Intermittent cytomegalovirus infection alters neurobiological metabolism and induces cognitive deficits in mice.

Risk factors contributing to dementia are multifactorial. Accumulating evidence suggests a role for pathogens as risk factors, but data is largely correlative with few causal relationships. Here, we demonstrate that intermittent murine cytomegalovirus (MCMV) infection of mice, alters blood brain barrier (BBB) permeability and metabolic pathways. Increased basal mitochondrial function is observed in brain microvessels cells (BMV) exposed to intermittent MCMV infection and is accompanied by elevated levels of superoxide. Further, mice score lower in cognitive assays compared to age-matched controls who were never administered MCMV. Our data show that repeated systemic infection with MCMV, increases markers of neuroinflammation, alters mitochondrial function, increases markers of oxidative stress and impacts cognition. Together, this suggests that viral burden may be a risk factor for dementia. These observations provide possible mechanistic insights through which pathogens may contribute to the progression or exacerbation of dementia.

Glutaminase 1 isoform up-regulation associated with lipid metabolism disorder induced by methyl tertiary-butyl ether in male rats.

Methyl tertiary-butyl ether (MTBE) is a new unleaded gasoline additive, which is considered to be associated with abnormal lipid metabolism in many studies, but the metabolic characteristics and mechanism are still unclear. To observe the characteristics of lipid metabolism induced by MTBE and possible pathways, 21 male Wistar rats got intragastric administration for 24 weeks. The serum lipid metabolism indexes and metabolites were analyzed separately by a biochemical analyzer and untargeted metabolomics. And found that serum high-density lipoprotein cholesterol (HDL-C) levels in the exposure group were significantly reduced, and serum very low-density lipoprotein (VLDL) levels were significantly increased. In untargeted metabolomics, 190 differential metabolites were obtained. Among them, 23 metabolites were found to show the same trend in MTBE exposure groups, which might play a key role in systemic energy metabolism. Further metabolic pathways analysis showed that D-Glutamine, D-glutamate metabolism, and the other three pathways were affected by MTBE significantly. Therefore, we evaluated serum glutamine and glutamate levels and found that MTBE exposure significantly reduced glutamine levels and increased glutamate levels in rat serum and L-02 cells. Further, the key regulatory gene of glutamine metabolism, glutaminase 1 isoform (GLS1), was significantly up-regulated in rat liver and L-02 cells exposed to MTBE. While the effect of glutamine and glutamate metabolism induced by MTBE could be weakened by BPTES, an antagonist of GLS1. In conclusion, our results indicated that MTBE exposure could change the level of glutamine metabolism by promoting GLS1 expression and ultimately lead to abnormal lipid metabolism.

The Transcription Factor Shox2 Shapes Neuron Firing Properties and Suppresses Seizures by Regulation of Key Ion Channels in Thalamocortical Neurons.

Thalamocortical neurons (TCNs) play a critical role in the maintenance of thalamocortical oscillations, dysregulation of which can result in certain types of seizures. Precise control over firing rates of TCNs is foundational to these oscillations, yet the transcriptional mechanisms that constrain these firing rates remain elusive. We hypothesized that Shox2 is a transcriptional regulator of ion channels important for TCN function and that loss of Shox2 alters firing frequency and activity, ultimately perturbing thalamocortical oscillations into an epilepsy-prone state. In this study, we used RNA sequencing and quantitative PCR of control and Shox2 knockout mice to determine Shox2-affected genes and revealed a network of ion channel genes important for neuronal firing properties. Protein regulation was confirmed by Western blotting, and electrophysiological recordings showed that Shox2 KO impacted the firing properties of a subpopulation of TCNs. Computational modeling showed that disruption of these conductances in a manner similar to Shox2's effects modulated frequency of oscillations and could convert sleep spindles to near spike and wave activity, which are a hallmark for absence epilepsy. Finally, Shox2 KO mice were more susceptible to pilocarpine-induced seizures. Overall, these results reveal Shox2 as a transcription factor important for TCN function in adult mouse thalamus.

Early breastfeeding is associated with low risk of postpartum depression in Taiwanese women.

