A hybrid finite-discrete element method for modelling cracking processes in sandy mudstone containing a single edge-flaw under cyclic dynamic loading.

Rock mass deformation and failure are macroscopic manifestations of crack initiation, propagation, and coalescence. However, simulating the transition of rocks from continuous to discontinuous media under cyclic dynamic loading remains challenging. This study proposes a hybrid finite-discrete element method (HFDEM) to model crack propagation, incorporating a frequency-dependent cohesive-zone model. The mechanical properties of standard sandy mudstone under quasi-static and cyclic dynamic loading were simulated using HFDEM, and the method's reliability was verified through experimental comparison. The comparative analysis demonstrates that HFDEM successfully captures crack interaction mechanisms and accurately simulates the overall failure behavior of specimens. Additionally, the effects of pre-existing flaw inclination angle and dynamic loading frequency on rock failure mechanisms were investigated. The numerical results reveal that rock samples exhibit significantly higher compressive strength under dynamic loading compared to quasi-static loading, with compressive strength increasing with higher cyclic dynamic load frequencies. Furthermore, by analyzing the strength characteristics, crack propagation, and failure modes of the samples, insights into the failure mechanisms of rocks under different frequency loads were obtained. This study provides valuable insights into crack development and failure of rocks under seismic loads, offering guidance for engineering practices.

Pore Environmental Modification by Amino Groups in Robust Microporous MOFs for SF6 Capturing and SF6/N2 Separation.

Capturing and separating the greenhouse gas SF6 from nitrogen N2 have significant greenhouse mitigation potential and economic benefits. We used a pore engineering strategy to manipulate the pore environment of the metal-organic framework (MOF) by incorporating organic functional groups (-NH2). This resulted in an enhanced adsorption of SF6 and separation of the SF6/N2 mixture in the MOF. The introduction of amino (-NH2) groups into YTU-29 resulted in a reduction of the Brunauer-Emmett-Teller surface but an increase in interactions with SF6 within the confined pores. Water-stable YTU-29-NH2 showed a significantly higher SF6 uptake (95.5 cm3/g) than YTU-29 (77.4 cm3/g). The results of the breakthrough experiments show that YTU-29-NH2 has a significantly improved separation performance for SF6/N2 mixtures, with a high SF6 capture of 0.88 mmol/g compared to 0.56 mmol/g by YTU-29. This improvement is due to the suitable pore confinement and accessible -NH2 groups on pore surfaces. Considering its excellent regeneration ability and cycling performance, ultrastable YTU-29-NH2 demonstrates great potential for SF6 capturing and SF6/N2 separation.

Multifunctional Biomimetic Nanocarriers for Dual-Targeted Immuno-Gene Therapy Against Hepatocellular Carcinoma.

Growing evidences have proved that tumors evade recognition and attack by the immune system through immune escape mechanisms, and PDL1/Pbrm1 genes have a strong correlation with poor response or resistance to immune checkpoint blockade (ICB) therapy. Herein, a multifunctional biomimetic nanocarrier (siRNA-CaP@PD1-NVs) is developed, which can not only enhance the cytotoxic activity of immune cells by blocking PD1/PDL1 axis, but also reduce tumor immune escape via Pbrm1/PDL1 gene silencing, leading to a significant improvement in tumor immunosuppressive microenvironment. Consequently, the nanocarrier promotes DC cell maturation, enhances the infiltration and activity of CD8+ T cells, and forms long-term immune memory, which can effectively inhibit tumor growth or even eliminate tumors, and prevent tumor recurrence and metastasis. Overall, this study presents a powerful strategy for co-delivery of siRNA drugs, immune adjuvant, and immune checkpoint inhibitors, and holds great promise for improving the effectiveness and safety of current immunotherapy regimens.

Epidemiology and etiology of hand, foot, and mouth disease in Zhengzhou, China, from 2009 to 2021.

