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At the end of 2023, a large-scale rainfall/snowfall and freezing event occurred in northern and central Henan, featuring variable precipitation phases and accompanied by regional thunderstorms, which was relatively rare. This paper analyzed this process by using the data from conventional observations, ERA5 reanalysis, wind profile radar, and dual-polarization radar with a focus on the characteristics of precipitation phases and cause. The results are as follows. (1) At 500 hPa, the horizontal trough turned vertical, and the south branch trough moved eastward, while at 700 hPa, the southwest jet developed. Meanwhile, the ground was affected by the cold air from the east and the west successively, which led to the persistent large-scale freezing rain and snow weather in northern and central Henan. (2) The conditional instability above the cold cushion, the conditional symmetry instability near the frontal zone, and the upward branch of strong frontogenesis circulation provided a favorable condition for the occurrence and development of convective weather, which were the main causes of heavy rain and snow, thunderstorm, and hail. (3) During the process, the freezing rain corresponded to a "thick warm layer (100-200 hPa)-cold layer" stratification, with the ice pellets linking to a "layer of ice crystals - thin warm layer (50-100 hPa) - cold layer" stratification. While the pure snow and sleet corresponded to an entirely cold layer stratification and a shallow warm layer near the ground, respectively. (4) The horizontal wind field products of wind profile radar can qualitatively reflect the changes in the low-level southwest jet stream and the intensity of cold air near the ground. The differences in the vertical velocity products of different precipitation phases are significant, providing a reference for the monitoring and forecasting of short-term phase transitions. (5) The dual-polarization products revealed that the freezing rain and pure snow had the highest correlation coefficients (≥0.99), while the sleet had the lowest (0.85~0.9). The ice pellets showed a significant middle-layer melting, with a maximum differential reflectivity and a minimum correlation coefficient at that level.

Background and purpose: Rectal cancer occurs on the inner wall of the rectum, and metastasis-associated in colon cancer 1 (MACC1) can promote drug resistance in colon cancer cells. This study aimed to investigate the effect of MACC1 on oxaliplatin resistance in rectal cancer and its mechanism. Methods: Biosignal analysis of MACC1 and TCF7 expressions in rectal cancer tissues and signaling pathways enriched for MACC1 were carried out. The expressions of MACC1 and TCF7 in rectal cancer cells and rectal cancer oxaliplatin-resistant cells were detected by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR), cell viability was detected by cell counting kit-8 (CCK-8), and cell proliferation was detected by cell colony formation assay. ECAR values, lactate production and glucose consumption were detected by Seahorse Biosciences XF96. Western blot was used to detect the expressions of glycolysis-related proteins. Dual luciferase reporter gene and ChIP were used to validate the regulatory relationship between MACC1 and TCF7. Normality test and homogeneity of variance analysis was performed on the data of each group by GraphPad Prism 8.0. If it conformed to normal distribution, one-way ANOVA or t-test would be used for inter group comparison, otherwise the comparison between groups would be conducted using Wilcoxon rank sum test. Using a two-sided test, P

Abstract Silicon nitride (Si3N4) is a bioceramic material with potential applications. Customization and high reliability are the foundation for the widespread application of Si3N4 bioceramics. This study constructed a new microwave heating structure and successfully prepared 3D printed dense Si3N4 materials, overcoming the adverse effects of a large amount of 3D printed organic forming agents on degreasing and sintering processes, further improving the comprehensive performance of Si3N4 materials. Compared with control materials, the 3D printed Si3N4 materials by microwave sintering have the best mechanical performance: bending strength is 928 MPa, fracture toughness is 9.61 MPa·m1/2. Meanwhile, it has the best biocompatibility and antibacterial properties, and cells exhibit the best activity on the material surface. Research has shown that the excellent mechanical performance and biological activity of materials are mainly related to the high-quality degreasing, high cleanliness sintering environment, and high-quality liquid-phase sintering of materials in microwave environments.

Abstract Background In the post-pandemic era of higher education, hybrid teaching has emerged as a prevalent approach and is anticipated to persist as a defining trend in the future teaching reforms worldwide. However, despite its widespread adoption, certain limitations have become apparent. The objective of this study is to identify the genuine factors that impact students’ performance, explore strategies that teachers can employ to enhance their teaching effectiveness and enhance students’ academic self-efficacy. Methods The study was performed among undergraduate medical students enrolled in Physiology course at Harbin Medical University in 2020 and 2022. Since 2020, influenced by the COVID-19 pandemic, a hybrid teaching method based on an established offline teaching model called BOPPPS was implemented. A questionnaire was performed in both 2020 and 2022 to evaluate students’ satisfaction and efficiency of our hybrid teaching. A comparison was also carried out on the final examination scores of students majoring in Pharmacy and Clinical Pharmacy across the years 2020 to 2022. Results The final examination scores of students in 2022 were significantly lower than those in 2020 and 2021 both in Pharmacy and Clinical Pharmacy majors. There was also a decrease of the score in students of Clinical Pharmacy in 2021 compared to 2020. The questionnaire indicated that over half (52.0%) of the students in 2022 preferred offline teaching method, in contrast to 39.1% in 2020. There were obvious changes in students from 2020 to 2022 about the disadvantages of hybrid teaching, the improvement of students’ learning ability and the duration of students’ autonomous learning. Through cross statistical analysis, online learning styles, learning ability improvement and students’ learning burden have been identified as the primary factors influencing their preference for future teaching method. Conclusions Hybrid teaching is still a necessary trend in the future teaching reform base on its multiple advantages. However, in order to improve the teaching outcomes and foster students’ participation and learning initiatives, it is imperative to undertake additional reforms in the future teaching process.

Abstract Background T cells play a pivotal role in chemotherapy-triggered anti-tumor effects. Emerging evidence underscores the link between impaired anti-tumor immune responses and resistance to paclitaxel therapy in triple-negative breast cancer (TNBC). Tumor-related endothelial cells (ECs) have potential immunoregulatory activity. However, how ECs regulate T cell activity during TNBC chemotherapy remains poorly understood. Methods Single-cell analysis of ECs in patients with TNBC receiving paclitaxel therapy was performed using an accessible single-cell RNA sequencing (scRNA-seq) dataset to identify key EC subtypes and their immune characteristics. An integrated analysis of a tumor-bearing mouse model, immunofluorescence, and a spatial transcriptome dataset revealed the spatial relationship between ECs, especially Tumor necrosis factor receptor (TNFR) 2+ ECs, and CD8+ T cells. RNA sequencing, CD8+ T cell proliferation assays, flow cytometry, and bioinformatic analyses were performed to explore the immunosuppressive function of TNFR2 in ECs. The downstream metabolic mechanism of TNFR2 was further investigated using RNA sequencing, cellular glycolysis assays, and western blotting. Results In this study, we identified an immunoregulatory EC subtype, characterized by enhanced TNFR2 expression in non-responders. By a mouse model of TNBC, we revealed a dynamic reduction in the proportion of the CD8+ T cell-contacting tumor vessels that could co-localize spatially with CD8+ T cells during chemotherapy and an increased expression of TNFR2 by ECs. TNFR2 suppresses glycolytic activity in ECs by activating NF-κB signaling in vitro. Tuning endothelial glycolysis enhances programmed death-ligand (PD-L) 1-dependent inhibitory capacity, thereby inducing CD8+ T cell suppression. In addition, TNFR2+ ECs showed a greater spatial affinity for exhausted CD8+ T cells than for non-exhausted CD8+ T cells. TNFR2 blockade restores impaired anti-tumor immunity in vivo, leading to the loss of PD-L1 expression by ECs and enhancement of CD8+ T cell infiltration into the tumors. Conclusions These findings reveal the suppression of CD8+ T cells by ECs in chemoresistance and indicate the critical role of TNFR2 in driving the immunosuppressive capacity of ECs via tuning glycolysis. Targeting endothelial TNFR2 may serve as a potent strategy for treating TNBC with paclitaxel.

