Inappropriate use of antibiotic enhances antibiotic resistance dissemination in ESBL-EC: Role of ydcz in outer membrane vesicles biogenesis and protein transport.

Extended-spectrumß-lactam producing Escherichia coli (ESBL-EC) readily colonizes live poultry and serves as a major source of contamination in retail chicken meat, posing significant threats to public health. This study aims to investigate the impact of inappropriate antibiotic use on the dissemination and exacerbation of antibiotic resistance in ESBL-EC and explore the underlying molecular mechanisms. Through experimental analysis, we propose a hypothesis that inappropriate antibiotic use may exacerbate resistance by affecting vesicle formation and protein secretion. Experimental results demonstrate that under the influence of amoxicillin, the concentration of proteins secreted in outer membrane vehicles (OMVs) by ESBL-EC significantly increases, along with a significant upregulation in the expression of the CTX-M-55-type Extended-spectrum beta-lactamase (CTX-M-55). Proteomic analysis and differential gene knockout experiments identified the key protein YdcZ, associated with OMVs formation and protein transportation in ESBL-EC under amoxicillin treatment. Further investigations reveal direct interactions between YdcZ and other proteins (YdiH and BssR). Upon ydcz gene knockout, a significant decrease in protein concentration within OMVs is observed, accompanied by a noticeable reduction in protection against sensitive bacteria. These findings suggest a critical role of YdcZ in regulating the process of protein transportation to OMVs in ESBL-EC under the influence of amoxicillin. In summary, our research uncovers the significant role of inappropriate antibiotic use in promoting the secretion of OMVs by ESBL-EC, aiding the survival of antibiotic-sensitive bacteria in the vicinity of infection sites. These findings provide new insights into the mechanisms underlying antibiotic-induced bacterial resistance dissemination and offer novel avenues for exploring prevention and control strategies against bacterial resistance propagation.

Association Between Vitamin B12 Intake and Mortality in Patients with Colorectal Cancer: The US National Health and Nutrition Examination Survey, 1999-2018.

Vitamin B12 plays a role in DNA methylation, influencing the 1-carbon cycle; However, its effect on colorectal cancer (CRC) mortality remains uncertain. This study assessed the relationship between vitamin B12 intake and all-cause and cancer-specific mortality among CRC patients. We analyzed data from the NHANES from 1999 to 2018, using multivariable Cox regression, competing risk model, Kaplan-Meier survival curves, and stratified analysis with interaction effects. The studied involved 4,554 cancer patients (mean age 65.8 years, 47.6% males). Results from multivariate Cox regression indicated that each additional 1 mcg/day of dietary vitamin B12 independently increased the risk of all-cause (HR, 1.07; 95% CI: 1.04-1.09, p < 0.001) and cancer-specific mortality (HR, 1.04; 95% CI, 1.02-1.06; p < 0.001). Kaplan-Meier curves indicated a higher risk of all-cause mortality with increased vitamin B12 intake (Log rank p = 0.01). Subgroup analysis suggested that higher vitamin B12 intake correlated with increased all-cause mortality risk, especially in individuals with higher protein (HR, 1.04; 95% CI, 1.02-1.06; p = 0.019) or carbohydrate intake (HR, 1.03; 95% CI, 1.01-1.05; p = 0.04). Thus, higher vitamin B12 intake correlates with increased all-cause and cancer-specific mortality in CRC patients, particularly those with higher protein or carbohydrate intake.

Vacancy Suppression and Resonant Level Rendering Extraordinary Power Factor in Sn0.99In0.01Te/Tourmaline Composite.

