Broadband generation of a multi-polarization multi-beam using a receiving-transmitting metasurface.

Generating multiple beams in distinct polarization states is promising in multi-mode wireless communication but still remains challenging in metasurface design. Here, we theoretically and experimentally demonstrate a concept of broadband receiving-transmitting metasurface and its application to the generation of multi-polarization multi-beam. By employing U-slot patch, an efficient receiving-transmitting element with full phase coverage is designed within a wide bandwidth. Based on this architecture, a methodology is proposed to generate dual spin-decoupled beams and then developed into the strategy of generating multiple beams at different linear polarizations. To verify our strategy, two lens antennas, respectively radiating dual-spin dual-beam and quad-polarization quad-beam, are devised. With multi-polarization multi-beam radiated, the two lens antennas are both with whole aperture efficiency above 40% within the bandwidth of 10.6-12.3 GHz (14.8%), firmly validating our strategy and design.

MOF-Derived Oxygen-Deficient Titania-Mediated Photodynamic/Photothermal-Enhanced Immunotherapy for Tumor Treatment.

Immunotherapy has emerged as a revolutionizing therapeutic modality for cancer. However, its efficacy has been largely limited by a weak immune response and an immunosuppressive tumor microenvironment. Herein, we report a metal-organic framework (MOF)-derived titanium oxide nanoparticle (MCTx NP) as an immune booster that can greatly improve the immunotherapy efficacy by inducing "immunogenic cell death" (ICD) and remodeling the tumor microenvironment. The NPs, inheriting the characteristic structure of MIL-125 and enriched with oxygen vacancies (OVs), demonstrate both high photothermal conversion efficiency and a reactive oxygen species (ROS) generation yield upon near-infrared (NIR) activation. Moreover, the NPs can release O2 and reduce glutathione (GSH) in the tumor environment, showcasing their potential to reverse the immunosuppressive microenvironment. In vitro/vivo results demonstrate that MCTx NPs directly kill tumor cells and effectively eliminate primary tumors by exerting dual photodynamic/photothermal therapy under a single NIR irritation. At the same time, MCTx NPs augment the PD-L1 blockade efficacy by potently inducing ICDs and reversing the immunosuppressive tumor microenvironment, including promoting dendritic cell (DC) maturation, decreasing regulatory T cells (Tregs)' infiltration, and increasing cytotoxic T lymphocytes (CTLs) and helper T cells (Ths), resulting in effective distant tumor suppression. This work highlights MCTx NP-mediated photodynamic- and photothermal-enhanced immunotherapy as an effective strategy for tumor treatment.

The complete chloroplast genome of Arachis lutescens Krapov. & Rigoni (Fabaceae).

Arachis lutescens Krapov. & Rigoni 1958 is an important species due to their potentially extensive applications for cultivated peanut breeding. The whole chloroplast genome of A. lutescens was successfully assembled and annotated for the first time. The complete chloroplast genome of A. lutescens is a typically circular structure of 156,398 bp with a GC content of 36.3%. It comprises a large single-copy (LSC) region of 85,950 bp, a small single-copy (SSC) region of 18,800 bp, and two inverted repeat regions (IRs) of 25,824 bp, each. The plastome of A. lutescens contains a total of 125 genes, including 81 protein-coding genes, 36 tRNAs, and eight rRNAs. The phylogenetic analysis strongly supports the close relationship between A. lutescens and cultivated peanut clades. This study contributes to our understanding of the molecular characteristics and evolutionary relationships of this plant species.

Down-regulation of RTEL1 Improves M1/M2 Macrophage Polarization by Promoting SFRP2 in Fibroblasts-derived Exosomes to Alleviate COPD.

Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease worldwide. Macrophage polarization plays a substantial role in the pathogenesis of COPD. This study is aimed to explore the regulatory mechanism of regulator of telomere elongation 1 (RTEL1) in COPD. COPD model mouse was conducted by cigarette smoke (CS). The pathological features of lung in mice were observed by histological staining. After extracting exosomes, macrophages were co-cultured with fibroblasts-derived exosomes. Then, the effects of RTEL1 and exosomal secreted frizzled-related protein 2 (SFRP2) on macrophage proliferation, inflammation, apoptosis, and M1, M2 macrophage polarization (iNOS and CD206) were evaluated by cell counting kit-8, EdU assay, enzyme-linked immuno sorbent assay, and western blotting, respectively. CS-induced COPD model mouse was successfully constructed. Through in vitro experiments, knockdown of RTEL1 inhibited macrophage proliferation, inflammation (MMP9, IL-1ß and TNF-α), and promoted apoptosis (Bax, cleaved-caspase3, Bcl-2) in CS extract-induced lung fibroblasts. Meanwhile, RTEL1 knockdown promoted M1 and suppressed M2 macrophage polarization in COPD. Additionally, silencing SFRP2 in fibroblasts-derived exosomes reversed the effects of RTEL1 knockdown on proliferation, inflammation, apoptosis, and M1, M2 macrophage polarization. Collectively, down-regulation of RTEL1 improved M1/M2 macrophage polarization by promoting SFRP2 in fibroblasts-derived exosomes to alleviate CS-induced COPD.

Pyridostigmine attenuates hypertension by inhibiting activation of the renin-angiotensin system in the hypothalamic paraventricular nucleus.

Activation of the renin-angiotensin system (RAS) triggers oxidative stress and an inflammatory response in the hypothalamic paraventricular nucleus (PVN), in turn increasing the sympathetic hyperactivity that is a major cause of hypertension. Pyridostigmine has cardioprotective effects by suppressing the RAS of myocardial tissue. However, whether pyridostigmine attenuates hypertension by inhibiting the RAS of the PVN remains unclear. We thus investigated the effect and mechanism of pyridostigmine on two-kidney one-clip (2K1C)-induced hypertension. 2K1C rats received pyridostigmine, or not, for 8 weeks. Cardiovascular function, hemodynamic parameters, and autonomic activity were measured. The PVN levels of pro-/anti-inflammatory cytokines, oxidative stress, and RAS signaling molecules were evaluated. Our results showed that hypertension was accompanied by cardiovascular dysfunction and an autonomic imbalance characterized by enhanced sympathetic but diminished vagal activity. The PVN levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), reactive oxygen species (ROS), NOX-2, and malondialdehyde (MDA) increased; those of IL-10 and superoxide dismutase (SOD) decreased. Moreover, the RAS signaling pathway was activated, as evidenced by increased levels of the angiotensin-converting enzyme (ACE), angiotensin II (Ang II), and the Ang II type 1 receptor (AT1R) and a decreased AT2R level. Pyridostigmine lowered blood pressure and improved cardiovascular function, associated with restoration of the autonomic balance. Meanwhile, pyridostigmine decreased PVN IL-6, TNF-α, ROS, NOX-2, and MDA levels and increased IL-10 and SOD levels. Additionally, pyridostigmine suppressed PVN ACE, Ang II, and AT1R levels and increased AT2R expression. Pyridostigmine attenuated hypertension by inhibiting PVN oxidative stress and inflammation induced by the RAS.

Use of Optical Redox Imaging to Quantify Alveolar Macrophage Redox State in Infants: Proof of Concept Experiments in a Murine Model and Human Tracheal Aspirates Samples.

Emerging data indicate that lung macrophages (LM) may provide a novel biomarker to classify disease endotypes in bronchopulmonary dysplasia (BPD), a form of infant chronic lung disease, and that augmentation of the LM phenotype may be a potential therapeutic target. To contribute to this area of research, we first used Optical Redox Imaging (ORI) to characterize the responses to H2O2-induced oxidative stress and caffeine treatment in an in vitro model of mouse alveolar macrophages (AM). H2O2 caused a dose-dependent decrease in NADH and an increase in FAD-containing flavoproteins (Fp) and the redox ratio Fp/(NADH + Fp). Caffeine treatment did not affect Fp but significantly decreased NADH with doses of ≥50 µM, and 1000 µM caffeine treatment significantly increased the redox ratio and decreased the baseline level of mitochondrial ROS (reactive oxygen species). However, regardless of whether AM were pretreated with caffeine or not, the mitochondrial ROS levels increased to similar levels after H2O2 challenge. We then investigated the feasibility of utilizing ORI to examine macrophage redox status in tracheal aspirate (TA) samples obtained from premature infants receiving invasive ventilation. We observed significant heterogeneity in NADH, Fp, Fp/(NADH + Fp), and mitochondrial ROS of the TA macrophages. We found a possible positive correlation between gestational age and NADH and a negative correlation between mean airway pressure and NADH that provides hypotheses for future testing. Our study demonstrates that ORI is a feasible technique to characterize macrophage redox state in infant TA samples and supports further use of this method to investigate lung macrophage-mediated disease endotypes in BPD.

