Altered resting-state brain entropy in cerebral small vessel disease patients with cognitive impairment.

OBJECTIVE: Cerebral small vessel disease (CSVD) is a primary vascular disease of cognitive impairment. Previous studies have predominantly focused on brain linear features. However, the nonlinear measure, brain entropy (BEN), has not been elaborated. Thus, this study is aim to investigate if BEN abnormalities could manifest in CSVD patients with cognitive impairment. METHOD: 34 CSVD patients with cognitive impairment and 37 healthy controls (HCs) were recruited. Analysis of gray matter approximate entropy (ApEn) and sample entropy (SampEn) which are two indices of BEN were calculated. To explore whether BEN can provide unique information, we further performed brain linear methods, namely amplitude of low frequency fluctuation (ALFF) and regional homogeneity (ReHo), to observe their differences. The ratios of BEN/ALFF and BEN/ReHo which represent the coupling of nonlinear and linear features were introduced. Correlation analysis was conducted between imaging indices and cognition. Subsequently, the linear support vector machine (SVM) was used to assess their discriminative ability. RESULTS: CSVD patients exhibited lower ApEn and SamEn value in sensorimotor areas, which were correlated with worse memory and executive function. Additionally, the results of BEN showed little overlap with ALFF and ReHo in brain regions. Correlation analysis also revealed a relationship between the two ratios and cognition. SVM analysis utilizing BEN and its ratios as features achieved an accuracy of 74.64 % (sensitivity: 86.49 %; specificity: 61.76 %; and AUC: 0.82439). CONCLUSION: Our study reveals that the reduction of sensorimotor system complexity is correlated with cognition. BEN exhibits distinctive characteristics in brain activity. Combining BEN and the ratios can be new biomarkers to diagnose CSVD with cognitive impairment.

A highly sensitive fluorescence biosensor for aflatoxins B1 detection based on polydiacetylene liposomes combined with exonuclease III-assisted recycling amplification.

A fluorescence biosensor for determination of aflatoxin B1 (AFB1) based on polydiacetylene (PDA) liposomes and exonuclease III (EXO III)-assisted recycling amplification was developed. The AFB1 aptamer partially hybridizes with complementary DNA (cDNA), which is released upon recognition of AFB1 by the aptamer. Subsequently, the cDNA hybridizes with hairpin H to form double-stranded DNA that undergoes digestion by EXO III, resulting in the cyclic release of cDNA and generation of capture DNA for further reaction. The capture DNA then hybridizes with probe modified on PDA liposomes, leading to aggregation of liposomes and subsequent fluorescence production. This strategy exhibited a limit of detection of 0.18 ng/mL within the linear range 1-100 ng/mL with a determination coefficient > 0.99. The recovery ranged from 92.81 to 106.45%, with relative standard deviations (RSD) between 1.73 and 4.26%, for corn, brown rice, peanut butter, and wheat samples. The stability, accuracy, and specificity of the method demonstrated the applicability for real sample analysis.

Visible light-driven dearomative ring expansion of (aza)arenes to access dihydrofuran-based polycyclic compounds.

The dearomative expansion of aromatic rings has long been pursued by chemists due to its potential to provide tractable approaches for synthesizing valuable non-aromatic molecules. To circumvent the conventional use of hazardous and unstable diazo compounds, photochemical synthesis has recently emerged as a promising platform. However, protocols that can effectively handle both arenes and azaarenes remain scarce. Herein, we introduce a generic strategy that efficiently converts ß-(aza)aryl-ß-substituted enones into biologically significant cycloheptatriene derivatives, including their aza-variants. This method allows for the easy modulation of diverse functional groups on the product and demonstrates a wide substrate scope, evidenced by its excellent tolerance to various drug motifs and good compatibility with five-membered azaarenes undergoing ring expansion. Moreover, DFT calculations of plausible mechanisms have motivated the implementation of an important cascade diradical recombination strategy for 1,3-dienones, thus facilitating the synthesis of valuable 2-oxabicyclo[3.1.0]hex-3-ene derivatives.

Bifunctional Protein TC1 Mediated One-Pot Strategy for Robust Immobilization of DNA with High Accessibility.

