Association between dietary patterns and the risk of all-cause mortality among old adults with obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) was associated with the increased cardiovascular events and all-cause mortality. And anti-inflammatory dietary has potential to improve the prognosis of OSA. This study aimed to investigate the association of anti-inflammatory dietary patterns with all-cause mortality among individuals with OSA. METHODS: This retrospective cohort study involved 1522 older adults with OSA from 2005 to 2008 in the National Health and Nutrition Examinations Survey (NHANES). Mortality status was determined by routine follow-up through December 31, 2019, using the National Death Index. Anti-inflammatory dietary patterns included Alternate Mediterranean Diet Score (aMED), Healthy Eating Index-2015 (HEI-2015), and Alternate Healthy Eating Index-2010 (AHEI-2010). Weighted Cox proportional hazard regression models were performed to investigate the association between anti-inflammatory dietary pattern and all-cause mortality. RESULTS: After a median follow-up of 131 months, 604 participants were recorded all-cause mortality. The mean age of OSA patients was 68.99 years old, of whom 859 were male (52.34%). Higher adherence of aMED (HR = 0.61, 95%CI: 0.48 to 0.78) and HEI-2015 (HR = 0.75, 95%CI: 0.60 to 0.95) were associated with lower all-cause mortality risk in the elderly with OSA. Conversely, no association was found between AHEI-2010 dietary pattern and all-cause mortality in individuals with OSA. In the component analysis of aMED, it was found that a higher intake of vegetables and olive oil potentially contributes to the reduction all-cause mortality risk in the elderly with OSA (HR = 0.60, 95%CI: 0.48 to 0.76; HR = 0.67, 95%CI: 0.63 to 0.71). CONCLUSION: Higher adherence to the aMED and the HEI-2015 was associated with a lower risk of all-cause mortality in OSA. Future interventions in the elderly with OSA should considering adopting anti-inflammatory dietary patterns.

Methyl jasmonate-induced bHLH42 mediates tissue-specific accumulation of anthocyanins via regulating flavonoid metabolism-related pathways in Caitai.

Anthocyanin is a type of plant secondary metabolite beneficial to human health. The anthocyanin content of vegetable and fruit crops signifies their nutritional quality. However, the molecular mechanism of anthocyanin accumulation, especially tissue-specific accumulation, in Caitai, as well as in other Brassica rapa varieties, remains elusive. In the present study, taking advantage of three kinds of Caitai cultivars with diverse colour traits between leaves and stems, we conducted a comparative transcriptome analysis and identified the molecular pathway of anthocyanin biosynthesis in Caitai leaves and stems, respectively. Our further investigations demonstrate that bHLH42, which is robustly induced by MeJA, closely correlates with tissue-specific accumulation of anthocyanins in Caitai; bHLH42 upregulates the expression of flavonoid/anthocyanin biosynthetic pathway genes to activate anthocyanin biosynthesis pathway, importantly, overexpression of bHLH42 significantly improves the anthocyanin content of Caitai. Our analysis convincingly suggests that bHLH42 induced by jasmonic acid signalling plays a crucial role in tissue-specific accumulation of anthocyanins in Caitai.

Antifungal Tetrahydrocarbazole Compound CAR-8 Induces Endoplasmic Reticulum Stress in Candida albicans.

