Organism-wide, cell-type-specific secretome mapping of exercise training in mice.

There is a significant interest in identifying blood-borne factors that mediate tissue crosstalk and function as molecular effectors of physical activity. Although past studies have focused on an individual molecule or cell type, the organism-wide secretome response to physical activity has not been evaluated. Here, we use a cell-type-specific proteomic approach to generate a 21-cell-type, 10-tissue map of exercise training-regulated secretomes in mice. Our dataset identifies >200 exercise training-regulated cell-type-secreted protein pairs, the majority of which have not been previously reported. Pdgfra-cre-labeled secretomes were the most responsive to exercise training. Finally, we show anti-obesity, anti-diabetic, and exercise performance-enhancing activities for proteoforms of intracellular carboxylesterases whose secretion from the liver is induced by exercise training.

Assessing financial performance through green bond markets and energy reliance in Asian economies.

This article's overarching goal is to learn more about the effects of financial performance on the reliance upon or migration to energy efficiency sources in Asian countries using data envelopment analysis (DEA) and system GMM from 2017 to 2022. The results demonstrated the importance of relying on renewable energy sources when expanding the electricity sector effectively in an Asian environment. This same influence of green bond financing on energy investment during an eco-friendly improving economy is in addition to the proportion of renewable energy demands, power usage to gross domestic product, power manufacturing stretchability, electricity usage stretchability, or the overall impact of renewable energy transformation. The analysis revealed that the organizational climate has implicit implications that advance wage activity and that Asian financial systems drove a 30% point transition in the period studied from traditional power generation manufacturing and use methods toward sustainable energy. With this, we see a dramatic increase in the use of green power. This is largely attributable to the widespread use of green financing in constructing hydroelectric facilities throughout Asia. The theoretical underpinnings and empirical setting of the research are both original. Moreover, the association between green bond issuance and green, sustainable growth in industry and agriculture supports the response theory. Major governmental aspects include modernizing and expanding the finance system, updating national efficiency metrics, and creating a technological long-term infrastructure market. While previous studies have looked into the connections between green finance and economic growth, technological advancements in the energy sector, environmental responsibility, and renewable energy sources, this study is the first to focus on how green finance facilitates the shift to renewable energy in Asia's economies. The study's findings suggest how to manage renewable energy in Asia in a way that could work.

Genome-wide analysis of RNA-binding proteins co-expression with alternative splicing events in mitral valve prolapse.

Objectives: We investigated the role and molecular mechanisms of RNA-binding proteins (RBPs) and their regulated alternative splicing events (RASEs) in the pathogenesis of mitral valve prolapse (MVP). Methods: For RNA extraction, we obtained peripheral blood mononuclear cells (PBMCs) from five patients with MVP, with or without chordae tendineae rupture, and five healthy individuals. High-throughput sequencing was used for RNA sequencing (RNA-seq). Differentially expressed genes (DEGs) analysis, alternative splicing (AS) analysis, functional enrichment analysis, co-expression of RBPs, and alternative splicing events (ASEs) analysis were conducted. Results: The MVP patients exhibited 306 up-regulated genes and 198 down-regulated genes. All down- and up-regulated genes were enriched in both Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Furthermore, MVP was closely associated with the top 10 enriched terms and pathways. In MVP patients, 2,288 RASEs were found to be significantly different, and four suitable RASEs (CARD11 A3ss, RBM5 ES, NCF1 A5SS, and DAXX A3ss) were tested. We identified 13 RNA-binding proteins (RBPs) from the DEGs and screened out four RBPs (ZFP36, HSPA1A, TRIM21, and P2RX7). We selected four RASEs based on the co-expression analyses of RBPs and RASEs, including exon skipping (ES) of DEDD2, alternative 3' splice site (A3SS) of ETV6, mutually exclusive 3'UTRs (3pMXE) of TNFAIP8L2, and A3SS of HLA-B. Furthermore, the selected four RBPs and four RASEs were validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and showed high consistency with RNA sequencing (RNA-seq). Conclusion: Dysregulated RBPs and their associated RASEs may play regulatory roles in MVP development and may therefore be used as therapeutic targets in the future.

Factors related to postoperative vitreous hemorrhage after small-gauge vitrectomy in proliferative diabetic retinopathy patients.

