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Abstract Cellular senescence is characterized by a decrease in protein synthesis, although the underlying processes are mostly unclear. Chemical modifications to transfer RNAs (tRNAs) frequently influence tRNA activity, which is crucial for translation. We describe how tRNA N7-methylguanosine (m7G46) methylation, catalyzed by METTL1-WDR4, regulates translation and influences senescence phenotypes. Mettl1/Wdr4 and m7G gradually diminish with senescence and aging. A decrease in METTL1 causes a reduction in tRNAs, especially those with the m7G modification, via the rapid tRNA degradation (RTD) pathway. The decreases cause ribosomes to stall at certain codons, impeding the translation of mRNA that is essential in pathways such as Wnt signaling and ribosome biogenesis. Furthermore, chronic ribosome stalling stimulates the ribotoxic and integrative stress responses, which induce senescence-associated secretory phenotype. Moreover, restoring eEF1A protein mitigates senescence phenotypes caused by METTL1 deficiency by reducing RTD. Our findings demonstrate that tRNA m7G modification is essential for preventing premature senescence and aging by enabling efficient mRNA translation.

Abstract Genetic code expansion has emerged as a powerful tool for precisely introducing unnatural chemical structures into proteins to improve their catalytic functions. Given the high catalytic propensity of histidine in the enzyme pocket, increasing the chemical diversity of catalytic histidine could result in new characteristics of biocatalysts. Herein, we report the genetically encoded Nδ-Vinyl Histidine (δVin-H) and achieve the wild-type-like incorporation efficiency by the evolution of pyrrolysyl tRNA synthetase. As histidine usually acts as the nucleophile or the metal ligand in the catalytic center, we replace these two types of catalytic histidine to δVin-H to improve the performance of the histidine-involved catalytic center. Additionally, we further demonstrate the improvements of the hydrolysis activity of a previously reported organocatalytic esterase (the OE1.3 variant) in the acidic condition and myoglobin (Mb) catalyzed carbene transfer reactions under the aerobic condition. As histidine is one of the most frequently used residues in the enzyme catalytic center, the derivatization of the catalytic histidine by δVin-H holds a great potential to promote the performance of biocatalysts.

Abstract To detect and analyze the changes of microorganisms in expressed prostatic secretion (EPS) of patients with IIIB prostatitis before and after low-intensity pulsed ultrasound (LIPUS) treatment, and to explore the mechanism of LIPUS in the treatment of chronic prostatitis (CP). 25 patients (study power was estimated using a Dirichlet-multinomial approach and reached 96.5% at α = 0.05 using a sample size of 25) with IIIB prostatitis who were effective in LIPUS treatment were divided into two groups before and after LIPUS treatment. High throughput second-generation sequencing technique was used to detect and analyze the relative abundance of bacterial 16 s ribosomal variable regions in EPS before and after treatment. The data were analyzed by bioinformatics software and database, and differences with P

The deintercalation of weakly bonded A element affects the microstructure and properties of MAX phases and their reinforced composites. In this work, the effect of M-site element on the interaction of Al-containing M2AlC (M = V, Cr) phase and Ag, and the induced properties of Ag/M2AlC electrical contact materials (ECMs) were investigated. Though Ag and Al are soluble to each other and can form intermetallics, the variation of M element significantly affected the vacancy formation of Al, and thereby the interfacial reaction of Ag/M2AlC. The difficult formation of Al vacancy in V2AlC contributed to no obvious interfacial reaction in Ag/V2AlC. But the easy deintercalation of Al atoms in Cr2AlC led to their massive replacement by Ag, which generated Ag nano-twins and Cr3C2 with the same crystallographic relationship in one original Cr2AlC, and Cr7C3 and Ag3Al as well. Due to the distinct interactions, the resistivities of Ag/V2AlC and Ag/Cr2AlC increased by roughly 1 and 5 times after sintering, respectively. The low resistivity and proper hardness of the sintered Ag/V2AlC, which were very close to those of the “all-purpose” commercial Ag/CdO, contributed to its superior arc erosion resistance.