The development of new effective antifungal agents is essential to combat fungal infections. Tetrahydrocarbazole has been exploited as a promising skeleton against various pathogenic microorganisms and is used to search for novel active antifungal compounds. In this study, a library composed of small tetrahydrocarbazole compounds was screened, and a potent antifungal agent, CAR-8, was identified with a minimum inhibitory concentration of 2-4 µg/mL against Candida albicans. CAR-8 showed strong fungicidal activities and killed almost all C. albicans within 3 h at a concentration of 16 µg/mL. At concentrations of 2 and 8 µg/mL, CAR-8 significantly inhibited the formation of hyphae and biofilms. Moreover, CAR-8 at 10 and 20 mg/kg reduced the fungal load and improved the survival in the C. albicans infection model in the invertebrate Galleria mellonella. Transcriptome analysis revealed significant changes in the expression of genes associated with protein processing in the endoplasmic reticulum (ER), ER-associated degradation, and unfolded protein response (UPR), which suggested that CAR-8 treatment induced ER stress. Moreover, CAR-8 treatment resulted in various phenotypes similar to tunicamycin, a classical ER stress inducer. These included nonconventional splicing of HAC1 mRNA, the fragmented morphology of ER, the distribution changes of GFP-Snc1 in Saccharomyces cerevisiae, and cell apoptosis probably caused by ER stress. More importantly, the disruption of IRE1 or HAC1 increased the sensitivity of C. albicans to CAR-8, confirming that the UPR signaling pathway was critical for CAR-8 resistance. Overall, our study identifies a potent ER stress-induced antifungal compound that will help the discovery of new antifungal drugs.

Structurally diverse diterpenoids from the leaves of Croton mangelong and their anti-diabetic activity.

Eighteen compounds including eleven previously undescribed diterpenes were isolated from the leaves of Croton mangelong. The structures were determined by HRESIMS, IR, NMR, X-ray diffraction and ECD spectroscopic analysis. All isolates were assayed for their anti-hyperglycemic activities in insulin resistance (IR) 3T3-L1 adipocytes, and compound 4 was tested for its anti-diabetic activity in vivo. Results suggested compound 4 could effectively reduce blood glucose level in diabetic SD rats in a dose of 30 mg/kg.

Endoplasmic reticulum-targeted fluorescent probe with aggregation-induced emission features for imaging peroxynitrite in drug-induced liver injury model.

Drug-induced liver injury (DILI) poses a severe threat to public health. Endoplasmic reticulum (ER) stress contributes significantly to DILI pathogenesis, with peroxynitrite (ONOO-) identified as a pivotal indicator. However, the temporal and spatial fluctuations of ONOO- associated with ER stress in the pathogenesis of DILI remain unclear. Herein, a novel ER-specific near-infrared (NIR) probe (QM-ONOO) with aggregation-induced emission (AIE) features for monitoring ONOO- fluctuations in DILI was elaborately constructed. QM-ONOO exhibited excellent ER-targeting specificity, a large Stoke's shift, and a low detection limit (26.9 nM) toward ONOO-. QM-ONOO performed well in imaging both exogenous and endogenous ONOO- in HepG2 cells. Furthermore, molecular docking calculations validated the ER-targeting mechanism of QM-ONOO. Most importantly, using this probe allowed us to intuitively observe the dynamic fluctuations of ONOO- during the formation and remediation processes of DILI in the acetaminophen (APAP)-induced mouse model. Consequently, this work provides a promising tool for in-depth research of ONOO- associated pathological processes in DILI.

Changes in visual performance after implantation of different intraocular lenses.

AIM: To evaluate the trending visual performance of different intraocular lenses (IOLs) over time after implantation. METHODS: Ninety-one patients received cataract surgery with implantations of monofocal (Mon) IOLs, segmental refractive (SegRef) IOLs, diffractive (Dif) IOLs, and extended-depth-of-focus (EDoF) IOLs were included. The aberrations and optical quality collected with iTrace and OQAS within postoperative 6mo were followed and compared. RESULTS: Most of the visual parameters improved over the postoperative 6mo. The postoperative visual acuity (POVA) of the Mon IOL, SegRef IOL, and EDoF IOL groups achieved relative stability in earlier states compared with the Dif IOL group. Nevertheless, the overall visual performance of the 3 IOLs continued to upturn in small extents within the postoperative 6mo. The optical quality initially improved in the EDoF IOL group, then in the Mon IOL, SegRef IOL, and Dif IOL groups. POVA and objective visual performance of the Mon IOL and EDoF IOL groups, as well as POVA and visual quality of the Dif IOL group, improved in the postoperative 1mo and stabilized. Within the postoperative 6mo, gradual improvements were observed in the visual acuity and objective visual performance of the SegRef IOL group, as well as in the postoperative optical quality of the Dif IOL group. CONCLUSION: The visual performance is different among eyes implanted with different IOLs. The findings of the current study provide a potential reference for ophthalmologists to choose suitable IOLs for cataract patients in a personalized solution.

