Cities are the center of energy consumption. Electrification integrates urban energy structure and achieves the efficient use of clean energy. Exploring the urban impact of accelerated electrification under the low-carbon path is crucial to reducing urban pollution and carbon. Based on the Long-range Energy Alternative Planning System(LEAP-DG), this study set up three scenarios, including the baseline, low-carbon, and accelerated electrification scenarios, to evaluate the emission reduction potential of electrification under different power structures, quantify the contribution of key sectors, and discuss the coordinated emission reduction effect of Dongguan, a typical manufacturing city in Guangdong. The results showed that accelerated electrification under the low-carbon path would reduce the emission intensity of power pollutants, and in 2050, Dongguan will further reduce CO2, NOx, VOC, and CO by 7.35×106, 1.28×104, 1.62×104, and 8.13×104 t; SO2 and PM2.5 emission reductions on the consumption side and increased emissions on the production side had been balanced. Accelerated electrification in the industrial and transportation sectors would reduce CO2 and air pollutant emissions at the same time, and the transportation sector would benefit from the high conversion efficiency of fuel vehicles and electric vehicles, reducing CO2, CO, VOC, and NOx by 5.42×106, 7.76×104, 1.43×104, and 1.06×104 t, respectively, in 2050. In the building sector with high electrification rates, coal power was higher in extra electricity, increasing CO2 and pollutant emissions. Under the optimization of power supply structure, cities can reasonably adjust the electrification of different departments to achieve targeted pollution prevention and control.

Synovial sarcoma in the prevertebral space can mimic malignant neurogenic neoplasm: Case report and literature review.

Synovial sarcoma, a rare malignant neoplasm with a poor prognosis, accounts for approximately 5%-10% of all primary soft-tissue malignancies worldwide. Typically affecting adolescents and young adults, it primarily manifests near the joints of the lower extremities. This study aimed to demonstrate that this tumor can also affect the prevertebral space. A 32-year-old male patient presented at our outpatient clinic with a 2-month history of upper limb numbness and a 1-month complaint of palpable neck mass. Imaging studies revealed a bulky, lobulated, and heterogeneous mass exhibiting heterogeneous enhancement. Furthermore, the mass caused expansion of the neuroforamen in the neck, initially suggesting a diagnosis of malignant schwannoma. However, a histopathologic examination suggested synovial sarcoma. The article provided a comprehensive review of the clinical, pathological, and radiological features of this condition. Additionally, it explored current treatment options and prognoses by referencing relevant literature.

16S full-length gene sequencing analysis of intestinal flora in breast cancer patients in Hainan Province.

Breast cancer has become the number one cancer in the world, and intestinal flora may be closely linked to it. Geographic location also has an important impact on human intestinal flora. We conducted the first study on the intestinal flora of breast cancer patients and non-breast cancer patients in a tropical region - Hainan Province in China. At the same time, Pacbio platform based on third-generation sequencing was used for the first time to conduct 16S full-length sequencing of fecal microorganism DNA. We completed the species diversity analysis and differential species analysis of the intestinal flora between the two groups, inferred their functional genetic composition and performed functional difference analysis. There were statistically significant differences in alpha diversity between the two groups in Hainan Province. By species composition difference analysis, at the phylum level, Bacteroidales (P = 0.006) and Firmicutes (P = 0.002) was differed between the two groups, and at the genus level, 17 breast cancer-related differential species such as Bacteroides were screened. According to the five grouping methods including ER level, PR level, HER2 status, Ki67 index and histological grade of breast cancer patients, 4, 1, 9, 6, 5 differential microbiota were screened out respectively, which were in total 25 (P < 0.05 for all subgroups) . The functional prediction and difference analysis revealed two functional metabolisms with significant differences between the two groups of microbes (P < 0.05). These results suggest that breast cancer is associated with changes in the composition and function of intestinal flora. These microflora and functional differences may become biomarkers or new targets for diagnosis and treatment of breast cancer.

Comparative analysis of the gut microbiota of wild adult rats from nine district areas in Hainan, China.

