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The emergence of novel avian influenza reassortants in wild birds in recent years is a public health concern. However, the viruses that circulate in migratory birds are not fully understood. In this study, we summarized and categorized global H11 avian influenza viruses and reported that waterfowl and shorebirds are the major reservoirs of the identified H11 viruses. The surveillance data of the 35,749 faecal samples collected from wild bird habitats in eastern China over the past seven years revealed a low prevalence of H11 viruses in birds, with a positive rate of 0.067% (24 isolates). The phylogenetic analysis of the twenty viruses indicated that H11 viruses have undergone complex reassortment with viruses circulating in waterfowl and shorebirds. These tested viruses do not acquire mammalian adaptive mutations in their genomes and preferentially bind to avian-type receptors. Experimental infection studies demonstrated that the two tested H11N9 viruses of wild bird origin replicated and transmitted more efficiently in ducks than in chickens, whereas the pigeon H11N2 virus isolated from a live poultry market was more adapted to replicate in chickens than in ducks. In addition, some H11 isolates replicated efficiently in mice and caused body weight loss but were not lethal. Our study revealed the role of waterfowl and shorebirds in the ecology and evolution of H11 viruses and the potential risk of introducing circulating H11 viruses into ducks or chickens, further emphasizing the importance of avian influenza surveillance at the interface of migratory birds and poultry.

ObjectiveThis study aimed to explore the impact of exercise training modes on sensory and motor-related cortex excitability using functional near-infrared spectroscopy technology (fNIRS) and reveal specific cortical effects.Materials and methodsTwenty participants with no known health conditions took part in a study involving passive, active, and resistance tasks facilitated by an upper-limb robot, using a block design. The participants wore functional near-infrared spectroscopy (fNIRS) devices throughout the experiment to monitor changes in cortical blood oxygen levels during the tasks. The fNIRS optode coverage primarily targeted key areas of the brain cortex, including the primary motor cortex (M1), primary somatosensory cortex (S1), supplementary motor area (SMA), and premotor cortex (PMC) on both hemispheres. The study evaluated cortical activation areas, intensity, and lateralization values.ResultsPassive movement primarily activates M1 and part of S1, while active movement mainly activates contralateral M1 and S1. Resistance training activates brain regions in both hemispheres, including contralateral M1, S1, SMA, and PMC, as well as ipsilateral M1, S1, SMA, and PMC. Resistance movement also activates the ipsilateral sensorimotor cortex (S1, SMA, PMC) more than active or passive movement. Active movement has higher contralateral activation in M1 compared to passive movement. Resistance and active movements increase brain activity more than passive movement. Different movements activate various cortical areas equally on both sides, but lateralization differs. The correlation between lateralization of brain regions is significant in the right cortex but not in the left cortex during three movement patterns.ConclusionAll types of exercise boost motor cortex excitability, but resistance exercise activates both sides of the motor cortex more extensively. The PMC is crucial for intense workouts. The right cortex shows better coordination during motor tasks than the left. fNIRS findings can help determine the length of treatment sessions.

Abstract The Illumina HiSeq platform has been a commonly used option for bacterial genome sequencing. Now the BGI DNA nanoball (DNB) nanoarrays platform may provide an alternative platform for sequencing of bacterial genomes. To explore the impact of sequencing platforms on bacterial genome assembly, quality assessment, sequence alignment, functional annotation, mutation detection, and metagenome mapping, we compared genome assemblies based on sequencing of cultured bacterial species using the HiSeq 2000 and BGISEQ-500 platforms. In addition, simulated reads were used to evaluate the impact of insert size on genome assembly. Genome assemblies based on BGISEQ-500 sequencing exhibited higher completeness and fewer N bases in high GC genomes, whereas HiSeq 2000 assemblies exhibited higher N50. The majority of assembly assessment parameters, sequences of 16S rRNA genes and genomes, numbers of single nucleotide variants (SNV), and mapping to metagenome data did not differ significantly between platforms. More insertions were detected in HiSeq 2000 genome assemblies, whereas more deletions were detected in BGISEQ-500 genome assemblies. Insert size had no significant impact on genome assembly. Taken together, our results suggest that DNBSEQ platforms would be a valid substitute for HiSeq 2000 for bacterial genome sequencing.

Abstract In a variety of fields such as exploitation of geothermal energy and the reconstruction of nuclear waste storage, both of high-temperature and cooling process change the physical and mechanical properties of granite. Uniaxial compression tests were performed on five groups of granite samples at 25 °C, 200 °C, 400 °C, 600 °C and 800 °C after water cooling, and CT scanning, acoustic emission(AE) monitoring and X-ray diffraction(XRD) scanning were used to investigate the structure properties and failure characteristics of granite. It is found that the proportions of pore volume greater than 106 μm3 and less than 105 μm3 with are positively and negatively correlated with the thermal treatment temperature respectively. The mechanical properties of granite are significantly deteriorated by temperature gradient shock, and crack development scale during failure process overall increases as implied by AE response. The failure intensity index η is proposed to characterize the failure severity of granite, and the value of η descends with the increase of thermal treatment temperature, indicating the failure severity of granite is alleviated. Three types of loading failure mode are classified for water-cooled high-temperature granite. The failure mode of granite at 200 °C and 600 °C is tensile failure and tensile-shear failure respectively, while the granite samples are dominated by shear failure at 25 °C, 400 °C and 800 °C.

