F127-SE-tLAP thermosensitive hydrogel alleviates bleomycin-induced skin fibrosis via TGF-ß/Smad pathway.

BACKGROUND: Skin fibrosis affects the normal function of the skin. TGF-ß1 is a key cytokine that affects organ fibrosis. The latency-associated peptide (LAP) is essential for TGF-ß1 activation. We previously constructed and prepared truncated LAP (tLAP), and confirmed that tLAP inhibited liver fibrosis by affecting TGF-ß1. SPACE peptide has both transdermal and transmembrane functions. SPACE promotes the delivery of macromolecules through the stratum corneum into the dermis. This study aimed to alleviate skin fibrosis through the delivery of tLAP by SPACE. METHODS: The SPACE-tLAP (SE-tLAP) recombinant plasmid was constructed. SE-tLAP was purified by nickel affinity chromatography. The effects of SE-tLAP on the proliferation, migration, and expression of fibrosis-related and inflammatory factors were evaluated in TGF-ß1-induced NIH-3T3 cells. F127-SE-tLAP hydrogel was constructed by using F127 as a carrier to load SE-tLAP polypeptide. The degradation, drug release, and biocompatibility of F127-SE-tLAP were evaluated. Bleomycin was used to induce skin fibrosis in mice. HE, Masson, and immunohistochemistry were used to observe the skin histological characteristics. RESULTS: SE-tLAP inhibited the proliferation, migration, and expression of fibrosis-related and inflammatory factors in NIH-3T3 cells. F127-SE-tLAP significantly reduced ECM production, collagen deposition, and fibrotic pathological changes, thereby alleviating skin fibrosis. CONCLUSION: F127-SE-tLAP could increase the transdermal delivery of LAP, reduce the production and deposition of ECM, inhibit the formation of dermal collagen fibers, and alleviate the progression of skin fibrosis. It may provide a new idea for the therapy of skin fibrosis.

THSG alleviates cerebral ischemia/reperfusion injury via the GluN2B-CaMKII-ERK1/2 pathway.

BACKGROUND: The potential therapeutic targeting of PINK1-PARK2-mediated mitophagy against cerebral ischemia/reperfusion (CI/R) injury involves the pathophysiological processes of neurovascular unit (NVU) and is closely associated with N-methyl-D-aspartate receptors (NMDARs) commonly expressed in NVU. 2,3,5,4'-Tetrahydroxy-stilbene-2-O-ß-D-glucoside (THSG), a compound derived from the traditional Chinese medicine Polygonum multiflorum Thunb., has demonstrated notable neuroprotective properties against CI/R injury. However, it remains unclear whether THSG exerts its protective effects through GluN2B related PINK1/ PARK2 pathway. PURPOSE: This study aims to explore the pharmacological effects of THSG on alleviating CI/R injury via the GluN2B-CaMKII-ERK1/2 pathway. METHODS: THSG neuroprotection against CI/R injury was studied in transient middle cerebral artery occlusion/reversion (tMCAO/R) model rats and in oxygen and glucose deprivation/ reoxygenation (OGD/R) induced neurons. PINK1-PARK2-mediated mitophagy involvement in the protective effect of THSG was investigated in tMCAO/R rats and OGD/R-induced neurons via THSG and 3-methyladenine (3-MA) treatment. Furthermore, the beneficial role of GluN2B in reperfusion and its contribution to the THSG effect via CaMKII-ERK1/2 and PINK1-PARK2-mediated mitophagy was explored using the GluN2B-selective antagonist Ro 25-6981 both in vivo and in vitro. Finally, the interaction between THSG and GluN2B was evaluated using molecular docking. RESULTS: THSG significantly reduced infarct volume, neurological deficits, penumbral neuron structure, and functional damage, upregulated the inhibitory apoptotic marker Bcl-2, and suppressed the increase of pro-apoptotic proteins including cleaved caspase-3 and Bax in tMCAO/R rats. THSG (1 µM) markedly improved the neuronal survival under OGD/R conditions. Furthermore, THSG promoted PINK1 and PARK2 expression and increased mitophagosome numbers and LC3-II-LC3-I ratio both in vivo and in vitro. The effects of THSG were considerably abrogated by the mitophagy inhibitor 3-MA in OGD/R-induced neurons. Inhibiting GluN2B profoundly decreased mitophagosome numbers and OGD/R-induced neuronal viability. Specifically, inhibiting GluN2B abolished the protection of THSG against CI/R injury and reversed the upregulation of PINK1-PARK2-mediated mitophagy by THSG. Inhibiting GluN2B eliminated THSG upregulation of ERK1/2 and CaMKII phosphorylation. The molecular docking analysis results demonstrated that THSG bound to GluN2B (binding energy: -5.2 ± 0.11 kcal/mol). CONCLUSIONS: This study validates the premise that THSG alleviates CI/R injury by promoting GluN2B expression, activating CaMKII and ERK1/2, and subsequently enhancing PINK1-PARK2-mediated mitophagy. This work enlightens the potential of THSG as a promising candidate for novel therapeutic strategies for treating ischemic stroke.

