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Abstract In plants, the conserved plant-specific photoreceptor UV RESISTANCE LOCUS 8 (UVR8) perceives ultraviolet-B (UV-B) light and mediates UV-B-induced photomorphogenesis and stress acclimation. In this study, we reveal that UV-B light treatment shortens seedlings, increases stem thickness, and enhances UV-B stress tolerance in rice (Oryza sativa) via its two UV-B photoreceptors OsUVR8a and OsUVR8b. Although the rice and Arabidopsis (Arabidopsis thaliana) UVR8 (AtUVR8) photoreceptors all form monomers in response to UV-B light, OsUVR8a, and OsUVR8b function is only partially conserved with respect to AtUVR8 in UV-B-induced photomorphogenesis and stress acclimation. UV-B light and CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1) promote the nuclear accumulation of AtUVR8; by contrast, OsUVR8a and OsUVR8b constitutively localize to the nucleus via their own nuclear localization signals, independently of UV-B light and the RING-finger mutation of OsCOP1. We show that OsCOP1 negatively regulates UV-B responses, and shows weak interaction with OsUVR8s, which is ascribed to the N terminus of OsCOP1, which is conserved in several monocots. Furthermore, transcriptome analysis demonstrates that UV-B-responsive gene expression differs globally between Arabidopsis and rice, illuminating the evolutionary divergence of UV-B light signaling pathways between monocot and dicot plants.

Background/Objectives: Relapsed B-cell acute lymphoblastic leukemia (B-ALL) remains an unresolved matter of concern regarding adverse outcomes. This case study aimed to evaluate the effectiveness of blinatumomab, with or without door lymphocyte infusion (DLI), in treating measurable residual disease (MRD)-positive B-ALL. Methods: All patients who received blinatumomab salvage therapy were included in this study. Eleven patients were included in the study. All patients were evaluated for MRD-negativity. Results: Before starting blinatumomab therapy, seven patients tested positive for MRD, three tested negative, and one had refractory disease. Hematopoietic cell transplantation (HCT) was reserved for five patients with persistent MRD. Six patients became MRD-negative and subsequent HCT was not performed. Only two patients relapsed; one patient died of relapse, and the other one received carfilzomib-based therapy and was MRD-negative thereafter. Nine patients were MRD-negative at a median follow-up of 28 months (15–52 months). Two of three MRD-positive post-transplant patients remained in complete molecular remission after preemptive DLI at the last follow-up date. In the first salvage, blinatumomab may achieve complete remission and bridging to HCT in pediatric patients with end-of-induction MRD-positive B-cell precursor ALL. Conclusions: The decision on how to treat post-transplant relapse continues to affect survival outcomes. Blinatumomab combined with DLI may extend the armamentarium of release options for high-risk pediatric patients. This approach is encouraging for high-risk ALL patients who are MRD-positive post-transplantation.

Introduction: Vascular neointimal hyperplasia, a pathological process observed in cardiovascular diseases such as atherosclerosis and pulmonary hypertension, involves the abundant presence of vascular smooth muscle cells (VSMCs). The proliferation, migration, and autophagy of VSMCs are associated with the development of neointimal lesions. Circular RNAs (circRNAs) play critical roles in regulating VSMC proliferation and migration, thereby participating in neointimal hyperplasia. However, the regulatory roles of circRNAs in VSMC autophagy remain unclear. Objectives: We aimed to identify circRNAs that are involved in VSMC autophagy-mediated neointimal hyperplasia, as well as elucidate the underlying mechanisms. Methods: Dual-luciferase reporter gene assay was performed to validate two competing endogenous RNA axes, hsa_circ_0001402/miR-183-5p/FKBP prolyl isomerase like (FKBPL) and hsa_circ_0001402/miR-183-5p/beclin 1 (BECN1). Cell proliferation and migration analyses were employed to investigate the effects of hsa_circ_0001402, miR-183-5p, or FKBPL on VSMC proliferation and migration. Cell autophagy analysis was conducted to reveal the role of hsa_circ_0001402 or miR-183-5p on VSMC autophagy. The role of hsa_circ_0001402 or miR-183-5p on neointimal hyperplasia was evaluated using a mouse model of common carotid artery ligation. Results: Hsa_circ_0001402 acted as a sponge for miR-183-5p, leading to the suppression of miR-183-5p expression. Through direct interaction with the coding sequence (CDS) of FKBPL, miR-183-5p promoted VSMC proliferation and migration by decreasing FKBPL levels. Besides, miR-183-5p reduced BECN1 levels by targeting the 3′-untranslated region (UTR) of BECN1, thus inhibiting VSMC autophagy. By acting as a miR-183-5p sponge, overexpression of hsa_circ_0001402 increased FKBPL levels to inhibit VSMC proliferation and migration, while simultaneously elevating BECN1 levels to activate VSMC autophagy, thereby alleviating neointimal hyperplasia. Conclusion: Hsa_circ_0001402, acting as a miR-183-5p sponge, increases FKBPL levels to inhibit VSMC proliferation and migration, while enhancing BECN1 levels to activate VSMC autophagy, thus alleviating neointimal hyperplasia. The hsa_circ_0001402/miR-183-5p/FKBPL axis and hsa_circ_0001402/miR-183-5p/BECN1 axis may offer potential therapeutic targets for neointimal hyperplasia.

