Bidirectional association between perioperative skeletal muscle and subcutaneous fat in colorectal cancer patients and their prognostic significance.

Introduction: Low skeletal muscle mass and high adipose tissue coexist across the body weight spectrum and independently predict the survival ratio of colorectal cancer (CRC) patients. This combination may lead to a mutually exacerbating vicious cycle. Tumor-associated metabolic conditions primarily affect subcutaneous adipose tissue, but the nature and direction of its relationship with skeletal muscle are unclear. This study aims to examine the bidirectional causal relationship between skeletal muscle index (SMI) and subcutaneous fat index (SFI) during the perioperative period in CRC patients; as well as to validate the association between perioperative SMI, SFI, and CRC prognosis. Methods: This population-based retrospective cohort study included patients with stage I-III colorectal cancer who underwent radical resection at the Third Affiliated Hospital of Kunming Medical University between September 2012 and February 2019. Based on inclusion and exclusion criteria, 1,448 patients were analyzed. Preoperative (P1), 2 months postoperative (P2), and 5 months postoperative (P3) CT scans were collected to evaluate the skeletal muscle index (SMI; muscle area at the third lumbar vertebra divided by height squared) and subcutaneous fat index (SFI; subcutaneous fat area at the third lumbar vertebra divided by height squared). A random intercept cross-lagged panel model (RI-CLPM) was used to examine the intra-individual relationship between SMI and SFI, and Cox regression was employed to assess the association between SMI, SFI, recurrence-free survival (RFS), and overall survival (OS). Results: The median age at diagnosis was 59.00 years (IQR: 51.00-66.00), and 587 patients (40.54%) were female. RI-CLPM analysis revealed a negative correlation between SFI and subsequent SMI at the individual level: P1-P2 (ß = -0.372, p = 0.038) and P2-P3 (ß = -0.363, p = 0.001). SMI and SFI showed a negative correlation during P1-P2 (ß = -0.363, p = 0.001) but a positive correlation during P2-P3 (ß = 0.357, p = 0.006). No significant correlation was found between the random intercepts of SFI and SMI at the between-person level (r = 0.157, p = 0.603). The Cox proportional hazards multivariate regression model identified that patients with elevated SFI had poorer recurrence-free survival (HR, 1.24; 95% CI: 1.00-1.55). Compared to patients with normal preoperative SMI and SFI, those with low SMI or high SFI had poorer recurrence-free survival (HR, 1.26; 95% CI: 1.03-1.55) and overall survival (HR, 1.39; 95% CI: 1.04-1.87). However, no significant association between SMI and SFI and the prognosis of colorectal cancer patients was observed postoperatively. Conclusion: In CRC patients, preoperative muscle loss leads to postoperative fat accumulation, exacerbating muscle loss in a feedback loop. Elevated preoperative SFI predicts poorer survival outcomes. Monitoring SMI and SFI is crucial as prognostic indicators, despite non-significant postoperative associations. Further research is needed to improve patient outcomes.

Compound (E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one downregulation of Galectin-3 ameliorates Aß pathogenesis-induced neuroinflammation in 5 × FAD mice.