SnTe, as a potential medium-temperature thermoelectric material, reaches a maximum power factor (PF) usually above 750 K, which is not conducive to continuous high-power output in practical applications. In this study, PF is maintained at high values between 18.5 and 25 µW cm-1 K-2 for Sn0.99In0.01Te-x wt% tourmaline samples within the temperature range of 323 to 873 K, driving the highest PFeng of 1.2 W m-1 K-1 and PFave of 22.5 µW cm-1 K-2, over 2.5 times that of pristine SnTe. Such an extraordinary PF is attributed to the synergy of resonant levels and Sn vacancy suppression. Specifically, the Seebeck coefficient increases dramatically, reaching 88 µV K-1 at room temperature. Meanwhile, by Sn vacancy suppression, carrier concentration, and mobility are optimized to ≈1019 cm-3 and 740 cm2 V-1 s-1, respectively. With the tourmaline compositing, Sn vacancies are further suppressed and the thermal conductivity simultaneously decreases, with the minimum lattice thermal conductivity of 0.9 W m-1 K-1. Finally, the zT value ≈0.8 is obtained in the Sn0.99In0.01Te sample. The peak of the power output density reaches 0.89 W cm-2 at a temperature difference of 600 K. Such SnTe alloys with high and "temperature-independent" PF will offer an option for realizing high output power in thermoelectric devices.

Clinicopathologic and endoscopic features of sessile serrated lesions and conventional adenomas: a large inpatient population-based study in China.

Objectives: Sessile serrated lesions (SSLs) are precursors of sporadic colorectal cancer (CRC) and have distinct characteristics compared with conventional adenomas (CAs). Several lifestyle and environmental factors may play critical roles in the development of advanced lesions. Our aim is to describe the features of SSLs and CAs and further explore risk factors for advanced lesions. Methods: This is an observational study that collected demographic, endoscopic, and histological data from the China-Japan Friendship Hospital among the inpatient population with pathologically reported as SSL or CA between 2015 and 2022. We analyzed the clinicopathology and endoscopic differences between SSL alone, CA alone, and synchronous SSL+CA groups, and identified risk factors using multiple regression analysis. Results: A total of 9236 polyps from 6598 patients were included in the cohort. Patients with SSL+CA were more likely to be older (p=0.008), while individuals with SSL alone had a higher proportion of early-onset polyps (p<0.001), and SSLs were more common in advanced polyps than CAs (p<0.001). A greater proportion of advanced polyps in the SSL and CA groups were diagnosed as Yamada III, Yamada IV, and laterally spreading tumor (p=0.002, p<0.001, respectively), and multiple SSLs and CAs were more represented in nonadvanced polyps than in advanced polyps. In multiple regression analysis, older patients were more likely to develop advanced SSLs (aOR 1.05, 95% CI 1.02-1.09, p=0.005). Conclusion: SSLs and CAs have diverse demographic, endoscopic, and histological characteristics, and their advanced lesions share different risk factors, which advances the understanding of the etiology and progression of SSLs.

The Classification of Lumbar Spondylolisthesis X-Ray Images Using Convolutional Neural Networks.

We aimed to develop and validate a deep convolutional neural network (DCNN) model capable of accurately identifying spondylolysis or spondylolisthesis on lateral or dynamic X-ray images. A total of 2449 lumbar lateral and dynamic X-ray images were collected from two tertiary hospitals. These images were categorized into lumbar spondylolysis (LS), degenerative lumbar spondylolisthesis (DLS), and normal lumbar in a proportional manner. Subsequently, the images were randomly divided into training, validation, and test sets to establish a classification recognition network. The model training and validation process utilized the EfficientNetV2-M network. The model's ability to generalize was assessed by conducting a rigorous evaluation on an entirely independent test set and comparing its performance with the diagnoses made by three orthopedists and three radiologists. The evaluation metrics employed to assess the model's performance included accuracy, sensitivity, specificity, and F1 score. Additionally, the weight distribution of the network was visualized using gradient-weighted class activation mapping (Grad-CAM). For the doctor group, accuracy ranged from 87.9 to 90.0% (mean, 89.0%), precision ranged from 87.2 to 90.5% (mean, 89.0%), sensitivity ranged from 87.1 to 91.0% (mean, 89.2%), specificity ranged from 93.7 to 94.7% (mean, 94.3%), and F1 score ranged from 88.2 to 89.9% (mean, 89.1%). The DCNN model had accuracy of 92.0%, precision of 91.9%, sensitivity of 92.2%, specificity of 95.7%, and F1 score of 92.0%. Grad-CAM exhibited concentrations of highlighted areas in the intervertebral foraminal region. We developed a DCNN model that intelligently distinguished spondylolysis or spondylolisthesis on lumbar lateral or lumbar dynamic radiographs.

