Combined transcriptome and metabolome analysis revealed the molecular mechanisms of fruit skin coloration in pink strawberry.

Elucidating the key genes and metabolites responsible for fruit skin color is essential for the breeding of strawberry varieties with beautiful fruit color. Here, transcriptome and metabolome analyses were used to identify the key genes and metabolites associated with fruit skin color in strawberry accessions of red skin (Kaorino), white skin (2012-W02), and the pink skin (Fenyu NO.1, the F1 hybrid of Kaorino and 2012-W02). The metabolomic data showed that the content of anthocyanin-related metabolites, such as p-Coumaroyl quinic acid, 5-Hydroxyconiferyl alcohol and Coumestrol were significantly higher in red-skinned strawberry line Kaorino than in the white-skinned line 2012-W02. The flavonoids and isoflavonoids such as syringetin and 2,7,4'-trihydroxy-isoflavone, were less expressed in the Kaorino than in the other two accessions. Transcriptome analysis revealed that the expression of genes involved in anthocyanin biosynthesis, such as BZ1, F3H, CHS, CHI, DFR, 4CL, PAL, CCR, 4CL, F5H, REF1 and UGT72E, were also significantly upregulated in the red-skinned line Kaorino compared to the white-skinned line 2012-W02, while the HCT, CYP75B1, FG3, HIDH, IF7MAT, I2'H, and VR was downregulated in Kaorino. Combined transcriptome and metabolome analyses revealed that the pathways of isoflavonoid biosynthesis and flavone and flavonol biosynthesis, and the phenylpropanoid biosynthesis pathway essential for anthocyanin synthesis were commonly enriched by DRMs and DEGs. In addition, the metabolites of peonidin 3-O-glucoside, 2'-hydroxydaidzein and daidzin, and the genes of CYP93B2_16 and UGT73C6 were detected and most accumulated in pink-skinned Fenyu NO.1. This result suggested that the main strategy for obtaining a red skin color is to enhance the upstream pathway of anthocyanin biosynthesis, including the phenylpropanoid biosynthesis pathway, and to restrict the downstream steps in the flavonoid biosynthesis pathway, such as the branch pathway of flavone and flavonol biosynthesis and isoflavonoid biosynthesis.

Comprehensive risk factor-based nomogram for predicting one-year mortality in patients with sepsis-associated encephalopathy.

Sepsis-associated encephalopathy (SAE) is a frequent and severe complication in septic patients, characterized by diffuse brain dysfunction resulting from systemic inflammation. Accurate prediction of long-term mortality in these patients is critical for improving clinical outcomes and guiding treatment strategies. We conducted a retrospective cohort study using the MIMIC IV database to identify adult patients diagnosed with SAE. Patients were randomly divided into a training set (70%) and a validation set (30%). Least absolute shrinkage and selection operator regression and multivariate logistic regression were employed to identify significant predictors of 1-year mortality, which were then used to develop a prognostic nomogram. The model's discrimination, calibration, and clinical utility were assessed using the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analysis, respectively. A total of 3,882 SAE patients were included in the analysis. The nomogram demonstrated strong predictive performance with AUCs of 0.881 (95% CI: 0.865, 0.896) in the training set and 0.859 (95% CI: 0.830, 0.888) in the validation set. Calibration plots indicated good agreement between predicted and observed 1-year mortality rates. The decision curve analysis showed that the nomogram provided greater net benefit across a range of threshold probabilities compared to traditional scoring systems such as Glasgow Coma Scale and Sequential Organ Failure Assessment. Our study presents a robust and clinically applicable nomogram for predicting 1-year mortality in SAE patients. This tool offers superior predictive performance compared to existing severity scoring systems and has significant potential to enhance clinical decision-making and patient management in critical care settings.

Honeycomb Bionic Graphene Oxide Quantum Dot/Layered Double Hydroxide Composite Nanocoating Promotes Osteoporotic Bone Regeneration via Activating Mitophagy.

