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This article introduces a high-magnification electronic endoscope system that utilizes a continuous zoom optical design, enabling high-magnification imaging at the cellular level. By selecting an appropriate initial retrofocus structure, the optimized modulation transfer function (MTF) curve of the zoom objective lens approaches the diffraction limit. Additionally, the tip and operation parts of the system incorporate modular gas-tight sealing and multiple layers of protective structure. The design employs efficient sealing materials and precise packaging techniques to ensure the system’s sealing performance. The experimental results indicate that, under conventional imaging, the resolution is equivalent to 39.37 μm in object space, and the field of view angle is larger than 140 degrees. At magnified imaging, the resolution is equivalent to 2.78 μm in object space, and the observed actual field of view is greater than 800 μm×700 μm. When used with a 26-inch display monitor, the high-magnification electronic endoscope can achieve 500× optical magnification, allowing for the observation of features at the cellular level. Currently, this product has successfully achieved mass production and has undergone multiple animal trials, demonstrating its wide range of potential applications and significant clinical value.

The approval of Epidiolex, an anti-epileptic drug containing cannabidiol (CBD) as its active component, has brought hope to patients with refractory epilepsy. However, the anti-seizure effect of full-spectrum hemp extract (HE), a CBD-enriched hemp oil, remains unclear. In this study, we investigated the anti-seizure effect of HE using drug-induced seizure models. Our findings revealed that HE significantly reduced seizure susceptibility comparable to CBD at the same doses. Moreover, we explored the pharmacokinetic properties of CBD in HE and observed improved characteristics such as faster oral absorption, enhanced brain distribution, and slower elimination. We further assessed the anti-seizure effects of the other five main non-addictive components in HE. Among these components, cannabichromene (CBC) and cannabinol (CBN) showed significant anti-seizure effects. To gain insights into the mechanisms of CBC and CBN, we investigated their allosteric modulation on the GABAA receptor. Our results revealed that CBC enhanced GABA-induced currents in both Xenopus laevis oocytes and mouse primary cortical neurons. Additionally, we identified V436 in the β2 subunit of the GABAA receptor as a critical binding site for CBC. These findings provide compelling evidence for the anti-seizure activities of HE and shed light on its underlying mechanisms. Our study provides insights into the broader therapeutic potential of hemp extracts and suggests their possible development as anti-seizure treatments.

Abstract High vibration poses significant safety and operational risks to compressor components. This study presents a thorough investigation of the root causes analysis and corrective actions to resolve vibration-induced failures faced on the suction system of a reciprocating compressor. Excessive pressure pulsations in the suction bottle and strong mechanical coupling between the cylinders and suction bottle due to high cylinder gas forces were identified as the root causes of vibration-induced failure of the suction system. The proposed solutions to eliminate this problem were implemented by splitting the suction bottle into two parts and making one bottle as an acoustic filter (Helmholtz resonator). The acoustic filter was optimized for the suppression of pressure pulsations above its Helmholtz frequency and also for the avoidance of acoustic and mechanical resonance. After applying the proposed solutions, the modified suction system achieved a 14.3-61.1% reduction in vibration and a 75.56% reduction in peak-to-peak pressure pulsation for the compressor operating at 1000 rpm. The processing capacity of the compressor has been increased by 6.82%. An acoustic filter is an effective low-cost technical measure for reduction of pressure pulsation and fluid-induced vibration, which greatly increases the reliability of the entire compressor system.

Abstract In this study, the surface analysis, cross-section analysis and electrochemical analysis were used to explore the formation mechanism of Nb contents on the passive film of high-strength anti-seismic rebar in simulated concrete pore solution. The passivation experiments confirmed that the addition of Nb promoted the stability and compactness of surface passive film of Nb-containing rebar, and the passivation efficiency of Nb-containing rebar was stronger than that of CS rebar. Firstly, with the decreases of pH, the increases of Nb promoted that the outer layer of the passive film were mainly composed of Fe oxides and Fe oxyhydroxides, the inner layer were mainly composed of Fe oxides and Nb oxides. Secondly, the increases of Nb were beneficial to the formation of Nb oxides, which enhanced the passivation rate of the passive film and inhibited the degradation of Fe oxides, thus enhancing the thickness of surface passive film of Nb-containing rebar.

Abstract Tapping line detection and rubber tapping pose estimation are challenging tasks in rubber plantation environments for rubber tapping robots. This study proposed a method for tapping line detection and rubber tapping pose estimation based on improved YOLOv8 and RGB-D information fusion. Firstly, YOLOv8n was improved by introducing the CFB module into the backbone, adding an output layer into the neck, fusing the EMA attention mechanism into the neck, and modifying the loss function as NWD to realize multi-object detection and segmentation. Secondly, the trunk skeleton line was extracted by combining level set and ellipse fitting. Then, the new tapping line was located by combining edge detection and geometric analysis. Finally, the rubber tapping pose was estimated based on the trunk skeleton line and the new tapping line. The detection results from 597 test images showed the improved YOLOv8n’s detection mAP0.5, segmentation mAP0.5, and model size were 81.9%, 72.9%, and 6.06 MB, respectively. The improved YOLOv8n’s effect and efficiency were superior compared to other networks, and it could better detect and segment natural rubber tree image targets in different scenes. The pose estimation results from 300 new tapping lines showed the average success rate and average time consumed for rubber tapping pose estimation were 96% and 0.2818 s, respectively. The positioning errors in x, y, and z directions were 0.69 ± 0.51 mm, 0.73 ± 0.4 mm, and 1.07 ± 0.56 mm, respectively. The error angles in a, o, and n directions were 1.65° ± 0.68°, 2.53° ± 0.88°, and 2.26° ± 0.89°, respectively. Therefore, this method offers an effective solution for rubber tapping pose estimation and provides theoretical support for the development of rubber tapping robots.

Abstract Gliomas exhibit high heterogeneity and poor prognosis. Despite substantial progress has been made at the genomic and transcriptomic levels, comprehensive proteomic characterization and its implications remain largely unexplored. In this study, we perform proteomic profiling of gliomas using 343 formalin-fixed and paraffin-embedded tumor samples and 53 normal-appearing brain samples from 188 patients, integrating these data with genomic panel information and clinical outcomes. The proteomic analysis uncovers two distinct subgroups: Subgroup 1, the metabolic neural subgroup, enriched in metabolic enzymes and neurotransmitter receptor proteins, and Subgroup 2, the immune subgroup, marked by upregulation of immune and inflammatory proteins. These proteomic subgroups show significant differences in prognosis, tumorigenesis, microenvironment dysregulation, and potential therapeutics, highlighting the critical roles of metabolic and immune processes in glioma biology and patient outcomes. Through a detailed investigation of metabolic pathways guided by our proteomic findings, dihydropyrimidine dehydrogenase (DPYD) and thymidine phosphorylase (TYMP) emerge as potential prognostic biomarkers linked to the reprogramming of nucleotide metabolism. Functional validation in patient-derived glioma stem cells and animal models highlights nucleotide metabolism as a promising therapy target for gliomas. This integrated multi-omics analysis introduces a proteomic classification for gliomas and identifies DPYD and TYMP as key metabolic biomarkers, offering insights into glioma pathogenesis and potential treatment strategies.

