Theoretical Analysis of Thermophysical Properties of 3D Carbon/Epoxy Braided Composites with Varying Temperature.

A three-dimensional helix geometry unit cell is established to simulate the complex spatial configuration of 3D braided composites. Initially, different types of yarn factors, such as yarn path, cross-sectional shape, properties, and braid direction, are explained. Then, the multiphase finite element method is used to develop a new theoretical calculation procedure based on the unit cell for predicting the impacts of environmental temperature on the thermophysical properties of 3D four-direction carbon/epoxy braided composites. The changing rule and distribution characteristics of the thermophysical properties for 3D four-direction carbon/epoxy braided composites are obtained at temperatures ranging from room temperature to 200 °C. The influences of environmental temperature on the coefficients of thermal expansion (CTE) and the coefficients of thermal conduction (CTC) are evaluated, by which some important conclusions are drawn. A comparison is conducted between theoretical and experimental results, revealing that variations in temperature exert a notable influence on the thermophysical characteristics of 3D four-directional carbon/epoxy braided composites. The theoretical calculation procedure is an effective tool for the mechanical property analysis of composite materials with complex geometries.

Changed nocturnal levels of stress-related hormones couple with sleep-wake states in the patients with chronic insomnia disorder: A clinical pilot study.

OBJECTIVES: To explore the relationship between nocturnal levels of stress-related hormones and different sleep-wake states in chronic insomnia disorder (CID) patients. METHODS: Thirty-three CID patients and 34 good sleepers were enrolled and completed assessment of sleep log, Pittsburgh Sleep Quality Index and Insomnia Severity Index. During a-overnight polysomnography monitoring, the patients' vein bleeds were continually collected at different time points (pre-sleep, deep-sleep, 5-min or 30-min waking, and morning waking-up). The control subjects' bleeds were collected only at 22:00 and morning waking-up. The serum hormones were detected using enzyme-linked immunosorbent assay. RESULTS: Compared with at pre-sleep, the level of cortisol was significantly higher at morning waking-up respectively in two-group subjects (Ps < 0.001), with insignificant inter-group differences in cortisol, corticotropin releasing hormone and copeptin at the two time-points. In the patients, the nocturnal secretion curves of three hormones were similar, with the highest concentration at morning waking-up, followed by 30-min waking, 5-min waking, pre-sleep, and deep-sleep. The patients' cortisol (Z = 79.192, P < 0.001) and copeptin (Z = 12.333, P = 0.015) levels were statistically different at different time-points, with higher cortisol at morning waking-up relative to deep-sleep, pre-sleep and 5-min waking (Ps < 0.05), and at 30-min waking relative to deep-sleep and pre-sleep (Ps < 0.05), and higher copeptin at morning waking-up relative to deep-sleep (P < 0.05). CONCLUSIONS: In CID, the nocturnal wakes were instantaneously accompanied by high level, and deep sleep was accompanied by the lowest levels, of stress-related hormones, especially in cortisol, supporting the insomniac hypothesis of increased nocturnal pulse-release of cortisol.

Inhibitory effects and mechanisms of phenolic compounds in rapeseed oil on advanced glycation end product formation in chemical and cellular models in vitro.

Sinapic acid (SA), canolol (CAO) and canolol dimer (CAO dimer) are the main phenolic compounds in rapeseed oil. However, their possible efficacy against glycation remains unclear. This study aims to explore the impacts of these substances on the formation of advanced glycation end products (AGEs) based on chemical and cellular models in vitro. Based on fluorescence spectroscopy results, three chemical models of BSA-fructose, BSA-methylglyoxal (MGO), and arginine (Arg)-MGO showed that SA/CAO/CAO dimer could effectively reduce AGE formation but with different abilities. After SA/CAO/CAO dimer incubation, effective protection against BSA protein glycation was observed and three different MGO adducts were formed. In MGO-induced HUVEC cell models, only CAO and CAO dimer significantly inhibited oxidative stress and cell apoptosis, accompanied by the regulation of the Nrf2-HO-1 pathway. During the inhibition, 20 and 12 lipid mediators were reversed in the CAO and CAO dimer groups compared to the MGO group.

The mediating effect of family resilience between coping styles and caregiver burden in maintenance hemodialysis patients: a cross-sectional study.