Abstract Background Cardiometabolic multimorbidity (CMM) is a growing global health problem, and obstructive sleep apnea (OSA) is recognized as an important risk factor for cardiovascular disease. However, the impact of OSA on the prognosis of CMM patients remains unclear. Methods This study was a sub-study of OSA-acute coronary syndrome (ACS) and included 1, 927 hospitalized ACS patients. Patients were divided into the CMM group and the non-CMM group. OSA was diagnosed using the apnea-hypopnea index (AHI). The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE). The secondary endpoint included cardiac events, all-cause death and all repeat revascularizations. Results This study enrolled 1, 927 patients hospitalized for ACS, with a median follow-up of 3 years. Among them, 723 patients (37.5%) had CMM, while 1, 204 patients (62.5%) did not have CMM. Over half of the patients in each group had OSA. OSA patients exhibited worse cardiometabolic profiles than their non-OSA counterparts, including higher body mass index (BMI), glycemic indices, lipids and inflammation. In the CMM group, OSA patients had a significantly higher incidence of MACCE than non-OSA patients (34.7% vs. 23.7%, p = 0.004). These results remained significant after adjustment, indicating that OSA substantially increased the risk of MACCE in the CMM group (adjusted hazard ratio [HR]: 1.432; 95% confidence interval [CI]: 1.017–2.016; p = 0.040). Conversely, the incidence of MACCE was similar between OSA and non-OSA subgroups within the non-CMM cohort. Subgroup analyses showed that OSA increased the risk of MACCE in CMM patients aged ≥ 60 years (adjusted HR: 1.642; 95% CI: 1.031–2.615; p = 0.037) and in those with specific clinical characteristics. Conclusion OSA significantly impacts the prognosis of CMM patients, highlighting the need for targeted OSA screening and management strategies to improve outcomes in this population potentially.

Abstract Alkaline lakes are extreme environments inhabited by diverse microbial extremophiles. However, large-scale distribution patterns, environmental adaptations, community assembly, and evolutionary dynamics of microbial communities remain largely underexplored. This study investigated the characteristics of microbial communities on rare and abundant taxa in alkaline lake sediments in west and northwest China. We observed that abundant taxa varied significantly with geographical distance, while rare taxa remained unaffected by regional differences. The assembly process of abundant taxa was influenced by dispersal limitation, whilst rare taxa were predominantly driven by heterogeneous selection. Network analysis indicated that rare taxa as core species for community interactions and community stability. Rare taxa exhibited higher speciation and transition rate than abundant taxa, serving as a genetic reservoir and potential candidates to become abundance taxa, highlighting their crucial role in maintaining microbial diversity. These insights underscore the significant influence of rare taxa on ecosystem biodiversity and stability in alkaline lakes.

Abstract In this work, we investigate six helicity amplitudes of the four-body $$B_{(s)} \rightarrow (\pi \pi )(K\bar{K})$$ B ( s ) → ( π π ) ( K K ¯ ) decays via an angular analysis in the perturbative QCD (PQCD) approach. The $$\pi \pi $$ π π invariant mass spectrum is dominated by the vector resonance $$\rho (770)$$ ρ ( 770 ) together with scalar resonance $$f_0(980)$$ f 0 ( 980 ) , while the vector resonance $$\phi (1020)$$ ϕ ( 1020 ) and scalar resonance $$f_0(980)$$ f 0 ( 980 ) are expected to contribute in the $$K\bar{K}$$ K K ¯ invariant mass range. We extract the two-body branching ratios $$\mathcal{B}(B_{(s)}\rightarrow \rho \phi )$$ B ( B ( s ) → ρ ϕ ) from the corresponding four-body decays $$B_{(s)}\rightarrow \rho \phi \rightarrow (\pi \pi )(K \bar{K})$$ B ( s ) → ρ ϕ → ( π π ) ( K K ¯ ) based on the narrow width approximation. The predicted $$\mathcal{B}(B^0_{s}\rightarrow \rho \phi )$$ B ( B s 0 → ρ ϕ ) agrees well with the current experimental data within errors. The longitudinal polarization fractions of the $$B_{(s)}\rightarrow \rho \phi $$ B ( s ) → ρ ϕ decays are found to be as large as $$90\%$$ 90 % , basically consistent with the previous two-body predictions within uncertainties. In addition to the direct CP asymmetries, the triple-product asymmetries (TPAs) originating from the interference among various helicity amplitudes are also presented for the first time. Since the $$B_s^0\rightarrow \rho ^0\phi \rightarrow (\pi ^+\pi ^-)(K^+K^-)$$ B s 0 → ρ 0 ϕ → ( π + π - ) ( K + K - ) decay is induced by both tree and penguin operators, the values of the $$\mathcal{A}^\textrm{CP}_\textrm{dir}$$ A dir CP and $$\mathcal{A}^{1}_{\text {T-true}}$$ A T-true 1 are calculated to be $$(21.8^{+2.7}_{-3.3})\%$$ ( 21 . 8 - 3.3 + 2.7 ) % and $$(-10.23^{+1.73}_{-1.56})\%$$ ( - 10 . 23 - 1.56 + 1.73 ) % respectively. While for pure penguin decays $$B^0\rightarrow \rho ^0\phi \rightarrow (\pi ^+\pi ^-)(K^+K^-)$$ B 0 → ρ 0 ϕ → ( π + π - ) ( K + K - ) and $$B^+\rightarrow \rho ^+\phi \rightarrow (\pi ^+\pi ^0)(K^+K^-)$$ B + → ρ + ϕ → ( π + π 0 ) ( K + K - ) , both the direct CP asymmetries and “true” TPAs are naturally expected to be zero in the standard model (SM) due to the absence of the weak phase difference. The “fake” TPAs requiring no weak phase difference are usually none zero for all considered decay channels. The sizable “fake” $$\mathcal{A}^{1}_{\text {T-fake}}=(-20.92^{+6.26}_{-2.80})\%$$ A T-fake 1 = ( - 20 . 92 - 2.80 + 6.26 ) % of the $$B^0\rightarrow \rho ^0\phi \rightarrow (\pi ^+\pi ^-)(K^+K^-)$$ B 0 → ρ 0 ϕ → ( π + π - ) ( K + K - ) decay is predicted in the PQCD approach, which provides valuable information on the final-state interactions. The above predictions can be tested by the future LHCb and Belle-II experiments.

The atmospheric correction of hyperspectral data stands as a fundamental step in quantitative applications, crucial for the accurate analysis of hyperspectral information. Zhuhai-1 hyperspectral data, characterized by its high spatial and spectral resolution, holds substantial potential and advantages for the quantification of water body information. Nonetheless, the adoption of more precise physical models for atmospheric correction often demands extensive satellite and ground environmental parameters, which pose practical challenges in applying physical models The Dark Object Subtraction (DOS), leveraging the intrinsic spectral characteristics of the imagery, offers an efficient alternative for achieving improved atmospheric correction results tailored to the data and study area. In this context, this study presents a Dark Object Subtraction for Water body information extraction (DOSW), specifically designed to advance the quantification of water body information in Zhuhai-1 hyperspectral data. The proposed method is rigorously evaluated by comparing the correction results from the Foshan region and Feilaixia Reservoir with standard and measured spectra of typical objects. The results demonstrate the accuracy of DOSW in atmospheric correction, with correlation coefficients exceeding 0.7 when compared to standard spectra for three representative objects. Notably, DOSW achieves exceptional accuracy in water body correction, achieving a correlation coefficient of 0.95 and an RMSE of 0.002 in the Feilaixia Reservoir, and a correlation coefficient of 0.72 and an RMSE of 0.005 in the Foshan region. Overall, the results underscore the efficacy of DOSW in accurately addressing atmospheric correction challenges to Zhuhai-1 hyperspectral data, effectively meeting the requirements of hyperspectral quantification applications.

Introduction: High-altitude pulmonary edema (HAPE) is a severe and potentially fatal condition with limited treatment options. Although ceramide kinase (CERK)-derived ceramide-1-phosphate (C1P) has been demonstrated to offer protection against various pulmonary diseases, its effects on HAPE remain unclear. Objectives: Our study aimed to investigate the potential role of CERK-derived C1P in the development of HAPE and to reveal the molecular mechanisms underlying its protective effects. We hypothesized that CERK-derived C1P could protect against HAPE by stabilizing circadian rhythms and maintaining mitochondrial dynamics. Methods: To test our hypothesis, we used CERK-knockout mice and established HAPE mouse models using a FLYDWC50-1C hypobaric hypoxic cabin. We utilized a range of methods, including lipidomics, transcriptomics, immunofluorescence, Western blotting, and transmission electron microscopy, to identify the mechanisms of regulation. Results: Our findings demonstrated that CERK-derived C1P played a protective role against HAPE. Inhibition of CERK exacerbated HAPE induced by the hypobaric hypoxic environment. Specifically, we identified a novel mechanism in which CERK inhibition induced aryl hydrocarbon receptor nuclear translocator-like (ARNTL) autophagic degradation, inducing the circadian rhythm and triggering mitochondrial damage by controlling the expression of proteins required for mitochondrial fission and fusion. The decreased ARNTL caused by CERK inhibition impaired mitochondrial dynamics, induced oxidative stress damage, and resulted in defects in mitophagy, particularly under hypoxia. Exogenous C1P prevented ARNTL degradation, alleviated mitochondrial damage, neutralized oxidative stress induced by CERK inhibition, and ultimately relieved HAPE. Conclusions: This study provides evidence for the protective effect of C1P against HAPE, specifically, through stabilizing circadian rhythms and maintaining mitochondrial dynamics. Exogenous C1P therapy may be a promising strategy for treating HAPE. Our findings also highlight the importance of the circadian rhythm and mitochondrial dynamics in the pathogenesis of HAPE, suggesting that targeting these pathways may be a potential therapeutic approach for this condition.

