LncRNA CamK-A Regulates Ca2+-Signaling-Mediated Tumor Microenvironment Remodeling.

Cancer cells entail metabolic adaptation and microenvironmental remodeling to survive and progress. Both calcium (Ca2+) flux and Ca2+-dependent signaling play a crucial role in this process, although the underlying mechanism has yet to be elucidated. Through RNA screening, we identified one long noncoding RNA (lncRNA) named CamK-A (lncRNA for calcium-dependent kinase activation) in tumorigenesis. CamK-A is highly expressed in multiple human cancers and involved in cancer microenvironment remodeling via activation of Ca2+-triggered signaling. Mechanistically, CamK-A activates Ca2+/calmodulin-dependent kinase PNCK, which in turn phosphorylates IκBα and triggers calcium-dependent nuclear factor κB (NF-κB) activation. This regulation results in the tumor microenvironment remodeling, including macrophage recruitment, angiogenesis, and tumor progression. Notably, our human-patient-derived xenograft (PDX) model studies demonstrate that targeting CamK-A robustly impaired cancer development. Clinically, CamK-A expression coordinates with the activation of CaMK-NF-κB axis, and its high expression indicates poor patient survival rate, suggesting its role as a potential biomarker and therapeutic target.

Single cell analysis reveals the roles and regulatory mechanisms of type-I interferons in Parkinson's disease.

The pathogenesis of Parkinson's disease (PD) is strongly associated with neuroinflammation, and type I interferons (IFN-I) play a crucial role in regulating immune and inflammatory responses. However, the specific features of IFN in different cell types and the underlying mechanisms of PD have yet to be fully described. In this study, we analyzed the GSE157783 dataset, which includes 39,024 single-cell RNA sequencing results for five PD patients and six healthy controls from the Gene Expression Omnibus database. After cell type annotation, we intersected differentially expressed genes in each cell subcluster with genes collected in The Interferome database to generate an IFN-I-stimulated gene set (ISGs). Based on this gene set, we used the R package AUCell to score each cell, representing the IFN-I activity. Additionally, we performed monocle trajectory analysis, and single-cell regulatory network inference and clustering (SCENIC) to uncover the underlying mechanisms. In silico gene perturbation and subsequent experiments confirm NFATc2 regulation of type I interferon response and neuroinflammation. Our analysis revealed that microglia, endothelial cells, and pericytes exhibited the highest activity of IFN-I. Furthermore, single-cell trajectory detection demonstrated that microglia in the midbrain of PD patients were in a pro-inflammatory activation state, which was validated in the 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model as well. We identified transcription factors NFATc2, which was significantly up-regulated and involved in the expression of ISGs and activation of microglia in PD. In the 1-Methyl-4-phenylpyridinium (MPP+)-induced BV2 cell model, the suppression of NFATc2 resulted in a reduction in IFN-ß levels, impeding the phosphorylation of STAT1, and attenuating the activation of the NF-κB pathway. Furthermore, the downregulation of NFATc2 mitigated the detrimental effects on SH-SY5Y cells co-cultured in conditioned medium. Our study highlights the critical role of microglia in type I interferon responses in PD. Additionally, we identified transcription factors NFATc2 as key regulators of aberrant type I interferon responses and microglial pro-inflammatory activation in PD. These findings provide new insights into the pathogenesis of PD and may have implications for the development of novel therapeutic strategies.

Spatio-temporal spread and evolution of Lassa virus in West Africa.

