Rapid Detection of Bacterial Resistance to ß-Lactam Antibiotics with a Relay-Response Chemiluminescence Assay.

Bacterial resistance caused by ß-lactamases has been a major threat to public health around the world, seriously weakening the efficacy of ß-lactam antibiotics, the most widely used therapeutic agents against infectious diseases. To detect the bacterial resistance to ß-lactam antibiotics, particularly specific type of ß-lactam antibiotics, in a rapid manner, we report herein a relay-response chemiluminescence assay. This assay mainly consists of two reagents: a ß-lactam-caged thiophenol and a thiophenol-sensitive chemiluminescence reporter, both of which are synthetically feasible. The selective hydrolysis of ß-lactam by ß-lactamase leads to the releasing of free thiophenol, which then triggers the emission of a chemiluminescence signal in a relay manner. Three thiophenol-caged ß-lactams, structural analogues of cephalothin, cefotaxime, and meropenem, respectively, have been synthesized. And the application of this assay with these analogues of ß-lactam antibiotics allows fast detection of ß-lactamase-expressing resistant bacteria and, more impressively, provides detailed information on the resistant scope of bacteria.

Enhancement of the organic acid content and antioxidant capacity of yellow whey through fermentation with Lacticaseibacillus casei YQ336.

Fermentation is considered an effective tool for improving the functional characteristics of food. In this study, Lacticaseibacillus casei YQ336 was used to ferment yellow whey, and physical and chemical analysis was performed to identify the changes in the nutritional components and antioxidant activity of the fermented yellow whey. Non-targeted metabolomics was used to study the transformation of small molecular substances in the fermented yellow whey. After 48 h of pure culture fermentation with L. casei YQ336, the pH of yellow whey decreased significantly (p < 0.05). Meanwhile, the content of total acids, organic acids, sugars, total phenols, and total flavonoids and the antioxidant activity showed a significant increase (p < 0.05). A total of 628 differential metabolites were identified between fermented and unfermented yellow whey samples, of which 293 were upregulated and 335 were downregulated. After fermentation, due to the growth and metabolic activity of L. casei YQ336, meaningful metabolites such as homovanillic acid, lactic acid, oxalic acid, L-glutamic acid, and phenylalanine, as well as phenyllactic acid, gallic acid, and genistein were produced. This increased the organic acid content and antioxidant activity of yellow whey. The findings provide a theoretical and practical basis for further research on the bio-functional activity of yellow whey and the recycling and utilization of food by-products.

Lightweight RepVGG-Based Cross-Modality Data Prediction Method for Solid Rocket Motors.

Solid rocket motors (SRMs) have been popularly used in the current aerospace industry. Performance indicators, such as pressure and thrust, are of great importance for rocket monitoring and design. However, the measurement of such signals requires high economic and time costs. In many practical situations, the thrust measurement error is large and requires manual correction. In order to address this challenging problem, a lightweight RepVGG-based cross-modality data prediction method is proposed for SRMs. An end-to-end data prediction framework is established by transforming data across different modalities. A novel RepVGG deep neural network architecture is built, which is able to automatically learn features from raw data and predict new time-series data of different modalities. The effectiveness of the proposed method is extensively validated with the field SRM data. The accurate prediction of the thrust data can be achieved by exploring the pressure data. After calculation, the percentage error between the predicted data and the actual data is less than 5%. The proposed method offers a promising tool for cross-modality data prediction in real aerospace industries for SRMs.

Fermentation improves antioxidant capacity and γ-aminobutyric acid content of Ganmai Dazao Decoction by lactic acid bacteria.

Introduction: Ganmai Dazao Decoction is a traditional Chinese recipe, and is composed of licorice, floating wheat, and jujube. Methods: Effects of lactic acid bacteria fermentation on the physicochemical properties, antioxidant activity, and γ-aminobutyric acid of Ganmai Dazao Decoction were studied. The changes of small and medium molecules in Ganmai Dazao Decoction before and after fermentation were determined by LC-MS non-targeted metabolomics. Results: The results showed that the contents of lactic acid, citric acid, acetic acid, and total phenol content increased significantly, DPPH free radical clearance and hydroxyl free radical clearance were significantly increased. γ-aminobutyric acid content was 12.06% higher after fermentation than before fermentation. A total of 553 differential metabolites were detected and identified from the Ganmai Dazao Decoction before and after fermentation by partial least squares discrimination and VIP analysis. Discussion: Among the top 30 differential metabolites with VIP values, the content of five functional substances increased significantly. Our results showed that lactic acid bacteria fermentation of Ganmai Dazao Decoction improves its antioxidant effects and that fermentation of Ganmai Dazao Decoction with lactic acid bacteria is an innovative approach that improves the health-promoting ingredients of Ganmai Dazao Decoction.

