Associations of heavy metal exposure with diabetic retinopathy in the U.S. diabetic population: a cross-sectional study.

Background: Mounting evidence suggests a correlation between heavy metals exposure and diabetes. Diabetic retinopathy (DR) is a prevalent and irreversible complication of diabetes that can result in blindness. However, studies focusing on the effects of exposure to heavy metals on DR remain scarce. Thus, this study aimed to investigate the potential correlation between heavy metals exposure and DR. Methods: A total of 1,146 diabetics from the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018 were included in this study. Heavy metal levels were measured via urine testing. Weighted logistic regression, Bayesian kernel machine regression (BKMR), weighted quantile sum (WQS) regression, and restricted cubic spline (RCS) were utilized to investigate the potential relationships between exposure to 10 heavy metals and DR. Finally, subgroup analysis was conducted based on the glycemic control status. Results: Among the 1,146 participants, 239 (20.86%) were diagnosed with DR. Those with DR had worse glycemic control and a higher prevalence of chronic kidney disease compared to those without DR. Moreover, both the WQS regression and BKMR models demonstrated a positive relationship between exposure to mixed heavy metals and the risk of DR. The results of weighted logistic regression revealed a positive correlation between cobalt (Co) and antimony (Sb) exposure and the risk of DR (OR = 1.489, 95%CI: 1.064-2.082, p = 0.021; OR = 1.475, 95% CI: 1.084-2.008, p = 0.014), while mercury (Hg) exposure was found to promote DR exclusively in the group with good glycemic control (OR = 1.509, 95% CI: 1.157-1.967, p = 0.003). These findings were corroborated by the results of the RCS analysis. Conclusion: Heavy metal exposure is associated with an increased risk of DR, especially Sb, Co, and Hg exposure. Nevertheless, well-designed prospective studies are warranted to validate these findings.

Deciphering the interplay of HPV infection, MHC-II expression, and CXCL13+ CD4+ T cell activation in oropharyngeal cancer: implications for immunotherapy.

BACKGROUND: Human papillomavirus (HPV) infection has become an important etiological driver of oropharyngeal squamous cell carcinoma (OPSCC), leading to unique tumor characteristics. However, the interplay between HPV-associated tumor cells and tumor microenvironment (TME) remains an enigma. METHODS: We performed a single-cell RNA-sequencing (scRNA-seq) on HPV-positive (HPV+) and HPV-negative (HPV‒) OPSCC tumors, each for three samples, and one normal tonsil tissue. Ex vivo validation assays including immunofluorescence staining, cell line co-culture, and flow cytometry analysis were used to test specific subtypes of HPV+ tumor cells and their communications with T cells. RESULTS: Through a comprehensive single-cell transcriptome analysis, we uncover the distinct transcriptional signatures between HPV+ and HPV‒ OPSCC. Specifically, HPV+ OPSCC tumor cells manifest an enhanced interferon response and elevated expression of the major histocompatibility complex II (MHC-II), potentially bolstering tumor recognition and immune response. Furthermore, we identify a CXCL13+CD4+ T cell subset that exhibits dual features of both follicular and pro-inflammatory helper T cells. Noteworthily, HPV+ OPSCC tumor cells embrace extensive intercellular communications with CXCL13+CD4+ T cells. Interaction with HPV+ OPSCC tumor cells amplifies CXCL13 and IFNγ release in CD4+T cells, fostering a pro-inflammatory TME. Additionally, HPV+ tumor cells expressing high MHC-II and CXCL13+CD4+ T cell prevalence are indicative of favorable overall survival rates in OPSCC patients. CONCLUSIONS: Together, our study underscores a synergistic inflammatory immune response orchestrated by highly immunogenic tumor cells and CXCL13+CD4+ T cells in HPV+ OPSCC, offering useful insights into strategy development for patient stratification and effective immunotherapy in OPSCC.

Unveiling the innovative green synthesis mechanism of selenium nanoparticles by exploiting intracellular protein elongation factor Tu from Bacillus paramycoides. / 利用Bacillus paramycoidesç»†èƒžå† è›‹ç™½å»¶ä¼¸å› å­Tu揭示硒纳米颗粒的创新绿色合成机制.

