Interface-confined intermediate phase in TiO2 enables efficient photocatalysis.

As a prototypical photocatalyst, TiO[Formula: see text] has been extensively studied. An interesting yet puzzling experimental fact was that P25-a mixture of anatase and rutile TiO[Formula: see text]-outperforms the individual phases; the origin of this mysterious fact, however, remains elusive. Employing rigorous first-principles calculations, here we uncover a metastable intermediate structure (MIS), which is formed due to confinement at the anatase/rutile interface. The MIS has a high conduction-band minimum level and thus substantially enhances the overpotential of the hydrogen evolution reaction. Also, the corresponding band alignment at the interface leads to efficient separation of electrons and holes. The interfacial confinement additionally creates a wide distribution of the band gap in the vicinity of the interface, which in turn improves optical absorption. These factors all contribute to the enhanced photocatalytic efficiency in P25. Our insights provide a rationale to the puzzling superior photocatalytic performance of P25 and enable a strategy to achieve highly efficient photocatalysis via interface engineering.

Midbrain dopamine neurons arbiter OCD-like behavior.

The neurobiological understanding of obsessive-compulsive disorder (OCD) includes dysregulated frontostriatal circuitry and altered monoamine transmission. Repetitive stereotyped behavior (e.g., grooming), a featured symptom in OCD, has been proposed to be associated with perturbed dopamine (DA) signaling. However, the precise brain circuits participating in DA's control over this behavioral phenotype remain elusive. Here, we identified that DA neurons in substantia nigra pars compacta (SNc) orchestrate ventromedial striatum (VMS) microcircuits as well as lateral orbitofrontal cortex (lOFC) during self-grooming behavior. SNc-VMS and SNc-lOFC dopaminergic projections modulate grooming behaviors and striatal microcircuit function differentially. Specifically, the activity of the SNc-VMS pathway promotes grooming via D1 receptors, whereas the activity of the SNc-lOFC pathway suppresses grooming via D2 receptors. SNc DA neuron activity thus controls the OCD-like behaviors via both striatal and cortical projections as dual gating. These results support both pharmacological and brain-stimulation treatments for OCD.

Computational Screening of Promising Deep-Ultraviolet Light Emitters.

Deep-ultraviolet (DUV) light sources are technologically highly important, but DUV light-emitting materials are extremely rare; AlN and its alloys are the only materials known so far, significantly limiting the chemical and structural spaces for materials design. Here, we perform a high-throughput computational search for DUV light emitters based on a set of carefully designed screening criteria relating to the sophisticated electronic structure. In this way, we successfully identify 5 promising material candidates that exhibit comparable or higher radiative recombination coefficients than AlN, including BeGeN2, Mg3NF3, KCaBr3, KHS, and RbHS. Further, we unveil the unique features in the atomic and electronic structures of DUV light emitters and elucidate the fundamental genetic reasons why DUV light emitters are extremely rare. Our study not only guides the design and synthesis of efficient DUV light emitters but also establishes the genetic nature of ultrawide-band-gap semiconductors in general.

Utilization trend of prebiopsy multiparametric magnetic resonance imaging and its impact on prostate cancer detection: Real-world insights from a high-volume center in southwest China.