In this study, the synergistic effect of the Nb content and cooling rate on the microstructural transformation, precipitation behavior, and mechanical properties of hot-rolled rebar was studied using a Gleeble-3800 thermal simulation machine, scanning electron microscopy, transmission electron microscopy, and a universal tensile testing machine. The results showed that the synergistic effect of Nb content and cooling rate could optimize the microstructure and precipitation behavior of rebar, promote ferrite and pearlite transformation, and reduce the ferrite grain size, pearlite lamellar spacing, and precipitated phase size, thereby improving the strength and plasticity of Nb-containing rebar. When the cooling rate was 3 °C/s and the Nb content was 0.035 wt%, the ferrite grain size decreased to 21.45 μm, the pearlite lamellar spacing refined to 0.222 μm, and the particle size of the (Nb, Ti, V) C precipitates reduced to 5 nm. Accordingly, the yield and tensile strength increased to 779 ± 6 MPa and 973 ± 8 MPa, respectively, the elongation at fracture increased to 16.35%, and the microhardness increased to 311.39 ± 8.0 HV.

Abstract Aims Few studies have investigated differences in sequential transarterial chemoembolization (TACE), radiofrequency ablation (RFA), and simultaneous RFA‐TACE for the treatment of hepatocellular carcinoma (HCC) using the Milan criteria. This study explored the differences in safety and prognosis between sequential TACE‐RFA and simultaneous RFA‐TACE. Methods This retrospective real‐world study included 109 patients with HCC within the Milan criteria who underwent sequential TACE‐RFA (n = 75) or simultaneous RFA‐TACE (n = 34) at the Eastern Hepatobiliary Surgery Hospital between January 2017 and 2021. Postoperative complications, length of hospital stay, and long‐term prognosis were compared. The median follow‐up duration of these patients was 39.1 months. Overall survival (OS) and time to tumor recurrence (TTR) curves were plotted using the Kaplan−Meier method and were compared using the logarithmic rank test. Independent risk factors for OS and tumor recurrence (TR) were analyzed using the Cox risk regression model. Results Multivariate analysis showed that tumor diameter >3 cm (hazard ratio [HR]: 2.201, 95% confidence interval [CI]: 1.106–4.378, p = 0.025; HR: 2.236, 95% CI: 1.271–3.934, p = 0.005, respectively) and alpha‐fetoprotein (AFP) > 400 μg/L (HR: 2.362, 95% CI: 1.195–4.668, p = 0.013; HR: 1.798, 95% CI: 1.048–3.086, p = 0.033, respectively) were independent risk factors for OS and TTR, whereas the presence of multiple tumors (HR: 2.352, 95% CI: 1.127–4.907, p = 0.023) was an independent risk factor for TTR. Simultaneous RFA‐TACE did not have an effect on OS or TTR. After propensity score‐matched, comparable results were obtained and RFA‐TACE still had no effect on OS or TTR. No significant differences were observed in grade III/IV complications (2/75 [2.7%] vs. 1/34 [2.9%], p = 1.000) between the two groups. However, the RFA‐TACE group had fewer complications than the TACE‐RFA group (24/34 [70.6%] vs. 66/75 [88.0%], p = 0.026). The RFA‐TACE group had a shorter hospital stay and less total cost during hospitalization compared with the TACE‐RFA group (6.0 vs. 10.0 days, p

