Hydrosilylation Adducts to Produce Wide-Temperature Flexible Polysiloxane Aerogel under Ambient Temperature and Pressure Drying.

Despite incorporation of organic groups into silica-based aerogels to enhance their mechanical flexibility, the wide temperature reliability of the modified silicone aerogel is inevitably degraded. Therefore, facile synthesis of soft silicone aerogels with wide-temperature stability remains challenging. Herein, novel silicone aerogels containing a high content of Si are reported by using polydimethylvinylsiloxane (PDMVS), a hydrosilylation adduct with water-repellent groups, as a "flexible chain segment" embedded within the aerogel network. The poly(2-dimethoxymethylsilyl)ethylmethylvinylsiloxane (PDEMSEMVS) aerogel is fabricated through a cost-effective ambient temperature/pressure drying process. The optimized aerogel exhibits exceptional performance, such as ultra-low density (50 mg cm-3), wide-temperature mechanical flexibility, and super-hydrophobicity, in comparison to the previous polysiloxane aerogels. A significant reduction in the density of these aerogels is achieved while maintaining a high crosslinking density by synthesizing gel networks with well-defined macromolecules through hydrolytic polycondensation crosslinking of PDEMSEMVS. Notably, the pore/nanoparticle size of aerogels can be fine-tuned by optimizing the gel solvent type. The as-prepared silicone aerogels demonstrate selective absorption, efficient oil-water separation, and excellent thermal insulation properties, showing promising applications in oil/water separation and thermal protection.

Chemical-Physical Synergistic Assembly of MXene/CNT Nanocoatings in Silicone Foams for Reliable Piezoresistive Sensing in Harsh Environments.

Owing to their high sensitivity across a wide stress range, mechanical reliability, and rapid response time, flexible polymer foam piezoresistive sensors have been extensively used in various fields. The reliable application of these sensors under harsh environments, however, is severely limited by structural devastation and poor interfacial bonding between polymers and conductive nanoparticles. To address the above issues, robust MXene/CNT nanocoatings on the foam surface, where the chemical assembly of MXene nanosheets and the physical anchoring of CNTs lead to strong interfacial bonding, are designed and described, which endows foams with structural reliability and unexpected multi-functionalities without compromising their instinct properties. The optimized foam nanocomposites thus maintain outstanding wide-temperature flexibility (-60-210 °C) and elasticity (≈3% residual strain after 1000 cycles). Moreover, the nanocomposites display good sensitivity at a relatively wide stress range of 0-70% and remarkable stability under acidic and alkaline settings. Furthermore, the foams with exceptional fire resistance (UL-94 V-0 rating) can provide stable sensing behavior (over 300 cycles) even after being exposed to flames for 5 s, making them one of the most reliable sensing materials so far. Clearly, this work widens applications of flexible piezoresistive sensors based on silicone foam nanocomposites for various harsh environments.

Engineered EVs with pathogen proteins: promising vaccine alternatives to LNP-mRNA vaccines.

Extracellular vesicles (EVs) are tiny, lipid membrane-bound structures that are released by most cells. They play a vital role in facilitating intercellular communication by delivering bioactive cargoes to recipient cells and triggering cellular as well as biological responses. EVs have enormous potential for therapeutic applications as native or engineered exosomes. Native EVs are naturally released by cells without undergoing any modifications to either the exosomes or the cells that secrete them. In contrast, engineered EVs have been deliberately modified post-secretion or through genetic engineering of the secreting cells to alter their composition. Here we propose that engineered EVs displaying pathogen proteins could serve as promising alternatives to lipid nanoparticle (LNP)-mRNA vaccines. By leveraging their unique characteristics, these engineered EVs have the potential to overcome certain limitations associated with LNP-mRNA vaccines.

Design, synthesis and biological evaluation of thieno[3,2-c]pyrazol-urea derivatives as potent glycogen synthase kinase 3ß inhibitors based on the DFG-out conformation.

