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Abstract Background The study was designed to investigate microvascular and morphological changes in retinal vein occlusion (RVO) using multimodal imaging after intravitreal ranibizumab (IVR) with or without triamcinolone acetonide (IVTA) injections. Methods This was a retrospective and observational study. Fifty patients (52 eyes) diagnosed with RVO were enrolled. Best corrected visual acuity (BCVA), ophthalmoscopy, fundus fluorescein angiography (FFA), spectral domain optical coherence tomography (SDOCT), and optical coherence tomography angiography (OCTA) were employed sequentially both before treatment and at the last visit after treatment. Results The mean logMAR VAs in BRVO eyes decreased significantly after treatment (P = 0.029). OCTA showed there was a significant difference in foveal avascular zone (FAZ) in BRVO eyes (P = 0.024), superificial foveal vessel density in both CRVO (P = 0.0004) and BRVO eyes (P = 0.02155). OCT showed the foveal thickness had significant differences after treatment in both CRVO (P

BackgroundThe prognostic value and immune significance of T-cell proliferation regulators (TCRs) in hepatocellular carcinoma (HCC) have not been previously reported. This study aimed to develop a new prognostic model based on TCRs in patients with HCC.MethodThis study used The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) and International Cancer Genome Consortium-Liver Cancer-Riken, Japan (ICGC-LIRI-JP) datasets along with TCRs. Differentially expressed TCRs (DE-TCRs) were identified by intersecting TCRs and differentially expressed genes between HCC and non-cancerous samples. Prognostic genes were determined using Cox regression analysis and were used to construct a risk model for HCC. Kaplan-Meier survival analysis was performed to assess the difference in survival between high-risk and low-risk groups. Receiver operating characteristic curve was used to assess the validity of risk model, as well as for testing in the ICGC-LIRI-JP dataset. Additionally, independent prognostic factors were identified using multivariate Cox regression analysis and proportional hazards assumption, and they were used to construct a nomogram model. TCGA-LIHC dataset was subjected to tumor microenvironment analysis, drug sensitivity analysis, gene set variation analysis, and immune correlation analysis. The prognostic genes were analyzed using consensus clustering analysis, mutation analysis, copy number variation analysis, gene set enrichment analysis, and molecular prediction analysis.ResultsAmong the 18 DE-TCRs, six genes (DCLRE1B, RAN, HOMER1, ADA, CDK1, and IL1RN) could predict the prognosis of HCC. A risk model that can accurately predict HCC prognosis was established based on these genes. An efficient nomogram model was also developed using clinical traits and risk scores. Immune-related analyses revealed that 39 immune checkpoints exhibited differential expression between the high-risk and low-risk groups. The rate of immunotherapy response was low in patients belonging to the high-risk group. Patients with HCC were further divided into cluster 1 and cluster 2 based on prognostic genes. Mutation analysis revealed that HOMER1 and CDK1 harbored missense mutations. DCLRE1B exhibited an increased copy number, whereas RAN exhibited a decreased copy number. The prognostic genes were significantly enriched in tryptophan metabolism pathways.ConclusionsThis bioinformatics analysis identified six TCR genes associated with HCC prognosis that can serve as diagnostic markers and therapeutic targets for HCC.

Abstract Background The aim of this study was to evaluate the effectiveness of team-, case-, lecture-, and evidence-based learning (TCLEBL) methods in cultivating students’ clinical and research abilities, as compared to traditional lecture-based learning (LBL) approaches. Methods Forty-one medical postgraduates were divided into two groups, a TCLEBL group and an LBL group. Teaching effectiveness was evaluated through student- and teacher-feedback questionnaires, scores from theoretical examinations and written literature reviews, and student learning burdens. Results Compared to the LBL approach, both teachers and students were more satisfied with the TCLEBL model (p

Trace metals play a vital role in a variety of biological processes, but excessive amounts can be toxic and are receiving increasing attention. Trace metals in the environment are released from natural sources, such as rock weathering, volcanic eruptions, and other human activities, such as industrial emissions, mineral extraction, and vehicle exhaust. Lifestyle, dietary habits and environmental quality are the main sources of human exposure to trace metals, which play an important role in inducing human reproductive infertility. The purpose of this review is to summarize the distribution of various trace metals in oocyte and to identify the trace metals that may cause oocyte used in the design and execution of toxicological studies.

