Dual-specificity phosphatase 26 protects against kidney injury caused by ischaemia-reperfusion through restraint of TAK1-JNK/p38-mediated apoptosis and inflammation of renal tubular epithelial cells.

Dual-specificity phosphatase 26 (DUSP26) acts as a pivotal player in the transduction of signalling cascades with its dephosphorylating activity. Currently, DUSP26 attracts extensive attention due to its particular function in several pathological conditions. However, whether DUSP26 plays a role in kidney ischaemia-reperfusion (IR) injury is unknown. Aims of the current work were to explore the relevance of DUSP26 in kidney IR damage. DUSP26 levels were found to be decreased in renal tubular epithelial cells following hypoxia-reoxygenation (HR) and kidney samples subjected to IR treatments. DUSP26-overexpressed renal tubular epithelial cells exhibited protection against HR-caused apoptosis and inflammation, while DUSP26-depleted renal tubular epithelial cells were more sensitive to HR damage. Upregulation of DUSP26 in rat kidneys by infecting adenovirus expressing DUSP26 markedly ameliorated kidney injury caused by IR, while also effectively reducing apoptosis and inflammation. The mechanistic studies showed that the activation of transforming growth factor-ß-activated kinase 1 (TAK1)-JNK/p38 MAPK, contributing to kidney injury under HR or IR conditions, was restrained by increasing DUSP26 expression. Pharmacological restraint of TAK1 markedly diminished DUSP26-depletion-exacebated effects on JNK/p38 activation and HR injury of renal tubular cells. The work reported a renal-protective function of DUSP26, which protects against IR-related kidney damage via the intervention effects on the TAK1-JNK/p38 axis. The findings laid a foundation for understanding the molecular pathogenesis of kidney IR injury and provide a prospective target for treating this condition.

Serum CXCL13 level is related to treatment response and predicts disease prognosis in Waldenström macroglobulinemia.

Waldenström macroglobulinemia (WM) is a type of B-cell lymphoma that produces IgM. Our study aimed to investigate the role of CXCL13, a chemokine essential for B lymphocytes, in the evaluation of treatment response and prognosis in WM. We collected serum samples and clinical data from 72 WM patients, with 69 patients receiving systemic therapy and 3 patients opting not to receive treatment. Serum CXCL13 levels at baseline and after six months of treatments were measured by enzyme-linked immunosorbent assay. The median serum level of CXCL13 was 1 539.2 pg/ml (range 10.0-21 389.9) at baseline and significantly decreased to 123.1 pg/ml (range 0.0-6 741.5) after 6 months of treatments. At baseline, higher CXCL13 levels were associated with lower hemoglobin levels (p = 0.001), higher ß2-microglobulin levels (p = 0.001), lower albumin levels (p = 0.046), and higher IPSS-WM scores (p = 0.013). After 6 months of treatment, patients who achieved PR/VGPR had significantly lower CXCL13 levels compared to those with SD (70.2 pg/ml vs 798.6 pg/ml, p = 0.002). The median follow-up period was 40 months (range 4.2-188). Eight patients died during the follow-up period. Overall survival differed based on CXCL13 levels. When grouped by baseline CXCL13 levels, the median OS was 60.0 months in patients with serum CXCL13 > 2 000 pg/ml, while it was not reached in patients with low CXCL13 levels (p < 0.001). Based on CXCL13 levels after the treatments, the median OS was 74.0 months in patients with serum CXCL13 > 200 pg/ml, while it was not reached in patients with CXCL13 ≤ 200 pg/ml. In a subgroup of 28 patients with a series of serum samples, the increase of serum CXCL13 level was associated with disease progression or the start of next-line therapy (p < 0.001). Our study concludes that serum CXCL13 levels decrease in WM patients treated with various regimens and correlate with treatment response. Detecting serum CXCL13 at baseline or after treatment help in predicting prognosis.

Effect of AR gene-specific knockout on the process of radiation-induced pulmonary fibrosis and its mechanism.

