Expression of interleukin-8 and integrin ß3 predicts prognosis of patients with hepatocellular carcinoma after hepatectomy.

As important components in the tumor microenvironment, interleukin-8 (IL-8) and integrin ß3 play a key role in the progression and metastasis of hepatocellular carcinoma (HCC). This study aimed to determine the expression of IL-8 and integrin ß3 and their prognostic value in patients with HCC after hepatectomy. We investigated the expression of IL-8 and integrin ß3, their clinical significance, as well as their correlation in the cancer tissue of 130 patients with HCC using immunohistochemistry. The prognostic value of IL-8 and integrin ß3 was investigated through the follow-up of patients with HCC after hepatectomy. In HCC, IL-8 expression had a positive correlation with integrin ß3 expression. Increased expressions of IL-8 and integrin ß3 were indicators of tumor progression and poor prognosis in patients with HCC after hepatectomy. IL-8 positive specimens exhibited a higher proportion of macrovascular invasion, larger tumor size, poor differentiation, and advanced tumor-node-metastasis (TNM) stage (P < .05, respectively). Integrin ß3 positive group exhibited a higher proportion of TNM III-staged tumors (P < .05). The results indicated that macrovascular invasion, advanced TNM stage, and integrin ß3 expression were independent unfavorable prognostic factors in HCC after hepatectomy. Integrin ß3 expression was proved to be an independent unfavorable prognostic factor in HCC after hepatectomy. Targeting integrin ß3 might be a potential therapeutic approach in preventing tumor progression in HCC.

N-Methyl-d-Aspartate Receptor Antibody and Sensory Gating Deficits in Non-smoking, Minimal Antipsychotic Medication Exposure, and First-Episode Patients With Schizophrenia.

BACKGROUND AND HYPOTHESIS: Sensory gating deficit is considered a pathophysiological feature of schizophrenia, which has been linked to N-methyl-d-aspartate receptor (NMDAR) hypofunction as one of the potential underlying mechanisms. Here, we hypothesize that higher levels of NMDAR antibody (Ab) may contribute to the sensory gating deficits in schizophrenia. STUDY DESIGN: We enrolled 72 non-smoking inpatients with first-episode schizophrenia (FES), most of them with only a relatively short duration of exposure to antipsychotic medications, and 51 non-smoking healthy controls (HC). Sensory gating was measured by P50 evoked potentials ratio and the difference between the two stimuli in an auditory paired-stimuli paradigm and serum NMDAR Ab levels were quantified by enzyme-linked immunosorbent assay. STUDY RESULTS: The FES group showed higher serum NMDAR Ab levels [(9.23 ±â€…4.15) ng/mL vs. (7.08 ±â€…2.83) ng/mL; P = .002], higher P50 ratio (P = .002), and less P50 difference (P = .001) than HC. In partial correlation analysis, serum NMDAR Ab levels were positively correlated with the P50 ratio (r = 0.36, P = .003) and negatively with the P50 difference (r = -0.39, P = .001) in the FES group. The NMDAR Ab levels mediated the diagnosis of schizophrenia and P50 sensory gating deficits (P50 ratio and P50 difference). CONCLUSIONS: Autoimmunity targeting NMDAR is a crucial intermediate mechanism in impaired sensory gating in patients with schizophrenia. The findings support early intervention targeting NMDAR for patients with schizophrenia.

High Efficiency n-Type Doping of Organic Semiconductors by Cation Exchange.