Abstract Direct solar-to-hydrogen conversion from pure water using all-organic heterogeneous catalysts remains elusive. The challenges are twofold: (i) full-band low-frequent photons in the solar spectrum cannot be harnessed into a unified S 1 excited state for water-splitting based on the common Kasha-allowed S 0 → S 1 excitation; (ii) the H+ → H2 evolution suffers the high overpotential on pristine organic surfaces. Here, we report an organic molecular crystal nanobelt through the self-assembly of spin-one open-shell perylene diimide diradical anions (:PDI2-) and their tautomeric spin-zero closed-shell quinoid isomers (PDI2-). The self-assembled :PDI2-/PDI2- crystal nanobelt alters the spin-dependent excitation evolution, leading to spin-allowed S 0 S 1 → 1 (TT) → T 1 + T 1 singlet fission under visible-light (420 nm~700 nm) and a spin-forbidden S 0 → T 1 transition under near-infrared (700 nm~1100 nm) within spin-hybrid chromophores. With a triplet-triplet annihilation upconversion, a newly formed S 1 excited state on the diradical-quinoid hybrid induces the H+ reduction through a favorable hydrophilic diradical-mediated electron transfer, which enables simultaneous H2 and O2 production from pure water with an average apparent quantum yield over 1.5% under the visible to near-infrared solar spectrum.

Abstract Background As indispensable reserves for the nursing workforce, undergraduate nursing students must possess self-directed learning abilities to consistently update their professional knowledge and adapt to the evolving demands of professional development. The acquisition of self-directed learning abilities can help undergraduate nursing students augment their theoretical knowledge and refine their clinical practice skills, thus fulfilling the demand from patients for high-quality nursing services. Hence, comprehending and investigating the factors that influence the development of self-directed learning abilities in nursing students is of paramount importance for nursing education and advancement of the nursing profession. Objectives This study investigated the status of and associations between perceived stress, psychological capital, and self-directed learning abilities among undergraduate nursing students. Additionally, it examines the mediating role of psychological capital in the relationship between perceived stress and self-directed learning abilities. Thus, aiming to provide nursing educators with new directions for enhancing self-directed learning abilities. Design A cross-sectional descriptive study. Methods In February and March 2023, 900 undergraduate nursing students from 10 nursing schools completed an online questionnaire. The questionnaire included measures of perceived stress, psychological capital, and self-directed learning ability. Data were analyzed using SPSS 27.0 and the PROCESS macro tool. Results The scores for perceived stress, psychological capital, and self-directed learning ability among undergraduate nursing students were 40.07 ± 5.90, 99.89 ± 16.59, and 87.12 ± 9.20, respectively. Self-directed learning abilities were negatively correlated with perceived stress (r = -0.415, p

Abstract Boron-doped polycyclic aromatic hydrocarbons exhibit excellent optical properties, and regulating their photophysical processes is a powerful strategy to understand the luminescence mechanism and develop new materials and applications. Herein, an electrochemically responsive B–O dynamic coordination bond is proposed, and used to regulate the photophysical processes of boron-nitrogen-doped polyaromatic hydrocarbons. The formation of the B–O coordination bond under a suitable voltage is confirmed by experiments and theoretical calculations, and B–O coordination bond can be broken back to the initial state under opposite voltage. The whole process is accompanied by reversible changes in photophysical properties. Further, electrofluorochromic devices are successfully prepared based on the above electrochemically responsive coordination bond. The success and harvest of this exploration are beneficial to understand the luminescence mechanism of boron-nitrogen-doped polyaromatic hydrocarbons, and provide ideas for design of dynamic covalent bonds and broaden material types and applications.

Abstract Introduction Ixekizumab, an interleukin 17A (IL-17A) inhibitor, has demonstrated rapid and sustained improvement in the signs and symptoms in patients with active radiographic axial spondyloarthritis (r-axSpA) in global and Chinese populations. We studied the effect of ixekizumab on patient-reported outcomes (PROs) (including patient global, spinal pain, stiffness, and fatigue) and overall health-related quality of life (HRQoL) of ixekizumab in the phase 3 study in China. Methods In this Chinese phase 3, randomized, double-blind, placebo-controlled study, patients with r-axSpA were randomized (1:1) to receive ixekizumab 80 mg every 4 weeks (IXEQ4W; starting dose 160 mg) or placebo for 16 weeks. At week 16, patients receiving placebo were switched to IXEQ4W, and those receiving IXEQ4W continued, until week 52. Data for patient global, spinal pain, spinal pain at night, stiffness, and fatigue were collected through week 52. Minimally clinical important differences (MCIDs) were determined for spinal pain and spinal pain at night. The subgroup analyses by baseline disease duration since diagnosis and baseline C-reactive protein (CRP) level were conducted post hoc. Results Compared with placebo, patients treated with IXEQ4W reported significantly greater improvement with a rapid onset in changes from baseline of PROs (patient global, spinal pain, spinal pain at night, stiffness, and fatigue) through week 16. Improvements were maintained through week 52. A similar trend of improvement was also observed in MCID response in spinal pain and spinal pain at night. The improvement in overall HRQoL was supported by EQ-5D-5L assessment. Subgroup analyses demonstrated that IXEQ4W provided significantly greater efficacy at week 16 compared with placebo, irrespective of baseline disease duration or baseline CRP level. Conclusion IXEQ4W provided rapid and sustained improvement in clinically relevant PROs and overall HRQoL through 1-year treatment in Chinese patients with r-axSpA. Regardless of the baseline disease duration or baseline CRP level, consistent efficacy was observed. Trial Registration ClinicalTrials.gov identifier NCT04285229.

Objective(s): Tubal factor infertility (TFI) is common female infertility responsible for a large portion of female factor infertility. This study reveals the effect of the quercetin of Huoxuehuayu Tongluo Decoction with azithromycin on the pregnancy rate and inflammation of TFI female rats.Materials and Methods: Female Sprague Dawley rats were constructed into the TFI model and treated with quercetin, Huoxuehuayu Tongluo Decoction, and combination therapy (quercetin and azithromycin). Pregnancy rate and litter size were measured. Network pharmacology was applied to analyze the interaction between Huoxuehuayu Tongluo Decoction and TFI. The combination of quercetin and IL-6 was analyzed by molecular docking. HE staining and electron microscopy were used to observe the histopathology and ultrastructure of fallopian tube tissues. The TNF-α, IL-1β, IL-6, IL-8, and MPO levels were detected by ELISA. The activation of JAK/STAT, MAPK, and NF-κB p65 pathways was detected by western blot or immunohistochemistry.Results: Quercetin was the main active component of Huoxuehuayu Tongluo Decoction, and could bind to IL-6 in TFI. Target genes were enriched in the IL-17 signaling pathway, JAK-STAT signaling pathway, inflammatory disease, etc. Under the quercetin and azithromycin combination therapy, both rat pregnancy rates and litter sizes increased significantly. quercetin and azithromycin alleviated the symptoms of hydrosalpinx and inflammatory damage in fallopian tube tissues. The phosphorylation of JAK/STAT and MAPK pathways and NF-κB p65 translocation to the nucleus were significantly inhibited by the quercetin and azithromycin therapy.Conclusion: Quercetin and azithromycin combination therapy inhibited inflammation and phosphorylation of JAK/STAT and MAPK pathways to improve TFI inflammation and pregnancy function.

Semiconductor photocatalysts often exhibit low CO2 reduction activity due to inherent limitations. Photothermal (PTT) processes have emerged as crucial for enhancing this activity, yet investigations in this area remain sparse. This study introduces a novel CoFe2O3.5S0.5 photothermal catalyst, synthesized via hydrothermal methods with particle sizes ranging from 5 to 10 nm. Comparative analysis reveals that the CO yield from the as-prepared catalyst surpasses that of CoFe2O4 by 8.9 times, achieving 100% selectivity. The integration of sulfur significantly boosts near-infrared light absorption and promotes the conversion of light to thermal energy, enabling the catalyst to reach 185 °C within 300 ss. This rapid temperature escalation facilitates the swift separation of charge carriers. Additionally, the adsorption of CO2 and the dynamics of surface intermediates were thoroughly examined using in situ FTIR spectroscopy and theoretical models, identifying COOH* as the pivotal intermediate and the bottleneck in the reaction pathway. Our findings rectify gaps in prior studies and offer a foundational reference for further exploration of product selectivity in the photocatalytic reduction of CO2.