BACKGROUND: The role of anticoagulation or antiplatelet on post-vitrectomy vitreous hemorrhage (POVH) in patients with proliferative diabetic retinopathy (PDR) is rarely investigated in the small-gauge vitrectomy era. We investigate the relationship between the long-term use of those medications and POVH in a group of PDR patients. METHODS: A retrospective cohort study was carried out in a group of PDR patients who underwent small-gauge vitrectomy in our center. The baseline data on diabetes, diabetic complications, long-term use of anticoagulants and antiplatelet agents, ocular findings, and vitrectomy details were collected. The occurrence of POVH was recorded during at least three-month follow-up. Factors related to POVH were analyzed using logistic analysis. RESULTS: During a median follow-up of 16 weeks, 5% (11/220) of patients had POVH, and 75 had received antiplatelet or anticoagulation agents before the operation. Factors related to persistent POVH were the use of antiplatelet or anticoagulation agents (5.98, 1.75-20.45, p = 0.004), the presence of myocardial revascularization (130.65, 3.53-4834.50, p = 0.008), the presence of coronary artery disease (CAD) treated with medicine (56.52, 1.99-1604.06, p = 0.018), and younger age (0.86, 0.77-0.96, p = 0.012). For those receiving preoperative antiplatelet or anticoagulation agents, the probability of developing POVH was higher in the patients whose previous therapy was adjusted compared to those with continued therapy (p = 0.02 by Log-rank test). CONCLUSIONS: We identified long-term use of anticoagulation or antiplatelet medication, the presence of CAD, and younger age as three independent factors related to POVH. In PDR patients on long-term antiplatelet or anticoagulation medications, particular attention should be given to controlling intraoperative bleeding, and follow-up for POVH should be scheduled.

Buyang huanwu decoction (BYHWD) alleviates sepsis-induced myocardial injury by suppressing local immune cell infiltration and skewing M2-macrophage polarization.

OBJECTIVE: To investigate the therapeutic effect of Buyang huanwu decoction (BYHWD) on sepsis-induced myocardial injury (SIMI) and explore the mechanism by which BYHWD mitigates SIMI. METHODS: The Lipopolysaccharide (LPS)-induced SIMI mouse model was established to detect the effect of BYHWD-low (1 mg/kg), BYHWD-middle (5 mg/kg), and BYWHD-high (20 mg/kg) on SIMI. The survival of these BYHWD-treated septic mice was investigated. The histology of myocardial tissues was determined by hematoxylin and eosin (H&E) staining. The apoptotic index and inflamed microenvironment of myocardial tissues were assessed by immunofluorescent staining (IF) and flow cytometry analysis. Liquid chromatography-mass spectrometry (LC-MS/MS) was employed to determine the key chemical components in the serum of BYHWD-loaded septic mice. Immunoblotting assay was utilized to detect NF-κB and TGF-ß signaling activity, and M1/M2-macrophage markers using RAW264.7 cells. RESULTS: The high dosage of BYHWD (BYHWD-high, 20 mg/Kg) significantly attenuated SIMI and improved the survival of septic mice. The BYHWD-high solution markedly reduced myocardial cell apoptosis and mitigated the inflamed microenvironment by suppressing CD45+ immune cell infiltration. Importantly, BYHWD decreased macrophage accumulation and promoted an M2-macrophage polarization. Paeoniflorin (PF) and calycosin-7-O-ß-glucoside (CBG) were identified as the key molecules in BYWHD with therapeutic effect. PF (10 µM) and CBG (1 µM) inhibited NF-κB signaling, meanwhile they upregulated the TGF-ß pathway, thereby facilitating an M2-macrophage phenotypic transition in RAW264.7 cells. CONCLUSIONS: BYHWD, with two effective components PF and CBG, can mitigate SIMI by suppressing the inflamed myocardial microenvironment and skewing an immunosuppressive M2-macrophage phenotype.

Metal-insulator crossover in monolayer MoS2.