Achieving efficient doping in n-type conjugated polymers is crucial for their application in electronic devices. In this study, an n-type doping method is developed based on cation exchange that maintains a high doping level while ensuring a high degree of structural order, leading to significantly improved electrical conductivity. By investigating various dopants and ionic liquids, it is discovered that the choice of dopant influences doping efficiency, while the selection of ionic liquid affects cation exchange efficiency. Through careful selection of suitable dopants and ionic liquids, High doping levels are achieved remarkably in a short period, resulting in the highest conductivity (nearly 1 × 10- 2 S cm-¹) compared to other doping methods for poly{[N,N'-bis(2-octyldodecyl)-naphthalene-1,4,5,8-bis(dicarboximide)-2,6-diyl]-alt-5,5'-(2,2'-bithiophene)} (N2200). The findings highlight the robustness and efficiency of cation exchange doping as an effective approach for achieving high-quality n-type doping in conjugated polymers, thereby opening new avenues for the development of advanced polymer-based electronic devices.

The application of machine learning for identifying frailty in older patients during hospital admission.

BACKGROUND: Early identification of frail patients and early interventional treatment can minimize the frailty-related medical burden. This study investigated the use of machine learning (ML) to detect frailty in hospitalized older adults with acute illnesses. METHODS: We enrolled inpatients of the geriatric medicine ward at Taichung veterans general hospital between 2012 and 2022. We compared four ML models including logistic regression, random forest (RF), extreme gradient boosting, and support vector machine (SVM) for the prediction of frailty. The feature window as well as the prediction window was set as half a year before admission. Furthermore, Shapley additive explanation plots and partial dependence plots were used to identify Fried's frailty phenotype for interpreting the model across various levels including domain, feature, and individual aspects. RESULTS: We enrolled 3367 patients. Of these, 2843 were frail. We used 21 features to train the prediction model. Of the 4 tested algorithms, SVM yielded the highest AUROC, precision and F1-score (78.05%, 94.53% and 82.10%). Of the 21 features, age, gender, multimorbidity frailty index, triage, hemoglobin, neutrophil ratio, estimated glomerular filtration rate, blood urea nitrogen, and potassium were identified as more impactful due to their absolute values. CONCLUSIONS: Our results demonstrated that some easily accessed parameters from the hospital clinical data system can be used to predict frailty in older hospitalized patients using supervised ML methods.

Mediated relationship between Vitamin D deficiency and reduced pulmonary function by copper in Taiwanese young adults.

BACKGROUND: Vitamin D deficiency is prevalent worldwide and associated with worse outcomes in various lung diseases. This study examines the association between vitamin D deficiency and pulmonary function in healthy young adults. METHODS: This prospective cohort study (2017-2019) explored the impact of vitamin D deficiency on pulmonary function in a community-based young adult population. Pulmonary function was assessed via spirometry, with serum 25-hydroxyvitamin D [25(OH)D] and urinary copper levels quantified. Multivariate regression was used to estimate the relationship between vitamin D levels and lung function, with mediation analysis evaluating copper's role. RESULTS: The study included 1034 participants, average age 33.45 years, 41.93 % male. The median 25(OH)D level was 19.20 ng/mL (Interquartile Range: 13.48-24.90 ng/mL). Over half (54.74 %) had 25(OH)D levels below 20 ng/mL. Higher 25(OH)D levels were associated with better forced vital capacity (FVC) and forced expiratory volume in one second (FEV1). Trends suggested subgroup differences, but these were not statistically significant, indicating a consistent effect of 25(OH)D on pulmonary function across groups. SEM analysis suggested urinary copper as a mediator between 25(OH)D levels and FVC. CONCLUSION: Vitamin D deficiency is significantly associated with reduced pulmonary function in young adults in Taiwan.

