Genomic Characterization and Resistance Features of Streptococcus agalactiae Isolated from Non-pregnant Adults in Shandong, China.

BACKGROUND: Streptococcus agalactiae is a recognized pathogen that primarily affects infants and pregnant women. However, its increasingly important role in causing invasive infections among non-pregnant adults has become a significant health concern due to the severity and variety of its clinical impacts. METHODS: Nonduplicate S. agalactiae clinical strains associated with clinical infections (n=139) were isolated from non-pregnant adults in Shandong, China. Antibiotic susceptibility testing, whole-genome sequencing, and genomic analyses were conducted to characterize the genome and identify resistance features of these strains. RESULTS: The strains exhibited universal susceptibility to penicillin, ampicillin, cefotaxime, meropenem, linezolid, and vancomycin. Notably, high resistance rates were observed for erythromycin (91.4%), clindamycin (89.2%), levofloxacin (84.2%), tetracycline (54.0%) and, to a lesser extent, chloramphenicol (12.9%). Serotyping revealed seven serotypes and one non-typeable strain. Serotypes Ia, Ib, III, and V predominated, representing 95.7% of the strains. Nineteen sequence types were categorized into seven clonal complexes, with CC10 being the most prevalent at 48.9%. The resistance genes mreA (100%), ermB (70.5%), and tetM (46.0%) were commonly detected. All the isolates carried at least one pilus backbone determinant and one alpha-like protein gene, with the PI-1+PI-2a and the bca gene being the most frequent at 84.2% and 54.7%, respectively. CONCLUSIONS: While S. agalactiae strains in non-pregnant adults retain sensitivity to ß-lactam antibiotics, the elevated resistance to erythromycin, clindamycin, levofloxacin, and tetracycline is concerning. Given the growing elderly population worldwide, the burden of S. agalactiae infections is significant. Continuous surveillance of serotype distribution and antibiotic resistance patterns is imperative for targeted prevention and therapeutic strategies.

Unveiling the Emergence and Genetic Diversity of OXA-48-like Carbapenemase Variants in Shewanella xiamenensis.

An increase in the carbapenem-hydrolyzing capacity of class D ß-lactamase has been observed in strains of multiple species, posing a significant challenge to the control of antibiotic resistance. In this study, we aimed to investigate the genetic diversity and phylogenetic characteristics of new blaOXA-48-like variants derived from Shewanella xiamenensis. Three ertapenem-non-susceptible S. xiamenensis strains were identified, one isolated from the blood sample of an inpatient, the other two isolated from the aquatic environment. Phenotypic characterization confirmed that the strains were carbapenemase producers and exhibited antimicrobial resistance patterns to ertapenem, with some showing lower susceptibility to imipenem, chloramphenicol, ciprofloxacin, and tetracycline. No significant resistance to cephalosporins was observed. Sequence analysis revealed that one strain harbored blaOXA-181 and the other two strains harbored blaOXA-48-like genes, with open reading frame (ORF) similarities with blaOXA-48 ranging from 98.49% to 99.62%. The two novel blaOXA-48-like genes, named blaOXA-1038 and blaOXA-1039, respectively, were cloned and expressed in E. coli. The three OXA-48-like enzymes demonstrated significant hydrolysis activity against meropenem, and the classical ß-lactamase inhibitor had no significant inhibitory effect. In conclusion, this study demonstrated the diversity of the blaOXA gene and highlighted the emergence of novel OXA carbapenemases in S. xiamenensis. Further attention to S. xiamenensis and OXA carbapenemases is recommended for the effective prevention and control of antibiotic-resistant bacteria.

Tetrahydroxy stilbene glycoside ameliorates neuroinflammation for Alzheimer's disease via cGAS-STING.