Objective: To explore the effect of oleuropein on sepsis-induced acute lung injury (ALI) in vitro and in vivo and investigate the underlying mechanism. Methods: In an lipopolysaccharide (LPS)-mediated cell model of sepsis-induced ALI and a cecal ligation and puncture-induced mouse model of septic ALI, CCK-8 assay and flow cytometry analysis were used to detect cell activity and apoptosis. ELISA and relevant assay kits were used to measure the levels of inflammatory cytokines and oxidative stress, respectively. Western blot was applied to determine the expression of apoptosis- and AMP-activated protein kinase (AMPK)/nuclear factor erythroid 2-related factor-2 (Nrf-2)/heme oxygenase-1 (HO-1) signaling-associated proteins. JC-1 staining, adenosine triphosphate (ATP) assay kit, and MitoSOX Red assays were performed to detect mitochondrial membrane potential, ATP content, and mitochondrial ROS formation, respectively. Moreover, lung injury was evaluated by measuring lung morphological alternations, lung wet-to-dry ratio, myeloperoxidase content, and total protein concentration. Results: Oleuropein reduced inflammatory reaction, oxidative damage, and apoptosis, and ameliorated mitochondrial dysfunction in LPS-exposed BEAS-2B cells and mice with septic ALI. Besides, oleuropein activated the AMPK/Nrf-2/HO-1 signaling pathway. However, these effects of oleuropein were abrogated by an AMPK inhibitor compound C. Conclusions: Oleuropein can protect against sepsis-induced ALI in vitro and in vivo by activating the AMPK/Nrf-2/HO-1 signaling, which might be a potential therapeutic agent for the treatment of sepsis-induced ALI.

IgA nephropathy (IgAN), the most common form of primary glomerulonephritis, is predominant in young adults and children. Corticosteroid therapy has been controversial over several past decades. TESTING (Therapeutic Effects of Steroids in IgA Nephropathy Global) study, initiated in 2012, is an international, multicenter, double-blinded, randomized and placebo-controlled trial for evaluating oral methylprednisolone’s safety and long-term efficacy under conditions of optimized supportive treatment in IgAN patients at an elevated risk of progression. After one decade of efforts, successful completion of TESTING indicated that a 6 to 9 month course of oral methylprednisolone has been an effective regimen of protecting kidney function in high-risk IgAN patients. Some safety concerns persisted. Compared with a full-dose regimen, reduced-dose regimen was beneficial with higher safety. Overall, the TESTING trial provided more robust data regarding the treatment dosage and safety of corticosteroids. It has important implications for IgAN children. With a deeper pathogenetic understanding of IgAN, ongoing studies of novel therapeutic regimens shall further optimize the benefit-risk ratio.

Severe fever with thrombocytopenia syndrome (SFTS) is a recently identified infectious ailment triggered by a new strain of bunyavirus. It is distinguished by elevated fatality rates, ranging from 12 % to 30 %. The mechanism underlying the development of severe illness caused by SFTS bunyavirus (SFTSV) is not yet fully understood. To evaluate the role of the TLR2 receptor pathway in regulating Treg function in the progression of SFTS disease and possible mechanisms, sequential serum samples from 29 patients with SFTS (15 mild, 14 severe cases) were examined. Flow cytometry was employed to scrutinize the phenotypic and functional characteristics of TLR2 expression on circulating CD4 T cells, CD8 T cells, and Tregs. In all admitted patients, the evaluation of correlations between the frequencies of the aforementioned cells and SFTS index (SFTSI) was conducted. For SFTS, the levels of TLR2 on CD4 T cells and Tregs were significantly heightened when compared to those in healthy subjects. Additionally, the expression of TLR2 on Tregs exhibited a positive correlation with Ki-67 expression in Tregs and the severity of disease. Additionally, compared with those in uninfected controls, the expression levels of NF-κB in Tregs were significantly increased. Collectively, Tregs may be activated and proliferate through the stimulation of the TLR2/NF-кB pathway in reaction to SFTSV infection.

Sodium‐ion batteries (NIBs) as one of the next‐generation energy storage devices are gradually used in energy field and entering lithium‐ion batteries (LIBs) market. Graphite with low price exhibits excellent Li+ reversible intercalation properties, which has been widely applied in anodes of LIBs. But it has low capacity for sodium because of its weak chemical bonding with sodium. Here, a defect engineered graphite with low graphitization structure is reported. This graphite demonstrates a defect adsorption and solvated ion intercalation of sodium ions by introducing more active sites and ether electrolytes, effectively improving the storage capacity of sodium. Further experiments and characterization show defects increased after ball milling with surface area increased, and the favorable defects on the interface of graphite are significantly increased. The defect engineered graphite absorbs more sodium‐ions and exhibits capacitive characteristics with fast sodiation/desodiation process, leading to an improved capacity storage than the defect‐free graphite. Meanwhile, the defect engineered graphite can deliver a capacity of 175 mAh g−1, and maintain a good capacity retention of 84% at 5 A g−1 after 6000 cycles. This work discovers a general methodology to obtain defect engineered graphite, which will provide an experimental strategy to achieve large‐scale industrialization for low‐cost NIBs.

