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Background: Picarbutrazox is a new tetrazolyloxime fungicide discovered in 2014 by Nippon Soda. It is mostly used to protect against Phytophthora spp. and Pythium spp. However, little is known of its inhibition spectrum, protective and curative activity, and systemic translocation in plants., Results: While picarbutrazox did not show obvious antifungal activity, it exhibited significant activity against oomycetes, including Phytophthora spp., Pythium spp. and Phytopythium spp.. The effective concentration for 50% growth inhibition (EC 50 ) values of picarbutrazox against 16 oomycetes ranged from 3.1 × 10 -4 and 7.27 × 10 -3  μg mL -1 . Furthermore, picarbutrazox could markedly inhibited the mycelial development, sporangia production, zoospore release, and cyst germination of Phytophthora capsici, with EC 50 values of 1.34 × 10 -3 , 1.11 × 10 -3 , 4.85 × 10 -3 , and 5.88 × 10 -2  μg mL -1 , respectively. Additionally, under greenhouse conditions, the protective and curative activities of picarbutrazox at 200 mg L -1 (100%, 41.03%) against the P. capsici infection in peppers were higher than those of the reference fungicide dimethomorph at 200 mg L -1 (77.52%, 36.15%). High-performance liquid chromatography analysis confirmed that picarbutrazox showed excellent systemic translocation in pepper plants., Conclusion: The results showed that picarbutrazox markedly inhibited the important plant oomycete pathogens including Phytophthora spp., Pythium spp. and Phytopythium spp.. It also displayed excellent protective, curative and systemic translocation activity. Picarbutrazox thus has significant potential for preventing and controlling diseases caused by oomycetes. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Local oxidative stress in diseases or injury severely hinders cell homeostasis and organ regeneration. Antioxidant therapy is an effective strategy for oxidative stress treatment. Biomaterials with good biocompatibility and reactive oxygen species (ROS) scavenging ability are good choices for antioxidant therapeutics. However, there are few natural biomaterials that are identified with both biocompatibility and strong antioxidant activity. Here, we show, for the first time, that silk fibroin (SF) is a strong antioxidant, which can eliminate ROS in both cells and zebrafish. We further demonstrate that the β-sheet structures turn into a random coiled structure when SF is treated with hydrogen peroxide. The content of β-sheet structures can be increased by heating, thus enhancing the antioxidation properties of SF. Therefore, SF can serve as a good antioxidant biomaterial for therapeutics, and its β-sheet structure-based antioxidation mechanism provides a novel theoretical basis, which could be a new cue for more antioxidant biomaterial discovery and identification., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The heterogeneity of hepatocellular carcinoma (HCC) can prevent effective treatment, emphasizing the need for more effective therapies. Herein, we employed arsenene nanosheets coated with manganese dioxide and polyethylene glycol (AMPNs) for the degradation of Pin1, which is universally overexpressed in HCC. By employing an "AND gate", AMPNs exhibited responsiveness toward excessive glutathione and hydrogen peroxide within the tumor microenvironment, thereby selectively releasing As x O y to mitigate potential side effects of As 2 O 3 . Notably, AMPNs induced the suppressing Pin1 expression while simultaneously upregulation PD-L1, thereby eliciting a robust antitumor immune response and enhancing the efficacy of anti-PD-1/anti-PD-L1 therapy. The combination of AMPNs and anti-PD-1 synergistically enhanced tumor suppression and effectively induced long-lasting immune memory. This approach did not reveal As 2 O 3 -associated toxicity, indicating that arsenene-based nanotherapeutic could be employed to amplify the response rate of anti-PD-1/anti-PD-L1 therapy to improve the clinical outcomes of HCC patients and potentially other solid tumors (e.g., breast cancer) that are refractory to anti-PD-1/anti-PD-L1 therapy.

Bio-oil derived from biomass fast pyrolysis can be upgraded to gasoline and diesel alternatives by catalytic hydrodeoxygenation (HDO). Here, the novel nitrogen-doped carbon-alumina hybrid supported cobalt (Co/NCA n , n = 1, 2.5, 5) catalyst is established by a coagulation bath technique. The optimized Co/NCA 2.5 catalyst presented 100 % conversion of guaiacol, high selectivity to cyclohexane (93.6 %), and extremely high deoxygenation degree (97.3 %), respectively. Therein, the formation of cyclohexanol was facilitated by stronger binding energy and greater charge transfer between Co and NC which was unraveled by density functional theory calculations. In addition, the appropriate amount of Lewis acid sites enhanced the cleavage of the C-O bond in cyclohexanol, finally resulting in a remarkable selectivity for cyclohexane. Finally, the Co/NCA 2.5 catalyst also exhibited excellent selectivity (93.1 %) for high heating value hydrocarbon fuel in crude bio-oil HDO. This work provides a theoretical basis on N dopants collaborating alumina hybrid catalysts for efficient HDO reaction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Postoperative urination dysfunction is a common complication after surgery in patients with cervical cancer. Portable bladder ultrasound are commonly utilized in clinical practice for measuring residual urine volume. This study aimed to the effect of bladder function training combined with portable ultrasound monitoring on bladder function recovery in patients with cervical cancer after training., Methods: A total of 40 postoperative patients with cervical cancer were randomly divided into a control group (A) and an experimental group (B) of 20 cases each. Group A was given routine postoperative care, while group B was given bladder function training. Urgent urine bladder volume were taken twice daily after removal of the urinary catheter and monitored for five consecutive days. The difference of urgent urine bladder volume and bladder filling rate were compared by t -test and chi-square test respectively. The 36-item Short Form Health Survey (SF-36) was used to evaluate the quality of life of patients before and after intervention, and compared by Mann-Whitney U test., Results: There was no significant difference in preoperative urgent urine volume between the two groups. After catheter removal, the bladder volume of patients in the B increased, while the bladder volume of patients in the A increased less and fluctuated greatly. The bladder filling rate in the A was significantly lower than that in the B (5/15 vs 17/18, p  < 0.05). After intervention, the quality of life of the experimental group was better than that of the control group, including scores of general health, mental health, vitality, and physical role ( p  < 0.05)., Conclusion: Postoperative cervical cancer patients trained to hold urine by portable ultrasound monitoring are able to recover bladder function., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Malus 'Baiyun' (registration no. 20210210), a new crabapple cultivar, was registered in 2021 by the Nanjing Forestry Unversity. However, the difficult rooting has greatly limited the production of high-quality M . 'Baiyun' in industrialization development. There is thus a pressing need to develop an organogenesis protocol for the in vitro propagation of M. 'Baiyun' to alleviate a shortage of high-quality M. 'Baiyun' seedlings. The results showed that choosing the apical bud in mid-March was an excellent explant material. To promote proliferation, the highest proliferation (6.27) of apical shoots was cultured on Murashige and Skoog (MS) medium supplemented with 0.5 mg·L -1 6-benzylaminopurine(6-BA) + 0.05 mg·L -1 indole-3-butyric acid (IBA). Subsequently, a 100% rooting rate, average number of roots per shoot of 6.2 and maximum length of roots of 4.96 cm were obtained on half-strength Murashige and Skoog (1/2 MS) medium with the application of 0.5 mg·L -1 naphthaleneacetic acid (NAA) or 0.6 mg·L -1 NAA + 0.7 mg·L -1 IBA. Additionally, thick and lateral roots were obtained with 0.6 mg·L -1 NAA + 0.7 mg·L -1 IBA. Our study is the first to establish an effective organogenesis protocol for new crabapple cultivars using stem segments.