BACKGROUND: Primary caregivers of hemodialysis patients suffer from varying degrees of stress from their patients. Caring for hemodialysis patients can expose caregivers to many problems, leading to an increased burden of care and even impacting the quality of care. The purpose of our study was to examine whether family resilience could be a mediating variable moderating the relationship between patient coping styles and caregiver burden. METHODS: The study was a cross-sectional and descriptive-analytical study that interviewed 173 pairs of hemodialysis patients and their caregivers at a blood purification center in a public hospital in China. The Brief Coping Styles Scale (Chinese version) was used to assess individuals' coping styles for disease and treatment. From the caregiver's perspective, the Family Resilience Assessment Scale (Chinese version) was used to understand the resilience of families, and the Zarit Caregiver Burden Scale was used to capture the caregiver's subjective experience of burden. Statistical analyses were conducted using SPSS version 23 and Amos version 26 to analyze the relationships between variables to examine for correlation and construct mediated effects models. RESULTS: Coping styles showed a significant positive correlation with family resilience (r = 0.347, P < 0.01) and a negative correlation with caregiver burden (r = -0.379, P < 0.01). A significant negative correlation was found between family resilience and caregiver burden (r = -0.503, P < 0.01). In the mediation model, patient coping styles directly impacted caregiver burden significantly (95% CI [-0.372, -0.058]), and coping styles indirectly impacted caregiver burden by family resilience in a significant way (95% CI [-0.275, -0.098]). CONCLUSIONS: Patient coping styles directly affect caregiver burden. Family resilience is a mediating variable between patients' coping styles and the burden on caregivers.

Integration of One-Dimensional (1D) Lead-Free Perovskite Microbelts onto Silicon for Ultraviolet-Visible-Near-Infrared (UV-vis-NIR) Heterojunction Photodetectors.

Lead-free perovskites are considered to be candidates for next-generation photodetectors, because of their excellent charge carrier transport properties and low toxicity. However, their application in integrated circuits is hindered by their inadequate performance and size restrictions. To aim at the development of lead-free perovskite-integrated optoelectronic devices, a CsAg2I3/silicon (CAI/Si) heterojunction is presented in this work by using a spatial confinement growth method, where the in-plane growth of CAI microbelts with high-quality single-crystal characteristics is primarily dependent on the concentration of surrounding precursor solution. The fabricated photodetectors based on the CAI/Si heterojunctions exhibit a broad-spectrum detection capability in the ultraviolet-visible-near-infrared (UV-vis-NIR) range. In addition, the photodetectors show good photoelectric detection performance, including a maximum responsivity of 48.5 mA/W and detectivity of 1.13 × 1011 Jones, respectively. Besides, the photodetectors have a rapid response of 6.5/224 µs and good air stability for over 2 months. This work contributes a new idea to design next-generation optoelectronic devices with high integration density.

Sulforaphane effectively inhibits HBV by altering Treg/Th17 immune balance and the MIF-macrophages polarizing axis in vitro and in vivo.

BACKGROUND: Hepatitis B virus (HBV) infection is a major public health problem. After HBV infection, viral antigens shift the immune balance in favor of viral escape. Sulforaphane (SFN) is a traditional Chinese medicine.It regulates multi-biological activities, including anti-inflammation, anticancer, and antiviral. However, few studies reported that SFN can inhibit HBV infection before. METHODS: An immunocompetent HBV CBA/CaJ mouse model and a co-culture model were used to explore the effect of SFN on HBV and whether SFN altered the immune balance after HBV infection. RESULTS: We found that SFN was able to reduce HBV DNA, cccDNA, HBsAg, HBeAg, and HBcAg levels in serum and liver tissues of HBV-infected mice. In vitro and in vivo experiments showed that SFN could significantly increase the expression of Cd86 and iNOS and inhibit the expression of Arg1 on macrophages after HBV infection. After SFN administration, Th17 markers in liver tissue and serum were significantly increased. There was no significant changes in the proportion of Treg cells in peripheral blood, but a significant increase in the proportion of Th17 cells and decrease of the Treg/Th17 ratio. Using a network pharmacology approach, we predicted macrophage migration inhibitory factor (MIF) as a potential target of SFN and further validated that MIF expression was significantly increased after HBV infection and SFN significantly inhibited MIF expression both in vitro and in vivo. There was an upward trend in HBV markers (p>0.05) after MIF overexpression. Overexpression of MIF combined with the use of SFN resulted in a significant reversion in the expression of HBV markers and polarization of macrophages towards the M1 phenotype. CONCLUSION: Our results indicated that immunocompetent HBV CBA/CaJ mouse model is a good model to evaluate HBV infection. SFN could inhibit the expression of HBV markers, promote polarization of macrophages towards the M1 phenotype after HBV infection, change the proportion of Treg and Th17 cells. Our findings demonstrate that SFN inhibit HBV infection by inhibiting the expression of MIF and promoting the polarization of macrophages towards the M1 phenotype, which illustrates a promising therapeutic approach in HBV infection.

