Bionic e-skin with precise multi-directional droplet sliding sensing for enhanced robotic perception.

Electronic skins with deep and comprehensive liquid information detection are desired to endow intelligent robotic devices with augmented perception and autonomous regulation in common droplet environments. At present, one technical limitation of electronic skins is the inability to perceive the liquid sliding information as realistically as humans and give feedback in time. To this critical challenge, in this work, a self-powered bionic droplet electronic skin is proposed by constructing an ingenious co-layer interlaced electrode network and using an overpass connection method. The bionic skin is used for droplet environment reconnaissance and converts various dynamic droplet sliding behaviors into electrical signals based on triboelectricity. More importantly, the two-dimensional sliding behavior of liquid droplets is comprehensively perceived by the e-skin and visually fed back in real-time on an indicator. Furthermore, the flow direction warning and intelligent closed-loop control of water leakage are also achieved by this e-skin, achieving the effect of human neuromodulation. This strategy compensates for the limitations of e-skin sensing droplets and greatly narrows the gap between artificial e-skins and human skins in perceiving functions.

Comparative efficacy of totally thoracoscopic, mini-thoracotomy, and mini-sternotomy approaches in aortic valve replacement.

Aortic valve replacement (AVR) is a critical procedure for patients with aortic valve diseases. This study compares the effectiveness of three minimally-invasive surgical approaches for AVR: totally thoracoscopic (TT), right anterior mini-thoracotomy, and upper mini-sternotomy. We analyzed retrospective data from 130 patients who underwent one of these surgeries, focusing on various factors such as duration of hospital stay, operation time, times for cardiopulmonary bypass and aortic cross-clamping, postoperative complications, levels of cardiac biomarkers, pain intensity using the Visual Analog Scale, and mid-term survival rates. Results show that while the TT method had the longest operation times, it also had the shortest hospital stays and faster pain reduction post-surgery. Although the TT group initially showed higher cardiac biomarker levels after surgery, these levels normalized by the third day, similar to the other groups. There were no significant differences in mid-term survival and major adverse cardiac and cerebrovascular event (MACCE) rates among the groups. These findings suggest that the TT method, despite longer surgical times, offers a quicker initial recovery, making it a viable option for AVR.

Risk factors for COVID-19 and their association with mortality in Ecuadorian patients admitted to the ICU: A retrospective cohort multicentric study.

Several risk factors were associated with mortality in patients with coronavirus disease 2019 (COVID-19) infection in intensive care units (ICU). We assessed the effect of risk factors related to the characteristics and clinical history of the population, laboratory test results, drug management, and type of ventilation on the probability of survival/discharge from the ICU. A retrospective cohort multicentric study of adults with COVID-19 admitted to the ICU between March 2020 and December 2021. Data were collected from 6 hospitals in 5 cities in Ecuador. The primary outcome was ICU survival/discharge. Survival analysis was conducted using semi-parametric Cox proportional hazards models. Of those admitted to the ICU with COVID-19, (n = 991), mean age was 56.76 ±â€…13.14, and 65.9% were male. Regarding the primary outcome, 51.1% (n = 506) died and 48.9% (n = 485) survived. Of the group that died, their mean age was higher than the survivors (60.7 vs 52.60 years, respectively), and they had a higher prevalence of comorbidities such as arterial hypertension (37.2% vs 20.4%, respectively) and diabetes mellitus (26.9% vs 15.7%, respectively), with P < .001. In ventilatory management, 32.7% of patients used noninvasive ventilation and high-flow nasal cannula, and 67.3% required invasive ventilatory support. After adjusting for confounders, Cox regression analysis showed that patients were less likely to be discharged alive from the ICU if they met the following conditions: arterial hypertension (hazard ratio [HR] = 0.83 95% CI 0.723-0.964), diabetes mellitus (HR = 0.80 95% CI 0.696-0.938), older than 62 years (HR = 0.86 95% CI 0.790-0.956), obese (body mass index ≥ 30) (HR = 0.78 95% CI 0.697-0.887), 1 unit increase in SOFA score (HR = 0.94 95% CI 0.937-0.961), PaO2/FiO2 ratio <100 mm Hg (HR = 0.84 95% CI 0.786-0.914), and the use of invasive mechanical ventilation (HR = 0.68 95% CI 0.614-0.769). Risk factors associated with increased mortality were older age, obesity, arterial hypertension, and diabetes. Factors such as male gender, chronic obstructive pulmonary disease, acute kidney injury, and cancer reported in other investigations did not have the same effect on mortality in our study.

