What is the optimal number of embryos to transfer for POSEIDON group 1 and group 2? A retrospective study.

BACKGROUND: The 2016 Patient-Oriented Strategy Encompassing IndividualizeD Oocyte Number (POSEIDON) criteria redefined the poor responders as low prognosis patients. The embryo transfer strategy for POSEIDON patients remained to be addressed. This study aimed to investigate the optimized number of embryos to transfer for unexpected low-prognosis patients (POSEIDON Group 1 and Group 2) with blastocyst transfer in their first frozen cycle. METHODS: A retrospective cohort study of 2970 patients who underwent frozen-thawed embryo transfer (FET) between January 2018 and December 2021. Patients from POSEIDON Group 1 (N = 219) and Group 2 (N = 135) who underwent blastocyst transfer in their first FET cycles were included and divided into the elective single embryo transfer (eSET) group and the double embryo transfer (DET) group. RESULTS: For POSEIDON Group 1, the live birth rate per embryo transfer of the DET group was slightly higher than the eSET group (52.17% vs 46.15%, OR 0.786, 95% CI 0.462-1.337, P = 0.374; adjusted OR (aOR) 0.622, 95% CI 0.340-1.140, P = 0.124), while a significant increase of 20.00% in the multiple birth rate was shown. For Group 2, higher live birth rates were observed in the DET group compared to the eSET group (38.46% vs 20.48%, OR 0.412, 95% CI 0.190-0.892, P = 0.024; aOR 0.358, 95% CI 0.155-0.828, P = 0.016). The difference in the multiple birth rate was 20.00% without statistical significance. Univariate and multivariate analyses revealed that age (OR 0.759, 95% CI .624-0.922, P = 0.006 and OR 0.751, 95% CI 0.605-0.932, P = 0.009) and the number of transferred embryos (OR 0.412, 95% CI 0.190-0.892, P = 0.024 and OR 0.367, 95% CI 0.161-0.840, P = 0.018) were significant variables for the live birth rate in POSEIDON Group 2. CONCLUSIONS: The findings in the present study showed that eSET was preferred in the first frozen cycle for POSEIDON Group 1 to avoid unnecessary risks. Double embryo transfer strategy could be considered to improve the success rate for POSEIDON Group 2 with caution. Further stratification by age is needed for a more scientific discussion about the embryo transfer strategy for POSEIDON patients.

Linking periodontitis with 20 cancers, emphasis on oropharyngeal cancer: a Mendelian randomization analysis.

While associations between periodontitis and an elevated risk of cancer have been suggested, the results of existing observational studies have been inconsistent, also leaving room for further investigation into the underlying mechanisms. This study was designed to delve into the possible causal link between periodontitis and 20 standard cancers while concurrently identifying potential mediators. We initiated a Mendelian randomization analysis that drew from either publicly accessible or personally obtained genome-wide association study (GWAS) datasets. The inverse variance weighting (IVW) method served as our primary tool for analysis. To ensure the strength and consistency of our results, we implemented additional strategies, including weighted median, weighted mode, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO), bolstered by funnel plots. Our analysis unveiled an elevated risk of head and neck cancer concomitant with periodontitis (p = 0.041, OR 0.999, 95% CI 0.999-1.000), specifically a heightened risk of oropharyngeal cancer (p = 0.022, OR 0.999, 95% CI 0.999-1.000). As a result of probing into potential mediators, Fusobacterium nucleatum emerged as a likely intermediary in the promoting effect of periodontitis on oropharyngeal cancer (p = 0.021, OR 0.999, 95% CI 0.998-1.000). Inversely, basal cell carcinoma and endometrial cancer demonstrated an association with an increased incidence of periodontitis (basal cell carcinoma: p = 0.020, OR 0.987, 95% CI 0.976-0.998; endometrial cancer: p = 0.027, OR 0.984, 95% CI 0.970-0.998). However, periodontitis exerted no significant causal impact on the 19 other common cancers or the three subtypes of head and neck cancer. To conclude, our results support the theory that periodontitis contributes to an enhanced risk of head and neck cancer, particularly oropharyngeal cancer, with Fusobacterium nucleatum functioning as a potential intermediary.

Does this child just have an atrial septal defect? More potentiality of interventional therapy: A rare case report.

