LncRNA TGFB2-OT1 Promotes Progression and Angiogenesis in Hepatocellular Carcinoma by Dephosphorylating ß-Catenin.

Introduction: Hepatocellular carcinoma (HCC) was the sixth most prevalent cancer worldwide. Long non-coding RNA TGFB2-OT1 has been proven to mediate inflammation and autophagy in vascular endothelial cells. However, its function in HCC is still unknown. Methods: We analyzed the relationship between TGFB2-OT1 expression and the clinicopathological features of 202 HCC patients. RT-qPCR was used to analyze the TGFB2-OT1 expression in HCC cell lines and tissues. In vitro and in vivo assays were conducted to verify the effect of TGFB2-OT1 on the phenotype of HCC. RNA pull-down assays were applied to reveal the proteins binding to the TGFB2-OT1. Western-blot assays were conducted to analyze the protein expression in HCC cell lines. Results: TGFB2-OT1 was found to be highly expressed in HCC samples and hepatoma cells. TGFB2-OT1 expression was significantly associated with age (P = 0.001), cirrhosis (P = 0.003), tumor size (P < 0.001), tumor encapsulation (P = 0.029), tumor protruding from the liver surface (P = 0.040), and alpha fetoprotein (AFP, P < 0.001) levels. TGFB2-OT1 promoted proliferation, migration, invasion, and angiogenesis in HCC cells, both in vitro and in vivo. TGFB2-OT1 binds to ß-catenin and competitively impaired the binding of ß-catenin to GSK3ß, thus suppressing the phosphorylation of ß-catenin at Ser33, Ser37, and Thr41. Conclusion: TGFB2-OT1 is overexpressed in HCC and predicts the poor prognosis of HCC patients. TGFB2-OT1 impedes the phosphorylation of ß-catenin and acts as an alternative activator of the Wnt/ß-catenin pathway to promote the progression and angiogenesis of HCC.

Humoral responses after primary and booster SARS-CoV-2 inactivated vaccination in patients with chronic hepatitis B virus infection: a longitudinal observational study.

Given the pandemic of severe acute respiratory syndrome coronavirus 2 Omicron variants, booster vaccination (BV) using inactivated virus vaccines (the third dose) has been implemented in China. However, the immune responses after BV, especially those against Omicron, in patients with chronic hepatitis B virus (HBV) infection (CHB) are unclear. In this prospective longitudinal study, 114 patients with CHB and 68 healthy controls (HCs) were recruited after receiving inactivated vaccination. The anti-receptor-binding domain (RBD) immunoglobulin G (IgG), neutralizing antibodies (NAbs), neutralization against Omicron (BA2.12.1, BA.4/5), and specific B/T cells were evaluated. In patients, anti-RBD IgG was elevated significantly after BV; the titers were as high as those in HCs. Similar results were obtained for the NAbs. However, compared with that against wild type (WT), the neutralization against Omicron was compromised after BV. The frequency of RBD+ atypical memory B cells increased, but spike-specific cluster of differentiation 4+ /8+ T cells remained unchanged after BV. Moreover, no serious adverse events or HBV reactivation were observed after BV. These results suggest that BV significantly enhanced antibody responses against WT; however, it resulted in compromised antibody responses against Omicron in patients with CHB. Hence, new all-in-one vaccines and optimal vaccination strategies should be studied promptly. This article is protected by copyright. All rights reserved.

Electroenzymatic Reduction of Furfural to Furfuryl Alcohol by an Electron Mediator and Enzyme Orderly Assembled Biocathode.

The electroenzymatic valorization of biomass derivatives into valuable biochemicals has a promising outlook. However, bottlenecks including poor electron transfer between the electrode surface and oxidoreductase, inefficient regeneration of cofactors, and high cost of enzymes and electron mediators hindered the realistic applications of the technique. Herein, to address the above technical barriers, a novel bio-electrocatalytic system that integrates the electrochemical NADH regeneration and enzymatic reaction was constructed, using an orderly assembled composite bioelectrode consisting of an outer immobilized enzyme layer and a sandwiched redox mediator rhodium complex layer. The as-prepared composite bioelectrode was further applied for the highly selective hydrogenation of furfural into furfural alcohol. Results indicated that the enzyme activity was significantly improved, while the furfural valorization was promoted by effective interfacial electron transition and co-factor regeneration on the composite bioelectrode. Considerable high furfural conversion (96.4%) can be achieved accompanied by a furfural alcohol selectivity of 90.0% at -1.2 V (vs Ag/AgCl). The novel composite bioelectrode also showed good stability and reusability. Up to 85.1% of the original furfural alcohol selectivity can be preserved after 10 times of recycling. This work presents a promising green alternative for the valorization of furfural, which also shows great potential extending to the valorization of other biomass compounds.

