Clinical efficacy and immune response of neoadjuvant camrelizumab plus chemotherapy in resectable locally advanced oesophageal squamous cell carcinoma: a phase 2 trial.

BACKGROUND: Neoadjuvant immunotherapy is under intensive investigation for esophageal squamous cell carcinoma (ESCC). This study assesses the efficacy and immune response of neoadjuvant immunochemotherapy (nICT) in ESCC. METHODS: In this phase II trial (ChiCTR2100045722), locally advanced ESCC patients receiving nICT were enrolled. The primary endpoint was the pathological complete response (pCR) rate. Multiplexed immunofluorescence, RNA-seq and TCR-seq were conducted to explore the immune response underlying nICT. RESULTS: Totally 42 patients were enrolled, achieving a 27.0% pCR rate. The 1-year, 2-year DFS and OS rates were 89.2%, 64.4% and 97.3%, 89.2%, respectively. RNA-seq analysis highlighted T-cell activation as the most significantly enriched pathway. The tumour immune microenvironment (TIME) was characterised by high CD4, CD8, Foxp3, and PD-L1 levels, associating with better pathological regression (TRS0/1). TIME was categorised into immune-infiltrating, immune-tolerant, and immune-desert types. Notably, the immune-infiltrating type and tertiary lymphoid structures correlated with improved outcomes. In the context of nICT, TIM-3 negatively influenced treatment efficacy, while elevated TIGIT/PD-1 expression post-nICT correlated positively with CD8+ T cell levels. TCR-seq identified three TCR rearrangements, underscoring the specificity of T-cell responses. CONCLUSIONS: Neoadjuvant camrelizumab plus chemotherapy is effective for locally advanced, resectable ESCC, eliciting profound immune response that closely associated with clinical outcomes.

Integration analysis of miRNA-mRNA pairs between two contrasting genotypes reveals the molecular mechanism of jujube (Ziziphus jujuba Mill.) response to high-temperature stress.

With global warming, high temperature (HT) has become one of the most common abiotic stresses resulting in significant crop yield losses, especially for jujube (Ziziphus jujuba Mill.), an important temperate economic crop cultivated worldwide. This study aims to explore the coping mechanism of jujube to HT stress at the transcriptional and post-transcriptional levels, including identifying differentially expressed miRNAs and mRNAs as well as elucidating the critical pathways involved. High-throughput sequencing analyses of miRNA and mRNA were performed on jujube leaves, which were collected from "Fucumi" (heat-tolerant) and "Junzao" (heat-sensitive) cultivars subjected to HT stress (42 °C) for 0, 1, 3, 5, and 7 days, respectively. The results showed that 45 known miRNAs, 482 novel miRNAs, and 13,884 differentially expressed mRNAs (DEMs) were identified. Among them, integrated analysis of miRNA target genes prediction and mRNA-seq obtained 1306 differentially expressed miRNAs-mRNAs pairs, including 484, 769, and 865 DEMIs-DEMs pairs discovered in "Fucuimi", "Junzao" and two genotypes comparative groups, respectively. Furthermore, functional enrichment analysis of 1306 DEMs revealed that plant-pathogen interaction, starch and sucrose metabolism, spliceosome, and plant hormone signal transduction were crucial pathways in jujube leaves response to HT stress. The constructed miRNA-mRNA network, composed of 20 DEMIs and 33 DEMs, displayed significant differently expressions between these two genotypes. This study further proved the regulatory role of miRNAs in the response to HT stress in plants and will provide a theoretical foundation for the innovation and cultivation of heat-tolerant varieties.

Fibrotic Matrix Induces Mesenchymal Transformation of Epithelial Cells in Oral Submucous Fibrosis.

