Elucidating the transport of water and ions in the nanochannel of covalent organic frameworks by molecular dynamics.

Inspired by biological channels, achieving precise separation of ion/water and ion/ion requires finely tuned pore sizes at molecular dimensions and deliberate exposure of charged groups. Covalent organic frameworks (COFs), a class of porous crystalline materials, offer well-defined nanoscale pores and diverse structures, making them excellent candidates for nanofluidic channels that facilitate ion and water transport. In this study, we perform molecular simulations to investigate the structure and kinetics of water and ions confined within the typical COFs with varied exposure of charged groups. The COFs exhibit vertically arrayed nanochannels, enabling diffusion coefficients of water molecules within COFs to remain within the same order of magnitude as in the bulk. The motion of water molecules manifests in two distinct modes, creating a mobile hydration layer around acid groups. The ion diffusion within COFs displays a notable disparity between monovalent (M+) and divalent (M2+) cations. As a result, the selectivity of M+/M2+ can exceed 100, while differentiation among M+ is less pronounced. In addition, our simulations indicate a high rejection (R > 98%) in COFs, indicating their potential as ideal materials for desalination. The chemical flexibility of COFs indicates that would hold significant promise as candidates for advanced artificial ion channels and separation membranes.

Full-length GSDME mediates pyroptosis independent from cleavage.

Gasdermin (GSDM) family proteins, known as the executors of pyroptosis, undergo protease-mediated cleavage before inducing pyroptosis. We here discovered a form of pyroptosis mediated by full-length (FL) GSDME without proteolytic cleavage. Intense ultraviolet-C irradiation-triggered DNA damage activates nuclear PARP1, leading to extensive formation of poly(ADP-ribose) (PAR) polymers. These PAR polymers are released to the cytoplasm, where they activate PARP5 to facilitate GSDME PARylation, resulting in a conformational change in GSDME that relieves autoinhibition. Moreover, ultraviolet-C irradiation promotes cytochrome c-catalysed cardiolipin peroxidation to elevate lipid reactive oxygen species, which is then sensed by PARylated GSDME, leading to oxidative oligomerization and plasma membrane targeting of FL-GSDME for perforation, eventually inducing pyroptosis. Reagents that concurrently stimulate PARylation and oxidation of FL-GSDME, synergistically promoting pyroptotic cell death. Overall, the present findings elucidate an unreported mechanism underlying the cleavage-independent function of GSDME in executing cell death, further enriching the paradigms and understanding of FL-GSDME-mediated pyroptosis.

Half-Sandwich Iridium Complexes: A Recyclable and Stable Catalyst for Dehydrogenation of Alcohols to Carboxylic Acids.

A series of acylhydrazone-based N,N-chelate half-sandwich iridium complexes have been synthesized through a facile route in good yields. The dehydrogenation of a series of aromatic and aliphatic primary alcohols to corresponding carboxylic acids has been accomplished catalyzed by the prepared air stable iridium complexes under mild reaction conditions. Carboxylic acids were obtained in high yields under open flask condition with broad substrates and good tolerance to sensitive functional groups. Such a half-sandwich iridium catalyst system exhibited high catalytic activity and stability, and a high TOF of 316.7 h-1 could be achieved with a catalyst loading as low as 0.05 mol %. Furthermore, the sustainable catalyst could be reused at least five times without obviously losing its activity, highlighting its potential application in industry. Molecular structure of iridium complex 1 was confirmed by single-crystal X-ray analysis.

[Air Pollutant Spatiotemporal Evolution Characteristics and Effects on Human Health in Xi'an City].