Comparing levonorgestrel intrauterine system versus hysteroscopic niche resection in women with postmenstrual spotting related to a niche in the uterine cesarean scar: a randomized, open label, controlled trial.

BACKGROUND: Postmenstrual spotting and chronic pelvic pain after cesarean delivery (CD) are associated with the presence of niches. Levonorgestrel intrauterine system (LNG-IUS 52 mg) and hysteroscopic niche resection have been shown to relieve niche-related symptoms six months after the intervention. OBJECTIVE: This trial aimed to compare the effectiveness of LNG-IUS 52 mg with hysteroscopic niche resection in reducing niche-related postmenstrual spotting. STUDY DESIGN: This randomized, open-label, controlled trial was conducted at a medical center in Shanghai, China. Women with symptoms of postmenstrual spotting after CD, with a niche depth of at least 2 mm and residual myometrium of at least 2.2 mm on magnetic resonance imaging (MRI), and no intention to conceive within the next year were randomly assigned to receive treatment with LNG-IUS 52 mg or hysteroscopic niche resection. The primary outcome was the reduction in postmenstrual spotting 6 months after randomization, defined as the percentage of women with a reduction of at least 50% in spotting days from baseline. Efficacy and safety were assessed using intention-to-treat analysis. RESULTS: Between September 2019 and January 2022, 208 women were randomized into the LNG-IUS group (N=104) or the hysteroscopic niche resection group (N=104). At the 6th month follow-up, a 50% reduction in spotting had occurred in 78.4% (80/102) of women in the LNG-IUS group and in 73.1% (76/104) of women in the hysteroscopic niche resection group (RR=1.07, [95%CI 0.92-1.25]; P=0.370). Spotting decreased over time (Ptrend=0.001), with a stronger reduction being observed in the LNG-IUS group (P=0.001). There was also a significant interaction between time and treatment (P=0.007). From nine months onwards, a more significant reduction in spotting was observed in the LNG-IUS group than in the hysteroscopic niche resection group (9th month 89.2% vs. 72.1%, RR=1.24, [95% CI 1.08-1.42]; 12th month 90.2% vs. 70.2%, RR=1.29, [95% CI 1.12-1.48]). Moreover, compared with the hysteroscopic niche resection group, the LNG-IUS group had significantly fewer postmenstrual spotting days and total bleeding days from six months onwards (all P <0.001) as well as less pelvic pain from three months onwards (all P <0.010). No intervention-related complications were reported in any group. During follow-up, 11 (10.8%) women reported hormone-related side-effects and two women (2.0%) in the LNG-IUS group had spontaneous partial expulsion. Meanwhile, three unintended pregnancies were reported in the hysteroscopic niche resection group. CONCLUSION: In women with niche-related postmenstrual spotting, LNG-IUS was not more effective than hysteroscopic niche resection in reducing the number of spotting days by at least 50% at 6 months. However, the LNG-IUS was superior in reducing spotting from 9 months onwards, as it reduced the absolute number of spotting days from six months onwards and pelvic pain from three months onwards.

Exploring the causal effects of the gut microbiome on serum lipid levels: A two-sample Mendelian randomization analysis.

