BACKGROUND: Ki-67 and human epidermal growth factor receptor 2 (HER2) are known oncogenes involved in bladder cancer (BCa) patient risk stratification. Preoperative assessment of their expression level can assist in clinical treatment decision-making. Recently, amide proton transfer-weighted (APTw) MRI has shown promising potential in the diagnosis of several malignancies. However, few studies reported the value of APTw imaging in evaluating Ki-67 and HER2 status of BCa. PURPOSE: To investigate the feasibility of APTw MRI in assessing the aggressive and proliferative potential regarding the expression levels of Ki-67 and HER2 in BCa. STUDY TYPE: Retrospective. SUBJECTS: 114 patients (mean age, 64.78 ± 11.93 [SD] years; 97 men) were studied. FIELD STRENGTH/SEQUENCE: APTw MRI acquired by a three-dimensional fast-spin-echo sequence at 3.0 T MRI system. ASSESSMENT: Patient pathologic findings, included histologic grade and the expression status of Ki-67 and HER2, were reviewed by one uropathologist. The APTw values of BCa were independently measured by two radiologists and were compared between high-/low-tumor grade group, high-/low-Ki-67 expression group, and high-/low-HER2 expression group. STATISTICAL TESTS: The interclass correlation coefficient, independent sample t-test, Mann-Whitney U test, Spearman's rank correlation, and receiver operating characteristic curve (ROC) analysis were used. P < 0.05 was considered statistically significant. RESULTS: Significantly higher APTw values were found in high-grade BCa patients (7.72% vs. 4.29%, P < 0.001), high-Ki-67 expression BCa patients (8.40% vs. 3.25%, P < 0.001) and HER2 positive BCa patients (8.24% vs. 5.40%, P = 0.001). APTw values were positively correlated with Ki-67 (r = 0.769) and HER2 (r = 0. 356) expression status. The area under the ROC curve of the APTw values for detecting Ki-67 and HER2 expression status were 0.883 (95% CI: 0.790-0.945) and 0.713 (95% CI: 0.592-0.816), respectively. DATA CONCLUSIONS: APTw MRI is a potential method to assess the biological and proliferation potential of BCa. TECHNICAL EFFICACY: Stage 2.
In plant-pathogen interactions, pathogens display tissue specificity, infecting and causing disease in particular tissues. However, the involvement of microRNAs/microRNA-like RNAs (miRNAs/milRNAs) in tissue-specific regulation during plant-pathogen interactions remains largely unexplored. This study investigates the differential expression of miRNAs/milRNAs, as well as their corresponding target genes, in interactions between Valsa mali (Vm) and different apple tissues. The results demonstrated that both apple miRNAs and Vm milRNAs exhibited distinct expression profiles when Vm infected bark and leaves, with functionally diverse corresponding target genes. Furthermore, one apple miRNA (Mdo-miR482a) and one Vm milRNA (Vm-milR57) were identified as exhibiting tissue-specific expression in interactions between Vm and apple bark or leaves. Mdo-miR482a was exclusively up-regulated in response to Vm infection in bark and target a nucleotide-binding leucine-rich repeat (NLR) gene of apple. When Mdo-miR482a was transiently over-expressed or silenced, the resistance was significantly reduced or improved. Similarly, transient expression of the NLR gene also showed an increase in resistance. Vm-milR57 could target two essential pathogenicity-related genes of Vm. During Vm infection in bark, the expression of Vm-milR57 was down-regulated to enhance the expression of the corresponding target gene to improve the pathogenicity. The study is the first to reveal tissue-specific characteristics of apple miRNAs and Vm milRNAs in interactions between Vm and different apple tissues, providing new insights into adaptive regulation in tissue-specific interactions between plants and fungi.