Targeting Non-Alcoholic Fatty Liver Disease with Hawthorn Ethanol Extract (HEE): A Comprehensive Examination of Hepatic Lipid Reduction and Gut Microbiota Modulation.

Recent studies have highlighted the lipid-lowering ability of hawthorn ethanol extract (HEE) and the role played by gut flora in the efficacy of HEE. Our study sought to explore the effects of HEE on non-alcoholic fatty liver disease (NAFLD) in normal flora and pseudo germ-free mice. The results showed that HEE effectively diminished hepatic lipid accumulation, ameliorated liver function, reduced inflammatory cytokine levels and blood lipid profiles, and regulated blood glucose levels. HEE facilitated triglyceride breakdown, suppressed fatty acid synthesis, and enhanced intestinal health by modulating the diversity of the gut microbiota and the production of short-chain fatty acids in the gut. In addition, HEE apparently helps to increase the presence of beneficial genera of bacteria, thereby influencing the composition of the gut microbiota, and the absence of gut flora affects the efficacy of HEE. These findings reveal the potential of hawthorn for the prevention and treatment of NAFLD and provide new perspectives on the study of functional plants to improve liver health.

A Processible and Ultrahigh-temperature Organic Photothermal Material through Spontaneous and Quantitative [2+2] Cycloaddition-Cycloreversion.

Energy conversion, particularly light to heat conversion, has garnered significant attention owing to its prospect in renewable energy exploitation and utilization. Most previous efforts have focused on developing organic photothermal materials for low-temperature applications, whereas the importance of simplifying the preparation methods of photothermal materials and enhancing their maximum photothermal temperature have been less taken. Herein, we prepare an organic near-infrared (NIR) photothermal material namely ATT by a spontaneous [2+2] cycloaddition-cycloreversion reaction. In addition to the solution-based method, ATT could also be readily preapred by ball milling in a high yield of 90% in just 15 min. ATT powder exhibits a broad absorption extending beyond 2000 nm, excellent processability, and thermal stability. Remarkably, ATT powder can reach an unprecedently temperature as high as 450 °C while maintaining excellent photostability upon photoirradiation. Leveraging its extraordinary photothermal and processable properties, ATT was used in the high-temperature applications, such as photo-ignition, photo-controlled metal processing and high-temperature shape memory, all of which offer spatiotemporal control capabilities. This work provides a new approach to prepare organic photothermal materials with high temperatures, and pave the way for their applications in extreme environments.

Triglyceride-glucose index and health outcomes: an umbrella review of systematic reviews with meta-analyses of observational studies.

BACKGROUND: Numerous meta-analyses have explored the association between the triglyceride-glucose (TyG) index and diverse health outcomes, yet the comprehensive assessment of the scope, validity, and quality of this evidence remains incomplete. Our aim was to systematically review and synthesise existing meta-analyses of TyG index and health outcomes and to assess the quality of the evidence. METHODS: A thorough search of PubMed, EMBASE, and Web of Science databases was conducted from their inception through to 8 April 2024. We assessed the quality of reviews using A Measurement Tool to Assess Systematic Reviews (AMSTAR) and the certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. This study was registered with PROSPERO (CRD: 42024518587). RESULTS: Overall, a total of 95 associations from 29 meta-analyses were included, investigating associations between TyG index and 30 health outcomes. Of these, 83 (87.4%) associations were statistically significant (P < 0.05) according to the random effects model. Based on the AMSTAR tool, 16 (55.2%) meta-analyses were high quality and none was low quality. The certainty of the evidence, assessed by the GRADE framework, showed that 6 (6.3%) associations were supported by moderate-quality evidence. When compared with the lowest category of the TyG index, the risk of contrast-induced nephropathy (CIN) [relative risk (RR) = 2.25, 95%CI 1.82, 2.77], the risk of stroke in patients with diabetes mellitus (RR = 1.26, 95%CI 1.18, 1.33) or with acute coronary syndrome disease (RR = 1.56, 95%CI 1.06, 2.28), the prognosis of coronary artery disease (CAD)-non-fatal MI (RR = 2.02, 95%CI 1.32, 3.10), and the severity of CAD including coronary artery stenosis (RR = 3.49, 95%CI 1.71, 7.12) and multi-vessel CAD (RR = 2.33, 95%CI 1.59, 3.42) increased with high TyG index. CONCLUSION: We found that the TyG index was positively associated with many diseases including the risk of CIN and stroke, the prognosis of CAD, and the severity of CAD which were supported by moderate-quality evidence. TyG index might be useful to identify people at high-risk for developing these diseases.

