Role of ESCCAL-1 in regulating exocytosis of AuNPs in human esophageal squamous carcinoma cells.

Exocytosis is a critical factor for designing efficient nanocarriers and determining cytotoxicity. However, the research on the exocytosis mechanism of nanoparticles, especially the role of long non-coding RNAs (lncRNA), has not been reported. In this study, the exocytosis of AuNPs in the KYSE70 cells and the involved molecular pathways of exocytosis are analyzed. It demonstrates that nanoparticles underwent time-dependent release from the cells by exocytosis, and the release of ß-hexosaminidase confirms that AuNPs are excreted through lysosomes. Mechanistic studies reveal that lncRNA ESCCAL-1 plays a vital role in controlling the exocytosis of AuNPs through activation of the MAPK pathway, including the phosphorylation of ERK and JNK. The study implies that the ESCCAL-1-mediated pathway plays an important role in the exocytosis of AuNPs in KYSE70 cells. This finding has implications for the role of ESCCAL-1 on the drug resistance of esophagus cancer by controlling lysosome-mediated exocytosis.

Low hysteresis, water retention, anti-freeze multifunctional hydrogel strain sensor for human-machine interfacing and real-time sign language translation.

Hydrogel strain sensors have received increasing attention due to their potential applications in human-machine interfaces and flexible electronics. However, they usually suffer from both mechanical and electrical hysteresis and poor water retention, which limit their practical applications. To address this challenge, a poly(acrylic acid-co-acrylamide) hydrogel crosslinked by silica nanoparticles is fabricated via photo polymerization and salting-out of hydrophilic ions for the strain sensor. The resulting hydrogel strain sensor possessed low electrical hysteresis (1.6%), low mechanical hysteresis (<7%), high cycle stability (>10 000 cycles), high durability, water retention and anti-freezing ability. Moreover, this strain sensor can be used as a wearable sensor for real-time control of robotic hands and hand gesture recognition. Finally, a sign language translation system has been demonstrated with the aid of machine learning, achieving recognition rates of over 98% for 15 different sign languages. This work offers a promising prospect for human-machine interfaces, smart wearable devices, and the Internet of Things.

Bioinspired Mechanically Robust and Recyclable Hydrogel Microfibers Based on Hydrogen-Bond Nanoclusters.

Mechanically robust hydrogel fibers have demonstrated great potential in energy dissipation and shock-absorbing applications. However, developing such materials that are recyclable, energy-efficient, and environmentally friendly remains an enormous challenge. Herein, inspired by spider silk, a continuous and scalable method is introduced for spinning a polyacrylamide hydrogel microfiber with a hierarchical sheath-core structure under ambient conditions. Applying pre-stretch and twist in the as-spun hydrogel microfibers results in a tensile strength of 525 MPa, a toughness of 385 MJ m-3, and a damping capacity of 99%, which is attributed to the reinforcement of hydrogen-bond nanoclusters within the microfiber matrix. Moreover, it maintains both structural and mechanical stability for several days, and can be directly dissolved in water, providing a sustainable spinning dope for re-spinning into new microfibers. This work provides a new strategy for the spinning of robust and recyclable hydrogel-based fibrous materials.

Endoplasmic reticulum stress: bridging inflammation and obesity-associated adipose tissue.

Obesity presents a significant global health challenge, increasing the susceptibility to chronic conditions such as diabetes, cardiovascular disease, and hypertension. Within the context of obesity, lipid metabolism, adipose tissue formation, and inflammation are intricately linked to endoplasmic reticulum stress (ERS). ERS modulates metabolism, insulin signaling, inflammation, as well as cell proliferation and death through the unfolded protein response (UPR) pathway. Serving as a crucial nexus, ERS bridges the functionality of adipose tissue and the inflammatory response. In this review, we comprehensively elucidate the mechanisms by which ERS impacts adipose tissue function and inflammation in obesity, aiming to offer insights into targeting ERS for ameliorating metabolic dysregulation in obesity-associated chronic diseases such as hyperlipidemia, hypertension, fatty liver, and type 2 diabetes.

