Comprehensive exercise reduces traumatic brain injury deficits via improving the neural network function of hippocampal CA1 and medial entorhinal cortex.

The present study aimed to investigate the alterations in functional interaction between hippocampal CA1 and medial entorhinal cortex (MEC) after moderate traumatic brain injury (TBI) in C57BL/6J mice, and the possible beneficial effects of comprehensive exercise (CE). Following TBI, two microelectrodes were implanted into CA1 and MEC for extracellular recording. We found a clear synchronization of neuronal firing in CA1 and MEC, particularly within 100 Hz and peaked at 20-30 Hz range. TBI induced a significant reduction (P < 0.001) of the coherences of firing between 20-40 Hz frequency band. The mean power spectral densities (PSD) of all group mice in MEC were steadily larger than the values in CA1 in both 20-40 Hz and 56-100 Hz ranges. TBI induced significant and consistent increases of averaged 20-40 Hz or 56-100 Hz PSD (P < 0.001 or P < 0.01) in both CA1 and MEC. Injured mice displayed more varied firing patterns, and showed increased burst frequency (BF), burst duration (BD), inter-spike intervals (ISI) and inter-burst interval (IBI). Injured mice also showed worsened neurological function, sleep, gait performance, and working memory. CE facilitated the restoration of aforementioned electrophysiological characteristics and functional deficits in TBI mice. These results suggest that the beneficial effects of CE on TBI functional deficits may be partly attributed to improved neuronal network interaction between CA1 and MEC.

Scalable Synthesis of Robust MOF for Challenging Ethylene Purification and Propylene Recovery with Record Productivity.

Ethylene (C2H4) purification and propylene (C3H6) recovery are highly relevant in polymer synthesis, yet developing physisorbents for these industrial separation faces the challenges of merging easy scalability, economic feasibility, high moisture stability with great separation efficiency. Herein, we reported a robust and scalable MOF (MAC-4) for simultaneous recovery of C3H6 and C2H4. Through creating nonpolar pores decorated by accessible N/O sites, MAC-4 displays top-tier uptakes and selectivities for C2H6 and C3H6 over C2H4 at ambient conditions. Molecular modelling combined with infrared spectroscopy revealed that C2H6 and C3H6 molecules were trapped in the framework with stronger contacts relative to C2H4. Breakthrough experiments demonstrated exceptional separation performance for binary C2H6/C2H4 and C3H6/C2H4 as well as ternary C3H6/C2H6/C2H4 mixtures, simultaneously affording record productivities of 27.4 and 36.2 L kg-1 for high-purity C2H4 (≥99.9 %) and C3H6 (≥99.5 %). MAC-4 was facilely prepared at deckgram-scale under reflux condition within 3 hours, making it as a smart MOF to address challenging gas separations.

Long-term spaceflight composite stress induces depressive behaviors in model rats through disrupting hippocampus synaptic plasticity.

INTRODUCTION: Long-term spaceflight composite stress (LSCS) can cause adverse effects on human systems, including the central nervous system, which could trigger anxiety and depression. AIMS: This study aimed to identify changes in hippocampus synaptic plasticity under LSCS. METHODS: The present study simulated the real long-term space station environment by conducting a 42-day experiment that involved simulating microgravity, isolation, noise, circadian rhythm disruptions, and low pressure. The mood and behavior of the rats were assessed by behavior test. Transmission electron microscopy and patch-clamp were used to detect the changes in synapse morphology and electrophysiology, and finally, the expression of NMDA receptor channel proteins was detected by western blotting. RESULTS: The results showed that significant weight loss, anxiety, and depressive behaviors in rats were observed after being exposed to LSCS environment for 42 days. The synaptic structure was severely damaged, manifested as an obvious decrease in postsynaptic density thickness and synaptic interface curvature (p < 0.05; p < 0.05, respectively). Meanwhile, LTP was significantly impaired (p < 0.0001), and currents in the NMDAR channel were also significantly reduced (p < 0.0001). Further analysis found that LSCS decreased the expression of two key subtype proteins on this channel. CONCLUSION: These results suggested that LSCS-induced depressive behaviors by impairing synaptic plasticity in rat hippocampus.

Multi-omics reveal mechanisms underlying chronic kidney disease of unknown etiology (CKDu) pathogenesis using zebrafish.