Glycogen synthase kinase 3ß (GSK-3ß) is a potential therapeutic target for the treatment of a variety of human diseases. Here, we report the design and synthesis of a series of thieno[3,2-c]pyrazol-urea derivatives and evaluation of their GSK-3ß inhibitory activity. Among these analogues, the compound without substitution on terminal phenyl ring (3a) was found to be the most potent GSK-3ß inhibitor with an IC50 of 74.4 nM, while substitution on the terminal phenyl (3b-3p) led to decreased potency, independent of the position, size, or electronic properties of the substituents. Kinase selectivity assay revealed that 3a showed good selectivity over a panel of kinases, but was less selective over CDK1, CDK2 and CDK5. Additionally, the pharmacological properties of the synthesized compounds were investigated computationally by the SwissADME and the results showed that most of the compounds have good ADME profiles.

Engineering Sulfur-Containing Polymeric Fire-Retardant Coatings for Fire-Safe Rigid Polyurethane Foam.

With the advantages of lightweight and low thermal conductivity properties, polymeric foams are widely employed as thermal insulation materials for energy-saving buildings but suffer from inherent flammability. Flame-retardant coatings hold great promise for improving the fire safety of these foams without deteriorating the mechanical-physical properties of the foam. In this work, four kinds of sulfur-based flame-retardant copolymers are synthesized via a facile radical copolymerization. The sulfur-containing monomers serve as flame-retardant agents including vinyl sulfonic acid sodium (SPS), ethylene sulfonic acid sodium (VS), and sodium p-styrene sulfonate (VSS). Additionally, 2-hydroxyethyl acrylate (HEA) and 4-hydroxybutyl acrylate are employed to enable a strong interface adhesion with polymeric foams through interfacial H-bonding. By using as-synthesized waterborne flame-retardant polymeric coating with a thickness of 600 µm, the coated polyurethane foam (PUF) can achieve a desired V-0 rating during the vertical burning test with a high limiting oxygen index (LOI) of >31.5 vol%. By comparing these sulfur-containing polymeric fire-retardant coatings, poly(VS-co-HEA) coated PUF demonstrates the best interface adhesion capability and flame-retardant performance, with the lowest peak heat release rate of 166 kW m-2 and the highest LOI of 36.4 vol%. This work provides new avenues for the design and performance optimization of advanced fire-retardant polymeric coatings.

Facile and Efficient Synthesis of Fluorosilicone Polymers by Using an Optimized Gradient Ring-Opening Reaction.

Fluorosilicone rubber is essential for sealing in extreme temperatures and non-polar environments due to its exceptional adaptability. However, achieving a high yield of fluorosilicone polymers with medium and high fluorine content remains a challenge. Herein, a facile gradient strategy is developed that involves modifying the method of cyclic monomer addition based on the rate of ring-opening polymerization (ROP), to improve yield and adjust fluorine content precisely. The polymerization process is designed and tailored based on the reaction rates of anionic ring-opening polymerization (AROP) and cationic ring-opening polymerization (CROP) via an efficient gradient strategy. The effects of the polymerization process on the viscosity and yield of vinyl fluorosilicone polymers and hydrofluorosilicone polymers are investigated and optimized. Notably, the as-prepared vinyl-terminated fluoromethylsilane with 60% fluorine content (FMS-Vi-60F) has a high yield (86.6%) and high viscosity (150 000 mPa·s) in a short reaction time, which is superior to previous methods. Clearly, the gradient ring-opening method developed in this work provides a facile and efficient synthesis for fabricating fluorosilicone polymers with a high yield and tunable fluorine content.

Safety and efficacy of day anterior cervical discectomy and fusion procedure for degenerative cervical spondylosis: a retrospective analysis.