Selenium nanoparticles (SeNPs) have garnered extensive research interest and shown promising applications across diverse fields owing to their distinctive properties, including antioxidant, anticancer, and antibacterial activity (Ojeda et al., 2020; Qu et al., 2023; Zambonino et al., 2021, 2023). Among the various approaches employed for SeNP synthesis, green synthesis has emerged as a noteworthy and eco-friendly methodology. Keshtmand et al. (2023) underscored the significance of green-synthesized SeNPs, presenting a compelling avenue in this domain. This innovative strategy harnesses the potential of natural resources, such as plant extracts or microorganisms, to facilitate the production of SeNPs.

Prevalence and Risk Factors of Ocular Demodex at Ultra-High Altitude and Sea Level: A Cross-Sectional Study of Shigatse and Shanghai.

Purpose: Demodex infestation is a risk factor for several ocular surface diseases. However, the prevalence of ocular Demodex infection in the ultra-high altitude population is not clear. This study aimed to compare the prevalence and factors associated with Demodex in populations residing in ultra-high altitude region and sea level areas. Methods: Consecutive patients who visited Shigatse People's Hospital (> 4,000 m) and Shanghai Tongren Hospital (sea level) for eye complaints between January 2023 and January 2024 were included. Subjects were divided into ultra-high altitude and sea level groups. All subjects underwent eyelash epilation for ocular Demodex identification and counting. Demographic and lifestyle information was also collected. Results: A total of 517 subjects were eligible, including 255 subjects in the ultra-high-altitude group and 262 subjects in the sea level group. In the overall analysis, the prevalence of ocular Demodex infection was significantly different between the ultra-high-altitude and sea level groups (15.7% vs. 33.2%, P < 0.001). Multiple logistic regression showed that age, time spent outdoors, and makeup were associated with ocular Demodex infection in both groups. In addition, in the ultra-high-altitude group, people who wear sun hats outdoors were more likely to be infected with Demodex. Conclusion: The infection rate of ocular Demodex in the residents of ultra-high altitude area was significantly lower than that in the residents of sea level area, which may be related to lower ambient temperature, lower humidity, and higher solar radiation. Additionally, age, time spent outdoors, and makeup may be associated with ocular Demodex infection.

Insufficient Plasma Melatonin and Its Association With Neuropsychiatric Impairments in Patients With T2DM.

Purpose: Type 2 diabetes mellitus (T2DM) is associated with multiple neuropsychiatric impairments, including cognitive dysfunction, and melatonin (MLT) plays a crucial role in maintaining normal neuropsychiatric functions. This study is aimed at investigating the change in plasma MLT levels and its association with neuropsychiatric impairments in T2DM patients. Methods: One hundred twenty-six T2DM patients were recruited, and their demographics and clinical data were collected. Apart from the plasma glycated hemoglobin (HbA1c) levels and other routine metabolic indicators, the plasma concentrations of MLT, C-reactive protein (CRP), Interleukin 6 (IL-6), soluble myeloid triggered receptor 1 (sTREM 1), and receptor 2 (sTREM 2) were measured. Moreover, the executive function and depressive tendency were evaluated via the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) and the Epidemiological Research Center Depression Scale (CES-D), respectively. Result: Compared with the low HbA1c group, the T2DM patients in the high HbA1c group presented lower plasma MLT levels but higher plasma concentrations of inflammatory biomarker levels, together with higher scores in the BRIEF-A and CES-D scales. Moreover, results of the Pearson correlation test showed that the plasma MLT levels were negatively correlated with the BRIEF-A and CES-D scores, as well as plasma concentrations of HbA1c and inflammatory indications, indicating that MLT may mediate their neuroinflammation and neuropsychiatric impairments. Furthermore, the ROC curve results indicated that plasma MLT levels have a predictive effect on executive impairment and depressive status in T2DM patients. Conclusion: MLT levels decreased in patients with T2DM and were associated with neuropsychiatric impairments and inflammatory status, and MLT might be developed as a therapeutic agent and predictive indicator for T2DM-associated executive impairment and depression status.

