Regulating Cu Oxidation State for Electrocatalytic CO2 Conversion into CO with Near-Unity Selectivity via Oxygen Spillover.

Cu-based catalysts are the most intensively studied in the field of electrocatalytic CO2 reduction reaction (CO2RR), demonstrating the capacity to yield diverse C1 and C2+ products albeit with unsatisfactory selectivity. Manipulation of the oxidation state of Cu sites during CO2RR process proves advantageous in modulating the selectivity of productions, but poses a formidable challenge. Here, an oxygen spillover strategy is proposed to enhance the oxidation state of Cu during CO2RR by incorporating the oxygen donor Sb2O4. The Cu-Sb bimetallic oxide catalyst attains a remarkable CO2-to-CO selectivity approaching unity, in stark contrast to the diverse product distribution observed with bare CuO. The exceptional Faradaic efficiency of CO can be maintained across a wide range of potential windows of ≈700 mV in 1 m KOH, and remains independent of the Cu/Sb ratio (ranging from 0.1:1 to 10:1). Correlative calculations and experimental results reveal that oxygen spillover from Sb2O4 to Cu sites maintains the relatively high valence state of Cu during CO2RR, which diminishes the binding strength of *CO, thereby achieving heightened selectivity in CO production. These findings propose the role of oxygen spillover in CO2RR over Cu-based catalysts, and shed light on the rational design of highly selective CO2 reduction catalysts.

g-C3N4 as ballistic electron transport "Tunnel" in CsPbBr3-based ternary photocatalyst for gas phase CO2 reduction.

Perovskite CsPbBr3 quantum dot shows great potential in artificial photosynthesis, attributed to its outstanding optoelectronic properties. Nevertheless, its photocatalytic activity is hindered by insufficient catalytic active sites and severe charge recombination. In this work, a CsPbBr3@Ag-C3N4 ternary heterojunction photocatalyst is designed and synthesized for high-efficiency CO2 reduction. The CsPbBr3 quantum dots and Ag nanoparticles are chemically anchored on the surface of g-C3N4 sheets, forming an electron transfer tunnel from CsPbBr3 quantum dots to Ag nanoparticles via g-C3N4 sheets. The resulting CsPbBr3@Ag-C3N4 ternary photocatalyst, with spatial separation of photogenerated carriers, achieves a remarkable conversion rate of 19.49 µmol·g-1·h-1 with almost 100 % CO selectivity, a 3.13-fold enhancement in photocatalytic activity as compared to CsPbBr3 quantum dots. Density functional theory calculations reveal the rapid CO2 adsorption/activation and the decreased free energy (0.66 eV) of *COOH formation at the interface of Ag nanoparticles and g-C3N4 in contrast to the g-C3N4, leading to the excellent photocatalytic activity, while the thermodynamically favored CO desorption contributes to the high CO selectivity. This work presents an innovative strategy of constructing perovskite-based photocatalyst by modulating catalyst structure and offers profound insights for efficient CO2 conversion.

Age Gelation in Direct Steam Infusion Ultra-High-Temperature Milk: Different Heat Treatments Produce Different Gels.

To investigate the gelation process of direct ultra-high-temperature (UHT) milk, a pilot-scale steam infusion heat treatment was used to process milk samples over a wide temperature of 142-157 °C for 0.116-6 s, followed by storage at 4 °C, 25 °C, and 37 °C. The results of the physicochemical properties of milk showed that the particle sizes and plasmin activities of all milk samples increased during storage at 25 °C, but age gelation only occurred in three treated samples, 147 °C/6 s, 142 °C/6 s, and 142 °C/3 s, which all had lower plasmin activities. Furthermore, the properties of formed gels were further compared and analyzed by the measures of structure and intermolecular interaction. The results showed that the gel formed in the 147 °C/6 s-treated milk with a higher C* value had a denser network structure and higher gel strength, while the 142 °C/6 s-treated milk had the highest porosity. Furthermore, disulfide bonds were the largest contributor to the gel structure, and there were significant differences in disulfide bonds, hydrophobic interaction forces, hydrogen bonds, and electrostatic force among the gels. Our results showed that the occurrence of gel was not related to the thermal load, and the different direct UHT treatments produced different age gels in the milk.

Genetically determined type 1 diabetes mellitus and risk of osteoporosis.