Establishment and validation of a clinical risk scoring model to predict fatal risk in SFTS hospitalized patients.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infection with a high case fatality rate. Significant gaps remain in studies analyzing the clinical characteristics of fatal cases. METHODS: From January 2017 to June 2023, 427 SFTS cases were included in this study. A total of 67 variables about their demographic, clinical, and laboratory data were collected. Univariate logistic regression and the least absolute shrinkage and selection operator (LASSO) method was used to screen predictors from the cohort. Multivariate logistic regression was used to identify independent predictors and nomograms were developed. Calibration, decision curves and area under the curve (AUC) were used to assess model performance. RESULTS: The multivariate logistic regression analysis screened out the four most significant factors, including age > 70 years (p = 0.001, OR = 2.516, 95% CI 1.452-4.360), elevated serum PT (p < 0.001, OR = 1.383, 95% CI 1.143-1.673), high viral load (p < 0. 001, OR = 1.496, 95% CI 1.290-1.735) and high level of serum urea (> 8.0 µmol/L) (p < 0.001, OR = 4.433, 95% CI 1.888-10.409). The AUC of the nomogram based on these four factors was 0.813 (95% CI, 0.758-0.868). The bootstrap resampling internal validation model performed well, and decision curve analysis indicated a high net benefit. CONCLUSIONS: The nomogram based on age, elevated PT, high serum urea level, and high viral load can be used to help early identification of SFTS patients at risk of fatality.

Suicidality, perceived chronic stress, and stress-induced cortisol changes of individuals with schizophrenia.

The associations of suicidality with stress are poorly studied in schizophrenia. The study aimed to determine whether suicidality was correlated with perceived chronic stress and the cortisol fluctuations under stress tasks in schizophrenia. High suicidality was defined as a lifetime history of suicide attempts or suicidal ideation in the past 2 weeks. Individuals with schizophrenia and high suicidality (SZ-HS, n = 59), with low suicidality (SZ-LS, n = 207), and healthy controls (HC, n = 196) finished the Perceived Stress Scale. Then, they participated in an experiment that induced stress using the Paced Auditory Serial Addition Task and the Mirror Tracing Persistence Task. Negative affect was measured at baseline and after finishing each task. The salivary cortisol was collected before-, after 20 min, and after 40 min of the tasks. SZ-HS had elevated perceived stress than SZ-LS and HC. Mixed effect models showed that stress tasks induced cortisol changes in all groups; cortisol of SZ-LS was reduced more than HC, but SZ-HS and SZ-LS did not differ in cortisol fluctuations. SZ-HS and SZ-LS experienced similar negative affect changes during tasks and the difference in withdrawal rates was nonsignificant. SZ-HS had an increased error rate than SZ-LS. In conclusion, suicidality was correlated with high-level perceived stress but did not result in differences in cortisol reactivities under stress tasks. It suggests the inconsistency between appraisal of stress and biological stress system disturbance among SZ-HS compared to SZ-LS.

Genetic variation and molecular profiling of congenital malformations of the female genital tract based on whole-genome sequencing.

BACKGROUND: Congenital malformations of the female genital tract (CM-FGT) are characterized by abnormal development of the fallopian tubes, uterus, and vagina, often accompanied by malformations in the urinary system, bones and hearing. However, no definitive pathogenic genes and molecular genetic causes have been identified. METHODS: We present the largest whole-genome sequencing study of CM-FGT to date, analyzing 590 individuals in China: 95 patients, 442 case-controls, and 53 familial controls. RESULTS: Among the patients, 5.3% carried known CM-FGT-related variants. Pedigree and case-control analyses in two dimensions of coding and non-coding regulatory regions revealed seven novel de novo copy number variations, 12 rare single-nucleotide variations, and 10 rare 3' untranslated region (UTR) mutations in genes related to CM-FGT, particularly highlighting ASH1L as a pathogenic gene. Single-cell sequencing data showed that the majority of CM-FGT-related risk genes are spatiotemporally specifically expressed early in uterus development. CONCLUSIONS: In conclusion, this study identified novel variants related to CM-FGT, particularly highlighting ASH1L as a pathogenic gene. The findings provide insights into the genetic variants underlying CM-FGT, with single-cell sequencing data revealing spatiotemporal specific expression patterns of key risk genes early in uterine development. This study significantly advances the understanding of CM-FGT etiology and genetic landscape, offering new opportunities for prenatal screening.

Declined nutrients stability shaped by water residence times in lakes and reservoirs under climate change.