Milk production is an essential economic trait in cattle, and understanding the genetic regulation of this trait can enhance breeding strategies. The discoidin domain receptor 1 (DDR1) gene has been identified as a key candidate gene that influences milk production, and ETS homologous factor (EHF) is recognized as a critical transcription factor that regulates DDR1 expression. Codon usage bias, which affects gene expression and protein function, has not been fully explored in cattle. This study aims to examine the codon usage bias of DDR1 and EHF transcription factors to understand their roles in dairy production traits. Data from 24 species revealed that both DDR1 and EHF predominantly used G/C-ending codons, with the GC3 content averaging 75.49% for DDR1 and 61.72% for EHF. Synonymous codon usage analysis identified high-frequency codons for both DDR1 and EHF, with 17 codons common to both genes. Correlation analysis indicated a negative relationship between the effective number of codons and codon adaptation index for both DDR1 and EHF. Phylogenetic and clustering analyses revealed similar codon usage patterns among closely related species. These findings suggest that EHF plays a crucial role in regulating DDR1 expression, offering new insights into genetically regulating milk production in cattle.

BackgroundStroke survivors often face challenges in motor learning and motivation during rehabilitation, which can impede their recovery progress. Traditional rehabilitation methods vary in effectiveness, prompting the exploration of novel approaches such as reward strategies. Previous research indicates that rewards can enhance rehabilitation motivation and facilitate motor learning. However, most reward paradigms have utilized fixed reward amounts, which also have limitations. Exploring alternative, more effective reward strategies, such as probabilistic rewards, is warranted to optimize stroke patient rehabilitation.MethodsA total of 81 stroke patients will be recruited and randomly assigned to control, fixed reward, or probabilistic reward groups at a ratio of 1:1:1 using a randomized number table method. Participants will undergo 10 days of daily hand motor function rehabilitation training, with sessions lasting 20 min each. The training will involve pegboard tests and box and block tests. Control group participants will receive standard training, while fixed reward group members will receive monetary incentives for completing tests, and probabilistic reward group members will have the chance to win monetary rewards through a lottery box. Rehabilitation motivation and motor performance and functional near-infrared spectroscopy brain imaging will be conducted at designated time points. The primary outcome measure is the stroke rehabilitation motivation scale, and the second outcome measures include motor performance, simple test for evaluating hand function, motivation and pleasure scale self-report, and Pittsburgh rehabilitation participation scale.DiscussionReward-based training enhance rehabilitation participation and adherence, it also improve motor learning speed and memory retention of stroke patients. The fixed reward applied in the past studies could diminish the sensitivity of stroke patients to rewards, while probabilistic reward may provide unpredictable or variable incentives or reinforcements for motor rehabilitation. This study will compare the efficacy of different reward strategies in enhancing motor learning ability and rehabilitation motivation among stroke patients. By conducting a randomized controlled trial, the study seeks to provide valuable insights into optimizing stroke rehabilitation protocols and improving patient outcomes.Clinical Trial Registration:https://www.chictr.org.cn/, ChiCTR2400082419.

IntroductionFaecalibacterium is one of the most abundant bacteria in the gut microbiota of healthy adults, highly regarded as a next-generation probiotic. However, the functions of Faecalibacterium genomes from cultured strains and the distribution of different species in populations may differ among different sources.MethodsWe here performed an extensive analysis of pan-genomes, functions, and safety evaluation of 136 Faecalibacterium genomes collected from 10 countries.ResultsThe genomes are clustered into 11 clusters, with only five of them were characterized and validly nomenclated. Over 80% of the accessory genes and unique genes of Faecalibacterium are found with unknown function, which reflects the importance of expanding the collection of Faecalibacterium strains. All the genomes have the potential to produce acetic acid and butyric acid. Nine clusters of Faecalibacterium are found significantly enriched in the healthy individuals compared with patients with type II diabetes..DiscussionThis study provides a comprehensive view of genomic characteristic and functions and of culturable Faecalibacterium bacterium from human gut, and enables clinical advances in the future.

ObjectiveInsufficient motivation among post-stroke survivors may be an important factor affecting their motor function recovery. This study seeks to investigate the relationship between motivation and functional recovery in stroke patients undergoing rehabilitation training.Materials and methods103 stroke patients with upper limb impairments were studied during their hospital stays. Assessments were done before and after rehabilitation training to measure motivation, emotional state, motor function, and independence in daily activities. Data analysis was conducted to examine the distribution of these factors among the participants. Pearson and Spearman correlation analyses were used to study the relationships between motivation, emotional state, and motor function. Patients were divided into high and low motivation groups based on the Rehabilitation Motivation Scale (RMS), and chi-square and rank-sum tests were used to compare functional differences before and after treatment among patients with varying levels of motivation.Results66 participants were found to have low motivation in the initial assessment of the RMS (64.08%). Consistency in motivation levels was observed among patients with high motivation (r = 0.648, P

Abstract The Lachnospiraceae family holds promise as a source of next‐generation probiotics, yet a comprehensive delineation of its diversity is lacking, hampering the identification of suitable strains for future applications. To address this knowledge gap, we conducted an in‐depth genomic and functional analysis of 1868 high‐quality genomes, combining data from public databases with our new isolates. This data set represented 387 colonization‐selective species‐level clusters, of which eight genera represented multilineage clusters. Pan‐genome analysis, single‐nucleotide polymorphism (SNP) identification, and probiotic functional predictions revealed that species taxonomy, habitats, and geography together shape the functional diversity of Lachnospiraceae. Moreover, analyses of associations with atherosclerotic cardiovascular disease (ACVD) and inflammatory bowel disease (IBD) indicated that several strains of potentially novel Lachnospiraceae species possess the capacity to reduce the abundance of opportunistic pathogens, thereby imparting potential health benefits. Our findings shed light on the untapped potential of novel species enabling knowledge‐based selection of strains for the development of next‐generation probiotics holding promise for improving human health and disease management.