Abstract Background Alzheimer's disease (AD) is a prevalent irreversible neurodegenerative condition marked by gradual cognitive deterioration and neuronal loss. The mammalian Ste20-like kinase (MST1)–Hippo pathway is pivotal in regulating cell apoptosis, immune response, mitochondrial function, and oxidative stress. However, the association between MST1 and mitochondrial function in AD remains unknown. Therefore, this study investigates the effect of MST1 on neuronal damage and cognitive impairment by regulating mitochondrial homeostasis in AD. Methods In this study, 4- and 7-month-old 5xFAD mice were selected to simulate the early and middle stages of AD, respectively; age-matched wild-type mice served as controls for comparative analysis. Adeno-associated virus (AAV) was injected into the hippocampus of mice. Four weeks post-injection, cognitive function, neuronal damage indicators, and mitochondrial morphology, dynamics, oxidative stress, ATP, and apoptosis-related indicators were evaluated. Additionally, RNA-sequencing was performed on the hippocampal tissue of 5xFAD mice and MST1-knockdown 5xFAD mice. Subsequently, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed on differentially expressed genes to elucidate the potential mechanism of MST1. In vitro studies were performed to investigate the effects of MST1 on SH-SY5Y model cell viability and mitochondrial function and validate the potential underlying molecular mechanisms. Results MST1 overexpression accelerated neuronal degeneration and cognitive deficits in vivo while promoting oxidative stress and mitochondrial damage. Similarly, in vitro, MST1 overexpression facilitated apoptosis and mitochondrial dysfunction. MST1 knockdown and chemical inactivation reduced cognitive decline, mitochondrial dysfunction, and neuronal degeneration. Mechanistically, MST1 regulated the transcription of mitochondrial genes, including MT-ND4L, MT-ATP6, and MT-CO2, by binding to PGC1α. Moreover, MST1 influenced cellular oxidative stress through the PI3K-Akt-ROS pathway, ultimately disrupting mitochondrial homeostasis and mediating cell damage. Conclusions Cumulatively, these results suggest that MST1 primarily regulates mitochondrial DNA transcription levels by interacting with PGC1α and modulates cellular oxidative stress through the PI3K-Akt-ROS pathway, disrupting mitochondrial homeostasis. This discovery can be exploited to potentially enhance mitochondrial energy metabolism pathways by targeting MST1, offering novel potential therapeutic targets for treating AD. Graphical Abstract

Abstract Background For older adults with subjective cognitive decline (SCD), physical activity is now recognized as an effective means to reduce the risk of Alzheimer’s disease. However, this population often exhibits lower levels of physical activity. This study aimed to establish physical activity promoting indicators system for older adults with SCD, providing comprehensive targets for interventions and promoting relevant policies. Method A modified Delphi technique was used to seek opinions from experts about what should be used and prioritised as indicators of promoting physical activity in older adults with SCD. Expert consultations were conducted from January to March 2024. Data were analyzed using SPSS 27.0 and Excel software. Descriptive statistics were used for expert demographics, while coefficients were calculated to assess expert authority (Cr), and coordination (Kendall’s W). Weights for indicators were determined through the order diagram. Results Based on a literature review and the Wuli-Shili-Renli system framework, we initially identified 59 indicators, comprising primary (3 dimensions), secondary (11 items), and tertiary (45 items) indicators. Fifteen expert panelists were invited to participate in the study. Of these, 11 out of 18 completed round 1 (61.1% response rate), all 11 completed round 2 (100.0% response rate), and all 11 completed the third and final round (100.0% response rate). Ultimately, consensus was reached on 3 primary, 9 secondary, and 44 tertiary indicators. The order diagram determined weights for primary indicators as follows: foundational system (0.4242), operational system (0.2879), and personnel system (0.2879). Conclusion The system of 56 physical activity-promoting indicators constructed for older adults with SCD through the Delphi method provides theoretical support for policy formulation and allocation of funds to comprehensively promote physical activity behaviors among this population.

Abstract Head and neck squamous cell carcinoma (HNSCC) is notorious for poor prognoses, and effective biomarkers are urgently needed for early diagnosis of HNSCC patients. We investigate the role of alkaline ceramidase 1 (ACER1) and its relationship with immune infiltration in HNSCC. The differential expression and clinical prognostic significance of ACER1 in HNSCC patients are explored using bioinformatics methods and verified in human HNSCC samples. Genetic mutation, DNA methylation and drug sensitivity linked with ACER1 are examined. The potential biological function of ACER1 co-expression genes is assessed, and a series of functional assays are performed on ACER1in vitro. The results comprehensively reveal a relationship between ACER1 and immune infiltration in HNSCC patients. ACER1 expression is significantly downregulated in HNSCC tissues and closely correlated with better prognoses for HNSCC patients, and this prognostic significance is determined by distinct clinical characteristics. Genetic alteration and promoter hypomethylation of ACER1 are involved in progression of HNSCC, and ACER1 expression is significantly related to several drug sensitivities. Functional analysis shows that ACER1 co-expression genes are mainly enriched in the sphingolipid signaling pathway associated with inhibition of tumorigenesis, leading to better prognoses for HNSCC patients. In vitro, ACER1 overexpression inhibits proliferation and migration, induces apoptosis, and promotes adhesion of Fadu and SCC9 cells. In addition, high ACER1 expression is closely linked with infiltration levels of immune cells, and strongly associated with biomarkers of immune cells in HNSCC, suggesting the important role of ACER1 in regulating tumor immunity in HNSCC patients. In summary, ACER1 may be a useful indicator for diagnosis and prognosis, and may regulate immune infiltration in HNSCC patients, thus promising targeted immunotherapy for HNSCC.

Abstract In myelodysplastic syndromes (MDS), the IL-1β pathway is upregulated, and previous studies using mouse models of founder MDS mutations demonstrated that it enhances hematopoietic stem and progenitor cells’ (HSPCs’) aberrant differentiation towards the myeloid lineage at the expense of erythropoiesis. To evaluate whether targeting the IL-1β signaling pathway can rescue ineffective erythropoiesis in patients with MDS, we designed a phase 2 non-randomized single-arm clinical trial (NCT04239157) to assess the safety profile and efficacy of the IL-1β inhibitor canakinumab in previously treated lower-risk MDS patients. We enrolled 25 patients with a median age of 74 years; 60% were male, 16% had lower-risk MDS, 84% had intermediate-1 risk MDS according to the International Prognostic Scoring System score, and 80% failed hypomethylating agent therapy. The study met the primary endpoint of defining the clinical activity of canakinumab, and the secondary objective of determining the safety profile, including the rate of transfusion independence, the duration of response, progression-free survival, leukemia-free survival, and overall survival. The overall response rate was 17.4%, with all responses including hematological improvement. Sequential post-hoc prospective single-cell RNA sequencing analyses of HSPCs and bone marrow mononuclear cells at different time points during therapy showed that canakinumab’s on-target effects in hematopoietic populations expressing the IL-1β receptor decreased the TNF-mediated inflammatory signaling pathway but rescued ineffective erythropoiesis only in the context of lower genetic complexity. This study demonstrates that better stratification strategies could target lower-risk MDS patients more effectively.

Abstract The study focusing on developing an artificial neural network (ANN) model in accordance with genetic characteristics of osteosarcoma (OS) to accurately speculate OS cases. In the present study, we identified 467 DEGs through differentially acting gene investigation and that 345 exist suppressed and 122 exist stimulated. The resultant of GO enrichment analysis displayed the functions mainly included T cell activation, secretory granule lumen, antioxidant property etc. The pathways identified in the differentially acting genes (DAGs) were greatly interacted with Phagosome, Staphylococcus aureus infection, Human T − cell leukemia virus 1 infection, etc. Next, we found out top ten hub DEGs (HDEGs) by PPI network analysis. In addition, through the validation of ANN itself and Test set samples, it was proved that the prediction performance of our constructed ANN model is accurate and reliable. Finally, the penetration of immune cells and its interaction with target CDEGs were examined, and variations in penetration of 22 types of immune cells amongst different classes were found, additionally correlation amongst immune cells and between immune cells and target CDEGs. Furthermore, we analyzed the expression of the top two CDEGs (YES1 and MFNG) in OS tissues and normal tissues, also the interrelationship among the activity of YES1 and MFNG in OS tissues and clinicopathological properties of OS cases. Furthermore, the correlation analysis between the top two CDEGs and immune infiltrating cells was performed in OS tissues. Our research results revealed that CDEGs-based ANN model is effective at predicting OS patients, which facilitates early diagnosis and treatment of OS.