Numerous studies have proved that epithelial-mesenchymal transition (EMT) of lung epithelial cells is one of the important causes of radiation-induced pulmonary fibrosis (RIPF). Aldose reductase (AR) is a monomer enzyme in the polyglycolic metabolic pathway and belongs to the aldo-keno reductase protein superfamily. Our previous studies have found that AR as one of the most significantly up-regulated genes was associated with the development of bleomycin-induced PF in rats. It is not clear whether aldose reductase is related to the regulation of radiation-induced EMT and mediates RIPF. AR-knockout mice, wild-type mice and lung epithelial cells were induced by radiation to establish a RIPF animal model and EMT system, to explore whether AR is mediation to RIPF through the EMT pathway. In vivo, AR deficiency significantly alleviated radiation-induced histopathological changes, reduced collagen deposition and inhibited collagen I, matrix metalloproteinase 2 (MMP2) and Twist1 expression. In addition, AR knockout up-regulated E-cadherin expression and up-regulated α-SMA and Vimentin expression. In vitro, AR, collagen I and MMP2 expression were increased in lung epithelial cells after radiation, which was accompanied by Twist1 expression up-regulation and EMT changes evidenced by decreased E-cadherin expression and increased α-SMA and Vimentin expression. Knockdown or inhibition of AR inhibited the expressions of Twist1, MMP2 and collagen I, and reduced cell migration and reversed radiation-induced EMT. These results indicated that aldose reductase may be related to radiation-induced lung epithelial cells EMT, and that inhibition of aldose reductase might be a promising treatment for RIPF.

Public Attitudes Toward Anxiety Disorder on Sina Weibo: Content Analysis.

BACKGROUND: Anxiety disorder has become a major clinical and public health problem, causing a significant economic burden worldwide. Public attitudes toward anxiety can impact the psychological state, help-seeking behavior, and social activities of people with anxiety disorder. OBJECTIVE: The purpose of this study was to explore public attitudes toward anxiety disorders and the changing trends of these attitudes by analyzing the posts related to anxiety disorders on Sina Weibo, a Chinese social media platform that has about 582 million users, as well as the psycholinguistic and topical features in the text content of the posts. METHODS: From April 2018 to March 2022, 325,807 Sina Weibo posts with the keyword "anxiety disorder" were collected and analyzed. First, we analyzed the changing trends in the number and total length of posts every month. Second, a Chinese Linguistic Psychological Text Analysis System (TextMind) was used to analyze the changing trends in the language features of the posts, in which 20 linguistic features were selected and presented. Third, a topic model (biterm topic model) was used for semantic content analysis to identify specific themes in Weibo users' attitudes toward anxiety. RESULTS: The changing trends in the number and the total length of posts indicated that anxiety-related posts significantly increased from April 2018 to March 2022 (R2=0.6512; P<.001 to R2=0.8133; P<.001, respectively) and were greatly impacted by the beginning of a new semester (spring/fall). The analysis of linguistic features showed that the frequency of the cognitive process (R2=0.1782; P=.003), perceptual process (R2=0.1435; P=.008), biological process (R2=0.3225; P<.001), and assent words (R2=0.4412; P<.001) increased significantly over time, while the frequency of the social process words (R2=0.2889; P<.001) decreased significantly, and public anxiety was greatly impacted by the COVID-19 pandemic. Feature correlation analysis showed that the frequencies of words related to work and family are almost negatively correlated with those of other psychological words. Semantic content analysis identified 5 common topical areas: discrimination and stigma, symptoms and physical health, treatment and support, work and social, and family and life. Our results showed that the occurrence probability of the topical area "discrimination and stigma" reached the highest value and averagely accounted for 26.66% in the 4-year period. The occurrence probability of the topical area "family and life" (R2=0.1888; P=.09) decreased over time, while that of the other 4 topical areas increased. CONCLUSIONS: The findings of our study indicate that public discrimination and stigma against anxiety disorder remain high, particularly in the aspects of self-denial and negative emotions. People with anxiety disorders should receive more social support to reduce the impact of discrimination and stigma.

"Green" Extraction and On-Site Rapid Detection of Aflatoxin B1, Zearalenone and Deoxynivalenol in Corn, Rice and Peanut.