Abstract Yuxi, located in China’s central plateau of Yunnan, is grappling with ecological and environmental challenges as it continues to develop its economy. While ecological quality assessment serves as the foundation for ecological protection, it is pivotal to have reliable and long-term methods for assessing the ecological status to support informed decision-making in ecological protection. Reliable and long-term methods for assessing ecological status in order to facilitate informed decision-making in ecological protection are applied. This study utilized Landsat data to reconstruct four indices (greenness, wetness, dryness, and heat) during the vegetation growth in Yuxi from 2000 to 2020 that employs Harmonic Analysis of Time Series (HANTS) method. Subsequently, the annual Remote Sensing Ecological Index (RSEI) was computed by using the reconstructed indices to evaluate ecological quality in Yuxi. Additionally, spatiotemporal patterns and determinants of Yuxi’s ecological quality are unveiled through Sen’s slope estimator and Mann–Kendall test (Sen + MK) trend analysis, spatial auto-correlation analysis, and geographical detectors applied to year-by-year RSEI data. The findings in the paper indicate that the accuracy of the RSEI is significantly influenced by the vegetation season, suggesting that constructing the RSEI model with data from the vegetation growth season is crucial. Moreover, the HANTS optimization method effectively enhances the ecological indices used in the RSEI model, leading to smoother and more continuous filling of missing data. The difference between the reconstructed RSEI and the original RSEI falls within the range of − 0.15 to 0.15. Yuxi has an average RSEI of 0.54 to emphasis a moderate level of comprehensive ecological quality. Compared with river valley plains, the ecological quality of mountainous areas is higher, and the ecological quality of Yuxi presents a distinct center-edge pattern. From 2000 to 2020, Yuxi’s ecological quality exhibited fluctuations, with a slight overall improvement. Land use patterns, particularly in forestry land and impervious surfaces, are identified as the main drivers of these changes. The research offers valuable insights for scientific decision-making related to sustainable development and ecological protection.

Abstract Hydrothermal carbonization (HTC) has been regarded as a promising technique for turning wet biomass into hydrochar due to its low energy consumption, low exhaust gas emissions, etc. In addition, hydrochar is an important source of dissolved organic matter (DOM), which plays a crucial part in the migration and destiny of pollutants in the environmental medium. However, there are limited studies that focus on the factors that influence the formation of DOM in hydrochar, such as hydrothermal temperature. Therefore, the current study comprehensively characterized the optical properties of DOM within hydrochar derived from sawdust (HDOM) under different hydrothermal temperatures (150–300 °C) by Ultraviolet–visible (UV–Vis) and fluorescence spectroscopy, as well as its complexation characteristic with Cu(II). The findings revealed that the organic carbon content of HDOM reached a peak of 37.3 mg L−1 when the temperature rose to 240 °C and then decreased as the temperature increased. UV–Vis spectroscopy analysis showed that the absorption capacity of HDOM at 275 nm increases with temperature and reaches a maximum value at 240 °C, indicating that high temperature promotes the formation of monocyclic aromatic compounds. High temperature enhances the aromaticity, hydrophobicity, and humification degree of HDOM, thus improving its stability and aromaticity. The E3/E4 ratios are all greater than 3.5, confirming that the main component of HDOM is fulvic acid, which corresponds to 3D-EEM and Pearson's correlation coefficient analysis. The humification index (HIX) of HDOM increased with the rise in hydrothermal temperature (150–240 °C), as observed by the three-dimensional excitation-emission matrix spectroscopy (3D-EEMs). After reaching its peak at 240 °C, the HIX value gradually dropped in line with the trend of the DOC change. Moreover, the bioavailability (BIX) value of DOM was all high and greater than 1, indicating all the HDOM are readily bioavailable. Two microbial humic substances (C1 and C4), a humic-like substance (C2), and a protein-like substance (C3) were discovered in DOM by integrating 3D-EEMs with parallel factor analysis (PARAFAC). Their fluorescence intensity decreases as the Cu(II) concentration increases, indicating the formation of complexes with Cu(II). As the temperature rises, the binding ability of DOM and Cu(II) changes significantly, reaching the optimum at 300 °C. Meanwhile, the substance C2 has the strongest binding ability with Cu(II). This research emphasizes the significance of spectroscopy analysis in determining the evolution of hydrochar-derived DOM, the potential for heavy metal binding and migration, and its characteristics and features. Graphical Abstract