Global supply chains amplify economic costs of future extreme heat risk.

Evidence shows a continuing increase in the frequency and severity of global heatwaves1,2, raising concerns about the future impacts of climate change and the associated socioeconomic costs3,4. Here we develop a disaster footprint analytical framework by integrating climate, epidemiological and hybrid input-output and computable general equilibrium global trade models to estimate the midcentury socioeconomic impacts of heat stress. We consider health costs related to heat exposure, the value of heat-induced labour productivity loss and indirect losses due to economic disruptions cascading through supply chains. Here we show that the global annual incremental gross domestic product loss increases exponentially from 0.03 ± 0.01 (SSP 245)-0.05 ± 0.03 (SSP 585) percentage points during 2030-2040 to 0.05 ± 0.01-0.15 ± 0.04 percentage points during 2050-2060. By 2060, the expected global economic losses reach a total of 0.6-4.6% with losses attributed to health loss (37-45%), labour productivity loss (18-37%) and indirect loss (12-43%) under different shared socioeconomic pathways. Small- and medium-sized developing countries suffer disproportionately from higher health loss in South-Central Africa (2.1 to 4.0 times above global average) and labour productivity loss in West Africa and Southeast Asia (2.0-3.3 times above global average). The supply-chain disruption effects are much more widespread with strong hit to those manufacturing-heavy countries such as China and the USA, leading to soaring economic losses of 2.7 ± 0.7% and 1.8 ± 0.5%, respectively.

Relationship between Glucagon-like Peptide-1 Receptor Agonists and Cardiovascular Disease in Chronic Respiratory Disease and Diabetes.

The purpose of this paper is to assess the effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on stroke or heart disease in patients having chronic respiratory disease and diabetes (CD) with underlying diseases related to COVID-19. From 1998 to 2019, we adjusted competing risk by assessing the effect of GLP-1RAs on stroke or heart disease in a CD cohort after propensity matching based on the Taiwan National Health Insurance Research Database. We also used the time-dependent method to examine the results. GLP-1 RA and non-GLP-1 RA user groups included 15,801 patients (53% women and 46% men with a mean age of 52.6 ± 12.8 years). The time between the diagnoses of DM and the initial use of the GLP-1 RA among the stroke subcohort (<2000 days) was shorter than that of the heart disease subcohort (>2000 days) (all p-values < 0.05). The overall risks of stroke, ischemic, and hemorrhagic stroke were significantly lower in GLP-1 RA users than nonusers. The adjusted subhazard ratio (aSHR) was 0.76 [95% CI 0.65-0.90], 0.77 [95% CI 0.64-0.92], and 0.69 [95% CI 0.54-0.88] (p < 0.05 for all). Furthermore, a ≥351-day use had a significantly lower stroke risk than GLP-1 RA nonusers (aSHR 0.35 [95% CI 0.26-0.49]). The time-dependent method revealed the same result, such as lower stroke, and ischemic or hemorrhagic stroke risk. In contrast, the cardiac arrhythmia incidence was higher in GLP-1 RA users with an aSHR of 1.36 [95% CI 1.16-1.59]. However, this risk disappeared after the ≥351-day use with 1.21 (0.98, 1.68) aSHR. Longer GLP-1 RA use was associated with a decreased risk of ischemic or hemorrhagic stroke and the risk of cardiac arrhythmia disappears in a CD cohort. Both a shorter lag time use of the GLP-1 RA and a longer time use of GLP-1 RA were associated with a decreased risk of ischemic or hemorrhagic stroke in the CD cohort. The GLP-1 RA use in the early stage and optimal time use in the CD cohort may avoid the stroke risk.

Electrochemical reductive removal of trichloroacetic acids by a three-dimensional binderless carbon nanotubes/ CoP/Co foam electrode: Performance and mechanism.