Per- and polyfluoroalkyl substances and human health outcomes: An umbrella review of systematic reviews with meta-analyses of observational studies.

BACKGROUND: Although evidence on the association between per- and polyfluoroalkyl substances (PFASs) and human health outcomes has grown exponentially, specific health outcomes and their potential associations with PFASs have not been conclusively evaluated. METHODS: We conducted a comprehensive search through the databases of PubMed, Embase, and Web of Science from inception to February 29, 2024, to identify systematic reviews with meta-analyses of observational studies examining the associations between the PFASs and multiple health outcomes. The quality of included studies was evaluated using the A Measurement Tool to Assess Systematic Reviews (AMSTAR) tool, and credibility of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria. The protocol of this umbrella review (UR) had been registered in PROSPERO (CRD 42023480817). RESULTS: The UR identified 157 meta-analyses from 29 articles. Using the AMSTAR measurement tool, all articles were categorized as of moderate-to-high quality. Based on the GRADE assessment, significant associations between specific types of PFASs and low birth weight, tetanus vaccine response, and triglyceride levels showed high certainty of evidence. Moreover, moderate certainty of evidence with statistical significance was observed between PFASs and health outcomes including lower BMI z-score in infancy, poor sperm progressive motility, and decreased risk of preterm birth as well as preeclampsia. Fifty-two (33%) associations (e.g., PFASs and gestational hypertension, cardiovascular disease, etc) presented low certainty evidence. Additionally, eighty-five (55%) associations (e.g., PFASs with infertility, lipid metabolism, etc) presented very low certainty evidence. CONCLUSION: High certainty of evidence supported that certain PFASs were associated with the incidence of low birth weight, low efficiency of the tetanus vaccine, and low triglyceride levels.

Micropatterned Polymer Nanoarrays with Distinct Superwettability for a Highly Efficient Sweat Collection and Sensing Patch.

Wearable sweat sensor offers a promising means for noninvasive real-time health monitoring, but the efficient collection and accurate analysis of sweat remains challenging. One of the obstacles is to precisely modulate the surface wettability of the microfluidics to achieve efficient sweat collection. Here a facile initiated chemical vapor deposition (iCVD) method is presented to grow and pattern polymer nanocone arrays with distinct superwettability on polydimethylsiloxane microfluidics, which facilitate highly efficient sweat transportation and collection. The nanoarray is synthesized by manipulating monomer supersaturation during iCVD to induce controlled nucleation and preferential vertical growth of fluorinated polymer. Subsequent selective vapor deposition of a conformal hydrogel nanolayer results in superhydrophilic nanoarray floor and walls within the microchannel that provide a large capillary force and a superhydrophobic ceiling that drastically reduces flow friction, enabling rapid sweat transport along varied flow directions. A carbon/hydrogel/enzyme nanocomposite electrode is then fabricated by sequential deposition of highly porous carbon nanoparticles and hydrogel nanocoating to achieve sensitive and stable sweat detection. Further encapsulation of the assembled sweatsensing patch with superhydrophobic nanoarray imparts self-cleaning and water-proof capability. Finally, the sweat sensing patch demonstrates selective and sensitive glucose and lactate detection during the on-body test.

Quantitative Optical Redox Imaging of Melanoma Xenografts with Different Metastatic Potentials.