Abstract This phase II trial aimed to determine the efficacy and safety of induction chemoimmunotherapy of camrelizumab plus modified TPF in locally advanced hypopharyngeal squamous cell carcinoma (LA HSCC) (NCT04156698). The primary endpoint was objective response rate (ORR), and secondary endpoints were 3-year overall survival (OS), progression-free survival (PFS), larynx preservation rate (LPR), and metastasis-free survival (MFS). Patients (cT3-4aN0-2M0), regardless of sex, received induction chemoimmunotherapy for three cycles: camrelizumab 200 mg d1, docetaxel 75 mg/m2 d1, cisplatin 25 mg/m2 d1-3, and capecitabine 800 mg/m2 bid d1-14, q21d. Patients were assigned to radioimmunotherapy if they had a complete or partial response, those with stable or progressive disease underwent surgery and adjuvant (chemo)radiotherapy. Camrelizumab was maintained post-radioimmunotherapy. Fifty-one patients were enrolled with a median follow-up duration of 23.7 months. After induction therapy, the ORR was 82.4% (42/51), meeting the prespecified endpoint. Grade 3/4 adverse events occurred in 26 patients, and no treatment-related death occurred. As three-year outcomes were immature, two-year OS, PFS and LPR were reported. As no distant metastatic event had occurred, MFS was not reported here. The two-year OS, PFS, and LPR rates were 83.0%, 77.1%, and 70.0%, respectively. The induction chemoimmunotherapy of camrelizumab plus TPF showed a high ORR rate with an acceptable safety profile in LA HSCC.

The razor clam (Sinonovacula constricta, Class Bivalvia) is a kind of burial filter-feeding shellfish. Salinity fluctuation is an important source of pressure for water habitats. High salinity in some coastal areas of Shandong and Jiangsu impact the survival and germplasm conservation of razor clam. To study the ecological behavior response of S. constricta to high salt culture environment, two populations of razor clams were used, including "Shenzhe No.1" population (SZSC) and a natural population (ZRSC). The semi-lethal salinity level of each population was determined. The effects of control group (20) and high salinity (24, 28, 32) on burrowing and feeding behavior of razor clams were studied. The differences in burrowing indices and feeding physiology between the two populations were compared. In the burrowing behavior experiment, two groups were set; razor clams from the temporary pond were put into each salinity group to start the experiment, while the other group of razor clams were stressed under each salinity condition for 24 h and then put into each salinity group to start the experiment. The results showed that the 120 h LC50 of SZSC was 34.04, while the 120 h LC50 of ZRSC was 32.04. The burrowing behavior of razor clams could be divided into four periods: The preparation period of shell closure, the period of axe foot movement, mud digging period, and the end period of mud diving. In the non-stressed group, the burrowing time of 50% (BT50) of SZSC was significantly higher than that of ZRSC (P0.05). The BT50 of SZSC was closer to that of the control group at 24 and 28 salinity, and the vitality of SZSC was significantly better than that of ZRSC after 24 h of salinity stress. Under high salinity, the distribution of SZSC in mud was more concentrated than that in ZRSC, and the burrowing depth was shallower. In terms of feeding physiology, the feeding rate of SZSC was significantly higher than that of ZRSC under high salinity (P

Abstract Background Cytoplasmic male sterility (CMS) has greatly improved the utilization of heterosis in crops due to the absence of functional male gametophyte. The newly developed sporophytic D1 type CMS (CMS-D1) rice exhibits unique characteristics compared to the well-known sporophytic CMS-WA line, making it a valuable resource for rice breeding. Results In this research, a novel CMS-D1 line named Xingye A (XYA) was established, characterized by small, transparent, and shriveled anthers. Histological and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assays conducted on anthers from XYA and its maintainer line XYB revealed that male sterility in XYA is a result of delayed degradation of tapetal cells and abnormal programmed cell death (PCD) of microspores. Transcriptome analysis of young panicles revealed that differentially expressed genes (DEGs) in XYA, compared to XYB, were significantly enriched in processes related to chromatin structure and nucleosomes during the microspore mother cell (MMC) stage. Conversely, processes associated with sporopollenin biosynthesis, pollen exine formation, chitinase activity, and pollen wall assembly were enriched during the meiosis stage. Metabolome analysis identified 176 specific differentially accumulated metabolites (DAMs) during the meiosis stage, enriched in pathways such as α-linoleic acid metabolism, flavone and flavonol biosynthesis, and linolenic acid metabolism. Integration of transcriptomic and metabolomic data underscored the jasmonic acid (JA) biosynthesis pathway was significant enriched in XYA during the meiosis stage compared to XYB. Furthermore, levels of JA, MeJA, OPC4, OPDA, and JA-Ile were all higher in XYA than in XYB at the meiosis stage. Conclusions These findings emphasize the involvement of the JA biosynthetic pathway in pollen development in the CMS-D1 line, providing a foundation for further exploration of the molecular mechanisms involved in CMS-D1 sterility.