OBJECTIVE: Our study aimed to develop a day anterior cervical discectomy and fusion (ACDF) procedure to treat degenerative cervical spondylosis (DCS). The goal was to analyze its clinical implications, safety, and early effects to provide a better surgical option for eligible DCS patients. METHODS: A retrospective analysis was performed to identify DCS patients who underwent day ACDF from September 2022 to August 2023. The operative time, intraoperative blood loss, postoperative drainage, preoperative and postoperative visual analog scale (VAS) scores, neck disability index (NDI) scores, Japanese Orthopedic Association (JOA) scores, JOA recovery rate (RR), incidence of dysphagia-related symptoms, 30-day hospital readmission rate, and incidence of other complications were recorded to evaluate early clinical outcomes. Radiography was performed to assess the location of the implants, neurological decompression, and cervical physiological curvature. RESULTS: All 33 patients (23 women and 10 men) underwent successful surgery and experienced significant symptomatic and neurological improvements. Among them, 26 patients underwent one-segment ACDF, 5 underwent two-segment ACDF, and 2 underwent three-segment ACDF. The average operative time was 71.1 ± 20.2 min, intraoperative blood loss was 19.1 ± 6.2 mL, and postoperative drainage was 9.6 ± 5.8 mL. The preoperative VAS and NDI scores improved postoperatively (7.1 ± 1.2 vs. 3.1 ± 1.3 and 66.7% ± 4.8% vs. 24.1% ± 2.5%, respectively), with a significant difference (P < 0.01). Moreover, the preoperative JOA scores improved significantly postoperatively (7.7 ± 1.3 vs. 14.2 ± 1.4; P < 0.01) with an RR of 93.9% in good or excellent. Postoperative dysphagia-related symptoms occurred in one patient (3.0%). During the follow-up period, no patient was readmitted within 30 days after discharge; however, an incisional hematoma was reported in one patient on the 6th day after discharge, which was cured by pressure dressing. The postoperative radiographs revealed perfect implant positions and sufficient nerve decompression in all patients. Furthermore, the preoperative cervical physiological curvature improved significantly after the operation (14.5° ± 4.0° vs. 26.3° ± 5.4°; P < 0.01). CONCLUSIONS: Day ACDF has good safety and early clinical efficacy, and it could be an appropriate choice for eligible DCS patients.

Effects of 0.4 T, 3.0 T and 9.4 T static magnetic fields on development, behaviour and immune response in zebrafish (Danio rerio).

Magnetic Resonance Imaging (MRI) is widely applied in medical diagnosis due to its excellent non-invasiveness. With the increasing intensity of static magnetic field (SMF), the safety assessment of MRI has been ongoing. In this study, zebrafish larvae were exposed to SMFs of 0.4, 3.0, and 9.4 T for 2 h (h), and we found that there was no significant difference in the number of spontaneous tail swings, heart rate, and body length of zebrafish larvae in the treatment groups. The expression of development-related genes shha, pygo1, mylz3 and runx2b in the three SMF groups was almost not significantly different from the control group. Behavior tests unveiled a notable reduction in both the average speed and duration of high-speed movements in zebrafish larvae across all three SMF groups. In addition, the 0.4 and 3.0 T SMFs increased the migration of neutrophils in caudal fin injury, and the expression of pro-inflammatory cytokines was also increased. To explore the mechanism of SMFs on zebrafish immune function, this study utilized aanat2-/- mutant fish to demonstrate the effect of melatonin (MT) involvement in SMFs on zebrafish immune function. This study provides experimental data for understanding the effects of SMFs on organisms, and also provides a new insight for exploring the relationship between magnetic fields and immune function.

Predicting long-term prognosis after percutaneous coronary intervention in patients with new onset ST-elevation myocardial infarction: development and external validation of a nomogram model.

BACKGROUND: The triglyceride glucose (TyG) index is a well-established biomarker for insulin resistance (IR) that shows correlation with poor outcomes in patients with coronary artery disease. We aimed to integrate the TyG index with clinical data in a prediction nomogram for the long-term prognosis of new onset ST-elevation myocardial infarction (STEMI) following primary percutaneous coronary intervention (PCI) . METHODS: This retrospective study included new-onset STEMI patients admitted at two heart centers for emergency PCI from December 2015 to March 2018 in development and independent validation cohorts. Potential risk factors were screened applying least absolute shrinkage and selection operator (LASSO) regression. Multiple Cox regression was employed to identify independent risk factors for prediction nomogram construction. Nomogram performance was assessed based on receiver operating characteristic curve analysis, calibration curves, Harrell's C-index and decision curve analysis (DCA). RESULTS: In total, 404 patients were assigned to the development cohort and 169 to the independent validation cohort. The constructed nomogram included four clinical variables: age, diabetes mellitus, current smoking, and TyG index. The Harrell's C-index values for the nomogram were 0.772 (95% confidence interval [CI]: 0.721-0.823) in the development cohort and 0.736 (95%CI: 0.656-0.816) in the independent validation cohort. Significant correlation was found between the predicted and actual outcomes in both cohorts, indicating that the nomogram is well calibrated. DCA confirmed the clinical value of the development prediction nomogram. CONCLUSIONS: Our validated prediction nomogram based on the TyG index and electronic health records data was shown to provide accurate and reliable discrimination of new-onset STEMI patients at high- and low-risk for major adverse cardiac events at 2, 3 and 5 years following emergency PCI.

