Prognostic significance of peripheral and tumor-infiltrating lymphocytes in newly diagnosed stage III/IV non-small-cell lung cancer.

Background and aim: Lymphocytes are effector cells that fight cancer by killing tumor cells. Here, we aim to explore the prognostic significance of both peripheral and tumor-infiltrating lymphocytes (TILs) in newly diagnosed stage III/IV non-small-cell lung cancer (NSCLC). Materials and methods: In total, 105 cases of newly diagnosed stage III/IV NSCLC from July 2017 to October 2022 at the Tianjin Beichen Hospital were retrospectively investigated. Peripheral blood samples at the time of diagnosis and tumor tissue slices from these patients were collected. General peripheral blood cell composition and TILs were measured and analyzed via an automatic blood analyzer and immunofluorescence staining analysis. The overall survival (OS) time of all patients was also obtained and analyzed. Results: The median overall survival (mOS) of all patients is 12 months. The 1-, 2-, and 3-year overall survival rates were 60.5, 28.4, and 18.6%, respectively. Peripheral lymphocyte and neutrophil percentages, serum C-reactive protein (CRP) expression, tumor size, and tumor pathology are the prognostic factors of OS for newly diagnosed stage III/IV NSCLC patients. Moreover, patients with high tumor CD4+ and CD8+ T cell infiltration survived significantly longer compared to patients with low tumor CD4+ and CD8+ T cell infiltration (p < 0.0001 and p = 0.011, respectively). Compared to low tumor CD33+ cell infiltration, high tumor CD33+ cell infiltration was associated with worse OS (p = 0.018). High tumor CD8+ T cell infiltration was associated with lower peripheral lymphocyte number, lower serum CRP expression, smaller tumor size, and better tumor pathology (p = 0.012, p = 0.040, p = 0.012, and p = 0.029, respectively). Conclusion: Increased numbers of peripheral lymphocytes, CD33+ cells, CD4+ TILs, and CD8+ TILs were significantly associated with OS in newly diagnosed stage III/IV NSCLC patients, which were positively associated with several basic clinical factors.

Validation of the Capacity for the Psychotherapy Process Scale for Use in Adolescent Patients.

Although pre-treatment assessments of the capacity for the psychotherapy process can aid in identifying patients experiencing great difficulties in therapy and in tailoring therapies for individual patients, limited information exists for adolescents. To address this gap, this study followed the World Health Organization's age standards for adolescents (younger adolescents aged 10-14 years; older adolescents aged 15-19 years), examined the psychometric properties of the Capacity for Psychotherapy Process Scale (CFPPS; mainly used for adult patients) in these two groups of adolescents, and compared their capacities for the psychotherapy process. The participants were 434 younger adolescent (mean age = 13.00 ± 1.08 years; 70.0% female) and 883 older adolescent outpatients (mean age = 16.68 ± 1.29 years; 62.3% female) at the department of psychiatry of the hospital in Guangzhou, China. The results of exploratory and confirmatory factor analyses validated the 5-factor model (motivation, belief, self-revelation, persistence, and insight) in both groups. The scale also demonstrated good internal consistency. Furthermore, the CFPPS exhibited small or no associations with pre-treatment sleep problems, depression symptoms, or anxiety symptoms but was a significant predictor of working alliance and psychological benefit in therapy. The capacity for the psychotherapy process among younger adolescents was lower than that among older adolescents. The CFPPS appears to be a reliable and validated instrument for measuring the capacity for the psychotherapy process among adolescent outpatients in China. Therapists should provide therapy tailored to the Chinese adolescents' capacity. Future studies are needed to examine the predictive utility of the CFPPS for the whole sessions of the psychotherapy.

The Association between Discrepancies in Parental Emotional Expressivity, Adolescent Loneliness and Depression: A Multi-Informant Study Using Response Surface Analysis.