Alzheimer's disease (AD) is characterized by ß-amyloid (Aß) aggregation and neuroinflammation, leading to a progressive synaptic loss and cognitive decline. Recent evidence highlights Galectin-3 (Gal-3) as a crucial factor in Aß pathogenesis, yet effective strategies to simultaneously target Gal-3 and Aß are currently insufficient. This study assesses the therapeutic efficacy of D30, an innovative anti-AD compound manifested promising effects on reducing Aß deposition and alleviating neuronal damage in scopolamine-induced AD models. In our study, we administered neurotoxic oligomeric Aß (oAß) to mice and observed increased Gal-3 deposition and microglial activation in the hippocampus, leading to significant cognitive impairments. Similarly, in the 5 × FAD mouse model, known for Aß overproduction, there was a progressive rise in Gal-3 levels and glial cell activation. We then investigated the effects of D30 on 5 × FAD mice, focusing on its modulation of Gal-3 and Aß and impact on neuroinflammatory responses. D30 effectively reduced Aß monomer production by inhibiting the expression of Amyloid Precursor Protein (APP) and presenilin 1 (PS1), as well as decreasing Aß oligomer aggregation. Treatment with D30 not only improved cognitive functions but also reversed dendritic spine loss and increased PSD95 expression in 5 × FAD mice. Notably, D30 significantly lowered Gal-3 levels in both plasma and hippocampal tissues. Mechanistic studies revealed that D30 binds to Gal-3 and disrupts the interaction between Gal-3 and the triggering receptor expressed on myeloid cells 2 (TREM2), as confirmed by fluorescence resonance energy transfer (FRET) and microscale thermophoresis (MST). Our findings underscore the interaction between Gal-3 and Aß in AD and its role in systemic inflammation using the 5 × FAD mouse model. Being able to target and regulate Gal-3 together with Aß is crucial for preventing neuroinflammation and protecting neurons, D30 emerged as a novel compound with promising potential for AD treatment. AIMS: Alzheimer's disease (AD) is characterized by ß-amyloid (Aß) aggregation and neuroinflammation, leading to progressive synaptic loss and cognitive decline. Recent evidence suggests that Galectin-3 (Gal-3) plays a critical role in Aß pathogenesis. However, strategies to simultaneously target Gal-3 and Aß are currently insufficient. This study evaluates the therapeutic efficacy of D30, in reducing Gal-3 and Aß pathogenesis. MATERIALS AND METHODS: We applied exogenous oligomeric Aß and used 5 × FAD mice to assess the impact of Aß on Gal-3 deposition, microglial activation, and cognitive function. Thy1-EGFP mice were employed to observe dendritic spines. Comprehensive evaluations of D30's effects included behavioral studies, transcriptomic analysis, Western blotting, and immunofluorescent staining. The interaction between D30 and Gal-3 was examined using fluorescence resonance energy transfer (FRET) and microscale thermophoresis (MST). KEY FINDINGS: D30 effectively reduced Aß monomer production by inhibiting Amyloid Precursor Protein (APP) and presenilin 1 (PS1) expression, and decreased Aß aggregation. Treatment with D30 improved cognitive functions, reversed dendritic spine loss, and increased PSD95 expression in 5 × FAD mice. Additionally, D30 significantly lowered Gal-3 levels in both plasma and hippocampal tissues. D30 binds to Gal-3 and disrupts the interaction between Gal-3 and TREM2, as confirmed by FRET and MST. SIGNIFICANCE: Our findings underscore the interaction between Gal-3 and Aß in AD and its role in systemic inflammation using the 5 × FAD mouse model. Being able to target and regulate Gal-3 together with Aß is crucial for preventing neuroinflammation and protecting synapses, D30 emerged as a novel compound with promising potential for AD treatment.

Inhibition of BCAT1 expression improves recurrent miscarriage by regulating cellular dysfunction and inflammation of trophoblasts.

Sustained or chronic inflammation in the placenta can result in placental insufficiency, leading to adverse reproductive outcomes such as pregnancy loss. Branched-chain amino acid transaminase 1 (BCAT1) expresses in the placenta and is involved in the pathological inflammatory response, but its role in recurrent miscarriage (RM) has not been fully investigated. In the present study, we delved into the effects of BCAT1 on trophoblast inflammation induced by lipopolysaccharide (LPS) and a mouse model of pregnancy loss induced by LPS. In vitro, after the HTR-8/SVneo cells were treated with LPS and BCATc inhibitor 2 (a selective BCAT inhibitor), the cell apoptosis was verified by TUNEL assay, and the activity of caspase-3 and caspase-9 was detected. Real-time PCR, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence (IF) were used to determine the expression of inflammatory cytokines (TNF-α, IL-6, and IL-1ß) and inflammasomes (NLRP3 and ASC) in LPS-treated trophoblast cells. Western blot analysis was performed to verify the expression of phospho-IκBα (p-IκBα) in cells and NF-κB p65 in the nuclei. IF staining was used to detect the nuclear translocation of NF-κB p65. The DNA binding activity of NF-κB was detected by an electrophoretic mobility shift assay (EMSA). The results demonstrated that inhibition of BCAT1 reduced trophoblast apoptosis, suppressed the release of proinflammatory cytokines, and prevented NLRP3 inflammasome activation in response to LPS. Additionally, BCAT1 inhibition blocked the activation of the NF-κB pathway in trophoblasts. This study highlights the potential therapeutic role of targeting BCAT1 in preventing adverse reproductive outcomes associated with chronic placental inflammation.

