Osteocalcin of maternal and embryonic origins synergize to establish homeostasis in offspring.

Many physiological osteocalcin-regulated functions are affected in adult offspring of mothers experiencing unhealthy pregnancy. Furthermore, osteocalcin signaling during gestation influences cognition and adrenal steroidogenesis in adult mice. Together these observations suggest that osteocalcin may broadly function during pregnancy to determine organismal homeostasis in adult mammals. To test this hypothesis, we analyzed in unchallenged wildtype and Osteocalcin-deficient, newborn and adult mice of various genotypes and origin maintained on different genetic backgrounds, the functions of osteocalcin in the pancreas, liver and testes and their molecular underpinnings. This analysis revealed that providing mothers are Osteocalcin-deficient, Osteocalcin haploinsufficiency in embryos hampers insulin secretion, liver gluconeogenesis, glucose homeostasis, testes steroidogenesis in adult offspring; inhibits cell proliferation in developing pancreatic islets and testes; and disrupts distinct programs of gene expression in these organs and in the brain. This study indicates that osteocalcin exerts dominant functions in most organs it influences. Furthermore, through their synergistic regulation of multiple physiological functions, osteocalcin of maternal and embryonic origins contributes to the establishment and maintenance of organismal homeostasis in newborn and adult offspring.

Prediction of Optical Properties in Particulate Media Using Double Optimization of Dependent Scattering and Particle Distribution.

The prediction of optical properties dominated by light scattering in particulate media composed of high-concentration and polydisperse particles is greatly important in various optical applications. However, the accuracy and efficiency of light propagation simulations are still limited by the huge computational burden and complex interactions between dense and polydisperse particles. Here, we proposed a new optimization strategy that can effectively and accurately predict optical properties based on Monte Carlo simulation with particle size and dependent scattering corrections. Both the scattering parameters of particles and the experimental reflectance spectrum are fully examined for verification. Furthermore, using the weighted solar reflectance of particulate media as a representative optical property, both numerical simulations and experiments confirm the superiority and universality of the proposed optimization approach in a variety of materials systems. Moreover, our work can guide the design of particulate media with specific optical features insightfully and will be applicable in many fields involving multiparticle scattering.

An Economic Evaluation of Family-Based Versus Traditional Helicobacter pylori Screen-and-Treat Strategy: Based on Real-World Data and Microsimulation Model.

OBJECTIVE: There is an economic evaluation on the family-based Helicobacter pylori screen-and-treat strategy (FBHS) in China. This study aimed to compare the cost-effectiveness of the FBHS with the traditional H. pylori screen-and-treat strategy (TBHS). MATERIALS AND METHODS: A seven-state microsimulation model, including H. pylori infection and gastric cancer states, was constructed on the basis of the target family samples from 29 provinces in China. Taking a lifetime horizon from a healthcare system perspective, the long-term costs and health outcomes of the FBHS and TBHS screening strategies were simulated separately, and economic evaluations were performed. The model parameters were primarily derived from real-world data, published literature, and expert opinions. The primary outcome was the incremental cost-effectiveness ratio (ICER) expressed as cost/quality-adjusted life-year (QALY) gained. One-way sensitivity analysis, probabilistic sensitivity analysis, and scenario analysis were performed to assess the uncertainty of the results. RESULTS: The base-case analysis revealed that the average costs for FBHS and TBHS were 563.67 CNY and 574.08 CNY, respectively, with corresponding average QALYs of 14.83 and 14.79. The ICER for the comparison between the two strategies was -214.07, indicating that FBHS was an absolutely dominant strategy with better cost-effectiveness. The results of both one-way sensitivity analysis and probabilistic sensitivity analysis were robust. When taking into account the added benefit of the higher H. pylori eradication rate in FBHS, the average costs were further reduced, and the average QALYs were increased, solidifying its position as an unequivocally dominant strategy. CONCLUSION: The FBHS is an absolutely dominant and cost-effective strategy that enables an optimized allocation of screening resources. Decision-makers should prioritize FBHS when developing H. pylori prevention and control strategies.

