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Dryocosmus kuriphilus, commonly known as the chestnut gall wasp, belongs to the family Cynipidae and is native to China. It is a highly invasive insect species causing serious damage to chestnut trees and has rapidly spread to various continents, including Europe, North America, and Oceania. The D. kuriphilus has become one of the important pests of chestnut plants in the world and is listed as a quarantine object by the European and Mediterranean Plant Protection Organization (EPPO). In this study, we used PacBio long reads, Illumina short reads, and Hi-C sequencing data to construct a chromosome-level assembly of the D. kuriphilus genome. The assembled genome includes 14,729 contigs with a total length of 2.28 Gb and a contig N50 of 0.8 Mb. With Hi-C technology, 2.17 Gb (95.02%) of contigs were anchored and oriented into the 10 pseudochromosomes with the scaffold N50 of 198.8 Mb and the scaffold N90 of 158.8 Mb. In total, 24,086 protein-coding genes were predicted in the assembled D. kuriphilus genome as the reference gene set. A total of 1.82 Gb repeats (occupying 79.7% of the genome), including 1.42 Gb of transposable elements and 0.40 Gb of tandem repeats, were identified in D. kuriphilus genome. In the evaluation of completeness, the BUSCO analysis determined a level of 98.1% completeness for the assembled genome sequences based on the Insecta database (OrthoDB version 10). The high-quality genome assembly of D. kuriphilus will not only provide a valuable reference for the study of its evolutionary history and genetic structure but also facilitate the research of host-pest interactions and invasiveness. Moreover, this genome assembly will promote in the development of effective management strategies to mitigate the economic and ecological impacts of this invasive pest on chestnut trees and ecosystems.

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We design a multi-effective nanoplatform (CeO2:Nd@SiO2@CeO2:Yb,Er@SiO2-RB/MB/CD36) with down/upconversion dual-mode emissions and targeting ability in foam macrophages. Under NIR excitation, this nanoplatform can realize in vivo NIR-II imaging and PDT/PTT coordinated therapy for early AS simultaneously.

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Both boron neutron capture therapy (BNCT) and photothermal therapy (PTT) have been applied to tumor treatment in clinical. However, their therapeutic efficacy is limited. For BNCT, the agents not only exhibit poor targeting ability but also permit only a single irradiation session within a course due to significant radiation risks. In the context of PTT, despite enhanced selectivity, the limited photothermal effect fails to meet clinical demands. Hence, the imperative arises to combine these two therapies to enhance tumor-killing capabilities and improve the targeting of BNCT agents by leveraging the advantages of PTT agents. In this study, we synthesized a potential responsive agent by linking 4-mercaptophenylboronic acid (MPBA) and IR-780 dye that served as the agents for BNCT and PTT, respectively, which possesses the dual capabilities of photothermal effects and thermal neutron capture. Results from both in vitro and in vivo research demonstrated that IR780-MPBA effectively inhibits tumor growth through its photothermal effect with no significant toxicity. Furthermore, IR780-MPBA exhibited substantial accumulation in tumor tissues and superior tumor-targeting capabilities compared with MPBA, which demonstrated that IR780-MPBA possesses significant potential as a combined antitumor therapy of PTT and BNCT, presenting a promising approach for antitumor treatments.

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Magnetic tunneling junctions (MTJs) lie in the core of magnetic random access memory, holding promise in integrating memory and computing to reduce hardware complexity, transition latency, and power consumption. However, traditional MTJs are insensitive to light, limiting their functionality in in-memory sensing─a crucial component for machine vision systems in artificial intelligence applications. Herein, the convergence of magnetic memory with optical sensing capabilities is achieved in the all-two-dimensional (2D) magnetic junction Fe3GaTe2/WSe2/Fe3GaTe2, which combines 2D magnetism and optoelectronic properties. The clean intrinsic band gap and prominent photoresponse of interlayer WSe2 endow the tunneling barrier with optical tunability. The on-off states of junctions and the magnetoresistance can be flexibly controlled by the intensity of the optical signal at room temperature. Based on the optical-tunable magnetoresistance in all-2D magnetic junctions, a machine vision system with the architecture of in-memory sensing and computing is constructed, which possesses high performance in image recognition. Our work exhibits the advantages of 2D magneto-electronic devices and extends the application scenarios of magnetic memory devices in artificial intelligence.