Chronic kidney disease of unknown etiology (CKDu) is an endemic disease in the dry zone of farming communities, Sri Lanka. The drinking water in a CKDu prevalent area contains a high concentration of F-, hardness and other environmental pollutants, including heavy metals and microcystin, which are considered possible etiology of CKDu in these areas. Here, multi-omics data with host transcriptome, metabolome and gut microbiomes were obtained using simulated local drinking water of Sri Lanka after their exposure to adult zebrafish. Based on an integrated multi-omics analysis in the context of host physiology in the kidney injury samples with different pathologic grades, two common pathways necroptosis and purine metabolism were identified as potentially important pathways that affect kidney injury. The key metabolite acetyl adenylate in the purine metabolism pathway was significantly positively correlated with Comamonas (rho = 0.72) and significantly negatively correlated with Plesiomonas (rho = -0.58). This crucial metabolite and two key gut bacteria genera may not only be potential markers but also potential therapeutic targets in the uric acid metabolic pathway, which is an important factor in the pathogenesis of acute kidney injury (AKI) in general, as well as of chronic kidney disease (CKD). Based on this, we revealed the urea metabolism pathway of kidney injury in zebrafish and provided a new avenue for the treatment of CKDu in Sri Lanka.

Active Sites Decorated Nonpolar Pore-Based MOF for One-step Acquisition of C2 H4 and Recovery of C3 H6.

Herein, a 2-fold interpenetrated metal-organic framework (MOF) Zn-BPZ-TATB with accessible N/O active sites in nonpolar pore surfaces was reported for one-step C2 H4 purification from C2 H6 or C3 H6 mixtures as well as recovery of C3 H6 from C2 H6 /C3 H6 /C2 H4 mixtures. The MOF exhibits the favorable C2 H6 and C3 H6 uptakes (>100 cm3 g-1 at 298 K under 100 kPa) as well as selective adsorption of C2 H6 and C3 H6 over C2 H4 . The C3 H6 - and C2 H6 -selective feature were investigated detailedly by experimental tests as well as sorption kinetic studyies. Molecular modelling revealed the multiple interactions between C3 H6 or C2 H6 molecules and methyl groups as well as triazine rings in pores. Zn-BPZ-TATB not only can directly generate 323.4 L kg-1 and 15.4 L kg-1 of high-purity (≥99.9 %) C2 H4 from C3 H6 /C2 H4 and C2 H6 /C2 H4 mixtures, but also provide a large high-purity (≥99.5 %) C3 H6 recovery capacity of 60.1 L kg-1 from C3 H6 /C2 H4 mixtures. More importantly, the high-purity C3 H6 (≥99.5 %) and C2 H4 (≥99.9 %) with the productivities of 38.2 and 12.7 L kg-1 can be simultaneously obtained from C2 H6 /C3 H6 /C2 H4 mixtures through a single adsorption/desorption cycle.

Probiotics mitigate kidney damage after exposure to Sri Lanka's local groundwater from chronic kidney disease with uncertain etiology (CKDu) prevalent area in zebrafish.

Groundwater in Sri Lanka, contaminated with environmental toxins, is suspected to potentially induce chronic kidney disease of uncertain etiology (CKDu) in humans. This study aims to elucidate the potential mitigating effects of probiotics on kidney damage induced by exposure to this local groundwater (LW) in zebrafish. We used zebrafish as a model organism and exposed them to local groundwater to evaluate the risk of CKDu. Probiotics were then added at a concentration of 108 colony-forming units per milliliter (CFU/mL). Our findings revealed that exposure to local groundwater resulted in abnormalities, such as tail deletion and spinal curvature in zebrafish larvae. However, the addition of probiotics mitigated these effects, improving the hatching rate, heart rate, length, weight, deformity rate, survival rate, and abnormal behavior of zebrafish. It also positively influenced the differential expression levels of kidney development and immunity-related genes (dync2h1, foxj1, pkd2, gata3, slc20a1, il1ß, and lyso). Furthermore, exposure to LW decreased both the diversity and abundance of microbiota in zebrafish larvae. However, treatment with probiotics, such as L. plantarum and L. rhamnosus partially restored the disrupted gut microbiota and significantly impacted the cellular process pathways of the microbial community, as determined by KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis. In conclusion, this study highlights the risks associated with Sri Lanka's local groundwater from a CKDu prevalent area and confirms the beneficial effects of different probiotics. These findings may provide new insights into bacterial function in host kidney health.

