Metabolic dysfunction-associated fatty liver disease increases the risk of complications after radical resection in patients with hepatocellular carcinoma.

BACKGROUND AND AIMS: The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) in hepatocellular carcinoma (HCC) patients is increasing, yet its association with postoperative complications of HCC remains unclear. The aim of this study was to investigate the impact of MAFLD on complications after radical resection in HCC patients. METHODS: Patients with HCC who underwent radical resection were included. Patients were stratified into MAFLD group and non-MAFLD group. Clinical features and post-hepatectomy complications were compared between the two groups, and logistic regression analysis was used to determine independent risk factors associated with post-hepatectomy complications. RESULTS: Among the 936 eligible patients with HCC who underwent radical resection, concurrent MAFLD was diagnosed in 201 (21.5%) patients. Compared to the non-MAFLD group, the MAFLD group exhibited a higher incidence of complications, including infectious and major complications after radical resection in HCC patients. The logistic regression analysis found that MAFLD was an independent risk factor for complications, including infectious and major complications in HCC patients following radical resection (OR 1.565, 95%CI 1.109-2.343, P = 0.012; OR 2.092, 95%CI 1.386-3.156, P < 0.001; OR 1.859, 95% CI 1.106-3.124, P = 0.019; respectively). Subgroup analysis of HBV-related HCC patients yielded similar findings, and MAFLD patients with type 2 diabetes mellitus (T2DM) exhibited a higher incidence of postoperative complications compared to those without T2DM (all P < 0.05). CONCLUSIONS: Concurrent MAFLD was associated with an increased incidence of complications after radical resection in patients with HCC, especially MAFLD with T2DM.

Chronic Pancreatitis-Associated Metabolic Bone Diseases: Epidemiology, Mechanisms, and Clinical Advances.

Chronic pancreatitis (CP) is a progressive inflammatory disease with an increasing global prevalence. In recent years, a strong association between CP and metabolic bone diseases (MBDs), especially osteoporosis, has been identified, attracting significant attentions in the research field. Epidemiological data suggest a rising trend in the incidence of MBDs among CP patients. Notably, recent studies have highlighted a profound interplay between CP and altered nutritional and immune profiles, offering insights into its linkage with MBDs.At molecular level, CP introduces a series of biochemical disturbances that compromise bone homeostasis. One critical observation is the disrupted metabolism of vitamin D and vitamin K, both essential micronutrients for maintaining bone integrity, in CP patients. In this review, we provide physio-pathological perspectives on the development and mechanisms of CP-related MBDs. We also outline some of the latest therapeutic strategies for treating patients with CP-associated MBDs, including stem cell transplantation, monoclonal antibodies, and probiotic therapy. In summary, CP-associated MBDs represent a rising medical challenge, involving multiple tissues and organs, complex disease mechanisms, and diverse treatment approaches. More in-depth studies are required for understanding the complex interplay between CP and MBDs to facilitate the development of more specific and effective therapeutic approaches.

Single-cell RNA sequencing reveals roles of unique retinal microglia types in early diabetic retinopathy.

BACKGROUND: The pathophysiological mechanisms of diabetic retinopathy (DR), a blinding disease, are intricate. DR was thought to be a microvascular disease previously. However, growing studies have indicated that the retinal microglia-induced inflammation precedes microangiopathy. The binary concept of microglial M1/M2 polarization paradigms during inflammatory activation has been debated. In this study, we confirmed microglia had the most significant changes in early DR using single-cell RNA sequencing. METHODS: A total of five retinal specimens were collected from donor SD rats. Changes in various cells of the retina at the early stage of DR were analyzed using single-cell sequencing technology. RESULTS: We defined three new microglial subtypes at cellular level, including two M1 types (Egr2+ M1 and Egr2- M1) and one M2 type. We also revealed the anatomical location between these subtypes, the dynamic changes of polarization phenotypes, and the possible activation sequence and mutual activation regulatory mechanism of different cells. Furthermore, we constructed an inflammatory network involving microglia, blood-derived macrophages and other retinal nonneuronal cells. The targeted study of new disease-specific microglial subtypes can shorten the time for drug screening and clinical application, which provided insight for the early control and reversal of DR. CONCLUSIONS: We found that microglia show the most obvious differential expression changes in early DR and reveal the changes in microglia in a high-glucose microenvironment at the single-cell level. Our comprehensive analysis will help achieve early reversal and control the occurrence and progression of DR.