BACKGROUND: Observational evidence suggests that type 1 diabetes mellitus (T1DM) is associated with the risk of osteoporosis (OP). Nevertheless, it is not apparent whether these correlations indicate a causal relationship. To elucidate the causal relationship, a two-sample Mendelian randomization (MR) analysis was performed. METHODS: T1DM data was obtained from the large genome-wide association study (GWAS), in which 6683 cases and 12,173 controls from 12 European cohorts were involved. Bone mineral density (BMD) samples at four sites were extracted from the GEnetic Factors for OSteoporosis (GEFOS) consortium, including forearm (FA) (n = 8,143), femoral neck (FN) (n = 32,735), lumbar spine (LS) (n = 28,498), and heel (eBMD) (n = 426,824). The former three samples were from mixed populations and the last one was from European. Inverse variance weighting, MR-Egger, and weighted median tests were used to test the causal relationship between T1DM and OP. A series of sensitivity analyses were then conducted to verify the robustness of the results. RESULTS: Twenty-three independent SNPs were associated with FN-BMD and LS-BMD, twenty-seven were associated with FA-BMD, and thirty-one were associated with eBMD. Inverse variance-weighted estimates indicated a causal effect of T1DM on FN-BMD (odds ratio (OR) =1.033, 95 % confidence interval (CI): 1.012-1.054, p = 0.002) and LS-BMD (OR = 1.032, 95 % CI: 1.005-1.060, p = 0.022) on OP risk. Other MR methods, including weighted median and MR-Egger, calculated consistent trends. While no significant causation was found between T1DM and the other sites (FA-BMD: OR = 1.008, 95 % CI: 0.975-1.043, p = 0.632; eBMD: OR = 0.993, 95 % CI: 0.985-1.001, p = 0.106). No significant heterogeneity (except for eBMD) or horizontal pleiotropy was found for instrumental variables, suggesting these results were reliable and robust. CONCLUSIONS: This study shows a causal relationship between T1DM and the risk of some sites of OP (FN-BMD, LS-BMD), allowing for continued research to discover the clinical and experimental mechanisms of T1DM and OP. It also contributes to the recommendation if patients with T1DM need targeted care to promote bone health and timely prevention of osteoporosis.

Destabilization of ultra-instantaneous UHT sterilization milk stored at different temperatures.

Ultra-instantaneous UHT (UI-UHT, > 155°C, < 0.1 s) treated milk exhibits higher retention of active protein than regular UHT milk. However, UI-UHT products demonstrate increased susceptibility to destabilization during storage. This study aimed at monitoring the destabilizing process of UI-UHT milk across different storage temperatures and uncovering its potential mechanisms. Compared with regular UHT treatment, ultra-instantaneous treatment markedly accelerated the milk's destabilization process. Aged gel formation occurred after 45 d of storage at 25°C, while creaming and sedimentation were observed after 15 d at 37°C. To elucidate the instability mechanism, measurements of plasmin activity, protein hydrolysis levels, and proteomics of the aged gel were conducted. In UI-UHT milk, plasmin activity, and protein hydrolysis levels significantly increased during storage. Excessive protein hydrolysis at 37°C resulted in sedimentation, while moderate hydrolysis and an increase in protein particle size at 25°C resulted in aged gel formation. Proteomics analysis results indicated that the aged gel from UI-UHT milk contained intact caseins, major whey proteins, and their derived peptides. Furthermore, specific whey proteins including albumin, lactotransferrin, enterotoxin-binding glycoprotein PP20K, and MFGM proteins were identified in the gel. Additionally, MFGM proteins in UI-UHT milk experienced considerable hydrolysis during storage, contributing to fat instability. This study lays a theoretical foundation for optimizing UI-UHT milk storage conditions to enhance the quality of liquid milk products.

Cloning and expression analysis of Janus activated kinase family genes from spotted seabass (Lateolabrax maculatus).