Development of an assay system for the analysis of host RISC activity in the presence of a potyvirus RNA silencing suppressor, HC-Pro.

BACKGROUND: To investigate the mechanism of RNA silencing suppression, the genetic transformation of viral suppressors of RNA silencing (VSRs) in Arabidopsis integrates ectopic VSR expression at steady state, which overcomes the VSR variations caused by different virus infections or limitations of host range. Moreover, identifying the insertion of the transgenic VSR gene is necessary to establish a model transgenic plant for the functional study of VSR. METHODS: Developing an endogenous AGO1-based in vitro RNA-inducing silencing complex (RISC) assay prompts further investigation into VSR-mediated suppression. Three P1/HC-Pro plants from turnip mosaic virus (TuMV) (P1/HC-ProTu), zucchini yellow mosaic virus (ZYMV) (P1/HC-ProZy), and tobacco etch virus (TEV) (P1/HC-ProTe) were identified by T-DNA Finder and used as materials for investigations of the RISC cleavage efficiency. RESULTS: Our results indicated that the P1/HC-ProTu plant has slightly lower RISC activity than P1/HC-ProZy plants. In addition, the phenomena are consistent with those observed in TuMV-infected Arabidopsis plants, which implies that HC-ProTu could directly interfere with RISC activity. CONCLUSIONS: In this study, we demonstrated the application of various plant materials in an in vitro RISC assay of VSR-mediated RNA silencing suppression.

Multimodal data-driven prognostic model for predicting new-onset ST-elevation myocardial infarction following emergency percutaneous coronary intervention.

OBJECTIVES: We developed a nomogram model derived from inflammatory indices, clinical data, and imaging data to predict in-hospital major adverse cardiac and cerebrovascular events (MACCEs) following emergency percutaneous coronary intervention (PCI) in patients with new-onset ST-elevation myocardial infarction (STEMI). METHODS: Patients with new-onset STEMI admitted between June 2020 and November 2022 were retrospectively reviewed. Data pertaining to coronary angiograms, clinical data, biochemical indices, and in-hospital clinical outcomes were derived from electronic medical records. Lasso regression model was employed to screen risk factors and construct a prediction model. RESULTS: Overall, 547 patients with new-onset STEMI who underwent PCI were included and assigned to the training cohort (n = 384) and independent verification cohort (n = 163). Six clinical features (age, diabetes mellitus, current smoking, hyperuricemia, neutrophil-to-lymphocyte ratio, and Gensini score) were selected by LASSO regression to construct a nomogram to predict the risk of in-hospital MACCEs. The area-under-the-curve (AUC) values for in-hospital MACCEs risk in the training and independent verification cohorts were 0.921 (95% CI 0.881-0.961) and 0.898 (95% CI 0.821-0.976), respectively. It was adequately calibrated in both training cohort and independent verification cohorts, and predictions were correlated with actual outcomes. Decision curve analysis demonstrated that the nomogram was capable of predicting in-hospital MACCEs with good clinical benefit. CONCLUSIONS: Our prediction nomogram based on multi-modal data (inflammatory indices, clinical and imaging data) reliably predicted in-hospital MACCEs in new-onset STEMI patients with emergency PCI. This prediction nomogram can enable individualized treatment strategies.

Synthesis and biological evaluation of thieno[3,2-c]pyrazol-3-amine derivatives as potent glycogen synthase kinase 3ß inhibitors for Alzheimer's disease.