Xi'an is the political, economic, and cultural center of northwest China with a developed industry. Air pollution incidents have brought great challenges to the high-quality development of the social economy. It is vital to study air pollution characteristics and clarify their impact on human health. In this study, we first analyzed the spatiotemporal variations in air pollutants in the study region from 2015 to 2021. Then, the air quality index (AQI), aggregate air quality index (AAQI), and health risk-based air quality index (HAQI) were used to assess health risks. Based on these, the AirQ2.2.3 model was used to quantify health effects. The results showed that the major pollutants were PM10, PM2.5, and O3. The main pollution characteristics of the study area were terrain characteristics and the mixed pollution of anthropogenic emissions. Compared to that of AQI, AAQI and HAQI showed better classification performance for pollution levels. HAQI revealed that approximately 80 % of the population was exposed to unhealthy air throughout the year in the study region. People were most exposed to unhealthy air in winter, followed by autumn and spring, and the least in summer. The AirQ2.2.3 model quantified the total mortality proportions attributable to PM2.5, PM10, SO2, CO, NO2, and O3, which were 0.99 %, 2.04 %, 0.41 %, 1.72 %, 8.76 %, and 3.67 %, respectively. The attributable proportion of mortality of the respiratory system and cardiovascular diseases was consistent with the change rule of total mortality.

Heavy-Quark Pair Production at Lepton Colliders at NNNLO in QCD.

We compute the total cross section and invariant mass distribution for heavy-quark pair production in e^{+}e^{-} annihilation at the next-to-next-to-next-to-leading order in QCD. The obtained results are expressed as piecewise functions defined by several deeply expanded power series, facilitating a rapid numerical evaluation. Utilizing top-pair production at a collision energy of 500 GeV as a benchmark, we observe a correction of approximately 0.1% for the total cross section and around 10% for the majority of the invariant mass distribution range. These results play a crucial role in significantly reducing theoretical uncertainty: the scale dependence has been diminished to 0.06% for the total cross section and to 5% for the invariant mass distribution. This reduction of uncertainty meets the stringent requirements of future lepton colliders.

Visible-Light-Driven Inactivation of Bacteria and H2 Generation Catalyzed by Oxygen-Vacancy-Rich One-Dimensional/Two-Dimensional W18O49/g-C3N4 Z-Scheme Heterostructures.

Z-scheme heterostructure-based photocatalysts consist of a reduction photocatalyst and an oxidation photocatalyst, enabling them to possess a high capacity for both reduction and oxidation. However, the coupling reaction between photocatalytic H2 generation through water reduction and sterilization using Z-scheme systems has been rarely reported. Herein, 1D W18O49 nanowires embedded over 2D g-C3N4 nanosheets are well-constructed as an integrated Z-scheme heterojunction. Experimental results and density functional theory calculations not only demonstrate the achievement of efficient interfacial charge separation and transport, leading to prolonged lifetime of photogenerated charge carriers, but also directly confirm the mechanism of Z-scheme charge transfer. As expected, the optimized W18O49/g-C3N4 nanostructure exhibits superior photocatalytic sterilization activity against Staphylococcus aureus as well as excellent H2 generation performance under visible-light irradiation (λ ≥ 420 nm). Due to its nontoxic nature, W18O49/g-C3N4 holds great potential in eradicating bacterial infections in living organisms.

Sensing of mitochondrial DNA by ZBP1 promotes RIPK3-mediated necroptosis and ferroptosis in response to diquat poisoning.

Diquat (DQ) poisoning is a severe medical condition associated with life-threatening implications and multiorgan dysfunction. Despite its clinical significance, the precise underlying mechanism remains inadequately understood. This study elucidates that DQ induces instability in the mitochondrial genome of endothelial cells, resulting in the accumulation of Z-form DNA. This process activates Z-DNA binding protein 1 (ZBP1), which then interacts with receptor-interacting protein kinase 3 (RIPK3), ultimately leading to RIPK3-dependent necroptotic and ferroptotic signaling cascades. Specific deletion of either Zbp1 or Ripk3 in endothelial cells simultaneously inhibits both necroptosis and ferroptosis. This dual inhibition significantly reduces organ damage and lowers mortality rate. Notably, our investigation reveals that RIPK3 has a dual role. It not only phosphorylates MLKL to induce necroptosis but also phosphorylates FSP1 to inhibit its enzymatic activity, promoting ferroptosis. The study further shows that deletion of mixed lineage kinase domain-like (Mlkl) and the augmentation of ferroptosis suppressor protein 1 (FSP1)-dependent non-canonical vitamin K cycling can provide partial protection against DQ-induced organ damage. Combining Mlkl deletion with vitamin K treatment demonstrates a heightened efficacy in ameliorating multiorgan damage and lethality induced by DQ. Taken together, this study identifies ZBP1 as a crucial sensor for DQ-induced mitochondrial Z-form DNA, initiating RIPK3-dependent necroptosis and ferroptosis. These findings suggest that targeting the ZBP1/RIPK3-dependent necroptotic and ferroptotic pathways could be a promising approach for drug interventions aimed at mitigating the adverse consequences of DQ poisoning.