To develop imaging biomarkers for tumors aggressiveness, our previous optical redox imaging (ORI) studies of the reduced nicotinamide adenine dinucleotide (NADH) and oxidized flavoproteins (Fp, containing flavin adenine dinucleotide, i.e., FAD) in tumor xenografts of human melanoma associated the high optical redox ratio (ORR = Fp/(Fp + NADH)) and its heterogeneity to the high invasive/metastatic potential, without having reported quantitative results for NADH and Fp. Here, we implemented a calibration procedure to facilitate imaging the nominal concentrations of tissue NADH and Fp in the mouse xenografts of two human melanoma lines, an indolent less metastatic A375P and a more metastatic C8161. Images of the redox indices (NADH, Fp, ORR) revealed the existence of more oxidized areas (OAs) and more reduced areas (RAs) within individual tumors. ORR was found to be higher and NADH lower in C8161 compared to that of A375P xenografts, both globally for the whole tumors and locally in OAs. The ORR in the OA can differentiate xenografts with a higher statistical significance than the global averaged ORR. H&E staining of the tumors indicated that the redox differences we identified were more likely due to intrinsically different cell metabolism, rather than variations in cell density.

Exploring the relationship between illness perception, self-management and quality of life among HIV-positive men who have sex with men.

AIMS: This study aimed to explore the mediating effect of self-management (SM) on the relationship between illness perception and quality of life (QOL) among Human immunodeficiency virus (HIV)-positive men who have sex with men (MSM). DESIGN: A cross-sectional study. METHODS: We explored the effect of illness perception and self-management on QOL using the multiple regression model. Moreover, we conducted a simple mediation analysis to examine the role of SM in the relationship between illness perception and QOL. In addition, a parallel mediation analysis was performed to investigate the differences in domains of SM on the relationship between illness perception and QOL. RESULTS: Among 300 Chinese HIV-positive MSM, the mean score of SM was 39.9 ± 6.97, with a range of 14.0-54.0. The higher score in SM indicated a higher level of HIV SM. SM was negatively related to illness perception (r = -0.47) while positively related to QOL (r = 0.56). SM partially mediated the relationship between illness perception and QOL, accounting for 25.3% of the total effect. Specifically, both daily self-management health practices and the chronic nature of the self-management domain played a parallel role in mediating the relationship between illness perception and QOL. CONCLUSION: Our study demonstrated that SM was a significant factor influencing QOL among HIV-positive MSM. Focusing on daily self-management health practices and the chronic nature of self-management could be the potential key targets for enhancing HIV self-management strategies. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: This study emphasized the role of SM in the well-being of HIV-positive MSM and underscored the importance of developing interventions that integrate SM strategies to improve QOL in this population. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

The Role of Autophagy in Vascular Endothelial Cell Health and Physiology.

Autophagy is a highly conserved cellular recycling process which enables eukaryotes to maintain both cellular and overall homeostasis through the catabolic breakdown of intracellular components or the selective degradation of damaged organelles. In recent years, the importance of autophagy in vascular endothelial cells (ECs) has been increasingly recognized, and numerous studies have linked the dysregulation of autophagy to the development of endothelial dysfunction and vascular disease. Here, we provide an overview of the molecular mechanisms underlying autophagy in ECs and our current understanding of the roles of autophagy in vascular biology and review the implications of dysregulated autophagy for vascular disease. Finally, we summarize the current state of the research on compounds to modulate autophagy in ECs and identify challenges for their translation into clinical use.

Validation of biomarkers and immunotherapy in head and neck squamous cell carcinoma using bioinformatics and Mendelian randomization.