177Lu- prostate specific membrane antigen (PSMA) radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China. Based on domestic clinical practice and experimental data and referred to international experience and viewpoints, the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Abstract A large-scale shaking table test of a living stump slope with a geometric similarity ratio of 1:7 was designed and completed. The peak acceleration, acceleration amplification factor, and displacement response patterns of living stumps slopes under different types of seismic waves and excitation intensities were obtained. The time-frequency and energy variation characteristics were analyzed using the Hilbert-Huang Transform (HHT). The results showed that: (1) Regardless of the type of seismic wave, the peak acceleration and acceleration amplification factor of the living stumps slope surface are positively correlated with relative height and seismic excitation intensity. When the excitation intensity is ≤ 0.4 g, the acceleration amplification effect is more pronounced; when the excitation intensity is > 0.4 g, the acceleration amplification effect weakens. (2) Under the action of different seismic waves, the peak displacement of slope surface shows amplification effect along the elevation, and increases with the increase of excitation intensity. In addition, the incremental displacement gradually decreases from the toe to the top of the slope, which is expressed as D2 > D3 > D1 > D4 > D5. The peak displacement at the top of the slope is the greatest, but the incremental displacement is the smallest; the peak displacement at the toe of the slope is the smallest, but the incremental displacement is relatively large. (3) Regardless of the type of seismic wave, living stumps slope shows the characteristics of filtering the low-frequency components of the seismic waves and amplifying their high-frequency components. At the same time, the seismic Hilbert energy gradually accumulates along the elevation. PSHEA and PMSA significantly increase with elevation and excitation intensity, and they reach the maximum at the top of the slope. (4) The seismic Hilbert energy is positively correlated with the relative height and excitation intensity, and reaches the maximum at the top of the slope. With the accumulation of seismic Hilbert energy increases, the dynamic response parameters such as peak acceleration, acceleration amplification coefficient and displacement also increase synchronously, reaching the maximum at the top of the slope. The research conclusions can provide an experimental basis for the seismic design of living stumps slopes.

Abstract Impaired intestinal homeostasis is a major pathological feature of inflammatory bowel diseases (IBD). Mannose and selenium (Se) both demonstrate potential anti-inflammatory and anti-oxidative properties. However, most lectin receptors bind free monosaccharide ligands with relatively low affinity and most Se species induce side effects beyond a very narrow range of dosage. This has contributed to a poorly explored therapies for IBD that combine mannose and Se to target intestinal epithelial cells (IECs) for normalization gut homeostasis. Herein, a facile and safe strategy for ulcerative colitis (UC) treatment was developed using optimized, mannose-functionalized Se nanoparticles (M-SeNPs) encapsulated within a colon-targeted hydrogel delivery system containing alginate (SA) and chitosan (CS). This biocompatible nanosystem was efficiently taken up by IECs and led to increased expression of Se-dependent glutathione peroxidases (GPXs), thereby modulating IECs’ immune response. Using a mouse model of DSS-induced colitis, (CS/SA)-embedding M-SeNPs (C/S-MSe) were found to mitigate oxidative stress and inflammation through the inhibition of the NF-kB pathway in the colon. This stabilized mucosal homeostasis of IECs and ameliorated colitis-related symptoms, thereby providing a potential new approach for treatment of IBD.

Abstract In this study, XPS sputtering depth, SEM and electrochemical tests (CV, EIS, M-S, i-t, DPP) were used to study the structural composition and formation mechanism of surface passive film of Nb microalloyed rebar in SCPS with different pH. The results showed that after passivation for 10 d in SCPS with different pH, compared with CS rebar, the stability and compactness of surface passive film of 34Nb rebar gradually increased with the decreases of pH. Firstly, with the decreases of pH, the outer layer of surface passive film of 34Nb rebar was composed of Fe oxides and Fe hydroxides, and the inner layer was composed of Fe oxides and Nb oxides, thus increasing the mass ratio of Fe3+/Fe2+ and Nb2O5/(NbO2 + NbO). Secondly, with the decreases of pH, the addition of Nb promoted the formation of Fe oxides in 34Nb rebar, obtaining the excellent Rct, Ecorr and Ep. Finally, with the decreases of pH, the addition of Nb promoted the enrichment of Nb oxides in 34Nb rebar, inhibiting the degradation of Fe oxides, and the passive film exhibited the P-N type semiconductor, thus significantly decreasing the carrier density and enhancing the passivation rate of 34Nb rebar.

The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis. Microglia, as innate immune cells, play important roles in the maintenance of central nervous system homeostasis, injury response, and neurodegenerative diseases. Lactate has been considered a metabolic waste product, but recent studies are revealing ever more of the physiological functions of lactate. Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions, macrophage polarization, neuromodulation, and angiogenesis and has also been implicated in the development of various diseases. This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation, histone versus non-histone lactylation, and therapeutic approaches targeting lactate. Finally, we summarize the current research on microglia lactylation in central nervous system diseases. A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.

Abstract Background Osteoporosis is a major health concern for postmenopausal women, and the effect of simvastatin (Sim) on bone metabolism is controversial. This study aimed to investigate the effect of simvastatin on the bone microstructure and bone mechanical properties in ovariectomized (OVX) mice. Methods 24 female C57BL/6J mice (8-week-old) were randomly allocated into three groups including the OVX + Sim group, the OVX group and the control group. At 8 weeks after operation, the L4 vertebral bones were dissected completely for micro-Computed Tomography (micro-CT) scanning and micro-finite element analysis (µFEA). The differences between three groups were compared using ANOVA with a LSD correction, and the relationship between bone microstructure and mechanical properties was analyzed using linear regression. Results Bone volume fraction, trabecular number, connectivity density and trabecular tissue mineral density in the OVX + Sim group were significantly higher than those in the OVX group (P

Abstract Background Many studies have explored the clinicopathological features and prognosis between colorectal mucinous adenocarcinoma (MAC) and adenocarcinoma (AC) and have given different results. This meta-analysis summarizes previous evidence and evaluates the clinicopathological and prognostic features of MAC relative to AC in colorectal cancers (CRCs). Methods The meta-analysis was conducted by searching the databases of PubMed, China National Knowledge Infrastructure (CNKI), WANFANG data, Embase, and Web of Science. Pooled odds ratios (ORs) and hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated to assess the clinicopathological and prognostic differences between MAC and AC. Results Fifty-six studies involving 803157 patients met the inclusion criteria and were included in this meta-analysis. The clinicopathological features of MAC were greatly different from AC, except for lymphatic invasion (OR = 1.07, 95% CI: 0.99–1.15, P = 0.09) and perineural invasion (OR = 0.92, 95% CI: 0.79–1.06, P = 0.09). Further investigation found that MAC predicted poor OS (HR = 1.04, 95% CI: 1.03–1.04, P

