Single-cell sequencing reveals the impact of endothelial cell PIEZO1 expression on thoracic aortic aneurysm.

INTRODUCTION: Thoracic aortic aneurysm (TAA) is a severe vascular disease that threatens human life, characterized by focal dilatation of the entire aortic wall, with a diameter 1.5 times larger than normal. PIEZO1, a mechanosensitive cationic channel, monitors mechanical stimulations in the environment, transduces mechanical signals into electrical signals, and converts them into biological signals to activate intracellular signaling pathways. However, the role of PIEZO1 in TAA is still unclear. METHODS: We analyzed a single-cell database to investigate the expression level of PIEZO1 in TAA. We constructed a conditional knockout mouse model of Piezo1 and used the PIEZO1 agonist Yoda1 to intervene in the TAA model mice established by co-administration of BAPN and ANG-II. Finally, we explored the effect of Yoda1 on TAA in vitro. RESULTS AND DISCUSSION: We observed decreased PIEZO1 expression in TAA at both RNA and protein levels. Single-cell sequencing identified a specific reduction in Piezo1 expression in endothelial cells. Administration of PIEZO1 agonist Yoda1 prevented the formation of TAA. In PIEZO1 endothelial cell conditional knockout mice, Yoda1 inhibited TAA formation by interfering with PIEZO1. In vivo and in vitro experiments demonstrated that the effect of Yoda1 on endothelial cells involved macrophage infiltration, extracellular matrix degradation, and neovascularization. This study highlights the role of PIEZO1 in TAA and its potential as a therapeutic target, providing opportunities for clinical translation.

C-H Functionalization-Enabled 11-Step Semisynthesis of (-)-Veragranine A and Characterization of Synthetic Analogs in Osteoarthritis-related Pain Treatment.

We report an efficient semisynthesis of the cholestane steroidal alkaloid (-)-veragranine A with a 6/6/6/5/6/6 hexacyclic ring system, eight stereocenters, and a unique C12-C23 linkage. Our synthesis features a Schönecker-Baran C-H oxidation at C12, a Suzuki-Miyaura cross-coupling to form the C12-C23 bond, and a hydrogen atom transfer (HAT)-initiated Minisci C-H cyclization to forge the C20-C22 bond with desired stereochemistry at C20. These enabling transformations significantly enhanced the overall synthetic efficiency and delivered (-)-veragranine A in 11 steps and over 200 mg from cheap and readily available dehydroepiandrosterone. In addition, this approach allowed flexible syntheses of novel synthetic analogs for biological evaluations in sensory neurons in vitro and in an in vivo model of arthritic pain, from which two novel lead compounds were identified for further development.

Identification of candidate genes controlling cold tolerance at the early seedling stage from Dongxiang wild rice by QTL mapping, BSA-Seq and RNA-Seq.