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STUDY OBJECTIVE: Although mean/static compliance of bladder filling can be readily assayed via cystometry, a protocol measuring compliance dynamics at a specific stage of bladder filling has not been established in human patients. For patients with pelvic organ prolapse (POP), the objective benefits of robotic-assisted sacrocolpopexy (RSCP) surgical intervention for restoring bladder functions, primarily urine storage, have yet to be established. Also, bladder compliance is a viscoelastic parameter crucially defines the storage function. Therefore, we aimed to investigate the impact of RSCP on bladder compliance of POP patients using a pressure-volume analysis (PVA), which graphically illustrate bladder compliance. DESIGN: A retrospective pre- and post-operative study. SETTING: Multiple hospitals in Taiwan. PATIENTS: 27 female POP patients (stage ≥ II). INTERVENTION: RSCP for POP repair. MEASUREMENTS AND MAIN RESULTS: We retrospectively reviewed the pre- and post-operative PVAs for women with POP, who underwent RSCP. The mean compliance of the entire (Cm), the early half (C1/2), and the late half (C2/2) of bladder filling were analyzed as primary outcomes. Changes in intra-vesical volume (ΔVive) and detrusor pressure (ΔPdet) of bladder filling, ΔPdet in the early (ΔPdet1/2) and late (ΔPdet2/2) filling, and post-voiding residual volume (Vres) were analyzed as secondary outcomes. Compared with the pre-operative control, RSCP increased Cm (p=0.010, N=27) and C2/2 (p<0.001, N=27) but negligibly affected C1/2 (p=0.457, N=27). Mechanistically, RSCP decreased ΔPdet (p=0.001, N=27) without significantly affecting ΔVive (p=0.863, N=27). Furthermore, RSCP decreased the ΔPdet2/2 (p<0.001, N=27) but not ΔPdet1/2 (p=0.295, N=27). CONCLUSIONS: This is the first report of applying PVA in assaying dynamics of bladder compliance in patients with POP. Our results suggest that RSCP improved bladder storage in women with POP since it increased bladder compliance, particularly in the late filling possibly by restoring the anatomical location and geometric conformation for bladder expansion. CLINICAL TRIAL REGISTRATION: This study was registered in ClinicalTrials.gov (https://clinicaltrials.gov/study/NCT05682989); registration number: NCT05682989 submitted on 12/28, 2022.

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The preferable antigen delivery profile accompanied by sufficient adjuvants favors vaccine efficiency. Mitochondria, which feature prokaryotic characteristics and contain various damage-associated molecular patterns (DAMPs), are easily taken up by phagocytes and simultaneously activate innate immunity. In the current study, we established a mitochondria engineering platform for generating antigen-enriched mitochondria as cancer vaccine. Ovalbumin (OVA) and tyrosinase-related protein 2 (TRP2) were used as model antigens to synthesize fusion proteins with mitochondria-localized signal peptides. The lentiviral infection system was then employed to produce mitochondrial vaccines containing either OVA or TRP2. Engineered OVA- and TRP2-containing mitochondria (OVA-MITO and TRP2-MITO) were extracted and evaluated as potential cancer vaccines. Impressively, the engineered mitochondria vaccine demonstrated efficient antitumor effects when used as both prophylactic and therapeutic vaccines in murine tumor models. Mechanistically, OVA-MITO and TRP2-MITO potently recruited and activated dendritic cells (DCs) and induced a tumor-specific cell-mediated immunity. Moreover, DC activation by mitochondria vaccine critically involves TLR2 pathway and its lipid agonist, namely, cardiolipin derived from the mitochondrial membrane. The results demonstrated that engineered mitochondria are natively well-orchestrated carriers full of immune stimulants for antigen delivery, which could preferably target local dendritic cells and exert strong adaptive cellular immunity. This proof-of-concept study established a universal platform for vaccine construction with engineered mitochondria bearing alterable antigens for cancers as well as other diseases.