Background: The gut microbiome was reported to be associated with dyslipidemia in previous observational studies. However, whether the composition of the gut microbiome has a causal effect on serum lipid levels remains unclear. Objective: A two-sample Mendelian randomization (MR) analysis was conducted to investigate the potential causal relationships between gut microbial taxa and serum lipid levels, including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and log-transformed triglyceride (TG) levels. Materials and methods: Summary statistics of genome-wide association studies (GWASs) for the gut microbiome and four blood lipid traits were obtained from public datasets. Five recognized MR methods were applied to assess the causal estimates, among which, the inverse-variance weighted (IVW) regression was used as the primary MR method. A series of sensitivity analyses were performed to test the robustness of the causal estimates. Results: The combined results from the five MR methods and sensitivity analysis showed 59 suggestive causal associations and four significant causal associations. In particular, genus Terrisporobacter was associated with higher LDL-C (P IVW = 3.01 × 10-6) and TC levels (P IVW = 2.11 × 10-4), phylum Actinobacteria was correlated with higher LDL-C level (P IVW = 4.10 × 10-4), and genus Oscillospira was associated with lower TG level (P IVW = 2.19 × 10-6). Conclusion: This research may provide novel insights into the causal relationships of the gut microbiome on serum lipid levels and new therapeutic or prevention strategies for dyslipidemia.

Acetylation of GhCaM7 enhances cotton resistance to Verticillium dahliae.

Protein lysine acetylation is an important post-translational modification mechanism involved in cellular regulation in eukaryotes. Calmodulin (CaM) is a ubiquitous Ca2+ sensor in eukaryotes and is crucial for plant immunity, but it is so far unclear whether acetylation is involved in calmodulin-mediated plant immunity. Here, we found that GhCaM7 is acetylated upon Verticillium dahliae (V. dahliae) infection and a positive regulator of V. dahliae resistance. Overexpressing GhCaM7 in cotton and Arabidopsis enhances V. dahliae resistance and knocking-down GhCaM7 makes cotton more susceptible to V. dahliae. Transgenic Arabidopsis plants overexpressing GhCaM7 with mutation at the acetylation site are more susceptible to V. dahliae than transgenics overexpressing the wild-type GhCaM7, implying the importance of the acetylated GhCaM7 in response to V. dahliae infection. Y2H, BiFC, LCI and Co-IP assays demonstrated interaction between GhCaM7 and an osmotin protein GhOSM34 that was shown to have a positive role in V. dahliae resistance. GhCaM7 and GhOSM34 are co-localized in the cell membrane. Upon V. dahliae infection, the Ca2+ content reduces almost instantly in plants with down-regulated GhCaM7 or GhOSM34. Down-regulating GhOSM34 enhances accumulation of Na+ and increases cell osmotic pressure. Comparative transcriptomic analyses between cotton plants with an increased or reduced expression level of GhCaM7 and wild-type plants indicate the involvement of JA signaling pathways and reactive oxygen species in GhCaM7-enabled disease resistance. Together, these results demonstrate the involvement of calmodulin protein in the interaction between cotton and V. dahliae, and more importantly, the involvement of the acetylated calmodulin in the interaction.

Plant-based diets and the risk of pancreatic cancer: a large prospective multicenter study.

BACKGROUND: Plant-based diets have been recommended for improving health outcomes, including cancer. However, previous studies on plant-based diets and the risk of pancreatic cancer are scarce and fail to consider plant food quality. OBJECTIVES: We sought to examine the potential associations of 3 plant-based diet indices (PDIs) with the risk of pancreatic cancer in a US population. METHODS: A population-based cohort of 101,748 US adults was identified from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. The overall PDI, healthful PDI (hPDI), and unhealthful PDI (uPDI) were constructed to qualify adherence to overall, healthy, and less healthy plant-based diets, respectively, with higher scores indicating better adherence. Multivariable Cox regression was used to compute hazard ratios (HRs) for pancreatic cancer incidence. Subgroup analysis was conducted to identify the potential effect modifiers. RESULTS: Over a mean follow-up of 8.86 years, 421 pancreatic cancer cases occurred. Participants in the highest compared with the lowest quartiles of overall PDI had a lower risk of pancreatic cancer [HRquartile 4 versus 1: 0.74; 95% confidence interval (CI): 0.57, 0.96; Ptrend = 0.023]. A stronger inverse association was observed for hPDI (HRquartile 4 versus 1: 0.56; 95% CI: 0.42, 0.75; Ptrend < 0.001). Conversely, uPDI was positively associated with the risk of pancreatic cancer (HRquartile 4 versus 1: 1.38; 95% CI: 1.02, 1.85; Ptrend = 0.012). Subgroup analyses revealed a stronger positive association for uPDI in participants with BMI <25 (HRquartile 4 versus 1: 3.22; 95% CI: 1.56, 6.65) than in those with BMI ≥25 (HRquartile 4 versus 1: 1.08; 95% CI: 0.78, 1.51) (Pinteraction = 0.001). CONCLUSIONS: In this US population, adherence to a healthy plant-based diet confers a lower risk of pancreatic cancer, whereas adherence to a less healthy plant-based diet confers a higher risk. These findings highlight the importance of considering plant food quality in preventing pancreatic cancer.

