ABSTRACT
Arsenic (As) methylation in soils affects the environmental behavior of As, excessive accumulation of dimethylarsenate (DMA) in rice plants leads to straighthead disease and a serious drop in crop yield. Understanding the mobility and transformation of methylated arsenic in redox-changing paddy fields is crucial for food security. Here, soils including un-arsenic contaminated (N-As), low-arsenic (L-As), medium-arsenic (M-As), and high-arsenic (H-As) soils were incubated under continuous anoxic, continuous oxic, and consecutive anoxic/oxic treatments respectively, to profile arsenic methylating process and microbial species involved in the As cycle. Under anoxic-oxic (A-O) treatment, methylated arsenic was significantly increased once oxygen was introduced into the incubation system. The methylated arsenic concentrations were up to 2-24 times higher than those in anoxic (A), oxic (O), and oxic-anoxic (O-A) treatments, under which arsenic was methylated slightly and then decreased in all four As concentration soils. In fact, the most plentiful arsenite S-adenosylmethionine methyltransferase genes (arsM) contributed to the increase in As methylation. Proteobacteria (40.8%-62.4%), Firmicutes (3.5%-15.7%), and Desulfobacterota (5.3%-13.3%) were the major microorganisms related to this process. These microbial increased markedly and played more important roles after oxygen was introduced, indicating that they were potential keystone microbial groups for As methylation in the alternating anoxic (flooding) and oxic (drainage) environment. The novel findings provided new insights into the reoxidation-driven arsenic methylation processes and the model could be used for further risk estimation in periodically flooded paddy fields.
Subject(s)
Arsenic , Oryza , Soil Microbiology , Soil Pollutants , Soil , Arsenic/analysis , Soil Pollutants/analysis , Methylation , Soil/chemistry , Microbiota , Oxidation-Reduction , Bacteria/metabolismABSTRACT
Bacterial infections claim millions of lives every year, with the escalating menace of microbial antibiotic resistance compounding this global crisis. Nanozymes, poised as prospective substitutes for antibiotics, present a significant frontier in antibacterial therapy, yet their precise enzymatic origins remain elusive. With the continuous development of nanozymes, the applications of elemental N-modulated nanozymes have spanned multiple fields, including sensing and detection, infection therapy, cancer treatment, and pollutant degradation. The introduction of nitrogen into nanozymes not only broadens their application range but also holds significant importance for the design of catalysts in biomedical research. The synergistic interplay between W and N induces pivotal alterations in electronic configurations, endowing tungsten nitride (WN) with a peroxidase-like functionality. Furthermore, the introduction of N vacancies augments the nanozyme activity, thus amplifying the catalytic potential of WN nanostructures. Rigorous theoretical modeling and empirical validation corroborate the genesis of the enzyme activity. The meticulously engineered WN nanoflower architecture exhibits an exceptional ability in traversing bacterial surfaces, exerting potent bactericidal effects through direct physical interactions. Additionally, the topological intricacies of these nanostructures facilitate precise targeting of generated radicals on bacterial surfaces, culminating in exceptional bactericidal efficacy against both Gram-negative and Gram-positive bacterial strains along with notable inhibition of bacterial biofilm formation. Importantly, assessments using a skin infection model underscore the proficiency of WN nanoflowers in effectively clearing bacterial infections and fostering wound healing. This pioneering research illuminates the realm of pseudoenzyme activity and bacterial capture-killing strategies, promising a fertile ground for the development of innovative, high-performance artificial peroxidases.