Breastfeeding during the first week postpartum is recognised as essential, affecting the mother's mental health. The human milk from early breastfeeding also protects against infections via the secretory IgA antibodies and plays an important role in the newborn's development. At a Baby-Friendly Hospital, early breastfeeding was promoted to increase the benefits for the newborn, but few focussed on the mother's health. The association between breastfeeding and postpartum depression (PPD) has not been fully addressed. This study aimed to investigate the relationship between breastfeeding and postpartum depression (PPD) and it included 333 Taiwanese pregnant women. Women who had a higher score of Edinburgh Postnatal Depression Scale (EPDS) were significant older (age ≥ 35, p < .037), had a caesarean section delivery (p < .001), and a higher score of Brief Symptom Rating Scale-5 (p < .001). Higher scores on EPDS were significantly associated with lower rates of breastfeeding, which reflected cessation of breastfeeding as an important risk factor for PPD (Odds ratio: 2.159, CI: 1.220-3.821, p = .008). Other risk factors included caesarean section delivery (Odds ratio: 2.814, CI: 1.617-4.899, p < .001) and age ≥35 years (Odds ratio: 1.821, CI: 1.057-3.137, p = .031).IMPACT STATEMENTWhat is already known on this subject: Breastfeeding during the first week postpartum is recognised as essential, affecting the mother's mental health. The human milk from early breastfeeding also protects against infections via the secretory IgA antibodies and plays an important role in the newborn's development. The detail association between breastfeeding and postpartum depression has not yet been fully addressed.What the results of this study add: Higher scores on EPDS were significantly associated with lower rates of breastfeeding, which reflected cessation of breastfeeding as an important risk factor for PPD (Odds ratio: 2.159, CI: 1.220-3.821, p = .008). Other risk factors included caesarean section delivery (Odds ratio: 2.814, CI: 1.617-4.899, p < .001) and age ≥35 years (Odds ratio: 1.821, CI: 1.057-3.137, p = .031).What the implications are of these findings for clinical practice and/or further research? The early breastfeeding was significantly associated with postpartum depression. Other risk factors included caesarean section delivery and age ≥35 years.

Occurrence and characteristics of blaOXA-181-carrying Klebsiella aerogenes from swine in China.

OBJECTIVES: Klebsiella aerogenes is a largely understudied opportunistic pathogen that can cause sepsis and lead to high mortality rates. In this study, we reported the occurrence of carbapenem-resistant blaOXA-181-carrying Klebsiella aerogenes from swine in China and elucidate their genomic characteristics. METHODS: A total of 126 samples, including 109 swine fecal swabs, 14 environmental samples, and three feed samples were collected from a pig farm in China. The samples were enriched with LB broth culture and then inoculated into MacConkey agar plates for bacterial isolation. After PCR detection of carbapenemases genes, the blaOXA-181-carrying isolates were subjected to antimicrobial susceptibility testing, and whole-genome sequence analysis. RESULTS: Four Klebsiella aerogenes isolates carrying the blaOXA-181 gene were obtained from swine faecal samples. All the 4 strains were belonged to ST438. The blaOXA-181 genes were located in IncX3-ColKP3 hybrid plasmids with the core genetic structure of IS26-ΔIS3000-ΔISEcp1-blaOXA-181-ΔlysR-ΔereA-ΔrepA-ISKpn19-tinR-qnrS1-ΔIS2-IS26, which suggests the potential for horizontal transfer and further dissemination of this resistance gene among Enterobacteriaceae and other sources. CONCLUSIONS: This study represents the first instance of OXA-181-producing K. aerogenes being identified from swine faeces in China. It is crucial to maintain continuous monitoring and ongoing attention to the detection of K. aerogenes carrying blaOXA-181 and other resistance genes in pigs.

Evaluating CO2 Capture Performance of Trisolvent MEA-BEA-AMP with Heterogeneous Catalysts in a Novel Bench-Scale Pilot Plant.