The common mycotoxins in polluted grains are aflatoxin B1(AFB1), zearalenone (ZEN) and deoxynivalenol (DON). Because of the potential threat to humans and animals, it is necessary to detect mycotoxin contaminants rapidly. At present, later flow immunoassay (LFIA) is one of the most frequently used methods for rapid analysis. However, multistep sample pretreatment processes and organic solvents are also required to extract mycotoxins from grains. In this study, we developed a one-step and "green" sample pretreatment method without using organic solvents. By combining with LFIA test strips and a handheld detection device, an on-site method for the rapid detection of AFB1, ZEN and DON was developed. The LODs for AFB1, ZEN and DON in corn are 0.90 µg/kg, 7.11 µg/kg and 10.6 µg/kg, respectively, and the working ranges are from 1.25 µg/kg to 40 µg/kg, 20 µg/kg to 2000 µg/kg and 35 µg/kg to 1500 µg/kg, respectively. This method has been successfully applied to the detection of AFB1, ZEN and DON in corn, rice and peanut, with recoveries of 89 ± 3%-106 ± 3%, 86 ± 2%-108 ± 7% and 90 ± 2%-106 ± 10%, respectively. The detection results for the AFB1, ZEN and DON residues in certified reference materials by this method were in good agreement with their certificate values.

A unified serum IgG4 cut-off level for the diagnosis of IgG4-related disease using a wide array of kits.

OBJECTIVES: An immunoglobulin G4 (IgG4) level above 1350 mg/L is one of the comprehensive criteria for the diagnosis of IgG4-related disease (IgG4-RD). The purpose of this study was to evaluate the differences in IgG4 levels determined using reagents from two main manufacturers and their concordance with clinical diagnosis. METHODS: IgG4 levels were measured in 309 patients, including 146, 40, 42, 41, and 40 patients with untreated IgG4-RD, pancreatic cancer, primary Sjogren syndrome, systemic lupus erythematosus, and idiopathic retroperitoneal fibrosis, respectively, and 141 healthy controls. The results obtained using the Binding Site and Siemens reagents were compared in patients with IgG4-RD. RESULTS: The serum IgG4 level measured using the Siemens reagent was almost two times that measured using the Binding Site reagent. The rate of IgG4-negative patients, which was 19.9% based on measurement using the Binding Site reagent, was only 4.8% based on measurement using the Siemens reagent (p < .001). CONCLUSIONS: There were significant differences in serum IgG4 levels based on commonly used reagents from different manufacturers. The IgG4 cut-off level of 1350 mg/L was not suitable for all detection reagents. Clinicians and patients should be cognizant of these differences associated with the specific detection reagents when evaluating the test results.

IL-17 in intervertebral disc degeneration: Mechanistic insights and therapeutic implications.

Intervertebral disc degeneration (IDD) serves as an independent risk factor for lower back pain and is closely associated with spinal musculoskeletal disorders, including lumbar disc herniation, radiculopathy, and myelopathy. Interleukin-17 (IL-17), also named IL-17A, is a critical signature cytokine of T-helper 17 cells. Upon binding to the IL-17 receptor A/C heterodimeric complex, IL-17 can trigger multiple signal transduction pathways to stimulate gene transcription and increase messenger RNA stability. IL-17 expression is significantly increased in degenerative disc tissue and shows a positive correlation with disease severity. IL-17 has been shown to accelerate the development of IDD by promoting extracellular matrix degradation, enhancing inflammatory response, inducing neoangiogenesis, and inhibiting nucleus pulposus cell autophagy and proliferation. Targeting IL-17 represents a novel and promising approach for the therapeutic intervention of IDD. In this review, we summarized the recent progression about the role of IL-17 in IDD and highlighted its therapeutic implications.

Deep Hierarchical Ensemble Model for Suicide Detection on Imbalanced Social Media Data.