MiR-196a-5p hinders vascular smooth muscle cell proliferation and vascular remodeling via repressing BACH1 expression.

Hyperproliferation of vascular smooth muscle cells (VSMCs) is a driver of hypertensive vascular remodeling. This study aimed to uncover the mechanism of BTB and CNC homology 1 (BACH1) and microRNAs (miRNAs) in VSMC growth and hypertensive vascular remodeling. With the help of TargetScan, miRWalk, miRDB, and miRTarBase online database, we identified that BACH1 might be targeted by miR-196a-5p, and overexpressed in VSMCs and aortic tissues from spontaneously hypertensive rats (SHRs). Gain- and loss-of-function experiments demonstrated that miR-196a-5p suppressed VSMC proliferation, oxidative stress and hypertensive vascular remodeling. Double luciferase reporter gene assay and functional verification showed that miR-196a-5p cracked down the transcription and translation of BACH1 in both Wistar Kyoto rats (WKYs) and SHRs. Silencing BACH1 mimicked the actions of miR-196a-5p overexpression on attenuating the proliferation and oxidative damage of VSMCs derived from SHRs. Importantly, miR-196a-5p overexpression and BACH1 knockdown cooperatively inhibited VSMC proliferation and oxidative stress in SHRs. Furthermore, miR-196a-5p, if knocked down in SHRs, aggravated hypertension, upregulated BACH1 and promoted VSMC proliferation, all contributing to vascular remodeling. Taken together, targeting miR-196a-5p to downregulate BACH1 may be a promising strategy for retarding VSMC proliferation and hypertensive vascular remodeling.

Edible CO2-Responsive Wormlike Micelles with Docosahexaenoic Acid.

Due to their unique microstructure and modifiable rheological properties, wormlike micelles that respond to environmental stimulation have garnered significant interest in recent years. Among them, CO2-responsive wormlike micelles have the advantages of simple preparation and controllable properties, which have significant development potential in the food chemistry field of thickeners. In this study, CO2-responsive wormlike micelles were prepared using docosahexaenoic acid (DHA), pyridoxamine (PA), and glucosamine (GA); the stimulus-responsive behaviors and mechanisms of the two systems, namely, NaDHA/PA and NaDHA/GA, were investigated using dynamic light scattering (DLS) and cryo-transmission electron microscopy (Cryo-TEM). The nearly unaltered viscosity of the systems confirmed the cyclic reversibility of the CO2 response of the two systems when the two mixed solutions were converted back to aqueous liquids 10 times. The preparation and properties of DHA-based CO2-responsive wormlike micelles are expected to advance fundamental research and establish the theoretical groundwork for their practical application in controllable thickening agents in food chemistry.

Sophoricoside ameliorates methicillin-resistant Staphylococcus aureus-induced acute lung injury by inhibiting Bach1/Akt pathway.