To reduce the huge energy cost of CO2 capture technology applicable in industry, the CO2 absorption-desorption performance was conducted in a novel bench-scale pilot plant with hot water as a heat source. The trisolvent MEA(monoethanol amine)-BEA(butylethanol amine)-AMP(2-amino-2-methyl-1-propanol) was prepared at a specific concentration to analyze the CO2 capture performance and compared with 5 M MEA as the benchmark. Meanwhile, several solid acid catalysts, blended H-ZSM-5/γ-Al2O3(1/2), or HND-8, were packed in the desorber, and the solid base catalyst, CaCO3 or CaMg(CO3)2, was packed in the absorber with random packing. The CO2 absorption efficiency (AE), cyclic capacity (CC), and heat duty (HD) were tested onto MEA-BEA-AMP and MEA under various operating conditions. Experimental results indicated that the performance of 4.3 mol/L MEA-BEA-AMP was significantly better than 5 M MEA under both catalytic and noncatalytic operation. The most energy efficient combination of this study was discovered as 0.3 + 2 + 2 mol/L MEA-BEA-AMP, with 50 g (CaCO3/CaMg(CO3)2) in the absorber and 150 g H-ZSM-5/γ-Al2O3(1/2) in the desorber. The heat duty reached as low as 2.4 GJ/tCO2 at a FG of 7.0 L/min and a FL of 70 mL/min. These results were highly applicable in an industrial amine scrubbing pilot plant for CO2 capture.

The Effects of Physical Activity on Experimental Models of Vascular Dementia: A Systematic Review and Meta-Analysis.

Background: Physical activity is associated with improved brain health and cognition in humans. However, the validity, range, and quality of evidence for the beneficial outcomes linked to exercise in experimental models of vascular dementia (VaD) have not been evaluated. We performed a systematic review and meta-analysis of studies that assessed the effect of exercise intervention on models of VaD to provide an unbiased and comprehensive determination of the cognitive function and brain morphology benefits of exercise. Summary: A systematic search in three databases as well as study design characteristics and experimental data extraction were completed in December 2021. We investigated the effects of exercise on cognitive function and brain-morphology outcomes in VaD models. Twenty-five studies were included for systematic review, while 21 studies were included in the meta-analysis. These studies included seven models of VaD in rats (60%, 15 studies), mice (36%, 9 studies), and pigs (4%, 1 study). None of the included studies used aged animals, and the majority of studies (80%) used only male animals. Key Message Exercise improves cognition but increased neuro-inflammation in VaD models: Exercise improved cognitive function as well as some markers of brain morphology in models of VaD. However, exercise increased anxiety and neuro-inflammatory signals in VaD models. Further, we observed increased reporting anomalies such as a lack of blinding to group treatment or data analysis and randomization of animals to groups. Our report could help in the appropriate design of experimental studies seeking to investigate the effects of exercise as a non-pharmacological intervention on VaD models with a high translational impact.

Mediation effect of serum zinc on insulin secretion inhibited by methyl tert-butyl ether in gas station workers.

Methyl tert-butyl ether (MTBE), a type of gasoline additive, has been found to affect insulin function and glucose homeostasis in animal experiments, but there is still no epidemiological evidence. Zinc (Zn) is a key regulatory element of insulin secretion and function, and Zn homeostasis can be disrupted by MTBE exposure through inducing oxidative stress. Therefore, we suspected that Zn might be involved and play an important role in the process of insulin secretion inhibited by MTBE exposure. In this study, we recruited 201 male subjects including occupational and non-occupational MTBE exposure from Anhui Province, China in 2019. Serum insulin and functional analog fibroblast growth factor 1 (FGF1) and blood MTBE were detected by Elisa and headspace solid-phase microextraction and gas chromatography-high-resolution mass spectrometry. According to MTBE internal exposure level, the workers were divided into low- and high-exposed groups and found that the serum insulin level in the high-exposed group was significantly lower than that in the low-exposed group (p = 0.003) while fasting plasma glucose (FPG) level increased obviously in the high-exposed group compared to the low-exposed group (p = 0.001). Further analysis showed that MTBE exposure level was positively correlated with FPG level, but negatively correlated with serum insulin level, which suggested that the FPG level increase might be related to the decrease of serum insulin level induced by MTBE exposure. The results of further mediation effect analysis showed that changes in serum zinc levels played a major intermediary role in the process of insulin secretion inhibition and blood glucose elevation caused by MTBE exposure. In addition, a significant negative correlation was found between MTBE exposure and serum Zn level, which might play a strong mediating effect on the inhibition of insulin secretion induced by MTBE exposure. In conclusion, our study provided evidence that MTBE could inhibit insulin secretion and interfere with Zn metabolism in gas station workers for the first time, and found that Zn might play an important mediation effect during the process of inhibiting insulin secretion and interfering with glucose metabolism induced by MTBE exposure.