Elucidating environmental factors and their combined effects on CKDu in Sri Lanka using zebrafish.

Chronic kidney disease with uncertain etiology (CKDu) in Sri Lanka has attracted much attention as a global health issue. However, how environmental factors in local drinking water induce kidney damage in organisms is still elusive. We investigated multiple environmental factors including water hardness and fluoride (HF), heavy metals (HM), microcystin-LR (MC-LR), and their combined exposure (HFMM) to elucidate their toxic effects on CKDu risk in zebrafish. Acute exposure affected renal development and inhibited the fluorescence of Na, K-ATPase alpha1A4:GFP zebrafish kidney. Chronic exposure influenced the body weight of both genders of adult fish and induced kidney damage by histopathological analyses. Furthermore, the exposure significantly disturbed differential expression genes (DEGs), diversity and richness of gut microbiota, and critical metabolites related to renal functions. The transcriptomic analysis revealed that kidney-related DEGs were linked with renal cell carcinoma, proximal tubule bicarbonate reclamation, calcium signaling pathway, and HIF-1 signaling pathway. The significantly disrupted intestinal microbiota was closely related to the environmental factors and H&E score, which demonstrated the mechanisms of kidney risks. Notably, the Spearman correlation analysis indicated that the changed bacteria such as Pseudomonas, Paracoccus, and ZOR0006, etc were significantly connected to the DEGs and metabolites. Therefore, the assessment of multiple environmental factors provided new insights on "bio-markers" as potential therapies of the target signaling pathways, metabolites, and gut bacteria to monitor or protect residents from CKDu.

A nickel-based metal-organic framework as a new cathode for chloride ion batteries with superior cycling stability.

Chloride ion batteries (CIBs) have drawn growing attention as attractive candidates for large-scale energy storage technology because of their high theoretical energy densities (2500 W h L-1), dendrite-free characteristics and abundance of chloride-containing materials available worldwide. However, the further development of CIBs is greatly limited by sluggish Cl- diffusion and distinct structural variation of cathode materials, resulting in severe decayed capacity and inferior rate performance. Metal-organic framework (MOF) materials possess regular pores/channels and flexible structural designability to accommodate charge carrier ions, but the application of MOFs in anion-type batteries has not been reported. Here, we demonstrate the first example of Ni(dpip) with two different opening sizes of tubular channels serving as the cathode for high performance CIBs. The Ni-based MOF exhibited a stable reversible capacity of 155 mA h g-1 with an admirable low capacity decay of 0.026% per cycle over 500 cycles and superior kinetics with a 10-10 cm2 s-1 average diffusion coefficient for chloride ions as well. The high performance of the Ni(dpip) cathode results from the synergetic redox couples of Ni metal nodes and N-ligands, the unique double-channel structure for reversible Cl-storage, and the low chloride diffusion energy barrier. This work switches on the new application of MOF-based materials as cathodes for CIBs.

Introducing high-valence molybdenum to stimulate lattice oxygen in a NiCo LDH cathode for chloride ion batteries.

Layered double hydroxides (LDHs) have been intensively investigated as promising cathodes for the new concept chloride ion battery (CIB) with multiple advantages of high theoretical energy density, abundant raw materials and unique dendrite-free characteristics. However, driven by the great compositional diversity, a complete understanding of interactions between metal cations, as well as a synergetic effect between metal cations and lattice oxygen on LDH host layers in terms of the reversible Cl-storage capability, is still a crucial but elusive issue. In this work, we synthesized a series of chloride-inserted trinary Mox-doped NiCo2-Cl LDH (x = 0, 0.1, 0.2, 0.3, 0.4, and 0.5) with gradient oxygen vacancies as enhanced cathodes toward CIBs. The combination of advanced spectroscopic techniques and theoretical calculations reveals that the Mo dopant facilitates oxygen vacancy formation and varies the valence states of coordinated transition metals, which can not only tune the electronic structure effectively and promote Cl-ion diffusion, but improve the redox activity of LDHs. The optimized Mo0.3NiCo2-Cl LDH delivers a reversible discharge capacity of 159.7 mA h g-1 after 300 cycles at 150 mA g-1, which is almost a triple enhancement compared to that of NiCo2Cl LDH. The superior Cl-storage of trinary Mo0.3NiCo2Cl LDH is attributed to the reversible intercalation/deintercalation of chloride ions in the LDH gallery along with the oxidation state changes in Ni0/Ni2+/Ni3+, Co0/Co2+/Co3+ and Mo4+/Mo6+ couples. This simple vacancy engineering strategy provides critical insights into the significance of the chemical interaction of various components on LDH laminates and aims to effectively design more LDH-based cathodes for CIBs, which can even be extended to other halide-ion batteries like fluoride ion batteries and bromide ion batteries.