Water quality stability in lakes and reservoirs is essential for drinking water safety and ecosystem health, especially given the frequent occurrence of extreme climate events. However, the relationship between water quality stability and water residence time (WRT) has not been well elucidated. In this study, we explored the relationship based on nitrogen (N) and phosphorus (P) concentrations data in 11 lakes and 49 reservoirs in the Yangtze-Huaihe River basin from 2010 to 2022. Additionally, we examined the effects of hydrometeorological characteristics, the geomorphology of water bodies and catchments, and land use on the WRT, establishing a link between climate change and the stability of N and P in these water bodies. The results showed that a significant correlation between the stability of N and P in lakes and reservoirs and their WRT. The longer WRT tends to coincide with decreased stability and higher nutrient concentrations. Hydrometeorological factors are the primary factors on the WRT, with precipitation exerting the greatest effect, particularly under extreme drought. In recent years, extreme climatic events have intensified the fluctuations of WRT, resulting in a renewed increase in N and P concentrations and deterioration in stability. These findings highlight the importance of incorporating meteorological and hydrological factors alongside reinforcing ecological restoration into lake and reservoir management strategies, and providing a scientific basis for future efforts aimed at enhancing lake and reservoir water quality stability and safeguarding aquatic ecosystems.

Immunosuppressive effects of triptolide via interleukin-2/receptor signaling.

BACKGROUND: Triptolide (TP) has been confirmed to possess many beneficial functions including anti-inflammation and immunosuppression. OBJECTIVE: The present study aimed to explore the potential involvement of IL-2/IL-2R pathway in the immunosuppressive activities of TP. METHODS: Cultured CTLL-2 cells were utilized to evaluate the potential benefits of TP. Then cell viability was determined by CCK-8 assay, IFN-γ level by ELISA assay, Annexin V-FITC/PI double-staining and CD25 expression by flow cytometry, and protein expression by western blotting. Additionally, rhIL-2-driven lymphocytes following ConA activation were investigated. The interactions of TP with IL-2 and IL-2Rα were investigated by binding assays and molecular dynamics simulations. RESULTS: TP treatment attenuated IFN-γ level and cell viability in both rhIL-2-induced CTLL-2 cells and rhIL-2-driven splenic lymphocytes. TP treatment increased cellular apoptosis/necrosis and cleaved PARP-1 level, while suppressed c-Myc level in rhIL-2-induced CTLL-2 cells. Additionally, TP treatment reduced CD25 expression on CTLL-2 cell surface. Notably, the phosphorylation protein levels in IL-2R signaling pathways were inhibited by TP exposure prior to rhIL-2 stimulation. SPR and BLI assays verified TP that directly bound to rhIL-2 and rmIL-2Rα, respectively. Molecular simulations suggested that TP bound at the interface of IL-2 and IL-2Rα near the hydrophobic patch composed of F62, L92 on IL-2 and L23, I46, V139 on IL-2Rα, resulting in decreased binding free energy between IL-2 and IL-2Rα. CONCLUSIONS: These findings collectively emphasized that TP interfered IL-2/IL-2Rα interactions, down-regulated IL-2Rα expression, and inhibited IL-2R signaling pathways activation, thereby leading to the immune cells being desensitized to rhIL-2 and exhibiting immunosuppressive properties.

A novel angiotensin I-converting enzyme inhibitory peptide APPLRP from Grifola frondosa ameliorated the Ang II-induced vascular modeling in zebrafish model by mediating smooth muscle cells.