MTBE exposure may increase the risk of insulin resistance in male gas station workers.

Insulin resistance is closely related to many metabolic diseases and has become a serious public health problem worldwide. So, it is crucial to find its environmental pathogenic factors. Methyl tert-butyl ether (MTBE), a widely used unleaded gasoline additive, has been proven to affect glycolipid metabolism. However, results from population studies are lacking. For this purpose, the potential relationships between MTBE exposure and the triglyceride glucose (TyG) index, a useful surrogate marker of insulin resistance, were evaluated using a small-scale occupational population. In this study, 201 participants including occupational and non-occupational MTBE exposure workers were recruited from the Occupational Disease Prevention and Control Hospital of Huaibei, and their health examination information and blood samples with informed consent were collected. The internal exposure levels were assessed by detecting blood MTBE using solid-phase-micro-extraction gas chromatography-mass spectrometry. Then the adjusted linear regression model was used to assess the relationship between MTBE exposure and fasting plasma glucose (FPG), or TyG index. Then, receiver-operating-characteristic (ROC) curves were performed to calculate the optimal cut-off points. Multivariable and hierarchical logistic regression models were used to analyze the impact of MTBE exposure on the risk of insulin resistance. Obvious correlations were observed between blood MTBE levels with TyG index (p = 0.016) and FPG (p = 0.001). Further analysis showed that using the mean of the TyG index (8.77) as a cutoff value had a good effect on reflecting the risk of insulin resistance. Multivariable logistic regression analysis also indicated that MTBE exposure was an independent risk factor for a high TyG index (OR = 1.088, p = 0.038), which indicated that MTBE exposure might be a new environmental pathogenic factor leading to insulin resistance, and MTBE exposure might increase the risk of insulin resistance by independently elevating the TyG index in male gas station workers.

Distribution and Spread of the Mobilized RND Efflux Pump Gene Cluster tmexCD-toprJ in Klebsiella pneumoniae from Different Sources.

In this study, we screened the tmexCD-toprJ gene cluster among 1,541 samples obtained from patients, healthy individuals, companion animals, pigs, chicken, and pork and chicken meat in Yangzhou, China. As a result, nine strains from humans, animals, and foods were positive for tmexCD1-toprJ1, which was located on plasmids or the chromosome. Seven different sequence types (STs) were identified, including ST15 (n = 2), ST580, ST1944, ST2294, ST5982, ST6262 (n = 2), and ST6265. All the positive strains were clustered into two distinct clades, and they shared a 24,087-bp core structure of tmexCD1-toprJ1, bounded by IS26 in the same orientation. IS26 could facilitate rapid and wide dissemination of tmexCD1-toprJ1 in Enterobacteriaceae from various sources. IMPORTANCE Tigecycline has been regarded as one of the last-resort antibiotics available for the treatment of infections caused by carbapenem-resistant Enterobacterales. The plasmid-mediated resistance-nodulation-division-type efflux pump gene cluster tmexCD-toprJ is a newly identified tigecycline resistance determinant. In this study, we revealed that tmexCD-toprJ has disseminated among Klebsiella pneumoniae strains from poultry, food markets, and patients. It is critical to strengthen continuous monitoring, and control measures should be implemented to prevent the further dissemination of tmexCD-toprJ.

Low prevalence of mobilized resistance genes blaNDM, mcr-1, and tet(X4) in Escherichia coli from a hospital in China.

The emergence and spread of carbapenemase genes, colistin resistance genes mcr-1, and tigecycline resistance gene tet(X) represent a significant threat to clinical therapy and public health. In this study, we investigated the presence of carbapenemase genes, mcr-1, and tet(X) in 298 Escherichia coli strains obtained from a teaching hospital in China. In total, eight (2.68%), six (2.01%), and one (0.34%) E. coli isolates carried blaNDM, mcr-1, and tet(X4), respectively. The blaNDM gene was located on IncX3 (n = 4), F2:A-:B- (n = 3), and F2:A1:B1 (n = 1) plasmids, with high similarity to multiple plasmids belonging to the same incompatibility type from Enterobacteriaceae. Six MCR-producing strains contained mcr-1-carrying IncI2 plasmids, organized similarly to other mcr-1-bearing IncI2 plasmids from animals in China. The blaCTX-M-55/64/132/199 gene located within a typical transposition unit (ISEcp1-blaCTX-M-orf477Δ) was inserted near dnaJ to generate 5-bp direct repeats in four mcr-1-positive plasmids. The tet(X) and another four resistance genes [aadA2, tet(A), floR, and Δlnu(F)] were co-located on an IncX1 plasmid, highly similar to other tet(X4)-carrying IncX1 plasmids from Escherichia and Klebsiella of animal or food origin, except that the conjugative transfer region of IncX1 plasmids was absent in our plasmid. Although a low prevalence of blaNDM, mcr-1, and tet(X) was observed in E. coli from patients in this study, their dissemination associated with some successful pandemic plasmids is of great concern. The continued surveillance of these crucial resistance genes in patients should be strengthened.