Janus kinases (JAKs) are important components of the JAK-STAT signaling pathway and play vital roles in innate immunity, autoimmune diseases, and inflammation. However, information about JAKs remains largely unknown in the spotted seabass, a fish species of Perciformes with great commercial value in the aquaculture industry. The aims of this study are to obtain the complete cDNA sequences of JAKs (JAK1, JAK2A, JAK2B, JAK3 and TYK2) from spotted seabass and to investigate their roles upon stimulation with lipopolysaccharides (LPS) and Edwardsiella tarda, using RT-PCR, PCR and qRT-PCR methods. All five JAK genes from the spotted seabass, each encode more than 1100 amino acids residues. JAK1 and JAK3 consist of 24 exons and 23 introns, whereas JAK2A, JAK2B and TYK2 consist of 23 exons and 22 introns. Furthermore, these five spotted seabass JAKs share high sequence identities with those of other fish species in protein domain analysis, synteny analysis, and phylogenetic analysis. Moreover, these five JAK genes were ubiquitously expressed in all tissues examined from healthy fish, and inducible expressions of JAKs were observed in the intestine, gill, head kidney, and spleen following LPS treatment or E. tarda infection. These findings indicate that all these JAK genes are involved in the antibacterial immunity of the spotted seabass and provide a basis for further understanding the mechanism of JAKs antibacterial response in the spotted sea bass.

Pulse pressure variation guided goal-direct fluid therapy decreases postoperative complications in elderly patients undergoing laparoscopic radical resection of colorectal cancer: a randomized controlled trial.

OBJECTIVE: The use of goal-directed fluid therapy (GDFT) has been shown to reduce complications and improve prognosis in high-risk abdominal surgery patients. However, the utilization of pulse pressure variation (PPV) guided GDFT in laparoscopic surgery remains a subject of debate. We hypothesized that utilizing PPV guidance for GDFT would optimize short-term prognosis in elderly patients undergoing laparoscopic radical resection for colorectal cancer compared to conventional fluid therapy. METHODS: Elderly patients undergoing laparoscopic radical resection of colorectal cancer were randomized to receive either PPV guided GDFT or conventional fluid therapy and explore whether PPV guided GDFT can optimize the short-term prognosis of elderly patients undergoing laparoscopic radical resection of colorectal cancer compared with conventional fluid therapy. RESULTS: The incidence of complications was significantly lower in the PPV group compared to the control group (32.8% vs. 57.1%, P = .009). Additionally, the PPV group had a lower occurrence of gastrointestinal dysfunction (19.0% vs. 39.3%, P = .017) and postoperative pneumonia (8.6% vs. 23.2%, P = .033) than the control group. CONCLUSION: Utilizing PPV as a monitoring index for GDFT can improve short-term prognosis in elderly patients undergoing laparoscopic radical resection of colorectal cancer. REGISTRATION NUMBER: ChiCTR2300067361; date of registration: January 5, 2023.

Selecting Monoclonal Cell Lineages from Somatic Reprogramming Using Robotic-Based Spatial-Restricting Structured Flow.

Somatic cell reprogramming generates induced pluripotent stem cells (iPSCs), which serve as a crucial source of seed cells for personalized disease modeling and treatment in regenerative medicine. However, the process of reprogramming often causes substantial lineage manipulations, thereby increasing cellular heterogeneity. As a consequence, the process of harvesting monoclonal iPSCs is labor-intensive and leads to decreased reproducibility. Here, we report the first in-house developed robotic platform that uses a pin-tip-based micro-structure to manipulate radial shear flow for automated monoclonal iPSC colony selection (~1 s) in a non-invasive and label-free manner, which includes tasks for somatic cell reprogramming culturing, medium changes; time-lapse-based high-content imaging; and iPSCs monoclonal colony detection, selection, and expansion. Throughput-wise, this automated robotic system can perform approximately 24 somatic cell reprogramming tasks within 50 days in parallel via a scheduling program. Moreover, thanks to a dual flow-based iPSC selection process, the purity of iPSCs was enhanced, while simultaneously eliminating the need for single-cell subcloning. These iPSCs generated via the dual processing robotic approach demonstrated a purity 3.7 times greater than that of the conventional manual methods. In addition, the automatically produced human iPSCs exhibited typical pluripotent transcriptional profiles, differentiation potential, and karyotypes. In conclusion, this robotic method could offer a promising solution for the automated isolation or purification of lineage-specific cells derived from iPSCs, thereby accelerating the development of personalized medicines.

Progress in the study of reproductive toxicity of platinum-based antitumor drugs and their means of prevention.

Platinum-based antitumor drugs are broad-spectrum agents with unique mechanisms of action. Combination chemotherapy regimens based on platinum drugs are commonly used in cancer treatment. However, these drugs can cause various adverse reactions in the human body through different routes of administration, including reproductive toxicity, genetic toxicity, and embryonic developmental toxicity. Preventing adverse effects is crucial to enhance patients' quality of life and reduce healthcare costs. This article discusses the types and developmental history of antitumor active platinum compounds, their mechanisms of action, routes of administration, and their potential reproductive, genetic, and embryonic developmental toxicity. This text explores preventive measures based on animal experimental results. Its aim is to provide references for personalized treatment and occupational protection when using platinum drugs. The continuous progress of science and technology, along with the deepening of medical research, suggests that the application of platinum drugs will broaden. Therefore, the development of new platinum drugs will be an important direction for future research.

