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Abstract Low-load resistance training with blood flow restriction (LRT-BFR) has shown potential to improve muscle strength and mass in different populations; however, there remains limited evidence in sarcopenic people diagnosed with sarcopenia criteria. This study systematically compared the effectiveness of LRT-BFR and conventional high-intensity resistance training (CRT) on clinical muscle outcomes (muscle mass, strength and performance), cardiovascular disease (CVD) risk factors and sarcopenia-related biomarkers of older people with sarcopenia. Twenty-one older individuals (aged 65 years and older) diagnosed with sarcopenia were randomly assigned to the LRT-BFR (20%–30% one-repetition maximum (1RM), n = 10) or CRT (60%–70% 1RM, n = 11) group. Both groups underwent a supervised exercise program three times a week for 12 weeks. The primary outcome was knee extensor strength (KES), and the secondary outcomes included body composition (body mass, body mass index and body fat percentage), muscle mass [appendicular skeletal muscle mass index (ASMI)], handgrip strength, physical performance [short physical performance battery (SPPB) and 6-m walk], CVD risk factors [hemodynamic parameters (systolic and diastolic blood pressure and heart rate (SBP, DBP and HR)) and lipid parameters (total cholesterol, triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein)], sarcopenia-related blood biomarkers [inflammatory biomarkers, hormones (growth hormone (GH) and insulin-like growth factor 1) and growth factors (myostatin and follistatin)] and quality of life [Short Form 36 Health Survey (SF-36)]. Both interventions remarkably improved the body composition, KES, 6-m walk, SBP, HDL, TG, GH, FST and SF-36 scores. CRT significantly improved the ASMI (p

Bisphenol AP (BPAP), an environmental endocrine disruptor, may cause neurodevelopmental disorders affecting human health. Studies have shown that BPAP impacts hormone synthesis and metabolism, causes social behavior abnormalities, and induces anxiety-like behavioral impairments in mice. However, evidence for the neurobehavioral effects of BPAP is still lacking. Here, we examined the toxic effects of BPAP on neurodevelopment using a Drosophila model. We assessed the role of BPAP exposure in autism-like behavior and explored the underlying mechanisms. Our findings indicated that BPAP exposure reduced pupation and eclosion rates and delayed growth in Drosophila. Furthermore, BPAP exposure caused autism-like behaviors, characterized by increased grooming times and aberrant social interactions, along with abnormalities in locomotor activity, as well as learning and memory ability. Mechanistically, we found that BPAP decreases the number of neuroblasts (NBs) and mature intermediate neural progenitors (INPs) in the 3rd larval brain, impairing axon guidance in the mushroom body of the adult Drosophila brain. Additionally, our transcriptome analysis revealed that BPAP exposure alters the expression of neurodevelopment-related genes (Nplp3, sand, lush, and orco) and affects the estrogen signaling pathway (Hsp70Ab, Hsp70Bc, Hsp70Ba, and Hsp70Bb). These changes potentially explain the BPAP-induced autism-like behavior in Drosophila.

ABSTRACTChina, with the third largest share of global tuberculosis cases, faces a substantial challenge in its healthcare system as a result of the high burden of multidrug-resistant and rifampicin-resistant tuberculosis (MDR/RR-TB). This study employs a genomic epidemiological approach to assess recent tuberculosis transmissions between individuals, identifying potential risk factors and discerning the role of transmitted resistant isolates in the emergence of drug-resistant tuberculosis in China. We conducted a population-based retrospective study on 5052 Mycobacterium tuberculosis (MTB) isolates from 70 surveillance sites using whole genome sequencing (WGS). Minimum spanning tree analysis identified resistance mutations, while epidemiological data analysis pinpointed transmission risk factors. Of the 5052 isolates, 23% (1160) formed 452 genomic clusters, with 85.6% (387) of the transmissions occurring within the same counties. Individuals with younger age, larger family size, new cases, smear positive, and MDR/RR were at higher odds for recent transmission, while higher education (university and above) and occupation as a non-physical workers emerged as protective factors. At least 61.4% (251/409) of MDR/RR-TB were likely a result of recent transmission of MDR/RR isolates, with previous treatment (crude OR = 2.77), smear-positive (cOR = 2.07) and larger family population (cOR = 1.13) established as risk factors. Our findings highlight that local transmission remains the predominant form of TB transmission in China. Correspondingly, drug-resistant tuberculosis is primarily driven by the transmission of resistant tuberculosis isolates. Targeted interventions for high-risk populations to interrupt transmission within the country will likely provide an opportunity to reduce the prevalence of both tuberculosis and drug-resistant tuberculosis.

IntroductionEarly and accurate diagnosis of tuberculosis (TB) is crucial for initiating timely treatment and preventing new infections. In this study, we introduced the iFIND TBR assay, an automated all-in-one tuberculosis detection approach that simultaneously detect Mycobacterium tuberculosis (MTB) and rifampicin (RIF) resistance.MethodsThe limits of detection (LOD), sensitivity, specificity, and RIF-R rpoB mutation detection of the iFIND TBR were tested on Mycobacterium tuberculosis DNA or sputum samples spiked with known numbers of M.tuberculosis H37Rv. Frozen clinical samples from patients suspected of having TB were also tested.ResultsThe LOD of the iFIND TBR for MTB detection were 13.34 CFU/ml (95% CI, 11.71-16.47), and for RIF resistance was 109.79CFU/mL (95% CI, 95-138.19). The iFIND TBR assay accurately distinguish MTB strains from non-tuberculous mycobacteria (NTM) without any cross reactivity. Testing on 157 clinical sputum samples, compared with the bacteriologically TB standard, the overall sensitivity and specificity of the iFIND TBR was 100% (95%CI, 94.64, 100) and 85.29% (95% CI, 74.61, 92.72), respectively. When assessing RIF susceptibility, the iFIND TBR achieved a sensitivity of 98.15% (95% CI, 90.11–99.95) and a specificity of 85.71% (95% CI, 67.33–95.97), compared with phenotypic drug susceptibility testing. Discordant RIF susceptibility results were more frequently observed in samples exhibiting heteroresistance.DiscussionThese findings demonstrate that iFIND TBR assay performs well in detecting TB and RIF resistance, and shows promise as a point-of-care tool in resource-limited areas.

Background: Patients with tuberculosis resistant to isoniazid but susceptible to rifampicin (Hr-Rs TB) remain a neglected demographic, despite a high disease burden and poor outcomes of these patients. The aim of this study was to investigate the characteristics of isoniazid-resistance-related mutations in Mycobacterium tuberculosis and resistance rates to drugs included in WHO-recommended regimens for Hr-Rs patients. Methods: Mycobacterium tuberculosis isolates (n = 4922) obtained from national tuberculosis drug-resistance surveillance were subjected to whole-genome sequencing to identify Hr-Rs strains. The minimal inhibitory concentrations (MICs) were established for the Hr-Rs strains to determine the isoniazid resistance levels. We also identified drug-resistance-associated mutations for five drugs (fluoroquinolones, ethambutol, pyrazinamide, streptomycin, and amikacin) in the Hr-Rs strains. Results: Of the 4922 strains, 384 (7.8 %) were Hr-Rs. The subculture of seven strains failed, so 377 (98.2 %) strains underwent phenotypic MIC testing. Among the 384 genotypic Hr-Rs strains, 242 (63.0 %) contained the katG Ser315Thr substitution; 115 (29.9 %) contained the -15C>T in the promoter region of the fabG1 gene; and 16 (4.2 %) contained Ser315Asn in the katG gene. Of the 239 strains with the Ser315Thr substitution, 229 (95.8 %) had MIC ≥ 2 µg/mL, and of the 114 strains with the -15C>T mutation, 103 (90.4 %) had 0.25 µg/mL ≤ MIC ≤ 1 µg/mL. The genotypic resistance rates were 0.8 % (3/384) for pyrazinamide, 2.3 % (9/384) for ethambutol and fluoroquinolones; 39.6 % (152/384) of the strains were resistant to streptomycin, but only 0.5 % (2/384) of the strains were resistant to amikacin. Conclusion: Ser315Thr in katG was the predominant mutation conferring the Hr-Rs phenotype, followed by the fabG1 -15C>T mutation. The combination of rifampicin, pyrazinamide, ethambutol, and levofloxacin should be effective in the treatment of patients with Hr-Rs tuberculosis because the resistance rates for these drugs in China are low.

