Interfacial Self-Assembly Nanostructures: Constructions and Applications.

Interfacial self-assembly nanoarrays refer to the spontaneously organized nanostructures at interfaces, relying on the intrinsic properties of involved materials, such as surface energy, molecular structure, and interactions. In recent years, the exponential growth of self-assembly nanotechnology has substantially expanded the utility of nanomaterials. Particularly, non-covalent interactions-based interfacial self-assembly represents a viable and promising approach for the synthesis of novel nanostructure. This review introduces the significance and current development status of interfacial self-assembly technology, focusing on the driving mode, application, and prospects of interfacial self-assembly nanoarrays over the past few years.

Impact of risk factors on intervened and non-intervened coronary lesions.

INTRODUCTION: In-stent restenosis (ISR) and aggravated non-intervened coronary lesions (ANL) are two pivotal aspects of disease progression in patients with coronary artery disease (CAD). Established risk factors for both include hyperlipidemia, hypertension, diabetes, chronic kidney disease, and smoking. However, there is limited research on the comparative risk factors for the progression of these two aspects of progression. The aim of this study was to analyze and compare the different impacts of identical risk factors on ISR and ANL. METHODS: This study enrolled a total of 510 patients with multiple coronary artery lesions who underwent repeated coronary angiography (CAG). All patients had previously undergone percutaneous coronary intervention (PCI) and presented non-intervened coronary lesions in addition to the previously intervened vessels. RESULTS: After data analysis, it was determined that HbA1c (OR 1.229, 95% CI 1.022-1.477, P=0.028) and UA (OR 1.003, 95% CI 1.000-1.005, P=0.024) were identified as independent risk factors for ISR. Furthermore, HbA1c (OR 1.215, 95% CI 1.010-1.460, P=0.039), Scr (OR 1.007, 95% CI 1.003-1.017, P=0.009), and ApoB (OR 1.017, 95% CI 1.006-1.029, P=0.004) were identified as independent risk factors for ANL. The distribution of multiple blood lipid levels differed between the ANL only group and the ISR only group. Non-HDL-C (2.17 mmol/L vs. 2.44 mmol/L, P=0.007) and ApoB (63.5 mg/dL vs. 71.0 mg/dL, P=0.011) exhibited significantly higher values in the ANL only group compared to the ISR only group. CONCLUSIONS: Blood glucose levels and chronic kidney disease were identified as independent risk factors for both ISR and ANL, while elevated lipid levels were only significantly associated with ANL. In patients with non-intervened coronary lesions following PCI, it is crucial to assess the concentration of non-HDL-C and ApoB as they serve as significant risk factors.

Corrigendum: Long non-coding RNA AL139385.1 as a novel prognostic biomarker in lung adenocarcinoma.

[This corrects the article DOI: 10.3389/fonc.2022.905871.].

Dysregulated Mitochondrial Calcium Causes Spiral Artery Remodeling Failure in Preeclampsia.

BACKGROUND: Calcium deficiency in women is strongly linked to an increased risk of developing preeclampsia. Mitochondrial calcium ([Ca2+]m) homeostasis is essential to regulate vascular smooth muscle cell (VSMC) function. However, the role of [Ca2+]m in preeclampsia development remains largely unknown. METHODS: To investigate this, human spiral arteries obtained from normotensive and preeclamptic women were collected for vascular function, RNA sequencing, and VSMC studies. N(ω)-nitro-L-arginine methyl ester-induced preeclampsia animal experiments were established to investigate the effects of intervening in [Ca2+]m to improve the outcome for preeclamptic mothers or their infants. RESULTS: Our initial findings revealed compromised vessel function in spiral arteries derived from patients with preeclampsia, as evidenced by diminished vasoconstriction and vasodilation responses to angiotensin II and sodium nitroprusside, respectively. Moreover, the spiral artery VSMCs from patients with preeclampsia exhibited phenotypic transformation and proliferation associated with the disrupted regulatory mechanisms of [Ca2+]m uptake. Subsequent in vitro experiments employing gain- and loss-of-function approaches demonstrated that the mitochondrial Na+/Ca2+ exchanger played a role in promoting phenotypic switching and impaired mitochondrial functions in VSMCs. Furthermore, mtNCLX (mitochondrial Na+/Ca2+ exchanger) inhibitor CGP37157 significantly improved VSMC phenotypic changes and restored mitochondrial function in both patients with preeclampsia-derived VSMCs and the preeclampsia rat model. CONCLUSIONS: This study provides comprehensive evidence supporting the disrupted regulatory mechanisms of [Ca2+]m uptake in VSMCs of spiral arteries of patients with preeclampsia and further elucidates its correlation with VSMC phenotypic switching and defective spiral artery remodeling. The findings suggest that targeting mtNCLX holds promise as a novel therapeutic approach for managing preeclampsia.