Discerning the Relevance of Singlet Oxygen in Pollutant Degradation in Peroxymonosulfate Activation Processes.

Significant efforts have recently been exerted toward construction of singlet oxygen (1O2)-dominated catalytic oxidation systems for selective removal of organic contaminants from wastewater, with peroxides serving as the chemical source. However, the relevance of 1O2 in the removal of pollutants remains ambiguous and requires elucidation. In this study, we scrupulously exclude the significant role of 1O2 in contaminant degradation in various peroxymonosulfate (PMS) activation systems. Multiple experimental results indicate that the activation of PMS catalyzed by CuO, MnO2, Fe-doped g-C3N4 (Fe-CN), or N-doped graphite does not predominantly follow the 1O2 pathway. More importantly, the reactivity of 1O2 is remarkably overestimated in the literature, given its inferior capacity in degradation of a range of heterocyclic contaminants and aromatic compounds possessing electron-withdrawing groups. In addition, the strong physical quenching effect of water, coupled with the low oxidizing ability of 1O2, would notably reduce the utilization efficiency of peroxide, which is particularly apparent in the degradation of micropollutants. We reckon that this study is expected to end the long-running dispute associated with the relevance of 1O2 in pollutant removal.

Effect of da Vinci robot versus thoracoscopic surgery on lung function and oxidative stress levels in NSCLC patients: a propensity score-matched study.

BACKGROUND: To evaluate the short-term efficacy, lung function, and oxidative stress levels between the robotic-assisted thoracoscopic surgery (RATS) and video-assisted thoracoscopic surgery group (VATS) for non-small cell lung cancer (NSCLC). METHODS: We conducted a retrospective cohort study, selecting 248 NSCLC patients who underwent minimally invasive lobectomy at the Department of Thoracic Surgery, Gansu Provincial People's Hospital, from August 2019 to February 2023. There were 105 patients in the RATS group and 143 patients in the VATS group. The patients in the two groups were subjected to 1:1 propensity score matching analysis (PSM), and the perioperative indicators were recorded. The levels of oxidative stress factors (superoxide dismutase, SOD; malondialdehyde, MDA) and inflammatory factors were measured 1 day before surgery and 3 days after surgery, respectively. Pulmonary function and patient quality of life were measured at 1 day preoperatively and 3 months postoperatively. RESULTS: There are 93 patients in each group after PSM. Compared to the VATS group, the RATS group had shorter operation time, less intraoperative blood loss, greater number and groups of lymph nodes cleared, and shorter postoperative hospital stay. The SOD level in the RATS group was higher and the MDA level was lower than that in the VATS group after surgery. Postoperative inflammatory cytokine levels were less elevated in the RATS group than in the VATS group. At 3 months postoperatively, FVC%, FEV1%, and GQOLI-74 scores were higher in the RATS group than in the VATS group. CONCLUSION: Compared to VATS lobectomy, RATS lobectomy has the advantages of shorter operative time, lesser bleeding, more lymph node dissection, faster postoperative recovery, and lesser impact on postoperative lung function. It is also capable of reducing the postoperative oxidative stress and inflammatory response, which can improve patients' quality of life.

Cost-effectiveness analysis of tislelizumab vs. camrelizumab for the treatment of second-line locally advanced or metastatic esophageal squamous cell carcinoma.

