Acarbose enhances the efficacy of immunotherapy against solid tumours by modulating the gut microbiota.

The crucial role of gut microbiota in shaping immunotherapy outcomes has prompted investigations into potential modulators. Here we show that oral administration of acarbose significantly increases the anti-tumour response to anti-PD-1 therapy in female tumour-bearing mice. Acarbose modulates the gut microbiota composition and tryptophan metabolism, thereby contributing to changes in chemokine expression and increased T cell infiltration within tumours. We identify CD8+ T cells as pivotal components determining the efficacy of the combined therapy. Further experiments reveal that acarbose promotes CD8+ T cell recruitment through the CXCL10-CXCR3 pathway. Faecal microbiota transplantation and gut microbiota depletion assays indicate that the effects of acarbose are dependent on the gut microbiota. Specifically, acarbose enhances the efficacy of anti-PD-1 therapy via the tryptophan catabolite indoleacetate, which promotes CXCL10 expression and thus facilitates CD8+ T cell recruitment, sensitizing tumours to anti-PD-1 therapy. The bacterial species Bifidobacterium infantis, which is enriched by acarbose, also improves response to anti-PD-1 therapy. Together, our study endorses the potential combination of acarbose and anti-PD-1 for cancer immunotherapy.

Relationship between problematic smartphone use and sleep problems: The roles of sleep-related compensatory health beliefs and bedtime procrastination.

Objective: Concerns regarding sleep problems in emerging adults and their antecedents, such as problematic smartphone use (PSU), have been growing. This study tested the association between PSU and sleep problems and further investigated the mechanisms of this relationship based on the theory of compensatory health beliefs (CHBs). Methods: This study included 999 participants (74.87% female) in China, aged 17 to 25 years (M = 21.16; standard deviation = 1.60), who voluntarily filled in an anonymous survey. Results: The findings showed positive correlations between sleep problems and PSU, sleep-related CHBs, and bedtime procrastination (rs = .25-.52, p < .001). Furthermore, the positive link between PSU and sleep problems was mediated by bedtime procrastination alone (ß=.21, 95% confidence interval (CI) [.17, .26]) or a serial path of sleep-related CHBs and bedtime procrastination (ß=.04, 95% CI [.02, .05]). Conclusion: This study provides a new perspective to understand the internal mechanism underlying the PSU-sleep problem link. Interventions for sleep disorders ought to consider the theoretical guidelines of the CHBs model to reduce the risk of bedtime procrastination and sleep disorders in emerging adults.

Hypoxia-responsive micelles deprive cofactor of stearoyl-CoA desaturase-1 and sensitize ferroptotic ovarian cancer therapy.

Ferroptosis has been recognized as a promising therapeutic strategy for cancer due to its unique mechanism of action. However, the upregulation of stearoyl-CoA desaturase 1 (SCD1) in ovarian cancer leads to resistance to ferroptotic therapy. Zinc ion (Zn2+) serves as the cofactor of SCD1. It was hypothesized that selective deprivation of Zn2+ from SCD1 could sensitize ferroptotic ovarian cancer therapy. Here, we report a hypoxia-responsive polymer micelle for enhanced ferroptosis of ovarian cancer cells. A SCD1 inhibitor, PluriSIn 1 (Plu), and a ferroptosis inducer, Auranofin (Aur), were co-encapsulated in nitroimidazole-bearing micelles. Under the hypoxic tumor microenvironment, the conversion of nitroimidazole to aminoimidazole triggered the cargo release and induced the depletion of antioxidant molecules (e.g., glutathione, thioredoxin, and NADPH). Meanwhile, because of the strong coordination between aminoimidazole and Zn2+ compared to that of histidine and Zn2+, such conversion can deprive the metal cofactor of SCD1, hence sensitizing the action of Plu and Aur. The proof-of-concept was demonstrated in cell and animal models with minimal systemic toxicity. The current work integrates ferroptosis induction with SCD1 inhibition in a hypoxia-responsive vehicle, offering a promising strategy for addressing the ferroptosis resistance and opening novel avenues for managing the difficult-to-treat ovarian cancer.

Hydrology controls sulfuric acid-mediated weathering in an orogenic regime of southwestern Taiwan.