Abnormal osteogenic and remodeling microenvironment due to osteoblast apoptosis are the primary causes of delayed fracture healing in osteoporotic patients. Magnesium (Mg) alloys exhibit biodegradability and appropriate elastic moduli for bone defects in osteoporosis, but the effect on the local bone remodeling disorder is still insufficient. Inspired by the "honeycomb," layered double hydroxide (LDH) with regular traps with graphene oxide quantum dots (GOQDs) inlayed is constructed by pulsed electrodeposition to generate GOQD/LDH composite nanocoatings on the surfaces of Mg alloy substrates. The honeycomb bionic multi-layer stereoscopic structure shows good regulation of the degradation of Mg alloy for the support of healing time required for osteoporotic bone defect. Within its lattice, the local microenvironment conducive to osteogenesis is provided by both the rescue effect of GOQD and LDH. The osteoblast apoptosis is rescued due to the activation of mitophagy to clear dysfunctional mitochondria, where the upregulation of BNIP3 phosphorylation played a key role. The osteoporotic rat model of femoral defects confirmed the improvement of bone regeneration and osseointegration of GOQD/LDH coating. In summary, honeycomb bionic composite nanocoatings with controllable degradation and excellent pro-osteogenic performance demonstrated a promising design strategy on Mg alloy implants in the therapy of osteoporotic bone defects.

SPACE: Spatially variable gene clustering adjusting for cell type effect for improved spatial domain detection.

Recent advances in spatial transcriptomics have significantly deepened our understanding of biology. A primary focus has been identifying spatially variable genes (SVGs) which are crucial for downstream tasks like spatial domain detection. Traditional methods often use all or a set number of top SVGs for this purpose. However, in diverse datasets with many SVGs, this approach may not ensure accurate results. Instead, grouping SVGs by expression patterns and using all SVG groups in downstream analysis can improve accuracy. Furthermore, classifying SVGs in this manner is akin to identifying cell type marker genes, offering valuable biological insights. The challenge lies in accurately categorizing SVGs into relevant clusters, aggravated by the absence of prior knowledge regarding the number and spectrum of spatial gene patterns. Addressing this challenge, we propose SPACE, SPatially variable gene clustering Adjusting for Cell type Effect, a framework that classifies SVGs based on their spatial patterns by adjusting for confounding effects caused by shared cell types, to improve spatial domain detection. This method does not require prior knowledge of gene cluster numbers, spatial patterns, or cell type information. Our comprehensive simulations and real data analyses demonstrate that SPACE is an efficient and promising tool for spatial transcriptomics analysis.

BayesKAT: bayesian optimal kernel-based test for genetic association studies reveals joint genetic effects in complex diseases.

Genome-wide Association Studies (GWAS) methods have identified individual single-nucleotide polymorphisms (SNPs) significantly associated with specific phenotypes. Nonetheless, many complex diseases are polygenic and are controlled by multiple genetic variants that are usually non-linearly dependent. These genetic variants are marginally less effective and remain undetected in GWAS analysis. Kernel-based tests (KBT), which evaluate the joint effect of a group of genetic variants, are therefore critical for complex disease analysis. However, choosing different kernel functions in KBT can significantly influence the type I error control and power, and selecting the optimal kernel remains a statistically challenging task. A few existing methods suffer from inflated type 1 errors, limited scalability, inferior power or issues of ambiguous conclusions. Here, we present a new Bayesian framework, BayesKAT (https://github.com/wangjr03/BayesKAT), which overcomes these kernel specification issues by selecting the optimal composite kernel adaptively from the data while testing genetic associations simultaneously. Furthermore, BayesKAT implements a scalable computational strategy to boost its applicability, especially for high-dimensional cases where other methods become less effective. Based on a series of performance comparisons using both simulated and real large-scale genetics data, BayesKAT outperforms the available methods in detecting complex group-level associations and controlling type I errors simultaneously. Applied on a variety of groups of functionally related genetic variants based on biological pathways, co-expression gene modules and protein complexes, BayesKAT deciphers the complex genetic basis and provides mechanistic insights into human diseases.

miR-3188 inhibits hepatitis B virus transcription by targeting Bcl-2.