Precision information extraction for rare disease epidemiology at scale.

BACKGROUND: The United Nations recently made a call to address the challenges of an estimated 300 million persons worldwide living with a rare disease through the collection, analysis, and dissemination of disaggregated data. Epidemiologic Information (EI) regarding prevalence and incidence data of rare diseases is sparse and current paradigms of identifying, extracting, and curating EI rely upon time-intensive, error-prone manual processes. With these limitations, a clear understanding of the variation in epidemiology and outcomes for rare disease patients is hampered. This challenges the public health of rare diseases patients through a lack of information necessary to prioritize research, policy decisions, therapeutic development, and health system allocations. METHODS: In this study, we developed a newly curated epidemiology corpus for Named Entity Recognition (NER), a deep learning framework, and a novel rare disease epidemiologic information pipeline named EpiPipeline4RD consisting of a web interface and Restful API. For the corpus creation, we programmatically gathered a representative sample of rare disease epidemiologic abstracts, utilized weakly-supervised machine learning techniques to label the dataset, and manually validated the labeled dataset. For the deep learning framework development, we fine-tuned our dataset and adapted the BioBERT model for NER. We measured the performance of our BioBERT model for epidemiology entity recognition quantitatively with precision, recall, and F1 and qualitatively through a comparison with Orphanet. We demonstrated the ability for our pipeline to gather, identify, and extract epidemiology information from rare disease abstracts through three case studies. RESULTS: We developed a deep learning model to extract EI with overall F1 scores of 0.817 and 0.878, evaluated at the entity-level and token-level respectively, and which achieved comparable qualitative results to Orphanet's collection paradigm. Additionally, case studies of the rare diseases Classic homocystinuria, GRACILE syndrome, Phenylketonuria demonstrated the adequate recall of abstracts with epidemiology information, high precision of epidemiology information extraction through our deep learning model, and the increased efficiency of EpiPipeline4RD compared to a manual curation paradigm. CONCLUSIONS: EpiPipeline4RD demonstrated high performance of EI extraction from rare disease literature to augment manual curation processes. This automated information curation paradigm will not only effectively empower development of the NIH Genetic and Rare Diseases Information Center (GARD), but also support the public health of the rare disease community.

Artificial photo-enzymatic reduction of carbon dioxide into methanol using electron mediator and co-factor assembled ZnIn2S4 nanoflower.

High trapping of visible light, low electron-hole recombination, and quickly emigrating electrons are the major objectives for the designation of highly effective photocatalysts in biocatalytic artificial photosynthesis systems. In this study, a polydopamine (PDA) layer that contained electron mediator ([M]) and co-factor (NAD+) functionalized polymer was assembled on the outer surface of ZnIn2S4 nanoflower, and the as-prepared nanoparticle (ZnIn2S4/PDA@poly/[M]/NAD+) was used for photo-enzymatic methanol production from CO2. Owing to effectively trapping visible light, shortening the electron transfer distance, and eliminating the recombination of electron-holes, a high NADH regeneration of 80.7 ± 1.43 % can be realized by the novel ZnIn2S4/PDA@poly/[M]/NAD+. Results also showed a maximum methanol production of 116.7 ± 11.8 µM was obtained in the corresponding artificial photosynthesis system. In this process, attributed to the successful immobilization of the small blocks including the electron mediator and co-factor on the surface of the photocatalyst, the enzymes and nanoparticles in the hybrid bio-photocatalysis system can be easily preserved by the mature ultrafiltration membrane in the bottom of the photoreactor. The ZnIn2S4/PDA@poly/[M]/NAD+ photocatalyst also exhibited good stability and recyclability for methanol production. The novel concept presented in this study shows great promise for other sustainable chemical productions via artificial photo-enzymatic catalysis.