Abstract Hepatocellular carcinoma (HCC) represents a major global health threat with diverse and complex pathogenesis. Aldo–keto reductase family 1 member B10 (AKR1B10), a tumor-associated enzyme, exhibits abnormal expression in various cancers. However, a comprehensive understanding of AKR1B10's role in HCC is lacking. This study aims to explore the expression characteristics of AKR1B10 in HCC and its correlation with clinicopathological features, survival prognosis, and tumor immune microenvironment, further investigating its role and potential regulatory mechanisms in HCC. This study conducted comprehensive analyses using various bioinformatics tools and databases. Initially, differentially expressed genes related to HCC were identified from the GEO database, and the expression of AKR1B10 in HCC and other cancers was compared using TIMER and GEPIA databases, with validation of its specificity in HCC tissue samples using the HPA database. Furthermore, the relationship of AKR1B10 expression with clinicopathological features (age, gender, tumor size, staging, etc.) of HCC patients was analyzed using the TCGA database's LIHC dataset. The impact of AKR1B10 expression levels on patient prognosis was evaluated using Kaplan–Meier survival analysis and the Cox proportional hazards model. Additionally, the correlation of AKR1B10 expression with tumor biology-related signaling pathways and tumor immune microenvironment was studied using databases like GSEA, Targetscan, and others, identifying microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) that regulate AKR1B10 expression to explore potential regulatory mechanisms. Elevated AKR1B10 expression was significantly associated with gender, primary tumor size, and fibrosis stage in HCC tissues. High AKR1B10 expression indicated poor prognosis and served as an independent predictor for patient outcomes. Detailed mechanism analysis revealed a positive correlation between high AKR1B10 expression, immune cell infiltration, and pro-inflammatory cytokines, suggesting a potential DANCR-miR-216a-5p-AKR1B10 axis regulating the tumor microenvironment and impacting HCC development and prognosis. The heightened expression of AKR1B10 in HCC is not only related to significant clinical-pathological traits but may also influence HCC progression and prognosis by activating key signaling pathways and altering the tumor immune microenvironment. These findings provide new insights into the role of AKR1B10 in HCC pathogenesis and highlight its potential as a biomarker and therapeutic target.

Abstract Several studies have reported the effects of DJ-1 gene and miR-199a/b-3p on HCC development. However, whether miR-199a/b-3p regulates HCC progression through a novel compensatory signaling pathway involving DJ-1, Ras, and PI3K/AKT remains unknown. We used (TCGA, HPA, miRWalk and Target scan) databases, cancer and para-tissue HCC patients, dual-luciferase reporter gene analysis, proteomic imprinting, qPCR, cell proliferation, scratch, transport, and flow cytometry to detect the molecular mechanism of DJ-1 and miR-199a/b-3p co-expression in HCC cell lines. Bioinformatics analysis showed that DJ-1 was highly expressed in HCC ((P

Abstract Background The Value of Golgi protein 73 (GP73) in the diagnosis of Hepatocellular carcinoma (HCC) remains controversial, especially in its differentiation between HCC and cirrhosis. Besides, some papers showed that GP73 levels are correlated with liver fibrosis. This study conducts a meta-analysis to evaluate the value of GP73 in diagnosing HCC and differential diagnosing HCC from liver cirrhosis. Methods 36 studies with a sample size of 8314 cases concerning the accuracy of GP73 in the diagnosis of HCC were selected through a systematic review. Seven of these studies included a total of 438 HCC samples and 426 cirrhosis samples and calculated the sensitivity and specificity of GP73 for differential diagnosing HCC from cirrhosis. QUADAS (quality assessment of diagnostic accuracy studies) was used to evaluate the quality of literature. Statistical analyses were performed using StataSE16 software. Results The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and the area under the curve were 0.79(95%CI 0.74–0.83),0.85(95%CI 0.80–0.89),5.4(95%CI 3.8–7.5), 0.25(95%CI 0.20–0.31), 22(95%CI 13–35), and 0.88 for GP73 diagnosing HCC;0.74(95%CI 0.64–0.81),0.70(95%CI 0.49–0.85),2.40(95%CI 1.3–4.7),0.38(95%CI 0.23–0.61),6(95%CI 2–19), and 0.78 for GP73 differential diagnosing HCC from liver cirrhosis. Conclusion The results suggest that GP73 has a high diagnostic value for HCC and a moderate value for differential diagnosis of HCC from liver cirrhosis.

