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Understanding and quantifying the resilience of forests to disturbances are increasingly important for forest management. Historical fire suppression, logging, and other land uses have increased densities of shade tolerant trees and fuel buildup in the western United States, which has reduced the resilience of these forests to natural disturbances. One way to mitigate this problem is to use fuel treatments such as stand thinning and prescribed burning. In this study, we investigated changes in forest structure in the Lassen and Plumas National Forests of northern California following a large wildfire. We used long-term field data and aerial photos to examine what management techniques can be effectively used to restore a healthy forest structure and increase the resilience of forests to drought and wildfires. Forest resilience was quantitatively modeled using the forest vegetation simulator and analyzed under varied thinning practices and fuel management scenarios. Results showed that trees below 1,219 m in elevation had the least mortality and gained the most biomass. Trees taller than 45.7 m lost the most biomass. We found that thinning basal area to 16.1 m2·hm−2 resulted in the highest resilience score for California mixed conifer forest stands and thinning to 9.2 m2·hm−2 resulted in the highest resilience score for Jeffrey pine stands. Structural diversity had a negative relationship with resilience score. Understanding forest structure, forest resilience, and the factors that make trees vulnerable to mortality will allow managers to better plan fuel treatments for these forests.

Abstract To mitigate and adapt to climate change, forest carbon sequestration and diversity of the ecosystem must be included in forest management planning, while satisfying the demand for wood products. The future provisions of ecosystem services under six realistic management scenarios were assessed to achieve that goal. These services were carbon sequestration, types and quantities of roundwood harvested, and different indicators of forest health—biomass of major species, species diversity, and variation of tree age. A spatially explicit forest succession model was combined with statistical analyses to conduct the assessment at the level of both the whole forest landscape and different ecological zones (ecozones) within. An important aspect of this study was to explore the effects of the biophysical heterogeneity of different ecological zones on the outcomes of different management scenarios. The study area was located in an area of the southern Appalachian Mountains in North Carolina with high tree diversity and active forest management activities. Along with a range of management practices, such richness in diversity allowed us to examine the complexity of the interaction between management activities and species competition. The results showed that fire suppression had a greater effect on increasing biomass carbon sequestration than any management scenario that involves harvest and replanting afterward, but at the expense of other indicators of forest health. The effect of fire on species composition was the largest in the xeric parts of the study area. Based on the study results, it was proposed that a low harvest intensity with a mix of fire and fire suppression across the landscape would best balance the need for roundwood products, biomass carbon sequestration, and desirable species composition. This study also demonstrated that the combination of a spatially explicit forest succession model and statistical analyses could be used to provide a robust and quantifiable projection of ecosystem service provisions and possible trade‐offs under different management scenarios.

Many previous studies have shown that land use patterns are the main factors influencing soil infiltration. Thus, increasing soil infiltration and reducing runoff are crucial for soil and water conservation, especially in semi-arid environments. To explore the effects of agroforestry systems on soil infiltration and associated properties in a semi-arid area of the Loess Plateau in China, we compared three plant systems: a walnut (Juglans regia) monoculture system (JRMS), a wheat (Triticum aestivum) monoculture system (TAMS), and a walnut-wheat alley cropping system (JTACS) over a period of 11 years. Our results showed that the JTACS facilitated infiltration, and its infiltration rate temporal distribution showed a stronger relationship coupled with the rainfall temporal distribution compared with the two monoculture systems during the growing season. However, the effect of JTACS on the infiltration capacity was only significant in shallow soil layer, i.e., the 0-40 cm soil depth. Within JTACS, the speed of the wetting front's downward movement was significantly faster than that in the two monoculture systems when the amount of rainfall and its intensity were higher. The soil infiltration rate was improved, and the two peaks of soil infiltration rate temporal distribution and the rainfall temporal distribution coupled in rainy season in the alley cropping system, which has an important significance in soil and water conservation. The results of this empirical study provide new insights into the sustainability of agroforestry, which may help farmers select rational planting patterns in this region, as well as other regions with similar climatic and environmental characteristics throughout the world.