Chemical weathering is a pivotal geochemical process that shapes the carbon cycling and climates in the critical zone. Among its critical drivers, river discharge holds a particular significance, especially in the orogenic landscapes. Here, we examined the impact of discharge on mineral weathering in southwestern (SW) Taiwan by analyzing river water chemistry across a wide discharge range. Current observations indicated that carbonate contributes significantly to total weathering (50-80 %), with sulfuric acid accounting for one-half to two-thirds of carbonate weathering. A statistically strong correlation between river discharge and sulfuric acid-mediated carbonate weathering was highlighted, while the silicate weathering remained constant. This relationship suggests an increased influx of fresh minerals, such as pyrite, into the weathering regime as water flow increases. Our model identifies a critical discharge threshold of 4.6 m3 s-1, determining whether mineral weathering acts as a net source or sink of CO2. Consequently, mineral weathering in SW Taiwan acts as a net CO2 sink during dry periods but turns into a net source during wet periods. Through analyzing a decade of daily discharge data, we found mineral weathering in SW Taiwan is a net CO2 source, with a 2.6-fold increase in annual mean discharge causing a 3.8-fold increase in net CO2 flux. This pattern is likely to be applicable to other similar minerals containing mountain-building regions, highlighting the significant role of hydrology in determining weathering sources and their potential impact on the carbon cycle balance.

SOX11 as a prognostic biomarker linked to m6A modification and immune infiltration in renal clear cell carcinoma.

Background: The prognosis for patients with kidney renal clear cell carcinoma (KIRC) remains unfavorable, and the understanding of SRY-box transcription factor 11 (SOX11) in KIRC is still limited. The purpose of this paper is to explore the role of SOX11 in the prognosis of KIRC. Methods: We analyzed SOX11 expression in KIRC and adjacent normal tissues using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Our study aims to establish a correlation between SOX11 expression and clinical pathological features. Differentially expressed genes (DEGs) were assessed using R software. Furthermore, we conducted Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses and gene set enrichment analysis (GSEA). Integration of data from the Tumor Immune Estimation Resource (TIMER) and TCGA databases allowed us to assess the association between SOX11 expression and immune infiltration in KIRC. Additionally, we analyzed the association between SOX11 gene expression and N6-methyladenosine (m6A) modification in KIRC using TCGA and GEO data. Results: Our findings revealed high SOX11 expression in KIRC, which showed a significant correlation with tumor staging and prognosis. GO/KEGG and GSEA analyses indicated that SOX11 was closely associated with sodium ion transport, synaptic vesicle circulation, and oxidative phosphorylation. Analysis of the TIMER and TCGA databases demonstrated correlations of SOX11 expression levels with the presence of CD8+ T lymphocytes, neutrophils, CD4+ T cells, as well as B cells. Moreover, both the TCGA and GEO datasets showed a substantial association between SOX11 and m6A modification-related genes, namely ZC3H13, FTO, METTL14, YTHDC1, IGF2BP1, and IGF2BP2. Conclusions: SOX11 exhibits a correlation with m6A modification and immune infiltration, suggesting its potential as a prognostic biomarker for KIRC.

Multimodal imaging diagnosis and analysis of prognostic factors in patients with adult-onset Coats disease.