GAS6-AS1 drives bladder cancer progression by increasing MMP7 expression in a ceRNA- and RBP-dependent manner.

Numerous recent studies have underscored the indispensable roles of long non-coding RNAs (lncRNAs) in various diseases. However, their precise mechanisms in urinary bladder cancer (UBC) remain to be further elucidated. To delve into this inquiry, online databases were analyzed to identify differentially expressed lncRNAs in UBC, followed by the functional experiments in vivo and in vitro functional experiments. GAS6-AS1 exhibited high expression levels in UBC tissues and was shown to regulate the proliferation, migration, invasion, and cell cycle progression of UBC cells in vitro and in vivo. Then, a series of molecular biology experiments, including RNA pull-down, dual-luciferase reporter gene assays, RNA immunoprecipitation (RIP) assays, fluorescent in situ hybridization (FISH), and the triplex-capture assay demonstrated its interaction with miR-367-3p and PRC1. Mechanistically, GAS6-AS1 was found to enhance MMP7 expression by sequestering miR-367-3p. Moreover, GAS6-AS1 inhibited APC transcription by binding with PRC1, thereby activating several oncogenes downstream of the WNT pathway. To sum up, GAS6-AS1 promotes UBC progression through two distinct axes: the GAS6-AS1/miR-367-3p/MMP7 axis and the GAS6-AS1/PRC1/APC/Wnt/MMP7 axis, respectively. As a potential biomarker for UBC, GAS6-AS1 holds promising prospects for the diagnosis, treatment, and prognosis of UBC.

Association between stress hyperglycemia ratio and in-hospital outcomes: findings from the improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS) Project.

BACKGROUND: Stress hyperglycemia ratio (SHR) could provide accurate information on the acute status of hyperglycemia. The relationship between SHR and acute coronary syndrome (ACS) prognosis remains unclear. This study was conducted to identity the association between SHR and in-hospital outcomes in patients with ACS. METHODS: A total of 12,010 patients were eventually enrolled in the study. The relationship between SHR and in-hospital major adverse cardiovascular events (MACEs) was then modeled by restricted cubic spline (RCS) curves, and all patients were divided into three groups according to the results. The multivariate logistic regression analysis was used to determine the associations between the SHR and in-hospital outcomes, described as odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses were also performed on different diseases. RESULTS: The median age of this cohort was 63 (54, 71) years old, and 8942 (74.5%) were male. Group 1 was defined as SHR < 0.6 (n = 426), Group 2 was defined as SHR between 0.6 and 1 (n = 5821), and Group 3 was defined as SHR > 1 (n = 5763). Compared with Group 2, Group 1 (OR = 1.891, 95% CI: 1.028-3.479, P < 0.001) and Group 3 (OR = 1.868, 95% CI: 1.434-2.434, P < 0.001) had higher risks of suffering from in-hospital MACEs. SHR was associated with higher risks of in-hospital MACEs in the subgroups of DM [OR = 2.282, 95% CI: 1.477-3.524). CONCLUSIONS: Both low and high SHR levels were independently associated with in-hospital MACEs. Young males with DM, hypertension, and decreased renal function had much higher risks of suffering from SHR-correlated MACEs.

Immunotherapeutic hydrogel for co-delivery of STAT3 siRNA liposomes and lidocaine hydrochloride for postoperative comprehensive management of NSCLC in a single application.