BACKGROUND: To promote carcinogenesis through diverse molecular pathways involving dysregulation of gene expression and abnormalities. METHODS: We employed Mendelian randomization (MR) to uncover causal relationships between genetic factors and HNSCC. We used the Inverse Variance Weighted (IVW) method as the primary MR analysis, and validated the results through complementary approaches like MR-Egger regression, weighted median, and mode analyses. RESULTS: Our analysis identified 2210 genes that are differentially expressed in head and neck cancer (HNSCC) compared to normal tissues. Within the protein interaction network, the genes IL1B, CXCL8, CXCL1, and CCL2 stood out as central hubs. Further investigation revealed that these key genes are involved in important biological processes like skin development, wound healing, and fat metabolism. Notably, our Mendelian randomization analysis provided evidence for a causal relationship between the expression of the IL1B gene and the development of HNSCC. CONCLUSIONS: Our analysis identified 5 key genes - IL1B, CXCL8, CXCL1, CCL2, and IL1B - that show significant changes in expression in head and neck cancer. These genes could serve as important new biomarkers to help diagnose this disease and track how it progresses over time. Importantly, these genes are involved in regulating the immune system, suggesting that the body's immune response plays a critical role in head and neck cancer. This provides new avenues for future research to better understand the complex gene expression patterns underlying this type of cancer. Further investigation of these key genes and their regulatory networks could lead to important insights and potential new treatment approaches.

Mechanism study of ubiquitination in T cell development and autoimmune disease.

T cells play critical role in multiple immune processes including antigen response, tumor immunity, inflammation, self-tolerance maintenance and autoimmune diseases et. Fetal liver or bone marrow-derived thymus-seeding progenitors (TSPs) settle in thymus and undergo T cell-lineage commitment, proliferation, T cell receptor (TCR) rearrangement, and thymic selections driven by microenvironment composed of thymic epithelial cells (TEC), dendritic cells (DC), macrophage and B cells, thus generating T cells with diverse TCR repertoire immunocompetent but not self-reactive. Additionally, some self-reactive thymocytes give rise to Treg with the help of TEC and DC, serving for immune tolerance. The sequential proliferation, cell fate decision, and selection during T cell development and self-tolerance establishment are tightly regulated to ensure the proper immune response without autoimmune reaction. There are remarkable progresses in understanding of the regulatory mechanisms regarding ubiquitination in T cell development and the establishment of self-tolerance in the past few years, which holds great potential for further therapeutic interventions in immune-related diseases.

Pirfenidone alleviates fibrosis by acting on tumour-stroma interplay in pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a malignancy with a 5-year survival rate of 12%. The abundant mesenchyme is partly responsible for the malignancy. The antifibrotic therapies have gained attention in recent research. However, the role of pirfenidone, an FDA-approved drug for idiopathic pulmonary fibrosis, remains unclear in PDAC. METHODS: Data from RNA-seq of patient-derived xenograft (PDX) models treated with pirfenidone were integrated using bioinformatics tools to identify the target of cell types and genes. Using confocal microscopy, qRT-PCR and western blotting, we validated the signalling pathway in tumour cells to regulate the cytokine secretion. Further cocultured system demonstrated the interplay to regulate stroma fibrosis. Finally, mouse models demonstrated the potential of pirfenidone in PDAC. RESULTS: Pirfenidone can remodulate multiple biological pathways, and exerts an antifibrotic effect through inhibiting the secretion of PDGF-bb from tumour cells by downregulating the TGM2/NF-kB/PDGFB pathway. Thus, leading to a subsequent reduction in collagen X and fibronectin secreted by CAFs. Moreover, the mice orthotopic pancreatic tumour models demonstrated the antifibrotic effect and potential to sensitise gemcitabine. CONCLUSIONS: Pirfenidone may alter the pancreatic milieu and alleviate fibrosis through the regulation of tumour-stroma interactions via the TGM2/NF-kB/PDGFB signalling pathway, suggesting potential therapeutic benefits in PDAC management.

Survival and neurological function in patients treated with extracorporeal membrane oxygenation and therapeutic hypothermia: a protocol for updating a systematic review.

INTRODUCTION: The widespread application of extracorporeal membrane oxygenation (ECMO) has enhanced clinical outcomes for patients experiencing cardiac arrest. However, its effectiveness is still limited and falls short of the desired level. Therapeutic hypothermia, which maintains body temperatures between 32°C and 36°C in cardiac arrest patients treated with ECMO, has been proposed as a potential means of neuroprotection and increased survival rates. Nevertheless, it remains controversial, and its impact on patient complications has yet to be fully understood. Thus, this paper aims to update the protocol for a systematic review of patients treated with ECMO and therapeutic hypothermia, in order to explore its effects on survival and neurological function. METHOD AND ANALYSIS: This protocol has been developed in compliance with the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols 2015. The following databases will be systematically searched: PubMed, Web of Science, Cochrane Library, Embase, Ovid, CNKI, Wanfang and China Biology Medicine Disc. The database search strategy will use a combination of subject terms and free-text keywords. The search will encompass articles from the inception of each database up to 15 June 2023. Inclusion criteria encompass randomised controlled trials, cohort studies, case-control studies and quasi-experimental studies. Two researchers will independently review articles and extract relevant data based on these criteria. Any disagreements will be resolved through discussion. Data analysis will be performed using Review Manager software. ETHICS AND DISSEMINATION: Since no patient data were collected in this study, ethical approval was not required. Research findings will be released in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023435353.

