A NRAS mRNA G-quadruplex structure-targeting small-molecule ligand reactivating DNA damage response in human cancer cells for combination therapy with clinical PI3K inhibitors.

The Neuroblastoma RAS (NRAS) oncogene homologue plays crucial roles in diverse cellular processes such as cell proliferation, survival, and differentiation. Several strategies have been developed to inhibit NRAS or its downstream effectors; however, there is no effective drug available to treat NRAS-driven cancers and thus new approaches are needed to be established. The mRNA sequence expressing NRAS containing several guanine(G)-rich regions may form quadruplex structures (G4s) and regulate NRAS translation. Therefore, targeting NRAS mRNA G4s to repress NRAS expression at translational level with ligands may be a feasible strategy against NRAS-driven cancers but it is underexplored. We reported herein a NRAS mRNA G4-targeting ligand, B3C, specifically localized in cytoplasm in HeLa cells. It effectively downregulates NRAS proteins, reactivates the DNA damage response (DDR), causes cell cycle arrest in G2/M phase, and induces apoptosis and senescence. Moreover, combination therapy with NARS mRNA G4-targeting ligands and clinical PI3K inhibitors for cancer cells inhibition treatment is unexplored, and we demonstrated that B3C combining with PI3Ki (pictilisib (GDC-0941)) showed potent antiproliferation activity against HeLa cells (IC50 = 1.03 µM (combined with 10 µM PI3Ki) and 0.42 µM (combined with 20 µM PI3Ki)) and exhibited strong synergistic effects in inhibiting cell proliferation. This study provides new insights into drug discovery against RAS-driven cancers using this conceptually new combination therapy strategy.

Intrinsically stretchable fully π-conjugated polymer film via fluid conjugated molecular external-plasticizing for flexible light-emitting diodes.

Fully π-conjugated polymers with rigid aromatic units are promising for flexible optoelectronic devices, but their inherent brittleness poses a challenge for achieving high-performance, intrinsically stretchable fully π-conjugated polymer. Here, we are establishing an external-plasticizing strategy using semiconductor fluid plasticizers (Z1 and Z2) to enhance the optoelectronic, morphological, and stretchable properties of fully π-conjugated polymer films for flexible light-emitting diodes. The synergistic effect of hierarchical structure and optoelectronic properties of Z1 in poly(9,9-di-n-octylfluorene-alt-benzothiadiazole) (F8BT) films enable excellent stretchable deformability (~25%) and good conductivity. PLEDs based on F8BT/Z1 films show stable electroluminescence and efficiency under 15% stretch and 100 cycles at 10% strain, revealing outstanding stress tolerance. This strategy is also improving the stretchable properties of polymers like poly(9,9-di-n-octylfluorenyl-2,7-diyl) (PFO) and poly(2-methoxy-5(2'-ethyl)hexoxy-phenylenevinylene) (Super Yellow), demonstrating its general applicability. Therefore, this strategy can provide effective guidance for designing high-performance stretchable fully π-conjugated polymers films for flexible electronic devices.

HDL Levels as a Novel Predictor of Long-Term Adverse Outcomes in Patients with Heart Failure: A Retrospective Cohort Study.

Background: The role of high-density lipoprotein cholesterol (HDL-C) in heart failure (HF) outcomes is contentious. We aimed to assess HDL-C's prognostic value in HF patients. Methods: In this retrospective cohort study (2012-2022) at the First Affiliated Hospital of Xinjiang Medical University, we analyzed 4442 patients, categorized by HDL-C quartiles. We applied the Cox proportional hazards model to assess survival and report hazard ratios (HR) with 95% confidence intervals (CI). Results: Over a decade, we recorded 1354 fatalities (42.3%) and 820 readmissions. The third HDL-C quartile (0.93-1.14 mmol/L) showed the lowest mortality rates, with reduced risks in the second and third quartiles compared to the first (Q2 HR=0.809, 95% CI 0.590-1.109; Q3 HR=0.794, 95% CI 0.564-1.118). The fourth quartile presented a lower mortality risk compared to the first (Q4 HR=0.887, 95% CI 0.693-1.134). A significant correlation existed between HDL-C levels and cardiovascular risk (HR=0.85, 95% CI 0.75-0.96, p<0.01). Conclusion: HDL-C levels exhibit a complex association with mortality in HF, indicating the importance of HDL-C in HF prognosis and the need for tailored management strategies.

