Structural basis of water-mediated cis Watson-Crick/Hoogsteen base-pair formation in non-CpG methylation.

Non-CpG methylation is associated with several cellular processes, especially neuronal development and cancer, while its effect on DNA structure remains unclear. We have determined the crystal structures of DNA duplexes containing -CGCCG- regions as CCG repeat motifs that comprise a non-CpG site with or without cytosine methylation. Crystal structure analyses have revealed that the mC:G base-pair can simultaneously form two alternative conformations arising from non-CpG methylation, including a unique water-mediated cis Watson-Crick/Hoogsteen, (w)cWH, and Watson-Crick (WC) geometries, with partial occupancies of 0.1 and 0.9, respectively. NMR studies showed that an alternative conformation of methylated mC:G base-pair at non-CpG step exhibits characteristics of cWH with a syn-guanosine conformation in solution. DNA duplexes complexed with the DNA binding drug echinomycin result in increased occupancy of the (w)cWH geometry in the methylated base-pair (from 0.1 to 0.3). Our structural results demonstrated that cytosine methylation at a non-CpG step leads to an anti→syntransition of its complementary guanosine residue toward the (w)cWH geometry as a partial population of WC, in both drug-bound and naked mC:G base pairs. This particular geometry is specific to non-CpG methylated dinucleotide sites in B-form DNA. Overall, the current study provides new insights into DNA conformation during epigenetic regulation.

Walnut protein isolate based emulsion as a promising delivery system enhanced lutein bioaccessibility.

Lutein, a natural pigment with multiple beneficial bioactivities, faces limitations in food processing due to its instability. In this study, we constructed four modified walnut protein isolate (WNPI) based emulsions as emulsion-based delivery systems (EBDS) for lutein fortification. The modification treatments enhanced the encapsulation efficiency of the WNPI-based EBDS on lutein. The modified WNPI-based EBDS exhibited improved storage and digestive stability, as well as increased lutein delivery capability in simulated gastrointestinal conditions. After in vitro digestion, the lutein retention in the modified WNPI-based EBDS was higher than in the untreated WNPI-based EBDS, with a maximum retention of 49.67 ± 1.10 % achieved after ultrasonic modification. Furthermore, the modified WNPI-based EBDS exhibited an elevated lutein bioaccessibility, reaching a maximum value of 40.49 ± 1.29 % after ultrasonic modification, nearly twice as high as the untreated WNPI-based EBDS. Molecular docking analysis indicated a robust affinity between WNPI and lutein, involving hydrogen bonds and hydrophobic interactions. Collectively, this study broadens WNPI's application and provides a foundation for fortifying other fat-soluble bioactive substances.

Causal association of circulating cytokines with the risk of lung cancer: a Mendelian randomization study.

Background: Lung cancer is the deadliest and most prevalent malignancy worldwide. While smoking is an established cause, evidence to identify other causal factors remains lacking. Current research indicates chronic inflammation is involved in tumorigenesis and cancer development, though the specific mechanisms underlying the role of inflammatory cytokines in lung cancer pathogenesis remain unclear. This study implemented Mendelian randomization (MR) analysis to investigate the causal effects of circulating cytokines on lung cancer development. Methods: We performed a two-sample MR analysis in Europeans utilizing publicly available genome-wide association study summary statistics. Single nucleotide polymorphisms significantly associated with cytokine were selected as genetic instrumental variables. Results: Genetically predicted levels of the chemokine interleukin-18 (IL-18) (OR = 0.942, 95% CI: 0.897-0.990, P = 0.018) exerted significant negative causal effects on overall lung cancer risk in this analysis. Examining specific histologic subtypes revealed further evidence of genetic associations. Stem cell factor (SCF) (OR = 1.150, 95% CI: 1.021-1.296, P = 0.021) and interleukin-1beta (IL-1ß) (OR = 1.152, 95% CI: 1.003-1.325, P = 0.046) were positively associated with lung adenocarcinoma risk, though no inflammatory factors showed causal links to squamous cell lung cancer risk. Stratified by smoking status, interferon gamma-induced protein 10 (IP-10) (OR = 0.861, 95% CI: 0.781-0.950, P = 0.003) was inversely associated while IL-1ß (OR = 1.190, 95% CI: 1.023-1.384, P = 0.024) was positively associated with lung cancer risk in ever smokers. Among never smokers, a positive association was observed between lung cancer risk and SCF (OR = 1.474, 95% CI: 1.105-1.964, P = 0.008). Importantly, these causal inferences remained robust across multiple complementary MR approaches, including MR-Egger, weighted median, weighted mode and simple mode regressions. Sensitivity analyses also excluded potential bias stemming from pleiotropy. Conclusion: This MR study found preliminary evidence that genetically predicted levels of four inflammatory cytokines-SCF, IL-1ß, IL-18, and IP-10-may causally influence lung cancer risk in an overall and subtype-specific manner, as well as stratified by smoking status. Identifying these cytokine pathways that may promote lung carcinogenesis represents potential new targets for the prevention, early detection, and treatment of this deadly malignancy.