BACKGROUND: Wild rats have the potential to hold zoonotic infectious agents that can spread to humans and cause disease. AIM: To better understand the composition of gut bacterial communities in rats is essential for preventing and treating such diseases. As a tropical island located in the south of China, Hainan province has abundant rat species. Here, we examined the gut bacterial composition in wild adult rats from Hainan province. METHODS: Fresh fecal samples were collected from 162 wild adult rats, including three species (Rattus norvegicus, Leopoldamys edwardsi, and Rattus losea), from nine regions of Hainan province between 2017-2018. RESULTS: We analyzed the composition of gut microbiota using the 16S rRNA gene amplicon sequencing. We identified 4903 bacterial operational taxonomic units (30 phyla, 175 families, and 498 genera), which vary between samples of different rat species in various habitats at various times of the year. In general, Firmicutes were the most abundant phyla, followed by Bacteroidetes (15.55%), Proteobacteria (6.13%), and Actinobacteria (4.02%). The genus Lactobacillus (20.08%), unidentified_Clostridiales (5.16%), Romboutsia (4.33%), unidentified_Ruminococcaceae (3.83%), Bacteroides (3.66%), Helicobacter (2.40%) and Streptococcus (2.37%) were dominant. CONCLUSION: The composition and abundance of the gut microbial communities varied between rat species and locations. This work provides fundamental information to identify microbial communities useful for disease control in Hainan province.

SHP2: its association and roles in systemic lupus erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease. Src homology 2 domain containing protein tyrosine phosphatase (SHP2) is a member of the protein tyrosine phosphatases (PTPs) family. To date, relationship between SHP2 and SLE pathogenesis is not elucidated. METHOD: We measured plasma levels of SHP2 in 328 SLE patients, 78 RA patients, 80 SS patients and 79 healthy controls by ELISA, and discussed association of SHP2 in SLE patients, potential of plasma SHP2 as a SLE biomarker. Moreover, histological and serological changes were evaluated by flow cytometry, HE/Masson examination, immunofluorescence test in pristane-induced lupus mice after SHP2 inhibitor injection to reveal role of SHP2 in lupus development. RESULTS: Results indicated that SHP2 plasma levels were upregulated in SLE patients and correlated with some clinical, laboratory characteristics such as proteinuria, pyuria, and may be a potential biomarker for SLE. After SHP2 inhibitor treatment, hepatosplenomegaly and histological severity of the kidney in lupus mice were improved. SHP2 inhibitor reversed DCs, Th1, and Th17 cells differentiation and downregulated inflammatory cytokines (IL-4, IL-6, IL-10, IL-17A, IFN-γ and TNF-α) and autoantibodies (ANA, anti-dsDNA) production in pristane-lupus mice. CONCLUSION: In summary, SHP2 correlated with SLE pathogenesis and promoted the development of lupus.

Alteration of Gut Microbiota in Individuals at High-Risk for Rheumatoid Arthritis Associated With Disturbed Metabolome and the Initiation of Arthritis Through the Triggering of Mucosal Immunity Imbalance.

OBJECTIVE: In this study, we aimed to decipher the gut microbiome (GM) and serum metabolic characteristic of individuals at high risk for rheumatoid arthritis (RA) and to investigate the causative effect of GM on the mucosal immune system and its involvement in the pathogenesis of arthritis. METHODS: Fecal samples were collected from 38 healthy individuals and 53 high-risk RA individuals with anti-citrullinated protein antibody (ACPA) positivity (Pre-RA), 12 of 53 Pre-RA individuals developed RA within 5 years of follow-up. The differences in intestinal microbial composition between the healthy controls and Pre-RA individuals or among Pre-RA subgroups were identified by 16S ribosomal RNA sequencing. The serum metabolite profile and its correlation with GM were also explored. Moreover, antibiotic-pretreated mice that received GM from the healthy control or Pre-RA groups were then evaluated for intestinal permeability, inflammatory cytokines, and immune cell populations. Collagen-induced arthritis (CIA) was also applied to test the effect of fecal microbiota transplantation (FMT) from Pre-RA individuals on arthritis severity in mice. RESULTS: Stool microbial diversity was lower in Pre-RA individuals than in healthy controls. The bacterial community structure and function significantly differed between healthy controls and Pre-RA individuals. Although there were differences to some extent in the bacterial abundance among the Pre-RA subgroups, no robust functional differences were observed. The metabolites in the serum of the Pre-RA group were dramatically different from those in the healthy controls group, with KEGG pathway enrichment of amino acid and lipid metabolism. Moreover, intestinal bacteria from the Pre-RA group increased intestinal permeability in FMT mice and zonula occludens-1 expression in the small intestine and Caco-2 cells. Moreover, Th17 cells in the mesenteric lymph nodes and Peyer's patches were also increased in mice receiving Pre-RA feces compared to healthy controls. The changes in intestinal permeability and Th17-cell activation prior to arthritis induction enhanced CIA severity in PreRA-FMT mice compared with HC-FMT mice. CONCLUSION: Gut microbial dysbiosis and metabolome alterations already occur in individuals at high risk for RA. FMT from preclinical individuals triggers intestinal barrier dysfunction and changes mucosal immunity, further contributing to the development of arthritis.