BACKGROUND: The lack of effective treatments for methicillin-resistant Staphylococcus aureus (MRSA) infection, which often leads to severe acute lung injury (ALI), poses a grave threat to human life. Sophoricoside (SOP), an isoflavone glycoside abundant in the fruit of traditional Chinese herbal Sophora japonica l., showed anti-inflammatory effects against atopic dermatitis, allergic inflammation, and lipopolysaccharide-induced ALI. However, its effect and underlying mechanism on MRSA-induced ALI remain unclear. PURPOSE: The aim of this study is to assess the protective effect of SOP in MRSA-induced ALI and elucidate its underlying molecular mechanisms. METHODS: In vivo experiments were conducted using wild-type mice to establish MRSA-induced ALI mouse model, and the effects of SOP on ALI were evaluated by hematoxylin-eosin staining, flow cytometry, quantitative real-time polymerase chain reaction, and several biochemical indicators. Adoptive transfer experiments and BTB and CNC homology 1 knockout (Bach1-/-) mice were also utilized in this study. In vitro studies employed murine macrophages RAW264.7 cells, primary bone marrow-derived macrophages (BMDMs), and primary lung macrophages to explore the underlying molecular mechanisms. RESULTS: The administration of SOP ameliorated MRSA-induced ALI by improving pulmonary histological damages, reducing neutrophil infiltration, suppressing oxidative stress levels, and decreasing the expression of inflammatory cytokines. In isolation experiments with ALI mouse lung macrophages and macrophage adoptive transfer experiments, SOP prevented macrophage activation, thereby reducing the production of proinflammatory cytokines. In vitro experiments demonstrated that SOP decreased the expression of inflammatory mediators in lipoteichoic acid (LTA)-stimulated RAW264.7 cells, BMDMs, and primary lung macrophages. Additionally, SOP inhibited protein kinase B (Akt) phosphorylation and treatment with MK2206-a specific inhibitor of Akt-eliminated SOP's ability to suppress LTA-stimulated macrophage inflammation. Furthermore, stimulation with LTA or MRSA up-regulated Bach1 expression; however, deletion of Bach1 abolished the inhibitory effect of SOP on p-Akt activation as well as inflammation and ALI development. CONCLUSION: This study provides the first evidence that SOP effectively mitigates MRSA-induced ALI via suppressing macrophage activation through the inhibition of Bach1/Akt pathway. These findings highlight the potential of SOP as a novel therapeutic agent for treating MRSA-induced ALI.

Neuroprotective effects of chlorogenic acid: Modulation of Akt/Erk1/2 signaling to prevent neuronal apoptosis in Parkinson's disease.

As a prevalent neurodegenerative disorder, Parkinson's disease is associated with oxidative stress. Our recent investigations revealed that reactive oxygen species (ROS) and PD-toxins like 6-hydroxydopamine (6-OHDA) can induce neuronal apoptosis through over-activation of Akt signaling. Chlorogenic acid (CGA), a natural acid phenol abundant in the human diet, is well-documented for its ability to mitigate intracellular ROS. In this study, we utilized CGA to treat experimental models of PD both in vitro and in vivo. Our study results demonstrated that SH-SY5Y and primary neurons exhibited cell apoptosis in response to 6-OHDA. Pretreatment with CGA significantly attenuated PD toxins-induced large amount of ROS, inhibiting Erk1/2 activation, preventing Akt inhibition, and hindering neuronal cell death. Combining the Erk1/2 inhibitor U0126 with CGA could reverse 6-OHDA-induced Akt inhibition, ROS, and apoptosis in the cells. Crucially, the Akt activator SC79 and ROS scavenger NAC both could eliminate excessive ROS via Akt and Erk1/2 signaling pathways, and CGA further potentiated these effects in PD models. Behavioral experiments revealed that CGA could alleviate gait abnormalities in PD model mice. The neuroprotective effects have been demonstrated in several endocrine regions and in the substantia nigra tissue, which shows the positive tyrosine hydroxylase (TH). Overall, our results suggest that CGA prevents the activation of Erk1/2 and inactivation of Akt by removing excess ROS in PD models. These findings propose a potential strategy for mitigating neuronal degeneration in Parkinson's disease by modulating the Akt/Erk1/2 signaling pathway through the administration of CGA and/or the use of antioxidants to alleviate oxidative stress.

A positive feedback loop between PLD1 and NF-κB signaling promotes tumorigenesis of nasopharyngeal carcinoma.

Phospholipase D (PLD) lipid-signaling enzyme superfamily has been widely implicated in various human malignancies, but its role and underlying mechanism remain unclear in nasopharyngeal carcinoma (NPC). Here, we analyze the expressions of 6 PLD family members between 87 NPC and 10 control samples through transcriptome analysis. Our findings reveal a notable upregulation of PLD1 in both NPC tumors and cell lines, correlating with worse disease-free and overall survival in NPC patients. Functional assays further elucidate PLD1's oncogenic role, demonstrating its pivotal promotion of critical tumorigenic processes such as cell proliferation and migration in vitro, as well as tumor growth in vivo. Notably, our study uncovers a positive feedback loop between PLD1 and the NF-κB signaling pathway to render NPC progression. Specifically, PLD1 enhances NF-κB activity by facilitating the phosphorylation and nuclear translocation of RELA (p65), which in turn binds to the promoter of PLD1, augmenting its expression. Moreover, RELA overexpression significantly rescues the inhibitory effects in PLD1-depleted NPC cells. Importantly, the application of the PLD1 inhibitor, VU0155069, significantly inhibits NPC tumorigenesis in a patient-derived xenograft model. Together, our findings identify PLD1/NF-κB signaling as a positive feedback loop with promising therapeutic and prognostic potential in NPC.