Single-cell transcriptomic analysis reveals the developmental trajectory and transcriptional regulatory networks of pigment glands in Gossypium bickii.

Comprehensive utilization of cottonseeds is limited by the presence of pigment glands and its inclusion gossypol. The ideal cotton has glandless seeds but a glanded plant, a trait found in only a few Australian wild cotton species, including Gossypium bickii. Introgression of this trait into cultivated species has proved to be difficult. Understanding the biological processes toward pigment gland morphogenesis and the associated underlying molecular mechanisms will facilitate breeding of cultivated cotton varieties with the trait of glandless seeds and glanded plant. In this study, single-cell RNA sequencing (scRNA-seq) was performed on 12 222 protoplasts isolated from cotyledons of germinating G. bickii seeds 48 h after imbibition. Clustered into 14 distinct clusters unsupervisedly, these cells could be grouped into eight cell populations with the assistance of known cell marker genes. The pigment gland cells were well separated from others and could be separated into pigment gland parenchyma cells, secretory cells, and apoptotic cells. By integrating the pigment gland cell developmental trajectory, transcription factor regulatory networks, and core transcription factor functional validation, we established a model for pigment gland formation. In this model, light and gibberellin were verified to promote the formation of pigment glands. In addition, three novel genes, GbiERF114 (ETHYLENE RESPONSE FACTOR 114), GbiZAT11 (ZINC FINGER OF ARABIDOPSIS THALIANA 11), and GbiNTL9 (NAC TRANSCRIPTION FACTOR-LIKE 9), were found to affect pigment gland formation. Collectively, these findings provide new insights into pigment gland morphogenesis and lay the cornerstone for future cotton scRNA-seq investigations.

Clustering rare diseases within an ontology-enriched knowledge graph.

Objective: Identifying sets of rare diseases with shared aspects of etiology and pathophysiology may enable drug repurposing and/or platform based therapeutic development. Toward that aim, we utilized an integrative knowledge graph-based approach to constructing clusters of rare diseases. Materials and Methods: Data on 3,242 rare diseases were extracted from the National Center for Advancing Translational Science (NCATS) Genetic and Rare Diseases Information center (GARD) internal data resources. The rare disease data was enriched with additional biomedical data, including gene and phenotype ontologies, biological pathway data and small molecule-target activity data, to create a knowledge graph (KG). Node embeddings were used to convert nodes into vectors upon which k-means clustering was applied. We validated the disease clusters through semantic similarity and feature enrichment analysis. Results: A node embedding model was trained on the ontology enriched rare disease KG and k-means clustering was applied to the embedding vectors resulting in 37 disease clusters with a mean size of 87 diseases. We validate the disease clusters quantitatively by looking at semantic similarity of clustered diseases, using the Orphanet Rare Disease Ontology. In addition, the clusters were analyzed for enrichment of associated genes, revealing that the enriched genes within clusters were shown to be highly related. Discussion: We demonstrate that node embeddings are an effective method for clustering diseases within a heterogenous KG. Semantically similar diseases and relevant enriched genes have been uncovered within the clusters. Connections between disease clusters and approved or investigational drugs are enumerated for follow-up efforts. Conclusion: Our study lays out a method for clustering rare diseases using the graph node embeddings. We develop an easy to maintain pipeline that can be updated when new data on rare diseases emerges. The embeddings themselves can be paired with other representation learning methods for other data types, such as drugs, to address other predictive modeling problems. Detailed subnetwork analysis and in-depth review of individual clusters may lead to translatable findings. Future work will focus on incorporation of additional data sources, with a particular focus on common disease data.

Traditional Chinese Medicine constitution types of high-normal blood pressure: A meta-analysis.

