Impact of residual antibiotics on microbial decomposition of livestock manures in Eutric Regosol: Implications for sustainable nutrient recycling and soil carbon sequestration.

The land application of livestock manure has been widely acknowledged as a beneficial approach for nutrient recycling and environmental protection. However, the impact of residual antibiotics, a common contaminant of manure, on the degradation of organic compounds and nutrient release in Eutric Regosol is not well understood. Here, we studied, how oxytetracycline (OTC) and ciprofloxacin (CIP) affect the decomposition, microbial community structure, extracellular enzyme activities and nutrient release from cattle and pig manure using litterbag incubation experiments. Results showed that OTC and CIP greatly inhibited livestock manure decomposition, causing a decreased rate of carbon (28%-87%), nitrogen (15%-44%) and phosphorus (26%-43%) release. The relative abundance of gram-negative (G-) bacteria was reduced by 4.0%-13% while fungi increased by 7.0%-71% during a 28-day incubation period. Co-occurrence network analysis showed that antibiotic exposure disrupted microbial interactions, particularly among G- bacteria, G+ bacteria, and actinomycetes. These changes in microbial community structure and function resulted in decreased activity of urease, ß-1,4-N-acetyl-glucosaminidase, alkaline protease, chitinase, and catalase, causing reduced decomposition and nutrient release in cattle and pig manures. These findings advance our understanding of decomposition and nutrient recycling from manure-contaminated antibiotics, which will help facilitate sustainable agricultural production and soil carbon sequestration.

Allosensitisation in NHP results in cross-reactive anti-SLA antibodies not detected by a lymphocyte-based flow cytometry crossmatch.

Xenotransplantation is a potential option for individuals for whom an acceptable human allograft is unavailable. Individuals with broadly reactive HLA antibodies due to prior exposure to foreign HLA are potential candidates for a clinical xenotransplant trial. It remains controversial if allosensitisation results in the development of cross-reactive antibodies against SLA. This may require increased histocompatibility scrutiny for highly sensitised individuals prior to enrollment in a clinical trial. Serum samples were obtained from non-human primates sensitised via serial skin transplantation from maximally MHC-mismatched donor, as reported. Sera from pre- and post-allosensitisation timepoints were assessed in a flow crossmatch (FXM) for IgM and IgG binding to pig splenocytes with or without red blood cell adsorption. Xenoreactive antibodies were eluted from pig splenocytes and screened on a single antigen HLA bead assay. A MHC Matchmaker algorithm was developed to predict potential conserved amino acid motifs among the pig, NHP, and human. Our sensitised NHP model was used to demonstrate that allosensitisation does not result in an appreciable difference in xenoreactive antibody binding in a cell-based FXM. However, antibody elution and screening on single antigen HLA beads suggest the existence of potential cross-reactive antibodies against SLA. The cross-reactive IgG after allosensitisation were predicted by comparing the recipient Mamu alleles against its previous allograft donor Mamu alleles and the donor pig SLA alleles. Our study suggests that allosensitisation could elevate cross-reactive antibodies, but a more sensitive assay than a cell-based FXM is required to detect them. The MHC Matchmaker algorithm was developed as a potential tool to help determine amino acid motif conservation and reactivity pattern.

Salvaging the transected hypoglossal nerve using descendens hypoglossi in patients undergoing hypoglossal-facial nerve anastomosis for facial palsy: a randomized clinical trial.