Chemical exposure and local hypoxia caused by mask-wearing may result in skin physiology changes. The effects of methylparaben (MeP), a commonly used preservative in personal care products, and hypoxia on skin health were investigated by HaCaT cell and ICR mouse experiments. MeP exposure resulted in lipid peroxidation and interfered with cellular glutathione metabolism, while hypoxia treatment disturbed phenylalanine, tyrosine, and tryptophan biosynthesis pathways and energy metabolism to respond to oxidative stress. A hypoxic environment increased the perturbation of MeP on the purine metabolism in HaCaT cells, resulting in increased expression of proinflammatory cytokines. The synergistic effects were further validated in a mouse model with MeP dermal exposure and “mask-wearing” treatment. CAT, PPARG, and MMP2 were identified as possible key gene targets associated with skin health risks posed by MeP and hypoxia. Network toxicity analysis suggested a synergistic effect, indicating the risk of skin inflammation and skin barrier aging.

ABSTRACT: Objectives: The characteristic and performance of Broth microdilution (BMD) plates for drug susceptibility of Mycobacterium tuberculosis have not been systematically evaluated in China. This study was designed to review the key information and assess the performance of BMD plates by analysis of proficiency testing results. Methods: We retrospectively analysed the proficiency testing results of phenotypic drug susceptibility testing (PT-DST) of 45 laboratories using BMD plates in China in 2021. Critical information, such as drug layout, concentration range of each drug, plate storage conditions and duration, operating procedures, and interpretation criteria for binary results were compared. The performance was also analysed. Results: Eight types of BMD plates produced by four manufactures were reported. The drug layout, number of drugs on plates, and concentration range varied a lot between different plates. The total sensitivity and specificity of BMD plates for drug susceptibility of Mycobacterium tuberculosis to ten drugs (isoniazid (INH), rifampin (RIF), kanamycin (KAM), amikacin (AM), levofloxacin (LFX), moxifloxacin (MFX), bedaquiline (BDQ), linezolid (LZD), clofazimine (CFZ), and delamanid (DLM)) were 93.9% (95% CI 92.–94.9) and 99.1% (95% CI 98.8–99.3), respectively. The lowest sensitivity was 84.8% (95% CI 80.3–88.4) for LFX and 86.4% (95% CI 82.5–89.6) for MFX, or 87.5% (95% CI 84.2–90.2) for Y1 plate and 87.9% (95% CI 83.5–91.1) for T plate. The lowest specificity was 94.4% (95% CI 91.4–96.4) for DLM, or 97.9% (95% CI 96.8–98.7) for B3 plate. Conclusion: Commercial BMD plates in China showed varied drug layouts and operational procedures, indicating the urgency of standardization. The lower performance for some drugs showed the low quality of the plates utilized or lack of proficiency of lab staffs in operating and interpreting results.

Abstract Ageing exhibits common and distinct features in various tissues, making it critical to decipher the tissue-specific ageing mechanisms. MiRNAs are essential regulators in ageing and are recently highlighted as a class of intercellular messengers. However, little is known about the tissue-specific transcriptomic changes of miRNAs during ageing. C. elegans is a well-established model organism in ageing research. Here, we profile the age-dependent miRNAomic changes in five isolated worm tissues. Besides the diverse ageing-regulated miRNA expression across tissues, we discover numerous miRNAs in the tissues without their transcription. We further profile miRNAs in the extracellular vesicles and find that worm miRNAs undergo inter-tissue trafficking via these vesicles in an age-dependent manner. Using these datasets, we uncover the interaction between body wall muscle-derived mir-1 and DAF-16/FOXO in the intestine, suggesting mir-1 as a messenger in inter-tissue signalling. Taken together, we systematically investigate worm miRNAs in the somatic tissues and extracellular vesicles during ageing, providing a valuable resource to study tissue-autonomous and nonautonomous functions of miRNAs in ageing.

Improving the three-dimensional reconstruction of underwater scenes is a challenging and hot topic in the field of underwater robot vision system research. High dynamic interference underwater has always been one of the key issues affecting the 3D reconstruction of underwater scenes. However, due to the complex underwater environment and insufficient light, existing target detection algorithms cannot meet the requirements. This paper uses the YOLOv8 network as the basis of the algorithm and proposes an underwater dynamic target detection algorithm based on improved YOLOv8. This algorithm first improves the feature extraction layer of the YOLOv8 network, improves the convolutional network structure of Bottleneck, reduces the amount of calculation and improves detection accuracy. Secondly, it adds an improved SE attention mechanism to make the network have a better feature extraction effect; in addition, the confidence box loss function of the network is improved, and the CIoU loss function is replaced by the MPDIoU loss function, which effectively improves the model convergence speed. Experimental results show that the mAP value of the improved YOLOv8 underwater dynamic target detection algorithm proposed in this article can reach 95.1%, and it can detect underwater dynamic targets more accurately, especially small dynamic targets in complex underwater scenes.

The chloride ion permeability resistance of recycled aggregate concrete (RAC) is influenced by multiple factors, and the prediction model for this resistance based on machine learning is still limited. In the paper, six impact factors (IFs), including the carbonation of recycled coarse aggregates (YN), the replacement ratio of recycled coarse aggregates (r), the bending load level (L), the carbonation time (t) and temperature (T) of RAC, and the replacement ratio of carbonated recycled fine aggregates (f), were considered to conduct a chloride penetration test on RAC. Based on the experimental data, four algorithms, including artificial neural network (ANN), support vector machine (SVM), random forest (RF) and extreme gradient boosting (XGBoost), were adopted to establish the machine learning prediction models and study the relationships between the electric flux of RAC and the IFs. The results showed that the predicted values of all four models were in good agreement with the experimental values, and the XGBoost model had the best prediction performance on the testing set. Based on the XGBoost model, the LIME method was adopted to solve the interpretability problem in the prediction process. The importance ranking of IFs on the electric flux was r > t > f > T > L > YN. A graphical user interface (GUI) was developed based on Python 3.8 software to facilitate the use of machine learning models for the chloride ion permeability resistance of RAC. The research results can provide an accurate prediction of the electric flux of RAC.