AIM: To describe the multimodal imaging features, treatment, and outcomes of patients diagnosed with adult-onset Coats disease. METHODS: This retrospective study included patients first diagnosed with Coats disease at ≥18 years of age between September 2017 and September 2021. Some patients received anti-vascular endothelial growth factor (VEGF) therapy (conbercept, 0.5 mg) as the initial treatment, which was combined with laser photocoagulation as needed. All the patients underwent best corrected visual acuity (BCVA) and intraocular pressure examinations, fundus color photography, spontaneous fluorescence tests, fundus fluorescein angiography, optical coherence tomography (OCT), OCT angiography, and other examinations. BCVA alterations and multimodal image findings in the affected eyes following treatment were compared and the prognostic factors were analyzed. RESULTS: The study included 15 patients who were aged 24-72 (57.33±12.61)y at presentation. Systemic hypertension was the most common associated systemic condition, occurring in 13 (86.7%) patients. Baseline BCVA ranged from 2.0 to 5.0 (4.0±1.1), which showed improvement following treatment (4.2±1.0). Multimodal imaging revealed retinal telangiectasis in 13 patients (86.7%), patchy hemorrhage in 5 patients (33.3%), and stage 2B disease (Shield's staging criteria) in 11 patients (73.3%). OCT revealed that the baseline central macular thickness (CMT) ranged from 129 to 964 µm (473.0±230.1 µm), with 13 patients (86.7%) exhibiting a baseline CMT exceeding 250 µm. Furthermore, 8 patients (53.3%) presented with an epiretinal membrane at baseline or during follow-up. Hyper-reflective scars were observed on OCT in five patients (33.3%) with poor visual prognosis. Vision deteriorated in one patient who did not receive treatment. Final vision was stable in three patients who received laser treatment, whereas improvement was observed in one of two patients who received anti-VEGF therapy alone. In addition, 8 of 9 patients (88.9%) who received laser treatment and conbercept exhibited stable or improved BCVA. CONCLUSION: Multimodal imaging can help diagnose adult-onset Coats disease. Anti-VEGF treatment combined with laser therapy can be an option for improving or maintaining BCVA and resolving macular edema. The final visual outcome depends on macular involvement and the disease stage.

Camrelizumab, apatinib and hepatic artery infusion chemotherapy combined with microwave ablation for advanced hepatocellular carcinoma.

BACKGROUND: Hepatic arterial infusion chemotherapy and camrelizumab plus apatinib (TRIPLET protocol) is promising for advanced hepatocellular carcinoma (Ad-HCC). However, the usefulness of microwave ablation (MWA) after TRIPLET is still controversial. AIM: To compare the efficacy and safety of TRIPLET alone (T-A) vs TRIPLET-MWA (T-M) for Ad-HCC. METHODS: From January 2018 to March 2022, 217 Ad-HCC patients were retrospectively enrolled. Among them, 122 were included in the T-A group, and 95 were included in the T-M group. A propensity score matching (PSM) was applied to balance bias. Overall survival (OS) was compared using the Kaplan-Meier curve with the log-rank test. The overall objective response rate (ORR) and major complications were also assessed. RESULTS: After PSM, 82 patients were included both the T-A group and the T-M group. The ORR (85.4%) in the T-M group was significantly higher than that (65.9%) in the T-A group (P < 0.001). The cumulative 1-, 2-, and 3-year OS rates were 98.7%, 93.4%, and 82.0% in the T-M group and 85.1%, 63.1%, and 55.0% in the T-A group (hazard ratio = 0.22; 95% confidence interval: 0.10-0.49; P < 0.001). The incidence of major complications was 4.9% (6/122) in the T-A group and 5.3% (5/95) in the T-M group, which were not significantly different (P = 1.000). CONCLUSION: T-M can provide better survival outcomes and comparable safety for Ad-HCC than T-A.

Polygonatum sibiricum Polysaccharides Alleviate Depressive-like Symptoms in Chronic Restraint Stress-Induced Mice via Microglial Regulation in Prefrontal Cortex.

Microglia respond to stressors by secreting cytokines or growth factors, playing a crucial role in maintaining brain homeostasis. While the antidepressant-like effects of Polygonatum sibiricum polysaccharides (PSPs) have been observed in mice, their potential effectiveness involving microglial regulation remains unknown. This study investigates the antidepressant-like mechanism of PSP by regulating microglial phenotype and signaling pathways in the prefrontal cortex of chronic restraint stress (CRS)-induced mice. PSP was extracted, purified, characterized, and orally administered to CRS mice. High-performance gel permeation chromatography (HPGPC) revealed that PSP has a molecular weight of 5.6 kDa. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) showed that PSP exhibited a layered structure with densely packed, irregular surfaces. PSP treatment significantly increased sucrose preference (low: 71%, p < 0.01; medium: 69%, p < 0.05; high: 75%, p < 0.001 vs. CRS: 58%) and reduced immobility time (low: 74 s, p < 0.01; medium: 68 s, p < 0.01; high: 79 s, p < 0.05 vs. CRS: 129 s), indicating the alleviation of depressive-like behaviors. PSP inhibited microglial activation (PSP, 131/mm2 vs. CRS, 173/mm2, p = 0.057), reversing CRS-induced microglial hypertrophy and hyper-ramification. Furthermore, PSP inactivated microglial activation by inhibiting NLRP3/ASC/caspase-1/IL-1ß signaling pathways, increasing BDNF synthesis and activating brain-derived neurotrophic factor (BDNF)-mediated neurogenesis (PSP, 80/per DG vs. CRS, 49/per DG, p < 0.01). In conclusion, PSP exerts antidepressant-like effects through the regulation of microglial activity and neuroinflammatory pathways, indicating it as a potential natural compound for depression treatment.