Immobilizing DNA with high accessibility at the interface is attractive but challenging. Current methods often involve multiple chemical reactions and derivatives. In this study, an endonuclease, TC1, is introduced to develop a robust strategy for immobilizing DNA with enhanced accessibility. TC1 enables direct immobilization of DNA onto a solid support through self-catalytic DNA covalent coupling and robust solid adsorption capabilities. This method demonstrates high accessibility to target molecules, supported by the improved sensitivity of DNA hybridization and aptamer-target recognition assays. TC1-mediated DNA immobilization is a one-pot reaction that does not require chemical derivatives, making it promising for the development of high-performance DNA materials and technologies.

Association between household size and risk of incident dementia in the UK Biobank study.

Currently, the relationship between household size and incident dementia, along with the underlying neurobiological mechanisms, remains unclear. This prospective cohort study was based on UK Biobank participants aged ≥ 50 years without a history of dementia. The linear and non-linear longitudinal association was assessed using Cox proportional hazards regression and restricted cubic spline models. Additionally, the potential mechanisms driven by brain structures were investigated by linear regression models. We included 275,629 participants (mean age at baseline 60.45 years [SD 5.39]). Over a mean follow-up of 9.5 years, 6031 individuals developed all-cause dementia. Multivariable analyses revealed that smaller household size was associated with an increased risk of all-cause dementia (HR, 1.06; 95% CI 1.02-1.09), vascular dementia (HR, 1.08; 95% CI 1.01-1.15), and non-Alzheimer's disease non-vascular dementia (HR, 1.09; 95% CI 1.03-1.14). No significant association was observed for Alzheimer's disease. Restricted cubic splines demonstrated a reversed J-shaped relationship between household size and all-cause and cause-specific dementia. Additionally, substantial associations existed between household size and brain structures. Our findings suggest that small household size is a risk factor for dementia. Additionally, brain structural differences related to household size support these associations. Household size may thus be a potential modifiable risk factor for dementia.

Enantioselective [2π + 2σ] Cycloadditions of Bicyclo[1.1.0]butanes with Vinylazaarenes through Asymmetric Photoredox Catalysis.

Here we present a highly enantioselective [2π + 2σ] photocycloaddition of bicyclo[1.1.0]butanes (BCBs). The reaction uses a variety of vinylazaarenes as partners and is catalyzed by a polycyclic aromatic hydrocarbon (PAH)-containing chiral phosphoric acid as a bifunctional chiral photosensitizer. A wide array of pharmaceutically important bicyclo[2.1.1]hexane (BCH) derivatives have been synthesized with high yields, enantioselectivity, and diastereoselectivity. In addition to the diverse 1-ketocarbonyl-3-substituted BCBs, α/ß-substituted vinylazaarenes are compatible with such an unprecedented photoredox catalytic pathway, resulting in the successful assembly of an all-carbon quaternary stereocenter or two adjacent tertiary stereocenters on the product.

Bacterial community structure analysis of sludge from Taozi lake and isolation of an efficient 17ß-Estradiol (E2) degrading strain Sphingobacterium sp. GEMB-CSS-01.

Environmental challenges arising from organic pollutants pose a significant problem for modern societies. Efficient microbial resources for the degradation of these pollutants are highly valuable. In this study, the bacterial community structure of sludge samples from Taozi Lake (polluted by urban sewage) was studied using 16S rRNA sequencing. The bacterial phyla Proteobacteria, Bacteroidetes, and Chloroflexi, which are potentially important in organic matter degradation by previous studies, were identified as the predominant phyla in our samples, with relative abundances of 48.5%, 8.3%, and 6.6%, respectively. Additionally, the FAPROTAX and co-occurrence network analysis suggested that the core microbial populations in the samples may be closely associated with organic matter metabolism. Subsequently, sludge samples from Taozi Lake were subjected to enrichment cultivation to isolate organic pollutant-degrading microorganisms. The strain Sphingobacterium sp. GEMB-CSS-01, tolerant to sulfanilamide, was successfully isolated. Subsequent investigations demonstrated that Sphingobacterium sp. GEMB-CSS-01 efficiently degraded the endocrine-disrupting compound 17ß-Estradiol (E2). It achieved degradation efficiencies of 80.0% and 53.5% for E2 concentrations of 10 mg/L and 20 mg/L, respectively, within 10 days. Notably, despite a reduction in degradation efficiency, Sphingobacterium sp. GEMB-CSS-01 retained its ability to degrade E2 even in the presence of sulfanilamide concentrations ranging from 50 to 200 mg/L. The findings of this research identify potential microbial resources for environmental bioremediation, and concurrently provide valuable information about the microbial community structure and patterns within Taozi Lake.