[Growth decline characteristics of Picea schrenkiana at different altitudes in Yili River Basin, western Tian-shan Mountains, Xinjiang, China]. / 新疆天山西部伊犁河流域不同海拔雪岭云杉生长衰退特征.

Picea schrenkiana is the dominant tree species in Ili River Basin located in the western Tianshan Mountains of Xinjiang. We investigated the growth decline characteristics of P. schrenkiana at different altitudes (1800, 2300 and 2800 m) based on tree-ring index (TRI) and percentage growth change (GC), aiming to understand the growth response of P. schrenkiana to drought events at different altitudes and the impacts of altitude on tree growth decline in this region. The results showed that P. schrenkiana experienced multiple decline events at low-altitude (1800 m). TRI and GC identified inconsistent occurrence time of the decline events. The variations of TRI indicated that P. schrenkiana at low-altitude experienced two large-scale declines during 1927-1933 and 2017-2014, respectively. The variations of GC identified four decline events, including 1891-1893, 1924-1926, 1973-1975, and 2004-2009. The radial growth of P. schrenkiana across altitudes from low to high was significantly affected by the Palmer drought severity index (PDSI) of the previous growing season. The impact of current PDSI on P. schrenkiana during the growing season initially enhanced but later decreased with increasing altitude. In the extreme drought year 1917, the magnitude of growth decline increased with altitude. At low-altitude (1800 m), the TRI was 0.65, which was 35% lower than the normal level. At mid-altitude (2300 m) and high-altitude (2800 m), it was 0.56 and 0.54, respectively, being 40% lower than the average level. The drought event in 1917 had a 2-year legacy effect on the growth of P. schrenkiana at all the altitudes, with the TRI in 1920 recovered to exceeding 0.9, being close to the normal level. The impact of altitude on drought-induced forest decline was significant. Tree growth in low-altitude areas was more vulnerable to drought events due to the relatively poorer water and temperature conditions at low-altitude, which could lead to multiple large-scale decline events. In mid- and high-altitude areas, where hydrothermal conditions were more favorable, trees could experience even more severe decline during extreme droughts.

An injectable chitosan-based hydrogel incorporating carbon dots with dual enzyme-mimic activities for synergistically treatment of bacteria infected wounds.

Bacterial infections pose a serious threat to human health, and the emergence of superbugs and the growing antibiotic resistance phenomenon have made the development of novel antimicrobial products. In this paper, an ultrasmall Cu, N co-doped carbon dots (CDs-Cu-N) with excellent peroxidase mimic activity and enhanced catalase mimic activity was successfully prepared and anchored to an injectable chitosan (CS)-based hybrid hydrogel. As expected, the CDs-Cu-N-H2O2-CS hybrid hydrogel maintains the excellent enzyme-mimicking properties of CDs-Cu-N and shows superior antibacterial property, which has been proven to effectively promote the healing of S. aureus-infected wounds with good biocompatibility. Benefitting from the dual-enzyme-mimic activity of CDs-Cu-N, the hybrid hydrogel not only can catalyze the generation of highly toxic ROS from low concentration of H2O2 to inhibit the bacterial infections, but also can significantly promote the wound tissue repair and regeneration by improving the anoxic microenvironment and promoting neovascularization. In addition, this hybrid hydrogel also possessed excellent injectability and moldability. It can adapt to various the irregular shapes of acute wounds, maintaining a moist and safe microenvironment while prolonging the action time of nanozyme on wounds, thus promoting wound healing. This injectable hybrid hydrogel shows great potential applications in the field of wound infection management.