Effectiveness of psychoeducational interventions on psychological distress and health-related quality of life among patients with maintenance hemodialysis: a systematic review and meta-analysis.

OBJECTIVE: To examine the effectiveness of psychoeducational interventions on depression, anxiety, and health-related quality of life (HRQOL) for people undergoing maintenance hemodialysis (MHD). METHODS: This review used systematic review and meta-analysis as the research design. Nine databases, including PubMed, Web of Science, Embase, CINAHL Complete, Cochrane Library, CNKI, WanFang, VIP, and Chinese Biomedical Literature Database, were searched from the inception to the 8th of July 2023. Two reviewers independently identified randomized controlled trials (RCT) examining the effects of psychoeducational interventions on MHD patients. RESULTS: Fourteen studies involving 1134 MHD patients were included in this review. The results of meta-analyses showed that psychoeducational intervention had significant short-term (< 1 m) (SMD: -0.87, 95% CI: -1.54 to -0.20, p = 0.01, I2 = 91%; 481 participants), and medium-term (1-3 m) (SMD: -0.29, 95% CI: -0.50 to -0.08, p = 0.01, I2 = 49%; 358 participants) on anxiety in MHD patients, but the effects could not be sustained at longer follow-ups. Psychoeducational interventions can also have short-term (< 1 m) (SMD: -0.65, 95% CI: -0.91 to -0.38, p < 0.00001, I2 = 65%; 711 participants) and medium-term (1-3 m) (SMD: -0.42, 95% CI: -0.76 to -0.09, p = 0.01, I2 = 69%; 489 participants) effects in reducing depression levels in MHD patients. Psychoeducational interventions that use coping strategies, goal setting, and relaxation techniques could enhance the QOL in MHD patients in the short term (< 1 m) (SMD: 0.86, 95% CI: 0.42 to 1.30, p = 0.02, I2 = 86%; 241 participants). CONCLUSIONS: Psychoeducational interventions have shown great potential to improve anxiety, depression, and quality of life in patients with MHD at the short- and medium-term follow-ups.Trial registration number: CRD42023440561.

Apoptosis of Dendritic Cells and Autoimmune Disease.

Dendritic cells (DCs), the most efficient antigen-presenting cells (APCs), bridge the innate and adaptive immune systems. As such, the turn-over of DCs is critical during autoimmune responses, and the dysregulation of DC apoptosis could cause severe immune destruction in the host. For example, reduction of immunogenic DCs by increased apoptosis could lead to immune tolerance to pathogen infection that might allow exposure of nuclear autoantigens, whereas reduced apoptosis could result in long-term lymphocyte activation to break the immune tolerance for the development of autoimmune disease. Thus, keeping a balance between survival and apoptosis of DCs is crucial to maintain immune homeostasis. In this review, we summarize the recent development on the factors inducing DC apoptosis and their underlying mechanisms to provide insights into the immunopathogenesis of some autoimmune diseases, which could lead to effective therapeutic interventions in the clinics.

Association between CYP2C9 and VKORC1 genetic polymorphisms and efficacy and safety of warfarin in Chinese patients.

OBJECTIVES: Genetic variation has been a major contributor to interindividual variability of warfarin dosage requirement. The specific genetic factors contributing to warfarin bleeding complications are largely unknown, particularly in Chinese patients. In this study, 896 Chinese patients were enrolled to explore the effect of CYP2C9 and VKORC1 genetic variations on both the efficacy and safety of warfarin therapy. METHODS AND RESULTS: Univariate analyses unveiled significant associations between two specific single nucleotide polymorphisms rs1057910 in CYP2C9 and rs9923231 in VKORC1 and stable warfarin dosage ( P  < 0.001). Further, employing multivariate logistic regression analysis adjusted for age, sex and height, the investigation revealed that patients harboring at least one variant allele in CYP2C9 exhibited a heightened risk of bleeding events compared to those with the wild-type genotype (odds ratio = 2.16, P  = 0.04). Moreover, a meta-analysis conducted to consolidate findings confirmed the associations of both CYP2C9 (rs1057910) and VKORC1 (rs9923231) with stable warfarin dosage. Notably, CYP2C9 variant genotypes were significantly linked to an increased risk of hemorrhagic complications ( P  < 0.00001), VKORC1 did not demonstrate a similar association. CONCLUSION: The associations found between specific genetic variants and both stable warfarin dosage and bleeding risk might be the potential significance of gene detection in optimizing warfarin therapy for improving patient efficacy and safety.