Grifola frondosa has garnered significant popularity as an edible mushroom attributable to its exceptional taste and nutritional benefits. This study isolated APPLRP, a potent ACE-inhibitory peptide, from the alcohol-soluble fraction of Grifola frondosa. The underlying mechanisms of APPLRP in antihypertension were explored through computational chemistry, cell experiments, and zebrafish model. Results demonstrated that APPLRP was an active competitive ACE inhibitor (IC50 = 29.93 µM) that could bind to the active pocket S2 and S1' of ACE. APPLRP exhibited resistance to pepsin and pancreatin digestion. In vitro experiments revealed that APPLRP significantly attenuated Ang II-induced VSMCs proliferation and migration by down-regulating AT1R expression and inhibiting ERK1/2 and STAT3 phosphorylation. APPLRP intervention significantly ameliorated myocardial fibrosis, as evidenced by reductions in cardiac output, blood flow velocity, and cardiac collagen deposition levels in Ang II-induced hypertensive zebrafish model. Furthermore, APPLRP improved vascular remodeling in hypertensive zebrafish, indicated by increased vessel diameter and decreased vessel wall thickness. Notably, APPLRP treatment resulted in down-regulation of ACE and up-regulation of ACE2 expression in the vessels of hypertensive zebrafish. These findings indicated that APPLRP was a representative component of Grifola frondosa peptides, and its antihypertensive effects were associated with ACE inhibition and the improvement of VSMCs-mediated vascular remodeling.

Analysis of risk factors for liver metastasis in patients with gastric cancer and construction of prediction model: A multicenter study.

BACKGROUND: To retrospectively analyze the risk factors of liver metastases in patients with gastric cancer in a single center, and to establish a Nomogram prediction model to predict the occurrence of liver metastases. METHODS: A total of 96 patients with gastric cancer who were also diagnosed with liver metastasis (GCLM) and treated in our center from January 1, 2010 to December 31, 2020 were included. The clinical data of 1095 patients with gastric cancer who were diagnosed without liver metastases (GC) in our hospital from January 1, 2014 to December 31, 2017 were retrospectively compared by univariate and multivariate logistic regression. 309 patients diagnosed with gastric cancer in another medical center from January 1, 2014 to December 31, 2018 were introduced as external validation cohorts. RESULTS: Based on the training cohort, multivariate analysis revealed that tumor site (OR = 0.55, P = 0.046), N stage (OR = 4.95, P = 0.004), gender (OR = 0.04, P = 0.001), OPNI (OR = 0.95, P = 0.041), CEA (OR = 1.01, P = 0.018), CA724 (OR = 1.01, P = 0.006), CA242 (OR = 1.01, P = 0.006), WBC (OR = 1.13, P = 0.024), Hb (OR = 0.98, P < 0.001) were independent risk factors for liver metastasis in patients with gastric cancer, and Nomogram was established based on this analysis (C-statistics = 0.911, 95%CI 0.880-0.958), and the C-statistics of the external validation cohorts achieved 0.926. ROC analysis and decision curve analysis (DCA) revealed that the nomogram provided superior diagnostic value than single variety. CONCLUSIONS: By innovatively introducing a new tumor location classification method, systemic inflammatory response indicators such as NLR and PLR, and nutritional index OPNI, the risk factors of gastric cancer liver metastasis were determined and a predictive Nomogram model was established, which can provide clinical prediction for patients with gastric cancer liver metastasis.

Research on Microstructure, Mechanical Properties, and High-Temperature Stability of Hot-Rolled Tungsten Hafnium Alloy.

W-(0, 0.1, 0.3, 0.5) wt.% Hf (mass fraction, wt.%) materials were fabricated by the powder metallurgy method and hot rolling. The microstructure, mechanical properties, and high-temperature stability of alloys with varying compositions were systematically studied. The active element Hf can react with the impurity O segregated at the grain boundary to form fine dispersed HfO2 particles, refining the grains and purifies and strengthening the grain boundary. The average size of the sub-grains in the W-0.3 wt.% Hf alloy is 4.32 µm, and the number density of the in situ-formed second phase is 6.4 × 1017 m-3. The W-0.3 wt.% Hf alloy has excellent mechanical properties in all compositions of alloys. The ultimate tensile strength (UTS) is 1048 ± 17.02 MPa at 100 °C, the ductile fracture occurs at 150 °C, and the total elongation (TE) is 5.91 ± 0.41%. The UTS of the tensile test at 500 °C is 614 ± 7.55 MPa, and the elongation is as high as 43.77 ± 1.54%. However, more Hf addition will increase the size of the second-phase particles and reduce the number density of the second-phase particles, resulting in a decrease in the mechanical properties of the tungsten alloy. The isochronal annealing test shows that the recrystallization temperature of W-Hf alloy is 1400 °C, which is 200 °C higher than rolling pure tungsten.