Photodynamic and nitric oxide therapy-based synergistic antimicrobial nanoplatform: an advanced root canal irrigation system for endodontic bacterial infections.

BACKGROUND: The main issues faced during the treatment of apical periodontitis are the management of bacterial infection and the facilitation of the repair of alveolar bone defects to shorten disease duration. Conventional root canal irrigants are limited in their efficacy and are associated with several side effects. This study introduces a synergistic therapy based on nitric oxide (NO) and antimicrobial photodynamic therapy (aPDT) for the treatment of apical periodontitis. RESULTS: This research developed a multifunctional nanoparticle, CGP, utilizing guanidinylated poly (ethylene glycol)-poly (ε-Caprolactone) polymer as a carrier, internally loaded with the photosensitizer chlorin e6. During root canal irrigation, the guanidino groups on the surface of CGP enabled effective biofilm penetration. These groups undergo oxidation by hydrogen peroxide in the aPDT process, triggering the release of NO without hindering the production of singlet oxygen. The generated NO significantly enhanced the antimicrobial capability and biofilm eradication efficacy of aPDT. Furthermore, CGP not only outperforms conventional aPDT in eradicating biofilms but also effectively promotes the repair of alveolar bone defects post-eradication. Importantly, our findings reveal that CGP exhibits significantly higher biosafety compared to sodium hypochlorite, alongside superior therapeutic efficacy in a rat model of apical periodontitis. CONCLUSIONS: This study demonstrates that CGP, an effective root irrigation system based on aPDT and NO, has a promising application in root canal therapy.

Protein phosphorylation and kinases: Potential therapeutic targets in necroptosis.

Necroptosis is a pivotal contributor to the pathogenesis of various human diseases, including those affecting the nervous system, cardiovascular system, pulmonary system, and kidneys. Extensive investigations have elucidated the mechanisms and physiological ramifications of necroptosis. Among these, protein phosphorylation emerges as a paramount regulatory process, facilitating the activation or inhibition of specific proteins through the addition of phosphate groups to their corresponding amino acid residues. Currently, the targeting of kinases has gained recognition as a firmly established and efficacious therapeutic approach for diverse diseases, notably cancer. In this comprehensive review, we elucidate the intricate role of phosphorylation in governing key molecular players in the necroptotic pathway. Moreover, we provide an in-depth analysis of recent advancements in the development of kinase inhibitors aimed at modulating necroptosis. Lastly, we deliberate on the prospects and challenges associated with the utilization of kinase inhibitors to modulate necroptotic processes.

Association between triglyceride-glucose index and colorectal polyps: A retrospective cross-sectional study.