Predictive Value of CCQ and its Subdomains for Hospitalized Exacerbations in Chronic Obstructive Pulmonary Disease: A 3-Year Observational Prospective Study.

BACKGROUND: The prediction capacity of the Clinical COPD Questionnaire (CCQ) and its functional, symptom, and mental subdomain for COPD hospitalized exacerbation were rarely studied. OBJECTIVE: To examine the prognostic capacity of the total CCQ and its three subdomains for 3-year COPD hospitalized exacerbations. METHODS: We analyzed the predictive ability of total CCQ score and its subdomains for hospitalized exacerbations in an observational cohort of 987 subjects with stable COPD from the RealDTC, an ongoing multicenter prospective study. Hospitalized exacerbations were prospectively collected every 6 month for a maximum of 3 years. RESULTS: The total CCQ and its functional and symptom domain, but not the mental domain, were significantly associated with 3-year hospitalized exacerbations by multivariate Cox regression analysis. The predictive capacity of functional domain was similar to that of the total CCQ, but significantly stronger than the symptom and mental domain by ROC analysis (P < 0.05). ROC curves also showed that the AUC of exacerbation history combined with CCQ functional domain was larger than that of exacerbation history alone (P < 0.0001). Additionally, the predictive value of multivariable models that contains CCQ functional domain was significantly better than the corresponding model without CCQ functional domain (P < 0.05). CONCLUSIONS: The total CCQ and its functional and symptom domain were independent risk factors of 3-year hospitalized exacerbations. The prognostic capacity of the functional domain was similar to that of total CCQ, and was significantly stronger than the symptom and mental domain. The CCQ functional domain was able to increase the predictive power of exacerbation history and other multivariable prediction models, indicating it may have an important role in the multivariable prediction tool for hospitalized exacerbation, and its combination with other clinical variables might be used as a low-cost approach for assessments of the disease severity and severe exacerbation in COPD patients in the future.

Investigating Mechanisms of Sophora davidii (Franch.) Skeels Flower Extract in Treating LPS-induced Acute Pneumonia Based on Network Pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: In TCM opinion, most of pneumonia is related to "lung heat". Sophora davidii (Franch.) Skeels flower was first documented in "Guizhou Herbal Medicine", and was recorded as having functions of clearing heat, detoxifying, and cooling blood. It can be used to treat lung heat cough. AIM OF THE STUDY: To investigate main mechanisms of Sophora davidii flower extract (SDFE) in Treating LPS-induced acute Pneumonia. MATERIALS AND METHODS: Acute pneumonia models on BEAS-2B cells and rats were established using LPS. The rat model was used to verified the protective effects of SDFE through HE staining, lung tissue W/D ratio assay, white blood cell count analysis, and ammonia-induced coughing test. Network pharmacology was applied to predict the active compounds, core targets and main pathways of SDFE in treating acute pneumonia. Western Blot and ELISA kits were employed to validate representative proteins in selected pathway in vivo and in vitro. RESULTS: HE staining, lung tissue W/D ratio assay, white blood cell count analysis, and ammonia-induced coughing test showed SDFE could improve pathological features (leukocyte infiltration, pulmonary edema, lung injury and cough). Network pharmacology indicated MAPK/NF-κB pathway was the most relevant pathway. SDFE could significantly inhibit the expression of Fos and Jun, and the phosphorylation levels of p38, ERK, JNK, NF-κB and IκB. It also down-regulated the expression of pro-inflammatory factors (TNF-α, IL-6 and IL-1ß). CONCLUSIONS: SDFE can exert protective effects against acute pneumonia through the MAPK/NF-κB signaling pathway.

Enhancing Multi-Object Detection in Ultrasound Images Through Semi-Supervised Learning, Focal Loss and Relation of Frame.