BACKGROUND: The cold tolerance of rice is closely related to its production and geographic distribution. The identification of cold tolerance-related genes is of important significance for developing cold-tolerant rice. Dongxiang wild rice (Oryza rufipogon Griff.) (DXWR) is well-adapted to the cold climate of northernmost-latitude habitats ever found in the world, and is one of the most valuable rice germplasms for cold tolerance improvement. RESULTS: Transcriptome analysis revealed genes differentially expressed between Xieqingzao B (XB; a cold sensitive variety) and 19H19 (derived from an interspecific cross between DXWR and XB) in the room temperature (RT), low temperature (LT), and recovery treatments. The results demonstrated that chloroplast genes might be involved in the regulation of cold tolerance in rice. A high-resolution SNP genetic map was constructed using 120 BC5F2 lines derived from a cross between 19H19 and XB based on the genotyping-by-sequencing (GBS) technique. Two quantitative trait loci (QTLs) for cold tolerance at the early seedling stage (CTS), qCTS12 and qCTS8, were detected. Moreover, a total of 112 candidate genes associated with cold tolerance were identified based on bulked segregant analysis sequencing (BSA-seq). These candidate genes were divided into eight functional categories, and the expression trend of candidate genes related to 'oxidation-reduction process' and 'response to stress' differed between XB and 19H19 in the RT, LT and recovery treatments. Among these candidate genes, the expression level of LOC_Os12g18729 in 19H19 (related to 'response to stress') decreased in the LT treatment but restored and enhanced during the recovery treatment whereas the expression level of LOC_Os12g18729 in XB declined during recovery treatment. Additionally, XB contained a 42-bp deletion in the third exon of LOC_Os12g18729, and the genotype of BC5F2 individuals with a survival percentage (SP) lower than 15% was consistent with that of XB. Weighted gene coexpression network analysis (WGCNA) and modular regulatory network learning with per gene information (MERLIN) algorithm revealed a gene interaction/coexpression network regulating cold tolerance in rice. In the network, differentially expressed genes (DEGs) related to 'oxidation-reduction process', 'response to stress' and 'protein phosphorylation' interacted with LOC_Os12g18729. Moreover, the knockout mutant of LOC_Os12g18729 decreased cold tolerance in early rice seedling stage signifcantly compared with that of wild type. CONCLUSIONS: In general, study of the genetic basis of cold tolerance of rice is important for the development of cold-tolerant rice varieties. In the present study, QTL mapping, BSA-seq and RNA-seq were integrated to identify two CTS QTLs qCTS8 and qCTS12. Furthermore, qRT-PCR, genotype sequencing and knockout analysis indicated that LOC_Os12g18729 could be the candidate gene of qCTS12. These results are expected to further exploration of the genetic mechanism of CTS in rice and improve cold tolerance of cultivated rice by introducing the cold tolerant genes from DXWR through marker-assisted selection.

Current Understanding of Timing of Surgical Repair for Ventricular Septal Rupture following Acute Myocardial Infarction.

BACKGROUND: Ventricular septal rupture (VSR) is a mechanical issue that can occur following an acute myocardial infarction (AMI) and has a high mortality rate. It requires a comprehensive, team-based approach for prompt diagnosis and maintaining stable blood flow. While the occurrence of VSR has lessened over the past hundred years and advancements have been made in treatment techniques, the mortality rate within 30 days can still surpass 40 percent. Surgery is the primary treatment method. For patients with stable blood flow, it is generally considered safer to perform surgery 4-6 weeks after the AMI to repair the VSR. However, the timing of surgery for patients with early instability in their blood flow is still a topic of debate. SUMMARY: There is a lack of set criteria and standards to determine the best time for surgery in patients with VSR following an infarction who have unstable blood flow, especially when considering the use of blood circulation support devices and other techniques for maintaining blood flow that are used in clinical settings. KEY MESSAGES: This review outlines the features of different mechanical circulatory support devices utilized in treating VSR, along with the current scoring system designed to direct the treatment approach for VSR patients.

Neural Interface-Based Motor Neuroprosthesis in Poststroke Upper Limb Neurorehabilitation: An Individual Patient Data Meta-analysis.

OBJECTIVE: To determine the efficacy of neural interface-based neurorehabilitation, including brain-computer interface, through conventional and individual patient data (IPD) meta-analysis and to assess clinical parameters associated with positive response to neural interface-based neurorehabilitation. DATA SOURCES: PubMed, EMBASE, and Cochrane Library databases up to February 2022 were reviewed. STUDY SELECTION: Studies using neural interface-controlled physical effectors (functional electrical stimulation and/or powered exoskeletons) and reported Fugl-Meyer Assessment-upper-extremity (FMA-UE) scores were identified. This meta-analysis was prospectively registered on PROSPERO (#CRD42022312428). PRISMA guidelines were followed. DATA EXTRACTION: Changes in FMA-UE scores were pooled to estimate the mean effect size. Subgroup analyses were performed on clinical parameters and neural interface parameters with both study-level variables and IPD. DATA SYNTHESIS: Forty-six studies containing 617 patients were included. Twenty-nine studies involving 214 patients reported IPD. FMA-UE scores increased by a mean of 5.23 (95% confidence interval [CI]: 3.85-6.61). Systems that used motor attempt resulted in greater FMA-UE gain than motor imagery, as did training lasting >4 vs ≤4 weeks. On IPD analysis, the mean time-to-improvement above minimal clinically important difference (MCID) was 12 weeks (95% CI: 7 to not reached). At 6 months, 58% improved above MCID (95% CI: 41%-70%). Patients with severe impairment (P=.042) and age >50 years (P=.0022) correlated with the failure to improve above the MCID on univariate log-rank tests. However, these factors were only borderline significant on multivariate Cox analysis (hazard ratio [HR] 0.15, P=.08 and HR 0.47, P=.06, respectively). CONCLUSION: Neural interface-based motor rehabilitation resulted in significant, although modest, reductions in poststroke impairment and should be considered for wider applications in stroke neurorehabilitation.

