N-succinyl-chitosan as ecofriendly pesticide carriers: Nano encapsulation and synergistic antifungal effect on 4-hydroxyphenyl-2-propenyl-1-one derivatives based on chalcone structure.

INTRODUCTION: Traditional pesticides have poor-water solubility, high toxicity and low bioavailability. Therefore, it is of great significance for the sustainable and healthy development of the pesticide industry to develop efficient and ecofriendly new chemical pesticide products and formulations. OBJECTIVES: This study aims to synthesize a series of derivatives based on chalcone structure (HPPO), and then use the amphiphilic and self-assembly characteristics of N-succinyl-chitosan (NSCS) to prepare HPPO@NSCS nanoparticles (HPPO@NSCS NPs) in order to realize the green application of HPPO, and investigate the antifungal activity and mechanisms of HPPO@NSCS NPs. METHODS: NSCS was synthesized by structural modification using chitosan as the carrier. Based on its amphiphilic and self-assembly characteristics, HPPO-16@NSCS NPs were reasonably prepared by combining with active small molecule HPPO-16. Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), dynamic light scattering (DLS), fluorescence spectroscopy (FS) and high-performance liquid chromatography (HPLC) were used to characterize the physicochemical properties of NSCS and HPPO-16@NSCS NPs. The inhibitory activity of nanopesticides against Rhizoctonia solani (R. solani) was tested in vivo and in vitro. The mechanism of antifungal action was discussed from the observation of pathogen morphology, fluorescence staining and enzyme activity determination. RESULTS: 28 small molecules based on chalcone structure (HPPO-1-28), NSCS and HPPO-16@NSCS were successfully synthesized. The application of HPPO-16@NSCS could impair the development, cell structure, cellular energy utilization, and metabolism pathways of the fungi. The protective effects of HPPO-16@NSCS NPs on rice leaves and leaf sheaths were 80.9 and 76.1 %, respectively, which were better than those of azoxystrobin. CONCLUSION: This study reveals that these simple chalcone derivatives can be further explored as viable antibacterial alternatives and NSCS as a novel pesticide matrix can be used for the delivery of more insoluble pesticides.

Dual-mode nanoprobe strategy integrating ultrasound and near-infrared light for targeted and synergistic arterial thrombolysis.

Efficient thrombolysis in time is crucial for prognostic improvement of patients with acute arterial thromboembolic disease, while limitations and complications still exist in conventional thrombolytic treatment methods. Herein, our study sought to investigate a novel dual-mode strategy that integrated ultrasound (US) and near-infrared light (NIR) with establishment of hollow mesoporous silica nanoprobe (HMSN) which contains Arginine-glycine-aspartate (RGD) peptide (thrombus targeting), perfluoropentane (PFP) (thrombolysis with phase-change and stable cavitation) and indocyanine green (ICG) (thrombolysis with photothermal conversion). HMSN is used as the carrier, the surface is coupled with targeted RGD to achieve high targeting and permeability of thrombus, PFP and ICG are loaded to achieve the collaborative diagnosis and treatment of thrombus by US and NIR, so as to provide a new strategy for the integration of diagnosis and treatment of arterial thrombus. From the in vitro and in vivo evaluation, RGD/ICG/PFP@HMSN can aggregate and penetrate at the site of thrombus, and finally establish the dual-mode directional development and thrombolytic treatment under the synergistic effect of US and NIR, providing strong technical support for the accurate diagnosis and treatment of arterial thrombosis.

Evaluating a river's ecological health: A multidimensional approach.

Evaluating the health of river surface water is essential, as rivers support significant biological resources and serve as vital drinking water sources. While the Water Quality Index (WQI) is commonly employed to evaluate surface water quality, it fails to consider biodiversity and does not fully capture the ecological health of rivers. Here we show a comprehensive assessment of the ecological health of surface water in the lower Yangtze River (LYR), integrating chemical and biological metrics. According to traditional WQI metrics, the LYR's surface water generally meets China's Class II standards. However, it also contains 43 high-risk emerging contaminants; nitrobenzenes are found at the highest concentrations, representing 25-90% of total detections, while polycyclic aromatic hydrocarbons present the most substantial environmental risks, accounting for 81-93% of the total risk quotient. Notably, the plankton-based index of biological integrity (P-IBI) rates the ecological health of the majority of LYR water samples (59.7%) as 'fair', with significantly better health observed in autumn compared to other seasons (p < 0.01). Our findings suggest that including emerging contaminants and P-IBI as additional metrics can enhance the traditional WQI analysis in evaluating surface water's ecological health. These results highlight the need for a multidimensional assessment approach and call for improvements to LYR's ecological health, focusing on emerging contaminants and biodiversity rather than solely on reducing conventional indicators.