Abstract Background Clinical nurses play a vital role in healthcare. Their innovative behavior is crucial for improving patient care, advancing the profession, and ensuring the healthcare industry’s continued success. Many studies have highlighted the importance of nurse innovative behavior, but the link between their innovative behavior, structural empowerment, and decent work perception remains unclear. Objectives This study aimed to investigate the relationship between innovative behavior, structural empowerment, and decent work perception among the Chinese clinical nurses and identify the mediating role of decent work perception. Methods A cross-sectional correlational design was employed, and from July 2023 to April 2024, 1,513 clinical nurses were recruited from 8 tertiary grade-A hospitals across three cities in China. Data from the Demographic Characteristics Questionnaire, the Nurse Innovation Behavior Scale, the Conditions of Work Effectiveness Questionnaire-II, and the Decent Work Perception Scale were collected through convenience sampling and analyzed using descriptive statistics, univariate correlation, and process plug-in mediation effect analyses. Results The total scores of innovative behavior, structural empowerment, and decent work perception were 28.36 ± 6.25, 51.15 ± 12.63, and 42.97 ± 9.25, respectively. Innovative behavior was significantly, moderately and positively correlated with structural empowerment (r = 0.657, p

Abstract Objective This study explored the effectiveness of combining problem-based learning (PBL) and case-based learning (CBL) in the clinical teaching of ectopic pregnancy. Methods: Fifth-year students majoring in clinical medicine were recruited from the Department of Gynecology at the Hengyang Central Hospital and Hainan General Hospital between September 2023 and June 2024. The students were randomly assigned to either the combined PBL-CBL or the traditional group. At the end of the class, both groups of students were required to complete a post-class quiz and an anonymous questionnaire. Results The basic knowledge score in the combined PBL-CBL group was significantly higher than that in the traditional group (42.6 ± 3.6 vs 35.0 ± 2.3, p = 0.000). Similarly, the case analysis score was higher in the combined PBL-CBL group than that in the traditional group (37.1 ± 6.2 versus 33.8 ± 5.7, p = 0.013). The scores for learning motivation, understanding, student–teacher interaction, communication skills, clinical thinking skills, self-learning skills, knowledge absorption, and satisfaction with the course in the combined PBL-CBL group were significantly higher than those in the traditional group (p

Cervical cancer is one of the most malignant gynaecological tumors characterised with the aggressive behaviour of the tumor cells. In spite of the development of different strategies for the treatment of cervical cancer, the tumor cells have developed resistance to conventional therapeutics. On the other hand, nanoparticles have been recently applied for the treatment of human cancers through delivery of drugs and facilitate tumor suppression. The stimuli-sensitive nanostructures can improve the release of therapeutics at the tumor site. In the present review, the nanostructures for the treatment of cervical cancer are discussed. Nanostructures can deliver both chemotherapy drugs and natural compounds to increase anti-cancer activity and prevent drug resistance in cervical tumor. Moreover, the genetic tools such as siRNA can be delivered by nanoparticles to enhance their accumulation at tumor site. In order to enhance selectivity, the stimuli-responsive nanoparticles such as pH- and redox-responsive nanocarriers have been developed to suppress cervical tumor. Moreover, nanoparticles can induce photo-thermal and photodynamic therapy to accelerate cell death in cervical tumor. In addition, nanobiotechnology demonstrates tremendous potential in the treatment of cervical cancer, especially in the context of tumor immunotherapy. Overall, metal-, carbon-, lipid- and polymer-based nanostructures have been utilized in cervical cancer therapy. Finally, hydrogels have been developed as novel kinds of carriers to encapsulate therapeutics and improve anti-cancer activity.