The genus Bifidobacterium widely exists in human gut and has been increasingly used as the adjuvant probiotics for the prevention and treatment of diseases. However, the functional differences of Bifidobacterium genomes from different regions of the world remain unclear. We here describe an extensive study on the genomic characteristics and function annotations of 1512 genomes (clustered to 849 non-redundant genomes) of Bifidobacterium cultured from human gut. The distribution of some carbohydrate-active enzymes varied among different Bifidobacterium species and continents. More than 36% of the genomes of B. pseudocatenulatum harbored biosynthetic gene clusters of lanthipeptide-class-iv. 99.76% of the cultivated genomes of Bifidobacterium harbored genes of bile salt hydrolase. Most genomes of B. adolescentis, and all genomes of B. dentium harbored genes involved in gamma-aminobutyric acid synthesis. B. longum subsp. infantis were characterized harboring most genes related to human milk oligosaccharide utilization. Significant differences between the distribution of antibiotic resistance genes among different species and continents revealed the importance to use antibiotics precisely in the clinical treatment. Phages infecting Bifidobacterium and horizontal gene transfers occurring in genomes of Bifidobacterium were dependent on species and region sources, and might help Bifidobacterium adapt to the environment. In addition, the distribution of Bifidobacterium in human gut was found varied from different regions of the world. This study represents a comprehensive view of characteristics and functions of genomes of cultivated Bifidobacterium from human gut, and enables clinical advances in the future.

Abstract Microseismic (MS) events generated during coal and rock hydraulic fracturing (HF) include wet events caused by fracturing fluid injection, in addition to dry events caused by stress perturbations. The mixture of these two events makes effective fracturing MS events pickup difficult. This study is based on physical experiments of different coal and rock HF and uniaxial compression. The differences of waveform characteristic parameters of various coal and rock ruptures were analyzed using the Hilbert–Huang transform, leading to some useful conclusions. The phase characteristics of the acoustic emission (AE) energy differed significantly and responded well to the pumping pressure curve. The AE waveforms of HF exhibit similar energy and frequency distribution characteristics after Empirical mode decomposition. The main frequency bands for coal, sandstone, and shale samples are 100–300 kHz, while the mudstone sample is in the range of 50–150 kHz. The decay ratios for coal, sandstone, shale and mudstone samples are 0.78, 0.83, 0.67 and 0.85, respectively. When compared to the uniaxial compression test, the main frequency bands of HF were reduced for coal, sandstone and mudstone samples, whereas shale remained essentially unchanged. The duration, instantaneous energy, and total energy of the HF waveform are smaller than those of uniaxial compression, while the decay ratio is greater, especially for the mudstone samples. The waveform characteristic parameters, trained using the multilayer perceptron neural network, can effectively identify HF and uniaxial compression events with an accuracy of 96%.

Abstract The oral cavity harbors highly diverse communities of microorganisms. However, the number of isolated species and high-quality genomes is limited. Here we present a Cultivated Oral Bacteria Genome Reference (COGR), comprising 1089 high-quality genomes based on large-scale aerobic and anaerobic cultivation of human oral bacteria isolated from dental plaques, tongue, and saliva. COGR covers five phyla and contains 195 species-level clusters of which 95 include 315 genomes representing species with no taxonomic annotation. The oral microbiota differs markedly between individuals, with 111 clusters being person-specific. Genes encoding CAZymes are abundant in the genomes of COGR. Members of the Streptococcus genus make up the largest proportion of COGR and many of these harbor entire pathways for quorum sensing important for biofilm formation. Several clusters containing unknown bacteria are enriched in individuals with rheumatoid arthritis, emphasizing the importance of culture-based isolation for characterizing and exploiting oral bacteria.

The principle of acupoint stimulation efficacy is based on traditional meridian theory. However, the molecular mechanisms underlying the therapeutic effects of acupoints in treating diseases remain unclear in modern scientific understanding. In this study, we selected the ST36 acupoint for investigation and summarized all relevant literature from the PubMed database over the past 10 years. The results indicate that stimulation of ST36 single acupoints has therapeutic effects mainly in models of respiratory, neurological, digestive, endocrine and immune system diseases. And it can affect the inflammatory state, oxidative stress, respiratory mucus secretion, intestinal flora, immune cell function, neurotransmitter transmission, hormone secretion, the network of Interstitial Cells of Cajal (ICC) and glucose metabolism of the organism in these pathological states. Among them, acupuncture at the ST36 single point has the most prominent function in regulating the inflammatory state, which can mainly affect the activation of MAPK signaling pathway and drive the ''molecular-cellular'' mode involving macrophages, T-lymphocytes, mast cells (MCs) and neuroglial cells as the core to trigger the molecular level changes of the acupuncture point locally or in the target organ tissues, thereby establishing a multi-system, multi-target, multi-level molecular regulating mechanism. This article provides a comprehensive summary and discussion of the molecular mechanisms and effects of acupuncture at the ST36 acupoint, laying the groundwork for future in-depth research on acupuncture point theory.