Ischemic heart disease (IHD) is a condition where the heart muscle does not receive enough blood flow, leading to cardiac dysfunction. Restoring blood flow to the coronary artery is an effective clinical therapy for myocardial ischemia. This strategy helps lower the size of the myocardial infarction and improves the prognosis of patients. Nevertheless, if the disrupted blood flow to the heart muscle is restored within a specific timeframe, it leads to more severe harm to the previously deprived heart tissue. This condition is referred to as myocardial ischemia/reperfusion injury (MIRI). Until now, there is a dearth of efficacious strategies to prevent and manage MIRI. Hormones are specialized substances that are produced directly into the circulation by endocrine organs or tissues in humans and animals, and they have particular effects on the body. Hormonal medications utilize human or animal hormones as their active components, encompassing sex hormones, adrenaline medications, thyroid hormone medications, and others. While several studies have examined the preventive properties of different endocrine hormones, such as estrogen and hormone analogs, on myocardial injury caused by ischemia-reperfusion, there are other hormone analogs whose mechanisms of action remain unexplained and whose safety cannot be assured. The current study is on hormones and hormone medications, elucidating the mechanism of hormone pharmaceuticals and emphasizing the cardioprotective effects of different endocrine hormones. It aims to provide guidance for the therapeutic use of drugs and offer direction for the examination of MIRI in clinical therapy.

The biogenic synthesis of silver nanoparticles (AgNPs) by microorganisms has been a subject of increasing attention. Despite extensive studies on this biosynthetic pathway, the mechanisms underlying the involvement of proteins and enzymes in AgNPs production have not been fully explored. Herein, we reported that Burkholderia contaminans ZCC was able to reduce Ag+ to AgNPs with a diameter of (10±5) nm inside the cell. Exposure of B. contaminans ZCC to Ag+ ions led to significant changes in the functional groups of cellular proteins, with approximately 5.72% of the (C-OH) bonds being converted to (C-C/C-H) (3.61%) and CO (2.11%) bonds, and 4.52% of the CO (carbonyl) bonds being converted to (C-OH) bonds. Furthermore, the presence of Ag+ and AgNPs induced the ability of extracellular electron transfer for ZCC cells via specific membrane proteins, but this did not occur in the absence of Ag+ ions. Proteomic analysis of the proteins and enzymes involved in heavy metal efflux systems, protein secretion system, oxidative phosphorylation, intracellular electron transfer chain, and glutathione metabolism suggests that glutathione S-transferase and ubiquinol-cytochrome c reductase iron-sulfur subunit play importance roles in the biosynthesis of AgNPs. These findings contribute to a deeper understanding of the functions exerted by glutathione S-transferase and ferredoxin-thioredoxin reductase iron-sulfur subunits in the biogenesis of AgNPs, thereby hold immense potential for optimizing biotechnological techniques aimed at enhancing the yield and purity of biosynthetic AgNPs.

Abstract In this study, the form factors of $$B_{(s)}$$ B ( s ) to light D-wave tensor mesons with $$J^{PC} = 2^{--}$$ J PC = 2 - - ( $$\rho _2$$ ρ 2 , $$\omega _2$$ ω 2 , $$K_2$$ K 2 and $$\phi _2$$ ϕ 2 ) are calculated via the light cone sum rules (LCSR) in the framework of heavy quark effective eld theory (HQEFT). Firstly, the expressions of form factors in terms of the light cone distribution amplitudes (LCDAs) of tensor mesons are derived via the LCSR at the leading order of heavy quark expansion. Similar to the case of $$2^{++}$$ 2 + + tensor mesons, the penguin type form factors can be obtained directly from the corresponding semileptonic ones. Considering the light tensor meson LCDAs to twist-3 and quark mass corrections, we give the numerical results of form factors systematically. Based on the form factors given here, we investigate the branching ratios, longitudinal polarization fractions and forward-backward asymmetries of relevant charged current induced semileptonic decays. Our results may be tested by more precise experiments in the future.

Abstract Background Double-balloon enteroscopy (DBE) is a standard method for diagnosing and treating small bowel disease. However, DBE may yield false-negative results due to oversight or inexperience. We aim to develop a computer-aided diagnostic (CAD) system for the automatic detection and classification of small bowel abnormalities in DBE. Design and methods A total of 5201 images were collected from Renmin Hospital of Wuhan University to construct a detection model for localizing lesions during DBE, and 3021 images were collected to construct a classification model for classifying lesions into four classes, protruding lesion, diverticulum, erosion & ulcer and angioectasia. The performance of the two models was evaluated using 1318 normal images and 915 abnormal images and 65 videos from independent patients and then compared with that of 8 endoscopists. The standard answer was the expert consensus. Results For the image test set, the detection model achieved a sensitivity of 92% (843/915) and an area under the curve (AUC) of 0.947, and the classification model achieved an accuracy of 86%. For the video test set, the accuracy of the system was significantly better than that of the endoscopists (85% vs. 77 ± 6%, p

