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JOURNAL/nrgr/04.03/01300535-202503000-00032/figure1/v/2024-06-17T092413Z/r/image-tiff Salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, Sal) is a catechol isoquinoline that causes neurotoxicity and shares structural similarity with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, an environmental toxin that causes Parkinson's disease. However, the mechanism by which Sal mediates dopaminergic neuronal death remains unclear. In this study, we found that Sal significantly enhanced the global level of N6-methyladenosine (m6A) RNA methylation in PC12 cells, mainly by inducing the downregulation of the expression of m6A demethylases fat mass and obesity-associated protein (FTO) and alkB homolog 5 (ALKBH5). RNA sequencing analysis showed that Sal downregulated the Hippo signaling pathway. The m6A reader YTH domain-containing family protein 2 (YTHDF2) promoted the degradation of m6A-containing Yes-associated protein 1 (YAP1) mRNA, which is a downstream key effector in the Hippo signaling pathway. Additionally, downregulation of YAP1 promoted autophagy, indicating that the mutual regulation between YAP1 and autophagy can lead to neurotoxicity. These findings reveal the role of Sal on m6A RNA methylation and suggest that Sal may act as an RNA methylation inducer mediating dopaminergic neuronal death through YAP1 and autophagy. Our results provide greater insights into the neurotoxic effects of catechol isoquinolines compared with other studies and may be a reference for assessing the involvement of RNA methylation in the pathogenesis of Parkinson's disease.

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To investigate the associations between isocarbophos and isofenphos with impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM), and to assess the mediation roles of inflammation cells. There were 2701 participants in the case-control study, including 896 patients with T2DM, 900 patients with IFG, 905 subjects with NGT. Plasma isocarbophos and isofenphos concentrations were measured using gas chromatography and triple quadrupole tandem mass spectrometry. Generalized linear models were used to calculate the relationships between plasma isofenphos and isocarbophos levels with inflammatory factor levels and T2DM. Inflammatory cell was used as mediators to estimate the mediating effects on the above associations. Isocarbophos and isofenphos were positively related with T2DM after adjusting for other factors. The odds ratio (95% confidence interval) (OR (95%CI)) for T2DM was 1.041 (1.015, 1.068) and for IFG was 1.066 (1.009, 1.127) per unit rise in ln-isocarbophos. The prevalence of T2DM increased by 6.4% for every 1 unit more of ln-isofenphos (OR (95% CI): 1.064 (1.041, 1.087)). Additionally, a 100% rise in ln-isocarbophos was linked to 3.3% higher ln-HOMA2IR and a 0.029 mmol/L higher glycosylated hemoglobin (HbA1c) (95% CI: 0.007, 0.051). While a 100% rise in ln-isofenphos was linked to increase in ln-HOMA2 and ln-HOMA2IR of 5.8% and 3.4%, respectively. Furthermore, white blood cell (WBC) and neutrophilic (NE) were found to be mediators in the relationship between isocarbophos and T2DM, and the corresponding proportions were 17.12% and 17.67%, respectively. Isofenphos and isocarbophos are associated with IFG and T2DM in the rural Chinese population, WBC and NE have a significant role in this relationship.

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Currently, developing nonantibiotic growth promoters is a broad consensus in broiler industry, which is one of the effective ways to reduce drug-resistant strains. Chuanminshen violaceum is a traditional Chinese medicinal herb that is commonly used for its roots, while the stems and leaves are often discarded, resulting in a huge amount of waste. This study optimized the preparation process of water extract of Chuanminshen violaceum stems and leaves (CVSLE) by response surface analysis based on the yields of polysaccharide and protein. The CVSLE and herbal powder (CVSL) were then processed into granules before being used as feed additives. The Macleaya cordata powder was used as positive control. The results showed that the addition of CVSLE (0.5% of the feed) showed the highest growth-promoting activity than other CVSLE groups (0.2% and 1%), 1% CVSL group and positive control (0.05%). CVSLE at the dosage of 0.5% could significantly increase the ADG and reduce the FCR from d 21 to 42, d 0 to 42. The HI antibody titers against Newcastle disease virus and avian influenza virus were significantly enhanced at 21, 28 and 42 d. CVSLE did not affect the slaughtering performances, but could significantly elevate the spleen, thymus and bursa of Fabricius indices and the transcriptional levels of IL-2, IL-4, IL-10 and IFN-γ in spleen. The intestinal barrier function of broilers was significantly enhanced by increased levels of immune barrier (sIgA), physical barrier (ZO-1, OCL and Muc-2) and flora barrier (Lactobacillus and Bifidobacterium). These results suggest that CVSLE was a promising herbal additive candidate for broilers.

