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.

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.

Fabrication of high-performance cell-imprinted polymers based on AuNPs/MXene composites via metal-free visible light-induced ATRP.

Cell-imprinted polymers (CIPs) for yeasts were fabricated via metal-free visible-light-induced atom transfer radical polymerization (MVL ATRP) on the surface of a glassy carbon electrode (GCE) which had been modified with gold nanoparticles (AuNPs)/MXene (Ti3C2Tx) composites. Here, the AuNPs/Ti3C2Tx composites form a macroporous structure, which could improve the electron transfer rate of the materials and facilitate the leaving or rebinding of cells. Methacrylic acid (MAA) and N,N'-methylene bis-acrylamide (MBA) were selected as the functional monomer and cross-linker of CIPs, because they could form efficient hydrogen bonding with mannan from yeast cell walls. The obtained electrode (CIPs/AuNPs/Ti3C2Tx/GCE) was characterized by electrochemical impedance spectroscopy (EIS), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS). Further experiments indicated that the CIPs/AuNPs/Ti3C2Tx/GCE electrode could be utilized as an electrochemical biosensor to determine yeast cells by differential pulse voltammetry (DPV). The linear response range was 1.0 × 102 to 1.0 × 109 cells per mL and the detection limit was 20 cells per mL (S/N = 3). The CIPs/AuNPs/Ti3C2Tx/GCE electrode also showed good selectivity, repeatability, reproducibility, and regeneration. Finally, the proposed sensor was used to detect yeast cells in commercial samples of Saccharomyces boulardii sachets by a standard addition method. The obtained recovery was from 96.9 to 104.8% showing its potential applications in clinical and diagnostic research.

Cost-effectiveness analysis of recombinant factor IX Fc fusion protein compared with recombinant factor IX for the treatment of moderate-severe to severe hemophilia B in China.

OBJECTIVE: To evaluate the lifetime cost-effectiveness of recombinant factor IX Fc fusion protein (rFIXFc) and recombinant factor IX (rFIX) for the treatment of hemophilia B (HB) in China. METHODS: We developed a decision-analytic Markov model including three health states: alive, requiring surgery, and dead. This model estimated the lifetime cost and quality-adjusted life-years (QALYs) of prophylaxis in childhood, followed by on-demand treatment in adulthood for moderate-severe to severe HB patients from China's healthcare system perspective. Efficacy data derived from pivotal clinical trials, clinical guideline recommendations, and expert consultation were applied to two scenarios (full dose and low dose). One-way sensitivity analysis and probabilistic sensitivity analysis (PSA) were performed to assess the robustness of the model. OUTCOMES: Lifetime cost, QALYs, and the incremental cost-effectiveness ratio were calculated, and the results were compared with willingness-to-pay (WTP) thresholds of one to three times the gross domestic product per capita of China in 2021 ($12,551-$37,653). RESULTS: RFIXFc was associated with lower cost and more QALYs than rFIX in both scenarios, which suggested that it is a dominant strategy (more effective and cheaper) for moderate-severe to severe HB in China. In the full-dose scenario, rFIXFc saved more money and yielded more QALYs than in the low-dose scenario (low doses are the typical clinical reality in China). PSA demonstrated that rFIXFc had an over 90% probability of being cost-effective with full-dose and low-dose treatment at WTP thresholds of $12,551-$37,653. CONCLUSIONS: Compared with rFIX, rFIXFc appears to be a cost-effective option for the lifetime management of moderate-severe to severe HB patients in China.

Exploration of an alternative reconstructed individual patient data-based approach for budget impact analysis of anticancer drugs.

