Genetically determined blood pressure, antihypertensive drug classes, and frailty: A Mendelian randomization study.

Observational studies have suggested that the use of antihypertensive drugs was associated with the risk of frailty; however, these findings may be biased by confounding and reverse causality. This study aimed to explore the effect of genetically predicted lifelong lowering blood pressure (BP) through different antihypertensive medications on frailty. One-sample Mendelian randomization (MR) and summary data-based MR (SMR) were applied. We utilized two kinds of genetic instruments to proxy the antihypertensive medications, including genetic variants within or nearby drugs target genes associated with systolic/diastolic BP, and expression level of the corresponding gene. Among 298,618 UK Biobank participants, one-sample MR analysis observed that genetically proxied BB use (relative risk ratios, 0.76; 95% CI, 0.65-0.90; p = 0.001) and CCB use (0.83; 0.72-0.95; p = 0.007), equivalent to a 10-mm Hg reduction in systolic BP, was significantly associated with lower risk of pre-frailty. In addition, although not statistically significant, the effect directions of systolic BP through ACEi variants (0.72; 0.39-1.33; p = 0.296) or thiazides variants (0.74; 0.53-1.03; p = 0.072) on pre-frailty were also protective. Similar results were obtained in analyses for diastolic BP. SMR of expression in artery showed that decreased expression level of KCNH2, a target gene of BBs, was associated with lower frailty index (beta -0.02, p = 2.87 × 10-4). This MR analysis found evidence that the use of BBs and CCBs was potentially associated with reduced frailty risk in the general population, and identified KCNH2 as a promising target for further clinical trials to prevent manifestations of frailty.

A Study on the Preparation of a Vulcanizing Mixture and Its Application in Natural Rubber Latex.

The traditional preparation process of natural rubber latex requires tedious treatment of a variety of rubber additives. In this paper, a new process of wet mixed grinding was used to prepare a reinforced vulcanization mixture and a rapid vulcanization effect. The effect of different amounts of vulcanization mixtures on the mechanical properties of natural latex film was studied, and the pre-vulcanization process of latex and the vulcanization process of film were optimized. The results showed that with the increase in the amount of vulcanization mixture, the tensile strength increased from 5.96 MPa to 29.28 MPa, and the tear strength increased from 7.59 kN/m to 52.81 kN/m. When the vulcanization temperature of the latex film is heated from 80 °C to 100 °C, the vulcanization time is shortened by 5~6 times. The new vulcanization mixture prepared in this work has the characteristics of simple production and fast vulcanization speed, which provides a new solution for the development of the latex product industry.

APEX-pHLA: A novel method for accurate prediction of the binding between exogenous short peptides and HLA class I molecules.

Human leukocyte antigen (HLA) molecules play critically significant role within the realm of immunotherapy due to their capacities to recognize and bind exogenous antigens such as peptides, subsequently delivering them to immune cells. Predicting the binding between peptides and HLA molecules (pHLA) can expedite the screening of immunogenic peptides and facilitate vaccine design. However, traditional experimental methods are time-consuming and inefficient. In this study, an efficient method based on deep learning was developed for predicting peptide-HLA binding, which treated peptide sequences as linguistic entities. It combined the architectures of textCNN and BiLSTM to create a deep neural network model called APEX-pHLA. This model operated without limitations related to HLA class I allele variants and peptide segment lengths, enabling efficient encoding of sequence features for both HLA and peptide segments. On the independent test set, the model achieved Accuracy, ROC_AUC, F1, and MCC is 0.9449, 0.9850, 0.9453, and 0.8899, respectively. Similarly, on an external test set, the results were 0.9803, 0.9574, 0.8835, and 0.7863, respectively. These findings outperformed fifteen methods previously reported in the literature. The accurate prediction capability of the APEX-pHLA model in peptide-HLA binding might provide valuable insights for future HLA vaccine design.