New Model and Public Online Prediction Platform for Risk Stratification of Vocal Cord Leukoplakia.

OBJECTIVE: To extract texture features from vocal cord leukoplakia (VCL) images and establish a VCL risk stratification prediction model using machine learning (ML) techniques. METHODS: A total of 462 patients with pathologically confirmed VCL were retrospectively collected and divided into low-risk and high-risk groups. We use a 5-fold cross validation method to ensure the generalization ability of the model built using the included dataset and avoid overfitting. Totally 504 texture features were extracted from each laryngoscope image. After feature selection, 10 ML classifiers were utilized to construct the model. The SHapley Additive exPlanations (SHAP) was employed for feature analysis. To evaluate the model, accuracy, sensitivity, specificity, and the area under the receiver operating characteristic (ROC) curve (AUC) were utilized. In addition, the model was transformed into an online application for public use and further tested in an independent dataset with 52 cases of VCL. RESULTS: A total of 12 features were finally selected, random forest (RF) achieved the best model performance, the mean accuracy, sensitivity, specificity, and AUC of the 5-fold cross validation were 92.2 ± 4.1%, 95.6 ± 4.0%, 85.8 ± 5.8%, and 90.7 ± 4.9%, respectively. The result is much higher than the clinicians (AUC between 63.1% and 75.2%). The SHAP algorithm ranks the importance of 12 texture features to the model. The test results of the additional independent datasets were 92.3%, 95.7%, 90.0%, and 93.3%, respectively. CONCLUSION: The proposed VCL risk stratification prediction model, which has been developed into a public online prediction platform, may be applied in practical clinical work. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

TTYH3 promotes the malignant progression of oral squamous cell carcinoma SCC-9 cells by regulating tumor-associated macrophage polarization.

OBJECTIVE: This study was designed to investigate the biological role and the reaction mechanism of Tweety family member 3 (TTYH3) in oral squamous cell carcinoma (OSCC). DESIGN: The mRNA and protein expressions of TTYH3 were assessed with RT-qPCR and western blot. After silencing TTYH3 expression, the proliferation of OSCC cells were detected using cell counting kit-8 (CCK-8) assay, 5-ethynyl-2'-deoxyuridine (EdU) staining and colony formation assay. Cell migration and invasion were detected using wound healing and transwell. Gelatin zymography protease assay was used to detect matrix metalloproteinase-2 (MMP2) and matrix metalloproteinase-2 (MMP9) activity and western blot was used to detect the expressions of proteins associated with proliferation and epithelial-mesenchymal transition (EMT). The mRNA expression of TTYH3 in THP-1-derived macrophage was detected using real-time reverse transcriptase-polymerase chain reaction (RT-qPCR). The number of CD86-positive cells and CD206-positive cells was detected using immunofluorescence assay. RT-qPCR was used to detect the expressions of M2 markers arginase 1 (ARG1), chitinase-like 3 (YM1) and mannose receptor C-type 1 (MRC1). RESULTS: In this study, it was found that TTYH3 expression was upregulated in OSCC cell lines and TTYH3 knockdown could inhibit the proliferation, migration, invasion and EMT process in OSCC via suppressing M2 polarization of tumor-associated macrophages. CONCLUSIONS: Collectively, TTYH3 facilitated the progression of OSCC through the regulation of tumor-associated macrophages polarization.