Effects of health qigong exercise on upper extremity muscle activity, balance function, and quality of life in stroke patients.

Introduction: This study explored the effects of Qigong exercises on upper extremity muscle activity, balance function, and quality of life in stroke patients. Methods: A total of 30 stroke patients were randomly allocated to either control group or Qigong group. In the Qigong group, participants completed an intervention of Qigong Baduanjin over 8 weeks. Data on the electromyographic activities of the biceps brachii muscle, triceps brachii muscle, and muscle coordination were obtained using surface electromyography and the co-contraction ratio (CCR). Data on balance were obtained using the PK254P balance function detection system. Quality of life was measured using the brief version of the World Health Organization Quality of Life scale. Results: The results for the Qigong group showed a significant difference in CCR of the triceps brachii muscle (p < 0.01). Concerning balance (assessed using the open-eye test), there was a significant decrease (p < 0.05) in Y-axis trajectory deviations and the Y-axis speed in the Qigong group. In the closed-eye test, the peripheral area of the Qigong group was significantly lower than that of the control group (p < 0.05). Significant differences were also observed in physical health (p < 0.05), psychological health (p < 0.01), environment (p < 0.01), and the total scores for quality of life (p < 0.01) in the Qigong group. Discussion: We conclude that Qigong exercises improve the quality of life in stroke patients and have positive effects on the coordination of limb extremities and balance function.

Fermentation improves flavors, bioactive substances, and antioxidant capacity of Bian-Que Triple-Bean Soup by lactic acid bacteria.

The ancient traditional Chinese drink Bian-Que Triple-Bean Soup made by fermentation (FTBS) of Lactococcus lactis subsp. lactis YM313 and Lacticaseibacillus casei YQ336 is a potential functional drink. The effect of fermentation on the flavor and biological activity of FTBS was evaluated by analyzing its chemical composition. Five volatile flavors were detected in modified FTBS. Fermentation decreased the proportion of nonanal (beany flavor substances) but significantly increased the total flavone contents, phenol contents and many bioactive small molecule substances in FTBS. The changes of these substances led to the significant improvement of FTBS sensory evaluation, antioxidant activity and prebiotic potential. This research provides a theoretical basis for the application of Lactic acid bacteria (LAB) in the fermentation of edible plant-based foods and transformation from traditional food to industrial production.

Unconventional stabilization of the human T-cell leukemia virus type 1 immature Gag lattice.

Human T-cell leukemia virus type 1 (HTLV-1) has an atypical immature particle morphology compared to other retroviruses. This indicates that these particles are formed in a way that is unique. Here we report the results of cryo-electron tomography (cryo-ET) studies of HTLV-1 virus-like particles (VLPs) assembled in vitro, as well as derived from cells. This work shows that HTLV-1 employs an unconventional mechanism of Gag-Gag interactions to form the immature viral lattice. Analysis of high-resolution structural information from immature CA tubular arrays reveals that the primary stabilizing component in HTLV-1 is CA-NTD. Mutagenesis and biophysical analysis support this observation. This distinguishes HTLV-1 from other retroviruses, in which the stabilization is provided primarily by the CA-CTD. These results are the first to provide structural details of the quaternary arrangement of Gag for an immature deltaretrovirus, and this helps explain why HTLV-1 particles are morphologically distinct.

HIV-2 Immature Particle Morphology Provides Insights into Gag Lattice Stability and Virus Maturation.

