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Abstract Background In the central nervous system, type 2 vesicular monoamine transporters (VMAT2) are responsible for the reuptake of monoamines from synaptic junction back to pre-synaptic terminal vesicles. These transporters are functionally crucial as they reflect the integrity of monoamine neurons. D6-[18F]FP-(+)-DTBZ, a novel deuterated VMAT2 radioligand, has shown promise as a potential PET tracer for the diagnosis of Parkinson’s disease (PD). This study evaluates the biodistribution and dosimetry of D6-[18F]FP-(+)-DTBZ and includes a head-to-head comparison with its non-deuterated version, [18F]FP-(+)-DTBZ (AV-133), in healthy individuals and PD patients. Results The automated synthesis of D6-[18F]FP-(+)-DTBZ using the SPE method was accomplished in 35 min, yielding a high radiochemical purity (> 99%) and high radiochemical yields (35 ± 5%). The biodistribution and dosimetry study indicated an effective dose of 37.1 ± 7.2 μSv/MBq, with the liver receiving the highest radiation dose (289.6 ± 42.1 μGy/MBq), followed by pancreas (185.2 ± 29.1 μGy/MBq). Brain imaging with D6-[18F]FP-(+)-DTBZ exhibited a significantly increased uptake in VMAT2-rich regions, particularly the striatum. In a head-to-head comparison between [18F]FP-(+)-DTBZ and D6-[18F]FP-(+)-DTBZ, the latter exhibited approximately 15% higher SUVR in the caudate, putamen, and nucleus accumbens. Preliminary studies in PD patients showed a substantial reduction in VMAT2 uptake in the striatum, with the most pronounced decrease observed in the putamen (a 53% decline). Conclusions D6-[18F]FP-(+)-DTBZ is a safe and improved VMAT2-specific imaging agent, which may be suitable for diagnosing PD by evaluating changes in VMAT2 binding of monoamine neurons in the brain. Trial registration Chinese Clinical Trial Registry, ChiCTR2200057218, Registered 16 August 2021, https://www.chictr.org.cn/bin/project/edit?pid=142725 .

Abstract Liposarcoma (LPS) is the second most common kind of soft tissue sarcoma, and a heterogeneous malignant tumor derived from adipose tissue. Up to now, the prognostic value of BAG1 or BAG2 in LPS has not been defined yet. Expression profiling data of LPS patients were collected from TCGA and GEO database. Survival curves were plotted to verify the outcome differences of patients based on BAG1 or BAG2 expression. Univariate and multivariate Cox regression models were used to analyze the prognostic ability of BAG1 or BAG2. Chaperone’s regulators BAG1 and BAG2 were identified as prognostic biomarkers for LPS patients, which exhibited distinct expression patterns and survival outcome prediction performances. Patients with high BAG2 expression and/or low BAG1 expression had worse prognosis. Enrichment analysis showed that BAG1 was involved in negative regulation of TGF-β signaling. Low expression of BAG1 was associated with high abundance of regulatory T cells (Tregs). The 2-gene signature model further confirmed the improved risk assessment performance of BAG1 and BAG2: high risk patients displayed poor prognosis. BAG1 and BAG2 are supposed to be potential prognostic biomarkers for LPS and have impacts on liposarcomagenesis and immune infiltration in distinctive manners, which may function as potential therapy targets (BAG1 agonists/BAG2 inhibitors) for LPS.

Abstract Multiple synchronous lung cancers (MSLCs) constitute a unique subtype of lung cancer. To explore the genomic and immune heterogeneity across different pathological stages of MSLCs, we analyse 16 MSLCs from 8 patients using single-cell RNA-seq, single-cell TCR sequencing, and bulk whole-exome sequencing. Our investigation indicates clonally independent tumours with convergent evolution driven by shared driver mutations. However, tumours from the same individual exhibit few shared mutations, indicating independent origins. During the transition from pre-invasive to invasive adenocarcinoma, we observe a shift in T cell phenotypes characterized by increased Treg cells and exhausted CD8+ T cells, accompanied by diminished cytotoxicity. Additionally, invasive adenocarcinomas exhibit greater neoantigen abundance and a more diverse TCR repertoire, indicating heightened heterogeneity. In summary, despite having a common genetic background and environmental exposure, our study emphasizes the individuality of MSLCs at different stages, highlighting their unique genomic and immune characteristics.

Abstract Background Unfavorable temperatures significantly constrain the quality formation of Dendrobium officinale, severely limiting its food demand. Salicylic acid (SA) enhances the resistance of D. officinale to stress and possesses various analogs. The impact and mechanism of the SA family on improving the quality of D. officinale under adverse temperature conditions remains unclear. Results Combined with molecular docking analysis, chlorophyll fluorescence and metabolic analysis after treatments with SA analogues or extreme temperatures are performed in this study. The results demonstrate that both heat and cold treatments impede several main parameters of chlorophyll fluorescence of D. officinale, including the ΦPSII parameter, a sensitive growth indicator. However, this inhibition is mitigated by SA or its chemically similar compounds. Comprehensive branch imaging of ΦPSII values revealed position-dependent improvement of tolerance. Molecular docking analysis using a crystal structure model of NPR4 protein reveals that the therapeutic effects of SA analogs are determined by their binding energy and the contact of certain residues. Metabolome analysis identifies 17 compounds are considered participating in the temperature-related SA signaling pathway. Moreover, several natural SA analogs such as 2-hydroxycinnamic acid, benzamide, 2-(formylamino) benzoic acid and 3-o-methylgallic acid, are further found to have high binding ability to NPR4 protein and probably enhance the tolerance of D. officinale against unfavorable temperatures through flavone and guanosine monophosphate degradation pathways. Conclusions These results reveal that the SA family with a high binding capability of NPR4 could improve the tolerance of D. officinale upon extreme temperature challenges. This study also highlights the collaborative role of SA-related natural compounds present in D. officinale in the mechanism of temperature resistance and offers a potential way to develop protective agents for the cultivation of D. officinale.

Background/Aims: Cancer stem cells (CSCs) are believed to drive tumor development and metastasis. Activin and hepatocyte growth factor (HGF) are important cytokines with the ability to induce cancer stemness. However, the effect of activin and HGF combination treatment on CSCs is still unclear.Methods: In this study, we sequentially treated colorectal cancer cells with activin and HGF and examined CSC marker expression, self-renewal, tumorigenesis, and metastasis. The roles of forkhead box M1 (FOXM1) and sex-determining region Y-box 2 (SOX2), two stemness-related transcription factors, in activin/HGF-induced aggressive phenotype were explored.Results: Activin and HGF treatment increased the expression of CSC markers and enhanced sphere formation in colorectal cancer cells. The tumorigenic and metastatic capacities of colorectal cancer cells were enhanced upon activin and HGF treatment. Activin and HGF treatment preferentially promoted stemness and metastasis of CD133+ subpopulations sorted from colorectal cancer cells. FOXM1 was upregulated by activin and HGF treatment, and the knockdown of FOXM1 blocked activin/HGF-induced stemness, tumorigenesis, and metastasis of colorectal cancer cells. Similarly, SOX2 was silencing impaired sphere formation of activin/HGF-treated colorectal cancers. Overexpression of SOX2 rescued the stem cell-like phenotype in FOXM1-depleted colorectal cancer cells with activin and HGF treatment. Additionally, the inhibition of FOXM1 via thiostrepton suppressed activin/HGF-induced stemness, tumorigenesis and metastasis.Conclusions: Sequential treatment with activin and HGF promotes colorectal cancer stemness and metastasis through activation of the FOXM1/SOX2 signaling. FOXM1 could be a potential target for the treatment of colorectal cancer metastasis.