Development and application of a WebGIS-based prediction system for multi-criteria decision analysis of porcine pasteurellosis.

Porcine pasteurellosis is an infectious disease caused by Pasteurella multocida (P. multocida), which seriously endangers the healthy development of pig breeding industry. Early detection of disease transmission in animals is a crucial early warning for humans. Therefore, predicting risk areas for disease is essential for public health authorities to adopt preventive measures and control strategies against diseases. In this study, we developed a predictive model based on multi-criteria decision analysis (MCDA) and assessed risk areas for porcine pasteurellosis in the Chinese mainland. By using principal component analysis, the weights of seven spatial risk factors were determined. Fuzzy membership function was used to standardize all risk factors, and weight linear combination was used to create a risk map. The sensitivity of the risk map was analyzed by calculating the mean of absolute change rates of risk factors, as well as calculating an uncertainty map. The results showed that risk areas for porcine pasteurellosis were predicted to be locate in the south-central of the Chinese mainland, including Sichuan, Chongqing, Guangdong, and Guangxi. The maximum standard deviation of the uncertain map was less than 0.01and the ROC results showed that the prediction model has moderate predictive performance with the area under the curve (AUC) value of 0.80 (95% CI 0.75-0.84). Based on the above process, MCDA was combined with WebGIS technology to construct a system for predicting risk areas of porcine pasteurellosis. Risk factor data was directly linked to the developed model, providing decision support for disease prevention and control through monthly updates.

Prognostic Value of Coronary Angiography-Derived Index of Microcirculatory Resistance in Non-ST-Segment Elevation Myocardial Infarction Patients.

BACKGROUND: The index of microcirculatory resistance is a reliable measure for evaluating coronary microvasculature, but its prognostic value in patients with non-ST-segment elevation myocardial infarction (NSTEMI) remains unclear. OBJECTIVES: This study aimed to evaluate the prognostic impact of postpercutaneous coronary intervention (PCI) angiography-derived index of microcirculatory resistance (angio-IMR) in patients with NSTEMI. METHODS: The culprit vessel's angio-IMR was measured after PCI in 2,212 NSTEMI patients at 3 sites. The primary endpoint was 2-year major adverse cardiac events (MACEs), defined as a composite of cardiac death, readmission for heart failure, myocardial reinfarction, and target vessel revascularization. RESULTS: The mean post-PCI angio-IMR was 20.63 ± 4.17 in NSTEMI patients. A total of 206 patients were categorized as the high post-PCI angio-IMR group according to maximally selected log-rank statistics. Patients with angio-IMR >25 showed a higher rate of MACEs than those with angio-IMR ≤25 (32.52% vs 9.37%; P < 0.001). Post-PCI angio-IMR >25 was an independent predictor of MACEs (HR: 4.230; 95% CI: 3.151-5.679; P < 0.001) and showed incremental prognostic value compared with conventional risk factors (AUC: 0.774 vs 0.716; P < 0.001; net reclassification index: 0.317; P < 0.001; integrated discrimination improvement: 0.075; P < 0.001). CONCLUSIONS: In patients undergoing PCI for NSTEMI, an increased post-PCI angio-IMR is associated with a higher risk of MACEs. The addition of post-PCI angio-IMR into conventional risk factors significantly improves the ability to reclassify patients and estimate the risk of MACEs. (Angiograph-Derived Index of Microcirculatory Resistance in Patients With Acute Myocardial Infarction; NCT05696379).

Effect of henagliflozin on left ventricular mass index in dialysis patients with HFpEF (HELD-HF): protocol for a multicentre, randomised, double-blind, placebo-controlled trial.