OBJECTIVE: Hypoglossal-facial nerve anastomosis (HFA) is the most commonly used surgical treatment for severe facial palsy that does not respond to conservative treatments. A major complication of HFA is the loss of tongue function. The authors aimed to evaluate whether anastomosing the transected hypoglossal nerve using the ramus descendens hypoglossi could prevent tongue deviation and dysfunction in patients undergoing HFA. METHODS: In this randomized trial, adult patients with severe peripheral facial palsy (House-Brackmann grade V or VI) who did not respond to at least 6 months of conservative treatment were randomized at a 1:1 ratio to undergo either HFA alone (control group) or HFA plus anastomosis between the hypoglossal nerve and descendens hypoglossi (intervention group). The primary endpoint was tongue deviation angle at 12 months. Key secondary endpoints included tongue disability (chewing difficulty, swallowing defect, and articulation defect), tongue disability index (TDI; range 1-4, with a higher score indicating more severe disability), and facial nerve function. RESULTS: Twenty patients were enrolled (10 in each group). At 12 months, the tongue deviation angle was significantly lower in the intervention group than in the control group (7.8° ± 5.1° vs 23.6° ± 9.6°, p < 0.001). Although not statistically significant, the intervention group had lower rates of chewing difficulty (1/10 vs 3/10, p = 0.58), swallowing defect (1/10 vs 5/10, p = 0.14), and articulation defect (2/10 vs 6/10, p = 0.17). TDI was significantly lower in the intervention group (1.5 ± 0.6 vs 2.5 ± 0.3, p < 0.001). The percentage of the patients achieving House-Brackmann grade II or III was 80% in each group. CONCLUSIONS: Anastomosis of the descendens hypoglossi to the transected hypoglossal nerve attenuated tongue deviation in patients undergoing HFA for facial palsy, without compromising facial nerve function. Clinical trial registration no: ChiCTR2000034372 (Chinese Clinical Trials Registry).

Targeting focal adhesion kinase (FAK) in cancer therapy: A recent update on inhibitors and PROTAC degraders.

Focal adhesion kinase (FAK) is considered as a pivotal intracellular non-receptor tyrosine kinase, and has garnered significant attention as a promising target for anticancer drug development. As of early 2024, a total of 12 drugs targeting FAK have been approved for clinical or preclinical studies worldwide, including three PROTAC degraders. In recent three years (2021-2023), significant progress has been made in designing targeted FAK anticancer agents, including the development of a novel benzenesulfofurazan type NO-releasing FAK inhibitor and the first-in-class dual-target inhibitors simultaneously targeting FAK and HDACs. Given the pivotal role of FAK in the discovery of anticancer drugs, as well as the notable advancements achieved in FAK inhibitors and PROTAC degraders in recent years, this review is underbaked to present a comprehensive overview of the function and structure of FAK. Additionally, the latest findings on the inhibitors and PROTAC degraders of FAK from the past three years, along with their optimization strategies and anticancer activities, were summarized, which might help to provide novel insights for the development of novel targeted FAK agents with promising anticancer potential and favorable pharmacological profiles.

The genetic effects of hormones modulated by the Pituitary-Thyroid/Adrenal/Gonadal axis on the risk of developing venous thromboembolism: a mendelian randomization study.

BACKGROUND: The aim of this study was to explore the genetic effects of hormones modulated through the pituitary-thyroid/adrenal/gonadal axis on the risk of developing venous thromboembolism (VTE) and to investigate the potentially causal relationships between them. METHODS: A two-sample Mendelian randomization (MR) design was used. The single-nucleotide polymorphisms (SNPs) used as instrumental variables for various hormones and hormone-mediated diseases were derived from published genome-wide association studies (GWASs). Summary statistics for the risk of developing VTE (including deep venous thrombosis [DVT] and pulmonary embolism [PE]) were obtained from the UK Biobank and the FinnGen consortium. Inverse-variance weighting (IVW) was applied as the primary method to analyse causal associations. Other MR methods were used for supplementary estimates and sensitivity analysis. RESULTS: A genetic predisposition to greater free thyroxine (FT4) concentrations was associated with a greater risk of developing DVT (OR = 1.0007, 95%CI [1.0001-1.0013], p = 0.0174) and VTE (OR = 1.0008, 95%CI [1.0002-1.0013], p = 0.0123). Genetically predicted hyperthyroidism was significantly associated with an increased risk of developing DVT (OR = 1.0685, 95%CI [1.0139-1.1261], p = 0.0134) and VTE (OR = 1.0740, 95%CI [1.0165-1.1348], p = 0.0110). According to the initial MR analysis, testosterone concentrations were positively associated with the risk of developing VTE (OR = 1.0038, 95%CI [1.004-1.0072], p = 0.0285). After sex stratification, estradiol concentrations were positively associated with the risk of developing DVT (OR = 1.0143, 95%CI [1.0020-1.0267], p = 0.0226) and VTE (OR = 1.0156, 95%CI [1.0029-1.0285], p = 0.0158) in females, while the significant relationship between testosterone and VTE did not persist. SHBG rs858518 was identified as the only SNP that was associated with an increased risk of developing VTE, mediated by estradiol, in females. CONCLUSIONS: Genetically predicted hyperthyroidism and increased FT4 concentrations were positively associated with the risk of developing VTE. The effects of genetically predicted sex hormones on the risk of developing VTE differed between males and females. Greater genetically predicted estradiol concentrations were associated with an increased risk of developing VTE in females, while the SHBG rs858518 variant may become a potential prevention and treatment target for female VTE.