Abstract Anlotinib, as a promising oral small-molecule antitumor drug, its role in glioma has been only reported in a small number of case reports. Therefore, anlotinib has been considered as a promising candidate in glioma. The aim of this study was to investigate the metabolic network of C6 cells after exposure to anlotinib and to identify anti-glioma mechanism from the perspective of metabolic reprogramming. Firstly, CCK8 method was used to evaluate the effects of anlotinib on cell proliferation and apoptosis. Secondly, ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS)-based metabolomic and lipidomic were developed to characterize the metabolite and lipid changes in cell and cell culture medium (CCM) caused by anlotinib in the treatment of glioma. As a result, anlotinib had concentration-dependent inhibitory effect with the concentration range. In total, twenty-four and twenty-three disturbed metabolites in cell and CCM responsible for the intervention effect of anlotinib were screened and annotated using UHPLC-HRMS. Altogether, seventeen differential lipids in cell were identified between anlotinib exposure and untreated groups. Metabolic pathways, including amino acid metabolism, energy metabolism, ceramide metabolism, and glycerophospholipid metabolism, were modulated by anlotinib in glioma cell. Overall, anlotinib has an effective treatment against the development and progression of glioma, and these remarkable pathways can generate the key molecular events in cells treated with anlotinib. Future research into the mechanisms underlying the metabolic changes is expected to provide new strategies for treating glioma.

Abstract Clinical updates suggest conserving metastatic sentinel lymph nodes (SLNs) of breast cancer (BC) patients during surgery; however, the immunoadjuvant potential of this strategy is unknown. Here we leverage an immune-fueling flex-patch to animate metastatic SLNs with personalized antitumor immunity. The flex-patch is implanted on the postoperative wound and spatiotemporally releases immunotherapeutic anti-PD-1 antibodies (aPD-1) and adjuvants (magnesium iron-layered double hydroxide, LDH) into the SLN. Genes associated with citric acid cycle and oxidative phosphorylation are enriched in activated CD8+ T cells (CTLs) from metastatic SLNs. Delivered aPD-1 and LDH confer CTLs with upregulated glycolytic activity, promoting CTL activation and cytotoxic killing via metal cation-mediated shaping. Ultimately, CTLs in patch-driven metastatic SLNs could long-termly maintain tumor antigen-specific memory, protecting against high-incidence BC recurrence in female mice. This study indicates a clinical value of metastatic SLN in immunoadjuvant therapy.

Malignant melanoma cell-intrinsic PD-1:PD-L1 interaction thrusts tumorigenesis, angiogenesis, and radioresistance via mTOR hyperactivation to aggravate circumjacent aggression. Interdicting melanoma intrinsic growth signals, including the blockade of PD-L1 and mTOR signaling concurrently, cooperative with radiotherapy may provide a vigorous repertoire to alleviate the tumor encumbrance. Thence, we design a three-pronged platinum@polymer-catechol nanobraker to deliver mTOR inhibitor TAK228 and anti-PD-L1 antibody (aPD-L1) for impeding the melanoma-PD-1-driven aggression and maximizing the melanoma eradication. The aPD-L1 collaborated with TAK228 restrains melanoma cell-intrinsic PD-1: PD-L1 tumorigenic interaction via blocking melanoma-PD-L1 ligand and the melanoma-PD-1 receptor-driven mTOR signaling; corresponding downregulation of mTOR downstream protumorigenic cellular MYC and proangiogenic hypoxia-inducible factor 1-alpha is conducive to preventing tumorigenesis and angiogenesis, respectively. Further, high-Z metal platinum sensitizing TAK228-enhanced radiotherapy confers the nanobraker on remarkable tumoricidal efficacy. Hereto, the customized three-pronged nanobrakers efficiently suppress melanoma tumorigenesis and angiogenesis concomitant with the amplification of radiotherapeutic efficacy. Such an ingenious tactic may provide substantial benefits to clinical melanoma patients.

Abstract Background Osteonecrosis of the femoral head (ONFH) is still a challenge for orthopedists worldwide and can lead to disability if patients are not treated effectively. Danyu Gukang Pill (DGP), a traditional Chinese medicine (TCM) formulation, is recognized to be effective against ONFH. Nevertheless, its molecular mechanisms remain to be clarified. Methods The active ingredients of DGP were collected from the online databases according to oral bioavailability (OB) and drug-likeness (DL). The potential targets of DGP were retrieved from the TCMSP database, while the potential targets of ONFH were obtained from the GeneCards and NCBI databases. The functions and signaling pathways of the common targets of DGP and ONFH were enriched by GO and KEGG analyses. Subsequently, molecular docking and in vitro cell experiments were performed to further validate our findings. Results In total, 244 active ingredients of DGP and their corresponding 317 targets were obtained, and 40 ONFH-related targets were predicted. Afterwards, 19 common targets of DGP and ONFH were obtained and used as potential targets for the treatment of ONFH. Finally, combined with network pharmacology analysis, molecular docking and in vitro cell experiments, our study first demonstrated that the treatment effect of DGP on ONFH might be closely related to the two targets, HIF1A (HIF-1α) and VEGFA, and the HIF-1 signaling pathway. Conclusions This study is the first to investigate the molecular mechanisms of DGP in the treatment of ONFH based on network pharmacology. The results showed that DGP might up-regulate the expression of HIF-1α and VEGFA by participating in the HIF-1 signaling pathway, thus playing an anti-ONFH role.