The U -shape relationship between free fatty acid level and adverse outcomes in coronary artery disease patients with hypertension: evidence from a large prospective cohort study.

BACKGROUND: Evidence is scarce on the effect of free fatty acid (FFA) level in the prognosis of coronary artery disease (CAD) patients with hypertension. This study. METHODS: A large prospective cohort study with a follow-up period of average 2 years was conducted at Xinjiang Medical University Affiliated First Hospital from December 2016 to October 2021. A total of 10,395 CAD participants were divided into groups based on FFA concentration and hypertension status, and then primary outcome mortality and secondary endpoint ischemic events were assessed in the different groups. RESULTS: A total of 222 all-cause mortality (ACMs), 164 cardiac mortality (CMs), 718 major adverse cardiovascular events (MACEs) and 803 major adverse cardiovascular and cerebrovascular events (MACCEs) were recorded during follow-up period. A nonlinear relationship between FFA and adverse outcomes was observed only in CAD patients with hypertension. Namely, a "U -shape" relationship between FFA levels and long-term outcomes was found in CAD patients with hypertension. Lower FFA level (< 310 µmol/L), or higher FFA level (≥ 580 µmol/L) at baseline is independent risk factors for adverse outcomes. After adjustment for confounders, excess FFA increases mortality (ACM, HR = 1.957, 95%CI(1.240-3.087), P = 0.004; CM, HR = 2.704, 95%CI(1.495-4.890, P = 0.001) and MACE (HR = 1.411, 95%CI(1.077-1.848), P = 0.012), MACCE (HR = 1.299, 95%CI (1.013-1.666), P = 0.040) prevalence. Low levels of FFA at baseline can also increase the incidence of MACE (HR = 1.567,95%CI (1.187-2.069), P = 0.002) and MACCE (HR = 1.387, 95%CI (1.070-1.798), P = 0.013). CONCLUSIONS: Baseline FFA concentrations significantly associated with long-term mortality and ischemic events could be a better and novel risk biomarker for prognosis prediction in CAD patients with hypertension. TRIAL REGISTRATION: The details of the design were registered on https://www.chictr.org.cn/ (Identifier NCT05174143).

Clinical analysis of sirolimus therapy in children with refractory nephrotic syndrome.

To investigate the clinical efficacy of sirolimus in treating children with refractory nephrotic syndrome, the clinical data for 22 children from the Children's Hospital of Hebei Province were analyzed retrospectively. There were 16 boys and six girls, and the treatment period was from September 2015 to April 2021. There were two patients with steroid-dependent nephrotic syndrome (SDNS), six patients with frequently relapsing nephrotic syndrome (FRNS), and 14 patients with steroid-resistant nephrotic syndrome (SRNS). All patients were defined as having refractory nephrotic syndrome. There were 12 patients (including nine SRNS patients and three FRNS patients) with minimal change disease (MCD), three patients (three SRNS patients) with focal segmental glomerular sclerosis (FSGS), one FRNS patient with mesangial proliferative glomerulonephritis (MsPGN), and six patients without a kidney biopsy. Compared with levels before sirolimus treatment, 24-hour urine protein (24-h UP), low-density lipoprotein cholesterol (LDL-C), urea (Ur) and serum creatinine (SCr) levels were significantly lower (all p < 0.05). Moreover, albumin (Alb) was significantly increased (p < 0.05), and there were no significant differences in total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), immunoglobulin A (IgA), immunoglobulin G (IgG) or immunoglobulin M (IgM) (all p > 0.05) at the first follow-up. Sirolimus is effective as the first treatment of some children with refractory nephrotic syndrome, but its long-term efficacy and adverse reactions still require follow-up.