BACKGROUND: Lassa fever is a hemorrhagic disease caused by Lassa virus (LASV), which has been classified by the World Health Organization as one of the top infectious diseases requiring prioritized research. Previous studies have provided insights into the classification and geographic characteristics of LASV lineages. However, the factor of the distribution and evolution characteristics and phylodynamics of the virus was still limited. METHODS: To enhance comprehensive understanding of LASV, we employed phylogenetic analysis, reassortment and recombination detection, and variation evaluation utilizing publicly available viral genome sequences. RESULTS: The results showed the estimated the root of time of the most recent common ancestor (TMRCA) for large (L) segment was approximately 634 (95% HPD: [385879]), whereas the TMRCA for small (S) segment was around 1224 (95% HPD: [10301401]). LASV primarily spread from east to west in West Africa through two routes, and in route 2, the virus independently spread to surrounding countries through Liberia, resulting in a wider spread of LASV. From 1969 to 2018, the effective population size experienced two significant increased, indicating the enhanced genetic diversity of LASV. We also found the evolution rate of L segment was faster than S segment, further results showed zinc-binding protein had the fastest evolution rate. Reassortment events were detected in multiple lineages including sub-lineage IIg, while recombination events were observed within lineage V. Significant amino acid changes in the glycoprotein precursor of LASV were identified, demonstrating sequence diversity among lineages in LASV. CONCLUSION: This study comprehensively elucidated the transmission and evolution of LASV in West Africa, providing detailed insights into reassortment events, recombination events, and amino acid variations.

High-mind wandering correlates with high risk for problematic alcohol use in China and Germany.

Everyone experiences the natural ebb and flow of task-unrelated thoughts. Given how common the fluctuations in these thoughts are, surprisingly, we know very little about how they shape individuals' responses to alcohol use. Here, we investigated if mind wandering is associated with a risk of developing problematic alcohol use. We undertook an online survey among the general population in China (N = 1123) and Germany (N = 1018) from December 2021 to February 2022 and examined the subjective experience of mind wandering and problematic alcohol use through the Mind Wandering Questionnaire (MWQ) and the Alcohol Use Disorders Identification Test (AUDIT). We compared mind wandering and problematic alcohol use between two countries and investigated the association between MWQ scores with AUDIT scores. We found higher scores on the MWQ and a high percentage of problematic alcohol use (i.e., AUDIT score ≥ 8) in Germany (22.5%) as compared to in China (14.5%). Higher self-reported mind wandering was associated with higher AUDIT scores. AUDIT scores were increased mostly in male, elder, and high-mind wandering people. Our findings highlight that mind wandering and problematic alcohol use enhanced in Germany as compared to in China. Our study sheds light on the relationship between mind wandering and problematic alcohol use that may help to further investigate causal effects of interventions.

Prognostic Value of Neutrophil/Lymphocyte Ratio for Pulmonary Embolism: A Meta-Analysis and External Validation.

BACKGROUND: Prognostic value of neutrophil/lymphocyte ratio (NLR) for pulmonary embolism (PE) has been reported in several retrospective studies. The purpose of this investigation was to perform a pooled analysis and external validation of predictive value of NLR. METHODS: PubMed, Embase, and Cochrane databases were searched from inception to November 5, 2022. A random effects model was used. Grade was used to evaluate the certainty of evidence. External validation was conducted in clinical cohorts before and after a propensity scoring matching (PSM). Covariates include basic clinical characteristics, such as age, gender, etc. The value of NLR in prediction model was also evaluated. RESULTS: A total of 15 studies comprising 5,874 patients were included. Pooled risk ratio of NLR was 2.33 (95% confidence interval [CI]: 1.97-2.75), with an area under the curve of 0.78 (95% CI: 0.74-0.81), a sensitivity of 0.75 (95% CI: 0.71-0.79), a specificity of 0.67 (95% CI: 0.61-0.73), and a median cut-off value of 5.7. Grade of Recommendations Assessment Development and Evaluation (GRADE) certainty analysis showed the quality of the evidence was moderate. Before (n = 336) and after (n = 152) propensity scoring matching, risk ratio of NLR was 2.69 (95% CI: 1.04-6.97) and 6.58 (95% CI: 1.99-17.75). A prediction model consisting of NLR, age, D-dimer, and simplified PE severity index had an area under the curve of 0.809 (95% CI: 0.738-0.88), a sensitivity of 0.638 (95% CI: 0.511-0.745), and a specificity of 0.851 (95% CI: 0.709-0.917). Net reclassification index (12%, P = 0.035) and integrated discrimination improvement (17%, P = 0.022) indicated an improvement caused by NLR. CONCLUSIONS: Prognostic value of NLR for PE was confirmed by meta-analysis and validated in an independent cohort, deserving further clinical application.