Background: Acute liver injury (ALI) often precipitates severe liver function impairment and is associated with high mortality rates. Traditional Chinese Medicine (TCM) has demonstrated efficacy in mitigating hepatic damage by exhibiting anti-inflammatory effects, enhancing antioxidant activity, and modulating gut microbiota (GM). Numerous studies have identified similar or identical bioactive compounds within the Cornus Officinalis Fruit Coreon(COFO) and its flesh. Notably, Cornus Officinalis has been shown to possess potent hepatoprotective properties. However, studies on the pharmacological effects and mechanism of action of COFO for hepatoprotection have received little attention., Purpose: To elucidate the mechanisms underlying the COFO effect in ALI by integrating GM gene sequencing, quantifying Short-Chain Fatty Acids (SCFAs), and examining relevant signaling pathways., Materials and Methods: A rat model for carbon tetrachloride (CCl 4 )-induced ALI was established, and the best liver protective components of COFO were selected by pathological observation and biochemical determination. The therapeutic efficacy of COFO in mitigating liver injury was elucidated through an integrated approach that included network pharmacology, biochemical indexes, 16S rDNA sequencing analyses, short-chain fatty acids, Western blotting analysis of protein levels, and immunohistochemical evaluations., Results: Pharmacological evaluation established that the n-butanol fraction (CNBP) provided optimal hepatoprotective effects. Firstly, the chemical constituents of CNBP were characterized, and its principal anti-ALI targets, such as ALI, AKT1, TNF, and IL-6, were identified through network pharmacology analysis. Secondly, experimental validation revealed that CNBP may enhance the genetic diversity of the GM, augmenting the diversity of the microbial community, increasing the levels of three SCFAs, and activating key proteins in the AKT/Nrf2 signaling pathway (AKT1, TNF-α, IL-6, NF-κB p65, Nrf2, and HO-1). Consequently, CNBP exhibited hepatoprotective effects, with antioxidative and anti-inflammatory properties., Conclusion: CNBP may mitigate GM-induced disturbances, augment the levels of three SCFAs, activate the AKT/Nrf2 signaling pathway, and exhibit antioxidant and anti-inflammatory effects, thereby conferring hepatoprotective benefits., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier GmbH.)

The NLRP3 inflammasome functions as an inflammatory driver, but its relationship with lipid metabolic changes in early sepsis remains unclear. Here, we found that GITR expression in monocytes/macrophages was induced by lysophosphatidylcholine (LPC) and was positively correlated with the severity of sepsis. GITR is a costimulatory molecule that is mainly expressed on T cells, but its function in macrophages is largely unknown. Our in vitro data showed that GITR enhanced LPC uptake by macrophages and specifically enhanced NLRP3 inflammasome-mediated macrophage pyroptosis. Furthermore, in vivo studies using either cecal ligation and puncture (CLP) or LPS-induced sepsis models demonstrated that LPC exacerbated sepsis severity/lethality, while conditional knockout of GITR in myeloid cells or NLRP3/caspase-1/IL-1β deficiency attenuated sepsis severity/lethality. Mechanistically, GITR specifically enhanced inflammasome activation by regulating the posttranslational modification (PTM) of NLRP3. GITR competes with NLRP3 for binding to the E3 ligase MARCH7 and recruits MARCH7 to induce deacetylase SIRT2 degradation, leading to decreasing ubiquitination but increasing acetylation of NLRP3. Overall, these findings revealed a novel role of macrophage-derived GITR in regulating the PTM of NLRP3 and systemic inflammatory injury, suggesting that GITR may be a potential therapeutic target for sepsis and other inflammatory diseases. GITR exacerbates LPC-induced macrophage pyroptosis in sepsis via posttranslational regulation of NLRP3. According to the model, LPC levels increase during the early stage of sepsis, inducing GITR expression on macrophages. GITR not only competes with NLRP3 for binding to the E3 ligase MARCH7 but also recruits MARCH7 to induce the degradation of the deacetylase SIRT2, leading to decreasing ubiquitination but increasing acetylation of NLRP3 and therefore exacerbating LPC-induced NLRP3 inflammasome activation, macrophage pyroptosis and systemic inflammatory injury., (© 2024. The Author(s), under exclusive licence to CSI and USTC.)

Lead (Pb) is a major source of heavy metal contamination, and poses a threat to biodiversity and human health. Elevated levels of Pb can hinder insect growth and development, leading to apoptosis via mechanisms like oxidative damage. The midgut of silkworms is the main organ exposed to heavy metals. As an economically important lepidopteran model insect in China, heavy metal-induced stress on silkworms causes considerable losses in sericulture, thereby causing substantial economic damage. This study aimed to investigate Pb-induced detoxification-related genes in the midgut of silkworms using high-throughput sequencing methods to achieve a deeper comprehension of the genes' reactions to lead exposure. This study identified 11,567 unigenes and 14,978 transcripts. A total of 1265 differentially expressed genes (DEGs) were screened, comprising 907 upregulated and 358 downregulated genes. Subsequently, Gene Ontology (GO) classification analysis revealed that the 1265 DEGs were distributed across biological processes, cellular components, and molecular functions. This suggests that the silkworm midgut may affect various organelle functions and biological processes, providing crucial clues for further exploration of DEG function. Additionally, the expression levels of 12 selected detoxification-related DEGs were validated using qRT-PCR, which confirmed the reliability of the RNA-seq results. This study not only provides new insights into the detoxification defense mechanisms of silkworms after Pb exposure, but also establishes a valuable foundation for further investigation into the molecular detoxification mechanisms in silkworms.

Background: The aim of this study was to explore the association between lactate/albumin ratio and the prognosis of sepsis patients., Methods: A computerized search was performed in Pubmed, EMbase, Ovid, Medline, and Google Scholar to collate relevant studies. The results were compared using standardized mean differences (SMD)/odds ratio (OR) and 95% confidence intervals (CI). Prospective and retrospective cohort studies were both included in this study., Competing Interests: All the authors declare that they have no conflict of interest in this work., (2024 Xian Zhao, Qin Peng, Weiwei Li, Dongmei Hu, Yue Guan, Jingwen Wang, published by CEON/CEES.)

Background: Preoperative differentiation of the types of mediastinal tumors is essential. Magnetic resonance (MR) elastography potentially provides a noninvasive method to assess the classification of mediastinal tumor subtypes., Purpose: To evaluate the use of MR elastography in anterior mediastinal masses and to characterize the mechanical properties of tumors of different subtypes., Study Type: Prospective., Subjects: 189 patients with anterior mediastinal tumors (AMTs) confirmed by histopathology (62 thymomas, 53 thymic carcinomas, 57 lymphomas, and 17 germ cell tumors)., Field Strength/sequence: A gradient echo-based 2D MR elastography sequence and a diffusion-weighted imaging (DWI) sequence at 3.0 T., Assessment: Stiffness and apparent diffusion coefficients (ADC) were measured in AMTs using MR elastography-derived elastograms and DWI-derived ADC maps, respectively. The aim of this study is to identify whether MR elastography can differentiate between the histological subtypes of ATMs., Statistical Tests: One-way analysis of variance (ANOVA), two-way ANOVA, Pearson's linear correlation coefficient (r), receiver operating characteristic (ROC) curve analysis; P < 0.05 was considered significant., Results: Lymphomas had significantly lower stiffness than other AMTs (4.0 ± 0.63 kPa vs. 4.8 ± 1.39 kPa). The mean stiffness of thymic carcinomas was significantly higher than that of other AMTs (5.6 ± 1.41 kPa vs. 4.2 ± 0.94 kPa). Using a cutoff value of 5.0 kPa, ROC analysis showed that lymphomas could be differentiated from other AMTs with an accuracy of 59%, sensitivity of 97%, and specificity of 38%. Using a cutoff value of 5.1 kPa, thymic carcinomas could be differentiated from other AMTs with an accuracy of 84%, sensitivity of 67%, and specificity of 90%. However, there was an overlap in the stiffness values of individual thymomas (4.2 ± 0.71; 3.9-4.5), thymic carcinomas (5.6 ± 1.41; 5.0-6.1), lymphomas (4.0 ± 0.63; 3.8-4.2), and germ cell tumors (4.5 ± 1.79; 3.3-5.6)., Data Conclusion: MR elastography-derived stiffness may be used to evaluate AMTs of various histologies., Technical Efficacy: Stage 2., (© 2024 The Author(s). Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

This article aims to study the value of cerebrospinal fluid (CSF) immunoglobulin in differential diagnosis, prediction, and prognosis of tuberculous meningitis (TBM). The clinical data of 65 patients with TBM in our hospital were collected, and 65 patients with cryptococcal meningitis (CM) were enrolled in 1:1 matching. Relevant data were collected for comparison. CSFs IgG [331.51 (164.85, 645.00) vs 129.00 (55.05, 251.00) ng/mL], IgM [22.38 (8.52, 40.18) vs 6.08 (2.19, 23.30) ng/mL], and IgA [64.11 (21.44, 115.48) vs 16.55 (4.76, 30.36) ng/mL] in the TBM group were higher than those in the CM group ( P < 0.001). In the TBM group, after 24 weeks of treatment, the CSFs IgG, IgM, and IgA were significantly decreased, and the difference was statistically significant ( P < 0.05). The predictive results of CSF immunoglobulin for TBM showed that IgG, IgM, and IgA all had some predictive value for TBM, and the combined predictive value of the three was the highest, with an area under the curve of 0.831 (95% CI: 0.774-0.881). Logistic regression analysis of CSF immunoglobulins and TBM prognosis showed that IgG [odds ratio (OR) = 4.796, 95% confidence interval (CI): 2.575-8.864], IgM (OR = 3.456, 95% CI: 2.757-5.754), and IgA (OR = 4.371, 95% CI: 2.731-5.856) were TBM risk factors for poor prognosis in patients. The levels of IgG, IgM, and IgA in CSF were positively correlated with the severity of cranial magnetic resonance imaging (MRI) in TBM patients ( R 2 = 0.542, F = 65.392, P < 0.05). CSFs IgG, IgM, and IgA can be used as a routine monitoring index for TBM patients, which has a certain reference value in differential diagnosis and efficacy evaluation., Importance: In clinical practice, physicians can determine the physical conditions of patients based on the levels of cerebrospinal fluids (CSFs) IgG, IgM, and IgA. Higher levels of CSFs IgG, IgM, and IgA suggest more possibility of tuberculous meningitis and worse prognosis and magnetic resonance imaging manifestations., Competing Interests: The authors declare no conflict of interest.