As a serious worldwide problem, suicide often causes huge and irreversible losses to families and society. Therefore, it is necessary to detect and help individuals with suicidal ideation in time. In recent years, the prosperous development of social media has provided new perspectives on suicide detection, but related research still faces some difficulties, such as data imbalance and expression implicitness. In this paper, we propose a Deep Hierarchical Ensemble model for Suicide Detection (DHE-SD) based on a hierarchical ensemble strategy, and construct a dataset based on Sina Weibo, which contains more than 550 thousand posts from 4521 users. To verify the effectiveness of the model, we also conduct experiments on a public Weibo dataset containing 7329 users' posts. The proposed model achieves the best performance on both the constructed dataset and the public dataset. In addition, in order to make the model applicable to a wider population, we use the proposed sentence-level mask mechanism to delete user posts with strong suicidal ideation. Experiments show that the proposed model can still effectively identify social media users with suicidal ideation even when the performance of the baseline models decrease significantly.

Asymmetric Incorporation of Silver Nanoparticles in Polymeric Assemblies by Coassembly of Tadpole-Like Nanoparticles and Amphiphilic Block Copolymers.

A general approach to asymmetrically localize nanoparticles (NPs) in larger polymeric nanostructures is demonstrated by coassembly of tadpole-like silver NPs (AgNPs) and amphiphilic block copolymers (BCPs). The tadpole-like AgNPs are prepared by template synthesis using a tailor-made A(BC)20 star polymer, namely poly(ethylene glycol)[poly(acrylic acid)-block-polystyrene]20 [PEG(PAA-b-PS)20 ], as template resulting in AgNPs decorated with twenty short PS chains and one long PEG chain, named Ag@PEG(PS)20 . The asymmetric distribution of these AgNPs in various polymeric nanostructures, e.g., spherical micelles, cylindrical micelles, vesicles, and sponge phase, is achieved via coassembly of the as-prepared Ag@PEG(PS)20 and PEG-b-PS in solution driven by the anisotropic nature of the Ag@PEG(PS)20 . This report not only provides a new strategy for the fabrication of tadpole-like NPs but also offers opportunity for off-center distributing NPs in hybrid assemblies, which may find applications in, e.g., sensing, catalysis, and diagnostics.

MRG1/2 histone methylation readers and HD2C histone deacetylase associate in repression of the florigen gene FT to set a proper flowering time in response to day-length changes.

Day-length changes represent an important cue for modulating flowering time. In Arabidopsis, the expression of the florigen gene FLOWERING LOCUS T (FT) exhibits a 24-h circadian rhythm under long-day (LD) conditions. Here we focus on the chromatin-based mechanism regarding the control of FT expression. We conducted co-immunoprecipitation assays along with LC-MS/MS analysis and identified HD2C histone deacetylase as the binding protein of the H3K4/H3K36 methylation reader MRG2. HD2C and MRG1/2 regulate flowering time under LD conditions, but not under short-day conditions. Moreover, HD2C functions as an effective deacetylase in planta, mainly targeting H3K9ac, H3K23ac and H3K27ac. At dusk, HD2C is recruited to FT to deacetylate histones and repress transcription in an MRG1/2-dependent manner. More importantly, HD2C competes with CO for the binding of MRG2, and the accumulation of HD2C at the FT locus occurs at the end of the day. Our findings not only reveal a histone deacetylation mechanism contributing to prevent FT overexpression and precocious flowering, but also support the model in which the histone methylation readers MRG1/2 provide a platform on chromatin for connecting regulatory factors involved in activating FT expression in response to daylight and decreasing FT expression around dusk under long days.

Linking PHYTOCHROME-INTERACTING FACTOR to Histone Modification in Plant Shade Avoidance.