Objective: To detect levofloxacin (LFX) and moxifloxacin (MFX) resistance among rifampicin-resistant tuberculosis (RR-TB) isolates, and predict the resistance level based on specific mutations in gyrA and gyrB genes. Methods: A total of 686 RR-TB isolates were collected from Chinese Drug Resistance Surveillance Program from 2013 to 2020. The minimum inhibitory concentrations (MICs) of 12 anti-TB drugs were acquired using the broth microdilution method, followed by whole genome sequencing (WGS) analysis. Results: Among the 686 RR isolates, the most prevalent resistance was to isoniazid (80.5 %) and ethambutol (28.4 %), followed by LFX (26.1 %) and MFX (21.9 %). The resistance rate of LFX (26.1%–99.4 %) was higher than that of MFX (21.9%–83.3 %) across various drug resistance patterns. Of the 180 fluoroquinolones (FQs) resistant isolates, 168 (93.3 %) had mutations in quinolone-resistant determining regions (QRDRs) with 21 mutation types, and Asp94Gly (32.7 %, 55/168) was the predominant mutation. Isolates with mutations in Asp94Asn and Asp94Gly were associated with high levels of resistance to LFX and MFX. Using broth microdilution method as gold standard, the sensitivities of WGS for LFX and MFX were 93.3 % and 98.0 %, and the specificities were 98.6 % and 95.0 %, respectively. Conclusion: The resistance rate of LFX was higher than that of MFX among various drug resistance patterns in RR-TB isolates. The gyrA Asp94Gly was the predominant mutation type underlying FQs resistance. However, no significant difference was observed between mutation patterns in gyrA gene and resistance level of FQs.

Exposure to bisphenol S (BPS) is known to adversely affect neuronal development. As pivotal components of neuronal polarization, axons and dendrites are indispensable structures within neurons, crucial for the maintenance of nervous system function. Here, we investigated the impact of BPS exposure on axonal and dendritic development both in vivo and in vitro. Our results revealed that exposure to BPS during pregnancy and lactation led to a reduction in the complexity, density, and length of axons and dendrites in the prefrontal cortex (PFC) of offspring. Employing RNA sequencing technology to elucidate the underlying mechanisms of axonal and dendritic damage induced by BPS, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis highlighted a significant alteration in the oxidative phosphorylation (OXPHOS) pathway, essential for mitochondrial function. Subsequent experiments demonstrate BPS-induced impairment in mitochondrial function, including damaged morphology, decreased adenosine triphosphate (ATP) and superoxide dismutase (SOD) levels, and increased reactive oxygen species and malondialdehyde (MDA). These alterations coincided with the downregulated expression of OXPHOS pathway-related genes (ATP6V1B1, ATP5K, NDUFC1, NDUFC2, NDUFA3, COX6B1) and Myosin 19 (Myo19). Notably, Myo19 overexpression restored the BPS-induced mitochondrial dysfunction by alleviating the inhibition of OXPHOS pathway. Consequently, this amelioration was associated with a reduction in BPS-induced axonal and dendritic injury observed in cultured neurons of the PFC.

Abstract Background The dissemination of antibiotic resistance genes (ARGs) poses a substantial threat to environmental safety and human health. Herein, we present a longitudinal paired study across the swine lifetime from birth to market, coupled with metagenomic sequencing to explore the dynamics of ARGs and their health risk in the swine fecal microbiome. Results We systematically characterized the composition and distribution of ARGs among the different growth stages. In total, 829 ARG subtypes belonging to 21 different ARG types were detected, in which tetracycline, aminoglycoside, and MLS were the most abundant types. Indeed, 134 core ARG subtypes were shared in all stages and displayed a growth stage-associated pattern. Furthermore, the correlation between ARGs, gut microbiota and mobile genetic elements (MGEs) revealed Escherichia coli represented the main carrier of ARGs. We also found that in most cases, the dominant ARGs could be transmitted to progeny piglets, suggesting the potential ARGs generation transmission. Finally, the evaluation of the antibiotic resistance threats provides us some early warning of those high health risk ARGs. Conclusions Collectively, this relatively more comprehensive study provides a primary overview of ARG profile in swine microbiome across the lifetime and highlights the health risk and the intergenerational spread of ARGs in pig farm. Graphical Abstract

Abstract The piRNA pathway is essential for female fertility in golden hamsters and likely humans, but not in mice. However, the role of individual PIWIs in mammalian reproduction remains poorly understood outside of mice. Here, we describe the expression profiles, subcellular localization, and knockout-associated reproductive defects for all four PIWIs in golden hamsters. In female golden hamsters, PIWIL1 and PIWIL3 are highly expressed throughout oogenesis and early embryogenesis, while knockout of PIWIL1 leads to sterility, and PIWIL3 deficiency results in subfertility with lagging zygotic development. PIWIL1 can partially compensate for TE silencing in PIWIL3 knockout females, but not vice versa. PIWIL1 and PIWIL4 are the predominant PIWIs expressed in adult and postnatal testes, respectively, while PIWIL2 is present at both stages. Loss of any PIWI expressed in testes leads to sterility and severe but distinct spermatogenesis disorders. These findings illustrate the non-redundant regulatory functions of PIWI-piRNAs in gametogenesis and early embryogenesis in golden hamsters, facilitating study of their role in human fertility.

Heavy metal toxicity is a significant global health concern, with particular attention given to lead (Pb) exposure due to its adverse effects on cognitive development, especially in children exposed to low concentrations. While Pb neurotoxicity has been extensively studied, the analysis and molecular mechanisms underlying the transgenerational effects of Pb exposure-induced neurotoxicity remain poorly understood. In this study, we utilized Drosophila, a powerful developmental animal model, to investigate this phenomenon. Our findings demonstrated that Pb exposure during the developmental stage had a profound effect on the neurodevelopment of F0 fruit flies. Specifically, we observed a loss of correlation between the terminal motor area and muscle fiber area, along with an increased frequency of the β-lobe midline crossing phenotype in mushroom bodies. Western blot analysis indicated altered expression levels of synaptic vesicle proteins, with a decrease in Synapsin (SYN) and an increase in Bruchpilot (BRP) expression, suggesting changes in synaptic vesicle release sites. These findings were corroborated by electrophysiological data, showing an increase in the amplitude of evoked excitatory junctional potential (EJP) and an increase in the frequency of spontaneous excitatory junctional potential (mEJP) following Pb exposure. Importantly, our results further confirmed that the developmental neurotoxicity resulting from grandparental Pb exposure exhibited a transgenerational effect. The F3 offspring displayed neurodevelopmental defects, synaptic function abnormalities, and repetitive behavior despite lacking direct Pb exposure. Our MeDIP-seq analysis further revealed significant alterations in DNA methylation levels in several neurodevelopmental associated genes (eagle, happyhour, neuroglian, bazooka, and spinophilin) in the F3 offspring exposed to Pb. These findings suggest that DNA methylation modifications may underlie the inheritance of acquired phenotypic traits resulting from environmental Pb exposure.

The composition of Pseudostellaria heterophylla (Tai-Zi-Shen, TZS) is greatly influenced by the growing area of the plants, making it significant to distinguish the origins of TZS. However, traditional methods for TZS origin identification are time-consuming, laborious, and destructive. To address this, two or three TZS accessions were selected from four different regions of China, with each of these resources including distinct quality grades of TZS samples. The visible near-infrared (Vis/NIR) and short-wave infrared (SWIR) hyperspectral information from these samples were then collected. Fast and high-precision methods to identify the origins of TZS were developed by combining various preprocessing algorithms, feature band extraction algorithms (CARS and SPA), traditional two-stage machine learning classifiers (PLS-DA, SVM, and RF), and an end-to-end deep learning classifier (DCNN). Specifically, SWIR hyperspectral information outperformed Vis/NIR hyperspectral information in detecting geographic origins of TZS. The SPA algorithm proved particularly effective in extracting SWIR information that was highly correlated with the origins of TZS. The corresponding FD-SPA-SVM model reduced the number of bands by 77.2% and improved the model accuracy from 97.6% to 98.1% compared to the full-band FD-SVM model. Overall, two sets of fast and high-precision models, SWIR-FD-SPA-SVM and SWIR-FD-DCNN, were established, achieving accuracies of 98.1% and 98.7% respectively. This work provides a potentially efficient alternative for rapidly detecting the origins of TZS during actual production.