Predicting Kawasaki disease shock syndrome in children.

Background: Kawasaki disease shock syndrome (KDSS) is a critical manifestation of Kawasaki disease (KD). In recent years, a logistic regression prediction model has been widely used to predict the occurrence probability of various diseases. This study aimed to investigate the clinical characteristics of children with KD and develop and validate an individualized logistic regression model for predicting KDSS among children with KD. Methods: The clinical data of children diagnosed with KDSS and hospitalized between January 2021 and December 2023 were retrospectively analyzed. The best predictors were selected by logistic regression and lasso regression analyses. A logistic regression model was built of the training set (n = 162) to predict the occurrence of KDSS. The model prediction was further performed by logistic regression. A receiver operating characteristic curve was used to evaluate the performance of the logistic regression model. We built a nomogram model by visualizing the calibration curve using a 1000 bootstrap resampling program. The model was validated using an independent validation set (n = 68). Results: In the univariate analysis, among the 24 variables that differed significantly between the KDSS and KD groups, further logistic and Lasso regression analyses found that five variables were independently related to KDSS: rash, brain natriuretic peptide, serum Na, serum P, and aspartate aminotransferase. A logistic regression model was established of the training set (area under the receiver operating characteristic curve, 0.979; sensitivity=96.2%; specificity=97.2%). The calibration curve showed good consistency between the predicted values of the logistic regression model and the actual observed values in the training and validation sets. Conclusion: Here we established a feasible and highly accurate logistic regression model to predict the occurrence of KDSS, which will enable its early identification.

Associations of glymphatic function with structural network and cognition in self-limited epilepsy with centrotemporal spikes.

PURPOSE: To investigate glymphatic function by Virchow-Robin space (VRS) counts and volume in patients with newly diagnosed self-limited epilepsy with centrotemporal spikes (SeLECTS) and evaluate its relationship with structural connectivity and cognitive impairment. METHODS: Thirty-two children with SeLECTS and thirty-two age- and sex-matched typically developing (TD) children were enrolled in this study. VRS counts and volume were quantified. Structural networks were constructed and the topological metrics were analyzed. Wechsler Intelligence Scale (WISC) was used to assess cognitive function in all participants. Correlation analysis assessed the association between VRS counts and volume, network connectivity, and cognitive impairment. Mediation effects of topological metrics of the structural networks on the relationship between glymphatic function and cognitive impairment were explored. RESULTS: Patients with SeLECTS showed a higher VRS counts, VRS volume, and global shortest path length (Lp); they also showed a lower global efficiency (Eg). VRS counts and volume were significantly correlated with full-scale intelligence quotient (FIQ) (r_VRS counts = -0.520, r_VRS volume = -0.639), performance intelligence quotient (PIQ) (r_VRS counts = -0.693, r_VRS volume = -0.597), verbal intelligence quotient (VIQ) (r_VRS counts = -0.713, r_VRS volume = -0.699), Eg (r_VRS counts = -0.499, r_VRS volume = -0.490), and Lp (r_VRS volume = 0.671) in patients with SeLECTS. Eg mediated 24.59% of the effects for the relationship between VRS volume and FIQ. CONCLUSION: Glymphatic function may be impaired in SeLECTS reflected by VRS counts and volume. Glymphatic dysfunction may result in cognitive impairment by disrupting structural connectivity in SeLECTS.

LABS: linear amplification-based bisulfite sequencing for ultrasensitive cancer detection from cell-free DNA.