Taurochenodeoxycholic acid inhibits intestinal epithelial cell proliferation and induces apoptosis independent of the farnesoid X receptor.

Bile acids, such as taurochenodeoxycholic acid (TCDCA), are considered as functional small molecules involved in nutrition regulation or acting with adjuvant therapeutic effects against metabolic or immune diseases. The homeostasis of the intestinal epithelium depends on the conventional cellular proliferation and apoptosis of cells. Herein, mice and normal intestinal epithelial cells (IPEC-J2, a widely used normal intestinal epithelial cell line derived from porcine) were used as models to explore the regulatory effect of TCDCA on the proliferation of intestinal epithelial cells (IECs). In the mouse study, the oral gavage of TCDCA led to a significant reduction in weight gain, small intestinal weight, and the villus height of the intestinal epithelium while inhibiting the gene expression of Ki-67 in the intestinal epithelial crypts of mice (P < 0.05). TCDCA significantly downregulated the expression of the farnesoid X receptor (FXR) and upregulated the expression of caspase-9 in the jejunum (P < 0.05). The results of real-time quantitative PCR (RT-qPCR) suggested that TCDCA significantly inhibited the expression of tight junction proteins zonula occludens (ZO)-1, occludin, claudin-1, and mucin-2 (P < 0.05). In terms of apoptosis-related genes, TCDCA significantly inhibited the expression of Bcl2 and increased the expression of caspase-9 (P < 0.05). At the protein level, TCDCA decreased the expression of Ki-67 and PCNA, as well as FXR (P < 0.05). Caspase inhibitor Q-VD-OPh and guggulsterone, an FXR antagonist, significantly improved the inhibition of TCDCA-induced cell proliferation. Moreover, guggulsterone enhanced TCDCA-induced cell late apoptosis through flow cytometry and significantly lowered the TCDCA-induced up-regulated gene expression of caspase 9, despite both TCDCA and guggulsterone down-regulating the expression of FXR (P < 0.05). Overall, the effect of TCDCA on the induction of apoptosis is not dependent on FXR, whereas it would function via the activation of the caspase system. This provides a new perspective for the application of TCDCA or bile acid as functional small molecules in food, additives, and medicine.

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.

Improved multi-agent controllability processing technique based on equitable partition.

In this paper, we study the controllability of multi-agent systems by equitable partition and automorphism. For the case that cells are incompletely connected outside but completely connected inside, a necessary condition for controllability is given from the perspective of the rank of connection matrix. For the case of multiple cells being completely connected outside and incompletely connected inside, in terms of the eigenvalues and eigenvectors of L and Lπ, several sufficient and necessary conditions for controllability are presented. Once the quotient graph is controllable under single input or all nodes in nontrivial cells are leaders, the lower bound of controllable subspace is determined. Finally, we give the gap between the necessary condition and the sufficient condition for controllability from the aspect of equitable partition. One highlight of the results in this paper is that we show sufficient conditions to judge controllability by equitable partition and automorphism, which, for specific cases, provides one method that how to break through the defect that equitable partition can only obtain necessary conditions.