Incongruent perceptions of parental emotional expressivity between parents and adolescents may signify relational challenges, potentially impacting adolescents' socioemotional adjustment. Direct evidence is still lacking and father-adolescent discrepancies are overlooked. This study employed a multi-informant design to investigate whether both mother-adolescent and father-adolescent discrepancies in perceptions of parental expressivity are related to adolescents' mental well-being, specifically focusing on loneliness and depression. Analyzing data from 681 families (mean age of adolescents = 15.5 years old, 51.2% girls, 40% only-children) in China revealed that adolescents tended to perceive paternal and maternal emotional expressivity more negatively than their parents, particularly fathers. Polynomial regression and response surface analysis showed significant links between parent-adolescent congruence and incongruence and adolescent loneliness. (In)Congruence between adolescents and mothers or fathers predicted later adolescent depression, mediated by adolescent loneliness and varied by the dimension of emotional expressivity. These findings provide insights into the roles of mothers' and fathers' emotional expressivity in shaping children's mental well-being during adolescence.

Efficacy and Safety of CT-guided Percutaneous Cryoablation for Hepatocellular Carcinoma at High-risk Sites.

OBJECTIVE: This study aims to assess the efficacy and safety of CT-guided percutaneous cryoablation in treating hepatocellular carcinoma (HCC) located explicitly in high-risk sites. MATERIALS AND METHODS: Data were collected retrospectively from 685 HCC patients undergoing percutaneous cryoablation at Tianjin Medical University Cancer Hospital between January 2018 and December 2021. Of these, 106 patients had lesions in high-risk sites, defined as a minimum distance of less than 10 mm from the heart/great vessels, diaphragm, gastrointestinal tract, and gallbladder, as determined by preoperative CT or MRI imaging. Technical success rate, complete ablation rate, and complications at 1, 12, and 24 months post-surgery were evaluated. A statistical analysis of the ablation effect difference between the high-risk site and non-high-risk site groups was conducted, utilizing propensity score matching (PSM) to mitigate patient selection bias. Univariate and multivariate logistic regression analyzes were performed to identify risk factors for the incidence of coronary heart disease. RESULTS: The study comprised 106 cases in the high-risk group and 218 cases in the non-high-risk group. After PSM analysis until December 2021, 95 matched pairs were included. Both groups demonstrated a 100% intraoperative technical success rate, and no major complications related to cryoablation were observed. Follow-up ranged from 24 to 38 months. The complete ablation rate was 82.1% and 71.7% in the high-risk group and 83.9% and 73.9% in the non-high-risk group at 12 and 24 months, respectively. There was no significant difference in complete ablation rates between the two groups before and after PSM (P > 0.05). Multivariate analysis identified the distance between the tumor edge and high-risk site ≤ 5 mm and preoperative transarterial chemoembolization (TACE) treatment as independent risk factors for cryoablation effect. CONCLUSION: CT-guided percutaneous cryoablation proves to be a safe and effective approach for HCC patients with high-risk sites, serving as an alternative to surgical treatment.

Residual effects of chlorinated organic pollutants on microbial community and natural redox processes in coastal wetlands.

Chlorinated organic pollutants (COPs) are common in flooded environments. To examine the residual status and effects of COPs on flooded environments, a survey of 7 coastal wetlands in Zhejiang, East China was conducted. Total COP concentrations detected from 95.69 to 412.76 ng g-1 dw. Gamma-HCH and o,p'-DDT posed the greatest risk with exceedance rates of 100% according to sediment quality guidelines. Samples with higher COP pollution had higher microbial diversity, more complex microbial networks, more deterministic community assembly processes and lower microbiome stability, indicating an improved soil function for balance cycle of substances, especially for COP degradation. Further analysis using quantitative real-time PCR suggested COP-dechlorination interacted with natural redox processes, especially sulfate reduction and methanogenesis. The positive correlation between CH4 and pentachlorobenzene indicated a potential increase in greenhouse gas emissions caused by COP pollution. Correlation between dsr gene and COPs demonstrated the ability of sulfate-reducing bacteria to degrade COPs. Particularly, facultative OHRB such as sulfate-reducing bacteria hold significant importance in the process of COP-dechlorination. This finding provides a reference for COP pollution remediation. Collectively, our study offers new insight into the residual effect of COPs in coastal wetlands and contributes to an improved understanding of bioremediation strategies for COP pollution.