Partial discharge detection, diagnosis, and location technology based on a novel transient earth voltage-ultrasonic integrated sensor used for switchgear equipment.

Medium-voltage (MV) switchgear and gas insulated switchgear (GIS) are essential components of power-grid systems. Their safe operation is crucial for the electricity consumption of users. However, insulation faults often occur during the operation of MV switchgear and GIS because of pollution, humidity, heat, mechanical shock, and other factors. Partial discharge (PD) measurements are the most effective indicator to prevent insulation failure. Transient earth voltage (TEV) and ultrasonic methods are the most popular PD measurement methods for switchgear. Currently, these two methods are used widely and independently. In this study, a novel TEV-ultrasonic integrated sensor is proposed based on the independent structure of the TEV and the ultrasonic sensor. The performance parameters of the proposed sensor were tested on test platforms. PD measurement experiments were conducted in a 10 kV switchgear and 220 kV GIS to analyze the performance of the integrated sensor. The results show that the sensor can simultaneously measure the TEV and ultrasonic signals in the same location. The integrated sensor can realize effective and sensitive detection, precise location, and accurate diagnosis of PD in the MV switchgear and GIS.

[Occurrence and Risk Assessment of N-nitrosamines and Their Precursors in Qingjiang River Basin].

N-nitrosamines are a type of nitrogen-containing organic pollutant with high carcinogenicity and mutagenicity. In the main drinking water sources of small and medium-sized towns in China, the contamination levels of N-nitrosamines remain unclear. In addition, there is still lack of research on the concentration of N-nitrosamines and their precursors in tributary rivers. In this study, eight N-nitrosamines and their formation potentials （FPs） were investigated in the Qingjiang River, which is a primary tributary of the Yangtze River. The sewage discharge sites were also monitored, and the environmental influencing factors, carcinogenic and ecological risks caused by N-nitrosamines, and their precursors were evaluated. The results showed that six N-nitrosamines were detected in water samples of the Qingjiang River, among which NDMA [（10 ±15） ng·L-1], NDEA [（9.3 ±9.3） ng·L-1], and NDBA [（14 ±7.8） ng·L-1] were the dominant N-nitrosamines, whereas seven N-nitrosamines were detected in chloraminated water samples, among which NDMA-FP [（46 ±21） ng·L-1], NDEA-FP [（26 ±8.3） ng·L-1], and NDBA-FP [（22 ±13） ng·L-1] were the dominant N-nitrosamine FPs. The concentrations of N-nitrosamines in the middle reaches of the Qingjiang River were higher than those in the upper and lower reaches. Furthermore, the concentrations of N-nitrosamines in the sample sites of sewage discharge and tributaries were significantly higher than those in other sampling sites. The monitoring results at the direct sewage discharge points indicated that the main source of N-nitrosamines in river water was the sewage carrying N-nitrosamines and their precursors. In addition, the concentrations of the three dominant N-nitrosamines including NDMA, NDBA, and NDEA were positively correlated with each other, mainly because of their similar sewage sources. The average carcinogenic risk to residents due to N-nitrosamine in drinking water sources was 2.4×10-5, indicating a potential carcinogenic risk. Moreover, due to the high concentrations of N-nitrosamine formation potentials in the Qingjiang River, the carcinogenic risk of drinking water may be even higher. The ecological risk assessment showed that the ecological risk quotient values of N-nitrosamines in the Qingjiang River watershed were lower than 0.002, which was negligible.

Efficacy analysis of mechanical thrombectomy combined with prolonged mild hypothermia in the treatment of acute middle cerebral artery occlusion: a single-center retrospective cohort study.