Abstract Background Obesity is accompanied by inflammation, which significantly affects the homeostasis of the immune microenvironment. Hematopoietic stem cells (HSCs), residing primarily in the bone marrow, play a vital role in maintaining and producing diverse mature blood cell lineages for the adult hematopoietic and immune systems. However, how HSCs development is affected by obese-promoting inflammation, and the mechanism by which HSC hematopoietic potency is affected by inflammatory signals originating from the obese-promoting changes on bone marrow niche remain unclear. This study elucidates the relationship between obesity-promoting inflammation and HSC fate determination. Methods The obesity mice model was established by feeding C57BL/6J mice a high-fat diet (HFD) containing 60% kcal fat. After 6 weeks, HSCs were analyzed using flow cytometry and identified key inflammation cytokine. Transcriptome sequencing techniques were used to discern the distinct pathways in HSCs. Ultimately, confirming the biological mechanism of obesity-induced HSC fate changes via Anakinra blocking specific inflammatory signals. Results Obesity caused by HFD changed the physical and biochemical properties of the bone marrow niche. In the HFD mice, the population of long-term HSCs in the bone marrow was decreased and facilitated HSCs differentiation towards the myeloid lineage. In addition, HFD increased expression of the inflammatory factor IL-1β in the bone marrow, and a significantly increased expression of IL-1r1 and active p38/MAPK signaling pathway were detected in the HSCs. Inhibition of IL-1β further normalized the expression of genes in p38/MAPK pathway and reversed HSC fate. Conclusions These findings have been demonstrated that the p38/MAPK signaling pathway in HSCs is activated by elevated levels of IL-1β within the HSC niche in obese models, thereby regulating HSC differentiation. It suggested a direct link between obesity-promoting inflammation and myeloid differentiation bias of HSCs in the HFD mice. Graphical abstract

Abstract Recent studies have shown that aqueous U(VI) ions can be transformed into U(VI) precipitates through electrocatalytic redox reactions for uranium recovery. However, there have been no reports of U(IV) solids, such as UO2, using electrochemical methods under ambient conditions since low-valence states of uranium are typically oxidized to U(VI) by O2 or H2O2. Here we developed a secondary metal ion-induced strategy for electrocatalytic production of U(IV) solids from U(VI) solutions using a catalyst consisting of atomically dispersed gallium on hollow nitrogen-doped carbon capsules (Ga-Nx-C). This method relies on the presence of secondary metal ions, e.g., alkaline earth metals, transition metals, lanthanide metals, and actinide metals, which promote the generation of UO2 or bimetallic U(IV)-containing oxides through a two-electron transfer process. No U(IV) solid products were generated in the presence of alkali metal ions. Mechanistic studies revealed that the strong binding affinity between U(IV) and alkaline earth metals (Ca2+/Mg2+/Sr2+/Ba2+), transition metals (Ni2+/Zn2+/Pb2+/Fe3+, etc.) and lanthanide/actinide metals (Ce4+/Eu3+/Th4+/La3+) suppressed re-oxidation of U(IV) to U(VI), leading to the generation of U(IV)O2 and Mx(M = Ce, Eu, Th, La)U(IV)yO2. This work provides fundamental insights into the electrochemical behavior of uranium in aqueous media, whilst guiding uranyl capture from nuclear waste and contaminated water.

From 31 January to 5 February, 2024, Henan Province experienced a rare freezing rain and snow process characterized by a long duration,substantial cumulative precipitation,significant snow depth,low temperatures,and complex precipitation phases.Based on the national meteorological observation data,dual-polarization radar data,and hourly reanalysis data of ERA5,a diagnostic analysis of the event's extremity,phase evolution,and causes of the freezing rain and snow was conducted.The results are as follows.During the process,5 national meteorological stations reached or exceeded the maximum snow depth of the historical records in February.At many stations,the minimum temperature has reached or set a new historical record in early February.Precipitation was observed from at least 68.3% of national meteorological observation stations in a single day,with the longest continuous precipitation at a single station being nearly 29 hours.The stable maintenance of a large-scale circulation system was one of the main reasons for this process.The persistent intrusion of the strong cold air in the lower troposphere provided both dynamic uplift and sustained cooling conditions for the freezing rain and snow process.Exceptionally strong southerly airflow provided ample moisture and momentum,enhancing unstable stratification.For precipitation phase identification,relying solely on a single-layer temperature is insufficient.Instead,the entire atmospheric layer temperature should be considered to predict possible precipitation phases.When the entire atmospheric layer temperature is below 0℃,precipitation is pure snow.If there is a melting layer or the cloud consists of supercooled water droplets,mixed precipitation will occur.Dual-polarization radar's correlation coefficient and differential reflectivity products are useful for distinguishing between sleet and pure snow.A correlation coefficient close to 1 and differential reflectivity between-1 and 0 dB indicates pure snow,while a correlation coefficient less than 1 and differential reflectivity greater than 1 dB indicate sleet.

Abstract Vegetation growth may adapt to climate warming by adjusting the relationship between photosynthetic capacity and temperature. However, changes in the optimal temperature for ecosystem productivity during recent decades of warming remain uncertain. Here we provide empirical evidence that global optimal temperature increased at a rate of 0.017 ± 0.002 °C y−1 from 1982 to 2016, using multiple datasets of satellite-derived productivity and climate variables. Model simulations show that the optimal temperature will increase by 0.027 ± 0.001 °C y−1 until the end of 21st century. The global increasing optimal temperature is consistent with increasing mean air temperatures and model simulations further confirm the key role of temperature in regulating changes in optimal temperature, while being co-regulated by other factors, such as CO2 and precipitation. These results suggest that vegetation is acclimating to warming and that the negative impacts of climate change on ecosystem productivity may be less severe than previously thought.

Abstract Objective Transfer RNA-derived fragments (tRFs) are short non-coding RNA (ncRNA) sequences, ranging from 14 to 30 nucleotides, produced through the precise cleavage of precursor and mature tRNAs. While tRFs have been implicated in various diseases, including cancer, their role in lung adenocarcinoma (LUAD) remains underexplored. This study aims to investigate the impact of tRF-Val-CAC-010, a specific tRF molecule, on the phenotype of LUAD cells and its role in tumorigenesis and progression in vivo. Methods The expression level of tRF-Val-CAC-010 was quantified using quantitative real-time polymerase chain reaction (qRT-PCR). Specific inhibitors and mimics of tRF-Val-CAC-010 were synthesized for transient transfection. Cell proliferation was assessed using the Cell Counting Kit-8 (CCK-8), while cell invasion and migration were evaluated through Transwell invasion and scratch assays. Flow cytometry was utilized to analyze cell cycle and apoptosis. The in vivo effects of tRF-Val-CAC-010 on tumor growth and metastasis were determined through tumor formation and metastasis imaging experiments in nude mice. Results The expression level of tRF-Val-CAC-010 was upregulated in A549 and PC9 LUAD cells (P

Abstract Background Our study aimed to identify potential specific biomarkers for osteoarthritis (OA) and assess their relationship with immune infiltration. Methods We utilized data from GSE117999, GSE51588, and GSE57218 as training sets, while GSE114007 served as a validation set, all obtained from the GEO database. First, weighted gene co-expression network analysis (WGCNA) and functional enrichment analysis were performed to identify hub modules and potential functions of genes. We subsequently screened for potential OA biomarkers within the differentially expressed genes (DEGs) of the hub module using machine learning methods. The diagnostic accuracy of the candidate genes was validated. Additionally, single gene analysis and ssGSEA was performed. Then, we explored the relationship between biomarkers and immune cells. Lastly, we employed RT-PCR to validate our results. Results WGCNA results suggested that the blue module was the most associated with OA and was functionally associated with extracellular matrix (ECM)-related terms. Our analysis identified ALB, HTRA1, DPT, MXRA5, CILP, MPO, and PLAT as potential biomarkers. Notably, HTRA1, DPT, and MXRA5 consistently exhibited increased expression in OA across both training and validation cohorts, demonstrating robust diagnostic potential. The ssGSEA results revealed that abnormal infiltration of DCs, NK cells, Tfh, Th2, and Treg cells might contribute to OA progression. HTRA1, DPT, and MXRA5 showed significant correlation with immune cell infiltration. The RT-PCR results also confirmed these findings. Conclusions HTRA1, DPT, and MXRA5 are promising biomarkers for OA. Their overexpression strongly correlates with OA progression and immune cell infiltration.