Transcription of the covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) is subject to dual regulation by host factors and viral proteins. MicroRNAs (miRNAs) can regulate the expression of target genes at the post-transcriptional level. Systematic investigation of miRNA expression in HBV infection and the interaction between HBV and miRNAs may deepen our understanding of the transcription mechanisms of HBV cccDNA, thereby providing opportunities for intervention. miRNA sequencing and real-time quantitative PCR (qRT-PCR) were used to analyze miRNA expression after HBV infection of cultured cells. Clinical samples were analyzed for miRNAs and HBV transcription-related indicators, using qRT-PCR, enzyme-linked immunoassay (ELISA), and Western blot. miRNA mimics or inhibitors were used to study their effects on the HBV life cycle. The target genes of miR-3188 and their roles in HBV cccDNA transcription were also identified. The expression of 10 miRNAs, including miR-3188, which was significantly decreased after HBV infection, was measured in clinical samples from patients with chronic HBV infection. Overexpression of miR-3188 inhibited HBV transcription, whereas inhibition of miR-3188 expression promoted HBV transcription. Further investigation confirmed that miR-3188 inhibited HBV transcription by targeting Bcl-2. miR-3188 is a key miRNA that regulates HBV transcription by targeting the host protein Bcl-2. This observation provides insights into the regulation of cccDNA transcription and suggests new targets for anti-HBV treatment.

Potential diagnostic markers shared between non-alcoholic fatty liver disease and atherosclerosis determined by machine learning and bioinformatic analysis.

Background: Evidence indicates that chronic non-alcoholic fatty liver disease (NAFLD) can increase the risk of atherosclerosis (AS), but the underlying mechanism remains unclear. Objective: This study is intended for confirming key genes shared between NAFLD and AS, and their clinical diagnostic value to establish a foundation for searching novel therapeutic targets. Methods: We downloaded the Gene Expression Omnibus (GEO) datasets, GSE48452 and GSE89632 for NAFLD and GSE100927, GSE40231 and GSE28829 for AS. The progression of NAFLD co-expression gene modules were recognized via weighted gene co-expression network analysis (WGCNA). We screened for differentially expressed genes (DEGs) associated with AS and identified common genes associated with NAFLD and AS using Venn diagrams. We investigated the most significant core genes between NAFLD and AS using machine learning algorithms. We then constructed a diagnostic model by creating a nomogram and evaluating its performance using ROC curves. Furthermore, the CIBERSORT algorithm was utilized to explore the immune cell infiltration between the two diseases, and evaluate the relationship between diagnostic genes and immune cells. Results: The WGCNA findings associated 1,129 key genes with NAFLD, and the difference analysis results identified 625 DEGs in AS, and 47 genes that were common to both diseases. We screened the core RPS6KA1 and SERPINA3 genes associated with NAFLD and AS using three machine learning algorithms. A nomogram and ROC curves demonstrated that these genes had great clinical meaning. We found differential expression of RPS6KA1 in patients with steatosis and NASH, and of SERPINA3 only in those with NASH compared with normal individuals. Immune infiltration findings revealed that macrophage and mast cell infiltration play important roles in the development of NAFLD and AS. Notably, SERPINA3 correlated negatively, whereas RPS6KA1 correlated positively with macrophages and mast cells. Conclusion: We identified RPS6KA1 and SERPINA3 as potential diagnostic markers for NAFLD and AS. The most promising marker for a diagnosis of NAFLD and AS might be RPS6KA1, whereas SERPINA3 is the most closely related gene for NASH and AS. We believe that further exploration of these core genes will reveal the etiology and a pathological relationship between NAFLD and AS.

[Effect of high selenium on insulin signaling pathway PI3K-AKT-mTOR in L02 cells].

OBJECTIVE: To observe the effect of high selenium on insulin signaling pathway PI3K-AKT-mTOR in L02 cells. METHODS: One group of L02 cell was treated with different concentrations of selenomethionine(SeMet, 0.001, 0.0025, 0.005, 0.0075, 0.01, 0.025, 0.05, 0.075 and 0.1µmol/L) for 48 h, then cultured with serum-free medium for 4 h and stimulated with 1 µmol/L insulin for 15 min. The insulin signaling pathway(PI3K-AKT-mTOR) was detected by WB. Another group of L02 cell was treated with the same concentrations of SeMet as above for 48 h. The cell supernatant and lysates were collected for the analysis of SELENOP and GPX1, respectively by WB. RESULTS: The expressions of P-AKT-(Ser-473), P-AKT-(Thr-308), PI3K and mTOR in L02 cells under high-Se were decreased with the increase of SeMet concentration. The expressions of GPX1 and SELENOP were enhanced with the increase of SeMet. CONCLUSION: The insulin signaling pathway, PI3K-AKT-mTOR, was damaged in L02 cell under high-Se stress.

Recent advances in spatially variable gene detection in spatial transcriptomics.