Zinc gluconate improves atopic dermatitis by modulating CXCL10 release of keratinocytes via PPARα activation.

Atopic dermatitis (AD) is a chronic inflammatory skin condition with complex causes involving immune factors. The presence of essential trace elements that support immune system function can influence the development of this condition. This study investigated how serum trace elements impact the pathogenesis of atopic dermatitis. Upon analyzing serum microelements in AD patients and control subjects, it was observed that patients with AD had notably lower zinc levels. Genomic analysis of AD skin revealed distinct gene expression patterns, specifically the increased expression of CXCL10 in the epidermis. The heightened levels of CXCL10 in AD skin lesions were found to correlate with reduced serum zinc levels. Treatment with zinc gluconate showed reduced chemotactic response and CXCL10 release, suggesting its potential to regulate CXCL10 expression of keratinocytes in AD. The mechanism behind this involved the downregulation of STAT phosphorylation through activating PPARα. In the AD-like dermatitis mouse model, zinc gluconate therapy decreased serum IgE levels, alleviated skin lesion severity, reduced skin thickness, and lowered CXCL10 expression, demonstrating its efficacy in managing AD-like skin conditions. These findings indicate that zinc gluconate can reduce inflammation in keratinocytes by activating PPARα, inhibiting STAT signaling, and decreasing CXCL10 release, thus highlighting its potential as a therapeutic target for AD.

The impact of extreme precipitation on water use efficiency along vertical vegetation belts in Hengduan Mountain during 2001 and 2020.

In the context of climate change, extreme precipitation events are continuously increasing and impact the water­carbon coupling of ecosystems. The vertical vegetation zonation, as a characteristic of mountain ecosystems, reflects the differences in vegetation response to climate change at different elevations. In this study, we used the water use efficiency (WUE) as an indicator to evaluate the water­carbon relationship. By using MODIS data, we analyzed the spatiotemporal patterns of gross primary productivity (GPP), evapotranspiration (ET), and WUE from 2001 to 2020, as well as the responses of WUE to extreme wetness factor Number of precipitation days (R0.1), extreme dryness factor Consecutive dry days (CDD), and meteorological factors under the vertical vegetation zonation. Our results showed that annual GPP and ET displayed a significant increasing trend between 2001 and 2020, whereas WUE showed a weak decreasing trend. Spatially, GPP and WUE decreased with increasing elevation. Analyzing the WUE of mountainous ecosystems as a unified whole may not precisely capture the reactions of vegetation to severe rainfall occurrences. In fact, across different vegetation belts in mountainous areas, there exists a negative correlation between WUE and R0.1, and a positive correlation with CDD. In terms of meteorological factors, the temporal variation of GPP was primarily associated with vapor pressure deficit (VPD) and temperature (Ta), while those of ET was mainly related to soil water content (SWC). WUE was affected by a combination of meteorological factors and had a certain degree of variation between different altitude intervals. These findings contribute to a better understanding and prediction of the relationship between extreme rainfall climate and water­carbon coupling in mountainous areas.

Synergistic upregulation of PD­L1 in tumor cells and CD39 in tumor­infiltrating CD8+ T cells leads to poor prognosis in patients with hepatocellular carcinoma.