One-Step Purification and Immobilization of Glycosyltransferase with Zn-Ni MOF for the Synthesis of Rare Ginsenoside Rh2.

Uridine diphosphate (UDP)-glucosyltransferases (UGTs) have received increasing attention in the field of ginsenoside Rh2 conversion. By harnessing the metal chelation between transition metal ions and imidazole groups present on His-tagged enzymes, a specific immobilization of the enzyme within metal-organic frameworks (MOFs) is achieved. This innovative approach not only enhances the stability and reusability of the enzyme but also enables one-step purification and immobilization. Consequently, the need for purifying crude enzyme solutions is effectively circumvented, resulting in significant cost savings during experimentation. The use of immobilized enzymes in catalytic reactions has shown great potential for achieving higher conversion rates of ginsenoside Rh2. In this study, highly stable mesoporous Zn-Ni MOF materials were synthesized at 150 °C by a solvothermal method. The UGT immobilized on the Zn-Ni MOF (referred to as UGT@Zn-Ni MOF) exhibited superior pH adaptability and thermal stability, retaining approximately 76% of its initial activity even after undergoing 7 cycles. Furthermore, the relative activity of the immobilized enzyme remained at an impressive 80.22% even after 45 days of storage. The strong specific adsorption property of Zn-Ni MOF on His-tagged UGT was confirmed through analysis using polyacrylamide gel electrophoresis. UGT@Zn-Ni MOF was used to catalyze the conversion reaction, and the concentration of rare ginsenoside Rh2 was generated at 3.15 µg/mL. The results showed that Zn-Ni MOF is a material that can efficiently purify and immobilize His-tagged enzyme in one step and has great potential for industrial applications in enzyme purification and ginsenoside synthesis.

Joint Exposure to Ambient Air Pollutants, Genetic Risk, and Ischemic Stroke: A Prospective Analysis in UK Biobank.

BACKGROUND: Our primary objective was to assess the association between joint exposure to various air pollutants and the risk of ischemic stroke (IS) and the modification of the genetic susceptibility. METHODS: This observational cohort study included 307 304 British participants from the United Kingdom Biobank, who were stroke-free and possessed comprehensive baseline data on genetics, air pollutant exposure, alcohol consumption, and dietary habits. All participants were initially enrolled between 2006 and 2010 and were followed up until 2022. An air pollution score was calculated to assess joint exposure to 5 ambient air pollutants, namely particulate matter with diameters equal to or <2.5 µm, ranging from 2.5 to 10 µm, equal to or <10 µm, as well as nitrogen oxide and nitrogen dioxide. To evaluate individual genetic risk, a polygenic risk score for IS was calculated for each participant. We adjusted for demographic, social, economic, and health covariates. Cox regression models were utilized to estimate the associations between air pollution exposure, polygenic risk score, and the incidence of IS. RESULTS: Over a median follow-up duration of 13.67 years, a total of 2476 initial IS events were detected. The hazard ratios (95% CI) of IS for per 10 µg/m3 increase in particulate matter with diameters equal to or <2.5 µm, ranging from 2.5 to 10 µm, equal to or <10 µm, nitrogen dioxide, and nitrogen oxide were 1.73 (1.33-2.14), 1.24 (0.88-1.70), 1.13 (0.89-1.33), 1.03 (0.98-1.08), and 1.04 (1.02-1.07), respectively. Furthermore, individuals in the highest quintile of the air pollution score exhibited a 29% to 66% higher risk of IS compared with those in the lowest quintile. Notably, participants with both high polygenic risk score and air pollution score had a 131% (95% CI, 85%-189%) greater risk of IS than participants with low polygenic risk score and air pollution score. CONCLUSIONS: Our findings suggested that prolonged joint exposure to air pollutants may contribute to an increased risk of IS, particularly among individuals with elevated genetic susceptibility to IS.

Network Meta-Analysis of Different Thrombolytic Strategies for the Treatment of Central Retinal Artery Occlusion.