Alzheimer's disease (AD), also known as senile dementia, is the most common degenerative disease of the central nervous system. Neuroinflammation is currently believed to be a crucial factor in the progression of AD, while its exact mechanism remains unclear. In this study, we demonstrated that AD transgenic mice exhibited cognitive deficits accompanied by the elevated serum and brain inflammation. Treating with a natural active ingredient tetrahydroxy stilbene glucoside (TSG) from the Chinese herb Polygonum multiflorum that has been well known for its unique anti-aging effect, learning-memory ability of AD mice was distinctly improved. Meanwhile, it was observed that the expressions of serum inflammatory cytokines and the activation of microglia in cerebral cortex and hippocampus were suppressed after TSG treatment, which was probably attributable to the decrease of cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) triggered immune response and NLRP3 inflammasome activation. Furthermore, cell culture experiments employing LPS combined with IFN-γ induced microglia activation showed that TSG reversed the polarization status of M1-type microglia to restore the quiescence, and cGAS-STING elevation was observed in the activated microglia and normalized by TSG incubation. In addition, TSG suppressed the production of inflammatory cytokines such as IL-1ß, IL-6, TNF-α, IFN-α and IFN-ß, as well as the expression of IFN regulatory proteins such as IFIT1 and IRF7 in the LPS/IFN-γ-stimulated inflammatory response in BV2 cell. Finally, it was also verified that TSG are, in part, through a cGAS-STING dependent pathway and triggered NLRP3 inflammasome activation to inhibit neuroinflammation through interfering with cGAS-STING inhibitors. Taken together, our findings highlight the health benefits of TSG and its potential application in preventing cognitive disorders by inhibiting neuroinflammation through cGAS-STING signaling pathway in AD.

Molecular characteristics and antibiotic resistance mechanisms of clindamycin-resistant Streptococcus agalactiae isolates in China.

Streptococcus agalactiae (Group B Streptococcus, GBS) is a major cause of neonatal infections with high morbidity and mortality, and clindamycin is the main antibiotic used to treat GBS infections in patients allergic to penicillin. We aimed to analyse the antibiotic sensitivity, sequence types, serotypes, virulence factors, and antibiotic resistance mechanisms of clinically isolated clindamycin-resistant S. agalactiae and provide basic data for the treatment, prevention, and control of clinical infection of S. agalactiae. A total of 110 strains of clindamycin-resistant S. agalactiae were collected from two tertiary hospitals in Hebei, China. We performed antibiotic sensitivity tests for 11 antibiotics on these strains and whole-genome sequencing analysis. All the strains were susceptible to penicillin, ampicillin, linezolid, vancomycin, tigecycline, and quinupristin-dalfopristin. Resistance to erythromycin, levofloxacin, tetracycline, and chloramphenicol were also observed. Genome sequence analysis revealed that all strains belonged to 12 sequence types (STs) related to six cloning complexes (CCs), namely CC10, CC19, CC23, CC651, CC1, and CC17. Five serotypes were identified, including IA, IB, II, III, and V. The most prominent resistance genes were mreA (100%) and ermB (81.8%). Furthermore, cfb, cylE, pavA and the gene cluster related to the pili were 100% present in all strains, followed by lmb (95.5%) and srr1 (67.2%). This study found that clindamycin-resistant S. agalactiae showed polymorphisms in molecular types and serotypes. Furthermore, multiple virulence factor genes have been identified in their genomes.

Tetrahydroxy stilbene glucoside alters neurogenesis and neuroinflammation to ameliorate radiation-associated cognitive disability via AMPK/Tet2.

Along with the extensive application of radiation in medical, military and other fields, human beings carry a greater risk of exposure to radiation environment that causes a range of physical injure, particularly to the brain in cognition. However, the radiation-associated cognitive disability is poorly understood and there is no effective prevention or long-term treatment. Here, we demonstrate that neurogenesis and neuroinflammation disorder are primarily involved in the pathophysiological basis of irradiation-induced cognitive decline. Furthermore, we discovered that tetrahydroxy stilbene glucoside (TSG), a natural active ingredient from Heshouwu that has been well known for its unique anti-aging effect as the Chinese herb, can be a promising mitigator to improve learning-memory ability by facilitating the neurogenesis in the proliferation and differentiation of the surviving neural progenitor cells via AMPK/Tet2, and attenuating the neuroinflammation in the microglial NLRP3 inflammasomes activation via AMPK in vivo. Additionally, TSG was also revealed to activate AMPK by molecular docking and kinase enzyme system assay in vitro. Taken together, our findings identify TSG, as the AMPK activator, prevents radiation-induced cognitive dysfunction by regulating neurogenesis and neuroinflammation via AMPK/Tet2 in rodents, and represents a very promising candidate for developing drugs that can be used for radiation-associated brain injury.

CoS2-TiO2@C Core-Shell fibers as cathode host material for High-Performance Lithium-Sulfur batteries.