Role of Thiamine Supplementation in the Treatment of Chronic Heart Failure: An Updated Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Chronic heart failure (CHF) has always posed a significant threat to human survival and health. The efficacy of thiamine supplementation in CHF patients remains uncertain. HYPOTHESIS: Receiving supplementary thiamine may not confer benefits to patients with CHF. METHODS: A comprehensive search was conducted across the Cochrane Library, PubMed, EMBASE, ClinicalTrials.gov, and Web of Science databases up until May 2023 to identify articles investigating the effects of thiamine supplementation in CHF patients. Predefined criteria were utilized for selecting data on study characteristics and results. RESULTS: Seven randomized, double-blind, controlled trials (five parallel trials and two crossover trials) involving a total of 274 patients were enrolled. The results of the meta-analysis pooling these studies did not reveal any significant effect of thiamine treatment compared with placebo on left ventricular ejection fraction (WMD = 1.653%, 95% CI:  -1.098 to 4.405, p = 0.239, I2 = 61.8%), left ventricular end-diastolic volume (WMD = -6.831 mL, 95% CI:  -26.367 to 12.704, p = 0.493, I2 = 0.0%), 6-min walking test (WMD = 16.526 m, 95% CI:  -36.582 to 69.634, p = 0.542, I2 = 66.3%), N-terminal pro-B type natriuretic peptide (WMD = 258.150 pg/mL, 95% CI:  -236.406 to 752.707, p = 0.306, I2 = 21.6%), or New York Heart Association class (WMD = -0.223, 95% CI:  -0.781 to 0.335, p = 0.434, I2 = 87.1%). However, it effectively improved the status of thiamine deficiency (TD). CONCLUSIONS: Our meta-analysis indicates that thiamine supplementation does not have a direct therapeutic effect on CHF, except for correcting TD.

The Mitochondrial-Derived Peptide MOTS-c Alleviates Radiation Pneumonitis via an Nrf2-Dependent Mechanism.

Radiation pneumonitis (RP) is a prevalent and fatal complication of thoracic radiotherapy due to the lack of effective treatment options. RP primarily arises from mitochondrial injury in lung epithelial cells. The mitochondrial-derived peptide MOTS-c has demonstrated protective effects against various diseases by mitigating mitochondrial injury. C57BL/6 mice were exposed to 20 Gy of lung irradiation (IR) and received daily intraperitoneal injections of MOTS-c for 2 weeks. MOTS-c significantly ameliorated lung tissue damage, inflammation, and oxidative stress caused by radiation. Meanwhile, MOTS-c reversed the apoptosis and mitochondrial damage of alveolar epithelial cells in RP mice. Furthermore, MOTS-c significantly inhibited oxidative stress and mitochondrial damage in MLE-12 cells and primary mouse lung epithelial cells. Mechanistically, MOTS-c increased the nuclear factor erythroid 2-related factor (Nrf2) level and promoted its nuclear translocation. Notably, Nrf2 deficiency abolished the protective function of MOTS-c in mice with RP. In conclusion, MOTS-c alleviates RP by protecting mitochondrial function through an Nrf2-dependent mechanism, indicating that MOTS-c may be a novel potential protective agent against RP.

Infection with COVID-19 Complicated by Sinus Arrest.

As a respiratory tract-transmitted disease, coronavirus disease 2019 (COVID-19) exerts a profound immune injury effect, leading not only to pulmonary impairment but also to cardiac complications. We present a case of a 79-year-old woman, who had previously contracted COVID-19 and subsequently developed sinus arrest (SA) following her second infection. The longest asystole time detected by Holter monitoring was 7.2 seconds. Although the patient met criteria for permanent pacemaker implantation, her family declined this intervention and conservative management was pursued instead. However, after a period of observation, the patient's SA resolved. The present case study describes a patient who experienced SA upon reinfection with COVID-19, which was not present during the initial infection. It emphasizes the impact of COVID-19 on cardiac health, particularly its potential to induce arrhythmias. In addition, it is worth noting that the arrhythmia induced by a COVID-19 infection may show reversibility, suggesting that a permanent pacemaker might not be the priority option if further pacing therapy is being considered.