Background: Hand, foot, and mouth disease (HFMD) is a common childhood infectious disease caused by a variety of enteroviruses (EVs). To explore the epidemiological characteristics and etiology of HFMD in Zhengzhou, China, we conducted a systematic analysis of HFMD surveillance data from Zhengzhou Center for Disease Control and Prevention from January 2009 to December 2021 (https://wjw.zhengzhou.gov.cn/). Methods: Surveillance data were collected from Zhengzhou Center for Disease Control and Prevention from January 2009 to December 2021 (https://wjw.zhengzhou.gov.cn/). Cases were analyzed according to the time of onset, type of diagnosis, characteristics, viral serotype, and epidemiological trends. Results: We found that the primary causative agent responsible for the HFMD outbreaks in Zhengzhou was Enterovirus A71 (EVA-71) (48.56%) before 2014. After 2015, other EVs gradually became the dominant strains (57.68%). The data revealed that the HFMD epidemics in Zhengzhou displayed marked seasonality, with major peaks occurring from April to June, followed by secondary peaks from October to November, except in 2020. Both the severity and case-fatality ratio of HFMD decreased following the COVID-19 pandemic (severity ‰: 13.46 vs. 0.17; case-fatality ‰: 0.21 vs. 0, respectively). Most severe cases were observed in patients aged 1 year and below, accounting for 45.81%. Conclusions: Overall, the incidence rate of HFMD decreased in Zhengzhou following the introduction of the EVA-71 vaccine in 2016. However, it is crucial to acknowledge that HFMD prevalence continues to exhibit a distinct seasonal pattern and periodicity, and the occurrence of other EV infections poses a new challenge for children's health.

Efficient Vibration Measurement and Modal Shape Visualization Based on Dynamic Deviations of Structural Edge Profiles.

As a non-contact method, vision-based measurement for vibration extraction and modal parameter identification has attracted much attention. In most cases, artificial textures are crucial elements for visual tracking, and this feature limits the application of vision-based vibration measurement on textureless targets. As a computation technique for visualizing subtle variations in videos, the video magnification technique can analyze modal responses and visualize modal shapes, but the efficiency is low, and the processing results contain clipping artifacts. This paper proposes a novel method for the application of a modal test. In contrast to the deviation magnification that exaggerates subtle geometric deviations from only a single image, the proposed method extracts vibration signals with sub-pixel accuracy on edge positions by changing the perspective of deviations from space to timeline. Then, modal shapes are visualized by decoupling all spatial vibrations following the vibration theory of continuous linear systems. Without relying on artificial textures and motion magnification, the proposed method achieves high operating efficiency and avoids clipping artifacts. Finally, the effectiveness and practical value of the proposed method are validated by two laboratory experiments on a cantilever beam and an arch dam model.

Clinical characteristics and outcomes of lung transplantation in patients with severe COVID-19 infection: A systematic review and meta-analysis.

OBJECTIVES: To synthesize the clinical experience of patients with COVID-19-associated acute respiratory distress syndrome (ARDS) or pulmonary fibrosis (PF) receiving lung transplantation (LTx) and compare the characteristics and outcomes of COVID-19 and non-COVID-19 LTx patients. METHODS: A literature search of online databases (PubMed, Web of Science, Embase, the Cochrane Library, China Science and Technology Journal Database, and Wan Fang databases) was performed regarding LTx for COVID-19-associated ARDS or PF. This study was registered on PROSPERO (CRD2024507647). RESULTS: Eight eligible studies were included with 478 COVID-19 LTx patients and 163 non-COVID-19 LTx patients. In COVID-19 LTx patients, the pooled hospital mortality and follow-up survival rate was 0.00% (95%CI 0.00-0.03) and 87.40% (95%CI 0.76-0.96). Compared to non-COVID-19 LTx patients, COVID-19 LTx patients were associated with significantly higher rate of primary graft dysfunction (odds ratio [OR] 8.72, 95%CI 3.54-21.47, P < 0.001) but significantly higher follow-up survival rate (OR 2.48, 95%CI 1.02-6.01, P = 0.04), within an overall similar follow-up period. CONCLUSIONS: For patients with COVID-19-associated ARDS or PF, LTx offers acceptable short-term outcomes and is suggested as a viable lifesaving treatment.