A High-Nickel Layered Double Hydroxides Cathode Boosting the Rate Capability for Chloride Ion Batteries with Ultralong Cycling Life.

Chloride-ion batteries (CIBs) have drawn growing attention in large-scale energy storage applications owing to their comprehensive merits of high theoretical energy density, dendrite-free characteristic, and abundance of chloride-containing materials. Nonetheless, cathodes for CIBs are plagued by distinct volume effect and sluggish Cl- diffusion kinetics, leading to inferior rate capability and short cycling life. Herein, an unconventional Ni5 Ti-Cl LDH is reported with a high nickel ratio as a cathode material for CIB. The reversible capacity of Ni5 Ti-Cl LDH retains 127.9 mAh g-1 over 1000 cycles at a large current density of 1000 mA g-1 , which exceeds that of ever reported CIBs, with extraordinary low volume change of 1.006% during a whole charge/discharge process. Such superior Cl-storage performance is attributed to synergetic contributions consisting of high redox activity from Ni2+ /Ni3+ and pinning Ti that restrains local structural distortion of LDH host layers and enhances adsorption intensity of chloride atoms during the reversible Cl- intercalation/de-intercalation in LDH gallery, which are revealed by a comprehensive study including X-ray photoelectron spectroscopy, kinetic investigations, and DFT calculations. This work provides an effective strategy to design low-cost LDHs materials for high-performance CIBs, which are also applicable to other types of halide-ion batteries (e.g., fluoride-ion and bromide-ion batteries).

[Study on mechanism of Rehmanniae Radix Praeparata for treatment of osteoarthritis based on network pharmacology and molecular docking].

The mechanism of Rehmanniae Radix Praeparata against osteoarthritis was investigated based on network pharmacology, molecular docking, and in vitro experiments in the present study. Osteoclast models were established via receptor activator of nuclear factor-κB ligand(RANKL) and macrophage colony-stimulating factor(M-CSF) inducing RAW264.7 cells. Further, the influence of Rehmanniae Radix Praeparata on the activity of tartrate-resistant acid phosphatase(TRAP) was evaluated and the efficacy of Rehmanniae Radix Praeparata in the treatment of osteoarthritis was verified. The active components of Rehmanniae Radix Praeparata were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and literature, and the potential targets of the components were collected from SwissTargetPrediction. Osteoarthritis disease targets were searched in Online Mendelian Inheritance in Man(OMIM), Therapeutic Target Database(TTD), GeneCards, and DisGeNET. The intersection targets of Rehmanniae Radix Praeparata and osteoarthritis were obtained by Venny platform. The protein-protein interaction(PPI) network was constructed by Cytoscape 3.8.2, and key targets were obtained based on topology algorithm. The Database for Annotation, Visualization and Integrated Discovery(DAVID) was used to perform Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. Finally, the mRNA expression of the key targets was determined by RT-qPCR and the binding activity between the components and key targets was validated by molecular docking. The results showed that Rehmanniae Radix Prae-parata inhibited the TRAP activity, thus inhibiting bone resorption by osteoclasts and treating osteoarthritis. By network pharmacology, 14 active components of Rehmanniae Radix Praeparata and 126 intersection targets were obtained. The network pharmacology enrichment results revealed 432 biological processes and 139 signaling pathways. Key targets such as proto-oncogene tyrosine-protein kinase Src(SRC), signal transducer and activator of transcription 3(STAT3) and transcription factor p65(RELA) were obtained according to the degree in topological analysis. SRC was highly expressed in osteoclasts, which accelerated the development of osteoarthritis. Therefore, SRC was selected for subsequent verification, and Rehmanniae Radix Praeparata decreased the gene expression level of SRC. The molecular docking showed that acteoside, isoacteoside, raffinose had good bonding activity with SRC, suggesting that they might be the critical components in treating osteoarthritis. In conclusion, Rehmanniae Radix Praeparata can inhibit bone resorption by osteoclasts and balance the metabolism of articular cartilage and subchondral bone via acting on SRC, thus playing a therapeutic role in osteoarthritis. In addition, Rehmanniae Radix Praeparata may exert overall efficacy on osteoarthritis through other targets such as STAT3 and RELA, and other related pathways such as PI3 K-AKT and IL-17 signaling pathways.