The immune escape of tumor cells and functional status of tumor-infiltrating T cells may serve pivotal roles in the tumor immune microenvironment and progression of hepatocellular carcinoma (HCC). The present study enrolled 91 patients with HCC and examined programmed cell death ligand 1 (PD-L1) expression in tumor cells and CD39 expression in tumor-infiltrating CD8+ T cells in patient samples using multiplex immunofluorescence assays. The impact of PD-L1 and CD39 expression levels on the prognosis of patients with HCC was investigated utilizing Kaplan-Meier analyses. The individual upregulation of PD-L1 in tumor cells, as well as the individual upregulation of CD39 expression in tumor-infiltrating CD8+ T cells did not significantly affect the prognosis of patients with HCC. However, the simultaneous upregulation of both PD-L1 in tumor cells and CD39 in tumor-infiltrating CD8+ T cells was associated with reduced overall survival in patients with HCC. Therefore, the results of the present study suggested that the interplay between tumor cell immune escape and tumor-infiltrating immune cell functional status within the tumor immune microenvironment may have had a substantial impact on the prognosis of patients with HCC. Mechanistically, increased expression levels of PD-L1 in tumor cells may improve the immune escape capacity of tumors, whilst upregulation of CD39 in tumor-infiltrating T cells may be associated with T cell exhaustion. Therefore, the upregulation of PD-L1 expression in tumor cells, in conjunction with the exhaustion of tumor-infiltrating CD8+ T cells, could serve as a future potential prognostic indicator of patients with HCC.

Reducing annotating load: Active learning with synthetic images in surgical instrument segmentation.

Accurate instrument segmentation in the endoscopic vision of minimally invasive surgery is challenging due to complex instruments and environments. Deep learning techniques have shown competitive performance in recent years. However, deep learning usually requires a large amount of labeled data to achieve accurate prediction, which poses a significant workload. To alleviate this workload, we propose an active learning-based framework to generate synthetic images for efficient neural network training. In each active learning iteration, a small number of informative unlabeled images are first queried by active learning and manually labeled. Next, synthetic images are generated based on these selected images. The instruments and backgrounds are cropped out and randomly combined with blending and fusion near the boundary. The proposed method leverages the advantage of both active learning and synthetic images. The effectiveness of the proposed method is validated on two sinus surgery datasets and one intraabdominal surgery dataset. The results indicate a considerable performance improvement, especially when the size of the annotated dataset is small. All the code is open-sourced at: https://github.com/HaonanPeng/active_syn_generator.

The potential of integrating stereotactic ablative radiotherapy techniques with hyperfractionation for lung cancer.

BACKGROUND: Limited literature exists on the feasibility and effectiveness of integrating stereotactic ablative radiotherapy (SABR) techniques with hyperfractionated regimens for patients with lung cancer. This study aims to assess whether the SABR technique with hyperfractionation can potentially reduce lung toxicity. METHODS: We utilized the linear-quadratic model to find the optimal fraction to maximize the tumor biological equivalent dose (BED) to normal-tissue BED ratio. Validation was performed by comparing the SABR plans with 50 Gy/5 fractions and hyperfractionationed plans with 88.8 Gy/74 fractions with the same tumor BED and planning criteria for 10 patients with early-stage lung cancer. Mean lung BED, Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP), critical volume (CV) criteria (volume below BED of 22.92 and 25.65 Gy, and mean BED for lowest 1000 and 1500 cc) and the percentage of the lung receiving 20Gy or more (V20) were compared using the Wilcoxon signed-rank test. RESULTS: The transition point occurs when the tumor-to-normal tissue ratio (TNR) of the physical dose equals the TNR of α/ß in the BED dose-volume histogram of the lung. Compared with the hypofractionated regimen, the hyperfractionated regimen is superior in the dose range above but inferior below the transition point. The hyperfractionated regimen showed a lower mean lung BED (6.40 Gy vs. 7.73 Gy) and NTCP (3.50% vs. 4.21%), with inferior results concerning CV criteria and higher V20 (7.37% vs. 7.03%) in comparison with the hypofractionated regimen (p < 0.01 for all). CONCLUSIONS: The hyperfractionated regimen has an advantage in the high-dose region of the lung but a disadvantage in the low-dose region. Further research is needed to determine the superiority between hypo- and hyperfractionation.

Effects of biodegradable microplastics and straw addition on soil greenhouse gas emissions.