Numerous chlorinated disinfection by-products (DBPs) are produced during the chlorination disinfection of water. Among them, chloroacetic acids (CAAs) are of great concern due to their potential human carcinogenicity. In this study, effective electrocatalytic dechlorination of trichloroacetic acids (TCAA), a typical CAAs, was achieved in the electrochemical system with the three-dimensional (3D) self-supported CoP on cobalt foam modified by carbon nanotubes (CNT/CoP/CF) as the cathode. At a 10 mA cm-2 current density, 74.5% of TCAA (500 µg L-1) was converted into AA within 100 min. In-situ growth of CoP increased the effective electrochemical surface area of the electrode. Electrodeposited CNT promoted electron transfer from the electrode surface to TCAA. Therefore, the production of surface-adsorbed atomic hydrogen (H*) on CNT/CoP/CF was improved, further resulting in excellent electrochemical dechlorination of TCAA. The dechlorination pathway of TCAA proceeded into acetic acids via direct electronic transfer and H*-mediated reduction on CNT/CoP/CF electrode. Additionally, the electroreduction efficiency of CNT/CoP/CF for TCAA exceeded 81.22% even after 20 cycles. The highly efficient TCAA reduction performance (96.57%) in actual water revealed the potential applicability of CNT/CoP/CF in the complex water matrix. This study demonstrated that the CNT/CoP/CF is a promising non-noble metal cathode to remove chlorinated DBPs in practice.

ESBL-Escherichia coli extracellular vesicles mediate bacterial resistance to ß-lactam and mediate horizontal transfer of blaCTX-M-55.

OBJECTIVES: Extracellular vesicles (EVs) have become the focus of research as an emerging method of horizontal gene transfer. In recent years, studies on the association between EVs and the spread of bacterial resistance have emerged, but there is a lack of research on the role of EVs secreted by extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli in the spread of ß-lactam resistance. Therefore, the aim of this study was to investigate the role of EVs in the transmission of ß-lactam resistance. METHODS: In this study, the role of EVs in the transmission of ß-lactam resistance in E. coli was evaluated by the EVs-mediated bacterial resistance to ß-lactam antibiotics test and the EVs-mediated blaCTX-M-55 transfer experiments using EVs secreted by ESBL-E. coli. RESULTS: The results showed that ESBL-EVs were protective against ß-lactam antibiotic-susceptible bacteria, and this protective effect was dependent on the integrity of the EVs and showed dose- and time-dependent effects. At the same time, ESBL-EVs can also mediate the horizontal transmission of blaCTX-M-55, and EVs-mediated gene transfer is selective, preferring to transfer in more closely related species. CONCLUSIONS: In this study, we demonstrated the important role of EVs in the transmission of ß-lactam resistance in chicken ESBL-E. coli, and evaluated the risk of EVs-mediated horizontal gene transfer, which provided a theoretical basis for elucidating the mechanism of EVs-mediated resistance transmission.

AAV-Mediated Gene Therapy Restores Hearing in Patients with DFNB9 Deafness.

Mutations in OTOFERLIN (OTOF) lead to the autosomal recessive deafness 9 (DFNB9). The efficacy of adeno-associated virus (AAV)-mediated OTOF gene replacement therapy is extensively validated in Otof-deficient mice. However, the clinical safety and efficacy of AAV-OTOF is not reported. Here, AAV-OTOF is generated using good manufacturing practice and validated its efficacy and safety in mouse and non-human primates in order to determine the optimal injection dose, volume, and administration route for clinical trials. Subsequently, AAV-OTOF is delivered into one cochlea of a 5-year-old deaf patient and into the bilateral cochleae of an 8-year-old deaf patient with OTOF mutations. Obvious hearing improvement is detected by the auditory brainstem response (ABR) and the pure-tone audiometry (PTA) in these two patients. Hearing in the injected ear of the 5-year-old patient can be restored to the normal range at 1 month after AAV-OTOF injection, while the 8-year-old patient can hear the conversational sounds. Most importantly, the 5-year-old patient can hear and recognize speech only through the AAV-OTOF-injected ear. This study is the first to demonstrate the safety and efficacy of AAV-OTOF in patients, expands and optimizes current OTOF-related gene therapy and provides valuable information for further application of gene therapies for deafness.

Effects of Adjuvant Chemotherapy on Early-onset Stage II Colon Cancer at Different Tumor Sites.