INTRODUCTION: Heart failure with preserved ejection fraction (HFpEF) is a prevalent comorbidity among patients with end-stage kidney disease. Although sodium-glucose cotransporter 2 inhibitors are validated in treating heart failure and ameliorating left ventricular hypertrophy among non-dialysis patients, the effects on dialysis patients are unknown. We previously investigated the pharmacokinetics of henagliflozin in patients undergoing haemodialysis (HD) or peritoneal dialysis (PD) and clarified its safety. METHODS AND ANALYSIS: This multicentre, randomised, double-blind, placebo-controlled trial is being conducted at three hospitals in Shanghai, China. A target of 108 HD or PD patients with HFpEF are randomly allocated to treatment group (henagliflozin 5 mg/day in addition to standard therapy) or control group (placebo with standard therapy) at a ratio of 1:1. All subjects will be followed up for 24 weeks. The primary outcome is change in echocardiography-measured left ventricular mass index. The secondary interests include changes in left atrial volume index, E/e', e' and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Intergroup comparisons of change in echocardiography-related outcomes from baseline to 24 weeks are based on a linear regression model adjusted for baseline values (analysis of covariance), and repeated measure analysis of variance with Bonferroni adjustment is employed for comparison of change in NT-proBNP. Subgroup analyses of the primary and secondary outcomes are conducted to determine whether the effect of henagliflozin varies according to dialysis modality. The χ2 method is used to compare the occurrence of adverse events and severe adverse events. ETHICS AND DISSEMINATION: This trial has been approved by the Ethics Committee of Renji Hospital, School of Medicine, Shanghai Jiao Tong University (LY2023-127-B). All participants provide written informed consent before screening. The results of the trial will be disclosed completely in international peer-reviewed journals. Both positive and negative results will be reported. TRIAL REGISTRATION NUMBER: ChiCTR2300073169.

Delineating the stepwise millisecond allosteric activation mechanism of the class C GPCR dimer mGlu5.

Two-thirds of signaling hormones and one-third of approved drugs exert their effects by binding and modulating the G protein-coupled receptors (GPCRs) activation. While the activation mechanism for monomeric GPCRs has been well-established, little is known about GPCRs in dimeric form. Here, by combining transition pathway generation, extensive atomistic simulation-based Markov state models, and experimental signaling assays, we reveal an asymmetric, stepwise millisecond allosteric activation mechanism for the metabotropic glutamate receptor subtype 5 receptor (mGlu5), an obligate dimeric class C GPCR. The dynamic picture is presented that agonist binding induces dimeric ectodomains compaction, amplified by the precise association of the cysteine-rich domains, ultimately loosely bringing the intracellular 7-transmembrane (7TM) domains into proximity and establishing an asymmetric TM6-TM6 interface. The active inter-domain interface enhances their intra-domain flexibility, triggering the activation of micro-switches crucial for downstream signal transduction. Furthermore, we show that the positive allosteric modulator stabilizes both the active inter-domain 7TM interface and an open, extended intra-domain ICL2 conformation. This stabilization leads to the formation of a pseudo-cavity composed of the ICL2, ICL3, TM3, and C-terminus, which facilitates G protein coordination. Our strategy may be generalizable for characterizing millisecond events in other allosteric systems.

Combined risk estimates of diabetes and coronary angiography-derived index of microcirculatory resistance in patients with non-ST elevation myocardial infarction.

BACKGROUND: Diabetes mellitus (DM) and coronary microvascular dysfunction (CMD) increase the risk of adverse cardiac events in patients with non-ST-segment elevation myocardial infarction (NSTEMI). This study aimed to evaluate the combined risk estimates of DM and CMD, assessed by the angiography-derived index of microcirculatory resistance (angio-IMR), in patients with NSTEMI. METHODS: A total of 2212 patients with NSTEMI who underwent successful percutaneous coronary intervention (PCI) were retrospectively enrolled from three centers. The primary outcome was a composite of cardiac death or readmission for heart failure at a 2-year follow-up. RESULTS: Post-PCI angio-IMR did not significantly differ between the DM group and the non-DM group (20.13 [17.91-22.70] vs. 20.19 [18.14-22.77], P = 0.530). DM patients exhibited a notably higher risk of cardiac death or readmission for heart failure at 2 years compared to non-DM patients (9.5% vs. 5.4%, P < 0.001). NSTEMI patients with both DM and CMD experienced the highest cumulative incidence of cardiac death or readmission for heart failure at 2 years (24.0%, P < 0.001). The combination of DM and CMD in NSTEMI patients were identified as the most powerful independent predictor for cardiac death or readmission for heart failure at 2 years (adjusted HR: 7.894, [95% CI, 4.251-14.659], p < 0.001). CONCLUSIONS: In patients with NSTEMI, the combination of DM and CMD is an independent predictor of cardiac death or readmission for heart failure. Angio-IMR could be used as an additional evaluation tool for the management of NSTEMI patients with DM. TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov ; Unique identifier: NCT05696379.