Background/Aims: Gastric intestinal metaplasia (GIM), a common precancerous lesion of gastric cancer, can be caused by bile acid reflux. GATA binding protein 4 (GATA4) is an intestinal transcription factor involved in the progression of gastric cancer. However, the expression and regulation of GATA4 in GIM has not been clarified.Methods: The expression of GATA4 in bile acid-induced cell models and human specimens was examined. The transcriptional regulation of GATA4 was investigated by chromatin immunoprecipitation and luciferase reporter gene analysis. An animal model of duodenogastric reflux was used to confirm the regulation of GATA4 and its target genes by bile acids.Results: GATA4 expression was elevated in bile acid-induced GIM and human specimens. GATA4 bound to the promoter of mucin 2 (MUC2) and stimulate its transcription. GATA4 and MUC2 expression was positively correlated in GIM tissues. Nuclear transcription factor-κB activation was required for the upregulation of GATA4 and MUC2 in bile acid-induced GIM cell models. GATA4 and caudal-related homeobox 2 (CDX2) reciprocally transactivated each other to drive the transcription of MUC2. In chenodeoxycholic acid-treated mice, MUC2, CDX2, GATA4, p50, and p65 expression levels were increased in the gastric mucosa.Conclusions: GATA4 is upregulated and can form a positive feedback loop with CDX2 to transactivate MUC2 in GIM. NF-κB signaling is involved in the upregulation of GATA4 by chenodeoxycholic acid.

Abstract Purpose Previous studies suggest an association between chronic kidney disease (CKD) and cognitive impairment. The purpose of this study was to explore the association between the diverse stages of CKD and the cognitive performance of elderly American adults. Methods Data from the National Health and Nutrition Examination Survey (NHANES) 2011–2014 were used. Multivariate adjusted logistic regression, subgroup analysis, and the restricted cubic spline model were used to assess the associations of CKD stage and estimated glomerular filtration rate (eGFR) with cognitive performance. The measures used to evaluate cognitive function included the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) test, the Animal Fluency test, and the Digit Symbol Substitution test (DSST). Results This study included 2234 participants aged ≥ 60 years. According to the fully adjusted model, stages 3–5 CKD were significantly associated with the CERAD test score (OR = 0.70, 95% CI [0.51, 0.97], p = 0.033), the Animal Fluency test score (OR = 0.64, 95% CI [0.48, 0.85], p = 0.005), and the DSST score (OR = 0.60, 95% CI [0.41, 0.88], p = 0.013). In addition, the incidence of poor cognitive function increased with decreasing eGFR, especially for individuals with low and moderate eGFRs. Both the DSST score (p nonlinearity

Background. Obesity and related metabolic diseases are becoming a worldwide epidemic, leading to increased mortality and heavy medical costs. Our Chinese herbal formula Xiao-Gao-Jiang-Zhuo (XGJZ) has remarkable effects on curing obese patients in the clinic, but the cellular and molecular basis remains unknown. This study aimed to reveal the molecular mechanism involved in adipogenesis in vitro. Methods. Chinese herbal formula XGJZ-containing serum was prepared from XGJZ-treated obesity model rats. The function of XGJZ-containing serum was validated in 3T3-L1 preadipocytes. Oil O staining was performed to determine intracellular lipid accumulation in differentiated 3T3-L1 cells. The expression of pro-adipogenic transcription factors was measured to further validate the adipogenesis of 3T3-L1 adipocytes. The contents of triglyceride (TG), free fatty acid (FFA), and glycerin, along with the activities of lipid metabolism-related enzymes (including FAT, FATP1, DGAT, GPAT, ATGL, and HSL) were measured to study the lipogenesis in 3T3-L1 adipocytes. Results. XGJZ-containing serum inhibited 3T3-L1 differentiation, decreased intracellular lipid accumulation, and suppressed the expression of pro-adipogenic transcription factors in differentiated 3T3-L1 cells. The contents of TG, FFA, and glycerin were decreased when treated with XGJZ-containing serum, which also modulated lipid metabolism-related enzyme activities. The activities of fatty acid transporters (FAT, FATP1) and lipid mobilization enzymes (ATGL, HSL) were promoted, while activities of triglyceride biosynthesis enzymes (DGAT, GPAT) were attenuated in differentiated 3T3-L1 cells. Conclusion. XGJZ-containing serum has inhibitory effects on adipogenesis in 3T3-L1 preadipocytes, affirming the effect of XGJZ in treating obesity. It provides evidence for the mechanism of obesity.

Pancreatic malignant neoplasm is an extremely deadly malignancy well known for its resistance to traditional therapeutic approaches. Enhanced treatments are imperative for individuals diagnosed with pancreatic cancer (PC). Recent investigations have shed light on the wide-ranging anticancer properties of genetic therapy facilitated by oncolytic vaccinia virus. To illuminate the precise impacts of Aphrocallistes vastus lectin-armed oncolytic vaccinia virus (oncoVV-AVL) on PC, AsPC-1 and PANC-1 cells underwent treatment with oncoVV-AVL. Our findings revealed that oncoVV-AVL possesses the capacity to heighten oncolytic effects on PC cells and incite the production of diverse cytokines like tumor necrosis factor-α, interleukin-6 (IL-6), IL-8, and interferon-I (IFN-I), without triggering antiviral responses. Additionally, oncoVV-AVL can significantly elevate the levels of ROS in PC cells, initiating an oxidative stress response that promotes viral replication, apoptosis, and autophagy. Moreover, in xenograft tumor models, oncoVV-AVL notably restrained PC growth, enhanced IFN-γ levels in the bloodstream, and reprogrammed macrophages. Our investigation indicates that oncoVV-AVL boosts the efficacy of antitumor actions against PC tumors by orchestrating reactive oxygen species-triggered viral replication, fostering M1 polarization, and reshaping the tumor microenvironment to transform cold PC tumors into hot ones. These findings imply that oncoVV-AVL could present a novel therapeutic approach for treating PC tumors.

ABSTRACTSystemic low-grade inflammation is a feature of chronic disease. C-reactive protein (CRP) is a common biomarker of inflammation and used as an indicator of disease risk; however, the role of inflammation in disease is not completely understood. Methylation is an epigenetic modification in the DNA which plays a pivotal role in gene expression. In this study we evaluated differential DNA methylation patterns associated with blood CRP level to elucidate biological pathways and genetic regulatory mechanisms to improve the understanding of chronic inflammation. The racially and ethnically diverse participants in this study were included as 50% White, 41% Black or African American, 7% Hispanic or Latino/a, and 2% Native Hawaiian, Asian American, American Indian, or Alaska Native (total n = 13,433) individuals. We replicated 113 CpG sites from 87 unique loci, of which five were novel (CADM3, NALCN, NLRC5, ZNF792, and cg03282312), across a discovery set of 1,150 CpG sites associated with CRP level (p

ObjectiveCurrently, distinct use of clinical data, routine laboratory indicators or the detection of diabetic autoantibodies in the diagnosis and management of diabetes mellitus is limited. Hence, this study was aimed to screen the indicators, and to establish and validate a multifactorial logistic regression model nomogram for the non-invasive differential prediction of type 1 diabetes mellitus.MethodsClinical data, routine laboratory indicators, and diabetes autoantibody profiles of diabetic patients admitted between September 2018 and December 2022 were retrospectively analyzed. Logistic regression was used to select the independent influencing factors, and a prediction nomogram based on the multiple logistic regression model was constructed using these independent factors. Moreover, the predictive accuracy and clinical application value of the nomogram were evaluated using Receiver Operating Characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and clinical impact curves (CIC).ResultsA total of 522 diabetic patients were included in this study. These patients were randomized into training and validation sets in a 7:3 ratio. The predictors screened included age, prealbumin (PA), high-density lipoprotein cholesterol (HDL-C), islet cells autoantibodies (ICA), islets antigen 2 autoantibodies (IA-2A), glutamic acid decarboxylase antibody (GADA), and C-peptide levels. Based on these factors, a multivariate model nomogram was constructed, which had an Area Under Curve (AUC) of 0.966 and 0.961 for the training set and validation set, respectively. Subsequently, the calibration curves demonstrated a strong accuracy of the graph; the DCA and CIC results indicated that the graph could be used as a non-invasive valid predictive tool for the differential diagnosis of type 1 diabetes mellitus, clinically.ConclusionThe established prediction model combining patient’s age, PA, HDL-C, ICA, IA-2A, GADA, and C-peptide can assist in differential diagnosis of type 1 diabetes mellitus and type 2 diabetes mellitus and provides a basis for the clinical as well as therapeutic management of the disease.