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STUDY DESIGN: Qualitative studies. OBJECTIVES: Spinal cord injury (SCI) is one of the most devastating injuries to the central nervous system that places a major burden on society. Neuromodulation technology involving spinal cord stimulation (SCS) and sacral nerve modulation (SNM) is a promising technique for patients with SCI. However, there has been no bibliometric analysis of research in this field to date. SETTING: Not applicable. METHODS: Systematic analyses of countries, institutions, authors, journals, co-cited documents, keywords, genes and diseases were performed. Related gene and disease data from the citexs platform were also reviewed. A total of 7437 articles on SCS and SNM in SCI were retrieved from the Web of Science database. The search time was limited to 1985-01-01 to 2022-12-31. RESULTS: We identified a significant increase in research output on SCS and SNM in SCI in recent years, with a concentrated period of high publication activity. Multiple publications were identified on neuropathic pain, electronic stimulation, TNF, BDNF and STAT3 gene expression, indicating that complications and potential therapeutic strategies for SCI are a key focus in the field. CONCLUSION: Our study provides insights that may help to advance scientific research and potentially improve outcomes in patients with SCI.

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The treatment of bladder cancer is limited by low drug efficacy and drug resistance. Hence, this study aimed to screen and identify potential drug precursors and investigate their mechanism of action. A set of camptothecin derivatives showing high anti-tumor potential was selected from early-stage research or literature and synthesized to construct a compound library. A total of 135 compounds were screened in T24 and J82 cells, revealing that FL118 significantly inhibited the proliferation of GC (gemcitabine + cisplatin)-sensitive/insensitive cells. FL118 exhibited excellent penetration and killing ability in organoids and three GC-insensitive patient-derived xenografts. Chemical proteomic and docking calculations were employed to identify binding proteins, indicating that FL118 can bind into H2A.X and its entwined DNA. The results of Cellular thermal shift assay and surface plasmon resonance (Kd = 3.77E-6) support the above findings. Fluorescence localization revealed widespread binding of FL118 within the cell nucleus. Furthermore, WB showed that FL118 increased cellular DNA damage, resulting in significant cell cycle inhibition. The binding of FL118 to H2A.X hindered the damage repair process, leading to apoptosis. Controllable adverse reactions were observed in mice treated with FL118. In conclusion, FL118 may be a superior anti-bladder cancer compound that acts as a molecular glue binding to both H2A.X and DNA. The resistance mediated by the DNA damage repair to DNA damage caused by GC regimen can be reversed by FL118. This distinct mechanism of FL118 has the potential to complement existing mainstream treatment approaches for bladder cancer.

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This study investigated the influence of Konjac Glucomannan (KGM) with varying degrees of polymerization (DKGMx) on the gelatinization and retrogradation characteristics of wheat starch, providing new insights into starch-polysaccharide interactions. This research uniquely focuses on the effects of DKGMx, utilizing multidisciplinary approaches including Rapid Visco Analysis (RVA), Differential Scanning Calorimetry (DSC), rheological testing, Low-Field Nuclear Magnetic Resonance (LF-NMR), and molecular simulations to assess the effects of DKGMx on gelatinization temperature, viscosity, structural changes post-retrogradation, and molecular interactions. Our findings revealed that higher degrees of polymerization (DP) of DKGMx significantly enhanced starch's pasting viscosity and stability, whereas lower DP reduced viscosity and interfered with retrogradation. High DP DKGMx promoted retrogradation by modifying moisture distribution. Molecular simulations revealed the interplay between low DP DKGMx and starch molecules. These interactions, characterized by increased hydrogen bonds and tighter binding to more starch chains, inhibited starch molecular rearrangement. Specifically, low DP DKGMx established a dense hydrogen bond network with starch, significantly restricting molecular mobility and rearrangement. This study provides new insights into the role of the DP of DKGMx in modulating wheat starch's properties, offering valuable implications for the functional improvement of starch-based foods and advancing starch science.

