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ABSTRACT The combination of aztreonam with ceftazidime/avibactam is considered a potential therapeutic approach for the treatment of infections caused by metallo-β-lactamase (MBL)-producing isolates. In this study, in vitro antibacterial activity of aztreonam with avibactam against 204 carbapenemase-producing Enterobacterales was determined by broth disk elution (BDE) method of two detection volumes (5- and 2-mL broth), with broth microdilution (BMD) method as a reference. For the BDE-5mL test, the categorical agreement (CA) of ATM+CZA-lo tube (aztreonam/ceftazidime/avibactam: 6/6/4 mg/L) was 99.5%, with 0.5% major error (ME) and 0% very major error (VME); the CA of 2ATM+CZA-lo tube (12/6/4 mg/L) was 100%, with no ME and VME. For the BDE-2mL test, the CA of ATM+2CZA-hi tube (15/10/4 mg/L) was 98.5%, with 0% ME and 37.5% VME; the CA of 2ATM+2CZA-hi tube (30/10/4 mg/L) was 97.1%, with 0% ME and 75% VME. The BDE-5 mL test is an economical and practical method for clinical microbiology laboratories to determine the antibacterial susceptibility of aztreonam with avibactam against Enterobacterales, especially the 2ATM+CZA-lo tube with a final concentration of 12/6/4 mg/L of aztreonam/ceftazidime/avibactam.IMPORTANCEInfections caused by metallo-β-lactamase (MBL)-producing Enterobacterales are increasingly reported worldwide, and it is a significant challenge for clinical infection treatment. MBLs are adept at hydrolyzing almost all traditional β-lactam antibiotics except aztreonam, and the enzyme activity cannot be inhibited by traditional or novel β-lactamase inhibitors. The good thing is that the combination of aztreonam with ceftazidime/avibactam has been proven to be one of the potential therapeutic approaches for treating infections related with MBL-producing isolates. Broth microdilution (BMD) method is recommended as a reference method for its accuracy, but it is too complex to perform in most routine laboratories. Finding a more convenient, practical, and accurate susceptibility testing method for aztreonam/avibactam in clinical microbiology laboratories is very necessary. Here, we evaluated the performance of broth disk elution (BDE) method for aztreonam in combination with ceftazidime/avibactam against Enterobacterales isolates, with BMD as a reference.

At present, soil contaminated with arsenic (As) and antimony (Sb) is escalating at an alarming rate, which is harmful to human health. In this study, Fe- and Mn-modified activated carbon (AC) and biochar (BC) were prepared and compared for the remediation of As- and Sb-contaminated soil. The effects on the speciation of As and Sb, soil pH, organic matter (SOM), and enzyme activity with various dosages and remediation times were investigated. The results showed that on the whole, the best stabilization effect of As and Sb was achieved with 3% FeMnBC. Furthermore, with increases in time and dosage, the immobilization effect on As and Sb was more significant. Fe/Mn-modified AC and BC enhanced soil pH, with 3% MnAC being particularly effective; 3% AC and 3% FeMnAC demonstrated the most pronounced enhancement in SOM. The modified carbon materials exhibited a dramatic increase in enzymatic activity. In particular, urease activity showed an increasing trend, and catalase activity first decreased and then increased over 30 days. Among the treatments, 3% MnAC showed the most significant enhancements in catalase and urease activities, whereas 1% FeMnBC had the most pronounced effect on increasing sucrase activity. This study provides theoretical support for the remediation of soil co-contaminated with As and Sb by Fe/Mn-modified AC and BC.