Large pieces of plastic are transformed into microplastic particles through weathering, abrasion, and ultraviolet radiation, significantly impacting the soil ecosystem. However, studies on biodegradable microplastics replacing traditional microplastics as agricultural mulching films to drive the biogeochemical processes influenced by GHG are still in their initial stages, with limited relevant reports available. This study sought to investigate the effects of microplastic and straw addition on CO2 and N2O emissions in different soils. Herein, yellow-brown soil (S1) and fluvo-aquic soil (S2) were utilized, each treated with three different concentrations of PLA (polylactic acid) microplastics (0.25%, 2%, and 7% w/w) at 25 °C for 35 days, with and without straw addition. The results showed that straw (1% w/w) significantly increased soil CO2 by 4.1-fold and 3.2-fold, respectively, and N2O by 1.8-fold and 1.8-fold, respectively, in cumulative emissions in S1 and S2 compared with the control. PLA microplastics significantly increased CO2 emissions by 71.5% and 99.0% and decreased N2O emissions by 30.1% and 24.7% at a high concentration (7% w/w, PLA3) in S1 and S2 compared with the control, respectively. The same trend was observed with the addition of straw and microplastics together. Structural equation modeling and redundancy analysis confirmed that soil physiochemical parameters, enzyme and microbial activities are key factors regulating CO2 and N2O emissions. The addition of microplastics is equivalent to the addition of carbon sources, which can significantly affect DOC, MBC, SOC and the abundance of carbon-associated bacteria (CbbL), thereby increasing soil CO2 emissions. The addition of microplastics alone inhibited the activity of nitrogen cycling enzymes (urease activity), increasing the abundance of denitrifying microbes. However, adding a high amount of microplastics and straw together released plastic additives, inhibiting microbial abundance and reducing the nitrogen cycle. These effects decreased NH4+-N and increased NO3--N, resulting in decreased N2O emissions. This study indicates that biodegradable microplastics could reduce soil plastic residue pollution through degradation. However, their use could also increase CO2 emissions and decrease N2O emissions. Consequently, this research lays the groundwork for further investigation into the implications of utilizing biodegradable microplastics as agricultural mulch, particularly concerning soil geochemistry and GHG emissions.

[Effects of Straw Addition on N2O and CO2 Emissions from Red Soil Subjected to Different Long-Term Fertilization].

Straw return, as an important measure for soil fertility improvement in farmland, significantly affects the emissions of greenhouse gases N2O and CO2. Thus, the collected soil samples from five long-term (30-year) fertilization treatments (no fertilization, CK; recommended chemical fertilizer, F; 200 % of recommended chemical fertilizer, 2F; pig manure, M; and chemical fertilizer combined with pig manure, FM) were amended with and without straw and incubated under constant temperature and humidity conditions (25 ℃ and 65 % maximum field water holding capacity) for 20 days so as to investigate the key factors influencing N2O and CO2 emissions in response to straw addition in long-term fertilization treatments. The results showed that fertilization significantly increased N2O emissions. Compared to those under the unfertilized treatment[(22.05 ±2.09) µg·kg-1, calculated as nitrogen, the same as below], cumulative N2O emissions from the chemical fertilizer treatments significantly increased by 119 %-195 %[(48.38 ±20.81) µg·kg-1 and (65.13 ±12.55) µg·kg-1 from the F and 2F treatments, respectively], and those from the manure treatments increased by 275 %-399 %[(82.72 ±12.73) µg·kg-1 and (1 101.99 ±425.71) µg·kg-1 from the M and FM treatments, respectively]. Soil NO3--N, DOC, and DTN were the main factors influencing N2O emissions from fertilized treatments in the absence of straw addition. Straw addition significantly increased cumulative N2O emissions by 345 % and 247 % in the 2F and M treatments, respectively, compared to those in the corresponding fertilized treatments without straw addition, with no significant effect on N2O emissions in the CK, F, and FM treatments. Straw addition increased DOC content and microbial activity and decreased soil NO3--N and DTN contents, thereby increasing N2O emissions. Fertilization also significantly increased CO2 emissions. Compared to those from the unfertilized treatment, cumulative CO2 emissions from the manure treatments significantly increased by 120 %-130 %[(122.11 ±4.3) mg·kg-1 (calculated as carbon, the same as below) and (116.47 ±4.55) mg·kg-1 from the M and FM treatments, respectively], and those in the 2F treatment increased by 28 %[(65.13 ±12.55) mg·kg-1]. In the absence of straw addition, soil MBC, DOC, and DTN were the main factors influencing CO2 emissions. Compared to those in the treatments without straw addition, straw addition significantly increased cumulative CO2 emissions by 660 %-1132 % among fertilization treatments, due to increased DOC and MBC contents and enhanced microbial activity. In conclusion, straw addition significantly increased N2O and CO2 emissions through increased soil DTN consumption and DOC content among fertilization treatments. In soils treated with manure amendment, straw return should be rationally considered for the purpose of balancing the comprehensive trade-offs between fertility improvement and greenhouse gas emissions.

One-Pot Hydrothermal-Derived rGO/MXene/Sulfur Composite Aerogels as Free-Standing Cathodes in Lithium-Sulfur Batteries.