Nitrogen-Mediated Promotion of Cobalt-Based Oxygen Evolution Catalyst for Practical Anion-Exchange Membrane Electrolysis.

Scarce and expensive iridium oxide is still the cornerstone catalyst of polymer-electrolyte membrane electrolyzers for green hydrogen production because of its exceptional stability under industrially relevant oxygen evolution reaction (OER) conditions. Earth-abundant transition metal oxides used for this task, however, show poor long-term stability. We demonstrate here the use of nitrogen-doped cobalt oxide as an effective iridium substitute. The catalyst exhibits a low overpotential of 240 mV at 10 mA cm-2 and negligible activity decay after 1000 h of operation in an alkaline electrolyte. Incorporation of nitrogen dopants not only triggers the OER mechanism switched from the traditional adsorbate evolution route to the lattice oxygen oxidation route but also achieves oxygen nonbonding (ONB) states as electron donors, thereby preventing structural destabilization. In a practical anion-exchange membrane water electrolyzer, this catalyst at anode delivers a current density of 1000 mA cm-2 at 1.78 V and an electrical efficiency of 47.8 kW-hours per kilogram hydrogen.

Injectable and Near-Infrared Light-Controllable Fibrin Hydrogels with Antimicrobial and Immunomodulating Properties for Infected Wound Healing.

The management of infected wounds poses a significant challenge due to the growing issue of antibiotic resistance, underscoring the urgent necessity to innovate and implement alternative therapeutic strategies. These strategies should be capable of eliminating bacterial infections in infected wounds while circumventing the induction of multi-drug resistance. In the current study, we developed an easily prepared and injectable fibrin gel (FG) loaded with nanoparticles (NPs) that exhibit antibacterial and immunomodulatory properties to facilitate the healing of infected wounds. Initially, a novel type of NP was generated through the electrostatic interaction between the photothermal agent, mPEG-modified polydopamine (MPDA), and the nitric oxide (NO) donor, S-nitrosocysteamine (SNO). This interaction resulted in the formation of NPs referred to as SNO-loaded MPDA (SMPDA). Subsequently, the SMPDA was encapsulated into the FG using a double-barreled syringe, thereby producing the SMPDA-loaded FG (SMPDA/G). Experimental results revealed that SMPDA/G could effectively eliminate bacterial infections and alter the immune microenvironment. This efficacy is attributed to the synergistic combination of NO therapy and photothermal therapy, along with the role of SMPDA in facilitating M2 macrophage polarization within the gel. Accordingly, these findings suggest that the SMPDA/G holds substantial promise for clinical application in infected wound healing.

Exploring the evolving roles and clinical significance of circRNAs in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) represents the predominant malignancies in the head and neck region, and has limited therapeutic alternatives. Circular RNAs (circRNAs), a substantial category of non-coding RNA molecules, exert influential roles in human disease development and progression, employing various mechanisms such as microRNA sponging, interaction with RNA-binding proteins, and translational capabilities. Accumulating evidence highlights the differential expression of numerous circRNAs in HNSCC, and numerous dysregulated circRNAs underscore their crucial involvement in malignant advancement and resistance to treatment. This review aims to comprehensively outline the characteristics, biogenesis, and mechanisms of circRNAs, elucidating their functional significance in HNSCC. In addition, we delve into the clinical implications of circRNAs, considering their potential as biomarkers or targets for diagnosis, prognosis, and therapeutic applications in HNSCC. The discussion extends to exploring future challenges in the clinical translation of circRNAs, emphasizing the need for further research.