The widespread application of nanoparticles (NPs) in agriculture has not only enhanced the efficiency of agrochemical use but also introduced environmental pollution, potentially impacting human health through absorption and accumulation in edible plants. The purpose of this study was to evaluate the toxic effects and ecological risks of Cu2O nanoparticles (nCu2O) in the life cycle of soybean, and to provide a theoretical basis for the safe application of NPs in agriculture. Soybeans were grown in natural soil modified with nCu2O, bulk cuprous oxide (bCu2O) and copper sulfate (CuSO4) at concentrations of 0, 50, 200, and 800 mg/kg. Samples and grains from treated soybeans were collected at the flowering, podding, and seed-filling stages for analysis. The results indicated that treatments with nCu2O, bCu2O, and Cu2+ reduced the chlorophyll content in soybean leaves, thereby affecting photosynthesis. Significant reductions were observed in the net photosynthetic rate (Pn), the transpiration rate (Tr), stomatal conductance (Gs), the quantum yield of photosystem II (Y(II)), photochemical quenching (qP), and the electron transport rate (ETR) at high concentrations. However, the toxicity of nCu2O to photosynthesis recovers as the plant grows. Almost all treatments increased the levels of antioxidant enzymes (SOD, POD, CAT) and reduced oxidative stress. In the nCu2O and bCu2O treatments, grain protein content was significantly reduced, while fat and water content increased. Phosphorus (P) content decreased, whereas sulfur (S), potassium (K), magnesium (Mg) and calcium (Ca) contents increased. The accumulation of copper in plants followed the order nCu2O > bCu2O > Cu2+, with the bCu2O treatment being slightly more toxic than the nCu2O treatment, and both being more toxic than the Cu2+ treatment. The above data indicated that nCu2O had a dose-dependent effect, which significantly inhibited soybean growth and changed grain quality at high concentrations.

Abstract Background Increasing evidence has suggested that Corynebacterium kroppenstedtii is associated with some cases of granulomatous mastitis, mostly based on pathology or microbiology. We aimed to identify the clinical characteristics and treatment regimens for granulomatous mastitis with Corynebacterium kroppenstedtii infection. Understanding these clinical features is essential for patient care. Methods We retrospectively collected data on 201 patients who were pathologically diagnosed with granulomatous mastitis and had microbiological results of either Corynebacterium kroppenstedtii or no bacterial growth and recorded and analysed their demographics, clinical characteristics, and clinical outcomes. Results There were 107 patients in the CK group and 94 patients in the negative group. Sinus formation (x2 = 13.028, p = 0.000), time to complete remission at the first treatment period (Z = -3.027, p = 0.002), diameter of breast mass at first-time medical consultancy (Z = -2.539, p = 0.011) and recurrence (x2 = 4.953, p = 0.026) were statistically significant. Age (Z = -1.046, p = 0.295), laterality (x2 = 4.217, p = 0.121), time to presentation since the last delivery (x2 = 0.028, p = 0.868), BMI (Z = -0.947, p = 0.344), lactation time (Z = -1.378, p = 0.168), parity (x2 = 1.799, p = 0.180), gravida (Z = -0.144, p = 0.885), history of lactational mastitis or abscess (x2 = 0.115, p = 0.734), local trauma (x2 = 0.982, p = 0.322), hyperprolactinemia (x2 = 0.706, p = 0.401), erythema nodosum (x2 = 0.292, p = 0.589), and nipple discharge (x2 = 0.281, p = 0.596) did not demonstrate statistical significance. Regarding recurrence related to therapeutic strategy, except for surgery combined with immunosuppressants (x2 = 9.110, p = 0.003), which was statistically significant, none of the other treatment regimens reached statistical significance. The recurrence rate of patients in the CK group using rifampicin in their treatment course was 22.0% (x2 = 4.892, p = 0.027). Conclusions Granulomatous mastitis accompanied by Corynebacterium kroppenstedtii more easily forms sinuses and has a higher recurrence rate. Both of the clinical characteristics may indicate that Corynebacterium kroppenstedtii plays an important role in the development and progression of granulomatous mastitis. Lipophilic antibiotics may be essential for granulomatous mastitis with Corynebacterium kroppenstedtii infection.