Sliding limited penetrable visibility graph for establishing complex network from time series.

This study proposes a novel network modeling approach, called sliding window limited penetrable visibility graph (SLPVG), for transforming time series into networks. SLPVG takes into account the dynamic nature of time series, which is often affected by noise disturbances, and the fact that most nodes are not directly connected to distant nodes. By analyzing the degree distribution of different types of time series, SLPVG accurately captures the dynamic characteristics of time series with low computational complexity. In this study, the authors apply SLPVG for the first time to diagnose compensation capacitor faults in jointless track circuits. By combining the fault characteristics of compensation capacitors with network topological indicators, the authors find that the betweenness centrality reflects the fault status of the compensation capacitors clearly and accurately. Experimental results demonstrate that the proposed model achieves a high accuracy rate of 99.1% in identifying compensation capacitor faults. The SLPVG model provides a simple and efficient tool for studying the dynamics of long time series and offers a new perspective for diagnosing compensation capacitor faults in jointless track circuits. It holds practical significance in advancing related research fields.

Four new species of Anyphaena Sundevall, 1833 from Xizang, China (Araneae, Anyphaenidae).

Four new species of the genus Anyphaena Sundevall, 1833 collected from Xizang, China, are described: A.cibagou Wang & Mi, sp. nov. (♂♀), A.linzhi Wang & Mi, sp. nov. (♂♀), A.shufui Wang & Mi, sp. nov. (♀) and A.yejiei Wang & Mi, sp. nov. (♀). Diagnostic photos of the habitus and copulatory organs and a distributional map are provided.

Design of application-oriented disease diagnosis model using a meta-heuristic algorithm.

BACKGROUND: Healthcare is crucial to patient care because it provides vital services for maintaining and restoring health. As healthcare technology evolves, cutting-edge tools facilitate faster diagnosis and more effective patient treatment. In the present age of pandemics, the Internet of Things (IoT) offers a potential solution to the problem of patient safety monitoring by creating a massive quantity of data about the patient through the linked devices around them and then analyzing it to estimate the patient's current status. Utilizing the IoT-based meta-heuristic algorithm allows patients to be remotely monitored, resulting in timely diagnosis and improved care. Meta-heuristic algorithms are successful, resilient, and effective in solving real-world enhancement, clustering, predicting, and grouping. Healthcare organizations need an efficient method for dealing with big data since the prevalence of such data makes it challenging to analyze for diagnosis. The current techniques used in medical diagnostics have limitations due to imbalanced data and the overfitting issue. OBJECTIVE: This study introduces the particle swarm optimization and convolutional neural network to be used as a meta-heuristic optimization method for extensive data analysis in the IoT to monitor patients' health conditions. METHOD: Particle Swarm Optimization is used to optimize the data used in the study. Information for a diabetes diagnosis model that includes cardiac risk forecasting is collected. Particle Swarm Optimization and Convolutional Neural Networks (PSO-CNN) results effectively make illness predictions. Support Vector Machine has been used to predict the possibility of a heart attack based on the classification of the collected data into projected abnormal and normal ranges for diabetes. RESULTS: The results of the simulations reveal that the PSO-CNN model used to predict diabetic disease increased in accuracy by 92.6%, precision by 92.5%, recall by 93.2%, F1-score by 94.2%, and quantization error by 4.1%. CONCLUSION: The suggested approach could be applied to identify cancer cells.