Maternal separation (MS) represents a profound early life stressor with enduring impacts on neuronal development and adult cognitive function in both humans and rodents. MS is associated with persistent dysregulations in neurotransmitter systems, including the serotonin (5-HT) pathway, which is pivotal for mood stabilization and stress-coping mechanisms. Although the novel cannabinoid receptor, GPR55, is recognized for its influence on learning and memory, its implications on the function and synaptic dynamics of 5-HT neurons within the dorsal raphe nucleus (DRN) remain to be elucidated. In this study, we sought to discern the repercussions of GPR55 activation on 5-HT synthesis within the DRN of adult C57BL/6J mice that experienced MS. Concurrently, we analyzed potential alterations in excitatory synaptic transmission, long-term synaptic plasticity, and relevant learning and memory outcomes. Our behavioral assessments indicated a marked amelioration in MS-induced learning and memory deficits following GPR55 activation. In conjunction with this, we noted a substantial decrease in 5-HT levels in the MS model, while GPR55 activation stimulated tryptophan hydroxylase 2 synthesis and fostered the release of 5-HT. Electrophysiological patch-clamp analyses highlighted the ability of GPR55 activation to alleviate MS-induced cognitive deficits by modulating the frequency and magnitude of miniature excitatory postsynaptic currents within the DRN. Notably, this cognitive enhancement was underpinned by the phosphorylation of both NMDA and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. In summary, our findings underscore the capacity of GPR55 to elevate 5-HT synthesis and modify synaptic transmissions within the DRN of juvenile mice, positing GPR55 as a promising therapeutic avenue for ameliorating MS-induced cognitive impairment.
The increasing use of ceftazidime-avibactam has led to the emergence of a wide range of ceftazidime-avibactam-resistant blaKPC-2 variants. Particularly, the conventional carbapenemase phenotypic assay exhibited a high false-negative rate for KPC-2 variants. In this study, three colloidal gold immunoassays, including the Gold Mountainriver CGI test, Dynamiker CGI test and NG-Test CARBA5, and GeneXpert Carba-R, were used to detect the presence of KPC-2 carbapenemase and its various variants in 42 Klebsiella pneumoniae strains. These strains covered blaKPC-2 (13/42) and 16 other blaKPC-2 variants including blaKPC-12 (1/42), blaKPC-23 (1/42), blaKPC-25 (1/42), blaKPC-33 (6/42), blaKPC-35 (1/42), blaKPC-44 (1/42), blaKPC-71 (1/42), blaKPC-76 (8/42), blaKPC-78 (1/42), blaKPC-79 (1/42), blaKPC-100 (1/42), blaKPC-127 (1/42), blaKPC-128 (1/42), blaKPC-144 (1/42), blaKPC-157 (2/42), and blaKPC-180 (1/42). For KPC-2 strains, all four assays showed 100% negative percentage agreement (NPA) and 100% positive percentage agreement (PPA) with sequencing results. For all 16 KPC-2 variants, GeneXpert Carba-R showed 100% NPA and 100% PPA, and the three colloidal gold immunoassays showed 100% NPA, while the PPAs of the Gold Mountainriver CGI test, Dynamiker CGI test, and NG-Test CARBA5 were 87.5%, 87.5%, and 68.8%, respectively. We also found a correlation between the mutation site in the amino acid of the variants and false-negative results by colloidal gold immunoassays. In conclusion, the GeneXpert Carba-R has been proven to be a reliable method in detecting KPC-2 and its variants, and the colloidal gold immunoassay tests offer a practical and cost-effective approach for their detection. For the sample with a negative result by a colloidal gold immunoassay test but not matching the drug-resistant phenotype, it is recommended to retest using another type of kit or the GeneXpert Carba-R assay, which can significantly improve the accuracy of detection.
OBJECTIVES: The objective of this study was to evaluate the potential relationship between sleep disturbances and various types of constipation in patients. METHODS: We conducted systematic searches in the research databases PubMed, EMBASE, Web of Science, and Cochrane Library to identify qualifying studies. Using Stata software version 14.0, we calculated the Odds Ratio (OR) and 95 % confidence interval (CI) for constipation in patients with sleep disorders. If P > 0.1 and I2 ≤ 50 %, we employed a fixed-effects model; otherwise, we applied a random-effects model. We assessed publication bias using funnel plots and Egger's test. RESULT: The pooled analysis demonstrated that individuals with sleep disorders were associated with an increased risk of all-cause constipation (OR = 1.47; 95 %CI: 1.31-1.64; I2 = 88.8 %, Pï¼0.001). Specifically, both children (OR = 1.29; 95 %CI: 1.16-1.42; I2 = 63.8 %, Pï¼0.001) and adults (OR = 1.65; 95 %CI: 1.39-1.97; I2 = 92.4 %, Pï¼0.001) with a history of sleep disorders exhibited an increased risk of all-cause constipation.. Furthermore, patients with a history of insufficient sleep were also associated with an increased risk of constipation (OR = 1.33; 95 %CI: 1.20-1.46; I2 = 6.7 %, Pï¼0.001). Additionally, patients with poor sleep quality were found to have an increased risk of constipation (OR = 1.56; 95 %CI: 1.0-2.45; I2 = 90.9 %, P = 0.05). Lastly, patients with insomnia were found to have the highest risk of constipation (OR = 1.94; 95 %CI: 1.37-2.76; I2 = 97.8 %, Pï¼0.001). CONCLUSION: This meta-analysis indicates that sleep disorders are associated with an elevated risk of constipation. Insomnia, poor sleep quality, and insufficient sleep duration all contribute to elevating the risk of constipation. These findings emphasize the significance of recognizing sleep disorders as an independent risk factor for constipation in both children and adults.