OBJECTIVE: To identify musculoskeletal anatomical structures in real time by using deep learning techniques. METHODS: An automated annotation system based on deep learning neural networks was designed to aid in the real-time identification of anatomical structures. Additionally, novel algorithms aimed at diminishing model training duration while enhancing accuracy were introduced. In this study, we proposed a semi-supervised learning (SSL) approach that substantially reduced annotation time. We also adopted the focal loss (FL) method to enhance the accuracy of challenging structures. Additionally, during the inference stage, we harnessed the temporal continuity of video frames, which involved leveraging information from preceding frames to facilitate recognition of structures in the current image. Training the model through a combination of SSL and FL yielded superior performance compared with supervised learning, while also substantially mitigating any expense linked to annotations. During inference, the incorporation of frame continuity helped to avoid discontinuity and bolster accuracy. RESULTS: Forearm tissue detection was demonstrated by properly configuring the SSL approach, including FL and the filtering threshold. Comparable performance with supervised learning was achieved while only using 30% of the training data. The real-time experimental results also demonstrated that implementing relation of frame reduced the number of missing frames during inference and successfully increased the confidence scores of detected objects. CONCLUSION: This proposed system has the potential to aid medical professionals in efficiently and effectively diagnosing musculoskeletal disorders, ultimately leading to enhanced patient outcomes.

Cultivating Connections: An Interprofessional Peer Support Model.

Peer support models have existed for decades in behavioral health care and are being developed for health care professionals to help address high rates of burnout and stress in the health care environment. Such models typically involve individuals from the same profession. With the concurrent increase of interprofessional integrated behavioral health care models, interprofessional peer support seems a viable model. This Open Forum describes how a peer support program for physicians and faculty scientists evolved to include a broader range of health care professionals, providing a framework for interprofessional peer support programs for the behavioral health care workforce.

A highly sensitive SERS sensor based on PVDF/Au nanofibers for trace analysis of nitrite ions.

Nitrite ions present a significant risk to both environmental and human health, necessitating precise and sensitive detection methods. Herein, we fabricated a highly sensitive SERS sensor based on PVDF/Au nanofibers for nitrite ion detection. The synthesis of PVDF nanofibers involved the utilization of electrospinning apparatus, while the uniformity and high density of SERS activity "hot spots" were achieved by directly coating plasma gold nanoparticles onto the PVDF surface adopting thermal evaporation. The efficient charge transfer of the interface dipole layer directly generated on the surface of PVDF nanofibers was achieved through thermal evaporation. The enhanced Raman responses were due to the combined effects of local surface plasmon resonance of Au nanoparticles and photoelectric and piezoelectric properties of PVDF. It is noteworthy that the prepared SERS substrate exhibited high sensitivity towards rhodamine 6G, boasting an enhancement factor of 9.4 × 107 and a detection limit spanning from 10-6-10-11 M. Furthermore, the PVDF/Au membrane functionalized with p-aminothiophenol (PATP) effectively captured NO2- ions at concentrations as low as 10-8 M and successfully detected NO2- in river water samples. Additionally, the SERS substrate has good repeatability and stability, and can be applied to trace detection in food safety and medical diagnosis.

De novo design of type-l photosensitizer agents based on structure-inherent low triplet energy for hypoxia photodynamic therapy.

Photodynamic therapy (PDT), owing to its low invasiveness, high efficiency, fewer side effects, spatiotemporal controllability and good selectivity, has attracted increasing attention for its tremendous potential in revolutionizing conventional strategies of tumor treatment. However, hypoxia is a common feature of most malignancies and has become the Achilles' heel of PDT. Currently, Type II photosensitizers (PSs) have inadequate efficacy for PDT due to the inherent oxygen consumption of the anoxic tumor microenvironment. Moreover, due to the absence of a general molecular design strategy and the limitations imposed by the energy gap law, Type-I PSs are less reported. Therefore, the development of Type-I PSs with hypoxia resistant capabilities is urgently required. Herein, in this study, we have obtained pure Type-I materials for the first time by employing a strategy that decreases the triplet energy levels of the π-conjunction bridge. A sufficient donor-acceptor interaction reduces the lowest triplet energy level and aids in the transfer of excitons from singlet to triplet levels. With this strategy, dibenzofulvene derivatives (FEs) displayed purely Type-I ROS generation. Among them, FE-TMI exhibits superior Type-I reactive oxygen species-generation performance, showcasing the great potential of PDT in treating tumor cells under hypoxic conditions and several types of solid tumors in mouse in vivo experiments. This work provides a practical solution for the future design of Type-I PDT materials and is aimed at enhancing PDT efficiency.