Despite standard treatment for non-small cell lung cancer (NSCLC) being surgical resection, cancer recurrence and complications, such as induction of malignant pleural effusion (MPE) and significant postoperative pain, usually result in treatment failure. In this study, an alginate-based hybrid hydrogel (SOG) is developed that can be injected into the resection surface of the lungs during surgery. Briefly, endoplasmic reticulum-modified liposomes (MSLs) pre-loaded with the signal transducer and activator of transcription 3 (STAT3) small interfering RNA and lidocaine hydrochloride are encapsulated in SOG. Once applied, MSLs strongly downregulated STAT3 expression in the tumor microenvironment, resulting in the apoptosis of lung cancer cells and polarization of tumor-associated macrophages towards the M1-like phenotype. Meanwhile, the release of lidocaine hydrochloride (LID) was beneficial for pain relief and natural killer cell activation. Our data demonstrated MSL@LID@SOG not only efficiently inhibited tumor growth but also potently improved the quality of life, including reduced MPE volume and pain relief in orthotopic NSCLC mouse models, even with a single administration. MSL@LID@SOG shows potential for comprehensive clinical management upon tumor resection in NSCLC, and may alter the treatment paradigms for other cancers.

A new diagnostic technique for identifying Angiostrongylus spp. larvae in intermediate snail species by examining the buccal cavity.

BACKGROUND: Angiostrongyliasis is a zoonotic parasitic disease caused by the rat lungworm Angiostrongylus cantonensis. The intermediate hosts of A. cantonensis are gastropods, and snail species such as Pomacea canaliculata play a key role in the transmission of human angiostrongyliasis. Detecting A. cantonensis infection in snails is an important component of epidemiological surveillance and the control of angiostrongyliasis. METHODS: In this study, a new method for diagnosing A. cantonensis infection in gastropods was developed by recovering larvae from the buccal cavity of three snail species. The entire buccal cavity of a snail was extracted, and the tissue was pressed between two microscope slides to observe whether A. cantonensis larvae were present. Our new method was compared with traditional pathogenic detection methods of lung microscopy, tissue homogenization, and artificial digestion. We artificially infected 160 P. canaliculata, 160 Cipangopaludina chinensis, and 160 Bellamya aeruginosa snails with A. cantonensis. Then, the four different detection methods were used to diagnose infection in each snail species at 7, 14, 21, and 28 days post exposure. RESULTS: We found no significant difference in the percentages of infected P. canaliculata snails using the four methods to detect A. cantonensis larvae. The radula pressing method had a mean detection rate of 80%, while the lung microscopy (81.3%), tissue homogenization (83.8%), and artificial digestion (85%) methods had slightly greater detection rates. Similarly, the percentages of infected C. chinensis snails that were detected using the radula pressing (80%), tissue homogenization (82.1%), and artificial digestion (83.8%) methods were not significantly different. Finally, the percentages of infected B. aeruginosa snails that were detected using the radula pressing (81.3%), tissue homogenization (81.9%), and artificial digestion (81.4%) methods were not significantly different. These results showed that the radula pressing method had a similar detection rate to traditional lung microscopy, tissue homogenization, or artificial digestion methods. CONCLUSIONS: This study demonstrates a new method for the qualitative screening of gastropods that act as intermediate hosts of A. cantonensis (and other Angiostrongylus species), provides technical support for the control of human angiostrongyliasis, and furthers research on A. cantonensis.

Regulating interface interaction in alumina/graphene composites with nano alumina coating transition layers.

The structure and properties of graphene/alumina composites are affected by the interface interaction. To demonstrate the influence of interface interaction on the structure of composite materials, a composite without graphene/matrix alumina interface was designed and prepared. We introduced a nano transition layer into the composite by pre-fabricating nano alumina coating on the surface of graphene, thus regulating the influence of interface interaction on the structure of the composite. According to the analysis of laser micro Raman spectroscopy, the structure of graphene was not seriously damaged during the modification process, and graphene was subjected to tensile or compressive stress along the 2D plane. The fracture behavior of the modified graphene/alumina composites is similar to that of pure alumina, but significantly different from that of pure graphene/alumina composites. The elastic modulus and hardness of composite material G/A/A are higher, while its microstructure has better density and uniformity. In situ HRSEM observation showed that there was a transition layer of alumina in the modified graphene/alumina composite. The transition layer blocks or buffers the interfacial stress interaction, therefore, the composite material exhibits a fracture behavior similar to that of pure alumina at this time. This work demonstrates that interface interactions have a significant impact on the structure and fracture behavior of graphene/alumina composites.

Synthesis, Screening, and Evaluation of Theranostic Molecular CPCR4-Based Probe Targeting CXCR4.