BACKGROUND: Although physician-pharmacist collaborative clinics for diabetes management have been shown to be effective and cost-effective worldwide, there is limited understanding of the factors that influence their sustainable implementation. This study aims to identify the associated factors and provide sustainability strategy to better implement physician-pharmacist collaborative clinics for diabetes management in primary healthcare centers in China. METHODS: A sample of 43 participants were participated in face-to-face, in-depth, semi-structured interviews. Consolidated Framework for Implementation Research was used to identify facilitators and barriers to implementing physician-pharmacist collaborative clinics for diabetes management in primary healthcare centers, and to explore discriminating factors between low and high implementation units. A sustainable strategy repository based on dynamic sustainability framework was established to inform further implementation. RESULTS: This study demonstrated that clear recognition of intervention benefits, urgent needs of patients, adaptive and tailored plan, highly collaborative teamwork and leadership support were the major facilitators, while the major barriers included process complexity, large number and poor health literacy of patients in primary areas, inappropriate staffing arrangements, weak financial incentives and inadequate staff competencies. Six constructs were identified to distinguish between high and low implementation units. Sixteen strategies were developed to foster the implementation of physician-pharmacist collaborative clinics, targeting Intervention, Practice setting, and Ecological system. CONCLUSION: This qualitative study demonstrated facilitators and barriers to implementing physician-pharmacist collaborative clinics for diabetes management in primary healthcare centers and developed theory-based strategies for further promotion, which has the potential to improve the management of diabetes and other chronic diseases in under-resourced areas.
Cadmium poses a severe health risk, impacting various bodily systems. Monitoring human exposure is vital. Urine and blood cadmium serve as critical biomarkers. However, current urine and blood cadmium detection methods are expensive and complex. Being cost-effective, user-friendly, and efficient, visual biosensing offers a promising complement to existing techniques. Therefore, we constructed a cadmium whole-cell biosensor using CadR10 and deoxyviolacein pigment in this study. We assessed the sensor for time-dose response, specific response to cadmium, sensitivity response to cadmium, and stability response to cadmium. The results showed that (1) the sensor had a preferred signal-to-noise ratio when the incubation time was 4 h; (2) the sensor showed excellent specificity for cadmium compared to the group 12 metals and lead; (3) the sensor was responsive to cadmium down to 1.53 nM under experimental conditions and had good linearity over a wide range from 1.53 nM to 100 µM with good linearity (R2 = 0.979); and (4) the sensor had good stability. Based on the excellent results of the performance tests, we developed a cost-effective, high-throughput method for detecting urinary and blood cadmium. Specifically, this was realized by adding the blood or urine samples into the culture system in a particular proportion. Then, the whole-cell biosensor was subjected to culture, n-butanol extraction, and microplate reading. The results showed that (1) at 20% urine addition ratio, the sensor had an excellent curvilinear relationship (R2 = 0.986) in the range of 3.05 nM to 100 µM, and the detection limit could reach 3.05 nM. (2) At a 10% blood addition ratio, the sensor had an excellent nonlinear relationship (R2 = 0.978) in the range of 0.097-50 µM, and the detection limit reached 0.195 µM. Overall, we developed a sensitive and wide-range method based on a whole-cell biosensor for the detection of cadmium in blood and urine, which has the advantages of being cost-effective, ease of operation, fast response, and low dependence on instrumentation and has the potential to be applied in the monitoring of cadmium exposure in humans as a complementary to the mainstream detection techniques.