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BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) risk persists in chronic hepatitis B (CHB) patients despite antiviral therapy. The relationship between pre-treatment baseline hepatitis B virus (HBV) viral load and HCC risk during antiviral treatment remains uncertain. METHODS: This multinational cohort study aimed to investigate the association between baseline HBV viral load and on-treatment HCC risk in 20,826 noncirrhotic, hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients with baseline HBV DNA levels ≥2,000 IU/mL (3.30 log10 IU/mL) who initiated entecavir or tenofovir treatment. The primary outcome was on-treatment HCC incidence, stratified by baseline HBV viral load as a categorical variable. RESULTS: In total, 663 patients developed HCC over a median follow-up of 4.1 years, with an incidence rate of 0.81 per 100 person-years (95% confidence interval [CI], 0.75-0.87). Baseline HBV viral load was significantly associated with HCC risk in a non-linear parabolic pattern, independent of other factors. Patients with baseline viral load between 6.00 and 7.00 log10 IU/mL had the highest on-treatment HCC risk (adjusted hazard ratio, 4.28; 95% CI, 2.15-8.52; P < .0001) compared to those with baseline viral load ≥8.00 log10 IU/mL, who exhibited the lowest HCC risk. CONCLUSION: Baseline viral load showed a significant, non-linear, parabolic association with HCC risk during antiviral treatment in noncirrhotic CHB patients. Early initiation of antiviral treatment based on HBV viral load may help prevent irreversible HCC risk accumulation in CHB patients.

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Coccidiosis, caused by a protozoan parasite of the genus Eimeria, is one of the most severe contagious parasite diseases affecting the poultry industry worldwide. Using phytogenics to prevent chicken coccidiosis is a strategy aimed at combating the increasing issue of drug-resistant strains of Eimeria spp. This study demonstrates the anticoccidial activities of a medicinal herb, Trifolium pratense (TP) powder, and its ethanolic extract (designated TPE) against Eimeria spp. TPE exhibited significant suppressive activity against E. maxima oocyst sporulation and E. tenella sporozoite invasion and reproduction in Madin-Darby bovine kidney cells. Furthermore, administration of basal chicken diets containing TP powder or TPE to Eimeria-infected chickens significantly reduced the output of oocysts and severity of intestinal lesions. Dietary supplementation with TP significantly improved relative weight gain in E. tenella- and E. acervulina-infected chickens, while there was no significant improvement in E. maxima-infected chickens. The anticoccidial activities of TP and TPE on E. acervulina, E. tenella and E. maxima were further supported by anticoccidial index scores, which showed greater efficacy than those of amprolium, a commercial coccidiostat used in poultry. TP supplementation positively impacted the primary metabolism of chickens challenged with E. tenella or E. acervulina. The chemical fingerprints of TPE were established using liquid column chromatography; TPE contained 4 major compounds: ononin, sissotrin, formononetin, and biochanin A. In addition, various spectrometric methods were used to ensure the batch-to-batch consistency of TP/TPE. In conclusion, T. pratense is demonstrated to be a novel phytogenic supplement that can be used to control Eimeria-induced coccidiosis in chickens.