Chemokines and chemokine receptors are indispensable to play a key role in the development of malignant tumors. As one of the most widely expressed chemokine receptors, chemokine (C-X-C motif) receptor 4 (CXCR4) has been a popular research focus. In most tumors, CXCR4 expression is significantly upregulated. Moreover, integrated nuclide diagnosis and therapy targeting CXCR4 show great potential. [68Ga]Ga-pentixafor, a radioligand targeting CXCR4, exhibits a strong affinity for CXCR4 both in vivo and in vitro. However, [177Lu]Lu-pentixather, the therapeutic companion of [68Ga]Ga-pentixafor, requires significant refinement to mitigate its pronounced hepatic biodistribution. The objective of this study was to synthesize theranostic molecular tracers with superior CXCR4 targeting functions. The Daudi cell line, which highly expressed CXCR4, and the MM.1S cell line, which weakly expressed CXCR4, were used in this study. Based on the pharmacophore cyclo (-d-Tyr-n-me-d-Orn-l-Arg-L-2-NAL-Gly-) (CPCR4) of pentixafor, six tracers were synthesized: [124I]I-1 ([124I]I-CPCR4), [99mTc]Tc-2 ([99mTc]Tc-HYNIC-CPCR4), [124I]I-3 ([124I]I-pentixafor), [18F]AlF-4 ([18F]AlF-NETA-CPCR4), [99mTc]Tc-5 ([99mTc]Tc-MAG3-CPCR4) and [124I]I-6 ([124I]I-pentixafor-Ga) and their radiochemical purities were all higher than 95%. After positron emission tomography (PET)/single-photon emission computed tomography (SPECT) imaging, the [124I]I-6 group exhibited the best target-nontarget ratio. At the same time, comparing the [68Ga]Ga-pentixafor group with the [124I]I-6 group, we found that the [124I]I-6 group had a better target-nontarget ratio and lower uptake in nontarget organs. Therefore, compound 6 was selected for therapeutic radionuclide (131I) labeling, and the tumor-bearing animal models were treated with [131I]I-6. The volume of the tumor site was significantly reduced in the treatment group compared with the control group, and no significant side effects were found. [124I]I-6 and [131I]I-6 showed excellent affinity for targeting CXCR4, and they showed great potential for the integrated diagnosis and treatment of tumors with high CXCR4 expression.

Mid-term clinical outcomes of totally endoscopic repair for mitral regurgitation in Barlow's disease.

OBJECTIVE: This study aimed to confirm the safety and feasibility of totally endoscopic repair for mitral regurgitation (MR) in Barlow's disease. METHODS: From June 2018 to December 2022, 21 consecutive Barlow's disease patients (aged 33 ± 12 years; 57.1% male) underwent totally endoscopic mitral valve (MV) repair with leaflets folding, multiple artificial chordae implantation and ring annuloplasty. The safety and feasibility of this technique was evaluated by its mid-term clinical outcomes. RESULTS: There was no operative death or complications. The mean cardiopulmonary bypass (CPB) time was 190 ± 41 (128-267) min, and the aortic cross-clamp time was 145 ± 32 (66-200) min. The average number of artificial chordae implantation was 2.9 ± 0.7 (1-4) pairs. The mean MV coaptation length was 1.4 ± 0.3 (0.8-1.8) cm, and the median transvalvular gradient was 1 [interquartile range (IQR), 1-2] mmHg. During a median follow-up time of 24 (IQR, 10-38) months, all patients showed persistent effective valve function with no significant MR or systolic anterior motion. CONCLUSIONS: Totally endoscopic repair was a safe, effective, and reproducible procedure with satisfied mid-term clinical outcomes for MR in Barlow's disease. However, further randomized and long-term follow-up studies were warranted to determine its clinical effects.

A WeChat-based nursing intervention program improves the postoperative rehabilitation of breast cancer patients: results from a randomized controlled trial.