Preparation of pH-responsive chitosan microspheres containing aminopeptidase and their application in accelerating cheese ripening.

Microencapsulated enzymes have been found to effectively accelerate cheese ripening. However, microencapsulated enzyme release is difficult to control, often resulting in enzyme release during cheese processing, and causing texture and flavor defects. This study aims to address this issue by developing aminopeptidase-loaded pH-responsive chitosan microspheres (A-CMs) for precise enzyme release during cheese ripening. An aminopeptidase with an isoelectric point (pH 5.4) close to the pH value of cheese ripening was loaded on chitosan microspheres through electrostatic interaction. Turbidity titration measurements revealed that pH 6.5 was optimal for binding aminopeptidase and microspheres, affording the highest loading efficiency of 58.16%. Various characterization techniques, including scanning electron microscopy, energy dispersive spectroscopy, and fourier-transform infrared spectroscopy confirmed the successful loading of aminopeptidase molecules on the chitosan microspheres. In vitro release experiments conducted during simulated cheese production demonstrated that aminopeptidase release from A-CMs was pH-responsive. The microspheres retained the enzyme during the coagulation and cheddaring processes (pH 5.5-6.5), and only released it after entering the cheese ripening stage (pH 5.0-5.5). By loading aminopeptidase on chitosan microspheres, the loss rate of the enzyme in cheese whey was reduced by approximately 79%. Furthermore, compared with cheese without aminopeptidase and cheese with aminopeptidase added directly, the cheeses made with A-CMs exhibited the highest proteolysis level and received superior sensory ratings for taste and smell. The content of key aroma substances, such as 2/3-methylbutanal and ethyl butyrate in cheese with A-CMs was more than 15 times higher than the others. This study provides an approach for accelerating cheese ripening through the use of microencapsulated enzymes.

Molecular characterization, expression analysis and subcellular location of the members of STAT family from spotted seabass (Lateolabrax maculatus).

The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway is a pervasive intracellular signal transduction pathway, involving in biological processes such as cell proliferation, differentiation, apoptosis and immune regulation. In this study, seven STAT genes, STAT1, STAT1-like, STAT2, STAT3, STAT4, STAT5a and STAT5b, were identified and characterized in spotted seabass (Lateolabrax maculatus). Analyses of multiple sequence alignment, genomic organization, phylogeny and conserved synteny were conducted to infer the evolutionary conservation of these genes in the STAT family. The results of the bioinformatics analysis assumed that STAT1 and STAT1-like might be homologous to STAT1a and STAT1b, respectively. Furthermore, the expression of the seven genes were detected in eight tissues of healthy spotted seabass, which revealed that they were expressed in a variety of tissues, mainly in gill, spleen and muscle, and extremely under-expression in liver. The expression of the seven genes in gill, head-kidney, spleen and intestine were significantly induced by lipopolysaccharide (LPS) or Edwardsiella tarda challenge. The expression of most of the LmSTATs were up-regulated, and the highest expression levels at 12 h after LPS stimulation, however, the LmSTATs were down-regulated by E. tarda infection. The results of subcellular localization show that the native LmSTAT1, LmSTAT1-like, LmSTAT2, LmSTAT3 and LmSTAT5a were localized in the cytoplasm, but they were translocated into the nucleus after LPS stimulation. Whereas, LmSTAT4 and LmSTAT5b were translocation into the nucleus whether with LPS stimulation or not. Overall, this is the first study to systematically revealed the localization of STAT members in fish, and indicated that LmSTATs participate in the process of protecting the host from pathogens invasion in the form of entry into nucleus.

Efficacy and Safety of Biosimilar QL1207 vs. the Reference Aflibercept for Patients with Neovascular Age-Related Macular Degeneration: A Randomized Phase 3 Trial.