Case Report of bla NDM-7-Harboring IncX3 Plasmid in ST196 Klebsiella quasipneumoniae in China.

Klebsiella quasipneumoniae isolate SBH035 was recovered from a patient in Jiangsu Province, China. The isolate showed resistance to ampicillin, cefazolin, cefotaxime, meropenem, ceftazidime-avibactam, and fosfomycin. The carbapenemase-encoding gene bla NDM-7 was identified, and whole genome sequencing analysis indicated that bla NDM-7 was located in an IncX3 plasmid with a conserved structure of IS26-ΔcutA-tat-trpF-ble MBL -bla NDM-7-ISAba125-IS3000-ΔTn2. To date, this is the first identification of a bla NDM-7-harboring IncX3 plasmid in ST196 K. quasipneumoniae from a patient in China. Greater attention to controlling the dissemination of IncX3 plasmids is needed owing to potential horizontal transfer via mobile genetic elements.

Deep Learning for 3D Point Clouds: A Survey.

Point cloud learning has lately attracted increasing attention due to its wide applications in many areas, such as computer vision, autonomous driving, and robotics. As a dominating technique in AI, deep learning has been successfully used to solve various 2D vision problems. However, deep learning on point clouds is still in its infancy due to the unique challenges faced by the processing of point clouds with deep neural networks. Recently, deep learning on point clouds has become even thriving, with numerous methods being proposed to address different problems in this area. To stimulate future research, this paper presents a comprehensive review of recent progress in deep learning methods for point clouds. It covers three major tasks, including 3D shape classification, 3D object detection and tracking, and 3D point cloud segmentation. It also presents comparative results on several publicly available datasets, together with insightful observations and inspiring future research directions.

[Determination of three benzodiazepines in human urine by solid-phase extraction with poly [2-(acryloyloxy) ethyl] trimethyl ammonium chloride-co-ethylene glycol dimethacrylate monolithic column coupled with high performance liquid chromatography].

A polymer monolithic column was prepared in a syringe by using [2-(acryloyloxy) ethyl] trimethyl ammonium chloride (DAC) as a monomer and ethylene glycol dimethacrylate (EDMA) as a crosslinker. The obtained monolith was developed as a solid-phase extraction sorbent and used with high performance liquid chromatography (HPLC) for the analysis of three benzodiazepines (BZDs) including bromazepam (BRZ), lorazepam (LRZ) and diazepam (DZP) in urine. The effects of reaction time and the solid-phase extraction conditions (washing solution, elution solvent and volume) on the extraction efficiencies of the three BZDs were investigated. The monolithic column was successfully prepared within 4 h, and it offered 100% adsorption efficiency for the three BZDs. The urine sample (4 mL) was loaded on the monolith, washed with 4 mL of H2O, and eluted with 1 mL of ethyl acetate. Under the optimized conditions, the linear ranges were 4.0-1000 ng/mL for the three BZDs, with correlation coefficients (r) of 0.999. The limits of detection (S/N=3) and limits of quantification (S/N=10) of the three BZDs were in the range of 1.0-1.2 ng/mL and 3.3-4.0 ng/mL, respectively. The recoveries at three spiked levels (10, 25 and 50 ng/mL) of the three BZDs ranged from 81.4% to 102%, with intra-day and inter-day relative standard deviations (n=3) of 1.2%-4.5% and 2.5%-8.3%. The polymer monolithic column provided effective purification for the three BZDs in urine and the enrichment factor was 12-15. This polymer monolithic adsorbent has the advantages of easy preparation and high extraction efficiency. It is successfully applied to the determination of the three BZDs in urine samples.