Prognostic Value of Murray Law-Based QFR (µQFR)-Guided Virtual PCI in Patients With Physiological Ischemia.

BACKGROUND: Quantitative flow ratio (QFR)-based virtual percutaneous coronary intervention (PCI) is associated with improved post-PCI physiological results. Murray law-based QFR (µQFR) is a new method for physiological assessment that has higher feasibility and efficiency. The purpose of this study was to investigate the performance of µQFR-guided virtual PCI in improving post-PCI outcomes. METHODS: The QUITE RIGHT study (Quantitative Flow Ratio Virtual Stenting and Angiography Guided Percutaneous Coronary Intervention) is a prospective, multicenter, blinded, randomized, controlled superiority study. Eligible patients were randomized 1:1 to either the µQFR-guided virtual PCI group or the angiography-guided PCI group. The primary end point was the proportion of the target vessels with a post-PCI µQFR ≥0.90, accepted as an optimal post-PCI physiological outcome. RESULTS: A total of 622 patients with 666 vessels were enrolled. The optimal physiological outcome was reached more often in the µQFR-guided virtual PCI group (absolute difference, 9.1% [95% CI, 4.53-13.76]; P<0.001). The µQFR-guided virtual PCI group had a better QFR value, a lower contrast agent dose and x-ray dose, and a more appropriate stent length than the angiography-guided group. CONCLUSIONS: The QUITE RIGHT study showed that the µQFR-guided virtual PCI strategy is superior to angiography-guided PCI in terms of physiological outcomes. The µQFR-guided virtual PCI strategy is associated with lower contrast and x-ray doses and a more appropriate stent length. REGISTRATION: URL: https://www.chictr.org.cn/; Unique identifier: ChiCTR2100045452.

Polystyrene influence on Pb bioavailability and rhizosphere toxicity: Challenges for ramie (Boehmeria nivea L.) in soil phytoremediation.

Microplastics (MPs) and heavy metals often coexist in soil, however their interactions and effects on the soil-plant system remain largely unclear. In this study, ramie (Boehmeria nivea L.) was exposed to soil contaminated with lead (Pb) and polystyrene (PS) of different sizes, dosages, and surface-charged functional groups. This design aimed to simulate the effects of MPs on phytoremediation. The experimental results revealed that PS exacerbated the damaging effects of Pb on ramie. Compared to the effect of Pb alone, PS-COOH had a greater influence on root vigor, leading to a 15.6 % reduction in the active absorption ratio. Laser scanning confocal microscope showed PS entered the roots. Adsorption/desorption experiments demonstrated that PS had a weaker adsorption capacity for Pb than soil but a greater desorption rate than soil when simulating rhizosphere secretion. Moreover, PS reduced soil pH and increased the reducible state of Pb by 6-12 %. After 100 days of phytoremediation, Pb content in the soil with PS-5 µm was 150 µg g-1 less than that in the soil without PS. These results demonstrated that PS improved Pb bioavailability and enhanced the efficiency of Pb uptake by ramie. The redundancy analysis demonstrated that PS mitigated the toxicity of Pb to rhizosphere microorganisms, potentially via its effects on metal chemical fractions, dehydrogenase activity (S-DHA), cation exchange capacity (CEC), and soil organic matter (SOM). This study indicates that the presence of PS could potentially enhance the phytoremediation efficiency of ramie in Pb-contaminated land by influencing soil microenvironmental properties. This study provides insights into the complex interactions of MPs with soil-plant-microbial systems during metal remediation, thereby enhancing our understanding of their environmental impacts.

Nitrogen fixation by alkali and alkaline earth metal hydrides assisted by plasma.

The chemical behaviors of alkali and alkaline earth metal hydrides including LiH, KH, MgH2, CaH2, and BaH2 under nitrogen plasma differ significantly from one another, exhibiting an ammonia production trend that contrasts with that observed under thermal conditions. A prominent feature of KH is its ability to facilitate plasma-assisted N2 fixation without generating H2 byproduct, showing high atomic economy in utilization of hydride ions for N2 reduction.

Creating a bacterium that forms eukaryotic nucleosome core particles.