Abstract Background To describe the risk factors and clinical characteristics of macular epiretinal membrane (MEM) disease in patients up to the age of 40 years and to evaluate the therapeutic effect of IVTA on MEM. Methods Clinical records were reviewed and the etiology of each case and the age distribution data were collected in this retrospective, cohort study. The clinical characteristics of MEM and the factors affecting VA were analyzed. Additionally, we contrasted the effects of MEM peeling with and without intravitreal triamcinolone acetonide on visual acuity (VA) and central foveal thickness (CFT). Results In young patients, the incidence of partial posterior vitreous detachment (P-PVD) was considerably higher in IMEM than SMEM (P = 0.007). Furthermore, patients with stage 3 MEM had lower BCVA values than patients with stage 4 MEM (P

The risk of germline copy number variants (CNVs) in BRCA1 and BRCA2 pathogenic variant carriers in breast cancer is assessed, with CNVs overlapping SULT1A1 decreasing breast cancer risk in BRCA1 carriers.

Objective To evaluate the biological effect of cinobufagin(Cin) on nasopharyngeal carcinoma (NPC) cells lines(CNE2 and HONE1) and the mechanism of its efficacy. Methods CNE2 and HONE1 cells were treated with different concentrations (0, 5, 15 and 45 mg/L) of Cin for 24, 48 and 72 h respectively and cell viability was detected by CCK-8 assay. After 48 hrs, cell morphology was observed by phase contrast microscopy; cell apoptosis was detected by TUNEL fluorescence staining; the level of reactive oxygen species (ROS) in cells were assessed by DCF fluorescence assay; the expression levels of apoptosis-related proteins were detected by Western blot. Results Cin inhibited the cell activity of NPC cells in a concentration-dependent manner (P＜0.05, P＜0.01 or P＜0.001) and the cells showed filament and sparse morphology. Cin promoted apoptosis and increased intracellular ROS level in NPC cells (P＜0.05, P＜0.01 or P＜0.001). Cin inhibited the expression of Bax and mitochondrial cytochrome c (Cytc) (P＜0.05, P＜0.01 or P＜0.001) but promoted the expression of Bcl-2, cleaved caspase-3 and cytoplasmic Cytc (P＜0.01 or P＜0.001). Conclusions Cin can inhibit cell proliferation and promote apoptosis of NPC cells.

Abstract Background Intravitreal injection of anti-vascular endothelial growth factor (VEGF) has become first line therapy for diabetic macular edema. This study evaluated the efficacy and safety of intravitreal injection of Ranibizumab (IVR) as pre-treatment for pars plana vitrectomy in proliferative diabetic retinopathy (PDR) patients with vitreous hemorrhage. Methods This pilot randomized controlled trial included 48 eyes with vitreous hemorrhage resulting from active PDR. Eyes were treated with IVR 1 or 3 days before vitrectomy or a sham subconjunctival injection 3 days before surgery. The occurrence of new tractional retinal detachment (TRD), total operation time, and intraoperative findings were compared. The concentrations of VEGF and connective tissue growth factor (CTGF) in aqueous humor and plasma collected at the time of IVR and vitrectomy were determined by ELISA. Results None of the patients who received IVR experienced new TRD. Ranibizumab injection improved intraoperative outcomes. The mean concentrations of VEGF in aqueous humor were significantly lower after than before IVR in patients who received IVR 1 and 3 days before surgery (P

Harnessing the rhizospheric microbiome, including phosphorus mineralizing bacteria (PMB), is a promising technique for maintaining sustainability and productivity in intensive agricultural systems. However, it is unclear as to which beneficial taxonomic group populations in the rhizosphere are potentially associated with the changes in soil microbiomes shifted by fertilization regimes. Herein, we analyzed the diversity and community structure of total bacteria and PMB in the rhizosphere of maize (Zea mays L.) grown in soils under 25 years of four fertilization regimes (compost, biocompost, chemical, or non-fertilized) via selective culture and Illumina sequencing of the 16S rRNA genes. Plant development explained more variations (29 and 13%, respectively) in the composition of total bacteria and PMB in the rhizosphere of maize than the different fertilization regimes. Among those genera enriched in the rhizosphere of maize, the relative abundances of Oceanobacillus, Bacillus, Achromobacter, Ensifer, Paracoccus, Ramlibacter, and Luteimonas were positively correlated with those in the bulk soil. The relative abundance of Paracoccus was significantly higher in soils fertilized by compost or biocompost than the other soils. Similar results were also observed for PMB affiliated with Ensifer, Bacillus, and Streptomyces. Although plant development was the major factor in shaping the rhizospheric microbiome of maize, fertilization regimes might have modified beneficial rhizospheric microbial taxa such as Bacillus and Ensifer.

Variable number tandem repeats (VNTRs) are implicated in human diseases yet have been difficult to analyse computationally. Here, the authors describe a neural network method, adVNTR-NN, that allows rapid and accurate genotyping of VNTRs from large whole genome sequencing datasets.