Insecticidal Activity and Molecular Target by Morphological Analysis, RNAseq, and Molecular Docking of the Aryltetralin Lignan Lactone Helioxanthin, Isolated from Taiwania flousiana Gaussen.

Botanical insecticides are considered an environmentally friendly approach to insect control because they are easily biodegraded and cause less environmental pollution compared to traditional chemical pesticides. In this study, we reported the insecticidal activities of the ingredients from Taiwania flousiana Gaussen (T. flousiana). Five compounds, namely helioxanthin (C1), taiwanin E (C2), taiwanin H (C3), 7,4'-dimethylamentoflavone (C4), and 7,7″-di-O-methylamentoflavone (C5), were isolated and tested against the second, third, and fourth instar larvae of Aedes aegypti. Our results indicated that all five compounds showed insecticidal activities, and helioxanthin, which is an aryltetralin lignan lactone, was the most effective with LC50 values of 0.60, 2.82, and 3.12 mg/L, respectively, 48 h after application, with its activity against the second instar larvae similar to that of pyrethrin and better than that of rotenone. Further studies found that helioxanthin accumulated in the gastric cecum and the midgut and caused swelling of mitochondria with shallow matrices and fewer or disappeared crista. Additionally, our molecular mechanisms studies indicated that the significantly differentially expressed genes (DEGs) were mainly associated with mitochondria and the cuticle, among which the voltage-dependent anion-selective channel (VDAC) gene was the most down-regulated by helioxanthin, and VDAC is the potential target of helioxanthin by binding to specific amino acid residues (His 122 and Glu 147) via hydrogen bonds. We conclude that aryltetralin lignan lactone is a potential class of novel insecticides by targeting VDAC.

Disulfide-constrained peptide scaffolds enable a robust peptide-therapeutic discovery platform.

Peptides present an alternative modality to immunoglobulin domains or small molecules for developing therapeutics to either agonize or antagonize cellular pathways associated with diseases. However, peptides often suffer from poor chemical and physical stability, limiting their therapeutic potential. Disulfide-constrained peptides (DCP) are naturally occurring and possess numerous desirable properties, such as high stability, that qualify them as drug-like scaffolds for peptide therapeutics. DCPs contain loop regions protruding from the core of the molecule that are amenable to peptide engineering via direct evolution by use of phage display technology. In this study, we have established a robust platform for the discovery of peptide therapeutics using various DCPs as scaffolds. We created diverse libraries comprising seven different DCP scaffolds, resulting in an overall diversity of 2 x 1011. The effectiveness of this platform for functional hit discovery has been extensively evaluated, demonstrating a hit rate comparable to that of synthetic antibody libraries. By utilizing chemically synthesized and in vitro folded peptides derived from selections of phage displayed DCP libraries, we have successfully generated functional inhibitors targeting the HtrA1 protease. Through affinity maturation strategies, we have transformed initially weak binders against Notch2 with micromolar Kd values to high-affinity ligands in the nanomolar range. This process highlights a viable hit-to-lead progression. Overall, our platform holds significant potential to greatly enhance the discovery of peptide therapeutics.

Assessing wound complications in gastroscopy with Streptomyces protease enzyme combined with Shutai.