Retrovirus immature particle morphology consists of a membrane enclosed, pleomorphic, spherical and incomplete lattice of Gag hexamers. Previously, we demonstrated that human immunodeficiency virus type 2 (HIV-2) immature particles possess a distinct and extensive Gag lattice morphology. To better understand the nature of the continuously curved hexagonal Gag lattice, we have used the single particle cryo-electron microscopy method to determine the HIV-2 Gag lattice structure for immature virions. The reconstruction map at 5.5 Å resolution revealed a stable, wineglass-shaped Gag hexamer structure with structural features consistent with other lentiviral immature Gag lattice structures. Cryo-electron tomography provided evidence for nearly complete ordered Gag lattice structures in HIV-2 immature particles. We also solved a 1.98 Å resolution crystal structure of the carboxyl-terminal domain (CTD) of the HIV-2 capsid (CA) protein that identified a structured helix 12 supported via an interaction of helix 10 in the absence of the SP1 region of Gag. Residues at the helix 10-12 interface proved critical in maintaining HIV-2 particle release and infectivity. Taken together, our findings provide the first 3D organization of HIV-2 immature Gag lattice and important insights into both HIV Gag lattice stabilization and virus maturation.

Resistance Risk Assessment for the New OSBP Inhibitor Y18501 in Pseudoperonospora cubensis and Point Mutations (G705V, L798W, and I812F) in PscORP1 that Confer Resistance.

Y18501 is a new oxysterol-binding protein inhibitor (OSBPI) that shows strong inhibitory activity against Pseudoperonospora cubensis. In this study, the sensitivities of 159 Ps. cubensis isolates to Y18501 were determined, with EC50 values ranging from 0.001 to 11.785 µg/mL, indicating that a Y18501-resistant subpopulation has appeared in the field. Ten Y18501-resistant mutants were obtained by fungicide adaptation and displayed fitness equal to or stronger than their parental isolates, which suggests that the resistance risk of Ps. cubensis to Y18501 is high. The consecutive applications of Y18501 in the field resulted in the rapid resistance of Ps. cubensis and decreased control efficacy of cucumber downy mildew (CDM), which could be alleviated by compounding with mancozeb. A positive cross-resistance was detected between Y18501 and oxathiapiprolin. The amino acid substitutions G705V, L798W, and I812F in PscORP1 conferred resistance to Y18501 in Ps. cubensis, which was validated by molecular docking and molecular dynamics simulations.

Follow-up outcomes of asymptomatic brucellosis: a systematic review and meta-analysis.

Balancing the potentially serious outcomes of asymptomatic brucellosis and "waiting" for treatment in clinical practice is an urgent issue. Therefore, we assessed the follow-up outcomes and epidemiological characteristics of asymptomatic brucellosis in the absence of treatment to provide evidence-based clinical clues. We searched eight databases in which 3610 studies from 1990 to 2021 were related to the follow-up outcomes of asymptomatic brucellosis. Thirteen studies, involving 107 cases, were finally included. Regarding the follow-up outcomes, we examined the presence or absence of symptoms and decreased serum agglutination test (SAT) titre. During the 0.5-18 months follow-up period, the pooled prevalence of appearing symptomatic was 15.4% (95% CI 2.1%-34.3%), cases that remained asymptomatic were 40.3% (95% CI 16.6%-65.8%), and decreased SAT titre was observed in 36.5% (95% CI 11.6%-66.1%). Subgroup analysis indicated that the pooled prevalence of appearing symptomatic with follow-up times of less than 6 months, 6-12 months, and 12-18 months was 11.5%, 26.4%, and 47.6%, respectively. The student subgroup had a higher prevalence of symptoms (46.6%) than the occupational and family populations. In conclusion, asymptomatic brucellosis has a high likelihood of appearing symptomatic and its severity may be underestimated. Active screening of occupational and family populations should be enhanced, and special attention should be paid to high-titre students for early intervention, if necessary. Additionally, future prospective, long-term, and large-sample follow-up studies are essential.

Changes Observed in Potential Key Candidate Genes of Peripheral Immunity Induced by Tai Chi among Patients with Parkinson's Disease.