BACKGROUND: Data on the utilization and effects of prebiopsy prostate multiparametric magnetic resonance imaging (mpMRI) to support its routine use in real-world setting are still scarce. OBJECTIVE: To evaluate the change of clinical practice of prebiopsy mpMRI over time, and assess its diagnostic accuracy. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively analyzed data from 6168 patients who underwent primary prostate biopsy (PBx) between January 2011 and December 2021 and had prostate-specific antigen (PSA) values ranging from 3 to 100 ng/mL. INTERVENTION: Prebiopsy MRI at the time of PBx. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We performed general linear regression and to elucidate trends in the annual use of prebiopsy mpMRI and conducted multivariable logistic regression to evaluate the potential benefits of incorporating prebiopsy mpMRI for prostate cancer (PCa) detection. RESULTS AND LIMITATIONS: The utilization of prebiopsy mpMRI significantly increased from 9.2% in 2011 to 75.0% in 2021 (p < 0.001). In addition, prebiopsy mpMRI significantly reduced negative PBx by 8.6% while improving the detection of clinically significant PCa (csPCa) by 7.0%. Regression analysis showed that the utilization of prebiopsy mpMRI was significantly associated with a 48% (95% confidence interval [CI]: 1.19-1.84) and 36% (95% CI: 1.12-1.66) increased PCa detection rate in the PSA 3-10 ng/mL and 10-20 ng/mL groups, respectively; and a 34% increased csPCa detection rate in the PSA 10-20 ng/mL group (95% CI: 1.09-1.64). The retrospective design and the single center cohort constituted the limitations of this study. CONCLUSIONS: Our study demonstrated a notable rise in the utilization of prebiopsy mpMRI in the past decade. The adoption of this imaging technique was significantly associated with an increased probability of detecting prostate cancer. PATIENT SUMMARY: From 2011 to 2021, we demonstrated a steady increase in the utilization of prebiopsy mpMRI among biopsy-naïve men. We also confirmed the positive impact of prebiopsy mpMRI utilization on the detection of prostate cancer.

Versatile CYP98A enzymes catalyse meta-hydroxylation reveals diversity of salvianolic acids biosynthesis.

Salvianolic acids (SA), such as rosmarinic acid (RA), danshensu (DSS), and their derivative salvianolic acid B (SAB), etc. widely existed in Lamiaceae and Boraginaceae families, are of interest due to medicinal properties in the pharmaceutical industries. Hundreds of studies in past decades described that 4-coumaroyl-CoA and 4-hydroxyphenyllactic acid (4-HPL) are common substrates to biosynthesize SA with participation of rosmarinic acid synthase (RAS) and cytochrome P450 98A (CYP98A) subfamily enzymes in different plants. However, in our recent study, several acyl donors and acceptors included DSS as well as their ester-forming products all were determined in SA-rich plants, which indicated that previous recognition to SA biosynthesis is insufficient. Here, we used Salvia miltiorrhiza, a representative important medicinal plant rich in SA, to elucidate the diversity of SA biosynthesis. Various acyl donors as well as acceptors are catalysed by SmRAS to form precursors of RA and two SmCYP98A family members, SmCYP98A14 and SmCYP98A75, are responsible for different positions' meta-hydroxylation of these precursors. SmCYP98A75 preferentially catalyses C-3' hydroxylation, and SmCYP98A14 preferentially catalyses C-3 hydroxylation in RA generation. In addition, relative to C-3' hydroxylation of the acyl acceptor moiety in RA biosynthesis, SmCYP98A75 has been verified as the first enzyme that participates in DSS formation. Furthermore, SmCYP98A enzymes knockout resulted in the decrease and overexpression leaded to dramatic increase of SA accumlation. Our study provides new insights into SA biosynthesis diversity in SA-abundant species and versatility of CYP98A enzymes catalytic preference in meta-hydroxylation reactions. Moreover, CYP98A enzymes are ideal metabolic engineering targets to elevate SA content.

An activity-based sensing fluorogenic probe for monitoring O-methyltransferase in plants.

Activity-based sensing probes are powerful tools for monitoring enzymatic activities in complex biological samples such as cellular and live animals; however, their application in plants remains challenging. Herein, fourteen activity-based fluorescent probes were assayed against Arabidopsis O-methyltransferases (AtOMTs). One probe, 3-BTD, displayed a high selectivity, reactivity, and fluorescence response toward AtOMTs especially the isoform AtCCoAOMT. We further characterized the features of this probe and explored whether it could be used to detect OMT activities in living plant cells. Our results show that 3-BTD can be used to visualize OMT activity in Arabidopsis, and no fluorescent signal was observed in the comt/ccoaomt double mutant, indicating that it has good specificity. Interestingly, in contrast to the observation that AtCCoAOMT-YFP accumulated in both cytoplasm and nucleus, OMT enzymatic activity tracked by 3-BTD probe was found only in the cytoplasm. This underscores the importance of activity-based sensing in studying protein function. Moreover, 3-BTD can be successfully applied in OMT visualization of different plants. This study indicates that 3-BTD can serve as a potential probe for in situ monitoring the real activity of OMT in multiple plants and provides a strategy for visualizing the activity of other enzymes in plants.