Development and validation of LCMM prediction algorithms to estimate recovery pattern of postoperative AKI in type A aortic dissection: a retrospective study.

Background: Postoperative acute kidney injury (PO-AKI) is a prevalent complication among patients with acute type A aortic dissection (aTAAD) for which unrecognized trajectories of renal function recovery, and their heterogeneity, may underpin poor success in identifying effective therapies. Methods: This was a retrospective, single-center cohort study in a regional Great Vessel Center including patients undergoing aortic dissection surgery. Estimated glomerular filtration rate (eGFR) recovery trajectories of PO-AKI were defined through the unsupervised latent class mixture modeling (LCMM), with an assessment of patient and procedural characteristics, complications, and early-term survival. Internal validation was performed by resampling. Results: A total of 1,295 aTAAD patients underwent surgery and 645 (49.8%) developed PO-AKI. Among the PO-AKI cohort, the LCMM identified two distinct eGFR trajectories: early recovery (ER-AKI, 51.8% of patients) and late or no recovery (LNR-AKI, 48.2% of patients). Binary logistic regression identified five critical determinants regarding poor renal recovery, including chronic kidney disease (CKD) history, renal hypoperfusion, circulation arrest time, intraoperative urine, and myoglobin. LNR-AKI was associated with increased mortality, continuous renal replacement therapies, mechanical ventilation, ICU stay, and hospital stay. The assessment of the predictive model was good, with an area under the curve (AUC) of 0.73 (95% CI: 0.69-0.76), sensitivity of 61.74%, and specificity of 75.15%. The internal validation derived a consistent average AUC of 0.73. The nomogram was constructed for clinicians' convenience. Conclusion: Our study explored the PO-AKI recovery patterns among surgical aTAAD patients and identified critical determinants that help to predict individuals at risk of poor recovery of renal function.

Two-Dimensional Ultrasound-Based Radiomics Nomogram for Diabetic Kidney Disease: A Pilot Study.

Objective: To establish a radiomics nomogram based on two-dimensional ultrasound for risk assessment of diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). Methods: This study retrospectively collected two-dimensional ultrasound images and clinical data from 52 patients with T2DM who underwent renal biopsy in our hospital from January 2023 to August 2023. Based on the pathological results, all patients were categorized into two groups: DKD (n=33) and non-DKD (n=19). The radiomic features of the segmented kidney in ultrasound pictures were retrieved and selected to calculate each patient's rad-score. A predictive nomogram based on rad-score and clinical features was then constructed and validated based on the calibration curve. Results: The rad-score for all patients were computed based on five imaging characteristics extracted from the ultrasound images. The predictive nomogram was developed with the rad-score, diabetic retinopathy, duration of diabetes, and glycosylated hemoglobin. Moreover, This radiomics nomogram showed outstanding calibration capability, discrimination as well as therapeutic usefulness. Conclusion: We constructed a nomogram based on two-dimensional ultrasound for DKD in T2DM patientsThe model has been proven to have good predictive performance, showing its potential in identifying DKD in T2DM patients and assisting in making appropriate early interventions.

Detection of genetic mutations underlying early-onset systemic lupus erythematosus.