Development of a nomogram for predicting acute pain among patients after abdominal surgery: A prospective observational study.

AIMS: To develop a nomogram to provide a screening tool for recognising patients at risk of post-operative pain undergoing abdominal operations. BACKGROUND: Risk prediction models for acute post-operative pain can allow initiating prevention strategies, which are valuable for post-operative pain management and recovery. Despite the increasing number of studies on risk factors, there were inconsistent findings across different studies. In addition, few studies have comprehensively explored predictors of post-operative acute pain and built prediction models. DESIGN: A prospective observational study. METHODS: A total of 352 patients undergoing abdominal operations from June 2022 to December 2022 participated in this investigation. A nomogram was developed for predicting the probability of acute pain after abdominal surgery according to the results of binary logistic regression. The nomogram's predictive performance was assessed by discrimination and calibration. Internal validation was performed via Bootstrap with 1000 re-samplings. RESULTS: A total of 139 patients experienced acute post-operative pain following abdominal surgery, with an incidence of 39.49%. Age <60, marital status (unmarried, divorced, or widowed), consumption of intraoperative remifentanil >2 mg, indwelling of drainage tubes, poor quality sleep, high pain catastrophizing, low pain self-efficacy, and PCIA not used were predictors of inadequate pain control in patients after abdominal surgery. Using these variables, we developed a nomogram model. All tested indicators showed that the model has reliable discrimination and calibration. CONCLUSIONS: This study established an online dynamic predictive model that can offer an individualised risk assessment of acute pain after abdominal surgery. Our model had good differentiation and calibration and was verified internally as a useful tool for risk assessment. RELEVANCE TO CLINICAL PRACTICE: The constructed nomogram model could be a practical tool for predicting the risk of experiencing acute post-operative pain in patients undergoing abdominal operations, which would be helpful to realise personalised management and prevention strategies for post-operative pain. REPORTING METHOD: The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines were adopted in this study. PATIENT OR PUBLIC CONTRIBUTION: Before the surgery, research group members visited the patients who met the inclusion criteria and explained the purpose and scope of the study to them. After informed consent, they completed the questionnaire. The patients' pain scores (VAS) were regularly assessed and documented by the bedside nurse for the first 3 days following surgery. Other information was obtained from medical records.

Revisiting the World's Strictest COVID-19 Lockdown: Formidable Mental Health Challenges.

INTRODUCTION: Many nations have implemented lockdowns to prevent and minimize the spread of infections in healthcare settings. However, the impact of lockdown duration on mental health remains controversial. METHODS: We conducted a retrospective study using online questionnaires to assess the mental health status of the general population during the Shanghai lockdown period from March to May 2022. The mental health of the participants was evaluated by the 12-item General Health Questionnaire (GHQ-12), in which a cut-off score of 12 or more indicated psychological distress. A logistic regression model was used to evaluate the relationship between lockdown duration and mental health. RESULTS: Among 2139 participants (mean age: 26.12 years, standard deviation: 6.37, 731 females; 1378 unmarried; 1099 Shanghai residents), approximately 47% reported psychological distress (GHQ-12≥12). Participants exposed to lockdown reported significantly higher GHQ-12 scores (11.93±6.81 vs. 8.73±6.35, p<0.001). In our logistic regression model, participants who experienced the longest lockdown (43-61 days) had a significantly higher risk of psychological distress compared with those who did not (odds ratio: 3.10, 95% confidence interval: 2.06-4.70, p<0.001). DISCUSSION: Lockdown duration significantly affects mental health, with longer lockdown duration being associated with worse mental health status. The relationship between lockdown and mental health should not be neglected in case of lockdown in response to future pandemics.

Biomechanical properties of lumbar vertebral ring apophysis cage under endplate injury: a finite element analysis.