Stepwise changes in flavonoids in spores/pollen contributed to terrestrial adaptation of plants.

Protecting haploid pollen and spores against UV-B light and high temperature, 2 major stresses inherent to the terrestrial environment, is critical for plant reproduction and dispersal. Here, we show flavonoids play an indispensable role in this process. First, we identified the flavanone naringenin, which serves to defend against UV-B damage, in the sporopollenin wall of all vascular plants tested. Second, we found that flavonols are present in the spore/pollen protoplasm of all euphyllophyte plants tested and that these flavonols scavenge reactive oxygen species to protect against environmental stresses, particularly heat. Genetic and biochemical analyses showed that these flavonoids are sequentially synthesized in both the tapetum and microspores during pollen ontogeny in Arabidopsis (Arabidopsis thaliana). We show that stepwise increases in the complexity of flavonoids in spores/pollen during plant evolution mirror their progressive adaptation to terrestrial environments. The close relationship between flavonoid complexity and phylogeny and its strong association with pollen survival phenotypes suggest that flavonoids played a central role in the progression of plants from aquatic environments into progressively dry land habitats.

Diabetes and aortic dissection: unraveling the role of 3-hydroxybutyrate through mendelian randomization.

BACKGROUND: In observational and experimental studies, diabetes has been reported as a protective factor for aortic dissection. 3-Hydroxybutyrate, a key constituent of ketone bodies, has been found to favor improvements in cardiovascular disease. However, whether the protective effect of diabetes on aortic dissection is mediated by 3-hydroxybutyrate is unclear. We aimed to investigate the causal effects of diabetes on the risk of aortic dissection and the mediating role of 3-hydroxybutyrate in them through two-step Mendelian randomization. MATERIALS AND METHODS: We performed a two-step Mendelian randomization to investigate the causal connections between diabetes, 3-hydroxybutyrate, and aortic dissection and calculate the mediating effect of 3-hydroxybutyrate. Publicly accessible data for Type 1 diabetes, Type 2 diabetes, dissection of aorta and 3-hydroxybutyrate were obtained from genome-wide association studies. The association between Type 1 diabetes and dissection of aorta, the association between Type 2 diabetes and dissection of aorta, and mediation effect of 3-hydroxybutyrate were carried out separately. RESULTS: The IVW method showed that Type 1 diabetes was negatively associated with the risk of aortic dissection (OR 0.912, 95% CI 0.836-0.995), The weighted median, simple mode and weighted mode method showed consistent results. The mediated proportion of 3-hydroxybutyrate on the relationship between Type 1 diabetes and dissection of aorta was 24.80% (95% CI 5.12-44.47%). The IVW method showed that Type 2 diabetes was negatively associated with the risk of aortic dissection (OR 0.763, 95% CI 0.607-0.960), The weighted median, simple mode and weighted mode method showed consistent results. 3-Hydroxybutyrate does not have causal mediation effect on the relationship between Type 2 diabetes and dissection of aorta. CONCLUSION: Mendelian randomization study revealed diabetes as a protective factor for dissection of aorta. The protective effect of type 1 diabetes on aortic dissection was partially mediated by 3-hydroxybutyrate, but type 2 diabetes was not 3-hydroxybutyrate mediated.

Preoperative N-terminal Pro-B-type Natriuretic Peptide and High-sensitivity Cardiac Troponin T and Outcomes after Major Noncardiac Surgery: A Prospective Cohort Study.