PURPOSE: Intravenous and intra-arterial thrombolytic strategies have been used to treat central retinal artery occlusion (CRAO); however, previous meta-analyses evaluated the efficacy of these two thrombolytic strategies separately but did not compare them. This network meta-analysis aimed to evaluate the comparative efficacy and safety of different thrombolytic methods for treating CRAO. METHODS: We searched PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfangdata to identify relevant studies published before 1 January 2023. We used the "network" command in STATA 14.0 software to perform network meta-analysis. In addition, we calculated the surface under the cumulative ranking (SUCRA) to rank all currently available thrombolytic strategies. RESULTS: We included 12 studies in the final data analysis. Results suggested that, compared with standard treatment (ST), intravenous tissue plasminogen activator (IVtPA) (OR, 5.78; 95% CI, 2.07 to 16.11) and intra-arterial urokinase (IAUK) (OR, 2.78; 95% CI, 1.10 to 7.02) and intra-arterial tPA (IAtPA) (OR, 2.45; 95% CI, 1.04 to 5.77) achieved better visual improvement. The differences in visual improvement among IVtPA, IAUK, and IAtPA are insignificant. Furthermore, compared with ST, administration of IVtPA within 4.5 hours of CRAO onset (OR, 8.87; 95% CI, 3.35 to 23.48) rather than administration after 4.5 hours of onset (OR, 3.09; 95% CI, 0.81 to 11.70) achieved better visual improvement. In addition, compared to ST, all available thrombolytic strategies we evaluated were associated with a higher risk of adverse events, but these strategies did not differ. Based on the results of SUCRA, IVtPA had the highest ranking probability in visual improvement (91.9%) but had a relatively lower ranking probability of adverse events (60.1%). CONCLUSION: Both intravenous and intra-arterial thrombolytic strategies are effective for treating CRAO, but SUCRA results show that IVtPA may be the optimal strategy for treating CRAO. Furthermore, based on the results of subgroup analysis, we further speculate that IVtPA injection within 4.5 hours of the onset of CRAO should be the optimal thrombolytic option for treating CRAO. However, due to the limitations of all eligible studies, more studies are still required in the future to validate our findings.

Two undescribed benzopyran derivatives from Ranunculus sceleratus L. with their in vitro anti-inflammatory activity in lipopolysaccharide-activated RAW 264.7 cells.

Previous studies on Ranunculus sceleratus L. have shown the existence of coumarins and their anti-inflammatory effect. Phytochemical work was conducted to investigate the bioactive compounds, leading to the isolation of two undescribed benzopyran derivatives, namely ranunsceleroside A (1) and B (3), together with two known coumarins (2, 4) from the whole plant of R. sceleratus L. All compounds were structurally identified by extensive spectroscopic analysis and then investigated for their inhibitory effect on nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) production induced by lipopolysaccharide (LPS) in RAW 264.7 murine macrophages, repectively. As a result, compound 1-4 presented inhibitory effects on the production of NO, TNF-α, IL-1ß, and IL-6 in a concentration-dependent manner, which provides a potential chemical basis for the traditional use of R. sceleratus L. as an anti-inflammatory plant.

Clinical analysis of acute postoperative pain after total laparoscopic hysterectomy for adenomyosis and uterine fibroids - a prospective observational study.

OBJECTIVE: To investigate the outcome of total laparoscopic hysterectomy (TLH) and postoperative pain characteristics and compare the pain severity after TLH for adenomyosis or uterine fibroids. METHODS: This prospective observational study collected 101 patients received TLH for adenomyosis (AD group) including 41 patients were injected goserelin (3.6 mg) 28 days before TLH, while other adenomyosis patients received TLH without preoperative treatment, and 113 patients received TLH for uterine fibroids (UF group). Pain scores were evaluated at different time sites from operation day to postoperative 72 h using the numeric rating scale. Clinical data were collected from clinical record. RESULTS: Operative time and anaesthetic time were longer in the AD group than those in the UF group (66.88 ± 8.65 vs. 64.46 ± 7.21, p = 0.04; 83.95 ± 10.05 vs. 79.77 ± 6.88, p < 0.01), severe endometriosis was quite more common in AD group (23.76% vs. 2.65%, p < 0.01). Postoperative usage of Flurbiprofen in AD group were more than that of UF group (15.48 ± 38.00 vs. 4.79 ± 18.16, p = 0.02). Total pains and abdominal visceral pains of AD group were more severe compared with UF group in motion and rest pattern at several time sites, while incision pain and shoulder pain were similar. The total postoperative pains after goserelin preoperative treatment in AD group were less than that without goserelin preoperative treatment (p < 0.05). The levels of serum NPY, PGE2 and NGF after laparoscopic hysterectomy of adenomyosis reduced with GnRH agonist pretreatment. CONCLUSIONS: Acute postoperative pain for adenomyosis and uterine fibroids showed considerably different severity, postoperative total pain and abdominal visceral pains of TLH for adenomyosis were more severe compared with uterine fibroids. While patients received goserelin before laparoscopic hysterectomy of adenomyosis suffered from less severity of postoperative total pain than that without goserelin preoperative treatment.