INTRODUCTION: This trial aimed to compare the efficacy and safety between biosimilar QL1207 and the reference aflibercept for the treatment of neovascular age-related macular degeneration (nAMD). METHODS: This randomized, double-blind, phase 3 trial was conducted at 35 centers in China. Patients aged ≥ 50 years old with untreated subfoveal choroidal neovascularization secondary to nAMD and best-corrected visual acuity (BCVA) letter score of 73-34 were eligible. Patients were randomly assigned to receive intravitreous injections of QL1207 or aflibercept 2 mg (0.05 ml) in the study eye every 4 weeks for the first 3 months, followed by 2 mg every 8 weeks until week 48, stratified by baseline BCVA ≥ or < 45 letters. The primary endpoint was BCVA change from baseline at week 12. The equivalence margin was ± 5 letters. The safety, immunogenicity, pharmacokinetics (PK), and plasma vascular endothelial growth factor (VEGF) concentration were also evaluated. RESULTS: A total of 366 patients were enrolled (QL1207 group, n = 185; aflibercept group, n = 181) from Aug 2019 to Jan 2022 with comparable baseline characteristics. The least-squares mean difference in BCVA changes was - 1.1 letters (95% confidence interval - 3.0 to 0.7; P = 0.2275) between the two groups, within the equivalence margin. The incidences of treatment-emergent adverse events (TEAE; QL1207: 71.4% [132/185] vs. aflibercept: 71.8% [130/181]) and serious TEAE (QL1207: 14.1% [26] vs. aflibercept: 12.7% [23]) appeared comparable between treatment groups, and no new safety signal was found. Anti-drug antibody, PK profiles, and VEGF concentration were similar between the two groups. CONCLUSIONS: QL1207 has equivalent efficacy to aflibercept for nAMD with similar safety profiles. It could be used as an alternative anti-VEGF agent for clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05345236 (retrospectively registered on April 25, 2022); National Medical Products Administration of China: CTR20190937 (May 20, 2019).

Endoscopic management of duodenal perforation caused by foreign bodies in adults: A retrospective study.

BACKGROUND AND AIMS: Duodenal perforation caused by foreign bodies (FBs) is very rare but is an urgent emergency that traditionally requires surgical intervention. Several case reports have reported the successful endoscopic removal of duodenal perforating FBs. Here we aimed to evaluate the safety and efficacy of endoscopic management of duodenal perforating FBs in adults. METHODS: Between October 2004 and October 2022, 12,851 patients with endoscopically diagnosed gastrointestinal FBs from four tertiary hospitals in China were retrospectively reviewed. Patients were enrolled if they were endoscopically and/or radiographically diagnosed with duodenal perforating FBs. RESULTS: The incidence of duodenal total FBs and perforating FBs was 1.9% and 0.3%, respectively. Thirty-four patients were enrolled. Endoscopic removal was achieved in 25 patients (73.5%), and nine patients (26.5%) received surgery. For the endoscopic group, most perforating FBs were located in the duodenal bulb (36.0%) and descending part (28.0%). The adverse events included 3 mucosal injuries and 1 localized peritonitis. All patients were cured after conventional treatment. In the surgical group, most FBs were lodged in the descending part (55.6%). One patient developed localized peritonitis and one patient died of multiple organ failure. The significant features of FBs requiring surgery included FB over 10 cm, both sides perforation, multiple perforating FBs and massive pus overflow. CONCLUSION: Endoscopic removal of duodenal perforating FBs is safe and effective, and can be the first choice of treatment for experienced endoscopists. Surgical intervention may be required for patients with FBs over 10 cm, both sides perforation, multiple perforating FBs, or severe infections.

Mitigating Lattice Distortion of High-Voltage LiCoO2 via Core-Shell Structure Induced by Cationic Heterogeneous Co-Doping for Lithium-Ion Batteries.

Inactive elemental doping is commonly used to improve the structural stability of high-voltage layered transition-metal oxide cathodes. However, the one-step co-doping strategy usually results in small grain size since the low diffusivity ions such as Ti4+ will be concentrated on grain boundaries, which hinders the grain growth. In order to synthesize large single-crystal layered oxide cathodes, considering the different diffusivities of different dopant ions, we propose a simple two-step multi-element co-doping strategy to fabricate core-shell structured LiCoO2 (CS-LCO). In the current work, the high-diffusivity Al3+/Mg2+ ions occupy the core of single-crystal grain while the low diffusivity Ti4+ ions enrich the shell layer. The Ti4+-enriched shell layer (~ 12 nm) with Co/Ti substitution and stronger Ti-O bond gives rise to less oxygen ligand holes. In-situ XRD demonstrates the constrained contraction of c-axis lattice parameter and mitigated structural distortion. Under a high upper cut-off voltage of 4.6 V, the single-crystal CS-LCO maintains a reversible capacity of 159.8 mAh g-1 with a good retention of ~ 89% after 300 cycles, and reaches a high specific capacity of 163.8 mAh g-1 at 5C. The proposed strategy can be extended to other pairs of low- (Zr4+, Ta5+, and W6+, etc.) and high-diffusivity cations (Zn2+, Ni2+, and Fe3+, etc.) for rational design of advanced layered oxide core-shell structured cathodes for lithium-ion batteries.