Oral submucous fibrosis (OSF) is a potentially malignant disorder of the oral mucosa; however, whether and how the fibrotic matrix of OSF is involved in the malignant transformation of epithelial cells remains unknown. Herein, oral mucosa tissue from patients with OSF, OSF rat models, and their controls were used to observe the extracellular matrix changes and epithelial-mesenchymal transformation (EMT) in fibrotic lesions. Compared with controls, oral mucous tissues from patients with OSF showed an increased number of myofibroblasts, a decreased number of blood vessels, and increased type I and type III collagen levels. In addition, the oral mucous tissues from humans and OSF rats showed increased stiffness, accompanied by increased EMT activities of epithelial cells. The EMT activities of stiff construct-cultured epithelial cells were increased significantly by exogenous piezo-type mechanosensitive ion channel component 1 (Piezo1) activation, and decreased by yes-associated protein (YAP) inhibition. During ex vivo implantation, oral mucosal epithelial cells of the stiff group showed increased EMT activities and increased levels of Piezo1 and YAP compared with those in the sham and soft groups. These results indicate that increased stiffness of the fibrotic matrix in OSF led to increased proliferation and EMT of mucosal epithelial cells, in which the Piezo1-YAP signal transduction is important.

Remnant cholesterol and the risk of aortic valve calcium progression: insights from the MESA study.

BACKGROUND: Remnant cholesterol (RC) is implicated in the risk of cardiovascular disease. However, comprehensive population-based studies elucidating its association with aortic valve calcium (AVC) progression are limited, rendering its precise role in AVC ambiguous. METHODS: From the Multi-Ethnic Study of Atherosclerosis database, we included 5597 individuals (61.8 ± 10.1 years and 47.5% men) without atherosclerotic cardiovascular disease at baseline for analysis. RC was calculated as total cholesterol minus high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), as estimated by the Martin/Hopkins equation. Using the adjusted Cox regression analyses, we examined the relationships between RC levels and AVC progression. Furthermore, we conducted discordance analyses to evaluate the relative AVC risk in RC versus LDL-C discordant/concordant groups. RESULTS: During a median follow-up of 2.4 ± 0.9 years, 568 (10.1%) participants exhibited AVC progression. After adjusting for traditional cardiovascular risk factors, the HRs (95% CIs) for AVC progression comparing the second, third, and fourth quartiles of RC levels with the first quartile were 1.195 (0.925-1.545), 1.322 (1.028-1.701) and 1.546 (1.188-2.012), respectively. Notably, the discordant high RC/low LDL-C group demonstrated a significantly elevated risk of AVC progression compared to the concordant low RC/LDL-C group based on their medians (HR, 1.528 [95% CI 1.201-1.943]). This pattern persisted when clinical LDL-C threshold was set at 100 and 130 mg/dL. The association was consistently observed across various sensitivity analyses. CONCLUSIONS: In atherosclerotic cardiovascular disease-free individuals, elevated RC is identified as a residual risk for AVC progression, independent of traditional cardiovascular risk factors. The causal relationship of RC to AVC and the potential for targeted RC reduction in primary prevention require deeper exploration.

Subthalamic nucleus deep brain stimulation in primary Meige syndrome: motor and non-motor outcomes.

BACKGROUND AND PURPOSE: Deep brain stimulation (DBS) has emerged as a promising treatment for movement disorders. This prospective study aims to evaluate the effects of bilateral subthalamic nucleus DBS (STN-DBS) on motor and non-motor symptoms in patients with primary Meige syndrome. METHODS: Thirty patients who underwent bilateral STN-DBS between April 2017 and June 2020 were included. Standardized and validated scales were utilized to assess the severity of dystonia, health-related quality of life, sleep, cognitive function and mental status at baseline and at 1 year and 3 years after neurostimulation. RESULTS: The Burke-Fahn-Marsden Dystonia Rating Scale movement scores showed a mean improvement of 63.0% and 66.8% at 1 year and 3 years, respectively, after neurostimulation. Similarly, the Burke-Fahn-Marsden Dystonia Rating Scale disability scores improved by 60.8% and 63.3% at the same time points. Postoperative quality of life demonstrated a significant and sustained improvement throughout the follow-up period. However, cognitive function, mental status, sleep quality and other neuropsychological functions did not change after 3 years of neurostimulation. Eight adverse events occurred in six patients, but no deaths or permanent sequelae were reported. CONCLUSIONS: Bilateral STN-DBS is a safe and effective alternative treatment for primary Meige syndrome, leading to improvements in motor function and quality of life. Nevertheless, it did not yield significant amelioration in cognitive, mental, sleep status and other neuropsychological functions after 3 years of neurostimulation.