Abstract Proprotein convertase subtilisin/kexin type 9 (PCSK9) increases plasma low‐density lipoprotein‐cholesterol (LDL‐C) by decreasing the expression of the LDL‐receptor on hepatic cells. Ongericimab (JS002) is a novel PCSK9 monoclonal antibody that exhibits a long‐acting LDL‐C lowering effect by exclusively inhibiting PCSK9 in pre‐clinical studies. Two randomized, double‐blind, placebo‐controlled trials were conducted to evaluate the safety, tolerability, efficacy, immunogenicity, pharmacokinetic, and pharmacodynamic profiles of ongericimab in healthy subjects and patients with hypercholesterolemia. Eighty‐four healthy subjects in the phase Ia study received a single dose of placebo or ongericimab (15–450 mg). Ninety patients with hypercholesterolemia in the phase Ib/II study received placebo or ongericimab 150 mg Q2W, 300 mg Q4W, or 450 mg Q4W for 12 weeks. Ongericimab exhibited non‐linear kinetics. The apparent clearance decreased as the dosage increased, with terminal elimination half‐life (t1/2) values of 4.5–6.5 days. Overall, ongericimab was well tolerated in both studies. A single dose of ongericimab reduced LDL‐C levels by 30%–73% in healthy subjects, and repeated doses of ongericimab reduced LDL‐C levels by 67%–80% in patients with hypercholesterolemia. At the end of the dosing interval in the phase Ib/II study, over 70% of patients' LDL‐C levels decreased by more than 50% from baseline. The results showed that ongericimab had a significant long‐acting LDL‐C lowering effect with good safety and potential for clinical application.

Due to the substantial production and use of antibiotics, they inevitably remain in aquatic environments, posing a serious threat to aquatic ecosystems. However, there are currently no criteria of antibiotics for ecological risk in the water environment. In the present study, three types of antibiotics (tetracyclines, sulfonamides and quinolones) that are often detected in water environments were investigated. Toxicity data regarding bacteria, algae, plants, invertebrates and vertebrates were selected, and the species sensitivity distribution was used to obtain the ecological risk criteria of antibiotics to aquatic organisms. Animals are the least sensitive to antibiotics. The overall toxicity of antibiotics is most sensitive to bacteria and cyanobacteria, followed by green algae and plants. The recommended ecological criteria for tetracyclines, quinolones, and sulfonamides are 22, 17, and 94 μg/L, respectively. Ofloxacin needs to be used with caution because it has a small acute predicted no-effect concentration (PNEC) of 0.6 μg/L. The ecological risk criterion for chronic toxicity of total antibiotics was determined to be 1.4 μg/L. The PNECs measured for the quinolone, tetracycline, and sulfonamide antibiotics were 0.5, 2.2, and 2.4 μg/L, respectively. Norfloxacin had the highest chronic toxicity zone of 353, indicating that chronic poisoning is most likely to occur. Moreover, there was an exponential correlation between acute PNEC and chronic PNEC. In addition, a quantitative structure–activity relationship model was constructed for acute ecological risk criteria of antibiotics to aquatic organisms. These findings can expand the ecological risk threshold data on the effects of antibiotics on aquatic organisms, and provide a theoretical basis for the environmental risk assessment of antibiotics.

Red pepper (Capsicum annuum var. conoides) is commonly used for dried pepper production in China, and the drying process, particularly the during duration, profoundly affects its quality. The findings indicate that prolonged exposure to high temperatures during thermal drying results in significant darkening, an evident decrease in red and yellow tones, and gradual transformation of the pepper's microscopic structure from granular to compact, along with 88% reduction in moisture content and 81% decrease in thickness. The capsaicinoid content increased, resulting in a 4.3-fold increase in spiciness after drying compared to that of fresh pepper. The pepper aroma shifts from fruity, choking, and grassy to herb, dry wood, and smoky. Compounds such as 2-Acetylfuran, furfural, 2-methylfuran, 1-methylpyrrole, 2-methylpyrazine, and 2,5-dimethylpyrazine exhibited positive correlations with drying time, whereas ethyl 2-methylpropanoate, ethyl butanoate, ethyl 2-methylbutanoate, ethyl hexanoate, and 3-methylbutyl butanoate showed negative correlations, indicating their potential as markers for monitoring thermal drying processes.

Background: The perioperative period of tumor surgery commonly utilizes dexmedetomidine as an adjuvant analgesic for anesthesia. Nevertheless, there is a paucity of research investigating its influence on the prognosis of colorectal cancer (CRC). This article primarily aims to examine the correlation between the intraoperative administration of dexmedetomidine and recurrence-free survival (RFS) and overall survival (OS) of colorectal cancer patients, as well as its prognostic implications on survival. Methods: According to the exclusion criteria, 76 patients undergoing laparoscopic radical resection of CRC under general anesthesia were enrolled at Huizhou Central People's Hospital in 2014. Kaplan-Meier method was used for univariate survival analysis of clinical prognostic factors, RFS, and OS in patients with CRC Cox regression analysis was used for multivariate survival analysis. Results: A total of 76 patients with CRC were enrolled in this study. Among them, 36 patients were treated with dexmedetomidine (group D), and 40 patients were not treated with dexmedetomidine (group C) during the operation. Survival analysis showed that the RFS and OS of patients in group D were significantly higher than those in group C (P = 0.046 and P = 0.021, respectively). Multivariate regression analysis demonstrated that the intraoperative administration of dexmedetomidine independently predicted a protective effect on OS (P = 0.025). Conclusions: The intraoperative application of dexmedetomidine as an adjuvant analgesic has a protective effect on the prognosis and survival of patients with CRC and can improve the overall survival rate. Additionally, it influences the recurrence status of patients to a certain extent. These results suggest that dexmedetomidine significantly benefits on the long-term prognosis of patients with CRC.

Previous studies suggested that pyrethroid exposure was associated with elevated type 2 diabetes (T2D) risk, while it remains uncertain whether genetic predisposition modifies this association. A nested case-control study within the prospective Dongfeng-Tongji cohort comprised 1832 T2D cases, age- (±5 years) and sex-matched controls with qualified genotyping data. Serum pyrethroids were measured by gas chromatography-tandem mass spectrometry. Overall diabetes-related genetic risk score (GRS) or pathway-specific GRS, including unweighted GRSs (uGRS) and weighted GRSs (wGRS), was developed by genetic variants identified in Asian populations. Higher overall diabetes-related GRS and GRS specific to the pathway of impaired beta cell function (Beta-cell GRS) were associated with a higher incident T2D risk. Beta-cell uGRS significantly modified the association of serum permethrin (Pinteraction=0.04) and deltamethrin (Pinteraction=0.01) with T2D. Specifically, for each doubling increase in serum deltamethrin, the odds ratios (ORs) (95 % confidence intervals [CIs]) for T2D were 1.23 (0.98–1.56) and 0.91 (0.77–1.07) in the highest and lowest Beta-cell uGRS group, as well as 1.23 (1.02–1.47) and 0.95 (0.78–1.15) for Beta-cell wGRS group, respectively. When considering jointly, those with the highest deltamethrin levels and highest Beta-cell GRS had a substantially higher T2D risk, compared with the reference group (OR for uGRS: 3.79 [95 % CI: 2.03–7.07], Pinteraction=0.03 and 3.23 [95 % CI: 1.78–5.87], Pinteraction=0.05 for wGRS). Our findings suggested that genetic susceptibility to impaired beta-cell function should be considered for T2D prevention targeting pyrethroid exposure, particularly deltamethrin.

Background Patients with acute coronary syndrome without standard modifiable cardiovascular risk factors (SMuRFs; hypertension, smoking, dyslipidemia, diabetes) have not been well studied, with little known about their characteristics, quality of care, or outcomes. We sought to systematically analyze patients with ACS without SMuRFs, especially to evaluate the effectiveness of guideline‐directed medical therapy for these patients. Methods and Results In the CCC‐ACS (Improving Care for Cardiovascular Disease in China‐Acute Coronary Syndrome) project (2014–2019), we examined the presence and absence of SMuRFs and features among 89 462 patients with initial acute coronary syndrome. The main outcome was in‐hospital all‐cause mortality. Among eligible patients, 11.0% had none of the SMuRFs (SMuRF‐less). SMuRF‐less patients had higher in‐hospital mortality (unadjusted hazard ratio [HR], 1.49 [95% CI, 1.19–1.87]). After adjustment for clinical characteristics and treatments, the associations between SMuRF status and in‐hospital mortality persisted (adjusted HR, 1.35 [95% CI, 1.07–1.70]). Guideline‐directed optimal medical therapy (receiving angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers, β‐blockers, and statins) was not associated with lower mortality (adjusted HR, 0.98 [95% CI, 0.58–1.67]) in SMuRF‐less patients, unlike the association in patients with SMuRFs (adjusted HR, 0.80 [95% CI, 0.66–0.98]). Sensitivity analyses were consistent with these results. Conclusions SMuRF‐less patients were associated with an increased risk of in‐hospital mortality. Guideline‐directed medical therapy was less effective in SMuRF‐less patients than in patients with SMuRFs. Dedicated studies are needed to confirm the optimal therapy for SMuRF‐less patients. REGISTRATION URL: https://www.clinicaltrials.gov; Unique identifier: NCT02306616.