Abstract Background Intraventricular hemorrhage (IVH) refers to bleeding within the brain’s ventricular system, and hydrocephalus is a life-threatening complication of IVH characterized by increased cerebrospinal fluid accumulation in the ventricles resulting in elevated intracranial pressure. IVH poses significant challenges for healthcare providers due to the complexity of the underlying pathophysiology and lack of standardized treatment guidelines. Herein, we performed a systematic review of the treatment strategies for hydrocephalus secondary to IVH. Methods This systematic review was prospectively registered with PROSPERO (CRD42023450786). The search was conducted in PubMed, Cochrane Library, and Web of Science on July 15, 2023. We included original studies containing valid information on therapy management and outcome of hydrocephalus secondary to primary, spontaneous, and subarachnoid or intracranial hemorrhage following IVH in adults that were published between 2000 and 2023. Glasgow Outcome Scale (GOS) or modified Ranking Scale (mRS) scores during follow-up were extracted as primary outcomes. The risk of bias was assessed using the Newcastle–Ottawa Scale for Cohort Studies or Cochrane Risk of Bias 2.0 Tool. Results Two hundred and seven patients from nine published papers, including two randomized controlled trials, were included in the analysis. The GOS was used in five studies, while the mRS was used in four. Seven interventions were applied, including craniotomy for removal of hematoma, endoscopic removal of hematoma with/without endoscopic third ventriculostomy (ETV), traditional external ventricular drainage (EVD), and various combinations of EVD, lumbar drainage (LD), and intraventricular fibrinolysis (IVF). Endoscopic removal of hematoma was performed in five of nine studies. Traditional EVD had no obvious benefit compared with new management strategies. Three different combinations of EVD, LD, and IVF demonstrated satisfactory outcomes, although more studies are required to confirm their reliability. Removal of hematoma through craniotomy generated reliable result. Generally, endoscopic removal of hematoma with ETV, removal of hematoma through craniotomy, EVD with IVF, and EVD with early continuous LD were useful. Conclusion EVD is still crucial for the management of IVH and hydrocephalus. Despite a more reliable result from the removal of hematoma through craniotomy, a trend toward endoscopic approach was observed due to a less invasive profile.

Abstract Developing mild photocatalytic bromination strategies using sustainable bromo source has been attracting intense interests, but there is still much room for improvement. Full utilization of redox centers of photocatalysts for efficient generation of Br+ species is the key. Herein we report heterogenous organophotocatalytic HBr oxidation coupled with oxygen reduction to furnish Br2 and H2O2 for effective bromination of arenes over Al2O3 supported perylene-3,4,9,10-tetracarboxylic dianhydride (PTCDA). Mechanism studies suggest that O-vacancy in Al2O3 can provide Lewis-acid-type anchoring sites for O2, enabling unexpected dual-electron transfer from anchored photoexcited PTCDA to chemically bound O2 to produce H2O2. The in-situ generated H2O2 and Br2 over redox centers work together to generate HBrO for bromination of arenes. This work provides new insights that heterogenization of organophotocatalysts can not only help to improve their stability and recyclability, but also endow them with the ability to trigger unusual reaction mode via cooperative catalysis with supports.