Upregulated LncRNA H19 Sponges MiR-106a-5p and Contributes to Aldosterone-Induced Vascular Calcification via Activating the Runx2-Dependent Pathway.

BACKGROUND: Excess aldosterone is implicated in vascular calcification (VC), but the mechanism by which aldosterone-MR (mineralocorticoid receptor) complex promotes VC is unclear. Emerging evidence indicates that long-noncoding RNA H19 (H19) plays a critical role in VC. We examined whether aldosterone-induced osteogenic differentiation of vascular smooth muscle cells (VSMCs) through H19 epigenetic modification of Runx2 (runt-related transcription factor-2) in a MR-dependent manner. METHODS: We induced in vivo rat model of chronic kidney disease using a high adenine and phosphate diet to explore the relationship among aldosterone, MR, H19, and VC. We also cultured human aortic VSMCs to explore the roles of H19 in aldosterone-MR complex-induced osteogenic differentiation and calcification of VSMCs. RESULTS: H19 and Runx2 were significantly increased in aldosterone-induced VSMC osteogenic differentiation and VC, both in vitro and in vivo, which were significantly blocked by the MR antagonist spironolactone. Mechanistically, our findings reveal that the aldosterone-activated MR bound to H19 promoter and increased its transcriptional activity, as determined by chromatin immunoprecipitation, electrophoretic mobility shift assay, and luciferase reporter assay. Silencing H19 increased microRNA-106a-5p (miR-106a-5p) expression, which subsequently inhibited aldosterone-induced Runx2 expression at the posttranscriptional level. Importantly, we observed a direct interaction between H19 and miR-106a-5p, and downregulation of miR-106a-5p efficiently reversed the suppression of Runx2 induced by H19 silencing. CONCLUSIONS: Our study clarifies a novel mechanism by which upregulation of H19 contributes to aldosterone-MR complex-promoted Runx2-dependent VSMC osteogenic differentiation and VC through sponging miR-106a-5p. These findings highlight a potential therapeutic target for aldosterone-induced VC.

Emerging Roles of Mitogen-Activated Protein Kinase Signaling Pathways in the Regulation of Fruit Ripening and Postharvest Quality.

Fleshy fruit ripening is a unique biological process that involves dramatic changes in a diverse array of cellular metabolisms. The regulation of these metabolisms is essentially mediated by cellular signal transduction of internal (e.g., hormones) and external cues (i.e., environmental stimuli). Mitogen-activated protein kinase (MAPK) signaling pathways play crucial roles in a diverse array of biological processes, such as plant growth, development and biotic/abiotic responses. Accumulating evidence suggests that MAPK signaling pathways are also implicated in fruit ripening and quality formation. However, while MAPK signaling has been extensively reviewed in Arabidopsis and some crop plants, the comprehensive picture of how MAPK signaling regulates fruit ripening and quality formation remains unclear. In this review, we summarize and discuss research in this area. We first summarize recent studies on the expression patterns of related kinase members in relation to fruit development and ripening and then summarize and discuss the crucial evidence of the involvement of MAPK signaling in fruit ripening and quality formation. Finally, we propose several perspectives, highlighting the research matters and questions that should be afforded particular attention in future studies.

Physical Grinding of Prefabricated Co3O4 and MCM-22 Zeolite for Fischer-Tropsch Synthesis: Impact of Pretreatment Procedure on the Dispersion and Catalytic Performance.