Abstract Extracellular vesicles (EVs) are lipid nanoparticles and play an important role in cell‐cell communications, making them potential therapeutic agents and allowing to engineer for targeted drug delivery. The expanding applications of EVs in next generation medicine is still limited by existing tools for scaling standardized EV production, single EV tracing and analytics, and thus provide only a snapshot of tissue‐specific EV cargo information. Here, we present the Snorkel‐tag, for which we have genetically fused the EV surface marker protein CD81, to a series of tags with an additional transmembrane domain to be displayed on the EV surface, resembling a snorkel. This system enables the affinity purification of EVs from complex matrices in a non‐destructive form while maintaining EV characteristics in terms of surface protein profiles, associated miRNA patterns and uptake into a model cell line. Therefore, we consider the Snorkel‐tag to be a widely applicable tool in EV research, allowing for efficient preparation of EV standards and reference materials, or dissecting EVs with different surface markers when fusing to other tetraspanins in vitro or in vivo.

Commented article: XIE, J. Y.; CHEN, X. M. Contemporary Art: Cultivating Feng Zikai's Teachings. Trans/Form/Ação: Unesp journal of philosophy, v. 47, n. 4, e02400120, 2024. Available at: https://revistas.marilia.unesp.br/index.php/transformacao/article/view/15089.

Medicinal herbs can be used for the development of antioxidant and anticancer platforms. However, the mechanisms by which the bioactive materials show these properties remain largely unclear. Also, a detailed understanding of the interaction between small compounds and carrier proteins like albumin can provide useful information about the regulation of their stability and circulation time properties. In this paper, the interaction of rhamnazin (C17H14O7), an O-methylated flavonol exists in Rhamnus petiolaris, with human serum albumin (HSA) was investigated. Also, the antioxidant and anti-lung cancer effects of rhamnazin were assessed. The results showed that a static rhamnazin-HSA complex was formed by the contribution of hydrophobic forces, which led to an increase in the content of the α-helix structure of HSA. Cellular assays revealed that rhamnazin (10 µM) recovered cell viability in human proximal renal tubular epithelial cells (HK2) reduced by H2O2 (0.5 mM) through reduction of ROS, restoration of CAT and SOD activities and GSH content, regulation of Bax, Bcl-2, and caspase-3. Moreover, the anti-lung cancer data demonstrated that rhamnazin induced apoptosis on lung adenocarcinoma A549 cells associated with a p53-dependent manner via overexpression of apoptotic Bax and caspase-3 and down-regulation of anti-apoptotic Bcl-2. To summarize, the potential binding of rhamnazin and HSA, as well as its antioxidant/anticancer properties, are critical for understanding the solubility and stability of this bioactive compound in plasma, as well as its therapeutic implications.

Background: Glioblastoma (GBM) is a very common primary malignant tumor of the central nervous system (CNS). Aging, macrophage, autophagy, and methylation related genes are hypothesized to be crucial to its pathogenesis. In this study, we aimed to explore the role of these genes in the prognosis of GBM. Methods: The RNA sequence (RNA-seq) and clinical information were downloaded from The Cancer Genome Atlas database (TCGA) and the Chinese Glioma Genome Atlas database (CGGA). We performed univariate and least absolute shrinkage and selection operator (LASSO) multivariate Cox regression analysis to identify risk signatures related to overall survival (OS). We further developed a nomogram to predict individual outcomes. In addition, the immune microenvironment was analyzed by CIBERSORT. Results: 256 differentially expressed genes (DEGs) were obtained based on aging, macrophage, autophagy, and methylation related genes between GBM samples and normal tissues in TCGA-GBM cohort. We identified five optimal risk signatures with prognostic values in TCGA-GBM cohort and established a prognostic risk score model. The validity of the model was verified in the CGGA cohort and Huanhu cohort. Finally, we constructed a nomogram for clinical application by combining age, O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status, and risk score. Activated NK cells and resting mast cells were highly expressed and memory B cells, plasma cells, resting NK cells, M1 macrophages, and neutrophils exhibited low expression in the high-risk score group. GBM patients with a low-risk score had a higher Tumor Immune Dysfunction and Exclusion (TIDE) score. The risk score of hot tumors was higher than that of the cold tumors. Additionally, 29 genes involved in glucose and lipid metabolism were highly expressed with a high-risk score. 31 metabolism-related pathways were significantly different between high-risk and low-risk groups. Conclusions: We constructed and validated a novel prognostic model for GBM. Aging, macrophage, autophagy, and methylation related genes may serve as prognostic and therapeutic biomarkers. The model developed may assist in guiding treatment for GBM patients. Our research had great significance in accurately predicting the prognosis of GBM and may offer reference for immunotherapy decision for GBM patients.

Objectives Cancer screening aims to detect and treat malignant lesions at an early stage and to prolong patients’ lifetime. There is still a lack of effective cancer screening programs in China. We initiated a screening project in 2018 and this study presented the cancer screening status in China. Methods We conducted a cross-sectional study in one cancer-care medical center of China. The screening program included routine blood tests, plasma tumor markers, gastric endoscopy, colonoscopy, ultrasound, and computed tomography (CT) scans. Screening results were presented as sensitivity, specificity and positive predictive values (PPVs). Results Twenty-three (1.46%) out of 1,576 participants were eventually diagnosed with malignant tumors or high-grade intraepithelial neoplasia (HGIN). A family history of malignancy (78.26% in diagnosed cancer and HGIN vs. 46.36% in the others) was the only statistically significant parameter associated with cancer detection (p = 0.002). None of the common tumor markers were associated with the cancers screened. Except for colonoscopy (50.00%) and ultrasound for renal cancer (66.67%), the sensitivities of most screening methods were 100%. The specificities of all the screening means were above 96%. Most PPVs ranged from 30–60%. Conclusion We emphasized risk stratification for early cancer screening, such as a family history of cancer. The survey illustrated that gastric endoscopy, colonoscopy, ultrasound, and lung CT for early cancer screening had high specificity, reasonable sensitivity, and PPV. We anticipated this report would motivate larger-sample studies to estimate the risk-to-benefit ratio of cancer screening and urge the establishment of a native Chinese screening project and even guidelines.

Abstract Background PTEN loss has been identified in various tumor types and is linked to unfavorable clinical outcomes. In addition to PTEN mutation, multiple mechanisms contribute to PTEN loss during tumor development. However, the natural selection process of PTEN-deficient tumor cells remains unclear. Here, we aimed at further elucidating the role of PTEN-L in tumor progression. Methods PTEN knockout cell lines were generated using CRISPR/Cas9 technology. Ni-NTA affinity column chromatography was employed for PTEN-L purification. Tumor cell metastasis was evaluated in murine models and observed using the IVIS Spectrum Imaging System. RNA-sequencing, western blotting, PCR, flow cytometry, and cell proliferation assays were employed to investigate tumor cell dormancy and related mechanisms. Results The chemotherapeutic drugs, cisplatin, paclitaxel, and doxorubicin, induced tumor cells to secrete PTEN-long (PTEN-L), which shields PTEN-deficient tumor cells from chemotherapy-induced apoptosis better than it shields PTEN-intact cells. Further investigation revealed that PTEN-L treatment induced dormancy in PTEN-null tumor cells, characterized by an increase in p16 and p27 levels, cell-cycle arrest, reduced cell proliferation, and enhanced DNA repair. Furthermore, PTEN-L treatment selectively promoted the accumulation and growth of PTEN-null tumor cells in the lungs of C57BL/6J mice, while evading immune surveillance. Mechanistically, PTEN-L induced dormancy in PTEN-null tumor cells by activating the p38 signaling pathway. Addition of a p38 inhibitor effectively reversed dormancy and growth of PTEN-deficient tumor cells in the lungs. We also demonstrated that PTEN expression played a pivotal role in determining the outcome of PTEN-L-mediated antitumor therapy. Conclusions In summary, PTEN-L was identified as a potent inducer of dormancy in PTEN-deficient tumor cells, which increased their efficient selection within the tumor microenvironment.