The impact of deep learning based- psychological capital with ideological and political education on entrepreneurial intentions.

The aim of this study is to investigate the influence of psychological capital on college students' entrepreneurial intentions. Through a combination of relevant analysis and linear regression, the primary focus is on exploring the relationship between psychological capital and its four dimensions with entrepreneurial intentions. Firstly, the items in the psychological capital questionnaire were revised to align more closely with entrepreneurial contexts. Subsequently, the average deviations and standard deviations of each dimension of psychological capital were analyzed. Then, the correlation between psychological capital and entrepreneurial intentions was examined to explore the extent of their relationship. Finally, regression analysis was conducted on both psychological capital and entrepreneurial intentions, and utilizing a recurrent neural network model, the covariant relationship between entrepreneurial psychological capital and intentions was explored. The results indicated that the average scores for entrepreneurial self-efficacy, optimism, hope, and resilience were 3.91, 4.27, 4.19, and 4.15, respectively. The average value of psychological capital was 4.13, indicating a moderately high level. The correlation analysis between psychological capital and entrepreneurial intentions yielded a result of 0.562, indicating a moderate degree of correlation. The correlation coefficients of the four dimensions with entrepreneurial intentions were 0.390, 0.494, 0.531, and 0.467, respectively. The standardized coefficients for psychological capital and its four dimensions were 0.564, 0.382, 0.510, 0.536, and 0.468, all of which were statistically significant. Overall, psychological capital exhibited better predictive power for entrepreneurial intentions than its individual dimensions. The results from the deep learning model similarly demonstrated the positive role of psychological capital in entrepreneurial intentions, though the influence of ideological and political education (IPE) factors was relatively weaker. In conclusion, both psychological capital and IPE have a promotive effect on entrepreneurial intentions. This study provides a reference for the accurate evaluation of college students' entrepreneurial intentions.

PADI3 inhibits epithelial-mesenchymal transition by targeting CKS1-induced signal transduction in colon cancer.

BACKGROUND: Protein arginine deiminase 3 (PADI3) is involved in various biological processes of human disease. PADI3 has recently received increasing attention due to its role in tumorigenesis. In a previous study, we found that PADI3 plays a tumor suppressor role in colon cancer by inducing cell cycle arrest, but its critical role and mechanism in cancer metastasis remain obscure. In this study, we fully studied the role of PADI3 in colon cancer cell metastasis. METHODS: The expression levels of related proteins were detected by Western blotting, and Transwell and wound healing assays were used to examine the cell migration ability. Flow cytometry was used to measure and exclude cell apoptosis-affected cell migration. Both overexpression and rescue experiments were employed to elucidate the molecular mechanism of CKS1 in colon cancer cells. RESULTS: The expression levels of PADI3 and CKS1 are negatively related, and PADI3 can promote CKS1 degradation in a ubiquitin-dependent manner. PADI3 can suppress colon cancer cell migration and reduce the wound healing speed by inhibiting CKS1 expression. The molecular mechanism showed that CKS1 can promote EMT by increasing Snail and N-cadherin expression and suppressing E-cadherin expression. PADI3, as a suppressor of CKS1, can block the process of EMT by impairing CKS1-induced Snail upregulation and E-cadherin downregulation; however, the expression of N-cadherin cannot be rescued. CONCLUSIONS: CKS1 promotes EMT in colon cancer by regulating Snail/E-cadherin expression, and this effect can be reversed by PADI3 via the promotion of CKS1 degradation in a ubiquitylation-dependent manner.

Preparation of fibre-reinforced PLA-collagen@PLA-PCL@PCL-gelatin three-layer vascular graft by EDC/NHS cross-linking and its performance study.