ObjectiveThis study aims to elucidate the intervention effects of saponin components from Polygala tenuifolia Willd (Polygalaceae) on dementia, providing experimental evidence and new insights for the research and application of saponins in the field of dementia.Materials and MethodsThis review is based on a search of the PubMed, NCBI, and Google Scholar databases from their inception to 13 May 2024, using terms such as “P. tenuifolia,” “P. tenuifolia and saponins,” “toxicity,” “dementia,” “Alzheimer’s disease,” “Parkinson’s disease dementia,” and “vascular dementia.” The article summarizes the saponin components of P. tenuifolia, including tenuigenin, tenuifolin, polygalasaponins XXXII, and onjisaponin B, as well as the pathophysiological mechanisms of dementia. Importantly, it highlights the potential mechanisms by which the active components of P. tenuifolia prevent and treat diseases and relevant clinical studies.ResultsThe saponin components of P. tenuifolia can reduce β-amyloid accumulation, exhibit antioxidant effects, regulate neurotransmitters, improve synaptic function, possess anti-inflammatory properties, inhibit neuronal apoptosis, and modulate autophagy. Therefore, P. tenuifolia may play a role in the prevention and treatment of dementia.ConclusionThe saponin components of P. tenuifolia have shown certain therapeutic effects on dementia. They can prevent and treat dementia through various mechanisms.

Summary: The medial entorhinal cortex (MEC) is crucial for contextual memory, yet its role in context-induced retrieval of morphine withdrawal memory remains unclear. This study investigated the role of the MEC and its projection neurons from MEC layer 5 to the basolateral amygdala (BLA) (MEC−BLA neurons) in context-induced retrieval of morphine withdrawal memory. Results show that context activates the MEC in morphine withdrawal mice, and the inactivation of the MEC inhibits context-induced retrieval of morphine withdrawal memory. At neural circuits, context activates MEC−BLA neurons in morphine withdrawal mice, and the inactivation of MEC−BLA neurons inhibits context-induced retrieval of morphine withdrawal memory. But MEC−BLA neurons are not activated by conditioning of context and morphine withdrawal, and the inhibition of MEC−BLA neurons do not influence the coupling of context and morphine withdrawal memory. These results suggest that MEC−BLA neurons are critical for the retrieval, but not for the formation, of morphine withdrawal memory.

IntroductionPrevious studies have demonstrated that frailty is associated with depressive symptoms among older people and significantly increase the risk of difficulty in activities of daily living (ADL). However, uncertainties remain regarding the mechanisms behind such relationship. The aim of this study was to investigate the mediating effect of ADL in the relationship between frailty and depressive symptoms among older adults in China, and to explore to what extend sleep duration moderated the association between ADL and depressive symptoms.MethodsIn this study, we carried out cross-sectional descriptive analysis and 1,429 participants were included in the analysis. A survey was conducted using questionnaires and instruments measuring frailty, depressive symptoms, ADL and sleep duration. Bootstrap analyses served to explore the impact of ADL in mediating frailty and depressed symptoms, as well as the effect of sleep duration in moderating ADL and depressive symptoms.ResultsCompared to the robust group, the mediating effects of ADL between frailty and depressive symptoms were significant in the prefrail group and the frail group. The interaction term between sleep duration and ADL was significantly presented in the regression on depressive symptoms. Specifically, the Johnson–Neyman technique determined a range from 8.31 to 10.19 h for sleep duration, within which the detrimental effect of frailty on depressive symptoms was offset.ConclusionSleep duration moderated the indirect effect of ADL on the association between frailty and depressive symptoms. This provides support for unraveling the underlying mechanism of the association between frailty and depressive symptoms. Encouraging older adults to enhance ADL and obtain appropriate sleep duration might improve depressive symptoms for older adults with frailty and prefrailty.

Insulation failure significantly contributes to the unpredictable shutdown of power equipment. Compared to the partial discharge and high-frequency (HF) injection methods, the HF common-mode (CM) leakage current method offers a non-intrusive and highly sensitive alternative. However, the detection of HF CM currents is susceptible to interference from differential-mode (DM) currents, which exhibit high-amplitude and multifrequency components during normal operation. To address this challenge, this paper proposes a double-ring current sensor based on the principle of magnetic shielding for inverter-fed machine winding insulation monitoring. The inner ring harnesses the magnetic aggregation effect to isolate the DM current magnetic field, whereas the outer ring serves as the magnetic core of the Rogowski current sensor, enabling HF CM current monitoring. First, the magnetic field distributions of the CM and DM currents were analyzed. Then, a correlation between the sensor parameters and signal-to-noise ratio of the target HF CM current was established. Finally, an experimental study was conducted on a 3-kW PMSM for verification. The results indicate that the proposed double-ring HF CM sensor can effectively mitigate DM current interference. Compared to a single-ring sensor, a reduction of approximately 40% in the DM component was achieved, which significantly enhanced the precision of online insulation monitoring.

Abstract Background Associations between adjuvant chemotherapy (ACT) and the improvement in survival for patients with pT2N0M0 non‐small cell lung cancer (NSCLC) who received R0 resection remain controversial. This study aimed to evaluate the value of ACT for patients with pT2N0M0 NSCLCs, and to identify the subgroups who could benefit from ACT. Methods Multivariable Cox proportional hazards regression models were used to estimate independent prognostic factors. High‐risk factor (HRF) included visceral pleural invasion (VPI), lymphovascular invasion (LVI) and poor differentiation/undifferentiated tumors. Results Of the 899 patients, 277 (30.8%) patients received ACT. More younger patients (p

Existing vehicle position estimation methods are mostly based on Global Positioning System (GPS) or a fusion of GPS and machine learning methods to realize vehicle position estimation. While highway tunnels are many, GPS signals are easy to be interfered, and the vehicle loading rate of GPS devices is limited, this kind of method can not be realized in a wide range of applications. In this context, taking into account the ETC equipment that has been deployed and applied in large scale in China, the vehicle equipment loading rate is over 90%, but the ETC gantry interval is large, and it is not possible to effectively perceive the vehicle driving status inside the segment. Therefore, this paper is based on the ETC transaction data to build the basic driving characteristics and short-term driving style of the vehicle history segment, using GPS positioning data to build the internal characteristics of the segment, including the characteristics of the road structure within the segment, the pattern of change of the vehicle position, so as to put forward the highway in-transit vehicle position estimation method that considers the road characteristics and short-term driving style. Firstly, the SC-Kmeans-Bilstm vehicle segment speed prediction model based on PCA optimization is constructed by fusing vehicle short-term driving styles; secondly, the road model within the segment is constructed by using moving average and wavelet smoothing methods; lastly, the vehicle position data is temporally stabilized using linear interpolation and first-order inverse difference, and vehicle position estimation within the highway segment is realized by using DLCNN-LSTM-ATTENTION fusion model based on L1 regularization by combining vehicle segment speeds, road characteristics, and vehicle base driving characteristics. Among them, the short-term driving style helps us to obtain the vehicle segment speed more accurately, and the addition of the road model makes this method better explain the variability of the data. The experimental results show that the present method can achieve on- travel vehicle position estimation within 2km with an error of less than 50m in a full-sample highway environment, and can provide over-the-horizon sensing for intelligent vehicles.