INTRODUCTION AND IMPORTANCE: Partially anomalous pulmonary venous connection (PAPVC) is a rare congenital heart disease, often concomitant with atrial septal defects (ASDs). PAPVC usually tends to be treated by surgery, but the case we report will open up new perspectives for the interventional treatment of PAPVC present with ASD. CASE PRESENTATION: We present a case of a 2-year-old 11 kg boy transthoracic echocardiography showed secundum-type ASD. A supracardiac-PAPVC was accidentally detected during cardiac catheterization, and an abnormal pulmonary vein connection was detected with a vertical vein (VV) opening. Ultimately, ASD and VV were both occluded. CLINICAL DISCUSSION: Surgical therapy of PAPVC is the first line treatment of most centers in the world. However, the main complications after surgical repair of PAPVC raise our concerns, such as pulmonary stenosis, caval vein stenosis and sinus node dysfunction. Therefore, percutaneous closure of PAPVC can be an alternative method. This case of percutaneous interventional closure of ASD and supracardiac PAPVC through a vertical vein in the same surgery was first reported. Patients with ASD tend to have missed diagnoses of PAPVC. We can evaluate it by transesophageal echocardiography (TEE), cardiac magnetic resonance imaging (CMR) and computed tomography (CT). CONCLUSIONS: This case suggests that the effect of interventional therapy is quite reliable. For children with ASD, attention should be paid to the omission of the presence or absence of PAPVC before surgery. During interventional therapy, a guide wire rather than a catheter should be preferred to explore the atrial septum and pulmonary veins to avoid a missed diagnosis of PAPVC.

PLD2 deficiency alleviates endothelial glycocalyx degradation in LPS-induced ARDS/ALI.

- Acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) is a life-threatening condition marked by severe lung inflammation and increased lung endothelial barrier permeability. Endothelial glycocalyx deterioration is the primary factor of vascular permeability changes in ARDS/ALI. Although previous studies have shown that phospholipase D2 (PLD2) is closely related to the onset and progression of ARDS/ALI, its role and mechanism in the damage of endothelial cell glycocalyx remains unclear. We used LPS-induced ARDS/ALI mice (in vivo) and LPS-stimulated injury models of EA.hy926 endothelial cells (in vitro). We employed C57BL/6 mice, including wild-type and PLD2 knockout (PLD2-/-) mice, to establish the ARDS/ALI model. We applied immunofluorescence and ELISA to examine changes in syndecan-1 (SDC-1), matrix metalloproteinase-9 (MMP9), inflammatory cytokines (TNF-α, IL-6, and IL-1ß) levels and the effect of external factors, such as phosphatidic acid (PA), 1-butanol (a PLD inhibitor), on SDC-1 and MMP9 expression levels. We found that PLD2 deficiency inhibits SDC-1 degradation and MMP9 expression in LPS-induced ARDS/ALI. Externally added PA decreases SDC-1 levels and increases MMP9 in endothelial cells, hence underlining PA's role in SDC-1 degradation. Additionally, PLD2 deficiency decreases the production of inflammatory cytokines (TNF-α, IL-6, and IL-1ß) in LPS-induced ARDS/ALI. In summary, these findings suggest that PLD2 deficiency plays a role in inhibiting the inflammatory process and protecting against endothelial glycocalyx injury in LPS-induced ARDS/ALI.

Evaluation of appropriateness of alerts overrides and physicians' responses of the medication-related clinical decision support system in China, a hospital-based study.

This study was designed to investigate the state quo of the appropriateness of alerts overrides of the medication-related clinical decision support system (MRCDSS) in China. The medication-related alerts in one hospital from Jan 2022 to Dec 2022 were acquired and sampled. Rates of alert overrides, appropriateness of alert generation and physicians' responses were observed. Total 14,612 medication-related alerts (≤ level 3) were recorded, of those, 12,659 (86.6%) alerts were overridden. The top 3 alert types were: drug and diagnosis contraindications (23.8%), drug and test value contraindications (23.3%), and compatibility issues (17.7%). Of all sampled 1,501 alerts, 80.2% of them were appropriately overridden by the physicians. The appropriate rate of alert generation was 57.9% and the inappropriate rate was 42.1%. The inappropriate rate of physicians' responses was 17.8%, and 2.0% physicians' responses were undetermined. A few medications accounted for over 10% of overrides, 88.3% of "overridden reasons" inputted by the physicians were meaningless characters or values, indicating an obvious "alert fatigue" in these physicians. Our results indicated that the overridden rate of MRCDSS in China was still high, and appropriateness of generation of alert was quite low. These data indicated that the MRCDSS currently using in China still needs constantly optimization and timely maintenance. Proper sensitivity to reduce triggering of useless alerts and generation of alert fatigue might play a vital role. We believed that these findings are helpful for better understanding the state quo of MRCDSS in China and providing useful insights for future developing and improving MRCDSS.