OBJECTIVES: Left-sided colon cancer (LSCC) and right-sided colon cancer (RSCC) have shown distinct clinical and prognostic features. We investigated the effect of adjuvant chemotherapy (ACT) on cause-specific survival (CSS) in patients with stage II LSCC and RSCC. METHODS: Using the Surveillance, Epidemiology and End Results (SEER) database, a cohort of patients with stage II colon cancer, aged between 20 and 49 years was identified. Both Cox proportional hazards regression and Kaplan-Meier survival analysis as well as propensity score matching were used. RESULTS: Overall, 5633 patients were eligible. Patients with RSCC were more likely to be male, black, and younger, with a poor grade and histologic type, and were more likely to have more regional nodes examined and larger tumor size. After propensity score matching, CSS was significantly superior in patients with RSCC compared to those with LSCC (Hazard Ratio (HR): 0.80, 95% CI: 0.68-0.95, P =0.01). However, no survival benefit was observed for patients with LSCC after ACT (HR: 1.10, 95% CI: 0.90-1.35, P =0.35), and surprisingly, ACT was found to do more harm than good in patients with RSCC (HR: 1.31, 95% CI: 1.05-1.63, P =0.02). Even among patients with high-risk features such as T4 stage and regional nodes examined<12 in both groups, ACT still did not improve CSS except for T4 stage LSCC (HR: 0.65, 95% CI: 0.44-0.97, P =0.02). CONCLUSIONS: The results of this analysis indicate that the prognosis of RSCC is better than that of LSCC in stage II colon cancer, and ACT did not improve CSS in patients with either LSCC or RSCC. Even in patients with parts of high-risk features, ACT still did not improve CSS, except for T4 stage LSCC.

Limonoids and alkaloids from Tetradium austrosinense (Hand.-Mazz.) T.G.Hartley.

A pair of new enantiomeric indolopyridoquinazoline-type alkaloids, (+)-1,7S,8R- and (-)-1,7R,8S-trihydroxyrutaecarpine (3a and 3b), and a new limonoid-tyrosamine hybrid, austrosinin (8), along with six known alkaloids and limonoids, were isolated from the stems with leaves of Tetradium austrosinense. Their structures were elucidated on the basis of analysis of MS, NMR, ECD and time-dependent density functional theory-based electronic circular dichroism (TDDFT-ECD) calculations, as well as proposed biosynthetic pathway. An anti-inflammatory bioassay in vitro showed 8 had significant immunosuppressive effect against the production of pro-inflammatory cytokine TNF-α in lipopolysaccharide (LPS)-stimulated RAW264.7 cells.

The Impact of Parental Preconception Body Mass Index on the Outcomes of in vitro Fertilization-Embryo Transfer and Newborns' Outcomes.

Objective: Associations between parental pre-pregnancy BMI in IVF/ICSI fresh embryo transfer cycles and neonatal outcomes were investigated through a retrospective analysis. Methods: A retrospective analysis of Couples who underwent IVF/ICSI fresh embryo transfer 1340 cycles from January 2019 to December 2021 was conducted in the Department of Reproductive Medicine of our hospital. Based on the preconception BMI of parents, they were divided into four groups: Group A (both father and mother with BMI < 25 kg/m²), Group B (father with BMI < 25 kg/m² and mother with BMI ≥ 25 kg/m²), Group C (father with BMI ≥ 25 kg/m² and mother with BMI < 25 kg/m²), and Group D (both father and mother with BMI ≥ 25 kg/m²). The differences in baseline characteristics, fertilization and embryo development, pregnancy outcomes, and neonatal outcomes were compared among the groups. Results: In the IVF cycles, Group A had a higher rate of normal fertilization compared to three other groups, Group A is significantly higher than Group D, with statistical significance (P < .05). In the ICSI cycles, there were no significant differences among the four groups regarding normal fertilization rate, day 3 high-quality embryo rate, blastocyst formation rate, and high blastocyst rate. Univariate and multivariate analysis results showed no significant differences in clinical pregnancy and live birth rates among the four groups. However, Group D had a significantly higher rate of preterm birth than other three groups, with statistical significance (P < .05). Conclusion: To achieve better clinical outcomes and neonatal outcomes, overweight or obese couples should lose weight before undergoing IVF/ICSI treatment.