BACKGROUND: Patients undergoing noncardiac surgery have varying risk of cardiovascular complications. This study evaluated preoperative N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T to enhance cardiovascular events prediction for major noncardiac surgery. METHODS: This prospective cohort study included adult patients with cardiovascular disease or risk factors undergoing elective major noncardiac surgery at four hospitals in China. Blood samples were collected within 30 days before surgery for NT-proBNP and high-sensitivity troponin T (hs-TnT) measurements. The primary outcome was a composite of any cardiovascular events within 30 days after surgery. Logistic regression models were used to assess associations, and the predictive performance was evaluated primarily using area under the receiver operating characteristics curve (AUC) and fraction of new predictive information. RESULTS: Between June 2019 and September 2021, a total of 2,833 patients were included, with 435 (15.4%) experiencing the primary outcome. In the logistic regression model that included clinical variables and both biomarkers, the odds ratio for the primary outcome was 1.68 (95% CI, 1.37 to 2.07) when comparing the 75th percentile to the 25th percentile of NT-proBNP distribution, and 1.91 (95% CI, 1.50 to 2.43) for hs-TnT. Each biomarker enhanced model discrimination beyond clinical predictors, with a change in AUC of 0.028 for NT-proBNP and 0.029 for high-sensitivity cardiac troponin T, and a fraction of new information of 0.164 and 0.149, respectively. The model combining both biomarkers demonstrated the best discrimination, with a change in AUC of 0.042 and a fraction of new information of 0.219. CONCLUSIONS: Preoperative NT-proBNP and hs-TnT both improved the prediction for cardiovascular events after noncardiac surgery in addition to clinical evaluation, with their combination providing maximal predictive information.

IL-6/STAT3 axis is hijacked by GCRV to facilitate viral replication via suppressing type â IFN signaling.

Grass carp reovirus (GCRV) infections and hemorrhagic disease (GCHD) outbreaks are typically seasonally periodic and temperature-dependent, yet the molecular mechanism remains unclear. Herein, we depicted that temperature-dependent IL-6/STAT3 axis was exploited by GCRV to facilitate viral replication via suppressing type Ⅰ IFN signaling. Combined multi-omics analysis and qPCR identified IL-6, STAT3, and IRF3 as potential effector molecules mediating GCRV infection. Deploying GCRV challenge at 18 °C and 28 °C as models of resistant and permissive infections and switched to the corresponding temperatures as temperature stress models, we illustrated that IL-6 and STAT3 expression, genome level of GCRV, and phosphorylation of STAT3 were temperature dependent and regulated by temperature stress. Further research revealed that activating IL-6/STAT3 axis enhanced GCRV replication and suppressed the expression of IFNs, whereas blocking the axis impaired viral replication. Mechanistically, grass carp STAT3 inhibited IRF3 nuclear translocation via interacting with it, thus down-regulating IFNs expression, restraining transcriptional activation of the IFN promoter, and facilitating GCRV replication. Overall, our work sheds light on an immune evasion mechanism whereby GCRV facilitates viral replication by hijacking IL-6/STAT3 axis to down-regulate IFNs expression, thus providing a valuable reference for targeted prevention and therapy of GCRV.

Decoding active compounds and molecular targets of herbal medicine by high-throughput metabolomics technology: A systematic review.

Clinical experiences of herbal medicine (HM) have been used to treat a variety of human intractable diseases. As the treatment of diseases using HM is characterized by multi-components and multi-targets, it is difficult to determine the bio-active components, explore the molecular targets and reveal the mechanisms of action. Metabolomics is frequently used to characterize the effect of external disturbances on organisms because of its unique advantages on detecting changes in endogenous small-molecule metabolites. Its systematicity and integrity are consistent with the effective characteristics of HM. After HM intervention, metabolomics can accurately capture and describe the behavior of endogenous metabolites under the disturbance of functional compounds, which will be used to decode the bioactive ingredients of HM and expound the molecular targets. Metabolomics can provide an approach for explaining HM, addressing unclear clinical efficacy and undefined mechanisms of action. In this review, the metabolomics strategy and its applications in HM are systematically introduced, which offers valuable insights for metabolomics methods to characterizing the pharmacological effects and molecular targets of HM.

The Association Between Sarcopenia and Stress Urinary Incontinence Among Older Adults in India: A Cross-Sectional Study.