Efficacy and Safety of Interleukin-1 Inhibitors in the Management of Patients with Recurrent Pericarditis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The efficacy and safety of interleukin-1 (IL-1) inhibitors in patients with recurrent pericarditis (RP) remain to be determined. OBJECTIVE: We aimed to conduct a meta-analysis to investigate the impact of IL-1 inhibitors on patients suffering from RP. METHODS: The Cochrane Library, PubMed, EMBASE, ClinicalTrials.gov, and Web of Science databases were systematically searched to identify articles investigating the effects of IL-1 inhibitors in patients with RP up until January 2024. Relevant data on study characteristics and results were selected based on predefined criteria. The results were combined using a random effects model. RESULTS: The study included a total of 102 patients from three open-label randomized controlled trials. Overall, the use of IL-1 inhibitors, in comparison to placebo, demonstrated a significant reduction in the risk of pericarditis recurrence [risk ratio (RR) 0.13; 95% confident interval (CI) 0.05-0.30; p < 0.05; I2 = 0%]. However, the administration of IL-1 inhibitors may lead to certain adverse events (AEs), including infections and injection-site reactions. The risk of AEs is significantly higher with IL-1 inhibitors compared with placebo (RR 1.88; 95% CI 1.30-2.72; p < 0.05; I2 = 0%). Nevertheless, the occurrence of serious AEs among patients was relatively rare, and no fatalities were reported. CONCLUSION: This meta-analysis showed that IL-1 inhibitors can effectively reduce the risk of recurrence in patients with RP and are relatively safe. REGISTRATION: PROSPERO identifier number CRD42023492904.

The Role of Angiotensin II Receptor Blockers in the Management of Hypertrophic Cardiomyopathy: An Updated Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: The use of angiotensin II receptor blockers (ARBs) in the treatment of hypertrophic cardiomyopathy (HCM) remains a subject of controversy. METHODS: We conducted a comprehensive search of the Cochrane Library, PubMed, EMBASE, ClinicalTrials.gov, and Web of Science databases until October 2023 to identify articles investigating the effects of ARBs in patients diagnosed with HCM. Predefined criteria were utilized for selecting data on study characteristics and results. RESULTS: The study included a total of 387 patients from 6 randomized controlled trials, which were reported in 7 articles. The results of the meta-analysis revealed that the utilization of ARBs did not yield a reduction in left ventricular (LV) mass (p = 0.07) and maximum LV wall thickness (p = 0.25), nor did it demonstrate any improvement in LV fibrosis (p = 0.39). Furthermore, there was no significant impact observed on early diastolic mitral annular velocity (p = 0.19) and LV ejection fraction (p = 0.44). CONCLUSIONS: The administration of ARBs does not appear to yield improvements in cardiac structure, function, and myocardial fibrosis in patients with HCM.

Therapeutic efficacy of a novel self-assembled immunostimulatory siRNA combining apoptosis promotion with RIG-I activation in gliomas.