Background: In postoperative setting, breast cancer (BC) patients can experience adverse effects, including fatigue, sleep disorders, and pain, which substantially affect their health-related quality of life (HRQoL). This study sought to assess the effectiveness of a WeChat-based multimodal nursing program (WCBMNP) that was specifically designed for the rehabilitation of women following BC surgery. Methods: BC patients were randomly, single-blinded allocated to either the intervention (n=62) or control (n=63) cohorts. Over a period of 6 months (24 weeks), the intervention cohort received a WCBMNP in addition to routine nursing care, while the control cohort received routine nursing care only. To evaluate patients' fear of cancer recurrence (FCR), their overall fear score was assessed using the Japanese version of the Concerns About Recurrence Scale (CARS-J) for primary outcome. The initial outcome (HRQoL) and secondary results, such as fatigue, sleep, and pain, were examined using the Functional Assessment of Cancer Therapy-Breast (FACT-B, version 4.0) and Nursing Rating Scale (NRS), respectively. Results: Two hundred and ten participants, 85 participants were excluded. Compared to the controls (n=63), the intervention cohort (n=62) showed statistically significant improvements in their CARS-J scores. The intervention cohort aggregate scores on the FACT-B improved significantly but were affected by the compounding influences of cohort dynamics, temporal progression, and their interaction. Similar improvements were observed in the social/family and functional well-being domains. Emotional well-being was improved based on the effects of time and group-time interaction. In the intervention cohort, the "BC-specific subscale for additional concerns" was affected by group and time, whereas physical well-being was only affected by time. Conversely, there were no statistically significant changes in the variables of fatigue, sleep, and pain. Conclusions: The WCBMNP reduced FCR and significantly increased the HRQoL of female patients with BC postoperatively. The WCBMNP could be implemented as a postoperative rehabilitation intervention in this patient population to improve outcomes. Trial Registration: Chinese Clinical Trial Registry (ChiCTR2400081557).

Closing the gap: Solving complex medically relevant genes at scale.

Comprehending the mechanism behind human diseases with an established heritable component represents the forefront of personalized medicine. Nevertheless, numerous medically important genes are inaccurately represented in short-read sequencing data analysis due to their complexity and repetitiveness or the so-called 'dark regions' of the human genome. The advent of PacBio as a long-read platform has provided new insights, yet HiFi whole-genome sequencing (WGS) cost remains frequently prohibitive. We introduce a targeted sequencing and analysis framework, Twist Alliance Dark Genes Panel (TADGP), designed to offer phased variants across 389 medically important yet complex autosomal genes. We highlight TADGP accuracy across eleven control samples and compare it to WGS. This demonstrates that TADGP achieves variant calling accuracy comparable to HiFi-WGS data, but at a fraction of the cost. Thus, enabling scalability and broad applicability for studying rare diseases or complementing previously sequenced samples to gain insights into these complex genes. TADGP revealed several candidate variants across all cases and provided insight into LPA diversity when tested on samples from rare disease and cardiovascular disease cohorts. In both cohorts, we identified novel variants affecting individual disease-associated genes (e.g., IKZF1, KCNE1). Nevertheless, the annotation of the variants across these 389 medically important genes remains challenging due to their underrepresentation in ClinVar and gnomAD. Consequently, we also offer an annotation resource to enhance the evaluation and prioritization of these variants. Overall, we can demonstrate that TADGP offers a cost-efficient and scalable approach to routinely assess the dark regions of the human genome with clinical relevance.

Elevated Plasma Lipoprotein(a) Level and Atherosclerotic Cardiovascular Disease Risks: A Large Clinical Retrospective Study.

Patients with well-controlled low-density lipoprotein cholesterol (LDL-C) levels still suffer from the progress of the atherosclerotic cardiovascular disease (ASCVD) and can develop adverse outcomes. We conducted this study to analyze the relationship between elevated lipoprotein(a) [Lp(a)] levels and ASCVD risk. We enrolled 8070 patients in the ASCVD group and 440 participants in the non-ASCVD group [median age of 60 years; 6376 (74.9%) were male]. Multivariate logistic regression models were used to identify the relationships between the lipids and ASCVD. These models showed that the Lp(a) level was a significant independent risk factor for ASCVD [odds ratio (OR) = 1.025, confidence interval (CI) = 1.020-1.029, P < .001]. The different categories analysis showed the OR of the high Lp(a)/low LDL-C group was 9.612 [CI = 6.206-14.887], P < .001. Our study demonstrated that elevated Lp(a) levels were associated with the increased ASCVD risk. Also, the patients with low LDL-C but high Lp(a) levels still had a higher risk of developing ASCVD than the low Lp(a)/high LDL-C group. In addition, elevated Lp(a) levels were associated with a higher ASCVD risk in males, hypertensive, and diabetic patients.