BACKGROUND: Colorectal polyps (CPs) are frequently occurring abnormal growths in the colorectum, and are a primary precursor of colorectal cancer (CRC). The triglyceride-glucose (TyG) index is a novel marker that assesses metabolic health and insulin resistance, and has been linked to gastrointestinal cancers. AIM: To investigate the potential association between the TyG index and CPs, as the relation between them has not been documented. METHODS: A total of 2537 persons undergoing a routine health physical examination and colonoscopy at The First People's Hospital of Kunshan, Jiangsu Province, China, between January 2020 and December 2022 were included in this retrospective cross-sectional study. After excluding individuals who did not meet the eligibility criteria, descriptive statistics were used to compare characteristics between patients with and without CPs. Logistic regression analyses were conducted to determine the associations between the TyG index and the prevalence of CPs. The TyG index was calculated using the following formula: Ln [triglyceride (mg/dL) × glucose (mg/dL)/2]. The presence and types of CPs was determined based on data from colonoscopy reports and pathology reports. RESULTS: A nonlinear relation between the TyG index and the prevalence of CPs was identified, and exhibited a curvilinear pattern with a cut-off point of 2.31. A significant association was observed before the turning point, with an odds ratio (95% confidence interval) of 1.70 (1.40, 2.06), P < 0.0001. However, the association between the TyG index and CPs was not significant after the cut-off point, with an odds ratio (95% confidence interval) of 0.57 (0.27, 1.23), P = 0.1521. CONCLUSION: Our study revealed a curvilinear association between the TyG index and CPs in Chinese individuals, suggesting its potential utility in developing colonoscopy screening strategies for preventing CRC.

Deciphering the binding behavior and interaction mechanism of apigenin and α-glucosidase based on multi-spectroscopic and molecular simulation studies.

This study investigated the molecular mechanism underlying the binding interaction between apigenin (API) and α-glucosidase (α-glu) by a combination of experimental techniques and computational simulation strategies. The spontaneously formation of stable API-α-glu complex was mainly driven by hydrogen bonds and hydrophobic forces, leading to a static fluorescence quenching of α-glu. The binding of API induced secondary structure and conformation changes of α-glu, decreasing the surface hydrophobicity of protein. Computational simulation results demonstrated that API could bind into the active cavity of α-glu via its interaction with active residues at the binding site. The important roles of key residues responsible for the binding stability and affinity between API and α-glu were further revealed by MM/PBSA results. In addition, it can be found that the entrance of active site tended to close after API binding as a result of its interaction with gate keeping residues. Furthermore, the structural basis for the binding interaction behavior of API was revealed and visualized by weak interaction analysis. The findings of our study revealed atomic-level mechanism of the interaction between API, which might shed light on the development of better inhibitors.

H2S-Releasing Versatile Montmorillonite Nanoformulation Trilogically Renovates the Gut Microenvironment for Inflammatory Bowel Disease Modulation.

Abnormal activation of the intestinal mucosal immune system, resulting from damage to the intestinal mucosal barrier and extensive invasion by pathogens, contributes to the pathogenesis of inflammatory bowel disease (IBD). Current first-line treatments for IBD have limited efficacy and significant side effects. An innovative H2S-releasing montmorillonite nanoformulation (DPs@MMT) capable of remodeling intestinal mucosal immune homeostasis, repairing the mucosal barrier, and modulating gut microbiota is developed by electrostatically adsorbing diallyl trisulfide-loaded peptide dendrimer nanogels (DATS@PDNs, abbreviated as DPs) onto the montmorillonite (MMT) surface. Upon rectal administration, DPs@MMT specifically binds to and covers the damaged mucosa, promoting the accumulation and subsequent internalization of DPs by activated immune cells in the IBD site. DPs release H2S intracellularly in response to glutathione, initiating multiple therapeutic effects. In vitro and in vivo studies have shown that DPs@MMT effectively alleviates colitis by eliminating reactive oxygen species (ROS), inhibiting inflammation, repairing the mucosal barrier, and eradicating pathogens. RNA sequencing revealed that DPs@MMT exerts significant immunoregulatory and mucosal barrier repair effects, by activating pathways such as Nrf2/HO-1, PI3K-AKT, and RAS/MAPK/AP-1, and inhibiting the p38/ERK MAPK, p65 NF-κB, and JAK-STAT3 pathways, as well as glycolysis. 16S rRNA sequencing demonstrated that DPs@MMT remodels the gut microbiota by eliminating pathogens and increasing probiotics. This study develops a promising nanoformulation for IBD management.