Oral microbiota in periodontitis patients with and without type 2 diabetes mellitus and their shifts after the nonsurgical periodontal therapy.

Objective: To investigate the shift in the oral microbiota of periodontitis patients with and without type 2 diabetes mellitus (T2DM) undergoing nonsurgical periodontal treatment and its implications. Methods: Eleven patients with chronic periodontitis and eleven patients with chronic periodontitis and diabetes from the Second Affiliated Hospital of Chongqing Medical University received nonsurgical periodontitis treatment and were re-evaluated 3 months later. DNA from the saliva and subgingival plaques was amplified and sequenced using 16S ribosomal RNA (16S rRNA) gene sequencing for microbiome profiling. Clinical indexes at the onset and after periodontal therapy were recorded and compared. Results: The species richness and dominant microbiota of periodontitis patients with and without T2DM changed significantly after nonsurgical periodontal treatment in both saliva and subgingival plaques. The periodontal condition of the patients was also effectively improved three months after therapy. Glycemic control in patients with periodontitis and T2DM was improved. Additionally, nonsurgical periodontal therapy could increase in subgingival microbial diversity and the proportion of health-associated bacteria but a proportional reduction in pathogenic bacteria in periodontitis patients with T2DM. Network analysis revealed fewer links and a lower level of centralization in the chronic periodontitis (CP) group after treatment. However, more links and a higher network density of the networks were found in the CP + T2DM group, suggesting a more stable microbial community after treatment. Conclusions: There were significant differences in both the structural composition and reaction of the oral microbiota to periodontal treatment between periodontitis patients with and without T2DM. Nonsurgical periodontal treatment can improve metabolic control, decrease the proportion of periodontal pathogens in oral conditions, and help stabilize microbial communities in patients with periodontitis and T2DM. Furthermore, nonsurgical periodontal treatment may be a potential supplementary approach for managing T2DM.

Molecular and immunological characteristics of patients with CMTM6 low expression colorectal cancer.

CKLF-like MARVEL transmembrane domain-containing 6 (CMTM6), a regulator of programmed cell death ligand 1 (PD-L1), has attracted extensive attention due to its role in tumors. However, research on the expression of CMTM6 in colorectal cancer (CRC) and its relationship with PD-L1 expression and immune cell infiltration is limited. We used The Cancer Genome Atlas database to mine and analyze data from patients with CRC using bioinformatics methods. We investigated the expression of CMTM6 in CRC and its relationship with PD-L1 expression and immune cell infiltration. Immunohistochemistry and PCR were performed to detect CMTM6 and PD-L1 expression in CRC tissues. Differential gene expression analysis was performed using the edgeR package in R and immune cell infiltration analysis was performed using the ssGSEA algorithm. Additionally, GO and KEGG enrichment analyses were conducted to identify the biological processes and pathways associated with low CMTM6 expression. Our study found that CMTM6 expression was significantly upregulated in CRC tissues compared to that in adjacent normal tissues. Patients with high CMTM6 expression exhibited significantly increased levels of PD-L1 expression and higher levels of tumor-infiltrating immune cells compared to patients with low CMTM6 expression. GO and KEGG analyses suggested that CMTM6 may be involved in multiple immune regulatory pathways in CRC.

In stage IV pulmonary adenocarcinoma patients, treatment with Traditional Chinese Medicine alone gives prognostically superior results to treatment with Platinum-Based Chemotherapy alone.

BACKGROUND: About 30% of pulmonary stage IV adenocarcinomas die within 3 months of diagnosis. Western medical treatments with Platinum-Based Chemotherapy=PBC and tyrosine-kinase inhibitors Targeted Therapy=TT can improve prognosis. In China, Traditional Chinese Medicine herbal treatments (TCM) are often used in addition to PBC and TT. A considerable number of patients refuse Western medical treatments and use TCM alone. However, the survival impact of the latter is unknown. HYPOTHESES TESTED: Treatment with TCM alone is prognostically superior to PBC alone. Addition of PBC or TT or both TT to TCM improves survival. METHODS: In this prospective observational, non-interventional study of 1017 consecutive first-onset stage IV NSCLC patients with up to 10 years follow-up, 261 who Died of Disease (DOD) within 3 months were omitted, as they never got the optimal Western medical therapies. All 218 non-adenocarcinomas were also omitted, leaving 538 stage IV adenocarcinomas treated by TCM alone (n = 29), PBC alone (N = 19) and TCM and other Western medical combinations (299 TCM and PBC, 50 TCM and TT, 141 TCM and PBC and TT) with 3 - 120 months follow-up. Survivals were compared using Alive with Disease (AWD) and DOD as endpoints. RESULTS: The patients treated only with TCM had 7 months better median survival than those that received PBC alone (17 and 10 months). The patients that received TCM and PBC had a better median survival (24 months) than TCM alone and much better than PBC alone. None of the patients that received TCM alone survived > 54 months, whereas 18% of TCM and PBC patients survived much longer. Over the observation period of 3 - 120 months, survivals of TCM and TT, TCM and PBC and TT, and TCM and PBC were not different and therefore grouped as TCM and Western medicines. Median survival times of PBC alone and TCM alone were lower than that of TCM and Western medical treatments (p < 0.0001, 10, 17 and 27 months). CONCLUSIONS: Pulmonary stage IV adenocarcinoma patients with at least 3 months survival, treated with TCM alone have a significantly better survival than those treated with PBC alone. Adding Western PBC, TT or both to TCM further improves prognosis.