PurposeWe sought to reveal the expression profiles of transfer RNA-derived small RNAs (tsRNAs) and microRNAs (miRNAs) in the vitreous humor of patients with proliferative diabetic retinopathy (PDR).MethodsVitreous humor samples were obtained from PDR patients and a control group for this study. Sequencing of small RNAs was conducted to assess the expression profiles of tsRNAs and miRNAs in both groups, which was followed by validation using reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR). Bioinformatics analyses were conducted to predict the target genes and their potential biological functions and signaling pathways.ResultsA total of 37 tsRNAs and 70 miRNAs with significant differences were screened out from the vitreous humor samples of PDR patients compared to controls. Following validation by RT-qPCR, the target genes of the validated tsRNAs and miRNAs were predicted, and Gene Ontology analysis indicated that the target genes of the tsRNAs were most enriched in the cellular macromolecule metabolic process, cytoplasm, and ion-binding, while those of the miRNAs were most abundant in the regulation of major metabolic process, cytoplasm, and protein-binding. In addition, Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the target genes of said tsRNAs and miRNAs were most enriched in the adenosine monophosphate-activated protein kinase signaling pathway and Th17 cell differentiation, respectively.ConclusionsThe present study identified altered tsRNAs and miRNAs in vitreous humor samples of PDR patients, which may play important roles in the pathogenesis of PDR and could be considered potential therapeutic targets in the treatment of PDR.

Background Adoptive cell therapy (ACT) using genetically modified T cells has evolved into a promising treatment option for patients with cancer. However, even for the best-studied and clinically validated CD19-targeted chimeric antigen receptor (CAR) T-cell therapy, many patients face the challenge of lack of response or occurrence of relapse. There is increasing need to improve the efficacy of ACT so that durable, curative outcomes can be achieved in a broad patient population.Methods Here, we investigated the impact of indomethacin (indo), a non-steroidal anti-inflammatory drug (NSAID), on the efficacy of ACT in multiple preclinical models. Mice with established B-cell lymphoma received various combinations of preconditioning chemotherapy, infusion of suboptimal dose of tumor-reactive T cells, and indo administration. Donor T cells used in the ACT models included CD4+ T cells expressing a tumor-specific T cell receptor (TCR) and T cells engineered to express CD19CAR. Mice were monitored for tumor growth and survival. The effects of indo on donor T cell phenotype and function were evaluated. The molecular mechanisms by which indo may influence the outcome of ACT were investigated.Results ACT coupled with indo administration led to improved tumor growth control and prolonged mouse survival. Indo did not affect the activation status and tumor infiltration of the donor T cells. Moreover, the beneficial effect of indo in ACT did not rely on its inhibitory effect on the immunosuppressive cyclooxygenase 2 (COX2)/prostaglandin E2 (PGE2) axis. Instead, indo-induced oxidative stress boosted the expression of death receptor 5 (DR5) in tumor cells, rendering them susceptible to donor T cells expressing TNF-related apoptosis-inducing ligand (TRAIL). Furthermore, the ACT-potentiating effect of indo was diminished against DR5-deficient tumors, but was amplified by donor T cells engineered to overexpress TRAIL.Conclusion Our results demonstrate that the pro-oxidative property of indo can be exploited to enhance death receptor signaling in cancer cells, providing rationale for combining indo with genetically modified T cells to intensify tumor cell killing through the TRAIL-DR5 axis. These findings implicate indo administration, and potentially similar use of other NSAIDs, as a readily applicable and cost-effective approach to augment the efficacy of ACT.