To improve the mess-specific activity of Co supported on zeolite catalysts in Fischer-Tropsch (FT) synthesis, the Co-MCM-22 catalyst was prepared by simply grinding the MCM-22 with nanosized Co3O4 prefabricated by the thermal decomposition of the Co(II)-glycine complex. It is found that this novel strategy is effective for improving the mess-specific activity of Co catalysts in FT synthesis compared to the impregnation method. Moreover, the ion exchange and calcination sequence of MCM-22 has a significant influence on the dispersion, particle size distribution, and reduction degree of Co. The Co-MCM-22 prepared by the physical grinding of prefabricated Co3O4 and H+-type MCM-22 without a further calcination process exhibits a moderate interaction between Co3O4 and MCM-22, which results in the higher reduction degree, higher dispersion, and higher mess-specific activity of Co. Thus, the newly developed method is more controllable and promising for the synthesis of metal-supported catalysts.

In-hospital outcomes in patients with and without epilepsy diagnosed with COVID-19-A cohort study.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) is associated with mortality in persons with comorbidities. The aim of this study was to evaluate in-hospital outcomes in patients with COVID-19 with and without epilepsy. METHODS: We conducted a retrospective study of patients with COVID-19 admitted to a multicenter health system between March 15, 2020, and May 17, 2021. Patients with epilepsy were identified using a validated International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)/ICD-10-CM case definition. Logistic regression models and Kaplan-Meier analyses were conducted for mortality and non-routine discharges (i.e., not discharged home). An ordinary least-squares regression model was fitted for length of stay (LOS). RESULTS: We identified 9833 people with COVID-19 including 334 with epilepsy. On univariate analysis, people with epilepsy had significantly higher ventilator use (37.70% vs 14.30%, p < .001), intensive care unit (ICU) admissions (39.20% vs 17.70%, p < .001) mortality rate (29.60% vs 19.90%, p < .001), and longer LOS (12 days vs 7 days, p < .001). and fewer were discharged home (29.64% vs 57.37%, p < .001). On multivariate analysis, only non-routine discharge (adjusted odds ratio [aOR] 2.70, 95% confidence interval [CI] 2.00-3.70; p < .001) and LOS (32.50% longer, 95% CI 22.20%-43.60%; p < .001) were significantly different. Factors associated with higher odds of mortality in epilepsy were older age (aOR 1.05, 95% CI 1.03-1.08; p < .001), ventilator support (aOR 7.18, 95% CI 3.12-16.48; p < .001), and higher Charlson comorbidity index (CCI) (aOR 1.18, 95% CI 1.04-1.34; p = .010). In epilepsy, admissions between August and December 2020 or January and May 2021 were associated with a lower odds of non-routine discharge and decreased LOS compared to admissions between March and July 2020, but this difference was not statistically significant. SIGNIFICANCE: People with COVID-19 who had epilepsy had a higher odds of non-routine discharge and longer LOS but not higher mortality. Older age (≥65), ventilator use, and higher CCI were associated with COVID-19 mortality in epilepsy. This suggests that older adults with epilepsy and multimorbidity are more vulnerable than those without and should be monitored closely in the setting of COVID-19.

Different Metabolic Phenotypes of Obesity and Risk of Coronary Artery Calcium Progression and Incident Cardiovascular Disease Events: The CARDIA Study.

BACKGROUND: To investigate whether obesity with or without metabolic syndrome is prospectively associated with coronary artery calcium (CAC) progression and incident cardiovascular disease events. METHODS: A total of 1730 participants from the CARDIA study (Coronary Artery Risk Development in Young Adults) were included (age, 40.1±3.6 years; 38.3% men), who completed computed tomography of CAC at baseline (year 15: 2000-2001) and follow-up (year 20 or 25). Metabolically healthy obesity (MHO) was defined as body mass index≥30 kg/m2 without any metabolic syndrome components in our main analysis. Sensitivity analyses were conducted for several conditions characterizing 4 metabolic phenotypes. RESULTS: During a mean follow-up of 9.1 years, 439 participants had CAC progression. MHO subjects had a significantly higher risk of CAC progression than their metabolically healthy normal weight counterparts (adjusted hazard ratios [95% CIs] from 1.761 [1.369-2.264] to 2.047 [1.380-3.036]) depending on the definition of MHO adopted. Obesity with unhealthy metabolic profile remained the highest significant risk of CAC progression and cardiovascular disease events whatever the definitions adopted for metabolically unhealthy status. Up to 60% of participants with MHO converted to metabolically unhealthy obesity from year 15 to year 20 or year 25. Further sensitivity analysis showed that MHO throughout carried a similar risk of incident cardiovascular disease events compared with metabolically healthy normal weight throughout. CONCLUSIONS: Different metabolic phenotypes of obesity beginning at a young age exhibit distinct risks of CAC progression and subsequent cardiovascular disease events in later midlife. MHO represents an intermediate phenotype between metabolically low- to high-risk obese individuals. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT00005130.