The nucleosome is one of the hallmarks of eukaryotes, a dynamic platform that supports many critical functions in eukaryotic cells. Here, we engineer the in vivo assembly of the nucleosome core in the model bacterium Escherichia coli. We show that bacterial chromosome DNA and eukaryotic histones can assemble in vivo to form nucleosome complexes with many features resembling those found in eukaryotes. The formation of nucleosomes in E. coli was visualized with atomic force microscopy and using tripartite split green fluorescent protein. Under a condition that moderate histones expression was induced at 1 µM IPTG, the nucleosome-forming bacterium is viable and has sustained growth for at least 110 divisions in longer-term growth experiments. It exhibits stable nucleosome formation, a consistent transcriptome across passages, and reduced growth fitness under stress conditions. In particular, the nucleosome arrays in E. coli genic regions have profiles resembling those in eukaryotic cells. The observed compatibility between the eukaryotic nucleosome and the bacterial chromosome machinery may reflect a prerequisite for bacteria-archaea union, providing insight into eukaryogenesis and the origin of the nucleosome.

Murepavadin Enhances the Killing Efficacy of Ciprofloxacin against Pseudomonas aeruginosa by Inhibiting Drug Efflux.

Pseudomonas aeruginosa is a multidrug-resistant Gram-negative pathogen and one of the leading causes of ventilator-associated pneumonia and infections in patients with chronic obstructive pulmonary disease and cystic fibrosis. Murepavadin is a peptidomimetic that specifically targets outer-membrane lipopolysaccharide transport protein LptD of P. aeruginosa. In this study, we find that murepavadin enhances the bactericidal efficacy of ciprofloxacin. We further demonstrate that murepavadin increases intracellular accumulation of ciprofloxacin by suppressing drug efflux. In addition, the murepavadin-ciprofloxacin combination exhibits a synergistic bactericidal effect in an acute murine pneumonia model. In conclusion, our results identify an effective drug combination for the treatment of P. aeruginosa infections.

The role and mechanism of dapagliflozin in Alzheimer disease: A review.

Alzheimer disease (AD), as the main type of dementia, is primarily characterized by cognitive dysfunction across multiple domains. Current drugs for AD have not achieved the desired clinical efficacy due to potential risks, inapplicability, high costs, significant side effects, and poor patient compliance. However, recent findings offer new hope by suggesting that sodium-glucose cotransporter 2 inhibitors (SGLT-2i) may possess neuroprotective properties, potentially opening up novel avenues for the treatment of AD. This review delves deeply into the multifaceted mechanisms of action of SGLT-2i in AD, encompassing antioxidative stress, antineuroinflammation, upregulation of autophagy, antiapoptosis, acetylcholinesterase inhibitor activity, and protection of endothelial cells against atherosclerosis and damage to the blood-brain barrier, among others. Furthermore, it provides an overview of recent advances in clinical research on this drug. These findings suggest that SGLT-2i is poised to emerge as a pivotal candidate for the treatment of AD, given its diverse functional effects.

Ocular adverse events associated with antibody-drug conjugates in oncology: a pharmacovigilance study based on FDA adverse event reporting system (FAERS).