ABSTRACT
Background: Automated tumor segmentation and survival prediction are critical to clinical diagnosis and treatment. This study aimed to develop deep-learning models for automatic tumor segmentation and survival prediction in magnetic resonance imaging (MRI) of cervical cancer (CC) by combining deep neural networks and Transformer architecture. Methods: This study included 406 patients with CC, each with comprehensive clinical information and MRI scans. We randomly divided patients into training, validation, and independent test cohorts in a 6:2:2 ratio. During the model training, we employed two architecture types: one being a hybrid model combining convolutional neural network (CNN) and ransformer (CoTr) and one of pure CNNs. For survival prediction, the hybrid model combined tumor image features extracted by segmentation models with clinical information. The performance of the segmentation models was evaluated using the Dice similarity coefficient (DSC) and 95% Hausdorff distance (HD95). The performance of the survival models was assessed using the concordance index. Results: The CoTr model performed well in both contrast-enhanced T1-weighted (ceT1W) and T2-weighted (T2W) imaging segmentation tasks, with average DSCs of 0.827 and 0.820, respectively, which outperformed other the CNN models such as U-Net (DSC: 0.807 and 0.808), attention U-Net (DSC: 0.814 and 0.811), and V-Net (DSC: 0.805 and 0.807). For survival prediction, the proposed deep-learning model significantly outperformed traditional methods, yielding a concordance index of 0.732. Moreover, it effectively divided patients into low-risk and high-risk groups for disease progression (P<0.001). Conclusions: Combining Transformer architecture with a CNN can improve MRI tumor segmentation, and this deep-learning model excelled in the survival prediction of patients with CC as compared to traditional methods.
ABSTRACT
Selenium (Se), a component of selenoproteins and selenocompounds in the human body, is crucial for the development of male reproductive organs, DNA synthesis, thyroid hormone, metabolism, and defence against infections and oxidative damage. In the testis, it must exceed a desirable level since either a shortage or an overabundance causes aberrant growth. The antioxidant properties of selenium are essential for preserving human reproductive health. Selenoproteins, which have important structural and enzymatic properties, control the biological activities of Se primarily. These proteins specifically have a role in metabolism and a variety of cellular processes, such as the control of selenium transport, thyroid hormone metabolism, immunity, and redox balance. Selenium nanoparticles (SeNPs) are less hazardous than selenium-based inorganic and organic materials. Upon being functionalized with active targeting ligands, they are both biocompatible and capable of efficiently delivering combinations of payloads to particular cells. In this review, we discuss briefly the chemistry, structure and functions of selenium and milestones of selenium and selenoproteins. Next we discuss the various factors influences male infertility, biological functions of selenium and selenoproteins, and role of selenium and selenoproteins in spermatogenesis and male fertility. Furthermore, we discuss the molecular mechanism of selenium transport and protective effects of selenium on oxidative stress, apoptosis and inflammation. We also highlight critical contribution of selenium nanoparticles on male fertility and spermatogenesis. Finally ends with conclusion and future perspectives.
ABSTRACT
There is an urgent need for highly active, durable, and low-cost electrocatalysts to overcome the shortcomings of high overpotential in the oxygen evolution reaction (OER) process. In this work, the nickel-iron hydroxysulfate rich in sulfate and oxygen vacancies (SO42-@Fe-NiOOH-Ov/NiS) is legitimately constructed. SO42-@Fe-NiOOH-Ov/NiS only requires a low overpotentials of 190 mV and 232 mV at 10 mA cm-2 and 100 mA cm-2 current densities in 1 M KOH, with excellent stability for 200 h at 100 mA cm-2 current density. In situ Raman spectroscopy and Fourier transform infrared spectroscopy demonstrated the stable adsorption of more SO42- on the surface of catalyst. Density functional theory calculations testify surface reconstruction, doped Fe and oxygen vacancies significantly reduced the adsorption energy of sulfate on the surface. More importantly, the formation of *OOH to O2 is facilitated by the highly hydrogen bonding between SO42- and *OOH, accelerating the OER process.
ABSTRACT
Tire wear particles (TWPs) in stormwater runoff have been widely detected and were generally classified into microplastics (MPs). TWPs and conventional MPs can be intercepted and accumulated in stormwater filtration systems, but their impacts on filtration, adsorption and microbial degradation processes of conventional pollutants (organic matters, nitrate and ammonium) have not been clarified. TWPs are different from MPs in surface feature, chemical components, adsorption ability and leaching of additives, which might lead to their different impacts on conventional pollutants removal. In this study, five different levels of aged polyethylene MPs (PEMPs) and aged TWPs contamination in stormwater filtration systems were simulated using thirty-three filtration columns. Results showed that ultraviolet aging treatment was less influential for the aging of TWPs than that of PEMPs, the specific surface area of aged PEMPs (1.603 m2/g) was over two times of unaged TWPs (0.728 m2/g) in the same size. Aged PEMPs and aged TWPs had different impacts on conventional pollutants removal performance and microbial communities, and the difference might be enlarged with exposure duration. The intensified aged PEMPs contamination generally promoted conventional pollutants removal, whereas aged TWPs showed an opposite trend. Mild contamination (0.01% and 0.1%, wt%) of aged PEMP/TWPs was beneficial to the richness and diversity of microbial communities, whereas higher contamination of aged PEMPs/TWPs was harmful. Aged PEMPs and TWPs had different impact on microbial community structure. Overall, the study found that TWPs were more detrimental than PEMPs in filtration systems. The research underscores the need for more comprehensive investigation into the occurrence, effects and management strategies of TWPs, as well as the importance of distinguishing between TWPs and MPs in future studies.