Abstract Dust can be regarded as environmental medium that indicates the level and spatial distribution of polycyclic aromatic hydrocarbons (PAHs) coming from different pollution sources. In this study, samples including road dust, roof dust, and bare soil near an iron and steel enterprise (ISE) in Laiwu city of North China were collected. To assess the environment impact, atmosphere particulates and one flue dust from a coking plant were simultaneously sampled. Sixteen USEPA PAHs were detected quantitatively by Gas Chromatography Mass Spectrometry (GC–MS). A laser particle size analyzer was used to obtain the grain size of the dust particle samples. The results showed that PAH concentrations displayed great variability in the dust samples. The ∑16PAHs concentration was found to be between 0.460 and 46.970 μg/g (avg ± sd 10.892 ± 1.185 μg/g) in road dust, between 0.670 and 17.140 μg/g (avg ± sd 6.751 ± 0.692 μg/g) in roof dust, and 13.990 ± 1.203 μg/g in bare soil. In the environment atmosphere sites, the ∑16 PAHs value in PM2.5 constituted a very large proportion of PM10, indicating that PAHs in finer particle sizes should be given greater emphasis. The ∑16PAHs concentration was relatively high in the area close to the ISE because of the great impact of the ISE industrial activities. PAH concentration curves were similar, and the most abundant individual PAHs in the atmosphere sites were BbF, BkF, and Flu, and BbF, BkF, and Chry in dusts. Toxicity analysis revealed that PAHs with four rings, including carcinogenic PAHs, were the dominant pollutants in the studied area. The toxic equivalency value (TEQBaP), the carcinogenic health risk assessment value recommended by the US EPA, was calculated for seven carcinogenic PAHs, revealing that they account for more than 93.0% of the total TEQBap of the 16 PAHs and indicating the major toxic equivalent concentration contributor. Incremental lifetime cancer risk (ILCR) estimation results showed that PAHs tended to bring about great health risks through skin contact, followed by ingestion and inhalation. By comparison, road dust exhibited greater carcinogenic risks than roof dust, and bare soil may undergo heavier pollution. Therefore, the results of this study would be helpful in the effort to understand the PAHs pollution from the steel industry, which will provide some guidance for the probabilistic assessment of local health risks.

Breast cancer risk for BRCA1/BRCA2 mutation carriers varies depending on other genetic factors. Here, the authors perform a case-only genome-wide association study and highlight novel loci associated with breast cancer risk for BRCA1/BRCA2 mutation carriers.

Women who carry pathogenic mutations in BRCA1 and BRCA2 have a lifetime risk of developing breast cancer of up to 80%. However, risk estimates vary in part due to genetic modifiers. We investigated the association of the RAD52 S346X variant as a modifier of the risk of developing breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2. The RAD52 S346X allele was associated with a reduced risk of developing breast cancer in BRCA2 carriers [per‐allele hazard ratio (HR) = 0.69, 95% confidence interval (CI) 0.56–0.86; P = 0.0008] and to a lesser extent in BRCA1 carriers (per‐allele HR = 0.78, 95% CI 0.64–0.97, P = 0.02). We examined how this variant affected DNA repair. Using a reporter system that measures repair of DNA double‐strand breaks (DSBs) by single‐strand annealing (SSA), expression of hRAD52 suppressed the loss of this repair in Rad52−/− mouse embryonic stem cells. When hRAD52 S346X was expressed in these cells, there was a significantly reduced frequency of SSA. Interestingly, expression of hRAD52 S346X also reduced the stimulation of SSA observed upon depletion of BRCA2, demonstrating the reciprocal roles for RAD52 and BRCA2 in the control of DSB repair by SSA. From an immunofluorescence analysis, we observed little nuclear localization of the mutant protein as compared to the wild‐type; it is likely that the reduced nuclear levels of RAD52 S346X explain the diminished DSB repair by SSA. Altogether, we identified a genetic modifier that protects against breast cancer in women who carry pathogenic mutations in BRCA2 (P = 0.0008) and to a lesser extent BRCA1 (P = 0.02). This RAD52 mutation causes a reduction in DSB repair by SSA, suggesting that defects in RAD52‐dependent DSB repair are linked to reduced tumor risk in BRCA2‐mutation carriers.

The properties of plant rhizosphere are dynamic and heterogeneous, serving as different habitat filters for or against certain microorganisms. Herein, we studied the spatial distribution of bacterial communities in the rhizosphere of pepper plants treated with a disease-suppressive or non-suppressive soil. The bacterial richness was significantly (p < 0.05) higher in plants treated with the disease-suppressive soil than in those treated with the non-suppressive soil. Bacterial richness and evenness greatly differed between root parts, with decrease from the upper taproot to the upper fibrous root, the lower taproot, and the lower fibrous root. As expected, the bacterial community in the rhizosphere differed between suppressive and non-suppressive soil. However, the spatial variation (36%) of the bacterial community in the rhizosphere was much greater than that explained by soils (10%). Taxa such as subgroups of Acidobacteria, Nitrosospira, and Nitrospira were known to be selectively enriched in the upper taproot. In vitro Bacillus antagonists against Phytophthora capsici were also preferentially colonized in the taproot, while the genera such as Clostridium, Rhizobium, Azotobacter, Hydrogenophaga, and Magnetospirillum were enriched in the lower taproot or fibrous root. In conclusion, the spatial distribution of bacterial taxa and antagonists in the rhizosphere of pepper sheds light on our understanding of microbial ecology in the rhizosphere.