Abstract As essential components of ionic polymer electrolytes (IPEs), ionic liquids (ILs) with high ionic conductivity and wide electrochemical window are promising candidates to enable safe and high-energy-density lithium metal batteries (LMBs). Here, we describe a machine learning workflow embedded with quantum calculation and graph convolutional neural network to discover potential ILs for IPEs. By selecting subsets of the recommended ILs, combining with a rigid-rod polyelectrolyte and a lithium salt, we develop a series of thin (~50 μm) and robust (>200 MPa) IPE membranes. The Li|IPEs|Li cells exhibit ultrahigh critical-current-density (6 mA cm−2) at 80 °C. The Li|IPEs|LiFePO4 (10.3 mg cm−2) cells deliver outstanding capacity retention in 350 cycles (>96% at 0.5C; >80% at 2C), fast charge/discharge capability (146 mAh g−1 at 3C) and excellent efficiency (>99.92%). This performance is rarely reported by other single-layer polymer electrolytes without any flammable organics for LMBs.

Mycobacterial membrane proteins play a pivotal role in the bacterial invasion of host cells; however, the precise mechanisms underlying certain membrane proteins remain elusive. Mycolicibacterium smegmatis (Ms) msmeg5257 is a hemolysin III family protein that is homologous to Mycobacterium tuberculosis (Mtb) Rv1085c, but it has an unclear function in growth. To address this issue, we utilized the CRISPR/Cas9 gene editor to construct Δmsmeg5257 strains and combined RNA transcription and LC-MS/MS protein profiling to determine the functional role of msmeg5257 in Ms growth. The correlative analysis showed that the deletion of msmeg5257 inhibits ABC transporters in the cytomembrane and inhibits the biosynthesis of amino acids in the cell wall. Corresponding to these results, we confirmed that MSMEG5257 localizes in the cytomembrane via subcellular fractionation and also plays a role in facilitating the transport of iron ions in environments with low iron levels. Our data provide insights that msmeg5257 plays a role in maintaining Ms metabolic homeostasis, and the deletion of msmeg5257 significantly impacts the growth rate of Ms. Furthermore, msmeg5257, a promising drug target, offers a direction for the development of novel therapeutic strategies against mycobacterial diseases.

ABSTRACTDysregulation of the gut microbiota by environmental factors is associated with a variety of autoimmune and immune-mediated diseases. In addition, naturally-occurring extracellular antibiotic resistance genes (eARGs) might directly enter the gut via the food chain. However, following gut microbiota exposure to eARGs, the ecological processes shaping the microbiota community assembly, as well as the interplay between the microbiota composition, metabolic function, and the immune responses, are not well understood. Increasing focus on the One Health approach has led to an urgent need to investigate the direct health damage caused by eARGs. Herein, we reveal the significant influence of eARGs on microbiota communities, strongly driven by stochastic processes. How eARGs-stimulate variations in the composition and metabolomic function of the gut microbiota led to cytokine responses in mice of different age and sex were investigated. The results revealed that cytokines were significantly associated with immunomodulatory microbes, metabolites, and ARGs biomarkers. Cytokine production was associated with specific metabolic pathways (arachidonic acid and tryptophan metabolic pathways), as confirmed by ex vivo cytokine responses and recovery experiments in vivo. Furthermore, the gut microbial profile could be applied to accurately predict the degree of intestinal inflammation ascribed to the eARGs (area under the curve = 0.9616). The present study provided a comprehensive understanding of the influence of an eARGs on immune responses and intestinal barrier damage, shedding light on the interplay between eARGs, microbial, metabolites, and the gut antibiotic resistome in modulating the human immune system.

Abstract North China, characterized by its strong land–atmosphere coupling, also has a high concentration of atmospheric aerosols from anthropogenic emissions. However, the impact of aerosols on land–atmosphere coupling in this region remains partially unclear. Here, we use Weather Research and Forecasting model coupled with Chemistry (WRF‐Chem) experiments to show that the aerosol radiative effect weakens land–atmosphere coupling in North China. This weakening occurs across all five indexes used to measure different aspects of land–atmosphere coupling. Notably, the weakening is more pronounced for indexes that describe surface coupling compared to the index that characterizes the coupling between the planetary boundary layer (PBL) and clouds. The mechanisms underlying the aerosol influence can be primarily attributed to the reduction of land surface fluxes and their sensitivities to soil moisture, while the weakened entrainment of moisture at the upper boundary of the PBL may also contribute to the effects.

Abstract Background Direct-acting antivirals (DAAs) for hepatitis C treatment in China became available since 2017. This study expects to generate evidence to inform decision-making in a nationwide scale-up of DAA treatment in China. Methods We described the number of standard DAA treatment at both national and provincial levels in China from 2017 to 2021 based on the China Hospital Pharmacy Audit (CHPA) data. We performed interrupted time series analysis to estimate the level and trend changes of the monthly number of standard DAA treatment at national level. We also adopted the latent class trajectory model (LCTM) to form clusters of the provincial-level administrative divisions (PLADs) with similar levels and trends of number of treatment, and to explore the potential enablers of the scale-up of DAA treatment at provincial level. Results The number of 3-month standard DAA treatment at national level increased from 104 in the last two quarters of 2017 to 49,592 in the year of 2021. The estimated DAA treatment rates in China were 1.9% and 0.7% in 2020 and 2021, which is far below the global target of 80%. The national price negotiation at the end of 2019 resulted in DAA inclusion by the national health insurance in January 2020. In that month, the number of treatment increased 3668 person-times (P

Abstract Background The main protease (Mpro) is a crucial target for severe acute respiratory syndrome coronavirus (SARS-CoV-2). Chitooligosaccharide (CS) has broad-spectrum antiviral activity and can effectively inhibit the activity of SARS-CoV. Here, based on the high homology between SARS-CoV-2 and SARS-CoV, this study explores the effect and mechanism of CS with various molecular weights on the activity of SARS-CoV-2 Mpro. Methods We used fluorescence resonance energy transfer (FRET), UV–Vis, synchronous fluorescence spectroscopy, circular dichroism (CD) spectroscopy and computational simulation to investigate the molecular interaction and the interaction mechanism between CS and SARS-CoV-2 Mpro. Results Four kinds of CS with different molecular weights significantly inhibited the activity of Mpro by combining the hydrogen bonding and the salt bridge interaction to form a stable complex. Glu166 appeared to be the key amino acid. Among them, chitosan showed the highest inhibition effect on Mpro enzyme activity and the greatest impact on the spatial structure of protein. Chitosan would be one of the most potential anti-viral compounds. Conclusion This study provides the theoretical basis to develop targeted Mpro inhibitors for the screening and application of anti-novel coronavirus drugs.

Key Message The incorporation of antibiotics to field-collected Chilo suppressalis larvae significantly reduce bacterial quantities and affect larval performance on rice plants. Field-collected Chilo suppressalis larvae deposit abundant bacteria onto feeding sites through oral secretion, which modulate defense responses in rice plants. Bacteria isolated from larval oral secretion (such as Enterobacter and Acinetobacter) contribute to preventing rice plants to fully activate jasmonic acid-mediated antiherbivore defenses. Our results indicate insect-associated bacteria play an important role for C. suppressalis to adapt to rice plants, which could also be treated as targets for developing novel pest management strategies.