Abstract Background Diabetic sarcopenia is a disease‐related skeletal muscle disorder that causes progressive symptoms. The complete understanding of its pathogenesis is yet to be unravelled, which makes it difficult to develop effective therapeutic strategies. This study investigates how MFG‐E8 affects mitophagy and the protective role of D‐pinitol (DP) in diabetic sarcopenia. Methods In vivo, streptozotocin‐induced diabetic SAM‐R1 (STZ‐R1) and SAM‐P8 (STZ‐P8) mice (16‐week‐old) were used, and STZ‐P8 mice were administrated of DP (150 mg/kg per day) for 6 weeks. Gastrocnemius muscles were harvested for histological analysis including transmission electron microscopy. Proteins were evaluated via immunohistochemistry (IHC), immunofluorescence (IF), and western blotting (WB) assay. In vitro, advanced glycation end products (AGEs) induced diabetic and D‐galactose (DG) induced senescent C2C12 models were established and received DP, MFG‐E8 plasmid (Mover)/siRNA (MsiRNA), or 3‐MA/Torin‐1 intervention. Proteins were evaluated by IF and WB assay. Immunoprecipitation (IP) and co‐immunoprecipitation (CO‐IP) were used for hunting the interacted proteins of MFG‐E8. Results In vivo, sarcopenia, mitophagy deficiency, and up‐regulated MFG‐E8 were confirmed in the STZ‐P8 group. DP exerted protective effects on sarcopenia and mitophagy (DP + STZ‐P8 vs. STZ‐P8; all P

In order to study the effect of hypoxia combined with acid stress on GABA enrichment in adzuki bean and mung bean, germination time, germination temperature, hypoxia time and L-glutamic acid concentration were investigated by single factor. Based on the stress conditions identified for high GABA sprouted beans, GABA-enriched adzuki and mung beans were mixed with rice, and D-mixture design was used to optimize processing conditions for these sprouted bean/rice mixtures. Results showed that hypoxia combined with acid stress promoted GABA enrichment in adzuki and mung beans. In sprouted adzuki beans, GABA reached levels as high as 158.32±3.24 mg/100 g under the germination time of 48 h, germination temperature of 40 ℃, 15 h exposure to hypoxia, and L-glutamic acid concentration of 2.5 mg/mL. Mung bean stress conditions were: Germination time of 24 h, germination temperature of 35 ℃, 15 h exposure to hypoxia, and L-glutamic acid concentration of 2.5 mg/mL, the content of GABA was 141.57±4.35 mg/100 g. On this basis, the sprouted beans and rice formulation was optimized by D-mixture design as follows: Rice 76%, sprouted mung beans 11%, and sprouted adzuki beans 13%. Under this composition, the GABA content of sprouted bean/rice mixture was 23.73±1.03 mg/100 g, and the average sensory score was 88.76±2.47. The taste, color, and aroma of the sprouted bean/rice mixture fell within acceptable ranges, and the active ingredient GABA was enriched, enhancing the nutritional and functional properties of sprouted beans/rice. This study provided a theoretical reference for the further development of rice/grain mixtures.

The prevalent practice of substituting fishmeal with plant protein frequently leads to disturbances in bile acid metabolism, subsequently increasing the incidence of metabolic liver diseases. Bile acid nutrients such as cholesterol, taurine and glycine have been shown to enhance bile acid synthesis and confer beneficial effects on growth. Therefore, this study aimed to investigate the effects of cholesterol-taurine-glycine (Ch-Tau-Gly) supplement on bile acid metabolism and liver health in spotted seabass (Lateolabrax maculatus) fed a plant-based diet. Two isonitrogenous and isolipidic diets were formulated: (1) plant protein-based diet (PP); (2) PP supplemented 0.5% cholesterol, 0.5% taurine and 1.3% glycine (CTG). Each experimental diet was randomly fed to quadruplicate groups of 30 feed-trained spotted seabass in each tank. The results revealed that supplementing plant-based diet with Ch-Tau-Gly supplement led to an increase in carcass ratio (meat yield) in spotted seabass (P