Limited Impacts of Water Diversion on Micro-eukaryotic Community along the Eastern Route of China's South-to-North Water Diversion Project.

The Eastern Route of the South-to-North Water Diversion Project (ER-SNWDP) represents a crucial initiative aimed at alleviating water scarcity in China's northern region. Understanding the dynamics governing the composition and assembly processes of micro-eukaryotic communities within the canal during different water diversion periods holds paramount significance for the effective management of the ER-SNWDP. Our study systematically tracks the dynamics of the micro-eukaryotic community and its assembly processes along the 1045.4 km of canals and four impounded lakes, totaling 3455 km2, constituting the ER-SNWDP during a complete water diversion cycle, utilizing high-throughput sequencing, bioinformatics tools, and null modeling algorithms. The primary objectives of this study are to elucidate the spatial-temporal succession of micro-eukaryotic communities as the water diversion progresses, to delineate the relative importance of deterministic and stochastic processes in community assembly, and to identify the pivotal factors driving changes in micro-eukaryotic communities. Our findings indicate notable variations in the composition and diversity of micro-eukaryotic communities within the ER-SNWDP across different water diversion periods and geographic locations (P < 0.05). This variation is influenced by a confluence of temporal and environmental factors, with limited impacts from water diversion. In essence, the assembly of micro-eukaryotic communities within the ER-SNWDP primarily stemmed from heterogeneous selection driven by deterministic processes. Water diversion exhibited a tendency to decrease community beta diversity while augmenting the influence of stochastic processes in community assembly, albeit this effect attenuated over time. Furthermore, our analysis identified several pivotal environmental parameters, notably including nitrite-nitrogen, nitrate-nitrogen, orthophosphate, and water temperature, as exerting significant effects on micro-eukaryotic communities across different water diversion periods. Collectively, our study furnishes the inaugural comprehensive exploration of the dynamics, assembly processes, and influencing factors governing micro-eukaryotic communities within the ER-SNWDP, thus furnishing indispensable insights to inform the water quality management of this important project.

Optimal methods of vitamin D supplementation to prevent acute respiratory infections: a systematic review, dose-response and pairwise meta-analysis of randomized controlled trials.

BACKGROUND: Vitamin D supplementation may prevent acute respiratory infections (ARIs). This study aimed to identify the optimal methods of vitamin D supplementation. METHODS: PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and the ClinicalTrials.gov registry were searched from database inception through July 13, 2023. Randomized-controlled trials (RCTs) were included. Data were pooled using random-effects model. The primary outcome was the proportion of participants with one or more ARIs. RESULTS: The analysis included 43 RCTs with 49320 participants. Forty RCTs were considered to be at low risk for bias. The main pairwise meta-analysis indicated there were no significant preventive effects of vitamin D supplementation against ARIs (risk ratio [RR]: 0.99, 95% confidence interval [CI]: 0.97 to 1.01, I2 = 49.6%). The subgroup dose-response meta-analysis indicated that the optimal vitamin D supplementation doses ranged between 400-1200 IU/day for both summer-sparing and winter-dominant subgroups. The subgroup pairwise meta-analysis also revealed significant preventive effects of vitamin D supplementation in subgroups of daily dosing (RR: 0.92, 95% CI: 0.85 to 0.99, I2 = 55.7%, number needed to treat [NNT]: 36), trials duration < 4 months (RR: 0.81, 95% CI: 0.67 to 0.97, I2 = 48.8%, NNT: 16), summer-sparing seasons (RR: 0.85, 95% CI: 0.74 to 0.98, I2 = 55.8%, NNT: 26), and winter-dominant seasons (RR: 0.79, 95% CI: 0.71 to 0.89, I2 = 9.7%, NNT: 10). CONCLUSION: Vitamin D supplementation may slightly prevent ARIs when taken daily at doses between 400 and 1200 IU/d during spring, autumn, or winter, which should be further examined in future clinical trials.