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Reference crop evapotranspiration (ET0) is a crucial variable for estimating the ecological water demand of vegetation. Under climate change, the trends of ET0 change vary in different regions. The study of spatial and temporal variations in ET0 and attribution analysis at the regional scale is more conducive to the regional agricultural water management and ecological water demand estimation under the changing environment. We analyzed the change trend, spatial distribution and the contribution of meteorological factors to annual ET0 change of the Fenwei Plain during a historical period (1985-2015) and a future period (2030-2060) based on the latest climate data and high-precision grid data from the Sixth International Coupled Model Intercomparison Project (CMIP6). The results showed that the meteorological data from CMIP6 could be used for the prediction of ET0 after bias correction, and that the prediction accuracy of the multi-model ensemble approach (R2 of 82.9%, RMSE of 14.9 mm) was higher than that of a single climate model. ET0 in the Fenwei Plain showed a significant decreasing trend in the historical period, but a non-significant increasing and significant increasing trend in the future period under the SSP245 and SSP585 scenarios, respectively. The vapor pressure deficit had the largest contribution to the ET0 change in both the historical and future periods, and was the primary meteorological factor affecting the ET0 change in the Fenwei Plain under the climate change. Solar radiation and wind speed were important meteorological factors affecting the ET0 change in the historical period, while temperature and wind speed were the important meteorological factors affecting the ET0 change in the future period. The meteorological factors that had great contribution to ET0 change were due to the larger multi-year relative change rates, rather than the high sensitivity of these meteorological factors to ET0. The ET0 of the plain under the SSP245 and SSP585 scenarios increased by 4.2% and 3.1% in the future period, respectively, compared with the historical period. The differences in the spatial distribution of the result were mainly from the eastern and western regions of the plain. Based on the high-precision spatial and temporal distribution of ET0, the spatial and temporal data could be used as a reference for the development of various adaptation for climate change in the Fenwei Plain.

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BACKGROUND: There are few studies on the safety of sub-maximal exercise testing of aerobic exercise in apparently healthy Chinese populations. The purpose of this study was to explore the frequency of exercise electrocardiography (ECG) abnormalities and the corresponding exercise intensities, as well as the associated influencing factors, during a symptom-limited stepwise incremental cardiopulmonary exercise test (CPET) in an apparently healthy Chinese population. METHODS: A cross-sectional study was done in four communities, one urban and one rural in the North (Beijing) and in the South (Hezhou, Guangxi) of China from 1 January 2017 to 31 December 2018, respectively. Total of 1642 participants was recruited, 918 were eligible and completed demographic indicators, routine blood indicators, physical activity status, symptom-limited CPET and exercise ECG were included in the analysis. RESULTS: Of the exercise ECG outcomes, 10 (1.1%) were positive and occurred at exercise intensities ≥ 62.50% heart rate reserve (HRR); 44 (4.8%) were equivocal and 864 (94.1%) were normal. Individuals with Cardiovascular Disease Risk Factor (CVDRF) = 3-4 were 2.6 times more likely to have a equivocal and abnormal exercise ECG than those with CVDRF = 0-2. Exercise ECGs of individuals with CVDRF = 5-7 were 5.4 times more likely to be positive and abnormal than exercise ECGs of individuals with CVDRF = 0-2. CONCLUSIONS: The exercise intensity of 62.5% HRR can be used as a safe upper limit for safe participation in exercise in apparently healthy Chinese population; the greater the number of CVDRFs, the greater the likelihood of cardiovascular risk during exercise.