Driving Force Analysis of Natural Wetland in Northeast Plain Based on SSA-XGBoost Model.

Globally, natural wetlands have suffered severe ecological degradation (vegetation, soil, and biotic community) due to multiple factors. Understanding the spatiotemporal dynamics and driving forces of natural wetlands is the key to natural wetlands' protection and regional restoration. In this study, we first investigated the spatiotemporal evolutionary trends and shifting characteristics of natural wetlands in the Northeast Plain of China from 1990 to 2020. A dataset of driving-force evaluation indicators was constructed with nine indirect (elevation, temperature, road network, etc.) and four direct influencing factors (dryland, paddy field, woodland, grassland). Finally, we built the driving force analysis model of natural wetlands changes to quantitatively refine the contribution of different driving factors for natural wetlands' dynamic change by introducing the sparrow search algorithm (SSA) and extreme gradient boosting algorithm (XGBoost). The results showed that the total area of natural wetlands in the Northeast Plain of China increased by 32% from 1990 to 2020, mainly showing a first decline and then an increasing trend. Combined with the results of transfer intensity, we found that the substantial turn-out phenomenon of natural wetlands occurred in 2000-2005 and was mainly concentrated in the central and eastern parts of the Northeast Plain, while the substantial turn-in phenomenon of 2005-2010 was mainly located in the northeast of the study area. Compared with a traditional regression model, the SSA-XGBoost model not only weakened the multicollinearity of each driver but also significantly improved the generalization ability and interpretability of the model. The coefficient of determination (R2) of the SSA-XGBoost model exceeded 0.6 in both the natural wetland decline and rise cycles, which could effectively quantify the contribution of each driving factor. From the results of the model calculations, agricultural activities consisting of dryland and paddy fields during the entire cycle of natural wetland change were the main driving factors, with relative contributions of 18.59% and 15.40%, respectively. Both meteorological (temperature, precipitation) and topographic factors (elevation, slope) had a driving role in the spatiotemporal variation of natural wetlands. The gross domestic product (GDP) had the lowest contribution to natural wetlands' variation. This study provides a new method of quantitative analysis based on machine learning theory for determining the causes of natural wetland changes; it can be applied to large spatial scale areas, which is essential for a rapid monitoring of natural wetlands' resources and an accurate decision-making on the ecological environment's security.

Cloud height and thickness measurement based on a superconducting nanowire single-photon detector.

At present, the methods for measuring cloud height and thickness mainly include using micro-pulse lidar and microwave radiometer data. To further study cloud height and thickness, a superconducting nanowire single-photon detector (SNSPD) is applied to a lidar system for the first time, to the best of our knowledge, to analyze the cloud height and thickness. In the experiment, a 1.2-m-diameter horizon telescope is used for laser emitting and echo receiving, a 1064 nm near-IR pulse laser with a single pulse energy of 4 mJ is used as the system emission laser, and a 4-pixel SNSPD array detector is used as the end receiver to complete the echo photon reception. By analyzing the experimental data, the distributions of cloud height and cloud thickness can be obtained using the laser ranging system. The cloud cover condition on a certain day was measured, and the obtained cloud bottom height was about 1222 m, cloud top height was about 1394 m, and cloud cover thickness was about 172 m. The difference between the cloud cover thickness and the forecast value was 28 m. The cloud cover height and thickness measured by this method are true and credible.

[Rapid determination of five halobenzoquinones in aquatic products by QuEChERS-ultra performance liquid chromatography-tandem mass spectrometry].