Engineering the thermal stability of a polyphosphate kinase by ancestral sequence reconstruction to expand the temperature boundary for an industrially applicable ATP regeneration system.

ATP-dependent energy-consuming enzymatic reactions are widely used in cell-free biocatalysis. However, the direct addition of large amounts of expensive ATP can greatly increase cost, and enzymatic production is often difficult to achieve as a result. Although a polyphosphate kinase (PPK)-polyphosphate-based ATP regeneration system has the potential to solve this challenge, the generally poor thermal stability of PPKs limits the widespread use of this method. In this paper, we evaluated the thermal stability of a PPK from Sulfurovum lithotrophicum (SlPPK2). After directed evolution and computation-supported design, we found that SlPPK2 is very recalcitrant and cannot acquire beneficial mutations. Inspired by the usually outstanding stability of ancestral enzymes, we reconstructed the ancestral sequence of the PPK family and used it as a guide to construct three heat-stable variants of SlPPK2, of which the L35F/T144S variant has a half-life of more than 14 h at 60°C. Molecular dynamics simulations were performed on all enzymes to analyze the reasons for the increased thermal stability. The results showed that mutations at these two positions act synergistically from the interior and surface of the protein, leading to a more compact structure. Finally, the robustness of the L35F/T144S variant was verified in the synthesis of nucleotides at high temperature. In practice, the use of this high-temperature ATP regeneration system can effectively avoid byproduct accumulation. Our work extends the temperature boundary of ATP regeneration and has great potential for industrial applications.IMPORTANCEATP regeneration is an important basic applied study in the field of cell-free biocatalysis. Polyphosphate kinase (PPK) is an enzyme tool widely used for energy regeneration during enzymatic reactions. However, the thermal stability of the PPKs reported to date that can efficiently regenerate ATP is usually poor, which greatly limits their application. In this study, the thermal stability of a difficult-to-engineer PPK from Sulfurovum lithotrophicum was improved, guided by an ancestral sequence reconstruction strategy. The optimal variant has a 4.5-fold longer half-life at 60°C than the wild-type enzyme, thus enabling the extension of the temperature boundary for ATP regeneration. The ability of this variant to regenerate ATP was well demonstrated during high-temperature enzymatic production of nucleotides.

Metabolomic and transcriptomic profiling reveals the effect of dietary protein and lipid levels on growth performance in loach (Paramisgurnus dabryanus).

The subject of this study was to explore the optimum requirements of loach (Paramisgurnus dabryanus) regarding dietary proteins and lipids and discuss the underlying mechanism. We designed nine diets to determine the effects of different levels of dietary crude protein (CP: 30%, 35%, and 40%) and ether extract (EE: 6%, 10%, and 14%) on the growth performance and metabolism of P. dabryanus. In total, 2160 healthy P. dabryanus (5.19 ± 0.01 g) were divided into nine groups with four replications at 60 fish per barrel stocking density. The trial lasted for eight weeks. Serum and liver samples were gathered for metabolomic and transcriptomic analyses. The results showed that the specific growth rate of P. dabryanus in the CP40EE10 group was the fastest and notably higher than that in other groups (P< 0.05). Analysis of the metabolome results found that the mTOR signaling pathway, glycerophospholipid metabolism, D-arginine and D-ornithine metabolism were significantly enriched pathways in the CP40EE10 group compared with the other groups (P< 0.05). Moreover, the transcriptomic analysis of differentially expressed genes (DEGs) showed that the expression of ARG (arginase) involved in protein synthesis was significantly upregulated in the CP40EE10 group compared to the slowest growing group (P< 0.05). Additionally, the expression of SPLA2 (secretory phospholipase A2) involved in lipid metabolism and FBP (fructose-1,6-bisphosphatase) involved in glucose metabolism were all significantly downregulated in the CP30EE6 group compared with the CP40EE10 group (P< 0.05). Furthermore, the analysis of differentially expressed metabolites (DEMs) and DEGs co-enriched in the KEGG pathway revealed that the significantly enriched pathways were arginine and proline metabolism, glycerophospholipid metabolism, and glycolysis/gluconeogenesis in CP40EE10 compared with other groups (P< 0.05). We conclude that including 40% CP and 10% EE in the P. dabryanus diet could result in a better growth rate. We hypothesized from metabolomic and transcriptomic analyses that the CP40EE10 diet might promote the growth of P. dabryanus by promoting protein synthesis, lipid metabolism, and energy production.