Genome-scale CRISPR-Cas9 screen identifies PAICS as a therapeutic target for EGFR wild-type non-small cell lung cancer.

Epidermal growth factor receptor-targeted (EGFR-targeted) therapies show promise for non-small cell lung cancer (NSCLC), but they are ineffective in a third of patients who lack EGFR mutations. This underlines the need for personalized treatments for patients with EGFR wild-type NSCLC. A genome-wide CRISPR/Cas9 screen has identified the enzyme phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS), which is vital in de novo purine biosynthesis and tumor development, as a potential drug target for EGFR wild-type NSCLC. We have further confirmed that PAICS expression is significantly increased in NSCLC tissues and correlates with poor patient prognosis. Knockdown of PAICS resulted in a marked reduction in both in vitro and in vivo proliferation of EGFR wild-type NSCLC cells. Additionally, PAICS silencing led to cell-cycle arrest in these cells, with genes involved in the cell cycle pathway being differentially expressed. Consistently, an increase in cell proliferation ability and colony number was observed in cells with upregulated PAICS in EGFR wild-type NSCLC. PAICS silencing also caused DNA damage and cell-cycle arrest by interacting with DNA repair genes. Moreover, decreased IMPDH2 activity and activated PI3K-AKT signaling were observed in NSCLC cells with EGFR mutations, which may compromise the effectiveness of PAICS knockdown. Therefore, PAICS plays an oncogenic role in EGFR wild-type NSCLC and represents a potential therapeutic target for this disease.

The persistent inflammation in COPD: is autoimmunity the core mechanism?

COPD poses a significant global public health challenge, primarily characterised by irreversible airflow restriction and persistent respiratory symptoms. The hallmark pathology of COPD includes sustained airway inflammation and the eventual destruction of lung tissue structure. While multiple risk factors are implicated in the disease's progression, the underlying mechanisms remain largely elusive. The perpetuation of inflammation is pivotal to the advancement of COPD, emphasising the importance of investigating these self-sustaining mechanisms for a deeper understanding of the pathogenesis. Autoimmune responses constitute a critical mechanism in maintaining inflammation, with burgeoning evidence pointing to their central role in COPD progression; yet, the intricacies of these mechanisms remain inadequately defined. This review elaborates on the evidence supporting the presence of autoimmune processes in COPD and examines the potential mechanisms through which autoimmune responses may drive the chronic inflammation characteristic of the disease. Moreover, we attempt to interpret the clinical manifestations of COPD through autoimmunity.

Calpain inhibition protects against atrial fibrillation by mitigating diabetes-associated atrial fibrosis and calcium handling dysfunction in type 2 diabetes mice.

BACKGROUND: Diabetes mellitus (DM) is a major risk factor for atrial structural remodeling and atrial fibrillation (AF). Calpain activity is hypothesized to promote atrial remodeling and AF. OBJECTIVE: The purpose of this study was to investigate the role of calpain in diabetes-associated AF, fibrosis, and calcium handling dysfunction. METHODS: DM-associated AF was induced in wild-type (WT) mice and in mice overexpressing the calpain inhibitor calpastatin (CAST-OE) using high-fat diet feeding followed by low-dose streptozotocin injection (75 mg/kg). DM and AF outcomes were assessed by measuring blood glucose levels, fibrosis, and AF susceptibility during transesophageal atrial pacing. Intracellular Ca2+ transients, spontaneous Ca2+ release events, and intracellular T-tubule membranes were measured by in situ confocal microscopy. RESULTS: WT mice with DM had significant hyperglycemia, atrial fibrosis, and AF susceptibility with increased atrial myocyte calpain activity and Ca2+ handling dysfunction relative to control treated animals. CAST-OE mice with DM had a similar level of hyperglycemia as diabetic WT littermates but lacked significant atrial fibrosis and AF susceptibility. DM-induced atrial calpain activity and downregulation of the calpain substrate junctophilin-2 were prevented by CAST-OE. Atrial myocytes of diabetic CAST-OE mice exhibited improved T-tubule membrane organization, Ca2+ handling, and reduced spontaneous Ca2+ release events compared to littermate controls. CONCLUSION: This study confirmed that DM promotes calpain activation, atrial fibrosis, and AF in mice. CAST-OE effectively inhibits DM-induced calpain activation and reduces atrial remodeling and AF incidence through improved intracellular Ca2+ homeostasis. Our results support calpain inhibition as a potential therapy for preventing and treating AF in DM patients.