In this study, a three-layer small diameter artificial vascular graft with a structure similar to that of natural blood vessels was first constructed by triple-step electrospinning technology, in which polylactic acid (PLA) and collagen (COL) were used for the inner layer, polylactic acid and polycaprolactone (PCL) was used for the middle layer and polycaprolactone and gelatin was used for the outer layer. The properties of the artificial vascular graft were adjusted by the EDC/NHS cross-linking agent through the reaction between the collagen or gelatine and EDC/NHS. The mechanical and hydrophilic properties of the cross-linked artificial vessels were substantially enhanced, with a maximum stress of 9.56 MPa in the axial direction and 9.31 MPa in the radial direction for the P/C (4:1) vascular graft, which exceeded that of many textile-based and natural vascular grafts. The increased hydrophilicity of the inner layer of the vessel before crosslinking was due to the addition of COL, and the inner layer of the artificial vessel after crosslinking had a substantial increase in hydrophilicity due to the production of a more hydrophilic urea derivative. The increased hydrophilicity led to easier cell adhesion to the inner layer of the artificial vessel, especially for the P/C (2:1) vascular graft, where the cell proliferation rate and adhesion were high due to COL incorporation and cross-linking. The three-layer vascular grafts studied did not lead to haemolysis. Therefore, the EDC/NHS cross-linked three-layer vascular graft had good mechanical properties, hydrophilicity, anticoagulation and could enhance cell adhesion and proliferation.

Association between the C-Reactive Protein-Albumin-Lymphocyte (CALLY) Index and Adverse Clinical Outcomes in CAD Patients after PCI: Findings of a Real-World Study.

Background: The C-reactive protein-albumin-lymphocyte (CALLY) index is a novel inflammatory biomarker, and its association with the prognosis of coronary artery disease (CAD) after percutaneous coronary intervention (PCI) has not previously been studied. Therefore, this study aimed to investigate the effect of using the CALLY index on adverse outcomes in CAD patients undergoing PCI. Methods: From December 2016 to October 2021, we consecutively enrolled 15,250 CAD patients and performed follow-ups for primary endpoints consisting of all-cause mortality (ACM) and cardiac mortality (CM). The CALLY index was computed using the following formula: (albumin × lymphocyte)/(C-reactive protein (CRP) × 10 4 ). The average duration of the follow-up was 24 months. Results: A total of 3799 CAD patients who had undergone PCI were ultimately enrolled in the present study. The patients were divided into four groups according to the CALLY index quartiles: Q1 ( ≤ 0.69, n = 950), Q2 (0.69-2.44, n = 950), Q3 (2.44-9.52, n = 950), and Q4 ( > 9.52, n = 949). The low-Q1 group had a significantly higher prevalence of ACM (p < 0.001), CM (p < 0.001), major adverse cardiac events (MACEs) (p = 0.002), and major adverse cardiac and cerebrovascular events (MACCEs) (p = 0.002). Kaplan-Meier analysis revealed that a low CALLY index was significantly linked with adverse outcomes. After univariate and multivariate Cox regression analysis, the risk of ACM, CM, MACEs, and MACCEs decreased by 73.7% (adjust hazard risk [HR] = 0.263, 95% CI: 0.147-0.468, p < 0.001), 70.6% (adjust HR = 0.294, 95% CI: 0.150-0.579, p < 0. 001), 37.4% (adjust HR = 0.626, 95% CI: 0.422-0.929, p = 0.010), and 41.5% (adjust HR = 0.585, 95% CI: 0.401-0.856, p = 0.006), respectively, in the Q4 quartiles compared with the Q1 quartiles. Conclusions: This study revealed that a decreased CALLY index was associated with worse prognoses for CAD patients after PCI. The categorization of patients with a decreased CALLY index could provide valuable evidence for the risk stratification of adverse outcomes in CAD patients after PCI. Clinical Trial Registration: The details are available at http://www.chictr.org.cn (Identifier: NCT05174143).