Due to the limitations of low coverage, high repetition rate, and slow convergence speed of the basic genetic algorithm (GA) in robot complete coverage path planning, the state transition matrix of the Markov chain is introduced to guide individual mutation based on the genetic mutation path planning algorithm, which can improve the quality of population individuals, enhancing the search ability and convergence speed of the genetic algorithm. The proposed improved genetic algorithm is used for complete coverage path planning simulation analysis in different work areas. The analysis results show that compared to traditional genetic algorithms, the improved genetic algorithm proposed in this paper reduces the average path length by 21.8%, the average number of turns by 6 times, the repetition rate by 83.8%, and the coverage rate by 7.76% in 6 different work areas. The results prove that the proposed improved genetic algorithm is applicable in complete coverage path planning. To verify whether the Markov chain genetic algorithm (MCGA) proposed is suitable for agricultural robot path tracking and operation, it was used to plan the path of an actual land parcel. An automatic navigation robot can track the planned path, which can verify the feasibility of the MCGA proposed.

Glioblastoma, a formidable brain tumor characterized by dysregulated NAD metabolism, poses a significant therapeutic challenge. The NAMPT inhibitor FK866, which induces NAD depletion, has shown promise in controlling tumor proliferation and modifying the tumor microenvironment. However, the clinical efficacy of FK866 as a single drug therapy for glioma is limited. In this study, we aim to disrupt NAD metabolism using fluorinated NAD precursors and explore their synergistic effect with FK866 in inducing cytotoxicity in glioblastoma cells. The synthesized analogue of nicotinamide riboside (NR), ara-F nicotinamide riboside (F-NR), inhibits nicotinamide ribose kinase (NRK) activity in vitro, reduces cellular NAD levels, and enhances FK866’s cytotoxicity in U251 glioblastoma cells, indicating a collaborative impact on cell death. Metabolic analyses reveal that F-NR undergoes conversion to fluorinated nicotinamide mononucleotide (F-NMN) and other metabolites, highlighting the intact NAD metabolic pathway in glioma cells. The activation of SARM1 by F-NMN, a potent NAD-consuming enzyme, is supported by the synergistic effect of CZ-48, a cell-permeable SARM1 activator. Temporal analysis underscores the sequential nature of events, establishing NAD depletion as a precursor to ATP depletion and eventual massive cell death. This study not only elucidates the molecular intricacies of glioblastoma cell death but also proposes a promising strategy to enhance FK866 efficacy through fluorinated NAD precursors, offering potential avenues for innovative therapeutic interventions in the challenging landscape of glioblastoma treatment.

Abstract Background Patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer and primary resistance to trastuzumab have a poor clinical outcome and lack good evidence to inform clinical decision. This study investigated the efficacy and safety of pyrotinib plus capecitabine in this population. Methods This phase 2 trial was conducted at 16 sites in China. Patients received oral pyrotinib 400 mg once daily and capecitabine 1000 mg/m2 twice a day on days 1–14 of each 21-day cycle until disease progression or intolerable toxicity. The primary endpoint was investigator-assessed progression-free survival (PFS). Results Between June 2019 and September 2021, 100 patients were enrolled with a median age of 51 years (range, 24–69). All patients had been treated with trastuzumab and 21 (21.0%) patients had prior use of pertuzumab. As of August 31, 2022, the median follow-up duration was 20.1 months (range, 1.3–38.2). The median PFS was 11.8 months (95% confidence interval [CI], 8.4–15.1), which crossed the pre-specified efficacy boundary of 8.0 months. The objective response rate was 70.0% (70/100), with a median duration of response of 13.8 months (95% CI, 10.2–19.3). The disease control rate was 87.0% (87/100). The median overall survival was not reached. The most common grade ≥ 3 treatment-emergent adverse event was diarrhea (24 [24.0%]). No treatment-related deaths occurred. Conclusions Pyrotinib plus capecitabine can be considered to be a treatment option in HER2-positive advanced breast cancer patients who have shown primary resistance to trastuzumab. Even in the era of modern anti-HER2 treatments, this clinical setting warrants more investigations to meet unmet needs. Trial registration ClinicalTrials.gov, NCT04001621. Retrospectively registered on June 28, 2019.