With the emergence of advanced spatial transcriptomic technologies, there has been a surge in research papers dedicated to analyzing spatial transcriptomics data, resulting in significant contributions to our understanding of biology. The initial stage of downstream analysis of spatial transcriptomic data has centered on identifying spatially variable genes (SVGs) or genes expressed with specific spatial patterns across the tissue. SVG detection is an important task since many downstream analyses depend on these selected SVGs. Over the past few years, a plethora of new methods have been proposed for the detection of SVGs, accompanied by numerous innovative concepts and discussions. This article provides a selective review of methods and their practical implementations, offering valuable insights into the current literature in this field.

Allele-specific control of rodent and human lncRNA KMT2E-AS1 promotes hypoxic endothelial pathology in pulmonary hypertension.

Hypoxic reprogramming of vasculature relies on genetic, epigenetic, and metabolic circuitry, but the control points are unknown. In pulmonary arterial hypertension (PAH), a disease driven by hypoxia inducible factor (HIF)-dependent vascular dysfunction, HIF-2α promoted expression of neighboring genes, long noncoding RNA (lncRNA) histone lysine N-methyltransferase 2E-antisense 1 (KMT2E-AS1) and histone lysine N-methyltransferase 2E (KMT2E). KMT2E-AS1 stabilized KMT2E protein to increase epigenetic histone 3 lysine 4 trimethylation (H3K4me3), driving HIF-2α-dependent metabolic and pathogenic endothelial activity. This lncRNA axis also increased HIF-2α expression across epigenetic, transcriptional, and posttranscriptional contexts, thus promoting a positive feedback loop to further augment HIF-2α activity. We identified a genetic association between rs73184087, a single-nucleotide variant (SNV) within a KMT2E intron, and disease risk in PAH discovery and replication patient cohorts and in a global meta-analysis. This SNV displayed allele (G)-specific association with HIF-2α, engaged in long-range chromatin interactions, and induced the lncRNA-KMT2E tandem in hypoxic (G/G) cells. In vivo, KMT2E-AS1 deficiency protected against PAH in mice, as did pharmacologic inhibition of histone methylation in rats. Conversely, forced lncRNA expression promoted more severe PH. Thus, the KMT2E-AS1/KMT2E pair orchestrates across convergent multi-ome landscapes to mediate HIF-2α pathobiology and represents a key clinical target in pulmonary hypertension.

Increased Expression of PHGDH Under High-Selenium Stress In Vivo.

The purpose of this study is to explore the glycolytic remodeling under high-selenium (Se) stress. Three groups of male C57BL/6J mice were fed on diets with different Se contents (0.03, 0.15, and 0.30 mg Se/kg). Glucose tolerance test (GTT) and insulin tolerance test (ITT) were measured at the third month. Mice were killed at the fourth month. Plasma, liver, and muscle tissues were fetched for biochemistry and Se analysis. The expressions of insulin signaling pathway (PI3K-AKT-mTOR), glutathione peroxidase 1 (GPX1), selenoprotein N (SELENON), 3-phosphoglycerate dehydrogenase (PHGDH), serine hydroxymethyltransferases 1 (SHMT1), 5,10-methylenetetrahydrofolate reductase (MTHFR), and methionine synthase (MS) were analyzed by western blotting (WB) in liver and muscle tissues. The results of GTT and ITT showed that glucose tolerance and insulin tolerance were both abnormal in the 0.03 mg Se/kg and 0.3 mg Se/kg groups. Se concentrations in plasma, liver, and muscle of 0.03 mg Se/kg group were significantly lower than that of 0.15 mg Se/kg and 0.30 mg Se/kg groups (p < 0.05 or p < 0.01). The expressions of P-Akt (Thr-308) in muscle (p < 0.05) and PI3K and mTOR in liver (p < 0.001) of 0.30 mg Se/kg group were downregulated. The expressions of GPX1 in liver and muscle (p < 0.05 and p < 0.001), SELENON in muscle (p < 0.05), PHGDH in liver and muscle (p < 0.05), and SHMT1 (p < 0.05), MTHFR (p < 0.001), and MS (p < 0.001) in muscle of 0.3 mg Se/kg group were upregulated. The de novo serine synthesis pathway (SSP) was found to be activated in liver and muscle tissues of mice with a high-Se diet for the first time.