Dear-DIAXMBD: Deep Autoencoder Enables Deconvolution of Data-Independent Acquisition Proteomics.

Data-independent acquisition (DIA) technology for protein identification from mass spectrometry and related algorithms is developing rapidly. The spectrum-centric analysis of DIA data without the use of spectra library from data-dependent acquisition data represents a promising direction. In this paper, we proposed an untargeted analysis method, Dear-DIAXMBD, for direct analysis of DIA data. Dear-DIAXMBD first integrates the deep variational autoencoder and triplet loss to learn the representations of the extracted fragment ion chromatograms, then uses the k-means clustering algorithm to aggregate fragments with similar representations into the same classes, and finally establishes the inverted index tables to determine the precursors of fragment clusters between precursors and peptides and between fragments and peptides. We show that Dear-DIAXMBD performs superiorly with the highly complicated DIA data of different species obtained by different instrument platforms. Dear-DIAXMBD is publicly available at https://github.com/jianweishuai/Dear-DIA-XMBD.

Evaluation of DDA Library-Free Strategies for Phosphoproteomics and Ubiquitinomics Data-Independent Acquisition Data.

Phosphoproteomics and ubiquitinomics data-independent acquisition (DIA) mass spectrometry (MS) data is typically analyzed by using a data-dependent acquisition (DDA) spectral library. The performance of various library-free strategies for analyzing phosphoproteomics and ubiquitinomics DIA MS data has not been evaluated. In this study, we systematically compare four commonly used DDA library-free approaches including Spectronaut's directDIA, DIA-Umpire, DIA-MSFragger, and in silico-predicted library for analysis of phosphoproteomics SWATH, DIA, and diaPASEF data as well as ubiquitinomics diaPASEF data. Spectronaut's directDIA shows the highest sensitivity for phosphopeptide detection not only in synthetic phosphopeptide samples but also in phosphoproteomics SWATH-MS and DIA data from real biological samples, when compared to the other three library-free strategies. For phosphoproteomics diaPASEF data, Spectronaut's directDIA and the in silico-predicted library based on DIA-NN identify almost the same number of phosphopeptides as a project-specific DDA spectral library. However, only about 30% of the total phosphopeptides are commonly identified, suggesting that the library-free strategies for phospho-diaPASEF data need further improvement in terms of sensitivity. For ubiquitinomics diaPASEF data, the in silico-predicted library performs the best among the four workflows and detects ∼50% more K-GG peptides than a project-specific DDA spectral library. Our results demonstrate that Spectronaut's directDIA is suitable for the analysis of phosphoproteomics SWATH-MS and DIA MS data, while the in silico-predicted library based on DIA-NN shows substantial advantages for ubiquitinomics diaPASEF MS data.

Clinical effect and follow-up of laparoscopic radical proximal gastrectomy for upper gastric carcinoma.