In contemporary society, the improper use of antibiotics leads to their persistent presence in the ecological environment. Due to the diverse physical and chemical properties of antibiotics, their spatial and temporal distribution in the environment varies. Moreover, antibiotics can stimulate the emergence of antibiotic resistance genes (ARGs), which complicates the monitoring and regulation of antibiotics and poses a significant threat to both aquatic and terrestrial environments. This study investigated the distribution of 15 antibiotics and 11 typical ARGs across four categories at 19 sites of drinking water sources in Wuhan, China. The findings revealed that the concentration of antibiotics during the dry season (nd~61,883 ng/L) was significantly higher compared to both the normal water season (nd~49,883 ng/L) and the wet season (nd~28,686 ng/L). Sulfamethoxazole (SMX), sulfamethoxazole (SMD), sulfadiazine (SD), and roxithromycin (RTM) were the predominant antibiotics in the target water environments. The study indicated that most of the antibiotics analyzed posed little to no risk to aquatic organisms. The primary ARGs detected in the surface water of the study area were sul1, qnrD, and tetO. Furthermore, some ARGs showed a negative correlation with their respective antibiotics. Additional research is necessary to evaluate the impact of these emerging pollutants (antibiotics and ARGs) on the safety of high-quality drinking water for residents in Wuhan City.

Accurate crop classification is of vital importance for agricultural water management. Most researchers have achieved crop classification by model optimization in the same temporal and regional domain by adjusting the value of input features. This study aims to improve the accuracy of crop classification across temporal and spatial domains. Sentinel-2 satellite imagery is employed for crop classification training and prediction in selected farming areas of Heilongjiang Province by calculating vegetation indices and constructing sequential input feature datasets. The HUNTS filtering method was used to mitigate the influence of cloud cover, which increased the stability and completeness of the input feature data across different years. To address the issue of shifts in the input feature values during cross-scale classification, this study proposes the hypothesis testing distribution method (HTDM). This method balances the distribution of input feature values in the test set even without knowing the crop distribution, thereby enhancing the accuracy of the classification test set. The results indicate that the HTDM significantly improves prediction accuracy in cases of substantial image quality variance. In 2022, the recognition accuracy for crop types at all farms processed by the HTDM was above 87%, showcasing the strong robustness of the HTDM.

Mitochondrial dysfunction is one of the key features of acute kidney injury (AKI) and associated fibrosis. Leucine-rich repeat kinase 2 (LRRK2) is highly expressed in kidneys and regulates mitochondrial homeostasis. How it functions in AKI is unclear. Herein we reported that LRRK2 was dramatically downregulated in AKI kidneys. Lrrk2−/− mice exhibited less severity of AKI when compared to wild-type counterparts with less mitochondrial fragmentation and decreased reactive oxygen species (ROS) production in proximal renal tubular cells (PTCs) due to mitofusin 2 (MFN2) accumulation. Overexpression of LRRK2 in human PTC cell lines promoted LRRK2-MKK4/JNK-dependent phosphorylation of MFN2Ser27 and subsequently ubiquitination-mediated MFN2 degradation, which in turn exaggerated mitochondrial damage upon ischemia/reperfusion (I/R) mimicry treatment. Lrrk2 deficiency also alleviated AKI-to-chronic kidney disease (CKD) transition with less fibrosis. In vivo pretreatment of LRRK2 inhibitors attenuated the severity of AKI as well as CKD, potentiating LRRK2 as a novel target to alleviate AKI and fibrosis.

We examine the impact of Confucian philosophy on external pay gaps, and find that a Confucianist atmosphere is negatively associated with firms’ external pay gaps for both executives and employees. Mechanistically, the Confucian concept of “righteousness” reduces the self-interested motivation of management, in turn reducing executives’ external pay gap; “humaneness” causes management to focus on protecting employees’ rights and interests, benefiting employees’ compensation; and “honesty” improves information disclosure, reducing the external compensation gap for both executives and general employees. The inhibitory effect of Confucian culture on the external pay gap is greater in regions with weak formal institutions and non-state-owned firms, while foreign cultural shocks attenuate the Confucian influence. Finally, the Confucian culture-driven reduction of the external pay gap improves enterprises’ economic efficiency.