IntroductionIn aquatic animals, colors not only reflect their sensory qualities but also affect their nutritional components and market price. Noble scallop Chlamys nobilis is an importantly economical bivalve cultured in the south sea of China and renowned for its various shell colors.MethodsIn this study, the nutrient compositions were compared among golden, yellow, and brown shell colour noble scallops originating from the same population for breeding new varieties.ResultsAmong three colour scallops, there is no significant difference in the content of moisture, ash, and total protein content (TPC) but significant differences in total carotenoid content (TCC), total lipid content (TLC), and amino acids (AAs) (P < 0.05), with the TCC of the brown scallop being about 2 times lower. The yellow scallop contained the same nutrients as TCC, TLC, ∑PUFAs (including EPA and DHA), and n-3/n-6 as the golden scallop, and both were significantly higher than the brown scallop (P < 0.05), but they had significantly lower ∑SFAs than the latter (P < 0.05). The correlation between the nutrient indices and the shell color of scallops was 67.5%. There is a significantly positive correlation between TCC and ∑PUFAs (P < 0.05), while a significantly negative correlation exists between TCC and ∑SFAs (P < 0.05). More importantly, the yellow scallop had significantly higher EAAs and FAAs than the golden scallop (P < 0.05).DiscussionThis study showed that the yellow noble scallop not only enriched in carotenoids and PUFAs but also enriched in amino acids. Therefore, the yellow scallop is more benefit to human health, which can provide high-quality food for customers.

To identify important functional genes of the large yellow croaker (Larimichthys crocea) under starvation stress, the expression changes of genes in muscles tissue of fish fasted for 0, 4, 8, 12, 16, and 20 d were analyzed with RNA-seq technology. Sequencing results showed that a total of 507 million clean reads were generated. Totals of 662, 998, 1015, 1260, and 1122 of differentially expressed genes (DEGs) were obtained at 4, 8, 12, 16, and 20 d, respectively, using starvation 0 d as control. Gene ontology (GO) classification and analysis showed that DEGs could be classified into 42 categories of biological processes, cellular components, and molecular functions. Of these, DEGs are enriched in regulations such as metabolic process, cellular process and single-organism process. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that DEGs involved a total of 22 pathways, eight of which were metabolic pathways. With fewer pathways enrichment entry in early starvation stages, but more pathways enrichment entry in late starvation stages (such as at 16 days of starvation), DEGs were significantly enriched in glycolysis/gluconeogenesis, biosynthesis of amino acids, carbon metabolism, fructose and mannose metabolism, methane metabolism and carbon fixation in photosynthetic organisms. After 20 days of starvation, DEGs began to be significantly enriched in the immune pathway, indicating that at this time, fish began to show an immunomodulatory response. This study systematically disclosed the changes of muscle tissue genes in large yellow croaker under starvation stress. The obtained results contribute to research on environmental stress in teleost fish.

ABSTRACT: Salmonella infection is a major concern in poultry production which poses potential risks to food safety. Our previous study confirmed that Lactiplantibacillus plantarum (LP) postbiotic exhibited a strong antibacterial capacity on Salmonella in vitro. This study aimed to investigate the beneficial effects and underlying mechanism of LP postbiotic on Salmonella-challenged broilers. A total of 240 one-day-old male yellow-feathered broilers were pretreated with 0.8% deMan Rogosa Sharpe (MRS) medium or 0.8% LP postbiotic (LP cell-free culture supernatant, LPC) in drinking water for 28 d, and then challenged with 1×109 CFU Salmonella enterica serovar Enteritidis (SE). Birds were sacrificed 3 d postinfection. Results showed that LPC maintained the growth performance by increasing body weight (BW), average daily gain (ADG), and average daily feed intake (ADFI) in broilers under SE challenge. LPC significantly attenuated SE-induced intestinal mucosal damage. Specifically, it decreased the intestinal injury score, increased villus length and villus/crypt, regulated the expression of intestinal injury-related genes (Villin, matrix metallopeptidase 3 [MMP3], intestinal fatty acid-binding protein [I-FABP]), and enhanced tight junctions (zona occludens-1 [ZO-1] and Claudin-1). SE infection caused a dramatic inflammatory response, as indicated by the up-regulated concentrations of interleukin (IL)-1β, IL-6, TNF-α, and the downregulation of IL-10, while LPC pretreatment markedly reversed this trend. We then found that LPC inhibited the activation of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome by decreasing the gene expression of Caspase‐1, IL-lβ, and IL-18. Furthermore, LPC suppressed NLRP3 inflammasome activation by inhibiting nuclear factor-kappa B (NF-κB) signaling pathway (the reduced levels of toll-like receptor 4 [TLR4], myeloid differentiation factor 88 [MyD88], and NF-κB). Finally, our results showed that LPC regulated gut microbiota by enhancing the percentage of Ligilactobacillus and decreasing Alistipes and Barnesiella. In summary, we found that LP postbiotic was effective to protect broilers against Salmonella infection, possibly through suppressing NLRP3 inflammasome and optimizing gut microbiota. Our study provides the potential of postbiotics on prevention of Salmonella infection in poultry.

ObjectivesTo investigate the safety and efficacy of the delipid extracorporeal lipoprotein filter from plasma (DELP) system, a new low-density lipoprotein cholesterol (LDL-C) adsorption system, in acute ischemic stroke (AIS) patients.Patients and methodsIn the present study, a total of 180 AIS patients were enrolled during March 2019 to February 2021. They were divided into DELP group (n1 = 90) and the control group (n2 = 90). The treatment protocol and vascular access of DELP treatment was established and evaluated. For the DELP group, clinical data and laboratory results including plasma lipid and safety parameters before and after the apheresis were collected and analyzed. For all participants, neurological scores were assessed and recorded.ResultsFor the DELP group, 90 patients including 70 males and 20 females were included. The mean LDL-C was significantly decreased from 3.15 ± 0.80 mmol/L to 2.18 ± 0.63 mmol/L (30.79%, p

Abstract Background Lung adenocarcinoma (LUAD) is a fatal form of lung cancer with a poor prognosis. Coagulation system had been confirmed closely related to tumor progression and the hypercoagulable state encouraged the immune infiltration and development of tumor cells, leading to a poor prognosis in cancer patients. However, the use of the coagulation‐related genes (CRGs) for prognosis in LUAD has yet to be determined. In this study, we constructed an immune‐related signature (CRRS) and identified a potential coagulation‐related biomarker (P2RX1). Methods We obtained a total of 209 CRGs based on two coagulation‐related KEGG pathways, then developed the CRRS signature by using the TCGA‐LUAD RNA‐seq data via the procedure of LASSO‐Cox regression, stepwise‐Cox regression, univariate and multivariate Cox regression. Grouped by the CRRS, Kaplan–Meier survival curves and receiver operating characteristic curves were drawn for the training and validation sets, respectively. In addition, single‐sample gene set enrichment analysis was exploited to explore immune infiltration level. Moreover, immunophenotypes and immunotherapy grouped by CRRS were further analyzed. Results We developed an immune‐related signature (CRRS) composed of COL1A2, F2, PLAUR, C4BPA, and P2RX1 in LUAD. CRRS was an independent risk factor for overall survival and displayed stable and powerful performance. Additionally, CRRS possessed distinctly superior accuracy than traditional clinical variables and molecular features. Functional analysis indicated that the differentially high expressed genes in the low‐risk group significantly enriched in T cell and B cell receptor signaling pathways. The low‐risk group was sensitive to anti‐PD‐1/PD‐L1 immunotherapy and displayed abundant immune infiltration and immune checkpoint gene expression. Finally, we identified an independent prognostic gene P2RX1. Low expression of P2RX1 associated with poor overall survival and decreased immune infiltration. Conclusions Our study revealed a significant correlation between CRRS and immune infiltration. CRRS could serve as a promising tool to improve the clinical outcomes for individual LUAD patients.