Rapid quantitative evaluation of total polar materials (TPM) in frying oil based on an "off-on" fluorescence viscosity response probe.

The content of total polar material (TPM) is considered as a comprehensive indicator to evaluate the quality of edible oils which should be discarded and no longer be used when TPM content exceeding 27 %. Nevertheless, there is currently a lack of a convenient and efficient TPM detection method, which is a meaningful challenge. With the increase of TPM content, the viscosity of frying oil grows, and the two maintain a satisfactory positive correlation. Consequently, an "off-on" fluorescence probe TCF-PR method based on viscosity-response has been developed. There exists a good linear relationship between the fluorescence intensity of the probe and the TPM content of soybean oil ((R2 = 0.9936) and salad oil (R2 = 0.9878), accompanying with the advantage of fast response (3 s), which means the rapid detection of TPM can be realized to determine the quality of frying oil in the field of food safety.

Regulation of the migration of colorectal cancer stem cells via the TLR4/MyD88 signaling pathway by the novel surface marker CD14 following LPS stimulation.

Cell surface markers are most widely used in the study of cancer stem cells (CSCs). However, cell surface markers that are safely and stably expressed in CSCs have yet to be identified. Colonic CSCs express leukocyte CD14. CD14 binding to the ligand lipopolysaccharide (LPS) is involved in the inflammatory response via the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signaling pathway. TLR4 and MyD88 have been reported to promote the proliferation, metastasis and tumorigenicity of colon cancer cells, which is consistent with the characteristics of CSCs. In the present study, the proposed experimental method to detect cell proliferation, metastasis and tumorigenesis was used to confirm that, under LPS stimulation, CD14 promoted the proliferation, migration and tumorigenesis of colonic CSCs via the TLR4/MyD88 signaling pathway. Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays were used to assess the proliferation and migration of the cells. Colony formation and nude mouse xenograft assays were used to assess the capacity of cells to form tumors. Using western blotting and reverse transcription-quantitative PCR, the mRNA and protein levels of CD14, TLR4 and MyD88 were examined. It was confirmed that CD14 promoted the proliferation, metastasis and tumorigenesis of colon CSCs in response to LPS stimulation via the TLR4/MyD88 signaling pathway, and CD14+ colon cancer cells were successfully isolated and sorted. According to the results of proliferation assay, it was determined that CD14 regulated the LPS-induced proliferation of colon CSCs. CD14, TLR4 and MyD88 protein and mRNA expression was upregulated in colon CSCs in response to LPS stimulation. This indicates a potential novel target for colon CSC-related studies.

Synergistic effects of CuS/TiO2 heterointerfaces: Enhanced cathodic CO2 reduction and anodic CH3OH oxidation for paired electrosynthesis of formate.

The electrochemical reduction of carbon dioxide into energy-carrying compounds or value-added chemicals is of great significance for diminishing the greenhouse effect. However, it is still imperative to replace the less-value anodic oxygen evolution reaction (OER) to improve the technical economy. Herein, we firstly reported a bifunctional CuS/TiO2 catalyst for both anodic methanol oxidation reaction (MOR) and cathodic carbon dioxide reduction (CO2R). The in-built abundant CuS/TiO2 heterointerfaces are found to boost the CO2R and MOR to produce formate. Based on the unique bifunctionality of CuS/TiO2, a paired electrosynthesis of formate was performed with a total Faradaic efficiency (FE) of about 170 %, in which the cathodic CO2R achieved a formate FE of about 70 %, and the anodic MOR exhibited an almost 100 % formate FE.

Words for the hearts: a corpus study of metaphors in online depression communities.

