CYSLTR1 antagonist inhibits Th17 cell differentiation by regulating the NF-κB signaling for the treatment of psoriasis.

Cysteinyl leukotriene receptor 1 (CYSLTR1) is observed to increase in psoriatic skin lesions. Montelukast, a CYSLTR1 antagonist, effectively treats inflammatory disorders, such as rheumatoid arthritis, multiple sclerosis, and atopic dermatitis. Thus, blocking CYSLTR1 may be a promising strategy for psoriasis immunotherapy. We prepared a montelukast sodium cream and solution and investigated their effects on psoriasis-like skin lesions induced by imiquimod (IMQ). After the treatment, serum, skin, and spleen samples were collected for evaluation. We treated human T helper (Th) 17 cells with montelukast in vitro to study its effect on Th17 differentiation and nuclear factor kappa-B (NF-κB) signaling. We also created a keratinocyte proliferation model induced by M5 cytokines and assessed the influence of montelukast on key psoriasis-related genes. We induced psoriasis in CYSLTR1 knockout (KO) mice using IMQ to explore the role of CYSLTR1 in psoriasis development. Montelukast sodium cream and solution effectively reduced the psoriasis area and severity index (PASI) and alleviated disease symptoms in IMQ-induced mice. Furthermore, reduced infiltration of inflammatory cells (Th1, Th17, and T follicular helper [Tfh] cells), decreased mRNA expression of cytokines in the skin (interleukin [IL]-17/F and IL-23), and lower serum concentrations of various cytokines (IL-2, IL-6, IL-13, and IL-17A/F) were observed. Montelukast cream and solution also decreased spleen size and the proportion of Th17 and Tfh cells, and significantly inhibited NF-κB signaling-related genes after application. Moreover, montelukast inhibited Th17 cell differentiation and suppressed NF-κB signaling in vitro. CYSLTR1 KO mice induced with IMQ showed improvement in PASI scores, serum IL-17A/F levels, and lower Th1 and Th17 cells in the spleen and skin compared to wild-type mice. Montelukast also suppressed the proliferation and inflammatory response of keratinocytes by regulating NF-κB signaling. Collectively, our results strongly indicate that inhibition of CYSLTR1 signaling to target the Th17 response holds significant promise as a therapeutic approach to manage psoriasis.

PREX2 contributes to radiation resistance by inhibiting radiotherapy-induced tumor immunogenicity via cGAS/STING/IFNs pathway in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) lacks established biomarkers or molecular targets for predicting or enhancing radiation response. Phosphatidylinositol-3,4,5-triphosphate-dependent Rac exchange factor 2 (PREX2) exhibits intricate implications in tumorigenesis and progression. Nevertheless, the precise role and underlying mechanisms of PREX2 in CRC radioresistance remain unclear. METHODS: RNA-seq was employed to identify differentially expressed genes between radioresistant CRC cell lines and their parental counterparts. PREX2 expression was scrutinized using Western blotting, real-time PCR, and immunohistochemistry. The radioresistant role of PREX2 was assessed through in vitro colony formation assay, apoptosis assay, comet assay, and in vivo xenograft tumor models. The mechanism of PREX2 was elucidated using RNA-seq and Western blotting. Finally, a PREX2 small-molecule inhibitor, designated PREX-in1, was utilized to enhance the efficacy of ionizing radiation (IR) therapy in CRC mouse models. RESULTS: PREX2 emerged as the most significantly upregulated gene in radioresistant CRC cells. It augmented the radioresistant capacity of CRC cells and demonstrated potential as a marker for predicting radioresistance efficacy. Mechanistically, PREX2 facilitated DNA repair by upregulating DNA-PKcs, suppressing radiation-induced immunogenic cell death, and impeding CD8+ T cell infiltration through the cGAS/STING/IFNs pathway. In vivo, the blockade of PREX2 heightened the efficacy of IR therapy. CONCLUSIONS: PREX2 assumes a pivotal role in CRC radiation resistance by inhibiting the cGAS/STING/IFNs pathway, presenting itself as a potential radioresistant biomarker and therapeutic target for effectively overcoming radioresistance in CRC.

Resting-state functional connectivity of amygdala subregions predicts treatment outcome for cognitive behavioral therapy in obsessive-compulsive disorder at a 4-month follow-up.