Objectives: Ischemia/reperfusion injury (IRI) is one of the most vital pathogenesis leading to kidney injury but lacks effective prevention and treatment strategies. This study was conducted to investigate the influences of ischemic preconditioning (IPC) on the pathological process of mouse renal IRI (RIRI) and to figure out the role of autophagy of proximal tubular cells (PTCs) in this process. Methods: C57BL/6J mice were randomized to three groups, i.e., sham-operated group, ischemia/reperfusion (I/R) group, and IPC + I/R group. Meanwhile, 3-methyladenine, an autophagy inhibitor, was administered when further verification was needed. Histological and functional severity of kidney injury, the autophagy and apoptosis activity of PTCs, as well as the characterization of the immune cell infiltration landscape in kidney tissues were investigated. Furthermore, HK-2 cells and primary cultured PTC were cultured to set up the hypoxic preconditioning and hypoxia/reoxygenation model for in vitro simulation and verification, and a microarray dataset derived from the Gene Expression Omnibus database was analyzed to explore the transcriptome profiles after IPC. Results: IPC could significantly attenuate I/R-induced kidney injury functionally and histologically both in the acute and recovery phase of RIRI by enhancing the autophagy activity of PTCs. Cell autophagy could regulate the release of monocyte chemoattractant protein-1, and sequentially decrease macrophages infiltration in kidney tissues in the acute phase of RIRI, thus mediating the reno-protective effect. Conclusions: IPC could attenuate mouse RIRI-induced kidney injury. IPC-mediated activation of autophagy of PTCs plays a vital role in affording protection in RIRI-induced kidney injury.

Environmental problems, including air pollution, have upset the balance between the environment and economic development. In the face of worsening air pollution, growing attention is being paid to the role of financial institutions. To investigate how finance affects air pollution, this study used data from 30 Chinese provinces from 2014–2020, while considering industrial structure optimization and energy structure as threshold variables to propose a panel threshold model, which elucidates a nonlinear relationship between green finance and air quality in China. The panel data are sorted based on urbanization level, resource dependence, and geospatial distribution to examine the heterogeneous effects of green finance on air pollution. The analysis demonstrated that green finance considerably improves the overall air quality in Chinese provinces, but the effect is gradually weakened with the optimization of industrial structure and the improvement of clean energy efficiency. Moreover, green finance exerts a greater inhibitory impact on air pollution through industrial structure optimization compared to the impact of energy structure optimization. Regional variations in the environmental benefits of green finance were discerned. Resource dependence exacerbates the inhibiting impact of green finance on air pollution in the resource-based regions, while urbanization weakens the environmental benefits of green finance in urbanized regions. In terms of geographical distribution, green finance exhibited the best effect on air quality in western China. These findings shed the light on the positive role of green finance on air quality in China, thereby highlighting its importance for the air quality improvement programs of the provincial scales in China.

Dielectric polymer film capacitors with a high-power density as well as efficient charge and discharge rates have great potential for application to fulfill the miniaturized and lightweight requirements of the electronic and stationary power systems. It was reported that the elastic recovery rate and energy storage density of poly (vinylidene fluoride-chlorotrifluoroethylene) [P(VDF-CTFE)] polymer film can be enhanced through thermostatic uniaxial stretching. But it is unknown about the relationship between the stretching rate and above properties. In this study, we investigated the effect of different stretching rates on the conformation, elastic recovery, dielectric constant, and energy storage density of stretched P(VDF-CTFE) polymer films. It was found that the stretching rate significantly affected the formation of polar [Formula: see text]-crystal phase, causing different dielectric properties. The degrees of elastic recovery of P(VDF-CTFE) film vary with stretching rates. Among them, the elastic recovery rate of the P(VDF-CTFE) 94/6 film is 46.5% at a stretching rate of 15 mm/min, the dielectric constant is 12.25 at 100 Hz, and the energy density reaches 3.95 J/cm3 with the energy loss of 39% at 200 MV/m field.