Therapeutic effects of treat and repair strategy in pediatric patients with pulmonary arterial hypertension and simple congenital heart defects.

Surgical indications for patients with pulmonary arterial hypertension (PAH) and congenital heart defects are controversial. The treat and repair strategy has demonstrated efficacy in adult populations, but there have been no studies on pediatric patients. This study included pediatric patients with PAH and simple congenital heart defects who underwent corrective repair between 2012 and 2021. According to the preoperative treatment strategies, the patients were divided into a regular strategy group (Group 1) and a treat-and-repair strategy group (Group 2). Postoperative recovery and follow-up results were compared between the two groups. A total of 33 patients were included in this study. Group 1 consisted of 19 patients, whereas Group 2 consisted of 14 patients. The pulmonary vascular resistance index in Group 2 was higher than that in Group 1 (10.9 ± 4.1 vs. 8.2 ± 1.6 WU, p = 0.031). There were no differences in postoperative recovery between the two groups (p > 0.05). During follow-up, five patients were lost (three in Group 1 and two in Group 2). The median follow-up period was 59 months. One patient died in Group 1, and two patients died in Group 2. There was no significant difference in the survival curve (p = 0.39). At the last follow-up, another seven patients had experienced a non-low-risk condition, with a total of three non-low-risk patients in Group 1 and seven in Group 2, including one patient in each group who had a history of ICU admission. According to the ROC curve, a preoperative PVRi <8.2 WU×m2 can predict postoperative persistent low-risk state, PVRi <5.2 WU×m2 can avoid postoperative death and/or ICU administration. In pediatric patients with PAH and simple congenital heart defects, the treat and repair strategies may provide surgery opportunities, PVRi should be <8 WU×m2, and <5.2 WU×m2 is the best choice.

Spray performance simulation and experiment analysis of a greenhouse fixed-pipe twin-fluid cold fogger with different nozzle settings.

BACKGROUND: High-efficient pesticide application equipment for protected cultivation is scarce. In response, a fixed-pipe twin-fluid clod fogger (FTCF) was proposed as a potential solution. To investigate the optimal nozzle layout and spray performance, a computational fluid dynamics (CFD) model was used to study the airflow distribution and spray deposition of a FTCF with different nozzle settings using the Euler-Lagrange approach. Specifically, two piping configurations, middle-cross-inverted (MCI) and bilateral-malposed-opposite (BMO), were combined with three nozzle spacings (2 m, 3 m, 4 m) resulting in six nozzle settings. Additionally, a greenhouse spray trial was conducted to test the performance of FTCF with the selected nozzle settings and to validate the model. RESULTS: The simulation results revealed that MCI piping configuration exhibited a stronger airflow disturbance compared to BMO configuration, indicating a more significant air-guided effect in the MCI configuration. Combining this finding with the ground droplet distribution analysis of MCI piping configuration, it was observed that MCI-2 m had the lowest coefficient of variation (CV) for ground deposition (20.56%). Consequently, MCI-2 m was determined as the most optimal nozzle setting. Verification results demonstrated a high consistency between experimental and simulated spray deposition results. CONCLUSIONS: The FTCF system effectively generated a three-dimensional airflow field throughout the greenhouse environment. Furthermore, jet flow produced by FTCF disrupted the overall airflow pattern within the greenhouse space which facilitated droplet suspension and dispersion. This study provides valuable insights and innovative ideas for enhancing pesticide application technologies in protected cultivations. © 2024 Society of Chemical Industry.

Stereocontrol in an intermolecular Schmidt reaction of equilibrating hydroxyalkyl allylic azides.

A selective intermolecular Schmidt reaction of equilibrating hydroxyalkyl allylic azides is reported to afford N-hydroxyalk-1-en-3-yl lactams in modest to high yields. For prochiral and chiral ketones, modest to high 1,5-diastereoselectivity was achieved, and the mechanistic analysis is supported by DFT calculation.

Healthcare-associated infection management in 62 ICUs for patients with congenital heart disease in China: a survey study.