Quinone outside inhibitor (QoI) has been applied to manage taro leaf blight caused by Phytophthora colocasiae in southeastern of China for many years. The risk of P. colocasiae to QoI and the potential resistant mechanism remain unknown. In this study, the 74 P. colocasiae strains were sampled from southeastern of China. Sequence analysis of the QoI target Cytb showed one nucleotide variant in the fragment of this gene in this population, producing two haplotypes. The nucleotide variant leads to codon change at 142 (GGT to GCT) producing A142 (alanine) and G142 (glycine) in Hap&#95;1 and Hap&#95;2 strains, respectively. The sensitivity differentiation to azoxystrobin of two haplotypes were observed in vitro. The Hap&#95;1 and Hap&#95;2 strains were confirmed resistant and sensitive by control efficacy of label rate fungicide application, which was 3.0% and 88.8% treated with 500 μg/mL azoxystrobin, respectively. In addition, 10.0 μg/mL azoxystrobin plus 50 μg/mL salicylhydroxamic acid (SHAM) supplemented in PDA medium was identified as a discriminatory dose for differentiation of these two phenotype strains. The azoxystrobin resistant frequency reached 86.5%, indicating prevalence of QoI resistance in the field. Further fitness related features showed that no significant difference in temperature sensitivity, mycelial growth rate, sporangia production, zoospore release and aggressiveness between azoxystrobin-resistant and sensitive strains indicating no potential fitness cost for azoxystrobin resistance. Taken together, azoxystrobin resistance need to be taken into consideration to manage taro leaf blight in southeastern of China., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The three-dimensional (3D) organization of genome is fundamental to cell biology. To explore 3D genome, emerging high-throughput approaches have produced billions of sequencing reads, which is challenging and time-consuming to analyze. Here we present Microcket, a package for mapping and extracting interacting pairs from 3D genomics data, including Hi-C, Micro-C, and derivant protocols. Microcket utilizes a unique read-stitch strategy that takes advantage of the long read cycles in modern DNA sequencers; benchmark evaluations reveal that Microcket runs much faster than the current tools along with improved mapping efficiency, and thus shows high potential in accelerating and enhancing the biological investigations into 3D genome. Microcket is freely available at https://github.com/hellosunking/Microcket ., (© 2024. The Author(s).)

Biochar, with its dual roles of soil remediation and carbon sequestration, is gradually demonstrating great potential for sustainability in agricultural and ecological aspects. In this study, a porous biochar derived from walnut shell wastes was prepared via a facile pyrolysis coupling with in-situ alkali etching method. An incubation study was conducted to investigate its performance in stabilizing copper (Cu) and lead (Pb) co-contaminated soils under different utilization types. The biochar effectively decreased the bioavailable Cu (8.5-91.68%) and Pb (5.03-88.54%), while increasing the pH, CEC, and SOM contents in both soils. Additionally, the results of sequential extraction confirmed that biochar promoted the transformation of the labile fraction of Cu and Pb to stable fractions. The mechanisms of Cu and Pb stabilization were found to be greatly dependent on the soil types. For tea plantation yellow soil, the main approach for stabilization was the complexation of heavy metals with abundant organic functional groups and deprotonation structure. Surface electrostatic adsorption and cation exchange contributed to the immobilization of Cu and Pb in vegetable-cultivated purple soil. This research provides valuable information for the stabilization of Cu and Pb co-contaminated soils for different utilization types using environmentally-friendly biochar., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Silk fibroin (SF), which is extensively utilized in tissue engineering and vascular grafts for enhancing vascular regeneration, has not been thoroughly investigated for its epigenetic effects on endothelial cells (EC). This study employed RNA sequencing analysis to evaluate the activation of histone modification regulatory genes in EC treated with SF. Subsequent investigations revealed elevated H3K9me3 levels in SF-treated EC, as evidenced by immunofluorescence and western blot analysis. The study utilized H2B-eGFP endothelial cells to demonstrate that SF treatment results in the accumulation of H2B-marked chromatin in the nuclear inner cavities of EC. Inhibition of H3K9me3 levels by a histone deacetylase inhibitor TSA decreased cell proliferation. Furthermore, the activation of the MAPK signaling pathway using chromium picolinate decreased the proliferative activity and H3K9me3 level in SF-treated EC. SF also appeared to enhance cell growth and proliferation by modulating the H3K9me3 level and reorganizing chromatin, particularly after oxidative stress induced by H 2 O 2 treatment. In summary, these findings indicate that SF promotes EC proliferation by increasing the H3K9me3 level even under stress conditions., Competing Interests: The authors have no conflicts to disclose., (© 2024 Author(s).)

Botrytis cinerea is one of the most destructive pathogens worldwide. It can damage over 200 crops, resulting in significant yield and quality losses. Cyclobutrifluram, a new generation of succinate dehydrogenase inhibitors, exhibits excellent inhibitory activity against B. cinerea. However, the baseline sensitivity and resistance of B. cinerea to cyclobutrifluram remains poorly understood. This study was designed to monitor the sensitivity frequency distribution, assess the resistance risk, and clarify the resistance mechanism of B. cinerea to cyclobutrifluram. The baseline sensitivity of B. cinerea isolates to cyclobutrifluram was 0.89 μg/mL. Cyclobutrifluram-resistant B. cinerea populations are present in the field. Six resistant B. cinerea isolates investigated in this study possessed enhanced compound fitness index compared to the sensitive isolates according to mycelial growth, mycelial dry weight, conidiation, conidial germination rate, and pathogenicity. Cyclobutrifluram exhibited no cross-resistance with tebuconazole, fludioxonil, cyprodinil, or iprodione. Sequence alignment revealed that BcSDHB from cyclobutrifluram-resistant B. cinerea isolates had three single substitutions (P225F, N230I, or H272R). Molecular docking verified that these mutations in BcSDHB conferred cyclobutrifluram resistance in B. cinerea. In conclusion, the resistance risk of B. cinerea to cyclobutrifluram is high, and the point mutations in BcSDHB (P225F, N230I, or H272R) confer cyclobutrifluram resistance in B. cinerea. This study provided important insights into cyclobutrifluram resistance in B. cinerea and offered valuable information for monitoring and managing cyclobutrifluram resistance in the future., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Brown rot disease, caused by Monilinia fructicola, poses a significant challenge to peach production in China. The efficacy of mefentrifluconazole, a new triazole fungicide, in controlling brown rot in peaches has been remarkable. However, the resistance risk and mechanism associated with this fungicide remain unclear. This study was designed to assess the resistance risk of M. fructicola to mefentrifluconazole and reveal the potential resistance mechanism., Results: The mean median effective concentration (EC 50 ) of 101 M. fructicola isolates to mefentrifluconazole was 0.003 μg mL -1 , and the sensitivity exhibited a unimodal distribution. Seven mefentrifluconazole-resistant mutants were generated from three parental isolates in the laboratory through fungicide adaption. The biological characteristics of the resistant mutants revealed that three of them exhibited enhanced survival fitness compared to the parental isolates, whereas the remaining four mutants displayed reduced survival fitness. Mefentrifluconazole showed strong positive cross-resistance with fenbuconazole, whereas no cross-resistance was observed with pyrimethanil, procymidone or pydiflumetofen. No overexpression of MfCYP51 gene was detected in the resistant mutants. Multiple sequence alignment revealed that three resistant mutants (MXSB2-2, Mf12-1 and Mf12-2) had a point mutation (G461S) in MfCYP51 protein. Molecular docking techniques confirmed the contribution of this point mutation to mefentrifluconazole resistance., Conclusion: The risk of M. fructicola developing resistance to mefentrifluconazole is relatively low-to-medium and point mutation G461S in MfCYP51 could confer mefentrifluconazole resistance in M. fructicola. This study provided essential data for monitoring the emergence of resistance and developing resistance management strategies for mefentrifluconazole. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Programmed death-ligand 1 (PD-L1) is a promising target for cancer immunotherapy due to its ability to inhibit T cell activation; however, its expression on various noncancer cells may cause on-target off-tumor toxicity when designing PD-L1-targeting Chimeric Antigen Receptor (CAR) T cell therapies. Combining rational design and directed evolution of the human fibronectin-derived monobody scaffold, "PDbody" was engineered to bind to PD-L1 with a preference for a slightly lower pH, which is typical in the tumor microenvironment. PDbody was further utilized as a CAR to target the PD-L1-expressing triple negative MDA-MB-231 breast cancer cell line. To mitigate on-target off-tumor toxicity associated with targeting PD-L1, a Cluster of Differentiation 19 (CD19)-recognizing SynNotch IF THEN gate was integrated into the system. This CD19-SynNotch PDbody-CAR system was then expressed in primary human T cells to target CD19-expressing MDA-MB-231 cancer cells. These CD19-SynNotch PDbody-CAR T cells demonstrated both specificity and efficacy in vitro , accurately eradicating cancer targets in cytotoxicity assays. Moreover, in an in vivo bilateral murine tumor model, they exhibited the capability to effectively restrain tumor growth. Overall, CD19-SynNotch PDbody-CAR T cells represent a distinct development over previously published designs due to their increased efficacy, proliferative capability, and mitigation of off-tumor toxicity for solid tumor treatment.