Objective: This study aims to investigate the impact of noise reduction nursing in ward on patients who underwent intracranial aneurysm embolization. Methods: Between April 2020 and March 2021, Funan County People’s Hospital implemented standard nursing care for patients who underwent intracranial aneurysm embolization, comprising 55 patients admitted during this period, constituting the control group. Subsequently, from April 2021 to March 2022, the hospital introduced noise reduction nursing measures in wards. A total of 65 patients admitted during this period were included in the study group. Data on noise levels, emotional states, and sleep statuses were collected from both groups. The comprehensive impact of noise reduction nursing on the mental and physical health of patients who underwent intracranial aneurysm embolization was evaluated. Results: Before propensity score matching (PSM), significant differences were observed in age and intracranial aneurysm diameter between the two groups (P < 0.05). However, following PSM, a total of 102 patients were included in the analysis, and no significant differences in baseline data were observed between the two groups (P > 0.05). The noise level in the study group’s ward was significantly lower than that in the control group (P < 0.05). In addition, post-management, the study group exhibited lower Self-rating Anxiety Scale scores and total scores of Pittsburgh Sleep Quality Index compared with the control group. Moreover, the Glasgow Coma Scale score was higher in the study group, demonstrating statistical significance (P < 0.05). Conclusion: The implementation of noise reduction nursing in wards effectively controls ward noise levels and improves negative mood and sleep quality among patients who underwent intracranial aneurysm embolization. These findings indicate that noise reduction nursing facilitates postoperative rehabilitation and enhances patient outcomes.

Abstract Ignition electrodes have an immense impact on the accurate measurement of the flame propagation spherical radius. In this study, a flame-radius calculation method is designed. The method is able to eliminate effects due to the ignition electrodes. The adaptability and optimization effects of the proposed method are analyzed. The results show that the ratio of the angle is affected by the ignition electrodes under the Han II method. There are three obvious divisions include a high-value area, a sharp-variation area, and a mild-variation area. The ratio of the angle affected by the ignition electrodes is only applicable to the mild-variation region when the flame presents respective convex and concave distributions. For these distributions, the increment rate of the mean radius is 0.4–0.85% and 0.42–3.19%. The reduced rate of the standard deviation of the radius extraction value is 11.91–22.1% and 5.13–17.99%, and the reduced rate of the radius extraction value range is 20.32–39.51% and 0.32–8.09%.

Abstract RNA polymerases must transit through protein roadblocks to produce full-length transcripts. Here we report real-time measurements of Escherichia coli RNA polymerase passing through different barriers. As intuitively expected, assisting forces facilitated, and opposing forces hindered, RNA polymerase passage through lac repressor protein bound to natural binding sites. Force-dependent differences were significant at magnitudes as low as 0.2 pN and were abolished in the presence of the transcript cleavage factor GreA, which rescues backtracked RNA polymerase. In stark contrast, opposing forces promoted passage when the rate of RNA polymerase backtracking was comparable to, or faster than the rate of dissociation of the roadblock, particularly in the presence of GreA. Our experiments and simulations indicate that RNA polymerase may transit after roadblocks dissociate, or undergo cycles of backtracking, recovery, and ramming into roadblocks to pass through. We propose that such reciprocating motion also enables RNA polymerase to break protein-DNA contacts that hold RNA polymerase back during promoter escape and RNA chain elongation. This may facilitate productive transcription in vivo.

Abstract Gastric cancer (GC), notorious for its poor prognosis, often advances to peritoneal dissemination, a crucial determinant of detrimental outcomes. This study intricately explores the role of the TGFβ-Smad-LIF axis within the tumor microenvironment in propagating peritoneal metastasis, with a specific emphasis on its molecular mechanism in instigating Neutrophil Extracellular Traps (NETs) formation and encouraging GC cellular functions. Through a blend of bioinformatics analyses, utilizing TCGA and GEO databases, and meticulous in vivo and in vitro experiments, LIF was identified as pivotally associated with GC metastasis, notably, enhancing the NETs formation through neutrophil stimulation. Mechanistically, TGF-β was substantiated to elevate LIF expression via the activation of the Smad2/3 complex, culminating in NETs formation and consequently, propelling peritoneal metastasis of GC. This revelation uncovers a novel potential therapeutic target, promising a new avenue in managing GC and mitigating its metastatic propensities.

Abstract The gradual evolution of pharmacogenomics has shed light on the genetic basis for inter-individual drug response variations across diverse populations. This study aimed to identify pharmacogenomic variants that differ in Zhuang population compared with other populations and investigate their potential clinical relevance in gene-drug and genotypic-phenotypic associations. A total of 48 variants from 24 genes were genotyped in 200 Zhuang subjects using the Agena MassARRAY platform. The allele frequencies and genotype distribution data of 26 populations were obtained from the 1000 Genomes Project, followed by a comparison and statistical analysis. After Bonferroni correction, significant differences in genotype frequencies were observed of CYP3A5 (rs776746), ACE (rs4291), KCNH2 (rs1805123), and CYP2D6 (rs1065852) between the Zhuang population and the other 26 populations. It was also found that the Chinese Dai in Xishuangbanna, China, Han Chinese in Beijing, China, and Southern Han Chinese, China showed least deviation from the Zhuang population. The Esan in Nigeria, Gambian in Western Division, The Gambia, and Yoruba in Ibadan, Nigeria exhibited the largest differences. This was also proved by structural analysis, Fst analysis and phylogenetic tree. Furthermore, these differential variants may be associated with the pharmacological efficacy and toxicity of Captopril, Amlodipine, Lisinopril, metoclopramide, and alpha-hydroxymetoprolol in the Zhuang population. Our study has filled the gap of pharmacogenomic information in the Zhuang population and has provided a theoretical framework for the secure administration of drugs in the Zhuang population.

To enhance the performance of aviation piston engine starters in high-altitude environments, this study investigated their transient starting characteristics under low-temperature and low-pressure conditions using a high-altitude simulation chamber. Experiments were conducted across ambient temperatures from −60 to 15 °C and pressures from 35 to 95 kPa. The results show that the ambient temperature significantly impacts the transient characteristics of the motor, particularly at the initiation stage, whereas pressure has a weaker effect. For every 5 °C drop in temperature, the peak starting current increases by 1.95 A. From 15 to −60 °C, the maximum difference in the starting current pulse width is 11.64 ms. Furthermore, as the ambient temperature decreases, the average current after the motor stabilizes increases, and the average speed decreases.

Carbon capture and storage (CCS) technology is a crucial and effective tool to achieve China’s dual carbon goals. The primary locations suitable for underground CO2 storage include depleted oil and gas reservoirs, deep saline aquifers, and deep unmineable coal seams. Among these, deep saline aquifers are widely distributed in most of the world’s sedimentary basins, and they offer significant advantages—such as substantial storage capacity, well-established technology, high safety standards, and cost effectiveness—making them crucial geological reservoirs for carbon dioxide storage. In comparison to foreign countries’ projects on CO2 capture, utilization, and storage (CCUS) technology, China’s initiatives have been implemented more recently, and no research has been conducted on the geological storage of CO2 in the deep saline aquifers within the study area. In this study, we systematically analyzed the key factors for the geological storage of CO2 in saline reservoirs within the northwest plain of Shandong Province: the Paleogene Shahejie Formation saline aquifer, and the lower reservoir of the Minghuazhen Formation saline aquifer located east of the Zhanhua–Lijin–Dongying line. The CO2 geological storage potential of these aquifers was assessed using the evaluation methodology of the United States Department of Energy, yielding a result of 30.355 billion tons. An evaluation index system of CO2 geological storage suitability was established. Evaluation indices for regions in the study area were assigned according to this evaluation index, and the score and grade of each unit were obtained. The results indicated that the Huimin latent fault depression, Dongying latent fault depression, Dezhou latent fault depression, and Dongming–Shenxian latent fault depression are suitable prospective areas for CO2 geological storage in the saline aquifers of Shandong Province’s northwest plain.