BACKGROUND: Esophageal carcinoma is a type of cancer that occurs in the esophagus. For patients with locally advanced or metastatic esophageal squamous cell carcinoma who have either experienced disease progression following first-line standard chemotherapy or are intolerant to it, the prognosis is typically poor. Additionally, these patients often bear a substantial economic burden during the course of their treatment. Tislelizumab is a selective PD-1 inhibitor with efficacy proven in locally advanced or metastatic esophageal squamous cell carcinoma. The study aims to evaluate the cost-effectiveness of tislelizumab versus camrelizumab as the second-line treatment in locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) patients in China. METHODS: From the perspective of China's healthcare system, the partitioned survival model with three health states was established in a 3-week cycle and a lifetime horizon. Anchored matching adjusted indirect comparison was used for survival analyses based on individual patient data from RATIONALE 302 trial and the published ESCORT study due to the lack of head-to-head clinical trials. Only direct medical costs were included. Costs and utility values were derived from local charges, the published literature, and related databases. Sensitivity analyses and a scenario analysis were also performed to verify the robustness of the model results. RESULTS: Compared with camrelizumab monotherapy, tislelizumab monotherapy incurred a lower lifetime cost ($8,346 vs. $8,851) and yielded higher quality-adjusted life-years (QALYs) (0.87 vs. 0.63), which resulted in an incremental cost-effectiveness ratio (ICER) of -$2,051/QALY. Tislelizumab monotherapy is a dominant option over camrelizumab monotherapy in China. The three primary parameters upon which this result was most sensitive were the unit cost of camrelizumab, the unit cost of tislelizumab, and the duration of reactive cutaneous capillary endothelial proliferation (RCCEP). According to the probabilistic sensitivity analysis (PSA), tislelizumab monotherapy was 100% cost-effective when the WTP was 1-3 times GDP per capita in China($11,207/QALY∼$33,621/QALY). Scenario analysis showed that the result was consistent. CONCLUSION: Tislelizumab monotherapy is a dominant option compared with camrelizumab monotherapy as the second-line treatment for locally advanced or metastatic ESCC in China.

Predictive performance of the variation rate of the driving pressure on the outcome of invasive mechanical ventilation in patients with acute respiratory distress syndrome.

PURPOSE: To assess the value of the driving pressure variation rate (ΔP%) in predicting the outcome of weaning from invasive mechanical ventilation in patients with acute respiratory distress syndrome. METHODS: In this case-control study, a total of 35 patients with moderate-severe acute respiratory distress syndrome were admitted to the intensive care unit between January 2022 and December 2022 and received invasive mechanical ventilation for at least 48 h were enrolled. Patients were divided into successful weaning group and failed weaning group depending on whether they could be removed from ventilator support within 14 days. Outcome measures including driving pressure, PaO2:FiO2, and positive end-expiratory pressure, etc. were assessed every 24 h from day 0 to day 14 until successful weaning was achieved. The measurement data of non-normal distribution were presented as median (Q1, Q3), and the differences between groups were compared by Wilcoxon rank sum test. And categorical data use the Chi-square test or Fisher's exact test to compare. The predictive value of ΔP% in predicting the outcome of weaning from the ventilator was analyzed using receiver operating characteristic curves. RESULTS: Of the total 35 patients included in the study, 17 were successful vs. 18 failed in weaning from a ventilator after 14 days of mechanical ventilation. The cut-off values of the median ΔP% measured by Operator 1 vs. Operator 2 in the first 4 days were ≥ 4.17% and 4.55%, respectively (p < 0.001), with the area under curve of 0.804 (sensitivity of 88.2%, specificity of 64.7%) and 0.770 (sensitivity of 88.2%, specificity of 64.7%), respectively. There was a significant difference in mechanical ventilation duration between the successful weaning group and the failure weaning group (8 (6, 13) vs. 12 (7.5, 17.3), p = 0.043). The incidence of ventilator-associated pneumonia in the successful weaning group was significantly lower than in the failed weaning group (0.2‰ vs. 2.3‰, p = 0.001). There was a significant difference noted between these 2 groups in the 28-day mortality (11.8% vs. 66.7%, p = 0.003). CONCLUSION: The median ΔP% in the first 4 days of mechanical ventilation showed good predictive performance in predicting the outcome of weaning from mechanical ventilation within 14 days. Further study is needed to confirm this finding.