Background: Older adults in low- and middle-income countries (LMICs) often suffer from both sarcopenia and stress urinary incontinence (SUI), two conditions that can significantly impact their health. However, the relationship between these conditions has not been thoroughly explored. Methods: We conducted a cross-sectional study using data from older adults aged 50 years or older from the first wave of the Longitudinal Ageing Study in India (LASI). Participants with complete data on sarcopenia and SUI were included, excluding female participants who were still menstruating. Sarcopenia was defined as decreased grip strength and slow movement. SUI was assessed based on questionnaire responses about whether the participant had ever passed urine when sneezing, coughing, laughing, or lifting heavy objects. We analyzed the data using multiple logistic regression analysis, interaction tests, and stratified analysis. Results: Our results showed that sarcopenia was positively correlated with SUI in male participants after adjusting for adequate confounding factors (odds ratio [OR] = 1.37, 95% confidence interval [CI] [1.20, 1.56], p < 0.001). This correlation remained stable after adjusting for additional confounding factors (OR = 1.27, 95% CI [1.11, 1.45], p < 0.001). In female participants, a stable correlation between sarcopenia and SUI was also observed after adjusting for appropriate confounding factors (OR = 1.11, 95% CI [1.01, 1.23], p = 0.037). According to the results of interaction tests and stratified analysis, the positive correlation between sarcopenia and SUI is notably stronger among men who abstain from alcohol and women who haven't undergone hysterectomy. Conclusions: Sarcopenia and SUI were positively correlated in older Indian adults, regardless of gender. Drinking and a history of hysterectomy may be important influencing factors for both male and female older adults. Further large-scale clinical trials are necessary to confirm this association.

Investigation of nutrition status and analysis of 180-day readmission factors in elderly hospitalized patients with COPD.

BACKGROUND AND OBJECTIVE: Malnutrition is prevalent among elderly patients with COPD, who also experience a high rate of readmission. Therefore, it is imperative to investigate the nutrition status of these patients, identify risk factors for readmission, and offer insights for clinical management. To achieve this, a cross-sectional study was conducted to investigate factors influencing nutrition status using GLIM criteria and explore the 180-day readmission factors among hospitalized elderly COPD patients. METHORDS AND RESULTS: The data were collected from a hospital in Southwest China, encompassing a cohort of 319 eligible patients. Among elderly hospitalized COPD patients, the prevalence of malnutrition was 49.53% (158/319). Multivariate logistic regression revealed malnutrition (OR = 3.184), very severe airway obstruction (OR = 3.735), and Number of comorbidities ≥ 3 (OR = 5.754) as significant risk factors for 180-day readmission. CONCLUSIONS: These findings suggest that malnutrition is a prevalent issue among elderly hospitalized patients with COPD and constitutes one of the risk factors contributing to the 180-day readmission rate. Therefore, timely identification and treatment for malnourished patients are crucial.

Comparing Efficacies of Different Exercises on Androgen Deprivation Therapy Adverse Effects in Prostate Cancer Patients: A Network Meta-Analysis.

INTRODUCTION: Previous studies showed exercise have efficacies for androgen deprivation therapy (ADT) adverse effects. To compare the efficacies of different exercises on ADT adverse effects, we conducted the network meta-analysis (NMA). METHODS: Literature retrieval was performed in PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL). Nineteen studies (1,184 participants) were included. All analyses were performed in R 4.1.2 or RevMan 5.4.1. RESULTS: NMA results showed that compared with the control group, both aerobic + resistance training (ART) (MD = 5.92, 95% CI: 0.38; 11.46) and resistance exercise (RE) (MD = 5.62, 95% CI: 2.70; 8.55) improved quality of life (QoL). ART (P score: 0.72) may have superiority over RE (P score: 0.7). ART (MD = -10.89, 95% CI: -17.67; -4.11) significantly improved the performance of 400-m test. RE could significantly improve leg strength (MD = 118, 95% CI: 78.75; 157.25) and chest strength (MD = 13.30, 95% CI: 4.07; 22.53). RE ranked first for strength improvements of leg and chest. CONCLUSION: ART showed better efficacy for the QoL and significantly improved the performance of 400-m test. RE might be superior for the strengths of leg and chest. ART may be appropriate for patients with less significant muscle strength decline but also other adverse effects of ADT, such as decreased cardiopulmonary function.

Metabolomics for Clinical Biomarker Discovery and Therapeutic Target Identification.