We report on transport measurements in monolayer MoS2devices, close to the bottom of the conduction band edge. These devices were annealedin situbefore electrical measurements. This allows us to obtain good ohmic contacts at low temperatures, and to measure precisely the conductivity and mobility via four-probe measurements. The measured effective mobility up to µeff= 180 cm2/Vs is among the largest obtained in CVD-grown MoS2monolayer devices. These measurements show that electronic transport is of the insulating type for σ≤ 1.4e2/h and n ≤ 1.7×1012cm-2, and a crossover to a metallic regime is observed above those values. In the insulating regime, thermally activated transport dominates at high temperature (T > 100 K). At lower temperatures, conductivity is driven by Efros-Schklovkii variable range hopping in all measured devices, with a universal and constant hopping prefactor, that is a clear indication that hopping is not phonon-mediated. At higher carrier density, and high temperature, the conductivity is well modeled by the Boltzmann equation for a non-interacting Fermi gas, taking into account both phonon and impurity scatterings. Finally, even if this apparent metal-insulator transition can be explained by phonon-related phenomena at high temperature, the possibility of a genuine 2D MIT cannot be ruled out, as we can observe a clear power-law diverging localization length close to the transition, and a one-parameter scaling can be realized. .

Vitamin B6 regulates IL-33 homeostasis to alleviate type 2 inflammation.

Interleukin-33 (IL-33) is a crucial nuclear cytokine that induces the type 2 immune response and maintains immune homeostasis. The fine-tuned regulation of IL-33 in tissue cells is critical to control of the type 2 immune response in airway inflammation, but the mechanism is still unclear. Here, we found that healthy individuals had higher phosphate-pyridoxal (PLP, an active form of vitamin B6) concentrations in the serum than asthma patients. Lower serum PLP concentrations in asthma patients were strongly associated with worse lung function and inflammation. In a mouse model of lung inflammation, we revealed that PLP alleviated the type 2 immune response and that this inhibitory effect relied on the activity of IL-33. A mechanistic study showed that in vivo, pyridoxal (PL) needed to be converted into PLP, which inhibited the type 2 response by regulating IL-33 stability. In mice heterozygous for pyridoxal kinase (PDXK), the conversion of PL to PLP was limited, and IL-33 levels were increased in the lungs, aggravating type 2 inflammation. Furthermore, we found that the mouse double minute 2 homolog (MDM2) protein, an E3 ubiquitin-protein ligase, could ubiquitinate the N-terminus of IL-33 and sustain IL-33 stability in epithelial cells. PLP reduced MDM2-mediated IL-33 polyubiquitination and decreased the level of IL-33 through the proteasome pathway. In addition, inhalation of PLP alleviated asthma-related effects in mouse models. In summary, our data indicate that vitamin B6 regulates MDM2-mediated IL-33 stability to constrain the type 2 response, which might help develop a potential preventive and therapeutic agent for allergy-related diseases.

As-grown Miniaturized True Zero-order Waveplates Based on Low-dimensional Ferrocene Crystals.

As basic optical elements, waveplates with anisotropic electromagnetic responses are imperative for manipulating light polarization. Conventional waveplates are manufactured from bulk crystals (e.g., quartz and calcite) through a series of precision cutting and grinding steps, which typically result in large size, low yield, and high cost. In this study, we use a bottom-up method to grow ferrocene crystals with large anisotropy to demonstrate self-assembled ultrathin true zero-order waveplates without additional machining processing, which is particularly suited for nanophotonic integration. The van der Waals ferrocene crystals exhibit high birefringence (Δn (experiment) = 0.149  ±  0.002 at 636 nm), low dichroism Δκ (experiment) = -0.0007 at 636 nm), and a potentially broad operating range (550 nm to 20 µm) as suggested by Density Functional Theory (DFT) calculations. In addition, the grown waveplate's highest and the lowest principal axes (n1 and n3 , respectively) are in the a-c plane, where the fast axis is along one natural edge of the ferrocene crystal, rendering them readily usable. The as-grown, wavelength-scale-thick waveplate allows the development of further miniaturized systems via tandem integration. This article is protected by copyright. All rights reserved.

Single-cell transcriptomics reveals that tumor-infiltrating natural killer cells are activated by localized ablative immunotherapy and share anti-tumor signatures induced by immune checkpoint inhibitors.