Structure-directed linker optimization of novel HEPTs as non-nucleoside inhibitors of HIV-1 reverse transcriptase.

1-[(2-Hydroxyethoxy)methyl]-6-(phenylthio)thymines (HEPTs) have been previously described as an important class of HIV-1 nonnucleoside reverse transcriptase inhibitors (NNRTIs). In our continuously pursuing HEPT optimization efforts, a series of novel HEPTs, featuring -C(OH)CH2R, -CC, or -CHCH2R linker at the benzylic α-methylene unit, were developed as NNRTIs. Among these new HEPTs, the compound C20 with -CHCH3 group at the benzylic α-methylene unit conferred the highest potency toward WT HIV-1 and selectivity (EC50 = 0.23 µM, SI = 150.20), which was better than the lead compound HEPT (EC50 = 7 µM, SI = 106). Also, C20 was endowed with high efficacy against clinically relevant mutant strains (EC50(L100I) = 1.07 µM; EC50(K103N) = 4.33 µM; EC50(Y181C) = 5.57 µM; EC50(E138K) = 1.06 µM; EC50(F227L+V106A) = 5.45 µM) and wild-type HIV-1 reverse transcriptase (RT) with an IC50 value of 0.55 µM. Molecular docking and molecular dynamics simulations, as well as preliminary structure-activity relationship (SAR) analysis of these new compounds, provided a deeper insight into the key structural features of the interactions between HEPT analogs and HIV-1 RT and laid the foundation for further modification on HEPT scaffold.

A Superior Two-Dimensional Phosphorus Flame Retardant: Few-Layer Black Phosphorus.

The usage of flame retardants in flammable polymers has been an effective way to protect both lives and material goods from accidental fires. Phosphorus flame retardants have the potential to be follow-on flame retardants after halogenated variants, because of their low toxicity, high efficiency and compatibility. Recently, the emerging allotrope of phosphorus, two-dimensional black phosphorus, as a flame retardant has been developed. To further understand its performance in flame-retardant efficiency among phosphorus flame retardants, in this work, we built model materials to compare the flame-retardant performances of few-layer black phosphorus, red phosphorus nanoparticles, and triphenyl phosphate as flame-retardant additives in cellulose and polyacrylonitrile. Aside from the superior flame retardancy in polyacrylonitrile, few-layer black phosphorus in cellulose showed the superior flame-retardant efficiency in self-extinguishing, ~1.8 and ~4.4 times that of red phosphorus nanoparticles and triphenyl phosphate with similar lateral size and mass load (2.5~4.8 wt%), respectively. The char layer in cellulose coated with the few-layer black phosphorus after combustion was more continuous and smoother than that with red phosphorus nanoparticles, triphenyl phosphate and blank, and the amount of residues of cellulose coated with the few-layer black phosphorus in thermogravimetric analysis were 10 wt%, 14 wt% and 14 wt% more than that with red phosphorus nanoparticles, triphenyl phosphate and blank, respectively. In addition, although exothermic reactions, the combustion enthalpy changes in the few-layer black phosphorus (-127.1 kJ mol-1) are one third of that of red phosphorus nanoparticles (-381.3 kJ mol-1). Based on a joint thermodynamic, spectroscopic, and microscopic analysis, the superior flame retardancy of the few-layer black phosphorus was attributed to superior combustion reaction suppression from the two-dimensional structure and thermal nature of the few-layer black phosphorus.