Abstract Intratumoral CD8+ T cells are crucial for effective cancer immunotherapy, but an immunosuppressive tumor microenvironment (TME) contributes to dysfunction and insufficient infiltration. Drug repurposing has successfully led to new discoveries among existing clinical drugs for use as immune modulators to ameliorate immunosuppression in TME and reactivate T‐cell‐mediated antitumor immunity. However, due to suboptimal tumor bioavailability, the full potential of immunomodulatory effects of these old drugs has not been realized. The self‐degradable PMI nanogels carrying two repurposed immune modulators, imiquimod (Imi) and metformin (Met), are reported for TME‐responsive drug release. It remodels the TME through the following aspects: 1) promoting dendritic cells maturation, 2) repolarizing M2‐like tumor‐associated macrophages, and 3) downregulating PD‐L1 expression. Ultimately, PMI nanogels reshaped the immunosuppressive TME and efficiently promote CD8+ T cell infiltration and activation. These results support that PMI nanogels can potentially be an effective combination drug for enhancing the antitumor immune response of anti‐PD‐1 antibodies.

Type 2 diabetes mellitus (T2DM) is a common and multiple endocrine metabolic disease. When pancreatic β cell in case of dysfunction, the synthesis and secretion of insulin are reduced. This study is to explore the effect of cordycepin (the molecular formula C10H13N5O3), a natural adenosine isolated from Cordyceps militaris, on high glucose/lipid-induced glucotoxicity and lipotoxicity in INS-1 cells. Our results showed that cordycepin improved cell viability, improved cell energy metabolism and promoted insulin synthesis and secretion. The mechanism may be related to that cordycepin reduces intracellular reactive oxygen species (ROS), increases ATP content in cells, causes membrane depolarization and balances the steady state of Ca2+ concentration, cordycepin inhibits cell apoptosis, which may be related to the downregulation of proteins level of c-Jun N-terminal kinases (JNK) phosphorylation, cytochrome c (Cyt-c), Cleaved Capase-3, the mRNA level of JNK, Cyt-c, Capase-3 and upregulation of proteins/mRNA level of pancreatic and duodenal homeobox factor-1 (PDX-1). These results suggest that cordycepin can inhibit cell apoptosis and protect cell number by downregulating ROS/JNK mitochondrial apoptosis pathway under high glucose/lipid environment, thereby improving the function of pancreatic islet cells, providing a theoretical basis for the related research on the prevention and control of cordycepin on T2DM.

Unmanned aerial vehicles (UAVs) lifelong flight is essential to accomplish various tasks, e.g., aerial patrol, aerial rescue, etc. However, traditional UAVs have limited power to sustain their flight and need skilled operators manually control their charging process. Manufacturers and users are eagerly seeking a reliable autonomous battery-changing solution. To address this need, we propose and design an autonomous battery-changing system for UAVs using the theory of inventive problem solving (TRIZ) and user-centered design (UCD) methods. For practical application, we employ UCD to thoroughly analyze user requirements, identify multiple pairs of technical contradictions, and solve these inconsistencies using TRIZ theory. Furthermore, we design an autonomous battery-changing hardware system that meets user requirements and realizes the battery change process after the automatic landing of UAVs. Finally, we conduct experiments to validate our system’s effectiveness. The experimental results show that our battery-changing system can implement the autonomous battery-changing task, and our system has high efficiency and robustness in the real environment.

BackgroundStroke survivors often exhibit low motivation for rehabilitation, hindering their ability to effectively complete rehabilitation training task effectively and participate in daily activities actively. Reward strategies have been identified as an effective method for boosting rehabilitation motivation, but their long-term efficacy remains uncertain. Transcranial direct current stimulation (tDCS) has been recognized as a technique that facilitates plastic changes and functional reorganization of cortical areas. Particularly, tDCS can improve the functional connectivity between brain regions associated with goal-directed behavior when applied to the left dorsolateral prefrontal cortex (dlPFC). Combing reward strategies with tDCS (RStDCS) has been shown to motivate healthy individuals to exert more effort in task performance. However, research exploring the combined and sustained effects of these strategies on rehabilitation motivation in stroke survivors is lacking.Methods and designEighty-seven stroke survivors with low motivation and upper extremity dysfunction will be randomized to receive either conventional treatment, RS treatment, or RStDCS treatment. The RStDCS group will receive reward strategies combined with anodal tDCS stimulation of the left dlPFC. The RS group will receive reward strategies combined with sham stimulation. The conventional group will receive conventional treatment combined with sham stimulation. tDCS stimulation is performed over 3 weeks of hospitalization, 20 min/time, five times a week. Reward strategies refers to personalized active exercise programs for patients during hospitalization and at home. Patients can voluntarily choose tasks for active exercise and self-report to the therapist so as to punch a card for points and exchange gifts. The conventional group will receive home rehabilitation instructions prior to discharge. Rehabilitation motivation, measured using RMS. RMS, FMA, FIM, and ICF activity and social engagement scale will be compared at baseline, 3 weeks, 6 weeks, and 3 months post-enrollment to evaluate patients’ multifaceted health condition based on the ICF framework.DiscussionThis study integrates knowledge from social cognitive science, economic behavioral science, and other relevant fields. We utilize straightforward and feasible reward strategies, combined with neuromodulation technology, to jointly improve patients’ rehabilitation motivation. Behavioral observations and various assessment tools will be used to monitor patients’ rehabilitation motivation and multifaceted health condition according to the ICF framework. The aim is to provide a preliminary exploration path for professionals to develop comprehensive strategies for improving patient rehabilitation motivation and facilitating a complete “hospital—home—society” rehabilitation process.Clinical trial registrationhttps://www.chictr.org.cn/showproj.aspx?proj=182589, ChiCTR2300069068