OBJECTIVE: This study aimed to compare the biomechanical properties of lumbar interbody fusion involving two types of cages. The study evaluated the effectiveness of the cage spanning the ring apophysis, regardless of the endplate's integrity. METHODS: A finite element model of the normal spine was established and validated in this study. The validated model was then utilized to simulate Lateral Lumbar Interbody Fusion (LLIF) with posterior pedicle screw fixation without posterior osteotomy. Two models of interbody fusion cage were placed at the L4/5 level, and the destruction of the bony endplate caused by curetting the cartilaginous endplate during surgery was simulated. Four models were established, including Model 1 with an intact endplate and long cage spanning the ring apophysis, Model 2 with endplate decortication and long cage spanning the ring apophysis, Model 3 with an intact endplate and short cage, and Model 4 with endplate decortication and short cage. Analyzed were the ROM of the fixed and adjacent segments, screw rod system stress, interface stress between cage and L5 endplate, trabecular bone stress on the upper surface of L5, and intervertebral disc pressure (IDP) of adjacent segments. RESULTS: There were no significant differences in ROM and IDP between adjacent segments in each postoperative model. In the short cage model, the range of motion (ROM), contact pressure between the cage and endplate, stress in L5 cancellous bone, and stress in the screw-rod system all exhibited an increase ranging from 0.4% to 79.9%, 252.9% to 526.9%, 27.3% to 133.3%, and 11.4% to 107%, respectively. This trend was further amplified when the endplate was damaged, resulting in a maximum increase of 88.6%, 676.1%, 516.6%, and 109.3%, respectively. Regardless of the integrity of the endplate, the long cage provided greater support strength compared to the short cage. CONCLUSIONS: Caution should be exercised during endplate preparation and cage placement to maintain the endplate's integrity. Based on preoperative X-ray evaluation, the selection of a cage that exceeds the width of the pedicle by at least 5 mm (ensuring complete coverage of the vertebral ring) has demonstrated remarkable biomechanical performance in lateral lumbar interbody fusion procedures. By opting for such a cage, we expect a reduced occurrence of complications, including cage subsidence, internal fixation system failure, and rod fracture.

Longitudinal metabolomics profiling of serum amino acids in rotenone-induced Parkinson's mouse model.

Recently, the detailed etiology and pathogenesis of Parkinson's disease (PD) have not been fully clarified yet. Increasing evidences suggested that the disturbance of peripheral branched-chain amino acids (BCAAs) metabolism can promote the occurrence and progression of neurodegenerative diseases through neuroinflammatory signaling. Although there are several studies on the metabolomics of PD, longitudinal study of metabolic pathways is still lacking. Therefore, the purpose of the present study was to determine the longitudinal alterations in serum amino acid profiles in PD mouse model. Gas chromatography-mass spectrometry (GC-MS) was applied to detect serum amino acid concentrations in C57BL/6 mice after 0, 3 and 4 weeks of oral administration with rotenone. Then the data were analysed by principal component analysis (PCA) and orthogonal projection to latent structures (OPLS) analysis. Finally, the correlations between different kinds of serum amino acids and behaviors in rotenone-treated mice were also explored. Compared with 0-week mice, the levels of L-isoleucine and L-leucine were down-regulated in 3-week and 4-week mice, especially in 4-week mice. Moreover, the comprehensive analysis showed that L-isoleucine and L-leucine were negatively correlated with pole-climbing time and positively correlated with fecal weight and water content of PD mice. These results not only suggested that L-isoleucine and L-leucine may be potential biomarkers, but also pointed out the possibility of treating PD by intervening in the circulating amino acids metabolism.

Neuroleptic malignant-like syndrome associated multiple system atrophy: report on three cases.