Objective: To evaluate the safety and clinical effect of tubular esophagogastric anastomosis in laparoscopic radical proximal gastrectomy. Methods: A retrospective analysis was conducted involving 191 patients who underwent laparoscopic radical proximal gastrectomy in the Department of Gastrointestinal Surgery, Qilu Hospital of Shandong University from January 2017 to October 2020. Patients were divided into tubular esophagogastric anastomosis group (TG group) and traditional esophagogastric anastomosis group (EG group) according to the digestive tract reconstruction. Their intraoperative conditions, perioperative recovery and postoperative follow-up were compared. Patients were also divided into indocyanine green group and non-indocyanine green group according to whether or not indocyanine green tracer technology was used during the operation. Their intraoperative condition and perioperative recovery were compared and analyzed after propensity score matching. Results: The operation was successfully completed in all patients. Compared with the EG group, the TG group had less volume of gastric tube drainage, shorter gastric tube drainage time and proton pump inhibitors application time, and lower reuse rate of proton pump inhibitors. However, the TG group had a higher anastomotic stenosis at three months after surgery, as measured using anastomotic width and dysphagia score. Nevertheless, the incidence of reflux esophagitis and postoperative quality of life score in the TG group were lower compared with the EG group at 1st and 2nd year after surgery. In the indocyanine green analysis, the indocyanine green group had significantly shorter total operation time and lymph node dissection time and less intraoperative blood loss compared with the non-indocyanine green group. However, compared with the non-indocyanine green group, more postoperative lymph nodes were obtained in the indocyanine green group. Conclusion: Laparoscopic radical proximal gastrectomy is safe and effective treatment option for upper gastric cancer. Tubular esophagogastric anastomosis has more advantages in restoring postoperative gastrointestinal function and reducing reflux, but it has a higher incidence of postoperative anastomotic stenosis compared with traditional esophagogastrostomy. The application of indocyanine green tracer technique in laparoscopic radical proximal gastrectomy has positive significance.

The role of serum metrics in anti- VEGF treatment for macular edema induced by retinal vein occlusion.

AIM: To evaluate association between pretreatment serum metrics and best corrected visual acuity ( BCVA) of patients with macular edema secondary to retinal vein occlusion and its subtypes after intravitreal ranibizumab or conbercept implant. METHODS: This prospective research included 201 patients(201 eyes) who were diagnosed with macular edema secondary to retinal vein occlusion at Heibei Eye Hospital between January 2020 and January 2021, who all received intravitreal anti- vascular endothelial growth factor treatment. Serum metrics were measured before the first treatment, and correlations between BCVA and each of four parameters- platelets, neutrophil- to- lymphocyte ratio(NLR), platelet- to- lymphocyte ratio(PLR) and monocyte- to- lymphocyte ratio(MLR)- were analyzed to identify predictors of effective intravitreal injection treatment outcomes. RESULTS: The mean platelets was significantly different in the effective and ineffective group for RVO-ME (273.02 ± 41.49 × 109/L,214.54 ± 44.08 × 109/L P < 0.01),BRVO-ME (269.43 ± 49.52 × 109/L,214.72 ± 40.42 × 109/L P < 0.01), and CRVO-ME (262.32 ± 32.41 × 109/L,209.27 ± 42 0.91 × 109/L P < 0.01). The cutoff value of the platelets was 266.500, the area under the curve was 0.857,and the sensitivity and specificity were 59.8% and 93.6%, respectively. The mean PLR was significantly different in the effective and ineffective group for RVO-ME (154.66 ± 49.60, 122.77± 44.63 P < 0.01),BRVO-ME (152.24 ± 54.99, 124.72 ± 41.46 P = 0.003), and CRVO-ME (152.06±44.23, 118.67 ± 41.80 P = 0.001). The cutoff value of the platelets was 126.734, the area under the curve was 0.699, and the sensitivity and specificity were 70.7% and 63.3%, respectively. There were no statistical differencies between the effective and ineffective group(RVO- ME and its subtypes) in NLR and MLR. CONCLUSION: Higher pretreatment platelets and PLR were associated with BCVA in patients with RVO- ME and its subtypes who were treated with anti- VEGF drugs. The platelets and PLR may be used as predictive and prognostic tools for effective intravitreal injection treatment outcomes.

[Excess Oxygen Supply for Different Time Periods Affect Energy Metabolism in Rat Alveolar Epithelial Type â ¡ Cells].