In randomized clinical trials with right-censored time-to-event outcomes, the popular log-rank test without adjusting for baseline covariates is asymptotically valid for treatment effect under simple randomization of treatments but is too conservative under covariate-adaptive randomization. The stratified log-rank test, which adjusts baseline covariates in the test procedure by stratification, is asymptotically valid regardless of what treatment randomization is applied. In the literature, however, under simple randomization there is no affirmative conclusion about whether the stratified log-rank test is asymptotically more powerful than the unstratified log-rank test. In this article we show when the stratified and unstratified log-rank tests aim for the same null hypothesis and that, under simple randomization, the stratified log-rank test is asymptotically more powerful than the unstratified log-rank test in the region of alternative hypothesis that is specified by a Cox proportional hazards model. We also provide some discussion about why we do not have an affirmative conclusion in general.

Abstract Background The impact of retirement on physical activity among older individuals remains ambiguous. This study aims to investigate the influence of retirement on physical activity and delineate the trajectories of physical activity changes during the retirement transition among elderly Chinese residents. Additionally, we endeavor to examine the factors that contribute to each trajectory. Methods This longitudinal cohort study used data from four surveys of the China Health and Retirement Longitudinal Study and included a sample of 428 individuals who underwent formal retirement and provided information on physical activity. We employed generalized estimating equation to explore the impact of the retirement transition on physical activity among Chinese older adults. Latent class growth analysis was used to identify distinct trajectories of physical activity, and binary logistic regression was performed to identify pre-retirement factors influencing changes in physical activity. Results Our findings indicate that retirement can lead to a decline in physical activity among older Chinese residents (OR = 0.85, 95%CI 0.75 ~ 0.97). We identified three distinct trajectories of physical activity during the retirement transition: Trajectory 1 – “sustained low level of physical activity” (7.94%); Trajectory 2 – “middle level of physical activity with gradual decline” (69.16%); Trajectory 3 – “sustained high level of physical activity with significant fluctuations” (22.90%). Furthermore, we discovered that individuals in the “middle level of physical activity and gradual decline” trajectory were more likely to have an annual income exceeding 40,000 yuan (OR = 9.69, 95%CI 1.12 ~ 83.63), reside in urban areas (OR = 2.27, 95%CI 1.14 ~ 4.52), and have a fondness for playing Mahjong (OR = 2.42, 95%CI 1.18 ~ 5.00) compared to those in the “sustained high level of physical activity with significant fluctuations” trajectory. Additionally, having an annual income exceeding 40,000 yuan (OR = 19.67, 95%CI 1.30 ~ 298.61) predicted membership in the “sustained low level of physical activity” trajectory when compared to the “sustained high level of physical activity with significant fluctuations” trajectory. Conclusion Retirement represents a substantial milestone in the life course and is associated with notable alterations in physical activity patterns. Among older Chinese residents, the trajectories of physical activity during the retirement transition exhibit diverse paths and are influenced by pre-retirement factors, including annual income, residential location, and hobbies. The findings of this study have important implications for the formulation of policies aimed at promoting healthy aging among individuals approaching retirement age.

Oncolytic virotherapy is expected to provide a new treatment strategy for cancer. Aphrocallistes vastus lectin (AVL) is a Ca2+-dependent lectin receptor containing the conserved domain of C-type lectin and the hydrophobic N-terminal region, which can bind to the bird’s nest glycoprotein and D-galactose. Our previous studies suggested that the oncolytic vaccinia virus (oncoVV) armed with the AVL gene exerted remarkable replication and antitumor effects in vitro and in vivo. In this study, we found that oncoVV-AVL may reprogram the metabolism of hepatocellular carcinoma cells to promote ROS, and elevated ROS subsequently promoted viral replication and induced apoptosis. This study will provide a new theoretical basis for the application of oncoVV-AVL in liver cancer.

Abstract Gastrointestinal (GI) cancer is the most common cancer in the world and one of the main causes of cancer-related death. Clinically, surgical excision and chemotherapy are the main treatment methods for GI cancer, which is unfortunately accompanied with serious adverse reactions and drug toxicity, bringing irreversible damage to patients and seriously affecting the quality of life. Ganoderma lucidum (G. lucidum) has a long history of medicinal and edible use in China. Its bioactive compounds mainly include polysaccharides, triterpenes, and proteins, which have potential anti-tumor activities by inhibiting proliferation, inducing apoptosis, inhibiting metastasis, and regulating autophagy. Currently, there is no in-depth review on the anti-tumor effect of G. lucidum in GI cancer. Therefore, this review is an attempt to compile the basic characteristics, anti-GI caner mechanisms, and clinical application of G. lucidum, aiming to provide a reference for further research on the role of G. lucidum in the prevention and treatment of GI cancer from the perspective of traditional Chinese and western medicine. Graphical Abstract

Abstract Background Luminal breast cancer (BC) is the predominant subtype of breast cancer with a sustained risk of late recurrence and death. Understanding the molecular mechanisms for the oncogenesis of luminal BC would improve the prognosis for this large subset of patients. SPDEF was reported to be dysregulated in breast cancers. However, the biological functions and underlying molecular mechanism of SPDEF in luminal BC remains largely unknown. The aim of the present study was to elucidate the potential roles of SPDEF underlying subtype-specific functions in BC, especially in luminal subtypes. Methods The expressions and clinicopathological characteristics of SPDEF in luminal BC patients were evaluated bioinformatically. In vitro and in vivo assays were performed to investigate the oncogenic function and stemness maintenance of SPDEF in luminal BC. Chromatin immunoprecipitation (ChIP) and dual luciferase reporter assays were conducted to determine the transcription regulation of GALNT7 by SPDEF. GALNT7 levels in serum from luminal BC patients were further detected by enzyme-linked immunosorbent assay (ELISA). Results SPDEF is markedly upregulated in luminal BC and positively associated with tumor progression and poor prognosis. Furthermore, we confirmed that SPDEF enhanced the proliferation, migration, invasion and stemness of luminal BC cells in vitro as well the tumorigenicity in vivo. Mechanistically, we demonstrated the stimulative effect of SPDEF on the progression and stemness of luminal BC, which is mediated by its directly transcriptional target GALNT7. Clinically, we verified that the GALNT7 can be used as a noninvasive diagnostic marker. Noteworthy, the combined detection of serum GALNT7 and traditional tumor markers can enhance diagnostic accuracy thus is of vital importance in the early diagnosis of luminal BC. Conclusions Our study reveals a novel mechanism by which SPDEF transcriptionally activates GALNT7 via directly binding to its promoter to promote cell proliferation, motility and stemness, and led to luminal BC tumorigenesis and poor prognosis.