BACKGROUND: Current cancer therapies often fall short in addressing the complexities of malignancies, underscoring the urgent need for innovative treatment strategies. RNA interference technology, which specifically suppresses gene expression, offers a promising new approach in the fight against tumors. Recent studies have identified a novel immunostimulatory small-interfering RNA (siRNA) with a unique sequence (sense strand, 5'-C; antisense strand, 3'-GGG) capable of activating the RIG-I/IRF3 signaling pathway. This activation induces the release of type I and III interferons, leading to an effective antiviral immune response. However, this class of immunostimulatory siRNA has not yet been explored in cancer therapy. METHODS: IsiBCL-2, an innovative immunostimulatory siRNA designed to suppress the levels of B-cell lymphoma 2 (BCL-2), contains a distinctive motif (sense strand, 5'-C; antisense strand, 3'-GGG). Glioblastoma cells were subjected to 100 nM isiBCL-2 treatment in vitro for 48 h. Morphological changes, cell viability (CCK-8 assay), proliferation (colony formation assay), migration/invasion (scratch test and Transwell assay), apoptosis rate, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) were evaluated. Western blotting and immunofluorescence analyses were performed to assess RIG-I and MHC-I molecule levels, and ELISA was utilized to measure the levels of cytokines (IFN-ß and CXCL10). In vivo heterogeneous tumor models were established, and the anti-tumor effect of isiBCL-2 was confirmed through intratumoral injection. RESULTS: IsiBCL-2 exhibited significant inhibitory effects on glioblastoma cell growth and induced apoptosis. BCL-2 mRNA levels were significantly decreased by 67.52%. IsiBCL-2 treatment resulted in an apoptotic rate of approximately 51.96%, accompanied by a 71.76% reduction in MMP and a 41.87% increase in ROS accumulation. Western blotting and immunofluorescence analyses demonstrated increased levels of RIG-I, MAVS, and MHC-I following isiBCL-2 treatment. ELISA tests indicated a significant increase in IFN-ß and CXCL10 levels. In vivo studies using nude mice confirmed that isiBCL-2 effectively impeded the growth and progression of glioblastoma tumors. CONCLUSIONS: This study introduces an innovative method to induce innate signaling by incorporating an immunostimulatory sequence (sense strand, 5'-C; antisense strand, 3'-GGG) into siRNA, resulting in the formation of RNA dimers through Hoogsteen base-pairing. This activation triggers the RIG-I signaling pathway in tumor cells, causing further damage and inducing a potent immune response. This inventive design and application of immunostimulatory siRNA offer a novel perspective on tumor immunotherapy, holding significant implications for the field.

Luminescence properties and energy transfer of broadband NIR phosphor Li2MgZrO4: 1.0%Cr3+, y%Yb3.

The discovery of high thermal stability, broad-band near-infrared (NIR) fluorescent phosphors holds significant potential in applications such as non-destructive testing, promoting plant growth, and night vision devices. In this study, a novel broad-band NIR phosphors Li2MgZrO4 (LMZ): 1.0 %Cr3+, y%Yb3+ were synthesized via a high-temperature solid-state reaction method, with the optimal doping concentration found to be y = 1.5. These phosphors exhibited broad NIR emission in the range of 700-1050 nm by effective energy transfer from Cr3+ to Yb3+. The maximum full width at half maximum (FWHM) of the Cr3+/Yb3+ co-doped LMZ phosphor is 270 nm. The thermal stability of the phosphors was improved with Yb3+ co-doping. Additionally, energy transfer from Cr3+ to Yb3+ was confirmed through luminescence spectra and lifetime analysis. Finally, NIR pc-LED devices composed of a 460 nm ultraviolet chip and LMZ: 1.0 %Cr3+, 1.5 %Yb3+ phosphors were fabricated, offering a highly promising source of invisible light. These results demonstrate the wide-ranging potential applications of this novel, high thermal stability, and ultra-broad NIR emitting fluorescent phosphor.

Cellulose-based materials in environmental protection: A scientometric and visual analysis review.

As sustainable materials, cellulose-based materials have attracted significant attention in the field of environmental protection, resulting in the publication of numerous academic papers. However, there is a scarcity of literature that involving scientometric analysis within this specific domain. This review aims to address this gap and highlight recent research in this field by utilizing scientometric analysis and a historical review. As a result, 21 highly cited articles and 10 mostly productive journals were selected out. The scientometric analysis reveals that recent studies were objectively clustered into five interconnected main themes: extraction of cellulose from raw materials and its degradation, adsorption of pollutants using cellulose-based materials, cellulose-acetate-based membrane materials, nanocellulose-based materials, and other cellulose-based materials such as carboxymethyl cellulose and bacterial cellulose for environmental protection. Analyzing the distribution of author keywords and thoroughly examining relevant literature, the research focuses within these five themes were summarized. In the future, the development of eco-friendly and cost-effective methods for extracting and preparing cellulose and its derivatives, particularly nanocellulose-based materials, remains an enduring pursuit. Additionally, machine learning techniques holds promise for the advancement and application of cellulose-based materials. Furthermore, there is potential to expand the research and application scope of cellulose-based materials for environmental protection.