Abstract Background Lung cancer remains a major global health concern due to its high incidence and mortality rates. With advancements in medical treatments, an increasing number of early-stage lung cancer cases are being detected, making surgical treatment the primary option for such cases. However, this presents challenges to the physical and mental recovery of patients. Peplau known as the “mother of psychiatric associations” has formulated a theory of interpersonal relationships in nursing. Through effective communication between nurses and patients over four periods, she has established a good therapeutic nurse-patient relationship. Therefore, this study aimed to explore the effect of perioperative multimodal nursing based on Peplau’s interpersonal relationship theory on the rehabilitation of patients with surgical lung cancer. Methods We retrospectively analyzed 106 patients with non-small cell lung cancer who underwent thoracoscopic lobectomy at our department between June 2021 and April 2022. Patients were categorized into two groups according to the different nursing intervention techniques. The Peplau’s group comprised 53 patients who received targeted nursing interventions, and the control group comprised 53 patients who received conventional nursing care. We observed the patients’ illness uncertainty, quality of life, and clinical symptoms in both groups. Results Patients in the Peplau’s group had significantly lower illness uncertainty scores and a significantly higher quality of recovery than those in the control group. However, there were no significant differences in length of post-anesthesia care unit stay, complication rates, and visual analog scores between both groups. Conclusion The multimodal perioperative nursing based on Peplau’s interpersonal relationship theory not only reduces the illness uncertainty of patients with lung cancer surgery and improves their QoR but also expands the application of this theory in clinical practice, guiding perioperative nursing of patients with lung cancer. Implications These findings provide practical information for standardized care in a hectic anesthetic care setting. Impact The assessed anesthesia nursing model helps reduce uncertainty and promote early recovery in patients with cancer at various stages of their disease, which expands the scope of therapeutic practice and existing theories. It also serves as a guide for care in the anesthesia recovery room. Reporting method We adhered to the relevant Equator guidelines and the checklist of items in the case–control study report. Patient or public contribution Patients cooperated with medical staff to complete relevant scales.

AbstractContext Panax japonicus is the dried rhizome of Panax japonicus C.A. Mey. (Araliaceae). Saponins from Panax japonicus (SPJ) exhibit anti-oxidative and anti-aging effects.Objective We evaluated the neuroprotective effects of SPJ on aging rats.Materials and methods Sprague-Dawley rats (18-months-old) were randomly divided into aging and SPJ groups (n = 8). Five-month-old rats were taken as the adult control (n = 8). The rats were fed a normal chow diet or the SPJ-containing diet (10 or 30 mg/kg) for 4 months. An in vitro model was established by d-galactose (d-Gal) in the SH-SY5Y cell line and pretreated with SPJ (25 and 50 µg/mL). The neuroprotection of SPJ was evaluated via Nissl staining, flow cytometry, transmission electron microscopy and Western blotting in vivo and in vitro.Results SPJ improved the neuronal degeneration and mitochondrial morphology that are associated with aging. Meanwhile, SPJ up-regulated the protein levels of mitofusin 2 (Mfn2) and optic atrophy 1 (Opa1) and down-regulated the protein level of dynamin-like protein 1 (Drp1) in the hippocampus of aging rats (p

Diabetes, a metabolic disease caused by abnormally high levels of blood glucose, has a high prevalence rate worldwide and causes a series of complications, including coronary heart disease, stroke, peripheral vascular disease, end-stage renal disease, and retinopathy. Small-molecule compounds have been developed as drugs for the treatment of diabetes because of their oral advantages. Insulin secretagogues are a class of small-molecule drugs used to treat diabetes, and include sulfonylureas, non-sulfonylureas, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase 4 inhibitors, and other novel small-molecule insulin secretagogues. However, many small-molecule compounds cause different side effects, posing huge challenges to drug monotherapy and drug selection. Therefore, the use of different small-molecule drugs must be improved. This article reviews the mechanism, advantages, limitations, and potential risks of small-molecule insulin secretagogues to provide future research directions on small-molecule drugs for the treatment of diabetes.

China is now confronting the intertwined challenges of air pollution and climate change. Given the high synergies between air pollution abatement and climate change mitigation, the Chinese government is actively promoting synergetic control of these two issues. The Synergetic Roadmap project was launched in 2021 to track and analyze the progress of synergetic control in China by developing and monitoring key indicators. The Synergetic Roadmap 2022 report is the first annual update, featuring 20 indicators across five aspects: synergetic governance system and practices, progress in structural transition, air pollution and associated weather-climate interactions, sources, sinks, and mitigation pathway of atmospheric composition, and health impacts and benefits of coordinated control. Compared to the comprehensive review presented in the 2021 report, the Synergetic Roadmap 2022 report places particular emphasis on progress in 2021 with highlights on actions in key sectors and the relevant milestones. These milestones include the proportion of non-fossil power generation capacity surpassing coal-fired capacity for the first time, a decline in the production of crude steel and cement after years of growth, and the surging penetration of electric vehicles. Additionally, in 2022, China issued the first national policy that synergizes abatements of pollution and carbon emissions, marking a new era for China's pollution-carbon co-control. These changes highlight China's efforts to reshape its energy, economic, and transportation structures to meet the demand for synergetic control and sustainable development. Consequently, the country has witnessed a slowdown in carbon emission growth, improved air quality, and increased health benefits in recent years.