Parkinson's disease (PD) is a common progressive neurodegenerative disease characterized by motor dysfunction. Although the inhibition of inflammation by Tai Chi has been demonstrated to involve a peripheral cytokine response and may play an important role in improving the motor function of PD patients, the related specific molecular mechanisms of the peripheral immune response to Tai Chi are not fully understood. The microarray dataset 'GSE124676' for the peripheral immune response to Tai Chi of PD patients was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened and analyzed using weighted gene co-expression network analysis (WGCNA). A total of 136 DEGs were found in the PD patients after Tai Chi, suggesting an effect of Tai Chi on the peripheral immunity of PD patients. The DEGs are mainly involved in neutrophil activation, T-cell activation, and NOD-like receptor and IL-17 signaling pathways. Furthermore, six key candidate genes (FOS, FOSB, JUNB, ZFP36, CAMP and LCN2) that are involved in peripheral inflammation and the inhibition of inflammation induced by Tai Chi were observed. The results in the present study could be conducive to comprehensively understanding the molecular mechanism involved in the effect of Tai Chi on peripheral inflammation in PD patients and providing novel targets for future advanced research.

The Effects of Er Xian Decoction Combined with Baduanjin Exercise on Bone Mineral Density, Lower Limb Balance Function, and Mental Health in Women with Postmenopausal Osteoporosis: A Randomized Controlled Trial.

Background: Postmenopausal osteoporosis (PMOP) is a common disease in older women that can severely jeopardize their health. Previous studies have demonstrated the effect of Er xian decoction (EXD) or Baduanjin exercise (BE) on PMOP. However, reports on the effect of EXD combined with BE on PMOP are limited. This study aimed to investigate the impact of EXD combined with BE on bone mineral density (BMD), lower limb balance, and mental health in women with PMOP. Methods: A 1 : 1 : 1 simple randomization technique was employed. Fifty participants with postmenopausal osteoporosis were allocated to three groups: the EXD group (EXD = 15); the BE group (BE = 18); and the combined group (EXD + BE = 17). After both 8 weeks and 16 weeks of intervention treatment, participants improved significantly with respect to BMD and the one-leg standing test (OLST), Berg balance scale (BBS), timed up and go (TUG) test, self-anxiety scale (SAS), and self-rating depression scale (SDS). The results were used to compare the effect of the intervention on BMD, lower limb balance function, and mental health in patients with PMOP. Results: Compared to the EXD and BE groups, the EXD + BE group showed the strongest effects on BMD, lower limb balance function, and mental health (p < 0.01). A correlation between BMD and lower limb balance and mental health was noted in the EXD + BE group. The change in mental health (SAS score) was correlated with BMD (femoral neck) improvement. Conclusions: The present study demonstrates that EXD combined with BE (EXD + BE) may have a therapeutic advantage over both monotherapies for treating BMD, lower limb balance function, and mental health in patients with PMOP. The feasibility of the approach for a large-scale RCT was also confirmed. Er xian decoction combined with Baduanjin exercise (EXD + BE) might offer a viable treatment alternative for participants with postmenopausal osteoporosis given its promising effects in disease control and treatment, with good efficacy and safety profiles.

Human Immunodeficiency Virus Type 2 Capsid Protein Mutagenesis Reveals Amino Acid Residues Important for Virus Particle Assembly.

Human immunodeficiency virus (HIV) Gag drives virus particle assembly. The capsid (CA) domain is critical for Gag multimerization mediated by protein-protein interactions. The Gag protein interaction network defines critical aspects of the retroviral lifecycle at steps such as particle assembly and maturation. Previous studies have demonstrated that the immature particle morphology of HIV-2 is intriguingly distinct relative to that of HIV-1. Based upon this observation, we sought to determine the amino acid residues important for virus assembly that might help explain the differences between HIV-1 and HIV-2. To do this, we conducted site-directed mutagenesis of targeted locations in the HIV-2 CA domain of Gag and analyzed various aspects of virus particle assembly. A panel of 31 site-directed mutants of residues that reside at the HIV-2 CA inter-hexamer interface, intra-hexamer interface and CA inter-domain linker were created and analyzed for their effects on the efficiency of particle production, particle morphology, particle infectivity, Gag subcellular distribution and in vitro protein assembly. Seven conserved residues between HIV-1 and HIV-2 (L19, A41, I152, K153, K157, N194, D196) and two non-conserved residues (G38, N127) were found to significantly impact Gag multimerization and particle assembly. Taken together, these observations complement structural analyses of immature HIV-2 particle morphology and Gag lattice organization as well as provide important comparative insights into the key amino acid residues that can help explain the observed differences between HIV immature particle morphology and its association with virus replication and particle infectivity.

Human Retrovirus Genomic RNA Packaging.