Tyro3 receptor tyrosine kinase contributes to pathogenic phenotypes of fibroblast-like synoviocytes in rheumatoid arthritis and disturbs immune cell balance in experimental arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterized by synovitis and joint damage, the underlying causes of which remain unclear. Our prior investigations revealed a notable correlation between the expression of Tyro3 Protein Tyrosine Kinase (Tyro3TK) and the progression of RA. To further elucidate the pathogenic role of Tyro3TK in RA, we analyzed the influence of Tyro3TK on pathogenic phenotypes of RA fibroblast like synoviocyte (FLS) in vitro and compared disease severity, joint damages and immunological parameters of K/BxN serum transfer arthritis (STA) in Tyro3TK-/- deficient mice and wild type controls. Our findings underscored the remarkable effectiveness of Tyro3TK blockade, as evidenced by diminished secretion of inflammatory cytokines and matrix metalloproteinases (MMPs), curtailed migration and invasiveness of RAFLS, and attenuated differentiation of pathogenic helper T cell subsets mediated by RAFLS. Correspondingly, our in vivo investigations illuminated the more favorable outcomes in Tyro3TK-deficient mice, characterized by reduced joint pathology, tempered synovial inflammation, and restored immune cell equilibrium. These data suggested that Tyro3TK might contribute to aggravated autoimmune arthritis and immunological pathology and act as a potential therapeutic target for RA.

Effect of Early Versus Late Oral Feeding on Postoperative Complications and Recovery Outcomes for Patients with Esophageal Cancer: A Systematic Evaluation and Meta-Analysis.

BACKGROUND: This study aimed to systematically evaluate the effect of early oral feeding (EOF) versus late oral feeding (LOF) on postoperative complications and rehabilitation outcomes for patients with esophageal cancer. METHODS: This study searched relevant literature published up to March 2023 by computer retrieval of PubMed, Embase, The Cochrane Library, and Web of Science. A meta-analysis was performed using Review Manager 5.4 software to compare the effects of EOF and LOF on postoperative complications and recovery outcomes of patients with esophageal cancer. RESULTS: The study included 14 articles, including 9 retrospective studies, 4 randomized controlled trials (RCTs), and 1 prospective study. The 2555 patients included in the study comprised 1321 patients who received EOF and 1234 patients who received LOF. The results of the meta-analysis showed that compared with the LOF group, the EOF group has a shorter time to the first flatus postoperatively (mean difference [MD], - 1.12; 95% confidence interval [CI], (- 1.25 to - 1.00; P < 0.00001), a shorter time to the first defecation postoperatively (MD, - 1.31; 95% CI, - 1.67 to - 0.95;, P < 0.00001], and a shorter hospital stay postoperatively (MD, - 2.87; 95% CI, - 3.84 to - 1.90; P < 0.00001). The two groups did not differ significantly statistically in terms of postoperative anastomotic leakage rate (P = 0.10), postoperative chyle leakage rate (P = 0.10), or postoperative pneumonia rate (P = 0.15). CONCLUSION: Early oral feeding after esophageal cancer surgery can shorten the time to the first flatus and the first defecation postoperatively, shorten the hospital stay, and promote the recovery of patients. Moreover, it has no significant effect on the incidence of postoperative complications.

Yang-Lee Zeros, Semicircle Theorem, and Nonunitary Criticality in Bardeen-Cooper-Schrieffer Superconductivity.

Yang and Lee investigated phase transitions in terms of zeros of partition functions, namely, Yang-Lee zeros [Phys. Rev. 87, 404 (1952)PHRVAO0031-899X10.1103/PhysRev.87.404; Phys. Rev. 87, 410 (1952)PHRVAO0031-899X10.1103/PhysRev.87.410]. We show that the essential singularity in the superconducting gap is directly related to the number of roots of the partition function of a BCS superconductor. Those zeros are found to be distributed on a semicircle in the complex plane of the interaction strength due to the Fermi-surface instability. A renormalization-group analysis shows that the semicircle theorem holds for a generic quantum many-body system with a marginal coupling, in sharp contrast with the Lee-Yang circle theorem for the Ising spin system. This indicates that the geometry of Yang-Lee zeros is directly connected to the Fermi-surface instability. Furthermore, we unveil the nonunitary criticality in BCS superconductivity that emerges at each individual Yang-Lee zero due to exceptional points and presents a universality class distinct from that of the conventional Yang-Lee edge singularity.