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Background: The atherogenic index of plasma (AIP) is a biomarker for coronary heart disease, atherosclerosis, and metabolic syndrome. However, the mechanism of its action in the acute phase of acute pontine infarction remains unclear. This study investigated the association between the AIP and the short-term prognosis of acute pontine infarction. Methods: Clinical and laboratory index data of patients admitted to the hospital for acute pontine infarction were continuously included, and these patients were followed up for 90 days after disease onset. The modified Rankin Scale (mRS) was used to evaluate the 90-day clinical outcomes of the patients, and an mRS score ≥3 was used to define adverse functional outcomes. Univariate analysis was used to detect differences in the indicators between the two groups. Patients were then divided into three groups according to the quantile of the AIP (T1: AIP ≤ 0.029; T2, 0.029 < AIP ≤ 0.248; T3, AIP > 0.248), and a binary logistic regression model was used to assess risk factors for prognosis shortly after acute pontine infarction. Results: A total of 260 patients with acute pontine infarction (mean age=64.5±11.8 years) were included during the study period, and 68 (26.2%) patients had a poor 90-day prognosis. The AIP in the poor 90-day prognosis group was significantly greater (P <0.05) than that in the good 90-day prognosis group. The multivariate logistic regression analysis revealed that the AIP (OR=9.829; 95% CI: 2.837-34.051; p < 0.001), baseline NIHSS score (OR=1.663; 95% CI: 1.400-1.975; p < 0.001) and infarct volume (OR=1.762; 95% CI: 1.013-3.062; p=0.045) were significantly associated with poor 90-day prognosis in patients with acute pontine infarction. Conclusion: In patients with acute pontine infarction, the AIP may serve as an important biological marker of poor clinical prognosis and is independently associated with poor 90-day prognosis.

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Nerve injury can induce aberrant changes in the spine; these changes are due to, or at least partly governed by, transcription factors that contribute to the genesis of neuropathic allodynia. Here, we showed that spinal nerve ligation (SNL, a clinical neuropathic allodynia model) increased the expression of the transcription factor Tbx5 in the injured dorsal horn in male Sprague Dawley rats. In contrast, blocking this upregulation alleviated SNL-induced mechanical allodynia, and there was no apparent effect on locomotor function. Moreover, SNL-induced Tbx5 upregulation promoted the recruitment and interaction of GATA4 and Brd4 by enhancing its binding activity to H3K9Ac, which was enriched at the Trpv1 promotor, leading to an increase in TRPV1 transcription and the development of neuropathic allodynia. In addition, nerve injury-induced expression of Fbxo3, which abates Fbxl2-dependent Tbx5 ubiquitination, promoted the subsequent Tbx5-dependent epigenetic modification of TRPV1 expression during SNL-induced neuropathic allodynia. Collectively, our findings indicated that spinal Tbx5-dependent TRPV1 transcription signaling contributes to the development of neuropathic allodynia via Fbxo3-dependent Fbxl2 ubiquitination and degradation. Thus, we propose a potential medical treatment strategy for neuropathic allodynia by targeting Tbx5.Significance Statement Nerve injury-induced epigenetic changes in Tbx5 enhance TRPV1 expression in the dorsal horn, with Tbx5 recruiting GATA4 and Brd4 for epigenetic modification of TRPV1. The Fbxo3-mediated Fbxl2 ubiquitination pathway stabilizes Tbx5, increasing its transcriptional activity and enhancing TRPV1 expression, contributing to the initiation and maintenance of neuropathic pain via epigenetic reprogramming.

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Background: Spontaneous intracerebral hemorrhage (sICH) is a form of stroke with high mortality rates and significant neurological implications for patients. Abnormalities in lipid metabolism have been implicated in various cardiovascular diseases, yet their relationship with sICH remains insufficiently explored, particularly concerning their association with inflammatory factors. Methods: Employing a two-sample, two-step Mendelian Randomization approach, combined with data from GWAS datasets, to investigate the causal relationship between plasma lipid levels and sICH. Additionally, the role of inflammatory factors in this relationship was examined, and sensitivity analyses were conducted to ensure the robustness of the results. Results: The results indicate a significant causal relationship between 19 plasma lipid metabolites and sICH. Furthermore, mediation analysis revealed that three distinct lipids, namely Sterol ester (27:1/20:2), Phosphatidylcholine (16:0_20:4), and Sphingomyelin (d34:1), exert their influence on sICH through inflammatory factors. TRAIL (OR: 1.078, 95% CI: 1.016-1.144, p = 0.013) and HGF (OR: 1.131, 95% CI: 1.001-1.279, p = 0.049) were identified as significant mediators. Conclusion: This study provides new evidence linking abnormalities in lipid metabolism with sICH and elucidates the role of inflammatory factors as mediators. These findings contribute to a better understanding of the pathogenesis of sICH and offer novel insights and therapeutic strategies for its prevention and treatment.