Host-derived reactive oxygen species (ROS) are an important defense means to protect against pathogens. Although mitochondria are the main intracellular targets of ROS, how pathogens regulate mitochondrial physiology in response to oxidative stress remains elusive. Prohibitin 2 (PHB2) is an inner mitochondrial membrane (IMM) protein, recognized as a mitophagy receptor in animals and fungi. Here, we find that an ANK and FYVE domain-containing protein PsAF5, is an adapter of PsPHB2, interacting with PsATG8 under ROS stress. Unlike animal PHB2 that can recruit ATG8 directly to mitochondria, PsPHB2 in Phytophthora sojae cannot recruit PsATG8 to stressed mitochondria without PsAF5. PsAF5 deletion impairs mitophagy under ROS stress and increases the pathogen's sensitivity to H 2 O 2 , resulting in the attenuation of P. sojae virulence. This discovery of a PsPHB2-PsATG8 adapter (PsAF5) in plant-pathogenic oomycetes reveals that mitophagy induction by IMM proteins is conserved in eukaryotes, but with differences in the details of ATG8 recruitment., (© 2024. The Author(s).)

Introduction: African swine fever virus (ASFV) is a highly contagious virus that spreads rapidly and has a mortality rate of up to 100% in domestic pigs, leading to significant economic losses in the pig industry. The major capsid protein p72 of ASFV plays a critical role in viral invasion and immune evasion., Methods: In this study, we used yeast two-hybrid screening to identify host proteins interacting with p72 in porcine alveolar macrophages (PAMs) and verified these proteins using confocal microscopy and immunoprecipitation techniques., Results and Discussion: We validated 13 proteins that interact with p72, including CD63, B2M, YTHDF2, FTH1, SHFL, CDK5RAP3, VIM, PELO, TIMP2, PHYH, C1QC, CMAS, and ERCC1. Enrichment analysis and protein-protein interaction network analysis of these interacting proteins revealed their involvement in virus attachment, invasion, replication, assembly, and immune regulation. These findings provide new insights into the function of p72 and valuable information for future research on the interaction between ASFV and host proteins., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Weng, Zheng, Liang, Chen, Peng, Zhang, Gong and Zheng.)

Floral scent (FS) plays a crucial role in the ecological functions and industrial applications of plants. However, the physiological and metabolic mechanisms underlying FS formation remain inadequately explored. Our investigation focused on elucidating the differential formation mechanisms of 2-phenylethanol (2-PE) and benzyl alcohol (BA) by examining seven related enzyme concentrations and the content of soluble sugar, soluble proteins, carbon (C) and nitrogen (N), as well as the C/N ratio. The findings revealed that the peak content of 2-PE in M. 'Praire Rose' and BA in M. 'Lollipop' occurred during the end flowering stage (S4) and flowering stage (S3) periods, respectively. The enzyme concentration change trends of phenylpyruvate decarboxylase (PDL), phenylacetaldehyde reductase (PAR), soluble protein, C, N, and C/N ratio changes during the S3-S4 period in M. 'Praire Rose' and M. 'Lollipop' were entirely opposite. Correlation and PCA analysis demonstrated that the content of CYP79D73 (a P450) and N, and the C/N ratio were key factors in 2-PE production in M. 'Praire Rose'. The production of BA in M. 'Lollipop' was more influenced by the content of phenylacetaldehyde synthase (PAAS), CYP79D73, and soluble sugar. As CYP79D73 exits oppositely in correlation to 2-PE ( M. 'Praire Rose') and BA ( M. 'Lollipop'), it is hypothesized that CYP79D73 was postulated as the primary factor contributing to the observed differences of 2-PE ( M. 'Praire Rose') and BA ( M. 'Lollipop') formation. These results carry significant implications for crabapple aromatic flower breeding and the essential oil industry etc.

Background: Based on real-world medical data, the artificial neural network model was used to predict the risk factors of linezolid-induced thrombocytopenia to provide a reference for better clinical use of this drug and achieve the timely prevention of adverse reactions. Methods: The artificial neural network algorithm was used to construct the prediction model of the risk factors of linezolid-induced thrombocytopenia and further evaluate the effectiveness of the artificial neural network model compared with the traditional Logistic regression model. Results: A total of 1,837 patients receiving linezolid treatment in a hospital in Xi 'an, Shaanxi Province from 1 January 2011 to 1 January 2021 were recruited. According to the exclusion criteria, 1,273 cases that did not meet the requirements of the study were excluded. A total of 564 valid cases were included in the study, with 89 (15.78%) having thrombocytopenia. The prediction accuracy of the artificial neural network model was 96.32%, and the AUROC was 0.944, which was significantly higher than that of the Logistic regression model, which was 86.14%, and the AUROC was 0.796. In the artificial neural network model, urea, platelet baseline value and serum albumin were among the top three important risk factors. Conclusion: The predictive performance of the artificial neural network model is better than that of the traditional Logistic regression model, and it can well predict the risk factors of linezolid-induced thrombocytopenia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhao, Peng, Hu, Li, Ji, Dong, Huang, Piao, Ding and Wang.)

Mitochondria undergo fission and fusion that are critical for cell survival and cancer development, while the regulatory factors for mitochondrial dynamics remain elusive. Herein we found that RNA m 6 A accelerated mitochondria fusion of colorectal cancer (CRC) cells. Metabolomics analysis and function studies indicated that m 6 A triggered the generation of glutathione (GSH) via the upregulation of RRM2B-a p53-inducible ribonucleotide reductase subunit with anti-reactive oxygen species potential. This in turn resulted in the mitochondria fusion of CRC cells. Mechanistically, m 6 A methylation of A1240 at 3'UTR of RRM2B increased its mRNA stability via binding with IGF2BP2. Similarly, m 6 A methylation of A2212 at the coding sequence (CDS) of OPA1-an essential GTPase protein for mitochondrial inner membrane fusion-also increased mRNA stability and triggered mitochondria fusion. Targeting m 6 A through the methyltransferase inhibitor STM2457 or the dm 6 ACRISPR system significantly suppressed mitochondria fusion. In vivo and clinical data confirmed the positive roles of the m 6 A/mitochondrial dynamics in tumor growth and CRC progression. Collectively, m 6 A promoted mitochondria fusion via induction of GSH synthesis and OPA1 expression, which facilitated cancer cell growth and CRC development., (© The Author(s) 2024. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

An estimated 240 fungicides are presently in use, but the direct targets for the majority remain elusive, constraining fungicide development and efficient resistance monitoring. In this study, we found that Pcα-actinin knockout did not influence the sensitivity of Phytophthora capsici to fluopicolide, which is a notable oomycete inhibitor. Using a combination of Bulk Segregant Analysis Sequencing and Drug Affinity Responsive Target Stability (DARTS) assays, the vacuolar H + -ATPase subunit a (PcVHA-a) was pinpointed as the target protein of fluopicolide. We also confirmed four distinct point mutations in PcVHA-a responsible for fluopicolide resistance in P. capsici through site-directed mutagenesis. Molecular docking, ATPase activity assays, and a DARTS assay suggested a fluopicolide-PcVHA-a interaction. Sequence analysis and further molecular docking validated the specificity of fluopicolide for oomycetes or fish. These findings support the claim that PcVHA-a is the target of fluopicolide, proposing vacuolar H + -ATPase as a promising target for novel fungicide development.