Plant exosome-like nanovesicles derived from sesame leaves as carriers for luteolin delivery: Molecular docking, stability and bioactivity.

The growing recognition of luteolin (Lu) as a vital functional component is attributed to its notable bioactive properties. However, the effective use of Lu is hindered by its inherent limitations related to water solubility, stability, and bioavailability. Here, we aim to develop sesame leaves-derived exosome-like nanovesicles (Exo) for Lu delivery (Exo@Lu) as vehicles. The encapsulation mechanism, solubility, stability, and bioactivity of Exo@Lu were thoroughly evaluated. Exo enriched abundant lipids, proteins, and phenolic compounds with an encapsulation efficiency of âˆ¼ 91.9 % and a loading capacity of âˆ¼ 20.5 % for Lu. The primary binding forces responsible for the encapsulation were hydrogen bonds and van der Waals forces. After encapsulation, the water solubility and stability of Lu were significantly improved under various conditions, including thermal, light, storage, ionic strength, and pH. Exo@Lu maintained structural integrity during simulated digestion, enhancing bioaccessibility and efficacy in mitigating oxidative stress and inflammatory response compared to Exo and free Lu.

Two-Step Catalytic Against Polysulfide Shuttling to Enhance Redox Conversion for Advanced Lithium-Sulfur Batteries.

The development of lithium-sulfur batteries is seriously hindered by the shuttle effect of lithium polysulfides (LiPSs) and the low electrical conductivity of sulfur. To solve these problems, efficient catalysts can be used to improve the conversion rate of LiPSs and the conductivity of sulfur cathode. Herein, annealed melamine foam supported MoSe2 (NCF@MoSe2) is used as interlayer and the MoSe2/MoP heterojunction obtained by phosphating MoSe2 is further used as the catalyst material for metal fusion with a sulfur element. The interlayer can not only improve the electrical conductivity and effectively adsorb and catalyze LiPSs, but more importantly, the MoSe2/MoP heterojunction can also effectively adsorb and catalyze LiPSs, so that the batteries have a dual inhibition shuttling effect strategy. Furthermore, the rapid anchor-diffusion transition of LiPSs, and the suppression of shuttling effects by catalyst materials are elucidated using theoretical calculations and in situ Raman spectroscopy. The two-step catalytic strategy exhibits a high reversibility of 983 mAh g-1 after 200 cycles at 0.5 C and a high-rate capacity of 889 mAh g-1 at 5 C. This work provides a feasible solution for the rational design of interlayer and heterojunction materials and is also conducive to the development of more advanced Li-S batteries.

Improving the Thermostability of Thermomyces lanuginosus Lipase by Restricting the Flexibility of N-Terminus and C-Terminus Simultaneously via the 25-Loop Substitutions.

(1) Lipases are catalysts widely applied in industrial fields. To sustain the harsh treatments in industries, optimizing lipase activities and thermal stability is necessary to reduce production loss. (2) The thermostability of Thermomyces lanuginosus lipase (TLL) was evaluated via B-factor analysis and consensus-sequence substitutions. Five single-point variants (K24S, D27N, D27R, P29S, and A30P) with improved thermostability were constructed via site-directed mutagenesis. (3) The optimal reaction temperatures of all the five variants displayed 5 °C improvement compared with TLL. Four variants, except D27N, showed enhanced residual activities at 80 °C. The melting temperatures of three variants (D27R, P29S, and A30P) were significantly increased. The molecular dynamics simulations indicated that the 25-loop (residues 24-30) in the N-terminus of the five variants generated more hydrogen bonds with surrounding amino acids; hydrogen bond pair D254-I255 preserved in the C-terminus of the variants also contributes to the improved thermostability. Furthermore, the newly formed salt-bridge interaction (R27…E56) in D27R was identified as a crucial determinant for thermostability. (4) Our study discovered that substituting residues from the 25-loop will enhance the stability of the N-terminus and C-terminus simultaneously, restrict the most flexible regions of TLL, and result in improved thermostability.