Background: This study aimed to explore the relationship between MALAT1 and the prognosis of patients with hepatocellular carcinoma (HCC).Methods: We constructed a MALAT1 protein-protein interaction network using the STRING database and a network of competing endogenous RNAs (ceRNAs) using the StarBase database. Using data from the GEPIA2 database, we studied the association between genes in these networks and survival of patients with HCC. The potential mechanisms underlying the relationship between MALAT1 and HCC prognosis were studied using combined data from RNA sequencing, DNA methylation, and somatic mutation data from The Cancer Genome Atlas (TCGA) liver cancer cohort. Tumor tissues and 19 paired adjacent non-tumor tissues (PANTs) from HCC patients who underwent radical resection were analyzed for MALAT1 mRNA levels using real-time PCR, and associations of MALAT1 expression with clinicopathological features or prognosis of patients were analyzed using log-rank test and Gehan-Breslow-Wilcoxon test.Results: Five interacting proteins and five target genes of MALAT1 in the ceRNA network significantly correlated with poor survival of patients with HCC (p < 0.05). High MALAT1 expression was associated with mutations in two genes leading to poor prognosis and may upregulate some prognostic risk genes through methylation. MALAT1 was significantly co-expressed with various signatures of genes involved in HCC progression, including the cell cycle, DNA damage repair, mismatch repair, homologous recombination, molecular cancer m6A, exosome, ferroptosis, infiltration of lymphocyte (p < 0.05). The expression of MALAT1 was markedly upregulated in HCC tissues compared with PANTs. In Kaplan-Meier analysis, patients with high MALAT1 expression had significantly shorter progression-free survival (PFS) (p = 0.033) and overall survival (OS) (p = 0.023) than those with low MALAT1 expression. Median PFS was 19.2 months for patients with high MALAT1 expression and 52.8 months for patients with low expression, while the corresponding median OS was 40.5 and 78.3 months. In subgroup analysis of patients with vascular invasion, cirrhosis, and HBsAg positive or AFP positive, MALAT1 overexpression was significantly associated with shorter PFS and OS. Models for predicting PFS and OS constructed based on MALAT1 expression and clinicopathological features had moderate predictive power, with areas under the receiver operating characteristic curves of 0.661–0.731. Additionally, MALAT1 expression level was significantly associated with liver cirrhosis, vascular invasion, and tumor capsular infiltration (p < 0.05 for all).Conclusion:MALAT1 is overexpressed in HCC, and higher expression is associated with worse prognosis. MALAT1 mRNA level may serve as a prognostic marker for patients with HCC after hepatectomy.

The development of green finance and the promotion of green transformation and upgrading of high energy-consuming enterprises are of great significance for China to achieve the "double carbon" goal. This paper employs a dual fixed-effects model to examine the profound ramifications and intrinsic mechanisms of green finance development on the transformative innovation of high-energy-consumption enterprises, using a sample of 462 publicly traded high-energy-consuming corporations from the period spanning 2016 to 2020. The results show that the development of green finance promotes the transformation and innovation of energy-intensive enterprises and that market-incentivized environmental regulation plays a partially mediating role; the results of heterogeneity analysis show that green finance promotes the transformation and innovation of high energy-consuming enterprises with significant differences in different low-carbon pilot regions, company ownership, and enterprise size; the mechanism analysis shows that the development of green finance can increase government subsidies and alleviate financing constraints to promote the transformation and innovation of high energy-consuming enterprises; it is also found that the development of green finance can significantly improve the financial performance of enterprises. The research findings of this paper hold significant implications for promoting the sustainable development of green finance and high-energy consumption enterprises in China. They provide valuable insights and references for facilitating the green transformation and innovation of high-energy-consuming enterprises in China as well as other developing countries.