Survival outcomes of segmentectomy and lobectomy for early stage non-small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: The question of whether segmentectomy and lobectomy have similar survival outcomes for patients with early-stage non-small cell lung cancer (NSCLC) is a matter of debate. METHODS: A cohort study and randomized controlled trial were included, comparing segmentectomy and lobectomy, by utilizing computerized access to the Pubmed, Web of Science, and Cochrane Library databases up until July 2022. The Cochrane Collaboration tool was used to evaluate the randomized controlled trials, while the Newcastle-Ottawa Scale (NOS) was used to evaluate the cohort studies. Sensitivity analyses were also carried out. RESULTS: The analysis incorporated 17 literature studies, including one randomized controlled trial and 16 cohort studies, and was divided into a segmentectomy group (n = 2081) and a lobectomy group (n = 2395) based on the type of surgery the patient underwent. Each study was followed up from 27 months to 130.8 months after surgery. Over survival (OS): HR = 1.14, 95%CI(0.97,1.32), P = 0.10; disease-free survival (DFS): HR = 1.13, 95%CI(0.91,1.41), P = 0.27; recurrence-free survival (RFS): HR = 0.95, 95%CI(0.81,1.12), P = 0.54. CONCLUSION: The results of the study suggest that the survival outcomes of the segmentectomy group were not inferior to that of the lobectomy group. Segmentectomy should therefore be considered as a treatment option for early stage NSCLC.

The promotion mechanism of different nitrogen doping types on the catalytic activity of activated carbon electro-Fenton cathode: Simultaneous promotion of H2O2 generation and phenol degradation ability.

Doping with nitrogen atoms can improve the catalytic activity of activated carbon cathodes in electro-Fenton systems, but currently there is a lack of understanding of the catalytic mechanism, which limits the further development of high-performance activated carbon cathodes. Here, a multi-scale exploration was conducted using density functional theory and experimental methods to investigate the mechanism of different nitrogen doping types promoting the redox performance of activated carbon cathodes and the degradation of phenol. The density functional theory results indicate that the introduction of nitrogen atoms enhances the binding ability between carbon substrates and oxygen-containing substances, promotes the localization of surrounding electrons, and makes it easier for O2 to bind with protons and catalyze the hydrogenation reaction of *OOH. Due to its weak binding ability with oxygen-containing substances, AC is difficult to form H2O2, resulting in a tendency towards the 4e-ORR pathway. The binding energy between graphite-N carbon substrate and pyridine-N carbon substrate with *OOH is closer to the volcano top, so graphite n and pyridine n can better promote the selectivity of activated carbon for 2e-ORR. In addition, the calculation results also indicate that pyrrole-N and graphite-N are more capable of catalyzing the reaction energy barrier between ·OH and phenol. Finally, the simulation results were used to guide the modification of nitrogen doped activated carbon and experimental verification was carried out. The degradation results of phenol confirmed the efficient synergistic effect between different types of nitrogen doping, and the NAC-800 electrode exhibited efficient and stable characteristics. This work provides a guiding strategy for further developing stable and highly selective activated carbon cathode materials.

Genome-wide analysis of TOPLESS/TOPLESS-RELATED co-repressors and functional characterization of BnaA9.TPL regulating the embryogenesis and leaf morphology in rapeseed.

TOPLESS/TOPLESS-RELATED (TPL/TPR) proteins belong to the Groucho (Gro)/Tup1 family co-repressors and act as broad co-repressors that modulate multiple phytohormone signalling pathways and various developmental processes in plant. However, TPL/TPR co-repressors so far are poorly understood in the rapeseed, one of the world-wide important oilseed crops. In this study, we comprehensively characterized eighteen TPL/TPR genes into five groups in the rapeseed genome. Members of TPL/TPR1/TPR4 and TPR2/TPR3 had close evolutionary relationship, respectively. All TPL/TPRs had similar expression patterns and encode conserved protein domain. In addition, we demonstrated that BnaA9.TPL interacted with all known plant repression domain (RD) sequences, which were distributed in non-redundant 24,238 (22.6 %) genes and significantly enriched in transcription factors in the rapeseed genome. These transcription factors were largely co-expressed with the TPL/TPR genes and involved in diverse pathway, including phytohormone signal transduction, protein kinases and circadian rhythm. Furthermore, BnaA9.TPL was revealed to regulate apical embryonic fate by interaction with Bna.IAA12 and suppression of PLETHORA1/2. BnaA9.TPL was also identified to regulate leaf morphology by interaction with Bna.AS1 (Asymmetric leaves 1) and suppression of KNOTTED-like homeobox genes and YABBY5. These data not only suggest the rapeseed TPL/TPRs play broad roles in different processes, but also provide useful information to uncover more TPL/TPR-mediated control of plant development in rapeseed.