BACKGROUND: The duration of treatment (DOT) of the initial intervention and subsequent treatment is the key to determining the accuracy of anticancer-drug budget impact analysis (BIA) calculations. However, existing studies only use simple assumptions as a proxy for DOT, resulting in a high degree of bias. OBJECTIVES: To enhance the accuracy and reliability of anticancer-drug BIA and solve the problem regarding DOT, we propose an alternative individual patient data (IPD)-based approach that reconstructs IPD from the published Kaplan Meier survival curves to estimate DOT. METHODS: We developed a four-step methodological framework for this new approach, taking the use of pembrolizumab in treating microsatellite-instability-high (MSI-H) advanced colorectal cancer as an example: (1) reconstructing the IPD; (2) calculating the total DOT of the initial intervention and subsequent treatment for each patient; (3) assigning a randomized time and DOT; and (4) multiple replacement sampling and calculation of the mean value. RESULTS: Using this approach, the average DOT for the initial intervention and subsequent treatment in each year of the BIA time horizon can be calculated and used to calculate the resources consumed and costs in each year. In our example, the average DOT for the initial intervention with pembrolizumab from the first to the fourth year was 4.90, 6.60, 5.24, and 5.06 months, respectively, while the average DOT for subsequent treatment was 0.75, 2.84, 2.99, and 2.50 months, respectively. CONCLUSIONS: The reconstructed IPD-based approach can improve the accuracy and reliability of anticancer-drug BIA compared with conventional methods, and can be widely used, especially for anticancer drugs with excellent efficacy.

Investigation of thermal control in phase-changing ABO3 perovskites via first-principles predictions: general mechanism of emittance.

Phase-change thermal control has recently seen increased interest due to its significant potential for use in smart windows, building insulation, and optoelectronic devices in spacecraft. Tunable variation in infrared emittance can be achieved by thermally controlling the phase transitions of materials at different temperatures. A high emittance in the mid-infrared region is usually caused by resonant phonon vibrational modes. However, the fundamental mechanism of emittance variation during the phase-change process remains elusive. In this work, the electronic bandgaps, phononic structures, optical-spectrum properties, and formation energies of 76 kinds of phase-changing ABO3 perovskites were predicted based on first-principles calculations in the mid-infrared region. The variation in emittance between two phases of a single material was found to have an exponential correlation with the bandgap difference (R2 ∼ 0.92). Furthermore, a strong linear correlation (R2 ∼ 0.92) was found between the emittance variation and the formation-energy difference, and the emittance variation was also strongly correlated with the volume-distortion rate (R2 ∼ 0.90). Finally, it was concluded that a large lattice vibrational energy, a high formation energy, and a small cell volume are conducive to high emittance. This work provides a strong dataset for training machine-learning models, and it paves the way for further use of this novel methodology to seek efficient phase-change materials for thermal control.

Investigation of thermal control in phase-changing ABO3 perovskites via first-principles predictions: general mechanism of solar absorptivity.

The fundamental mechanism of solar absorbance during the phase-change process is investigated in ABO3 perovskites based on first-principles predictions. A Gaussian-like relationship between the solar absorbance and band gaps is established, which follows the Shockley-Queisser limiting efficiency. For ABO3 perovskites with bandgaps of Eg > 3.5 eV, a low solar absorbance is obtained, whereas a high solar absorbance is obtained for ABO3 perovskites, with band gaps ranging from 0.25 to 2.2 eV. The relationship between the orbital character of the density of states (DOS) and the absorption spectra reveals that ABO3 perovskites with magnetic (strongly interacting) and distorted crystal structures always exhibit a higher solar absorptivity. In contrast, non-magnetic and cubic ABO3 perovskites always exhibit a lower solar absorptivity. Moreover, the tunable solar absorptivity always undergoes a phase change from cubic to large distorted crystal structures in ABO3 perovskites with strong interactions. These results can be attributed to a rich structural, electronic, and magnetic phase diagram resulting from the strong interplay between the lattice, spin, and orbital degrees of freedom, which induce highly tunable optical characteristics in the phase-change process. The findings presented in this study are critical for the development of ABO3 perovskite-based smart thermal control materials in the spacecraft field.

Meta analysis of the diagnostic value of circulating miRNA in benign and malignant pulmonary nodules.