OBJECTIVES: All patients with congenital heart disease (CHD) receive postoperative management in ICUs. Infection prevention and control (IPC) has a significant impact on prognosis. This study provides a preliminary understanding of the fundamental aspects of IPC in ICUs following CHD surgery in China. METHODS: From September to October 2023, we initiated a survey on healthcare-associated infection (HAI) management in hospitals that perform CHD surgeries independently. The questionnaires were jointly completed by the ICU physicians and IPC personnel. Duplicate or unqualified questionnaires were excluded from the study. The contents of our questionnaires covered hospital and ICU capacity, performance of the infection control department, HAI surveillance, implementation of IPC measures, and antimicrobial stewardship (AMS). Qualified questionnaires were compared according to the volume of annual CHD surgeries performed in different ICUs. Group 1 was defined as volume more than 300 cases and group 2 was defined as volume less than or equal to 300 cases. RESULTS: Sixty-two of the 118 questionnaires were completed, with a response rate of 53%. The CHD surgical volume in 2022 of the 62 hospitals was 36342, accounting for 52% of the annual CHD surgical volume (69 672) across the country. The postoperative infection rates obtained from the 15 ICUs varied from 1.3 to 15%, with a median rate of 4.5%. A total of 16 ICUs provided data on drug-resistant bacteria, Klebsiella pneumoniae exhibiting the highest frequency. More than 95% of ICUs have established complete HAI management systems. Information-based HAI surveillance was conducted in 89% of ICUs. Approximately 67% of ICUs stopped prophylactic antibiotics within 48 hours after surgery. In complex cases, carbapenems were administered empirically in 89% of ICUs. Group 1 had an advantage over group 2 in preventing multi-drug-resistant organisms (all instruments should be used alone 100% vs. 86%, P =0.047; cleaning and disinfection of environmental surfaces, 100% vs. 81%, P =0.035; antibiotic consumption control 85% vs. 61%, P =0.044) and in preventing surgical site infections (perioperative blood glucose monitoring, 88% vs. 67%, P =0.048). However, Group 1 did not perform well in preventing catheter-related bloodstream infection (delayed catheter removal due to convenience of laboratory tests, 31% vs. 6%, P =0.021) and catheter-associated urinary tract infection (delayed catheter removal due to muscle relaxant administration, 88% vs. 58%, P =0.022). CONCLUSIONS: A relatively complete HAI management system has been established throughout the country in ICUs for CHD patients. Information-based surveillance of HAI needs to be promoted, and actions should be taken to facilitate the implementation of IPC measures and AMS bundles. Training and feedback are critical for implementing IPC measures.

Research hotspots and trends of complementary and alternative therapy for neuropathic pain: A bibliometric analysis.

BACKGROUND: Neuropathic pain (NP) is a common type of pain in clinic. Due to the limited effect of drug treatment, many patients with NP are still troubled by this disease. In recent years, complementary and alternative therapy (CAT) has shown good efficacy in the treatment of NP. As the interest in CAT for NP continues to grow, we conducted a bibliometric study of publications on CAT treatment for NP. The aim of this study is to analyze the development overview, research hotspots and future trends in the field of CAT and NP through bibliometric methodology, so as to provide a reference for subsequent researchers. METHODS: Publications on CAT in the treatment of NP from 2002 to 2022 were retrieved from the Web of Science Core Collection. Relevant countries, institutions, authors, journals, keywords, and references were analyzed bibliometrically using Microsoft Excel 2021, bibliometric platform, VOSviewer, and CiteSpace. RESULTS: A total of 898 articles from 46 countries were published in 324 journals, and they were contributed by 4455 authors from 1102 institutions. The most influential country and institution are China (n = 445) and Kyung Hee University (n = 63), respectively. Fang JQ (n = 27) and Evidence-Based Complementary and Alternative Medicine (n = 63) are the author and journal with the most publications in this field. The clinical efficacy, molecular biological mechanisms and safety of CAT for NP are currently hot directions. Low back pain, postherpetic neuralgia, acupuncture, and herbal are the hot topics in CAT and NP in recent years. CONCLUSION: This study reveals the current status and hotspots of CAT for NP. The study also indicates that the effectiveness and effect mechanism of acupuncture or herbs for treating emotional problems caused by low back pain or postherpetic neuralgia may be a trend for future research.