Early matrix softening contributes to vascular smooth muscle cell phenotype switching and aortic dissection through down-regulation of microRNA-143/145.

Thoracic aortic dissection (TAD) is characterized by extracellular matrix (ECM) dysregulation. Aberrations in the ECM stiffness can lead to changes in cellular functions. However, the mechanism by which ECM softening regulates vascular smooth muscle cell (VSMCs) phenotype switching remains unclear. To understand this mechanism, we cultured VSMCs in a soft extracellular matrix and discovered that the expression of microRNA (miR)-143/145, mediated by activation of the AKT signalling pathway, decreased significantly. Furthermore, overexpression of miR-143/145 reduced BAPN-induced aortic softening, switching the VSMC synthetic phenotype and the incidence of TAD in mice. Additionally, high-throughput sequencing of immunoprecipitated RNA indicated that the TEA domain transcription factor 1 (TEAD1) is a common target gene of miR-143/145, which was subsequently verified using a luciferase reporter assay. TEAD1 is upregulated in soft ECM hydrogels in vitro, whereas the switch to a synthetic phenotype in VSMCs decreases after TEAD1 knockdown. Finally, we verified that miR-143/145 levels are associated with disease severity and prognosis in patients with thoracic aortic dissection. ECM softening, as a result of promoting the VSMCs switch to a synthetic phenotype by downregulating miR-143/145, is an early trigger of TAD and provides a therapeutic target for this fatal disease. miR-143/145 plays a role in the early detection of aortic dissection and its severity and prognosis, which can offer information for future risk stratification of patients with dissection.

Application of nursing intervention based on Snyder's hope theory in individuals with spinal cord injury.

OBJECTIVE: To study the effect of nursing intervention derived from Snyder's hope theory in individuals with spinal cord injury. METHODS: We retrospectively analyzed clinical data of 80 patients with spinal cord injury who were admitted to General Hospital of Pingxiang Mining Group Co., from August 2021 to October 2023. According to different nursing methods, they were assigned into a control group (n = 40, routine curative care) and an observation group (n = 40, routine curative care plus nursing intervention derived from Snyder's hope theory). The two groups were compared in terms of emotional state, level of hope, living standard, occurrence of complications, and nursing satisfaction. According to the occurrence of complications after nursing, the patients were divided into a good prognosis group and a poor prognosis group, and the influencing factors for prognosis were analyzed by univariate analysis and logistic multivariate analysis. RESULTS: After nursing, the anxiety and depression scores decreased in both groups when compared to their pre-nursing scores, with lower scores in the observation group than in the controls (P<0.05). Also, the observation group exhibited significantly higher score of hope, higher score of quality of life, and lower occurrence of complications when compared to the control group (P<0.05). The nursing satisfaction rate in the observation group was 95.00% (38/40), which was noticeably greater than 65.00% (26/40) in the control group (P<0.05). Multivariate analysis showed that nursing methods (P = 0.007, OR = 7.828, 95% CI: 1.766-34.688) and HB after intervention (P = 0.029, OR = 0.965, 95% CI: 0.935-0.996) were the influencing factors of complications after nursing intervention in patients with SCI. CONCLUSION: The implementation of nursing intervention derived from Snyder's hope theory can decrease the anxiety and depression levels, lower the occurrence of complications, enhance the hope level, increase the satisfaction rate, and improve the overall quality of life in patients with spinal cord injury.

Factors associated with clinical nurse's mental health: a qualitative study applying the social ecological model.