Background: Cancer-related fatigue (CRF) is a common and burdensome symptom in cancer patients that is influenced by multiple factors. Identifying factors associated with CRF may help in developing tailored interventions for fatigue management. This study aimed to examine the correlates of CRF among colorectal cancer patients undergoing postoperative adjuvant therapy based on the theory of unpleasant symptoms. Methods: A cross-sectional study was implemented, and finally, a sample of 363 participants from one tertiary general hospital and one tertiary cancer hospital was purposively recruited. Data were collected using the general information questionnaire, cancer fatigue scale, the distress disclosure index, Herth hope index, and perceived social support scale. Univariate analysis and multiple linear regression analysis were performed to determine the correlates of CRF. Results: The mean score of CRF among colorectal cancer patients was 21.61 (SD = 6.16, 95% CI 20.98–22.25), and the fatigue degree rating was “moderate”. The multiple linear regression model revealed that 49.1% of the variance in CRF was explained by hope, sleep disorder, internal family support, self-disclosure, pain, and time since operation. Conclusions: Our study identified several significant, modifiable factors (self-disclosure, hope, internal family support, pain, and sleep disorder) associated with CRF. Understanding these correlates and developing targeted psychosocial interventions may be associated with the improvement of CRF in patients with colorectal cancer.

Abstract Background An over-expression of the epidermal growth factor receptor (EGFR) has been observed in colorectal cancer and is associated with aggressive disease and poor prognosis. SCT200 is a newly developed recombinant, fully humanized, anti-EGFR monoclonal antibody. This study aimed to evaluate its safety, tolerability, pharmacokinetics (PK), and efficacy in patients with wild-type KRAS/NRAS/BRAF metastatic colorectal cancer (mCRC). Methods This phase I study comprising dose-escalation phase and dose-expansion phase. SCT200 was administrated intravenously to groups of three to six patients. An every 3-week dosing cycle (0.5–15.0 mg/kg) and multiple dosing schedule were evaluated. Blood samples were collected at preset intervals for PK assessment, radiological imaging was used for efficacy assessment, and continuous safety monitoring was performed in each group during the study. Results From December 16, 2014 to December 31, 2018, fifty-six patients with wild-type K RAS/NRAS/BRAF mCRC receiving ≥ 1 dose of SCT200 were evaluated. Among them, 44.6% (25/56) of the patients failed at least two prior lines of chemotherapy. No dose-limiting toxicities occurred in any group. All of the patients experienced treatment-emergent adverse events (TEAEs). 96.4% (54/56) of patients experienced treatment-related adverse events (TRAEs), and 26.8% (15/56) of patients with Grade ≥ 3 TRAEs. No serious TRAEs were observed. The most common TRAEs were dermotoxicity and hypomagnesemia. PK analysis showed non-linear PK in the range of 0.5 - 8.0 mg/kg of single dose SCT200, the clearance decreased, and the elimination half-life (T1/2) prolonged following dose increase. In the multiple-dose period, the clearance decreased, peak concentration increased, and T1/2 prolonged during prolonged drug administration, and a steady state was reached after five consecutive dose of 6.0 mg/kg quaque week (QW). The objective response rate (ORR) was 30.4% (17/56, 95% confidence interval [CI], 18.8%–44.1%). The ORR in the dose-expansion group (6.0 mg/kg QW) was 48.0% (12/25, 95% CI, 27.8%–68.7%), the median progression-free survival was 5.2 months (95%CI, 3.6–5.5), and the median overall survival was 20.2 months (95%CI, 12.1-not reached). Conclusions SCT200 showed favorable safety, PK profile, and preliminary efficacy for patients with wild-type KRAS/NRAS/BRAF mCRC. Trial registration This study was registered with ClinicalTrials.gov ( NCT02211443 ).

As a result of the ban on bisphenol A (BPA), a hormone disruptor with developmental neurotoxicity, several BPA derivatives (BPs) have been widely used in industrial production. However, there are no effective methods for assessing the neurodevelopmental toxic effects of BPs. To address this, a Drosophila exposure model was established, and W1118 was reared in food containing these BPs. Results showed that each BPs displayed different semi-lethal doses ranging from 1.76 to 19.43 mM. Exposure to BPs delayed larval development and affected axonal growth, resulting in the abnormal crossing of the midline of axons in the β lobules of mushroom bodies, but the damage caused by BPE and BPF was relatively minor. BPC, BPAF, and BPAP have the most significant effects on locomotor behavior, whereas BPC exhibited the most affected social interactions. Furthermore, exposure to high-dose BPA, BPC, BPS, BPAF, and BPAP also significantly increased the expression of Drosophila estrogen-related receptors. These demonstrated that different kinds of BPs had different levels of neurodevelopmental toxicity, and the severity was BPZ > BPC and BPAF > BPB > BPS > BPAP ≈ BPAl ≈ BPF > BPE. Therefore, BPZ, BPC, BPS, BPAF, and BPAP should be evaluated as potential alternatives to BPA.

Aluminum toxicity poses a significant constraint on crop production in acidic soils. While phytohormones are recognized for their pivotal role in mediating plant responses to aluminum stress, the specific involvement of gibberellin (GA) in regulating aluminum tolerance remains unexplored. In this study, we demonstrate that external GA exacerbates the inhibitory impact of aluminum stress on root growth of rice seedlings, concurrently promoting reactive oxygen species (ROS) accumulation. Furthermore, rice plants overexpressing the GA synthesis gene SD1 exhibit enhanced sensitivity to aluminum stress. In contrast, the slr1 gain-of-function mutant, characterized by impeded GA signaling, displays enhanced tolerance to aluminum stress, suggesting the negative regulatory role of GA in rice resistance to aluminum-induced toxicity. We also reveal that GA application suppresses the expression of crucial aluminum tolerance genes in rice, including Al resistance transcription factor 1 (ART1), Nramp aluminum transporter 1 (OsNramp4), and Sensitive to Aluminum 1 (SAL1). Conversely, the slr1 mutant exhibits up-regulated expression of these genes compared to the wild type. In summary, our results shed light on the inhibitory effect of GA in rice resistance to aluminum stress, contributing to a theoretical foundation for unraveling the intricate mechanisms of plant hormones in regulating aluminum tolerance.

In coastal environments, squat reinforced concrete (RC) shear walls are susceptible to local accumulation of moisture and chloride salts, causing local corrosion in the shear walls, which in turn affects their seismic performance. Four squat RC shear wall specimens were designed considering the corrosion locations and the heights of the corroded area. The seismic performance of partially corroded squat RC shear wall specimens was analyzed through a quasi-static test. The results show that as the height of the corroded area increases from 15% to 25% of the total height, the area of the hysteresis loop of the shear walls obviously decreases. As the height of the corroded area increases from 0 to 15% and 25% of the total height, the peak and ultimate displacements of shear walls are, respectively, reduced by 6.7% and 19.2% in the positive loading direction, and are, respectively, reduced by 22.3% and 18.3% in the negative loading direction. Compared with the unilateral corroded shear wall, the area of the hysteresis loop and the stiffness of the bilateral corroded shear wall remain approximately unchanged, and the peak and ultimate displacements, the shear strain, and the ratio of shear deformation to horizontal displacement are reduced. Compared with the uncorroded shear wall, the hysteresis loop of the unilateral corroded shear wall is plump, the displacement ductility ratio and the plastic rotation angle are both increased, and the stiffness degradation is relatively slow.