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Sepsis represents a primary cause of acute kidney injury (AKI), yet the underlying mechanisms of septic AKI remain poorly understood. Thus, there exists an urgent need for a deeper understanding of its underlying mechanisms and the development of effective therapeutic strategies. Our study reveals a notable induction in microRNA-202-5p (miR-202-5p) levels within renal tubular cells in septic AKI both in vivo and in vitro models. Treatment of renal tubular cells with LPS induced NF-κB activation, which was linked to the induction of miR-202-5p. ChIP assays confirmed NF-κB binding to the miR-202-5p gene promoter upon LPS stimulation. Functionally, miR-202-5p mimics attenuated tubular cell death, kidney injury, and intra-renal inflammatory cytokine production, whereas inhibition of miR-202-5p conferred injurious effects in septic AKI. Notably, miR-202-5p suppressed the expression of High Mobility Group Box 2 (HMGB2) in both in vitro and in vivo septic AKI models. Luciferase microRNA target assays further validated HMGB2 as a direct target of miR-202-5p. Knockdown of HMGB2 inhibits LPS-induced NF-κB activation in septic AKI, as evidenced by HMGB2 siRNA transfection significantly inhibited the nuclear translocation of NF-κB. Together, these findings elucidate the NF-κB/miR-202-5p/HMGB2 negative feedback loop which can attenuate kidney injury by inhibiting renal inflammation in septic AKI. Our findings open new avenues for developing targeted therapies to manage septic AKI effectively.

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Importance: The effect of high-intensity noninvasive positive pressure ventilation (NPPV) on the need for endotracheal intubation in patients with an acute exacerbation of chronic obstructive pulmonary disease (COPD) is unknown. Objective: To determine whether the use of high-intensity NPPV vs low-intensity NPPV reduces the need for endotracheal intubation in patients with an acute exacerbation of COPD and hypercapnia. Design, Setting, and Participants: Randomized clinical trial conducted at 30 general respiratory non-intensive care unit wards of Chinese hospitals from January 3, 2019, to January 31, 2022; the last 90-day follow-up was on April 22, 2022. The included patients had an acute exacerbation of COPD and a Paco2 level greater than 45 mm Hg after receiving 6 hours of low-intensity NPPV. Interventions: Patients were randomized 1:1 to receive high-intensity NPPV with inspiratory positive airway pressure that was adjusted to obtain a tidal volume 10 mL/kg to 15 mL/kg of predicted body weight (n = 147) or to continue receiving low-intensity NPPV with inspiratory positive airway pressure that was adjusted to obtain a tidal volume of 6 mL/kg to 10 mL/kg of predicted body weight (n = 153). Patients in the low-intensity NPPV group who met the prespecified criteria for the need for endotracheal intubation were allowed to crossover to high-intensity NPPV. Main Outcomes and Measures: The primary outcome was the need for endotracheal intubation during hospitalization, which was defined by prespecified criteria. There were 15 prespecified secondary outcomes, including endotracheal intubation. Results: The trial was terminated by the data and safety monitoring board and the trial steering committee after an interim analysis of the first 300 patients. Among the 300 patients who completed the trial (mean age, 73 years [SD, 10 years]; 68% were men), all were included in the analysis. The primary outcome of meeting prespecified criteria for the need for endotracheal intubation occurred in 7 of 147 patients (4.8%) in the high-intensity NPPV group vs 21 of 153 (13.7%) in the low-intensity NPPV group (absolute difference, -9.0% [95% CI, -15.4% to -2.5%], 1-sided P = .004). However, rates of endotracheal intubation did not significantly differ between groups (3.4% [5/147] in the high-intensity NPPV group vs 3.9% [6/153] in the low-intensity NPPV group; absolute difference, -0.5% [95% CI, -4.8% to 3.7%], P = .81). Abdominal distension occurred more frequently in the high-intensity NPPV group (37.4% [55/147]) compared with the low-intensity NPPV group (25.5% [39/153]). Conclusions and Relevance: Patients with COPD and persistent hypercapnia in the high-intensity NPPV group (vs patients in the low-intensity NPPV group) were significantly less likely to meet criteria for the need for endotracheal intubation; however, patients in the low-intensity NPPV group were allowed to crossover to high-intensity NPPV, and the between-group rate of endotracheal intubation was not significantly different. Trial Registration: ClinicalTrials.gov Identifier: NCT02985918.