Objective To observe the effect of excess oxygen supply for different time periods on the mitochondrial energy metabolism in alveolar epithelial type Ⅱ cells. Methods Rat RLE-6TN cells were assigned into a control group (21% O2 for 4 h) and excess oxygen supply groups (95% O2 for 1,2,3,and 4 h,res-pectively).The content of adenosine triphosphate (ATP),the activity of mitochondrial respiratory chain complex V,and the mitochondrial membrane potential were determined by luciferase assay,micro-assay,and fluorescent probe JC-1,respectively.Real-time fluorescence quantitative PCR was employed to determine the mRNA levels of NADH dehydrogenase subunit 1 (ND1),cytochrome b (Cytb),cytochrome C oxidase subunit I (COXI),and adenosine triphosphatase 6 (ATPase6) in the core subunits of mitochondrial respiratory chain complexes Ⅰ,Ⅲ,Ⅳ,and Ⅴ,respectively. Results Compared with the control group,excess oxygen supply for 1,2,3,and 4 h down-regulated the mRNA levels of ND1 (q=24.800,P<0.001;q=13.650,P<0.001;q=9.869,P<0.001;q=20.700,P<0.001),COXI (q=16.750,P<0.001;q=10.120,P<0.001;q=8.476,P<0.001;q=14.060,P<0.001),and ATPase6 (q=22.770,P<0.001;q=15.540,P<0.001;q=12.870,P<0.001;q=18.160,P<0.001).Moreover,excess oxygen supply for 1 h and 4 h decreased the ATPase activity (q=9.435,P<0.001;q=11.230,P<0.001) and ATP content (q=5.615,P=0.007;q=5.029,P=0.005).The excess oxygen supply for 2 h and 3 h did not cause significant changes in ATPase activity (q=0.156,P=0.914;q=3.197,P=0.116) and ATP content (q=0.859,P=0.557;q=1.273,P=0.652).There was no significant difference in mitochondrial membrane potential among the groups (F=0.303,P=0.869). Conclusion Short-term excess oxygen supply down-regulates the expression of the core subunits of mitochondrial respiratory chain complexes and reduces the activity of ATPase,leading to the energy metabolism disorder of alveolar epithelial type Ⅱ cells.

Surface-Dependent Hydrogen Evolution Activity of Copper Foil.

Single-crystal planes are ideal platforms for catalytic research. In this work, rolled copper foils with predominantly (220) planes were used as the starting material. By using temperature gradient annealing, which caused grain recrystallization in the foils, they were transformed to those with (200) planes. In acidic solution, the overpotential of such a foil (10 mA cm-2) was found to be 136 mV lower than that of a similar rolled copper foil. The calculation results show that hollow sites formed on the (200) plane have the highest hydrogen adsorption energy and are active centers for hydrogen evolution. Thus, this work clarifies the catalytic activity of specific sites on the copper surface and demonstrates the critical role of surface engineering in designing catalytic properties.

Cynasibirolide A, One New Humulanolide Sesquiterpene from Cynanchum acutum subsp. sibiricum.

Cynasibirolide A (1), one new humulanolide sesquiterpene, together with four known analogs, asteriscanolide (2), (1S,8S)-8-hydroxyhumula-2Z,6E,9E-trien-1,12-olide (3), (1S,7R)-8-oxohumula-2Z,9E-dien-1,12-olide (4), and (+)-6,7,9,10-tetrahydroasteriscunolide (5) were isolated from the roots and rhizomes of Cynanchum acutum subsp. sibiricum. Their structures and configurations were elucidated by spectroscopic methods, including 2D-NMR techniques, and the structure of 1 was confirmed by single-crystal X-ray diffraction. All compounds were evaluated for their anti-complementary activity in vitro, and compound 3 exhibited anti-complement effect with CH50 value of 0.45 mM.

Quantitative proteomic analysis of exosomes from umbilical cord mesenchymal stem cells and rat bone marrow stem cells.

Exosomes derived from mesenchymal stem cells (MSCs) have been used for cancer treatment, however, an in-depth analysis of the exosomal proteomes is lacking. In this manuscript, we use the diaPASEF (parallel accumulation serial fragmentation combined with the data-independent acquisition) method to quantify exosomes derived from human umbilical cord mesenchymal stem cells (UCMSCs) and rat bone marrow stem cells (BMSCs), resulting in identification of 4200 human proteins and 5362 rat proteins. Comparison of human exosomal proteins and total cellular proteins reveals that some proteins exist in the exosomes exclusively that can be served as potential markers for exosomes. Quantitative proteomic analysis of exosomes from different passages of BMSCs shows that the proteins involved in TGF-ß signaling pathway are regulated in abundance, which could be markers for the therapeutic ability of BMSC exosomes. Collectively, the data presented by this study can be a resource for further study of exosome research.