BACKGROUND: The prevalence of burnout, depression, and anxiety among Chinese nurses was 34%, 55.5%, and 41.8% respectively. Mental health problems have significant impacts on their personal well-being, work performance, patient care quality, and the overall healthcare system. Mental health is influenced by factors at multiple levels and their interactions. METHODS: This was a descriptive qualitative study using phenomenological approach. We recruited a total of 48 nurses from a tertiary hospital in Changsha, Hunan Province, China. Data were collected through focus group interviews. Audio-recorded data were transcribed and inductively analysed. RESULTS: Four major themes with 13 subthemes were identified according to the social ecological model: (1) individual-level factors, including personality traits, sleep quality, workplace adaptability, and years of work experience; (2) interpersonal-level factors, encompassing interpersonal support and role conflict; (3) organization-level factors, such as organizational climate, organizational support, career plateau, and job control; and (4) social-level factors, which included compensation packages, social status, and legislative provision and policy. CONCLUSIONS: Our study provides a nuanced understanding of the multifaceted factors influencing nurses' mental health. Recognizing the interconnectedness of individual, interpersonal, organizational, and social elements is essential for developing targeted interventions and comprehensive strategies to promote and safeguard the mental well-being of nurses in clinical settings. TRIAL AND PROTOCOL REGISTRATION: The larger study was registered with Chinese Clinical Trial Registry: ChiCTR2300072142 (05/06/2023) https://www.chictr.org.cn/showproj.html?proj=192676 . REPORTING METHOD: This study is reported according to the Consolidated Criteria for Reporting Qualitative Research (COREQ).

Extravascular administration of IGF1R antagonists protects against aortic aneurysm in rodent and porcine models.

An abdominal aortic aneurysm (AAA) is a life-threatening cardiovascular disease. We identified plasma insulin-like growth factor 1 (IGF1) as an independent risk factor in patients with AAA by correlating plasma IGF1 with risk. Smooth muscle cell- or fibroblast-specific knockout of Igf1r, the gene encoding the IGF1 receptor (IGF1R), attenuated AAA formation in two mouse models of AAA induced by angiotensin II infusion or CaCl2 treatment. IGF1R was activated in aortic aneurysm samples from human patients and mice with AAA. Systemic administration of IGF1C, a peptide fragment of IGF1, 2 weeks after disease development inhibited AAA progression in mice. Decreased AAA formation was linked to competitive inhibition of IGF1 binding to its receptor by IGF1C and modulation of downstream alpha serine/threonine protein kinase (AKT)/mammalian target of rapamycin signaling. Localized application of an IGF1C-loaded hydrogel was developed to reduce the side effects observed after systemic administration of IGF1C or IGF1R antagonists in the CaCl2-induced AAA mouse model. The inhibitory effect of the IGF1C-loaded hydrogel administered at disease onset on AAA formation was further evaluated in a guinea pig-to-rat xenograft model and in a sheep-to-minipig xenograft model of AAA formation. The therapeutic efficacy of IGF1C for treating AAA was tested through extravascular delivery in the sheep-to-minipig model with AAA established for 2 weeks. Percutaneous injection of the IGF1C-loaded hydrogel around the AAA resulted in improved vessel flow dynamics in the minipig aorta. These findings suggest that extravascular administration of IGF1R antagonists may have translational potential for treating AAA.

Efficacy and Safety of Neoadjuvant Subcutaneous Envafolimab in dMMR/MSI-H Locally Advanced Colon Cancer.

BACKGROUND: Neoadjuvant immunotherapy with programmed death-ligand 1 blockade for colon cancer, especially for mismatch repair-deficient (dMMR)/high microsatellite instability (MSI-H) colon cancer, has gained considerable attention recently. OBJECTIVE: This study aimed to assess the safety and efficacy of neoadjuvant subcutaneous envafolimab in patients with dMMR/MSI-H locally advanced colon cancer. METHODS: Patients with dMMR/MSI-H locally advanced colon cancer treated with envafolimab at Sun Yat-sen University Cancer Center and Yunnan Cancer Hospital from October 2021 to July 2023 were retrospectively reviewed and analyzed. The primary endpoint was the pathological complete response (CR) rate, and secondary endpoints were treatment-related adverse events and complete clinical response rate. RESULTS: Overall, 15 patients were analyzed. After neoadjuvant immunotherapy with envafolimab, six patients achieved a CR, with five partial responses, and four stable disease. Three patients achieving a complete clinical response chose to accept a "watch and wait" strategy, and surgery was performed in 12 patients. Postoperative pathology results revealed seven patients achieved pathological CRs, and five patients achieved tumor regression grade 2, with 66.7% of the total CR rate. The most common treatment-related adverse events were pruritus and rash (40%), with no severe cases. No recurrences occurred over a 7.9-month follow-up. CONCLUSIONS: Envafolimab yielded promising surgical outcomes and safety in dMMR/MSI-H locally advanced colon cancer, representing a promising treatment modality for this population.