Rationale: Natural killer (NK) cells provide protective anti-cancer immunity. However, the cancer therapy induced activation gene signatures and pathways in NK cells remain unclear. Methods: We applied a novel localized ablative immunotherapy (LAIT) by synergizing photothermal therapy (PTT) with intra-tumor delivering of the immunostimulant N-dihydrogalactochitosan (GC), to treat breast cancer using a mammary tumor virus-polyoma middle tumor-antigen (MMTV-PyMT) mouse model. We performed single-cell RNA sequencing (scRNAseq) analysis to unveil the cellular heterogeneity and compare the transcriptional alterations induced by PTT, GC, and LAIT in NK cells within the tumor microenvironment (TME). Results: ScRNAseq showed that NK subtypes, including cycling, activated, interferon-stimulated, and cytotoxic NK cells. Trajectory analysis revealed a route toward activation and cytotoxicity following pseudotime progression. Both GC and LAIT elevated gene expression associated with NK cell activation, cytolytic effectors, activating receptors, IFN pathway components, and cytokines/chemokines in NK subtypes. Single-cell transcriptomics analysis using immune checkpoint inhibitor (ICI)-treated animal and human samples revealed that ICI-induced NK activation and cytotoxicity across several cancer types. Furthermore, ICI-induced NK gene signatures were also induced by LAIT treatment. We also discovered that several types of cancer patients had significantly longer overall survival when they had higher expression of genes in NK cells that were also specifically upregulated by LAIT. Conclusion: Our findings show for the first time that LAIT activates cytotoxicity in NK cells and the upregulated genes positively correlate with beneficial clinical outcomes for cancer patients. More importantly, our results further establish the correlation between the effects of LAIT and ICI on NK cells, hence expanding our understanding of mechanism of LAIT in remodeling TME and shedding light on the potentials of NK cell activation and anti-tumor cytotoxic functions in clinical applications.

Serum vitamin D levels and Sjogren's syndrome: bi-directional Mendelian randomization analysis.

BACKGROUND: Based on the results of existing observational studies, it can be found that the association between serum vitamin D levels and the risk of Sjogren's syndrome (SS) in humans is still controversial. Based on this situation, this study aimed to assess the causal relationship between serum vitamin D levels and SS by using the Mendelian randomization (MR) approach. METHODS: In this study, genome-wide association studies (GWAS) summary statistics on serum vitamin D levels [sample size = 417,580 (UK Biobank)] and SS [sample size = 416,757 (cases = 2495, controls = 414,262) (FinnGen)] were used. The bi-directional MR analysis was then used to assess possible causal relationships. The major analysis method of MR was performed using inverse-variance weighted (IVW), supplemented by MR-Egger and the weighted median approaches. In addition, sensitivity analyses were used to ensure the stability of the results, including Cochran's Q test, MR-PRESSO, MR-Egger intercept test, and the leave-one-out test. RESULTS: The MR suggested that no significant causal effects of serum 25(OH)D levels on SS risks were observed [odds ratio (OR) = 0.9824; 95% confidence interval (CI) = 0.7130 to 1.3538; P = 0.9137]. Similarly, no evidence supported the causal effects of SS on serum vitamin D levels (ß: 0.0076, 95% CI: - 0.0031 to 0.0183; P = 0.1640). CONCLUSION: This study found no obvious evidence that serum vitamin D level is causally associated with SS risks or vice versa. We call for larger sample size studies to further unravel the potential causal relationship and the exact mechanism.

Single-Atom Rh on High-Index CeO2 Facet for Highly Enhanced Catalytic CO Oxidation.

Reducible oxide-supported noble metal nanoparticles exhibit high activity in catalyzing many important oxidation reactions. However, atom migration under harsh reaction conditions leads to deactivation of the catalyst. Meanwhile, single-atom catalysts demonstrate enhanced stability, but often suffer from poor catalytic activity owing to the ionized surface states. In this work, we simultaneously address the poor activity and stability issues by synthesizing highly active and durable rhodium (Rh) single-atom catalysts through a "wrap-bake-peel" process. The pre-coated SiO2 layer during synthesis of catalyst plays a crucial role in not only protecting CeO2 support against sintering, but also donating electron to weaken the Ce-O bond, producing highly loaded Rh single atoms on the CeO2 support exposed with high-index {210} facets. Benefiting from the unique electronic structure of CeO2 {210} facets, more oxygen vacancies are generated along with the deposition of more electropositive Rh single atoms, leading to remarkably improved catalytic performance in CO oxidation.

Anthropogenic perturbation enhances the release of geogenic Mn to groundwater: Evidence from hydrogeochemical characteristics.