A novel method for simultaneously measuring boronophenylalanine uptake in brain tumor cells and number of cells using inductively coupled plasma atomic emission spectroscopy.

Boron neutron capture therapy (BNCT) combines neutron irradiation with boron compounds that are selectively uptaken by tumor cells. Boronophenylalanine (BPA) is a boron compound used to treat malignant brain tumors. The determination of boron concentration in cells is of great relevance to the field of BNCT. This study was designed to develop a novel method for simultaneously measuring the uptake of BPA by U87 and U251 cells (two brain tumor cell lines) and number of cells using inductively coupled plasma atomic emission spectroscopy (ICP-AES). The results revealed a linear correlation between phosphorus intensity and the numbers of U87 and U251 cells, with correlation coefficients (R2) of 0.9995 and 0.9994, respectively. High accuracy and reliability of phosphorus concentration standard curve were also found. Using this new method, we found that BPA had no significant effect on phosphorus concentration in either U87 or U251 cells. However, BPA increased the boron concentration in U87 and U251 cells in a concentration-dependent manner, with the boron concentration in U87 cells being higher than that in U251 cells. In both U87 and U251 cells, boron was mainly distributed in the cytoplasm and nucleus, accounting for 85% and 13% of the total boron uptake by U87 cells and 86% and 11% of the total boron uptake by U251 cells, respectively. In the U87 and U251 cell-derived xenograft (CDX) animal model, tumor exhibited higher boron concentration values than blood, heart, liver, lung, and brain, with a tumor/blood ratio of 2.87 for U87 cells and 3.11 for U251 cells, respectively. These results suggest that the phosphorus concentration in U87 and U251 cells can represent the number of cells and BPA is easily uptaken by tumor cells as well as in tumor tissue.

Adaptive metabolic response to short-term intensive fasting.

BACKGROUND & AIMS: Short-term intensive fasting (STIF), known as beego in Chinese phonetic articulation, has been practiced for more than two thousand years. However, the potential risk of STIF and the body's response to the risk have not been adequately evaluated. This study aims to address this issue, focusing on the STIF-triggered metabolic response of the liver and kidney. METHODS: The STIF procedure in the clinical trial includes a 7-day water-only intensive fasting phase and a 7-day gradual refeeding phase followed by a regular diet. The intensive fasting in humans was assisted with psychological induction. To gain insights not available in the clinical trial, we designed a STIF program for mice that resulted in similar phenotypes seen in humans. Plasma metabolic profiling and examination of gene expression as well as liver and kidney function were performed by omics, molecular, biochemical and flow cytometric analyses. A human cell line model was also used for mechanistic study. RESULTS: Clinically significant metabolites of fat and protein were found to accumulate during the fasting phase, but they were relieved after gradual refeeding. Metabolomics profiling revealed a universal pattern in the consumption of metabolic intermediates, in which pyruvate and succinate are the two key metabolites during STIF. In the STIF mouse model, the accumulation of metabolites was mostly counteracted by the upregulation of catabolic enzymes in the liver, which was validated in a human cell model. Kidney filtration function was partially affected by STIF but could be recovered by refeeding. STIF also reduced oxidative and inflammatory levels in the liver and kidney. Moreover, STIF improved lipid metabolism in mice with fatty liver without causing accumulation of metabolites after STIF. CONCLUSIONS: The accumulation of metabolites induced by STIF can be relieved by spontaneous upregulation of catabolic enzymes, suggesting an adaptive and protective metabolic response to STIF stress in the mammalian body.

A SELECTIVE REVIEW OF RECENT DEVELOPMENTS IN SPATIALLY VARIABLE GENE DETECTION FOR SPATIAL TRANSCRIPTOMICS.

With the emergence of advanced spatial transcriptomic technologies, there has been a surge in research papers dedicated to analyzing spatial transcriptomics data, resulting in significant contributions to our understanding of biology. The initial stage of downstream analysis of spatial transcriptomic data has centered on identifying spatially variable genes (SVGs) or genes expressed with specific spatial patterns across the tissue. SVG detection is an important task since many downstream analyses depend on these selected SVGs. Over the past few years, a plethora of new methods have been proposed for the detection of SVGs, accompanied by numerous innovative concepts and discussions. This article provides a selective review of methods and their practical implementations, offering valuable insights into the current literature in this field.

[Design and application of a B-ultrasound-guided deep vein puncture precise positioning device].