Site-selective fatty acid chain conjugation of the N-terminus of the recombinant human granulocyte colony-stimulating factor.

The clinical application of the recombinant human granulocyte colony-stimulating factor (rhG-CSF) is restricted by its short serum half-life. Herein, site-selective modification of the N-terminus of rhG-CSF with PAL-PEG3-Ph-CHO was used to develop a long-acting rhG-CSF. The optimized conditions for rhG-CSF modification with PAL-PEG3-Ph-CHO were: reaction solvent system of 3% (w/v) Tween 20 and 30 mM NaCNBH3 in acetate buffer (20 mmol/L, pH 5.0), molar ratio of PAL-PEG3-Ph-CHO to rhG-CSF of 6:1, temperature of 20°C, and reaction time of 12 h, consequently, achieving a PAL-PEG3-Ph-rhG-CSF product yield of 70.8%. The reaction mixture was purified via preparative liquid chromatography, yielding the single-modified product PAL-PEG3-Ph-rhG-CSF with a HPLC purity exceeding 95%. The molecular weight of PAL-PEG3-Ph-rhG-CSF was 19297 Da by MALDI-TOF-MS, which was consistent with the theoretical value. The circular dichroism analysis revealed no significant change in its secondary structure compared to unmodified rhG-CSF. The PAL-PEG3-Ph-rhG-CSF retained 82.0% of the in vitro biological activity of unmodified rhG-CSF. The pharmacokinetic analyses showed that the serum half-life of PAL-PEG3-Ph-rhG-CSF was 7.404 ± 0.777 h in mice, 4.08 times longer than unmodified rhG-CSF. Additionally, a single subcutaneous dose of PAL-PEG3-Ph-rhG-CSF presented comparable in vivo efficacy to multiple doses of rhG-CSF. This study demonstrated an efficacious strategy for developing long-acting rhG-CSF drug candidates.

Association between ACE1 and missed abortion: ACE1 promotes H2O2-induced trophoblast cell injury in vitro†.

The aim of this study was to evaluate the role of angiotensin-converting enzyme 1 (ACE1) in H2O2-induced trophoblast cell injury and the potential molecular mechanisms. Oxidative stress was modeled by exposing HTR-8/SVneo cells to 200 µM H2O2. Western blot and real-time quantitative PCR methods were used to detect protein and mRNA expression level of ACE1 in chorionic villus tissue and trophoblast HTR-8/SVneo cell. Inhibition of ACE1 expression was achieved by transfection with small interfering RNA. Then flow cytometry, Cell Counting Kit-8, and Transwell assay was used to assess apoptosis, viability, and migration ability of the cells. Reactive oxygen species (ROS) were detected by fluorescent probes, and malondialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH) activities were determined by corresponding detection kits. Angiotensin-converting enzyme 1 expression was upregulated in chorionic villus tissue of patients with missed abortion (MA) compared with individuals with normal early pregnancy abortion. H2O2 induced elevated ACE1 expression in HTR-8/SVneo cells, promoted apoptosis, and inhibited cell viability and migration. Knockdown of ACE1 expression inhibited H2O2-induced effects to enhance cell viability and migration and suppress apoptosis. Additionally, H2O2 stimulation caused increased levels of ROS and MDA and decreased SOD and GSH activity in the cells, whereas knockdown of ACE1 expression led to opposite changes of these oxidative stress indicators. Moreover, knockdown of ACE1 attenuated the inhibitory effect of H2O2 on the Nrf2/HO-1 pathway. Angiotensin-converting enzyme 1 was associated with MA, and it promoted H2O2-induced injury of trophoblast cells through inhibiting the Nrf2 pathway. Therefore, ACE1 may serve as a potential therapeutic target for MA.