Objective: We determined the distribution of constitutional types of high-normal blood pressure in Traditional Chinese Medicine (TCM) and provided evidence for the prevention of high-normal blood pressure and hypertension. Methods: Eight digital databases were searched from January 2011 to November 2022, including PubMed, EMBASE, Web of Science, EBSCOhost, CNKI, CBM, Wangfang, and CQVIP. We performed a meta-analysis with the random-effects model or fixed-effects model to describe the distribution of constitutional types of high-normal blood pressure in TCM. The studies were assessed based on heterogeneity testing and the potential for publication bias. The meta-analysis was performed on Stata software 15.0. Results: A total of 17 studies with 8118 participants were included in this meta-analysis. The proportion of the biased constitution (82.3%; 95% CI: 75.6%-89.1%, p < 0.001) was higher than the balanced constitution (17.3%; 95% CI: 10.7-23.8%, p < 0.001). Phlegm-dampness constitution, Yin-deficiency constitution, and damp-heat constitution accounted for 16.0% (95%CI: 10.5-21.5%, p < 0.001), 14.8% (95% CI: 11.0-18.6%, p < 0.001), 11.3% (95% CI: 8.0-14.5%, p < 0.001) of the total high-normal blood pressure cases, respectively. The subgroup analyses performed that region, age and gender were positively associated with the distribution of constitution types of high-normal blood pressure in TCM. Compared with the general population, the risk of high-normal blood pressure in people with the phlegm-dampness constitution, Yin-deficiency constitution, and blood-stasis constitution was 2.665 (95%CI: 2.286-3.106, p < 0.001), 2.378 (95%CI: 1.197-4.724, p = 0.013), 1.965 (95%CI: 1.634-2.363, p < 0.001) times of the general population, respectively. Meanwhile, the risk of high-normal blood pressure was lower in people with a balanced constitution (0.248, 95%CI: 0.165-0.372, p < 0.001). Conclusions: Phlegm-dampness constitution, Yin-deficiency constitution, and damp-heat constitution were the common constitution types of high-normal blood pressure. There might also be differences in the distribution characteristics of TCM constitution among people with high-normal blood pressure in different regions, ages, and genders. Finally, a balanced constitution might be a protective factor for hypertensive people.

Safety of adjuvant atezolizumab after pneumonectomy/bilobectomy in stage II-IIIA non-small cell lung cancer in the randomized phase III IMpower010 trial.

OBJECTIVE: Adjuvant atezolizumab is a standard of care after chemotherapy in completely resected stage II-IIIA programmed death ligand-1 tumor cell 1% or greater non-small cell lung cancer based on results from the phase III IMpower010 study. We explored the safety and tolerability of adjuvant atezolizumab by surgery type in IMpower010. METHODS: Patients had completely resected stage IB-IIIA non-small cell lung cancer (Union Internationale Contre le Cancer/American Joint Committee on Cancer, 7th Ed), received up to four 21-day cycles of cisplatin-based chemotherapy, and were randomized 1:1 to receive atezolizumab 1200 mg every 3 weeks (≤16 cycles or 1 year) or best supportive care. Adverse events and clinical characteristics were investigated by surgery type (pneumonectomy/bilobectomy or lobectomy/sleeve lobectomy) in the randomized stage II-IIIA population who received 1 or more atezolizumab dose or with 1 or more postbaseline assessment (safety evaluable) for best supportive care. RESULTS: Overall, 871 patients comprised the safety-evaluable randomized stage II-IIIA population. In the atezolizumab arm, 23% (100/433) received pneumonectomy/bilobectomy and 77% (332/433) received lobectomy/sleeve lobectomy. Atezolizumab discontinuation occurred in 32% (n = 32) and 35% (n = 115) of the pneumonectomy/bilobectomy and lobectomy/sleeve lobectomy groups, respectively. Grade 3/4 adverse events were reported in 21% (n = 21) and 23% (n = 76) of patients in the atezolizumab arms in the pneumonectomy/bilobectomy and lobectomy/sleeve lobectomy groups, respectively. In the atezolizumab arms of the surgery groups, 13% (n = 13) and 17% (n = 55) had an adverse event leading to hospitalization. Atezolizumab-related adverse events leading to hospitalization occurred in 5% (n = 5) and 7% (n = 23) of the surgery groups. CONCLUSIONS: These exploratory findings support use of adjuvant atezolizumab after platinum-based chemotherapy in patients with completely resected stage II-IIIA programmed death ligand-1 tumor cell 1% or more non-small cell lung cancer, regardless of surgery type.

Comparative effectiveness of transvaginal repair vs. hysteroscopic resection in patients with symptomatic uterine niche.