Two non-covalently linked copies of the retrovirus genome are specifically recruited to the site of virus particle assembly and packaged into released particles. Retroviral RNA packaging requires RNA export of the unspliced genomic RNA from the nucleus, translocation of the genome to virus assembly sites, and specific interaction with Gag, the main viral structural protein. While some aspects of the RNA packaging process are understood, many others remain poorly understood. In this review, we provide an update on recent advancements in understanding the mechanism of RNA packaging for retroviruses that cause disease in humans, i.e., HIV-1, HIV-2, and HTLV-1, as well as advances in the understanding of the details of genomic RNA nuclear export, genome translocation to virus assembly sites, and genomic RNA dimerization.

Stereochemically altered cephalosporins as potent inhibitors of New Delhi metallo-ß-lactamases.

Antibiotic resistance caused by ß-lactamases, particularly metallo-ß-lactamases, has been a major threat to public health globally. New Delhi metallo-ß-lactamase-1 (NDM-1) represents one of the most important metallo-ß-lactamases; the production of NDM-1 in bacterial pathogen significantly reduces the efficacy of ß-lactam antibiotics, including life-saving carbapenems. Herein, we have demonstrated stereochemically altered cephalosporins as potent inhibitors against NDM-1, as well as mutants of NDM. The structure and activity relationship (SAR) study on over twenty cephalosporin analogues discloses the stereochemistry and the substituents on 7-position and 3'-position of cephalosporin are critical to suppress the activity of NDM-1 and the optimal compound 1u exhibited an IC50 of 0.13 µM. Furthermore, a crystal complex of NDM-1 and 1u has been obtained, suggesting this cephalosporin derivative inhibits enzyme activity by the formation of a relatively stable hydrolytic product-NDM-1 intermediate. The discovery in this study may pave the way to turn cephalosporin, a natural substrate of ß-lactamase, into an effective NDM-1 inhibitor to combat antibiotic resistance.

Prevalence of Varied Coat Coloration in a Yellow-Throated Marten (Martes flavigula) Population.

Mammalian coat color is determined by heritable variations such as disease, nutrition, and hormone levels. Variation in animal coat color is also considered an environmental indicator and provides clues for the study of population genetics and biogeography. Records of abnormal coloration in the wild are rare, not only because it is often selected against, but also because of the difficulties in detection of the phenomenon. We used long-term camera-trapping data to first report abnormal coat coloration in yellow-throated marten (Martes flavigula) in China. Six types of abnormal coloration were found only in the Northeast Tiger and Leopard National Park, Northeast China, which were not reported in other regions in China. A total of 268 videos of Martes flavigula contained normal coloration, 455 videos of individuals of the species contained abnormal coloration, 437 contained the 'gloving' type (martens with de-pigmented front toes, paws or lower forelimbs), while the remaining other 18 videos contained five types (different degrees of white-spotting and dilution). The higher relative abundance index (0.428, 'gloving' to 0.329, normal) and wide distribution area of the 'gloving' type indicated that this abnormal coat coloration type is usual in Northeast China, which may reflect genetic variability in the local population. These records will contribute to further research on animal coat color and its corresponding adaptive strategy.

Prevalence and relevant factors of positive RF in brucellosis patients with arthralgia.

BACKGROUND: Brucellosis is a critical zoonotic disease in the world, it is the non-specific arthralgia that make brucellosis patients easily misdiagnosed as rheumatoid arthritis (RA) in endemic regions. Elevated rheumatoid factor (RF) is an essential indicator of RA, and the RF in brucellosis patients is significantly higher than healthy people. Therefore, this study further explored the distribution of RF and the relevant factors of the RF positivity in brucellosis patients with arthralgia, in order to strengthen the recognition of physicians for brucellosis patients with RF positivity, especially in brucellosis-endemic areas, so as to avoid misdiagnosis and untimely treatment that may lead to malignant outcomes. METHODOLOGY AND PRINCIPAL FINDINGS: The medical records of all 572 brucellosis inpatients were collected in the Sixth People's Hospital of Shenyang, China from 2015 to 2016. After excluding 106 patients without arthralgia, 5 patients who unwilling to perform RF testing and 16 patients with diseases that may affect RF, 445 brucellosis inpatients with arthralgia were involved in this retrospective cross-sectional study. 143 (32.1%) patients with RF >10 IU/ml were classified into the RF positive group, with an average level of 16.5[12.2, 34.7] IU/ml, of which 45 (10.1%) patients were high-positive with RF >30 IU/ml. Multivariate logistic regression model was used to further analyze the relevant factors of the RF positivity and found that age, wrist joint pain and elevated C-reactive protein (CRP) were positively associated with RF positivity, with OR of 1.02 (P = 0.024), 8.94 (P = 0.008) and 1.79 (P = 0.019), respectively. CONCLUSION: The prevalence of positive RF in brucellosis patients with arthralgia was critical, nearly one-third of patients had RF positive. Elderly men brucellosis patients with arthralgia, wrist joint pain and elevated CRP were at high risk of positive RF. It is reminded that physicians should focus on differential diagnosis during clinical diagnosis and treatment, especially in brucellosis-endemic regions.