Nanomaterial-based biosensors for the detection of foodborne bacteria: a review.

Ensuring food safety is a critical concern for the development and well-being of humanity, as foodborne illnesses caused by foodborne bacteria have increasingly become a major public health concern worldwide. Traditional food safety monitoring systems are expensive and time-consuming, relying heavily on specialized equipment and operations. Therefore, there is an urgent need to develop low-cost, user-friendly and highly sensitive biosensors for detecting foodborne bacteria. In recent years, the combination of nanomaterials with optical biosensors has provided a prospective future platform for the detection of foodborne bacteria. By harnessing the unique properties of nanomaterials, such as their high surface area-to-volume ratio and exceptional sensitivity, in tandem with the precision of optical biosensing techniques, a new prospect has opened up for the rapid and accurate identification of potential bacterial contaminants in food. This review focuses on recent advances and new trends of nanomaterial-based biosensors for the detection of foodborne pathogens, which mainly include noble metal nanoparticles (NMPs), metal organic frameworks (MOFs), graphene nanomaterials, quantum dot (QD) nanomaterials, upconversion fluorescent nanomaterials (UCNPs) and carbon dots (CDs). Additionally, we summarized the research progress of color indicators, nanozymes, natural enzyme vectors and fluorescent dye biosensors, focusing on the advantages and disadvantages of nanomaterial-based biosensors and their development prospects. This review provides an outlook on future technological directions and potential applications to help identify the most promising areas of development in this field.

Effect of Doping with Different Nb Contents on the Properties of CoCrFeNi High-Entropy Alloys.

A series of five-element CoCrFeNi-Nbx (x = 0, 1, 3, 5, 7, and 9 wt%) high-entropy alloys were prepared using high-energy ball milling and discharge plasma sintering methods. Then, the effects of doping with Nb elements on the organization and properties of the CoCrFeNi HEAs were systematically investigated by tensile testing, hardness testing, and examining their micro-morphologies. The results show that with the addition of the Nb element, the lattice distortion of the alloy due to the large size of the Nb atoms causes the microstructure of CoCrFeNi HEAs to change from a single-phase FCC structure to a dual-phase structure of FCC and Laves. With the increase in the Nb content, the increase in the volume fraction of the hard and brittle Laves phase leads to the enhancement of the HEA's tensile strength, yield strength, and hardness, and a decrease in plasticity. The Nb5 alloy showed the most excellent comprehensive performance, with a tensile strength, yield strength, and plasticity of 879.1 MPa, 491.8 MPa, and 39.8%, respectively, and all the properties were improved compared with those of the HEAs obtained by the arc melting method. The increase in the hardness of the HEAs was nearly proportional to the increase in the volume fraction of the Laves phase, which was the direct cause of the increase in the hardness of the HEA. Therefore, since the Laves phase is the direct cause of the increase in HEA hardness, the doping of CoCrFeNi HEAs with Nb can significantly improve the properties of HEAs.

Nutritional intervention is promising in alleviating liver injury during tuberculosis treatment: a review.

Liver injury is a main adverse effect of first-line tuberculosis drugs. Current management of tuberculosis-drug-induced liver injury (TBLI) mainly relies on withdrawing tuberculosis drugs when necessary. No effective treatment exists. Various nutrients and functional food ingredients may play a protective role in TBLI. However, a comprehensive review has not been conducted to compare the effects of these nutrients and functional food ingredients. We searched Pubmed and Web of Science databases from the earliest date of the database to March 2023. All available in-vitro, animal and clinical studies that examined the effects of nutritional intervention on TBLI were included. The underlying mechanism was briefly reviewed. Folic acid, quercetin, curcumin, Lactobacillus casei, spirulina and Moringa oleifera possessed moderate evidence to have a beneficial effect on alleviating TBLI mostly based on animal studies. The evidence of other nutritional interventions on TBLI was weak. Alleviating oxidative stress and apoptosis were the leading mechanisms for the beneficial effects of nutritional intervention on TBLI. In conclusion, a few nutritional interventions are promising for alleviating TBLI including folic acid, quercetin, curcumin, L. casei, spirulina and M. oleifera, the effectiveness and safety of which need further confirmation by well-designed randomized controlled trials. The mechanisms for the protective role of these nutritional interventions on TBLI warrant further study, particularly by establishing the animal model of TBLI using the tuberculosis drugs separately.