Chronic gastritis may predict risk of cerebral small vessel disease.

BACKGROUND AND PURPOSE: Chronic gastritis, especially that caused by helicobacter pylori (HP) infection, has been associated with increased risk of ischemic stroke. But the relationship between chronic gastritis and cerebral small vessel disease (CSVD) remains largely undetermined. This study aimed to determine the potential predictors for CSVD, with chronic gastritis and its proxies as alternatives. METHOD: Patients aged 18 years or older with indications for electronic gastroscopy were enrolled. Presence of CSVD was evaluated with brain magnetic resonance imaging (MRI) results. Degree of CSVD was scored according to established criteria. Logistic regression analysis was used for identifying possible risk factors for CSVD. RESULTS: Of the 1191 enrolled patients, 757 (63.6%) were identified as with, and 434 (36.4%) as without CSVD. Multivariate analysis indicated that patients with chronic atrophic gastritis had an increased risk for CSVD than those without (adjusted odds ratio = 1.58; 95% CI, 1.08-2.32; P < 0.05). CONCLUSIONS: Chronic atrophic gastritis is associated with the presence of CSVD. We should routinely screen the presence of CSVD for patients with chronic atrophic gastritis.

Comparison of Automated Spike Detection Software in Detecting Epileptiform Abnormalities on Scalp-EEG of Genetic Generalized Epilepsy Patients.

PURPOSE: Despite availability of commercial EEG software for automated epileptiform detection, validation on real-world EEG datasets is lacking. Performance evaluation of two software packages on a large EEG dataset of patients with genetic generalized epilepsy was performed. METHODS: Three epileptologists labelled IEDs manually of EEGs from three centres. All Interictal epileptiform discharge (IED) markings predicted by two commercial software (Encevis 1.11 and Persyst 14) were reviewed individually to assess for suspicious missed markings and were integrated into the reference standard if overlooked during manual annotation during a second phase. Sensitivity, precision, specificity, and F1-score were used to assess the performance of the software packages against the adjusted reference standard. RESULTS: One hundred and twenty-five routine scalp EEG recordings from different subjects were included (total recording time, 310.7 hours). The total epileptiform discharge reference count was 5,907 (including spikes and fragments). Encevis demonstrated a mean sensitivity for detection of IEDs of 0.46 (SD 0.32), mean precision of 0.37 (SD 0.31), and mean F1-score of 0.43 (SD 0.23). Using the default medium setting, the sensitivity of Persyst was 0.67 (SD 0.31), with a precision of 0.49 (SD 0.33) and F1-score of 0.51 (SD 0.25). Mean specificity representing non-IED window identification and classification was 0.973 (SD 0.08) for Encevis and 0.968 (SD 0.07) for Persyst. CONCLUSIONS: Automated software shows a high degree of specificity for detection of nonepileptiform background. Sensitivity and precision for IED detection is lower, but may be acceptable for initial screening in the clinical and research setting. Clinical caution and continuous expert human oversight are recommended with all EEG recordings before a diagnostic interpretation is provided based on the output of the software.