ABSTRACT
Vibrio parahaemolyticus, a prevalent foodborne pathogen found in both water and seafood, poses substantial risks to public health. The conventional countermeasure, antibiotics, has exacerbated the issue of antibiotic resistance, increasing the difficulty of controlling this bacterium. Phage lysins, as naturally occurring active proteins, offer a safe and reliable strategy to mitigate the impact of V. parahaemolyticus on public health. However, there is currently a research gap concerning bacteriophage lysins specific to Vibrio species. To address this, our study innovatively and systematically evaluates 37 phage lysins sourced from the NCBI database, revealing a diverse array of conserved domains and notable variations in similarity among Vibrio phage lysins. Three lysins, including Lyz_V_pgrp, Lyz_V_prgp60, and Lyz_V_zlis, were successfully expressed and purified. Optimal enzymatic activity was observed at 45â, 800 mM NaCl, and pH 8-10, with significant enhancements noted in the presence of 1 mM membrane permeabilizers such as EDTA or organic acids. These lysins demonstrated effective inhibition against 63 V. parahaemolyticus isolates from clinical, food, and environmental sources, including the reversal of partial resistance, synergistic interactions with antibiotics, and disruption of biofilms. Flow cytometry analyses revealed that the combination of Lyz_V_pgp60 and gentamicin markedly increased bacterial killing rates. Notably, Lyz_V_pgrp, Lyz_V_pgp60, and Lyz_V_zlis exhibited highly efficient biofilm hydrolysis, clearing over 90 % of preformed V. parahaemolyticus biofilms within 48 h. Moreover, these lysins significantly reduced bacterial loads in various food samples and environmental sources, with reductions averaging between 1.06 and 1.29 Log CFU/cm2 on surfaces such as stainless-steel and bamboo cutting boards and approximately 0.87 CFU/mL in lake water and sediment samples. These findings underscore the exceptional efficacy and versatile application potential of phage lysins, offering a promising avenue for controlling V. parahaemolyticus contamination in both food and environmental contexts.
Subject(s)
Bacteriophages , Vibrio parahaemolyticus , Vibrio parahaemolyticus/virology , Vibrio parahaemolyticus/drug effects , Viral Proteins/metabolism , Viral Proteins/genetics , Food Microbiology , Seafood/microbiology , Anti-Bacterial Agents/pharmacology , Biofilms/drug effects , Biofilms/growth & developmentABSTRACT
Herpes zoster (HZ), resulting from the reactivation of the varicella-zoster virus, is a significant disease. This study aimed to explore the factors influencing sensory neuron involvement in HZ at different locations and its association with postherpetic neuralgia (PHN). A total of 3143 cases were retrieved from an electronic medical record system, including 2676 cases of HZ and 467 cases of PHN. Gender, age, site of onset, past surgical history, and comorbidities were analyzed using a multifactorial logistic regression model. The results revealed correlations between age, gender, comorbidities (diabetes, coronary heart disease, percutaneous coronary intervention [PCI]), and sensory neuron involvement in HZ. Specifically, older age, female gender, and comorbid conditions such as diabetes/coronary heart disease were associated with sacral dorsal root ganglion (DRG) involvement, while PCI history was associated with lumbar DRG involvement. Additionally, sensory neuron involvement at different locations by HZ was linked to PHN. Furthermore, independent risk factors for PHN included thoracic DRG involvement, older age, and comorbidities (diabetes, surgical history, malignancy). It is crucial to prevent damage to the DRG, especially in individuals with comorbidities, through activities avoidance and active treatment, to minimize the occurrence of PHN.