The drugs of programmed cell death 1 and its ligand 1 immune checkpoint inhibitors have ushered in a new era of anti-tumor immunotherapy, which has shown outstanding efficacy in some tumors, such as Hodgkin lymphoma, but there is still low response rate in some kinds of tumors. In recent years, bispecific antibodies prepared by cell fusion, recombinant DNA, protein engineering and other technologies can specifically bind two antigens or epitopes at the same time or successively, play a synergistic role in tumor treatment, can effectively inhibit tumor immune escape, and improve the effect of anti-tumor treatment has become a hot spot in tumor research. This paper will summarize the clinical research and development of bispecific antibodies, to provide reference for the industry.

In recent years, China's anti-tumor drugs has shown a continuous growth trend, and the activity of anti-tumor research and development in China accounts for a higher proportion in the world. However, further analysis of research and development hotspots show that the research and development of anti-tumor drugs is uneven among different tumor types. Due to the small number of the patients, it is difficult to conduct clinical trials, resulting in less drug development in the field of rare tumors. However, patients' treatment needs will also bring potential opportunities for pharmaceutical companies. The development of basic research and the discovery of new molecular tumor typing make "rare tumors" a dynamic concept. The scope of "rare tumors" may gradually expand with the precise development of treatment; or as the knowledge of tumors gradually develops from histocytology to the molecular level, It is possible that certain tumors with specific mutations can be combined into a group of non-rare “pan-tumors”. Rare tumors are characterized by both rare diseases and tumors. Its drug research and development should not only meet the requirements of tumor drug research and development, but also adapt to the characteristics of rare diseases. Therefore, in the drug research and development, we can refer to the research and development principle of rare disease drugs, combine with the characteristics of tumor diseases, make full use of non-rare tumor clinical trials, make full use of scientific tools and exquisite trial design, and realize the promotion of the research and development of rare tumor drugs. This paper will summarize the thoughts in the review of new drugs in the field of rare tumors, in order to provide guidance for the industry.

ObjectiveFibromyalgia is a chronic musculoskeletal disorder characterized by generalized pain, which is also known as “muscular rheumatism” in Chinese medicine. We undertook this systematic review to evaluate the effectiveness of non-pharmacological traditional Chinese medicine (TCM) combined with conventional therapy on pain, health status, depression, and the quality of life of fibromyalgia patients.MethodsStudies were retrieved from five electronic databases (PubMed, the Cumulative Index to Nursing and Allied Health, Cochrane Library, Embase, and Web of Science) with publication date up to August 2022. We included randomized controlled trials examining the effects of a combination of non-pharmacological TCM and conventional therapy on pain intensity, health status, depression, and quality of life.ResultsFour randomized controlled trials with 384 fibromyalgia patients met the inclusion criteria. Results of the meta-analysis showed that non-pharmacological TCM combined with conventional therapy exerted significant positive effects on alleviating pain at the post-intervention time point than conventional therapy only (visual analog scale WMD1 = −1.410, P < 0.01; pressure pain threshold WMD2 = 0.830, P < 0.001, respectively). Significant differences in pain assessment were also observed between the two groups after a long-term follow-up (12 months) (WMD1 = −1.040 and WMD2= 0.380, all P < 0.05). The combination therapy group also showed a greater reduction in fibromyalgia impact questionnaire than the control group after a long-term follow-up (WMD = −6.690, P < 0.05). Depression and pain-related quality of life showed no difference between groups (all P > 0.05).ConclusionNon-pharmacological TCM combined with conventional therapy may be more effective in alleviating pain and improving health status than conventional therapy only. However, it remains some concerns over the safety and clinic application.Systematic review registrationIdentifier: CRD42022352991.

Abstract Background The use of beneficial microorganisms as an alternative for pest control has gained increasing attention. The objective of this study was to screen beneficial rhizosphere bacteria with the ability to enhance tomato anti-herbivore resistance. Results Rhizosphere bacteria in tomato field from Fuqing, one of the four locations where rhizosphere bacteria were collected in Fujian, China, enhanced tomato resistance against the tobacco cutworm Spodoptera litura, an important polyphagous pest. Inoculation with the isolate T6–4 obtained from the rhizosphere of tomato field in Fuqing reduced leaf damage and weight gain of S. litura larvae fed on the leaves of inoculated tomato plants by 27% in relative to control. Analysis of 16S rRNA gene sequence identities indicated that the isolate T6–4 was closely related to Stenotrophomonas rhizophila supported with 99.37% sequence similarity. In the presence of S. litura infestation, inoculation with the bacterium led to increases by a 66.9% increase in protease inhibitor activity, 53% in peroxidase activity and 80% in polyphenol oxidase activity in the leaves of inoculated plants as compared to the un-inoculated control. Moreover, the expression levels of defense-related genes encoding allene oxide cyclase (AOC), allene oxide synthase (AOS), lipoxygenase D (LOXD) and proteinase inhibitor (PI-II) in tomato leaves were induced 2.2-, 1.7-, 1.4- and 2.7-fold, respectively by T6–4 inoculation. Conclusion These results showed that the tomato rhizosphere soils harbor beneficial bacteria that can systemically induce jasmonate-dependent anti-herbivore resistance in tomato plants.

In order to harness a greater share of wind energy resources, offshore wind energy projects are venturing into deep-sea locations. In this progression, the issue of grid integration control becomes increasingly challenging. Traditional Model Predictive Control (MPC) has been introduced in offshore wind energy grid integration control due to its merits, such as not requiring modulators, dispensing with decoupling, incorporating constraint handling, and facilitating online optimization. However, it heavily relies on a model and consequently experiences a substantial loss of control effectiveness in the face of system parameter variations. In light of this, this study presents an active-disturbance-rejection-based three-vector sequence model predictive control approach. This method effectively mitigates the influence caused by changes in system parameters, endowing the system with self-disturbance rejection capabilities and enhancing its fault recovery abilities. The method employs self-disturbance control to track voltage reference values and employs the concept of sequence control to eliminate weighting factors in the cost function. Furthermore, it employs three-vector control to achieve error-free operation. The simulation results confirmed that the proposed method effectively minimizes voltage and power transients. It demonstrated superior control effectiveness and shorter response times, enabling the system to rapidly restore to a stable operational state following disturbances.

The rhizosphere harbors abundant plant growth-promoting rhizobacteria (PGPR) that are vital for plant health. In this study, we screened growth-promoting bacteria from tomato rhizosphere soil, verified their functions, and constructed the optimal combination of growth-promoting bacteria for promoting tomato growth. Furthermore, the effects of these bacteria on various physiological and biochemical parameters of tomato plants were evaluated. A total of 36 strains of rhizobacteria were isolated from tomato rhizosphere soil and their abilities to produce indole-3-acetic acid (IAA), solubilize phosphate and iron carriers were assessed. The bacterial strains with the highest capacities for IAA production (R62, R317), phosphate solubilization (R41, R219), and siderophore production (R25, R325) were selected to form three bacterial combinations: R62 + R219 + R317 + R325 (T1), R62 + R325 (T5), and R317 + R325 (T8). Fifteen days after inoculation, all three combinations showed a stimulatory effect on seedling growth compared to the un-inoculated control. Inoculation with T1, T5 and T8 increased the seedling vigor index by 173.7%, 204.1%, and 168.7%, respectively. Compared to the un-inoculated control, the T1 combination increased the activities of polyphenol oxidase, peroxidase, and the net photosynthetic rate by 132.7%, 18.7%, 58.5%, and upregulated the relative expression levels of the photosynthetic assimilation-related genes RbcL, RbcS, FBPase and FDA by 22.2-, 6.6-, 1.95-, and 2.0-fold, respectively. Our findings provide a potential for constructing rhizobacterial combinations of different functional groups for improving crop growth.