Owing to the low cost, high energy density, and high theoretical specific capacity, lithium-sulfur batteries have been deemed as a potential choice for future energy storage devices. However, they also have suffered from several scientific and technical issues including low conductivity, polysulfides migration, and volume changes. In this study, CoS2-TiO2@carbon core-shell fibers were fabricated through combination of coaxial electrospinning and selective vulcanization method. The core-shell fibers are able to efficiently host sulfur, confine polysulfides, and accelerate intermediates conversion. This electrode delivers an initial specific capacity of 1181.1 mAh g-1 and a high capacity of 736.5 mAh g-1 after 300 cycles with high coulombic efficiency over 99.5% (capacity decay of 0.06% per cycle). This strategy of isolating interactant and selective vulcanization provides new ideas for effectively constructing heterostructure materials for lithium-sulfur batteries.

Preoperative Systemic Therapy Versus Upfront Surgery in HER2-Positive Breast Cancer in the Real World.

PURPOSE: To compare survival in different strategies, preoperative systemic treatment versus upfront surgery, in HER2-positive early breast cancer patients in the real world. METHODS: According to the actual upfront treatment, eligible patients from 2012 to 2015 were classified as preoperative systemic treatment or upfront surgery group prospectively. The primary endpoint is disease-free survival; the second endpoint is overall survival. All the outcomes were examined in the propensity score matching model and inverse probability of treatment weighting model. RESULTS: Included in the analysis were 1,067 patients (215 in the preoperative systemic treatment group, 852 in the upfront surgery group). In the propensity score matching model (matching at 1:1 ratio), the disease-free survival of the preoperative systemic treatment group was significantly higher than that of the upfront surgery group (hazard ratio, 0.572, 95%CI, 0.371-0.881, P, 0.012). In the inverse probability of treatment weighting model, there was no significant difference in disease-free survival between the two groups (hazard ratio, 0.946, 95%CI, 0.763-1.172, P, 0.609). For overall survival, there was no significant difference between the two groups. CONCLUSION: The HER2-positive patients who accepted preoperative systemic treatment had better disease-free survival than those who underwent upfront surgery by real-world statistic methods. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, identifier NCT04249440.

Tetrahydroxy Stilbene Glucoside Ameliorates Cognitive Impairments and Pathology in APP/PS1 Transgenic Mice.

Cognitive impairment is the main clinical manifestation of Alzheimer's disease (AD), and amyloid-ß (Aß) deposition and senile plaques are the characteristic neuropathological hallmarks in AD brains. This study aimed to explore the effect and mechanism of tetrahydroxy stilbene glucoside (TSG) on cognitive function in APP/PS1 mice during long-term administration. Here, we treated APP/PS1 model mice of AD with different doses of TSG (50 mg/kg and 100 mg/kg) for 5 to 17 months by gavage, and we further observed whether TSG could ameliorate the cognitive decline in APP/PS1 mice using behavioral tests, and investigated the possible mechanisms by immunohistochemistry and Western blotting. Our results showed that TSG treatment rescued the spatial and non-spatial learning and memory impairments of APP/PS1 mice at Morris water maze test and novel object recognition test. Furthermore, Aß40/42 deposition in the cortex and hippocampus of APP/PS1 mice treated with TSG was significantly reduced compared to the wild type mice using the immunohistochemical technique. Finally, Western blotting showed that TSG primarily decreased the APP expression to avoid the Aß plaque deposition in the cortex and hippocampus of mice. These results reveal the beneficial effects of TSG in APP/PS1-AD mice, which may be associated with the reduction of Aß deposits in the brain.

Automatic mental health identification method based on natural gait pattern.

Mental health has become a global problem, as over 300 million people worldwide suffer from depression and 200 million from anxiety disorders, which are ranked by the World Health Organization (WHO) as the first and sixth leading causes of disability, respectively. Due to the limited health resources, the traditional method of mental health diagnosis as one-to-one consultation is difficult to meet the needs of the large number of mental subhealth population. In this article, we propose a new method for mental health recognition that could identify potentially clinically significant symptoms of depression and anxiety based on daily gait. Eighty-eight participants were recruited, and their gaits were recorded by a digital camera. Then they were required to complete two rating scales, the Patient Health Questionnaire (PHQ-9) and the seven-item Generalized Anxiety Disorder Scale (GAD-7), to measure their depression and anxiety levels. Specifically, 18 key points of each individual's body trunk were captured from video, and both time-domain features and frequency-domain behavioral features were extracted for each key point. Lastly, machine-learning algorithms were utilized to build the mental health recognition models. Results showed that the proposed method is feasible and effective, with a correlation coefficient of depression (measured by PHQ-9) recognition above 0.5 and anxiety (measured by GAD-7) recognition above 0.4, achieving medium correlation. This new, low-cost, and convenient mental health recognition pattern could be applied in daily monitoring of mental health and large-scale preliminary screening of mental diseases.