Deep venipuncture catheterization is a routine and basic operation in the treatment of critically ill patients, and it is the most effective way to quickly correct the shock. Clinical B-ultrasound guided deep vein catheters can improve the success rate of puncture, but in the process of operation, the short axis needs to be replaced by the long axis. In the replacement process, the stability of the novice is insufficient, the positioning is difficult, and the operation time is too long. If only short axis puncture is used, it is impossible to know whether the current position of the puncture needle, and the puncture may be too deep and stray into the artery. The accuracy of the 45 degree angle of the injection point requires a very experienced operator. In view of the above shortcomings, doctors in the department of critical care medicine of Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine designed a B-ultrasound puncture equipment, which has obtained the National Invention Patent of China (ZL 2016 1 0571557.X). The device is composed of B-ultrasound probe fixing frame, sliding scale plate, simulation slide rule, puncture needle, sliding device. By sliding device the angle of the pinhole channel, it is conducive to the accurate positioning of the puncture target, optimizing the operation procedure, improving the puncture speed and accuracy, effectively reducing the occurrence of puncture complications, ensuring patient safety, reducing unnecessary waste of human and material resources. It can reduce the workload of medical staff and is worthy of clinical practice.

BayesKAT: Bayesian Optimal Kernel-based Test for genetic association studies reveals joint genetic effects in complex diseases.

GWAS methods have identified individual SNPs significantly associated with specific phenotypes. Nonetheless, many complex diseases are polygenic and are controlled by multiple genetic variants that are usually non-linearly dependent. These genetic variants are marginally less effective and remain undetected in GWAS analysis. Kernel-based tests (KBT), which evaluate the joint effect of a group of genetic variants, are therefore critical for complex disease analysis. However, choosing different kernel functions in KBT can significantly influence the type I error control and power, and selecting the optimal kernel remains a statistically challenging task. A few existing methods suffer from inflated type 1 errors, limited scalability, inferior power, or issues of ambiguous conclusions. Here, we present a new Bayesian framework, BayesKAT( https://github.com/wangjr03/BayesKAT ), which overcomes these kernel specification issues by selecting the optimal composite kernel adaptively from the data while testing genetic associations simultaneously. Furthermore, BayesKAT implements a scalable computational strategy to boost its applicability, especially for high-dimensional cases where other methods become less effective. Based on a series of performance comparisons using both simulated and real large-scale genetics data, BayesKAT outperforms the available methods in detecting complex group-level associations and controlling type I errors simultaneously. Applied on a variety of groups of functionally related genetic variants based on biological pathways, co-expression gene modules, and protein complexes, BayesKAT deciphers the complex genetic basis and provides mechanistic insights into human diseases.

Treatment of filtration bleb dysfunction after glaucoma surgery by needle revision of filtration bleb combined with conbercept.

Filtration surgery (Trabeculectomy) is the main treatment for glaucoma. The scarring of the filtration bleb and obstruction of the outflow of aqueous humor through the filtration channel are the main reasons of the surgery failure. The objective of this study was to determine the clinical efficacy of needle revision of filtration blebs combined with subconjunctival injection of conbercept on the functional bleb formation in glaucoma patients with eye pressure out of control after trabeculectomy. A total of 48 eyes with poor filtration bleb function after trabeculectomy for glaucoma were treated with needle revision of filtration bleb combined with subconjunctival injection of conbercept. After the treatment, the patients were followed up for 3 months during which visual acuity, intraocular pressure, slit lamp and ultrasound biomicroscope examinations were performed. Intraoperative and postoperative complications were recorded. The visual acuity and intraocular pressure were significantly improved after the needle revision of filtration blebs. Among the 48 eyes, 39 eyes still had functional blebs at the end of the follow-up period, and filtration blebs failed in 9 eyes 2 to 8 weeks after the removal of the needle. The survival rate of filtration blebs at 3 months after needle revision was (79.06 ±â€…3.42%), and 81.25% (39/48) of the eyes showed good formation rate of functional bleb at the last follow-up. Three months after needle revision, there was local scar formation in some filtration blebs. Part of the filtration blebs showed mild thickening of the local subconjunctival tissue, and the filtration bleb was slightly raised and diffuse, showing a multi-cavity and thin-walled shape in some blebs. Ultrasound biomicroscopy examination showed relative structural manifestations. Subconjunctival hemorrhage occurred in 43 patients during and after the operation. Low intraocular pressure occurred in 8 patients with the lowest pressure of 5 mm Hg. Choroidal edema was observed in 3 patients. Five patients had intraoperative conjunctival hemorrhage in the anterior chamber, and hyphema occurred. All complications were self-limited and resolved without surgical intervention. Needle revision of filtration bleb combined with anti-VEGF drugs is a safe and effective method for the treatment of filtration bleb dysfunction after surgery of glaucoma.