Background: The mechanism of aneurysm wall enhancement (AWE) in middle cerebral artery (MCA) bifurcation aneurysms on vessel wall magnetic resonance imaging (VW-MRI) remains unclear. We aimed to explore the morphologically related hemodynamic mechanism for the AWE of MCA bifurcation aneurysms. Methods: Patients with unruptured MCA bifurcation aneurysms undergoing VW-MRI were enrolled. Logistic regression analyses were performed to determine the risk factors for AWE. Based on the results of retrospective analyses, bifurcation aneurysm silicone models with a specific aspect ratio (AR) were designed and underwent VW-MRI with different inlet velocities. Computational fluid dynamics (CFD) analyses were conducted on both silicone models and patients’ aneurysms. Results: A total of 104 aneurysms in 95 patients (mean age 60; 34 males) were included for baseline analysis and morphological analysis. Logistic regression analysis indicated AR (OR, 5.92; 95% CI, 2.00–17.55; p = 0.001) was associated with AWE. In the high-AR group of 45 aneurysms with AWE, the aneurysm sac exhibited lower blood flow velocity, lower wall shear stress, a larger proportion of low-flow regions and higher wall enhancement values. In total, 15 silicone models were analyzed, divided into three subgroups based on neck width (4 mm, 6 mm, and 8 mm). Each subgroup contained aneurysms with five different ARs: 1.0, 1.25, 1.5, 1.75, and 2.0. In silicone models, contrast enhancement (CE) was mainly located beneath the dome of the aneurysm wall. With the same inlet velocity, CE gradually increased as the AR increased. Similarly, at the same AR, CE increased as the inlet velocity decreased. CFD demonstrated a moderate positive correlation between the near-wall enhancement index and the ratio of the low-velocity area (r = 0.6672, p < 0.001). Conclusions: The AR is associated with the AWE of MCA bifurcation aneurysms. A high AR may promote wall enhancement by causing near-wall slow flow.

Summary: Background: The long-term survival and perioperative outcomes of robotic-assisted lobectomy (RAL) and video-assisted lobectomy (VAL) in resectable non-small-cell lung cancer (NSCLC) were found to be comparable in retrospective studies, but they have not been investigated in a randomized trial setting. We conducted the RVlob trial to investigate if RAL was non-inferior to VAL in patients with resectable NSCLC. Methods: In this single-center, open-label, and parallel-arm randomized controlled trial conducted in Ruijin Hospital (Shanghai, China) between May 2017 and May 2020, we randomly assigned patients with resectable NSCLC in a 1:1 ratio to receive either RAL or VAL. One of the primary endpoints was 3-year overall survival. Secondary endpoints included 3-year disease-free survival. The Kaplan–Meier approach was used to calculate overall survival and disease-free survival at 3 years. This study was registered with ClinicalTrials.gov, NCT03134534. Findings: A total of 320 patients were randomized to receive RAL (n = 157) or VAL (n = 163). The baseline characteristics of patients were well balanced between the two groups. After a median follow-up of 58.0 months, the 3-year overall survival was 94.6% (95% confidence interval [CI], 91.0–98.3) in the RAL group and 91.5% (95% CI, 87.2–96.0) in the VAL group (hazard ratio [HR] for death, 0.65; 95% CI, 0.33–1.28; P = 0.21); noninferiority of RAL was confirmed according to the predefined margin of −5% (absolute difference, 2.96%; a one-sided 90% CI, −1.39% to ∞; P = 0.0029 for noninferiority). The 3-year disease-free survival was 88.7% (95% CI, 83.6–94.1) in the RAL group and 85.4% (95% CI, 80.0–91.2) in the VAL group (HR for disease recurrence or death, 0.87; 95% CI, 0.50–1.52; P = 0.62). Interpretation: This study is the first randomized trial to show that RAL resulted in non-inferior overall survival compared with VAL in patients with resectable NSCLC. Based on our results, RAL is an equally oncologically effective treatment and can be considered as an alternative to VAL for resectable NSCLC. Funding: National Natural Science Foundation of China (82072557), National Key Research and Development Program of China (2021YFC2500900), Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant (20172005, the 2nd round of disbursement), program of Shanghai Academic Research Leader from Science and Technology Commission of Shanghai Municipality (20XD1402300), Novel Interdisciplinary Research Project from Shanghai Municipal Health Commission (2022JC023), and Interdisciplinary Program of Shanghai Jiao Tong University (YG2023ZD04).

Wheat (Triticum aestivum L.) is one of the world's most important staple crops, whose production is critical to feed the expanding population worldwide. The 90-kDa Heat Shock Protein 90 (HSP90) is a highly abundant chaperone protein involved in multiple cellular processes. It facilitates the folding of nascent preproteins for their maturation and functioning. This data described HSP90.2 clients identified from the whole genome of wheat. The HSP90.2 chaperome contains over 1500 proteins, most detected by the C terminus and full-length of HSP90.2. Over 60 % of the clients reside in the cytosol, nucleus, and chloroplasts. Cytoskeleton-related proteins are enriched in the chaperome of the N terminus of HSP90.2. The clients of the middle part of HSP90.2 contains several factors involved in ethylene biosynthesis and extracellular vesicle or organelle-related activities. Some clients related to plant hypersensitive response are induced by stripe rust. The presented dataset could isolate proteins regulated by HSP90.2 at the post-translational level.

Abstract Thanks to their excellent bond strength, phenyl‐based molecules with thiol anchoring groups are extensively employed to form stable single‐molecule junctions. However, two critical questions are still not answered which seriously hinder high‐yield establishing reliable molecular functional devices: (1) Whether molecular dimer junctions will be formed, and if this is the case, whether the dimerization is caused by intermolecular disulfide bonds or π–π stacking of phenyl rings; (2) Upon a mechanical‐compression force, is it possible that both anchoring groups of the molecule bond to the same electrode instead of bridging two opposite electrodes, which would drastically reduce the yield of the molecular junctions. Here, combining UV‐Vis/Raman spectroscopy of bulk molecules and conductance/flicker‐noise measurements of single molecules, we give compelling evidence that molecular dimers naturally form under ambient conditions, primarily via disulfide bonds rather than by π–π stacking. We further proposed a technique, named electrode‐compression‐hold‐on (ECHO), and reveal that the two thiol groups of phenyl‐backboned molecules will bond to the same electrode upon a compression force with a prolongated ECHO time. In contrast, the compression‐time‐dependent phenomenon is not observed for alkyl‐backboned molecules. The underlying mechanism for these unprecedented observations is elucidated, shedding light on the yield of molecular junctions.

Accurately predicting the binding affinities between Human Leukocyte Antigen (HLA) molecules and peptides is a crucial step in understanding the adaptive immune response. This knowledge can have important implications for the development of effective vaccines and the design of targeted immunotherapies. Existing sequence-based methods are insufficient to capture the structure information. Besides, the current methods lack model interpretability, which hinder revealing the key binding amino acids between the two molecules. To address these limitations, we proposed an interpretable graph convolutional neural network (GCNN) based prediction method named GIHP. Considering the size differences between HLA and short peptides, GIHP represent HLA structure as amino acid-level graph while represent peptide SMILE string as atom-level graph. For interpretation, we design a novel visual explanation method, gradient weighted activation mapping (Grad-WAM), for identifying key binding residues. GIHP achieved better prediction accuracy than state-of-the-art methods across various datasets. According to current research findings, key HLA-peptide binding residues mutations directly impact immunotherapy efficacy. Therefore, we verified those highlighted key residues to see whether they can significantly distinguish immunotherapy patient groups. We have verified that the identified functional residues can successfully separate patient survival groups across breast, bladder, and pan-cancer datasets. Results demonstrate that GIHP improves the accuracy and interpretation capabilities of HLA-peptide prediction, and the findings of this study can be used to guide personalized cancer immunotherapy treatment. Codes and datasets are publicly accessible at: https://github.com/sdustSu/GIHP.

IntroductionVariant pseudorabies virus (PRV) is a newly emerged zoonotic pathogen that can cause human blindness. PRV can take advantage of its large genome and multiple non-essential genes to construct recombinant attenuated vaccines carrying foreign genes. However, a major problem is that the foreign genes in recombinant PRV are only integrated into the genome for independent expression, rather than assembled on the surface of virion.MethodsWe reported a recombinant PRV with deleted gE/TK genes and an inserted porcine circovirus virus 2 (PCV2) Cap gene into the extracellular domain of the PRV gE gene using the Cre-loxP recombinant system combined with the CRISPR-Cas9 gene editing system. This recombinant PRV (PRV-Cap), with the envelope-embedded Cap protein, exhibits a similar replication ability to its parental virus.ResultsAn immunogenicity assay revealed that PRV-Cap immunized mice have 100% resistance to lethal PRV and PCV2 attacks. Neutralization antibody and ELISPOT detections indicated that PRV-Cap can enhance neutralizing antibodies to PRV and produce IFN-γ secreting T cells specific for both PRV and PCV2. Immunological mechanistic investigation revealed that initial immunization with PRV-Cap stimulates significantly early activation and expansion of CD69+ T cells, promoting the activation of CD4 Tfh cell dependent germinal B cells and producing effectively specific effector memory T and B cells. Booster immunization with PRV-Cap recalled the activation of PRV-specific IFN-γ+IL-2+CD4+ T cells and IFN-γ+TNF-α+CD8+ T cells, as well as PCV2-specific IFN-γ+TNF-α+CD8+ T cells.ConclusionCollectively, our data suggested an immunological mechanism in that the recombinant PRV with envelope-assembled PCV2 Cap protein can serve as an excellent vaccine candidate for combined immunity against PRV and PCV2, and provided a cost-effective method for the production of PRV- PCV2 vaccine.