Methylation-based liquid biopsies show promises in detecting cancer using circulating cell-free DNA; however, current limitations impede clinical application. Most assays necessitate substantial DNA inputs, posing challenges. Additionally, underrepresented tumor DNA fragments may go undetected during exponential amplification steps of traditional sequencing methods. Here, we report linear amplification-based bisulfite sequencing (LABS), enabling linear amplification of bisulfite-treated DNA fragments in a genome-wide, unbiased fashion, detecting cancer abnormalities with sub-nanogram inputs. Applying LABS to 100 patient samples revealed cancer-specific patterns, copy number alterations, and enhanced cancer detection accuracy by identifying tissue-of-origin and immune cell composition.

18ß-glycyrrhetinic acid ameliorates bleomycin-induced idiopathic pulmonary fibrosis via inhibiting TGF-ß1/JAK2/STAT3 signaling axis.

Idiopathic pulmonary fibrosis (IPF) is a debilitating and progressive lung disease with an unknown cause that has few treatment options. 18ß-Glycyrrhetinic acid (18ß-GA) is the main bioactive component in licorice, exhibiting anti-inflammatory and antioxidant effects, while also holding certain application value in the metabolism and regulation of steroids. In this study, we demonstrated that 18ß-GA effectively alleviates bleomycin (BLM)-induced IPF by inhibiting the TGF-ß1/JAK2/STAT3 signaling axis. In vivo experiments demonstrate that 18ß-GA significantly attenuates pulmonary fibrosis progression by reducing lung inflammation, improving lung function, and decreasing collagen deposition. In vitro experiments reveal that 18ß-GA inhibits the activation and migration of TGF-ß1-induced fibroblasts. Furthermore, it regulates the expression of vimentin, N-cadherin and E-cadherin proteins, thereby inhibiting TGF-ß1-induced epithelial-mesenchymal transition (EMT) in lung alveolar epithelial cells. Mechanistically, 18ß-GA ameliorates pulmonary fibrosis by modulating the TGF-ß1/JAK2/STAT3 signaling pathway in activated fibroblasts. Taken together, our findings demonstrate the potential and underlying mechanisms of 18ß-GA in ameliorating IPF, emphasizing its potential as a novel therapeutic drug for the treatment of this devastating disease.

Performance of Halo-Alkali-Tolerant Endophytic Bacteria on Hybrid Pennisetum and Bacterial Community under Varying Soil Conditions.

Halo-alkali soil threatens agriculture, reducing growth and crop yield worldwide. In this study, physicochemical and molecular techniques were employed to explore the potential of halo-alkali-tolerant endophytic bacteria strains Sphingomonas sp. pp01, Bacillus sp. pp02, Pantoea sp. pp04, and Enterobacter sp. pp06 to enhance the growth of hybrid Pennisetum under varying saline conditions. The strains exhibited tolerance to high salt concentrations, alkaline pH, and high temperatures. Under controlled conditions, all four strains showed significant growth-promoting effects on hybrid Pennisetum inoculated individually or in combination. However, the effects were significantly reduced in coastal saline soil. The best growth-promoting effect was achieved under greenhouse conditions, increasing shoot fresh and dry weights of hybrid Pennisetum by up to 457.7% and 374.7%, respectively, using irrigating trials. Metagenomic sequencing analysis revealed that the diversity and composition of rhizosphere microbiota underwent significant changes after inoculation with endophytic bacteria. Specifically, pp02 and co-inoculation significantly increased the Dyella and Pseudomonas population. Firmicutes, Mycobacteria, and Proteobacteria phyla were enriched in Bacillus PP02 samples. These may explain the best growth-promoting effects of pp02 and co-inoculation on hybrid Pennisetum under greenhouse conditions. Our findings reveal the performance of endophytic bacterial inoculants in enhancing beneficial microbiota, salt stress tolerance, and hybrid Pennisetum growth.

Stellate Ganglion Block Attenuates LPS-Induced Acute Lung Injury by Activating Sirt3 Regulation of Oxidative Stress and Inflammation.