Shade avoidance syndrome (SAS) allows a plant grown in a densely populated environment to maximize opportunities to access to sunlight. Although it is well established that SAS is accompanied by gene expression changes, the underlying molecular mechanism needs to be elucidated. Here, we identify the H3K4me3/H3K36me3-binding proteins, Morf Related Gene (MRG) group proteins MRG1 and MRG2, as positive regulators of shade-induced hypocotyl elongation in Arabidopsis (Arabidopsis thaliana). MRG2 binds PHYTOCHROME-INTERACTING FACTOR7 (PIF7) and regulates the expression of several common downstream target genes, including YUCCA8 and IAA19 involved in the auxin biosynthesis or response pathway and PRE1 involved in brassinosteroid regulation of cell elongation. In response to shade, PIF7 and MRG2 are enriched at the promoter and gene-body regions and are necessary for increase of histone H4 and H3 acetylation to promote target gene expression. Our study uncovers a mechanism in which the shade-responsive factor PIF7 recruits MRG1/MRG2 that binds H3K4me3/H3K36me3 and brings histone-acetylases to induce histone acetylations to promote expression of shade responsive genes, providing thus a molecular mechanistic link coupling the environmental light to epigenetic modification in regulation of hypocotyl elongation in plant SAS.

Theoretical Study of PAH Growth by Phenylacetylene Addition.

Although there was significant advancement on polycyclic aromatic hydrocarbon (PAH) formation, current mechanisms are still limited in providing an integrated and accurate scheme of PAH yield in combustion conditions; thus, a more detailed and comprehensive understanding is necessary. This work provides a systematic investigation of PAH growth by phenylacetylene addition. A combination of the density functional theory (DFT/B3LYP/6-311+G(d,p)) and the complete basis set method (CBS-QB3) is utilized to calculate the potential energy surfaces. The reaction system is initiated by the H elimination reaction of phenylacetylene + H → o-ethynylphenyl + H2, and then, the addition reaction of phenylacetylene and o-ethynylphenyl can produce PAHs with one, two, three, and four rings. The temperature- and pressure-dependent reaction rate coefficients are calculated via a combination of conventional transition state theory (TST) and Rice-Ramsperger-Kassel-Marcus (RRKM) theory with solving the master equation in the temperature range of 500-2500 K and at the pressure range of 0.01-10 atm. There are 263 species and 65 reactions in this reaction system. It shows that the rate constants of this reaction system are highly temperature-dependent and slightly sensitive to the pressure at temperatures lower than 1300 K. To evaluate the yield distributions of various PAH products in the whole reaction network, a closed 0-D batch reactor model in Chemkin is used to calculate the C6H5C2H-C2H2-H-Ar reaction system. The results showed that the prevailing products of this system are three-ring PAHs with side chain structures. Compared with the traditional HACA pathways, the investigated reaction system presents higher efficiency in large PAH formations, which could subsequently promote the formation of soot particles. The phenylacetylene and o-ethynylphenyl reaction network emphasizes the importance of species with side chains, and it enriches current PAH growth pathways aside from the addition of small species such as C2H2.

Regulation of arabidopsis flowering by the histone mark readers MRG1/2 via interaction with CONSTANS to modulate FT expression.

Day-length is important for regulating the transition to reproductive development (flowering) in plants. In the model plant Arabidopsis thaliana, the transcription factor CONSTANS (CO) promotes expression of the florigen FLOWERING LOCUS T (FT), constituting a key flowering pathway under long-day photoperiods. Recent studies have revealed that FT expression is regulated by changes of histone modification marks of the FT chromatin, but the epigenetic regulators that directly interact with the CO protein have not been identified. Here, we show that the Arabidopsis Morf Related Gene (MRG) group proteins MRG1 and MRG2 act as H3K4me3/H3K36me3 readers and physically interact with CO to activate FT expression. In vitro binding analyses indicated that the chromodomains of MRG1 and MRG2 preferentially bind H3K4me3/H3K36me3 peptides. The mrg1 mrg2 double mutant exhibits reduced mRNA levels of FT, but not of CO, and shows a late-flowering phenotype under the long-day but not short-day photoperiod growth conditions. MRG2 associates with the chromatin of FT promoter in a way dependent of both CO and H3K4me3/H3K36me3. Vice versa, loss of MRG1 and MRG2 also impairs CO binding at the FT promoter. Crystal structure analyses of MRG2 bound with H3K4me3/H3K36me3 peptides together with mutagenesis analysis in planta further demonstrated that MRG2 function relies on its H3K4me3/H3K36me3-binding activity. Collectively, our results unravel a novel chromatin regulatory mechanism, linking functions of MRG1 and MRG2 proteins, H3K4/H3K36 methylations, and CO in FT activation in the photoperiodic regulation of flowering time in plants.