Mefentrifluconazole, a triazole fungicide, exhibits remarkable efficacy in combating Fusarium spp. The mean EC 50 value of mefentrifluconazole against 124 isolates of Fusarium pseudograminearum was determined to be 1.06 μg/mL in this study. Fungicide taming produced five mefentrifluconazole-resistant mutants with resistance factors ranging from 19.21 to 111.34. Compared to the original parental isolates, the fitness of three resistant mutants was much lower, while the remaining two mutants displayed enhanced survival fitness. There was evidence of positive cross-resistance between tebuconazole and mefentrifluconazole. Mefentrifluconazole resistance in F. pseudograminearum can be conferred by FpCYP51B L144F , which was identified in four mutants according to molecular docking and site-directed transformation experiments. Overexpression of FpCYP51s was also detected in the resistant mutants. In conclusion, mefentrifluconazole has a low-to-medium resistance risk in F. pseudograminearum , and the L144F mutation in FpCYP51B and the increased expression level of FpCYP51s may be responsible for mefentrifluconazole resistance in F. pseudograminearum .

Toxic Microcystis blooms are widespread in aquatic bodies, posing major threats to aquatic and human life. Recently, bioflocculants have attracted considerable attention as a promising biomaterial for Microcystis management. In search of a novel organism that can produce an efficient bioflocculant for controlling harmful algae sustainably, the native gastropod Cipangopaludina chinensis was co-cultured continuously with toxic Microcystis under different initial algal cell densities. The bioflocculation effect of snail mucus on toxic Microcystis, microcystin removal, and toxin accumulation in snails was investigated. In addition, the properties of the adhesive mucus were characterized using microscopic, X-ray diffraction, infrared spectroscopy, and polysaccharide and proteome analyses. Microcystis cells were captured and flocculated by the snail mucus; removal efficiencies of up to 89.9% and 84.8% were achieved for microalgae and microcystin-leucine arginine (MC-LR), respectively, when co-cultured with C. chinensis for only one day. After nine-day exposure, less than 5.49 µg/kg DW microcystins accumulated in the snails, indicating safety for human consumption. The snail mucus contained 104.3 µg/mg protein and 72.7 µg/mg carbohydrate, which provide several functional groups beneficial for Microcystis bioflocculation. The main monosaccharide subunits of polysaccharides are galactose, galactosamine, glucosamine, fucose, glucose, and mannose. Most of them are key components of polysaccharides in many bioflocculants. Gene Ontology analysis indicated the protein enrichment in binding processes and catalytic activity, which may account for Microcystis bioflocculation via protein binding or enzymatic reactions. The findings indicate that native C. chinensis secretes adhesive mucus that can act as bioflocculant for toxic Microcystis from ambient water and can be an effective and eco-friendly tool for Microcystis suppression., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To investigate factors that may influence humoral immunity post-vaccination with a COVID-19-inactivated vaccine (SC2IV)., Methods: A total of 1596 healthy individuals from the Seventh Affiliated Hospital, Sun Yat-sen University (1217) and Shenzhen Baotian Hospital (379) were enrolled in this study among which 694 and 218 participants were vaccinated with two-dose SC2IV, respectively. Physical examination indices were recorded. The levels of neutralizing antibody (NA), Spike IgG, receptor-binding domain (RBD) IgG, RBD IgG + IgM + IgA, and nucleocapsid IgG of SARS-CoV-2 were measured by a non-virus ELISA kit. Multiple statistical analyses were carried out to identify factors that influence humoral immunity post-vaccination., Results: The two-dosage vaccination could induce NA in more than 90 % of recipients. The NA has the strongest correlation with anti-RBD IgG. Age is the most important independent index that affects the NA level, while basophil count, creatine kinase-MB, mean corpuscular hemoglobin, the ratio of albumin to urine creatinine, and thyroglobulin antibody have relatively minor contributions. Indices that affect the NA level were different between males and females. Antibodies targeting other epitopes of SARS-CoV-2 were detected in recipients without anti-RBD., Conclusions: The factors identified in association with the NA level post-vaccination may help to evaluate the protective effect, risk of re-infection, the severity of symptoms, and prognosis for vaccine recipients in clinical., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

In this study, we determined the sensitivity of 148 Phytophthora litchii isolates to cyazofamid, yielding a mean EC 50 value of 0.0091 ± 0.0028 μg/mL. Through fungicide adaptation, resistant mutants (RMs) carrying the F220L substitution in PlCyt b were derived from wild-type isolates. Notably, these RMs exhibited a lower fitness compared with the parental isolates. Molecular docking analysis further revealed that the F220L change contributed to a decrease in the binding energy between cyazofamid and PlCyt b. The total phenol and flavonoid contents in the litchi pericarp treated with cyazofamid on day 5 were significantly higher than in other treatments. Overall, the laboratory assessment indicated a moderate risk of cyazofamid resistance in P. litchii , but the emergence of the F220L change could lead to a high level of resistance. Thus, cyazofamid represents a promising agrochemical for controlling postharvest litchi downy blight and extending the shelf life of litchi fruits.

The cucumber target spot, caused by Corynespora cassiicola, is a major cucumber disease in China. Mefentrifluconazole, a new triazole fungicide, exhibits remarkable efficacy in controlling cucumber target spot. However, the resistance risk and mechanism remain unclear. In this study, the inhibitory activity of mefentrifluconazole against 101 C. cassiicola isolates was determined, and the results indicated that the EC 50 values ranged between 0.15 and 12.85 μg/mL, with a mean of 4.76 μg/mL. Fourteen mefentrifluconazole-resistant mutants of C. cassiicola were generated from six parental isolates in the laboratory through fungicide adaptation or UV irradiation. The resistance was relatively stable after ten consecutive transfers on a fungicide-free medium. No cross-resistance was observed between mefentrifluconazole and pyraclostrobin, fluopyram, prochloraz, mancozeb, or difenoconazole. Investigations into the biological characteristics of the resistant mutants revealed that six resistant mutants exhibited an enhanced compound fitness index (CFI) compared to the parental isolates, while others displayed a reduced or comparable CFI. The overexpression of CcCYP51A and CcCYP51B was detected in the resistant mutants, regardless of the presence or absence of mefentrifluconazole. Additionally, a two-way mixture of mefentrifluconazole and prochloraz at a concentration of 7:3 demonstrated superior control efficacy against the cucumber target spot, achieving a protection rate of 80%. In conclusion, this study suggests that the risk of C. cassiicola developing resistance to mefentrifluconazole is medium, and the overexpression of CcCYP51A and CcCYP51B might be associated with mefentrifluconazole resistance in C. cassiicola. The mefentrifluconazole and prochloraz two-way mixture presented promising control efficacy against the cucumber target spot., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Di(2-ethylhexyl) phthalate (DEHP) is a common plasticizer. Studies have revealed that DEHP exposure can cause kidney damage. Green tea is among the most popular beverages in China. Green tea polyphenols (GTPs) have been proven to have therapeutic effects on organ damage induced by heavy metal exposure. However, few studies have reported on GTP-relieving DEHP-induced kidney damage., Methods: C57BL/6J male mice aged 6-8 weeks were treated with distilled water (control group), 1,500 mg/kg/d DEHP + corn oil (model group), 1,500 mg/kg/d DEHP + corn oil + 70 mg/kg GTP (treatment group), corn oil (oil group), and 70 mg/kg GTP (GTP group) by gavage for 8 weeks, respectively. The renal function of mice and renal tissue histopathology of each group were evaluated. The renal tissues of mice in the model, treatment, and control groups were analyzed using high-throughput sequencing. We calculated the differentially expressed microRNAs (miRNAs) and messenger RNAs (mRNAs) using the limma R package, the CIBERSORT algorithm was used to predict immune infiltration, the starBase database was used to screen the miRNA-mRNA regulatory axis, and immunohistochemical analyses were performed to verify protein expression., Results: GTP alleviated the deterioration of renal function, renal inflammation and fibrosis, and mitochondrial and endoplasmic reticulum lesions induced by DEHP in mice. Differential immune infiltrations of plasma, dendritic, T, and B cells were noted between the model and treatment groups. We found that three differentially expressed miRNAs (mmu-miR-383-5p, mmu-miR-152-3p, and mmu-miR-144-3p), three differentially expressed mRNAs (Ddit4, Dusp1, and Snx18), and three differentially expressed proteins (Ddit4, Dusp1, and Snx18) played crucial roles in the miRNA-mRNA-protein regulatory axes when GTPs mitigate DEHP-induced kidney damage in mice., Conclusion: GTP can alleviate DEHP-induced kidney damage and regulate immune cell infiltration. We screened four important miRNA-mRNA-protein regulatory axes of GTP, mitigating DEHP-induced kidney damage in mice., (© 2023 S. Karger AG, Basel.)