Objective: To compare the efficacy of transvaginal repair and hysteroscopic resection in improving niche associated postmenstrual spotting. Methods: The improvement rate of postmenstrual spotting in women who underwent transvaginal repair or hysteroscopic resection treatment was assessed retrospectively in patients accepted at the Niche Sub-Specialty Clinic in International Peace Maternity and Child Health Hospital between June 2017 and June 2019. Postoperative spotting symptom within one year after surgery, pre- and postoperative anatomical indicators, women' satisfaction with menstruation and other perioperative parameters were compared between the two groups. Results: 68 patients in the transvaginal group and 70 patients in the hysteroscopic group were included for analysis. The improvement rate of postmenstrual spotting in the transvaginal group at the 3rd, 6th, 9th, and 12th months after surgery was 87%, 88%, 84%, and 85%, significantly higher than 61%, 68%, 66%, and 68% in the hysteroscopic group, respectively (P < 0.05). The total days of spotting improved significantly at the 3rd month after surgery but did not change over time within one year in each group (P > 0.05). After surgery, the disappearance rates of the niche are 68% in transvaginal group and 38% in hysteroscopic group, however, hysteroscopic resection had shorter operative time and hospitalization duration, less complications, and lower hospitalization costs. Conclusion: Both treatments can improve the spotting symptom and anatomical structures of uterine lower segments with niches. Transvaginal repair is better in thickening the residual myometrium than hysteroscopic resection, however, hysteroscopic resection has shorter operative time and hospitalization duration, less complications, and lower hospitalization costs.

Colnoy-stimulating factor 1 positive (CSF1+ ) secretory epithelial cells induce excessive trophoblast invasion in tubal pregnancy rupture.

Tubal ectopic pregnancy (TEP) occurs when an embryo aberrantly implants in the fallopian tube, leading to abortive or ruptured tubal ectopic pregnancy (AEP or REP). Poor outcomes of REP include maternal infertility or mortality. Current studies on the prevention and treatment of ruptured tubal ectopic pregnancy (REP) are unfortunately hampered by a lack of the cell spectrum and cell-cell communications in the maternal-foetal interface. Here, we investigate the mechanisms of tubal rupture through single-cell transcriptome profiling of the fallopian tube-trophoblast interface in REP, AEP and intrauterine pregnancy patients. In REP, extravillous trophoblast (EVTs) cells form a dominant cell population, displaying aggressive invasion and proliferation, with robust differentiation into three subsets. Cell communication analysis identified colony-stimulating factor 1 (CSF1), overexpressed by fallopian tube secretory epithelial cells in REP, with CSF1R on EVTs and macrophages, as a ligand/receptor pair that stimulates EVT invasion and macrophage accumulation. CSF1+ secretory epithelial cells stimulate EVTs migration and invasion, leading to a tubal rupture in REP. These results provide a mechanistic context and cellular milieu leading to tubal rupture, facilitating further study and development of therapeutics for REP in early pregnancy.

The implementation of a community-centered first aid education program for older adults-community health workers perceived barriers.

BACKGROUND: Older adults are a high-risk group for accidental injuries, and strengthening training in first aid for older adults can improve their first aid capabilities and minimize their post-accident mortality. Community health workers are the greatest option to equip older adults with first aid instruction and training. However, the development of first aid education for the public by community health workers fails to take into account the elderly population. In view of this, this study aims to explore the barriers and challenges of first aid training for older adults from the perspective of community health workers and to provide a basis for better first-aid training for older adults in the community. METHODS: This study adopted a qualitative research design. A total of 18 community health workers were recruited from two community health service centers in Qujing and one community health service center in Guangzhou from May to July 2022 to participate in the study. Participants were interviewed face-to-face using semi-structured in-depth interviews. The interview data were analyzed using Krippendorff's thematic clustering technique. RESULTS: The results of the study identified community health workers' perceived challenges and barriers to providing first aid training to older adults in the community as older adults-level barriers, community health workers-level barriers, management systems-level barriers, and society-level barriers. CONCLUSIONS: Community health workers are highly aware of multiple barriers and challenges in providing first aid training to community-based elderly populations. In particular, lack of professional training, heavy workloads, and limited resources and financial support. Therefore, supportive training, policies, and government funding are crucial for community health workers to conduct first aid training for older adults.