Objective: To determine the efficacy of mechanical thrombectomy combined with prolonged mild hypothermia compared with conventional treatment in managing acute middle cerebral artery occlusion, and to explore whether extending the duration of hypothermia can improve neurological function. Method: From 2018 to June 2023, a retrospective analysis was conducted on 45 patients with acute middle cerebral artery occlusion treated at the NICU of Suzhou Kowloon Hospital, affiliated with Shanghai Jiao Tong University School of Medicine. After thrombectomy, patients were admitted to the neurological intensive care unit (NICU) for targeted temperature management. Patients were divided into two groups: the mild hypothermia group (34.5-35.9°C) receiving 5-7 days of treatment, and the normothermia group (control group) whose body temperature was kept between 36 and 37.5°C using pharmacological and physical cooling methods. Baseline characteristics and temperature changes were compared between the two groups of patients. The primary outcome was the modified Rankin Scale (mRS) score at 3 month after surgery, and the secondary outcomes were related complications and mortality rate. Prognostic risk factors were investigated using both univariate and multivariate logistic regression analyses. Results: Among 45 patients, 21 underwent prolonged mild hypothermia, and 24 received normothermia, with no significant differences in baseline characteristics between the two groups. The duration of mild hypothermia ranged from 5 to 7 days. The incidence of chills (33.3% vs. 8.3%, p = 0.031) and constipation (57.1% vs. 20.8%, p = 0.028) was significantly higher in the mild hypothermia group compared with the control group. There was no significant difference in mortality rates between the mild hypothermia and the control group (4.76% vs. 8.33%, p = 1.000, OR = 1.75, 95% CI, 0.171-17.949). At 3 month, there was no significant difference in the modified mRS (0-3) score between the mild hypothermia and control groups (52.4% vs. 25%, p = 0.114, OR = 0.477, 95% CI, 0.214-1.066). Infarct core volume was an independent risk factor for adverse neurological outcomes. Conclusion: Prolonged mild hypothermia following mechanical thrombectomy had no severe complications and shows a trend to improve the prognosis of neurological function. The Infarct core volume on CTP was an independent risk factor for predicting neurological function.

Organic-Inorganic Hybrid Cuprous-Based Metal Halides with Unique Two-Dimensional Crystal Structure for White Light-Emitting Diodes.

Ternary cuprous (Cu+)-based metal halides, represented by cesium copper iodide (e.g., CsCu2I3 and Cs3Cu2I5), are garnering increasing interest for light-emitting applications owing to their intrinsically high photoluminescence quantum yield and direct bandgap. Toward electrically driven light-emitting diodes (LEDs), it is highly desirable for the light emitters to have a high structural dimensionality as it may favor efficient electrical injection. However, unlike lead-based halide perovskites whose light-emitting units can be facilely arranged in three-dimensional (3D) ways, to date, nearly all ternary Cu+-based metal halides crystallize into 0D or 1D networks of Cu-X (X = Cl, Br, I) polyhedra, whereas 3D and even 2D structures remain mostly uncharted. Here, by employing a fluorinated organic cation, we report a new kind of ternary Cu+-based metal halides, (DFPD)CuX2 (DFPD+ = 4,4-difluoropiperidinium), which exhibits unique 2D layered crystal structure. Theoretical calculations reveal a highly dispersive conduction band of (DFPD)CuBr2, which is beneficial for charge carrier injection. It is also of particular significance to find that the 2D (DFPD)CuBr2 crystals show appealing properties, including improved ambient stability and an efficient warm white-light emission, making it a promising candidate for single-component lighting and display applications.

Development and validation of a nomogram for predicting lymph node metastasis in early gastric cancer.