With the gradual development of offshore wind farms toward large-scale and long-distance trends, economically efficient methods for correcting and transmitting offshore wind energy have garnered increasing attention. The rational and effective evaluation of offshore wind power collection and transmission methods has become an urgent issue. To address this, a comprehensive evaluation model for collection and transmission systems, considering factors such as network losses, lifecycle costs, and reliability, was established. This proposed model was applied to multiple sets of typical collection and transmission scenarios, utilizing an improved TOPSIS comprehensive evaluation method based on dynamic combination weighting to achieve the comprehensive optimization of collection and transmission schemes. Case studies have validated the feasibility of the comprehensive evaluation model. The results indicate that with an increase in offshore distance, the AC/DC collection and transmission system is superior to the all-AC collection and transmission system, and the all-DC collection system exhibits potential cost advantages.

Aging, corrosive environments, and inadequate maintenance may result in performance deterioration of civil infrastructures, and finite element model updating is a commonly employed structural health monitoring procedure in civil engineering to reflect the current situation and to ensure the safety and serviceability of structures. Using the finite element model updating process to obtain the relationship between the structural responses and updating parameters, this paper proposes a method of using the wavelet neural network (WNN) as the surrogate model combined with the wind-driven optimization (WDO) algorithm to update the structural finite element model. The method was applied to finite element model updating of a continuous beam structure of three equal spans to verify its feasibility, the results show that the WNN can reflect the nonlinear relationship between structural responses and the parameters and has an outstanding simulation performance; the WDO has an excellent ability for optimization and can effectively improve the efficiency of model updating. Finally, the method was applied to update a real bridge model, and the results show that the finite element model update based on WDO and WNN is applicable to the updating of a multi-parameter bridge model, which has practical significance in engineering and high efficiency in finite element model updating. The differences between the updated values and measured values are all within the range of 5%, while the maximum difference was reduced from −10.9% to −3.6%. The proposed finite element model updating method is applicable and practical for multi-parameter bridge model updating and has the advantages of high updating efficiency, reliability, and practical significance.

PurposeThe objective was to evaluate the influence of low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) [Lp(a)] on clinical outcomes in patients undergoing coronary artery bypass grafting (CABG).MethodsThis is a secondary analysis of a 5-year follow-up of the DACAB trial (NCT02201771), in which 500 patients who underwent primary isolated CABG were randomized to three-antiplatelet therapy for 1 year after surgery. Of them, 459 patients were recruited in this secondary analysis. Baseline LDL-C and Lp(a) levels were collected, and repeated measurement of LDL-C levels during the follow-up were recorded. Cut-off values for LDL-C were set at 1.8 and 2.6 mmol/L; thus, the patients were stratified into LDL-C

Proanthocyanin (PA) dimers isolated from Acacia mearnsii bark were enzymatically acylated with palmitic acid as the acyl donor by immobilized Candida antarctica lipase on acrylic resin (Novozym 435). The acylation reaction conditions were optimized by comparing the amount of enzyme, the temperature, the reaction solvents, initial water content, substrate molar ratios and reaction time. The highest acylation conversion of 96.53% was achieved under the follow conditions: PA dimers/palmitic acid at a molar ratio of 1꞉10 in tert-amyl alcohol; initial water content of 5% at 60 °C for 12 h with 30 g/L enzyme dosage. Introducing palmitic acid into PA dimers significantly improved both the lipophilicity and antioxidant properties. The 1-octanol/water partition coefficient of the PA dimers and their derivatives showed that the lipophilicity of the derivatives were 2.4 times higher than that of the PA dimers. The derivatives exhibited strong antioxidant scavenging capacities, approximately 1.6 times greater than the original dimers. This work is of great significance to expand the application of natural PA dimers in cosmetic and food industries and also lay a foundation for the high value-added utilization of A. mearnsii.

Arbuscular mycorrhizal fungi (AMF) are considered biofertilizers for sustainable agriculture due to their ability to facilitate plant uptake of important mineral elements, such as nitrogen (N). However, plant mycorrhiza-dependent N uptake and interplant transfer may be highly context-dependent, and whether it is affected by aboveground herbivory remains largely unknown. Here, we used 15N labeling and tracking to examine the effect of aboveground insect herbivory by Spodoptera frugiperda on mycorrhiza-dependent N uptake in maize (Zea mays L.). To minimize consumption differences and 15N loss due to insect chewing, insect herbivory was simulated by mechanical wounding and oral secretion of S. frugiperda larvae. Inoculation with Rhizophagus irregularis (Rir) significantly improved maize growth, and N/P uptake. The 15N labeling experiment showed that maize plants absorbed N from soils via the extraradical mycelium of mycorrhizal fungi and from neighboring plants transferred by common mycorrhizal networks (CMNs). Simulated aboveground leaf herbivory did not affect mycorrhiza-mediated N acquisition from soil. However, CMN-mediated N transfer from neighboring plants was blocked by leaf simulated herbivory. Our findings suggest that aboveground herbivory inhibits CMN-mediated N transfer between plants but does not affect N acquisition from soil solutions via extraradical mycorrhizal mycelium.

Polyamines (PAs) are ubiquitous low-molecular-weight aliphatic polycations in all living organisms, which are crucial for plant response to abiotic and biotic stresses. The role of PAs in plant disease resistance has been well documented. However, their involvement in plant–pest interactions remains unclear. Here, the role of PAs in rice against striped stem borer (SSB, Chilo suppressalis Walker), a destructive pest in rice production worldwide, was investigated. SSB larval infestation led to a substantial accumulation of free putrescine (Put) in rice seedlings, which was in parallel with an elevated expression of host PA biosynthesis genes Arginine Decarboxylase1 (ADC1) and ADC2. Moreover, SSB larval oral secretion application with wounding further raised the transcripts of ADC1 and ADC2 in rice compared with wounding treatment alone. The larval growth on both rice plants and artificial diet was promoted by the exogenous application of PA and inhibited by a PA biosynthesis inhibitor. On the other hand, the rice defense responses, including polyphenol oxidase (PPO) and peroxidase (POD) activities, as well as protease inhibitor level, were enhanced by a Put supplement and reduced by an ADC inhibitor. Our results indicate that SSB herbivory triggers polyamine accumulation in host rice plants, which is beneficial to SSB in rice–SSB interaction.

Kiwifruit (Actinidia spp.) is susceptible to waterlogging stress. Although abundant wild germplasm resources exist among Actinidia plants for improving the waterlogging tolerance of kiwifruit cultivars, the underlying mechanisms remain largely unknown. Here, a comparative study was undertaken using one wild germplasm, Maorenshen (A. valvata Dunn, MRS), and one cultivar, Miliang-1 (A. chinensis var. deliciosa (A.Chev.) A.Chev. cv. Miliang-1, ML). Under stress, the ML plantlets were seriously damaged with wilted chlorotic leaves and blackened rotten roots, whereas the symptoms of injury in the MRS plantlets were much fewer, along with higher photosynthetic rates, chlorophyll fluorescence characteristics and root activity under stress conditions. However, neither aerenchyma in the root nor adventitious roots appeared in both germplasms upon stress exposure. The activities of pyruvate decarboxylase (PDC) and alcohol dehydrogenase (ADH), as well as their transcript levels, were constitutively higher in MRS than those in ML under both normal and stress conditions. Waterlogging stress significantly enhanced the PDC and ADH enzyme activities in both germplasms, which were 60.8% and 22.4% higher in the MRS roots than those in the ML roots under waterlogging stress, respectively. Moreover, MRS displayed higher activities of antioxidant enzymes, including SOD, CAT, and APX, as well as DPPH-radical scavenging ability, and decreased H2O2 and MDA accumulation under both normal and stress conditions. Our findings suggest that the waterlogging tolerance of the wild A. valvata germplasm was associated with high PDC and ADH, as well as antioxidant ability.