Roflumilast attenuates neuroinflammation post retinal ischemia/reperfusion injury by regulating microglia phenotype via the Nrf2/STING/NF-κB pathway.

PURPOSE: The abnormal polarisation of microglial cells (MGs) following retinal ischemia/reperfusion (RIR) initiates neuroinflammation and progressive death of retinal ganglion cells (RGCs), causing increasingly severe and irreversible visual dysfunction. Roflumilast (Roflu) is a promising candidate for treating neuroinflammatory diseases. This study aimed to explore whether Roflu displayed a cytoprotective effect against RIR-induced neuroinflammation and to characterise the underlying signalling pathway. METHODS: The effects and mechanism of Roflu against RIR injury were investigated in C57BL/6J mice and the BV2 cell line. We used quantitative real-time PCR and enzyme-linked immunosorbent assay to examine the levels of inflammatory factors. Furthermore, haematoxylin and eosin and immunofluorescence (IF) stainings were used to assess the morphology of the retina and the states of MGs and RGCs. Reactive oxygen species (ROS) levels were examined using a ROS assay kit, while whole-genome sequencing analysis was conducted to identify altered pathways and molecules. Western blotting and IF staining were used to quantify the proteins associated with the nuclear factor erythroid 2-related factor 2 (Nrf2)/stimulator of interferon gene (STING)/nuclear factor kappa beta (NF-κB) pathway. RESULTS: MG polarisation includes the pro-inflammatory and neurotoxic M1 phenotype as well as the anti-inflammatory and neuroprotective M2 phenotype. Roflu significantly attenuated MG activation and contributed to a shift in the MG phenotype from M1 to M2. Moreover, Roflu decreased ROS release and increased heme oxygenase 1 and NAD(P)H quinone oxidoreductase 1 expression. In vitro and in vivo experiments validated that Roflu exerted its neuroprotective effects primarily by upregulating the Nrf2/STING/NF-κB pathway. However, these effects were abrogated when the Nrf2 expression was inhibited by pharmacological or genetic manipulation. CONCLUSIONS: Roflu suppressed RIR-induced neuroinflammation by driving the shift of MG polarisation from M1 to M2 phenotype, which was mediated by the upregulation of the Nrf2/STING/NK-κB pathway.

The role and advantage of traditional Chinese medicine in the prevention and treatment of COVID-19.

The global coronavirus disease 2019 (COVID-19) pandemic has had a massive impact on global social and economic development and human health. By combining traditional Chinese medicine (TCM) with modern medicine, the Chinese government has protected public health by supporting all phases of COVID-19 prevention and treatment, including community prevention, clinical treatment, control of disease progression, and promotion of recovery. Modern medicine focuses on viruses, while TCM focuses on differential diagnosis of patterns associated with viral infection of the body and recommends the use of TCM decoctions for differential treatment. This differential diagnosis and treatment approach, with its profoundly empirical nature and holistic view, endows TCM with an accessibility advantage and high application value for dealing with COVID-19. Here, we summarize the advantage of and evidence for TCM use in COVID-19 prevention and treatment to draw attention to the scientific value and accessibility advantage of TCM and to promote the use of TCM in response to public health emergencies. Please cite this article as: Huang M, Liu YY, Xiong K, Yang FW, Jin XY, Wang ZQ, Zhang JH, Zhang BL. The role and advantage of traditional Chinese medicine in the prevention and treatment of COVID-19. J Integr Med. 2023; 21(5): 407-412.

Experimental and Numerical Investigation of the Tensile and Failure Response of Multiple-Hole-Fiber-Reinforced Magnesium Alloy Laminates under Various Temperature Environments.