A CLIC1 network coordinates matrix stiffness and the Warburg effect to promote tumor growth in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) features substantial matrix stiffening and reprogrammed glucose metabolism, particularly the Warburg effect. However, the complex interplay between these traits and their impact on tumor advancement remains inadequately explored. Here, we integrated clinical, cellular, and bioinformatics approaches to explore the connection between matrix stiffness and the Warburg effect in PDAC, identifying CLIC1 as a key mediator. Elevated CLIC1 expression, induced by matrix stiffness through Wnt/ß-catenin/TCF4 signaling, signifies poorer prognostic outcomes in PDAC. Functionally, CLIC1 serves as a catalyst for glycolytic metabolism, propelling tumor proliferation. Mechanistically, CLIC1 fortifies HIF1α stability by curbing hydroxylation via reactive oxygen species (ROS). Collectively, PDAC cells elevate CLIC1 levels in a matrix-stiffness-responsive manner, bolstering the Warburg effect to drive tumor growth via ROS/HIF1α signaling. Our insights highlight opportunities for targeted therapies that concurrently address matrix properties and metabolic rewiring, with CLIC1 emerging as a promising intervention point.

Association of apolipoprotein A1 levels with lumbar bone mineral density and ß-CTX in osteoporotic fracture individuals: a cross-sectional investigation.

Background: The relationship between the levels of high-density lipoprotein (HDL) and bone mineral density (BMD) is controversial. Furthermore, the specific role of apolipoprotein A1 (APOA1), a primary HDL component, in regulating BMD remains unclear. This study aimed to elucidate the correlation between APOA1 levels and lumbar BMD in patients with osteoporotic fracture (OPF) for novel insights into potential therapeutic strategies against osteoporosis. Methods: This study included 587 OPF patients enrolled at the Kunshan Hospital, Affiliated with Jiangsu University between January 2017 and July 2022. The patient's serum APOA1 levels were determined, followed by the assessment of lumbar BMD and C-terminal telopeptide of type I collagen (ß-CTX) as outcome variables. The association of APOA1 levels with lumbar BMD and ß-CTX was assessed via Generalized Estimating Equations (GEE) and spline smoothing plot analyses. A generalized additive model (GAM) helped ascertain non-linear correlations. Moreover, a subgroup analysis was also conducted to validate the result's stability. Results: It was observed that APOA1 levels were positively correlated with lumbar BMD (ß = 0.07, 95% CI: 0.02 to 0.11, p = 0.0045), indicating that increased APOA1 levels were linked with enhanced lumbar BMD. Furthermore, APOA1 levels were negatively related to ß-CTX (ß = -0.19, 95% CI: -0.29 to -0.09, p = 0.0003), suggesting APOA1 might reduce osteolysis. In addition, these findings were robustly supported by subgroup and threshold effect analyses. Conclusion: This study indicated that increased APOA1 levels were correlated with enhanced lumbar BMD and decreased osteolysis in OPF patients. Therefore, APOA1 may inhibit osteoclast activity to prevent further deterioration in osteoporotic patients. However, further research I warranted to validate these conclusions and elucidate the underlying physiologies.

Brucella rough RB51 infection activates P53-Slc7a11-Gpx4/GSH pathway to induce ferroptosis to attenuate the intracellular survival on macrophages.