The confinement and high utilization of sulfur in the cathodes is critical for improved cycling performance of lithium-sulfur batteries. In this case one-pot hydrothermal strategy is developed to produce rGO/MXene/sulfur composite aerogels where sulfur is in situ trapped in the 3D rGO/MXene conductive skeleton. The optimized composite aerogels as free-standing cathodes delivery a specific capacity of 951 mAhg-1 after 100 cycles at 0.2 C with a low fading rate of 0.062% per cycle. The excellent cycling performance is correlated with highly oxidized MXene and in situ formed sulfate/thiosulfate complex layer in the long-term cycles.

Single-port-plus-one robot-assisted laparoscopic Lich-Gregoir direct nipple ureteral extravesical reimplantation in pediatric primary obstructive megaureter, comparing to laparoscopic cohen.

PURPOSE: To compare the effects of a single-port-plus-one robotic laparoscopic-modified Lich-Gregoir direct nipple approach and traditional laparoscopic Cohen in treating pediatric primary obstructive megaureter. MATERIALS AND METHODS: The clinical data of 24 children with primary obstructive megaureter from January 2021 to November 2021 were analyzed retrospectively. Among them, 12 children (8 boys and 4 girls, the average age were 17.17 ± 6.31 months) treated with the laparoscopic Cohen method were defined as group C. The remaining 12 children (7 boys and 5 girls, the average age was 17.33 ± 6.99 months) underwent single-port-plus-one robotic laparoscopic-modified Lich-Gregoir direct nipple ureteral extravesical reimplantation were defined as group L. The parameters of pre-operation, intraoperative and postoperative were compared. RESULTS: There were no differences in the patient characteristics and average follow-up time between the two groups (P > 0.05).The obstruction resolution rate was 100% in both groups. The total operation time in group L is slightly longer than that in group C(P < 0.001),but the intraperitoneal operation time of the two groups was comparable(P > 0.05). The postoperative parameters included blood loss, gross haematuria time, indwelling catheterization time and hospitalization time in group L is shorter than group C(P < 0.05). One year post-operation, decreasing in ureteral diameter and APRPD, and increasing in DRF were remarkably observed in both two groups(P < 0.05). Ureteral diameter, APRPD, and DRF were not significantly different both in pre-operation and post-operation between Group L and Group C(P > 0.05). CONCLUSION: Single-port-plus-one robot-assisted laparoscopic-modified Lich-Gregoir direct nipple approach and traditional laparoscopic Cohen are both dependable techniques for ureteral reimplantation in the treatment of pediatric primary obstructive megaureter. Since Lich-Gregoir can preserve the physiological direction of the ureter and direct nipple reimplantation enhances the effect of anti-refluxing, this technique is favorable for being promoted and applied in robot surgery.

A multi-institutional meningioma MRI dataset for automated multi-sequence image segmentation.

Meningiomas are the most common primary intracranial tumors and can be associated with significant morbidity and mortality. Radiologists, neurosurgeons, neuro-oncologists, and radiation oncologists rely on brain MRI for diagnosis, treatment planning, and longitudinal treatment monitoring. However, automated, objective, and quantitative tools for non-invasive assessment of meningiomas on multi-sequence MR images are not available. Here we present the BraTS Pre-operative Meningioma Dataset, as the largest multi-institutional expert annotated multilabel meningioma multi-sequence MR image dataset to date. This dataset includes 1,141 multi-sequence MR images from six sites, each with four structural MRI sequences (T2-, T2/FLAIR-, pre-contrast T1-, and post-contrast T1-weighted) accompanied by expert manually refined segmentations of three distinct meningioma sub-compartments: enhancing tumor, non-enhancing tumor, and surrounding non-enhancing T2/FLAIR hyperintensity. Basic demographic data are provided including age at time of initial imaging, sex, and CNS WHO grade. The goal of releasing this dataset is to facilitate the development of automated computational methods for meningioma segmentation and expedite their incorporation into clinical practice, ultimately targeting improvement in the care of meningioma patients.

Diagnostic Abilities of Three-dimensional Anterior Segment Optical Coherence Tomography in Detecting Angle Closure.