Subject(s)
Herpes Zoster , Neuralgia, Postherpetic , Humans , Herpes Zoster/epidemiology , Herpes Zoster/complications , Male , Female , Aged , Middle Aged , Retrospective Studies , Neuralgia, Postherpetic/epidemiology , Risk Factors , Aged, 80 and over , Adult , Comorbidity , Ganglia, Sensory/virology , Herpesvirus 3, Human , Age Factors , Ganglia, Spinal/virology , Young Adult , Sex FactorsABSTRACT
Li-rich layered oxides are promising candidates for high-capacity Li-ion battery cathode materials. In this study, we employ first-principles calculations to investigate the effect of F doping on Li-rich Li2MnO3 layered cathode materials. Our findings reveal that both Li2MnO3 and Li2MnO2.75F0.25 exhibit significant volume changes (greater than 10%) during deep delithiation, which could hinder the cycling of more Li ions from these two materials. For Li2MnO3, it is observed that oxygen ions lose electrons to compensate for charge during the delithiation process, leading to a relatively high voltage plateau. After F doping, oxidation occurs in both the cationic (Mn) and anionic (O) components, resulting in a lower voltage plateau at the beginning of the charge, which can be attributed to the oxidation of Mn3+ to Mn4+. Additionally, F doping can somewhat suppress the release of oxygen in Li2MnO3, improving the stability of anionic oxidation. However, the increase of the activation barriers for Li diffusion can be observed after F doping, due to stronger electrostatic interactions between F- and Li+, which adversely affects the cycling kinetics of Li2MnO2.75F0.25. This study enhances our understanding of the impact of F doping in Li2MnO3 based on theoretical calculations.
ABSTRACT
OBJECTIVE: To study the effect of cluster nursing care based on 10S continuous quality improvement (CQI) on the incidence of postoperative delirium in patients with BPH. METHODS: This study included 96 BPH patients undergoing transurethral resection of the prostate (TURP) in our department from August 2021 to February 2023. We randomly divided the patients into two groups of equal number to receive routine postoperative nursing care (the control group) and postoperative cluster nursing care based on the 10S DQI mode (the observation group), respectively. We recorded and compared the delirium scores of the patients at 2, 6, 12 and 24 hours after operation, their status of recovery, scores on Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS) and quality of life (QOL), and incidence of complications between the two groups. RESULTS: Compared with the controls, the patients in the observation group showed significantly lower delirium scores at 2 h (12.72±3.54 vs 10.65±2.87, P<0.05), 6 h (20.17±4.92 vs 14.19±4.64, P<0.01), 12 h (16.82±4.24 vs 10.69±3.18, P<0.01) and 24 h (13.61±2.86 vs 9.13±2.12, P<0.01) after operation, and shorter time to ambulation (ï¼»3.65±1.41ï¼½ vs ï¼»2.84±0.83ï¼½ d, P<0.01) and time of postoperative catheterization (ï¼»6.28±1.65ï¼½ vs ï¼»4.28±1.14ï¼½ d, P<0.01), bladder irrigation (ï¼»3.41±1.08ï¼½ vs ï¼»2.25±0.71ï¼½ d, P<0.01) and hospitalization (ï¼»10.33±2.41ï¼½ vs ï¼»7.82±2.06ï¼½ d, P<0.01). No statistically significant differences were observed between the two groups in either the SAS and SDS scores (P >0.05) or the QOL scores before operation (P >0.05), but the former two were dramatically decreased (P<0.01) while the latter one increased in the observation group postoperatively (P<0.01). Postoperative complications included delirium, bladder spasm, urethral pain, and secondary bleeding, with a significantly lower total incidence rate in the observation than in the control group (12.50% vs 52.08%, P<0.01). CONCLUSION: Cluster nursing care based on 10S CQI can promote the postoperative recovery of BPH patients, improve their psychological status and quality of life, and reduce the incidence of delirium and complications.