Despite tremendous advances in gas therapy, there are major concerns about the inevitable concentration of toxicity and the ability to perform real-time tracking of drug delivery. Second near-infrared (NIR-II) window absorbing nanoplatforms hold great promise for precision medicine because of their excellent tissue penetration of light and non-invasive nature. In this study, we engineered an NIR-II laser-activated theranostic agent (named CP-bF@PEG) that was composed of amphiphilic polymers (Pluronic F127, with polyethylene glycol, PEG, moieties) coated with an NIR-II-absorbing conjugated polymer (PTTBBT, CP) and nitric oxide (NO) donor (benzofuroxan, bF), which served as an NIR-II photothermal inducer and NO nanogenerator. Under deep tissue penetration of NIR-II laser irradiation, CP-bF@PEG was found to possess fluorescence imaging ability to accurately identify tumor and excellent photothermal effect. Moreover, CP-bF@PEG could generate NO via glutathione activation in the tumor microenvironment in a controllable manner. This NIR-II-absorbing polymer for high-contrast NIR-II fluorescence imaging-guided precision photothermal therapy achieved synergistic effects with NO therapy, as evidenced by pronounced tumor therapeutic efficacy and few side effects. This nanotheranostic agent is a highly promising candidate for high-contrast NIR-II imaging-guided precision photothermal therapy combined with gas therapy against cancer.

Organic mechanophores have been widely adopted for polymer mechanotransduction. However, most examples of polymer mechanotransduction inevitably experience macromolecular chain rupture, and few of them mimic mussel’s mechanochemical regeneration, a mechanically mediated process from functional units to functional materials in a controlled manner. In this paper, inorganic mechanoluminescent (ML) materials composed of CaZnOS-ZnS-SrZnOS: Mn2+ were used as a mechanotransducer since it features both piezoelectricity and mechanolunimescence. The utilization of ML materials in polymerization enables both mechanochemically controlled radical polymerization and the synthesis of ML polymer composites. This procedure features a mechanochemically controlled manner for the design and synthesis of diverse mechanoresponsive polymer composites.

Abstract The oral microbiota contains billions of microbial cells, which could contribute to diseases in many body sites. Challenged by eating, drinking, and dental hygiene on a daily basis, the oral microbiota is regarded as highly dynamic. Here, we report significant human genomic associations with the oral metagenome from more than 1915 individuals, for both the tongue dorsum (n = 2017) and saliva (n = 1915). We identified five genetic loci associated with oral microbiota at study-wide significance (p

Gardenia blue is a natural blue pigment that is environmentally friendly, non-toxic, and stable. The hydrolysis of geniposide, catalyzed by β-glucosidase, is a critical step in the production process of gardenia blue. However, β-glucosidase is not resistant to high temperatures, limiting the production of gardenia blue. In this study, we investigated the effectiveness of a heat-resistant glucosidase obtained from Thermotoga maritima in the production of gardenia blue. The enzyme exhibited a maximum activity of 10.60 U/mL at 90 °C. Single-factor and orthogonal analyses showed that exogenously expressed heat-resistant glucosidase reacted with 470.3 μg/mL geniposide and 13.5 μg/mL glycine at 94.2 °C, producing a maximum yield of 26.2857 μg/mL of gardenia blue after 156.6 min. When applied to the dyeing of denim, gardenia blue produced by this method yielded excellent results; the best color-fastness was achieved when an iron ion mordant was used. This study revealed the feasibility and application potential of microbial production of gardenia blue.

PD-L1 is frequently expressed on the surface of cancer cells and can be excreted from cancer cells in exosomes. Here, the authors generate a nanotherapy that combines an inhibitor of exosome production and an inducer of ferroptosis, enhancing the response to immune checkpoint blockade therapy.

Yield is an important indicator in evaluating rice planting, and it is the collective result of various factors over multiple growth stages. To achieve a large-scale accurate prediction of rice yield, based on yield estimation models using a single growth stage and conventional spectral transformation methods, this study introduced the continuous wavelet transform algorithm and constructed models under the premise of combined multiple growth stages. In this study, canopy reflectance spectra at four important stages of rice elongation, heading, flowering and milky were selected, and then, a rice yield estimation model was constructed by combining vegetation index, first derivative and wavelet transform based on random forest algorithm or multiple stepwise regression. This study found that the combination of multiple growth stages significantly improved the model accuracy. In addition, after two validations, the optimal model combination for rice yield estimation is first derivative-wavelet transform-vegetation index-random forest model based on four growth stages, with the coefficient of determination (R2) of 0.86, the root mean square error (RMSE) of 35.50 g·m−2 and the mean absolute percentage error (MAPE) of 4.6% for the training set, R2 of 0.85, RMSE of 33.40 g.m−2 and MAPE 4.30% for the validation set 1, and R2 of 0.80, RMSE of 37.40 g·m−2 and MAPE of 4.60% for the validation set 2. The research results demonstrated that the established model could accurately predict rice yield, providing technical support and a foundation for large-scale statistical estimating of rice yield.