Heat shock proteins (HSPs) are a group of highly conserved proteins found in a wide range of organisms. In recent years, members of the HSP family were overexpressed in various tumors and widely involved in oncogenesis, tumor development, and therapeutic resistance. In our previous study, DNAJC24, a member of the DNAJ/HSP40 family of HSPs, was found to be closely associated with the malignant phenotype of hepatocellular carcinoma. However, its relationship with other malignancies needs to be further explored. Herein, we demonstrated that DNAJC24 exhibited upregulated expression in LUAD tissue samples and predicted poor survival in LUAD patients. The upregulation of DNAJC24 expression promoted proliferation and invasion of LUAD cells in A549 and NCI-H1299 cell lines. Further studies revealed that DNAJC24 could regulate the PI3K/AKT signaling pathway by affecting AKT phosphorylation. In addition, a series of experiments such as Co-IP and mass spectrometry confirmed that DNAJC24 could directly interact with PCNA and promoted the malignant phenotypic transformation of LUAD. In conclusion, our results suggested that DNAJC24 played an important role in the progression of LUAD and may serve as a specific prognostic biomarker for LUAD patients. The DNAJC24/PCNA/AKT axis may be a potential target for future individualized and precise treatment of LUAD patients.
Cell Proliferation , HSP40 Heat-Shock Proteins , Proliferating Cell Nuclear Antigen , Proto-Oncogene Proteins c-akt , Humans , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-akt/genetics , Phosphorylation , HSP40 Heat-Shock Proteins/metabolism , HSP40 Heat-Shock Proteins/genetics , Proliferating Cell Nuclear Antigen/metabolism , Proliferating Cell Nuclear Antigen/genetics , Male , Cell Line, Tumor , Female , Mice, Nude , Gene Expression Regulation, Neoplastic , Mice , Signal Transduction , Animals , Disease Progression , Mice, Inbred BALB C , Middle Aged , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Lung Neoplasms/genetics
The macrophage colony-stimulating factor 1 receptor (CSF1R) is almost exclusively expressed in microglia, representing a biomarker target for imaging of microglia availability. [11C]CPPC has specific binding affinity to CSF1R and suitable kinetic properties for in vivo PET imaging of microglia. However, previous studies reported a low radiochemical yield, motivating additional research to optimize [11C]CPPC radiochemistry. In this work, we report an automated radiosynthesis of [11C]CPPC on a Synthra MeIPlus module with improved radiochemical yield. The final [11C]CPPC product was obtained with excellent chemical/radiochemical purities and molecular activity, facilitating high-quality in-human PET imaging applications.
Direct electrosynthesis of hydrogen peroxide (H2O2) with high production rate and high selectivity through the two-electron oxygen reduction reaction (2e-ORR) offers a sustainable alternative to the energy-intensive anthraquinone technology but remains a challenge. Herein, a low-coordinated, 2D conductive Zn/Cu metal-organic framework supported on hollow nanocube structures (ZnCu-MOF (H)) is rationally designed and synthesized. The as-prepared ZnCu-MOF (H) catalyst exhibits substantially boosted electrocatalytic kinetics, enhanced H2O2 selectivity, and ultra-high Faradaic efficiency for 2e-ORR process in both alkaline and neutral conditions. Electrochemical measurements, operando/quasi in situ spectroscopy, and theoretical calculation demonstrate that the introduction of Cu atoms with low-coordinated structures induces the transformation of active sites, resulting in the beneficial electron transfer and the optimized energy barrier, thereby improving the electrocatalytic activity and selectivity.