Stellate ganglion blocks (SGBs) has been applied in clinics to alleviate pain-related syndromes for almost a century. In recent years, it has been reported that SGB can attenuate acute lung injury (ALI) in animals. However, the details of these molecular mechanisms remain complex and unclear. In this study, rats were randomly divided into four groups: group C (receiving no treatment), group NS (receiving the intratracheal instillation of normal saline), group L (receiving the intratracheal instillation of LPS) and group LS (receiving SGB after the intratracheal instillation of LPS). The pathological damage of lung tissue, arterial blood gases, the differentiation of alveolar macrophages (AMs) and inflammatory cytokines (IL-1ß, IL-6, IL-10) were detected. Furthermore, the oxidative stress indexes (ROS, CYP-D, T-SOD, Mn-SOD and CAT) in serum and the levels of Sirt3 signaling-associated proteins (JAK2/STAT3, NF-κb p65, CIRP and NLRP3) in the lungs were measured. The results revealed that SGB could attenuate lung tissue damage, improve pulmonary oxygenation, promote the differentiation of AMs to the M2 phenotype, decrease the secretion of IL-1ß and IL-6, and increase the secretion of IL-10. Meanwhile, SGB was found to inhibit the production of ROS and CYP-D, and enhance the activities of T-SOD, Mn-SOD and CAT. Furthermore, SGB upregulated Sirt3 and downregulated JAK2/STAT3 and NF-κb p65 phosphorylation, CIRP and NLRP3. Our work revealed that SGB could attenuate LPS-induced ALI by activating the Sirt3-mediated regulation of oxidative stress and pulmonary inflammation; this may shed new light upon the protection of SGB and provide a novel prophylactic strategy for LPS-induced ALI.

Integrated multi-omics analysis and machine learning to refine molecular subtypes, prognosis, and immunotherapy in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) has a malignant characteristic that is highly aggressive and prone to metastasis. There is still a lack of suitable biomarkers to facilitate the refinement of precision-based therapeutic regimens. We used a combination of 10 known clustering algorithms and the omics data from 4 dimensions to identify high-resolution molecular subtypes of LUAD. Subsequently, consensus machine learning-related prognostic signature (CMRS) was developed based on subtypes related genes and an integrated program framework containing 10 machine learning algorithms. The efficiency of CMRS was analyzed from the perspectives of tumor microenvironment, genomic landscape, immunotherapy, drug sensitivity, and single-cell analysis. In terms of results, through multi-omics clustering, we identified 2 comprehensive omics subtypes (CSs) in which CS1 patients had worse survival outcomes, higher aggressiveness, mRNAsi and mutation frequency. Subsequently, we developed CMRS based on 13 key genes up-regulated in CS1. The prognostic predictive efficiency of CMRS was superior to most established LUAD prognostic signatures. CMRS demonstrated a strong correlation with tumor microenvironmental feature variants and genomic instability generation. Regarding clinical performance, patients in the high CMRS group were more likely to benefit from immunotherapy, whereas low CMRS were more likely to benefit from chemotherapy and targeted drug therapy. In addition, we evaluated that drugs such as neratinib, oligomycin A, and others may be candidates for patients in the high CMRS group. Single-cell analysis revealed that CMRS-related genes were mainly expressed in epithelial cells. The novel molecular subtypes identified in this study based on multi-omics data could provide new insights into the stratified treatment of LUAD, while the development of CMRS could serve as a candidate indicator of the degree of benefit of precision therapy and immunotherapy for LUAD.

Application of Chromosomal Microarray Analysis in Genetic Reasons of Miscarriage Tissues.