Abstract Background and objective Thrombin-antithrombin complex (TAT) is a prethrombotic marker, and its application in ischemic stroke is still uncertain. The purpose of this systematic review and meta-analysis is to evaluate the relationship between plasma TAT and ischemic stroke base on the current evidence. Methods A systematic literature search was conducted for searching the relative studies that investigated the association of TAT and ischemic stroke in PubMed, EMBASE, and Cochrane library databases. Mean difference and 95% confidence interval as the effect sizes were synthesized by random effects model in Review Manager (RevMan) Version 5.4. The heterogeneity was investigated using the chi-square test and the possible sources of heterogeneity were explored by sensitivity analysis and meta-regression. The publication bias was estimated by Egger’s tests. Results A total of 12 eligible studies were included involving 1431 stroke cases and 532 healthy controls, of which six studies were eventually included in the meta-analysis. Plasma TAT in patients with ischemic stroke was significantly higher than that in healthy controls (MD 5.31, 95% CI = 4.12–6.51, P < 0.0001, I 2 = 97.8%). There is a difference of TAT level in the same period among cardioembolic, lacunar, and atherothrombotic stroke (all P < 0.0001), in which the cardioembolic stroke with the highest level. Meanwhile, it is significant of TAT levels among various phases of cardioembolic stroke and the acute phase are markedly elevated (MD 7.75, 95CI%, 6.07–9.43, P < 0.001). However, no difference was found in the atherothrombotic (P = 0.13) and lacunar stroke (P = 0.34). Besides, the higher TAT level is closely related to the poor prognosis of patients with ischemic stroke, including higher recurrence, mortality, unfavorable recovery (modified Rankin scale > 2), and poor revascularization. Conclusions This study suggested that plasma TAT levels are different in ischemic stroke subtypes, which are closely associated with the progression and might have an effect on the prognosis. Systematic review registration PROSPERO CRD: 42021248787

Over the past 2 years, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the coronavirus disease 2019 (COVID-19) and rapidly spread worldwide. In the process of evolution, new mutations of SARS-CoV-2 began to appear to be more adaptable to the diverse changes of various cellular environments and hosts. Generally, the emerging SARS-CoV-2 variants are characterized by high infectivity, augmented virulence, and fast transmissibility, posing a serious threat to the prevention and control of the global epidemic. At present, there is a paucity of effective measurements to cure COVID-19. It is extremely crucial to develop vaccines against SARS-CoV-2 and emerging variants to enhance individual immunity, but it is not yet known whether they are approved by the authority. Therefore, we systematically reviewed the main characteristics of the emerging various variants of SARS-CoV-2, including their distribution, mutations, transmissibility, severity, and susceptibility to immune responses, especially the Delta variant and the new emerging Omicron variant. Furthermore, we overviewed the suitable crowd, the efficacy, and adverse events (AEs) of current vaccines.

By studying the distribution and drug resistance of bacterial pathogens associated with lower respiratory tract infection (LRTI) in children in Chengdu and the effect of the COVID-19 on the distribution of pathogens and by analyzing the epidemic trend and drug resistance changes of the main pathogens of LRTI, this research is supposed to provide a useful basis for the prevention of LRTI in children and the rational use of drugs in clinical practice. Hospitalized children clinically diagnosed with LRTI in Chengdu Women and Children’s Central Hospital from 2011 to 2020 were selected as the study subjects. The pathogens of LRTI in children and the distribution of pathogens in different ages, genders, seasons, years, and departments and before and after the pandemic situation of COVID-19 were counted. The drug resistance distribution of the top six pathogens with the highest infection rate in the past three years and the trend of drug resistance in the past decade were analyzed. A total of 26,469 pathogens were isolated. Among them, 6240 strains (23.6%) were Gram-positive bacteria, 20152 strains (76.1%) were Gram-negative bacteria, and 73 strains (0.3%) were fungi. Klebsiella pneumoniae, Escherichia coli, Enterobacter cloacae, and Staphylococcus aureus were highly isolated in the group of infants aged 0-1 P