BACKGROUND: Multiple system atrophy (MSA) associated with neuroleptic malignant-like syndrome (NMLS) is rare and few cases have been described in the literature. CASE PRESENTATION: In the present study, three patients with MSA associated with NMLS were analyzed from January 2012 to January 2020 to characterize their clinical presentations. Data collected from the patients for analysis included general patient history, the fluctuation and severity of disease symptoms, the indicated therapies and disease progression at follow-up. All patients had histories of sudden withdrawal or reduction of levodopa prior to the onset of symptoms. Clinical presentations were characterized by hyperthermia, autonomic dysfunction, worsening of extrapyramidal symptoms, and elevated serum creatine kinase (CK) levels. During hospitalization, one patient rapidly progressed and died, while the other two patients were successfully treated. CONCLUSIONS: Early diagnosis and treatment are very important for patient outcomes in NMLS. Notably, the correct dose and time of administration of dopaminergic medication may be key in treating NMLS.

High level of TXNDC9 predicts poor prognosis and contributes to the NF-κB-regulated metastatic potential in gastric cancer.

Gastric cancer (GC) is the most frequent malignant tumor in the digestive system, with high metastasis potential and poor prognosis. This study aimed to investigate the prognostic value and biological function of thioredoxin domain-containing protein 9 (TXNDC9) in GC. The expression of TXNDC9 was analyzed based on The Cancer Genome Atlas (TCGA) database. The prognostic value of TXNDC9 was evaluated by Kaplan-Meier curves and Cox regression analysis. The mRNA and protein expression of TXNDC9 were analyzed using quantitative real-time PCR and western blot analysis. The effects of TXNDC9 on GC cell invasion and EMT were assessed in vitro, and its effects on tumorigenesis were confirmed using animal experiments. The activity of the NF-κB signaling pathway was examined by both in vitro and in vivo experiments. TXNDC9 was highly expressed in GC tissues and cell lines. A high level of TXNDC9 was associated with poor overall survival and served as an independent prognostic biomarker in GC patients. The knockdown of TXNDC9 led to restrained GC cell invasion, microtubule formation, and EMT in vitro, and suppressed tumorigenesis in vivo. In addition, the NF-κB signaling pathway was demonstrated to mediate the functional role of TXNDC9 in GC. In conclusion, this study found that high TXNDC9 predicted poor prognosis in GC, and served as an oncogene by enhancing tumor cell invasion and EMT through the NF-κB signaling pathway.

Role of the gut-microbiota-metabolite axis in the rotenone model of early-stage Parkinson's Disease.

Gastrointestinal symptoms are common in the early-stage Parkinson's disease (PD), but its potential pathogenesis remains unclear. Therefore, in the present study, we used the 16S ribosomal RNA gene sequencing and gas chromatography coupled with mass spectrometry-based metabolomics to investigate the alterations of gut microbiome and serum amino acid levels in the early-stage PD mice model induced with rotenone. The results demonstrated that the microbial taxa at phylum, family and genus levels remarkably altered in rotenone-induced mice relative to vehicle-induced mice. The rotenone-induced mice had higher relative abundance of Flavobacteriaceae, Staphylococcaceae, and Prevotellaceae as well as lower relative abundance of Lachnospiraceae_UCG-001, Ruminiclostridium, and Prevotellaceae_NK3B31_group than vehicle-induced mice. The evaluation of serum amino acids revealed the alterations in several classes of amino acids, including L-proline, L-alanine, L-serine, L-asparagine, L-threonine, L-glutamine, L-methionine, and L-4-hydroxyproline. Notably, the altered serum amino acid levels were significantly associated with the abundance of gut microbiota, especially Ruminococcaceae and Ruminiclostridium. Our study explored the possible role of the gut-microbiota-metabolite axis in the early-stage PD and provided the possibility of prevention and treatment of PD by gut-microbiota-metabolite axis in the future.

LncRNA wires up Hippo and Hedgehog signaling to reprogramme glucose metabolism.