Risk factors and consequences of mental health problems in nurses: A scoping review of cohort studies.

Mental health problems in nurses are prevalent and impairing. To date, no literature has comprehensively synthesised cohort evidence on mental health among nurses. This scoping review aimed to synthesise the existing literature on the risk factors and consequences of mental health problems in nurses. A systematic search was conducted on PubMed, EMBASE, Epistemonikos database, Web of Science, CINAHL, and PsycINFO from inception to March 2023. We identified 171 cohort studies from 16 countries, mostly (95.3%) from high-income economies. This review indicated that nurses worldwide encountered significant mental health challenges, including depression, cognitive impairment, anxiety, trauma/post-traumatic stress disorder, burnout, sleep disorder, and other negative mental health problems. These problems were closely related to various modifiable risk factors such as nurses' behaviours and lifestyles, social support, workplace bullying and violence, shift work, job demands, and job resources. Moreover, nurses' mental health problems have negative effects on their physical health, behaviour and lifestyle, occupation and organisation, and intrapersonal factors. These findings provided an enhanced understanding of mental health complexities among nurses, and shed light on policy enactment to alleviate the negative impact of mental health problems on nurses. Addressing mental health among nurses should be a top priority.

Rapid and multi-target genotyping of Helicobacter pylori with digital microfluidics.

Helicobacter pylori (H. pylori) infection correlates closely with gastric diseases such as gastritis, ulcers, and cancer, influencing more than half of the world's population. Establishing a rapid, precise, and automated platform for H. pylori diagnosis is an urgent clinical need and would significantly benefit therapeutic intervention. Recombinase polymerase amplification (RPA)-CRISPR recently emerged as a promising molecular diagnostic assay due to its rapid detection capability, high specificity, and mild reaction conditions. In this work, we adapted the RPA-CRISPR assay on a digital microfluidics (DMF) system for automated H. pylori detection and genotyping. The system can achieve multi-target parallel detection of H. pylori nucleotide conservative genes (ureB) and virulence genes (cagA and vacA) across different samples within 30 min, exhibiting a detection limit of 10 copies/rxn and no false positives. We further conducted tests on 80 clinical saliva samples and compared the results with those derived from real-time quantitative polymerase chain reaction, demonstrating 100% diagnostic sensitivity and specificity for the RPA-CRISPR/DMF method. By automating the assay process on a single chip, the DMF system can significantly reduce the usage of reagents and samples, minimize the cross-contamination effect, and shorten the reaction time, with the additional benefit of losing the chance of experiment failure/inconsistency due to manual operations. The DMF system together with the RPA-CRISPR assay can be used for early detection and genotyping of H. pylori with high sensitivity and specificity, and has the potential to become a universal molecular diagnostic platform.

Understanding mercury accumulation in mosses of two subalpine forests in China.