Touch initiated on-demand adhesion on rough surfaces.

Reversible adhesion with on-demand attachment and detachment is used by many animals for their locomotion. However, achieving robust and switchable adhesion on rough surfaces in artificial adhesives remains a significant challenge. Here, we present a snail mucus-inspired touch-initiate adhesive (TIA), showing robust adhesions on various surfaces. TIA is a polymeric hydrogel photo-cured with the presence of supersaturated sodium acetate (NaAc) in the precursor solution. TIA is soft and flexible at room temperature, allowing it to form conformal contact with objects with various surfaces. The contact with the target surface immediately initiates the crystallization of TIA, increasing the elastic modulus of TIA by an order of magnitude. The increased modulus and the interlocking with the target surfaces thus results in an adhesion strength up to 465.56 ± 84.05 kPa. TIA can be easily detached from the surface by heating to a temperature above 58 °C, showing an adhesion strength of 12.71 ± 2.73 kPa. The detached TIA, even cooled down to and kept at room temperature, is readily used for the subsequent adhesion. The study here not only provides a highly adhesive material for on-demand attachment to various surfaces, but also proposes a new design strategy to compose smart materials.

Facet-switching of rate-determining step on copper in CO2-to-ethylene electroreduction.

Reduction of carbon dioxide (CO2) by renewable electricity to produce multicarbon chemicals, such as ethylene (C2H4), continues to be a challenge because of insufficient Faradaic efficiency, low production rates, and complex mechanistic pathways. Here, we report that the rate-determining steps (RDS) on common copper (Cu) surfaces diverge in CO2 electroreduction, leading to distinct catalytic performances. Through a combination of experimental and computational studies, we reveal that C─C bond-making is the RDS on Cu(100), whereas the protonation of *CO with adsorbed water becomes rate-limiting on Cu(111) with a higher energy barrier. On an oxide-derived Cu(100)-dominant Cu catalyst, we reach a high C2H4 Faradaic efficiency of 72%, partial current density of 359 mA cm-2, and long-term stability exceeding 100 h at 500 mA cm-2, greatly outperforming its Cu(111)-rich counterpart. We further demonstrate constant C2H4 selectivity of >60% over 70 h in a membrane electrode assembly electrolyzer with a full-cell energy efficiency of 23.4%.

Effectiveness of anastomotic reinforcement sutures in reducing anastomotic leakage risk after laparoscopic rectal cancer surgery: a pooled and integration analysis.