Serum 5'-Nucleotidase as a Novel Predictor of Adverse Clinical Outcomes after Percutaneous Coronary Intervention in Patients with Coronary Artery Disease.

Background: The correlation between 5 ' -Nucleotidase ( 5 ' -NT) and the clinical outcomes in coronary artery disease (CAD) patients following percutaneous coronary intervention (PCI) is not clear. This study aims to clarify this relationship. Methods: The PRACTICE study enrolled 15,250 patients between December 2016 and October 2021. After filtering out those without 5 ' -NT data, a total of 6555 patients were analyzed with a median follow-up of 24 months. Based on the receiver operating characteristic (ROC) curve analysis, a 5 ' -NT level of 5.57 U/L was selected as the optimal cutoff value. All research samples were divided into high-value ( ≥ 5.57 U/L, n = 2346) and low-value groups ( < 5.57 U/L, n = 4209). Key clinical outcomes included all-cause death (ACD), cardiovascular death (CD), major adverse cardiovascular events (MACE), and major adverse cardiovascular and cerebrovascular events (MACCE). After separating patients into high and low value groups, multivariate Cox regression analysis was used to correct for potential confounding variables. Finally, risk ratios and their 95% confidence intervals (CIs) were calculated. Results: During the follow-up period, 129 instances of ACD were recorded-49 cases (1.2%) in the low-value group and 80 cases (3.4%) in the high-value group. Similarly, 102 CDs occurred, including 42 low-value group cases (1.0%) and 60 high-value group cases (2.6%). A total of 363 MACE occurred, including 198 low-value group cases (4.7%) and 165 high-value group cases (7%). A total of 397 cases of MACCE occurred, including 227 low-value group cases (5.4%) and 170 high-value group cases (7.2%). As serum 5 ' -NT increased, the incidence of ACD, CD, MACE and MACCE increased. After multivariate Cox regression, high 5 ' -NT levels were linked with a 1.63-fold increase in ACD risk (hazard ratio [HR] = 2.630, 95% CI: [1.770-3.908], p < 0.001) when compared to low 5 ' -NT patients. Similarly, the risk of CD, MACE, and MACCE increased by 1.298-fold (HR = 2.298, 95% CI: [1.477-3.573], p < 0.001), 41% (HR = 1.410, 95% CI: [1.124-1.768], p = 0.003) and 30.5% (HR = 1.305, 95% CI: [1.049-1.623], p = 0.017), respectively. Conclusions: high serum 5 ' -NT levels were independently correlated with adverse clinical outcomes in CAD patients following PCI, affirming its potential as a prognostic indicator.

IGFBP2/ITGA5 promotes gefitinib resistance via activating STAT3/CXCL1 axis in non-small cell lung cancer.

There is a paucity of comprehensive knowledge pertaining to the underlying mechanisms leading to gefitinib resistance in individuals diagnosed NSCLC harboring EGFR-sensitive mutations who inevitably develop resistance to gefitinib treatment within six months to one year. In our preceding investigations, we have noted a marked upregulation of IGFBP2 in the neoplastic tissues of NSCLC, predominantly in the periphery of the tissue, implying its plausible significance in NSCLC. Consequently, in the current research, we delved into the matter and ascertained the molecular mechanisms that underlie the participation of IGFBP2 in the emergence of gefitinib resistance in NSCLC cells. Firstly, the expression of IGFBP2 in the bronchoalveolar lavage fluid and lung cancer tissues of 20 NSCLC patients with gefitinib tolerance was found to be significantly higher than that of non-tolerant patients. Furthermore, in vitro and in vivo experiments demonstrated that IGFBP2 plays a significant role in the acquisition of gefitinib resistance. Mechanistically, IGFBP2 can activate STAT3 to enhance the transcriptional activity of CXCL1, thereby increasing the intracellular expression level of CXCL1, which contributes to the survival of lung cancer cells in the gefitinib environment. Additionally, we identified ITGA5 as a key player in IGFBP2-mediated gefitinib resistance, but it does not function as a membrane receptor in the process of linking IGFBP2 to intracellular signaling transduction. In conclusion, this study demonstrates the promoting role and mechanism of IGFBP2 in acquired gefitinib resistance caused by non-EGFR secondary mutations, suggesting the potential of IGFBP2 as a biomarker for gefitinib resistance and a potential intervention target.