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BACKGROUND: Japanese encephalitis (JE) is a severe infectious disease of the central nervous system. Vaccination with Vero cell culture-derived vaccines may effectively reduce JE incidence. RESEARCH DESIGN AND METHODS: In this single-center, randomized, blinded, positive-controlled clinical trial in China involving 600 healthy infants aged 6-11 months, participants were divided into experimental and control groups administered JEV-PI and JEV-LI, respectively. Antibody titers were determined after 0- and 7-day immunization schedules. A booster dose followed 12 months later. RESULTS: After primary vaccination and before booster vaccination, the positive conversion rate, geometric mean titer (GMT), and geometric mean increase (GMI) of JEV-PI-neutralizing antibodies exceeded those of JEV-LI. After booster immunization, the GMT and GMI of JEV-PI were higher than those of JEV-LI. After primary immunization, the local, systemic, and overall adverse reactions were of grades 1 and 2, with a low incidence of grade 3. After booster immunization, these differences were mainly grades 1 and 2, with no differences between JEV-PI and JEV-LI. CONCLUSION: JEV-PI is a promising vaccine as infants acquired long-lasting and highly neutralizing immune antibodies after inoculation with JEV-PI. TRIAL REGISTRATION: The trial was registered in the Chinese Clinical Trial Registry (https://www.chictr.org.cn/showproj.html?proj = 203130; registration number: ChiCTR2300074692; registration date: 14/08/2023).

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Grassland caterpillars (Lepidoptera: Lymantriinae: Gynaephora) are the most damaging pests to alpine meadows in the Qinghai-Tibetan Plateau (QTP). Here, we conducted extensive sampling from 39 geographic populations covering almost the entire distribution of the eight QTP Gynaephora (Hübner) species to investigate phylogeographic patterns and speciation based on two mitochondrial genes (COI and ND5). A total of 40 haplotypes were detected in the 39 populations, with >70% of all haplotypes not shared between populations. The monophyletic QTP Gynaephora migrated from non-QTP regions during the Pliocene, corresponding to the uplift of the QTP, suggesting a mode of transport into the QTP. Among the eight QTP Gynaephora species described by morphological characteristics, two species (G. alpherakii and G. menyuanensis) were recovered as monophyletic groups (Clades B and C), while the remaining six formed two monophyletic clades: Clade A (G. qinghaiensis, G. jiuzhiensis, and G. qumalaiensis) and Clade D (G. aureata, G. ruoergensis, and G. minora). These results suggested that the number of the QTP Gynaephora species may be overestimated and further studies based on both morphological and nuclear gene data are needed. Genetic differentiation and speciation of the QTP Gynaephora were likely driven by the QTP uplifts and associated climate fluctuations during the Pleistocene, indicated by divergence time estimation, suggesting that isolation and subsequent divergence was the dominant mode of speciation. The Sanjiangyuan region (i.e., Clade A, characterized by high genetic diversity) may have been a glacial refugium of the QTP Gynaephora, as supported by analyses of gene flow and biogeography. High levels of genetic diversity were found in QTP Gynaephora, without population expansion, which may explain the high-altitude adaptation and outbreaks of grassland caterpillars in alpine meadows of the QTP. This study provides the largest phylogeographic analysis of QTP Gynaephora and improves our understanding of the diversity and speciation of QTP insects.