Acute postoperative pain for adenomyosis and uterine fibroids showed considerably different severity, postoperative total pain and abdominal visceral pains of TLH for adenomyosis were more severe compared with uterine fibroids.Patients received goserelin before laparoscopic hysterectomy of adenomyosis suffered from less severity of postoperative total pain than that without goserelin preoperative treatment.

Enantioselective Chemodivergent Three-Component Radical Tandem Reactions through Asymmetric Photoredox Catalysis.

Chemodivergent synthesis has been achieved in asymmetric photocatalysis. Under a dual catalyst system consisting of a chiral phosphoric acid and DPZ as a photosensitizer, different inorganic bases enabled the formation of two sets of valuable products from the three-component radical tandem transformations of 2-bromo-1-arylenthan-1-ones, styrenes, and quinoxalin-2(1H)-ones. The key to success was the distinct pKa environment, in which the radicals that formed on the quinoxalin-2(1H)-one rings after two radical addition processes underwent either single-electron oxidation or single-electron reduction. In addition, this work represents the first use of quinoxalin-2(1H)-ones in asymmetric photoredox catalysis.

Asymmetric Olefin Isomerization via Photoredox Catalytic Hydrogen Atom Transfer and Enantioselective Protonation.

Asymmetric olefin isomerization can be appreciated as an ideal synthetic approach to access valuable enantioenriched C═C-containing molecules due to the excellent atom economy. Nonetheless, its occurrence usually requires a thermodynamic advantage, namely, a higher stability of the product to the substrate. It has thus led to rather limited examples of success. Herein, we report a photoredox catalytic hydrogen atom transfer (HAT) and enantioselective protonation strategy for the challenging asymmetric olefin isomerization. As a paradigm, by establishing a dual catalyst system involving a visible light photosensitizer DPZ and a chiral phosphoric acid, with the assistance of N-hydroxyimide to perform HAT, a wide array of allylic azaarene derivatives, featuring α-tertiary carbon stereocenters and ß-C═C bonds, was synthesized with high yields, ees, and E/Z ratios starting from the conjugated α-substituted alkenylazaarene E/Z-mixtures. The good compatibility of assembling deuterium on stereocenters by using inexpensive D2O as a deuterium source further underscores the broad applicability and promising utility of this strategy. Moreover, mechanistic studies have provided clear insights into its challenges in terms of reactivity and enantioselectivity. The exploration will robustly inspire the development of thermodynamically unfavorable asymmetric olefin isomerizations.

Nano-SiO2 reinforced alginate-chitosan-gelatin nanocomposite hydrogels with improved physicochemical properties and biological activity.