OBJECTIVE: A meta-analysis was conducted to assess the impact of miRNAs in circulation on diagnosing benign and malignant pulmonary nodules (BPNs and MPNs). METHODS: Electronic databases such as Embase, PubMed, Web of Science, and The Cochrane Library were utilized for diagnostic tests of circulating miRNAs to diagnose BPNs and MPNs from the library creation to February 2023. Meta-analysis of the included literature was performed using Stata 16, Meta-Disc 1.4, and Review Manager 5.4 software. This study determined the combined sensitivity, specificity, diagnostic ratio (DOR), positive/negative likelihood ratios (PLR/NLR), as well as value of area under the receiver operating characteristic (ROC) curve. RESULTS: This meta-analysis included 14 publications and 17 studies. According to our findings, the pooled sensitivity for miRNA in diagnosing benign and malignant pulmonary nodules was 0.82 [95% CI (0.74, 0.88)], specificity was 0.84 [95% CI (0.79, 0.88)], whereas the DOR was 22.69 [95% CI (13.87, 37.13)], PLR was 5.00 [95% CI (3.87, 6.46)], NLR was 0.22 [95% CI (0.15, 0.32)], and the area under the working characteristic curve (AUC) of the subject was 0.89 [95% CI (0.86, 0.91)]. CONCLUSION: Circulating miRNAs could be used with sensitivity, specificity, DOR, PLR, NLR, and AUC as biomarkers to diagnose pulmonary nodules (PNs). However, more research is needed to determine the optimum miRNA combinations for diagnosing PNs due to the significant heterogeneity on previous studies.

A quantitative study of airway ultrasound in predicting difficult laryngoscopy: A prospective study.

PURPOSE: As common clinical screening tests cannot effectively predict a difficult airway, and unanticipated difficult laryngoscopy remains a challenge for physicians. We herein used ultrasound to develop some point-of-care predictors for difficult laryngoscopy. METHODS: This prospective observational study included 502 patients who underwent laryngoscopy and a detailed sonographic assessment. Patients under 18 years old, or with maxillofacial deformities or fractures, limited mouth opening, limited neck movement or history of neck surgery were excluded from the study. Laryngoscopic views of all patients were scored and grouping using the modified Cormack-Lehane (CL) scoring system. The measurements acquired comprised tongue width, the longitudinal cross-sectional area of the tongue, tongue volume, the mandible-hyoid bone distance, the hyoid bone-glottis distance, the mandible-hyoid bone-glottis angle, the skin-thyrohyoid membrane distance, the glottis-superior edge of the thyroid cartilage distance (DGTC), the skin-hyoid bone distance, and the epiglottis midway-skin distance. ANOVA and Chi-square were used to compare differences between groups. Logistic regression was used to identify risk factors for difficult laryngoscopy and it was visualized by receiver operating characteristic curves and nomogram. R version 3.6.3 and SPSS version 26.0 were used for statistical analyses. RESULTS: Difficult laryngoscopy was indicated in 49 patients (CL grade Ⅲ - Ⅳ) and easy laryngoscopy in 453 patients (CL grade Ⅰ - Ⅱ). The ultrasound-measured mandible-hyoid bone-glottis angle and DGTC significantly differed between the 2 groups (p < 0.001). Difficult laryngoscopy was predicted by an area under the curve (AUC) of 0.930 with a threshold mandible-hyoid bone-glottis angle of 125.5° and by an AUC of 0.722 with a threshold DGTC of 1.22 cm. The longitudinal cross-sectional area of the tongue, tongue width, tongue volume, the mandible-hyoid distance, and the hyoid-glottis distance did not significantly differ between the groups. CONCLUSION: Difficult laryngoscopy may be anticipated in patients in whom the mandible-hyoid bone-glottis angle is smaller than 125.5° or DGTC is larger than 1.22 cm.