Chemical profile of phenolic extracts from rapeseed meal and inhibitory effects on α-glucosidase: UPLC-MS/MS analysis, multispectral approaches, molecular simulation and ADMET analysis.

Rapeseed meal (RSM) is the by-product of rapeseed processing that enriches phenolic compounds. However, the comprehensive characterization of its phenolic substances in terms of composition and potential activities remains incomplete, leading to limited utilization in the food industry. In this study, the phenolic profile from RSM (referred to as RMP) was identified, and their inhibitory effects on α-glucosidase were investigated. UPLC-MS/MS analysis showed that a total of 466 phenolic compounds were detected in RMP. The primary components were sinapic acid (SA), caffeic acid (CA), salicylic acid (SAA), and astragalin (AS). Multispectral approaches demonstrated significant inhibitory capacity of RMP against α-glucosidase with a half inhibition value (IC50) of 0.32 mg/mL, with a stronger inhibition compared to CA/SAA/AS (IC50: 4.0, 5.9, and 0.9 mg/mL) in addition to the previously reported SA, suggesting a synergistic effect. Both RMP and CA/SAA/AS altered the secondary structure of α-glucosidase to quench its intrinsic fluorescence. Molecular simulation results revealed that hydrogen bonds and van der Waals forces primarily contributed to the interaction between CA/SAA/AS and α-glucosidase, as well as verified the stability of the binding process over the entire simulation duration. The ADMET analysis showed that CYP2D6 was not inhibited by CA/SAA/AS, which had no AMES toxicity, hepatotoxicity, and skin sensitization. This finding suggests the potential of RMP against α-glucosidase for the treatment of diabetes.

Using UPLC-LTQ-Orbitrap-MS and HPLC-CAD to Identify Impurities in Cycloastragenol, Which Is a Pre-Clinical Candidate for COPD.

Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease that has become the third leading cause of death worldwide. Cycloastragenol (CAG), which is the genuine sapogenin of the main active triterpene saponins in Astragali radix, is a bioavailable pre-clinical candidate for chronic obstructive pulmonary disease (COPD), and it was investigated in our previous study. In order to progress medical research, it was first efficiently produced on a 2.5-kg scale via Smith degradation from astragaloside IV (AS-IV). Simultaneously, since the impurity profiling of a drug is critical for performing CMC documentation in pre-clinical development, a study on impurities was carried out. As these structures do not contain chromophores and possess weak UV absorption characteristics, HPLC-CAD and UPLC-LTQ-Orbitrap-MS were employed to carry out the quality control of the impurities. Then, column chromatography (CC), preparative thin-layer chromatography (PTLC), and crystallization led to the identification of 15 impurities from CAG API. Among these impurities, compounds 1, 4, 9, 10, 14, and 15 were elucidated via spectroscopic analysis, and 2-3, 5-8, and 11-13 were putatively identified. Interestingly, the new compounds 9 and 14 were rare 10, 19-secocycloartane triterpenoids that displayed certain anti-inflammatory activities against LPS-induced lymphocyte cells and CSE-induced MLE-12 cells. Additionally, a plausible structural transformation pathway of the degradation compounds from CAG or AS IV was proposed. The information obtained will provide a material basis to carry out the quality control and clinical safety assurance of API and related prescriptions. Reasonable guidance will also be provided regarding the compounds with weak UV absorption characteristics.

Improving the Thermostability of Serine Protease PB92 from Bacillus alcalophilus via Site-Directed Mutagenesis Based on Semi-Rational Design.