Correlation study on the relationship between dyslipidemia and carotid intima-media thickness in patients with diabetes mellitus.

Objective: To investigate the correlation between dyslipidemia and carotid intima-media thickness (IMT) in patients with diabetes mellitus. Methods: A descriptive research design was adopted in this study. One hundred and twenty patients with Type-2 diabetes mellitus who were admitted to the physical examination center of The Fourth Hospital of Hebei Medical University from June 2020 to June 2021 for physical examination were recruited to the experimental group. The 120 patients were divided into three groups according to carotid IMT: normal group, thickened group, and plaque group. Forty healthy people who underwent a physical examination during the same period were recruited as the control group. The differences in IMT in various parts of the experimental group and the control group and the differences in blood lipid indexes were compared and analyzed. In addition, the correlation between mean IMT of bilateral common carotid arteries and blood lipid levels in normal, thickened and plaque groups was compared and analyzed. Results: The intima-media thicknesses of the internal carotid artery and bilateral common carotid arteries of the patients in the experimental group were significantly thicker than those in the healthy control group, the levels of TC, TG and LDL were higher than those in the control group, while the level of HDL was lower than that in the control group, with a statistically significant difference (p=0.00). The levels of fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), TG, TC and LDL were positively correlated with the mean IMT of bilateral common carotid arteries (p<0.05), while the level of HDL was negatively correlated with the mean IMT of bilateral common carotid arteries (p<0.05). Conclusion: Dyslipidemia and glucose metabolism in patients with Type-2 diabetes mellitus have a close bearing on carotid IMT. Clinically, patients with Type-2 diabetes mellitus can be judged by monitoring carotid IMT for dyslipidemia, atherosclerosis and other related complications.

[Rapid characterization and identification of non-volatile constituents in Pogostemonis Herba by UPLC-Q-TOF-MS combined with UNIFI and an in-house library].

This study aimed to characterize and identify the non-volatile components in Pogostemonis Herba by using ultra-perfor-mance liquid chromatography-quadrupole-time of flight-mass spectrometry(UPLC-Q-TOF-MS) combined with UNIFI and an in-house library. The chemical components in 50% methanol extract of Pogostemonis Herba were detected by UPLC-Q-TOF-MS in both positive and negative MS~E continuum modes. Then, the MS data were processed in UNIFI combined with an in-house library to automatically characterize the metabolites. Based on the multiple adduct ions, exact mass, diagnostic fragment ions, and peak intensity of compounds and the fragmentation pathways and retention behaviors of reference substances, the structures identified by UNIFI were further verified and those of the unidentified compounds were tentatively elucidated. A total of 120 compound structures were identified or tentatively identified, including flavonoids, phenylpropanoids, phenolic acids, terpenes, fatty acids, alkaloids, and phenylethanoid glycosides. Sixteen of them were accurately identified by comparison with reference substances, and 53 compounds were reported the first time for Pogostemonis Herba. This study systematically characterized and identified the non-volatile compounds in Pogostemonis Herba for the first time. The findings provide a scientific basis for revealing the pharmacodynamic material basis, establishing a quality control system, and developing products of Pogostemonis Herba.

[Establishment of a nomogram model for predicting the risk of early-onset sepsis in very preterm infants]. / 预测极早产儿早发型败血症发生风险的列线图模型的构建.