Background: Macrophage-derived foam cells are a hallmark of atherosclerosis. Scavenger receptors, including lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (OLR-1), are the principal receptors responsible for the uptake and modification of LDL, facilitating macrophage lipid load and the uptake of oxidized LDL by arterial wall cells. Krüppel-like factor 15 (KLF15) is a transcription factor that regulates the expression of genes by binding to the promoter during transcription. Therefore, this study aimed to investigate the precise role of macrophage KLF15 in atherogenesis., Methods: We used two murine models of atherosclerosis: mice injected with an adeno-associated virus (AAV) encoding the Asp374-to-Tyr mutant version of human PCSK9, followed by 12 weeks on a high-fat diet (HFD), and ApoE -/-- mice on a HFD. We subsequently injected mice with AAV-KLF15 and AAV-LacZ to assess the role of KLF15 in the development of atherosclerosis in vivo. Oil Red O, H&E, and Masson's trichome staining were used to evaluate atherosclerotic lesions. Western blots and RT-qPCR were used to assess protein and mRNA levels, respectively., Results: We determined that KLF15 expression was downregulated during atherosclerosis formation, and KLF15 overexpression prevented atherosclerosis progression. KLF15 expression levels did not affect body weight or serum lipid levels in mice. However, KLF15 overexpression in macrophages prevented foam cell formation by reducing OLR-1-meditated lipid uptake. KLF15 directly targeted and transcriptionally downregulated OLR-1 levels. Restoration of OLR-1 reversed the beneficial effects of KLF15 in atherosclerosis., Conclusion: Macrophage KLF15 transcriptionally downregulated OLR-1 expression to reduce lipid uptake, thereby preventing foam cell formation and atherosclerosis. Thus, our results suggest that KLF15 is a potential therapeutic target for atherosclerosis., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Ltd.)

Phosphorus and nitrogen pollution from agricultural nonpoint sources heavily burden the water environment, and a scientific calculating system is needed to calculate the pollutant loads under the water pollution treatment. This study established a system to calculate the coefficients of agricultural nonpoint source pollutants into water bodies in the subregion in Poyang Lake basin in the middle reach of the Yangtze River combining with multiple driving factors. Validation results showed that the errors of the typical unit were 30.58% for total phosphorus (TP), 13.43% for total nitrogen (TN) and 33.93% for ammonia nitrogen (NH 3 -N), respectively. The errors of the subregion were 26.92% for TP, 31.83% for TN and 29.15% for NH 3 -N, respectively. Besides, there were higher TP and TN loads in the east area of subregion in both units and county scales, which indicated the heavy phosphorus and nitrogen burden on water environment. In contrast, higher NH 3 -N loads occurred in the north area of subregion. The establishment of coefficient system for agricultural pollutants into water bodies and the pollutant loads calculation would provide enlightenment for water pollution treatment and agricultural nonpoint source pollution controlling., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The SIMBA (Simultaneous Imaging and Manipulation of genomic loci by Biomolecular Assemblies) system is an innovative CRISPR-based imaging technique that leverages dCas9-SunTag and FRB-mCherry-HP1α, with scFv-FKBP acting as a bridge. This powerful system enables simultaneous visualization and manipulation of genomic loci. The dCas9-SunTag fusion protein allows for precise targeting of specific genomic sites, and the FRB-mCherry-HP1α fusion protein facilitates the condensation of chromatin at the targeted loci. The scFv-FKBP bridge protein links dCas9-SunTag and FRB-mCherry-HP1α, ensuring efficient and specific recruitment of HP1α to the desired genomic loci. This integrated approach allows us to visualize and manipulate genomic regions of interest, opening up new avenues for studying genome organization, gene expression regulation, and chromatin dynamics in living cells. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Cloning of genetic constructs Basic Protocol 2: Transient transfection in mammalian cells and live-cell imaging Basic Protocol 3: Generation of SIMBA-expressing stable cell lines Basic Protocol 4: Manipulation of genomic loci using SIMBA., (© 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.)

Tomato early blight is a significant disease that causes substantial losses to tomato yield and quality. Mefentrifluconazole, an isopropanol-azole subgroup of triazole fungicides, has been registered in China for controlling various plant diseases, including tomato early blight, grape anthracnose, and apple brown spot. However, limited information is available on the mefentrifluconazole resistance risk and mechanism in plant pathogens. The sensitivity to mefentrifluconazole of 122 isolates of Alternaria alternata, one of the causal agents of tomato early blight, collected from different provinces in China, was evaluated. The results showed a unimodal curve for the sensitivity frequency, with an average EC 50 of 0.306 μg/mL. Through fungicide adaption, six resistant mutants (N4, N5, T4, T5, NG1, and NG10) were obtained from three parental isolates, with a mutation frequency of 3.28 × 10 -4 and resistance factors ranging between 19 and 147. The survival fitness of the resistant mutants, except for NG1, was significantly lower than that of their parental isolates. Positive cross-resistance was observed between mefentrifluconazole and difenoconazole or fenbuconazole, whereas no cross-resistance was found with three non-DMI fungicides. Furthermore, three distinct point mutations were detected in the AaCYP51 protein of the resistant mutants: I300S in T4 and T5; A303T in N4, NG1, and NG10; and A303V in N5. Compared to the parental isolates, the AaCYP51 gene was overexpressed in all six resistant mutants when treated with mefentrifluconazole. In summary, the resistance risk of A. alternata to mefentrifluconazole was low, and point mutations and overexpression of the AaCYP51 gene were identified as contributing factors to mefentrifluconazole resistance in A. alternata., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Floral scent (FS) plays a pivotal role in maintaining ecological equilibrium within plant populations and ecosystems while also bearing significance for human well-being. Despite the growing interest in FS research, there exists a dearth of comprehensive analyses on research trends, contemporary topics, and their broader implications. In this study, we employ bibliometric techniques using data from the Web of Science Core Collection spanning 1987-2022 to offer a quantitative overview of the scientific literature surrounding FS by examining the annual publication outputs, popular research areas, temporal trends in keywords, geographic distribution of relevant studies, institutions, co-organizations, as well as relevant authors. Our findings reveal a marked upsurge in FS publications, notably within the domains of Food Science Technology, Plant Sciences, Chemistry, Agriculture, Biochemistry, and Molecular Biology. The research landscape in FS primarily encompasses evolutionary dynamics, volatile compound analyses, biosynthesis mechanisms, and essential oil properties. These research trends signify a transition from micro-level exploration, focusing on individual pollination ecological functions of FS, to a macro-perspective that emphasizes FS's overarching impact on species diversity and ecosystem stability. This shift extends from the investigation of singular sensory attributes of FS to a holistic evaluation of their role in food production, quality, and yield enhancement. It encompasses a move away from mere FS extraction towards the examination of antioxidant potential within phenolic compounds and other industrial applications. Thus, improving research methodologies, strengthening interdisciplinary collaboration on an international scale, and delving deeper into the multifaceted ecological functions of floral diversity and their societal implications will be paramount.

A high power single-frequency operation at 1112 nm with novel insertable monolithic planar ring oscillator based on a Nd:YAG/YAG bonded crystal is proposed. In a proof-of-principle experiment, a finely designed coating on the output surface is carried out to ensure single-wavelength oscillation at 1112 nm, together with a half-wave plate and a Tb 3 Ga 5 O 12 crystal inserted in the open space of the bonded block to realize the unidirectional operation with power scalability. Consequently, the single-frequency laser delivers an output power of 3.9 W at 1112.3 nm with a slope efficiency of 58.6% and an optical-to-optical efficiency of 17.7%. The power fluctuation is measured to be within ± 0.26% over 20 min, and the laser linewidth is estimated to be 4.15 MHz (Δλ = 0.017 pm).