In this paper, the tensile mechanical behavior and progressive damage morphology of glass-fiber-reinforced magnesium alloy laminate for different numbers of holes in a temperature range of 25-180 °C were investigated. In addition, based on extensive tensile tests, the tensile mechanical behavior and microscopic damage morphology of porous-glass-fiber-reinforced magnesium alloy laminates at different temperatures were observed by finite element simulation and scanning electron microscopy (SEM). Finally, the numerical simulation and experimental results were in good accordance with the prediction of mechanical properties and fracture damage patterns of the laminates, the average difference between the residual strength values of the specimens at ambient temperature was 5.57%, and the stress-strain curves were in good agreement. The experimental and finite element analysis results showed that the damaged area of the bonded layer tended to expand with the increase in the number of holes, which has a lesser effect on the ultimate tensile strength. As the temperature increased, the specimens changed from obvious fiber breakage (pull-out) and the resin matrix damage mode to matrix softening damage and interfacial delamination fracture damage. As the testing temperature of the specimens increased from 25 °C to 180 °C, the tensile strength of the specimens decreased by an average of 51.59%, while the tensile strength of the specimens showed a nonlinear decreasing trend. The damage mechanism of porous-glass-fiber-reinforced magnesium alloy laminates at different temperatures is discussed in this paper, which can provide a reference for engineering applications and design.

Crystalline versus Amorphous: High-Performance Hafnium Phosphonate Framework for the Separation of Uranium and Transuranium Elements.

Metal phosphonate frameworks (MPFs) consisting of tetravalent metal ions and aryl-phosphonate ligands feature a large affinity for actinides and excellent stabilities in harsh aqueous environments. However, it remains elusive how the crystallinity of MPFs influences their performance in actinide separation. To this end, we prepared a new category of porous, ultrastable MPF with different crystallinities for uranyl and transuranium separation. The results demonstrated that crystalline MPF was generally a better adsorbent for uranyl than the amorphous counterpart and ranked as the top-performing one for uranyl and plutonium in strong acidic solutions. A plausible uranyl sequestration mechanism was unveiled by using powder X-ray diffraction in tandem with vibrational spectroscopy, thermogravimetry, and elemental analysis.

Tumor aerobic glycolysis confers immune evasion through modulating sensitivity to T cell-mediated bystander killing via TNF-α.

Metabolic reprogramming toward glycolysis is a hallmark of cancer malignancy. The molecular mechanisms by which the tumor glycolysis pathway promotes immune evasion remain to be elucidated. Here, by performing genome-wide CRISPR screens in murine tumor cells co-cultured with cytotoxic T cells (CTLs), we identified that deficiency of two important glycolysis enzymes, Glut1 (glucose transporter 1) and Gpi1 (glucose-6-phosphate isomerase 1), resulted in enhanced killing of tumor cells by CTLs. Mechanistically, Glut1 inactivation causes metabolic rewiring toward oxidative phosphorylation, which generates an excessive amount of reactive oxygen species (ROS). Accumulated ROS potentiate tumor cell death mediated by tumor necrosis factor alpha (TNF-α) in a caspase-8- and Fadd-dependent manner. Genetic and pharmacological inactivation of Glut1 sensitizes tumors to anti-tumor immunity and synergizes with anti-PD-1 therapy through the TNF-α pathway. The mechanistic interplay between tumor-intrinsic glycolysis and TNF-α-induced killing provides new therapeutic strategies to enhance anti-tumor immunity.

The tumor immune microenvironment of nasopharyngeal carcinoma after gemcitabine plus cisplatin treatment.