High geogenic Mn groundwater is widespread around the world and has also proved to be harmful to human health, especially to the IQ of Children. The natural release of Mn from aquifer sediments in slightly reducing condition is believed to be the primary cause. However, there isn't enough evidence to prove that anthropogenic activities promote the reductive release of Mn. Here a Historical Petrochemical Waste Storage Site (HPWSS) was studied to evaluate its impact on groundwater quality. Significantly elevated Mn, as well as elevated TDS, anionic surfactants, and organic pollutants, were found in the shallow aquifer (9-15 m) groundwater compared to the surrounding area. The Mn was believed to be generated in-situ, while others are caused by anthropogenic pollution. The good correlations between Mn and NH4+, HCO3-, I, As, Co, V, Ti, respectively, showed the Mn mobilization was mainly attributed to the reductive dissolution of Mn oxides/hydroxides. The potential processes leading to this enhanced Mn release are discussed, including 1) the infiltration of high salinity water which solubilized sediment organic matter (OM); 2) the anionic surfactants that promoted the dissolution and mobilization of surface-derived organic pollutants as well as sediment OM. Any of these processes may have provided a C source to stimulate the microbial reduction of Mn oxides/hydroxides. This study showed the input of pollutants could change the redox and dissolution conditions of the vadose zone and aquifer, causing a secondary geogenic pollution risk in groundwater. Since Mn is easily mobilized in suboxic condition as well as its toxicity, the enhanced release due to anthropogenic perturbation merits more attention.

Longitudinal trajectories of illness perception regarding breast cancer-related lymphedema among women with breast cancer.

OBJECTIVE: To identify longitudinal trajectories of illness perception (IP) regarding breast cancer-related lymphedema (BCRL) in the first six months after surgery among women with breast cancer and to explore the predictive effects of demographics and clinical factors on IP trajectories. METHODS: From August 2019 to August 2021, a total of 352 patients participated in this study, 328 of whom were included in the data analysis. Demographic and clinical characteristics were collected at baseline (1-3 days after surgery). The BCRL-specific revised illness perception questionnaire was used to measure IP regarding BCRL at baseline and 1 month, 3 months and 6 months post-surgery. A multilevel model was conducted to analyze the data. RESULTS: Over the first six months post-surgery, the "timeline acute/chronic" and "illness coherence" dimensions showed positive growth trajectories; the "personal control" and "treatment control" dimensions presented negative growth trajectories; and the trajectories of identity, consequences, cyclicality and emotional influence perceptions regarding BCRL showed no significant changes. Age, education level, marital status, employment status, family monthly income per person, cancer stage and status of removed lymph nodes were indicated to be predictive factors of IP trajectories. CONCLUSIONS: The present study determined significant changes over the first six months post-surgery in four IP dimensions and predictive effects of some demographics and clinical details on IP trajectories. These findings may help healthcare providers know more about the dynamic characteristics of IPs regarding BCRL in patients with breast cancer and assist them in identifying patients with a tendency toward improper IP regarding BCRL.

Exercise Reduces Airway Smooth Muscle Contraction in Asthmatic Rats via Inhibition of IL-4 Secretion and Store-Operated Ca2+ Entry Pathway.

PURPOSE: Increased evidence has shown that aerobic exercise reduces airway hyperresponsiveness in asthmatic individuals. However, the underlying mechanisms of action remain elusive. This study aimed to investigate the effect of exercise on airway smooth muscle (ASM) contractile function in asthmatic rats, and uncover the possible involvement of interleukin 4 (IL-4) and the store-operated Ca2+ entry (SOCE) pathway. METHODS: In this study, chicken ovalbumin was used to induce asthma in male Sprague-Dawley rats. The exercise group received moderate-intensity aerobic exercise training for 4 weeks. IL-4 concentrations in bronchoalveolar lavage fluid (BALF) samples were evaluated by enzyme linked immunosorbent assay. The contractile function of the ASM was investigated using tracheal ring tension experiments and intracellular Ca2+ imaging techniques. Western blot analysis was used to evaluate expression levels of calcium-release activated calcium (CRAC) channel protein (Orai) and stromal interaction molecule 1 (STIM1) in ASM. RESULTS: Our data showed that the carbachol-stimulated, SOCE-mediated contraction of rat ASM was significantly increased in asthmatic rats, which could be abolished by exercise. Pharmacological studies revealed that GSK5498A and BTP-2, selective blockers of CRAC channels significantly inhibited SOCE-induced ASM contraction. In addition, exercise inhibited the up-regulation of IL-4 in BALF as well as STIM1 and Orai expression in the ASM of asthmatic rats. In line with these observations, we demonstrated that pretreatment of the ASM with IL-4 up-regulated the expression level of STIM1, Orai1 and Orai2, thereby promoting SOCE-mediated ASM contraction. CONCLUSIONS: The data in this study reveal that aerobic exercise may improve the ASM contractile function in asthmatic rats by inhibiting IL-4 secretion and by down-regulating the expression of STIM1, Orai1 and Orai2, thus decreasing excessive SOCE-mediated ASM contraction in asthmatic rats.