Predictive value of hematocrit, serum albumin level difference, and fibrinogen-to-albumin ratio for COVID-19-associated acute respiratory failure.

Background: Acute respiratory failure is the main clinical manifestation and a major cause of death in patients with COVID-19. However, few reports on its prevention and control have been published because of the need for laboratory predictive indicators. This study aimed to evaluate the predictive value of hematocrit level, serum albumin level difference, and fibrinogen-to-albumin ratio for COVID-19-associated acute respiratory failure. Material and methods: A total of 120 patients with COVID-19 from the First Affiliated Hospital of Anhui Medical University were selected between December 2022 and March 2023. Patients were divided into acute respiratory failure and non-acute respiratory failure groups and compared patient-related indicators between them using univariate and multivariate logistic regression analyses. Receiver operating characteristic analysis was performed to determine the discrimination accuracy. Results: In total, 48 and 72 patients were enrolled in the acute respiratory failure and non-acute respiratory failure groups, respectively. The Quick COVID-19 Severity Index scores, fibrinogen-to-albumin ratio, hematocrit and serum albumin level difference, fibrinogen, and hematocrit levels were significantly higher in the acute respiratory failure group than in the non-acute respiratory failure group. A Quick COVID-19 Severity Index >7, fibrinogen-to-albumin ratio >0.265, and hematocrit and serum albumin level difference >12.792 had a 96.14 % positive predictive rate and a 94.06 % negative predictive rate. Conclusion: Both fibrinogen-to-albumin ratio and hematocrit and serum albumin level difference are risk factors for COVID-19-associated acute respiratory failure. The Quick COVID-19 Severity Index score combined with fibrinogen-to-albumin ratio, and hematocrit and serum albumin level difference predict high and low risks with better efficacy and sensitivity than those of the Quick COVID-19 Severity Index score alone; therefore, these parameters can be used collectively as a risk stratification method for assessing patients with COVID-19.

Targeted genome editing restores auditory function in adult mice with progressive hearing loss caused by a human microRNA mutation.

Mutations in microRNA-96 (MIR96) cause autosomal dominant deafness-50 (DFNA50), a form of delayed-onset hearing loss. Genome editing has shown efficacy in hearing recovery through intervention in neonatal mice, yet editing in the adult inner ear is necessary for clinical applications, which has not been done. Here, we developed a genome editing therapy for the MIR96 mutation 14C>A by screening different CRISPR systems and optimizing Cas9 expression and the sgRNA scaffold for efficient and specific mutation editing. AAV delivery of the KKH variant of Staphylococcus aureus Cas9 (SaCas9-KKH) and sgRNA to the cochleae of presymptomatic (3-week-old) and symptomatic (6-week-old) adult Mir9614C>A/+ mutant mice improved hearing long term, with efficacy increased by injection at a younger age. Adult inner ear delivery resulted in transient Cas9 expression without evidence of AAV genomic integration, indicating the good safety profile of our in vivo genome editing strategy. We developed a dual-AAV system, including an AAV-sgmiR96-master carrying sgRNAs against all known human MIR96 mutations. Because mouse and human MIR96 sequences share 100% homology, our approach and sgRNA selection for efficient and specific hair cell editing for long-term hearing recovery lay the foundation for the development of treatment for patients with DFNA50 caused by MIR96 mutations.

Carbon-Boosted and Nitrogen-Stabilized Isolated Single-Atom Sites for Direct Dehydrogenation of Lower Alkanes.