Gemcitabine plus cisplatin (GP) chemotherapy is the standard of care for nasopharyngeal carcinoma (NPC). However, the mechanisms underpinning its clinical activity are unclear. Here, using single-cell RNA sequencing and T cell and B cell receptor sequencing of matched, treatment-naive and post-GP chemotherapy NPC samples (n = 15 pairs), we show that GP chemotherapy activated an innate-like B cell (ILB)-dominant antitumor immune response. DNA fragments induced by chemotherapy activated the STING type-I-interferon-dependent pathway to increase major histocompatibility complex class I expression in cancer cells, and simultaneously induced ILB via Toll-like receptor 9 signaling. ILB further expanded follicular helper and helper type 1 T cells via the ICOSL-ICOS axis and subsequently enhanced cytotoxic T cells in tertiary lymphoid organ-like structures after chemotherapy that were deficient for germinal centers. ILB frequency was positively associated with overall and disease-free survival in a phase 3 trial of patients with NPC receiving GP chemotherapy ( NCT01872962 , n = 139). It also served as a predictor for favorable outcomes in patients with NPC treated with GP and immunotherapy combined treatment (n = 380). Collectively, our study provides a high-resolution map of the tumor immune microenvironment after GP chemotherapy and uncovers a role for B cell-centered antitumor immunity. We also identify and validate ILB as a potential biomarker for GP-based treatment in NPC, which could improve patient management.

Anisotropic Microspheres-Cryogel Composites Loaded with Magnesium l-Threonate Promote Osteogenesis, Angiogenesis, and Neurogenesis for Repairing Bone Defects.

To achieve osteogenesis, angiogenesis, and neurogenesis for repairing bone defects, we constructed an anisotropic microspheres-cryogel composite loaded with magnesium l-threonate (MgT). These composites were prepared by the photo-click reaction of norbornene-modified gelatin (GB) in the presence of MgT-loaded microspheres through the bidirectional freezing method. The composites possessed an anisotropic macroporous (around 100 µm) structure and sustained release of bioactive Mg2+, which facilitate vascular ingrowth. These composites could significantly promote osteogenic differentiation of bone marrow mesenchymal stem cells, tubular formation of human umbilical vein vessel endothelial cells, and neuronal differentiation in vitro. Additionally, these composites significantly promoted early vascularization and neurogenesis as well as bone regeneration in the rat femoral condyle defects. In conclusion, owing to the anisotropic macroporous microstructure and bioactive MgT, these composites could simultaneously promote bone, blood vessel, and nerve regeneration, showing great potential for bone tissue engineering.

A novel strategy for Pu determination in water samples by automated separation in combination with direct ICP-MS/MS measurement.

Methods for Pu determination in water samples has been longtime studied but they generally involved tedious manual operations. In this context, we proposed a novel strategy for accurate determination of ultra-trace Pu in water samples by the combination of fully automated separation with direct ICP-MS/MS measurement. A recently commercialized extraction resin TK200 was used for single-column separation due to its distinctive nature. Acidified waters up to 1 L were directly loaded to the resin at high flow rate (15 mL min-1) with omitting the frequently used co-precipitation process. Small volumes of dilute HNO3 were used for column washing, and Pu was efficiently eluted within only 2 mL 0.5 mol L-1 HCl-0.1 mol L-1 HF with a stable recovery (65%). This separation procedure was fully automated under the control of user program, meanwhile the final eluent was compatible for direct ICP-MS/MS measurement without extra sample treatment. In that way, both the labor intensity and reagent consumption were minimized compared with existing methods. With the high decontamination (104 to 105) of U in the chemical separation and the further elimination of uranium hydrides under oxygen reaction model during ICP-MS/MS measurement, the overall interference yields of UH+/U+ and UH2+/U+ were down to 10-15. The limits of detection (LODs) of this method reached 0.32 µBq L-1 for 239Pu and 2.00 µBq L-1 for 240Pu, which were much lower than those stipulated in the general guidelines for drinking water standards, suggesting this method was promising in routine or emergency radiation monitoring. Furthermore, the established method was successfully applied in a pilot study to determine global fallout derived Pu in surface glacier samples with extremely low concentrations of 239+240Pu, which suggested the method would also be feasible in glacial chronology studies in the future.

Normal palpebral anthropometric measurements in Uygur population： A cross-sectional study.