Alginate (Alg) hydrogels possess desirable advantages for application in tissue engineering; however, they are limited by their weak mechanical properties, poor chronical stability in phosphate buffered saline, and absence of mammalian cell recognition sites, severely restricting their biomedical applications. To overcome these limitations, we integrated Alg hydrogels with nano-silica (SiO2) to produce nano-SiO2 reinforced Alg-chitosan-gelatin nanocomposite hydrogels (Alg/SiO2-CHI-GA NCH) for biomedical purposes, utilizing Chitosan (CHI) and gelatin (GA) in an alternate electrostatic adsorption. Specifically, we investigated the regulatory and promotional effects of the nano-SiO2 on the morphological structure, mechanical properties, thermal stability, rheological properties, swelling, biodegradability, biomineralization and cytocompatibility of the resultant Alg/SiO2-CHI-GA NCH. The experimental findings demonstrate that the constructed Alg/SiO2-CHI-GA NCH exhibited uniform morphology and a regular structure. Upon freeze-drying, the internal cross-sections of the NCH exhibited a honeycomb porous structure. Furthermore, the physicochemical properties and biological activities of the prepared Alg/SiO2-CHI-GA NCH were regulated to some extent by nano-SiO2 content. Notably, nano-SiO2 inclusion enhanced the attachment and viability of MG63 and MC3T3-E1 cells and induced three-dimensional cell growth in ALG/SiO2-CHI-GA NCH. Among the fabricated NCH, Alg/SiO2-CHI-GA NCH with 0.5% and 1.0% (w/v) nano-SiO2 exhibited significant proliferative activity, which is attributable to their high porosity and uniform cell adhesion. Furthermore, the alkaline phosphatase activity in the cells gradually increased with increasing of nano-SiO2 amount, indicating the favorable effect of nano-SiO2 on the osteogenic differentiation of MG63 and MC3T3-E1 cells. Our study findings provide a comprehensive foundation for the structural- and property-related limitations of Alg hydrogels in biomedicine, thereby expanding their potential applications in tissue engineering.

What impacts ecosystem services in tropical coastal tourism cities? A comparative case study of Haikou and Sanya, China.

The ecological environment of tourism-oriented towns is attracting increasing attention. Taking the cities of Haikou and Sanya as examples, we examined changes in six ecosystem services (ES), including water conservation (WC), crop production (CP), soil retention (SR), carbon storage (CS), habitat quality (HQ), and tourism recreation (TR) from 2005 to 2020. From the three perspectives of geographical environment, socioeconomic development, and tourism development force, 14 indicators were chosen to examine the impact on ES. Except for Haikou's TR, the other ES of Haikou and Sanya showed a decreasing trend from 2005 to 2020. The values of six ES were lower in coastal zones than in noncoastal zones, which were more obvious in Sanya. Specifically, the areas of low value in Sanya were concentrated in the coastal region, and the areas with low value in Haikou were primarily distributed in blocks along the coast and in bands or points in the central and southern areas. From the perspective of influencing factors, the natural environmental factors dominate in Haikou, followed by the socio-economic factors and finally the tourism development factors, while the natural environmental factors also dominate in Sanya, followed by the tourism development factors and finally the socio-economic factors. We provided recommendations for sustainable tourism development in Haikou and Sanya. This study has significant implications for both integrated management and scientific decision-making to enhance the ES of tourism destinations.

Intracranial Atherosclerotic Stenosis Is Associated with Cognitive Impairment in Patients with Nondisabling Ischemic Stroke: A pCASL-Based Study.

Background: Intracranial atherosclerotic stenosis (ICAS) is a key risk factor for vascular cognitive impairment. Cerebral blood flow (CBF) and the spatial coefficient of variation (sCoV) of CBF images (based on pseudocontinuous arterial spin labeling) are used to explore abnormal cerebral perfusion. We aimed to probe the mechanisms underlying cognitive impairment in patients with nondisabling anterior circulation macrovascular disease. Methods: This study included 47 patients with ICAS or occlusion and 40 controls. All participants underwent global and individual neuropsychology assessments and magnetic resonance imaging scan. The correlations between cognitive function and abnormal perfusion were explored. Results: The CBF in the ipsilateral middle cerebral artery (MCA) territory of the lesion side decreased significantly, while it increased on the contralateral side. CBF value had a significant correlation with the memory function in the right cerebral artery lesion group. The sCoV in both gray matter (GM) and the ipsilateral MCA territory of the lesion increased significantly. The sCoV value based on the GM territory or MCA territory was significantly correlated with global cognitive function, memory function, and executive function in patients with ICAS. Conclusions: The cognitive function of patients with severe ICAS or occlusion in anterior circulation was significantly impaired. sCoV could be a better indicator of cognitive impairment than CBF. Interventions to relieve vascular stenosis or occlusion and delay cognitive impairment or improve cognitive function should be actively considered.