Background: Fusarium pseudograminearum is one of the dominant pathogens of Fusarium crown rot (FCR) worldwide. Unfortunately, no fungicides have yet been registered for the control of FCR in wheat in China. Pydiflumetofen, a new-generation succinate dehydrogenase inhibitor, exhibits excellent inhibitory activity to Fusarium spp. A resistance risk assessment of F. pseudograminearum to pydiflumetofen and the resistance mechanism involved have not yet been investigated., Results: The median effective concentration (EC 50 ) value of 103 F. pseudograminearum isolates to pydiflumetofen was 0.0162 μg mL -1 , and the sensitivity exhibited a unimodal distribution. Four resistant mutants were generated by fungicide adaption, which possessed similar or impaired fitness compared to corresponding parental isolates based on the results of mycelial growth, conidiation, conidium germination rate, and virulence determination. Pydiflumetofen showed strong positive cross-resistance with cyclobutrifluram and fluopyram but no cross-resistance with carbendazim, phenamacril, tebuconazole, fludioxonil, or pyraclostrobin. Sequence alignment revealed that pydiflumetofen-resistant F. pseudograminearum mutants had two single-point mutations of A83V or R86K in FpSdhC 1 . Molecular docking further confirmed that point mutation of A83V or R86K in FpSdhC 1 could confer resistance of F. pseudograminearum to pydiflumetofen., Conclusion: Fusarium pseudograminearum shows an overall moderate risk of developing resistance to pydiflumetofen, and point mutation FpSdhC 1 A83V or FpSdhC 1 R86K could confer pydiflumetofen resistance in F. pseudograminearum. This study provided vital data for monitoring the emergence of resistance and developing resistance management strategies for pydiflumetofen. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Phytophthora capsici deploys effector proteins to manipulate host immunity and facilitate its colonization. However, the underlying mechanisms remain largely unclear. In this study, we demonstrated that a Sne-like (Snel) RxLR effector gene PcSnel4 is highly expressed at the early stages of P. capsici infection in Nicotiana benthamiana. Knocking out both alleles of PcSnel4 attenuated the virulence of P. capsici, while expression of PcSnel4 promoted its colonization in N. benthamiana. PcSnel4B could suppress the hypersensitive reaction (HR) induced by Avr3a-R3a and RESISTANCE TO PSEUDOMONAS SYRINGAE 2 (AtRPS2), but it did not suppress cell death elicited by Phytophthora infestin 1 (INF1) and Crinkler 4 (CRN4). COP9 signalosome 5 (CSN5) in N. benthamiana was identified as a host target of PcSnel4. Silencing NbCSN5 compromised the cell death induced by AtRPS2. PcSnel4B impaired the interaction and colocalization of Cullin1 (CUL1) and CSN5 in vivo. Expression of AtCUL1 promoted the degradation of AtRPS2 and disrupted HR, while AtCSN5a stabilized AtRPS2 and promoted HR, regardless of the expression of AtCUL1. PcSnel4 counteracted the effect of AtCSN5 and enhanced the degradation of AtRPS2, resulting in HR suppression. This study deciphered the underlying mechanism of PcSnel4-mediated suppression of HR induced by AtRPS2., Competing Interests: Conflict of interest statement. The authors declare that they have no conflict of interests., (© American Society of Plant Biologists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To study the clinical and neuroelectrophysiological features of botulism in children., Methods: A retrospective analysis was conducted on the clinical data of eight children who were diagnosed with botulism in the Department of Neurology, Hunan Children's Hospital, from August 2015 to October 2022., Results: All eight children were found to have symmetrical cranial nerve palsy and flaccid paralysis of the extremities, with a descending pattern. Seven children presented with respiratory muscle paralysis. Electrophysiological examinations revealed decreased compound muscle action potential (CMAP) amplitudes in 5 children, increased CMAP amplitudes exceeding 40.0% in 6 children during high-frequency repetitive nerve stimulation, and short duration, low amplitude, and polyphasic motor unit action potentials in 4 children., Conclusions: The main clinical features of botulism in children include symmetric, descending flaccid paralysis starting from cranial nerves, with the possibility of respiratory muscle paralysis. Electrophysiological abnormalities associated with it include decreased CMAP amplitudes, increased CMAP amplitudes during high-frequency repetitive nerve stimulation, and short duration, low amplitude, and polyphasic motor unit action potentials.

Background: Di (2-ethylhexyl) phthalate (DEHP) is a common plasticizer known to cause liver injury. Green tea is reported to exert therapeutic effects on heavy metal exposure-induced organ damage. However, limited studies have examined the therapeutic effects of green tea polyphenols (GTPs) on DEHP-induced liver damage., Aim: To evaluate the molecular mechanism underlying the therapeutic effects of GTPs on DEHP-induced liver damage., Methods: C57BL/6J mice were divided into the following five groups: Control, model [DEHP (1500 mg/kg bodyweight)], treatment [DEHP (1500 mg/kg bodyweight) + GTP (70 mg/kg bodyweight), oil, and GTP (70 mg/kg bodyweight)] groups. After 8 wk, the liver function, blood lipid profile, and liver histopathology were examined. Differentially expressed micro RNAs (miRNAs) and mRNAs in the liver tissues were examined using high-throughput sequencing. Additionally, functional enrichment analysis and immune infiltration prediction were performed. The miRNA-mRNA regulatory axis was elucidated using the starBase database. Protein expression was evaluated using immunohistochemistry., Results: GTPs alleviated DHEP-induced liver dysfunction, blood lipid dysregulation, fatty liver disease, liver fibrosis, and mitochondrial and endoplasmic reticulum lesions in mice. The infiltration of macrophages, mast cells, and natural killer cells varied between the model and treatment groups. mmu-miR-141-3p (a differentially expressed miRNA), Zcchc24 (a differentially expressed mRNA), and Zcchc24 (a differentially expressed protein) constituted the miRNA-mRNA-protein regulatory axis involved in mediating the therapeutic effects of GTPs on DEHP-induced liver damage in mice., Conclusion: This study demonstrated that GTPs mitigate DEHP-induced liver dysfunction, blood lipid dysregulation, fatty liver disease, and partial liver fibrosis, and regulate immune cell infiltration. Additionally, an important miRNA-mRNA-protein molecular regulatory axis involved in mediating the therapeutic effects of GTPs on DEHP-induced liver damage was elucidated., Competing Interests: Conflict-of-interest statement: The authors declare no competing financial interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

In high-speed railway operational monitoring network systems targeting railway infrastructure as its monitoring objective, there is a wide variety of sensor types with diverse operational requirements. These systems have varying demands on data transmission latency and network lifespan. Most of the previous research focuses only on prolonging network lifetime or reducing data transmission delays when designing or optimizing routing protocols, without co-designing the two. In addition, due to the harsh operating environment of high-speed railways, when the network changes dynamically, the traditional routing algorithm generates unnecessary redesigns and leads to high overhead. Based on the actual needs of high-speed railway operation environment monitoring, this paper proposes a novel Double Q-values adaptive model combined with the existing reinforcement learning method, which considers the energy balance of the network and real-time data transmission, and constructs energy saving and delay. The two-dimensional reward avoids the extra overhead of maintaining a global routing table while capturing network dynamics. In addition, the adaptive weight coefficient is used to ensure the adaptability of the model to each business of the high-speed railway operation environment monitoring system. Finally, simulations and performance evaluations are carried out and compared with previous studies. The results show that the proposed routing algorithm extends the network lifecycle by 33% compared to the comparison algorithm and achieves good real-time data performance. It also saves energy and has fewer delays than the other three routing protocols in different situations.