BACKGROUND: Cognitive behavioral therapy (CBT) is considered as the first-line treatment for obsessive-compulsive disorder (OCD). However, the underlying neural mechanisms through which CBT exerts its effects in OCD remain unclear. This study aims to investigate whether the improvement of clinical symptoms in OCD patients after CBT treatment is associated with changes in resting-state functional connectivity (FC) of the amygdala subregion, and whether these changes can be served as potential predictors of four-months treatment efficacy. METHODS: We collected resting-state functional magnetic resonance imaging (rs-fMRI) data from 57 OCD patients and 50 healthy subjects at baseline. In the patient group, rs-fMRI was also obtained after completion of an 8-week CBT treatment and 4 months post-treatment. A whole-brain rsFC analysis was conducted using the amygdala subregion as the seed point. We analyzed the FC patterns in relation to 4 months clinical outcomes to elucidate the long-term efficacy of CBT in OCD patients. RESULTS: Treatment responseat at pre-treatment was found to be associated with reduced rsFC between the left basolateral amygdala(BLA)and left superior temporal gyrus(STG) at baseline. Lower pre-treatment FC were negatively correlated with the severity of OCD symptoms as measured by the Yale-Brown Obsessive Compulsive Severity Scale (Y-BOCS). Moreover, the area under the receiver operating characteristic (ROC) curve for the FC between the left BLA and STG at the end of treatment was 73.0% and 70.4% for the effective-ineffective and remitted or unremitted groups, respectively. At the 4-month follow-up, the area under the ROC curve for the effective-ineffective and remitted or unremitted groups was 83.9% and 76.5%, respectively. CONCLUSION: These findings suggest that brain functional activity in patients with OCD can predict treatment response to CBT, and longitudinal changes in relevant brain functional activity following CBT treatment are associated with treatment response in OCD.

Enhanced metal-free photocatalyst performance by synergistic Coupling of internal magnetic field and piezoelectric field.

Graphitic carbon nitride (g-C3N4) is a promising metal-free photocatalyst; however, its high carrier recombination rate and insufficient redox capacity limit its degradation effect on antibiotics. In order to overcome these shortcomings, the photocatalytic activity is improved by regulating the spin polarization state, constructing the internal electric field, and applying the external piezoelectric field. In this paper, the chlorine-doped and nitrogen-deficient porous carbon nitride composite carbon quantum dots (Nv-Cl/UPCN@CQD) has been synthesized successfully. The doping position of chlorine and spin polarization properties are verified by DFT calculation. The key intermediates *O2- and *OOH for the synthesis of reactive oxygen species were detected by in-situ infrared testing, which promotes the production of •O2- and H2O2. The degradation rate constant of Nv-Cl/UPCN@CQD for removal of tetracycline is 8.45 times higher than that of g-C3N4. The active oxygen production and degradation efficiency of piezoelectric photocatalysis under the synergistic effect of intense stirring and vis-light irradiation are much higher than those of photocatalysis and piezoelectric catalysis, and the conversion of H2O2 to •OH is promoted by piezoelectric field. This paper provides a reliable way to improve the performance of piezoelectric photocatalysts by adjusting their energy band, electronic structure and piezoelectric force.

Multifunctional Conductive Double-Network Hydrogel Sensors for Multiscale Motion Detection and Temperature Monitoring.

As typical soft materials, hydrogels have demonstrated great potential for the fabrication of flexible sensors due to their highly compatible elastic modulus with human skin, prominent flexibility, and biocompatible three-dimensional network structure. However, the practical application of wearable hydrogel sensors is significantly constrained because of weak adhesion, limited stretchability, and poor self-healing properties of traditional hydrogels. Herein, a multifunctional sodium hyaluronate (SH)/borax (B)/gelatin (G) double-cross-linked conductive hydrogel (SBG) was designed and constructed through a simple one-pot blending strategy with SH and gelatin as the gel matrix and borax as the dynamic cross-linker. The obtained SBG hydrogels exhibited a moderate tensile strength of 25.3 kPa at a large elongation of 760%, high interfacial toughness (106.5 kJ m-3), strong adhesion (28 kPa to paper), and satisfactory conductivity (224.5 mS/m). In particular, the dynamic cross-linking between SH, gelatin, and borax via borate ester bonds and hydrogen bonds between SH and gelatin chain endowed the SBG hydrogels with good fatigue resistance (>300 cycles), rapid self-healing performance (HE (healing efficiency) ∼97.03%), and excellent repeatable adhesion. The flexible wearable sensor assembled with SBG hydrogels demonstrated desirable strain sensing performance with a competitive gauge factor and exceptional stability, which enabled it to detect and distinguish various multiscale human motions and physiological signals. Furthermore, the flexible sensor is capable of precisely perceiving temperature variation with a high thermal sensitivity (1.685% °C-1). As a result, the wearable sensor displayed dual sensory performance for temperature and strain deformation. It is envisioned that the integration of strain sensors and thermal sensors provide a novel and convenient strategy for the next generation of multisensory wearable electronics and lay a solid foundation for their application in electronic skin and soft actuators.