PRCIS: 3D-angle parameters and cutoff values for detecting angle closure were proposed. The 3D parameters demonstrated excellent diagnostic performance. Certain horizontal 2D parameters (i.e.,TISA-750, AOD-750, and AOD-500) can attain similar performance to their high-performing 3D counterparts. PURPOSE: To investigate the diagnostic performance of single horizontal 2-dimensional (2D) versus 3-dimensional (3D) angle parameters from swept-source anterior segment optical coherence tomography (CASIA2) in detecting angle closure. METHODS: The cross-sectional study included 118 phakic subjects (59 open-angle, 59 closed-angle). Angle opening distance (AOD), angle recess area (ARA), trabecular-iris space area (TISA) at 250, 500, and 750 µm from scleral spur were measured in 360° radial-scan images. The 3D information of each measurement was analyzed in two patterns: (1) average 3D parameter - the averaged value from 360-degree angle values, and (2) estimate 3D parameter - the estimation of surface area of circumferential angle inlet (using AOD) or circumferential angle volume (using ARA and TISA). The areas under receiver operating curve (AUCs) of eighteen 3D parameters were compared with 2D horizontal parameters. RESULTS: Among 3D parameters, AOD-500 estimate 3D gave the highest AUC (AUC 0.950, cut-off 6.09 mm2), followed by AOD-750 estimate 3D (AUC 0.948, cut-off 8.26 mm2). 3D parameters significantly increased the AUC of ARA-250 and TISA-250 (all P<0.02) compared to the 2D parameters. No significant improvement in AUC was demonstrated for AOD-250 and all parameters at 500 and 750 µm. No significant difference in AUC was found among the six maximum AUC parameters which were AOD-750 horizontal 2D, AOD-500 estimate 3D, TISA-750 horizontal 2D, AOD-500 horizontal 2D, AOD-750 estimate 3D and TISA-750 average 3D. CONCLUSIONS: The 3D-angle parameters had high performance in detecting angle closure. However, comparing a horizontal measurement to 3D parameters, the AUC improvement was mostly insignificant.

Clinical Characteristics and Fatality Risk Factors for Patients with Listeria monocytogenes Infection: A 12-Year Hospital-Based Study in Xi'an, China.

INTRODUCTION: Listeriosis is a severe food-borne disease caused by Listeria monocytogenes infection. The data of listeriosis in Xi'an population are limited. The aim of this study is to evaluate the clinical features and fatality risk factors for listeriosis in three tertiary-care hospitals in Xi'an, China METHODS: The characteristics of demographic data, underlying diseases, clinical manifestations, laboratory indicators, cranial imaging examination, antibiotics therapeutic schemes, and clinical outcomes were collected between 2011 and 2023. Logistic regression analysis was performed. RESULTS: Seventy-one etiologically confirmed listeriosis patients were enrolled, including 12 neonatal and 59 non-neonatal cases. The majority of neonatal listeriosis presented as preterm (50%) and fetal distress (75%). The main clinical manifestations of non-neonatal listeriosis included fever (88%), headache (32%), disorder of consciousness (25%), vomiting (17%), abdominal pain (12%), and convulsions (8%). The fatality rate in neonatal cases was higher than in non-neonatal listeriosis (42 vs. 17%). Although no deaths were reported in maternal listeriosis, only two of 23 patients had an uneventful obstetrical outcome. Five maternal listeriosis delivered culture-positive neonates, three of whom decreased within 1 week post-gestation due to severe complications. Twenty-eight cases were neurolisteriosis and 43 cases were bacteremia. Neurolisteriosis had a higher fatality rate compared with bacteremia listeriosis (36 vs. 12%). The main neuroradiological images were cerebral edema/hydrocephalus, intracranial infection, and cerebral hernia. Listeria monocytogenes showed extremely low resistance to ampicillin (two isolates) and penicillin (one isolate). The fatality risk factors were the involvement of the central nervous system, hyperbilirubinemia, and hyponatremia for all enrolled subjects. Hyperuricemia contributed to the elevation of fatality risk in non-neonatal listeriosis. CONCLUSIONS: When the patients suffered with symptoms of fever and central nervous system infection, they should be alert to the possibility of listeriosis. Early administration of ampicillin- or penicillin-based therapy might be beneficial for recovery of listeriosis.

Homeobox B4 optimizes the therapeutic effect of bone marrow mesenchymal stem cells on endotoxin-associated acute lung injury in rats.