OBJECTIVE: To provide a normative palpebral database for the Uygur subjects to determine norms that may contribute to the diagnosis and prognosis of eyelid diseases. Methods: The cross-sectional study was conducted from March to May 2021 at the First People's Hospital of Kashi, China, and comprised Uygur subjects of either gender aged 18-70 years. The slant, height and width of the palpebral fissure, vertical brow-upper lid distance, intercanthal distance, pupillary distance, brow height, crease height and levator function were measured. Data was analysed using SPSS 22. RESULTS: Of the 335 subjects having mean age 41.41±14.53 years, 165(49.3%) were males with mean age 41.08±14.23 years and 170(50.7%) were females with mean age 41.74±14.85 years. There were 107(31.9%) subjects aged 18-30 years, 115(34.3%) aged 31-50 years and 113(33.7%) aged 51-70 years. Mean palpebral fissure width and margin reflex distance of the palpebrae were significantly different in terms of gender (p<0.05). Age was also a significant factor on several counts (p<0.05). Conclusion: Anthropometric measurements of eyelid in Uygur subjects indicated certain peculiarities.

Impact of MAFLD on the complications after hepatectomy in patients with HBV-related hepatocellular carcinoma.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a term that was proposed in 2020 by a group of international experts. However, the impact of MAFLD on complications after hepatectomy in patients with hepatocellular carcinoma is not clear. The aim of this study is to explore the influence of MAFLD on the complications after hepatectomy in patients with hepatitis B virus-related hepatocellular carcinoma (HBV-HCC). Patients with HBV-HCC who underwent hepatectomy between January 2019 and December 2021 were consecutively enrolled. The predictors of complications after hepatectomy in HBV-HCC patients were retrospectively analyzed. Among the 514 eligible HBV-HCC patients, 117 (22.8%) were diagnosed with concurrent MAFLD. Post hepatectomy complications occurred in 101 patients (19.6%), including 75 patients (14.6%) with infectious complications and 40 patients (7.8%) with major complications. Univariate analysis showed that MAFLD was not the risk factor for complications after hepatectomy in patients with HBV-HCC (P > .05). However, univariate and multivariate analysis revealed that lean-MAFLD was an independent risk factor for post hepatectomy complications in patients with HBV-HCC (odds ratio 2.245; 95% confidence interval 1.243-5.362, P = .028). Similar results were found in the analysis of predictors for infectious and major complications after hepatectomy in patients with HBV-HCC. MAFLD commonly coexists with HBV-HCC and is not directly associated with complications after hepatectomy, but lean-MAFLD is an independent risk factor for post hepatectomy complications in patients with HBV-HCC.

Conjunctival sac microbiome in anophthalmic patients: Flora diversity and the impact of ocular prosthesis materials.

Purpose: To explore the changes of bacterial flora in anophthalmic patients wearing ocular prosthesis (OP) and the microbiome diversity in conditions of different OP materials. Methods: A cross-sectional clinical study was conducted, involving 19 OP patients and 23 healthy subjects. Samples were collected from the upper, lower palpebral, caruncle, and fornix conjunctiva. 16S rRNA sequencing was applied to identify the bacterial flora in the samples. The eye comfort of each OP patient was determined by a questionnaire. In addition, demographics information of each participant was also collected. Results: The diversity and richness of ocular flora in OP patients were significantly higher than that in healthy subjects. The results of flora species analysis also indicated that in OP patients, pathogenic microorganisms such as Escherichia Shigella and Fusobacterium increased significantly, while the resident flora of Lactobacillus and Lactococcus decreased significantly. Within the self-comparison of OP patients, compared with Polymethyl Methacrylate (PMMA), prosthetic material of glass will lead to the increased colonization of opportunistic pathogens such as Alcaligenes, Dermabacter and Spirochaetes, while gender and age have no significant impact on ocular flora. Conclusions: The ocular flora of OP patients was significantly different from that of healthy people. Abundant colonization of pathogenic microorganisms may have an important potential relationship with eye discomfort and eye diseases of OP patients. PMMA, as an artificial eye material, demonstrated potential advantages in reducing the colonization of opportunistic pathogens.

Ameliorating Effects of Vitamin K2 on Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice.