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Objective: In addition to the well-established advantage that strengthened pelvic musculature increases urethral resistance in stress urinary incontinence (SUI) patients, intra-vaginal electrical stimulation (iVES) has been shown in preclinical studies to improve bladder capacity via the pudendal-hypogastric mechanism. This study investigated whether iVES also benefits bladder storage in SUI patients by focusing on compliance, a viscoelastic parameter critically defining the bladder's storage function, in a clinical study. Moreover, the potential involvement of stimulation-induced neuromodulation in iVES-modified compliance was investigated by comparing the therapeutic outcomes of SUI patients treated with iVES to those who underwent a trans-obturator tape (TOT) implantation surgery, where a mid-urethral sling was implanted without electric stimulation. Patients and methods: Urodynamic and viscoelastic data were collected from 21 SUI patients treated with a regimen combining iVES and biofeedback-assisted pelvic floor muscle training (iVES-bPFMT; 20-min iVES and 20-min bPFMT sessions, twice per week, for 3 months). This regimen complied with ethical standards. Data from 21 SUI patients who received TOT implantation were retrospectively analyzed. Mean compliance (Cm), infused volume (Vinf), and threshold pressure (Pthr) from the pressure-flow/volume investigations were assessed. Results: Compared with the pretreatment control, iVES-bPFMT consistently and significantly increased Cm (18/21; 85%, p = 0.017, N = 21) and Vinf (16/21; 76%, p = 0.046; N = 21) but decreased Pthr (16/21; 76%, p = 0.026, N = 21). In contrast, TOT implantation did not result in consistent or significant changes in Cm, Vinf, or Pthr (p = 0.744, p = 0.295, p = 0.651, respectively; all N = 21). Conclusion: Our results provide viscoelastic and thermodynamic evidence supporting an additional benefit of iVES-bPFMT to bladder storage in SUI patients by modifying bladder compliance, possibly due to the potentiated hypogastric tone, which did not occur in TOT-treated SUI patients.Clinical trial registration: ClinicalTrials.gov, NCT02185235 and NCT05977231.

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BACKGROUND: Intensive care unit acquired weakness (ICUAW) is a common neuromuscular complication of critical illness, impacting patients' recovery and long-term outcomes. However, limited evidence is available on pooled prevalence and risk factors of ICUAW specifically in the COVID-19-infected population. METHODS: We searched on PubMed, Embase, Cochrane Library, Web of Science, PEDro, and EBSCOhost/CINAHL up to January 31, 2024. Data synthesis was conducted using the Freeman-Tukey double-arcsine transformation model for the pooled prevalence rate and odds ratios with corresponding 95% confidence intervals was used to identify risk factors. RESULTS: The pooled prevalence of ICUAW in COVID-19 patients was 55% in eight studies on 868 patients. Risk factors for developing ICUAW in these patients were: old age (WMD 4.78, 95% CI, 1.06-8.49), pre-existing hypertension (OR = 1.63, 95% CI, 1.02-2.61), medical intervention of prone position (OR = 5.21, 95% CI, 2.72-9.98), use of neuromuscular blocking agents (NMBA) (OR = 12.04, 95% CI, 6.20-23.39), needed tracheostomy (OR = 18.07, 95% CI, 5.64-57.92) and renal replacement therapy (RRT) (OR = 5.24, 95% CI = 2.36-11.63). CONCLUSIONS: The prevalence of ICUAW in patients with COVID-19 was considered relatively high. Older age, pre-existing hypertension, medical intervention of prone position, NMBA use, needed tracheostomy and RRT were likely risk factors. In the future, interdisciplinary medical team should pay attention to high-risk groups for ICUAW prevention and early treatments.