Halobenzoquinones (HBQs), which are emerging chlorinated disinfection byproducts (DBPs), have attracted increasing attention because they are frequently detected in treated tap water, entrainment water, etc. These compounds are mainly generated during the water treatment process using chlorine, chloramine, and chlorine dioxide as disinfectants, and display more toxic effects than regulated DBPs, such as trihalomethane and haloacetic acid. HBQs have been recognized as potential bladder carcinogens and are harmful to the nervous system. Additionally, they can exert genotoxic effects and cause oxidative damage to DNA and proteins. The risk of HBQs in aquatic products is expected to rise because the disinfection of public facilities has significantly increased in recent years. Therefore, developing a sensitive and accurate analytical method to detect HBQs in aquatic products is of great importance. Several analytical methods, including gas chromatography, gas chromatography-mass spectrometry, electrochemical methods, liquid chromatography, and liquid chromatography-tandem mass spectrometry, can be used to identify and quantify HBQs in water. However, to the best of our knowledge, no reports on the determination of HBQ levels in aquatic products are yet available. Further, pretreatment is essential for HBQ determination because of the complex matrix effects of aquatic products. Herein, a sensitive and accurate method based on the QuEChERS technique coupled with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed for the simultaneous determination of five HBQs in aquatic products. For the QuEChERS procedure, the pretreatment conditions, such as the extraction solvent and adsorbent species, were systematically optimized. The sample was extracted with 10 mL of 10% methanol acetonitrile solution (containing 0.1% formic acid), dehydrated, and centrifuged with sodium chloride and anhydrous magnesium sulfate. The supernatant was purified using a QuEChERS packing material consisting of 50 mg N-propylethylenediamine (PSA), 30 mg of graphitized carbon black (GCB), and 30 mg of neutral alumina (Al2O3), dried with nitrogen, and concentrated. The five HBQs were separated on a Waters ACQUITY UPLC BEH C18 column (100 mm×2.1 mm, 1.7 µm) using 0.25% acetonitrile formate solution and 0.25% formic acid aqueous solution as the mobile phase under a gradient elution program and then detected using UPLC-MS/MS with negative electrospray ionization (ESI-) under multiple reaction monitoring (MRM) mode. Quantitative analysis was performed using a matrix-matched external standard method. The five HBQs achieved rapid separation within 6 min, indicating that the proposed method has a much shorter separation time compared with previous studies. The matrix effect was evaluated by establishing a matrix-matched calibration curve. The results showed that 2,5-dichloro-1,4-benzoquinone (2,5-DCBQ) presented a matrix-enhancing effect, whereas the other HBQs displayed matrix-inhibiting effects. In particular, tetrachlorobenzoquinone (TCBQ) exhibited strong inhibitory effects. Under the optimized experimental conditions, the five HBQs demonstrated good linear relationships in the range of 1.0-50.0 µg/L, with correlation coefficients (r)≥0.9992. The detection limits of the method were 0.15-0.8 µg/kg, and the recoveries of the target compounds were 85.9%-116.5%. The relative standard deviations were 1.4%-8.2%, which indicates good reproducibility. The proposed method was successfully applied to actual sample detection, and 2,6-dichloro-3-methyl-1,4-benzoquinone (2,6-DCMBQ) was detected in grass carp. The proposed method is convenient, sensitive, accurate, and suitable for the simultaneous determination of five HBQs in aquatic products. Moreover, the developed method provides a reliable reference for the routine monitoring of trace HBQs in food samples.

[Determination of kojic acid in fermented foods by solid-phase extraction coupled with ultra performance liquid chromatography-tandem mass spectrometry].