Association between extremely high prognostic nutritional index and all-cause mortality in patients with coronary artery disease: secondary analysis of a prospective cohort study in China.

OBJECTIVES: Decreased prognostic nutritional index (PNI) was associated with adverse outcomes in many clinical diseases. This study aimed to evaluate the relationship between baseline PNI value and adverse clinical outcomes in patients with coronary artery disease (CAD). DESIGN: The Personalized Antiplatelet Therapy According to CYP2C19 Genotype in Coronary Artery Disease (PRACTICE) study, a prospective cohort study of 15 250 patients with CAD, was performed from December 2016 to October 2021. The longest follow-up period was 5 years. This study was a secondary analysis of the PRACTICE study. SETTING: The study setting was Xinjiang Medical University Affiliated First Hospital in China. PARTICIPANTS: Using the 50th and 90th percentiles of the PNI in the total cohort as two cut-off limits, we divided all participants into three groups: Q1 (PNI <51.35, n = 7515), Q2 (51.35 ≤ PNI < 59.80, n = 5958) and Q3 (PNI ≥ 59.80, n = 1510). The PNI value was calculated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mm3). PRIMARY OUTCOME: The primary outcome measure was mortality, including all-cause mortality (ACM) and cardiac mortality (CM). RESULTS: In 14 983 participants followed for a median of 24 months, a total of 448 ACM, 333 CM, 1162 major adverse cardiovascular events (MACE) and 1276 major adverse cardiovascular and cerebrovascular events (MACCE) were recorded. The incidence of adverse outcomes was significantly different among the three groups (p <0.001). There were 338 (4.5%), 77 (1.3%) and 33 (2.2%) ACM events in the three groups, respectively. A restricted cubic spline displayed a J-shaped relationship between the PNI and worse 5-year outcomes, including ACM, CM, MACE and MACCE. After adjusting for traditional cardiovascular risk factors, we found that only patients with extremely high PNI values in the Q3 subgroup or low PNI values in the Q1 subgroup had a greater risk of ACM (Q3 vs Q2, HR: 1.617, 95% CI 1.012 to 2.585, p=0.045; Q1 vs Q2, HR=1.995, 95% CI 1.532 to 2.598, p <0.001). CONCLUSION: This study revealed a J-shaped relationship between the baseline PNI and ACM in patients with CAD, with a greater risk of ACM at extremely high PNI values. TRIAL REGISTRATION NUMBER: NCT05174143.

Association of CTACK, IL-2, and IL-13 with increased risk of lung cancer: A Mendelian randomization study.