Purpose/significance: Humans understand, think, and express themselves through metaphors. The current paper emphasizes the importance of identifying the metaphorical language used in online health communities (OHC) to understand how users frame and make sense of their experiences, which can boost the effectiveness of counseling and interventions for this population. Methods/process: We used a web crawler to obtain a corpus of an online depression community. We introduced a three-stage procedure for metaphor identification in a Chinese Corpus: (1) combine MIPVU to identify metaphorical expressions (ME) bottom-up and formulate preliminary working hypotheses; (2) collect more ME top-down in the corpus by performing semantic domain analysis on identified ME; and (3) analyze ME and categorize conceptual metaphors using a reference list. In this way, we have gained a greater understanding of how depression sufferers conceptualize their experience metaphorically in an under-represented language in the literature (Chinese) of a new genre (online health community). Results/conclusion: Main conceptual metaphors for depression are classified into PERSONAL LIFE, INTERPERSONAL RELATIONSHIP, TIME, and CYBERCULTURE metaphors. Identifying depression metaphors in the Chinese corpus pinpoints the sociocultural environment people with depression are experiencing: lack of offline support, social stigmatization, and substitutability of offline support with online support. We confirm a number of depression metaphors found in other languages, providing a theoretical basis for researching, identifying, and treating depression in multilingual settings. Our study also identifies new metaphors with source-target connections based on embodied, sociocultural, and idiosyncratic levels. From these three levels, we analyze metaphor research's theoretical and practical implications, finding ways to emphasize its inherent cross-disciplinarity meaningfully.

Alanyl-Glutamine Dipeptide Attenuates Non-Alcoholic Fatty Liver Disease Induced by a High-Fat Diet in Mice by Improving Gut Microbiota Dysbiosis.

Non-alcoholic fatty liver disease (NAFLD) manifests as a persistent liver ailment marked by the excessive buildup of lipids within the hepatic organ accompanied by inflammatory responses and oxidative stress. Alanyl-glutamine (AG), a dipeptide comprising alanine and glutamine, is commonly employed as a nutritional supplement in clinical settings. This research aims to evaluate the impact of AG on NAFLD triggered by a high-fat diet (HFD), while concurrently delving into the potential mechanisms underlying its effects. The results presented herein demonstrate a notable reduction in the elevated body weight, liver mass, and liver index induced by a HFD upon AG administration. These alterations coincide with the amelioration of liver injury and the attenuation of hepatic histological advancement. Furthermore, AG treatment manifests a discernible diminution in oil-red-O-stained regions and triglyceride (TG) levels within the liver. Noteworthy alterations encompass lowered plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDLC) concentrations, coupled with elevated high-density lipoprotein cholesterol (HDLC) concentrations. The mitigation of hepatic lipid accumulation resultant from AG administration is aligned with the downregulation of ACC1, SCD1, PPAR-γ, and CD36 expression, in conjunction with the upregulation of FXR and SHP expression. Concomitantly, AG administration leads to a reduction in the accumulation of F4/80-positive macrophages within the liver, likely attributable to the downregulated expression of MCP-1. Furthermore, AG treatment yields a decline in hepatic MDA levels and a concurrent increase in the activities of SOD and GPX. A pivotal observation underscores the effect of AG in rectifying the imbalance of gut microbiota in HFD-fed mice. Consequently, this study sheds light on the protective attributes of AG against HFD-induced NAFLD through the modulation of gut microbiota composition.

Comparison of transfusion rates between robotic- and video-assisted lobectomy: a propensity score matching analysis.