Utilization of uranium resource in seawater are highly possible to meet the growth demands for the sustainable development of nuclear energy industry. Bio-adsorbents exhibit high performance in terms of adsorption selectivity, equilibrium speed, and environmental friendliness, while the high fabrication cost hinders their practical application. In this study, a low-cost soy protein isolate (SPI) is used to fabricate adsorbent named SPI hydrogel for uranium extraction. This is the first report on applying bio-adsorbents derived from low-cost natural proteins for uranium extraction. The SPI hydrogel showed high uranium adsorption capacity of 53.94 mg g -1 in simulated nuclear wastewater and 5.29 mg g -1 is achieved in natural seawater, which is higher than all currently available adsorbents based on non-modified natural biomolecules. The amino and oxygen-containing groups are identified as the functional groups for uranyl binding by providing four oxygen and two nitrogen atoms to form equatorial coordination with uranyl, which guarantees the high binding selectivity and affinity to uranyl ions. The low cost for accessing the raw material together with the environmental friendliness, high salt tolerance, high uranium adsorption ability, and high selectivity to uranium, make SPI hydrogel a promising adsorbent for uranium extraction from seawater and nuclear wastewater., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

An external-cavity dumped nanosecond (ns) ultra-broad-area laser diode (UBALD) at around 966 nm with high pulse energy is demonstrated. A 1 mm UBALD is used to produce high output power and high pulse energy. A Pockels cell (PC) combines with two polarization beam splitters (PBSs) and is employed to cavity-dump a UBALD operating at 10 kHz repetition rate. At a pump current of 23 A, 11.4 ns pulses with a maximum pulse energy of ≈1.9 µJ and a maximum peak power of ≈166 W are achieved. The beam quality factor is measured to be M x 2 =19.5 in the slow axis direction and M y 2 =2.17 in the fast axis direction. Moreover, maximum average output power stability is confirmed, with a power fluctuation of less than 0.8% rms over 60 min. To the best of our knowledge, this is the first high-energy external-cavity dumped demonstration from an UBALD.

Proteins containing both FYVE and serine/threonine kinase catalytic (STKc) domains are exclusive to protists. However, the biological function of these proteins in oomycetes has rarely been reported. In the Phytophthora sojae genome database, we identified five proteins containing FYVE and STKc domains, which we named PsZFPK1, PsZFPK2, PsZFPK3, PsZFPK4, and PsZFPK5. In this study, we characterized the biological function of PsZFPK1 using a CRISPR/Cas9-mediated gene replacement system. Compared with the wild-type strain, P6497, the PsZFPK1 -knockout mutants exhibited significantly reduced growth on a nutrient-rich V8 medium, while a more pronounced defect was observed on a nutrient-poor Plich medium. The PsZFPK1 -knockout mutants also showed a significant increase in sporangium production. Furthermore, PsZFPK1 was found to be essential for oospore production and complete virulence but dispensable for the stress response in P. sojae . The N-terminal region, FYVE and STKc domains, and T602 phosphorylation site were found to be vital for the function of PsZFPK1. Conversely, these domains were not required for the localization of PsZFPK1 protein in the cytoplasm. Our results demonstrate that PsZFPK1 plays a critical role in vegetative growth, sporangium formation, oospore production, and virulence in P. sojae .

Klebsiella pneumoniae is a widespread pathogen of several human diseases. The emergence of multidrug-resistant K. pneumoniae makes the treatment of these diseases a significant challenge. The application of bacteriophages is a potential approach for dealing with the emergence of multidrug-resistant pathogenic bacteria. This study isolates a novel bacteriophage vB&#95;KleM&#95;KB2 that infects the multidrug-resistant clinical isolates of K. pneumoniae. The bacteriophage exhibits a short latent period of 10 min, and can effectively lyse the bacterium within 60 min. Notably, the bacteriophage can completely inhibit the growth of the host bacterium at the initial concentration of 10 7  CFU/mL with a low multiplicity of infection of 0.001, which proves its high lytic activity. Furthermore, the bacteriophage shows high environmental tolerances, which can facilitate the practical application of the bacteriophage. Analysis of the bacteriophage genome shows that the bacteriophage possesses a novel genome sequence and can represent a new bacteriophage genus. Considering the high lytic activity, short latent period, high stability, and novel genetic background, bacteriophage vB&#95;KleM&#95;KB2 enriches the bacteriophage library and provides a new alternative for controlling the diseases caused by multidrug-resistant pathogenic K. pneumoniae., (© 2023. The Author(s).)

We present a multilevel synergically controlling wavefront correction method that can apply in a slab laser system. To fully utilize the response frequency and the stroke of actuators of the single deformable mirror (DM), we design a set of multilevel wavefront correction devices to reduce the root-mean square of wavefront aberration before the DM. As the wavefront of slab geometry solid-state lasers mainly consists of fourth and longitudinally distributed aberration, such as 5th, 9th, and 14th orders of Legendre polynomials. We design a precompensating level of the aberration with a slow-drift mirror, fast-steer mirror, one-dimensional adjustable slab-aberration compensator, and beam-shaping system to reduce these orders of wavefront aberration with low spatial resolution and large stroke. As the controlling bandwidth of different devices is diverse, the coupling oscillation between the precompensating level and adaptive optics (AO) level occurs, then we develop the multilevel synergically control to address the coupling. With the precompensating level, the experimental result shows the residual wavefront aberration of the slab laser is compensated well by the AO level effectively within the compensating capability. We clean up a 9.8 kW slab laser system with the beam quality β of far-field focus spots improved from 17.71 to 2.24 times the diffraction limit.

In this letter, a sub-pm linewidth, high pulse energy and high beam quality microsecond-pulse 766.699 nm Ti:sapphire laser pumped by a frequency-doubled Nd:YAG laser is demonstrated. At an incident pump energy of 824 mJ, the maximum output energy of 132.5 mJ at 766.699 nm with linewidth of 0.66 pm and a pulse width of 100 µs is achieved at a repetition rate of 5 Hz. To the best of our knowledge, this is the highest pulse energy at 766.699 nm with pulse width of hundred micro-seconds for a Ti:sapphire laser. The beam quality factor M 2 is measured to be 1.21. It could be precisely tuned from 766.623 to 766.755 nm with a tuning resolution of 0.8 pm. The wavelength stability is measured to be less than ±0.7 pm over 30 min. The sub-pm linewidth, high pulse energy and high beam quality Ti:sapphire laser at 766.699 nm can be used to create a polychromatic laser guide star together with a home-made 589 nm laser in the mesospheric sodium and potassium layer for the tip-tilt correction resulting in the near-diffraction limited imagery on a large telescope.

Amisulbrom is a novel quinone inside inhibitor, which exhibits excellent inhibitory activity against phytopathogenic oomycetes. However, the resistance risk and mechanism of amisulbrom in Phytophthora litchii are rarely reported. In this study, the sensitivity of 147 P. litchii isolates to amisulbrom was determined, with an average EC 50 of 0.24 ± 0.11 μg/mL. The fitness of resistant mutants, obtained by fungicide adaption, was significantly lower than that of the parental isolates in vitro . Cross-resistance was detected between amisulbrom and cyazofamid. Amisulbrom could not inhibit the cytochrome bc1 complex activity with H15Y and G30E + F220L point mutations in cytochrome b (Cyt b) in vitro . Molecular docking indicated that the H15Y or G30E point mutation can decrease the binding energy between amisulbrom and P. litchii Cyt b. In conclusion, P. litchii might have a medium resistance risk to amisulbrom, and a novel point mutation H15Y or G30E in Cyt b could cause high amisulbrom resistance in P. litchii .

This study examined volatile organic compounds (VOCs) emitted from the combustion of seven typical biomass fuel types in a traditional stove, elevated kang, and biomass furnace and from the combustion of three types of coal in coal furnaces. The results revealed that emission factors (EFs) of VOCs emitted from combustion processes ranged from 48.8 ± 29.1 mg/kg (for anthracite combustion in an outdoor boiler) to 5700 ± 6040 mg/kg (for sesame straw combustion in a traditional stove). Changing the fuel type engendered a more significant EF reduction (82.7%) than changing the stove type (51.8%). The emitted VOCs (including oxygenated VOCs, OVOCs) can be ordered as follows (in descending order) in terms of proportion: OVOCs > alkenes > aromatic VOCs > alkanes > halo hydrocarbons > alkynes. These results indicate solid fuel combustion processes warrant attention because they produce high OVOC emissions. The ozone formation potential (OFP) values derived for VOCs emitted from solid fuel combustion ranged from 5.83 ± 0.72 to 1910 ± 1750 mg/kg. Clean fuel and clean stove technologies both exhibited >80% efficiency levels in reducing OFP emissions (e.g., 80.6% reduction for the optimal fuel; 89.4% reduction for a clean stove). Therefore, the difference between VOC emission profiles from different combustion technologies should not be ignored. This study also noted substantial differences between VOC emissions from residential combustion and industrial combustion. Accordingly, attention should be paid to the local characteristics of fuels and stoves and to VOC emissions from residential combustion., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)