Introduction Airway epithelial mitochondrial injury is an important pathogenesis of chronic obstructive pulmonary disease (COPD). Cyclophilin D (CypD) is a component of mitochondrial permeability transition pore and related to mitochondrial damage. However, the role of CypD in airway epithelial mitochondrial injury and COPD pathogenesis remains unclear. Methods CypD expression in human airway epithelium was determined by immunohistochemistry, and mitochondrial structure of airway epithelial cell was observed under the transmission electron microscopy. The expression of CypD signaling pathway in cigarette smoke extract (CSE)-treated airway epithelial cells was measured by real-time PCR and Western-blot. CSE-induced damage of airway epithelial cell and mitochondria was further studied. Results Immunohistochemistry and transmission electron microscopy analysis revealed that CypD expression in airway epithelium was significantly increased associated with notable airway epithelial mitochondrial structure damage in the patients with COPD. The mRNA and protein expression of CypD was significantly increased in concentration- and time-dependent manners when airway epithelial cells were treated with CSE. CypD siRNA pretreatment significantly suppressed the increases of CypD and Bax expression, and reduced the decline of Bcl-2 expression in 7.5% CSE-treated airway epithelial cells. Furthermore, CypD silencing significantly attenuated mitochondrial damage and cell apoptosis, and increased cell viability when airway epithelial cells were stimulated with 7.5% CSE. Conclusion These data suggest that CypD signaling pathway is involved in the pathogenesis of COPD and provide a potential therapeutic target for COPD., Author(s): Rui Zhang [sup.1], Hu Shan [sup.1], Yuer Li [sup.1], Yuefeng Ma [sup.2], Shiyuan Liu [sup.2], Xiaohuan Liu [sup.1], Xia Yang [sup.1], Jie Zhang [sup.1], Ming Zhang [sup.1] Author Affiliations: [...]

Abstract The latest clinical trials have reported conflicting outcomes regarding the effectiveness of xenon anesthesia in preventing postoperative neurocognitive dysfunction; thus, this study assessed the existing evidence. We searched the PubMed, Embase, Cochrane Library, and Web of Science databases from inception to April 9, 2023, for randomized controlled trials of xenon anesthesia in postoperative patients. We included English-language randomized controlled studies of adult patients undergoing surgery with xenon anesthesia that compared its effects to those of other anesthetics. Duplicate studies, pediatric studies, and ongoing clinical trials were excluded. Nine studies with 754 participants were identified. A forest plot revealed that the incidence of postoperative neurocognitive dysfunction did not differ between the xenon anesthesia and control groups (P = 0.43). Additionally, xenon anesthesia significantly shortened the emergence time for time to opening eyes (P

Abstract Objectives To explore the association between computed tomography (CT)-measured sex-specific abdominal adipose tissue and the pathological grade of clear cell renal cell carcinoma (ccRCC). Methods This retrospective study comprised 560 patients (394 males and 166 females) with pathologically proven ccRCC (467 low- and 93 high-grade). Abdominal CT images were used to assess the adipose tissue in the subcutaneous, visceral, and intermuscular regions. Subcutaneous fat index (SFI), visceral fat index (VFI), intermuscular fat index (IFI), total fat index (TFI), and relative visceral adipose tissue (rVAT) were calculated. Univariate and multivariate logistic regression analyses were performed according to sex to identify the associations between fat-related parameters and pathological grade. Results IFI was significantly higher in high-grade ccRCC patients than in low-grade patients for both men and women. For male patients with high-grade tumors, the SFI, VFI, TFI, and rVAT were significantly lower, but not for female patients. In both univariate and multivariate studies, the IFI continued to be a reliable and independent predictor of high-grade ccRCC, regardless of sex. Conclusions Intermuscular fat index proved to be a valuable biomarker for the pathological grade of ccRCC and could be used as a reliable independent predictor of high-grade ccRCC for both males and females. Critical relevance statement Sex-specific fat adipose tissue can be used as a new biomarker to provide a new dimension for renal tumor-related research and may provide new perspectives for personalized tumor management decision-making approaches. Key points • There are sex differences in distribution of subcutaneous fat and visceral fat. • The SFI, VFI, TFI, and rVAT were significantly lower in high-grade ccRCC male patients, but not for female patients. • Intermuscular fat index can be used as a reliable independent predictor of high-grade ccRCC for both males and females. Graphical Abstract

Abstract Mechanical pressure overload and other stimuli often contribute to heart hypertrophy, a significant factor in the induction of heart failure. The UDP-glucose ceramide glycosyltransferase (UGCG) enzyme plays a crucial role in the metabolism of sphingolipids through the production of glucosylceramide. However, its role in heart hypertrophy remains unknown. In this study, UGCG was induced in response to pressure overload in vivo and phenylephrine stimulation in vitro. Additionally, UGCG downregulation ameliorated cardiomyocyte hypertrophy, improved cardiomyocyte mitochondrial oxidative stress, and reduced the ERK signaling pathway. Conversely, UGCG overexpression in cardiomyocytes promoted heart hypertrophy development, aggravated mitochondrial oxidative stress, and stimulated ERK signaling. Furthermore, the interaction between beta-1,4-galactosyltransferase 5 (B4GalT5), which catalyses the synthesis of lactosylceramide, and UGCG was identified, which also functions as a synergistic molecule of UGCG. Notably, limiting the expression of B4GalT5 impaired the capacity of UGCG to promote myocardial hypertrophy, suggesting that B4GalT5 acts as an intermediary for UGCG. Overall, this study highlights the potential of UGCG as a modulator of heart hypertrophy, rendering it a potential target for combating heart hypertrophy.