The advantages of the proposed novel magnetic energy-harvesting suspension (MEHS) are high safety, compact structure and convenient maintenance, compared with the previous studies. However, the force generated by the energy harvester with harvesting energy can affect the motion of the mechanical system. Therefore, this paper aims to analyze the ride comfort and road handling of the MEHS, and investigates the dynamic performance of the MEHS. Firstly, the structure and the working principle of the MEHS are illustrated and introduced, and the dynamic mechanism of the quarter-vehicle with the MEHS is revealed and investigated. Secondly, the effects of the electromechanical coupling coefficient and external load resistance on the dynamic performance are investigated by numerical calculation. An experimental setup is established to verify the dynamic performance of the proposed MEHS. According to the experimental results, the dynamic performance of the suspension is contradictory with the increase of the external load resistance at the periodic frequency 7 Hz. And compared with the passive suspension, the dynamic performance of the MEHS is changed at various excitations, in which the sprung displacement and relative dynamic load of the tire of MEHS at the periodic frequency 3.3 Hz are reduced by 39.45% and 41.18%, respectively. Overall, the external load resistance of the proposed MEHS can be utilized to realize the variable damping of the suspension system and reduce the effect of vibration on the suspension system at the resonance frequency. And the dynamic performance has been verified in the laboratory, which lays the foundation for the dynamic analysis in a real vehicle.

The gut microbiota is a complex ecosystem that is essential for the metabolism, immunity and health of the host. The gut microbiota also plays a critical role in nutrient absorption and metabolism, and nutrients can influence the growth and composition of the gut microbiota. To gain a better understanding of the relationship between the gut microbial composition and nutrient metabolism, we used a pig model by collecting the contents of the different intestinal locations from six pigs to investigate microbial composition in different intestinal locations based on 16S rRNA gene sequencing and the concentrations of short-chain fatty acids (SCFAs), amino acids, fat, and crude ash in different intestinal locations using gas chromatography and chemical analysis. The results showed that the richness and diversity of intestinal microbial communities gradually increased from the small intestine to the large intestine. The relative abundance of Proteobacteria was higher in the jejunum and ileum, whereas the proportion of Firmicutes was higher in the cecum and colon. The concentrations of SCFAs were higher in the cecum and colon (P < 0.05). The concentrations of amino acids were higher in the small intestine than in the large intestine, while the amino acid content was significantly higher in the ascending colon than in the transverse colon and descending colon. The correlation analysis revealed that Ruminococcaceae UCG-005, Coriobacteriaceae_uncultured, [Eubacterium] hallii group, Mogibacterium and Lachnospiraceae AC2044 group had a higher positive correlation with SCFAs, crude ash and fat but had a negative correlation with amino acids in different gut locations of pigs. These findings may serve as fundamental data for using nutrient metabolism to regulate human and animal gut microbes and health and provide guidance for exploring host-microbe bidirectional interaction mechanisms and driving pathways.

Fast tool servo systems with high precision and high speed pose significant challenges to servo control at the nano-scale. The saturation of the control actions, time delays and system uncertainties further complicate the control challenges. To address these problems, we propose a Smith predictor based robust anti-windup scheme in this article, such that high performance servo with nano-accuracy can be achieved in the case of saturations, time delays and model uncertainties. According to the input/output based equivalent representation, the saturation nonlinearity is transformed to the dead zone nonlinearity fulfilling a sector condition. Based on the Popov criterion, the stability conditions for the anti-windup compensator are derived, which are further formulated as an H∞ optimization problem with robustness against model uncertainties. The effectiveness of the proposed control architecture is verified through real-time experiments, where excellent servo performance, saturation compensation and robustness are demonstrated, outperforming existing results.

Abstract Panama disease (Fusarium wilt disease) caused by Fusarium oxysporum f. sp. cubense race 4 (FOC) severely threatens banana (Musa spp.) production worldwide. Intercropping of banana with Allium plants has shown a potential to reduce Panama disease. In this study, six cultivars of Chinese chive (Allium tuberosum Rottler) were selected to compare their differences in antifungal activity and active compounds. Three cultivars Duokang Fujiu 11, Fujiuhuang 2, and Duokang Sijiqing with higher levels of antifungal compounds were further used for intercropping with banana in the pots and field to compare their effects on growth and disease incidence of banana. The six cultivars showed significant differences in antifungal activity against FOC mycelia growth in both leaf volatiles and aqueous leachates. The aqueous leachates displayed stronger antifungal activity than the volatiles. FJH cultivar showed the best inhibitory effect among all six cultivars. Contents of three main antifungal compounds dipropyl trisulfide (DPT), dimethyl trisulfide (DMT), and 2-methyl-2-pentenal (MP) in volatiles and aqueous leachates varied considerably among cultivars. Pot and field experiments showed that intercropping with three selected Chinese chive cultivars significantly improved banana vegetative growth, increased photosynthetic characteristics and yield but decreased disease incidence of Panama disease. Our results indicate that intercropping with Chinese chive shows potential to reduce banana Panama disease and selection of appropriate cultivars is vital for effective disease control.

Abstract The rice striped stem borer (SSB, Chilo suppressalis) is one of the most destructive pests of rice plants. Si‐mediated rice defense against various pests has been widely reported, and sodium silicate (SS) has been used as an effective source of silicon for application to plants. However, there is quite limited information about the direct effects of Si application on herbivorous insects. SSB larval performance and their insecticide tolerance were examined after they had been reared either on rice plants cultivated in nutrient solution containing 0.5 and 2.0 mM SS or on artificial diets with 0.1% and 0.5% SS. SS amendment in either rice culture medium or artificial diets significantly suppressed the enzymatic activities of acetylcholinesterase, glutathione S‐transferases, and levels of cytochrome P450 protein in the midgut of C. suppressalis larvae. Larvae fed on diets containing SS showed lower insecticide tolerance. Additionally, RNA‐seq analysis showed that SS‐mediated larval insecticide tolerance was closely associated with fatty acid biosynthesis and pyruvate metabolism pathways. Our results suggest that Si not only enhances plant resistance against insect herbivore, but also impairs the insect's capacity to detoxify the insecticides. This should be considered as another important aspect in Si‐mediated plant–insect interaction and may provide a novel approach of pest management.

Abstract Objectives The purpose of this study was to evaluate the value of serum krebs von den lungen-6 (KL-6) level as a diagnostic indicator for connective tissue disease associated with interstitial lung disease (CTD-ILD). Methods One hundred fifty five patients with newly diagnosed CTD in our hospital were enrolled and divided into two groups by their ILD manifestations, the CTD-ILD group and the CTD group. In parallel, 61 patients with pulmonary infection and 60 cases of healthy subjects were also enrolled into the study. The difference of serum KL-6 level among the four groups were compared. In CTD-ILD group, carbon monoxide diffusing capacity (DLCo) and high-resolution computed tomography (HRCT) of lung were also tested. The serum KL-6 level of 32 patients from the CTD-ILD group who received cyclophosphamide (CTX) pulse therapy were sampled and measured, by enzyme linked immunosorbent assay (ELISA), at three time points: before treatment, 3 months after treatment and 6 months after treatment. Results The serum KL-6 level in the CTD-ILD group (1004.9 (676.41738.1) IU/ml) is significantly higher than three other groups (χ 2 = 72.29, P