Panax japonicus is an important medicinal plant, and flavonoids are one of its main secondary metabolites. In this study, the main roots, fibrous roots, stems, leaves and flowers of P. japonicus were analyzed using transcriptomics and widely targeted metabolomics. Through correlation analysis of transcription and metabolism, the flavonoid biosynthesis pathway in P. japonicus was analyzed, and the accumulation of flavonoid metabolites and the expression of related genes were investigated. Metabolomics revealed a total of 209 flavonoid metabolites in P. japonicus, among which flavonoids, flavonols, flavanones and flavanonols significantly accumulated in the flowers and leaves. Transcriptome sequencing revealed that key genes in the flavonoid pathway exhibited increased expression in the flowers and leaves. The expression patterns of key genes involved in flavonoid biosynthesis, including PjC4H, Pj4CL, PjCHS, PjCHI, PjF3H, PjF3’H, PjCYP, and PjPAL, are consistent with their upstream and downstream metabolites, demonstrating a significant positive correlation among them. In addition, the PjUGT gene is highly expressed in five tissues of P. japonicus, indicating that PjUGT is one of the key factors for the diversity of flavonoid glycosides. The WGCNA results showed that WRKY transcription factors exist widely in the candidate modules, and it was possible that PjWRKY transcription factors are involved in regulating the expression of key genes involved in flavonoid biosynthesis and the biosynthesis of flavonoid metabolites. This study reveals spatial differences in the accumulation patterns of flavonoid metabolites in different tissues and provides important clues for further understanding the regulatory mechanisms of flavonoid metabolism in P. japonicus, thus contributing to the optimization of germplasm resources of P. japonicus and the promotion of genetic diversity analysis.

The widespread use of spatial location-based services not only provides considerable convenience, but also exposes the downsides of location privacy leakage. Most of the existing user-side location privacy protection techniques are limited to planar locations. However, the extensive use of aircraft, sensor equipment and acquisition devices with positioning functions promotes the urgency of protecting the privacy of 3D spatial locations. Therefore, this study suggests a local differential privacy protection approach for 3D spatial locations. A 3D spatial decomposition and Hilbert encoding method are designed to reduce the 3D location data into one-dimensional encoding. The optimized random response mechanism was utilized to perturb the dimensional-reduced location encoding, which not only achieves user-side location privacy protection but also improves the accuracy of aggregated data on the server-side. Experiments on the real spatial location datasets show that the suggested method can reduce spatial location service quality loss, maintain the availability of perturbed spatial location and improve the operation efficiency of the spatial location perturbation algorithm.

Biosynthesis and biodegradation of microorganisms critically underpin the development of biotechnology, new drugs and therapies, and environmental remediation. However, most uncultured microbial species along with their metabolic capacities in extreme environments, remain obscured. Here we unravel the metabolic potential of microbial dark matters (MDMs) in four deep-inland hypersaline lakes in Xinjiang, China. Utilizing metagenomic binning, we uncovered a rich diversity of 3030 metagenome-assembled genomes (MAGs) across 82 phyla, revealing a substantial portion, 2363 MAGs, as previously unclassified at the genus level. These unknown MAGs displayed unique distribution patterns across different lakes, indicating a strong correlation with varied physicochemical conditions. Our analysis revealed an extensive array of 9635 biosynthesis gene clusters (BGCs), with a remarkable 9403 being novel, suggesting untapped biotechnological potential. Notably, some MAGs from potentially new phyla exhibited a high density of these BGCs. Beyond biosynthesis, our study also identified novel biodegradation pathways, including dehalogenation, anaerobic ammonium oxidation (Anammox), and degradation of polycyclic aromatic hydrocarbons (PAHs) and plastics, in previously unknown microbial clades. These findings significantly enrich our understanding of biosynthesis and biodegradation processes and open new avenues for biotechnological innovation, emphasizing the untapped potential of microbial diversity in hypersaline environments.

Introduction Benign prostatic hyperplasia (BPH) is a condition commonly seen among men aged over 40, significantly affecting their quality of life and typically accompanied by lower urinary tract symptoms (LUTS). Acupuncture presents a potentially effective treatment option; however, the exact effects remain uncertain. Therefore, we design this multicentre randomised trial to evaluate the efficacy and safety of electroacupuncture (EA) for relieving LUTS in men with BPH.Methods and analysis A two-arm, sham-controlled, subject-blinded and assessor-blinded trial will be conducted in 11 hospitals in China to compare EA with sham electroacupuncture (SA) in treating moderate to severe LUTS of BPH among men aged 40–80. A total of 306 eligible male patients will be recruited and assigned at a 1:1 ratio to receive either EA or SA for 24 sessions over a succession of 8 weeks, with 24 weeks of follow-up. The primary outcome will be the proportions of participants with at least 30% reduction in the International Prostate Symptom Score total score from baseline at weeks 8 and 20. All statistical analyses will be conducted in accordance with the intention-to-treat principle, and a two-tailed p value less than 0.05 will be considered statistically significant.Ethics and dissemination The trial has been approved by the institutional review board of Guang’anmen Hospital (2022-203-KY), as well as other recruitment centres. Each participant will receive the detailed information of the trial, and sign the written informed consent. The results of the trial are expected to be published in a peer-reviewed journal.Trial registration number NCT05585450.

Abstract Aims and Objectives This study aimed to investigate the current status of the core competencies and self‐directed learning ability of diabetes specialist nurses and to explore the relationship between these core competencies and their self‐directed learning ability. Design A cross‐sectional survey design was used. Methods This cross‐sectional study was conducted via a web‐based questionnaire platform in China from January 14 to April 24, 2023. The survey included a general information questionnaire, a diabetes specialist nurses' core competencies self‐assessment scale, and a nursing staff's self‐directed learning ability evaluation scale. The data was collected online. Descriptive, correlation and multiple linear regression analyses were conducted using SPSS 26.0 software. Results 118 diabetes specialist nurses from 11 cities participated in this study. A positive correlation was observed between the core competencies of diabetes specialist nurses and their self‐directed learning ability. The characteristics affecting the core competencies of diabetes specialist nurses included age, participation in external learning and communication and self‐directed learning. Conclusions The training of diabetes specialist nurses can focus on core competencies, and the ability to self‐direct learning can be used as an entry point to customize feasible theoretical and practical courses. The training system can further improve diabetes specialist nurses' core competencies and self‐directed learning abilities. Relevance to Clinical Practice A reference can be established that nursing managers and nursing educators can use to develop training programs for specialist nurses by validating the link between their core competencies and self‐directed learning skills. Patient or Public Contribution Participants were involved solely in the data collection process. No participant contributions were required for the study's design, outcome measurement or implementation.

Freezing rain is one of the most damaging weather phenomena in winter or early spring in many parts of the world, affecting traffic, power lines and agriculture. Thus, reliable and computationally efficient prediction of its occurrence is urgently needed in weather forecast operations. However, there are different thermodynamic processes that can lead to freezing rain, resulting in unsatisfactory forecasting performance of the state-of-the-art Numerical Weather Prediction (NWP) models. Here a data-driven forecasting method for freezing rain using machine learning technologies is proposed. Observations of weather phenomenon collected from 2 515 national weather stations of China for winter of 2016–2019 and the corresponding atmospheric predictors derived from ERA5 reanalysis are used. The prediction function is constructed based on the classification and regression tree, and the predicting variables include temporal and vertical profiles of fundamental thermodynamic and kinematic parameters from 500 hPa to 1000 hPa, with a total dimension of 2 304. The LightGBM (Light Gradient Boosting Machine) framework is adopted to train our prediction model and an algorithm-level approach of modifying the loss function is used to address the imbalance of classes to improve forecasting skill. Results show that the data-driven prediction model, namely DDFR (data driven forecast of freezing rain), out-performs the benchmark NWP, i.e., ECMWF IFS product. It's improvements in terms of TS score range from 120% to 258% depending on different forecast leading times, which range from 0 to 12 h. In addition, DDFR is applied in an operational NWP model of China. The problem of domain adaptation is tackled and transfer learning method is employed to adapt the original DDFR to this NWP model. The effectiveness of such adaptation has been demonstrated by its performance on both training and testing datasets.