Streptomyces can produce secondary metabolites with a wide range of activities and is often used in agriculture as a biocontrol strain to control soil-borne diseases. Screening and isolation from infected soil is an effective method to obtain active strains. In this study, the best antagonistic inter-root growth-promoting bacteria were isolated from grapevine inter-root soil samples, and strain F2 was identified as Streptomyces sp. based on morphological, physiological, and biochemical characteristics as well as 16S rDNA sequencing results. The results showed that the fermentation broth/liquid and sterile filtrate of strain F2 exhibited antagonistic effects against 10 plant pathogens, with an inhibition rate reaching up to 80%. Notably, two of them exhibited remarkable inhibitory effects against Phytophthora capsici with inhibition rates of 80.58% and 87.71%, respectively. The P. capsici leaf control experiment revealed that the control effect of strain F2 fermentation liquid on P. capsici filaments was 61.09%. Furthermore, indoor pot experiments demonstrated that the fermentation liquid of strain F2 had a significant inhibitory effect on pepper blight, with a maximum inhibition of 83.31%. Antagonistic factor analysis indicated that strain F2 had specific organophosphorus hydrolysis, nitrogen fixation, extracellular protease secretion, and IAA production capabilities. Additionally, root treatment with strain F2’s fermentation liquid significantly enhanced capsicum growth. Taking together, Streptomyces F2 not only exhibits a wide-spectrum antagonistic effect against plant pathogens but also promotes plant growth, which suggests that Streptomyces F2 can be used as an effective biological control resource and provides important theoretical support for the application of Streptomyces F2.

In clinical practice, infections caused by Aspergillus species are common and associated with high mortality rates. However, isolating Aspergillus from clinical samples and cultures is challenging, and serological tests cannot differentiate between strains. Furthermore, the complex cell wall structure in Aspergillus species hinders DNA extraction and subsequent nucleic acid detection. Aspergillus fumigatus, Aspergillus flavus, and Aspergillus niger are common and frequently encountered pathogenic species. This study aimed to establish an efficient and rapid method for detecting Aspergillus species in clinical samples. Fe3O4@PEI.NH2 nanoparticles with large particle sizes were employed to capture Aspergillus from the samples. Flexible silver nanowires (AgNWs) were prepared and used as the surface-enhanced Raman scattering (SERS) substrate for Aspergillus detection. Through SERS spectroscopy, the identification of captured Aspergillus species was confirmed. Furthermore, the SERS spectrum underwent principal component analysis employing orthogonal partial least-squares discrimination analysis (OPLS-DA) as a multivariate analysis technique to distinguish between the various Aspergillus species effectively. After 10-fold cross-validation, the trained model achieved a testing accuracy of 99.15%, indicating excellent classification performance. By utilizing pre-prepared Fe3O4@PEI.NH2 and AgNWs, the detection process was completed within 60 min without disrupting the cell wall of Aspergillus.

ABSTRACTSynbiotics are increasingly used by the general population to boost immunity. However, there is limited evidence concerning the immunomodulatory effects of synbiotics in healthy individuals. Therefore, we conducted a double-blind, randomized, placebo-controlled study in 106 healthy adults. Participants were randomly assigned to receive either synbiotics (containing Bifidobacterium lactis HN019 1.5 × 108 CFU/d, Lactobacillus rhamnosus HN001 7.5 × 107 CFU/d, and fructooligosaccharide 500 mg/d) or placebo for 8 weeks. Immune parameters and gut microbiota composition were measured at baseline, mid, and end of the study. Compared to the placebo group, participants receiving synbiotic supplementation exhibited greater reductions in plasma C-reactive protein (P = 0.088) and interferon-gamma (P = 0.008), along with larger increases in plasma interleukin (IL)-10 (P = 0.008) and stool secretory IgA (sIgA) (P = 0.014). Additionally, synbiotic supplementation led to an enrichment of beneficial bacteria (Clostridium_sensu_stricto_1, Lactobacillus, Bifidobacterium, and Collinsella) and several functional pathways related to amino acids and short-chain fatty acids biosynthesis, whereas reduced potential pro-inflammatory Parabacteroides compared to baseline. Importantly, alternations in anti-inflammatory markers (IL-10 and sIgA) were significantly correlated with microbial variations triggered by synbiotic supplementation. Stratification of participants into two enterotypes based on pre-treatment Prevotella-to-Bacteroides (P/B) ratio revealed a more favorable effect of synbiotic supplements in individuals with a higher P/B ratio. In conclusion, this study suggested the beneficial effects of synbiotic supplementation on immune parameters, which were correlated with synbiotics-induced microbial changes and modified by microbial enterotypes. These findings provided direct evidence supporting the personalized supplementation of synbiotics for immunomodulation.

Sparganosis is a rare parasitic infection caused by plerocercoid tapeworm larvae. We described a case of a 27-year-old man presenting with numbness in both legs and masses in the right lung and spine, initially thought to have spinal metastasis from lung cancer. However, after pathological and parasitological examinations, the patient was found to have spinal sparganosis, likely due to a history of consuming raw frogs. The patient was successfully treated with praziquantel, resulting in the recovery of muscle strength in his legs. This case highlights the importance of considering spinal sparganosis as a differential diagnosis in patients with spinal masses, especially those with a history of consuming raw or undercooked frogs. Accurate diagnosis and early treatment are crucial for managing this infection.