Cordycepin (known as 3-deoxyadenosine, CRD), a natural product from the valuable traditional Chinese medicine Cordyceps militaris, has been reported to improve cognitive function and modulate neuroprotective effects on the central nervous system (CNS). However, the modulating mechanisms of cordycepin on information processing in hippocampal CA1 pyramidal neurons are not fully understood. To clarify how cordycepin modulates synaptic responses of pyramidal neurons in rat hippocampal CA1 region, we conducted an electrophysiological experiment using whole-cell patch-clamp technique. The spontaneous and miniature excitatory postsynaptic currents (sEPSCs and mEPSCs, respectively) and the spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs, respectively) recorded by this technique evaluated pure single or multi-synapse responses and enabled us to accurately quantify how cordycepin influenced the pre and postsynaptic aspects of synaptic transmission. The present results showed that cordycepin significantly decreased the frequency of both glutamatergic and GABAergic postsynaptic currents without affecting the amplitude, while these inhibitory effects were antagonized by the A1 adenosine receptor antagonist (DPCPX), but not the A2A (ZM 241385), A2B (MRS1754) and A3 (MRS1191) adenosine receptor antagonists. Taken together, our results suggested that cordycepin had a clear presynaptic effect on glutamatergic and GABAergic transmission, and provided novel evidence that cordycepin suppresses the synaptic transmission through the activation of A1AR.

Sediments represent the major sink of antibiotics in aquatic systems. However, few studies have proposed effective models that can predict the adsorption capacity of sediments through their physicochemical parameters. Here, 49 sediment samples were collected from different locations in the Yangtze Estuary and its adjacent coastal areas. The sediments were characterized, and their adsorption behavior towards tetracycline (TC) was investigated. It was found that both the Langmuir and Freundlich models fit the TC adsorption data well, and the sediments in the mud area showed the highest adsorption capacity. Subsequently, through correlation analysis for the adsorption coefficients and physicochemical parameters of sediments, 11 models were established to predict the adsorption coefficients (Kd), in which clay and cation exchange capacity played significant roles. When the salinity was increased from 0 to 32.79‰, the Freundlich adsorption coefficient (Kf) of TC for most sediments was reduced by more than75% (except sediment C6). Therefore, the methods provided herein can be helpful in predicting the sorption behavior of antibiotics with similar structures toward TC by sediments in this region.

Stroke was one of the leading causes of death in the Chinese population in 2017. Most stroke survivors may suffer from different levels of disabilities, which prevents them from returning to their daily activities. The decreased upper limb function is considered as the principal factor that makes the patients have less access to their activities of daily livings. Occupational therapy (OT), aiming to enhance patients' functional performances and improve the participation in daily activities is usually applied from the onset of stroke. However, conventional OT intervention still has several problems that need to be solved, such as the inefficient use of human resources, inadequate upper limb functional training and non-continuous OT services. To address these difficulties and improve the patients' functional outcomes, intelligent rehabilitation equipment is combined with OT through evaluation and intervention. Based on this combination, OT can be provided in health care facilities, home, and community for patients with all phases of stroke. This combination promotes the transition of OT to digitization, intelligence and homogenization.

Detection of the Fusarium head blight (FHB) is crucial for wheat yield protection, with precise and rapid FHB detection increasing wheat yield and protecting the agricultural ecological environment. FHB detection tasks in agricultural production are currently handled by cloud servers and utilize unmanned aerial vehicles (UAVs). Hence, this paper proposed a lightweight model for wheat ear FHB detection based on UAV-enabled edge computing, aiming to achieve the purpose of intelligent prevention and control of agricultural disease. Our model utilized the You Only Look Once version 4 (YOLOv4) and MobileNet deep learning architectures and was applicable in edge devices, balancing accuracy, and FHB detection in real-time. Specifically, the backbone network Cross Stage Partial Darknet53 (CSPDarknet53) of YOLOv4 was replaced by a lightweight network, significantly decreasing the network parameters and the computing complexity. Additionally, we employed the Complete Intersection over Union (CIoU) and Non-Maximum Suppression (NMS) to regress the loss function to guarantee the detection accuracy of FHB. Furthermore, the loss function incorporated the focal loss to reduce the error caused by the unbalanced positive and negative sample distribution. Finally, mixed-up and transfer learning schemes enhanced the model’s generalization ability. The experimental results demonstrated that the proposed model performed admirably well in detecting FHB of the wheat ear, with an accuracy of 93.69%, and it was somewhat better than the MobileNetv2-YOLOv4 model (F1 by 4%, AP by 3.5%, Recall by 4.1%, and Precision by 1.6%). Meanwhile, the suggested model was scaled down to a fifth of the size of the state-of-the-art object detection models. Overall, the proposed model could be deployed on UAVs so that wheat ear FHB detection results could be sent back to the end-users to intelligently decide in time, promoting the intelligent control of agricultural disease.