Ulcerative colitis (UC) is a chronic recurrent inflammatory illness of the gastrointestinal system. The purpose of this study was to explore the alleviating effect of vitamin K2 (VK2) on UC, as well as its mechanism. C57BL/6J mice were given 3% DSS for seven days to establish UC, and they then received VK2 (15, 30, or 60 mg/kg·bw) and 5-aminosalicylic acid (100 mg/kg·bw) for two weeks. We recorded the clinical signs, body weights, colon lengths, and histological changes during the experiment. We detected the inflammatory factor expressions using enzyme-linked immunosorbent assay (ELISA) kits, and we detected the tight junction proteins using Western blotting. We analyzed the intestinal microbiota alterations and short-chain fatty acids (SCFAs) using 16S rRNA sequencing and targeted metabolomics. According to the results, VK2 restored the colon lengths, improved the colonic histopathology, reduced the levels of proinflammatory cytokines (such as IL-1ß, TNF-α, and IL-6), and boosted the level of the immunosuppressive cytokine IL-10 in the colon tissues of the colitis mice. Moreover, VK2 promoted the expression of mucin and tight junction proteins (such as occludin and zonula occludens-1) in order to preserve the intestinal mucosal barrier function and prevent UC in mice. Additionally, after the VK2 intervention, the SCFAs and SCFA-producing genera, such as Eubacterium_ruminantium_group and Faecalibaculum, were elevated in the colon. In conclusion, VK2 alleviated the DSS-induced colitis in the mice, perhaps by boosting the dominant intestinal microflora, such as Faecalibaculum, by reducing intestinal microflora dysbiosis, and by modulating the expression of SCFAs, inflammatory factors, and intestinal barrier proteins.

Relation of Red Cell Distribution Width to Glucose Metabolism and Adverse Long-Term Prognosis in Patients with Acute Coronary Syndrome.

Introduction: Red cell distribution width (RDW) reflects the heterogeneity of red blood cell size. However, few studies examined whether RDW is related to glucose metabolism indices, such as fasting blood glucose (FBG) and hemoglobin A1c (HbA1c), diabetic mellitus (DM) state or long-term outcomes of acute coronary syndrome (ACS) patients. Methods and Results: A total of 448 consecutive patients with ACS were enrolled in this study. All patients were followed up for major cardiovascular adverse events (MACEs), and the mean follow-up was 952 days. Linear regression analysis showed that RDW inversely correlated with FBG but not HbA1c or DM. Kaplan-Meier survival curve analysis demonstrated that higher RDW levels were significantly positively associated with MACEs in the whole study population and the ACS patients with high FBG but not the low FBG group. Cox multivariate regression analysis revealed the independent function of RDW on MACEs in all ACS patients and ACS patients with high FBG. The receiver operating characteristic (ROC) curve demonstrated the optimal cutoff value of RDW for MACEs. Conclusion: We first reported that higher RDW was associated with decreased FBG but not HbA1c or DM and an increased risk of MACEs in patients with ACS. This relationship was also found in ACS patients with higher FBG levels but not in ACS patients with lower FBG.

PBQ-Enhanced QUIC: QUIC with Deep Reinforcement Learning Congestion Control Mechanism.

Currently, the most widely used protocol for the transportation layer of computer networks for reliable transportation is the Transmission Control Protocol (TCP). However, TCP has some problems such as high handshake delay, head-of-line (HOL) blocking, and so on. To solve these problems, Google proposed the Quick User Datagram Protocol Internet Connection (QUIC) protocol, which supports 0-1 round-trip time (RTT) handshake, a congestion control algorithm configuration in user mode. So far, the QUIC protocol has been integrated with traditional congestion control algorithms, which are not efficient in numerous scenarios. To solve this problem, we propose an efficient congestion control mechanism on the basis of deep reinforcement learning (DRL), i.e., proximal bandwidth-delay quick optimization (PBQ) for QUIC, which combines traditional bottleneck bandwidth and round-trip propagation time (BBR) with proximal policy optimization (PPO). In PBQ, the PPO agent outputs the congestion window (CWnd) and improves itself according to network state, and the BBR specifies the pacing rate of the client. Then, we apply the presented PBQ to QUIC and form a new version of QUIC, i.e., PBQ-enhanced QUIC. The experimental results show that the proposed PBQ-enhanced QUIC achieves much better performance in both throughput and RTT than existing popular versions of QUIC, such as QUIC with Cubic and QUIC with BBR.