Current gastroscopy practices necessitate a balance between procedural efficiency and patient safety. It has been hypothesized that increasing procedure outcomes through the use of Streptomyces protease enzyme and Shutai is possible; however, precise nature of any potential adverse reactions and complications remains unknown. In Zhanjiang, China, 213 patients undergoing gastroscopy participated in this controlled trial. The subjects were allocated at random into two groups: control and treatment. The treatment group was administered topical Streptomyces protease enzyme and intravenous Shutai. Using chi-square and t-tests, information regarding patient demographics, adverse reactions, wound healing, procedure duration, distress levels, and satisfaction was gathered and analysed. The demographic and medical history characteristics of the groups were comparable. There was a greater prevalence of modest immediate reactions in the treatment group (p < 0.05), whereas there were no significant variations observed in delayed reactions and long-term complications (p > 0.05). The treatment group exhibited superior efficiency metrics, including shorter durations for diagnosis, procedure completion and recuperation (p < 0.05). The treatment group exhibited significantly higher patient satisfaction scores (p < 0.05). The incorporation of Streptomyces protease enzyme and Shutai into gastroscopy procedures resulted in significantly enhanced level of procedural efficacy and patient contentment while not introducing an additional risk of long-term complications. The increase in moderate immediate reactions that have been observed requires additional research in order to determine their clinical significance. Although these agents present a possible progression in the field of gastroscopy, their application should be tempered by the immediate adverse reactions that have been documented.

IGFBP-rP1 is a potential therapeutic target in androgenic alopecia.

The available interventions for androgenic alopecia (AGA), the most common type of hair loss worldwide, remain limited. The insulin growth factor (IGF) system may play an important role in the pathogenesis of AGA. However, the exact role of IGF binding protein-related protein 1 (IGFBP-rP1) in hair growth and AGA has not been reported. In this study, we first found periodic variation in IGFBP-rP1 during the hair cycle transition in murine hair follicles (HFs). We further demonstrated that IGFBP-rP1 levels were lower in the serum and scalp HFs of individuals with AGA than in those of healthy controls. Subsequently, we verified that IGFBP-rP1 had no cytotoxicity to human outer root sheath cells (HORSCs) and that IGFBP-rP1 reversed the inhibitory effects of DHT on the migration of HORSCs in vitro. Finally, a DHT-induced AGA mouse model was created. The results revealed that the expression of IGFBP-rP1 in murine HFs was downregulated after DHT treatment and that subcutaneous injection of IGFBP-rP1 delayed catagen occurrence and prolonged the anagen phase of HFs in mice with DHT-induced AGA. The present work shows that IGFBP-rP1 is involved in hair cycle transition and exhibits great therapeutic potential for AGA.

Oxidation with potassium ferrate for the one-pot preparation of carboxylated cellulose II nanocrystals.

Cellulose II nanocrystals (CNC II) possess a higher thermal stability and improved emulsifying capability than cellulose I nanocrystals (CNC I) owing to the higher density of their hydrogen bonds and more larger surface areas. Therefore, CNC II exhibit substantial advantages for value-added nanocomposite materials. Current CNC II preparation methods are mainly based on a two-pot reaction involving acid hydrolysis and crystal transformation. In this study, considering the oxidative nature of potassium ferrate (K2FeO4) in an alkaline environment containing a small amount of sodium hypochlorite (NaClO), a one-step and efficient approach was developed for the preparation of carboxyl-bearing CNC II from cotton pulp, affording a maximum CNC II yield of 45.14 %. Atomic force microscopy analysis revealed that the prepared CNCs exhibited a "rod-like" shape with a width of ~7 nm and a length of ~269 nm. The resulting CNC II also exhibited excellent thermal stability (Tonset = 311.4 °C). Furthermore, high-internal-phase Pickering emulsions (HIPPEs) stabilized by CNC II were prepared to stabilize liquid paraffin in the absence of surfactant. The results revealed that CNC II could be used as an effective emulsifier to fabricate the stable and gel-like HIPPEs, and are promising for the preparation of high value-added nanocomposite materials.

Crystallographic and biochemical analyses of a far-red allophycocyanin to address the mechanism of the super-red-shift.