Pregabalin inhibits purinergic P2Y2 receptor and TRPV4 to suppress astrocyte activation and to relieve neuropathic pain.

BACKGROUNDS: Transient receptor potential vanilloid 4 (TRPV4)-mediated astrocyte activation is critical to neuropathic pain. Pregabalin, a widely used drug to treat chronic pain, is reported to lower the intracellular calcium level. However, the molecular mechanism by which pregabalin decreases the intracellular calcium level remains unknown. Purinergic P2Y2 receptor-a member of the G protein-coupled receptor (GPCR) family-regulates calcium-related signal transduction in astrocyte activation. We investigated whether P2Y2 receptor is involved in the pharmacological effects of pregabalin on neuropathic pain. METHODS: Neuropathic pain was induced by chronic compression of the dorsal root ganglion (CCD) in rats. Paw withdrawal mechanical threshold (PWMT) was used for behavioral testing. Intracellular calcium concentration was measured using a fluorescent calcium indicator (Fluo-4 AM). RESULTS: We found that P2Y2 receptor protein was upregulated and astrocytes were activated in the experimental rats after CCD surgery. Lipopolysaccharide (LPS) increased the intracellular calcium concentration and induced astrocyte activation in cultured astrocytes but was prevented via P2Y2 receptor inhibitor AR-C118925 or pregabalin. Furthermore, plasmid-mediated P2Y2 receptor overexpression induced an elevation of the intracellular calcium levels and inflammation in astrocytes, which was abolished by the TRPV4 inhibitor HC-067047. AR-C118925, HC-067047, and pregabalin relieved neuropathic pain and inflammation in rats after CCD surgery. Finally, plasmid-mediated P2Y2 receptor overexpression induced neuropathic pain in rats, which was abolished by pregabalin administration. CONCLUSIONS: Pathophysiological variables that upregulated the P2Y2 receptor/TRPV4/calcium axis contribute to astrocyte activation in neuropathic pain. Pregabalin exerts an analgesic effect by inhibiting this pathway.

Topical Application of Baicalin Combined with Echinacoside Ameliorates Psoriatic Skin Lesions by Suppressing the Inflammation-Related TNF Signaling Pathway and the Angiogenesis-Related VEGF Signaling Pathway.

Baicalin (BAI), the main active component of Scutellaria baicalensis, has significant anti-inflammatory and antibacterial effects. Echinacoside (ECH), an active component from Echinacea purpurea, has significant antiangiogenesis and antioxidant effects. In previous studies, BAI or ECH has been used for some skin inflammation problems by topical treatment. Psoriasis (PSO) is a common inflammatory skin disease with typical features such as excessive inflammatory response and vascular proliferation in skin lesions. Because of the anti-inflammatory effect of BAI and the antiangiogenic activity of ECH, it is proposed that the combination of BAI and ECH can ameliorate psoriatic skin lesions better than a single component. This study aims to explore the effects and potential mechanisms of BAI combined with ECH on imiquimod (IMQ)-induced psoriatic skin lesions by topical treatment. Transcriptome analysis first showed that the TNF signaling pathway and the VEGF signaling pathway were significantly enriched in IMQ-induced psoriatic skin lesions. Topical application of BAI combined with ECH could ameliorate IMQ-induced skin lesions in mice, especially the better effects of B2-E1 (BAI/ECH = 2:1). Network pharmacology analysis and molecular docking indicated that BAI-treated PSO on the skin by regulating the TNF signaling pathway, and ECH treated PSO on the skin by regulating the VEGF signaling pathway. Meanwhile, the ELISA test and the qPCR assay showed that BAI combined with ECH could inhibit the expression of key cytokines and genes related to the TNF signaling pathway and the VEGF signaling pathway. Zebrafish experiments demonstrated the anti-inflammatory and antiangiogenic effects of BAI combined with ECH and revealed the potential mechanisms associated with regulating the inflammation-related TNF signaling pathway and the angiogenesis-related VEGF signaling pathway. This suggested that BAI combined with ECH may be a promising topical agent to ameliorate psoriatic skin lesions in the future.