BackgroundSpontaneous intracerebral hemorrhage (ICH) usually occurs in the basal ganglia and is highly lethal and disabling. The aim of this study was to evaluate the predictors of 30-day mortality in patients with severe spontaneous basal ganglia hemorrhage.MethodsThis retrospective study included patients with severe basal ganglia intracerebral hemorrhage treated in the Third Affiliated Hospital of Soochow University from 2012 to 2018. Demographic, clinical, laboratory and neuroradiological data were collected. The short-term prognosis was evaluated and divided into death within 30-days and survival over 30-days. We studied the factors affecting the prognosis of patients with severe intracerebral hemorrhage, analyzed the parameters related to neutrophil-to-lymphocyte (NLR) at admission, and evaluated the predictive effect of NLR on 30-day mortality.ResultsA total of 105 patients was included in this retrospective study. The 30-day death group had a larger hematoma, a higher probability of ventricular hemorrhage, a higher ICH score and a lower Glasgow Coma Scale (GCS) score on admission. Meanwhile, the patients in the death group had higher White blood cells (WBC) counts, neutrophil counts, NLRs and C-reactive protein (CRP) levels. The risk factors for 30-day death were related to the ICH volume, GCS score, ICH score, WBC count, neutrophil count, NLR and CRP. The univariate receiver operating characteristic (ROC) curve of the risk factors showed that the NLR had the best prediction performance. Mathematical predictive models for ICH patients showed that the model with NLR had better prediction accuracy.ConclusionsThe NLR is expected to be a potential biomarker for predicting the prognosis of patients with severe basal ganglia hemorrhage.

Whether the implementation of a national industrial policy can maintain stability in the financial market is a question of theoretical and practical significance. Using data from China’s non-financial listed firms from 2007 to 2020, we find that a national industrial policy lowers stock price crash risk. We find that the effect of an industrial policy on lowering stock price crash risk is more pronounced in regions with low levels of regional marketization and if firms have high external uncertainty, low total asset turnover, greater earnings management and receive small increments of long-term loans and fewer government subsidies, suggesting that industrial policies lower stock price crash risk by improving firm fundamentals and reducing external uncertainty, agency costs and information asymmetry.

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Intravesical bacillus Calmette-Guerin (BCG) instillation is recommended as an adjuvant therapy for intermediate-risk and high-risk non-muscle invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor (TURBt) with nearly 70% reoccurrence. In the present study, we investigated the dynamics of peripheral purified protein derivative (PPD)-specific immune responses along the treatment. Intravesical BCG instillation caused a significant increase in peripheral PPD-specific IFN-γ release of NMIBC patients, when compared to those receiving chemo-drug instillation. Through a follow-up study, we detected rapid increase in PPD-specific IFN-γ, IL-2, and IL-17A producing CD4+ and CD8+ T cells in the induction phase. Interestingly, the frequencies of PPD-specific IFN-γ and IL-2 producing CD4+ and CD8+ T cells decreased dramatically after induction treatment and were restored after BCG re-instillation, whereas IL-17A-producing T cells remained at the maintenance phase. However, we only observed that the percentages of peripheral CD8+ T cells were significantly higher in BCG responder patients than those in BCG refractory patients at the baseline with the potential of predicting the recurrence. A more dramatic increase in PPD-specific IFN-γ and IL-2 producing CD4+ and CD8+ T cells after one and two dose BCG instillations was observed in refractory NMIBC patients. Therefore, regional BCG instillation induced transient peripheral PPD-specific T cell responses, which could be restored through repetitive BCG instillation. Higher proportions of peripheral CD8+ T cells at baseline were associated with better responses to BCG instillation for the prevention of recurrence of bladder cancer.