OBJECTIVES: To identify risk factors associated with early-onset sepsis (EOS) in very preterm infants and develop a nomogram model for predicting the risk of EOS. METHODS: A retrospective analysis was conducted on 344 very preterm infants delivered at the First Affiliated Hospital of Zhengzhou University and admitted to the Department of Neonatology between January 2020 and December 2022. These infants were randomly divided into a training set (241 infants) and a validating set (103 infants) in a 7:3 ratio. The training set was further divided into two groups based on the presence or absence of EOS: EOS (n=64) and non-EOS (n=177). Multivariate logistic regression analysis was performed to identify risk factors for EOS in the very preterm infants. The nomogram model was developed using R language and validated using the validating set. The discriminative ability, calibration, and clinical utility of the model were assessed using receiver operating characteristic (ROC) curve analysis, calibration curve analysis, and decision curve analysis, respectively. RESULTS: The multivariate logistic regression analysis revealed that gestational age, need for tracheal intubation in the delivery room, meconium-stained amniotic fluid, serum albumin level on the first day of life, and chorioamnionitis were risk factors for EOS in very preterm infants (P<0.05). The area under the ROC curve for the training set was 0.925 (95%CI: 0.888-0.963), and that for the validating set was 0.796 (95%CI: 0.694-0.898), confirming the model's good discrimination. The Hosmer-Lemeshow goodness-of-fit test suggested that the model was well-fitting (P=0.621). The calibration curve analysis and decision curve analysis demonstrated that the model had high predictive efficacy and clinical applicability. CONCLUSIONS: Gestational age, need for tracheal intubation in the delivery room, meconium-stained amniotic fluid, serum albumin level on the first day of life, and chorioamnionitis are significantly associated with the development of EOS in very preterm infants.The nomogram model for predicting the risk of EOS in very preterm infants, constructed based on these factors, has high predictive efficacy and clinical applicability.

Constructing Stable Chromenoquinoline-Based Covalent Organic Frameworks via Intramolecular Povarov Reaction.

Chemically stable chromenoquinoline (CQ)-based covalent organic frameworks (COFs) were constructed by postsynthetic conversion of imine COFs. The key step of an intramolecular Povarov reaction can transform a preintegrated alkyne group to bridge the benzene rings on both sides of the imine linkage via chemical bonds, affording a ladder-type CQ linkage. This novel approach achieves a high cyclization degree of 80-90%, which endows the CQ-COFs with excellent chemical stability toward strong acid, base, and redox reagents. The synthetic approach can be applied to various monomers with different symmetries and functional core moieties. The absorption and fluorescence intensities of CQ-COFs are sensitive to acid, which allows for dual-mode sensing of strongly acidic environments.

The prognosis biomarkers based on m6A-related lncRNAs for myeloid leukemia patients.

BACKGROUND: Chronic myeloid leukemia (CML) and acute myeloid leukemia (AML) are two common malignant disorders in leukemia. Although potent drugs are emerging, CML and AML may still relapse after the drug treatment is stopped. N6-methyladenosine (m6A) and lncRNAs play certain roles in the occurrence and development of tumors, but m6A-modified LncRNAs in ML remain to be further investigated. METHODS: In this study, we extracted and analyzed the TCGA gene expression profile of 151 ML patients and the clinical data. On this basis, we then evaluated the immune infiltration capacity of ML and LASSO-penalized Cox analysis was applied to construct the prognostic model based on m6A related lncRNAs to verify the prognostic risk in clinical features of ML. Quantitative reverse transcription PCR was used to detect the expression level of LncRNA in in ML cell lines K562, MOLM13 and acute monocytic leukemia cell line THP-1. RESULTS: We found 70 m6A-related lncRNAs that were related to prognosis, and speculated that the content of stromal cells and immune cells would correlate with the survival of patients with ML. Next, Prognostic risk model of m6A-related lncRNAs was validated to have excellent consistency in clinical features of ML. Finally, we verified the expression levels of CRNDE, CHROMR and NARF-IT1 in ML cell lines K562, MOLM13 and acute monocytic leukemia cell line THP-1, which were significant. CONCLUSIONS: The research provides clues for the prognosis prediction of ML patients by using the m6A-related lncRNAs model we have created, and clarifies the accuracy and authenticity of it.

Optimizing the Bacteriostatic and Cytocompatibility Properties of Poly(hexamethylene guanidine) Hydrochloride (PHMG) via the Guanidine/Alkane Ratio.