Leukocyte immunoglobulin-like receptor B2 overexpression as a promising therapeutic target and noninvasive screening biomarker for colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) has become the second most deadly malignancy in the world, and the exploration of screening markers and precise therapeutic targets is urgent. Our previous research identified leukocyte immunoglobulin-like receptor B2 (LILRB2) protein as a characteristic protein of CRC, but the association between LILRB2 expression and clinicopathological features, the internal mechanism related to CRC progression, and screening diagnostic efficacy are not clear. Therefore, we hypothesized that LILRB2 is significantly highly expressed in CRC tissues, correlated with advanced stage and a poor prognosis, and could be used as a therapeutic target and potential screening biomarker for CRC. AIM: To explore whether LILRB2 can be used as a potential therapeutic target and noninvasive screening biomarker for CRC. METHODS: Patients who underwent radical surgery for CRC at China-Japan Friendship Hospital between February 2021 and October 2022 were included. Cancer and paracancerous tissues were collected to verify LILRB2 expression, and the association between LILRB2 expression and clinicopathological features was analysed. Serum was collected from CRC patients, adenoma patients and healthy controls during the same period to assess the diagnostic value of LILRB2 as a noninvasive screening biomarker, and its diagnostic value was further compared with that of the traditional markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). RESULTS: A total of 58 CRC patients were included, and LILRB2 protein was significantly overexpressed in cancer tissues compared with paracancerous tissues (P < 0.001). Angiopoietin-like protein 2 (ANGPTL2) protein, as the ligand of LILRB2, was synergistically overexpressed in CRC tissues (P < 0.001), and overexpression of LILRB2 and ANGPTL2 protein was significantly correlated with poor to moderate differentiation, vascular involvement, lymph node metastasis, distant metastasis, advanced tumor-node-metastasis stage and a poor prognosis (P < 0.05), which suggested that LILRB2 and ANGPTL2 are closely associated with CRC progression. In addition, serum LILRB2 concentrations increased stepwise in healthy individuals, adenoma patients and CRC patients with statistically significant differences. The sensitivity of serum LILRB2 for the diagnosis of CRC was 89.74%, the specificity was 88.89%, the area under the curve was 0.95, and the diagnostic efficacy was better than that of conventional CEA and CA19-9. CONCLUSION: LILRB2 protein can be used as a potential novel therapeutic target and noninvasive screening biomarker for CRC, which is beneficial for early screening and precise treatment.

Multi-Query Vehicle Re-Identification: Viewpoint-Conditioned Network, Unified Dataset and New Metric.

Existing vehicle re-identification methods mainly rely on the single query, which has limited information for vehicle representation and thus significantly hinders the performance of vehicle Re-ID in complicated surveillance networks. In this paper, we propose a more realistic and easily accessible task, called multi-query vehicle Re-ID, which leverages multiple queries to overcome viewpoint limitation of single one. Based on this task, we make three major contributions. First, we design a novel viewpoint-conditioned network (VCNet), which adaptively combines the complementary information from different vehicle viewpoints, for multi-query vehicle Re-ID. Moreover, to deal with the problem of missing vehicle viewpoints, we propose a cross-view feature recovery module which recovers the features of the missing viewpoints by learnt the correlation between the features of available and missing viewpoints. Second, we create a unified benchmark dataset, taken by 6142 cameras from a real-life transportation surveillance system, with comprehensive viewpoints and large number of crossed scenes of each vehicle for multi-query vehicle Re-ID evaluation. Finally, we design a new evaluation metric, called mean cross-scene precision (mCSP), which measures the ability of cross-scene recognition by suppressing the positive samples with similar viewpoints from the same camera. Comprehensive experiments validate the superiority of the proposed method against other methods, as well as the effectiveness of the designed metric in the evaluation of multi-query vehicle Re-ID. The codes and dataset are available at: https://github.com/zhangchaobin001/VCNet.

Easy-to-Prepare Flexible Multifunctional Sensors Assembled with Anti-Swelling Hydrogels.

Recent years have witnessed the development of flexible electronic materials. Flexible electronic devices based on hydrogels are promising but face the limitations of having no resistance to swelling and a lack of functional integration. Herein, we fabricated a hydrogel using a solvent replacement strategy and explored it as a flexible electronic material. This hydrogel was obtained by polymerizing 2-hydroxyethyl methacrylate (HEMA) in ethylene glycol and then immersing it in water. The synergistic effect of hydrogen bonding and hydrophobic interactions endows this hydrogel with anti-swelling properties in water, and it also exhibits enhanced mechanical properties and outstanding self-bonding properties. Moreover, the modulus of the hydrogel is tissue-adaptable. These properties allowed the hydrogel to be simply assembled with a liquid metal (LM) to create a series of structurally complex and functionally integrated flexible sensors. The hydrogel was used to assemble resistive and capacitive sensors to sense one-, two-, and three-dimensional strains and finger touches by employing specific structural designs. In addition, a multifunctional flexible sensor integrating strain sensing, temperature sensing, and conductance sensing was assembled via simple multilayer stacking to enable the simultaneous monitoring of underwater motion, water temperature, and water quality. This work demonstrates a simple strategy for assembling functionally integrated flexible electronics, which should open opportunities in next-generation electronic skins and hydrogel machines for various applications, especially underwater applications.