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Phosphatase and tensin homolog (PTEN) is vital for B cell development, acting as a key negative regulator in the PI3K signaling pathway. We used CD23-cre to generate PTEN-conditional knockout mice (CD23-cKO) to examine the impact of PTEN mutation on peripheral B cells. Unlike mb1-cre-mediated PTEN deletion in early B cells, CD23-cKO mutants exhibited systemic inflammation with increased IL-6 production in mature B cells upon CpG stimulation. Inflammatory B cells in CD23-cKO mice showed elevated phosphatidylinositol 3-phosphate [PI(3)P] levels and increased TLR9 endosomal localization. Pharmacological inhibition of PI(3)P synthesis markedly reduced TLR9-mediated IL-6. Single-cell RNA-sequencing (RNA-seq) revealed altered endocytosis, BANK1, and NF-κB1 expression in PTEN-deficient B cells. Ectopic B cell receptor (BCR) expression on non-inflammatory mb1-cKO B cells restored BANK1 and NF-κB1 expression, enhancing TLR9-mediated IL-6 production. Our study highlights PTEN as a crucial inflammatory checkpoint, regulating TLR9/IL-6 axis by fine-tuning PI(3)P homeostasis. Additionally, BCR downregulation prevents the differentiation of inflammatory B cells in PTEN deficiency.

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Cross-dehydrogenative couplings (CDC) present an efficient strategy for the assembly of biorelevant heterocycles, but are thus far largely limited to toxic transition metals and rather harsh reaction conditions. In sharp contrast, we, herein report on a mild photoelectrocatalyzed CDC-[4+2] annulation enabling the synthesis of functionalized isothiochromenes enabled by a proton-coupled electron transfer (PCET) strategy. The transformative photoelectrocatalysis obviated toxic transition-metal, high reaction temperatures, and stoichiometric chemical redox reagents. This approach was characterized by exceedingly mild conditions, ample substrate scope, and a commercially available catalyst. Gram-scale reactions and a telescoped synthesis route reflected the unique potential in the green synthesis of important S-heterocycles.

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Represented herein is the first 1,3-difunctionalization of alkenes via photocatalysis. A single cobaloxime is used to carry out two catalytic cycles in which cobaloxime is used not only as a photocatalyst to initiate the reaction but also as a metal catalyst for the ß-H elimination process. Electron-deficient alkenes, electron-rich alkenes, and unactivated alkenes could be directly converted to 1,3-bisphosphorylated products, even unsymmetric 1,3-bisphosphorylated products, with only H2 as a byproduct under extremely mild reaction conditions.

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Cadmium (Cd) contamination poses a significant threat to agriculture and human health due to its high soil mobility and toxicity. This review synthesizes current knowledge on Cd uptake, transport, detoxification, and transcriptional regulation in plants, emphasizing the roles of metal transport proteins and transcription factors (TFs). We explore transporter families like NRAMP, HMA, ZIP, ABC, and YSL in facilitating Cd movement within plant tissues, identifying potential targets for reducing Cd accumulation in crops. Additionally, regulatory TF families, including WRKY, MYB, bHLH, and ERF, are highlighted for their roles in modulating gene expression to counteract Cd toxicity. This review consolidates the existing literature on plant-Cd interactions, providing insights into established mechanisms and identifying gaps for future research. Understanding these mechanisms is crucial for developing strategies to enhance plant tolerance, ensure food safety, and promote sustainable agriculture amidst increasing heavy-metal pollution.

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