Boosting Ethane/Ethylene Separation by MOFs through the Amino-Functionalization of Pores.

Adsorption technology based on ethane-selective materials is a promising alternative to energy-intensive cryogenic distillation for separating ethane (C2 H6 ) and ethylene (C2 H4 ). We employed a pore engineering strategy to tune the pore environment of a metal-organic framework (MOF) through organic functional groups and boosted the C2 H6 /C2 H4 separation of the MOF. Introduction of amino (-NH2 ) groups into Tb-MOF-76 not only decreased pore sizes but also facilitated multiple guest-host interactions in confined pores. The NH2 -functionalized Tb-MOF-76(NH2 ) has increased C2 H6 and C2 H4 uptakes and C2 H6 /C2 H4 selectivity. The results of experimental and simulated transient breakthroughs reveal that Tb-MOF-76(NH2 ) has significantly improved one-step separation performance for C2 H6 /C2 H4 mixtures with a high C2 H4 (>99.95 %) productivity of 17.66 L kg-1 compared to 7.53 L kg-1 by Tb-MOF-76, resulting from the suitable pore confinement and accessible -NH2 groups on pore surfaces.

Exposure to Sri Lanka's local groundwater in a CKDu prevalent area causes kidney damage in zebrafish.

How local groundwater induces chronic kidney disease of unknown etiology (CKDu) in Sri Lanka is still elusive. This study aims to elucidate the impacts of Sri Lanka's local groundwater in a CKDu prevalent area and reveal the possible pathogenic mechanism of CKDu using zebrafish models. The drinking water from the local underground well in Vavuniya was sampled and the water quality parameters including Na+, Mg2+, K+, Ca2+, Cl-, NO3-, SO42-, and F- were analyzed. Then, local groundwater exposure to zebrafish larvae and 293T cells was performed, and water with high hardness and fluoride was prepared as parallel groups. Our result showed that exposure to Sri Lanka's local groundwater caused developmental toxicity, kidney damage, and pronephric duct obstruction as well as abnormal behavior in zebrafish. Similar results were also found after exposure to water with high hardness and fluoride in zebrafish. Further, the expression levels of marker genes related to renal development and functions (foxj1a, dync2h1, pkd2, gata3, and slc20a1) were significantly altered, which is also confirmed in the 293T cells. Taken together, those results indicated that Sri Lanka's local groundwater in a CKDu prevalent area could cause kidney damage, implying that high water hardness and fluorine might be the inducible environmental factors for the etiological cause of CKDu.

One-Step C2 H4 Purification from Ternary C2 H6 /C2 H4 /C2 H2 Mixtures by a Robust Metal-Organic Framework with Customized Pore Environment.

One-step C2 H4 purification from ternary C2 H6 /C2 H4 /C2 H2 mixtures by a single adsorbent is of great industrial significance, but few adsorbents achieve this separation. Herein, we report a robust metal-organic framework (MOF) that possesses methyl-decorated nonpolar pores and shows one-step C2 H4 purification (purity >99.9 %) from binary C2 H6 /C2 H4 mixtures and ternary C2 H6 /C2 H4 /C2 H2 mixtures. The methyl groups in pores provide a suitable pore environment to simultaneously enhance the adsorption capacity for C2 H2 and C2 H6 compared to C2 H4 . Simulations revealed the multiple interactions between C2 H6 or C2 H2 molecules and the pore wall, while the interactions with C2 H4 molecules are weak and also unfavorable due to the repulsion from methyl groups in pores. The MOF displays high C2 H6 and C2 H2 uptakes and benchmark C2 H6 /C2 H4 selectivity (2.2), surpassing all of the reported MOFs for one-step C2 H4 purification from ternary C2 H6 /C2 H4 /C2 H2 mixtures.