Compost is frequently served as the first reservoir for plants to recruit rhizosphere microbiome when used as growing substrate in the seedling nursery. In the present study, recruitment of rhizosphere microbiome from two composts by tomato, pepper, or maize was addressed by shotgun metagenomics and 16S rRNA amplicon sequencing. The 16S rRNA amplicon sequencing analysis showed that 41% of variation in the rhizosphere bacterial community was explained by compost, in contrast to 23% by plant species. Proteobacterial genera were commonly recruited by all three plant species with specific selections for Ralstonia by tomato and Enterobacteria by maize. These findings were confirmed by analysis of 16S rRNA retrieved from the shotgun metagenomics library. Approximately 70% of functional gene clusters differed more than sevenfold in abundance between rhizosphere and compost. Functional groups associated with the sensing and up-taking of C3 and C4 carboxylic acids, amino acids, monosaccharide, production of antimicrobial substances, and antibiotic resistance were over-represented in the rhizosphere. In summary, compost and plant species synergistically shaped the composition of the rhizosphere microbiome and selected for functional traits associated with the competition on root exudates.

Background: Exposure to polybrominated diphenyl ethers (PBDEs) may influence risk of developing post-menopausal breast cancer. Although mechanisms are poorly understood, epigenetic regulation of gene expression may play a role. Objectives: To identify DNA methylation (DNAm) changes associated with PBDE serum levels and test the association of these biomarkers with breast cancer risk. Methods: We studied 397 healthy women (controls) and 133 women diagnosed with breast cancer (cases) between ages 40 and 58 years who participated in the California Teachers Study. PBDE levels were measured in blood. Infinium Human Methylation EPIC Bead Chips were used to measure DNAm. Using multivariable linear regression models, differentially methylated CpG sites (DMSs) and regions (DMRs) associated with serum PBDE levels were identified using controls. For top-ranked DMSs and DMRs, targeted next-generation bisulfite sequencing was used to measure DNAm for 133 invasive breast cancer cases and 301 age-matched controls. Conditional logistic regression was used to evaluate associations between DMSs and DMRs and breast cancer risk. Results: We identified 15 DMSs and 10 DMRs statistically significantly associated with PBDE levels (FDR

Abstract Background This study aimed to investigate the benefits and challenges of the flipped classroom combined with team-, case-, lecture- and evidence-based learning (FC-TCLEBL) for ophthalmology teaching for eight-year program students. Methods FC-TCLEBL and the traditional lecture-based classroom (LBC) were compared based on student and teacher feedback questionnaires, student learning burden, and scores on standardized tests as well as their effects on the abilities of clinical thinking, scientific research, active-learning, practical application, humanistic care and communication with patients. Results Both the students and teachers were more satisfied with the FC-TCLEBL model. More students in the FC-TCLEBL group agreed that the course helped them to develop skills in creative thinking, problem solving, and teamwork. Students in the FC-TCLEBL group spent significantly more time preparing for class than those in the LBC group, but the time spent on review was significantly lower in the FC-TCLEBL group. The students from the FC-TCLEBL group performed better in a post-test on diabetic retinopathy (DR) as compared to the LBC group. Conclusions FC-TCLEBL teaching model is effective and suitable for ophthalmology teaching.

Diabetic retinopathy (DR) is a major cause of blindness worldwide and may be non-proliferative (NPDR) or proliferative (PDR). To investigate the metabolomic and lipidomic characteristics of plasma in DR patients, plasma samples were collected from patients with type 2 diabetes mellitus (DR group) with PDR (n = 27), NPDR (n = 18), or no retinopathy (controls, n = 21). Levels of 54 and 41 metabolites were significantly altered in the plasma of DR patients under positive and negative ion modes, respectively. By subgroup analysis, 74 and 29 significantly changed plasma metabolites were detected in PDR patients compared with NPDR patients under positive and negative ion modes, respectively. KEGG analysis indicated that pathways such as biosynthesis of amino acids and neuroactive ligand-receptor interaction were among the most enriched pathways in altered metabolites in the DR group and PDR subgroup. Moreover, a total of 26 and 41 lipids were significantly changed in the DR group and the PDR subgroup, respectively. The panel using the 29-item index could discriminate effectively between diabetic patients with and without retinopathy, and the panel of 22 items showed effective discrimination between PDR and NPDR. These results provide a basis for further research into the therapeutic targets associated with these metabolite and lipid alterations.