BACKGROUND: Lymph node metastasis (LNM) significantly impacts the treatment and prognosis of early gastric cancer (EGC). Consequently, the precise prediction of LNM risk in EGC patients is essential to guide the selection of appropriate surgical approaches in clinical settings. AIM: To develop a novel nomogram risk model for predicting LNM in EGC patients, utilizing preoperative clinicopathological data. METHODS: Univariate and multivariate logistic regression analyses were performed to examine the correlation between clinicopathological factors and LNM in EGC patients. Additionally, univariate Kaplan-Meier and multivariate Cox regression analyses were used to assess the influence of clinical factors on EGC prognosis. A predictive model in the form of a nomogram was developed, and its discrimination ability and calibration were also assessed. RESULTS: The incidence of LNM in the study cohort was 19.6%. Multivariate logistic regression identified tumor size, location, degree of differentiation, and pathological type as independent risk factors for LNM in EGC patients. Both tumor pathological type and LNM independently affected the prognosis of EGC. The model's performance was reflected by an area under the curve of 0.750 [95% confidence interval (CI): 0.701-0.789] for the training group and 0.763 (95%CI: 0.687-0.838) for the validation group. CONCLUSION: A clinical prediction model was constructed (using tumor size, low differentiation, location in the middle-lower region, and signet ring cell carcinoma), with its score being a significant prognosis indicator.

Metabolomics-based study on the significance of differential metabolite binding IgG isoforms in Hemolytic disease of newborn.

BACKGROUND: Hemolytic disease of the newborn (HDN) is a common condition that can have a severe impact on the health of newborns due to the hemolytic reactions it triggers. Although numerous studies have focused on understanding the pathogenesis of HDN, there are still many unanswered questions. METHODS: In this retrospective study, serum samples were collected from 15 healthy newborns and 8 infants diagnosed with hemolytic disease. The relationship between different metabolites and various IgG subtypes in Healthy, HDN and BLI groups was studied by biochemical technique and enzyme-linked immunosorbent assay (ELISA). Metabolomics analysis was conducted to identify the differential metabolites associated with HDN. Subsequently, Pearson's correlation analysis was used to determine the relation of these differential metabolites with IgG isoforms. The relationship between the metabolites and IgG subtypes was observed after treatment. RESULTS: The study results revealed that infants with hemolytic disease exhibited abnormal elevations in TBA, IgG1, IgG2a, IgG2b, IgG3, and IgG4 levels when compared to healthy newborns. Additionally, differences in metabolite contents were also observed. N, N-DIMETHYLARGININE showed negative correlations with TBA, IgG1, IgG2a, IgG2b, IgG3, and IgG4, while 2-HYDROXYBUTYRATE, AMINOISOBUTANOATE, Inosine, and ALLYL ISOTHIOCYANATE exhibited positive correlations with TBA, IgG1, IgG2a, IgG2b, IgG3, and IgG4. Through metabolomics-based research, we have discovered associations between differential metabolites and different IgG isoforms during the onset of HDN. CONCLUSION: These findings suggest that changes in metabolite and IgG isoform levels are linked to HDN. Understanding the involvement of IgG isoforms and metabolites can provide valuable guidance for the diagnosis and treatment of HDN.

Biomechanical comparison of the therapeutic effect of a novel proximal femoral bionic intramedullary nail and traditional inverted triangle hollow screw on femoral neck fracture.