Far-red absorbing allophycocyanins (APC), identified in cyanobacteria capable of FRL photoacclimation (FaRLiP) and low-light photoacclimation (LoLiP), absorb far-red light, functioning in energy transfer as light-harvesting proteins. We report an optimized method to obtain high purity far-red absorbing allophycocyanin B, AP-B2, of Chroococcidiopsis thermalis sp. PCC7203 by synthesis in Escherichia coli and an improved purification protocol. The crystal structure of the trimer, (PCB-ApcD5/PCB-ApcB2)3, has been resolved to 2.8 Å. The main difference to conventional APCs absorbing in the 650-670 nm range is a largely flat chromophore with the co-planarity extending, in particular, from rings BCD to ring A. This effectively extends the conjugation system of PCB and contributes to the super-red-shifted absorption of the α-subunit (λmax = 697 nm). On complexation with the ß-subunit, it is even further red-shifted (λmax, absorption = 707 nm, λmax, emission = 721 nm). The relevance of ring A for this shift is supported by mutagenesis data. A variant of the α-subunit, I123M, has been generated that shows an intense FR-band already in the absence of the ß-subunit, a possible model is discussed. Two additional mechanisms are known to red-shift the chromophore spectrum: lactam-lactim tautomerism and deprotonation of the chromophore that both mechanisms appear inconsistent with our data, leaving this question unresolved.

A novel natural variation in the promoter of GmCHX1 regulates conditional gene expression to improve salt tolerance in soybean.

Identification and characterization of soybean germplasm and gene(s)/allele(s) for salt tolerance is an effective way to develop improved varieties for saline soils. Previous studies identified GmCHX1 (Glyma03g32900) as a major salt tolerance gene in soybean, and two main functional variations were found in the promoter region (148/150 bp insertion) and the third exon with a retrotransposon insertion (3.78 kb). In the current study, we identified four salt-tolerant soybean lines, including PI 483460B (Glycine soja), carrying the previously identified salt-sensitive variations at GmCHX1, suggesting new gene(s) or new functional allele(s) of GmCHX1 in these soybean lines. Subsequently, we conducted quantitative trait locus (QTL) mapping in a recombinant-inbred line population (Williams 82 (salt-sensitive) × PI 483460B) to identify the new salt tolerance loci/alleles. A new locus, qSalt_Gm18, was mapped on chromosome 18 associated with leaf scorch score. Another major QTL, qSalt_Gm03, was identified to be associated with chlorophyll content ratio and leaf scorch score in the same chromosomal region of GmCHX1 on chromosome 3. Novel variations in a STRE (stress response element) cis-element in the promoter region of GmCHX1 were found to regulate the salt-inducible expression of the gene in these four newly identified salt-tolerant lines including PI 483460B. This new allele of GmCHX1 with salt-inducible expression pattern provides an energy cost efficient (conditional gene expression) strategy to protect soybean yield in saline soils without yield penalty under non-stress conditions. Our results suggest that there might be no other major salt tolerance locus similar to GmCHX1 in soybean germplasm, and further improvement of salt tolerance in soybean may rely on gene-editing techniques instead of looking for natural variations.

Construction of chitosan-derived porous nest-like C/SnO2 materials for microwave absorption.

Electromagnetic waves have an irreplaceable role as information carriers in civil and radar stealth fields, but they also lead to electromagnetic pollution and electromagnetic leakage. Therefore, electromagnetic wave absorbing materials that can reduce electromagnetic radiation have come into being. Especially, SnO2 has made a wave among many wave-absorbing materials as an easily tunable dielectric material, but it hardly has both broadband and powerful absorption properties. Here, the nested porous C/SnO2 composites derived from nitrogen-doped chitosan is obtained by freeze-drying and supplemented with carbonization treatment. The chitosan creates a nested cross-linked conductive network that can make part of the contribution to conduction loss. The amino groups contained in the molecule either help promote in situ nitrogen doping and trigger dipole polarization. The multiphase dissimilar interface between the nested carbon layer and the inner clad SnO2 formation is the major inducer of interfacial polarization. It reached intense absorption of -48.8 dB and bandwidth of 5.2 GHz at 3.46 mm. The interfacial polarization is confirmed to be the main force of dielectric loss by simulating the electromagnetic field distribution. In addition, the RCS simulation data assure the prospect of enticing applications of C/SnO2 composites in the field of radar stealth.

VDR Activation Attenuates Renal Tubular Epithelial Cell Ferroptosis by Regulating Nrf2/HO-1 Signaling Pathway in Diabetic Nephropathy.