The objective is to compare the perioperative blood transfusion rate and postoperative complications between robot-assisted surgery and thoracoscopic surgery in lung cancer patients. This is a single-center retrospective study. Patients underwent lung cancer minimally invasive resection at Fujian Cancer Hospital from April 1, 2022, to April 30, 2023, were enrolled in this study. Patients were divided into robotic-assisted lobectomy (RAL) and video-assisted lobectomy (VAL) groups according to the surgical methods. Data, including demographics, clinic variables, and endpoint outcomes were collected from the electronic medical record. Propensity score matching (PSM) was performed to analyze the baseline data of patients. The RAL group and the VAL group were matched 1:1. Then, the blood transfusion rates and short-term outcomes of the two groups were compared. A logistic regression was performed to analyze the independent risk factors of perioperative blood transfusion. A total of 558 patients were enrolled in this study. 166 of 558 patients were divided into the RAL group, and 392 patients were into the VAL group. A total of 118 patients were selected and analyzed following propensity score matching. After PSM, there was no difference in perioperative transfusion rates, including RBC transfusion and frozen plasma transfusion, between the VAL and RAL groups (P > 0.05). The RAL group had fewer days of drainage tubes (P = 0.036). There was no difference in other short-term outcomes, including the volume of thoracic drainage, the volume of intraoperative blood loss, the length of hospitalization, and the rate of postoperative pulmonary infection (P > 0.05). Volume of intraoperative blood loss, volume of thoracic drainage, and preoperative hemoglobin were independent risk factors of perioperative red blood cell or frozen plasma transfusion; however, RAL or VAL was not. The study showed that the rates of perioperative blood transfusion were comparable between RAL and VAL. RAL is superior for patient recovery in terms of short-term outcomes.

Association of nonalcoholic fatty liver disease with colorectal adenomatous polyps and non-adenomatous polyps: a cross-sectional study.

AIM: This study aimed to investigate the association between non-alcoholic fatty liver disease (NAFLD) and both colorectal adenomatous polyps and non-adenomatous polyps, in order to provide evidence for the prevention of colorectal cancer (CRC) in patients with NAFLD. METHODS: A retrospective, cross-sectional study was conducted at the First People's Hospital of Kunshan, Jiangsu, China. The study included 3028 adults who underwent abdominal ultrasonography and colonoscopy over a 5 year period. We compared characteristics among patients with adenomatous polyps, non-adenomatous polyps, and without colorectal polyps using descriptive statistics. Logistic regression analyses were used to detect associations between NAFLD with the prevalence of adenomatous polyps and non-adenomatous polyps. NAFLD was determined by abdominal ultrasound. Colorectal polyps were assessed by data in the colonoscopy report and pathology report. RESULTS: A total of 65% of patients with NAFLD had colorectal polys (52% adenomatous polyps and 13% non-adenomatous polyps), and 40% of patients without NAFLD had polyps (29% adenomatous polyps and 11% non-adenomatous polyps). After adjusting for confounding variables, NAFLD was significantly associated with the prevalence of adenomatous in males and females [odds ratio (OR) = 1.8, 95% confidence interval (CI): 1.6-2.2, P  < 0.01], but was not associated with non-adenomatous polyps (OR = 1.2, 95% CI:0.9-1.5, P  > 0.05). CONCLUSION: NAFLD is associated with an increased risk of colorectal adenomatous polyps compared to the absence of polyps, but not associated with an increased risk of non-adenomatous polyps. These results provide important evidence for the prevention of CRC in patients with NAFLD.

Application of recombinant TGF-ß1 inhibitory peptide to alleviate isoproterenol-induced cardiac fibrosis.

Cardiac fibrosis is a remodeling process of the cardiac interstitium, characterized by abnormal metabolism of the extracellular matrix, excessive accumulation of collagen fibers, and scar tissue hyperplasia. Persistent activation and transdifferentiation into myofibroblasts of cardiac fibroblasts promote the progression of fibrosis. Transforming growth factor-ß1 (TGF-ß1) is a pivotal factor in cardiac fibrosis. Latency-associated peptide (LAP) is essential for activating TGF-ß1 and its binding to the receptor. Thus, interference with TGF-ß1 and the signaling pathways using LAP may attenuate cardiac fibrosis. Recombinant full-length and truncated LAP were previously constructed, expressed, and purified. Their effects on cardiac fibrosis were investigated in isoproterenol (ISO)-induced cardiac fibroblasts (CFs) and C57BL/6 mice. The study showed that LAP and tLAP inhibited ISO-induced CF activation, inflammation, and fibrosis, improved cardiac function, and alleviated myocardial injury in ISO-induced mice. LAP and tLAP alleviated the histopathological alterations and inhibited the elevated expression of inflammatory and fibrosis-related markers in cardiac tissue. In addition, LAP and tLAP decreased the ISO-induced elevated expression of TGF-ß, αvß3, αvß5, p-Smad2, and p-Smad3. The study indicated that LAP and tLAP attenuated ISO-induced cardiac fibrosis via suppressing TGF-ß/Smad pathway. This study may provide a potential approach to alleviate cardiac fibrosis. KEY POINTS: • LAP and tLAP inhibited ISO-induced CF activation, inflammation, and fibrosis. • LAP and tLAP improved cardiac function and alleviated myocardial injury, inflammation, and fibrosis in ISO-induced mice. • LAP and tLAP attenuated cardiac fibrosis via suppressing TGF-ß/Smad pathway.