Background and objectives: Anastomotic leakage (AL) is one of the most serious complications after laparoscopic anus-preserving surgery for rectal cancer, which significantly prolongs the patient's hospital stay, leads to dysfunction, and even increases the patient's perioperative morbidity and mortality, and little is known about the effectiveness of anastomotic reinforcement sutures to prevent AL. Thus, this study was conducted to evaluate the efficacy of anastomotic reinforcement sutures as a means to prevent AL during laparoscopic surgery for rectal cancer. Methods: A comprehensive and systematic search was performed in the literature database by combining subject and free terms up to 10 October 2023. The overall literature included was integrated and analyzed using Stata 12.0 software and Review Manager version 5.4 software to assess the effect of anastomotic reinforcement sutures on the incidence of AL. Results: A total of 2,452 patients from 14 studies were included, and an integrated analysis showed that the use of anastomotic reinforcement sutures significantly reduced the incidence of AL [odds ratio (OR) = 0.26; 95% confidence interval (CI), 0.18-0.37; P < 0.00001; I2 = 0%]. However, the findings confirmed whether or not the anastomosis reinforced with sutures did not affect the incidence of anastomotic stenosis (OR = 0.69; 95% CI, 0.37-1.32; P = 0.27; I2 = 0%). We performed subgroup analyses of the results of the study, the randomized controlled studies (OR = 0.31; 95% CI, 0.15-0.65; P < 0.001) as well as retrospective studies (OR = 0.28; 95% CI, 0.19-0.41; P < 0.001), 3-0 sutures (OR = 0.28; 95% CI, 0.17-0.45; P < 0.001) versus 4-0 sutures (OR = 0.26; 95% CI, 0.13-0.53; P < 0.001), barbed wire sutures (OR = 0.26; 95% CI, 0.14-0.48; P < 0.001) versus non-barbed wire sutures (OR = 0.30; 95% CI, 0.20-0.46; P < 0.001), interrupted (OR = 0.30, 95% CI, 0.20-0.46; P < 0.001) versus continuous sutures (OR = 0.29, 95% CI, 0.16-0.51; P < 0.001) to the anastomosis, full-thickness suture (OR = 0.29; 95% CI, 0.16-0.51; P < 0.001) versus sutured with the seromuscular layer (OR = 0.27; 95% CI, 0.14-0.53; P < 0.001), anastomotic sutured in one (OR = 0.27; 95% CI, 0.14-0.53; P < 0.001) versus non-one circle (OR = 0.30; 95% CI, 0.20-0.44; P < 0.001), and reinforcing sutures to the dog-ear area (OR = 0.26; 95% CI, 0.14-0.50; P < 0.001) versus the non-dog-ear area (OR = 0.30; 95% CI, 0.20-0.45; P < 0.001), which have suggested that there is no significant difference between each other and that all of them reduce the incidence of AL. Conclusions: This study provides evidence that performing reinforcement suturing of the anastomosis during laparoscopic rectal surgery significantly lowers the incidence of postoperative AL but has no significant effect on anastomotic stenosis. It is important to note that further randomized controlled studies are required to confirm this conclusion. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022368631.

Clinical applications and cadaveric study of the free descending genicular artery perforator flap without the saphenous vein.

BACKGROUND: The descending genicular artery (DGA) and medial thigh region have been underused as donor sites for perforator flaps. This study evaluated the anatomical relationship between the perforators of the DGA and the saphenous vein (SV) to review the clinical applications of the free descending genicular artery perforator (DGAP) flap for locoregional reconstruction. METHODS: Fifteen cadavers were arterially perfused with red latex and dissected. Thirty-one patients with extremity tissue defects were treated with a free DGAP flap, including six patients who received a chimeric flap. The minimum distance between the DGAP and the SV was measured during surgery. RESULTS: In all patients, the skin branch of the descending genicular artery was found in the medial femoral condyle plane in front of the SV. The average distance between the descending genicular artery perforator and the SV was 3.71 ± 0.38 cm (range: 2.9-4.3 cm). Thirty flaps survived completely, and one flap developed partial necrosis; however, this flap healed two weeks after skin grafting. The average follow-up time was 11.23 months. CONCLUSIONS: We conclude that the SV can be preserved when harvesting the descending genicular artery perforator flap, causing less damage to the donor site and having no effect on flap survival. The free descending genicular artery perforator flap without the SV is a better therapy for complicated tissue defects.

Analysis of the seasonal water quality variation at the hydraulic junction of a dual-source water distribution system.

The implementation of a dual-source water supply system offers an increased level of reliability in water provision; however, intricate hydraulic dynamics introduce apprehensions regarding water safety at the hydraulic junction. In this study, we gathered data of the water quality at the hydraulic junction of a dual-source water supply system (plant A and plant B, sampling site A10 was near plant A, and sampling site A12 was near plant B) for one year in Suzhou Industrial Park. Our findings indicated that seasonal variations and water temperature exerted significant influence on the composition and formation of disinfection byproducts (DBPs). Notably, during the warmer months spanning from June to September, the concentration of trihalomethanes was the highest at the hydraulic junction, whereas the concentration of residual chloride was the lowest. The analysis on DBPs revealed that more Br-containing precursors in water in plant A resulted in the accumulation of more Br-containing DBPs at A10, whereas the highest concentration of Cl-containing DBPs accumulated at A12. The analysis of the dissolved organic matter (DOM) composition indicated an increase in concentration at A10 and A12 compared with that in plant A and plant B. The highest concentration of humic acids was observed at A10, whereas A12 accumulated the highest concentration of aromatic proteins and microbial metabolites. Owing to the fluctuations in water consumption patterns at the hydraulic junction, the water quality was susceptible to variability, thereby posing an elevated risk. Consequently, extensive efforts are warranted to ensure the maintenance of water safety and quality at this critical interface.