Abstract UBE2M, a NEDD8-conjugating enzyme, is dysregulated in various human cancers and promotes tumor cell proliferation. However, its role in estrogen receptor-positive (ER+) breast cancer remains unknown. We found that UBE2M expression was significantly higher in ER+ breast cancer tissues than in ER-negative (ER-) breast cancer tissues. Higher expression of UBE2M indicated a poorer prognosis in patients with ER+ breast cancer but not in those with ER- breast cancer. Of interest, a positive feedback loop was observed between UBE2M and ERα. Specifically, ERα enhanced the HIF-1α-mediated transcription of UBE2M. In turn, UBE2M maintained ERα expression by inhibiting its ubiquitination and degradation through UBE2M-CUL3/4A-E6AP-ERα axis. Functionally, silencing of UBE2M suppressed the growth of breast cancer cells by inducing cell cycle arrest and apoptosis and improved their sensitivity to fulvestrant both in vitro and in vivo. Altogether, our findings reveal that the UBE2M-ERα feedback loop drives breast cancer progression and fulvestrant resistance, suggesting UBE2M as a viable target for endocrine therapy of ER+ breast cancer.

Abstract In this study, the immersion test, surface analysis, cross-section analysis, quantitative analysis and electrochemical analysis were used to study the influence of Nb/V on the corrosion behavior of high-strength anti-seismic rebar in marine environments. The corrosion results clarified that the addition of Nb/V improved the corrosion resistance of the rebar, thereby reducing the corrosion rate of the rebar and improving the stability of corrosion layers. Firstly, the addition of Nb/V promoted the transformation of unstable Fe oxyhydroxides to stable Fe oxyhydroxides in the surface corrosion layers of the rebar, thus increasing the α/(β + γ) ratio, corrosion potential and total impedance value. Secondly, the addition of Nb/V induced the formation of Nb oxides and V oxides in the surface corrosion layers of the rebar, and the existence of these oxides repaired the surface defects of corrosion layers, thus enhancing the corrosion resistance performance of surface corrosion layers of the rebar.

Abstract Duchenne muscular dystrophy (DMD) affecting 1 in 3500–5000 live male newborns is the frequently fatal genetic disease resulted from various mutations in DMD gene encoding dystrophin protein. About 70% of DMD-causing mutations are exon deletion leading to frameshift of open reading frame and dystrophin deficiency. To facilitate translating human DMD-targeting CRISPR therapeutics into patients, we herein establish a genetically humanized mouse model of DMD by replacing exon 50 and 51 of mouse Dmd gene with human exon 50 sequence. This humanized mouse model recapitulats patient’s DMD phenotypes of dystrophin deficiency and muscle dysfunction. Furthermore, we target splicing sites in human exon 50 with adenine base editor to induce exon skipping and robustly restored dystrophin expression in heart, tibialis anterior and diaphragm muscles. Importantly, systemic delivery of base editor via adeno-associated virus in the humanized male mouse model improves the muscle function of DMD mice to the similar level of wildtype ones, indicating the therapeutic efficacy of base editing strategy in treating most of DMD types with exon deletion or point mutations via exon-skipping induction.

Abstract The expression dysregulation of microRNAs (miRNA) has been widely reported during cancer development, however, the underling mechanism remains largely unanswered. In the present work, we performed a systematic integrative study for genome-wide DNA methylation, copy number variation and miRNA expression data to identify mechanisms underlying miRNA dysregulation in lower grade glioma. We identify 719 miRNAs whose expression was associated with alterations of copy number variation or promoter methylation. Integrative multi-omics analysis revealed four subtypes with differing prognoses. These glioma subtypes exhibited distinct immune-related characteristics as well as clinical and genetic features. By construction of a miRNA regulatory network, we identified candidate miRNAs associated with immune evasion and response to immunotherapy. Finally, eight prognosis related miRNAs were validated to promote cell migration, invasion and proliferation through in vitro experiments. Our study reveals the crosstalk among DNA methylation, copy number variation and miRNA expression for immune regulation in glioma, and could have important implications for patient stratification and development of biomarkers for immunotherapy approaches.

To study the immunomodulatory effects and safety of an antioxidant supplement composed primarily of Haematococcus pluvialis, selenium-enriched yeast, bee pollen extract, and vitamin E. Three different dosages (0.1, 0.2, and 0.4 g/kg bw) were administered via gavage once daily for 30 days in mice. The impact of this antioxidant supplement was observed on various parameters, including spleen index, thymus index, splenic lymphocyte transformation activity, delayed-type hypersensitivity, antibody-producing cell levels, hemolytic complement 50 (HC50), carbon clearance rate, phagocytic activity of macrophages, and natural killer cell activity. The potential carcinogenicity of the test materials, and their genotoxic effects on cells and the reproductive system were assessed through the Ames test, bone marrow micronucleus assay, and mouse sperm abnormality test, respectively. Subacute toxicity was investigated through a 30 day feeding trial. Results showed that compared to the control group, the middle and high-dosage groups exhibited significant increase in OD difference by 10.32% (P

Alpinia oxyphylla, a perennial herb belonging to the Zingiberaceae family, has a long history of traditional medicinal use. The present study evaluated the efficacy of different concentrations of Alpinia oxyphylla essential oil (AEO) on the growth performance, serum antioxidation capacities, immune function, apparent digestibility of nutrients, and gut microbiota in fattening pigs. A total of 120 pigs were divided into five treatments, with six replicates each and four pigs per replicate. The pigs were fed a basal diet or basal diet with chlortetracycline (CTC) alone or AEO at 250, 500, and 1,000 mg/kg (referred to as groups AEO1, AEO2, and AEO3, respectively) for 35 days, preceded by a 7-day pre-feed period. The results show that there were no statistically significant differences in growth performance for any dose of AEO supplementation. AEO increased L-DLC content, total protein content and the activity of GSH in serum (p

Abstract Hepatocellular carcinoma (HCC) often occurs in the context of fibrosis or cirrhosis. Methylation of histone is an important epigenetic mechanism, but it is unclear whether histone methyltransferases are potent targets for fibrosis‐associated HCC therapy. ASH1L, an H3K4 methyltransferase, is found at higher levels in activated hepatic stellate cells (HSCs) and hepatoma cells. To determine the role of ASH1L in vivo, transgenic mice with conditional Ash1l depletion in the hepatocyte cell lineage (Ash1lflox/floxAlbcre) or HSCs (Ash1lflox/floxGFAPcreERT2) are generated, and these mice are challenged in a diethylnitrosamine (DEN)/carbon tetrachloride (CCl4)‐induced model of liver fibrosis and HCC. Depleting Ash1l in both hepatocytes and HSCs mitigates hepatic fibrosis and HCC development. Multicolor flow cytometry, bulk, and single‐cell transcriptomic sequencing reveal that ASH1L creates an immunosuppressive microenvironment. Mechanically, ASH1L‐mediated H3K4me3 modification increases the expression of CCL2 and CSF1, which recruites and polarizes M2‐like pro‐tumorigenic macrophages. The M2‐like macrophages further enhance tumor cell proliferation and suppress CD8+ T cell activation. AS‐99, a small molecule inhibitor of ASH1L, demonstrates similar anti‐fibrosis and tumor‐suppressive effects. Of pathophysiological significance, the increased expression levels of mesenchymal ASH1L and M2 marker CD68 are associated with poor prognosis of HCC. The findings reveal ASH1L as a potential small‐molecule therapeutic target against fibrosis‐related HCC.