The effect of childhood trauma on suicide risk: the chain mediating effects of resilience and mental distress.

BACKGROUND: Suicide is the fourth leading cause of death among young people aged 15-29 years. A large number of studies have found that mental disorder in adulthood is closely related to childhood trauma, and the relationship between childhood trauma and suicide risk is influenced by resilience and mental distress. This study aimed to explore the effects of childhood trauma on suicide risk among young people and the potential roles of resilience and mental distress in the relationship between childhood trauma on suicide risk. METHODS: A cross-sectional survey was conducted among 742 young adults who were in graduate school stage from multiple provinces and cities in China. The Childhood Trauma Questionnaire (CTQ-Short Form), Connor-Davison Resilience Scale (CD-RISC) and Suicide Behavior Questionnaire-Revised (SBQ-R) were used to measure young adults' childhood trauma, resilience and suicide risk, respectively. 9-items Patient Health Questionnaire (PHQ-9) and 7-items self-report Generalized Anxiety Disorder Scale (GAD-7) were used together to measure mental distress. Correlation analysis was performed to explore the initial relationships among the main variables. Structural equation modeling (SEM) was conducted to examine the chain mediating effects of resilience and mental distress in the relationship between childhood trauma and suicide risk. RESULTS: The structural equation modeling produced goodness of fit indices (χ2 /df = 3.668, p < 0.001, RMSEA = 0.060, NFI = 0.959, CFI = 0.969, GFI = 0.969, TLI = 0.955). Childhood trauma significantly predicted suicide risk (ß = 0.232, p < 0.001) and mental distress (ß = 0.181, p < 0.001), which had negative effect on resilience (ß = -0.233, p < 0.001). Resilience negatively affected mental distress (ß = -0.483, p < 0.001) and suicide risk (ß = -0.142, p = 0.001), while mental distress positively associated with suicide risk (ß = 0.219, p < 0.001). CONCLUSION: The current study revealed that resilience and mental distress played chain-mediating roles in the relationship between childhood trauma and suicide risk. This suggests that we should view the suicide risk of graduate students from a comprehensive perspective.

In silico evidence implicating novel mechanisms of Prunella vulgaris L. as a potential botanical drug against COVID-19-associated acute kidney injury.

COVID-19-associated acute kidney injury (COVID-19 AKI) is an independent risk factor for in-hospital mortality and has the potential to progress to chronic kidney disease. Prunella vulgaris L., a traditional Chinese herb that has been used for the treatment of a variety of kidney diseases for centuries, could have the potential to treat this complication. In this study, we studied the potential protective role of Prunella vulgaris in COVID-19 AKI and explored its specific mechanisms applied by network pharmacology and bioinformatics methods. The combination of the protein-protein interaction network and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment -target gene network revealed eight key target genes (VEGFA, ICAM1, IL6, CXCL8, IL1B, CCL2, IL10 and RELA). Molecular docking showed that all these eight gene-encoded proteins could be effectively bound to three major active compounds (quercetin, luteolin and kaempferol), thus becoming potential therapeutic targets. Molecular dynamics simulation also supports the binding stability of RELA-encoded protein with quercetin and luteolin. Together, our data suggest that IL6, VEGFA, and RELA could be the potential drug targets by inhibiting the NF-κB signaling pathway. Our in silico studies shed new insights into P. vulgaris and its ingredients, e.g., quercetin, as potential botanical drugs against COVID-19 AKI, and warrant further studies on efficacy and mechanisms.

Enhanced soil function and health by soybean root microbial communities during in situ remediation of Cd-contaminated soil with the application of soil amendments.