Lower olefins are widely used in the chemical industry as basic carbon-based feedstocks. Here, we report the catalytic system featuring isolated single-atom sites of iridium (Ir1) that can function within the entire temperature range of 300-600 °C and transform alkanes with conversions close to thermodynamics-dictated levels. The high turnover frequency values of the Ir1 system are comparable to those of homogeneous catalytic reactions. Experimental data and theoretical calculations both indicate that Ir1 is the primary catalytic site, while the coordinating C and N atoms help to enhance the activity and stability, respectively; all three kinds of elements cooperatively contribute to the high performance of this novel active site. We have further immobilized this catalyst on particulate Al2O3, and we found that the resulting composite system under mimicked industrial conditions could still give high catalytic performances; in addition, we have also developed and established a new scheme of periodical in situ regeneration specifically for this composite particulate catalyst.

Ruthenium-based single atom catalysts: synthesis and application in the electrocatalytic hydrogen evolution reaction.

Electrocatalytic water splitting is a promising production method for green hydrogen; however, its practical application is limited by the lack of robust catalysts for the cathode hydrogen evolution reaction (HER). Recently, the use of Ru in electrocatalytic HER has become a research hotspot because Ru has a metal-hydrogen bond strength similar to that of Pt - known for its excellent HER activity - but has a lower cost than Pt. Numerous modification strategies are available to further improve the HER activity of metal Ru such as vulcanisation, phosphating and atomisation. The atomisation strategy has attracted much attention owing to its extremely high Ru atomic utilisation efficiency and tunable electronic structures. However, isolated studies could not effectively address the bottlenecks. Therefore, to promote the effective exploration of Ru-based single-atom catalysts and clarify the research status in this field, studies on related topics (e.g. Ru single-atom catalysts, Ru dual-atom catalysts, composite catalysts containing single-atom Ru and Ru nanoparticles) have been systematically and briefly summarised herein. Finally, the research challenges and prospects of Ru-based single-atom catalysts in the HER field have been discussed, which may provide valuable insights for further research.

Viral and Bacterial Community Dynamics in Food Waste and Digestate from Full-Scale Biogas Plants.

Anaerobic digestion (AD) is commonly used in food waste treatment. Prokaryotic microbial communities in AD of food waste have been comprehensively studied. The role of viruses, known to affect microbial dynamics and metabolism, remains largely unexplored. This study employed metagenomic analysis and recovered 967 high-quality viral bins within food waste and digestate derived from 8 full-scale biogas plants. The diversity of viral communities was higher in digestate. In silico predictions linked 20.8% of viruses to microbial host populations, highlighting possible virus predators of key functional microbes. Lineage-specific virus-host ratio varied, indicating that viral infection dynamics might differentially affect microbial responses to the varying process parameters. Evidence for virus-mediated gene transfer was identified, emphasizing the potential role of viruses in controlling the microbiome. AD altered the specific process parameters, potentially promoting a shift in viral lifestyle from lysogenic to lytic. Viruses encoding auxiliary metabolic genes (AMGs) were involved in microbial carbon and nutrient cycling, and most AMGs were transcriptionally expressed in digestate, meaning that viruses with active functional states were likely actively involved in AD. These findings provided a comprehensive profile of viral and bacterial communities and expanded knowledge of the interactions between viruses and hosts in food waste and digestate.

Chitosan-modified molybdenum selenide mediated efficient killing of Helicobacter pylori and treatment of gastric cancer.

Helicobacter pylori (H. pylori) is one of the major causes of gastrointestinal diseases, including gastric cancer. However, the acidic environment of the stomach and H. pylori resistance severely impair the antimicrobial efficacy of oral drugs. Here, a biocompatible chitosan-modified molybdenum selenide (MoSe2@CS) was designed for the simultaneous photothermal treatment of H. pylori infection and gastric cancer. MoSe2@CS showed a photothermal conversion efficiency was as high as 45.7 %. In the H. pylori-infected mice model, MoSe2@CS displayed a high bacteriostasis ratio of 99.9 % upon near-infrared irradiation. The antimicrobial functionality was also proved by transcriptomic sequencing study, which showed that MoSe2@CS combined with NIR laser irradiation modulated the gene expression of a variety of H. pylori bioprocesses, including cell proliferation and inflammation-related pathways. Further gut flora analysis results indicated that MoSe2@CS mediated PTT of H. pylori did not affect the homeostasis of gut flora, which highlights its advantages over traditional antibiotic therapy. In addition, MoSe2@CS exhibited a good photothermal ablation effect and significantly inhibited gastric tumor growth in vitro and in vivo. The comprehensive application of MoSe2@CS in the PTT of H. pylori infection and gastric cancer provides a new avenue for the clinical treatment of H. pylori infection and related diseases.