Diabetic nephropathy (DN) is a serious microvascular complication of diabetes. Ferroptosis, a new form of cell death, plays a crucial role in the pathogenesis of DN. Renal tubular injury triggered by ferroptosis might be essential in this process. Numerous studies demonstrate that the vitamin D receptor (VDR) exerts beneficial effects by suppressing ferroptosis. However, the underlying mechanism has not been fully elucidated. Thus, they verified the nephroprotective effect of VDR activation and explored the mechanism by which VDR activation suppressed ferroptosis in db/db mice and high glucose-cultured proximal tubular epithelial cells (PTECs). Paricalcitol (PAR) is a VDR agonist that can mitigate kidney injury and prevent renal dysfunction. PAR treatment could inhibit ferroptosis of PTECs through decreasing iron content, increasing glutathione (GSH) levels, reducing malondialdehyde (MDA) generation, decreasing the expression of positive ferroptosis mediator transferrin receptor 1 (TFR-1), and enhancing the expression of negative ferroptosis mediators including ferritin heavy chain (FTH-1), glutathione peroxidase 4 (GPX4), and cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11). Mechanistically, VDR activation upregulated the NFE2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway to suppress ferroptosis in PTECs. These findings suggested that VDR activation inhibited ferroptosis of PTECs in DN via modulating the Nrf2/HO-1 signaling pathway.

Adsorption performance of ammonium molybdate modified Salix wood flour biochar for the treatment of monosodium glutamate wastewater.

ABSTRACTThe problem of wastewater pollution in the production of monosodium glutamate (MSG) is becoming more and more serious. A novel type of chemically modified Salix psammophila powder charcoal (SPPCAM) was synthesized to address the chemical oxygen demand (COD) and ammonia nitrogen (NH3-N) in MSG wastewater. SPPCAM was prepared by carbonization method, in which inorganic ammonium molybdate (AM) was used as modifier and Salix psammophila powder (SPP) was used as raw material. Under optimal treatment conditions, maximum removal rates (removal capacities) of 45.9% (3313.2 mg·L-1) for COD and 29.4% (23.2 mg·L-1) for NH3-N in MSG wastewater were achieved. The treatment results significantly outperforming the unmodified Salix psammophila powder charcoal (SPPC), which only achieved removal rates (removal capacities) of 10.6% (763.9 mg·L-1) for COD and 12.9% (10 mg·L-1) for NH3-N. SPPC and SPPCAM before and after preparation were analysed by FT-IR and XRD, and Mo ions in the form of Mo2C within SPPCAM were successfully loaded. SEM, EDS-Mapping, BET, and other methods were used to analyse SPPCAM before and after MSG wastewater treatment, demonstrating that SPPCAM effectively treated organic pollutants in monosodium glutamate wastewater. The NH3-N in the treated MSG wastewater has reached the standard of safe discharge.

Study on the structure characterization and swelling properties of the Fe3O4/CMS composite membrane.

In order to improve the functionality of cellulosic materials research and development of high performance soluble materials. Therefore, the Fe3O4/CMS composite membrane was prepared by using carboxymethyl salix powder (CMS) and Fe3O4 as raw materials, 1-propenyl-3-methylimidazolium chloride and dimethyl sulfoxide as dissolution system. The effects of swelling time, swelling temperature, pH and ionic strength on the swelling performance of Fe3O4/CMS composite membranes and the swelling kinetics of the composite membranes were studied. The structure of the composite membrane was characterized by SEM, FT-IR, XRD and TG. The results showed that the swelling degree reached 5.54 g·g-1, when the swelling time was 45 min, the swelling temperature was 65°C, the pH was 5 and the ionic strength was 0.08 mol·L-1. The initial phase of dissolution of the composite membrane fits well with the Fickian diffusion model, and the whole dissolution process belongs to the Schott model, indicating that the main role of the dissolution process is the diffusion of water molecules, while the composite membrane can be preserved for a long time at high temperature, which provides sustainability for the composite membrane. The characterization results showed that the surface of Fe3O4/CMS composite film was rough with small grooves. The O-H effect was enhanced and the Fe-O absorption peak appeared at 600 cm-1, indicating that Fe3O4 had been successfully loaded onto the cellulose membrane. The Fe3O4/CMS composite membrane belonged to cellulose type II structure, meanwhile, the composite membrane had good thermal stability.