BACKGROUND: The purpose of this prospective study was to evaluate the association of systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI), with PSCI in patients with acute ischemic stroke (AIS). METHODS: First-onset AIS patients were consecutively included from January 1, 2022 to March 1, 2023. The baseline information was collected at admission. Fasting blood was drawn the next morning. Cognitive function was assessed by the Montreal Cognitive Assessment (MoCA) 3 months after onset. Logistic regression analysis was performed to explore the correlation between SII, SIRI, and PSCI. Receiver operating characteristic (ROC) was conducted to evaluate the predictive ability of SII. RESULTS: 332 participants were recruited, and 193 developed PSCI. Compared with patients without PSCI, the patients with PSCI had higher SII (587.75 (337.42, 988.95) vs. 345.66 (248.44, 572.89), P<0.001) and SIRI (1.59 (0.95, 2.84) vs. 1.02 (0.63, 1.55), P=0.007). SII and SIRI negatively correlated with MoCA scores (both P<0.05). The multivariable logistic regression analysis indicated that SII was independently associated with PSCI (P<0.001), while SIRI was not. The optimal cutoff for SII to predict PSCI was 676.83×109/L. CONCLUSIONS: A higher level of SII upon admission was independently correlated to PSCI three months later in AIS patients.
The reliable and efficient nitrite production rate (NPR) through nitritation process is the prerequisite for the efficient running of subsequent processes, like the anammox process and the nitrite shunt. However, there has been scant research on stable and productive nitritation process in recent years. In this study, at a stable hydraulic retention time of 12.0 h and with precise and strict DO control, the upper limit of the NPR was initially investigated using a continuous-flow granular sludge reactor. The NPR of 1.69 kg/m3/d with a nitrite production efficiency of 81.97% was finally achieved, which set a record until now in similar research. The median sludge particle size of 270.0 µm confirmed the development of clearly defined granular sludge. The genus Nitrosomonas was the major ammonium oxidizing bacteria. In conclusion, this study provides valuable insights for the practical application of the effective nitritation process driving subsequent nitrogen removal processes.
Calcium oscillations are induced by different stresses. Calcium-dependent protein kinases (CDPKs/CPKs) are one major group of the plant calcium decoders that are involved in various processes including drought response. Some CPKs are calcium-independent. Here, we identified ZmCPK2 as a negative regulator of drought resistance by screening an overexpression transgenic maize pool. We found that ZmCPK2 does not bind calcium, and its activity is mainly inhibited during short term abscisic acid (ABA) treatment, and dynamically changed in prolonged treatment. Interestingly, ZmCPK2 interacts with and is inhibited by calcium-dependent ZmCPK17, a positive regulator of drought resistance, which is activated by ABA. ZmCPK17 could prevent the nuclear localization of ZmCPK2 through phosphorylation of ZmCPK2T60. ZmCPK2 interacts with and phosphorylates and activates ZmYAB15, a negative transcriptional factor for drought resistance. Our results suggest that drought stress-induced Ca2+ can be decoded directly by ZmCPK17 that inhibits ZmCPK2, thereby promoting plant adaptation to water deficit.
Ceftazidime-avibactam (CZA) is employed for the treatment of infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-KP). Resistance to CZA is frequently linked to point mutations in the blaKPC. We conducted in vitro simulations of in vivo blaKPC mutations using CZA. Four pre-therapy KPC-KP isolates (K1, K2, K3, and K4) were evaluated, all initially exhibited susceptibility to CZA and produced KPC-2. The crucial distinction was that following CZA treatment, the blaKPC-2 mutated in K1, K2, and K3, rendering them resistant to CZA, while K4 achieved microbiological clearance, and blaKPC-2 remained unaltered. The induction assay identified various blaKPC-2 variants, including blaKPC-25, blaKPC-127, blaKPC-100, blaKPC-128, blaKPC-137, blaKPC-138, blaKPC-144 and blaKPC-180. Our findings suggest that the resistance of KPC-KP to CZA primarily results from the emergence of KPC variants, complemented by increased blaKPC expression. A close correlation exists between avibactam concentration and the rate of increased CZA minimum Inhibitory concentration, as well as blaKPC mutation. Inadequate avibactam concentration is more likely to induce resistance in strains against CZA, there is also a higher likelihood of mutation in the blaKPC-2 and the optimal avibactam ratio remains to be determined. Simultaneously, we selected a blaKPC-33-producing K. pneumoniae strain (mutated from blaKPC-2) and induced it with imipenem and meropenem, respectively. The blaKPC-2 was detected during the process, indicating that the mutation is reversible. Clinical use of carbapenems to treat KPC variant strains increases the risk of infection, as the gene can mutate back to blaKPC-2, rendering the strain even more cross-resistant to carbapenems and CZA.