Subject(s)
Delirium , Postoperative Complications , Prostatic Hyperplasia , Quality Improvement , Quality of Life , Humans , Male , Delirium/prevention & control , Delirium/epidemiology , Delirium/etiology , Postoperative Complications/prevention & control , Postoperative Complications/epidemiology , Incidence , Prostatic Hyperplasia/surgery , Transurethral Resection of Prostate , Nursing Care , AgedABSTRACT
BACKGROUND: Breast cancer ranks as one of the most prevalent malignant tumors among women, significantly endangering their health and lives. While radical surgery has been a pivotal method for halting disease progression, it alone is insufficient for enhancing the quality of life for patients. AIM: To investigate the correlation between ultrasound characteristic parameters of breast cancer lesions and clinical efficacy in patients undergoing neoadjuvant chemotherapy (NAC). METHODS: Employing a case-control study design, this research involved 178 breast cancer patients treated with NAC at our hospital from July 2019 to June 2022. According to the Miller-Payne grading system, the pathological response, i.e. efficacy, of the NAC in the initial breast lesion after NAC was evaluated. Of these, 59 patients achieved a pathological complete response (PCR), while 119 did not (non-PCR group). Ultrasound characteristics prior to NAC were compared between these groups, and the association of various factors with NAC efficacy was analyzed using univariate and multivariate approaches. RESULTS: In the PCR group, the incidence of posterior echo attenuation, lesion diameter ≥ 2.0 cm, and Alder blood flow grade ≥ II were significantly lower compared to the non-PCR group (P < 0.05). The area under the curve values for predicting NAC efficacy using posterior echo attenuation, lesion diameter, and Alder grade were 0.604, 0.603, and 0.583, respectively. Also, rates of pathological stage II, lymph node metastasis, vascular invasion, and positive Ki-67 expression were significantly lower in the PCR group (P < 0.05). Logistic regression analysis identified posterior echo attenuation, lesion diameter ≥ 2.0 cm, Alder blood flow grade ≥ II, pathological stage III, vascular invasion, and positive Ki-67 expression as independent predictors of poor response to NAC in breast cancer patients (P < 0.05). CONCLUSION: While ultrasound characteristics such as posterior echo attenuation, lesion diameter ≥ 2.0 cm, and Alder blood flow grade ≥ II exhibit limited predictive value for NAC efficacy, they are significantly associated with poor response to NAC in breast cancer patients.
ABSTRACT
Breast cancer ranks as the most prevalent cancer globally, surpassing lung cancer, with recurrence/metastasis to be its main account for the cancer-related mortality. MicroRNAs (miRNAs) participate critically in various physiological and pathological processes through posttranscriptional regulation of downstream genes. Our preliminary findings identified miR-338-5p, potentially linked to metastasis in breast cancer, a previously unexplored area. Analysis of the GSE38867 dataset revealed the decreased miR-338-5p expression in metastatic breast cancer compared to normal tissues. Cellular function experiments and a xenograft tumor model demonstrated the inhibitory function of miR-338-5p on the progression of breast cancer in vitro and in vivo. Furthermore, it downregulated the expression of mesenchymal biomarkers and NOTCH1 significantly. With the predicting targets of miR-338-5p and transcription factors of the NOTCH1 gene, coupled with dual luciferase reporter assays, it is identified ETS1 as the interactor between miR-338-5p and NOTCH1. In breast cancer tissues, as well as in our xenograft tumor model, expression of ETS1 and NOTCH1 was positively correlated using immunohistochemical staining. This study reports, for the first time, on the miR-338-5p/ETS1/NOTCH1 axis and its pivotal role in breast cancer proliferation and metastasis. These findings propose a novel therapeutic strategy for breast cancer patients and lays a foundation for its clinical detection and treatment evaluation.
ABSTRACT
Here, we designed a ratiometric luminescent nanoprobe based on lanthanide-doped upconversion nanoparticles-CuMnO2 nanoassemblies for rapid and sensitive detection of reactive oxygen species (ROS) levels in living cells and mouse. CuMnO2 nanosheets exhibit a wide absorption range of 300-700 nm, overlapping with the visible-light emission of upconversion nanoparticles (UCNPs), resulting in a significant upconversion luminescence quenching. In an acidic environment, H2O2 can promote the redox reaction of CuMnO2, leading to its dissociation from the surface of UCNPs and the restoration of upconversion luminescence. The variation in luminescence intensity ratio (UCL475/UCL450) were monitored to detect ROS levels. The H2O2 nanoprobe exhibited a linear response in the range of 0.314-10 µM with a detection limit of 11.3 nM. The biological tests proved the excellent biocompatibility and low toxicity of obtained UCNPs-CuMnO2 nanoassemblies. This ratiometric luminescent nanoprobe was successfully applied for the detection of exogenous and endogenous ROS in live cells as well as in vivo ROS quantitation. The dual transition metal ions endow this probe efficient catalytic decomposition capabilities, and this sensing strategy broadens the application of UCNPs-based nanomaterials in the field of biological analysis and diagnosis.