PurposeChoroidal neovascularization (CNV) is the defining feature of neovascular age-related macular degeneration (nAMD). Gut microbiota might be deeply involved in the pathogenesis of nAMD. This study aimed to reveal the roles of the gut microbiome and fecal metabolome in a mouse model of laser-induced CNV.MethodsThe feces of C57BL/6J mice with or without laser-induced CNV were collected. Multi-omics analyses, including 16S rRNA gene sequencing and untargeted metabolomics, were conducted to analyze the changes in the gut microbial composition and the fecal metabolomic profiles in CNV mice.ResultsThe gut microbiota was significantly altered in CNV mice. The abundance of Candidatus_Saccharimonas was significantly upregulated in the feces of CNV mice, while 16 genera, including Prevotellaceae_NK3B31_group, Candidatus_Soleaferrea, and Truepera, were significantly more abundant in the controls than in the CNV group. Fecal metabolomics identified 73 altered metabolites (including 52 strongly significantly altered metabolites) in CNV mice compared to control mice. Correlation analysis indicated significant correlations between the altered fecal metabolites and gut microbiota genera, such as Lachnospiraceae_UCG-001 and Candidatus_Saccharimonas. Moreover, KEGG analysis revealed six pathways associated with these altered metabolites, such as the ABC transporter, primary bile acid biosynthesis and steroid hormone biosynthesis pathways.ConclusionThe study identified an altered fecal microbiome and metabolome in a CNV mouse model. The altered microbes, metabolites and the involved pathways might be associated with the pathogenesis of nAMD.

Cyclophosphamide (CTX) is a major component of the chemotherapy conditioning regimens used in the clinic to prepare cancer patients for hematopoietic stem cell transplantation or adoptive T cell therapy. Previous studies have shown that CTX given at nonmyeloablative doses in mice and patients leads to expansion of myeloid cells within which the monocytic subset exhibits immunosuppressive activity. However, the ontogeny and gene expression signature of these CTX-induced monocytes are not well-defined. Here, we report that the expansion of myeloid cells is a default process intrinsic to hematopoietic recovery after chemotherapy. During this process, the monocytes repopulated in mice acquire immunosuppressive activity, which can persist long after cessation of chemotherapy. Moreover, monocytes acquire a gene signature characteristic of neutrophil precursors, marked by increased proliferative capability and elevated expressions of multiple primary and secondary granules. We provide evidence that CTX-induced myeloid cell expansion is regulated by DNA methyltransferase 1 (Dnmt1) and dependent on chemotherapy-induced microbial translocation. These findings help advance our understanding of the differentiation, heterogeneity, and function of myeloid cells repopulating after chemotherapy.

Organic greenhouse farming is an innovative system that may maintain a high yield and healthy agroecosystem. There have been no rigorous studies on the comparison of total and nitrogen-cycling bacterial community in vegetable soils between organic and conventional farming management at large scale. A survey of bacterial community and nitrogen cycles from soils under organic and conventional greenhouse farming was performed at 30 sites, covering seven soil types with 4 to 18 years of organic farming history. Communities of the total, diazotrophs and ammonia-oxidizing bacteria were studied with high-throughput sequencing of the 16S rRNA, nifH and amoA genes, respectively. Organic greenhouse farming did not influence alpha diversities. Beta diversities among the total (26/30) and diazotrophic (17/19) bacteria differed between farming systems, but compositional differences in ammonia-oxidizing bacteria between the two farming systems were only detected at 6 sites. Despite the effects of farming system on most bacterial genera were varied across different sites, organic greenhouse farming persistently selected for a few genera, possibly for the biodegradation of organic carbon with high molecular weight (Hyphomicrobium, Rubinisphaera, Aciditerrimonas, Planifilum, Phaselicystis, and Ohtaekwangia), but against putative ammonia oxidizing (Nitrosospira, Nitrosopumilus) and diazotrophic (Bradyrhizobium) bacterial genera, as determined by 16S rRNA analysis. Diazotrophic bacteria affiliated with nifH cluster 1J were preferentially associated with organic greenhouse farming, in contrast to Paenibacillus borealis. In summary, this study provides insights into the complex effects of organic greenhouse farming on the total, diazotrophic and ammonia oxidizing bacterial communities across different environmental context.