The relationship between cardiometabolic index and pulmonary function among U.S. adults: insights from the National Health and Nutrition Examination Survey (2007-2012).

BACKGROUND: Previous findings have revealed that disorders of lipid metabolism may be a risk factor for pulmonary function damage; however, the combined effect of dyslipidemia and central obesity on pulmonary function is unclear. The cardiometabolic index (CMI) is a composite of serum lipids (triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C)) and visceral fat parameters (waist-to-height ratio (WHtR)). This research aimed to investigate the link between CMI and pulmonary function, employing large-scale demographic data sourced from the National Health and Nutrition Examination Survey (NHANES) database. METHODS: This cross-sectional study used data involving 4125 adults aged 20 and above collected by NHANES between 2007 and 2012. We defined CMI as the exposure variable and measured outcomes using forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC to evaluate pulmonary function. Weighted multiple linear regression models and subgroup analyses were employed to investigate separate relationships between CMI and pulmonary function. In addition, to investigate variations across different strata and evaluate the robustness of the findings, interaction tests and sensitivity analyses were conducted. RESULTS: Results from the weighted multiple linear regression analysis indicated a unit increase in log2-CMI was associated with a reduction of 82.63 mL in FEV1 and 112.92 mL in FVC. The negative association remained significant after transforming log2-CMI by quartile (Q). When the log2-CMI level reached Q4, ß coefficients (ß) were -128.49 (95% CI: -205.85, -51.13), -169.01 (95% CI: -266.72, -71.30), respectively. According to the interaction test findings, the negative association linking log2-CMI with FEV1 and FVC persists regardless of confounding factors including age, gender, BMI, physical activity (PA), and smoking status. A subsequent sensitivity analysis provided additional confirmation of the stability and reliability of the results. For females, the inflection points for the nonlinear relationships between log2-CMI and FEV1, as well as log2-CMI and FVC, were identified at 2.33 and 2.11, respectively. While in males, a consistent negative association was observed. CONCLUSIONS: Our findings suggest that higher CMI is associated with lower FEV1 and FVC. CMI may serve as a complementary consideration to the assessment and management of pulmonary function in clinical practice.

Urolithin A Protects against Hypoxia-Induced Pulmonary Hypertension by Inhibiting Pulmonary Arterial Smooth Muscle Cell Pyroptosis via AMPK/NF-κB/NLRP3 Signaling.

Recent studies confirmed that pyroptosis is involved in the progression of pulmonary hypertension (PH), which could promote pulmonary artery remodeling. Urolithin A (UA), an intestinal flora metabolite of ellagitannins (ETs) and ellagic acid (EA), has been proven to possess inhibitory effects on pyroptosis under various pathological conditions. However, its role on PH remained undetermined. To investigate the potential of UA in mitigating PH, mice were exposed to hypoxia (10% oxygen, 4 weeks) to induce PH, with or without UA treatment. Moreover, in vitro experiments were carried out to further uncover the underlying mechanisms. The in vivo treatment of UA suppressed the progression of PH via alleviating pulmonary remodeling. Pyroptosis-related genes were markedly upregulated in mice models of PH and reversed after the administration of UA. In accordance with that, UA treatment significantly inhibited hypoxia-induced pulmonary arterial smooth muscle cell (PASMC) pyroptosis via the AMPK/NF-κB/NLRP3 pathway. Our results revealed that UA treatment effectively mitigated PH progression through inhibiting PASMC pyroptosis, which represents an innovative therapeutic approach for PH.

RNA Helicase DDX5 Maintains Cardiac Function by Regulating CamkIIδ Alternative Splicing.