Novel Schiff's base-assisted synthesis of metal-ligand nanostructures for multi-functional applications: Detection of catecholamines/antibiotics, removal of tetracycline, and antifungal treatment against plant pathogens.

The development of nanozymes (NZ) for the simultaneous detection of multiple target chemicals is gaining paramount attention in the field of food and health sciences, and waste management industries. Nanozymes (NZ) effectively compensate for the environmental vulnerability of natural enzymes. Considering the development gap of NZ with diverse applications, we synthesized versatile Schiff's base ligands following a facile route and readily available starting reagents (glutaraldehyde, aminopyridines). DPDI, one of the synthesized ligands, readily reacted with transition metal ions (Cu+2, Ag+1, Zn+2 in specific) under ambient conditions, yielding the corresponding nanoparticles/MOF. The structures of ligands and their products were confirmed using various analytical techniques. The enzymatic efficacy of DPDI-Cu (km 0.25 mM=, Vmax = 10.75 µM/sec) surpassed Tremetese versicolor laccase efficacy (km 0. 5 mM=, Vmax = 2.15 µM/sec). Additionally, DPDI-Cu proved resilient to changing pH, temperature, ionic strength, organic solvent, and storage time compared to laccase and provided reusability. DPDI-Cu proved promising for colorimetric detection of dopamine, epinephrine, catechol, tetracycline, and quercetin. The mechanism of oxidative detection of TC was studied through LC/MS analysis. DPDI-Cu-bentonite composite efficiently adsorbed tetracycline with maximum Langmuir adsorption of 208 mg/g. Moreover, DPDI/Cu and DPDI-Ag nanoparticles possessed antifungal activity exhibiting a minimum inhibitory concentration of 400 µg/mL and 3.12 µg/mL against Aspergillus flavus. Florescent dye tracking and SEM/TEM analysis confirmed that DPDI-Ag caused disruption of the plasma membrane and triggered ROS generation and apoptosis-like death in fungal cells. The DPDI-Ag coating treatment of wheat seeds confirmed the non-phytotoxicity of Ag-NPs.

Impact of Invisalign® first system on molar width and incisor torque in malocclusion during the mixed dentition period.

In orthodontic treatment of patients during the mixed dentition period, arch expansion and opening deep overbite are one of the objectives to achieve proper alignment of the teeth and correction of sagittal and vertical discrepancies. However, the expected outcomes of most therapeutic regimens are not clear, making it impossible to standardize early treatment effects. Therefore, this study was designed to evaluate the impact of the Invisalign® First System on the dental arch circumference and incisor inclination in patients during the mixed dentition period. A total of 21 children during the mixed dentition period (10 females and 11 males, with an average age of 8.76 years) were included in this study. The patients received non-extraction treatment through Invisalign® First System clear aligners, and no other auxiliary devices were used except Invisalign® accessories. Subsequently, the cooperation degree of patients during treatment and the oral measurement parameters at the beginning (T1) and the end (T2) of treatment were collected. All patients showed moderate/good cooperation degree during treatment. Besides, horizontal width of the maxillary first molar increased significantly; the designed arch expansion was 4.1 mm (±1.4 mm), while the actual arch expansion was 3.0 mm (±1.7 mm). Furthermore, the torque expression rate of upper anterior teeth reached 56.53%. Invisalign® First System clear aligners can effectively correct the teeth of patients during the mixed dentition period, widen the circumference of dental arch, and control the torque of incisors.

Evaluations of secondary hypertension and laboratory data in the elderly population.

Secondary hypertension in the elderly poses many challenges and requires a comprehensive diagnostic and management approach. This review explores the prevalence, diagnostic strategies, and treatment modalities for secondary hypertension in elderly patients, focusing on etiologies including primary aldosteronism, renal vascular disease, renal parenchymal disease, obstructive sleep apnea, thyroid disorders, Cushing's syndrome, pheochromocytomas and paragangliomas, and drug-induced hypertension. Key considerations include age-related changes in physiology and atypical presentations of underlying conditions necessitating thorough screening with a combination of clinical evaluation, laboratory tests, and imaging studies. Collaboration among healthcare providers is essential to ensure a timely diagnosis and personalized management tailored to the unique needs of elderly patients. Further research is needed to address knowledge gaps and optimize clinical strategies for managing secondary hypertension in this population.