Mn2O3 as an Electron Shuttle between Peroxymonosulfate and Organic Pollutants: The Dominant Role of Surface Reactive Mn(IV) Species.

The environmentally benign Mn oxides play a crucial role in the transformation of organic contaminants, either through catalytically decomposing oxidants, e.g., peroxymonosulfate (PMS), or through directly oxidizing the target pollutants. Because of their dual roles and the complex surface chemical reactions, the mechanism involved in Mn oxide-catalyzed PMS activation processes remains obscure. Here, we clearly elucidate the mechanism involved in the Mn2O3 catalyzed PMS activation process by means of separating the PMS activation and the pollutant oxidation process. Mn2O3 acts as a shuttle that mediates the electron transfer from organic substrates to PMS, accompanied by the redox cycle of surface Mn(IV)/Mn(III). Multiple experimental results indicate that PMS is bound to the surface of Mn2O3 to form an inner-sphere complex, which then decomposes to form long-lived surface reactive Mn(IV) species, without the generation of sulfate radicals (SO4•-) and hydroxyl radicals (HO•). The surface reactive Mn(IV) species are proposed to be responsible for the degradation of organic contaminants (e.g., phenol) and the formation of singlet oxygen (1O2), followed by the regeneration of the surface Mn(III) sites on Mn2O3. This study advances the fundamental understanding of the underlying mechanism involved in transition metal oxide-catalyzed PMS activation processes.

Cost-effectiveness analysis of sintilimab plus bevacizumab biosimilar compared with lenvatinib as the first-line treatment of unresectable or metastatic hepatocellular carcinoma.

BACKGROUND: In recent years, programmed cell death protein-1 inhibitors, including sintilimab, have significantly prolonged the overall survival time of patients with unresectable or metastatic hepatocellular carcinoma (HCC); however, the cost-effectiveness of sintilimab is unclear. The aim of this study was to assess the cost-effectiveness of sintilimab plus bevacizumab biosimilar compared with lenvatinib as first-line treatment in patients with unresectable or metastatic HCC. METHODS: A lifetime partitioned survival model was developed to conduct a cost-effectiveness analysis of sintilimab plus bevacizumab biosimilar vs. lenvatinib for advanced HCC from a Chinese healthcare system perspective. The clinical and safety data were derived from two recent randomized clinical trials, the ORIENT-32 and REFLECT studies. Utility data were obtained from previous studies. Long-term direct medical costs and quality-adjusted life-years (QALYs) were predicted. Deterministic and probabilistic sensitivity analyses were performed to verify the robustness of the model. RESULTS: Compared with lenvatinib, combination therapy with sintilimab and bevacizumab biosimilar yielded an additional 0.493 QALYs at a higher cost ($33,102 vs. $21,037) (2021 US dollars). This resulted in a deterministic incremental cost-effectiveness ratio (ICER) of $24,462 per QALY in the base-case analysis. The ICERs were sensitive to the utility of post-progression and the cost of bevacizumab biosimilar. A lower ICER was estimated when the dose of bevacizumab biosimilar decreased from 15 mg to 7.5 mg per kilogram in the scenario analysis. In the probabilistic sensitivity analysis, the probability of being cost-effective for sintilimab treatment at willingness-to-pay (WTP) thresholds of one ($12,516) and three times the gross domestic product per capita in China ($37,547) were 11.6% and 88.6%, respectively. CONCLUSION: Sintilimab plus bevacizumab biosimilar is likely to be a cost-effective treatment option as a first-line treatment for unresectable or metastatic HCC in China when WTP threshold is over $23,650.

The correlation between volumetric bone mineral density and morphological parameters of the proximal femur and clinical outcomes in ankylosing spondylitis patients with hip involvement.