The interactions between soil microbiomes at various trophic levels are essential for restoring soil functions. Legumes are considered as "pioneer crops" in degraded or contaminated soils because they can fix nitrogen through symbiotic relationships with rhizobacteria, which promotes soil fertility. However, little is known about the abilities of legumes to contribute to the health of soil contaminated with cadmium (Cd). In this research, we applied a soil amendment (commercial Mg-Ca-Si conditioner, CMC) at two rates (1,500 and 3,000 kg/ha) in a Cd-contaminated soybean field. Bulk and rhizosphere soil samples were collected to assess the amendment-induced effects on four microbial lineages (bacteria, fungi, arbuscular mycorrhizal fungi [AMF], and nematodes) and their functions including Cd stabilization, nutrient cycling, and pathogen control. Compared with the control, both CMC application rates increased the pH and reduced labile Cd fraction in the bulk and rhizosphere soils. Although the total Cd concentrations in the soil were similar, the Cd accumulation in the grains was significantly reduced in treatments of soil amendments. It was observed that the application of CMC can significantly reduce the AMF diversity but increased the diversity of the other three communities. Moreover, the biodiversity within keystone modules (identified by co-occurrence network analysis) played key roles in driving soil multifunctionality. Specifically, key beneficial groups in module 2 such as Aggregicoccus (bacteria), Sordariomycetes (fungi), Glomus (AMF), and Bursaphelenchus (nematode) were strongly associated with soil multifunctionality. By co-culturing bacterial suspensions with the soybean root rot pathogen Fusarium solani in the in vitro assays, we experimentally validated that the application of CMC promoted the suppression of soil bacterial community on pathogens by inhibiting the mycelium growth and spore germination. Also, the bacterial community was more resistant to Cd stress in soils receiving CMC amendment. Our findings provide valuable theoretical references for enhancing soil functions and health via applying a soil amendment (CMC) during Cd-contaminated soil remediation. IMPORTANCE Restoration of microbiome-driven soil functions and health is of great importance during Cd-contaminated soil remediation via soil amendment. Soybean and its symbiotic mutualism can provide abundant nitrogen and phosphorus to relieve the nutrient deficiency of Cd-contaminated soil. This study provides a novel perspective on the potential role of applying a soil amendment (CMC) in enhancing the functions and health of Cd-contaminated soils. Our results showed the distinct differences in soil microbial community responding to amendment-induced changes in edaphic properties. The biodiversity within keystone modules had major contributions to the maintenance of the soil's multifunctionality and health. Additionally, a higher CMC application rate showed more beneficial effects. Collectively, our results enhance our understanding about the effects of applying CMC, together with soybean rotation, to enhance and maintain soil functions and health during the field Cd stabilization process.

Hepatic arterial infusion chemotherapy combined with anti-PD-1/PD-L1 immunotherapy and molecularly targeted agents for advanced hepatocellular carcinoma: a real world study.