BACKGROUND: Some solitary pulmonary nodules (SPNs) as early manifestations of lung cancer, it is difficult to determine its nature, which brings great trouble to clinical diagnosis and treatment. Radiomics can deeply explore the essence of images and provide clinical decision support for clinicians. The purpose of our study was to explore the effect of positron emission tomography (PET) with 2-deoxy-2-[fluorine-18] fluoro-d-glucose integrated with computed tomography (CT; 18F-FDG-PET/CT) combined with radiomics for predicting probability of malignancy of SPNs. METHODS: We retrospectively enrolled 190 patients with SPNs confirmed by pathology from January 2013 to December 2019 in our hospital. SPNs were benign in 69 patients and malignant in 121 patients. Patients were randomly divided into a training or testing group at a ratio of 7:3. Three-dimensional regions of interest (ROIs) were manually outlined on PET and CT images, and radiomics features were extracted. Synthetic minority oversampling technique (SMOTE) method was used to balance benign and malignant samples to a ratio of 1:1. In the training group, least absolute shrinkage and selection operator (LASSO) regression analyses and Spearman correlation analyses were used to select the strongest radiomics features. Three models including PET model, CT model, and joint model were constructed using multivariate logistic regression analysis. Receiver operating characteristic (ROC) curves, calibration curves, and decision curves were plotted to evaluate diagnostic efficiency, calibration degree, and clinical usefulness of all models in training and testing groups. RESULTS: The estimative effectiveness of the joint model was superior to the CT or PET model alone in the training and testing groups. For the joint model, CT model, and PET model, area under the ROC curve was 0.929, 0.819, 0.833 in the training group, and 0.844, 0.759, 0.748 in the testing group, respectively. Calibration and decision curves showed good fit and clinical usefulness for the joint model in both training and testing groups. CONCLUSION: Radiomics models constructed by combining PET and CT radiomics features are valuable for distinguishing benign and malignant SPNs. The combined effect is superior to qualitative diagnoses with CT or PET radiomics models alone.
Fluorodeoxyglucose F18 , Lung Neoplasms , Positron Emission Tomography Computed Tomography , Solitary Pulmonary Nodule , Humans , Solitary Pulmonary Nodule/diagnostic imaging , Solitary Pulmonary Nodule/pathology , Male , Female , Positron Emission Tomography Computed Tomography/methods , Retrospective Studies , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Middle Aged , Aged , Radiopharmaceuticals , Adult , Radiomics
Objective: Among adolescents with depression, the occurrence of non-suicidal self-injury (NSSI) behavior is prevalent, constituting a high-risk factor for suicide. However, there has been limited research on the neuroimaging mechanisms underlying adolescent depression and NSSI behavior, and the potential association between the two remains unclear. Therefore, this study aims to investigate the alterations in functional connectivity (FC) of the regions in the prefrontal cortex with the whole brain, and elucidates the relationship between these alterations and NSSI behavior in adolescents with depression. Methods: A total of 68 participants were included in this study, including 35 adolescents with depression and 33 healthy controls. All participants underwent assessments using the 17-item Hamilton Depression Rating Scale (17-HAMD) and the Ottawa Self-Harm Inventory. In addition, functional magnetic resonance imaging (fMRI) data of the participants' brains were collected. Subsequently, the FCs of the regions in the prefrontal cortex with the whole brain was calculated. The FCs showing significant differences were then subjected to correlation analyses with 17-HAMD scores and NSSI behavior scores. Result: Compared to the healthy control group, the adolescent depression group exhibited decreased FCs in several regions, including the right frontal eye field, left dorsolateral prefrontal cortex, right orbitofrontal cortex, left insula and right anterior cingulate coetex. The 17-HAMD score was positively correlated with the frequency of NSSI behavior within 1 year (rs = 0.461, p = 0.005). The FC between the right anterior cingulate cortex and the right precuneus showed a negative correlation with the 17-HAMD scores (rs = -0.401, p = 0.023). Additionally, the FC between the right orbitofrontal cortex and the right insula, demonstrated a negative correlation with the frequency of NSSI behavior within 1 year (rs = -0.438, p = 0.012, respectively). Conclusion: Adolescents with depression showed decreased FCs of the prefrontal cortex with multiple brain regions, and some of these FCs were associated with the NSSI frequency within 1 year. This study provided neuroimaging evidence for the neurophysiological mechanisms underlying adolescent depression and its comorbidity with NSSI behavior.