BACKGROUND: Alveolar capillary endothelial cell (EC) injury has a pivotal role in driving acute respiratory distress syndrome (ARDS) progression and maintaining endothelial homeostasis. A previous ex vivo study revealed that overexpression of homeobox B4 (HOXB4) in bone marrow mesenchymal stem cells (BMSCs) enhanced protection against lipopolysaccharide (LPS)-induced EC injury by activating the Wnt/ß-catenin pathway. This in vivo study was performed to verify whether BMSCs overexpressing HOXB4 exert similar protective effects on LPS-induced acute lung injury (ALI) in an animal model. METHODS: The ALI rat model was established by intraperitoneal injection of LPS. Wildtype BMSCs or BMSCs overexpressing HOXB4 were then injected via the tail vein. The lung characteristics of rats were visualized by computed tomography. Lung histopathological characteristics and collagen deposition were assessed by hematoxylin-eosin and Masson's staining, respectively, which were combined with the lung wet/dry ratio and proinflammatory factor levels in bronchoalveolar lavage fluid to further evaluate therapeutic effects. Expression of ß-catenin and VE-cadherin was assessed by western blotting and immunofluorescence. RESULTS: Compared with wildtype BMSCs, overexpression of HOXB4 optimized the therapeutic effects of BMSCs, which manifested as improvements in lung exudation and histopathological features, reduced lung collagen deposition, amelioration of lung permeability, attenuation of lung inflammation, and enhanced expression of ß-catenin and VE-cadherin proteins. CONCLUSIONS: HOXB4-overexpressing BMSCs optimized the protective effect against LPS-induced ALI by partially activating Wnt/ß-catenin signaling.

Diagnostic criteria of anterior segment swept-source optical coherence tomography to detect gonioscopic angle closure.

AIMS: To compare the diagnostic performance of 360° anterior segment optical coherence tomography assessment by applying normative percentile cut-offs versus iris trabecular contact (ITC) for detecting gonioscopic angle closure. METHODS: In this multicentre study, 394 healthy individuals were included in the normative dataset to derive the age-specific and angle location-specific normative percentiles of angle open distance (AOD500) and trabecular iris space area (TISA500) which were measured every 10° for 360°. 119 healthy participants and 170 patients with angle closure by gonioscopy were included in the test dataset to investigate the diagnostic performance of three sets of criteria for detection of gonioscopic angle closure: (1) the 10th and (2) the 5th percentiles of AOD500/TISA500, and (3) ITC (ie, AOD500/TISA500=0 mm/mm2). The number of angle locations with angle closure defined by each set of the criteria for each eye was used to generate the receiver operating characteristic (ROC) curve for the discrimination between gonioscopic angle closure and open angle. RESULTS: Of the three sets of diagnostic criteria examined, the area under the ROC curve was greatest for the 10th percentile of AOD500 (0.933), whereas the ITC criterion AOD500=0 mm showed the smallest area under the ROC (0.852) and the difference was statistically significant with or without adjusting for age and axial length (p<0.001). The criterion ≥90° of AOD500 below the 10th percentile attained the best sensitivity 87.6% and specificity 84.9% combination for detecting gonioscopic angle closure. CONCLUSIONS: Applying the normative percentiles of angle measurements yielded a higher diagnostic performance than ITC for detecting angle closure on gonioscopy.

Gut microbiome changes in mouse, Mongolian gerbil, and hamster models following Clostridioides difficile challenge.

Introduction: Clostridioides difficile infection (CDI), as well as its etiology and pathogenesis, have been extensively investigated. However, the absence of suitable CDI animal models that reflect CDI symptoms and the associated gut microbiome changes in humans has limited research progress in this field. Thus, we aimed to investigate whether Mongolian gerbils, which present a range of human pathological conditions, can been used in studies on CDI. Methods: In this study, we infected Mongolian gerbils and two existing CDI model animals, mice and hamsters, with the hypervirulent ribotype 027 C. difficile strain, and comparatively analyzed changes in their gut microbiome composition via 16S rRNA gene sequencing. Methods: In this study, we infected Mongolian gerbils and two existing CDI model animals, mice and hamsters, with the hypervirulent ribotype 027 C. difficile strain, and comparatively analyzed changes in their gut microbiome composition via 16S rRNA gene sequencing. Results: The results obtained showed that C. difficile colonized the gastrointestinal tracts of the three rodents, and after the C. difficile challenge, C57BL/6J mice did not manifest CDI symptoms and their intestines showed no significant pathological changes. However, the hamsters showed explosive intestinal bleeding and inflammation and the Mongolian gerbils presented diarrhea as well as increased infiltration of inflammatory cells, mucus secretion, and epithelial cell shedding in their intestinal tissue. Further, intestinal microbiome analysis revealed significant differences with respect to intestinal flora abundance and diversity. Specifically, after C. difficile challenge, the Firmicutes/Bacteroidetes ratio decreased for C57BL/6J mice, but increased significantly for Mongolian gerbils and hamsters. Furthermore, the abundance of Proteobacteria increased in all three models, especially in hamsters, while that of Verrucomicrobia only increased significantly in C57BL/6J mice and Mongolian gerbils. Our results also indicated that differences in the relative abundances of Lactobacillaceae and Akkermansia were primarily responsible for the observed differences in response to C. difficile challenge. Conclusion: Based on the observed responses to C. difficile challenge, we concluded for the first time that the Mongolian gerbil could be used as an animal model for CDI. Additionally, the taxa identified in this study may be used as biomarkers for further studies on CDI and to improve understanding regarding changes in gut microbiome in CDI-related diseases.