Autophagy-Modulated Biomaterial: A Robust Weapon for Modulating the Wound Environment to Promote Skin Wound Healing.

Autophagy, a self-renewal mechanism, can help to maintain the stability of the intracellular environment of organisms. Autophagy can also regulate several cellular functions and is strongly related to the onset and progression of several diseases. Wound healing is a biological process that is coregulated by different types of cells. However, it is troublesome owing to prolonged treatment duration and poor recovery. In recent years, biomaterials have been reported to influence the skin wound healing process by finely regulating autophagy. Biomaterials that regulate autophagy in various cells involved in skin wound healing to regulate the differentiation, proliferation and migration of cells, inflammatory responses, oxidative stress and formation of the extracellular matrix (ECM) have emerged as a key method for improving the tissue regeneration ability of biomaterials. During the inflammatory phase, autophagy enhances the clearance of pathogens from the wound site and leads to macrophage polarization from the M1 to the M2 phenotype, thus preventing enhanced inflammation that can lead to further tissue damage. Autophagy plays important roles in facilitating the formation of extracellular matrix (ECM) during the proliferative phase, removing excess intracellular ROS, and promoting the proliferation and differentiation of endothelial cells, fibroblasts, and keratinocytes. This review summarizes the close association between autophagy and skin wound healing and discusses the role of biomaterial-based autophagy in tissue regeneration. The applications of recent biomaterials designed to target autophagy are highlighted, including polymeric materials, cellular materials, metal nanomaterials, and carbon-based materials. A better understanding of biomaterial-regulated autophagy and skin regeneration and the underlying molecular mechanisms may open new possibilities for promoting skin regeneration. Moreover, this can lay the foundation for the development of more effective therapeutic approaches and novel biomaterials for clinical applications.

Online health community for change: Analysis of self-disclosure and social networks of users with depression.

Background: A key research question with theoretical and practical implications is to investigate the various conditions by which social network sites (SNS) may either enhance or interfere with mental well-being, given the omnipresence of SNS and their dual effects on well-being. Method/process: We study SNS' effects on well-being by accounting for users' personal (i.e., self-disclosure) and situational (i.e., social networks) attributes, using a mixed design of content analysis and social network analysis. Result/conclusion: We compare users' within-person changes in self-disclosure and social networks in two phases (over half a year), drawing on Weibo Depression SuperTalk, an online community for depression, and find: ① Several network attributes strengthen social support, including network connectivity, global efficiency, degree centralization, hubs of communities, and reciprocal interactions. ② Users' self-disclosure attributes reflect positive changes in mental well-being and increased attachment to the community. ③ Correlations exist between users' topological and self-disclosure attributes. ④ A Poisson regression model extracts self-disclosure attributes that may affect users' received social support, including the writing length, number of active days, informal words, adverbs, negative emotion words, biological process words, and first-person singular forms. Innovation: We combine social network analysis with content analysis, highlighting the need to understand SNS' effects on well-being by accounting for users' self-disclosure (content) and communication partners (social networks). Implication/contribution: Authentic user data helps to avoid recall bias commonly found in self-reported data. A longitudinal within-person analysis of SNS' effects on well-being is helpful for policymakers in public health intervention, community managers for group organizations, and users in online community engagement.

Structure Revisions of Phenolic Bisabolane Sesquiterpenes and a Ferroptosis Inhibitor from the Marine-Derived Fungus Aspergillus versicolor YPH93.