ABSTRACT
Cronobacter sakazakii is a notorious foodborne opportunistic pathogen, particularly affecting vulnerable populations such as premature infants, and poses significant public health challenges. This study aimed to elucidate the role of the envZ/ompR genes in environmental tolerance, pathogenicity, and protein regulation of C. sakazakii. An envZ/ompR knockout mutant was constructed and assessed for its impact on bacterial growth, virulence, environmental tolerance, and protein regulation. Results demonstrate that deletion of envZ/ompR genes leads to reduced growth rate and attenuated virulence in animal models. Additionally, the knockout strain exhibited compromised environmental tolerance, particularly in desiccation and oxidative stress conditions, along with impaired adhesion and invasion abilities in epithelial cells. Proteomic analysis revealed significant alterations in protein expression and phosphorylation patterns, highlighting potential compensatory mechanisms triggered by gene deletion. Furthermore, investigation into protein deamidation and glucose metabolism uncovered a link between envZ/ompR deletion and energy metabolism dysregulation. Interestingly, the downregulation of MalK and GrxC proteins was identified as contributing factors to altered desiccation tolerance and disrupted redox homeostasis, respectively, providing mechanistic insights into the phenotypic changes observed. Overall, this study enhances understanding of the multifaceted roles of envZ/ompR in C. sakazakii physiology and pathogenesis, shedding light on potential targets for therapeutic intervention and food safety strategies.
Subject(s)
Bacterial Proteins , Cronobacter sakazakii , Gene Expression Regulation, Bacterial , Cronobacter sakazakii/genetics , Cronobacter sakazakii/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Virulence , Humans , Animals , Enterobacteriaceae Infections/microbiology , Mice , Oxidative StressABSTRACT
OBJECTIVE: To present the real-world status and explore the predictors of the efficacy and prognosis of first-line treatment for unresectable hepatocellular carcinoma (uHCC). METHODS: Real-world data of uHCC patients who underwent first-line treatment at 4 hospitals in Northern Anhui, China, from July 2019 to December 2022 were retrospectively collected. The clinicopathological features, haematological indicators, including superoxide dismutase (SOD) and vascular endothelial growth factor-A (VEGF-A), efficacy and safety data were analysed. RESULTS: A total of 153 patients were enrolled and most of them treated with targeted therapy combined with immunotherapy (TI). Compared to patients treated with TI, patients who were administrated with TI plus locoregional therapy (TIL) showed longer median progression-free survival (mPFS) and median overall survival (mOS) times (both p < 0.05), with manageable safety profiles. Moreover, compared to patients with low baseline serum levels of SOD, patients with high baseline serum SOD levels had a better treatment efficacy and had longer mPFS and mOS times (all p < 0.05). Subgroup analyses indicated that patients with low SOD levels had longer mPFS times when receiving TIL than when receiving TI (p = 0.005), but, among patients with high SOD levels, their prognoses were not substantially different between TIL and TI (p > 0.05). Additionally, patients in the low-VEGF-A group had a longer mOS time than patients in the high-VEGF-A group (p = 0.004). In comparison with TI, TIL can improve the survival time among patients with high VEGF-A levels but not among patients with low VEGF-A levels. CONCLUSIONS: TI was the most commonly first-line systemic therapy for uHCC patients, with better efficacy and outcomes when combined with locoregional therapy in a certain population. Baseline serum SOD and VEGF-A were found to be potential predictive biomarkers for decision-making, treatment response, and outcome in patients with uHCC in the primary care setting.