B. abortus is a facultative intracellular bacterium that replicates within macrophages. Intracellular survival is one of the important indexes to evaluate the virulence of Brucella. Ferroptosis is a type of programmed cell death induced by the accumulation of free iron, reactive oxygen species (ROS), and toxic lipid peroxides, play roles on cancers, cardiovascular diseases, and inflammatory diseases. In this study, we found that Brucella rough strain RB51 induced ferroptosis on macrophages with reduced levels of host glutathione and glutathione peroxidase 4 (Gpx4), together with increased ferrous iron, lipid peroxidation, and ROS. The inhibitor ferrostatin-1 significantly reduced the ferroptosis of RB51-infected macrophages, confirming that ferroptosis occurred during infection with Brucella RB51. Furthermore, we found that RB51 infection induced ferroptosis is regulated by P53-Slc7a11-Gpx4/GSH signal pathway. Inhibiting P53 decreased the levels of ROS and lipid peroxidation, while the levels of Slc7a11, Gpx4 and GSH were rescued. More importantly, inhibiting ferroptosis by different ferroptosis inhibitors increased the intracellular survival of Brucella RB51, indicating ferroptosis functions on the attenuation of Brucella intracellular survival. Collectively, our observations demonstrate that Brucella RB51 infection induces ferroptosis on macrophages, which is regulated by P53-Slc7a11-Gpx4/GSH signal pathway and functions on the attenuation of intracellular survival of Brucella.

Alternating electric fields transform the intricate network of tumour vasculature into orderly parallel capillaries and enhance the anti-angiogenesis effect of bevacizumab.

The search for effective strategies to target tumour angiogenesis remains a critical goal of cancer research. We present a pioneering approach using alternating electric fields to inhibit tumour angiogenesis and enhance the therapeutic efficacy of bevacizumab. Chicken chorioallantoic membrane, cell viability and in vitro endothelial tube formation assays revealed that electric fields with a frequency of 1000 kHz and an electric intensity of 0.6 V/cm inhibited the growth of vascular endothelial cells and suppressed tumour-induced angiogenesis. In an animal U87MG glioma model, 1000 kHz electric fields inhibited tumour angiogenesis and suppressed tumour growth. As demonstrated by 3D vessel analysis, tumour vasculature in the control group was a stout, interwoven network. However, electric fields transformed it into slim, parallel capillaries that were strictly perpendicular to the electric field direction. This architectural transformation was accompanied by apoptosis of vascular endothelial cells and a notable reduction in tumour vessel number. Additionally, we found that the anti-angiogenesis and tumour-suppression effects of electric fields synergised with bevacizumab. The anti-angiogenic mechanisms of electric fields include disrupting spindle formation during endothelial cell division and downregulating environmental angiogenesis-related cytokines, such as interleukin-6, CXCL-1, 2, 3, 5 and 8, and matrix metalloproteinases. In summary, our findings demonstrate the potential of alternating electric fields (AEFs) as a therapeutic modality to impede angiogenesis and restrain cancer growth.

Theoretical Study of Molybdenum Separation from Molybdate Assisted by a Terahertz Laser.

Molybdenum (Mo) is a rare and important element extensively utilised in aerospace, radar communications, optoelectronic devices, and the military. This study proposes an environmentally friendly physical method based on photon-phonon resonance absorption for the separation of Mo from sodium molybdate (Na2MoO4). We examined the vibrational spectrum of Na2MoO4 using the CASTEP code, employing first-principles density functional theory. Through dynamic process analysis, we analysed the vibrational modes and assigned peaks corresponding to experimental infrared (IR) and Raman data. We focused on the vibrational modes associated with Mo and identified that the highest-intensity IR-active peak at 858 cm-1 corresponded to Mo-O bond asymmetric stretching. Therefore, we propose the use of a high-power terahertz laser at ~25 THz to facilitate the separation of Mo from Na2MoO4. Experimental investigations are expected in the future.