BACKGROUND: In recent years, relevant studies have reported that inflammatory cytokines are related to the occurrence of cancer. However, the correlation with lung cancer is not clear. This study used the Mendelian random grouping method to investigate the correlation between inflammatory factors and lung cancer in different populations. METHODS: We obtained the single nucleotide polymorphisms (SNPs) of inflammatory cytokines through the open database and the SNPs of lung cancer (European and East Asian) through the IEU OpenGWAS project. Inverse variance-weighted (IVW) MR analyses were used to determine the causalities of exposures and outcomes. Supplementary analyses were also performed using weighted median and MR-Egger regressions. Afterward, sensitivity analyses were performed to test the robustness. Search the ChEMBL database for target drugs and indications for CTACK, IL-2, and IL-13. RESULTS: By IVW method, we found that CTACK, IL-2, and IL-13 were associated with an increased risk of lung cancer in the European population (CTACK, OR = 1.098, 95 % CI 1.001-1.204, P = 0.047; IL-2, OR = 1.112, 95 % CI 1.009-1.225, P = 0.032; IL-13, OR = 1.068, 95 % CI 1.007-1.132, P = 0.029), while only IL-13 was associated with an increased risk of lung cancer in the East Asian population (IL-13, OR = 1.110, 95 % CI 1.010-1.220, P = 0.030). The weighted median and MR-Egger regression methods were in the same direction as the IVW effect sizes. Furthermore, no evidence of multidirectionality was detected using the MR-Egger intercept as a sensitivity analysis. Currently, there are no approved or phase III studied indications for CTACK, IL-2, and IL-13 targets in lung cancer. CONCLUSION: The study outcomes supported that the inflammatory cytokines CTACK, IL-2, and IL-13 increase the risk of lung cancer. There is a lack of indications for drugs in these three targets. We explored the causal relationship between inflammatory cytokines and lung cancer, providing a basis for future cancer prediction models and targets for anti-tumor therapy.

Albumin levels and cerebral collateral circulation in patients with acute ischemic stroke due to intracranial arteriosclerotic: A propensity score-matched analysis.

Cerebral collateral circulation (CC) is associated with the recurrence and severity of acute ischemic stroke (AIS), and early identification of poor CC is helpful for the prevention of AIS. In this study we evaluated the association between serum albumin levels and CC in AIS using logistic regression. Propensity score (PS) matching was used to eliminate the effect of confounders, and restricted cubic splines (RCS) were employed to explore potential nonlinear associations between albumin and CC. In unadjusted logistic regression analysis, lower albumin (OR = 0.85, 95% CI = 0.79-0.92) was associated with poor CC, and after adjusting for covariates, the odds of lower albumin for poor CC compared to good CC were 0.86 (95% CI = 0.79-0.94). In the PS cohort, the association of albumin with CC was consistent with those of the original cohort. RCS results showed a linear relationship between albumin and CC (P values of .006 and .08 for overall and nonlinear associations, respectively). The results of this study suggest that lower serum albumin is independently associated with an increased risk of poor CC, which may serve as an effective predictive indicator for poor CC in patients with severe intracranial atherosclerotic stenosis.

Making the Complicated Simple: A Minimizing Carrier Strategy on Innovative Nanopesticides.

The flourishing progress in nanotechnology offers boundless opportunities for agriculture, particularly in the realm of nanopesticides research and development. However, concerns have been raised regarding the human and environmental safety issues stemming from the unrestrained use of non-therapeutic nanomaterials in nanopesticides. It is also important to consider whether the current development strategy of nanopesticides based on nanocarriers can strike a balance between investment and return, and if the complex material composition genuinely improves the efficiency, safety, and circularity of nanopesticides. Herein, we introduced the concept of nanopesticides with minimizing carriers (NMC) prepared through prodrug design and molecular self-assembly emerging as practical tools to address the current limitations, and compared it with nanopesticides employing non-therapeutic nanomaterials as carriers (NNC). We further summarized the current development strategy of NMC and examined potential challenges in its preparation, performance, and production. Overall, we asserted that the development of NMC systems can serve as the innovative driving force catalyzing a green and efficient revolution in nanopesticides, offering a way out of the current predicament.

iGlarLixi for type 2 diabetes: a systematic review and meta-analysis.