OBJECTIVE: We aimed to investigate the presence of monogenic causes of systemic lupus erythematosus (SLE) in our early-onset SLE patients. METHODS: Fifteen pediatric SLE cases who had early disease onset (≤6 years) were enrolled in this study. All patients fulfilled the Systemic Lupus International Collaborating Clinics (SLICC) criteria. Genomic DNA was used for whole exome sequencing (WES). Pathogenic variants were confirmed by Sanger sequencing. RESULTS: The median age at diagnosis of 15 early-onset SLE patients included in the study was 4 (2-6) years (F/M = 12/3). Significant gene mutations were detected in five of these patients (33.3%). Patients 1 and 2 with homozygous DNASE1L3 mutations [c.320+4_320+7del and G188 A (c.563 G>C) variants] had skin involvement and oral ulcers. One of them (patient 1) had arthritis and nephritis, and another (patient 2) had nonscarring alopecia and thrombocytopenia. They are currently clinically inactive but have positive serological findings. Patient 3 with homozygous pathogenic ACP5 mutation [G109 R (c.325 G>A) variant] had arthritis, nephritis, short stature, and skeletal dysplasia. Patient 4 with a heterozygote novel IFIH1 mutation [L809 F (c.2425 C>T) variant] had skin findings and leukopenia. Patient 5 with novel C1S variant [homozygous C147 W (c.441 C>G) variant] had marked skin findings, oral ulcers, nonscarring alopecia, pancytopenia, and low total hemolytic complement CH50 level. All patients have responded to the treatments and have low Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, on therapy. CONCLUSION: Genetic causes should be investigated in early-onset SLE, for better management and genetic counseling. On the other hand, multicenter studies may help to further define genotype-phenotype associations.

Echocardiographic Measurements in Normal Chinese Adults (EMINCA) II focusing on left ventricular and left atrial size and function by three-dimensional echocardiography.

Current guidelines encourage large studies in a diverse population to establish normal reference ranges for three-dimensional (3D) echocardiography for different ethnic groups. This study was designed to establish the normal values of 3D-left ventricular (LV) and left atrial (LA) volume and function in a nationwide, population-based cohort of healthy Han Chinese adults. A total of 1117 healthy volunteers aged 18-89 years were enrolled from 28 collaborating laboratories in China. Two sets of 3D echocardiographic instruments were used, and full-volume echocardiographic images were recorded and transmitted to a core laboratory for image analysis with a vendor-independent off-line workstation. Finally, 866 volunteers (mean age of 48.4 years, 402 men) were qualified for final analysis. Most parameters exhibited substantial differences between different sex and age groups, even after indexation by body surface area. The normal ranges of 3D-LV and 3D-LA volume and function differed from those recommended by the American Society of Echocardiography and the European Association of Cardiovascular Imaging guidelines, presented by the World Alliance Societies of Echocardiography (WASE) study, and from the 2D values in the EMINCA study. The normal reference values of 3D echocardiography-derived LV and LA volume and function were established for the first time in healthy Han Chinese adults. Normal ranges of 3D-LV and 3D-LA echocardiographic measurements stratified with sex, age, and race should be recommended for clinical applications.

Sodium-glucose exchanger 2 inhibitor canagliflozin promotes mitochondrial metabolism and alleviates salt-induced cardiac hypertrophy via preserving SIRT3 expression.

INTRODUCTION: Excess salt intake is not only an independent risk factor for heart failure, but also one of the most important dietary factors associated with cardiovascular disease worldwide. Metabolic reprogramming in cardiomyocytes is an early event provoking cardiac hypertrophy that leads to subsequent cardiovascular events upon high salt loading. Although SGLT2 inhibitors, such as canagliflozin, displayed impressive cardiovascular health benefits, whether SGLT2 inhibitors protect against cardiac hypertrophy-related metabolic reprogramming upon salt loading remain elusive. OBJECTIVES: To investigate whether canagliflozin can improve salt-induced cardiac hypertrophy and the underlying mechanisms. METHODS: Dahl salt-sensitive rats developed cardiac hypertrophy by feeding them an 8% high-salt diet, and some rats were treated with canagliflozin. Cardiac function and structure as well as mitochondrial function were examined. Cardiac proteomics, targeted metabolomics and SIRT3 cardiac-specific knockout mice were used to uncover the underlying mechanisms. RESULTS: In Dahl salt-sensitive rats, canagliflozin showed a potent therapeutic effect on salt-induced cardiac hypertrophy, accompanied by lowered glucose uptake, reduced accumulation of glycolytic end-products and improved cardiac mitochondrial function, which was associated with the recovery of cardiac expression of SIRT3, a key mitochondrial metabolic regulator. Cardiac-specific knockout of SIRT3 not only exacerbated salt-induced cardiac hypertrophy but also abolished the therapeutic effect of canagliflozin. Mechanistically, high salt intake repressed cardiac SIRT3 expression through a calcium-dependent epigenetic modifications, which could be blocked by canagliflozin by inhibiting SGLT1-mediated calcium uptake. SIRT3 improved myocardial metabolic reprogramming by deacetylating MPC1 in cardiomyocytes exposed to pro-hypertrophic stimuli. Similar to canagliflozin, the SIRT3 activator honokiol also exerted therapeutic effects on cardiac hypertrophy. CONCLUSION: Cardiac mitochondrial dysfunction caused by SIRT3 repression is a critical promotional determinant of metabolic pattern switching underlying salt-induced cardiac hypertrophy. Improving SIRT3-mediated mitochondrial function by SGLT2 inhibitors-mediated calcium handling would represent a therapeutic strategy against salt-related cardiovascular events.