Background: Antibody-drug conjugates (ADCs) have emerged as the focus and hotspots in the cancer field, yet the accompanying ocular toxicity has often been underestimated. We aimed to comprehensively and comparatively analyze the risk of ocular toxicity associated with various ADCs using the FDA Adverse Event Reporting System (FAERS) database. Methods: Data were extracted from the FAERS database from Q3 2011 to Q3 2023. We analyzed the clinical characteristics of ADCs-related ocular adverse events (AEs). These data were further mined by proportional analysis and Bayesian approach to detect signals of ADCs-induced ocular AEs. Moreover, the time to onset of ocular toxicity was also evaluated. Results: A total of 1,246 cases of ocular AEs were attributed to ADCs. Ocular toxicity signals were observed in patients treated with belantamab mafodotin, brentuximab vedotin, enfortumab vedotin, mirvetuximab soravtansine, sacituzumab govitecan, trastuzumab deruxtecan, and trastuzumab emtansine. Of these, belantamab mafodotin, trastuzumab emtansine, and mirvetuximab soravtansine, whose payloads are microtubule polymerization inhibitors, were more susceptible to ocular toxicity. The ten most common ADCs-related ocular AEs signals are keratopathy [ROR = 1,273.52, 95% CI (1,129.26-1,436.21)], visual acuity reduced [ROR = 22.83, 95% CI (21.2-24.58)], dry eye [ROR = 9.69, 95% CI (8.81-10.66)], night blindness [ROR = 259.87, 95% CI (228.23-295.89)], vision blurred [ROR = 1.78, 95% CI (1.57-2.02)], photophobia [ROR = 10.45, 95% CI (9.07-12.05)], foreign body sensation in eyes [ROR = 23.35, 95% CI (19.88-27.42)], ocular toxicity [ROR = 144.62, 95% CI (117.3-178.32)], punctate keratitis [ROR = 126.21, 95% CI (101.66-156.69)], eye disorder [ROR = 2.71, 95% CI (2.21-3.32)]. In terms of onset time, sacituzumab govitecan displayed an earlier onset of 21 days, while trastuzumab deruxtecan exhibited the latest onset of 223 days. Conclusion: ADCs may increase the risk of ocular toxicity in cancer patients, leading to serious mortality. With the widespread application of newly launched ADCs, combining the FAERS data with other data sources is crucial for monitoring the ocular toxicity of ADCs. In addition, novel ocular toxicity signals not documented in product labeling were detected. Further research will be necessary to validate our findings in the future.

Repurposing antihypertensive drugs for pain disorders: a drug-target mendelian randomization study.

Objective: Addressing the rising prevalence of pain disorders and limitations of current analgesics, our study explores repurposing antihypertensive drugs for pain management, inspired by the link between hypertension and pain. We leverage a drug-target Mendelian Randomization (MR) approach to explore their dual benefits and establish causal connections. Methods: A comprehensive compilation of antihypertensive drug classes was undertaken through British National Formulary, with their target genes identified using the DrugBank database. Relevant single nucleotide polymorphisms (SNPs) associated with these targets were selected from published genomic studies on systolic blood pressure (SBP) as genetic instruments. These SNPs were validated through MR against acute coronary artery disease (CAD) to ensure genes not linked to CAD were excluded from acting as proxies for antihypertensive drugs. An MR analysis of 29 pain-related outcomes was conducted using the FinnGen R10 database employing the selected and validated genetic instruments. We utilized the Inverse Variance Weighted (IVW) method for primary analysis, applying Bonferroni correction to control type I error. IVW's multiplicative random effects (MRE) addressed heterogeneity, and MR-PRESSO managed pleiotropy, ensuring accurate causal inference. Results: Our analysis differentiates strong and suggestive evidence in linking antihypertensive drugs to pain disorder risks. Strong evidence was found for adrenergic neuron blockers increasing migraine without aura risk, loop diuretics reducing panniculitis, and vasodilator antihypertensives lowering limb pain risk. Suggestive evidence suggests alpha-adrenoceptor blockers might increase migraine risk, while beta-adrenoceptor blockers could lower radiculopathy risk. Adrenergic neuron blockers also show a potential protective effect against coxarthrosis (hip osteoarthritis) and increased femgenpain risk (pain and other conditions related to female genital organs and menstrual cycle). Additionally, suggestive links were found between vasodilator antihypertensives and reduced radiculopathy risk, and both alpha-adrenoceptor blockers and renin inhibitors possibly decreasing dorsalgianas risk (unspecified dorsalgia). These findings highlight the intricate effects of antihypertensive drugs on pain disorders, underlining the need for further research. Conclusion: The findings indicate that antihypertensive medications may exert varied effects on pain management, suggesting a repurposing potential for treating specific pain disorders. The results advocate for further research to confirm these associations and to explore underlying mechanisms, to optimize pain management practices.

Photolithography-Free, Solution-Processable Perovskite Electrodes for High-Performance Organic Transistors.