TI was the most commonly used first-line systemic therapy regimen for uHCC patients in Northern Anhui, China.TIL might conferred better therapeutic efficacy and outcome than TI in specific uHCC populations.The baseline serum SOD level was found to be positively correlated with first-line treatment efficacy and patients' prognosis in uHCC, and low-SOD patients with a dismal prognosis was identified to have potential to benefit from TIL.High baseline serum VEGF-A levels were associated with poor efficacy and short OS times in uHCC patients. For patients with a high baseline VEGF-A, TIL is recommended as the first-line treatment.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Vascular Endothelial Growth Factor A , Humans , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/blood , Liver Neoplasms/drug therapy , Liver Neoplasms/mortality , Liver Neoplasms/therapy , Liver Neoplasms/pathology , Male , Female , Middle Aged , Vascular Endothelial Growth Factor A/blood , Retrospective Studies , Prognosis , Aged , China , Superoxide Dismutase/blood , Immunotherapy/methods , Treatment Outcome , Progression-Free Survival , AdultABSTRACT
Dry eye disease (DED) is a common ocular condition affecting a significant portion of the global population, yet effective treatment options remain elusive. This study investigates the therapeutic potential of M2 macrophage-derived extracellular vesicles (M2-EVs) in a mouse model of DED. The DED model was established using 0.2% benzalkonium chloride (BAC) eye drops, applied twice daily for a week. Post induction, the mice were categorized into 5 groups: PBS, Sodium Hyaluronate (HA, 0.1%), Fluoromethalone (FM, 0.1%), M0-EVs, and M2-EVs. The efficacy of M2-EVs was assessed through tear production, corneal fluorescein staining and HE staining. RNA sequencing (RNA-seq) was employed to investigate the mechanisms underlying the therapeutic effects of M2-EVs in DED. Notably, the M2-EVs treated group exhibited the highest tear secretion, indicating improved tear film stability and reduced corneal surface damage. Histological analysis revealed better corneal structure organization in the M2-EVs group, suggesting enhanced ocular surface repair and corneal preservation. Furthermore, M2-EVs treatment significantly decreased pro-inflammatory cytokine levels and showed unique enrichment of genes related to retinal development. These findings suggest that M2-EVs could serve as a promising noninvasive therapeutic approach for human DED, targeting ocular surface inflammation.
ABSTRACT
OBJECTIVES: To study the clinical characteristics of children with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: A retrospective analysis was conducted on the clinical data of 25 children diagnosed with AAV at the Second Xiangya Hospital of Central South University from January 2010 to June 2022. RESULTS: Among the AAV children, there were 5 males and 20 females, with a median age of onset of 11.0 years. Involvement of the urinary system was seen in 18 cases (72%); respiratory system involvement in 10 cases (40%); skin involvement in 6 cases (24%); eye, ear, and nose involvement in 5 cases (20%); joint involvement in 4 cases (16%); digestive system involvement in 2 cases (8%). Eleven cases underwent kidney biopsy, with 5 cases (46%) showing focal type, 2 cases (18%) showing crescentic type, 2 cases (18%) showing mixed type, and 2 cases (18%) showing sclerotic type. Immune complex deposits were present in 5 cases (45%). Seven cases reached chronic kidney disease (CKD) stage V, with 2 cases resulting in death. Two cases underwent kidney transplantation. At the end of the follow-up period, 2 cases were at CKD stage II, and 1 case was at CKD stage III. Of the 16 cases of microscopic polyangiitis (MPA) group, 13 (81%) involved the urinary system. Of the 9 cases of granulomatosis with polyangiitis (GPA), 6 cases (66%) had sinusitis. Serum creatinine and uric acid levels were higher in the MPA group than in the GPA group (P<0.05), while red blood cell count and glomerular filtration rate were lower in the MPA group (P<0.05). CONCLUSIONS: AAV is more common in school-age female children, with MPA being the most common clinical subtype. The onset of AAV in children is mainly characterized by renal involvement, followed by respiratory system involvement. The renal pathology often presents as focal type with possible immune complex deposits. Children with MPA often have renal involvement, while those with GPA commonly have sinusitis. The prognosis of children with AAV is poor, often accompanied by renal insufficiency.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Humans , Female , Male , Child , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications , Retrospective Studies , Adolescent , Child, Preschool , Renal Insufficiency, Chronic/etiologyABSTRACT