A Molecular Dynamics Study on the Defect Formation and Mechanical Behavior of Molybdenum Disulfide under Irradiation.

Due to its appealing characteristics, molybdenum disulfide (MoS2) presents a promising avenue for the exploration of lubrication protection materials in high-energy irradiation scenarios. Herein, we present a comprehensive investigation into the defect behavior of multilayer MoS2 under argon (Ar) atom irradiation leveraging molecular dynamics simulations. We have demonstrated the energy shifts and structural evolution in MoS2 upon irradiation, including the emergence of Frenkel defects and intricate defect clusters. The structural damage exhibits an initial increase followed by a subsequent decrease as the incident kinetic energy increases, ultimately peaking at 2.5 keV. Moreover, we investigated the effect of postannealing on defect recovery and conducted the uniaxial tensile and interlayer shearing simulation in order to provide valuable insights for the defect evolution and its impact on mechanical and tribological properties. Furthermore, we have proposed the optimal annealing temperature. The current study reveals the atomic mechanisms underlying irradiation-induced damage on the structural integrity and mechanical performance of MoS2, thereby providing crucial guidance for its vital application in nuclear reactors and aerospace industries.

A prognostic nomogram for the cancer-specific survival rate of choroidal melanoma using the Surveillance, Epidemiology, and End Results database.

Objective: This study was conducted to develop a comprehensive nomogram for individuals with choroidal melanoma (CM) to determine their cancer-specific survival (CSS). Methods: Data of individuals with CM, diagnosed between 2004 and 2015, were accessed at the Surveillance, Epidemiology, and End Results (SEER) database. The selected individuals were randomly categorized into a training and validation cohort. Multivariate Cox regression analysis was applied to screen the relevant variables. Followed by the development of a nomogram based on independent variables. Ultimately, the net reclassification index (NRI), concordance index (C-index), calibration charts, integrated discrimination improvement (IDI), receiver operating characteristic curves (ROC), area under the curve (AUC), and decision-curve analysis (DCA), were utilized to evaluate the discrimination, accuracy, and effectiveness of the model. Results: This study enrolled 3,782 patients. Seven independent factors linked to prognosis were screened via multivariate Cox regression analysis, encompassing age at diagnosis; race; AJCC (American Joint Committee on Cancer) stage; histologic type; and therapy method of radiotherapy, surgery, and chemotherapy. The respective C-indexes of the training and validation cohorts were 0.709 and 0.726, indicative of the excellent accuracy of the nomogram. Furthermore, the AUCs of the training and validation cohorts across 3, 5, and 8 years were 0.767, 0.744, and 0.722 as well as 0.772, 0.770, and 0.753, respectively. Evident of the superiority of the established nomogram over the AJCC staging, both the NRI and IDI values exhibited improvement. The favorable clinical impact and good performance of the nomogram were evident via decision curve analyses (DCAs) and calibration plots, respectively. Conclusion: This research dealt with establishing and validating a nomogram as a prognostic tool for assessing the prognosis of adult patients with CM utilizing the SEER database. A comprehensive assessment of the nomogram via diverse variables demonstrated its accuracy in predicting the CSS probabilities of CM patients across 3, 5, and 8 years in clinical settings. Notably, its performance surpassed that of the AJCC staging system.

Chemical Constituents and Pharmacological Properties of Frankincense: Implications for Anticancer Therapy.