As links between genotype and phenotype, small-molecule metabolites are attractive biomarkers for disease diagnosis, prognosis, classification, drug screening and treatment, insight into understanding disease pathology and identifying potential targets. Metabolomics technology is crucial for discovering targets of small-molecule metabolites involved in disease phenotype. Mass spectrometry-based metabolomics has implemented in applications in various fields including target discovery, explanation of disease mechanisms and compound screening. It is used to analyze the physiological or pathological states of the organism by investigating the changes in endogenous small-molecule metabolites and associated metabolism from complex metabolic pathways in biological samples. The present review provides a critical update of high-throughput functional metabolomics techniques and diverse applications, and recommends the use of mass spectrometry-based metabolomics for discovering small-molecule metabolite signatures that provide valuable insights into metabolic targets. We also recommend using mass spectrometry-based metabolomics as a powerful tool for identifying and understanding metabolic patterns, metabolic targets and for efficacy evaluation of herbal medicine.

Constructing Donor-Acceptor Covalent Organic Frameworks for Highly Efficient H2O2 Photosynthesis Coupled with Oxidative Organic Transformations.

The development of photocatalytic systems that enable the simultaneous production of H2O2 and value-added organic chemicals presents a dual advantage: generating valuable products while maximizing the utilization of solar energy. Despite the potential, there are relatively few reports on photocatalysts capable of such dual functions. In this study, we synthesized a series of donor-acceptor covalent organic frameworks (COFs), designated as JUC-675 to JUC-677, to explore their photocatalytic efficiency in the co-production of H2O2 and N-benzylbenzaldimine (BBAD). Among them, JUC-675 exhibited exceptional performance, achieving a H2O2 production rate of 22.8 mmol g-1 h-1 with an apparent quantum yield of 15.7%, and its solar-to-chemical conversion efficiency was calculated to be 1.09%, marking it as the most effective COF-based photocatalyst reported to date. Additionally, JUC-675 demonstrated a high selectivity (99.9%) and yield (96%) for BBAD in the oxidative coupling of benzylamine. The underlying reaction mechanism was thoroughly investigated through validation experiments and density functional theory (DFT) calculations. This work represents a significant advancement in the design of COF-based photocatalysts and the development of efficient dual-function photocatalytic platforms, offering new insights and methodologies for enhanced solar energy utilization and the synthesis of value-added products.

Nanomedicine for urologic cancers: diagnosis and management.

Urologic cancers accounted for more than two million new cases and around 0.8 million deaths in 2020. Although surgery, chemotherapy, and radiotherapy, as well as castration for prostate cancer, remain the cornerstones for managing urologic neoplasms, they can result in severe adverse effects, poor patient compliance, and unsatisfactory survival rates, thus, it is essential to develop novel options that enable the early detection of these malignancies, together with providing accurate diagnoses, and more efficient treatment strategies. Nanomedicine represents an emerging approach that can deliver formulations or drugs across traditional biological barriers in the body and be directed to specific cell types within target organs via active targeting or passive targeting, thus, showing potential to improve the management of urologic cancers. In this review, we discussed the most recent updates on the application of nanomedicines in the diagnosis and treatment of urologic cancers, with focus on prostate, bladder and kidney tumors. We also presented the anti-tumor molecular mechanisms of newly designed nanomedicine for treating urologic cancers, mainly including image-guided surgery, chemotherapy, radiotherapy, gene therapy, immunotherapy, and their synergetic therapy. Current studies have demonstrated the potential advantages of nanomedicine over conventional approaches. However, most developments and new findings in this area have not been validated in clinical trials yet, and therefore, efforts shall be made to translate these research insights into clinical practices for urologic cancers.

Overexpressed ski efficiently promotes neurorestoration, increases neuronal regeneration, and reduces astrogliosis after traumatic brain injury.