Epigenetic regulation of programmed cell death in hypoxia-induced pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a severe progressive disease that may cause early right ventricular failure and eventual cardiac failure. The pathogenesis of PAH involves endothelial dysfunction, aberrant proliferation of pulmonary artery smooth muscle cells (PASMCs), and vascular fibrosis. Hypoxia has been shown to induce elevated secretion of vascular endothelial growth factor (VEGF), leading to the development of hypoxic PAH. However, the molecular mechanisms underlying hypoxic PAH remain incompletely understood. Programmed cell death (PCD) is a natural cell death and regulated by certain genes. Emerging evidence suggests that apoptotic resistance contributes to the development of PAH. Moreover, several novel types of PCD, such as autophagy, pyroptosis, and ferroptosis, have been reported to be involved in the development of PAH. Additionally, multiple diverse epigenetic mechanisms including RNA methylation, DNA methylation, histone modification, and the non-coding RNA molecule-mediated processes have been strongly linked to the development of PAH. These epigenetic modifications affect the expression of genes, which produce important changes in cellular biological processes, including PCD. Consequently, a better understanding of the PCD processes and epigenetic modification involved in PAH will provide novel, specific therapeutic strategies for diagnosis and treatment. In this review, we aim to discuss recent advances in epigenetic mechanisms and elucidate the role of epigenetic modifications in regulating PCD in hypoxia-induced PAH.

Methylation specific enzyme-linked oligonucleotide assays (MS-ELONA) for ultrasensitive DNA methylation analysis.

Methylation of the promoter region of cancer related genes plays a crucial role in the occurrence and development of cancer, and the degree of methylation has great potential for the early cancer diagnosis. At present, the technology used to quantify DNA methylation is mainly based on the DNA sequencing which are time-consuming and high-cost in the relating application. We have developed an ultrasensitive method of methylation specific enzyme-linked oligonucleotide assays (MS-ELONA) to detect and quantify the level of DNA methylation. We could detect as little as 2 pg of methylated DNA in the 100000-fold excess of unmethylated genes, and discriminate prostate cancer from benign prostatic hyperplasia (BPH) and control with serum samples. We also demonstrate the reversibility of DNA methylation modification by treatment with demethylation drugs. With 16-channel electrochemical work station, our research reveals a simple and inexpensive method to quantify the methylation level of specially appointed genes, and have the potential to be applied in the clinical research.

Advances in epigenetic modifications of autophagic process in pulmonary hypertension.

Pulmonary hypertension is characterized by pulmonary arterial remodeling that results in increased pulmonary vascular resistance, right ventricular failure, and premature death. It is a threat to public health globally. Autophagy, as a highly conserved self-digestion process, plays crucial roles with autophagy-related (ATG) proteins in various diseases. The components of autophagy in the cytoplasm have been studied for decades and multiple studies have provided evidence of the importance of autophagic dysfunction in pulmonary hypertension. The status of autophagy plays a dynamic suppressive or promotive role in different contexts and stages of pulmonary hypertension development. Although the components of autophagy have been well studied, the molecular basis for the epigenetic regulation of autophagy is less understood and has drawn increasing attention in recent years. Epigenetic mechanisms include histone modifications, chromatin modifications, DNA methylation, RNA alternative splicing, and non-coding RNAs, which control gene activity and the development of an organism. In this review, we summarize the current research progress on epigenetic modifications in the autophagic process, which have the potential to be crucial and powerful therapeutic targets against the autophagic process in pulmonary hypertension development.

Heterogeneous expression of mismatch repair proteins and interpretation of immunohistochemical results in colorectal cancer and endometrial cancer.