Wood, as a natural biomass material, has long been a research focus. Superhydrophobic modified wood, in particular, has shown great promise in a myriad of engineering applications such as architecture, landscape, and shipbuilding. However, commercial development has encountered significant resistance due to preparation difficulties and sometimes unsatisfactory performance. In this study, hydrophobic/superhydrophobic wood comodified with methyltrimethoxysilane (MTMS) and 1H,1H,2H,2H-perfluorodecyltrimethoxysilane (PFDTMS) was fabricated by a one-step sol-gel method that uses an in situ growth process. Low-molecular-weight MTMS was allowed to permeate the three-dimensional porous wood interior. Then, acid-base catalysts were used to regulate the hydrolytic condensation process of MTMS and PFDTMS composite silanes to generate micro/nano hierarchical structures with low surface energy on the wood surface. The physicochemical characteristics of modified wood were investigated and the reaction mechanism established. The modified wood displayed excellent internal hydrophobicity/surface superhydrophobicity, water-moisture resistance, and dimensional stability at low fluorine concentrations. The resulting superhydrophobic surface provided stain resistance, self-cleaning ability, and loading capacity in water while exhibiting good mechanochemical stability; wood mechanical strength was also enhanced. This methodology created a superhydrophobic surface and bulk hydrophobization of wood in one step. Beyond wood, this approach is expected to provide a promising approach for functional modification of other porous composite materials.
ABSTRACT
The construction of isotypic high-nuclearity inorganic cages with identical pristine parent structure and increasing nuclearity is highly important for molecular growth and structure-property relationship study, yet it still remains a great challenge. Here, we provide an in situ growth approach for successfully synthesizing a series of new giant hollow polymolybdate dodecahedral cages, Mo250, Mo260-I, and Mo260-E, whose structures are growth based on giant polymolybdate cage Mo240. Remarkably, they show two pathways of nuclear growth based on Mo240, that is, the growth of 10 and 20 Mo centers on the inner and outer surfaces to afford Mo250 and Mo260-I, respectively, and the growth of 10 Mo centers both on the inner and outer surfaces to give Mo260-E. To the best of our knowledge, this is the first study to display the internal and external nuclear growth of a giant hollow polyoxometalate cage. More importantly, regular variations in structure and nuclearity confer these polymolybdate cages with different optical properties, oxidative activities, and hydrogen atom transfer effect, thus allowing them to exhibit moderate to excellent photocatalytic performance in oxidative cross-coupling reactions between different unactivated alkanes and N-heteroarenes. In particular, Mo240 and Mo260-E with better comprehensive abilities can offer the desired coupling product with yield up to 92% within 1 h.
ABSTRACT
New anti-diabetic medications, including glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter 2 (SGLT2) inhibitors are recommended in guidelines to reduce cardio-renal events in type 2 diabetes mellitus (T2DM), independent of glucose control. Yet they might be underused in real world. This study aims to address the knowledge gap, prescription patterns and barriers faced by Chinese doctors. Cardio-Metabolic Survey was a cross-sectional study conducted among doctors managing diabetic patients in clinical practice, via a designated online questionnaire from May 1st, to Dec. 31th, 2022. A total of 358 doctors from 57 hospitals across Beijing participated in this survey, 34.9% from tertiary hospitals. Only 30-40% doctors demonstrated somewhat understanding of the mechanism and clinical applications of GLP-1RA or SGLT2 inhibitors. There is no difference in understanding of these two medications overall (p = 0.336). However, doctors in tertiary hospitals have a higher understanding of GLP-1RA and SGLT2 inhibitors compared to those in non-tertiary hospitals (p = 0.049, and 0.008, respectively). 40.2% doctors have never prescribed GLP-1RA, and 36.6% for SGLT2 inhibitors. The frequency of prescribing SGLT2 inhibitors was significantly higher than prescribing GLP-1RA (p = 0.005). The main barriers on prescription include high cost, poor adherence, side effects concern, and insufficient knowledge about these medications. Chinese doctors currently have limited understanding and low prescription frequency for GLP-1RA and SGLT2 inhibitors. Multifaceted approaches are needed to improve doctors' knowledge and strengthen their ability to manage T2DM effectively.