An axonemal intron splicing program sustains Plasmodium male development.

Differentiation of male gametocytes into flagellated fertile male gametes relies on the assembly of axoneme, a major component of male development for mosquito transmission of the malaria parasite. RNA-binding protein (RBP)-mediated post-transcriptional regulation of mRNA plays important roles in eukaryotic sexual development, including the development of female Plasmodium. However, the role of RBP in defining the Plasmodium male transcriptome and its function in male gametogenesis remains incompletely understood. Here, we performed genome-wide screening for gender-specific RBPs and identified an undescribed male-specific RBP gene Rbpm1 in the Plasmodium. RBPm1 is localized in the nucleus of male gametocytes. RBPm1-deficient parasites fail to assemble the axoneme for male gametogenesis and thus mosquito transmission. RBPm1 interacts with the spliceosome E complex and regulates the splicing initiation of certain introns in a group of 26 axonemal genes. RBPm1 deficiency results in intron retention and protein loss of these axonemal genes. Intron deletion restores axonemal protein expression and partially rectifies axonemal defects in RBPm1-null gametocytes. Further splicing assays in both reporter and endogenous genes exhibit stringent recognition of the axonemal introns by RBPm1. The splicing activator RBPm1 and its target introns constitute an axonemal intron splicing program in the post-transcriptional regulation essential for Plasmodium male development.

Synthesis and Biological Evaluation of Methoxypolyethylene-Glycol-Substituted Abiraterone Derivatives as Potential Antiprostate Cancer Agents.

Globally, prostate cancer is the most commonly diagnosed tumor and a cause of death in older men. Abiraterone, an orally administered irreversible CYP17 inhibitor, is employed to treat prostate cancer. However, abiraterone has several clinical limitations, such as poor water solubility, low dissolution rate, low bioavailability, and toxic side effects in the liver and kidney. Therefore, there is a need to identify high-efficiency and low-toxicity water-soluble abiraterone derivatives. In this work, we aimed to design and synthesize a series of abiraterone derivatives by methoxypoly(ethylene glycol) (mPEG) modification. Their antitumor activities and toxicology were analyzed in vitro and in vivo. The most potent compound, 2e, retained the principle of action on the CYP17 enzyme target and significantly improved the abiraterone water solubility, cell permeability, and blood safety. No significant abnormalities were observed in toxicology. mPEG-modification significantly improved abiraterone's antitumor activity and efficiency while reducing the associated toxic effects. The finding will provide a theoretical basis for future clinical application of mPEG-modified abiraterone.

Unraveling Stoichiometry Effect in Nickel-Tungsten Alloys for Efficient Hydrogen Oxidation Catalysis in Alkaline Electrolytes.

Anion-exchange membrane fuel cells provide the possibility to use platinum group metal-free catalysts, but the anodic hydrogen oxidation reaction (HOR) suffers from sluggish kinetics and its source is still debated. Here, over nickel-tungsten (Ni-W) alloy catalysts, we show that the Ni : W ratio greatly governs the HOR performance in alkaline electrolyte. Experimental and theoretical studies unravel that alloying with W can tune the unpaired electrons in Ni, tailoring the potential of zero charge and the catalytic surface to favor hydroxyl adsorption (OHad). The OHad species coordinately interact with potassium (K+) ions, which break the K+ solvation sheath to leave free water molecules, yielding an improved connectivity of hydrogen-bond networks. Consequently, the optimal Ni17W3 alloy exhibits alkaline HOR activity superior to the state-of-the-art platinum on carbon (Pt/C) catalyst and operates steadily with negligible decay after 10,000 cycles. Our findings offer new understandings of alloyed HOR catalysts and will guide rational design of next-generation catalysts for fuel cells.