Proteases have been widely employed in many industrial processes. In this work, we aimed to improve the thermostability of the serine protease PB92 from Bacillus alcalophilus to meet the high-temperature requirements of biotechnological treatments. Eight mutation sites (N18, S97-S101, E110, and R143) were identified, and 21 mutants were constructed from B-factor comparison and multiple sequence alignment and expressed via Bacillus subtilis. Among them, fifteen mutants exhibited increased half-life (t1/2) values at 65 °C (1.13-31.61 times greater than that of the wild type). Based on the composite score of enzyme activity and thermostability, six complex mutants were implemented. The t1/2 values of these six complex mutants were 2.12-10.05 times greater than that of the wild type at 65 °C. In addition, structural analysis revealed that the increased thermal stability of complex mutants may be related to the formation of additional hydrophobic interactions due to increased hydrophobicity and the decreased flexibility of the structure. In brief, the thermal stability of the complex mutants N18L/R143L/S97A, N18L/R143L/S99L, and N18L/R143L/G100A was increased 4-fold, which reveals application potential in industry.

Efficacy of washed microbiota transplantation for therapeutic targets of refractory functional constipation and the influencing factors: a single-center, retrospective, 24-week follow-up study.

BACKGROUND: The efficacy of washed microbiota transplantation (WMT) in terms of refractory functional constipation (FC)-related therapeutic targets and influencing factors have not been elucidated. This study aimed to assess the efficacy and influencing factors of WMT in treating refractory FC-related therapeutic targets. METHODS: The clinical data of patients diagnosed with refractory FC and received with WMT were retrospectively collected. The therapeutic targets included straining, hard stools, incomplete evacuation, a sense of anorectal obstruction, manual maneuvers, and decreased stool frequency. Each target was recorded as 1 (yes) or 0 (no). All patients were followed up for approximately 24 weeks from the end of the first course of WMT. The primary outcomes were the improvement rates for the individual therapeutic targets and the overall response in respect of the therapeutic targets decreased by 2 at weeks 4, 8, and 24. The secondary outcomes were the clinical remission rate (i.e., the proportion of patients with an average of 3 or more spontaneous complete bowel movements per week), clinical improvement rate (i.e., the proportion of patients with an average increase of 1 or more SCBMs/week or patients with remission), stool frequency, Wexner constipation score, Bristol Stool Form Scale (BSFS) score, and adverse events. The factors influencing the efficacy were also analyzed. RESULTS: Overall, 63 patients with 112 WMT courses were enrolled. The improvement rates at weeks 8 and 24 were 45.6% and 35.0%, 42.9% and 38.6%, 45.0% and 35.7%, 55.6% and 44.4%, and 60.9% and 50.0%, respectively, for straining, hard stools, incomplete evacuation, a sense of anorectal obstruction, and decreased stool frequency. The overall response rates were 49.2%, 50.8%, and 42.9%, respectively, at weeks 4, 8, and 24. The rates of clinical remission and clinical improvement were 54.0% and 68.3%, respectively, at weeks 4. The stool frequency, BSFS score, and Wexner constipation score tended to improve post-WMT. Only 22 mild adverse events were observed during the 112 WMT courses and the follow-up. The number of WMT courses was identified to be the independent factor influencing the efficacy. CONCLUSIONS: WMT is efficacious in improving refractory FC-related therapeutic targets. The effectiveness of WMT in the management of FC is enhanced with the administration of multiple courses.

The influence of social alienation on maintenance hemodialysis patients' coping styles: chain mediating effects of family resilience and caregiver burden.

Objective: Research on the possible impact of social alienation, family resilience, and caregiver burden on the coping styles of Chinese patients on maintenance hemodialysis (MHD) is scarce. We explore the influence of social alienation, family resilience, and caregiver burden on the coping styles of MHD patients, both directly and indirectly. Methods: We invited 173 MHD patients and their primary caregivers for a cross-sectional study; the study using convenience sampling method at the hemodialysis center of the First People's Hospital of Foshan. The Chinese version of the generalized social of alienation scale, the Chinese version of the simplified coping style questionnaire, and a sociodemographic questionnaire were completed by the MHD patients, while their primary caregivers had filled out the Chinese family resilience assessment scale, the Chinese version of the Zarit caregiver burden interview, and provided socio-demographic information. SPSS macro program PROCESS v3.3 Model 6 were used for analyses of chain-mediated effects. Results: In the mediating effects model, the direct influence of social alienation upon coping styles was significant (95% CI -0.050, -0.014), and social alienation indirectly impacted coping style by family resilience in a significant way (95% CI -0.012, -0.001) or caregiver burden (95% CI -0.013, -0.001). In addition, social alienation significantly impacted coping style by both family resilience and caregiver burden (95% CI -0.008, -0.001). Conclusion: Social alienation can exert both a direct and indirect influence on coping styles through the mediating factors of family resilience and caregiver burden. Clinicians can take interventions to strengthen family resilience and reduce caregiver burden, which may be useful in improving socially isolated behaviors and coping skills in MHD patients.