Abstract Background Clinically, although chemotherapy is one of the most commonly used methods of treating tumors, chemotherapeutic drugs can induce autophagic flux and increase tumor cell resistance, leading to drug tolerance. Therefore, theoretically, inhibiting autophagy may improve the efficacy of chemotherapy. The discovery of autophagy regulators and their potential application as adjuvant anti-cancer drugs is of substantial importance. In this study, we clarified that Fangjihuangqi Decoction (FJHQ, traditional Chinese medicine) is an autophagy inhibitor, which can synergistically enhance the effect of cisplatin and paclitaxel on non-small cell lung cancer (NSCLC) cells. Methods We observed the changes of autophagy level in NSCLC cells under the effect of FJHQ, and verified the level of the autophagy marker protein and cathepsin. Apoptosis was detected after the combination of FJHQ with cisplatin or paclitaxel, and NAC (ROS scavenger) was further used to verify the activation of ROS-MAPK pathway by FJHQ. Results We observed that FJHQ induced autophagosomes in NSCLC cells and increased the levels of P62 and LC3-II protein expression in a concentration- and time-gradient-dependent manner, indicating that autophagic flux was inhibited. Co-localization experiments further showed that while FJHQ did not inhibit autophagosome and lysosome fusion, it affected the maturation of cathepsin and thus inhibited the autophagic pathway. Finally, we found that the combination of FJHQ with cisplatin or paclitaxel increased the apoptosis rate of NSCLC cells, due to increased ROS accumulation and further activation of the ROS-MAPK pathway. This synergistic effect could be reversed by NAC. Conclusion Collectively, these results demonstrate that FJHQ is a novel late-stage autophagy inhibitor that can amplify the anti-tumor effect of cisplatin and paclitaxel against NSCLC cells.

Growing attention has been directed to the use of satellite imagery and open geospatial data to understand large-scale sustainable development outcomes. Health and education are critical domains of the Unites Nations’ Sustainable Development Goals (SDGs), yet existing research on the accessibility of corresponding services focused mainly on detailed but small-scale studies. This means that such studies lack accessibility metrics for large-scale quantitative evaluations. To address this deficiency, we evaluated the accessibility of health and education services in mainland China in 2021 using point-of-interest data, OpenStreetMap road data, land cover data, and WorldPop spatial demographic data. The accessibility metrics used were the least time costs of reaching hospital and school services and population coverage with a time cost of less than 1 h. On the basis of the road network and land cover information, the overall average time costs of reaching hospital and school were 20 and 22 min, respectively. In terms of population coverage, 94.7% and 92.5% of the population in China has a time cost of less than 1 h in obtaining hospital and school services, respectively. Counties with low accessibility to hospitals and schools were highly coupled with poor areas and ecological function regions, with the time cost incurred in these areas being more than twice that experienced in non-poor and non-ecological areas. Furthermore, the cumulative time cost incurred by the bottom 20% of counties (by GDP) from access to hospital and school services reached approximately 80% of the national total. Low-GDP counties were compelled to suffer disproportionately increased time costs to acquire health and education services compared with high-GDP counties. The accessibility metrics proposed in this study are highly related to SDGs 3 and 4, and they can serve as auxiliary data that can be used to enhance the evaluation of SDG outcomes. The analysis of the uneven distribution of health and education services in China can help identify areas with backward public services and may contribute to targeted and efficient policy interventions.

Abstract Several factors influence axial length in children with myopia treated using overnight orthokeratology. To identify these factors, this retrospective study collected axial length and corneal aberration data on 78 eyes before and 1-year after orthokeratology. Patients were divided according to axial elongation (cut-off, 0.25 mm/year). Baseline characteristics included age, sex, spherical equivalent refraction, pupil diameter, axial length, and orthokeratology lens type. Corneal shape effects were compared through tangential difference maps. Group differences in higher-order aberrations of a 4 mm zone were compared at baseline and 1-year following therapy. Binary logistic regression analysis was conducted to identify the variables determined for axial elongation. Significant differences between both groups included the initial age of wearing orthokeratology lenses, type of orthokeratology lens, size of central flattening area, corneal total surface C12 (1-year), corneal total surface C8 (1-year), corneal total surface spherical aberration (SA) (1-year root mean square [RMS] values), change in total corneal surface C12, and change in front and total corneal surface SA (RMS values). The age when wearing an orthokeratology lens was the most important factor influencing axial length in children with orthokeratology-treated myopia, followed by lens type and change in the C12 of the total corneal surface.

Abstract Background and Aims Distinguishing pancreatic cancer from nonneoplastic masses is critical and remains a clinical challenge. The study aims to construct a deep learning‐based artificial intelligence system to facilitate pancreatic mass diagnosis, and to guide EUS‐guided fine‐needle aspiration (EUS‐FNA) in real time. Methods This is a prospective study. The CH‐EUS MASTER system is composed of Model 1 (real‐time capture and segmentation) and Model 2 (benign and malignant identification). It was developed using deep convolutional neural networks and Random Forest algorithm. Patients with pancreatic masses undergoing CH‐EUS examinations followed by EUS‐FNA were recruited. All patients underwent CH‐EUS and were diagnosed both by endoscopists and CH‐EUS MASTER. After diagnosis, they were randomly assigned to undergo EUS‐FNA with or without CH‐EUS MASTER guidance. Results Compared with manual labeling by experts, the average overlap rate of Model 1 was 0.708. In the independent CH‐EUS video testing set, Model 2 generated an accuracy of 88.9% in identifying malignant tumors. In clinical trial, the accuracy, sensitivity, and specificity for diagnosing pancreatic masses by CH‐EUS MASTER were significantly better than that of endoscopists. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were respectively 93.8%, 90.9%, 100%, 100%, and 83.3% by CH‐EUS MASTER guided EUS‐FNA, and were not significantly different compared to the control group. CH‐EUS MASTER‐guided EUS‐FNA significantly improved the first‐pass diagnostic yield. Conclusion CH‐EUS MASTER is a promising artificial intelligence system diagnosing malignant and benign pancreatic masses and may guide FNA in real time. Trial registration number: NCT04607720.