Endoscopic thyroidectomy using gasless axillary approach for low-risk papillary thyroid carcinoma.

To evaluate the application of endoscopic thyroidectomy using gasless axillary approach (ET-GA) for low-risk papillary thyroid carcinoma (PTC). Patients with T1N0M0 Ⅰ PTC undergoing unilateral thyroid lobectomy with central neck dissection in Taizhou Cancer Hospital during January 2019 to June 2021 were enrolled in the study, including 35 cases treated with ET-GA (ET-GA group) and 35 cases treated with conventional open thyroidectomy (COT group). The surgical treatment effect, cosmetic effect and the effect on neck function were compared between two groups. Neck function was evaluated by neck pain score, neck injury index and dysphagia index. Cosmetic effect was evaluated by cosmetic effect satisfaction score. In the ET-GA group, all unilateral thyroid lobectomy with central neck dissection were successfully completed, and no case was converted to open surgery. The number of central lymph nodes dissected in the ET-GA was not statistically different from that in the COT group (>0.05), but the operation time was longer than that of the COT group (<0.01). In the ET-GA group, 2 cases (5.7%) had transient vocal cord paralysis and 1 case (2.9%) had postoperative bleeding. In the COT group, 1 case (2.9%) had transient vocal cord paralysis, no postoperative bleeding. There was no significant difference in the complication rate between two groups (>0.05). At and postoperatively, there was no significant difference in neck pain score and neck injury index between two groups (both >0.05); dysphagia index was lower in ET-GA group, but the difference was not statistically significant (>0.05). The cosmetic effect satisfaction score of ET-GA group was higher than that in the COT group at postoperatively (4.3±0.6 vs.1.0, <0.01). ET-GA has the same efficacy and safety as conventional open thyroidectomy in the treatment of low-risk PTC, and it improves the satisfaction of postoperative cosmetics.

Modular transitional nursing intervention improves pain-related self-management for cancer patients: Study protocol for a randomized controlled trial.

OBJECTIVE: To explore the effect of modular transitional nursing intervention on the improvement of self-management of the patients with cancer pain. METHOD: This study will be conducted from March 2021 to May 2022 at Affiliated Hospital of Beihua University. The experiment was granted through the Research Ethics Committee of Affiliated Hospital of Beihua University (4348-019). Eighty patients are analyzed in our study. The patients will be included if they are between 18 and 70 years old and are diagnosed with cancer, the pain intensity score on moderate level, the pain lasts for more than 3 days, and the patients who have signed the written informed consent. While the patients will be excluded if they have a documented history of drug or alcohol abuse, and patients with limited performance, and patients have a surgery in the past 3 days. The primary result mainly expresses as intergroup differences in self-management disorders (Barriers Questionnaire-II) associated with the cancer pain. And the secondary results include the quality of life (QOL) and pain intensity. All the analyses are implemented with SPSS for Windows Version 20.0. RESULTS: Table 1 will show the clinical outcomes between the 2 groups. CONCLUSION: A modular transitional nursing intervention appears to reduce pain in cancer patients. TRIAL REGISTRATION NUMBER: researchregistry6262.

Main Trend Extraction Based on Irregular Sampling Estimation and Its Application in Storage Volume of Internet Data Center.

The storage volume of internet data center is one of the classical time series. It is very valuable to predict the storage volume of a data center for the business value. However, the storage volume series from a data center is always "dirty," which contains the noise, missing data, and outliers, so it is necessary to extract the main trend of storage volume series for the future prediction processing. In this paper, we propose an irregular sampling estimation method to extract the main trend of the time series, in which the Kalman filter is used to remove the "dirty" data; then the cubic spline interpolation and average method are used to reconstruct the main trend. The developed method is applied in the storage volume series of internet data center. The experiment results show that the developed method can estimate the main trend of storage volume series accurately and make great contribution to predict the future volume value. .