Abstract Objective Although several mucosal flap techniques have been reported to improve the outcomes in Draf IIb and Draf III procedures, there is scant knowledge on frontal ostium neo‐osteogenesis after reconstruction with mucosa flap. This study evaluates the potential benefits of mucosa flaps on frontal ostium neo‐osteogenesis after frontal sinus drill‐out procedures. Methods Forty‐three patients who underwent extended Draf IIb and Draf III were enrolled. Among them, 20 patients had frontal neo‐ostium (FNO) reconstructed by mucosal flap (group A), and 23 patients did not have neo‐ostium reconstruction (group B). The cross‐sectional area of FNO, frontonasal bone, and the amount of frontal neo‐osteogenesis (FNOG) were measured with OsiriX®. In addition, the Global Osteitis Scoring Scale (GOSS), Lund–Mackay score (LMS), and Lund–Kennedy score (LKS) were also evaluated. Results At one year postoperatively, the remaining neo‐ostium area was significantly larger in group A (p = .001), and group A had significantly less FNOG (p

Abstract Background Although radiotherapy has improved local control in esophageal squamous cell carcinoma (ESCC), a considerable number of patients still experience relapse due to resistance. In this study, we aimed to evaluate the effects of cetuximab on radiosensitivity in two ESCC cell lines (ECA109 and TE‐13) and to investigate their underlying mechanisms. Methods Cells were pretreated with or without cetuximab before irradiation. The MTT assay and clonogenic survival assay were performed to evaluate cell viability and radiosensitivity. Flow cytometry was performed to analyze cell cycle distribution and apoptosis. The γH2AX foci were counted to determine cellular DNA‐repairing capacity via immunofluorescence assay. The phosphorylation of key molecules involved in the epidermal growth factor receptor (EGFR) signaling pathway and DNA double‐strand break (DSB) repair were measured by western blot. Results Cetuximab alone was not sufficient to suppress cell viability, but significantly enhanced radiation‐induced inhibition of clonogenic survival in ECA109 and TE‐13. The radiation sensitivity enhancement ratio (SER) was 1.341 and 1.237 for ECA109 and TE‐13, respectively. ESCC cells treated with cetuximab were arrested at the G2/M phase in response to radiation. No significant increase in apoptotic rate was observed in irradiated cells that were treated with cetuximab. The average number of γH2AX foci increased in the combination group (cetuximab and radiation). Cetuximab suppressed phosphorylation of EGFR and downstream ERK, but had no significant effect on AKT. Conclusions These results indicate the potential for use of cetuximab as an effective radiosensitizer in ESCC. Cetuximab promotes G2/M cycle arrest and reduces DSB repair, as well as inhibiting EGFR and downstream ERK pathways in ESCC.

Abstract Objective In this study of patients hospitalized during acute SARS‐CoV2 infection with 6‐months of follow‐up data, we identified risk factors associated with the development of neuro‐PASC. Methods We conducted an exploratory, observational single‐center cohort study of patients hospitalized for COVID‐19 from November 2020 to March 2022. Our primary outcome was persistent neurocognitive symptoms, defined as fatigue, headache, loss of taste/smell, brain fog, confusion, concentration/memory/word finding difficulty, and/or change in speech present at 1‐month and persisting for 6‐months following acute SARS‐CoV2 infection. Secondary outcomes included persistent impairment scores on PROMIS cognitive function and abilities scales. Multivariate logistic regression analyses identified potential risk factors for neuro‐PASC. Results Of 89 participants, 60% reported persistent neurocognitive symptoms at 6‐months; fatigue was the most prevalent, occurring in 53% of participants, followed by brain fog in 34% of participants. Lower self‐reported socioeconomic status and increased pre‐COVID‐19 anxiety scores on the Hospital Anxiety and Depression Scale were associated with increased odds of developing persistent neurocognitive symptoms. Being female and of Hispanic descent were associated with increased odds of persistent cognitive function and ability impairment. Interpretation Sociodemographic factors and pre‐COVID‐19 anxiety symptoms may be important risk factors for neuro‐PASC. These findings underscore the need to assess various sociodemographic factors in research on PASC. Our study also highlights premorbid mental health symptoms as a potential predictor of persistent neurocognitive symptoms following hospitalization with SARS‐CoV2 infection.

Colitis is a chronic bowel disease characterized by damage to the lining of the large intestine, with its precise underlying causes remaining incompletely understood. In this study, we provide evidence that circular RNA circNlgn plays a pivotal role in promoting the development of colitis. Colitis patients produce significant higher levels of circNlgn. Transgenic mice expressing circNlgn exhibit heightened susceptibility to colitis development and progression, primarily attributed to the presence of the protein isoform Nlgn173 encoded by circNlgn. Nlgn173 undergoes translocation into cell nuclei, where it interacts with actin, impeding the binding of actin-related protein 2 and 3 (Arp2/3) complex to actin molecules. Consequently, this leads to a reduction in actin polymerization. Mechanistically, Nlgn173 enhances tyrosine-53 phosphorylation of nuclear actin, diminishing its capacity to interact with the Arp2/3 complex and causing a decrease in filamentous actin levels. These alterations in actin dynamics result in inhibited cell cycle progression, increased apoptosis, and decreased proliferation of colonic epithelial cells, thereby exacerbating colitis development and progression. In contrast, the silencing of circNlgn or the targeted inhibition of Nlgn173 translation and nuclear translocation leads to the promotion of nuclear actin polymerization, enhanced cell survival, and reduced apoptosis and ultimately improves the outcome of colitis in vivo. Interestingly, nuclear actin polymerization is highly related with expression of PIAS3, which modulates signal transducer and activator of transcription 3 and NF-κB activity in colitis. Strategies such as circNlgn knockdown and targeting nuclear actin polymerization of the colonic epithelium may explore a novel avenue for acute ulcerative colitis clinical intervention.

Natural resistance-associated macrophage proteins (NRAMPs) are a class of metal transporters found in plants that exhibit diverse functions across different species. Transporter proteins facilitate the absorption, distribution, and sequestration of metallic elements within various plant tissues. Despite the extensive identification of NRAMP family genes in various species, a full analysis of these genes in tree species is still necessary. Genome-wide identification and bioinformatics analysis were performed to understand the roles of NRAMP genes in copper (CuCl2) stress in Kandelia obovata (Ko). In Arachis hypogaea L., Populus trichocarpa, Vitis vinifera, Phaseolus vulgaris L., Camellia sinensis, Spirodela polyrhiza, Glycine max L. and Solanum lycopersicum, a genome-wide study of the NRAMP gene family was performed earlier. The domain and 3D structural variation, phylogenetic tree, chromosomal distributions, gene structure, motif analysis, subcellular localization, cis-regulatory elements, synteny and duplication analysis, and expression profiles in leaves and CuCl2 were all investigated in this research. In order to comprehend the notable functions of the NRAMP gene family in Kandelia obovata, a comprehensive investigation was conducted at the genomic level. This study successfully found five NRAMP genes, encompassing one gene pair resulting from whole-genome duplication and a gene that had undergone segmental duplication. The examination of chromosomal position revealed an unequal distribution of the KoNRAMP genes across chromosomes 1, 2, 5, 7, and 18. The KoNRAMPs can be classified into three subgroups (I, II, and SLC) based on phylogeny and synteny analyses, similar to Solanum lycopersicum. Examining cis-regulatory elements in the promoters revealed five hormone-correlated responsive elements and four stress-related responsive elements. The genomic architecture and properties of 10 highly conserved motifs are similar among members of the NRAMP gene family. The conducted investigations demonstrated that the expression levels of all five genes exhibited alterations in response to different levels of CuCl2 stress. The results of this study offer crucial insights into the roles of KoNRAMPs in the response of Kandelia obovata to CuCl2 stress.

To improve the precision of estimation and power of testing hypothesis for an unconditional treatment effect in randomized clinical trials with binary outcomes, researchers and regulatory agencies recommend using g-computation as a reliable method of covariate adjustment. However, the practical application of g-computation is hindered by the lack of an explicit robust variance formula that can be used for different unconditional treatment effects of interest. To fill this gap, we provide explicit and robust variance estimators for g-computation estimators and demonstrate through simulations that the variance estimators can be reliably applied in practice.