To investigate the heterogeneous expression patterns of four mismatch repair (MMR) proteins in colorectal cancer (CRC) and endometrial cancer (EC), and their effects on the interpretation of immunohistochemical (IHC) results. A total of 1636 CRC and EC specimens were collected from two hospitals. Seventy-eight cases had heterogeneous expression of MMR proteins, including 49 CRC and 29 EC cases. Polymerase chain reaction-capillary electrophoresis (PCR-CE) was then performed to detect the microsatellite instability (MSI) status, and 44 cases were further verified by targeted next-generation sequencing (NGS). Heterogeneous expression of MMR proteins was observed in 66 cases (66/78, 84.6%) of proficient MMR (pMMR) and 12 cases (12/78, 15.4%) of deficient MMR (dMMR). The proportion of heterogeneous MMR protein expression in EC (12.0%) was higher than that in CRC (3.5%). The heterogeneous expression patterns were divided into focal clonal heterogeneity (6/78, 7.7%) and glandular mosaic heterogeneity (72/78, 92.3%). Surprisingly, three pMMR CRC cases showed isolated small focal clonal heterogeneity of mutS homologue 6 (MSH6), with < 15% positive tumour cells, which was validated as high MSI (MSI-H) with PCR-CE and NGS. However, the other three EC pMMR cases with > 50% focal clonal heterogeneity of MMR proteins were verified as microsatellite stable (MSS) or low MSI (MSI-L). Fifteen EC cases with glandular mosaic heterogeneous expression of MMR proteins included two MSI-H cases, which were validated using PCR-CE and NGS. Among the dMMR cases, only two EC cases with mutL homologue 1 (MLH1)/PMS1 homologue 2, mismatch repair system component (PMS2) loss and MSH2/MSH6 mosaic heterogeneous expression were confirmed as MSS using PCR-CE and NGS, which may be related to the mechanism of MLH1 promoter methylation. Thus, in CRC, only cases with small focal clonal heterogeneous expression of MSH6 have a high likelihood of MSI-H, and further PCR-CE or NGS testing is recommended. The possibility of MSI-H cannot be ruled out in EC cases with glandular mosaic heterogeneous expression of MMR proteins; PCR-CE or NGS detection is therefore necessary.

The ratio of monocyte count and high-density lipoprotein cholesterol mediates the association between urinary tungsten and cardiovascular disease: a study from NHANES 2005-2018.

Tungsten (W) is an emerging contaminant that can damage multiple systems in humans. However, studies of its effects on cardiovascular disease (CVD) are limited. The monocyte count to high-density lipoprotein cholesterol ratio (MHR) is a composite inflammatory index of great concern in recent years, derived from lipid and cell inflammation parameters, that is used to indicate the risk of CVD. This study aimed to investigate the association between urinary W and CVD in the general population and compare the mediating effects of lipids, cell inflammatory parameters, and MHR to find a better target for intervention. We analyzed data from 9137 (≥ 20 years) participants in the National Health and Nutrition Examination Survey (NHANES), from 2005 to 2018. Restricted cubic splines (RCS) and survey-weighted generalized linear models (SWGLMs) were used to assess the relationship between W and CVD. Mediated analyses were used to explore lipids, cell inflammatory parameters, and MHR in the possible mediating pathways between W and CVD. In SWGLM, we found that W enhances the risk of CVD, especially congestive heart failure (CHF), coronary heart disease (CHD), and angina pectoris (AP). Women, higher age groups (≥ 55 years), and those with hypertension were vulnerable to W in the subgroup analysis. Mediation analysis showed that monocyte count (MC), white blood cell count (WBC), high-density lipoprotein cholesterol (HDL), and MHR played a mediating role between W and CVD in proportions of 8.49%, 3.70%, 5.18%, and 12.95%, respectively. In conclusion, our study shows that urinary W can increase the risk of CVD, especially for CHF, CHD, and AP. Women, older age groups, and people with hypertension seem to be more vulnerable to W. In addition, MC, WBC, HDL, and MHR mediated the association between W and CVD, especially MHR, which suggests that we should consider it as a priority intervention target in the future.

Tendon-Inspired Anisotropic Hydrogels with Excellent Mechanical Properties for Strain Sensors.

Anisotropic conductive hydrogels mimicking the natural tissues with high mechanical properties and intelligent sensing have played an important role in the field of flexible electronic devices. Herein, tensile remodeling, drying, and subsequent ion cross-linking methods were used to construct anisotropic hydrogels, which were inspired by the orientation and functionality of tendons. Due to the anisotropic arrangement of the polymer network, the mechanical performance and electrical conductivity were greatly improved in specific directions. The tensile stress and elastic modulus of the hydrogel along the network orientation were 29.82 and 28.53 MPa, which were higher than those along the vertical orientation, 9.63 and 11.7 MPa, respectively. Moreover, the hydrogels exhibited structure-dependent anisotropic sensing. The gauge factors (GFs) parallel to the prestretching direction were greater than the GF along the vertical direction. Thus, the tendon-inspired conductive hydrogels with anisotropy could be used as flexible sensors for joint motion detection and voice recognition. The anisotropic hydrogel-based sensors are highly expected to promote the great development of emerging soft electronics and medical detection.