Construction of Si-Stereogenic Silanols by Palladium-Catalyzed Enantioselective C-H Alkenylation.

The construction of silicon-stereogenic silanols via Pd-catalyzed intermolecular C-H alkenylation with the assistance of a commercially available L-pyroglutamic acid has been realized for the first time. Employing oxime ether as the directing group, silicon-stereogenic silanol derivatives could be readily prepared with excellent enantioselectivities, featuring a broad substrate scope and good functional group tolerance. Moreover, parallel kinetic resolution with unsymmetric substrates further highlighted the generality of this protocol. Mechanistic studies indicate that L-pyroglutamic acid could stabilize the Pd catalyst and provide excellent chiral induction. Preliminary computational studies unveil the origin of the enantioselectivity in the C-H bond activation step.

The Effect of Sleep Quality on Coronary Lesion Severity and Prognosis in the Young Acute Coronary Syndrome Population.

This study aimed to explore the effect of long-term (≥1 year) sleep quality on coronary lesion complexity and cardiovascular prognosis in young acute coronary syndrome (ACS) patients. We consecutively recruited young patients aged from 18 to 44 years old with first-episode ACS and significant epicardial stenosis on coronary angiography from January 2016 to January 2017. Coronary lesion complexity was evaluated based on SYNTAX scores. Long-term sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) (PSQI ≤ 5 and PSQI > 5 groups). The primary endpoints were major adverse cardiovascular events (MACEs). A total of 466 young ACS patients (93.13% male; median age, 41 years) were included. Poor sleepers (PSQI > 5) had higher SYNTAX scores. After adjusting for confounders, PSQI scores (continuous variables, OR: 1.264; 95%CI: 1.166-1.371; p < 0.001) and PSQI grade (binary variable, OR: 3.864; 95%CI: 2.313-6.394; p = 0.001) were significantly associated with an increased risk of complex coronary lesions. During a median follow-up of 74 months, long-term poor sleep quality (PSQI > 5) was significantly associated with an increased risk of MACEs (HR: 4.266; 95%CI: 2.274-8.001; p < 0.001). Long-term poor sleep quality was a risk factor for complex coronary lesions and has adverse effects on cardiovascular prognosis in the young ACS population.

Prognosis of Elevated Mitral Valve Pressure Gradient After Transcatheter Edge-to-Edge Repair: Systematic Review and Meta-Analysis.

Elevation in mitral valve pressure gradient (MVPG) after mitral valve transcatheter edge-to-edge repair (M-TEER) is common, however, evidence on its prognosis is scarce and debatable. Thus, this study aims to investigate the impact of increased MVPG after M-TEER on outcomes. Studies reporting the associations between the elevated MVPG after M-TEER and outcomes were identified in a systematic search of published literatures. Associations were pooled by meta-analysis using a random-effects model. The primary outcome was the composite of all-cause mortality and heart failure (HF) hospitalization. Seven observational studies with 2,730 patients (mean age, 77.7 ± 9.3 years; male, 64.4%; functional mitral regurgitation [MR], 65.2%) were eligible for the present analysis. M-TEER was performed entirely using the MitraClip system (Abbott), followed by 29.7% of patients having increased MVPG. Elevated postprocedural MVPG was not associated with a higher risk of the primary outcome, compared to low MVPG [hazard ratio (HR) = 1.22; 95% confidence interval (CI) 0.95-1.58; p = 0.12; I2 = 53.5%). However, the prognosis of elevated MVPG was observed in degenerative MR patients (HR = 1.37; 95% CI 1.03-1.84; p = 0.03; I2 = 0%), whereas not in functional MR patients. Patients with low MVPG + high residual MR had a higher risk of the primary outcome than those with high MVPG + low residual MR after M-TEER (HR = 1.50; 95% CI 1.10-2.03; p = 0.01; I2 = 13%). In conclusion, elevated MVPG seems to predict adverse outcomes mainly in patients with degenerative MR. Future studies are needed to prove these findings.