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Background and Objective: The ideal candidate for a male sling (MS) should have a mild to moderate degree of stress urinary incontinence (SUI). This narrative review article evaluates the current MS devices in the commercial market and examines the role of MS as an effective and safe alternative treatment option for male SUI. Methods: The available literature on MS was reviewed and relevant clinical studies pertaining to each MS were summarised with emphasis on device design and technology as well as specific surgical findings relating to clinical outcomes. Key Content and Findings: Over the past two decades, there have been considerable scientific advances in MS design and technology, and MS is an attractive alternative for patients who might not require or want an artificial urinary sphincter. The modern MS can be classified as adjustable or non-adjustable types and is placed either through a retropubic or transobturator (TO) approach. Strict patient selection and counselling, selection of MS with proven clinical records, and safe surgical practice are paramount to ensure a high continence rate, good patient satisfaction, and low postoperative complications. Published data on various MS materials and devices showed reasonable clinical efficacy and safety outcomes, although many of these synthetic MS devices may not be available worldwide due to a lack of regulatory approval in many countries. While the ideal MS is probably yet to be developed, continued scientific advances in slings design, mesh technology, and more refined surgical techniques will improve the continence rate and deliver better safety records. Conclusions: As clinical data matures with longer-term outcomes coupled with advances in scientific designs and technology, the ability to have and select the optimal MS for a particular patient will come to fruition.

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Purpose: Autistic symptom improvement can be observed in children treated with acupuncture, but the mechanism is still being explored. In the present study, we used scalp acupuncture to treat autism rat model, and then their improvement in the abnormal behaviors and specific mechanisms behind were revealed by detecting animal behaviors, analyzing the RNA sequencing of the prefrontal cortex (PFC), and observing the ultrastructure of PFC neurons under the transmission electron microscope. Methods: On gestational day 12.5, Wistar rats were given valproic acid (VPA) by intraperitoneal injection, and their offspring were considered to be reliable rat models of autism. They were randomized to VPA or VPA-acupuncture group (n = 8). Offspring of Wistar pregnant rats that were simultaneously injected with saline were randomly selected as the wild-type group (WT). VPA_acupuncture group rats received acupuncture intervention at 23 days of age for 4 weeks, and the other two groups followed without intervention. After the intervention, all experimental rats underwent behavioral tests. Immediately afterward, they were euthanized by cervical dislocation, and their prefrontal cortex was isolated for RNA sequencing and transmission electron microscopy. Results: The main results are as follows: 1. Animal behavioural tests: VPA group rats showed more anxiety-like behaviour and repetitive, stereotyped behaviour than WT group rats. While VPA group rats showed less spatial exploration ability, activity level, social interaction, and social novelty preference than WT group rats. It was gratifying to observe that acupuncture indeed improved these abnormal behaviors of autism rat model. 2. RNA-sequencing: The three groups of rats differed in the expression and enrichment pathways of multiple genes related to synaptic function, neural signal transduction, immune-inflammatory responses and circadian rhythm regulation. Our experiments indicated that acupuncture can alleviate the major symptoms of ASD by improving these neurological abnormalities. 3. Under the transmission electron microscopy, several lysosomes and mitochondrial structural abnormalities were observed in the prefrontal neurons of VPA group rats, which were manifested as atrophy of the mitochondrial membrane, blurring or disappearance of the mitochondrial cristae, and even vacuolization. Moreover, the number of synapses and synaptic vesicles was relatively small. Conversely, the mitochondrial structure of rats in the WT group and VPA_acupuncture was normal, and the number of synapses and synaptic vesicles was relatively large. Conclusion: Acupuncture effectively improved the abnormal behaviors of autism rat model and the ultrastructure of the PFC neurons, which might worked by improving their abnormal synaptic function, synaptic plasticity promoting neuronal signal transduction and regulating immune-inflammatory responses.