An epigallocatechin gallate-amorphous calcium phosphate nanocomposite for caries prevention and demineralized enamel restoration.

Biomineralization with amorphous calcium phosphate (ACP) is a highly effective strategy for caries prevention and defect restoration. The identification and interruption of cariogenic biofilm formation during remineralization remains a challenge in current practice. In this study, an epigallocatechin gallate (EGCG)-ACP functional nanocomposite was developed to prevent and restore demineralization by integrating the antibacterial property of EGCG and the remineralization effect of ACP. The synthesized EGCG-ACP showed good biocompatibility with L-929 â€‹cells and human gingival fibroblasts. Under neutral conditions, the sustained release of ACP from EGCG-ACP restored the microstructure and mechanical properties of demineralized enamel. Under acidic conditions, protonated EGCG released from EGCG-ACP exerted a strong antibacterial effect, and the ACP release rate doubled within 4 â€‹h, resulting in the prevention of demineralization in the presence of cariogenic bacteria. The pH-responsive features of EGCG-ACP to promote the protonation of EGCG and ACP release facilitated its performance in remineralization effect to overcome the difficulty of restoring demineralized enamel in a cariogenic acidic environment, which was evidenced by the in vivo experiment carried out in a rat oral cariogenic environment. The results of this study indicate the potential of EGCG-ACP for the prevention of enamel demineralization and provide a theoretical basis its application in populations with high caries risk.

Short-term intensive fasting enhances the immune function of red blood cells in humans.

BACKGROUND: Fasting is known to influence the immune functions of leukocytes primarily by regulating their mobilization and redistribution between the bone marrow and the peripheral tissues or circulation, in particular via relocalization of leukocytes back in the bone marrow. However, how the immune system responds to the increased risk of invasion by infectious pathogens with fewer leukocytes in the peripheral blood during fasting intervention remains an open question. RESULTS: We used proteomic, biochemical and flow cytometric tools to evaluate the impact of short-term intensive fasting (STIF), known as beego, on red blood cells by profiling the cells from the STIF subjects before and after 6 days of fasting and 6 days of gradual refeeding. We found that STIF, by triggering the activation of the complement system via the complement receptor on the membrane of red blood cells, boosts fairly sustainable function of red blood cells in immune responses in close relation to various pathogens, including viruses, bacteria and parasites, particularly with the pronounced capacity to defend against SARS-CoV-2, without compromising their oxygen delivery capacity and viability. CONCLUSION: STIF fosters the immune function of red blood cells and therefore, it may be considered as a nonmedical intervention option for the stronger capacity of red blood cells to combat infectious diseases.

Myeloid cell leukemia-1 as a candidate prognostic biomarker in cancers: a systematic review and meta-analysis.

INTRODUCTION: Studies have shown that myeloma cell leukemia-1 (MCL-1) is associated with the prognosis of patients with cancer. To further validate the prognostic value of MCL-1 in cancer, a meta-analysis was conducted. METHODS: Six databases were searched using Boolean logic search formulas. Data were extracted from the included literature, and pooled odds ratio, hazard ratio, and 95% confidence interval were calculated to determine the relationship between MCL-1 levels and clinicopathological characteristics and prognosis of patients with cancer. When heterogeneity was found to be significant, a random effects model was used, otherwise, a fixed effects model was used. RESULTS: Twelve articles were included in this meta-analysis, totaling 2208 patients with cancer across 14 studies. A high MCL-1 expression level was associated with patients with high T stage, M stage, and TNM stage in some cancers. Additionally, high MCL-1 expression was likely to be observed in patients with poorly differentiated digestive system tumors and patients with lung adenocarcinoma. Notably, a higher expression of MCL-1 was found to be associated with shorter overall survival in patients with hematological tumors, digestive system tumors, and lung cancer. CONCLUSION: MCL-1 may be a prognostic biomarker in patients with some types of cancer.