The discovery of novel antitumor agents derived from natural plants is a principal objective of anticancer drug research. Frankincense, a widely recognized natural antitumor medicine, has undergone a systematic review encompassing its species, chemical constituents, and diverse pharmacological activities and mechanisms. The different species of frankincense include Boswellia serrata, Somali frankincense, Boswellia frereana, and Boswellia arabica. Various frankincense extracts and compounds exhibit antitumor, anti-inflammatory, and hepatoprotective properties and antioxidation, memory enhancement, and immunological regulation capabilities. They also have comprehensive effects on regulating flora. Frankincense and its principal chemical constituents have demonstrated promising chemoprophylactic and therapeutic abilities against tumors. This review provides a systematic summary of the mechanism of action underlying the antitumor effects of frankincense and its major constituents, thus laying the foundations for developing effective tumor-combating targets.

Transcutaneous auricular vagus nerve stimulation as a novel therapy connecting the central and peripheral systems: a review.

Currently, clinical practice and scientific research mostly revolve around a single disease or system, but the single disease-oriented diagnostic and therapeutic paradigm needs to be revised. This review describes how transcutaneous auricular vagus nerve stimulation (taVNS), a novel noninvasive neuromodulation approach, connects the central and peripheral systems of the body. Through stimulation of the widely distributed vagus nerve from the head to the abdominal cavity, this therapy can improve and treat central system disorders, peripheral system disorders, and central-peripheral comorbidities caused by autonomic dysfunction. In the past, research on taVNS has focused on the treatment of central system disorders by modulating this brain nerve. As the vagus nerve innervates the heart, lungs, liver, pancreas, gastrointestinal tract, spleen and other peripheral organs, taVNS could have an overall modulatory effect on the region of the body where the vagus nerve is widespread. Based on this physiological basis, we summarize the existing evidence of the taVNS ability to regulate cardiac function, adiposity, glucose levels, gastrointestinal function, and immune function, among others, to treat peripheral system diseases, and complex diseases with central and peripheral comorbidities. This review shows the successful examples and research progress of taVNS using peripheral neuromodulation mechanisms from more perspectives, demonstrating the expanded scope and value of taVNS to provide new ideas and approaches for holistic therapy from both central and peripheral perspectives.

Prognostic value and immunological role of MMRN1: a rising star in cancer.

BACKGROUND: Multimerin 1 (MMRN1) is a factor V binding protein, which can support platelet adhesion and thrombus formation. In recent years, the role of MMRN1 in cancer has begun to attract attention. But systematic studies in this area are lacking. Therefore, we used bioinformatics methods to analyze MMRN1 in tumors to reveal the possible role of MMRN1. METHODS: Using the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) database, we obtained relevant data for analyzing MMRN1. Using Gene Expression Profiling Interactive Analysis (GEPIA), Human Protein Atlas (HPA), TCGA, GeneMANIA, and cBioPortal, we explored the potential role of MMRN1 in different types of tumors. Tumor Immune System Interactions and Drug Bank (TISIDB) and Sangerbox were used to analyze the correlation between MMRN1 and tumor immunity. Gene set cancer analysis (GSCA) and UALCAN were used to analyze the methylation of MMRN1. GSCA was also used to analyze the drug sensitivity of MMRN1. RESULTS: MMRN1 is down-regulated in most cancer types and is closely related to the prognosis of cancer patients. Interestingly, in most tumors, MMRN1 is positively correlated with immune -related genes. In addition, we observed different levels of methylation and mutations in different types of tumors. Drug sensitivity analysis found that MMRN1 was negatively correlated with several drugs, including GW-2580 and TL-1-85, suggesting that it can be used to develop potential anticancer therapies. CONCLUSION: Our analysis demonstrated a significant relationship between MMRN1 and prognosis, tumor immunity, and drug sensitivity of several tumors. As a rising star in cancer, it needs further research.

Phase Transition and Luminescent Property Change Induced by Different Organic Cations in One-Dimensional Double Perovskites.