Traumatic brain injury (TBI) survivors suffer from long-term disability and neuropsychiatric sequelae due to irreparable brain tissue destruction. However, there are still few efficient therapies to promote neurorestoration in damaged brain tissue. This study aimed to investigate whether the pro-oncogenic gene ski can promote neurorestoration after TBI. We established a ski-overexpressing experimental TBI mouse model using adenovirus-mediated overexpression through immediate injection after injury. Hematoxylin-eosin staining, MRI-based 3D lesion volume reconstruction, neurobehavioral tests, and analyses of neuronal regeneration and astrogliosis were used to assess neurorestorative efficiency. The effects of ski overexpression on the proliferation of cultured immature neurons and astrocytes were evaluated using imaging flow cytometry. The Ski protein level increased in the perilesional region at 3 days post injury. ski overexpression further elevated Ski protein levels up to 14 days post injury. Lesion volume was attenuated by approximately 36-55% after ski overexpression, with better neurobehavioral recovery, more newborn immature and mature neurons, and less astrogliosis in the perilesional region. Imaging flow cytometry results showed that ski overexpression elevated the proliferation rate of immature neurons and reduced the proliferation rate of astrocytes. These results show that ski can be considered a novel neurorestoration-related gene that effectively promotes neurorestoration, facilitates neuronal regeneration, and reduces astrogliosis after TBI.

IL-27 mediates anti-inflammatory effect in cigarette smoke induced emphysema by negatively regulating IFN-γ producing cytotoxic CD8+ T cells in mice.

Chronic airway inflammation mediated by CD8+ T lymphocytes contributes to the pathogenesis of Chronic obstructive pulmonary disease (COPD). Deciphering the fingerprint of the chronic inflammation orchestrated by CD8+ T cells may allow the development of novel approaches to COPD management. Here, the expression of IL-27 and IFN-γ+ CD8+ Tc1 cells were evaluated in patients with COPD and in cigarette smoke-exposed mice. The production of IL-27 by marrow-derived dendritic cells (mDCs) in response to cigarette smoke extract (CSE) was assessed. The role of IL-27 in IFN-γ+ CD8+ Tc1 cells was explored. We demonstrated that elevated IL-27 was accompanied by an exaggerated IFN-γ+ CD8+ Tc1 response in a smoking mouse model of emphysema. We noted that lung dendritic cells were one of the main sources of IL-27 during chronic cigarette smoke exposure. Moreover, CSE directly induced the production of IL-27 by mDCs in vitro. IL-27 negatively regulated the differentiation of IFN-γ+ CD8+ Tc1 cells isolated from cigarette smoke-exposed mice in a STAT1- and STAT3-independent manner. Systemic administration of recombinant IL-27 attenuated IFN-γ+ CD8+ Tc1 response in the late phase of cigarette smoke exposure. Our results uncovered that IL-27 negatively regulates IFN-γ+ CD8+ Tc1 response in the late stage of chronic cigarette smoke exposure, which may provide a new strategy for the anti-inflammatory treatment of smoking-related COPD/emphysema.

Acute Kidney Injury After General Thoracic Surgery: A Systematic Review and Meta-analysis.

INTRODUCTION: The clinical importance of postoperative acute kidney injury (AKI) in patients undergoing general thoracic surgery is unclear. We aimed to systematically review the incidence, risk factors, and prognostic implications of AKI as a complication after general thoracic surgery. METHODS: We searched PubMed, EMBASE, and the Cochrane Library from January 2004 to September 2021. Observational or interventional studies that enrolled ≥50 patients undergoing general thoracic surgery and reported postoperative AKI defined using contemporary consensus criteria were included for meta-analysis. RESULTS: Thirty-seven articles reporting 35 unique cohorts were eligible. In 29 studies that enrolled 58,140 consecutive patients, the pooled incidence of postoperative AKI was 8.0% (95% confidence interval [CI]: 6.2-10.0). The incidence was 3.8 (2.0-6.2) % after sublobar resection, 6.7 (4.1-9.9) % after lobectomy, 12.1 (8.1-16.6) % after bilobectomy/pneumonectomy, and 10.5 (5.6-16.7) % after esophagectomy. Considerable heterogeneity in reported incidences of AKI was observed across studies. Short-term mortality was higher (unadjusted risk ratio: 5.07, 95% CI: 2.99-8.60) and length of hospital stay was longer (weighted mean difference: 3.53, 95% CI: 2.56-4.49, d) in patients with postoperative AKI (11 studies, 28,480 patients). Several risk factors for AKI after thoracic surgery were identified. CONCLUSIONS: AKI occurs frequently after general thoracic surgery and is associated with increased short-term mortality and length of hospital stay. For patients undergoing general thoracic surgery, AKI may be an important postoperative complication that needs early risk evaluation and mitigation.