The role of forest ecosystems in the global mercury (Hg) biogeochemical cycle is widely recognized; however, using litterfall as a surrogate to assess the Hg sink function of forests encounters limitations. We investigated the accumulation characteristics and influencing factors of Hg in mosses from two remote subalpine forests in southwestern China. The results indicated that there was high Hg accumulation in subalpine forest mosses, with average concentrations of 82 ± 49 ng g-1 for total mercury (THg) and 1.3 ± 0.8 ng g-1 for methylmercury (MeHg). We demonstrated that the accumulation capacity of Hg in mosses was significantly dependent on species and substrates (micro-habitats), the mosses on tree trunks exhibited significantly elevated Hg accumulation levels (THg 132 ± 56 ng g-1, MeHg 1.6 ± 0.2 ng g-1) compared to mosses in other substrates. The surface morphologies and biochemical components of leaf (phyllidia), such as cation exchange capacity (CEC), pectin, uronic acid, and metallothionein, play a crucial role in the accumulation of Hg by mosses. These findings provide valuable insights into Hg accumulation in forest mosses. Suggesting that the contribution of mosses Hg accumulation should be considered when assessing atmospheric Hg sinks of forests.

Quantitative analysis of the illegal addition of Atenolol in Panax notoginseng based on NIR-MIR spectral data fusion and calibration transfer.

To address the issue of the common illegal addition of Atenolol in Panax notoginseng, we propose an approach that realizes multivariate calibration transfer between different particle sizes based on near-infrared (NIR) and mid-infrared (MIR) spectral data fusion. To achieve high prediction accuracy, we construct three data fusion schemes (full-spectrum fusion, feature-level fusion, and decision-level fusion) that combine NIR and MIR spectral data. Among three data fusion schemes, the feature-level fusion based on the UVE-SPA-PLS model for 120-mesh spectral data achieves optimal prediction accuracy. Here, a Piecewise Direct Standardization (PDS) algorithm has been applied to calibration transfer from 100-mesh and 80-mesh to 120-mesh to reduce the influence of particle size and improve the robustness of the model. The correlation coefficient (R2) of 100-mesh, and 80-mesh prediction sets can reach 0.9861 and 0.9823, respectively. The corresponding root mean square error (RMSE) are 0.1545 and 0.2045, respectively. This research provides a method for illegal additions in precious herbs and reduces the effect of particle size on spectral modeling, enabling high-precision quantitative detection. In addition, it has important application prospects in reducing experimental losses of precious medicinal materials and ensuring the safe use of Chinese and Western medicines, which provides an alternative method for non-destructive testing.

Bleomycin induces senescence and repression of DNA repair via downregulation of Rad51.

BACKGROUND: Bleomycin, a potent antitumor agent, is limited in clinical use due to the potential for fatal pulmonary toxicity. The accelerated DNA damage and senescence in alveolar epithelial cells (AECs) is considered a key factor in the development of lung pathology. Understanding the mechanisms for bleomycin-induced lung injury is crucial for mitigating its adverse effects. METHODS: Human lung epithelial (A549) cells were exposed to bleomycin and subsequently assessed for cellular senescence, DNA damage, and double-strand break (DSB) repair. The impact of Rad51 overexpression on DSB repair and senescence in AECs was evaluated in vitro. Additionally, bleomycin was intratracheally administered in C57BL/6 mice to establish a pulmonary fibrosis model. RESULTS: Bleomycin exposure induced dose- and time-dependent accumulation of senescence hallmarks and DNA lesions in AECs. These effects are probably due to the inhibition of Rad51 expression, consequently suppressing homologous recombination (HR) repair. Mechanistic studies revealed that bleomycin-mediated transcriptional inhibition of Rad51 might primarily result from E2F1 depletion. Furthermore, the genetic supplement of Rad51 substantially mitigated bleomycin-mediated effects on DSB repair and senescence in AECs. Notably, decreased Rad51 expression was also observed in the bleomycin-induced mouse pulmonary fibrosis model. CONCLUSIONS: Our works suggest that the inhibition of Rad51 plays a pivotal role in bleomycin-induced AECs senescence and lung injury, offering potential strategies to alleviate the pulmonary toxicity of bleomycin.

KLF15 maintains contractile phenotype of vascular smooth muscle cells and prevents thoracic aortic dissection by interacting with MRTFB.