Ncf1 knockout in smooth muscle cells exacerbates angiotensin II-induced aortic aneurysm and dissection by activating the STING pathway.

AIMS: Aortic aneurysm and dissection (AAD) is caused by the progressive loss of aortic smooth muscle cells (SMCs) and is associated with a high mortality rate. Identifying the mechanisms underlying SMC apoptosis is crucial for preventing AAD. Neutrophil cytoplasmic factor 1 (Ncf1) is essential in reactive oxygen species production and SMC apoptosis; Ncf1 absence leads to autoimmune diseases and chronic inflammation. Here, the role of Ncf1 in angiotensin II (Ang II)-induced AAD was investigated. METHODS AND RESULTS: Ncf1 expression increased in injured SMCs. Bioinformatic analysis identified Ncf1 as a mediator of AAD-associated SMC damage. Ncf1 expression is positively correlated with DNA replication and repair in SMCs of AAD aortas. AAD incidence increased in Ang II-challenged Sm22CreNcf1fl mice. Transcriptomics showed that Ncf1 knockout activated the stimulator of interferon genes (STING) and cell death pathways. The effects of Ncf1 on SMC death and the STING pathway in vitro were examined. Ncf1 regulated the hydrogen peroxide-mediated activation of the STING pathway and inhibited SMC apoptosis. Mechanistically, Ncf1 knockout promoted the ubiquitination of nuclear factor erythroid 2-related factor 2 (NRF2), thereby inhibiting the negative regulatory effect of NRF2 on the stability of STING mRNA and ultimately promoting STING expression. Additionally, the pharmacological inhibition of STING activation prevented AAD progression. CONCLUSION: Ncf1 deficiency in SMCs exacerbated Ang II-induced AAD by promoting NRF2 ubiquitination and degradation and activating the STING pathway. These data suggest that Ncf1 may be a potential therapeutic target for AAD treatment.

Grazing exclusion alters soil methane flux and methanotrophic and methanogenic communities in alpine meadows on the Qinghai-Tibet Plateau.

Grazing exclusion (GE) is an effective measure for restoring degraded grassland ecosystems. However, the effect of GE on methane (CH4) uptake and production remains unclear in dominant bacterial taxa, main metabolic pathways, and drivers of these pathways. This study aimed to determine CH4 flux in alpine meadow soil using the chamber method. The in situ composition of soil aerobic CH4-oxidizing bacteria (MOB) and CH4-producing archaea (MPA) as well as the relative abundance of their functional genes were analyzed in grazed and nongrazed (6 years) alpine meadows using metagenomic methods. The results revealed that CH4 fluxes in grazed and nongrazed plots were -34.10 and -22.82 µg‧m-2‧h-1, respectively. Overall, 23 and 10 species of Types I and II MOB were identified, respectively. Type II MOB comprised the dominant bacteria involved in CH4 uptake, with Methylocystis constituting the dominant taxa. With regard to MPA, 12 species were identified in grazed meadows and 3 in nongrazed meadows, with Methanobrevibacter constituting the dominant taxa. GE decreased the diversity of MPA but increased the relative abundance of dominated species Methanobrevibacter millerae from 1.47 to 4.69%. The proportions of type I MOB, type II MOB, and MPA that were considerably affected by vegetation and soil factors were 68.42, 21.05, and 10.53%, respectively. Furthermore, the structural equation models revealed that soil factors (available phosphorus, bulk density, and moisture) significantly affected CH4 flux more than vegetation factors (grass species number, grass aboveground biomass, grass root biomass, and litter biomass). CH4 flux was mainly regulated by serine and acetate pathways. The serine pathway was driven by soil factors (0.84, p < 0.001), whereas the acetate pathway was mainly driven by vegetation (-0.39, p < 0.05) and soil factors (0.25, p < 0.05). In conclusion, our findings revealed that alpine meadow soil is a CH4 sink. However, GE reduces the CH4 sink potential by altering vegetation structure and soil properties, especially soil physical properties.