Abstract Combined hepatocellular‐cholangiocarcinoma (cHCC‐CC) and intrahepatic cholangiocarcinoma (ICC) are classified into one category, but comparison of prognosis of the two carcinomas remains controversial. The aim of the current study was to investigate surgical outcomes for patients with ICC or cHCC‐CC who underwent resection in order to elucidate whether the classification of ICC and cHCC‐CC is justified. Subjects were 61 patients with ICC and 29 patients with cHCC‐CC who underwent liver resection from 2001 to 2017. Clinic‐pathological data from the two groups were compared. Tumor number and vascular invasion were independent risk factors for recurrence‐free survival (RFS) in both groups (P 5 cm vs ≤5 cm, 0.5 years vs 4.0 years, P = .003). For patients with cHCC‐CC, tumor cut‐off size of 2 cm showed statistical significance in median RFS (>2 cm vs ≤2 cm, 0.6 years vs 2.6 years, P = .038). The median RFS of patients with cHCC‐CC was 0.9 years (95% confidence interval: 0.3‐1.6), which was poorer than that of patients with ICC (1.3 years, 0.5‐2.1) (P = .028); the rate of RFS at 5 years was 0% and 37.7% respectively. Our study supports the concept of classifying ICC and cHCC‐CC into different categories because of a significant difference in RFS between the two.

Phthalates (phthalic acid esters) have been widely applied as plasticizers. They are ubiquitous contaminants in soils, thereby posing a threat to human health. In this study, ecotoxicological effects of three typical PAEs (dimethyl phthalate-DMP, di-n-octyl phthalate-DOP and butyl benzyl phthalate-BBP) were investigated. As a biological indicator, earthworms (Eisenia fetida) were exposed to phthalates at various doses (0, 0.1, 1, 10 and 50 mg/kg) for different times (7, 14, 21, and 28 d). We evaluated the effects of phthalates on reactive oxygen species (ROS) generation, antioxidant enzymes (superoxide dismutase-SOD, peroxidase-POD and catalase-CAT) activities, glutathione S-transferase enzyme (GST) activity, malondialdehyde (MDA) content and DNA damage. Results showed that ROS content increased with increasing phthalates, whereas ROS content generally increased and then decreased with exposure time. However, antioxidant enzymes activities in earthworms displayed different trends. The GST activity in high-dose treatment group was significantly activated. For DMP and DOP, lipid peroxidation mainly occurred between 14 and 28 d, while for BBP, it primarily existed after 7 d and then disappeared after 28 d. Besides, comet assay indicated that there was a dose-response relationship between the DNA damage and phthalate dose, following DMP > DOP > BBP. Given their toxicity, it is important to understand the mechanisms associated with their eco-toxicity and to reduce their adverse impacts on the environment. Keywords: Phthalic acid esters, ROS, Antioxidant enzymes, Lipid peroxidation, DNA damage

Welding defect constitute a great danger to the safe usage of petroleum pipelines. In addition, manual welding defect detection has numerous deficiencies, such as subjectivity and inaccurate estimation of geometric parameters. Thus, we proposed an automatic welding defect detection system for X-ray images. In the system, five typical defects (cracks, lack of penetration, lack of fusion, round defects, and stripy defects) and non-defects were chosen for recognition. There are three stages in the system: defect extraction, defect detection, and defect recognition. In the first stage, background subtraction with an adaptive thresholding method was adopted to identify the potential defects. In the second stage, to extract real defects from the massive number of potential defects, the adaptive cascade boosting (AdaBoost) algorithm was employed for binary classification. Grayscale features and geometric properties of the defects were extracted for the classification. In the third stage, the AdaBoost algorithm was extended for multi-classification. In the process of distinguishing defects from non-defects, a high detection rate is necessary. To ensure the high true positive rate (TPR) and the low false positive rate (FPR), we proposed the cascade AdaBoost algorithm with penalty term. The accuracy of the defect detection was 85.5%, and the TPR was 91.66%. Moreover, three comparison tests of support vector machine (SVM), k-nearest neighbor (KNN), and random forest (RF) were employed to validate the superiority of AdaBoost. The experimental results indicate that the proposed detection system can be effective for defect detection.