Critical-sized bone defects present a formidable challenge in tissue engineering, necessitating innovative approaches that integrate osteogenesis and angiogenesis for effective repair. Inspired by the hierarchical porous structure of natural bone, this study introduces a novel method for the scalable production of ultra-long, copper-doped hydroxyapatite (Cu-HAp) fibers, utilizing the rapid gelation properties of guar gum (GG) under controlled conditions. These fibers serve as foundational units to fabricate three-dimensional porous scaffolds with a biomimetic hierarchical architecture. The scaffolds exhibit a broad pore size distribution (1–500 μm) and abundant nanoporous features, mimicking the native bone extracellular matrix. Physicochemical characterization and in vitro assays demonstrated that the copper doping significantly enhanced osteogenic and angiogenic activities, with optimized concentrations (0.8 % and 1.2 % Cu) facilitating the upregulation of osteogenesis-related genes and proteins, as well as promoting endothelial cell proliferation. In vivo studies further confirmed the scaffolds' efficacy, with the 1.2Cu-HAp group showing a remarkable increase in bone regeneration (bone volume/total volume ratio: 35.7 ± 1.87 %) within the defect site. This research offers a promising strategy for the rapid fabrication of multifunctional scaffolds that not only support bone tissue repair but also actively accelerate the healing process through enhanced vascularization.

The design and analysis of gas detection chips directly affect their detection efficiency and applicability. Detection devices are currently restricted by detection principles, facing drawbacks like intricate structural design, limited applicability, and low detection efficiency. We have designed a complete set of design and analysis scheme for a peptide gas detection chip. First, we selected specific and high-affinity peptide combinations from existing peptide-gas affinity datasets. Then, the peptide chip's arrangement was grouped according to the variations in peptides' affinity towards different gases. Peptides were arranged based on their affinity levels within each group, striking a balance between discrimination and flexibility in the design of the chip. Finally, we evaluated the analysis methods by generating simulated data based on a reference affinity matrix constructed from actual data. Due to the preprocessing role of chip design on affinity data, all methods can effectively accomplish gas classification. In gas concentration prediction tasks, our method reduced mean square error to 0.41, significantly outperforming other methods. This gas detection scheme shortens the development cycle of chip design and analysis methods, fully utilizing the specificity of peptides, enhancing gas analysis effectiveness, and demonstrating the agile development of gas detection chips.

To assess the impact of vaccines on clinical outcomes among hospitalized COVID-19-infected patients requiring oxygen supplementation during the Beijing Omicron outbreak. We conducted a retrospective cohort study at Beijing Chaoyang Hospital, Capital Medical University, from November 15, 2022, to March 31, 2023. Vaccination statuses were categorized into 3 doses, 2 doses, and unvaccinated (0 dose). The primary outcome was 28-day all-cause mortality. Secondary outcomes included poor outcomes, intensive care unit admission, cardiovascular thromboembolism events, and hospital readmission. Among the included patients, 117 were 2 doses, 285 received booster doses, and 503 were unvaccinated. After propensity score inverse probability weighting, the 3 doses group showed a significantly lower 28-day all-cause mortality compared to the unvaccinated group (inverse probability of treatment weighting-adjusted HR: 0.64, 95% CI: 0.50–0.81). No significant difference was observed in all-cause mortality between the 2 doses and unvaccinated groups. No significant differences were observed in secondary outcome analyses when comparing the 3 doses or 2 doses group to the unvaccinated group. Subgroup analysis revealed significant benefits of booster vaccination in patients with shorter symptom duration, lower Charlson Comorbidity Index, and without immunosuppression status. Our study highlights the significant reduction in all-cause mortality among hospitalized Omicron-infected patients who received a third dose vaccine. These findings underscore the importance of prioritizing booster vaccinations, especially among the elderly. Further research is warranted to confirm and extend these observations.

This study is intended to explore the effect of hypoxia-inducible factor-1α (HIF-1α) activation on lipid accumulation in the diabetic kidney. A type 1 diabetic rat model was established by STZ intraperitoneal injection. Cobalt chloride (CoCl2) and YC-1 were used as the HIF-1α activator and antagonist, respectively. CoCl2 treatment significantly increased HIF-1α expression, accelerated lipid deposition, and accelerated tubular injury in diabetic kidneys. In vitro, CoCl2 effectively stabilized HIF-1α and increased its transportation from the cytoplasm to the nucleus, which was accompanied by significantly increased lipid accumulation in HK-2 cells. Furthermore, results obtained in vivo showed that HIF-1α protein expression in the renal tubules of diabetic rats was significantly downregulated by YC-1 treatment. Meanwhile, lipid accumulation in the tubules of the DM + YC-1 group was markedly decreased in comparison to the DM + DMSO group. Accordingly, PAS staining revealed that the pathological injury caused to the tubular epithelial cells was alleviated by YC-1 treatment. Furthermore, the blood glucose level, urine albumin creatinine ratio, and NAG creatinine ratio in the DM + YC-1 group were significantly decreased compared to the DM + DMSO group. Moreover, the protein expression levels of transforming growth factor β1 (TGF-β1) and connective tissue growth factor (CTGF) in diabetic kidneys were decreased by YC-1 treatment. Our findings demonstrate that the activation of HIF-1α contributed to interstitial injury in a rat model of diabetic nephropathy and that the underlying mechanism involved the induction of lipid accumulation.

The spread of multidrug-resistant strains of Neisseria gonorrhoeae poses a great challenge in gonorrhea treatment. At present, vaccination is the best strategy for gonorrhea control. However, given the extensive antigenic variability of N. gonorrhoeae, the effectiveness of monovalent vaccines is limited. Therefore, increasing the coverage of vaccination by using a multivalent vaccine may be more effective. In this study, a trivalent vaccine comprising three conserved antigens, namely, the App passenger domain, MetQ, and neisserial heparin binding antigen (NHBA), was constructed, and its protective effect was evaluated. Trivalent vaccines induced stronger circulating IgG and IgA antibody responses in mice than monovalent vaccines, in addition to eliciting Th1, Th2, and Th17 immune responses. Antiserum generated by the trivalent vaccine killed N. gonorrhoeae strains (homologous FA1090 and heterologous FA19), exhibiting superior bactericidal capacity than NHBA and MetQ vaccine antisera against N. gonorrhoeae, but similar capacities to those of the App vaccine antiserum. In addition, the trivalent vaccine antiserum achieved greater inhibition of N. gonorrhoeae FA1090 strain adherence to ME-180 cells compared to that elicited by the monovalent vaccine antiserum. In a mouse vaginal infection model, the trivalent vaccine was modestly effective (9.2% decrease in mean area under curve compared to the pCold-TF control mice), which was somewhat better than the protection seen with the monovalent vaccines. Our findings suggest that recombinant multivalent vaccines targeting N. gonorrhoeae exhibit advantages in protective efficacy compared to monovalent vaccines, and future research on multivalent vaccines should focus on optimizing different antigen combinations.