Association between hemoglobin and non-alcoholic fatty liver disease (NAFLD) in United States adults: Results from NHANES 2017-2020.

Background: Non-alcoholic fatty liver disease (NAFLD), a chronic liver condition of increasing prevalence, is closely related to various metabolic disorders. Hemoglobin, a protein that transports oxygen in red blood cells, is the focus of this study, which seeks to investigate its potential association with NAFLD. Methods: We selected 6,516 eligible adult participants from the United States using the 2017-2020 National Health and Nutrition Examination Survey database for cross-sectional analyses. We analyzed the association of hemoglobin with NAFLD using weighted logistic regression models. Results: The study performed a weighted logistic regression modeling analysis, which verified that hemoglobin levels were positively associated with NAFLD, especially in the higher hemoglobin quartile groups. Subgroup analyses revealed no significant interactions, demonstrating the robustness of the model. The analysis of mediation effects showed that Gamma-Glutamyl Transferase, Alanine Aminotransferase, and triglycerides were important mediating variables in the relationship between hemoglobin and NAFLD. Conclusion: Increased hemoglobin levels were found to be significantly and independently associated with an increased NAFLD risk. This insight is crucial for the risk assessment and early detection of NAFLD, underscoring the need for heightened vigilance in individuals with higher hemoglobin levels.

The global burden of disease attributable to preterm birth and low birth weight in 204 countries and territories from 1990 to 2019: An analysis of the Global Burden of Disease Study.

Background: Preterm birth and low birth weight (PBLBW), recognised globally as primary contributors to infant mortality in children under five, have not been sufficiently investigated in terms of their worldwide impact. In this study we aimed to thoroughly evaluate the contemporary trends in disease burden attributable to PBLBW. Methods: We analysed data from 204 countries and territories between 1990-2019, as sourced from the 2019 Global Burden of Disease Study. We analysed the global incidence of mortality and disability-adjusted life years (DALYs) associated with PBLBW, stratified by age, gender, year, and geographic location, alongside the socio-demographic index (SDI). We calculated the annual percentage changes to evaluate the dynamic trends over time. We employed a generalised linear model and scrutinised the relationship between the SDI and the disease burden attributed to PBLBW. Results: In 2019, the global age-standardised rate of deaths and DALYs related to PBLBW showed significant declines. Over the period 1990-2019, both death and DALY rates displayed substantial downward trends, with similar change trends observed for both females and males. Age-specific ratios revealed a decrease in PBLBW-related deaths and DALYs with increasing age, primarily during the neonatal stages (zero to 27 days). The leading three causes of PBLBW-related DALYs in 2019 were neonatal disorders, lower respiratory infections, and sudden infant death syndrome. Furthermore, the association between SDI and PBLBW-related DALYs indicated that the age-standardised DALY rates in 204 countries and territories worldwide were negatively correlated with SDI in 2019. From 1990 to 2019, the age-standardised DALY rates decreased linearly in most regions, except sub-Saharan Africa. Conclusions: The persistent global burden of disease associated with PBLBW is particularly pronounced in neonates aged less than 28 days and in regions with low SDI. In this study, we highlighted the critical need for tailored interventions aimed at mitigating the detrimental effects of PBLBW to attain specific sustainable development goals, particularly those centred on enhancing child survival and overall well-being.

Clinical significance of TROAP in endometrial cancer and the antiproliferative and proapoptotic effects of TROAP knockdown in endometrial cancer cells: integrated utilization of bioinformatic analysis and in vitro test verification.