Double perovskites (DPs) have attracted attention in the field of luminescence due to their inherent broadband emission of self-trapping excitons. In this work, we choose [(CH3)3NCH2CHCH2]+ and [CH3CHOHCH2NH2]+ as organic cations to synthesize two new organic-inorganic hybrid DPs, [(CH3)3NCH2CHCH2]2KInCl6 (1) and [CH3CHOHCH2NH2]2KInCl6 (2). The [KCl6]3- and [InCl6]3- octahedra are interchangeably connected by sharing two opposite faces, forming a one-dimensional coordination chain. Each K atom coordinates with six chlorine atoms in 1, while it coordinates with two oxygen atoms in addition to the six chlorine atoms in 2. The coordination between ions K and O in compound 2 may have significantly reduced its luminescence. As a result, compound 1 shows bright-yellow light with a quantum yield of more than 90%, while 2 shows weak blue light with a quantum yield of only 0.98%. In addition, different from no phase transition found in 2, 1 undergoes a reversible phase transition at 324/307 K in the heating-cooling cycle. Through structural and spectral analysis and density functional theory calculation, we conclude that the larger degree of [InCl6]3- octahedral distortion and the larger anion distance (In···In) also cause the PLQY of compound 1 to be higher than that of compound 2.

Uniportal video-assisted thoracic surgery versus open thoracotomy for chronic pain after surgery: a prospective cohort study.

PURPOSE: The potential of uniportal video-assisted thoracic surgery (U-VATS) to reduce chronic pain after thoracic surgery (CPTS) compared to open thoracotomy (OT) remains unexplored. This prospective study aims to assess the incidence of CPTS following U-VATS or OT and identify associated risk factors. METHODS: Patients undergoing thoracic surgery were recruited from March 2021 to March 2022, categorized by surgical approach (U-VATS vs. OT). Standard clinical protocols for surgery, anesthesia, and analgesia were followed. Pain symptoms were assessed using the Short-form McGill Pain Questionnaire, with follow-ups up to 6 months. Perioperative factors influencing CPTS at 3 months were analyzed through univariate and multivariate methods. RESULTS: A total of 694 patients were analyzed. Acute pain after thoracic surgery (APTS) was significantly less severe in the U-VATS group (p < 0.001). U-VATS patients exhibited a lower incidence of CPTS at 3 months (63.4% vs. 80.1%, p < 0.001), with reduced severity among those experiencing CPTS (p = 0.007) and a decreased occurrence of neuropathic pain (p = 0.014). Multivariate analysis identified OT incision, moderate to severe APTS (excluding moderate static pain at 24 h postoperative), nocturnal surgery, and lung surgery as risk factors for CPTS. CONCLUSION: This study underscores the potential of U-VATS to reduce both the incidence and severity of CPTS at 3 months compared to OT. Furthermore, it highlights risk factors for CPTS, including OT incision, inadequately managed APTS, lung surgery, and nocturnal surgery. These findings emphasize the importance of considering surgical approach and perioperative pain management strategies to mitigate the burden of CPTS.

Spatial - temporal mapping of urine cadmium levels in China during 1980 - 2040: Dietary improvements lower exposure amid rising pollution.

Persistent cadmium exposure poses significant health risks to the Chinese population, underscored by its prevalence as an environmental contaminant. This study leverages a machine-learning model, fed with a comprehensive dataset of environmental and socio-economic factors, to delineate trends in cadmium exposure from 1980 to 2040. We uncovered that urinary cadmium levels peaked at 1.09 µg/g Cr in the mid-2000 s. Encouragingly, a decline is projected to 0.92 µg/g Cr by 2025, tapering further to 0.87 µg/g Cr by 2040. Despite this trend, regions heavily influenced by industrialization, such as Hunan and Guizhou, as well as industrial counties in Jilin, report stubbornly high levels of exposure. Our demographic analysis reveals a higher vulnerability among adults & adolescents over 14, with males displaying elevated cadmium concentrations. Alarmingly, the projected data suggests that by 2040, an estimated 41% of the population will endure exposure beyond the safety threshold set by the European Food Safety Authority. Our research indicates disproportionate cadmium exposure impacts, necessitating targeted interventions and policy reforms to protect vulnerable groups and public health in China.

Administration of Liposomal-Based Pde3b Gene Therapy Protects Mice Against Collagen-Induced Rheumatoid Arthritis via Modulating Macrophage Polarization.