The emergence of "superbugs" is not only problematic and potentially lethal for infected subjects but also poses serious challenges for the healthcare system. Although existing antibacterial agents have been effective in some cases, the side effects and biocompatibility generally present difficulties. The development of new antibacterial agents is therefore urgently required. In this work, we have adapted a strategy for the improvement of poly(hexamethylene guanidine) hydrochloride (PHMG), a common antibacterial agent. This involves copolymerization of separate monomer units in varying ratios to find the optimum ratio of the hydrocarbon to guanidine units for antibacterial activity. A series of these copolymers, designated as PGB, was synthesized. By varying the guanidine/hydrophobic ratio and the copolymer molecular weight, a structure-optimized PGB was identified that showed broad-spectrum antibacterial activity and excellent biocompatibility in solution. In an antibacterial assay, the copolymer with the optimum composition (hydrophobic unit content 25%) inhibited >99% Staphylococcus aureus and was compatible with mammalian cells. A polyurethane emulsion containing this PGB component formed transparent, flexible films (PGB-PU films) on a wide range of substrate surfaces, including soft polymers and metals. The PGB-PU films showed excellent bacteriostatic efficiency against nosocomial drug-resistant bacteria, such as Pseudomonas aeruginosa and methicillin-resistant S. aureus (MRSA). It is concluded that our PGB polymers can be used as bacteriostatic agents generally and in particular for the design of antibacterial surfaces in medical devices.

Associations of long-term physical activity trajectories with coronary artery calcium progression and cardiovascular disease events: results from the CARDIA study.

OBJECTIVE: The study aimed to assess the associations of physical activity (PA) trajectories across a 25-year span with coronary artery calcium (CAC) progression, and subsequent risk of cardiovascular disease (CVD) events. METHODS: We included 2497 participants from the Coronary Artery Disease Risk Development in Young Adults study who had computed tomography-assessment of CAC at baseline (year 15: 2000-2001) and follow-up (year 20 or 25) and at least three measures of PA from year 0 to year 25. Long-term PA trajectories were determined by latent class modelling using a validated questionnaire. RESULTS: Among the included participants, 1120 (44.9%) were men, 1418 (56.8%) were white, and the mean (SD) age was 40.4 (3.6) years. We identified three distinct PA trajectories based on PA average levels and change patterns: low (below PA guidelines, n=1332; 53.3%); moderate (meeting and slightly over PA guidelines, n=919; 36.8%) and high (about three times PA guidelines or more, n=246; 9.9%). During a mean (SD) follow-up of 8.9 (2.1) years, 640 (25.6%) participants had CAC progression. Participants in the high PA trajectory group had a higher risk of CAC progression than those in the low PA trajectory group after adjustment for traditional cardiovascular risk factors (HR 1.51; 95% CI 1.18 to 1.94). However, high PA trajectory was not associated with an increased risk of incident CVD events (HR 1.01; 95% CI 0.44 to 2.31) and the incidence of CVD events in participants with CAC progression was similar across all three PA trajectory groups (p=0.736). CONCLUSION: Long-term PA about three times the guidelines or more is independently associated with CAC progression; however, no additional risk of incident CVD events could be detected.

Effects of topological characteristics on rhythmic states of the D-dimensional Kuramoto model in complex networks.

Synchronization is a ubiquitous phenomenon in engineering and natural ecosystems. While the dynamics of synchronization modeled by the Kuramoto model are commonly studied in two dimensions and the state of dynamic units is characterized by a scalar angle variable, we studied the Kuramoto model generalized to D dimensions in the framework of a complex network and utilized the local synchronous order parameter between the agent and its neighbors as the controllable variable to adjust the coupling strength. Here, we reported that average connectivity of networks affects the time-dependent, rhythmic, cyclic state. Importantly, we found that the level of heterogeneity of networks governs the rhythmic state in the transition process. The analytical treatment for observed scenarios in a D-dimensional Kuramoto model at D=3 was provided. These results offered a platform for a better understanding of time-dependent swarming and flocking dynamics in nature.