BACKGROUND: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. RNA-binding proteins are identified as regulators of cardiac disease; DDX5 (dead-box helicase 5) is a master regulator of many RNA processes, although its function in heart physiology remains unclear. METHODS: We assessed DDX5 expression in human failing hearts and a mouse HF model. To study the function of DDX5 in heart, we engineered cardiomyocyte-specific Ddx5 knockout mice. We overexpressed DDX5 in cardiomyocytes using adeno-associated virus serotype 9 and performed transverse aortic constriction to establish the murine HF model. The mechanisms underlined were subsequently investigated using immunoprecipitation-mass spectrometry, RNA-sequencing, alternative splicing analysis, and RNA immunoprecipitation sequencing. RESULTS: We screened transcriptome databases of murine HF and human dilated cardiomyopathy samples and found that DDX5 was significantly downregulated in both. Cardiomyocyte-specific deletion of Ddx5 resulted in HF with reduced cardiac function, an enlarged heart chamber, and increased fibrosis in mice. DDX5 overexpression improved cardiac function and protected against adverse cardiac remodeling in mice with transverse aortic constriction-induced HF. Furthermore, proteomics revealed that DDX5 is involved in RNA splicing in cardiomyocytes. We found that DDX5 regulated the aberrant splicing of Ca2+/calmodulin-dependent protein kinase IIδ (CamkIIδ), thus preventing the production of CaMKIIδA, which phosphorylates L-type calcium channel by serine residues of Cacna1c, leading to impaired Ca2+ homeostasis. In line with this, we found increased intracellular Ca2+ transients and increased sarcoplasmic reticulum Ca2+ content in DDX5-depleted cardiomyocytes. Using adeno-associated virus serotype 9 knockdown of CaMKIIδA partially rescued the cardiac dysfunction and HF in Ddx5 knockout mice. CONCLUSIONS: These findings reveal a role for DDX5 in maintaining calcium homeostasis and cardiac function by regulating alternative splicing in cardiomyocytes, identifying the DDX5 as a potential target for therapeutic intervention in HF.

The genome of Vicia sativa ssp. amphicarpa provides insights into the role of terpenoids in antimicrobial resistance within subterranean fruits.

Vicia sativa ssp. amphicarpa is a unique forage crop capable of simultaneously producing fruits above and below ground, representing a typical amphicarpic plant. In this study, we sequenced and assembled seven pseudo-chromosomes of the genome of V. sativa ssp. amphicarpa (n = 7) yielding a genome size of 1.59 Gb, with a total annotation of 48 932 protein-coding genes. Long terminal repeat (LTR) elements constituted 62.28% of the genome, significantly contributing to the expansion of genome size. Phylogenetic analysis revealed that the divergence between V. sativa ssp. amphicarpa and V. sativa was around 0.88 million years ago (MYA). Comparative transcriptomic and metabolomic analysis of aerial and subterranean pod shells showed biosynthesis of terpenoids in the subterranean pod shells indicating a correlation between the antimicrobial activity of subterranean pod shells and the biosynthesis of terpenoids. Furthermore, functional validation indicates that overexpression of VsTPS5 and VsTPS16 enhances terpenoid biosynthesis for antibacterial activity. Metabolomic analysis suggests the involvement of terpenoids in the antimicrobial properties of subterranean pod shells. Deciphering the genome of V. sativa ssp. amphicarpa elucidated the molecular mechanisms behind the antimicrobial properties of subterranean fruits in amphicarpic plants, providing valuable insights for the study of amphicarpic plant biology.

Recent Progresses in the Multimodality Imaging Assessment of Myocardial Fibrosis.

Myocardial fibrosis, a common pathophysiological consequence of various cardiovascular diseases, is characterized by fibroblast activation and excessive deposition of extracellular matrix (ECM) collagen. Accumulating evidence indicates that myocardial fibrosis contributes to ventricular stiffness, systolic and diastolic dysfunction, and ultimately leads to the development of heart failure (HF). Early detection and targeted treatment of myocardial fibrosis is critical to reverse ventricular remodeling and improve clinical outcomes in patients with cardiovascular diseases. However, despite considerable progresses made in understanding molecular mechanisms of myocardial fibrosis, non-invasive imaging to assess myocardial fibrosis and guide clinical treatment is still not widely available, limiting the development of innovative treatment strategies. This review summarizes recent progresses of imaging modalities for detecting myocardial fibrosis, with a focus on nuclear medicine, echocardiography and cardiac magnetic resonance (CMR).

A National Study Exploring the Association between Fasting Duration and Mortality among the Elderly.