The accumulation of α-synuclein (α-syn), a key protein in Parkinson's disease (PD), contributes to progressive neuronal damage associated with mitochondrial dysfunction and interactions with various proteins. However, the precise mechanism by which α-syn affects energy metabolism remains unclear. In our study, we used human α-syn (hα-syn) transgenic mice, which exhibit progressive neuronal decline. Through an immunoprecipitation assay specific to hα-syn, we identified an enzyme in the mitochondrial tricarboxylic acid (TCA) cycle as a binding partner—mitochondrial aconitase 2 (ACO2), which converts citrate to isocitrate. Hα-syn increasingly interacted with ACO2 in mitochondria as mice aged, correlating with a progressive decrease in ACO2 activity. The overexpression of ACO2 and the addition of isocitrate, a downstream metabolite of ACO2, were observed to alleviate hα-syn-induced mitochondrial dysfunction and cytotoxicity. Furthermore, we designed an interfering peptide to block the interaction between ACO2 and hα-syn, which showed therapeutic effects in reducing hα-syn toxicity in vitro and in vivo. Our research establishes a direct link between α-syn and the TCA cycle and identifies ACO2 as a promising therapeutic target for improving mitochondrial function and reducing α-syn neurotoxicity in PD.

Background: Guillain-Barre syndrome (GBS), an autoimmune disease of the peripheral nervous system, is hallmarked by demyelination and immune cellular infiltration. Experimental autoimmune neuritis (EAN), considered a GBS prototype model, has been studied for its potential therapeutic benefits from lactobacilli. This study evaluated the protective role of Lactobacillus rhamnosus GG (GG) for treatment in EAN. T cell ratio, inflammation factors, sciatic nerve pathology, intestinal permeability, and gut inflammation were assessed on day 19 post-immunization to evaluate GG's effect on EAN. Fecal metabolomics and 16s rRNA microbiome analysis were conducted to elucidate its mechanism. Results: GG dynamically balanced CD4+/CD8+T cell ratio, reduced serum IL-1β and TNF-α expression, improved sciatic nerve demyelination and inflammation, and enhanced neurological scores during peak disease period. Intestinal mucosal damage was evident in EAN rats, with downregulated Occludin and ZO-1 and upregulated IL-1β, TNF-α, and Reg3γ. GG treatment restored intestinal mucosal integrity, upregulated Occludin and ZO-1, and downregulated IL-1, TNF-α, and Reg3γ. GG partially rectified the gut microbiota and metabolite imbalance in EAN rats. Conclusion: GG mitigates EAN through immune response modulation and inflammation reduction via the gut microbiota and metabolites.

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by gradual cognitive decline. Early-onset Alzheimer’s disease (EOAD) is defined as AD occurring before age 65. The main pathogenic gene variants associated with EOAD include PSEN1, PSEN2, and APP. IDE gene has been identified as a risk factor in the pathogenesis of AD. In this study, we report a 33-year-old male with mutations in the PSEN2 gene (c.640G > T, p.V214L) and IDE gene (c.782G > A, p.R261Q). PSEN2 V214L has been reported in five previous cases, and no reported cases have carried IDE R261Q. He had progressive memory decline, his sister carried the same gene mutations but had no clinical manifestations. Neuroimaging revealed mild cortical atrophy. The concentration of Aβ42 in cerebrospinal fluid (CSF) was obviously decreased. In silico predictive models suggested that these mutations are damaging. Our findings indicate that mutations in the PSEN2 and IDE genes may disrupt the normal functioning of their respective proteins, contributing to the pathogenesis of AD.

Abstract Artificial skin with tactile perceptions is anticipated to play a pivotal role in next‐generation robotic and medical devices. The primary challenge lies in creating a biomimetic system that seamlessly integrates with the human body and biological systems. The authors have developed an electronic skin (e‐skin) that imitates the biological sensorimotor loop through medium‐scale circuit integration, boasting low power consumption and solid‐state synaptic transistors.

Abstract Background Cerebral ischemic disease is a common cerebrovascular disease, especially ischemic stroke. Exercise has protective functions on brain tissues following cerebral ischemia‐reperfusion injury (CIRI), but its preventive effects and mechanisms in CIRI remain unclear. We aimed to investigate the effects and mechanisms of exercise preconditioning on CIRI. Methods The middle cerebral artery occlusion (MCAO) operation was prepared to establish CIRI rats. All rats were randomized into the MCAO, exercise (exercise preconditioning plus MCAO operation), vector (exercise preconditioning, MCAO operation plus intraventricular injection of empty vector), and tissue inhibitor of metalloprotease 1 overexpression (OE‐TIMP1, exercise preconditioning, MCAO operation plus intraventricular injection of OE‐TIMP1) groups. Results The results indicated that exercise preconditioning suppressed approximately 66.67% of neurological deficit scores and 73.79% of TIMP1 mRNA expression in MCAO rats, which were partially offset by OE‐TIMP1. The protective effects of exercise against neuron death status and cerebral infarction size in MCAO rats were reversed by OE‐TIMP1. It also confirmed that exercise weakened apoptosis and oxidative stress damage, with notable increases of B‐cell lymphoma‐2, superoxide dismutase, and glutathione peroxidase production, and evident decreases of BCL2‐associated X, caspase 3, and malondialdehyde in MCAO rats, while these effects were partially reversed by OE‐TIMP1. Additionally, the inhibitory effects of exercise on the protein levels of TIMP1, hypoxia‐inducible factor‐alpha, vascular endothelial growth factor receptor 2, vascular endothelial growth factor, and neurogenic locus notch homolog protein 1 in MCAO rats were partially reversed by OE‐TIMP1. Conclusion Altogether, exercise preconditioning had protective effects on CIRI by restraining TIMP1, which provided new therapeutic strategies for preventing CIRI.

Rapid and precise identification of glioma subtypes can assist surgeons in quickly determining patients’ conditions and developing treatment plans. However, current methods face challenges such as high cost and limited sensitivity, thereby significantly hindering diagnostic efficiency. In this paper, we proposed a spectral sensing strategy by introducing terahertz biosensors for glioma subtype recognition and therapeutic efficacy monitoring. Our findings demonstrated that both the resonance frequency and amplitude of the transmission spectra varied as the cell increased. The two-dimensional fingerprint diagram could help us rapidly recognize cell subtypes. Additionally, we conducted a theoretical analysis of the sensing performance. We confirmed that the high Q-factor (∼27.8) results from toroidal dipole resonance and examined the impact of dielectric loss and the refractive index of the analyte on the resonance dip. Furthermore, we applied the biosensor in therapeutic drug screening and showed that as the concentration of tubastatin A increased, the resonance frequency shifted from 183.1 GHz to 76.2 GHz. This result indicates that the toroidal dipole constructed by the metasurface enables ultrasensitive light-matter interactions that amplify subtle cellular changes to the resonance spectrum. The proposed THz meta-biosensor demonstrates significant potential for rapid intraoperative recognition of glioma cell subtypes and therapeutic efficacy monitoring.