Wheat spike number, which could be rapidly and accurately estimated by the image processing technology, serves as the basis for crop growth monitoring and yield prediction. In this research, simple linear iterative clustering (SLIC) was performed for superpixel segmentation of the digital images of field-grown wheat. Firstly, certain characteristic color parameters were extracted and analyzed from the digital images, and the classifiers with the highest accuracy were chosen for subsequent image classification. Next, the main body of wheat spike was extracted through a series of morphological transformation and estimate was performed for each region. Backbone of the head was extracted, and the number of inflection points of backbone was detected. Then the wheat spike number was determined by combining the estimate of inflection points of backbone and the estimate for each region. Finally, the wheat spike number estimate was verified under four nitrogen fertilizer levels. The results were as follows: (1) Super green value (Eg) and normalized red green index (Dgr) were used as classification features to recognize wheat spikes, soil and leaves; (2) compared with pixel-based image processing, wheat spike recognition effect was much better after superpixel segmentation, as the main body of wheat spike extracted was more clear and morphology more intact; and (3) wheat plants had better growth under high nitrogen fertilizer level, and the accuracy of wheat spike number estimation was also the highest, which was 94.01%. The growth status was the worst under no nitrogen fertilizer application, and the accuracy of wheat spikes number estimation was also the lowest, which was only 80.8%. After excluding the no nitrogen condition, the accuracy of wheat spikes number estimation among mixed samples with more uniform growth status was up to 93.8%, which was an increase by 10.1% than before the exclusion. Wheat spikes number estimate based on superpixel segmentation and color features was a rapid and accurate method that was applicable to the field environment. However, this method was not recommended for use when the growth status of wheat was poor or of high heterogeneity. The findings provided reference for field-grown wheat yield estimate.

To improve the performance of a high-pressure refueling liquid oxy-kerosene engine, the influence of drag-reducing additive on the heat transfer characteristics in the supercritical flow of kerosene in a microchannel for regenerative cooling is explored. The finite-volume CFD numerical simulation method is applied using the RNG k-ε turbulence model and enhanced wall function. The current work faithfully represents the effect of the drag-reducing additive in kerosene through numerical calculations by combining a 10-component model for the physical properties of the kerosene and the Carreau non-Newtonian fluid constitutive model from rheological measurements. Results suggest that the 10-component kerosene surrogate can describe the supercritical physical properties of kerosene. The inlet temperature, inlet velocity, and the heat flux on the channel wall are driving factors for the supercritical kerosene flow and heat transfer characteristics. The pressure influence on the heat transfer is negligible. With polymer additives, the loss in pressure drop and heat transfer performance of supercritical kerosene flow decrease 46.8% and 37.5% respectively. The enhancement of engine thrust caused by reduction in pressure drop is an attractive improvement of concern.

An efficient modified QuEChERS method combined with high performance liquid chromatography-tandem mass spectrometry detection (HPLC-MS/MS) was established and evaluated for the residue analysis of thifluzamide in rice grain, husk, straw, seedling, paddy water, and soil. Thifluzamide residues were extracted with acetonitrile, cleaned up with primary secondary amine (PSA), and then determined by HPLC-MS/MS. The fortified recoveries were 76%–106% with RSDs of 3%–13%. The results of the supervised field trials at two experiment sites showed that thifluzamide dissipated rapidly in paddy fields, and the half-lives in paddy water, soil, and rice seedling were 0.3–0.6 d, 1.8–3.6 d, and 4.3–13.9 d, respectively. At harvest time, when the preharvest interval (PHI) was set as 21 d, the final residues of thifluzamide in rice grains were below the maximum residue limit (MRL) of 0.5 mg/kg set by Japan, whereas the final residues in rice husk and straw were still high (the highest value reached 1.36 mg/kg in rice husk and 0.83 mg/kg in rice straw). The results indicated that the highest residue in rice grain was 0.23 mg/kg when PHI was 21 d, and only 6.9–11.0% of acute risk quotient of thifluzamide was occupied by the dietary daily intake in Chinese population consuming rice.

BACKGROUND: Biomass smoke is associated with the risk of chronic obstructive pulmonary disease (COPD), but few studies have elaborated approaches to reduce the risk of COPD from biomass burning. The purpose of this study was to determine whether improved cooking fuels and ventilation have effects on pulmonary function and the incidence of COPD. METHODS AND FINDINGS: A 9-y prospective cohort study was conducted among 996 eligible participants aged at least 40 y from November 1, 2002, through November 30, 2011, in 12 villages in southern China. Interventions were implemented starting in 2002 to improve kitchen ventilation (by providing support and instruction for improving biomass stoves or installing exhaust fans) and to promote the use of clean fuels (i.e., biogas) instead of biomass for cooking (by providing support and instruction for installing household biogas digesters); questionnaire interviews and spirometry tests were performed in 2005, 2008, and 2011. That the interventions improved air quality was confirmed via measurements of indoor air pollutants (i.e., SO₂, CO, CO₂, NO₂, and particulate matter with an aerodynamic diameter of 10 µm or less) in a randomly selected subset of the participants' homes. Annual declines in lung function and COPD incidence were compared between those who took up one, both, or neither of the interventions. Use of clean fuels and improved ventilation were associated with a reduced decline in forced expiratory volume in 1 s (FEV₁): decline in FEV₁ was reduced by 12 ml/y (95% CI, 4 to 20 ml/y) and 13 ml/y (95% CI, 4 to 23 ml/y) in those who used clean fuels and improved ventilation, respectively, compared to those who took up neither intervention, after adjustment for confounders. The combined improvements of use of clean fuels and improved ventilation had the greatest favorable effects on the decline in FEV₁, with a slowing of 16 ml/y (95% CI, 9 to 23 ml/y). The longer the duration of improved fuel use and ventilation, the greater the benefits in slowing the decline of FEV₁ (p