Accurate Spatio-Temporal Delivery of Nitric Oxide Facilitates the Programmable Repair of Avascular Dense Connective Tissues Injury.

Avascular dense connective tissues (e.g., the annulus fibrosus (AF) rupture, the meniscus tear, and tendons and ligaments injury) repair remains a challenge due to the "biological barrier" that hinders traditional drug permeation and limits self-healing of the injured tissue. Here, accurate delivery of nitric oxide (NO) to penetrate the "AF biological barrier" is achieved thereby enabling programmable AF repair. NO-loaded BioMOFs are synthesized and mixed in a modified polyvinyl alcohol and PCL-composited electrospun fiber membrane with excellent reactive oxygen species-responsive capability (LN@PM). The results show that LN@PM could respond to the high oxidative stress environment at the injured tissue and realize continuous and substantial NO release. Based on low molecular weight and lipophilicity, NO could penetrate through the "biological barrier" for accurate AF drug delivery. Moreover, the dynamic characteristics of the LN@PM reaction can be matched with the pathological microenvironment to initiate programmable tissue repair including sequential remodeling microenvironment, reprogramming the immune environment, and finally promoting tissue regeneration. This tailored programmable treatment strategy that matches the pathological repair process significantly repairs AF, ultimately alleviating intervertebral disc degeneration. This study highlights a promising approach for avascular dense connective tissue treatment through intelligent NO release, effectively overcoming "AF biological barriers" and programmable treatment.

S2I2N0-3 score predicts short- and long-term mortality and morbidity in HFrEF: a post-hoc analysis of the GUIDE-IT trial.

AIMS: This study investigated the S2I2N0-3 score, a simple tool comprising stroke history, insulin-treated diabetes, and N-terminal pro-brain natriuretic peptide, for forecasting mortality and morbidity in heart failure (HF) with reduced ejection fraction (HFrEF). METHODS AND RESULTS: Analysing 890 GUIDE-IT HFrEF trial participants, we stratified them by baseline S2I2N0-3 risk score into three risk groups. We examined the score's association with five adverse outcomes over short (90 days) and extended periods (median follow-up of 15 months) using Cox and competing risk models. Our analysis revealed significant positive associations between the S2I2N0-3 strata and adverse outcomes. When analysed as a continuous variable, each point increment of the S2I2N0-3 score was associated with a higher risk of short- and long-term cardiovascular death [short term: hazard ratio (HR) 1.43, 95% confidence interval (CI) 1.03-1.98; long term: HR 1.18, 95% CI 1.02-1.38], all-cause death (HR 1.52, 95% CI 1.12-2.07; HR 1.18, 95% CI 1.03-1.36), HF hospitalization (HR 1.39, 95% CI 1.20-1.62; HR 1.18, 95% CI 1.06-1.31), any hospitalization (HR 1.19, 95% CI 1.06-1.34; HR 1.09, 95% CI 1.00-1.19), and the composite outcome of cardiovascular death and HF hospitalization (HR 1.39, 95% CI 1.21-1.60; HR 1.17, 95% CI 1.06-1.30). The S2I2N0-3 demonstrated reliable prognostic value, with C-indices ranging from 0.619 to 0.753 across outcomes and time points. When compared with the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score using Z-statistics, net reclassification index, and integrated discrimination improvement, the S2I2N0-3 showed comparable predictive power for all outcomes during both short- and long-term follow-ups. CONCLUSIONS: The S2I2N0-3 risk score had modest predictive values for both short- and long-term clinical outcomes in HFrEF patients, offering equivalent performance to the established MAGGIC score.