Modified you-only-look-once model for joint source detection and azimuth estimation in a multi-interfering underwater acoustic environment.

The you-only-look-once (YOLO) model identifies objects in complex images by framing detection as a regression problem with spatially separated boundaries and class probabilities. Object detection from complex images is somewhat similar to underwater source detection from acoustic data, e.g., time-frequency distributions. Herein, YOLO is modified for joint source detection and azimuth estimation in a multi-interfering underwater acoustic environment. The modified you-only-look-once (M-YOLO) input is a frequency-beam domain (FBD) sample containing the target and multi-interfering spectra at different azimuths, generated from the received data of a towed horizontal line array. M-YOLO processes the whole FBD sample using a single-regression neural network and directly outputs the target-existence probability and spectrum azimuth. Model performance is assessed on both simulated and at-sea data. Simulation results reveal the strong robustness of M-YOLO toward different signal-to-noise ratios and mismatched ocean environments. As tested on the data collected in an actual multi-interfering environment, M-YOLO achieved near-100% target detection and a root mean square error of 0.54° in azimuth estimation.

Three-dimensional numerical study on wrinkling of vesicles in elongation flow based on the immersed boundary method.

We study the wrinkling dynamics of three-dimensional vesicles in a time-dependent elongation flow by utilizing an immersed boundary method. For a quasispherical vesicle, our numerical results well match the predictions of perturbation analysis, where similar exponential relationships between wrinkles' characteristic wavelength and the flow strength are observed. Using the same parameters as in the experiments by Kantsler et al. [V. Kantsler et al., Phys. Rev. Lett. 99, 178102 (2007)0031-900710.1103/PhysRevLett.99.178102], our simulations of an elongated vesicle are in good agreement with their results. In addition, we get rich three-dimensional morphological details, which are favorable to comprehend the two-dimensional snapshots. This morphological information helps identify wrinkle patterns. We analyze the morphological evolution of wrinkles using spherical harmonics. We find discrepancies in elongated vesicle dynamics between simulations and perturbation analysis, highlighting the importance of the nonlinear effects. Finally, we investigate the unevenly distributed local surface tension, which largely determines the position of wrinkles excited on the vesicle membrane.

SEEG-based reevaluation of epileptogenic networks and the predictive role for reoperation in MTLE patients with surgical failure.

OBJECTIVE: Approximately 20%-30% of mesial temporal lobe epilepsy (MTLE) patients got unfavorable seizure control after surgery, and there was a discrepancy about the reasons for the surgical failure. The functional connectivity (FC) patterns obtained from stereo-electroencephalography (SEEG) reveal information about the dynamics of the epileptic brain and the added value of extracting information that was not identifiable in the SEEG data using FC analysis. This study aims to find out the patterns of the potential epileptogenic network of failure patients and the electrophysiological predictors of reoperation. METHODS: From January 2012 to December 2019, the MTLE patients with surgical failure were reviewed, and all patients underwent SEEG-guided reoperation. The epileptogenic network was quantified by calculating FC indicators, including phase slope index (PSI), mutual information (MI) strength, imaginary coherence (icoh), and Granger causality. RESULTS: Ten patients with 13 seizures were included in the analysis, and 7 of them achieved a favorable outcome after the SEEG-guided reoperation. The surgical zone (SZ) with a favorable prognosis showed greater outward information flow than the non-SZ, whereas the SZ with an unfavorable prognosis showed greater inward information flow. The recurrent patients with favorable prognosis had strong connectivity between the posterior hippocampus, temporal neocortex, and insula, whereas the patients with unfavorable prognosis showed strong functional connectivity between the insula and temporal-parietal-occipital junction. The power spectrum of patients with favorable prognosis was significantly lower than that of patients with unfavorable prognosis, especially showing a more oscillation power of low frequency. SIGNIFICANCE: The SEEG-guided reoperation could achieve favorable seizure control outcomes for recurrent patients. The FCs were a potential indicator to help construct the temporal epileptic network and predictor for the reoperative prognosis in the recurrent patients.