Trophinin-associated protein (TROAP), a cytoplasmic protein essential for spindle assembly and centrosome integrity during mitosis, has been reported to serve as an oncogene in various tumors. However, its role in endometrial cancer (EC) progression is still undefined. TROAP expression in EC was analyzed via GEPIA and HPA databases. The diagnostic and prognostic values of TROAP were examined by ROC curve analysis and Kaplan-Meier plotter, respectively. Cell proliferation was evaluated using CCK-8 and EdU incorporation assays. Apoptosis was assessed using TUNEL and flow cytometry assays. GSEA was performed to explore TROAP-related pathways in EC. Expression of TROAP, proliferating cell nuclear antigen (PCNA), Ki-67, cleaved-caspase-3 (cl-caspase-3), caspase-3, active ß-catenin, and total ß-catenin was detected using western blot analysis. TROAP was upregulated in EC. TROAP served as a potential diagnostic and prognostic marker in EC patients. TROAP silencing suppressed proliferation and enhanced apoptosis in EC cells. GSEA revealed that EC and Wnt signaling pathways were related to the expression of TROAP. We further demonstrated that TROAP knockout repressed the Wnt/ß-catenin pathway in EC cells. Moreover, SKL2001, a Wnt/ß-catenin activator, partially abrogated the effects of TROAP silencing on EC cell proliferation and apoptosis, while the signaling inhibitor XAV-939 had the opposite effect. In conclusion, TROAP knockout retarded proliferation and elicited apoptosis in EC cells by blocking the Wnt/ß-catenin pathway.

Interface Engineering of the Cu1.5Mn1.5O4/CeO2 Heterostructure for Highly Efficient Electrocatalytic Nitrate Reduction to Ammonia.

The electrochemical nitrate reduction reaction (NO3RR) is considered a sustainable technology to convert the nitrate pollutants to ammonia. However, developing highly efficient electrocatalysts is necessary and challenging given the slow kinetics of the NO3RR with an eight-electron transfer process. Here, a Cu1.5Mn1.5O4 (CMO)/CeO2 heterostructure with rich interfaces is designed and fabricated through an electrospinning and postprocessing technique. Benefiting from the strong coupling between CMO and CeO2, the optimized CMO/CeO2-2 catalyst presents excellent NO3RR performance, with NH3 Faraday efficiency (FE) up to 93.07 ± 1.45% at -0.481 V vs reversible hydrogen electrode (RHE) and NH3 yield rate up to 48.06 ± 1.32 mg cm-2 h-1 at -0.681 V vs RHE. Theoretical calculations demonstrate that the integration of CeO2 with CMO modulates the adsorption/desorption process of the reactants and intermediates, showing a reduced energy barrier in the rate determination step of NO* to N* and achieving an outstanding NO3RR performance.

SIGLEC15, negatively correlated with PD-L1 in HCC, could induce CD8+ T cell apoptosis to promote immune evasion.

Functional roles of SIGLEC15 in hepatocellular carcinoma (HCC) were not clear, which was recently found to be an immune inhibitor with similar structure of inhibitory B7 family members. SIGLEC15 expression in HCC was explored in public databases and further examined by PCR analysis. SIGLEC15 and PD-L1 expression patterns were examined in HCC samples through immunohistochemistry. SIGLEC15 expression was knocked-down or over-expressed in HCC cell lines, and CCK8 tests were used to examine cell proliferative ability in vitro. Influences of SIGLEC15 expression on tumor growth were examined in immune deficient and immunocompetent mice respectively. Co-culture system of HCC cell lines and Jurkat cells, flow cytometry analysis of tumor infiltrated immune cells and further sequencing analyses were performed to investigate how SIGLEC15 could affect T cells in vitro and in vivo. We found SIGLEC15 was increased in HCC tumor tissues and was negatively correlated with PD-L1 in HCC samples. In vitro and in vivo models demonstrated inhibition of SIGLEC15 did not directly influence tumor proliferation. However, SIGLEC15 could promoted HCC immune evasion in immune competent mouse models. Knock-out of Siglec15 could inhibit tumor growth and reinvigorate CD8+ T cell cytotoxicity. Anti-SIGLEC15 treatment could effectively inhibit tumor growth in mouse models with or without mononuclear phagocyte deletion. Bulk and single-cell RNA sequencing data of treated mouse tumors demonstrated SIGLEC15 could interfere CD8+ T cell viability and induce cell apoptosis. In all, SIGLEC15 was negatively correlated with PD-L1 in HCC and mainly promote HCC immune evasion through inhibition of CD8+ T cell viability and cytotoxicity.