Background: Molecular targeted therapy combined with immunotherapy significantly improves the prognosis of patients with advanced liver cancer. Additionally, hepatic arterial infusion chemotherapy (HAIC) can improve the prognosis of patients with advanced liver cancer. This real-world study aimed to evaluate the clinical efficacy and safety of HAIC combined with molecular targeted therapy and immunotherapy in the treatment of primary unresectable hepatocellular carcinoma (uHCC). Methods: A total of 135 patients with uHCC were enrolled in this study. Progression-free survival (PFS) was the primary endpoint. The efficacy of the combination therapy was assessed based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) guidelines. Overall survival (OS), adverse events (AEs) and surgical conversion rate were the secondary endpoints. Univariate and multivariate Cox regression analyses were performed to examine independent prognostic factors. For sensitivity analysis, inverse probability weighting (IPW) was used to balance the influence of the tested confounding factors between groups to verify the robustness of conversion surgery for survival benefits. The E-values were estimated to assess robustness to unmeasured confounders. Results: The median number of therapies was three. Approximately 60% of the patients had portal vein tumour thrombosis (PVTT). The most common targeted drugs were lenvatinib and bevacizumab, whereas the most common immunotherapy drug was sintilimab. The overall objective response rate (ORR) was 54.1%, and the disease control rate (DCR) was 94.6%. A total of 97 (72%) patients experienced AEs of grades 3-4. Fatigue, pain and fever were the most common symptoms of grade 3-4 AEs. The median PFS was 28 months and 7 months in the successful and unsuccessful conversion groups, respectively. The median OS was 30 months and 15 months in the successful and unsuccessful conversion groups, respectively. Successful conversion surgery, sex, hapatic vein invasion, BCLC stage, baseline tumour size, AFP levels and maximum therapeutic response were independent prognostic factors for PFS. Successful conversion surgery, number of interventions, hapatic vein invasion and total bilirubin levels were independent prognostic factors for OS. After IPTW, no standardised differences exceeding 0.1 were found. IPW-adjusted Kaplan-Meier curves showed that successful conversion surgery was an independent prognostic factor for both PFS and OS. The E-values of successful conversion surgery were 7.57 and 6.53 for OS and PFS, respectively, which indicated a relatively robust impact of successful conversion surgery on the prognosis of patients. Conclusion: Patients with primary uHCC undergoing HAIC combined with immunotherapy and molecular targeted therapy have a higher tumour regression rate and the side effects are manageable. Patients undergoing surgery after combination therapy have survival benefits.

Cybervictimization and nonsuicidal self-injury: The mediating role of depressive symptoms and the moderating role of emotional reactivity.

BACKGROUND: Nonsuicidal self-injury (NSSI) has garnered growing attention in recent years, and cybervictimization (CV) has been identified as a risk factor for NSSI among adolescents. However, little is known about this association's longitudinal mediating and moderating mechanisms. Guided by the experiential avoidance model, the present study used a short longitudinal design to examine the mediating role of depressive symptoms and the moderating role of emotional reactivity between CV and NSSI. METHODS: A total of 577 Chinese middle school students (Mage = 14.38, SD = 0.67) completed the measures of CV, NSSI, depressive symptoms, and emotional reactivity. They provided data in two waves (T1 and T2, 6 months apart). RESULTS: The results found a longitudinal association between CV and NSSI as well as the mediating role of depressive symptoms. Moreover, emotional reactivity amplified the relationship between CV and NSSI via depressive symptoms; specifically, the relationship between depressive symptoms and NSSI was only significant for adolescents with high emotional reactivity. CONCLUSION: The current study has found that emotional reactivity moderated the indirect effect of depressive symptoms on the relationship between CV and NSSI. These findings have implications for the identification and intervention of NSSI in early adolescents.

Identification of the regulatory mechanism of ACE2 in COVID-19-induced kidney damage with systems genetics approach.

Studies showed that SARS-CoV-2 can directly target the kidney and induce renal damage. As the cell surface receptor for SARS-CoV-2 infection, the angiotensin-converting enzyme 2 (ACE2) plays a pivotal role for renal physiology and function. Thus, it is important to understand ACE2 through which pathway influences the pathogenesis of renal damage induced by COVID-19. In this study, we first performed an eQTL mapping for Ace2 in kidney tissues in 53 BXD mice strains. Results demonstrated that Ace2 is highly expressed and strongly controlled by a genetic locus on chromosome 16 in the kidney, with six genes (Dnase1, Vasn, Usp7, Abat, Mgrn1, and Rbfox1) dominated as the upstream modulator, as they are highly correlated with Ace2 expression. Gene co-expression analysis showed that Ace2 co-variates are significantly involved in the renin-angiotensin system (RAS) pathway which acts as a reno-protector. Importantly, we also found that Ace2 is positively correlated with Pdgf family members, particularly Pdgfc, which showed the most association among the 76 investigated growth factors. Mammalian Phenotype Ontology enrichment indicated that the cognate transcripts for both Ace2 and Pdgfc were mainly involved in regulating renal physiology and morphology. Among which, Cd44, Egfr, Met, Smad3, and Stat3 were identified as hub genes through protein-protein interaction analysis. Finally, in aligning with our systems genetics findings, we found ACE2, pdgf family members, and RAS genes decreased significantly in the CAKI-1 kidney cancer cells treated with S protein and receptor binding domain structural protein. Collectively, our data suggested that ACE2 work with RAS, PDGFC, as well as their cognate hub genes to regulate renal function, which could guide for future clinical prevention and targeted treatment for COVID-19-induced renal damage outcomes. KEY MESSAGES: • Ace2 is highly expressed and strongly controlled by a genetic locus on chromosome 16 in the kidney. • Ace2 co-variates are enriched in the RAS pathway. • Ace2 is strongly correlated with the growth factor Pdgfc. • Ace2 and Pdgfc co-expressed genes involved in the regulation of renal physiology and morphology. • SARS-CoV-2 spike glycoprotein induces down-regulation of Ace2, RAS, and Pdgfc.