Simultaneously Improved Activity and Stability for Acidic Water Oxidation of IrRu Oxides by a Dual Role of Tungsten Doping.

Acidic oxygen evolution reaction (OER) remains a significant challenge due to the low activity and/or poor stability of the catalysts, even with state-of-the-art catalysts such as IrO2 and RuO2. Herein, we propose a strategy to enhance both the catalytic activity and stability of IrRu oxides for acidic OER by doping non-noble metal W. The W-doped IrRu3Ox (W-IrRu3Ox) undergoes a process of W leaching and reconstruction during the OER, leading to a more uniform distribution of elements, while the electronegative nature of W influences the electronic structures of Ir and Ru in W-IrRu3Ox. The dual role of W in promoting the formation of active site Ir5+ and inhibiting the concentration of soluble Ru>4+ ions results in a synergistic enhancement of both the activity and stability of acidic OER. Remarkably, W-IrRu3Ox exhibits outstanding catalytic activity for the OER in 0.5 M H2SO4, with a high stability of more than 500 h. This work presents a novel and feasible strategy for the development of efficient and stable catalysts for acid OER, shedding light on the design of advanced electrocatalysts for energy conversion and storage applications.

Genetic evidence for causal effects of leukocyte counts on risk for rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by the accumulation of leukocytes and inflammatory mediators within the synovial tissue. Leukocyte counts are proposed to play a role in the pathogenesis of RA. However, the causality remains unclear. To investigate the causal relationship between various leukocytes and RA by implementing two-sample univariable Mendelian Randomization (MR) and multivariable MR. MR analysis was performed using respective genome-wide association study (GWAS) summary statistics for the exposure traits (eosinophil counts, neutrophil counts, lymphocyte counts, monocyte counts, basophil counts, and white blood cell counts) and outcome trait (RA). Summary statistics for leukocytes were extracted from the Blood Cell Consortium meta-analysis and INTERVAL studies. Public GWAS information for RA included 14,361 cases and 43,923 controls. Inverse variance weighted, weighted median, MR-Egger regression, MR pleiotropy residual sum and outlier, and multivariable MR analyses were performed in MR analysis. Univariable MR found elevated eosinophil counts (OR 1.580, 95% CI 1.389-2.681, p = 1.30 × 10-7) significantly increased the risk of RA. Multivariable MR further confirmed that eosinophil counts were a risk factor for RA. Increased eosinophils were associated with higher risk of RA. Further elucidations of the causality and mechanisms underlying are likely to identify feasible interventions to promote RA prevention.

Genetic Evidence Supporting a Causal Association Between mTOR-Dependent EIF-4E Circulating Protein Level and Osteoporosis.

INTRODUCTION: The mechanistic target of rapamycin (mTOR) regulates bone homeostasis, a crucial factor in osteoporosis (OP) development. However, most research is based on observational studies, and the causality remains uncertain. Therefore, we analyzed two samples of mendelian randomization (MR) to determine whether there is a causal relationship between mTOR-dependent circulating proteins and OP. METHODS: Mendelian weighting (weighted median [WM], inverse variance weighting [IVW], and MR-Egger regression) were applied to analyze the causality between bone phenotypes (bone mineral density [BMD] in forearm, femoral neck, lumbar spine, and heel) and mTOR-dependent circulating proteins (RP-S6K, 4EBP, EIF-4E, EIF-4A, and EIF-4G). Horizontal pleiotropy and heterogeneities were detected using Cochran's Q test, MR-Pleiotropy RE-Sidual Sum and Outlier (MR-PRESSO), and "leave-one-out" analysis. The proteomics-GWAS INTERVAL study was used to select the instrumental variables (IVs) for mTOR proteins. RESULTS: As phenotypes for OP, estimations of BMD were taken in four different sites: forearm (FA) (n = 8143), femoral neck (FN) (n = 32,735), lumbar spine (LS) (n = 28,498), and heel (eBMD) (n = 426,824). Based on IVW analysis, EIF4E is causally related to FA-BMD (OR = 0.938, 95% CI 0.887, 0.991, p = 0.024) but not to BMD elsewhere. CONCLUSION: MR analysis revealed a causal relationship between EIF-4E and FA-BMD, which may provide new insights into the underlying pathogenesis of OP and a new therapeutic target for OP.