Abstract Background Long-term smoking is a risk factor for chronic pain, and chronic nicotine exposure induces pain-like effects in rodents. The anterior cingulate cortex (ACC) has been demonstrated to be associated with pain and substance abuse. This study aims to investigate whether ACC microglia are altered in response to chronic nicotine exposure and their interaction with ACC neurons and subsequent nicotine-induced allodynia in mice. Methods We utilized a mouse model that was fed nicotine water for 28 days. Brain slices of the ACC were collected for morphological analysis to evaluate the impacts of chronic nicotine on microglia. In vivo calcium imaging and whole-cell patch clamp were used to record the excitability of ACC glutamatergic neurons. Results Compared to the vehicle control, the branch endpoints and the length of ACC microglial processes decreased in nicotine-treated mice, coinciding with the hyperactivity of glutamatergic neurons in the ACC. Inhibition of ACC glutamatergic neurons alleviated nicotine-induced allodynia and reduced microglial activation. On the other hand, reactive microglia sustain ACC neuronal excitability in response to chronic nicotine, and pharmacological inhibition of microglia by minocycline or liposome-clodronate reduces nicotine-induced allodynia. The neuron-microglia interaction in chronic nicotine-induced allodynia is mediated by increased expression of neuronal CX3CL1, which activates microglia by acting on CX3CR1 receptors on microglial cells. Conclusion Together, these findings underlie a critical role of ACC microglia in the maintenance of ACC neuronal hyperactivity and resulting nociceptive hypersensitivity in chronic nicotine-treated mice.

A comprehensive assessment of representative satellite-retrieved (Integrated Multi-satellite Retrievals for Global Precipitation Measurement (IMERG) and Tropical Rainfall Measuring Mission Multi-satellite Precipitation Analysis (TMPA)), reanalysis-based (fifth generation of atmospheric reanalysis by the European Centre for Medium Range Weather Forecasts (ERA5)), and gauge-estimated (Climate Prediction Center (CPC)) precipitation products was conducted using the data from 807 meteorological stations across mainland China from 2001 to 2017. Error statistical metrics, precipitation distribution functions, and extreme precipitation indices were used to evaluate the quality of the four precipitation products in terms of multi-timescale accuracy and extreme precipitation estimation. When the timescale increased from daily to seasonal scales, the accuracy of the four precipitation products first increased and then decreased, and all products performed best on the monthly timescale. Their accuracy ranking in descending order was CPC, IMERG, TMPA, and ERA5 on the daily timescale and IMERG, CPC, TMPA, and ERA5 on the monthly and seasonal timescales. IMERG was generally superior to its predecessor TMPA on the three timescales. ERA5 exhibited large statistical errors. CPC provided stable estimated values. For extreme precipitation estimation, the quality of IMERG was relatively consistent with that of TMPA in terms of precipitation distribution and extreme metrics, and IMERG exhibited a significant advantage in estimating moderate and heavy precipitation. In contrast, ERA5 and CPC exhibited poor performance with large systematic underestimation biases. The findings of this study provide insight into the performance of the latest IMERG product compared with the widely used TMPA, ERA5, and CPC datasets, and points to possible directions for improvement of multi-source precipitation data fusion algorithms in order to better serve hydrological applications.

PurposeTransforming growth factor β (TGFβ) is upregulated in many types of tumors and plays important roles in tumor microenvironment construction, immune escape, invasion, and metastasis. The therapeutic effect of antibodies and nuclide-conjugated drugs targeting TGFβ has not been ideal. Targeting TGFβ with small-molecule or peptide carriers labeled with diagnostic/therapeutic nuclides is a new development direction. This study aimed to explore and confirm the imaging diagnostic efficiency of TGFβ-targeting peptide P144 coupled with [68Ga] in a PANC-1 tumor model.ProceduresTGFβ-targeting inhibitory peptide P144 with stable activity was prepared through peptide synthesis and screening, and P144 was coupled with biological chelator DOTA and labeled with radionuclide [68Ga] to achieve a stable TGFβ-targeting tracer [68Ga]Ga-P144. This tracer was first used for positron emission tomography (PET) molecular imaging study of pancreatic cancer in a mouse PANC-1 tumor model.Results[68Ga]Ga-P144 had a high targeted uptake and relatively long uptake retention time in tumors and lower uptakes in non-target organs and backgrounds. Target pre-blocking experiment with the cold drug P144-DOTA demonstrated that the radioactive uptake with [68Ga]Ga-P144 PET in vivo, especially in tumor tissue, had a high TGFβ-targeting specificity. [68Ga]Ga-P144 PET had ideal imaging efficiency in PANC-1 tumor-bearing mice, with high specificity in vivo and good tumor-targeting effect.Conclusion[68Ga]Ga-P144 has relatively high specificity and tumor-targeted uptake and may be developed as a promising diagnostic tool for TGFβ-positive malignancies.