Glycogen synthase kinase 3ß (GSK-3ß) is a potential target for anti-Alzheimer's disease (AD) drug development. In this study, a series of novel thieno[3,2-c]pyrazol-3-amine derivatives was synthesized and evaluated as potential GSK-3ß inhibitors by structure-based drug design. The thieno[3,2-c]pyrazol-3-amine derivative 54 with a 4-methylpyrazole moiety which interacted with Arg141 by π-cation interaction was identified as a potent GSK-3ß inhibitor with an IC50 of 3.4 nM and an acceptable kinase selectivity profile. In the rat primary cortical neurons, compound 54 showed neuroprotective effects on Aß-induced neurotoxicity. Western blot analysis indicated that 54 inhibited GSK-3ß by up-regulating the expression of phosphorylated GSK-3ß at Ser9 and down-regulating the expression of phosphorylated GSK-3ß at Tyr216. Meanwhile, 54 decreased tau phosphorylation at Ser396 in a dose-dependent way. In astrocytes and microglia cells, 54 inhibited the expression of inducible nitric oxide synthase (iNOS), indicating that 54 showed an anti-neuroinflammatory effect. In the AlCl3-induced zebrafish AD model, 54 significantly ameliorated the AlCl3-induced dyskinesia, demonstrating its anti-AD activity in vivo.

Is serum hemoglobin level an independent prognostic factor for IgA nephropathy?: a systematic review and meta-analysis of observational cohort studies.

BACKGROUND: Decreased serum hemoglobin (Hb) level is associated with Immunoglobulin A nephropathy (IgAN) progression. However, whether serum Hb level is an independent prognostic factor of IgAN remains controversial. Herein, we aimed to investigate the prognostic value of serum Hb level in IgAN. METHODS: The Cochrane Library, Embase, PubMed and Open Grey databases were systematically searched and reviewed. Kidney disease progression of IgAN was defined as a doubling of serum creatinine (SCr), a 30% reduction in estimated glomerular filtration rate (eGFR), end-stage renal disease (ESRD), or death. We evaluated the hazard ratio (HR) between serum Hb level and the incidence of kidney disease progression in IgAN before and after adjusting for relevant covariates. RESULTS: We included nine studies with 10006 patients in the meta-analysis. As a continuous variable, we found that serum Hb was an independent prognostic factor of IgAN [unadjusted HR = 0.89, 95% confidence interval (CI) = 0.84-0.95, I2 = 98%; adjusted HR = 0.85, 95% CI = 0.79-0.91, I2 = 0%]. The sensitivity analysis confirmed the stability of these results. Consistently, as a dichotomous variable defined as the below/above cutoff for anemia, we observed a positive correlation between serum Hb and kidney disease progression in IgAN (unadjusted HR = 2.12, 95% CI = 1.44-3.12, I2 = 79%; adjusted HR = 1.65, 95% CI = 1.20-2.27, I2 = 0%). CONCLUSION: Serum Hb level was independently correlated with the incidence of kidney disease progression in IgAN.

A Simple Approach to Determine Single-Receiver Differential Code Bias Using Precise Point Positioning.

In this study, a precise single-receiver differential code bias (DCB) estimation method using the precise point positioning (PPP) model is presented. The first step is to extract the high-precision ionospheric observations, including DCBs, based on the PPP model. Then, the satellite DCBs are corrected using International GNSS Service (IGS) products. Lastly, the algorithm for the minimization of the standard deviation of vertical total electron content (VTECmstd) is employed to determine the value of receiver DCB. To check the method, GNSS data from more than 200 IGS stations around the globe on four days with various geomagnetic and solar activity circumstances are processed. The receiver DCBs are compared to those obtained using previous carried-to-code level (CCL) models. The experimental results show that, compared to the CCL model, the values of VTECmstd for most stations are significantly reduced, the mean number of stations with negative ionospheric measurements is reduced by 40% after correcting the receiver DCBs, and the mean error of estimated receiver DCBs is reduced by approximately 0.6 ns using the PPP model. These results suggest that this method can provide more high-precision receiver DCB estimation.

Facile Synthesis of Hollow Glass Microsphere Filled PDMS Foam Composites with Exceptional Lightweight, Mechanical Flexibility, and Thermal Insulating Property.