Rational N,P-Codoped pH-Activatable Red Carbon Dot for In Vitro and In Vivo Tumor Imaging.

Tumor detection and imaging via tumor microenvironmental indicators can have practical value. Here, a low-pH-responsive red carbon dot (CD) was prepared via a hydrothermal reaction for specific tumor imaging in vitro and in vivo. The probe responded to the acidic tumor microenvironment. The CDs are codoped by nitrogen and phosphorene and contain anilines on the surface. These anilines are efficient electron donors and modulate the pH response: Fluorescence is undetectable at common physical pH (>7.0), but red fluorescence (600-720 nm) increases with decreasing pH. The inactivation of fluorescence is due to three aspects: photoinduced electron transfer from anilines, deprotonation-induced energy states changing, and particle aggregation-induced quenching. It is believed that this pH-responsive character of CD is better than other reported CDs. Thus, in vitro images of HeLa cells show strong fluorescence that is 4-fold higher than normal cells. Subsequently, the CDs are used for in vivo imaging of tumors in mice. Tumors can be clearly observed within 1 h, and clearance of CDs will be finished within 24 h due to the small size of the CDs. The CDs offer excellent tumor-to-normal tissue (T/N) ratios and have great potential for biomedical research and disease diagnosis.

Strain Tunable Thermoelectric Material: Janus ZrSSe Monolayer.

Thermoelectric (TE) performance of the Janus ZrSSe monolayer under biaxial strain is systematically explored by the first-principles approach and Boltzmann transport theory. Our results show that the Janus ZrSSe monolayer has excellent chemical, dynamical, thermal, and mechanical stabilities, which provide a reliable platform for strain tuning. The electronic structure and TE transport parameters of the Janus ZrSSe monolayer can be obviously tuned by biaxial strain. Under 2% tensile strain, the optimal power factor PF of the n-type-doped Janus ZrSSe monolayer reaches 46.36 m W m-1 K-2 at 300 K. This value is higher than that of the most classical TE materials. Under 6% tensile strain, the maximum ZT values for the p-type- and n-type-doped Janus ZrSSe monolayers are 4.41 and 4.88, respectively, which are about 3.83 and 1.49 times the results of no strain, respectively. Such high TE performance can be attributed to high band degeneracy and short phonon relaxation time under strain, causing simultaneous increase of the Seebeck coefficient and suppression of the phonon thermal transport. Present work demonstrates that the Janus ZrSSe monolayer is a promising candidate as a strain-tunable TE material and stimulates further experimental synthesis.

Boosting thermoelectric performance of HfSe2 monolayer by selectivity chemical adsorption.

In this work, a strategy to boosting thermoelectric (TE) performance of 2D materials is explored. We find that, appropriate chemical adsorption of atoms can effectively increase the TE performance of HfSe2 monolayer. Our results show that the adsorption of Ni atom on HfSe2 monolayer (Ni-HfSe2) can improve the optimal power factor PF and ZT at 300 K, increased by more than ∼67% and ∼340%, respectively. The PF and ZT of Ni-HfSe2 at 300 K can reach 85.06 mW m-1 K-2 and 3.09, respectively. The detailed study reveal that the adsorption of Ni atom can induce additional conductional channels of electrons, enhance the coupling of acoustic-optical phonons and the phonon anharmonicity, resulting in an obvious increment of electrical conductivity (increased by more than ∼89%) in n-type doped system and an ultralow phonon thermal conductivity (1.17 W/mK at 300 K). The high electrical conductivity and ultralow phonon thermal conductivity results in the significant increments of PF and ZT. Our study also shows that, Ni-HfSe2 is a thermal, dynamic and mechanical stable structure, which can be employed in TE application. Our research indicates that selectivity chemical adsorption is a promising way to increase TE performance of 2D materials.