Kojic acid naturally appears in fermented foods and can be formed during the aerobic fermentation process induced by Aspergillus and Penicillium fungi. It is widely used in the food industry because it exhibits antibacterial and antifungal properties and does not affect food taste. However, recent studies indicate that kojic acid may be a potential carcinogen. Therefore, assessing the health risks of kojic acid in fermented foods are of great importance, and developing a sensitive and accurate analytical method for this compound is a significant endeavor. Much efforts have been devoted to the detection of kojic acid using electrochemistry, high performance liquid chromatography (HPLC), gas chromatography-mass spectrometry (GC-MS), and high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). HPLC and HPLC-MS/MS are the analytical techniques most often employed for this purpose. Of these two methods, HPLC-MS/MS displays excellent sensitivity and is the optimal selective technique. Pretreatment is usually necessary for kojic acid determination because of the complex matrix effects of fermented foods. However, few researches on the determination of kojic acid in food are available, and, to the best of our knowledge, the determination of kojic acid using solid-phase extraction (SPE) pretreatment has not been reported yet. Herein, a convenient, sensitive, and accurate method was developed to determine kojic acid in fermented foods using solid-phase extraction-ultra performance liquid chromatography-tandem mass spectrometry (SPE-UPLC-MS/MS). The pretreatment conditions, such as the extraction solvent, cartridge, rinse solvent, and eluent, were systematically optimized. The samples, including soy sauce, vinegar, liquor, sauce, fermented soya bean, and fermented bean curd, were extracted with 0.1% formic acid-absolute ethyl alcohol and purified using a PRiME HLB cartridge. Kojic acid was separated using an ACQUITY UPLC® BEH C18 column (100 mm×2.1 mm, 1.7 µm) with formic acid-acetonitrile (1∶999, v/v) and formic acid-5 mmol/L ammonium acetate (1∶999, v/v) solutions as the mobile phases under gradient elution mode. MS was performed in electrospray positive ionization (ESI+) and multiple reaction monitoring (MRM) modes. An internal standard method was used for quantification. Under optimized conditions, good linearity was achieved at mass concentrations of 5.0-100.0 µg/L, with a correlation coefficient (r) of 0.9994. The limits of detection and quantification of the method for kojic acid were 2-5 µg/kg and 6-15 µg/kg, respectively. Good recoveries of 86.8%-111.7%, intra-day precisions of 1.0%-7.9% (n=6), and inter-day precisions of 2.7%-10.2% (n=5) were also obtained. The matrix effect was evaluated by establishing a matrix-matching calibration curve, and weak inhibitory effects were found in vinegar and liquor; moderate inhibitory effects in fermented bean curd, fermented soya bean, and soy sauce; and a strong inhibitory effect in sauce. The developed method was used to detect kojic acid in 240 fermented foods, and the results showed that the detection rate of vinegar was the highest, followed by liquor, sauce, soy sauce, fermented soya bean, and fermented bean curd, the contents were 5.69-2272 µg/kg. Matrix interferences can be significantly reduced by optimizing the pretreatment and detection procedures. The proposed method is sensitive, accurate, and can be used to analyze kojic acid in fermented foods.

Vibration Suppression of a High-Rise Building With Adaptive Iterative Learning Control.

This article considers the design of an adaptive iterative learning controller for high-rise buildings with active mass dampers (AMDs). High-rise buildings in this article are seen as distributed parameter systems, in which the characteristics of every point in buildings should be considered. Two partial differential equations (PDEs) and several ordinary differential equations are used to describe the model of buildings. To achieve the control target that is to suppress the vibration induced by high winds, an adaptive iterative learning controller is proposed for the flexible building system with boundary disturbance. The convergency of the adaptive iterative learning control (AILC) approach is proven by serious theory analysis. In simulations and experiments, this article uses both the analysis of figures and quantitative analysis (root-mean-square values) to illustrate the efficiency of the AILC scheme.

Rapid determination of 14 odorous compounds in drinking water using gas chromatography-mass spectrometry coupled with headspace solid-phase microextraction pretreatment.

A sensitive and effective method was developed for the simultaneous determination of 14 odorous compounds in drinking water using gas chromatography-mass spectrometry (GC-MS) coupled with headspace solid phase microextraction (HS-SPME) pretreatment. The influencing factors including SPME fiber, ionic strength, temperature and time on the pretreatment procedure were evaluated systematically. Under the optimized conditions, 10 mL of the samples added with 1.0 g sodium chloride was extracted by CAR/PDMS fiber at 60 °C for 30 min and then desorbed at 280 °C for 3 min. The analytes achieved good linearity as the mass concentrations were in the range of 0.0020-10.0 µg L-1 with correlation coefficients higher than 0.9990. The limits of detection (LODs) ranging between 0.2 and 50 ng L-1 were lower than the olfactory threshold of these studied compounds. Satisfactory recoveries were obtained ranging from 84.8% to 110.6%, and good reproducibility indicated by relative standard deviation (RSD) in the range of 0.50-9.5% was obtained as well. The proposed method was convenient, sensitive and accurate, which was suitable for the routine monitoring 14 odorous compounds in water.

Nicandra physalodes Extract Exerts Antiaging Effects in Multiple Models and Extends the Lifespan of Caenorhabditis elegans via DAF-16 and HSF-1.