OBJECTIVE: A novel Proximal Femoral Bionic Nail (PFBN) has been developed by a research team for the treatment of femoral neck fractures. This study aims to compare the biomechanical properties of the innovative PFBN with those of the conventional Inverted Triangular Cannulated Screw (ITCS) fixation method through biomechanical testing. METHODS: Sixteen male femoral specimens preserved in formalin were selected, with the donors' age at death averaging 56.1 ± 6.3 years (range 47-64 years), and a mean age of 51.4 years. The femurs showed no visible damage and were examined by X-rays to exclude diseases affecting bone quality such as tumors, severe osteoporosis, and deformities. The 16 femoral specimens were randomly divided into an experimental group (n = 8) and a control group (n = 8). All femurs were prepared with Pauwels type III femoral neck fractures, fixed with PFBN in the experimental group and ITCS in the control group. Displacement and stress limits of each specimen were measured through cyclic compression tests and failure experiments, and vertical displacement and strain values under a 600 N vertical load were measured in all specimens through vertical compression tests. RESULTS: In the vertical compression test, the average displacement at the anterior head region of the femur was 0.362 mm for the PFBN group, significantly less than the 0.480 mm for the ITCS group (p < 0.001). At the fracture line area, the average displacement for the PFBN group was also lower than that of the ITCS group (0.196 mm vs. 0.324 mm, p < 0.001). The difference in displacement in the shaft area was smaller, but the average displacement for the PFBN group (0.049 mm) was still significantly less than that for the ITCS group (0.062 mm, p = 0.016). The situation was similar on the posterior side of the femur. The average displacements in the head area, fracture line area, and shaft area for the PFBN group were 0.300 mm, 0.168 mm, and 0.081 mm, respectively, while those for the ITCS group were 0.558 mm, 0.274 mm, and 0.041 mm, with significant differences in all areas (p < 0.001). The average strain in the anterior head area for the PFBN group was 4947 µm/m, significantly less than the 1540 µm/m for the ITCS group (p < 0.001). Likewise, in the fracture line and shaft areas, the average strains for the PFBN group were significantly less than those for the ITCS group (p < 0.05). In the posterior head area, the average strain for the PFBN group was 4861 µm/m, significantly less than the 1442 µm/m for the ITCS group (p < 0.001). The strain conditions in the fracture line and shaft areas also showed the PFBN group was superior to the ITCS group (p < 0.001). In cyclic loading experiments, the PFBN fixation showed smaller maximum displacement (1.269 mm vs. 1.808 mm, p < 0.001), indicating better stability. In the failure experiments, the maximum failure load that the PFBN-fixated fracture block could withstand was significantly higher than that for the ITCS fixation (1817 N vs. 1116 N, p < 0.001). CONCLUSION: The PFBN can meet the biomechanical requirements for internal fixation of femoral neck fractures. PFBN is superior in biomechanical stability compared to ITCS, particularly showing less displacement and higher failure resistance in cyclic load and failure experiments. While there are differences in strain performance in different regions between the two fixation methods, overall, PFBN provides superior stability.

Bi-regional dynamic contrast-enhanced MRI for prediction of microvascular invasion in solitary BCLC stage A hepatocellular carcinoma.

OBJECTIVES: To construct a combined model based on bi-regional quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), as well as clinical-radiological (CR) features for predicting microvascular invasion (MVI) in solitary Barcelona Clinic Liver Cancer (BCLC) stage A hepatocellular carcinoma (HCC), and to assess its ability for stratifying the risk of recurrence after hepatectomy. METHODS: Patients with solitary BCLC stage A HCC were prospective collected and randomly divided into training and validation sets. DCE perfusion parameters were obtained both in intra-tumoral region (ITR) and peritumoral region (PTR). Combined DCE perfusion parameters (CDCE) were constructed to predict MVI. The combined model incorporating CDCE and CR features was developed and evaluated. Kaplan-Meier method was used to investigate the prognostic significance of the model and the survival benefits of different hepatectomy approaches. RESULTS: A total of 133 patients were included. Total blood flow in ITR and arterial fraction in PTR exhibited the best predictive performance for MVI with areas under the curve (AUCs) of 0.790 and 0.792, respectively. CDCE achieved AUCs of 0.868 (training set) and 0.857 (validation set). A combined model integrated with the α-fetoprotein, corona enhancement, two-trait predictor of venous invasion, and CDCE could improve the discrimination ability to AUCs of 0.966 (training set) and 0.937 (validation set). The combined model could stratify the prognosis of HCC patients. Anatomical resection was associated with a better prognosis in the high-risk group (p < 0.05). CONCLUSION: The combined model integrating DCE perfusion parameters and CR features could be used for MVI prediction in HCC patients and assist clinical decision-making. CRITICAL RELEVANCE STATEMENT: The combined model incorporating bi-regional DCE-MRI perfusion parameters and CR features predicted MVI preoperatively, which could stratify the risk of recurrence and aid in optimizing treatment strategies. KEY POINTS: Microvascular invasion (MVI) is a significant predictor of prognosis for hepatocellular carcinoma (HCC). Quantitative DCE-MRI could predict MVI in solitary BCLC stage A HCC; the combined model improved performance. The combined model could help stratify the risk of recurrence and aid treatment planning.

Thymol Induces Fenton-Reaction-Dependent Ferroptosis in Vibrio parahemolyticus.