Solution-processable electrodes are promising for next-generation electronics due to their simplicity, cost-effectiveness, and potential for large-area fabrication. However, current solution-processable electrodes based on conductive polymers, carbon-based compounds, and metal nanowires face challenges related to stability, patterning, and production scalability. Here we introduce a novel approach using 3D tin halide perovskites (THPs) combined with a photolithography-free solution patterning technique to fabricate solution-processed electrodes. We demonstrate the preparation of highly conductive CsSnI3 films (234.9 S cm-1) and the fabrication of patterned 35 × 35 perovskite electrode arrays on a 4-in. silicon wafer. These electrodes, used as source/drain electrodes in organic transistors, resulted in devices showing high uniformity and stability. This electrode fabrication strategy is also applicable to other 3D THPs like FASnI3 and MASnI3, showcasing versatility for diverse applications. The results highlight the feasibility and advantages of using 3D THPs as solution-processable electrodes, providing a new material system for the advancement of solution-processed electronics.

Whether mTICI 3 or mTICI 2b is better in patients with vertebrobasilar artery occlusion undergoing endovascular treatment depends on pc-ASPECTS.

BACKGROUND: The clinical relevance of differentiating between mTICI (modified Thrombolysis In Cerebral Infarction) 2b and mTICI 3 in patients with vertebrobasilar artery occlusion (VBAO) remains unclear. This study aimed to investigate whether mTICI 3 improves functional outcomes compared with mTICI 2b in patients with VBAO and whether this improvement differs according to extent of ischemic damage. METHODS: This retrospective study enrolled patients with VBAO within 24 hours of the estimated occlusion time at 65 stroke centers in a nationwide registration in China. The primary outcome was favorable functional outcome (modified Rankin scale score 0-3) at 90 days. Patients were matched by final mTICI grade using propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). Logistic regression and ordinal regression models were used to assess the impact of mTICI 2b versus mTICI 3 grading on prognosis, based on different extent of ischemia damage (posterior circulation Alberta Stroke Program Early CT Score-pc-ASPECTS of 9-10, 7-8, and 3-6) and treatment strategies (bridging therapy and direct endovascular therapy (EVT)). RESULTS: A total of 2075 patients with VBAO and successful reperfusion were included, 652 patients (31.4%) achieved mTICI 2b and 1423 patients (68.6%) achieved mTICI 3. After adjustment for confounders, achieving mTICI 3 following EVT in patients with VBAO and pc-ASPECTS 9-10 (OR 1.54, 95% CI 1.16 to 2.03) and pc-ASPECTS 7-8 (OR 1.80, 95% CI (1.26 to 2.56) were associated with favorable functional outcome compared with mTICI 2b, especially in those receiving direct EVT. However, in patients with pc-ASPECTS≤6, functional outcomes at 90 days did not differ between mTICI 3 and mTICI 2b (OR 1.12, 95% CI 0.67 to 1.88), irrespective of using bridging therapy or direct EVT. CONCLUSION: In patients with VBAO undergoing EVT with pc-ASPECTS>6, achieving mTICI 3 favors better outcomes compared with mTICI 2b, especially in those receiving direct EVT. However, in patients with pc-ASPECTS≤6, mTICI 3 did not improve functional outcomes compared with mTICI 2b. Interventionalists should carefully assess the risk-benefit of additional maneuvers once mTICI 2b reperfusion is restored in EVT for patients with VBAO and pc-ASPECTS≤6. Further studies are needed to guide treatment decisions in these cases.

An organic cathode for low-temperature processed, flexible ternary organic solar cells with high-performance.

In this study, we developed a flexible cathode for fabricating high-performance ternary organic solar cells (OSCs). With solvent engineering and acid treatment, the conductivity of the poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) electrode was significantly enhanced with the sheet resistance reduced from 1081 to 83 Ω sq-1. After being coated with polyethylenimine, work function of the PEDOT:PSS electrode was tuned from -5.07 to -4.12 eV, which is beneficial for electron collection in OSCs. With this technique, the OSCs (on glass) showed an average power conversion efficiency (PCE) of 16.3%, which is comparable to that of conventional inverted OSCs with commonly used indium-tin oxide and sol-gel-processed zinc oxide. However, the processing temperature of the inverted OSCs was dramatically lowered from 200 to 120 °C. The flexible OSCs (on polyethylene naphthalate/PEDOT:PSS/PEIE) exhibited a high PCE of 14.1%. After being bended for 300 cycles, the PCE was only degraded by 8.5%, indicating the excellent bendability of the flexible OSCs with the organic cathode.