BACKGROUND: To measure volumetric bone mineral density (vBMD) with quantitative computed tomography (QCT) in the proximal femur of ankylosing spondylitis (AS) patients with hip involvement and analyze their correlations with radiographic and clinical parameters. METHODS: Sixty-five AS inpatients were enrolled in this study. The bone mineral density was measured by QCT and dual-energy x-ray absorptiometry (DXA), respectively. The morphological parameters of the proximal femur were measured on digital anteroposterior (AP) radiographs of the pelvis. The correlations between them were analyzed by SPSS software. RESULTS: The average trabecular vBMD measured at the femoral neck was 136.38 ± 25.58 mg/cm3. According to the BASRI-Hip score, group A consisted of 39 hips (0-2 score) and group B consisted of 26 hips (3-4 score). There were significant differences regarding trabecular CTXA equivalent T-score between group A and B at the femoral neck (p = 0.004); intertrochanteric region (p < 0.001) and greater trochanter (p = 0.001). The trabecular CTXA equivalent T-score at femoral neck had a negative correlation with disease duration (r = - 0.311, p = 0.012) and with CBR (r = - 0.319, p = 0.010). CONCLUSIONS: The low trabecular bone density at the site of the hip was associated with the duration of disease progression and degree of hip involvement. Meanwhile, it had a correlation with hip function status although we failed to confirm a significant relationship between hip vBMD and disease activity.

Overturned Loading of Inert CeO2 to Active Co3 O4 for Unusually Improved Catalytic Activity in Fenton-Like Reactions.

In the past decades, numerous efforts have been devoted to improving the catalytic activity of nanocomposites by either exposing more active sites or regulating the interaction between the support and nanoparticles while keeping the structure of the active sites unchanged. Here, we report the fabrication of a Co3 O4 -CeO2 nanocomposite via overturning the loading direction, i.e., loading an inert CeO2 support onto active Co3 O4 nanoparticles. The resultant catalyst exhibits unexpectedly higher activity and stability in peroxymonosulfate-based Fenton-like reactions than its analog prepared by the traditional impregnation method. Abundant oxygen vacancies (Ov with a Co⋅⋅⋅Ov ⋅⋅⋅Ce structure instead of Co⋅⋅⋅Ov ) are generated as new active sites to facilitate the cleavage of the peroxide bond to produce SO4 .- and accelerate the rate-limiting step, i.e., the desorption of SO4 .- , affording improved activity. This strategy is a new direction for boosting the catalytic activity of nanocomposite catalysts in various scenarios, including environmental remediation and energy applications.

Maize Plant Architecture Is Regulated by the Ethylene Biosynthetic Gene ZmACS7.

Plant height and leaf angle are two crucial determinants of plant architecture in maize (Zea mays) and are closely related to lodging resistance and canopy photosynthesis at high planting density. These two traits are primarily regulated by several phytohormones. However, the mechanism of ethylene in regulating plant architecture in maize, especially plant height and leaf angle, is unclear. Here, we characterized a maize mutant, Semidwarf3 (Sdw3), which exhibits shorter stature and larger leaf angle than the wild type. Histological analysis showed that inhibition of longitudinal cell elongation in the internode and promotion in the auricle were mainly responsible for reduced plant height and enlarged leaf angle in the Sdw3 mutant. Through positional cloning, we identified a transposon insertion in the candidate gene ZmACS7, encoding 1-aminocyclopropane-1-carboxylic acid (ACC) Synthase 7 in ethylene biosynthesis of maize. The transposon alters the C terminus of ZmACS7. Transgenic analysis confirmed that the mutant ZmACS7 gene confers the phenotypes of the Sdw3 mutant. Enzyme activity and protein degradation assays indicated that the altered C terminus of ZmACS7 in the Sdw3 mutant increases this protein's stability but does not affect its catalytic activity. The ACC and ethylene contents are dramatically elevated in the Sdw3 mutant, leading to reduced plant height and increased leaf angle. In addition, we demonstrated that ZmACS7 plays crucial roles in root development, flowering time, and leaf number, indicating that ZmACS7 is an important gene with pleiotropic effects during maize growth and development.