Central retinal vein occlusion with moyamoya disease: a case report.

Moyamoya disease is mainly caused by stenosis or occlusion of the terminal internal carotid artery, anterior cerebral artery, and proximal middle cerebral artery, and an abnormal vascular network is formed near the stenosis or occlusion of vascular lesions. Moyamoya disease can lead to a series of complications such as transient cerebral ischemia, cerebral infarction, and cerebral hemorrhage, which have been reported in the literature. Eye involvement with moyamoya disease is relatively rare in the literature. This article introduces a case of central retinal vein occlusion in a teenager related to moyamoya disease. The patient was only 16 years old and suddenly suffered from vision loss in the left eye. After detailed ophthalmological examination, she was diagnosed with central retinal vein occlusion in the left eye. In order to find the exact cause, we conducted head and neck CTA and brain DSA examinations on the patient, and finally found that the main cause of central retinal vein occlusion in this patient was moyamoya disease, which indicated that central retinal vein occlusion in young people may be caused by moyamoya disease in the early stage. This discovery has great clinical significance, for characteristic manifestations of the eye, suggesting that examination of moyamoya disease is a routine item for such patients, so as to achieve early detection, early diagnosis and early treatment, in order to avoid cerebral infarction, cerebral palsy, and serious or even life-threatening complications such as bleeding.

A simple and accurate method to quantify real-time contraction of vascular smooth muscle cell in vitro.

Vascular smooth muscle cells (VSMCs) constitute the medial layer of the blood vessel wall. Their contractile state regulates blood flow in physiological and pathological conditions. Current methods for assessing the contractility of VSMCs are not amenable to the high-throughput screening of pharmaceutical compounds. This study aimed to develop a method to address this shortcoming in the field. Real-time contraction was visualized in living VSMCs using the exogenous expression of green fluorescent protein (GFP). Image-Pro Plus software (IPPS) was used to measure various morphological cell indices. In phenylephrine-treated VSMCs, GFP fluorescence imaging was more accurate than brightfield imaging or phalloidin staining in representing VSMC morphology, as measured using IPPS. Among the multiple indices of VSMC shape, area and mean-diameter were more sensitive than length in reflecting the morphological changes in VSMC. We developed a new index, compound length, by combining the mean-diameter and length to differentiate contracted and uncontracted VSMCs. Based on the compound length, we further generated a contraction index to define a single-VSMC contractile status as single-VSMC contraction-index (SVCI). Finally, compound length and SVCI were validated to effectively assess cell contraction in VSMCs challenged with U46619 and KCl. In conclusion, GFP-based indices of compound length and SVCI can accurately quantify the real-time contraction of VSMCs. In future, the new method will be applied to high-throughput drug screening or basic cardiovascular research.

Insights into the relationships of modifying methods, structure, functional properties and applications of chitin: A review.

Chitin as the second plentiful polysaccharide has arouse widely attention due to its remarkable availability and biocompatibility. While the strong inter/intra molecular hydrogen bonds and crystallinity severely restrict its applications. Recently, multiple emerging technologies are increasingly used to modify chitin structure for the sake of obtaining excellent functional properties, as well as broadening the corresponding applications. Firstly, this review systematically outlines the features of single and combined methods for chitin modification. Then, the impacts of various modifying methods on the structural characteristics of chitin, including molecular weight, degree of acetylation and functional groups, are further summarized. In addition, the effects of these structural characteristics on the functional properties as well as its potential related applications are illustrated. The conclusion of this review provides better understanding of the relationships among the modifying methods, structure, properties and applications, contributing to chitin modification for the targeted purpose in the future study.

A global assessment of the mixed layer in coastal sediments and implications for carbon storage.

The sediment-water interface in the coastal ocean is a highly dynamic zone controlling biogeochemical fluxes of greenhouse gases, nutrients, and metals. Processes in the sediment mixed layer (SML) control the transfer and reactivity of both particulate and dissolved matter in coastal interfaces. Here we map the global distribution of the coastal SML based on excess 210Pb (210Pbex) profiles and then use a neural network model to upscale these observations. We show that highly dynamic regions such as large estuaries have thicker SMLs than most oceanic sediments. Organic carbon preservation and SMLs are inversely related as mixing stimulates oxidation in sediments which enhances organic matter decomposition. Sites with SML thickness >60 cm usually have lower organic carbon accumulation rates (<50 g C m-2 yr-1) and total organic carbon/specific surface area ratios (<0.4 mg m-2). Our global scale observations reveal that reworking can accelerate organic matter degradation and reduce carbon storage in coastal sediments.