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In crop genetic improvement, the introduction of C4 plants' characteristics, known for high photosynthetic efficiency and water utilization, into C3 plants has been a significant challenge. This study investigates the effects of the desert halophyte Suaeda aralocaspica SaPEPC1 gene from a single-cell C4 photosythetic pathway, on drought resistance and photosynthetic performance in Arabidopsis. We used transgenic Arabidopsis with Zea mays ZmPEPC1 from C4 plant with classic Kranz anatomical structure and Arabidopsis AtPEPC1 from C3 photosynthetic cycle plants as controls. The results demonstrated that C4 photosynthetic-type PEPCs could improve drought resistance in plants through stomatal closure, promoting antioxidant enzyme accumulation, and reducing reactive oxygen species (ROS) accumulation. Overexpression of SaPEPC1 was significantly more effective than ZmPEPC1 in enhancing drought tolerance. Notably, overexpressed SaPEPC1 significantly improved light saturation intensity, electron transport rate (ETR), photosynthetic rate (Pn), and photoprotection ability under intense light. Furthermore, overexpression SaPEPC1 or ZmPEPC1 enhanced the activity of key C4 photosynthetic enzymes, including phosphoenolpyruvate carboxylase (PEPC), pyruvate orthophosphate dikinase (PPDK) and NADP-malic enzyme (NADP-ME), and promoted photosynthetic product sugar accumulation. However, with AtPEPC1 overexpression showing no obvious improvement effect on drought and photosynthetic performance. Therefore, these results indicated that introducing C4-type PEPC into C3 plants can significantly enhance drought resistance and photosynthetic performance. However, SaPEPC1 from a single-cell C4 cycle plant exhibits more significant effect in ETR and PSII photosynthesis performance than ZmPEPC1 from a classical C4 anatomical structure plant, although the underlying mechanism requires further exploration.

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Purpose: This study aimed to explore the impact of HSPA13 on epithelial-mesenchymal transition (EMT) in retinal pigment epithelial (RPE) cells and proliferative vitreoretinopathy (PVR) development, along with its associated molecular mechanisms. Methods: HSPA13 expression was evaluated in epiretinal membranes (ERMs) from patients with PVR using immunohistochemistry. The effects of HSPA13 knockdown on TGFß1-induced EMT in hESC-RPE cells were studied through quantitative PCR (qPCR), Western blot, and wound healing assays. Intracellular Ca2+ levels were measured using Fluo-8/AM incubation. A rat PVR model was induced by the intravitreal injection of RPE cells combined with platelet-rich plasma (PRP). RNA-seq was applied to study the molecular mechanism of HSPA13 knockdown-mediated EMT inhibition. Results: HSPA13 was found in human ERMs and its expression increased with TGFß1 treatment in hESC-RPE cells. Knockdown of HSPA13 inhibited TGFß1-induced EMT and migration. In the PVR rat model, HSPA13 was expressed in the ERMs and its knockdown in RPE cells reduced the development of PVR. Consistent with these observations, RNA-seq showed a global suppression of TGFß1-induced EMT and migration by shHSPA13 in RPE cells. Mechanistically, TGFß1 treatment increased intracellular Ca2+ levels, leading to an upregulation of HSPA13 expression. Downregulation of HSPA13 hindered the phosphorylation of PI3K/Akt in TGFß1-induced RPE cells. Conclusions: Our study revealed the involvement of HSPA13 in PVR development, as well as in TGFß1-induced EMT of RPE through the PI3K/Akt signaling pathway. Targeting HSPA13-related pathways involved in regulating EMT in RPE cells could serve as a novel therapeutic approach for patients with PVR.

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Public health emergencies influence urban carbon emissions, yet an in-depth understanding of deviations between regional emissions under such emergencies and normal levels is lacking. Inspired by the concept of resilience, we introduce the concept of regional carbon resilience and propose four resilience indicators covering periods during and after emergencies. A synthetic difference-in-differences model is employed to compute these indicators, providing a more suitable approach than traditional methods assuming unchanged levels before and after emergencies. Using the COVID-19 pandemic in China as a case study, focusing on the power and industry sectors, we find that over 40% regions exhibit strong resilience (> 0.9). Average in-resilience (0.764 and 0.783) is higher than post-resilience (0.534 and 0.598) in both sectors, indicating lower resilience during than after emergencies. Significant differences in resilience performance exist across regions, with Hebei (0.93) and Hangzhou (0.92) as top performers, and Qinghai (0.29) and Guiyang (0.36) as the least resilient. Furthermore, a preliminary correlation analysis identifies 22 factors affecting carbon resilience; higher energy consumption, stronger industrial production, and a healthier regional economy positively contribute to resilience with coefficients over + 0.3, while pandemic severity negatively impacts resilience, with coefficients up to -0.58. These findings provide valuable references for policymaking to achieve carbon neutrality goals.