TRIM52 aggravated inflammation and pyroptosis in dextran sulfate sodium-induced inflammatory bowel disease through activation of the TLR4/NF-κBs pathway.

INTRODUCTION: Inflammatory bowel disease (IBD), which mainly leads to diarrhea, fatigue, stool blood, abdominal pain, and cramping, is threatening public health. Tripartite motif-containing 52 (TRIM52) has been reported to play an important role in inflammatory responses via activating the toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway. However, the causes of IBD need to be elucidated, and the function of TRIM52 in IBD remains unclear. Here, we demonstrated that TRIM52 aggravated inflammation and pyroptosis in dextran sulfate sodium (DSS)-induced IBD by activating TLR4/NF-κBs pathway. METHODS: The colitis model was established on mice through DSS induction. For the TRIM52 knockdown, the mice were infected with a recombinant adenoviral vector expressing sgRNAs targeting TRIM52. RT-qPCR, western blot, and immunohistochemistry were performed to verify TRIM52 expression in DSS-induced IBD. The body weight, disease activity index, colon length, and H&E staining were used to assess the IBD symptoms in mice with TRIM52 knockdown. The inflammatory responses were examined by RT-qPCR and ELISA measuring tumor necrosis factor-α (TNF-α), inter-leukin 6 (IL-6), and interleukin 1ß (IL-1ß). Furthermore, the pyroptosis in colon tissue was detected by western blot. Finally, the TLR4/NF-κBs pathway activity was also examined by western blot. RESULTS: TRIM52 expression was up-regulated in DSS-induced IBD, and knockdown of TRIM52 could alleviate the symptoms of IBD. TRIM52 knockdown retarded DSS-induced inflammatory response and inhibited DSS-induced pyroptosis in colon tissue. In addition, TRIM52 played a role in activating TLR4/NF-κBs pathway. CONCLUSION: Knockdown of TRIM52 alleviated inflammation and pyroptosis in IBD by regulating TLR4/NF-κBs pathway. TRIM52 is expected to be a novel diagnostic indicator for IBD and a target of therapeutic treatment.

Palladium(II)-Catalyzed Regioselective Hydroesterification of 1,3-Conjugated Enynes with Aryl Formates.

An effective Pd-catalyzed regioselective hydroesterification of 1,3-conjugated enynes with aryl formates was developed. Under the Pd-CyDPEphos catalytic system, the conjugated enynes reacted with phenyl formates and selectively provided the 2-ester-substituted 1,3-dienes in good yields with excellent regioselectivities.

Hyaluronic acid-functionalized redox-responsive organosilica nanoparticles for targeted resveratrol delivery to attenuate acrylamide-induced toxicity.

The purpose of this study is to construct a redox-responsive and targeted nanoparticle to effectively deliver resveratrol (Res) for alleviating acrylamide (ACR) toxicity. Here, Res-loaded tetrasulfide-containing organosilica nanoparticles (DSMSNs) functionalized with hyaluronic acid on the surface (DSMSNs@Res@HA) were prepared. The DSMSNs@Res@HA nanoparticles were spherical with an encapsulation efficiency of 46.68 ± 1.64 % and a hydrated particle size of about 237.73 nm. As expected, DSMSNs@Res@HA were capable of significantly protecting PC12 cells against ACR-induced damage in oxidative stress, mitochondrial membrane potential decrease, and cell apoptosis compared with free Res and DSMSNs@Res at the equivalent dose. Moreover, DSMSNs@Res@HA could be biodegraded and released Res in response to GSH stimulus. In vivo experiments suggested that DSMSNs@Res@HA significantly reduced histological damage in the brain, liver, and kidney of rats compared with free Res and DSMSNs@Res. After oral administration of DSMSNs@Res@HA, the intestinal flora of ACR-treated rats could be effectively regulated by improving the species uniformity and abundance as well as recovering the species diversity. According to these findings, DSMSNs@Res@HA is worth further investigation as a potential therapeutic nanomedicine to alleviate ACR toxicity and restore gut microbiota diversity.