Emergence of eravacycline heteroresistance in carbapenem-resistant Acinetobacter baumannii isolates in China.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is resistant to almost all antibiotics. Eravacycline, a newer treatment option, has the potential to treat CRAB infections, however, the mechanism by which CRAB isolates develop resistance to eravacycline has yet to be clarified. This study sought to investigate the features and mechanisms of eravacycline heteroresistance among CRAB clinical isolates. A total of 287 isolates were collected in China from 2020 to 2022. The minimum inhibitory concentration (MIC) of eravacycline and other clinically available agents against A. baumannii were determined using broth microdilution. The frequency of eravacycline heteroresistance was determined by population analysis profiling (PAP). Mutations and expression levels of resistance genes in heteroresistant isolates were determined by polymerase chain reaction (PCR) and quantitative real-time PCR (qRT-PCR), respectively. Antisense RNA silencing was used to validate the function of eravacycline heteroresistant candidate genes. Twenty-five eravacycline heteroresistant isolates (17.36%) were detected among 144 CRAB isolates with eravacycline MIC values ≤4 mg/L while no eravacycline heteroresistant strains were detected in carbapenem-susceptible A. baumannii (CSAB) isolates. All eravacycline heteroresistant strains contained OXA-23 carbapenemase and the predominant multilocus sequence typing (MLST) was ST208 (72%). Cross-resistance was observed between eravacycline, tigecycline, and levofloxacin in the resistant subpopulations. The addition of efflux pump inhibitors significantly reduced the eravacycline MIC in resistant subpopulations and weakened the formation of eravacycline heteroresistance in CRAB isolates. The expression levels of adeABC and adeRS were significantly higher in resistant subpopulations than in eravacycline heteroresistant parental strains (P < 0.05). An ISAba1 insertion in the adeS gene was identified in 40% (10/25) of the resistant subpopulations. Decreasing the expression of adeABC or adeRS by antisense RNA silencing significantly inhibited eravacycline heteroresistance. In conclusion, this study identified the emergence of eravacycline heteroresistance in CRAB isolates in China, which is associated with high expression of AdeABC and AdeRS.

Single-port plus one in pediatric robotic-assisted Lich-Gregoir ureteral reimplantation for vesicoureteral reflux, a comparative analysis with short-term outcomes.

OBJECTIVE: To observe the safety and short-term outcomes of a new way of laparoscopic trocar placement in pediatric robotic-assisted Lich-Gregoir ureteral reimplantation for vesicoureteral reflux. METHODS: The retrospective study included 32 patients under 14 years diagnosed with primary vesicoureteral reflux (VUR). All these patients underwent robotic-assisted Lich-Gregoir ureteral reimplantation in our department from December 2020 to August 2022. These patients were divided into the following groups according to the different ways of trocar placement: 13 patients in group single-port plus one (SR) and 19 patients in group multiple-port (MR). Patients' characteristics as well as their perioperative and follow-up data were collected and evaluated. RESULTS: There was no significant difference in the data regarding patients' characteristics and preoperative data. These data included the grade of vesicoureteral reflux according to the voiding cystourethrogram (VCUG), and the differential degree of renal function (DRF) at the following time points: preoperative, postoperative, and comparison of preoperative and postoperative. There was no difference between the two groups. During surgery, the time of artificial pneumoperitoneum establishment, ureteral reimplantation time, and total operative time in the SR group were longer than those in the MR group. Yet only the time of artificial pneumoperitoneum establishment shows a statistical difference (P < 0.0001). Also, the peri-operative data, including the volume of blood loss, fasting time, hospitalization, and length of time that a ureteral catheter remained in place, and the number of postoperative complications demonstrate no difference. In addition, the SFU grade and VCUG grade at the following time point also show no difference between the two groups. CONCLUSION: The study demonstrates that SR in robotic-assisted Lich-Gregoir ureteral reimplantation has reached the same surgical effects as MR. In addition, the single-port plus one trocar placement receives a higher cosmetic satisfaction score from parents and did not increase the surgical time and complexity.