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This experiment aimed to evaluate the effects of using sugarcane bagasse (SB) as a substitute for soybean hulls and wheat bran in the diet of pregnant sows on their reproductive performance and gut microbiota. A total of seventy-two primiparous sows were randomly divided into four treatment groups, with eighteen replicates of one sow each. The sows were fed a basal diet supplemented with 0% (CON), 5%, 10%, and 15% SB to replace soybean hulls from day 57 of gestation until the day of the end of the gestation period. The results showed that SB contains higher levels of crude fiber (42.1%) and neutral detergent fiber (81.3%) than soybean hulls, and it also exhibited the highest volumetric expansion when soaked in water (50 g expanding to 389.8 mL) compared to the other six materials we tested (vegetable scraps, soybean hulls, wheat bran, rice bran meal, rice bran, and corn DDGS). Compared with the CON, 5% SB significantly increased the litter birth weight of piglets. Meanwhile, 10% and 15% SB significantly increased the rates of constipation and reduced the contents of isobutyric acid and isovaleric acid in feces. Furthermore, 10% and 15% SB significantly disturbed gut microbial diversity with increasing Streptococcus and decreasing Prevotellaceae_NK3B31-group and Christensenellaceae_R-7-group genera in feces. Interestingly, Streptococcus had a significant negative correlation with isobutyric acid, isovaleric acid, and fecal score, while Prevotellaceae_NK3B31-group and Christensenellaceae_R-7-group had a positive correlation with them. In conclusion, our study indicates that 5% SB can be used as an equivalent substitute for soybean hulls to improve the reproductive performance of sows without affecting their gut microbiota.

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Seoul orthohantavirus (SEOV) has been identified as one of the main causative agents of hemorrhagic fever with renal syndrome (HFRS) in China. The virus was found circulating in rodent populations in almost all provinces of the country, reflecting the wide distribution of HFRS. Here, using the direct immunofluorescence assay (DFA) and real-time quantitative reverse transcription PCR (qRT-PCR) approach, we performed screening in 1784 small mammals belonging to 14 species of three orders captured in the main areas of HFRS endemicity in Yunnan province (southwestern China) and identified 37 SEOV-positive rats (36 Rattus norvegicus and 1 Rattus tanezumi). A 3-year surveillance of HFRS epidemics and dynamics of rodent reservoir density and virus prevalence implied a potential correlation between them. The subsequent meta-transcriptomic sequencing and phylogenetic analyses revealed three SEOV variants, among which two are completely novel. The ancestral character state reconstruction (ACSR) analysis based on both novel variants and documented strains from 5 continents demonstrated that SEOV appeared to originate near the southwestern area (Yunnan-Kweichow Plateau) of China, then could spread to other regions and countries by their rodent carriers, resulting in a global distribution today. In summary, these data furthered the understanding regards genetic diversity and the potential origin for SEOV. However, the expanding endemic foci in the province suggest that the virus is spreading over a wider region and is much more diverse than previous depicted, which means that increased sampling is necessary.

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It is crucial to explore the intrinsic mechanisms that influence thermometric sensitivity. This study investigates the optical performance of materials with the same crystal structure but different phonon energies. Ln2O2S:Er3+/Yb3+ (Ln = La/Gd/Y) phosphors with similar morphology and particle sizes were prepared to systematically study the influence of different phonon energy matrices on optical properties. The intrinsic mechanism was elucidated through the matching degree between the energy gap and phonon energy, Judd-Ofelt (J-O) theory, and quantum dielectric theory. It was ultimately concluded that the combination of high phonon energy with a large Ω2 and a small Ω6 is beneficial for enhancing the sensitivity of temperature sensing materials.