Seven new phenolic bisabolane sesquiterpenoids (1-7), along with 10 biogenetically related analogues (8-17), were obtained from the deep-sea-derived fungus Aspergillus versicolor YPH93. The structures were elucidated based on extensive analyses of the spectroscopic data. Compounds 1-3 are the first examples of phenolic bisabolanes that contain two hydroxy groups attached to the pyran ring. The structures of sydowic acid derivatives (1-6 and 8-10) were carefully studied, leading to the structure revisions of six known analogues, including a revision of the absolute configuration for sydowic acid (10). All metabolites were evaluated for their effects on ferroptosis. Compound 7 exerted inhibition on erastin/RSL3-induced ferroptosis with EC50 values ranging from 2 to 4 µM, while it exhibited no effects on TNFα-induced necroptosis or H2O2-induced cell necrosis.

Temperature-Dependent Affinity Changes in Substrate Binding Affect the Cleavage Activity of BthC2c1.

BACKGROUND: The CRISPR-Cas system is an adaptive immune mechanism for bacteria and archaea to resist foreign invasion. Currently, Cas9 and Cpf1 have been widely studied and applied in gene editing. C2c1 is a newly discovered CRISPR-Cas system endonuclease. It has broad application prospects due to its small molecular weight and high substrate recognition specificity. OBJECTIVES: Bacillus thermoamylovorans C2c1(BthC2c1) was expressed in E. coli C43 (DE3) competent cells, purified, and the BthC2c1-sgRNA-dsDNA complex was assembled. The effect of temperature on the cleavage ability of the BthC2c1 system was investigated. METHODS: The cDNA of BthC2c1 was cloned into the vector pGEX-6P-1. BthC2c1 was expressed in E. coli C43(DE3) cells and purified using a GST affinity column and FPLC. The sgRNAs were transcribed and purified in vitro, and the complexes were assembled by gel filtration chromatography. The enzyme cleavage activity of BthC2c1 at different temperatures was investigated using an in vitro cleavage assay. Microscale Thermophoresis detected the affinity of the BthC2c1-sgRNA complexes to substrate DNA. RESULTS: BthC2c1 proteins were prokaryotically expressed and purified. The complex of BthC2c1 with sgRNA and dsDNA was assembled. In vitro cleavage assay results showed that BthC2c1 cleaved the target DNA at temperatures ranging from 37°C to 67°C. The cleavage ability of BthC2c1 at 42oC was stronger than that at 37oC. The results of affinity detection showed that the affinity between the BthC2c1-sgRNA complex and ds36/36 at 42oC was stronger than that at 37oC. CONCLUSION: In this study, BthC2c1 was expressed, purified, and assembled into a complex with sgRNA and dsDNA. BthC2c1 cleaved DNA within the temperature range of 37oC to 67oC. The affinity of BthC2c1-sgRNA to DNA at 42°C was significantly enhanced than that at 37°C. It may be related to its stringent substrate recognition pattern, which differs from Cas9 and Cpf1. The temperature-dependent affinity changes of substrate binding may be part of the reason for the stronger cleavage activity of BthC2c1 at 42oC. This study may provide an experimental basis for optimizing and modifying the C2c1 gene editing system.

Palladium/PC-Phos-Catalyzed Asymmetric Heck/Tsuji-Trost Reactions of Amino-Tethered 1,3-Cyclohexadiene with Aryl and Alkenyl Halides.

Chiral perhydroindoles are found in a number of natural products and biologically active compounds. Therefore, the development of new asymmetric methodology for rapid access to this core is of high importance. Herein, we reported a highly regio- and diastereo-selective palladium/PC-Phos-catalyzed asymmetric Heck/Tsuji-Trost reactions of readily available amino tethered 1,3-cyclohexadienes with aryl and alkenyl halides, delivering various functionalized chiral hexahydroindoles in good yields with high enantioselectivity. The application of this reaction to the concise synthesis of (-)-α-Lycorane was demonstrated. DFT computation results indicate that the difference in ΔEdis of two migration insertion transition states determines the enantioselectivity of the reaction.