Association of antihypertensive drugs with fracture and bone mineral density: A comprehensive drug-target Mendelian randomization study.

Background: Observational studies have investigated the associations between antihypertensive drugs and fracture risk as well as bone mineral density (BMD), but yielding controversial results. Methods: In this study, a comprehensive drug-target Mendelian randomization (MR) analysis was conducted to systematically examine the associations between genetic proxies for eight common antihypertensive drugs and three bone health-related traits (fracture, total body BMD [TB-BMD], and estimated heel BMD [eBMD]). The main analysis used the inverse-variance weighted (IVW) method to estimate the causal effect. Multiple MR methods were also employed to test the robustness of the results. Results: The genetic proxies for angiotensin receptor blockers (ARBs) were associated with a reduced risk of fracture (odds ratio [OR] = 0.67, 95% confidence interval [CI]: 0.54 to 0.84; P = 4.42 × 10-4; P-adjusted = 0.004), higher TB-BMD (ß = 0.36, 95% CI: 0.11 to 0.61; P = 0.005; P-adjusted = 0.022), and higher eBMD (ß = 0.30, 95% CI: 0.21 to 0.38; P = 3.59 × 10-12; P-adjusted = 6.55 × 10-11). Meanwhile, genetic proxies for calcium channel blockers (CCBs) were associated with an increased risk of fracture (OR = 1.07, 95% CI: 1.03 to 1.12; P = 0.002; P-adjusted = 0.013). Genetic proxies for potassium sparing diuretics (PSDs) showed negative associations with TB-BMD (ß = -0.61, 95% CI: -0.88 to -0.33; P = 1.55 × 10-5; P-adjusted = 1.86 × 10-4). Genetic proxies for thiazide diuretics had positive associations with eBMD (ß = 0.11, 95% CI: 0.03 to 0.18; P = 0.006; P-adjusted = 0.022). No significant heterogeneity or pleiotropy was identified. The results were consistent across different MR methods. Conclusions: These findings suggest that genetic proxies for ARBs and thiazide diuretics may have a protective effect on bone health, while genetic proxies for CCBs and PSDs may have a negative effect.

Association between CD8+ tumor-infiltrating lymphocytes and prognosis of non-small cell lung cancer patients treated with PD-1/PD-L1 inhibitors: a systematic review and meta-analysis.

BACKGROUND: A meta-analysis method was used to investigate the prognostic value of CD8+ tumor-infiltrating lymphocytes (TILs) in non-small cell lung cancer (NSCLC) patients treated with PD-1/PD-L1 inhibitors. METHODS: A database search of PubMed, Embase, Web of Science and Cochrane Library up until 7 February, 2023. A clinical study on the relationship between CD8+ TILs and PD-1/PD-L1 inhibitors in the therapeutics of NSCLC. RevMan 5.3 and StataMP 17.0 software were used for meta-analysis. The outcome indicators incorporated overall survival (OS), progression-free survival (PFS) and objective response rate (ORR). RESULTS: Nineteen articles with 1488 patients were included. The analysis results showed that high CD8+ TILs were associated with better OS (HR = 0.60, 95% CI: 0.46-0.77; P < 0.0001), PFS (HR = 0.68, 95% CI: 0.53-0.88; P = 0.003) and ORR (OR = 2.26, 95% CI: 1.52-3.36; P < 0.0001) in NSCLC patients treated with PD-1/PD-L1 inhibitors. Subgroup analysis indicated that patients with high CD8+ TILs had good clinical prognostic benefits whether the location of CD8+ TILs was intratumoral or stromal, and compared with East Asian, high CD8+ TILs in Caucasians showed a better prognosis. High CD8+ TILs in peripheral blood did not improve OS (HR = 0.83, 95% CI: 0.69-1.01; P = 0.06) and PFS (HR = 0.93, 95% CI: 0.61-1.14; P = 0.76) in NSCLC patients receiving PD-1/PD-L1 inhibitors. CONCLUSION: In spite of the location of CD8+ TILs, high densities of CD8+ TILs were predictive of treatment outcomes in NSCLC patients treated with PD-1/PD-L1 inhibitors. However, high CD8+ TILs in peripheral blood had no predictive effect.