Early stimulation and responsive care: A mediator of caregivers' depression on the suspected developmental delay of left-behind children in China.

BACKGROUND: Due to multiple factors, left-behind children in rural areas suffer from neurodevelopment delay and their caregivers suffer from depressive symptoms. This study aimed to analyze the effect of caregivers' depressive symptoms on left-behind children's neurodevelopment, with early stimulation and responsive care mediating. METHODS: We conducted a cross-sectional survey in five counties in China. A total of 904 left-behind children aged 0-3 and their primary caregivers were enrolled. The Zung Self-rating Depression Scale (ZSDS) was used to measure caregivers' depressive symptoms. The Ages and Stages questionnaires-third edition (ASQ-3), which contains five domains: communication (CM), gross motor (GM), fine motor (FM), problem-solving (CG), and personal social (PS), was used to screen children for suspected developmental delay (SDD). RESULTS: 31.4 % of left-behind children suffered from SDD, while 39.7 % of left-behind children's caregivers experienced depressive symptoms. Caregivers' ZSDS scores were positively correlated with the SDD on four domains (FM, GM, CG, and PS), while Early stimulation and responsive care was negatively correlated with the SDD on four domains (CM, FM, CG, and PS). LIMITATIONS: The cross-sectional design limited the ability to ascertain causal relations. Besides, the findings may not be generalized to all regions of China due to the heterogeneity of the study population. CONCLUSIONS: Left-behind children under three years old in rural China were at high risk of SDD, while a substantial proportion of their caregivers had depressive symptoms. Caregivers' depressive symptoms may negatively affect the SDD of left-behind children through caregivers providing less early stimulation and responsive care.

Regulation of M1/M2 Polarization in LPS-Stimulated Macrophages by 1,25(OH)2D3.

Objective: This study aims to investigate the impact of 1,25(OH)2D3 on the polarization of LPS-stimulated macrophages and the underlying regulatory mechanisms. Methods: Primary macrophages were isolated and identified using immunofluorescence assays to detect macrophage biomarker expression levels. RT-PCR was employed to measure the expression of Arginase 1 (Arg-1), Interleukin-10 (IL-10), Inducible isoform of nitric oxide synthase (iNOS), and Tumor necrosis factor-α (TNF-α) in macrophages treated with various strategies. Western blotting assessed the protein expression levels of AKT1, p-AKT1, NF-κB p65, p-NF-κB p65, STAT3, and p-STAT3 in LPS-stimulated macrophages exposed to different concentrations of 1,25(OH)2D3. Results: As the LPS concentration increased from 0 to 0.5 mg/L, Arg-1, IL-10, iNOS, and TNF-α expression levels significantly increased. However, at LPS concentrations ranging from 1 mg/L to 10 mg/L, the expression of Arg-1, IL-10, iNOS, and TNF-α displayed a trend from increase to decline. The highest M2 polarization (Arg-1 and IL-10) was observed in macrophages stimulated with 0.5 mg/L LPS among the lower concentrations, while the highest M1 polarization (iNOS and TNF-α) was observed in macrophages stimulated with 5 mg/L LPS among the higher concentrations. Subsequent experiments utilized 0.5 mg/L and 5 mg/L LPS as incubation concentrations. Under LPS stimulation, iNOS was significantly upregulated, surpassing the expression level of IL-10, a marker of M2 macrophages. The introduction of 1,25(OH)2D3 facilitated M2 polarization, with 50 nM as the incubation concentration of 1,25(OH)2D3. Furthermore, 1,25(OH)2D3 reversed the elevated expression of p-AKT1, p-NF-κB p65, and p-STAT3 in macrophages stimulated with 5 mg/L LPS. Conclusions: 1,25(OH)2D3 effectively regulates the M1/M2 polarization in LPS-stimulated macrophages.