Aberrant Spontaneous Brain Activity and its Association with Cognitive Function in Non-Obese Nonalcoholic Fatty Liver Disease: A Resting-State fMRI Study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has been proven to be associated with an increased risk of cognitive impairment and dementia, and this association is more significant in non-obese NAFLD populations, but its pathogenesis remains unclear. Our study aimed to explore the abnormalities of spontaneous brain activity in non-obese NAFLD patients by resting-state fMRI (RS-fMRI) and their relationship with cognitive function. METHODS: 19 non-obese NAFLD, 25 obese NAFLD patients, and 20 healthy controls (HC) were enrolled. All subjects underwent RS-fMRI scan, psychological scale assessment, and biochemical examination. After RS-fMRI data were preprocessed, differences in low-frequency fluctuation amplitude (ALFF), regional homogeneity (ReHo) and functional connectivity (FC) were compared among the three groups. Furthermore, the relationship between RS-fMRI indicators and cognitive and clinical indicators were performed using correlation analysis. RESULTS: The cognitive function was declined in both NAFLD groups. Compared with obese NAFLD patients, non-obese NAFLD patients showed increased ALFF and ReHo in the left middle temporal gyrus (MTG), increased ReHo in the sensorimotor cortex and reduced FC between left MTG and right inferior frontal gyrus (IFG). Compared with HC, non-obese NAFLD patients showed increased ALFF and ReHo in the left calcarine cortex and fusiform gyrus (FG), decreased ALFF in the bilateral cerebellum, and reduced FC between left FG and right IFG and left angular gyrus. In addition to the same results, obese patients showed increased activity in different regions of the bilateral cerebellum, while decreased ALFF in the right superior frontal gyrus and ReHo in the right orbitofrontal cortex (OFC). Correlation analysis showed that in non-obese patients, the ALFF values in the FG and the FC values between the left MTG and the right IFG were associated with cognitive decline, insulin resistance, and fasting glucose disorder. CONCLUSIONS: Non-obese NAFLD patients showed abnormal local spontaneous activity and FC in regions involved in the sensorimotor, temporo-occipital cortex, cerebellum, and reward system (such as OFC), some of which may be the potential neural mechanism difference from obese NAFLD patients. In addition, the temporo-occipital cortex may be a vulnerable target for cognitive decline in non-obese NAFLD patients.

Identification of sugar transporter genes and their roles in the pathogenicity of Verticillium dahliae on cotton.

Introduction: Verticillium wilt (VW) caused by Verticillium dahliae is a soil-borne vascular fungal disease that severely affects cotton yield and fiber quality. Sugar metabolism plays an important role in the growth and pathogenicity of V. dahliae. However, limited information is known about the sugar transporter genes and their roles in the growth and pathogenicity of V. dahliae. Method: In this study, genome-wide identification of sugar transporter genes in V. dahliae was conducted and the expression profiles of these genes in response to root exudates from cotton varieties susceptible or resistant to V. dahliae were investigated based on RNA-seq data. Tobacco Rattle Virus-based host-induced gene silencing (TRV-based HIGS) and artificial small interfering RNAs (asiRNAs) were applied to investigate the function of candidate genes involved in the growth and pathogenic process of V. dahliae. Results: A total of 65 putative sugar transporter genes were identified and clustered into 8 Clades. Of the 65 sugar transporter genes, 9 were found to be induced only by root exudates from the susceptible variety, including VdST3 and VdST12 that were selected for further functional study. Silencing of VdST3 or VdST12 in host plants by TRV-based HIGS reduced fungal biomass and enhanced cotton resistance against V. dahliae. Additionally, silencing of VdST12 and VdST3 by feeding asiRNAs targeting VdST12 (asiR815 or asiR1436) and VdST3 (asiR201 or asiR1238) inhibited fungal growth, exhibiting significant reduction in hyphae and colony diameter, with a more significant effect observed for the asiRNAs targeting VdST12. The inhibitory effect of asiRNAs on the growth of V. dahliae was enhanced with the increasing concentration of asiRNAs. Silencing of VdST12 by feeding asiR815+asiR1436 significantly decreased the pathogenicity of V. dahliae. Discussion: The results suggest that VdST3 and VdST12 are sugar transporter genes required for growth and pathogenicity of V. dahliae and that asiRNA is a valuable tool for functional characterization of V. dahliae genes.