Thoracic aortic dissection (TAD) is a highly dangerous cardiovascular disorder caused by weakening of the aortic wall, resulting in a sudden tear of the internal face. Progressive loss of the contractile apparatus in vascular smooth muscle cells (VSMCs) is a major event in TAD. Exploring the endogenous regulators essential for the contractile phenotype of VSMCs may aid the development of strategies to prevent TAD. Krüppel-like factor 15 (KLF15) overexpression was reported to inhibit TAD formation; however, the mechanisms by which KLF15 prevents TAD formation and whether KLF15 regulates the contractile phenotype of VSMCs in TAD are not well understood. Therefore, we investigated these unknown aspects of KLF15 function. We found that KLF15 expression was reduced in human TAD samples and ß-aminopropionitrile monofumarate-induced TAD mouse model. Klf15KO mice are susceptible to both ß-aminopropionitrile monofumarate- and angiotensin II-induced TAD. KLF15 deficiency results in reduced VSMC contractility and exacerbated vascular inflammation and extracellular matrix degradation. Mechanistically, KLF15 interacts with myocardin-related transcription factor B (MRTFB), a potent serum response factor coactivator that drives contractile gene expression. KLF15 silencing represses the MRTFB-induced activation of contractile genes in VSMCs. Thus, KLF15 cooperates with MRTFB to promote the expression of contractile genes in VSMCs, and its dysfunction may exacerbate TAD. These findings indicate that KLF15 may be a novel therapeutic target for the treatment of TAD.

Identification of Circulating Inflammatory Proteins Associated with Calcific Aortic Valve Stenosis by Multiplex Analysis.

Calcific aortic valve stenosis (CAVS) is characterized by increasing inflammation and progressive calcification in the aortic valve leaflets and is a major cause of death in the aging population. This study aimed to identify the inflammatory proteins involved in CAVS and provide potential therapeutic targets. We investigated the observational and causal associations of 92 inflammatory proteins, which were measured using affinity-based proteomic assays. Firstly, the case-control cohort identified differential proteins associated with the occurrence and progression of CAVS. Subsequently, we delved into exploring the causal impacts of these associated proteins through Mendelian randomization. This involved utilizing genetic instruments derived from cis-protein quantitative loci identified in genome-wide association studies, encompassing a cohort of over 400,000 individuals. Finally, we investigated the gene transcription and protein expression levels of inflammatory proteins by single-cell and immunohistochemistry analysis. Multivariate logistic regression and spearman's correlation analysis showed that five proteins showed a significant positive correlation with disease severity. Mendelian randomization showed that elevated levels of two proteins, namely, matrix metallopeptidase-1 (MMP1) and sirtuin 2 (SIRT2), were associated with an increased risk of CAVS. Immunohistochemistry and single-cell transcriptomes showed that expression levels of MMP1 and SIRT2 at the tissue and cell levels were significantly higher in calcified valves than in non-calcified control valves. These findings indicate that MMP1 and SIRT2 are causally related to CAVS and open up the possibility for identifying novel therapeutic targets.

Deep learning or radiomics based on CT for predicting the response of gastric cancer to neoadjuvant chemotherapy: a meta-analysis and systematic review.