The feature of low-density and thermal insulation properties of polydimethylsiloxane (PDMS) foam is one of the important challenges of the silicone industry seeking to make these products more competitive compared to traditional polymer foams. Herein, we report a green, simple, and low-cost strategy for synthesizing ultra-low-density porous silicone composite materials via Si-H cross-linking and foaming chemistry, and the sialylation-modified hollow glass microspheres (m-HM) were used to promote the HM/PDMS compatibility. Typically, the presence of 7.5 wt% m-HM decreases the density of pure foam from 135 mg/cm-3 to 104 mg/cm-3 without affecting the foaming reaction between Si-H and Si-OH and produces a stable porous structure. The optimized m-HM-modified PDMS foam composites showed excellent mechanical flexibility (unchanged maximum stress values at a strain of 70% after 100 compressive cycles) and good thermal insulation (from 150.0 °C to 52.1 °C for the sample with ~20 mm thickness). Our results suggest that the use of hollow microparticles is an effective strategy for fabricating lightweight, mechanically flexible, and thermal insulation PDMS foam composite materials for many potential applications.

Novel insights into the association between seasonal variations, blood pressure, and blood pressure variability in patients with new-onset essential hypertension.

BACKGROUND: Blood pressure (BP) exhibits seasonal variations, with peaks reported in winter. However, the association between seasonal variations and blood pressure variability in patients with new-onset essential hypertension is not fully understood. This study evaluated the potential association of seasonal variations with new-onset essential hypertension. METHODS: This retrospective observational study recruited a total of 440 consecutive patients with new-onset essential hypertension who underwent 24-h ambulatory electrocardiograph (ECG) and BP measurement at our department between January 2019 and December 2019. Demographic and baseline clinical data including BP variability, heart rate variability, and blood tests were retrieved. Multivariate linear regression analysis was performed to identify factors independently associated with mean BP and BP variability. RESULTS: Among the 440 patients recruited, 93 cases were admitted in spring, 72 in summer, 151 in autumn, and 124 in winter. Univariate analysis revealed that systolic BP (SBP), diastolic BP (DBP), high-sensitivity C-reactive protein, SBP drop rate, DBP drop rate, 24-h standard deviation of SBP, 24-h standard deviation of DBP, 24-h SBP coefficient of variation, and 24-h DBP coefficient of variation were associated with patients admitted in winter (P < 0.05 for all). Multivariate linear regression analysis showed that winter was the influencing factor of 24-h standard deviation of SBP (B = 1.851, t = 3.719, P < 0.001), 24-h standard deviation of DBP (B = 1.176, t = 2.917, P = 0.004), 24-h SBP coefficient of variation (B = 0.015, t = 3.670, P < 0.001), and 24-h DBP coefficient of variation (B = 0.016, t = 2.849, P = 0.005) in hypertensive patients. CONCLUSIONS: Seasonal variations are closely associated with BP variability in patients with new-onset essential hypertension. Our study provides insight into the underlying pathogenesis of new-onset essential hypertension.

Neural Correlates of Temporal Presentness in the Precuneus: A Cross-linguistic fMRI Study based on Speech Stimuli.

The position of any event in time could be in the present, past, or future. This temporal discrimination is vitally important in our daily conversations, but it remains elusive how the human brain distinguishes among the past, present, and future. To address this issue, we searched for neural correlates of presentness, pastness, and futurity, each of which is automatically evoked when we hear sentences such as "it is raining now," "it rained yesterday," or "it will rain tomorrow." Here, we show that sentences that evoked "presentness" activated the bilateral precuneus more strongly than those that evoked "pastness" or "futurity." Interestingly, this contrast was shared across native speakers of Japanese, English, and Chinese languages, which vary considerably in their verb tense systems. The results suggest that the precuneus serves as a key region that provides the origin (that is, the Now) of our time perception irrespective of differences in tense systems across languages.

Synthesis and biological evaluation of thieno[3,2-c]pyrazol-3-amine derivatives as potent glycogen synthase kinase 3ß inhibitors for Alzheimer's disease.