Association between exposure to a mixture of metals, parabens, and phthalates and fractional exhaled nitric oxide: A population-based study in US adults.

The effects of environmental endocrine-disrupting chemicals (EDCs) (e.g., phthalates) on fractional exhaled nitric oxide (FeNO) in children have received much attention. However, few studies evaluated this relationship in adults, and the previous studies have considered only a unitary exposure or a set of similar exposures instead of mixed exposures, which contain complicated interactions. We aimed to evaluate simultaneously the relationship between three types of EDCs (six phthalate metabolites and two parabens in urine, two heavy metals in blood) and FeNO (as a continuous variable) in adults. Data of adults aged ≥20 years from the National Health and Nutrition Examination Survey (NHANES, 2007-2012) were collected and analyzed. The generalized linear (GLM) regression model was used to explore the association of chemicals with FeNO. The combined effect of 10 chemicals on the overall association with FeNO was evaluated by the weighted quantile sum regression (WQS) model. In addition, The Bayesian kernel machine regression (BKMR) model was explored to investigate the interaction and joint effects of multiple chemicals with FeNO. Of the 3296 study participants ultimately included, among the GLMs, we found that mercury (Hg) (ß = 0.84, 95%CI:0.32-1.36, FDR = 0.01) and methyl paraben (MPB) (ß = 0.47, 95%CI:0.16-0.78, FDR = 0.015) were positively correlated with FeNO. In the WQS model, the combined effect of chemicals almost had a significantly positive association with FeNO and the top three contributors to the WQS index were Hg (40.2%), MECPP (22.1%), and MPB (19.3%). BKMR analysis showed that there may be interactions between MPB and Hg, Mono (carboxyoctyl) phthalate (MCOP) and Hg and the overall effect of the mixture showed a positive correlation with FeNO. In conclusion, our study strengthens the credibility of the view that EDCs can affect respiratory health. In the future, we should be particularly careful with products containing Hg, MECPP, MPB, and MEHP for the prevention of respiratory diseases.

Functional Connectivity within the Frontal-Striatal Network Differentiates Checkers from Washers of Obsessive-Compulsive Disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a psychiatric disorder with high clinical heterogeneity manifested by the presence of obsessions and/or compulsions. The classification of the symptom dimensional subtypes is helpful for further exploration of the pathophysiological mechanisms underlying the clinical heterogeneity of OCD. Washing and checking symptoms are the two major symptom subtypes in OCD, but the neural mechanisms of the different types of symptoms are not yet clearly understood. The purpose of this study was to compare regional and network functional alterations between washing and checking OCD based on resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: In total, 90 subjects were included, including 15 patients in the washing group, 30 patients in the checking group, and 45 healthy controls (HCs). Regional homogeneity (ReHo) was used to compare the differences in regional spontaneous neural activity among the three groups, and local indicators were analyzed by receiver operating characteristic (ROC) curves as imaging markers for the prediction of the clinical subtypes of OCD. Furthermore, differently activated local brain areas, as regions of interest (ROIs), were used to explore differences in altered brain functioning between washing and checking OCD symptoms based on a functional connectivity (FC) analysis. RESULTS: Extensive abnormalities in spontaneous brain activity involving frontal, temporal, and occipital regions were observed in the patients compared to the HCs. The differences in local brain functioning between checking and washing OCD were mainly concentrated in the bilateral middle frontal gyrus, right supramarginal gyrus, right angular gyrus, and right inferior occipital gyrus. The ROC curve analysis revealed that the hyperactivation right middle frontal gyrus had a better discriminatory value for checking and washing OCD. Furthermore, the seed-based FC analysis revealed higher FC between the left medial superior frontal gyrus and right caudate nucleus compared to that in the healthy controls. CONCLUSIONS: These findings suggest that extensive local differences exist in intrinsic spontaneous activity among the checking group, washing group, and HCs. The neural basis of checking OCD may be related to dysfunction in the frontal-striatal network, which distinguishes OCD from washing OCD.