LncRNA SNHG14 activates autophagy via regulating miR-493-5p/Mef2c axis to alleviate osteoporosis progression.

Osteoporosis is a progressive bone disease caused by impaired function of endogenous bone marrow-derived mesenchymal stem cells (BMSCs). Herein, we investigated the mechanism of lncRNA SNHG14 in osteoporosis progression. BMSCs were isolated from BALB/c mice. The osteogenic ability of BMSCs was assessed by Alkaline phosphatase (ALP) and Alizarin Red S Staining (ARS) staining. The interaction between miR-493-5p and SNHG14 or myocyte enhancer factor 2 C (Mef2c) was confirmed by dual-luciferase reporter assay. Bone histomorphometry changes were evaluated to analyze SNHG14'roles in osteoporosis in vivo. Our results illustrated SNHG14 and Mef2c levels were increased in a time-dependent manner in BMSCs, and miR-493-5p expression was decreased. SNHG14 knockdown inhibited osteogenic differentiation of BMSCs, and SNHG14 upregulation had the opposite effect. SNHG14 overexpression elevated bone mineral density and bone trabecular number, and alleviated osteoporosis progression in vivo. Mechanically, miR-493-5p was a target of SNHG14, and miR-493-5p targeted the Mef2c gene directly. SNHG14 overexpression reversed the inhibition of miR-493-5p on the osteogenic ability of BMSCs, and miR-493-5p silencing accelerated BMSCs osteogenesis by activating Mef2c-mediated autophagy to accelerate BMSCs osteogenesis. In short, SNHG14 activated autophagy via regulating miR-493-5p/Mef2c axis to alleviate osteoporosis progression, which might provide a new molecular target for osteoporosis treatment.

Serum protein N-glycome patterns reveal alterations associated with endometrial cancer and its phenotypes of differentiation.

Background: Aberrant N-glycosylation and its involvement in pathogenesis have been reported in endometrial cancer (EC). Nevertheless, the serum N-glycomic signature of EC remains unknown. Here, we investigated serum N-glycome patterns of EC to identify candidate biomarkers. Methods: This study enrolled 34 untreated EC patients and 34 matched healthy controls (HC) from Peking Union Medical College Hospital. State-of-the-art MS-based methods were employed for N-glycans profiling. Multivariate and univariate statistical analyses were used to identify discriminative N-glycans driving classification. Receiver operating characteristic analyses were performed to evaluate classification accuracy. Results: EC patients displayed distinct differences in serum N-glycome and had abnormal high-mannose and hybrid-type N-glycans, fucosylation, galactosylation, and linkage-specific sialylation compared with HC. The glycan panel built with the four most discriminative and biologically important derived N-glycan traits could accurately identify EC (random forest model, the area under the curve [AUC]=0.993 [95%CI 0.955-1]). The performance was validated by two other models. Total hybrid-type N-glycans significantly associated with the differentiation types of EC could effectively stratify EC into well- or poorly-differentiated subgroups (AUC>0.8). Conclusion: This study provides the initial evidence supporting the utility of serum N-glycomic signature as potential markers for the diagnosis and phenotyping of EC.

MHA: a multimodal hierarchical attention model for depression detection in social media.

As a serious mental disease, depression causes great harm to the physical and mental health of individuals, and becomes an important cause of suicide. Therefore, it is necessary to accurately identify and treat depressed patients. Compared with traditional clinical diagnosis methods, a large amount of real and different types of data on social media provides new ideas for depression detection research. In this paper, we construct a depression detection data set based on Weibo, and propose a Multimodal Hierarchical Attention (MHA) model for social media depression detection. Multimodal data is fed into the model and the attention mechanism is applied within and between modalities at the same time. Experimental results show that the proposed model achieves the best classification performance. In addition, we propose a distribution normalization method, which can optimize the data distribution and improve the accuracy of depression detection.