The Hippo pathway plays essential roles in organ size control and cancer prevention via restricting its downstream effector, Yes-associated protein (YAP). Previous studies have revealed an oncogenic function of YAP in reprogramming glucose metabolism, while the underlying mechanism remains to be fully clarified. Accumulating evidence suggests long noncoding RNAs (lncRNAs) as attractive therapeutic targets, given their roles in modulating various cancer-related signaling pathways. In this study, we report that lncRNA breast cancer anti-estrogen resistance 4 (BCAR4) is required for YAP-dependent glycolysis. Mechanistically, YAP promotes the expression of BCAR4, which subsequently coordinates the Hedgehog signaling to enhance the transcription of glycolysis activators HK2 and PFKFB3. Therapeutic delivery of locked nucleic acids (LNAs) targeting BCAR4 attenuated YAP-dependent glycolysis and tumor growth. The expression levels of BCAR4 and YAP are positively correlated in tissue samples from breast cancer patients, where high expression of both BCAR4 and YAP is associated with poor patient survival outcome. Taken together, our study not only reveals the mechanism by which YAP reprograms glucose metabolism, but also highlights the therapeutic potential of targeting YAP-BCAR4-glycolysis axis for breast cancer treatment.

Screening of potential vaccine candidates against pathogenic Brucella spp. using compositive reverse vaccinology.

Brucella spp. are Gram-negative, facultative intracellular bacteria that cause brucellosis in humans and various animals. The threat of brucellosis has increased, yet currently available live attenuated vaccines still have drawbacks. Therefore, subunit vaccines, produced using protein antigens and having the advantage of being safe, cost-effective and efficacious, are urgently needed. In this study, we used core proteome analysis and a compositive RV methodology to screen potential broad-spectrum antigens against 213 pathogenic strains of Brucella spp. with worldwide geographic distribution. Candidate proteins were scored according to six biological features: subcellular localization, antigen similarity, antigenicity, mature epitope density, virulence, and adhesion probability. In the RV analysis, a total 32 candidate antigens were picked out. Of these, three proteins were selected for assessment of immunogenicity and preliminary protection in a mouse model: outer membrane protein Omp19 (used as a positive control), type IV secretion system (T4SS) protein VirB8, and type I secretion system (T1SS) protein HlyD. These three antigens with a high degree of conservation could induce specific humoral and cellular immune responses. Omp19, VirB8 and HlyD could substantially reduce the organ bacterial load of B. abortus S19 in mice and provide varying degrees of protection. In this study, we demonstrated the effectiveness of this unique strategy for the screening of potential broad-spectrum antigens against Brucella. Further evaluation is needed to identify the levels of protection conferred by the vaccine antigens against wild-type pathogenic Brucella species challenge.

Recombinant Human Thymosin Beta-4 Protects against Mouse Coronavirus Infection.

Coronaviruses (CoVs) are enveloped and harbor an unusually large (30-32 kb) positive-strand linear RNA genome. Highly pathogenic coronaviruses cause severe acute respiratory syndrome (SARS) (SARS-CoV and SARS-CoV-2) and Middle East respiratory syndrome (MERS) (MERS-CoV) in humans. The coronavirus mouse hepatitis virus (MHV) infects mice and serves as an ideal model of viral pathogenesis, mainly because experiments can be conducted using animal-biosafety level-2 (A-BSL2) containment. Human thymosin beta-4 (Tß4), a 43-residue peptide with an acetylated N-terminus, is widely expressed in human tissues. Tß4 regulates actin polymerization and functions as an anti-inflammatory molecule and an antioxidant as well as a promoter of wound healing and angiogenesis. These activities led us to test whether Tß4 serves to treat coronavirus infections of humans. To test this possibility, here, we established a BALB/c mouse model of coronavirus infection using mouse CoV MHV-A59 to evaluate the potential protective effect of recombinant human Tß4 (rhTß4). Such a system can be employed under A-BSL2 containment instead of A-BSL3 that is required to study coronaviruses infectious for humans. We found that rhTß4 significantly increased the survival rate of mice infected with MHV-A59 through inhibiting virus replication, balancing the host's immune response, alleviating pathological damage, and promoting repair of the liver. These results will serve as the basis for further application of rhTß4 to the treatment of human CoV diseases such as COVID-19.

Genome-wide identification and expression profiling of HD-ZIP gene family in Medicago truncatula.