Glycogen synthase kinase 3ß (GSK-3ß) catalyses the hyperphosphorylation of tau protein in the Alzheimer's disease (AD) pathology. A series of novel thieno[3,2-c]pyrazol-3-amine derivatives were designed and synthesised and evaluated as potential GSK-3ß inhibitors by structure-guided drug rational design approach. The thieno[3,2-c]pyrazol-3-amine derivative 16b was identified as a potent GSK-3ß inhibitor with an IC50 of 3.1 nM in vitro and showed accepted kinase selectivity. In cell levels, 16b showed no toxicity on the viability of SH-SY5Y cells at the concentration up to 50 µM and targeted GSK-3ß with the increased phosphorylated GSK-3ß at Ser9. Western blot analysis indicated that 16b decreased the phosphorylated tau at Ser396 in a dose-dependent way. Moreover, 16b effectively increased expressions of ß-catenin as well as the GAP43, N-myc, and MAP-2, and promoted the differentiated neuronal neurite outgrowth. Therefore, the thieno[3,2-c]pyrazol-3-amine derivative 16b could serve as a promising GSK-3ß inhibitor for the treatment of AD.

Is hyperuricemia an independent prognostic factor for IgA nephropathy: a systematic review and meta-analysis of observational cohort studies.

BACKGROUND: Hyperuricemia has been reported to be correlated with IgA nephropathy (IgAN). However, whether hyperuricemia or elevated serum uric acid (SUA) is an independent prognostic factor of IgAN remains unknown. Therefore, this systematic review and meta-analysis evaluated the prognostic value of hyperuricemia and elevated SUA in IgAN. METHODS: Databases including PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), and Open Gray were reviewed systematically. The kidney failure events of IgAN were defined as a doubling of serum creatinine, halving of eGFR, end-stage renal disease (ESRD), or death. The risk ratio (RR) between hyperuricemia and IgAN-caused kidney failure was evaluated before and after adjustment for relevant covariates. The RR between elevated SUA and IgAN-caused kidney failure was evaluated after adjustment for relevant covariates. RESULTS: A total of 11 548 patients from 14 studies were included in this meta-analysis. Hyperuricemia was found to be an independent prognostic factor of IgAN (unadjusted RR = 2.79, 95% CI = 1.93-4.03, p for heterogeneity <0.00001, I2 = 91%; adjusted RR = 2.12, 95% CI = 1.64-2.73, p for heterogeneity = 0.86, I2 = 0%). Subgroup and sensitivity analyses confirmed the stability of these results. Similarly, elevated SUA was positively correlated with kidney failure events of IgAN (adjusted RR = 1.25, 95% CI = 1.19-1.31, p for heterogeneity = 0.6, I2 = 0%). CONCLUSION: Our meta-analysis showed that hyperuricemia and elevated SUA were both independently associated with an increased incidence of kidney failure events in IgAN patients.

The Role of Small Extracellular Vesicles in the Progression of Colorectal Cancer and Its Clinical Applications.

Colorectal cancer (CRC) is one of the most common cancers worldwide and a longstanding critical challenge for public health. Screening has been suggested to effectively reduce both the incidence and mortality of CRC. However, the drawback of the current screening modalities, both stool-based tests and colonoscopies, is limited screening adherence, which reduces the effectiveness of CRC screening. Blood tests are more acceptable than stool tests or colonoscopy as a first-line screening approach. Therefore, identifying blood biomarkers for detecting CRC and its precancerous neoplasms is urgently needed to fulfill the unmet clinical need. Currently, many kinds of blood contents, such as circulating tumor cells, circulating tumor nucleic acids, and extracellular vesicles, have been investigated as biomarkers for CRC detection. Among these, small extracellular vesicles (sEVs) have been demonstrated to detect CRC effectively in recent reports. sEVs enable intercellular shuttling-for instance, trafficking between recipient cancer cells and stromal cells-which can affect tumor initiation, proliferation, angiogenesis, immune regulation; metastasis, the cancer-specific molecules, such as proteins, microRNAs, long noncoding RNAs, and circular RNAs, loaded into cancer-derived sEVs may serve as biomarkers for the detection of cancers, including CRC. Indeed, accumulating evidence has shown that nucleic acids and proteins contained in CRC-derived sEVs are effective as blood biomarkers for CRC detection. However, investigations of the performance of sEVs for diagnosing CRC in clinical trials remains limited. Thus, the effectiveness of sEV biomarkers for diagnosing CRC needs further validation in clinical trials.