Cybervictimization and non-suicidal self-injury among Chinese adolescents: A longitudinal moderated mediation model.

BACKGROUND: Cybervictimization is a risk factor for nonsuicidal self-injury (NSSI). However, there is a lack of evidence on how and under what conditions cybervictimization may influence NSSI. The present study investigated the mediating effect of self-esteem and the moderating effect of peer attachment on the relationship between cybervictimization and NSSI among Chinese adolescents. METHODS: Using three-wave longitudinal data for one year, a total of 1368 Chinese adolescents (60 % boys; Mage at Wave 1 = 15.05 years, SD = 0.85) completed the measurement using a self-report method. RESULTS: The longitudinal moderated mediation model revealed that cybervictimization is associated with NSSI via restraining the protective effect of self-esteem. Moreover, high peer attachment could buffer the negative effects of cybervictimization, and protect their self-esteem from being hurt, consequently reducing the likelihood of NSSI. LIMITATIONS: All variables in this study were self-reported, and the results should be cautiously generalized to other cultures, according to a sample of Chinese adolescents. CONCLUSIONS: Results highlight the relation between cybervictimization and NSSI. Recommended intervention and prevention strategies include enhancing the self-esteem of adolescents, breaking the cycle of cybervictimization to NSSI, and providing adolescents with more opportunities to build positive friendships with their peers to buffer the negative effects of cybervictimization.

Metagenomic and machine learning-aided identification of biomarkers driving distinctive Cd accumulation features in the root-associated microbiome of two rice cultivars.

Developing low-cadmium (Cd) rice cultivars has emerged as a promising avenue for food safety in Cd-contaminated farmlands. The root-associated microbiomes of rice have been shown to enhance rice growth and alleviate Cd stress. However, the microbial taxon-specific Cd resistance mechanisms underlying different Cd accumulation characteristics between different rice cultivars remain largely unknown. This study compared low-Cd cultivar XS14 and hybrid rice cultivar YY17 for Cd accumulation with five soil amendments. The results showed that XS14 was characterized by more variable community structures and stable co-occurrence networks in the soil-root continuum compared to YY17. The stronger stochastic processes in assembly of the XS14 (~25%) rhizosphere community than that of YY17 (~12%) suggested XS14 may have higher resistance to changes in soil properties. Microbial co-occurrence networks and machine learning models jointly identified keystone indicator microbiota, such as Desulfobacteria in XS14 and Nitrospiraceae in YY17. Meanwhile, genes involved in sulfur cycling and nitrogen cycling were observed among the root-associated microbiome of these two cultivars, respectively. Microbiomes in the rhizosphere and root of XS14 showed a higher diversity in functioning, with the significant enrichment of functional genes related to amino acid and carbohydrate transport and metabolism, and sulfur cycling. Our findings revealed differences and similarities in the microbial communities associated with two rice cultivars, as well as bacterial biomarkers predictive of Cd-accumulation capacity. Thus, we provide new insights into taxon-specific recruitment strategies of two rice cultivars under Cd stress and highlight the utility of biomarkers in offering clues for enhancing crop resilience to Cd stresses in the future.