(1) Background: The benefits of weight management are widely recognized, and prolonged fasting duration has become a common method for weight control. The suitability of time-restricted eating (TRE) for elderly individuals remains controversial. This study aims to examine the correlation between fasting duration and mortality within a nationally representative cohort of elderly individuals in the United States. (2) Methods: Data were extracted from a prospective cohort study conducted as part of the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. Participants aged over 60 with complete data on dietary intake and mortality follow-up information were included. Fasting duration was assessed using two 24 h dietary recalls. All the participants were categorized into fasting duration quartiles. Mortality outcomes were ascertained through the National Death Index. Cox proportional hazards regression models were utilized to analyze the association between fasting duration and mortality. (3) Results: The final analysis included 10,561 elderly participants (mean age 69.89, 45.58% male). Individuals with the longest fasting duration (over 12.38 h) had a significantly higher risk of CVD mortality compared to those with a normal fasting duration (10.58-12.38 h). This elevated CVD mortality risk was particularly pronounced in males, individuals over 70 years old, and non-shift workers. A non-linear relationship was observed between fasting duration and all-cause mortality and CVD mortality. (4) Conclusions: Prolonged fasting periods are associated with a higher risk of CVD mortality in the elderly population, although this correlation is not evident for all-cause, cancer, or other-cause mortality. A fasting duration of 11.49 h correlates with the lowest mortality risk. Additionally, elderly individuals with the shortest fasting duration exhibit elevated hazard ratios for both cancer and other-cause mortality. As with any health intervention, clinicians should exercise caution when recommending a fasting regimen that is personalized to the health condition of people who are older. Further research through randomized controlled trials should be conducted to comprehensively investigate the impact of TRE on mortality.

3D Porous Fibers with Spatial Traps and Excellent Zn2+ Transport Kinetics Enable Stable Zn-Based Aqueous Battery.

Adverse side reactions and uncontrolled Zn dendrites growth are the dominant factors that have restricted the application of Zn ion batteries. Herein, a 3D self-supporting porous carbon fibers (denoted as PCFs) host is developed with "trap" effect to adjust the Zn deposition. The unique open structural design of N-doped carbon can act as the zincophilic sites to induce uniform deposition and inhibit adverse side reactions. More importantly, the porous hollow PCFs host with "trap" effect can induce Zn deposition in the fiber by adjusting the local electric field and current density, thereby increasing the specific energy density of the battery and inhibiting dendrite growth. In addition, the 3D open frameworks can regulate Zn2+ flux to enable outstanding cycling performance at ultra-high current densities. As expected, the PCFs framework guarantees the uniform Zn plating and stripping with an outstanding stability over 6000 cycles at the current density of 40 mA cm-2. And the Zn@PCFs||MnO2 full battery shows an excellent lifespan over 1300 cycles at 2000 mA g-1.

The versatile binding landscape of the TAAR1 pocket for LSD and other antipsychotic drug molecules.

Increasing global concerns about psychoactive substance addiction and psychotic disorders highlight the need for comprehensive research into the structure-function relationship governing ligand recognition between these substances and their receptors in the brain. Recent studies indicate the significant involvement of trace amine-associated receptor 1 (TAAR1) in the signaling regulation of the hallucinogen lysergic acid diethylamide (LSD) and other antipsychotic drugs. This study presents structures of the TAAR1-Gs protein complex recognizing LSD, which exhibits a polypharmacological profile, and the partial agonist RO5263397, which is a drug candidate for schizophrenia and addiction. Moreover, we elucidate the cross-species recognition and partial activation mechanism for TAAR1, which holds promising implications from a drug discovery perspective. Through mutagenesis, functional studies, and molecular dynamics (MD) simulations, we provide a comprehensive understanding of a versatile TAAR1 pocket in recognizing various ligands as well as in the ligand-free state, underpinning the structural basis of its high adaptability. These findings offer valuable insights for the design of antipsychotic drugs.

SHAP based predictive modeling for 1 year all-cause readmission risk in elderly heart failure patients: feature selection and model interpretation.