The functional role of Pescadillo ribosomal biogenesis factor 1 in cancer.

Tumors are neogrowths formed by the growth of normal cells or tissues through complex mechanisms under the influence of many factors. The occurrence and development of tumors are affected by many factors. Pescadillo ribosomal biogenesis factor 1 (PES1) has been identified as a cancer-related gene. The study of these genes may open up new avenues for early diagnosis, treatment and prognosis of tumors. As a nucleolar protein and part of the Pes1/Bop1/WDR12 (PeBoW) complex, PES1 is involved in ribosome biogenesis and DNA replication. Many studies have shown that high expression of PES1 is often closely related to the occurrence, proliferation, invasion, metastasis, prognosis and sensitivity to chemotherapeutics of various human malignant tumors through a series of molecular mechanisms and signaling pathways. The molecules that regulate the expression of PES1 include microRNA (miRNA), circular RNA (circRNA), c-Jun, bromodomain-containing protein 4 (BRD4) and nucleolar phosphoprotein B23. However, the detailed pathogenic mechanisms of PES1 overexpression in human malignancies remains unclear. This article summarizes the role of PES1 in the carcinogenesis, prognosis and treatment of multiple tumors, and introduces the molecular mechanisms and signal transduction pathways related to PES1.

Acetylene Separation by a Ca-MOF Containing Accessible Sites of Open Metal Centers and Organic Groups.

Efficient separation of acetylene from a ternary acetylene-containing mixture is an important and vital task in petrochemical industry, which is difficult to achieve using a single material. Herein, a new Ca2+-based metal-organic framework (MOF) [Ca(dtztp)0.5(DMA)]·2H2O (1) was constructed using the N,O-donor ligand 2,5-di(2H-tetrazol-5-yl)terephthalic acid and the less-studied alkaline earth Ca2+ ions. The MOF shows a 3D honeycomb framework based on unique metal-carboxylate-azolate rod secondary building units. Owing to the presence of high-density organic hydrogen-bonding acceptors and open metal sites (OMSs), the activated MOF shows high adsorption capacity for C2H2 and selectivity for C2H2 over CO2, C2H4, C2H6, and CH4. Dynamic breakthrough experiments indicated the actual C2H2 separation potential of the MOF from binary (C2H2-C2H4 and C2H2-CO2) and ternary (C2H2-C2H4-CO2 and C2H2-C2H4-C2H6) mixtures. Simulations revealed that the synergistic interactions between the OMSs and N atoms in MOF and C2H2 molecules play an important role in the separation of C2H2.

A new metal-organic framework based on rare [Zn4F4] cores for efficient separation of C2H2.

Assembly via 1,4-benzenedicarboxylate linkers and Zn2+ ions afforded an MOF containing rare [Zn4F4] cubane core, showing excellent separation for C2H2-CO2 and C2H2-CH4 mixtures. Dynamic breakthrough experiments and grand canonical Monte Carlo calculations were carried out to confirm the feasibility of the MOF for the separation application of C2H2.

Aberrant DNA Methylation-Mediated FOXF2 Dysregulation Is a Prognostic Risk Factor for Gastric Cancer.

Background: The prognosis of gastric cancer (GC) patients is poor. The effect of aberrant DNA methylation on FOXF2 expression and the prognostic role of FOXF2 methylation in GC have not yet been identified. Methods: The RNA-Seq and gene methylation HM450 profile data were used for analyzing FOXF2 expression in GC and its association with methylation level. Bisulfite sequencing PCR (BSP) was performed to measure the methylation level of the FOXF2 promoter region in GC cell lines and normal GES-1 cells. The cells were treated with the demethylation reagent 5-Aza-dC, and the mRNA and protein expression levels of FOXF2 were then measured by qRT-PCR and western blot assays. The risk score system from SurvivalMeth was calculated by integrating the methylation level of the cg locus and the corresponding Cox regression coefficient. Results: FOXF2 was significantly downregulated in GC cells and tissues. On the basis of RNA-Seq and Illumina methylation 450 data, FOXF2 expression was significantly negatively correlated with the FOXF2 methylation level (Pearson's R = -0.42, p < 2.2e-16). The FOXF2 methylation level in the high FOXF2 expression group was lower than that in the low FOXF2 expression group. The BSP assay indicated that the methylation level of the FOXF2 promoter region in GC cell lines was higher than that in GES-1 cells. The qRT-PCR and western blot assay showed that FOXF2 mRNA and protein levels were increased in GC cells following treatment with 5-Aza-Dc. The methylation risk score model indicated that patients in the high risk group had poorer survival probability than those in the low risk group (HR = 1.84 (1.11-3.07) and p = 0.0068). FOXF2 also had a close transcriptional regulation network with four miRNAs and their corresponding target genes. Functional enrichment analysis of the target genes revealed that these genes were significantly related to several important signaling pathways. Conclusion: FOXF2 was downregulated due to aberrant DNA methylation in GC, and the degree of methylation in the promoter region of FOXF2 was related to the prognosis of patients. The FOXF2/miRNAs/target genes axis may play a vital biological regulation role in GC.