Abstract Background Esophageal cancer (EC) is a global health problem. Asia represents a huge burden of EC globally, and incidence and mortality vary considerably across different Asian regions. Methods Data on incidence, mortality, and preference were extracted from GLOBOCAN 2020. Age‐standardized incidence and mortality rates were calculated overall by sex, age, country, region, and continent. The predicted burden of incidence and mortality in 2040 was calculated based on global demographic projections. Results It was estimated there were 481 552 new cases of and 434 363 deaths from EC in Asia in 2020, accounting for 79.7% and 79.8% of world EC cases and deaths, respectively. EC incidence and mortality in Asia ranked the highest among all continents. Eastern Asia represents the highest age‐standardized world incidence rate (ASWIR) of 12.3 per 100 000 for all Asian regions. Western Asia represents the lowest ASWIR of 1.7 per 100 000, accounting for 0.7% of the globe. There exist obvious differences in epidemiological features in Asian countries, including incidence, mortality, prevalence, and mortality incidence ratio. There is forecast to be up to 781 000 new cases of EC in Asia by 2040, with increasing rates of 63% for incidence and 72% for mortality from 2020. Conclusions Asia has an increasing number of EC cases and deaths. Strategies for targeting in high‐incidence areas, the elderly, and survival should be prioritized to reduce the global EC burden, especially in low‐ and middle‐income countries in Asia.

Abstract Purpose Esophageal squamous cell carcinoma (ESCC) metastasizes in an unpredictable fashion to adjacent lymph nodes, including those along the recurrent laryngeal nerves (RLNs). This study is to apply machine learning (ML) for prediction of RLN node metastasis in ESCC. Methods The dataset contained 3352 surgically treated ESCC patients whose RLN lymph nodes were removed and pathologically evaluated. Using their baseline and pathological features, ML models were established to predict RLN node metastasis on each side with or without the node status of the contralateral side. Models were trained to achieve at least 90% negative predictive value (NPV) in fivefold cross-validation. The importance of each feature was measured by the permutation score. Results Tumor metastases were found in 17.0% RLN lymph nodes on the right and 10.8% on the left. In both tasks, the performance of each model was comparable, with a mean area under the curve ranging from 0.731 to 0.739 (without contralateral RLN node status) and from 0.744 to 0.748 (with contralateral status). All models showed approximately 90% NPV scores, suggesting proper generalizability. The pathology status of chest paraesophgeal nodes and tumor depth had the highest impacts on the risk of RLN node metastasis in both models. Conclusion This study demonstrated the feasibility of ML in predicting RLN node metastasis in ESCC. These models may potentially be used intraoperatively to spare RLN node dissection in low-risk patients, thereby minimizing adverse events associated with RLN injuries.

The MendelianRandomization package is a software package written for the R software environment that implements methods for Mendelian randomization based on summarized data. In this manuscript, we describe functions that have been added or edited in the package since version 0.5.0, when we last described the package and its contents. The main additions to the package since that time are: 1) new robust methods for performing Mendelian randomization, particularly in the cases of bias from weak instruments and/or winner’s curse, and pleiotropic variants, 2) methods for performing Mendelian randomization with correlated variants using dimension reduction to summarize large numbers of highly correlated variants into a limited set of principal components, 3) functions for calculating first-stage F statistics, representing instrument strength, in both univariable and multivariable contexts, and with uncorrelated and correlated genetic variants. We also discuss some pragmatic issues relating to the use of correlated variants in Mendelian randomization.

The MendelianRandomization package is a software package written for the R software environment that implements methods for Mendelian randomization based on summarized data. In this manuscript, we describe functions that have been added or edited in the package since version 0.5.0, when we last described the package and its contents. The main additions to the package since that time are: 1) new robust methods for performing Mendelian randomization, particularly in the cases of bias from weak instruments and/or winner’s curse, and pleiotropic variants, 2) methods for performing Mendelian randomization with correlated variants using dimension reduction to summarize large numbers of highly correlated variants into a limited set of principal components, 3) functions for calculating first-stage F statistics, representing instrument strength, in both univariable and multivariable contexts, and with uncorrelated and correlated genetic variants. We also discuss some pragmatic issues relating to the use of correlated variants in Mendelian randomization.

Summary: We sought to study the role of circulating cellular clusters (CCC) –such as circulating leukocyte clusters (CLCs), platelet-leukocyte aggregates (PLA), and platelet-erythrocyte aggregates (PEA)– in the immunothrombotic state induced by COVID-19. Forty-six blood samples from 37 COVID-19 patients and 12 samples from healthy controls were analyzed with imaging flow cytometry. Patients with COVID-19 had significantly higher levels of PEAs (p value

IntroductionSaccharomyces boulardii (S. boulardii) has shown clinical beneficial effect in inflammatory bowel diseases recently. However, the underlying mechanisms remain incompletely understood. The aim of present study was to tested whether S. boulardii targets gut microbiota to protect against the development of experimental colitis in mice.MethodsFemale C57BL/6 mice were gavaged with S. boulardii for 3 weeks before being challenged with dextran sulphate sodium to induce ulcerative colitis. Bodyweight, diarrhea severity, intestinal permeability, colonic histopathology, colonic inflammatory status, and epithelial cell death of mice were examined. The fecal microbiota and its metabolomic profiles were detected by 16S rDNA sequencing and UPLC-MS, respectively.Results and DiscussionSupplementation with S. boulardii significantly prevented weight loss and colon shortening, lowered colonic inflammation, ameliorated epithelial injury, and enhanced the intestinal barrier integrity in colitis mice. By inhibiting the abundance of pathogenic bacteria and increasing the probiotics abundance, S. boulardii improved the microbial diversity and restored the microbiota dysbiosis. Moreover, it also modulated microbial metabolome and altered the relative contents of metabolites involving amino acids, lipids, energy and vitamin metabolisms. These yeast-driven shifts in gut flora and metabolites are were associated with each other and with the inflammation profile in colitis. Collectively, S. boulardii exerts protective effects on colitis in mice by reshaping gut microbiome and its metabolic profile, indicating it as a promising therapeutic avenue.

Rapid progress in nanotechnology has advanced fundamental neuroscience and innovative treatment using combined diagnostic and therapeutic applications. The atomic scale tunability of nanomaterials, which can interact with biological systems, has attracted interest in emerging multidisciplinary fields. Graphene, a two-dimensional nanocarbon, has gained increasing attention in neuroscience due to its unique honeycomb structure and functional properties. Hydrophobic planar sheets of graphene can be effectively loaded with aromatic molecules to produce a defect-free and stable dispersion. The optical and thermal properties of graphene make it suitable for biosensing and bioimaging applications. In addition, graphene and its derivatives functionalized with tailored bioactive molecules can cross the blood–brain barrier for drug delivery, substantially improving their biological property. Therefore, graphene-based materials have promising potential for possible application in neuroscience. Herein, we aimed to summarize the important properties of graphene materials required for their application in neuroscience, the interaction between graphene-based materials and various cells in the central and peripheral nervous systems, and their potential clinical applications in recording electrodes, drug delivery, treatment, and as nerve scaffolds for neurological diseases. Finally, we offer insights into the prospects and limitations to aid graphene development in neuroscience research and nanotherapeutics that can be used clinically.

Background: Vaccination is the most effective way to prevent coronavirus disease 2019 (COVID-19). However, it is often less protective and does not significantly increase antibody levels, especially in individuals with impaired immune systems. Nevertheless, the immunocompetence can be enhanced using a natural immunomodulator, such as Dendrobium officinale aqueous extract (DoAE). Methods: To determine whether DoAE promotes antibody production, we treated healthy volunteers with DoAE during COVID-19 vaccination. Meanwhile, the control volunteers were given a placebo (cornstarch) during the vaccination. Antibody levels were measured at three-week intervals in the DoAE and control groups. Results: DoAE enhanced immunity and preserved immune cell homeostasis. However, the neutralizing antibody (nAb) levels in the DoAE group were lower than those in the control group. Analysis of the gut microbiota revealed that the abundance of anti-inflammatory flora was increased, while the pro-inflammatory flora was reduced in the DoAE group. Conclusion: DoAE has immunomodulatory and anti-inflammatory properties. Therefore, DoAE has the potential for COVID-19 prophylaxis, treatment, and recovery from the adverse effects of COVID-19. However, its anti-inflammatory activity affects the production of nAbs. Thus, DoAE may not be recommended for consumption during COVID-19 vaccination.