The association of depression with use of prescription drugs in adults with noncommunicable diseases: Based on NHANES in 2005-2016.

BACKGROUND: It is not clear how the noncommunicable diseases (NCDs) performed in the association of depression with use of prescription drugs. METHODS: This cross-sectional study involved 20,836 participants with at least one NCDs who aged over 20 years old in the National Health and Nutrition Examination Survey (NHANES) from 2005-2016. Ordinal logistic regression under complex sampling was used to examine the association of depression with use of prescription drugs in patients with different categories of NCDs. RESULT: Among patients with respiratory diseases (OR: 1.41, 95% CI: 1.13-1.76), genitourinary diseases (OR: 1.59, 95% CI: 1.28-1.98), and cardiovascular diseases (OR: 1.43, 95% CI: 1.27-1.60), the risk of depression was higher among those who used prescription drugs than those who did not. The results showed that the association of depression with use of prescription drugs was significantly stronger, especially in patients with genitourinary diseases ≥65 years of age (OR: 1.91, 95% CI: 1.01-3.61). Trend analysis showed that the categories of prescription drugs used and the risk of depression was significantly statistically different (P for trend <0.001). LIMITATIONS: Self-reported prevalence of depression may differ from actual prevalence of depression. The categories of NCDs studied in this article are limited and the association between specific drugs and depression is not analyzed. CONCLUSIONS: In patients with NCDs, use of prescription drugs increased the risk of depression, and this risk increased significantly, especially in patients with genitourinary diseases who aged over 65 years. The risk of depression was increasing with the categories of prescription drugs used.

Effects of mind-body exercise on cardiopulmonary function, blood pressure, and quality of life in CHD patients: A protocol for systematic review and meta-analysis.

BACKGROUND: Coronary heart disease (CHD) is one of the highest mortality diseases in the world, which seriously threatens human health and quality of life (QOL). The purpose of this study is to systematically analyze the effects of mind-body exercise on cardiopulmonary function, blood pressure and QOL in CHD patients, and to provide scientific evidence-based exercise prescription for patients with coronary heart disease. METHODS: This research review will include the following electronic databases from its establishment to December 2020: PubMed, EMBASE, Web of Science, Cochrane Library, the Chinese National Knowledge Infrastructure, the Chinese Science and Technology Periodical Database, and Wanfang. Objective to search randomized controlled trials (RCTs) about the effects of mind-body exercise on cardiopulmonary function, blood pressure and QOL in patients with coronary heart disease. CONCLUSION: This systematic review and meta-analysis will provide strong evidence for the efficacy and safety of mind-body exercise in patients with coronary heart disease. SYSTEMATIC REVIEW REGISTRATION: INPLASY202120016. ETHICS AND DISSEMINATION: Ethical approval will not be necessary since this systematic review and meta-analysis will not contain any private information of participants or violate their human rights.

Brucellosis screening and follow-up of seropositive asymptomatic subjects among household members of shepherds in China.

To measure the seroprevalence of high-exposure populations in brucellosis endemic areas and report the outcome and duration of seropositive asymptomatic subjects, we screened 595 family members of shepherds in Jilin Province, China and then followed up 15 seropositive asymptomatic subjects for 18 months. We found that the seropositive rate of 15.5%. Nearly half of seropositive asymptomatic subjects (7/15) developed into brucellosis in the short term; others were still seropositive asymptomatic or had decreased SAT titer in a longer time.