Bub1 is a critical component of the spindle assembly checkpoint (SAC) and closely linked to cell proliferation and differentiation. We previously found that spontaneous abortion embryos contained a low level of Bub1 protein but normal mRNA level, while the knockdown of Bub1 leads to abnormal numerical chromosomes in embryonic cells. Here, we investigated the mechanism through which governs the post-transcriptional regulation of Bub1 protein expression level. We first conducted bioinformatics analysis and identified eight putative miRNAs that may target Bub1. Luciferase reporter assay confirmed that miR-450a-3p can directly regulate Bub1 by binding to the 3'-untranslated region of Bub1 mRNA. We found that the overexpression of miR-450a-3p in mouse embryonic fibroblast (MEF) cells down-regulated Bub1 protein level, repressed cell proliferation, increased apoptosis and restricted most cells in G1 phase of the cell cycle. Furthermore, when the fertilized eggs were microinjected with miR-450a-3p mimics, the cleavage of zygotes was effectively suppressed. Our results strongly suggest that an abnormally decreased Bub1 level regulated by miRNAs may be implicated in the pathogenesis of spontaneous miscarriage. Therefore, the blockade of miR-450a-3p may be explored as a novel therapeutic strategy for preventing spontaneous miscarriages.

Light activation and inactivation of neurons by optogenetic techniques has emerged as an important tool for studying neural circuit function. To achieve a high resolution, new methods are being developed to selectively manipulate the activity of individual neurons. Here, we report that the combination of an acousto-optic device (AOD) and single-photon laser was used to achieve rapid and precise spatiotemporal control of light stimulation at multiple points in a neural circuit with millisecond time resolution. The performance of this system in activating ChIEF expressed on HEK 293 cells as well as cultured neurons was first evaluated, and the laser stimulation patterns were optimized. Next, the spatiotemporally selective manipulation of multiple neurons was achieved in a precise manner. Finally, we demonstrated the versatility of this high-resolution method in dissecting neural circuits both in the mouse cortical slice and the Drosophila brain in vivo. Taken together, our results show that the combination of AOD-assisted laser stimulation and optogenetic tools provides a flexible solution for manipulating neuronal activity at high efficiency and with high temporal precision.

With the rapid growth of the elderly population, dementia has become a global challenge that governments must address. Given the incurable nature of dementia, rehabilitation interventions starting in the mild cognitive impairment (MCI) stage may offer a solution. For a rehabilitation intervention to be implemented as early as possible, existing problems of identification of MCI and development of MCI-specific forms of rehabilitation must be addressed. Use of computer technologies such as virtual reality and artificial intelligence might be helpful in overcoming these problems. Multi-disciplinary integrated approaches to rehabilitation should be the direction that dementia-related rehabilitation takes in the future. In addition to early rehabilitation, prevention of cognitive decline through the development of public community-based services for the elderly might be a more reasonable approach. [ABSTRACT FROM AUTHOR]

In Japan, there is a growing initiative to construct centralized databases and platforms that can aggregate and manage a vast range of medical, health, and caregiving data for research and analysis. Recent advancements in artificial intelligence (AI), particularly in general-purpose models like the Segment Anything model and Chat GPT, promise significant progress towards utilizing such data-rich platforms effectively for healthcare. Traditionally, AI has displayed superior performance by learning specific images or languages, but now it is advancing towards creating models capable of learning universal traits from images and languages by training on extensive datasets. The challenge lies in the fact that these general-purpose models are trained on data that does not sufficiently incorporate medical information, making their direct application to healthcare difficult. However, the introduction of data platforms can potentially solve this problem. This would lead to the development of universally applicable models to process medical images and AI assistants that can support both doctors and patients. These medical AI assistants can function as a "sub-doctor" with extensive knowledge, assisting in comprehensive analysis of symptoms, early detection of rare diseases, and more. They can also serve as an intermediary between the doctor and the patient, helping to simplify consultations and enhance patient understanding of medical conditions and treatments. By bridging this gap, the AI assistant can help to reduce doctors' workload, improve the quality of healthcare, and facilitate early detection and prevention in the elderly population. [ABSTRACT FROM AUTHOR]