Underwater noise pollution has become a potential threat to aquatic animals in the natural environment. The main causes of such pollution are frequent human activities creating underwater environmental noise, including commercial shipping, offshore energy platforms, scientific exploration activities, etc. However, in aquaculture environments, underwater noise pollution has also become an unavoidable problem due to background noise created by aquaculture equipment. Some research has shown that certain fish show adaptability to noise over a period of time. This could be due to fish’s special auditory organ, i.e., their “inner ear”; meanwhile, otoliths and sensory hair cells are the important components of the inner ear and are also essential for the function of the auditory system. Recently, research in respect of underwater noise pollution has mainly focused on adult fish, and there is a lack of the research on the effects of underwater noise pollution on the development process of the auditory system in the embryonic development period. Thus, in this study, we collected embryo–larval samples of the small yellow croaker (Larimichthys polyactis) in four important stages of otic vesicle development through artificial breeding. Then, we used metabonomics and transcriptomics analyses to reveal the development process of the auditory system in the embryonic development period under background noise (indoor and underwater environment sound). Finally, we identified 4026 differentially expressed genes (DEGs) and 672 differential metabolites (DMs), including 37 DEGs associated with the auditory system, and many differences mainly existed in the neurula stage (20 h of post-fertilization/20 HPF). We also inferred the regulatory mode and process of some important DEGs (Dnmt1, CPS1, and endothelin-1) in the early development of the auditory system. In conclusion, we suggest that the auditory system development of L. polyactis begins at least in the neurula stage or earlier; the other three stages (tail bud stage, caudal fin fold stage, and heart pulsation stage, 28–35 HPF) mark the rapid development period. We speculate that the effect of underwater noise pollution on the embryo–larval stage probably begins even earlier.

Copper-containing amine oxidases (CuAOs) are known to have significant involvement in the process of polyamine catabolism, as well as serving crucial functions in plant development and response to abiotic stress. A genome-wide investigation of the CuAO protein family was previously carried out in sweet orange (Citrus sinensis) and sweet cherry (Prunus avium L.). Six CuAO (KoCuAO1-KoCuAO6) genes were discovered for the first time in the Kandelia obovata (Ko) genome through a genome-wide analysis conducted to better understand the key roles of the CuAO gene family in Kandelia obovata. This study encompassed an investigation into various aspects of gene analysis, including gene characterization and identification, subcellular localization, chromosomal distributions, phylogenetic tree analysis, gene structure analysis, motif analysis, duplication analysis, cis-regulatory element identification, domain and 3D structural variation analysis, as well as expression profiling in leaves under five different treatments of copper (CuCl2). Phylogenetic analysis suggests that these KoCuAOs, like sweet cherry, may be subdivided into three subgroups. Examining the chromosomal location revealed an unequal distribution of the KoCuAO genes across four out of the 18 chromosomes in Kandelia obovata. Six KoCuAO genes have coding regions with 106 and 159 amino acids and exons with 4 and 12 amino acids. Additionally, we discovered that the 2.5 kb upstream promoter region of the KoCuAOs predicted many cis elements linked to phytohormones and stress responses. According to the expression investigations, CuCl2 treatments caused up- and downregulation of all six genes. In conclusion, our work provides a comprehensive overview of the expression pattern and functional variety of the Kandelia obovata CuAO gene family, which will facilitate future functional characterization of each KoCuAO gene.

Pear black spot disease, caused by Alternaria alternata, is a devastating disease in pears and leads to enormous economic losses worldwide. In this investigation, we isolated a Streptomyces odonnellii SZF-179 from the rhizosphere soil of pear plants in China. Indoor confrontation experiments results showed that both SZF-179 and its aseptic filtrate had excellent inhibitory effects against A. alternata. Afterwards, the main antifungal compound of SZF-179 was identified as polyene, with thermal and pH stability in the environment. A microscopic examination of A. alternata mycelium showed severe morphological abnormalities caused by SZF-179. Protective studies showed that SZF-179 fermentation broth could significantly reduce the diameter of the necrotic lesions on pear leaves by 42.25%. Furthermore, the potential of fermentation broth as a foliar treatment to control black leaf spot was also evaluated. Disease indexes of ‘Hosui’ and ‘Wonwhang’ pear plants treated with SZF-179 fermentation broth were lower than that of control plants. Overall, SZF-179 is expected to be developed into a safe and broad-spectrum biocontrol agent. No studies to date have evaluated the utility of S. odonnellii for the control of pear black spot disease; our study fills this research gap. Collectively, our findings provide new insights that will aid the control of pear black spot disease, as well as future studies of S. odonnellii strains.

Due to the challenge of limited line of sight in the perception system of intelligent driving vehicles (cameras, radar, body sensors, etc.), which can only perceive threats within a limited range, potential threats outside the line of sight cannot be fed back to the driver. Therefore, this article proposes a safety perception detection method for beyond the line of sight for intelligent driving. This method can improve driving safety, enabling drivers to perceive potential threats to vehicles in the rear areas beyond the line of sight earlier and make decisions in advance. Firstly, the electronic toll collection (ETC) transaction data are preprocessed to construct the vehicle trajectory speed dataset; then, wavelet transform (WT) is used to decompose and reconstruct the speed dataset, and lightweight gradient noosting machine learning (LightGBM) is adopted to train and learn the features of the vehicle section speed. On this basis, we also consider the features of vehicle type, traffic flow, and other characteristics, and construct a quantitative method to identify potential threat vehicles (PTVs) based on a fuzzy set to realize the dynamic safety assessment of vehicles, so as to effectively detect PTVs within the over-the-horizon range behind the driver. We simulated an expressway scenario using an ETC simulation platform to evaluate the detection of over-the-horizon PTVs. The simulation results indicate that the method can accurately detect PTVs of different types and under different road scenarios with an identification accuracy of 97.66%, which verifies the effectiveness of the method in this study. This result provides important theoretical and practical support for intelligent driving safety assistance in vehicle–road collaboration scenarios.

Acoustic array sensor device for partial discharge detection is widely used in power equipment inspection with the advantages of non-contact and precise positioning compared with partial discharge detection methods such as ultrasonic method and pulse current method. However, due to the sensitivity of the acoustic array sensor and the influence of the equipment operation site interference, the acoustic array sensor device for partial discharge type diagnosis by phase resolved partial discharge (PRPD) map might occasionally presents incorrect results, thus affecting the power equipment operation and maintenance strategy. The acoustic array sensor detection device for power equipment developed in this paper applies the array design model of equal-area multi-arm spiral with machine learning fast fourier transform clean (FFT-CLEAN) sound source localization identification algorithm to avoid the interference factors in the noise acquisition system using a single microphone and conventional beam forming algorithm, improves the spatial resolution of the acoustic array sensor device, and proposes an acoustic array sensor device based on the acoustic spectrogram. The analysis and diagnosis method of discharge type of acoustic array sensor device can effectively reduce the system misjudgment caused by factors such as the resolution of the acoustic imaging device and the time domain pulse of the digital signal, and reduce the false alarm rate of the acoustic array sensor device. The proposed method is tested by selecting power cables as the object, and its effectiveness is proved by laboratory verification and field verification.