Thymol has efficient bactericidal activity against a variety of pathogenic bacteria, but the bactericidal mechanism against Vibrio parahemolyticus (V. parahemolyticus) has rarely been reported. In the current study, we investigated the bactericidal mechanism of thymol against V. parahemolyticus. The Results revealed that 150 µg/mL of thymol had 99.9% bactericidal activity on V. parahemolyticus. Intracellular bursts of reactive oxygen species (ROS), Fe2+accumulation, lipid peroxidation, and DNA breakage were checked by cell staining. The exogenous addition of H2O2 and catalase promoted and alleviated thymol-induced cell death to a certain extent, respectively, and the addition of the ferroptosis inhibitor Liproxstatin-1 also alleviated thymol-induced cell death, confirming that thymol induced Fenton-reaction-dependent ferroptosis in V. parahemolyticus. Proteomic analysis revealed that relevant proteins involved in ROS production, lipid peroxidation accumulation, and DNA repair were significantly upregulated after thymol treatment. Molecular docking revealed two potential binding sites (amino acids 46H and 42F) between thymol and ferritin, and thymol could promote the release of Fe2+ from ferritin proteins through in vitro interactions analyzed. Therefore, we hypothesized that ferritin as a potential target may mediate thymol-induced ferroptosis in V. parahemolyticus. This study provides new ideas for the development of natural inhibitors for controlling V. parahemolyticus in aquatic products.

Kinetics of hydrogen absorption/desorption in the Zr-2.5Nb alloy.

The Zr-2.5Nb alloy is a typical pressure tube material in heavy water nuclear reactors, and an increase of hydrogen isotope content in the alloy during service can pose major safety risks; hot vacuum extraction-mass spectrometry is an efficient method for evaluating hydrogen isotope concentrations in the Zr-2.5Nb alloy. This work investigates the kinetics and thermodynamic properties of deuterium (D) absorption and desorption of the Zr-2.5Nb alloy using the constant volume adsorption method and the hot vacuum extraction method. In addition to the previously reported volume contraction model, it was observed that at 600 °C and above, the reaction between D2 and Zr-2.5Nb is dominated by diffusion, while the reaction is predominantly influenced by surface adsorption and dissociation below 600 °C. Phase transition sequence of Zr-2.5Nb deuterides during non-isothermal desorption was established using quantitatively calibrated thermal desorption spectra combined with the phase transition process of deuteride decomposition. These results can provide important references for optimizing the process parameters of the hot vacuum extraction-mass spectrometry method.

KDM4C represses liver fibrosis by regulating H3K9me3 methylation of ALKBH5 and m6A methylation of snail1 mRNA.

OBJECTIVE: We aimed to disclose the molecular mechanism of snail1 in liver fibrosis. METHODS: Carbon tetrachloride (CCl4) was used to induce a liver fibrosis model in mice whereby serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were evaluated, and liver pathological alternations were assessed. Rat hepatic stellate cells (HSC-T6) were irritated with transforming growth factor (TGF)-ß1, followed by assessment of cell viability and migration. The levels of snail1, ALKBH5, and lysine specific demethylase 4C (KDM4C) were quantified by immunohistochemistry, western blot, or reverse transcription-quantitative polymerase chain reaction, in addition to α-smooth muscle actin (SMA), anti-collagen type I α1 (COL1A1), vimentin, and E-cadherin. Photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation and RNA stability were evaluated to determine the relationship between ALKBH5 and snail1. Changes in KDM4C-bound ALKBH5 promoter and enrichment of histone H3 lysine 9 trimethylation (H3K9me3) at the ALKBH5 promoter were determined using chromatin immunoprecipitation. RESULTS: In fibrosis mice, snail1 was upregulated while ALKBH5 and KDM4C were downregulated. KDM4C overexpression reduced serum ALT and AST levels, liver injury, and α-SMA, COL1A1 and VIMENTIN expressions but increased E-cadherin expression. However, the aforementioned trends were reversed by concurrent overexpression of snail1. In HSC-T6 cells exposed to TGF-ß1, ALKBH5 overexpression weakened cell viability and migration, downregulated α-SMA, COL1A1 and VIMENTIN, upregulated E-CADHERIN, and decreased m6A modification of snail1 and its mRNA stability. KDM4C increased ALKBH5 expression by lowering H3K9me3 level, but inhibited HSC-T6 cell activation by regulating the ALKBH5/snail1 axis. CONCLUSION: KDM4C decreases H3K9me3 methylation to upregulate ALKBH5 and subsequently inhibits snail1, ultimately impeding liver fibrosis.