Heart failure (HF) is a significant global public health concern with a high readmission rate, posing a serious threat to the health of the elderly population. While several studies have used machine learning (ML) to develop all-cause readmission risk prediction models for elderly patients with HF, few have integrated ML-selected features with those chosen by human experts to assess HF patients readmission. A retrospective analysis of 8396 elderly HF patients hospitalized at the Affiliated Hospital of North Sichuan Medical College from January 1, 2018 to December 31, 2021 was conducted. Variables selected by XGBoost, LASSO regression, and random forest constituted the machine group, while the human expert group comprised variables chosen by two experienced cardiovascular professors. The variables selected by both groups were combined to form a human-machine collaboration group. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). The SHapley Additive exPlanations (SHAP) method was used to elucidate the importance of each predictive feature, explain the impact of individual features on the model, and provide visual representation. A total of 73 features were included for model development. The human-machine collaboration model, utilizing CatBoost, achieved an AUC of 0.83617, an F1-score of 0.73521, and a Brier score of 0.16536 on the validation set. This model demonstrated superior predictive performance compared to those created solely by human experts or machine. The SHAP plot was then used to visually display the feature analysis of the human-machine collaboration model, revealing HGB, NT-proBNP, smoking history, NYHA classification, and LVEF as the 5 most important features. This study indicate that the human-machine collaboration model outperforms those relying solely on human expert selection or machine algorithm at predicting all-cause readmission in elderly HF patients. The application of the SHAP method enhanced the interpretability of the model outcomes, aiding clinicians in accurately pinpointing risk factors associated with HF readmission. This advancement enables the formulation of tailored treatment strategies, offering a more personalized approach to patient care.

Analysis of long non-coding RNA RMRP in the diagnosis and prognosis of coronary artery disease.

BACKGROUND: Long non-coding RNAs (lncRNAs) are abundant and closely related to the occurrence and development of human diseases. LncRNAs are known to play a key role in many cardiovascular diseases. The purpose of this study was to investigate the effect of the RNA component of mitochondrial RNA-processing endoribonuclease (RMRP) on the degree of coronary artery lesions and prognosis in patients with coronary artery disease (CAD). METHODS: Patients who underwent coronary angiography (CAG) and dynamical-single photon emission computed tomography (D-SPECT) were selected as study subjects, and the results of CAG were reviewed, and the patients were grouped according to SYNTAX score. Evaluate the factors affecting SYNTAX scores. The follow-up analysis was conducted, and the endpoint events were major adverse cardiovascular events (MACEs). Kaplan-Meier method was used to estimate the survival rate, and multivariate Cox regression was used to analyze the relationship between RMRP and MACEs. RESULTS: The expression level of serum RMRP in patients with CAD was significantly higher than that in healthy people. Multivariate Logistic regression analysis showed that age, low-density lipoprotein cholesterol (LDL-C), RMRP and rest left ventricular ejection fraction (LVEF) were independent factors that affected SYNTAX scores. There were 19 cases of MACEs in the high RMRP group and 9 cases in the low RMRP group, and there was a significant difference in the MACE free survival curve between the two groups. Multivariate Cox regression analysis showed that age, SYNTAX score, rest LVEF and RMRP were risk factors for MACEs. CONCLUSIONS: Serum RMRP is a key factor affecting the degree of coronary artery disease and prognosis in CAD patients.

Glutamine Protects against Mouse Abdominal Aortic Aneurysm through Modulating VSMC Apoptosis and M1 Macrophage Activation.

Glutamine (Gln), known as the most abundant free amino acid, is widely spread in human body. In this study, we demonstrated the protective effects of glutamine against mouse abdominal aortic aneurysm (AAA) induced by both angiotensin II (AngII) and calcium phosphate (Ca3(PO4)2) in vivo, which was characterized with lower incidence of mouse AAA. Moreover, histomorphological staining visually presented more intact elastic fiber and less collagen deposition in abdominal aortas of mice treated by glutamine. Further, we found glutamine inhibited the excessive production of reactive oxide species (ROS), activity of matrix metalloproteinase (MMP), M1 macrophage activation, and apoptosis of vascular smooth muscle cells (VSMCs) in suprarenal abdominal aortas of mice, what's more, the high expressions of MMP-2 protein, MMP-9 protein, pro-apoptotic proteins, and IL-6 as well as TNF-α in protein and mRNA levels in cells treated by AngII were down-regulated by glutamine. Collectively, these results revealed that glutamine protected against mouse AAA through inhibiting apoptosis of VSMCs, M1 macrophage activation, oxidative stress, and extracellular matrix degradation.