OBJECTIVES: To assess the efficacy and tolerability of iGlarLixi-a novel, fixed-ratio, soluble combination of insulin glargine and lixisenatide-for the treatment of type 2 diabetes (T2D). METHODS: The PubMed, Embase, Cochrane Library and ClinicalTrials.gov databases were searched from inception to November 15, 2023 to identify randomized controlled trials (RCTs) comparing iGlarLixi with a placebo or any other antidiabetic agent in adults with T2D. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated to evaluate the outcomes. RESULTS: A total of 10 trials enrolling 6071 T2D patients were included. Compared with placebos or other antidiabetic agents, iGlarLixi exerted beneficial effects on changes in HbA1c, the percentage of patients who achieved an HbA1c < 7%, the percentage of patients who achieved an HbA1c < 6.5%, the percentage of patients who achieved an HbA1c < 7.0% without weight gain and/or without severe or blood glucose-confirmed hypoglycemic episodes, changes in fasting plasma glucose, and changes in self-measured plasma glucose. Regarding safety, iGlarLixi did not increase the incidence of severe hypoglycemia or serious adverse events but did increase the incidence of gastrointestinal adverse events, symptomatic hypoglycemia, and adverse events (e.g., nausea, vomiting, diarrhea). CONCLUSIONS: iGlarLixi showed improved efficacy and safety in patients with T2D. Additional large, multicenter RCTs are warranted to obtain deeper insights into the efficacy and safety of iGlarLixi, thereby providing guidance for clinical treatment decisions.

The Simplified Thrombo-Inflammatory Score as a Novel Predictor of All-Cause Mortality in Patients with Heart Failure: A Retrospective Cohort Study.

Background: The simplified thrombo-inflammatory score (sTIPS) has recently emerged as a novel prognostic score. Hence, we investigated the prognostic value of sTIPS for predicting long-term mortality in patients with heart failure (HF). Methods: A total of 3741 patients were analyzed in this study. The sTIPS was calculated based on the white blood cell count (WBC) and the mean platelet volume to platelet count (MPV/PC) ratio at admission. The mean follow-up time was 22.75 months. Multivariable Cox regression analyses were used to investigate the associations between the sTIPS and all-cause mortality (ACM). Results: In the whole study population, multivariate Cox regression analysis showed that patients in both the sTIPS 2 and sTIPS 1 groups had significantly increased risk of ACM as compared with patients in the sTIPS 0 group (hazard ratio [HR]=1.706, 95% confidence interval [CI]: 1.405-2.072, P<0.001 and HR = 1.431, 95% CI 1.270-1.612, P<0.001). The same significant trend was observed in heart failure with preserved ejection fraction (HFpEF) patients (sTIPS1 vs sTIPS0: HR = 1.366, 95% CI 1.100-1.697, P = 0.005; sTIPS2 vs sTIPS0: HR = 1.995, 95% CI 1.460-2.725, P<0.001). However, only sTIPS 1 group had a significantly increased the risk of ACM compared to the sTIPS 0 group among patients with HFmrEF (sTIPS1 vs sTIPS0: HR = 1.648, 95% CI 1.238-2.194, P = 0.001) and HFrEF (sTIPS1 vs sTIPS0: HR = 1.322, 95% CI 1.021-1.712, P = 0.035). Conclusion: sTIPS is useful in predicting risk for long-term mortality in patients with HF.

Synthesis, optical properties, and application of novel chalcone skeleton as pH fluorescent probe: Based AIE + ESIPT strategy.

A series of "turn off" pH fluorescence probes with chalcone skeleton for basic system have been developed. The molecules emitted bright yellow fluorescence under acidic condition, resulting AIE coupled ESIPT characteristic and ICT process. What's more, the compounds exhibited excellent sensitivity and selectivity for detecting pH as a facile "On-Off" fluorescence probe, and the fluorescence of them were quenched with the ESIPT process interrupted under alkaline condition. Theoretical calculation for the related compounds also performed to verify the electron effect on photophysical properties and confirm the rational speculation on the mechanism.

A defect-enriched PdMo bimetallene for ethanol oxidation reaction and 4-nitrophenol reduction.

A defect-enriched PdMo bimetallene (d-PdMo) was prepared by a one-pot wet chemical reaction followed by post-treatment of oxidative etching. The introduction of defects can tailor the electronic structure of PdMo bimetallene and the prepared d-PdMo bimetallene exhibited excellent performance in the ethanol oxidation reaction (EOR) and 4-nitrophenol (4-NP) reduction reaction.