Background: Artificial intelligence (AI) models, clinical models (CM), and the integrated model (IM) are utilized to evaluate the response to neoadjuvant chemotherapy (NACT) in patients diagnosed with gastric cancer. Objective: The objective is to identify the diagnostic test of the AI model and to compare the accuracy of AI, CM, and IM through a comprehensive summary of head-to-head comparative studies. Methods: PubMed, Web of Science, Cochrane Library, and Embase were systematically searched until September 5, 2023, to compile English language studies without regional restrictions. The quality of the included studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) criteria. Forest plots were utilized to illustrate the findings of diagnostic accuracy, while Hierarchical Summary Receiver Operating Characteristic curves were generated to estimate sensitivity (SEN) and specificity (SPE). Meta-regression was applied to analyze heterogeneity across the studies. To assess the presence of publication bias, Deeks' funnel plot and an asymmetry test were employed. Results: A total of 9 studies, comprising 3313 patients, were included for the AI model, with 7 head-to-head comparative studies involving 2699 patients. Across the 9 studies, the pooled SEN for the AI model was 0.75 (95% confidence interval (CI): 0.66, 0.82), and SPE was 0.77 (95% CI: 0.69, 0.84). Meta-regression was conducted, revealing that the cut-off value, approach to predicting response, and gold standard might be sources of heterogeneity. In the head-to-head comparative studies, the pooled SEN for AI was 0.77 (95% CI: 0.69, 0.84) with SPE at 0.79 (95% CI: 0.70, 0.85). For CM, the pooled SEN was 0.67 (95% CI: 0.57, 0.77) with SPE at 0.59 (95% CI: 0.54, 0.64), while for IM, the pooled SEN was 0.83 (95% CI: 0.79, 0.86) with SPE at 0.69 (95% CI: 0.56, 0.79). Notably, there was no statistical difference, except that IM exhibited higher SEN than AI, while maintaining a similar level of SPE in pairwise comparisons. In the Receiver Operating Characteristic analysis subgroup, the CT-based Deep Learning (DL) subgroup, and the National Comprehensive Cancer Network (NCCN) guideline subgroup, the AI model exhibited higher SEN but lower SPE compared to the IM. Conversely, in the training cohort subgroup and the internal validation cohort subgroup, the AI model demonstrated lower SEN but higher SPE than the IM. The subgroup analysis underscored that factors such as the number of cohorts, cohort type, cut-off value, approach to predicting response, and choice of gold standard could impact the reliability and robustness of the results. Conclusion: AI has demonstrated its viability as a tool for predicting the response of GC patients to NACT Furthermore, CT-based DL model in AI was sensitive to extract tumor features and predict the response. The results of subgroup analysis also supported the above conclusions. Large-scale rigorously designed diagnostic accuracy studies and head-to-head comparative studies are anticipated. Systematic review registration: PROSPERO, CRD42022377030.

S100A8/A9 as a prognostic biomarker with causal effects for post-acute myocardial infarction heart failure.

Heart failure is the prevalent complication of acute myocardial infarction. We aim to identify a biomarker for heart failure post-acute myocardial infarction. This observational study includes 1062 and 1043 patients with acute myocardial infarction in the discovery and validation cohorts, respectively. The outcomes are in-hospital and long-term heart failure events. S100A8/A9 is screened out through proteomic analysis, and elevated circulating S100A8/A9 is independently associated with heart failure in discovery and validation cohorts. Furthermore, the predictive value of S100A8/A9 is superior to the traditional biomarkers, and the addition of S100A8/A9 improves the risk estimation using traditional risk factors. We finally report causal effect of S100A8/A9 on heart failure in three independent cohorts using Mendelian randomization approach. Here, we show that S100A8/A9 is a predictor and potentially causal medicator for heart failure post-acute myocardial infarction.

Chromosome-scale genome assemblies of Himalopsyche anomala and Eubasilissa splendida (Insecta: Trichoptera).

Trichoptera is one of the most evolutionarily successful aquatic insect lineages and is highly valued value in adaptive evolution research. This study presents the chromosome-level genome assemblies of Himalopsyche anomala and Eubasilissa splendida achieved using PacBio, Illumina, and Hi-C sequencing. For H. anomala and E. splendida, assembly sizes were 663.43 and 859.28 Mb, with scaffold N50 lengths of 28.44 and 31.17 Mb, respectively. In H. anomala and E. splendida, we anchored 24 and 29 pseudochromosomes, and identified 11,469 and 10,554 protein-coding genes, respectively. The high-quality genomes of H. anomala and E. splendida provide critical genomic resources for understanding the evolution and ecology of Trichoptera and performing comparative genomics analyses.