The development of safe and effective therapeutic interventions is an important issue for delaying aging and reducing the risk of aging-related diseases. Chinese herbal medicines for the treatment of aging and other complex diseases are desired due to their multiple components and targets. Through screening for effects on lifespan of 836 Chinese herbal medicine extracts, Nicandra physalodes extract (HL0285) was found to exhibit lifespan extension activity in Caenorhabditis elegans (C. elegans). In further experiments, HL0285 improved healthspan, enhanced stress resistance, and delayed the progression of neurodegenerative diseases in C. elegans. Additionally, it ameliorated senescence in human lung fibroblasts (MRC-5 cells) and reversed liver function damage and reduced senescence marker levels in doxorubicin- (Dox-) induced aging mice. In addition, the longevity effect of HL0285 in C. elegans was dependent on the DAF-16 and HSF-1 signaling pathways, as demonstrated by the results of the mutant lifespan, gene level, and GFP level assays. In summary, we discovered that HL0285 had an antiaging effect in C. elegans, MRC-5 cells, and Dox-induced aging mice and deserves to be explored in the future studies on antiaging agents.

[Mechanism of high mobility group protein B1 in lipopolysaccharide-induced acute lung injury/acute respiratory distress syndrome].

OBJECTIVE: To investigate the role and possible pathogenesis of high mobility group protein B1 (HMGB1) in lipopolysaccharide (LPS)-induced acute lung injury/acute respiratory distress syndrome (ALI/ARDS). METHODS: (1) In vivo, 24 SPFC57BL/6 male mice were randomly divided into normal control group, ALI/ARDS model group, ethyl pyruvate (EP) treatment group and EP control group, with 6 mice in each group. The ALI/ARDS model was established by intraperitoneal injection of 20 mg/kg LPS. Mice in normal control group and EP control group were intraperitoneally injected with the same amount of sterile normal saline. Then, mice in the EP treatment group and EP control group were intraperitoneally injected with 40 mg/kg HMGB1 inhibitor EP. After 6 hours, the mice were sacrificed and lung tissues were collected. The expressions of heparan sulfate (HS), syndecans-1 (SDC-1), heparanase (HPA) and matrix metalloproteinases-9 (MMP-9) in lung tissues were detected by immunofluorescence technique. Orbital blood of mice was collected and serum was extracted to detect the content of HMGB1 by enzyme linked immunosorbent assay (ELISA). (2) In vitro, human umbilical vein endothelial cells (HUVECs) were randomly divided into 6 groups: normal control group, HUVECs damage group (treated with 1 mg/L LPS for 6 hours), HMGB1 group (treated with 1 µmol/L recombinant HMGB1 for 6 hours), HMGB1+EP group (treated with recombinant HMGB1 for 1 hour and then added 1 µmol/L EP for 6 hours), LPS+EP group (treated with LPS for 1 hour and then added 1 µmol/L EP for 6 hours), EP group (treated with 1 µmol/L EP for 6 hours). The expressions of HS, SDC-1, HPA and MMP-9 in endothelial cells were detected by immunofluorescence technique. RESULTS: (1) In vivo, light microscopy showed that the alveolar space was thickened after LPS stimulation, and there were a large number of inflammatory cells infiltrating in the alveolar space. Compared with ALI/ARDS model group, the expressions of HS and SDC-1 in lung tissue of EP treatment group were significantly increased [HS (fluorescence intensity): 0.80±0.20 vs. 0.53±0.02, SDC-1 (fluorescence intensity): 0.72±0.02 vs. 0.51±0.01, both P < 0.05], and the expressions of HPA and MMP-9 were significantly decreased [HPA (fluorescence intensity): 2.36±0.05 vs. 3.00±0.04, MMP-9 (fluorescence intensity): 2.55±0.13 vs. 3.26±0.05, both P < 0.05]; there were no significant changes of the above indexes in EP control group. Compared with ALI/ARDS model group, the content of serum HMGB1 in EP treatment group decreased significantly (µg/L: 131.88±16.67 vs. 341.13±22.47, P < 0.05); there was no significant change in the EP control group. (2) In vitro, compared with HMGB1 group, the expressions of HS and SDC-1 in HMGB1+EP group were significantly higher [HS (fluorescence intensity): 0.83±0.07 vs. 0.56±0.03, SDC-1 (fluorescence intensity): 0.80±0.01 vs. 0.61±0.01, both P < 0.05], and the expressions of HPA and MMP-9 were significantly lower [HPA (fluorescence intensity): 1.30±0.02 vs. 2.29±0.05, MMP-9 (fluorescence intensity): 1.55±0.04 vs. 2.50±0.06, both P < 0.05]; the expression of HS, SDC-1, HPA and MMP-9 had no significant changes in EP group. CONCLUSIONS: HMGB1 participates in LPS-induced injury of endothelial cell glycocalyx, leading to increased lung permeability, and inhibition of HMGB1 can alleviate lung injury.

Conditional ablation of protein tyrosine phosphatase receptor U in midbrain dopaminergic neurons results in reduced neuronal size.