Objectives: Bladder cancer (BLCA) is the most common malignant tumor in the urinary system, while the prognosis of muscle-invasive bladder cancer (MIBC) is poor. Cuproptosis might be a promising therapeutic approach to trigger tumor cell death. This study aimed to figure out the role of cuproptosis in BLCA and constructed a new cuproptosis scoring system to guide clinical diagnosis and individualize treatments.Methods: Consensus clustering was used to classify 490 patients with BLCA from TCGA and GEO cohorts. Survival outcomes and functional enrichment analyses were performed between the different subtypes. The cuproptosis scoring system was constructed by LASSO-Cox analysis. ESTIMATE, CIBERSORT, and ssGSEA were used to investigate the tumor microenvironment (TME). Drug sensitivity was evaluated with pRRophetic. An immunotherapy cohort was used to investigate the treatment response. The cuproptosis scoring system was verified in our own cohort with quantitative real-time PCR.Results: An overview of 12 cuproptosis genes (CuGs) in the TCGA database was depicted. Based on the mRNA expression profiles of CuGs, patients were classified into two cuproptosis molecular patterns. Based on the differential genes between the two cuproptosis patterns, the patients were classified into two cuproptosis gene clusters. There were distinct survival outcomes, signaling pathways, and TME between the two subtypes. A 7-gene cuproptosis scoring system was constructed. Patients with high cuproptosis scores showed worse OS and more immunosuppressing TME than those with low cuproptosis scores. The two cuproptosis score groups had distinct mutation profiles. Patients with high cuproptosis scores tended to be sensitive to chemotherapy drugs, but insensitive to immune checkpoint inhibitors (ICIs) treatment.Conclusion: This study depicted the landscape of cuproptosis in BLCA. We constructed a cuproptosis scoring system to predict the prognosis of BLCA patients. There were significant differences in survival outcomes, TME, mutation profiles, and drug sensitivities in high and low cuproptosis score patients. The cuproptosis scoring system could help oncologists comprehensively understand the tumor characteristic of BLCA and make individualized treatment strategies.

BackgroundMillions of children experienced surgery procedures requiring general anesthesia (GA). Any potential neurodevelopmental risks of pediatric anesthesia can be a serious public health issue. Various animal studies have provided evidence that commonly used GA induced a variety of morphofunctional alterations in the developing brain of juvenile animals.MethodsWe conducted a systematic review to provide a brief overview of preclinical studies and summarize the existing clinical studies. Comprehensive literature searches of PubMed, EMBASE, CINAHL, OVID Medline, Web of Science, and the Cochrane Library were conducted using the relevant search terms “general anesthesia,” “neurocognitive outcome,” and “children.” We included studies investigating children who were exposed to single or multiple GA before 18, with long-term neurodevelopment outcomes evaluated after the exposure(s).ResultsSeventy-two clinical studies originating from 18 different countries published from 2000 to 2022 are included in this review, most of which are retrospective studies (n = 58). Two-thirds of studies (n = 48) provide evidence of negative neurocognitive effects after GA exposure in children. Neurodevelopmental outcomes are categorized into six domains: academics/achievement, cognition, development/behavior, diagnosis, brain studies, and others. Most studies focusing on children

Emerging evidence has shown the role of mesenchymal stem cell-derived exosome (MSC-exo) in inducing resistance of cancer cells to chemotherapy. However, it remains unclear whether the change of MSC-exo in response to chemotherapy also contributes to chemoresistance. In this study, we investigated the effect of a standard-of-care chemotherapeutic agent, doxorubicin (Dox), on MSC-exo and its contribution to the development of Dox resistance in breast cancer cells (BCs). We found that the exosome secreted by Dox-treated MSCs (Dt-MSC-exo) induced a higher degree of Dox resistance in BCs when compared with non-treated MSC-exo. By analysis of the MSC-exo-induced transcriptome change in BCs, we identified S100A6, a chemoresistant gene, as a top-ranked gene induced by MSC-exo in BCs, which was further enhanced by Dt-MSC-exo. Furthermore, we found that Dox induced the expression of miR-21-5p in MSCs and MSC-exo, which was required for the expression of S100A6 in BCs. Importantly, silencing of miR-21-5p expression in MSCs and MSC-exo abolished the resistance of BCs to Dox, indicating an exosomal miR-21-5p-regulated S100A6 in chemoresistance. Our study thus uncovered a novel mechanistic insight into the role of MSC-secreted exosome in the development of chemoresistance in the tumor microenvironment.