The Study on Cervical Cancer Burden in 127 Countries and Its Socioeconomic Influence Factors.

OBJECTIVES: To explore the relationship between cervical cancer burden and HDI and other socioeconomic influence factors in 127 countries. METHODS: Dividing 127 countries into low-, medium-, high-, ultrahigh-HDI groups, and using statistical method to compare the prevalence trend of cervical cancer in different HDI country groups. Then selecting mortality-to-incidence ratio (MIR) to measure the cancer burden as the dependent variable, HDI and other socioeconomic factors selected from 2020 Human Development Report as independent variables, and using multi-regression model to analyze the correlation between variables. RESULTS: Countries with higher HDI were found to have lower prevalence and mortality of cervical cancer, and vice versa. Besides that, air and water pollution, government-coordinated spending, and the intimate partner of 15-49-year-old women and girls have positive correlation impact on cervical cancer burden. DISCUSSION: The cancer prevention and control policies in countries with high HDI have achieved relatively ideal implementation effects. Countries with relatively backward social and economic development level, cancer prevention and control policies had little effect, such as lower HPV vaccination coverage, poor regional health resource allocation, and week public education awareness. Therefore, cervical cancer control plan must be integrated into national strategies and implemented in people-oriented comprehensive health services.

Protective role for C3aR in experimental chronic pyelonephritis.

Emerging evidence suggest that C3aR plays important roles in homeostasis, host defense and disease. Although it is known that C3aR is protective in several models of acute bacterial infections, the role for C3aR in chronic infection is largely unknown. Here we show that C3aR is protective in experimental chronic pyelonephritis. Global C3aR deficient (C3ar-/- ) mice had higher renal bacterial load, more pronounced renal histological lesions, increased renal apoptotic cell accumulation, tissue inflammation and extracellular matrix deposition following renal infection with uropathogenic E. coli (UPEC) strain IH11128, compared to WT control mice. Myeloid C3aR deficient (Lyz2-C3ar-/- ) mice exhibited a similar disease phenotype to global C3ar-/- mice. Pharmacological treatment with a C3aR agonist reduced disease severity in experimental chronic pyelonephritis. Furthermore, macrophages of C3ar-/- mice exhibited impaired ability to phagocytose UPEC. Our data clearly demonstrate a protective role for C3aR against experimental chronic pyelonephritis, macrophage C3aR plays a major role in the protection, and C3aR is necessary for phagocytosis of UPEC by macrophages. Our observation that C3aR agonist curtailed the pathology suggests a therapeutic potential for activation of C3aR in chronic infection.

3D CNT/MXene microspheres for combined photothermal/photodynamic/chemo for cancer treatment.

MXene nanosheets have shown exciting potential in nanomedicine because of their large surface area, intense near-infrared (NIR) absorbance, and good biocompatibility. However, their development in the direction of treating tumors is constrained by the limitations of existing design methodologies. These methodologies lack control over the size and distribution of tumors. Moreover, their photodynamic therapy (PDT) effect is poor. To address this unmet medical need, a simple strategy that processes MXene with carbon nanotube (CNT) into a three-dimensional (3D) honeycomb structure having anti aggregation capacity was established. The structure can be used in disease phototherapy against tumors, bacteria, and viruses, such as photothermal therapy (PTT), photodynamic therapy (PDT), and multimodal synergistic therapy. In the present study, 3D CNT/MXene microspheres were obtained by the template method and spray-drying method. The microspheres possessed special photothermal effects and photothermal stability under NIR laser irradiation. Furthermore, the developed microspheres could achieve a maximum of 85.6% drug loading capability of doxorubicin (DOX). Under light irradiation at 650 and 808 nm, 3D CNT/MXene microspheres could efficiently produce singlet oxygen due to the effectiveness of CNTs as carries for Titanium Dioxide (TiO2) photosensitizers present on the MXene surface. Furthermore, in vitro studies had showed that 3D CNT/MXene-DOX effectively inhibited the proliferation of HeLa cells. Hence, this study provides a promising platform for future clinical applications to realize PTT/PDT/chemotherapy combination cancer treatment based on MXene.