Protein tyrosine phosphatase receptor U (PTPRU) is involved in midbrain patterning during early stages of development and is continuously expressed in the adult midbrain areas where dopaminergic neurons reside in. However, whether PTPRU is also involved in the maintenance and survival of midbrain dopaminergic (mDA) neurons during the late stages of development or in the adult midbrain remains largely unknown. In the present study, Ptpru was ablated by crossing a floxed Ptpru mouse strain with tyrosine hydroxylase (TH)-Cre mice that express Cre recombinase in postmitotic mDA neurons. Conditional ablation of Ptpru in postmitotic mDA neurons resulted in a reduction of somatic and nuclear size in adulthood. However, TH-immunoreactivity of Ptpru-ablated mDA neurons and their projections to the striatum appeared undisturbed. We also investigated the maintenance of several mDA neuronal markers following Ptpru ablation and found no significant changes. Taken together, these findings suggest that PTPRU is involved in regulating the neuronal size of mDA neurons and provided mechanistic insights into the development and maintenance of mDA neurons.

Crotamiton derivative JM03 extends lifespan and improves oxidative and hypertonic stress resistance in Caenorhabditis elegans via inhibiting OSM-9.

While screening our in-house 1072 marketed drugs for their ability to extend the lifespan using Caenorhabditis elegans (C. elegans) as an animal model, crotamiton (N-ethyl-o-crotonotoluidide) showed anti-aging activity and was selected for further structural optimization. After replacing the ortho-methyl of crotamiton with ortho-fluoro, crotamiton derivative JM03 was obtained and showed better activity in terms of lifespan-extension and stress resistance than crotamiton. It was further explored that JM03 extended the lifespan of C. elegans through osmotic avoidance abnormal-9 (OSM-9). Besides, JM03 improves the ability of nematode to resist oxidative stress and hypertonic stress through OSM-9, but not osm-9/capsaicin receptor related-2 (OCR-2). Then the inhibition of OSM-9 by JM03 reduces the aggregation of Q35 in C. elegans via upregulating the genes associated with proteostasis. SKN-1 signaling was also found to be activated after JM03 treatment, which might contribute to proteostasis, stress resistance and lifespan extension. In summary, this study explored a new small molecule derived from crotamiton, which has efficient anti-oxidative, anti-hypertonic, and anti-aging effects, and could further lead to promising application prospects.

Characterization of cellular senescence in doxorubicin-induced aging mice.

With a rise in the need to develop anti-aging drugs, a growing number of in vivo studies evaluating the efficacy of potential drug candidates have used doxorubicin-induced aging mice. However, changes in the biomarkers of senescent cells have not been reported in detail in these animals. To lay a foundation for the use of doxorubicin-induced aging mice, we examined the biomarkers of hepatic and renal senescent cells in these mice. We found that the 5 mg/kg doxorubicin dose is optimal to induce cellular senescence in mice. Subsequently, using this dose, we found that doxorubicin-induced an increase in senescence-associated ß-galactosidase (SA-ß-gal) positive cells in the kidney and lipofuscin accumulation in the liver. Some markers of senescent cells (p21WAF1/CIP1, p16INK4A, and γH2AX) were also significantly upregulated by doxorubicin and then counteracted by metformin treatment. These preliminary findings support the application of doxorubicin-induced aging mice as an animal model to evaluate the efficacy of anti-aging drug candidates.

Anti-aging effects of chlorpropamide depend on mitochondrial complex-II and the production of mitochondrial reactive oxygen species.

Sulfonylureas are widely used oral anti-diabetic drugs. However, its long-term usage effects on patients' lifespan remain controversial, with no reports of influence on animal longevity. Hence, the anti-aging effects of chlorpropamide along with glimepiride, glibenclamide, and tolbutamide were studied with special emphasis on the interaction of chlorpropamide with mitochondrial ATP-sensitive K+ (mitoK-ATP) channels and mitochondrial complex II. Chlorpropamide delayed aging in Caenorhabditis elegans, human lung fibroblast MRC-5 cells and reduced doxorubicin-induced senescence in both MRC-5 cells and mice. In addition, the mitochondrial membrane potential and ATP levels were significantly increased in chlorpropamide-treated worms, which is consistent with the function of its reported targets, mitoK-ATP channels. Increased levels of mitochondrial reactive oxygen species (mtROS) were observed in chlorpropamide-treated worms. Moreover, the lifespan extension by chlorpropamide required complex II and increased mtROS levels, indicating that chlorpropamide acts on complex II directly or indirectly via mitoK-ATP to increase the production of mtROS as a pro-longevity signal. This study provides mechanistic insight into the anti-aging effects of sulfonylureas in C. elegans.