Application of computer tongue image analysis technology in the diagnosis of NAFLD.

Nonalcoholic fatty liver disease (NAFLD), a leading cause of chronic hepatic disease, can progress to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Therefore, it is extremely important to explore early diagnosis and screening methods. In this study, we developed models based on computer tongue image analysis technology to observe the tongue characteristics of 1778 participants (831 cases of NAFLD and 947 cases of non-NAFLD). Combining quantitative tongue image features, basic information, and serological indexes, including the hepatic steatosis index (HSI) and fatty liver index (FLI), we utilized machine learning methods, including Logistic Regression, Support Vector Machine (SVM), Random Forest (RF), Gradient Boosting Decision Tree (GBDT), Adaptive Boosting Algorithm (AdaBoost), Naïve Bayes, and Neural Network for NAFLD diagnosis. The best fusion model for diagnosing NAFLD by Logistic Regression, which contained the tongue image parameters, waist circumference, BMI, GGT, TG, and ALT/AST, achieved an AUC of 0.897 (95% CI, 0.882-0.911), an accuracy of 81.70% with a sensitivity of 77.62% and a specificity of 85.22%; in addition, the positive likelihood ratio and negative likelihood ratio were 5.25 and 0.26, respectively. The application of computer intelligent tongue diagnosis technology can improve the accuracy of NAFLD diagnosis and may provide a convenient technical reference for the establishment of early screening methods for NAFLD, which is worth further research and verification.

Trends in burden of multidrug-resistant tuberculosis in countries, regions, and worldwide from 1990 to 2017: results from the Global Burden of Disease study.

BACKGROUND: Antituberculosis-drug resistance is an important public health issue, and its epidemiological patterns has dramatically changed in recent decades. This study aimed to estimate the trends of multidrug-resistant tuberculosis (MDR-TB), which can be used to inform health strategies. METHODS: Data were collected from the Global Burden of Disease study 2017. The estimated annual percentage changes (EAPCs) were calculated to assess the trends of MDR-TB burden at global, regional, and national level from 1990 to 2017 using the linear regression model. RESULTS: Globally, the age-standardized rate (ASR) of MDR-TB burden including incidence, prevalence, death and disability-adjusted life years (DALYs) had pronounced increasing trends from 1990 to 1999, with the EAPCs were 17.63 [95% confidence interval (CI): 10.77-24.92], 17.57 (95% CI 11.51-23.95), 21.21 (95% CI 15.96-26.69), and 21.90 (95% CI 16.55-27.50), respectively. Particularly, the largest increasing trends were seen in areas and countries with low and low-middle sociodemographic index (SDI). However, the trends in incidence, prevalence, death and DALYs of MDR-TB decreased globally from 2000 to 2017, with the respective EAPCs were - 1.37 (95% CI - 1.62 to - 1.12), - 1.32 (95% CI - 1.38 to - 1.26), - 3.30 (95% CI - 3.56 to - 3.04) and - 3.32 (95% CI - 3.59 to - 3.06). Decreasing trends of MDR-TB were observed in most regions and countries, particularly that of death and DALYs in Slovenia were - 18.96 (95% CI - 20.82 to - 17.06) and -19.35 (95% CI - 21.10 to - 17.55), respectively. Whereas the pronounced increasing trends of MDR-TB occurred in Papua New Guinea, Singapore, and Australia. CONCLUSIONS: The ASR of MDR-TB showed pronounced decreasing trends from 2000 to 2017. However, the MDR-TB burden remains a substantial challenge to the TB control globally, and requires effective control strategies and healthcare systems.