Diversity-triggered bottom-up trophic interactions impair key soil functions under lindane pollution stress.

A growing amount of evidence suggests that microbial diversity loss may have negative effects on soil ecosystem function. However, less attention has been paid to the determinants of the relationship between community diversity and soil functioning under pollution stress. Here we manipulated microbial diversity to observe how biotic and abiotic factors influenced soil multi-functions (e.g. lindane degradation, soil respiration and nutrient cycling). Results showed that protist community was more sensitive to dilution, pollution stress, and sodium acetate addition than bacterial and fungal community. Acetate addition accelerated the lindane removal. Any declines in microbial diversity reduced the specialized soil processes (NO3-N production, and N2O flux), but increased soil respiration rate. Dilution led to a significant increase in consumers-bacterial and fungi-bacterial interaction as evidenced by co-occurrence network, which possibly played roles in maintaining microbiome stability and resilience. Interestingly, pollution stress and resource availability weaken the relationship between microbial diversity and soil functions through the bottom-up trophic interaction and environmental preference of soil microbiome. Overall, this work provides experimental evidence that loss in microbial diversity, accompanied with changes in trophic interactions mediated biotic and abiotic factors, could have important consequences for specialized soil functioning in farmland ecosystems.

Biochar affects methylmercury production and bioaccumulation in paddy soils: Insights from soil-derived dissolved organic matter.

Biochar has been used increasingly as a soil additive to control mercury (Hg) pollution in paddy rice fields. As the most active component of soil organic matter, soil dissolved organic matter (DOM) plays a vital role in the environmental fate of contaminants. However, there are very few studies to determine the impact of biochar on the Hg cycle in rice paddies using insights from DOM. This study used original and modified biochar to investigate their effect on DOM dynamics and their potential impact on methylmercury (MeHg) production and bioaccumulation in rice plants. Porewater DOM was collected to analyze the variations in soil-derived DOM in paddy soils. The results showed that the addition of biochar, whether in original or modified form, significantly reduced the bioaccumulation of MeHg in rice plants, especially in hulls and grains (p<0.05). However, MeHg production in soils was only inhibited by the modified biochar. Biochar addition induced a significant increase in DOM's aromaticity and molecular weight (p<0.05), which decreased Hg bioavailability. Furthermore, enhanced microbial activity was also observed in DOM (p<0.05), further increasing MeHg production in the soil. Thus, the effect of biochar on the fate of Hg cycle involves competition between the two different roles of DOM. This study identified a specific mechanism by which biochar affects Hg behavior in rice paddy soil and contributes to understanding the more general influence of biochar in agriculture and contaminant remediation.

The benefits of career adaptability on African international students' perception of social support and quality of life in China during the COVID-19 pandemic.

With economic globalization, there has been a rapid increase in the number of sojourners in the workforce and in international education. However, little is known about the impact of career adaptability (a key psychosocial resource for managing career transitions) on international students' adaptation in cross-cultural contexts, particularly their quality of life during the COVID-19 pandemic. Based on career construct theory, this study examined how career adaptability directly and indirectly enhances international students' quality of life through perceived online and offline social support, and how the COVID-19 pandemic affected their adaptation in cross-cultural context. With a sample of 328 African international students in China, we found that career adaptability and perceived online/ offline social support were positively related to the quality of life during the COVID-19 pandemic. Furthermore, perceived offline social support, but not perceived online social support, was an adapting response through which career adaptability enhances international students' quality of life in cross-cultural context. The mediating effect of perceived offline social support diminished when the self-rated COVID-19 impact on international students was severe. These findings provide a basis for future psychosocial interventions to enhance international students' adaptation to cross-cultural contexts during and after the COVID-19 pandemic.