Ternary choline chloride/benzene sulfonic acid/ethylene glycol deep eutectic solvents for oxidative desulfurization at room temperature.

Deep eutectic solvents (DESs) have been extensively studied as promising green solvents to attain a better removal efficiency of sulfide. A new DES system formed from choline chloride (ChCl), benzene sulfonic acid (BSA), and ethylene glycol (EG) as a class of ternary DESs was prepared and used in the oxidative desulfurization (ODS) of different sulfides. Ternary DESs have distinct advantages such as volatility and high activity compared with organic acid-based binary DESs. Under the optimum conditions with VDES/VOil = 1 : 5, O/S (molar ratio of oxygen to sulfur) = 5, and T = 25 °C, the desulfurization efficiencies of dibenzothiophene (DBT), 4,6-dimethyldibenzothiophene (4,6-DMDBT), and benzothiophene (BT) were all achieved to 100% in 2 h. Through experimental and density functional theory (DFT) calculation methods, this new system as a class of ternary DESs shows good stability and excellent desulfurization performance at room temperature. The investigation of this study could supply a new idea of ternary DESs for oxidative desulfurization.

Dynamic Surface Reconstruction of Amphoteric Metal (Zn, Al) Doped Cu2 O for Efficient Electrochemical CO2 Reduction to C2+ Products.

The recognition of the surface reconstruction of the catalysts during electrochemical CO2 reduction (CO2RR) is essential for exploring and comprehending active sites. Although the superior performance of Cu-Zn bimetallic sites toward multicarbon C2+ products has been established, the dynamic surface reconstruction has not been fully understood. Herein, Zn-doped Cu2 O nano-octahedrons are used to investigate the effect of the dynamic stability by the leaching and redeposition on CO2RR. Correlative characterizations confirm the Zn leaching from Zn-doped Cu2 O, which is redeposited at the surface of the catalysts, leading to dynamic stability and abundant Cu-Zn bimetallic sites at the surface. The reconstructed Zn-doped Cu2 O catalysts achieve a high Faradaic efficiency (FE) of C2+ products (77% at -1.1 V versus reversible hydrogen electrode (RHE)). Additionally, similar dynamic stability is also discovered in Al-doped Cu2 O for CO2RR, proving its universality in amphoteric metal-doped catalysts. Mechanism analyses reveal that the OHC-CHO pathway can be the C-C coupling processes on bare Cu2 O and Zn-doped Cu2 O, and the introduction of Zn to Cu can efficiently lower the energy barrier for CO2RR to C2 H4 . This research provides profound insight into unraveling surface dynamic reconstruction of amphoteric metal-containing electrocatalysts and can guide rational design of the high-performance electrocatalysts for CO2RR.

Comprehensive analysis of the role of a four-gene signature based on EMT in the prognosis, immunity, and treatment of lung squamous cell carcinoma.

Epithelial-mesenchymal transition (EMT), a biological process through which epithelial cells transform into mesenchymal cells, contributes to tumor progression and metastasis. However, a comprehensive analysis of the role of EMT-related genes in Lung squamous cell carcinoma (LUSC) is still lacking. In this study, data were downloaded from available databases, including The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database. The association between differentially expressed EMT-related genes (EMT-RDGs) and LUSC prognosis, drug sensitivity, mutation, and immunity was analyzed using bioinformatics methods. In the results, Lasso and univariate Cox regression analyses identified four EMT-RDGs that were differentially expressed, and used to establish a prognostic model capable of distinguishing between high- and low-risk groups. Then, prognostic factors were identified by multivariate Cox regression analysis and used to construct a nomogram. The high-risk group had a significantly poorer prognosis than the low-risk group. The tumor immune environment was significantly different between the two groups, with the low-risk group exhibiting a better response to immunotherapy. In addition, the half-maximal inhibitory concentration prediction indicating that the constructed model could effectively predict sensitivity to chemotherapy. This study provides new reference for further exploration of new clinical therapeutic strategies for LUSC.