Background: Rheumatoid arthritis (RA) is a chronic and systemic autoimmune disease characterized by synovial inflammation and joint destruction. Despite progress in RA therapy, it remains difficult to achieve long-term remission in RA patients. Phosphodiesterase 3B (Pde3b) is a member of the phosphohydrolyase family that are involved in many signal transduction pathways. However, its role in RA is yet to be fully addressed. Methods: Studies were conducted in arthritic DBA/1 mice, a suitable mouse strain for collagen-induced rheumatoid arthritis (CIA), to dissect the role of Pde3b in RA pathogenesis. Next, RNAi-based therapy with Pde3b siRNA-loaded liposomes was assessed in a CIA model. To study the mechanism involved, we investigated the effect of Pde3b knockdown on macrophage polarization and related signaling pathway. Results: We demonstrated that mice with CIA exhibited upregulated Pde3b expression in macrophages. Notably, intravenous administration of liposomes loaded with Pde3b siRNA promoted the macrophage anti-inflammatory program and alleviated CIA in mice, as indicated by the reduced inflammatory response, synoviocyte infiltration, and bone and cartilage erosion. Mechanistic study revealed that depletion of Pde3b increased cAMP levels, by which it enhanced PKA-CREB-C/EBPß pathway to transcribe the expression of anti-inflammatory program-related genes. Conclusion: Our results support that Pde3b is involved in the pathogenesis of RA, and Pde3b siRNA-loaded liposomes might serve as a promising therapeutic approach against RA.

A group of emerging heterocyclic nitrogenous disinfection byproducts: Formation and cytotoxicity of halopyridinols in drinking water.

Recently, a new group of halopyridinol disinfection byproducts (DBPs) was reported in drinking water. The in vivo developmental and acute toxicity assays have shown that they were more toxic than a few commonly known aliphatic DBPs such as bromoform and iodoacetic acid. However, many pyridinol DBPs with the same main structures but different halogen substitutions were still unknown due to complicated water quality conditions and various disinfection methods applied in drinking water treatment plants. Studies on their transformation mechanisms in drinking water disinfection were quite limited. In this study, comprehensive detection and identification of halopyridinols were conducted, and five new halopyridinols were first reported, including 2-chloro-3-pyridinol, 2,6-dichloro-3-pyridinol, 2-bromo-5-chloro-3-pyridinol, 2,4,6-trichloro-3-pyridinol and 2,5,6-trichloro-3-pyridinol. Formation conditions and mechanisms of the halopyridinols were explored, and results showed that chlorination promoted their formation compared with chloramination. Halopyridinols were intermediate DBPs that could undergo further transformation/degradation with increasing contact time, disinfectant dose, bromide concentration, and pH. The in vitro cytotoxicity of the halopyridinols was evaluated using human hepatocellular carcinoma cells. Results showed that the cytotoxicity of 3,5,6-trichloro-2-pyridinol was the highest (EC50 = 474.3 µM), which was 13.0 and 1.6 times higher than that of 2-bromo-3-pyridinol (EC50 = 6214.5 µM) and tribromomethane (EC50 = 753.6 µM), respectively.

Carbon nanotubes integrated photonic barcodes in Herringbone Microfluidics for Multiplex Biomarker Quantification.

Early monitoring of cardiovascular disease (CVD) is crucial for its treatment and prognosis. Hence, highly specific and sensitive detection method is urgently needed. In this study, we propose a novel herringbone microfluid chip with aptamer functionalized core-shell photonic crystal (PhC) barcode integration for high throughput multiplex CVD detection. Based on the PhC derived from co-assembled carboxylated single-wall carbon nanotubes and silicon dioxide nanoparticles, we obtain core-shell PhC barcodes by hydrogel replicating and partially etching. These core-shell PhC barcodes not only retain the original structural colors coding element, but also fully expose a large number of carboxyl elements in the ore for the probe immobilization. We further combine the functionalized barcodes with herringbone groove microfluidic chip to elucidate its acceptability in testing clinical sample. It is demonstrated that the special design of microfluidic chip can significantly enhance fluid vortex resistance and contact frequency, improving the sample capture efficiency and detection sensitivity. These features indicate that our core-shell PhC barcodes-integrated herringbone microfluidic system possesses great potential for multiplex biomarker detection in clinical application.