A lateral flow immunoassay method for the rapid detection of acetochlor and alachlor in vegetable oil by sensitivity enhancement by using dimethyl-ß-cyclodextrin.

Acetochlor is an endocrine disruptor. The acetochlor residue is strongly lipophilic and can be enriched into products during the manufacturing process. In this study, we found that dimethyl-ß-cyclodextrin (DM-ß-CD) solution could decrease the apparent oil/water partition coefficient (Koil-w) of acetochlor and increase the sensitivity of fluorescence lateral flow immunoassay (LFIA) for acetochlor simultaneously. Based on this, a simple LFIA method for the determination of acetochlor and alachlor residues in vegetable oil was established. The detection process only involves vortex mixing of an oil sample and dimethyl-ß-cyclodextrin solution in a 1 : 3 (V/V) ratio, loading the water phase onto the immunoassay strips and reading the results. Under optimized conditions, the LOD for acetochlor in oil was 3.53 ng g-1, and the working range was 12.03-2000.00 ng g-1. The recoveries of spiked samples ranged from 91.69% ± 1.12% to 112.23% ± 2.20%. Meanwhile, the cross reactivity for alachlor was 108.22%, while for other investigated acetochlor analogues it was less than 1%, and the recoveries of alachlor were from 92.90% ± 8.03% to 113.53% ± 3.40%, which indicate that this method can detect acetochlor and alachlor simultaneously. Compared with the traditional detection method, the pre-treatment process of the proposed method is "green" and simple, and can be applied to the on-site rapid detection of acetochlor and alachlor in vegetable oil and can provide inspiration for the detection of other lipophilic pollutants.

[IL-33 up-regulates eIF3a expression by activating NF-κB signaling pathway to mediate the proliferation and differentiation of mouse pulmonary myofibroblasts and aggravate pulmonary fibrosis].

Objective To investigate the effects and mechanism of Interleukin-33 (IL-33) mediated proliferation and differentiation of pulmonary myofibroblasts (MFbs) in pulmonary fibrosis (PF). Methods C57BL/6 mice were randomly divided into four groups: a control group, a bleomycin (BLM) group, a BLM combined with IL-33 group and a BLM combined with anti-IL-33 antibody group, 12 mice in each group. The PF model was induced by intratracheal injection of BLM (5000 U/kg). The degrees of fibrosis were examined using HE and Masson staining. ELISA was used to measure the plasma levels of IL-33. Immunohistochemical staining was used to measure the expression of alpha smooth muscle actin (α-SMA) in lung tissue. Primary pulmonary fibroblasts were isolated and cultured from lung tissues of mice. The cells were divided into four groups: a control group, an IL-33 group, an IL-33 combined with dimethyl sulfoxide (DMSO) group and an IL-33 combined with pyrrolidine dithiocarbamate (PDTC) group. The cells were treated with DMSO or PDTC for 1 hour and then with IL-33 for 48 hours. Cell proliferation was measured by 5-ethynyl-2'-deoxyuridine (EdU) assay and cell cycle was measured by flow cytometry. TranswellTM assay was used to analyze cell migration. Real-time quantitative PCR was used to measure the expression of collagen type I (Col1), Col3 and α-SMA mRNA. The protein levels of IL-33, Col1, Col3, α-SMA, eukaryotic initiation factor 3a (eIF3a), phosphorylated IκBα (p-IκBα) (total lysate), p-NF-κB p65(total lysate) and NF-κB p65 (nucleus) were measured by Western blot analysis. Results In vivo, compared with the control group, the expressions of IL-33, p-IκBα (total lysate), p-NF-κB p65 (total lysate), NF-κB p65(nucleus), eIF3a, α-SMA, Col1 and Col3 in the BLM group significantly increased. Compared with the BLM group, the expressions of p-IκBα (total lysate), p-NF-κB p65 (total lysate), NF-κB p65 (nucleus), eIF3a, α-SMA, Col1 and Col3 in the IL-33 group increased further and the PF was further aggravated. But the effect of anti-IL-33 antibody was just opposite to that of IL-33. In vitro, IL-33 markedly induced the proliferation and migration of pulmonary fibroblasts, and significantly up-regulated the expression of p-IκBα (total lysate), p-NF-κB p65(total lysate), NF-κB p65 (nucleus), eIF3a, α-SMA, Col1 and Col3. But all these effects of IL-33 were reversed by pyrrolidine dithiocarbamate. Conclusion The results suggest that IL-33 may promote the expression of eIF3a by activating NF-κB signaling pathway, thus inducing the proliferation and differentiation of MFbs and promoting the occurrence and development of PF.