AbstractCeftazidime-avibactam resistance attributable to the blaKPC-2 gene mutation is increasingly documented in clinical settings. In this study, we characterized the mechanisms leading to the development of ceftazidime-avibactam resistance in ST11-K47 hypervirulent Klebsiella pneumoniae that harbored the blaKPC-135 gene. This strain possessed fimbriae and biofilm, demonstrating pathogenicity. Compared with the wild-type KPC-2 carbapenemase, the novel KPC-135 enzyme exhibited a deletion of Glu168 and Leu169 and a 15-amino acid tandem repeat between Val262 and Ala276. The blaKPC-135 gene was located within the Tn6296 transposon truncated by IS26 and carried on an IncFII/IncR-type plasmid. Compared to the blaKPC-2-positive cloned strain, only the MIC of ceftazidime increased against blaKPC-135-positive K. pneumoniae and wasn't inhibited by avibactam (MIC 32 µg/mL), while clavulanic acid and vaborbactam demonstrated some inhibition. Kinetic parameters revealed that KPC-135 exhibited a lower Km and kcat/Km with ceftazidime and carbapenems, and a higher (â¼26-fold) 50% inhibitory concentration with avibactam compared to KPC-2. The KPC-135 enzyme exerted a detrimental effect on fitness relative to the wild-type strain. Furthermore, this strain possessed hypervirulent determinants, which included the IncHI1B/FIB plasmid with rmpA2 and expression of type 1 and 3 fimbriae. In conclusion, we reported a novel KPC variant, KPC-135, in a clinical ST11-K47 hypervirulent K. pneumoniae strain, which conferred ceftazidime-avibactam resistance, possibly through increased ceftazidime affinity and decreased avibactam susceptibility. This strain simultaneously harbored resistance and virulence genes, posing an elevated challenge in clinical treatment.
Human brucellosis caused by Brucella is a widespread zoonosis that is prevalent in many countries globally. The high homology between members of the Brucella genus and Ochrobactrum spp. often complicates the determination of disease etiology in patients. The efficient and reliable identification and distinction of Brucella are of primary interest for both medical surveillance and outbreak purposes. A large amount of genomic data for the Brucella genus was analyzed to uncover novel probes containing single-nucleotide polymorphisms (SNPs). GAMOSCE v1.0 software was developed based on the above novel eProbes. In conjunction with clinical requirements, an RPA-Cas12a detection method was developed for the on-site determination of B. abortus and B. melitensis by fluorescence and lateral flow dipsticks (LFDs). We demonstrated the potential of these probes for rapid and accurate detection of the Brucella genus and five significant Brucella species in silico using GAMOSCE. GAMOSCE was validated on different Brucella datasets and correctly identified all Brucella strains, demonstrating a strong discrimination ability. The RPA-Cas12a detection method showed good performance in detection in clinical blood samples and veterinary isolates. We provide both in silico and on-site methods that are convenient and reliable for use in local hospitals and public health programs for the detection of brucellosis.
Attention deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) are highly comorbid. Many prior investigations have found that ADHD relates to anatomical abnormalities in gray matter. The abnormal gray matter of ADHD comorbid ODD is still poorly understood. This study aimed to explore the effect of comorbid ODD on gray matter volume (GMV) and functional alterations in ADHD. All data were provided by the ADHD-200 Preprocessed Repository, including 27 ADHD-only children, 27 ADHD + ODD children, and 27 healthy controls aged 9-14 years. Voxel-based morphometry (VBM) and functional connectivity (FC) of resting-state functional magnetic resonance imaging (fMRI) were used to compare the difference in GMV and FC between ADHD + ODD, ADHD-only, and healthy children. The results showed that ADHD children with comorbid ODD had a more significant reduction in cerebellar volume, mainly in the anterior regions of the cerebellum (Cerebellum_4_5). The Cerebellum_4_5 showed increased functional connectivity with multiple cortical regions. These brain regions include numerous executive functioning (EF) and brain default mode network (DMN) nodes. The GMV abnormalities and excessive connectivity between brain regions may further exacerbate the emotional and cognitive deficits associated with ADHD.