BackgroundThis meta-analysis aimed to investigate the effects of traditional Chinese exercises on stroke and explore the dose-response relationship between the type of exercise and exercise duration with respect to physical and mental health.MethodsWe searched PubMed, Web of Science, EBSCO, China National Knowledge Infrastructure (CNKI), Wan Fang Database, and China Science and Technology Journal Database to identify published randomized controlled trials (RCTs) related to stroke patients and traditional Chinese exercise that met the evaluation criteria, from the inception of the database until September 2022. After assessing the quality of the literature, we used RevMan5.4 for data analysis.ResultsA total of 27 RCTs were included. The results of the meta-analysis revealed that motor function [MD = 4.79, 95% CI: (4.14, 5.43), p

Shellfish cultivation is a sustainable method of providing human food and can help remove large amounts of CO2 from the atmosphere. Over the last two decades, longline-based structures have dominated farming systems. So far, the innovative technologies for open-ocean shellfish farming remain stagnant and need to be developed. As such, this paper preliminarily studies the operation and survivability abilities of an innovative shellfish farm under extreme wave conditions. To that end, an efficient numerical scheme with a robust implicit finite element method is established. First, the numerical modeling of a single module of the shellfish farm is conducted and the numerical results are verified against physical model tests. Then, the numerical modeling is implemented in a full-scale shellfish farm containing nine floating rafts with suspended lantern nets in a 3×3 configuration exposed to extreme wave conditions. Different angles of wave attack and shellfish rafts with and without lantern nets are fully considered, allowing an assessment of the operation and survivability abilities of the shellfish farm under extreme wave conditions in various situations. The results highlight that the angle of wave attack significantly affected the energy absorption of the mooring system. Moreover, non-linear instability such as subharmonics, which existed in the motion dynamics, can be manipulated to avoid resonant motions. This study provides insights into the evaluation of the safety design of a shellfish farm at both operational and survivability levels. The numerical method can also model other advanced offshore marine structures with multi-modules, such as floating bridges, airports, and even floating energy islands.

Background China’s plasmapheresis donation policy differs from that of Western countries. The association between regular plasmapheresis donation and donor health in China is still unknown.Objectives To investigate the association of regular plasmapheresis donation with serum protein and electrolyte levels and provide scientific evidence for policy improvement.Design Multicentre cross-sectional study.Setting and participants A total of 767 regular and 726 new donors from the provinces of Sichuan, Hunan, Henan and Yunnan were recruited from September 2021 to October 2022.Primary and secondary outcome measures Our primary outcome focused on measuring the levels of serum protein and electrolyte levels, including total serum protein (TSP), IgG, albumin (Alb), haemoglobin (Hb), calcium, potassium (K+) and magnesium (Mg2+). The secondary outcome assessed their abnormal rates.Results Male and female donors in the high donation frequency group (>16 donations per year) exhibited lower IgG levels compared with new donors (p=0.008 for male donors and p=0.007 for female donors). Additionally, female donors with high donation frequency and a high total number of lifetime donations (>100 donations) had significantly lower Hb concentrations than new donors. However, no significant changes were observed in TSP, Alb, calcium, K+ and Mg2+ levels. There were also no statistically significant differences in the rates of abnormal protein and electrolyte values below the respective threshold levels between new and regular donors.Conclusions Plasmapheresis donation is not associated with an increased risk of abnormalities in the analysed parameters. However, the results provide preliminary evidence supporting the routine inclusion of IgG screening for donors, as plasmapheresis donation is associated with a decrease in IgG levels. Particular attention should be paid to the Hb levels of female donors, especially those who donate frequently. Testing of TSP at each donation may not be necessary.

Background Antibody-drug conjugates (ADCs) offer a promising approach, combining monoclonal antibodies with chemotherapeutic drugs to target cancer cells effectively while minimizing toxicity.Methods This study examined the therapeutic efficacy and potential mechanisms of a bispecific ADC (BsADC) in laryngeal squamous cell carcinoma. This BsADC selectively targets the immune checkpoints programmed cell death ligand-1 (PD-L1) and B7-H3, and the precise delivery of the small-molecule toxin monomethyl auristatin E.Results Our findings demonstrated that the BsADC outperformed its bispecific antibody and PD-L1 or B7-H3 ADC counterparts, particularly in terms of in vitro/in vivo tumor cytotoxicity, demonstrating remarkable immune cytotoxicity. Additionally, we observed potent activation of tumor-specific immunity and significant induction of markers of immunogenic cell death (ICD) and potential endoplasmic reticulum stress.Conclusion In conclusion, this novel BsADC, through immune checkpoint inhibition and promotion of ICD, amplified durable tumor immune cytotoxicity, providing novel insights and potential avenues for future cancer treatments and overcoming resistance.

Periodontitis is a chronic inflammatory disease that can result in the irreversible loss of tooth-supporting tissues and elevate the likelihood and intensity of systemic diseases. The presence of reactive oxygen species (ROS) and associated related oxidative stress is intricately linked to the progression and severity of periodontal inflammation. Targeted removal of local ROS may serve to attenuate inflammation, improve the unfavorable periodontal microenvironment and potentially reverse ensuing pathological cascades. These ROS scavenging nanoparticles, which possess additional characteristics such as anti-inflammation and osteogenic differentiation, are highly sought after for the treatment of periodontitis. In this study, negative charged human serum albumin-crosslinked manganese-doped self-assembling Prussian blue nanoparticles (HSA-MDSPB NPs) were fabricated. These nanoparticles demonstrate the ability to scavenge multiple ROS including superoxide anion, free hydroxyl radicals, singlet oxygen and hydrogen peroxide. Additionally, HSA-MDSPB NPs exhibit the capacity to alleviate inflammation in gingiva and alveolar bone both in vitro and in vivo. Furthermore, HSA-MDSPB NPs have been shown to play a role in promoting the polarization of macrophages from the M1 to M2 phenotype, resulting in reduced production of pro-inflammatory cytokines. More attractively, HSA-MDSPB NPs have been demonstrated to enhance cellular osteogenic differentiation. These properties of HSA-MDSPB NPs contribute to decreased inflammation, extracellular matrix degradation and bone loss in periodontal tissue. In conclusion, the multifunctional nature of HSA-MDSPB NPs provides a promising therapeutic approach for the treatment of periodontitis.

Henan encountered a multi-stage severe convective weather event (hereinafter referred to as "6.13" event) accompanied by local tornado on 13 June 2022. Using conventional observation data, regional automatic weather station data, satellite cloud images, Doppler weather radar data, ERA5 reanalysis data and other relevant data, we conducted an analysis on atmospheric circulation environment and the evolution characteristics of mesoscale systems for the "6.13" event. In addition, we discussed the initiation and maintenance mechanisms of convection in the different periods of this event and the radar characteristics of the local tornado in Puyang of Henan. Results are as follows. (1) The "6.13" event occurs under the northwest airflow behind the northeast cold vortex trough, and it is characterized by wide impact range, long duration and multiple types of disaster weather. (2) Radar detection results show that the severe convective systems in the "6.13" event passed through Henan in three periods one after another, and strong echoes in each period lasts for 8-9 hours, with the moving speed of 30-50 km·h-1. Most of the severe convective systems are multi-cells that all moved from northwest to southeast, with some of their areas overlapping under the guidance of northwest airflow. (3) Maintenance of the strong conditional instability and the moderate to strong vertical wind shear over Henan is an important cause for multi-stage severe convective weather in the "6.13" event lasting for a long time. The first period of local severe convection in Henan is mainly triggered by the convergence line or convergence center in the boundary layer formed by the combined effect of daily changes of wind field, local cold air activity, topographic distribution, while the second and third periods of severe convection are triggered by the gust front or outflow boundary accompanied by the surface mesoscale thunderstorm high formed by the strong developing convection systems in the surrounding area in the previous period or the same period. (4) The local tornado in Puyang is generated by a rapidly developing supercell storm. The hook echo and mesoscale cyclonic vortex appear 12 minutes after this supercell storm, and the tornado vortex characteristics (TVS) appear 18 minutes later. The hook echo and mesoscale cyclonic vortex are 6 minutes ahead of the occurrence of tornado, which can provide a reference information for early warning local tornadoes.