Background: The potential causes of miscarriage are very complex, including genetic, immune, infectious, and endocrine factors. 50%-60% of miscarriages are caused by chromosomal abnormalities. Chromosomal microarray analysis (CMA) is a key tool in this context, capable of detecting not only copy number variations (CNV) but also loss of heterozygosity (LOH). CMA has been used as a tool to investigate the genetic reasons for miscarriage. Methods: In our study, chromosomal microarray analysis (CMA) conducted 1220 miscarriage villous tissues. The results from this technology were used to identify the genetic reasons for miscarriage and evaluated strategies for subsequent pre-pregnancy planning. Results: Here, the abnormality rate of miscarriage was 56.07%(684/1220). The aneuploidy rate accounted for 81.14%(555/684), and was significantly higher in group >35-year-old age. The second most common genetic reason for miscarriage was polyploidy, accounting for 10.09%(69/684). Additionally, we discovered loss of heterozygosity (LOH) in a small percentage of cases, accounting for 2.20%(15/684) reason for miscarriage genetic reasons, due to the advantage of CMA can detect isodisomy (a kind of uniparental disomy). 45 cases (6.58%) with copy number variants, which due to the CMA can detect copy number variations. Conclusion: Our study indicated that miscarriage villous tissues should be performed genetic analysis, seek help from professional genetic counseling.

Phase 2 Trial of Deucravacitinib in Psoriatic Arthritis: Biomarkers Associated With Disease Activity, Pharmacodynamics, and Clinical Responses.

OBJECTIVE: Our objective was to evaluate the association of serum biomarkers with baseline psoriatic arthritis (PsA) disease activity, pharmacodynamic effects of deucravacitinib on biomarker levels, and the relationship between biomarkers and clinical responses to deucravacitinib. METHODS: The phase 2 trial (ClinicalTrials.gov identifier: NCT03881059) randomly assigned 203 patients with PsA 1:1:1 to placebo, deucravacitinib at 6 mg once daily (QD), or deucravacitinib at 12 mg QD. Serum biomarkers associated with the interleukin 23 (IL-23) pathway (IL-17A, ß-defensin [BD-2], and IL-19), type I interferon pathway, inflammation, and collagen matrix turnover were measured by immunoassay. Clinical responses (≥75% improvement from baseline in the Psoriasis Area and Severity Index [PASI75] and ≥20% improvement from baseline in American College of Rheumatology criteria [ACR20] responses) were measured at week 16. Hematologic variables were also assessed. RESULTS: IL-17A, BD-2, and IL-19 had a modest association with PASI scores (r = 0.4, r = 0.56, and r = 0.5, respectively) at baseline. In deucravacitinib groups, IL-17A, BD-2, IL-19, C-X-C motif ligand 9 (CXCL9), CXCL10, C-reactive protein, matrix metalloproteinase 3, and collagen type 4 degradation marker levels were significantly reduced at week 16 versus baseline (P < 0.01); higher levels of IL-23 pathway-associated biomarkers predicted higher PASI75 and ACR20 response rates in deucravacitinib-treated patients. Significantly higher PASI75 response rates were seen in patients with high baseline IL-17A (odds ratio 15.76) and BD-2 levels (odds ratio 15.41) versus low baseline IL-17A and BD-2 levels. Changes in hematologic variables that are characteristic of JAK inhibition were not observed with deucravacitinib. CONCLUSION: Deucravacitinib significantly impacted biomarkers associated with Tyk2 signaling pathways of key inflammatory cytokines, including IL-23 and type I interferon, and those related to collagen matrix turnover. These biomarkers may predict treatment responses to deucravacitinib.

Minnelide exhibits antileukemic activity by targeting the Ars2/miR-190a-3p axis.