Human Umbilical Cord Blood-Derived Mesenchymal Stem Cell Transplantation for Patients with Decompensated Liver Cirrhosis.

BACKGROUND OR PURPOSE: Although human umbilical cord blood-derived mesenchymal stem cell transplantation (HUCB-MSCT) resulted in a good short-term therapeutic effect on patients with decompensated liver cirrhosis (DLC), the long-term survival remained unclear. This study aimed to evaluate the impact of HUCB-MSCT on long-term outcomes in patients with DLC. METHODS: This retrospective cohort study included hospitalized patients with decompensated cirrhosis in Liuzhou Hospital of Traditional Chinese Medicine between November 2010 and February 2013. The primary outcome was overall survival (OS). The secondary outcomes were 3-year and 5-year survival rates and the occurrence rate of hepatocellular carcinoma (HCC). RESULTS: A total of 201 subjects were enrolled, including 36 patients who underwent HUCB-MSCT (SCT group) and 165 patients who did not (non-SCT group). After PSM (1:2), there were 36 patients in the SCT group and 72 patients in non-SCT group. The 3-year and 5-year survival rates of the two groups were 83.3% vs. 61.8% and 63.9% vs. 43.6%, and median OS time was 92.50 and 50.80 months, respectively. HUCB-MSCT treatment was found to be an independent beneficial factor for patient OS (hazard ratio = 0.47; 95% CI: 0.29-0.76; P = 0.002). There was no significant difference in the occurrence rate of HCC between the two groups (P = 0.410). DISCUSSION OR CONCLUSIONS: HUCB-MSCT may improve long-term OS without increasing the occurrence of HCC in patients with DLC. TRIAL REGISTRATION: The Chinese Clinical Trial Registry (ChiCTR2100047550).

Peripheral CD8+CD28+ T lymphocytes predict the efficacy and safety of PD-1/PD-L1 inhibitors in cancer patients.

Background: Programmed cell death protein-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors works by reactivating immune cells. Considering the accessibility of noninvasive liquid biopsies, it is advisable to employ peripheral blood lymphocyte subsets to predict immunotherapy outcomes. Methods: We retrospectively enrolled 87 patients with available baseline circulating lymphocyte subset data who received first-line PD-1/PD-L1 inhibitors at Peking Union Medical College Hospital between May 2018 and April 2022. Immune cell counts were determined by flow cytometry. Results: Patients who responded to PD-1/PD-L1 inhibitors had significantly higher circulating CD8+CD28+ T-cell counts (median [range] count: 236 [30-536] versus 138 [36-460]/µL, p < 0.001). Using 190/µL as the cutoff value, the sensitivity and specificity of CD8+CD28+ T cells for predicting immunotherapy response were 0.689 and 0.714, respectively. Furthermore, the median progression-free survival (PFS, not reached versus 8.7 months, p < 0.001) and overall survival (OS, not reached versus 16.2 months, p < 0.001) were significantly longer in the patients with higher CD8+CD28+ T-cell counts. However, the CD8+CD28+ T-cell level was also associated with the incidence of grade 3-4 immune-related adverse events (irAEs). The sensitivity and specificity of CD8+CD28+ T cells for predicting irAEs of grade 3-4 were 0.846 and 0.667, respectively, at the threshold of CD8+CD28+ T cells ≥ 309/µL. Conclusions: High circulating CD8+CD28+ T-cell levels is a potential biomarker for immunotherapy response and better prognosis, while excessive CD8+CD28+ T cells (≥ 309/µL) may also indicate the emergence of severe irAEs.