The ability of a rhizosphere-derived microbial product (composed of a consortium of a strain of Bacillus subtilis and a strain of Trichoderma harzianum) to suppress common scab disease in potato caused by Streptomyces spp. was examined over a two-year period. Relative to the condition in which 0 kg·ha−1 of the designated microbial product was applied (control), the disease index decreased by 30.6%–46.1%, and yield increased by 23.0%–32.2% in treatments in which 225 or 300 kg·ha−1 of the microbial product was administered, respectively. The bacterial communities present in the rhizosphere were assessed at an early stage of tuber formation, a time at which tubers are susceptible to common scab. Potato plants in which soils were treated with 225 or 300 kg·ha−1 of the microbial product harbored rhizospheric microbiota with lower α-diversity and an increased relative abundance of taxa representing the beneficial bacteria. In summary, a select microbial product composed of a consortium of Bacillus subtilis and Trichoderma harzianum effectively suppressed common scab disease and increased tuber yield by establishing a high relative abundance of beneficial bacteria in the rhizosphere. Keywords: Potato common scab, Microbial product, Rhizosphere bacterial communities, Bacillus subtilis, Trichoderma harzianum

Abstract Background Breast cancer is a partially heritable trait and genome-wide association studies (GWAS) have identified over 180 common genetic variants associated with breast cancer. We have previously performed breast cancer GWAS in Latinas and identified a strongly protective single nucleotide polymorphism (SNP) at 6q25, with the protective minor allele originating from indigenous American ancestry. Here we report on fine mapping of the 6q25 locus in an expanded sample of Latinas. Methods We performed GWAS in 2385 cases and 6416 controls who were either US Latinas or Mexican women. We replicated the top SNPs in 2412 cases and 1620 controls of US Latina, Mexican, and Colombian women. In addition, we validated the top novel variants in studies of African, Asian and European ancestry. In each dataset we used logistic regression models to test the association between SNPs and breast cancer risk and corrected for genetic ancestry using either principal components or genetic ancestry inferred from ancestry informative markers using a model-based approach. Results We identified a novel set of SNPs at the 6q25 locus associated with genome-wide levels of significance (p = 3.3 × 10− 8 - 6.0 × 10− 9) not in linkage disequilibrium (LD) with variants previously reported at this locus. These SNPs were in high LD (r 2 > 0.9) with each other, with the top SNP, rs3778609, associated with breast cancer with an odds ratio (OR) and 95% confidence interval (95% CI) of 0.76 (0.70–0.84). In a replication in women of Latin American origin, we also observed a consistent effect (OR 0.88; 95% CI 0.78–0.99; p = 0.037). We also performed a meta-analysis of these SNPs in East Asians, African ancestry and European ancestry populations and also observed a consistent effect (rs3778609, OR 0.95; 95% CI 0.91–0.97; p = 0.0017). Conclusion Our study adds to evidence about the importance of the 6q25 locus for breast cancer susceptibility. Our finding also highlights the utility of performing additional searches for genetic variants for breast cancer in non-European populations.

The AC/DC hybrid distribution network is one of the trends in distribution network development, which poses great challenges to the traditional distribution transformer. In this paper, a new topology suitable for AC/DC hybrid distribution network is put forward according to the demands of power grid, with advantages of accepting DG and DC loads, while clearing DC fault by blocking the clamping double sub-module (CDSM) of input stage. Then, this paper shows the typical structure of AC/DC distribution network that is hand in hand. Based on the new topology, this paper designs the control and modulation strategies of each stage, where the outer loop controller of input stage is emphasized for its two-control mode. At last, the rationality of new topology and the validity of control strategies are verified by the steady and dynamic state simulation. At the same time, the simulation results highlight the role of PET in energy regulation. Keywords: AC/DC hybrid distribution network, Power electronic transformer (PET), Clamping double sub-module (CDSM), Energy router

Prostate cancer (PrCa) involves a large heritable genetic component. Here, the authors perform multivariate fine-mapping of known PrCa GWAS loci, identifying variants enriched for biological function, explaining more familial relative risk, and with potential application in clinical risk profiling.

AIM: To explore the clinical feature and genetic etiology of a Chinese Knobloch syndrome family. METHODS: Ocular examinations and magnetic resonance imagings (MRIs) were performed on the family. Whole exome sequencing was conducted on the two patients. Sanger sequencing was utilized to validate the presence of variation in the family as well as in 100 normal controls. Real-time quantitative polymerase chain reaction (PCR) was used to detect the expression level of COL18A1 in peripheral blood lymphocytes of the patients and normal carriers. RESULTS: The affected subjects presented with vision loss, exotropia, cataracts, retinal detachment, and other complications. A homozygous c.4759_4760delCT (p.Leu1587ValfsX72) mutation (rs398122391) in COL18A1 was identified in the two patients, cosegregating with the phenotypes, and did not be detected in 100 normal controls. This mutation caused significant decreased expression of COL18A1 mRNA in the patients. CONCLUSION: The findings strongly indicate that this mutation is the disease-causing mutation. Moreover, this is the first Knobloch syndrome pedigree reported in the Chinese population.