BACKGROUND: The identification of a novel and effective strategy for the clinical treatment of acute leukemia (AL) is a long-term goal. Minnelide, a water-soluble prodrug of triptolide, has recently been evaluated in phase I and II clinical trials in patients with multiple cancers and has shown promise as an antileukemic agent. However, the molecular mechanism underlying minnelide's antileukemic activity remains unclear. PURPOSE: To explore the molecular mechanisms by which minnelide exhibits antileukemic activity. METHODS: AL cells, primary human leukemia cells, and a xenograft mouse model were treated with triptolide and minnelide. The molecular mechanism was elucidated using western blotting, immunoprecipitation, flow cytometry, GSEA and liquid chromatography-mass spectrometry analysis. RESULTS: Minnelide was highly effective in inhibiting leukemogenesis and improving survival in two complementary AL mouse models. Triptolide, an active form of minnelide, causes cell cycle arrest in G1 phase and induces apoptosis in both human AL cell lines and primary AL cells. Mechanistically, we identified Ars2 as a new chemotherapeutic target of minnelide for AL treatment. We found that triptolide directly targeted Ars2, resulting in the downregulation of miR-190a-3p, which led to the disturbance of PTEN/Akt signaling and culminated in G1 cell cycle arrest and apoptosis. CONCLUSIONS: Our findings demonstrate that targeting Ars2/miR-190a-3p signaling using minnelide could represent a novel chemotherapeutic strategy for AL treatment and support the evaluation of minnelide for the treatment of AL in clinical trials.

The relationship between Mycoplasma and Kawasaki disease in pediatric patients: An updated systematic review and meta-analysis.

Objectives: This study aimed to clarify the relationship between Mycoplasma pneumoniae (M. pneumoniae) and Kawasaki disease by conducting an updated systemic review and meta-analysis of published studies. Materials and methods: Studies mentioning M. pneumoniae and Kawasaki disease before October 2022 were included in this meta-analysis. The pooled prevalence was calculated, and the log odds ratio in the random effects model was applied to estimate the pooled prevalence of M. pneumoniae infection in pediatric patients with Kawasaki disease. In addition, the clinical parameters, such as hemoglobin and erythrocyte sedimentation rate, were analyzed. Six studies with a total of 1,859 pediatric patients with Kawasaki disease were enrolled. The focused outcome was the pooled prevalence and clinical parameters. Results: The pooled prevalence of M. pneumoniae infection was statistically significant in pediatric patients with Kawasaki disease. In addition, the values of hemoglobin and erythrocyte sedimentation rate were significantly different between M. pneumoniae-infected and non-M. pneumoniae-infected patients with Kawasaki disease. Other clinical parameters were not significantly different between M. pneumoniae-infected and non-M. pneumoniae-infected patients with Kawasaki disease. Conclusion: The results suggest that M. pneumoniae infection is significantly prevalent in pediatric patients with Kawasaki disease. The lower values of hemoglobin and erythrocyte sedimentation rate in M. pneumoniae-infected patients with Kawasaki disease might be needed to investigate further.

A highly selective and sensitive rhodamine B-based chemosensor for Sn4+ in water-bearing and biomaging and biosensing in zebrafish.

A novel colorimetric-fluorescent dual-mode chemosensor (JT5) based on rhodamine B has been produced for monitoring Sn4+ in the DMSO/H2O (4:1, v/v) medium. It has high sensitivity, a low detection limit, a short response time (1 s) and high stability, and can still be maintained after two weeks with the red dual fluorescence/ colorimetric response. Enhancement of red fluorescence (591 nm) and red colorimetric (567 nm) response of JT5 by Sn4+ addition. The electrostatic potential of the sensor JT5 molecule was simulated to speculate on the sensing mechanism, and the IR, mass spectrometry and 1H NMR titration were utilized to further demonstrate that JT5 was coordinated to Sn4+ with a 1:1 type, the rhodamine spironolactam ring of JT5 opens up to form a penta-membered ring with Sn4+, meanwhile, its system may have chelation enhanced fluorescence (CHEF) effect. In addition, theoretical calculations were carried out to give the energy gaps of JT5 and [JT5 + Sn4+] as well as to simulate the electronic properties of the maximal absorption peaks. Notably, the sensor JT5 was successfully applied to monitoring Sn4+ in zebrafish, and the JT5-loaded filter paper provided a solid-state platform for detecting Sn4+ by both naked eye and fluorescent methods. In summary, this work contributes to monitoring Sn4+ in organisms and solid-state materials and promotes understanding of Sn4+ functions in biological systems, environments, and solid-state materials.