The homeodomain-leucine zipper (HD-ZIP) transcription factors are important regulators in various developmental processes and responses to environmental stimuli. Currently, little information is available for HD-ZIP gene family in Medicago truncatula. Here we perform a genome-wide analysis of HD-ZIP gene family in M. truncatula. Totally 52 M. truncatula HD-ZIPs (MtHDZs) were identified and classified into four distinctive subfamilies (I to IV). Members clustered in the same subfamily shared similar gene structure and protein motifs. Fifty-one MtHDZs were non-evenly distributed on eight chromosomes. Segmental duplication and purifying selection mainly contributed to the expansion and retention of M. truncatula HD-ZIP gene family. Expression profiling using the publicly available microarray data revealed that MtHDZ genes exhibited distinctive tissue-specific patterns and divergent responses to drought and salt stresses. In addition, the expression profile between each paralogous pair diverged differentially. Our results identified potential targets for the genetic improvement of abiotic stress tolerance in Medicago.

Lamb Wave-Based Damage Localization Feature Enhancement and Extraction Method for Stator Insulation of Large Generators Using VMD and Wavelet Transform.

Lamb waves are used to locate any damage in the stator insulation structure of large generators. However, it is difficult to extract the features of Lamb wave signals in a strong background noise environment, thus significantly reducing the accuracy with which the damage is located. This paper proposes a method based on variational mode decomposition (VMD) and wavelet transform to enhance and extract the location features of stator insulation damage signals of large motors. First, considering that the characteristics of VMD are sensitive to noise, the Lamb wave detection signal is decomposed, denoised, and reconstructed; the reconstructed signal is then wavelet-transformed to extract the time of flight (TOF) of the damage-scattered wave as the damage location feature; finally, the damage location is determined using the TOF features. The proposed method is experimentally tested and verified under various noise environments. The results show that the VMD and wavelet transform methods can significantly improve the signal-to-noise ratio of Lamb wave detection signals and the accuracy with which the damage is located under strong background noise. This study extends the applicability of Lamb wave-based non-destructive detection of stator insulation damage in complex environments.

Effects of dietary grape pomace on the intestinal microbiota and growth performance of weaned piglets.

Grape pomace (GP) is an abundant by-product from wine production and is rich in phenolic compounds, unsaturated fatty acids, dietary fibre and beneficial bacteria. In this study, weaned piglets were fed a basic diet supplemented with 5% GP for 4 weeks. Compared with those in the control (CON) group, it was found that the proportion of Lactobacillus delbrueckii, Olsenella umbonata and Selenomonas bovis in the caecum and the villus height and villus height/crypt depth ratio (VCR) of the jejunum were both significantly increased in the GP group (p < 0.05). Meanwhile, at the mRNA expression level, several proinflammatory cytokines (IL-1ß, IL-8, IL-6 and TNF-α) were significantly downregulated (p < 0.05) in piglet caecal tissue, and the short-chain fatty acid receptors (GPR41 and GPR43) were not significantly upregulated. In contrast, the levels of IgG was significantly increased (p < 0.05) in the sera of weaned piglets in the GP group. However, no difference in growth performance between the two groups of piglets was detected. These results show that GP had no adverse effects on the growth performance of piglets, but GP can promote the content of some beneficial bacteria in the caecum; this effect is conducive to improving the disease resistance potential of piglets.

Exosomal protein CD82 as a diagnostic biomarker for precision medicine for breast cancer.

CD82, a member of the tetraspanin superfamily, has been proposed to exert its activity via tetra-transmembrane protein enriched microdomains (TEMs) in exosomes. The present study aimed to explore the potential of the exosome protein CD82 in diagnosing breast cancers of all stages and various histological subtypes in patients. The results strongly suggest that CD82 expression in breast cancer tissue was significantly lower than that in healthy and benign breast disease tissues. There was a significant negative correlation between CD82 expression in tissues and CD82 content in exosomes, which indicated that CD82 expression was redistributed from tissues to the blood with the development and metastasis of breast cancer.