Efficacy and safety of piperacillin-tazobactam compared with meropenem in treating complicated urinary tract infections including acute pyelonephritis due to extended-spectrum ß-lactamase-producing Enterobacteriaceae.

Introduction: Extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae pose a huge threat to human health, especially in the context of complicated urinary tract infections (cUTIs). Carbapenems and piperacillin-tazobactam (PTZ) are two antimicrobial agents commonly used to treat cUTIs. Methods: A monocentric retrospective cohort study focused on the treatment of cUTIs in adults was conducted from January 2019 to November 2021. Patients with a positive urine culture strain yielding ≥ 103 colony-forming units per milliliter (CFU/mL), and sensitive to PTZ and carbapenems, were included. The primary endpoint was clinical success after antibiotic therapy. The secondary endpoint included rehospitalization and 90-day recurrence of cUTIs caused by ESBL-producing Enterobacteriaceae. Results: Of the 195 patients included in this study, 110 were treated with PTZ while 85 were administered meropenem. The rate of clinical cure was similar between the PTZ and meropenem groups (80% vs. 78.8%, p = 0.84). However, the PTZ group had a lower duration of total antibiotic use (6 vs. 9; p < 0.01), lower duration of effective antibiotic therapy (6 vs. 8; p < 0.01), and lower duration of hospitalization (16 vs. 22; p < 0.01). Discussion: In terms of adverse events, the safety of PTZ was higher than that of meropenem in the treatment of cUTIs.

scRAA: the development of a robust and automatic annotation procedure for single-cell RNA sequencing data.

A critical task in single-cell RNA sequencing (scRNA-Seq) data analysis is to identify cell types from heterogeneous tissues. While the majority of classification methods demonstrated high performance in scRNA-Seq annotation problems, a robust and accurate solution is desired to generate reliable outcomes for downstream analyses, for instance, marker genes identification, differentially expressed genes, and pathway analysis. It is hard to establish a universally good metric. Thus, a universally good classification method for all kinds of scenarios does not exist. In addition, reference and query data in cell classification are usually from different experimental batches, and failure to consider batch effects may result in misleading conclusions. To overcome this bottleneck, we propose a robust ensemble approach to classify cells and utilize a batch correction method between reference and query data. We simulated four scenarios that comprise simple to complex batch effect and account for varying cell-type proportions. We further tested our approach on both lung and pancreas data. We found improved prediction accuracy and robust performance across simulation scenarios and real data. The incorporation of batch effect correction between reference and query, and the ensemble approach improve cell-type prediction accuracy while maintaining robustness. We demonstrated these through simulated and real scRNA-Seq data.

Astragaloside IV-mediated inhibition of oxidative stress by upregulation of ghrelin in type 2 diabetes-induced cognitive impairment.

This study is to observe the upregulation effect of astragaloside IV on ghrelin in diabetic cognitive impairment (DCI) rats and to investigate the pathway in prevention and treatment by reducing oxidative stress. The DCI model was induced with streptozotocin (STZ) in conjunction with a high-fat and high-sugar diet and divided into three groups: model, low-dose (40 mg/kg), and high-dose (80 mg/kg) astragaloside IV. After 30 days of gavage, the learning and memory abilities of rats, as well as their body weight and blood glucose levels, were tested using the Morris water maze and then detection of insulin resistance, SOD activity, and serum MDA levels. The whole brain of rats was sampled for hematoxylin-eosin and Nissl staining to observe pathological changes in the hippocampal CA1 region. Immunohistochemistry was used to detect ghrelin expression in the hippocampal CA1 region. A Western blot was used to determine changes in GHS-R1α/AMPK/PGC-1α/UCP2. RT-qPCR was used to determine the levels of ghrelin mRNA. Astragaloside IV reduced nerve damage, increased superoxide dismutase (SOD) activity, decreased MDA levels, and improved insulin resistance. Ghrelin levels and expression increased in serum and hippocampal tissues, and ghrelin mRNA levels increased in rat stomach tissues. According to Western blot, it increased the expression of the ghrelin receptor GHS-R1α and upregulated the mitochondrial function associated-protein AMPK-PGC-1α-UCP2. Astragaloside IV increases ghrelin expression in the brain to reduce oxidative stress and delay diabetes-induced cognitive impairment. It may be related to the promotion of ghrelin mRNA levels.