Functional diversity of apoptotic vesicle subpopulations from bone marrow mesenchymal stem cells in tissue regeneration.

Apoptosis releases numerous apoptotic vesicles that regulate processes such as cell proliferation, immunity, and tissue regeneration and repair. Now, it has also emerged as an attractive candidate for biotherapeutics. However, apoptotic vesicles encompass a diverse range of subtypes, and it remains unclear which specific subtypes play a pivotal role. In this study, we successfully isolated different apoptotic vesicle subtypes based on their sizes and characterized them using NTA and TEM techniques, respectively. We compared the functional variances among the distinct subtypes of apoptotic vesicles in terms of stem cell proliferation, migration, and differentiation, as well as for endothelial cell and macrophage function, effectively identifying subtypes that exhibit discernible functional differences. ApoSEV (with diameter <1000 nm) promoted stem cell proliferation, migration, and multi-potent differentiation, and accelerated skin wound healing of diabetes mouse model, while apoBD (with diameter >1000 nm) played the opposite effect on cell function and tissue regeneration. Lastly, employing protein analysis and gene sequencing techniques, we elucidated the intrinsic mechanisms underlying these differences between different subtypes of apoEVs. Collectively, this study identified that apoptotic vesicle subtypes possessed distinct bio-functions in regulating stem cell function and behaviour and modulating tissue regeneration, which primarily attribute to the distinct profiling of protein and mRNA in different subtypes. This comprehensive analysis of specific subtypes of apoEVs would provide novel insights for potential therapeutic applications in cell biology and tissue regeneration.

Matrine Enhances the Antitumor Efficacy of Chidamide in CTCL by Promoting Apoptosis.

BACKGROUND: Cutaneous T-cell Lymphoma (CTCL) is a rare group of non-Hodgkin lymphoma originating from the skin, which is characterized by T-cell lymphoproliferative disorders. Chidamide, a Chinese original antineoplastic agent with independent intellectual property rights, and matrine, an extract of Chinese herbal medicine, both have been reported to exert effects on the treatment of tumors individually. However, chidamide combined with matrine has not been tested for the treatment of CTCL. METHODS: Both HH and Hut78 CTCL cell lines were treated with chidamide (0.4 µmol/L), matrine (0.6 g/L), or chidamide combined with matrine for 24, 48, and 72 h. Cell viability was estimated by MTS assay at each time point. Flow cytometry was then conducted to detect cell apoptosis. The exact mechanism of chidamide combined with matrine on CTCL cells was detected by Western blotting and further validated in xenograft models of NOD/SCID mice. RESULTS AND DISCUSSION: Compared to the single drug, chidamide combined with matrine showed a more significant effect on proliferation inhibition and apoptosis induction on CTCL cells both in vitro and in vivo. The results from the in vitro and in vivo studies suggested that matrine could enhance the anti-tumor effect of chidamide by increasing the protein expression of cleaved caspase- 3 and decreasing the expression of E-cadherin, NF-κB, p-Bad, and Bcl-2 to activate apoptosis. CONCLUSION: Our data have demonstrated chidamide combined with matrine to exhibit elevated antitumor activity in both CTCL cells and xenograft models of NOD/SCID mice, which may be a potential treatment option for CTCL.

Assessments for multi-heritage couple therapy: A review of existing tools.

As diversity in the United States increases, marriage and family therapists are encountering more multi-heritage couples in therapy. Recent research shows that around 11% of adults are married to someone from a different racial or ethnic group, rising to 19% among new marriages. Multi-heritage couples encompass inherent differences in race, ethnicity, religion, gender, sexual orientation, national origin, and culture. This article addresses the unique challenges faced by multi-heritage couples in therapy and explores the strengths and weaknesses of existing assessment tools suitable for their needs. The study highlights a limited number of existing tools that are available for therapists working with multi-heritage couples. Consequently, the article suggests future directions to enhance the development of assessment tools tailored to the specific needs of multi-heritage couples.

Wearable Microneedle Patch for Colorimetric Detection of Multiple Signature Biomarkers in vivo Toward Diabetic Diagnosis.

Type 2 diabetes is rapidly emerging as a global public health problem. While blood glucose monitoring has been the primary method of managing diabetes for decades, the increasing global prevalence of the disease suggests that there might be a need to identify additional biomarkers for a more precise early diagnosis. Herein, a microneedle patch based wearable sensor is developed for the purpose of diabetic diagnosis. Utilizing methacrylic acid modified gelatin and polyvinyl alcohol in the fabrication of microneedles has improved their mechanical properties for skin penetration and increased swelling capacity for interstitial fluid extraction, thanks to the double crosslinking mechanism. The fabricated microneedles are further integrated with test paper functionalized with enzyme and dye molecules to detect multiple signature biomarkers of diabetes in vivo through a colorimetric reaction. Such a wearable microneedle patch  holds significant promise for the real-time monitoring of various biomarkers related to chronic diseases and aging.

Predictive analysis and correlational exploration of public and academic attention in secondary vocational education.

Secondary vocational education (SVE) is responsible for cultivating talents with moral and technical skills, receiving widespread attention from scholars and the public. Studying the two attentions can broaden the research perspectives and promote the development of SVE. However, there are the following problems: 1) the public attention and academic attention of SVE cannot be accurately characterized; 2) the relationship between the public attention and academic attention of SVE cannot be clear; 3) the impact of public attention and academic attention on SVE cannot be predicted. To address the above issues, this paper puts forward the PLSH (Pearson correlation-Linear regression, Seasonal autoregressive integrated moving average (SARIMA), and Holt-winters model) framework. It involves four research steps: 1) public attention and academic attention are obtained for SVE; 2) the correlation between them is analyzed and a linear model is developed; 3) the performance of the SARIMA model and Holt-winters model are conducted, and the best model is adopted to predict the public attention; 4) academic attention is predicted using the results from the previous step. The study shows that the PLSH framework can characterize academic and public attention to SVE, effectively reflecting their correlation and predicting their growth trends.

Lactate levels in the brain and blood of schizophrenia patients: A systematic review and meta-analysis.

BACKGROUND: The pathophysiological mechanisms of schizophrenia are still unclear. Converging evidence suggests that energy metabolism abnormalities are involved in schizophrenia, and support its role in the pathophysiology of this disease. Lactate plays an important role in energy metabolism. Many studies have reported changes in the levels of lactate in the brain and serum of schizophrenia patients; however, the results from these studies are not consistent. To overcome this limitation, the goal of the present meta-analysis is to analyze the changes in lactate levels in the brain and blood of schizophrenia patients. METHODS: For this systematic review and meta-analysis, we performed a thorough search of relevant literature in the English language, using the MEDLINE, Cochrane, and Embase databases. RESULTS: In the present meta-analysis, 20 studies were scrutinized, including 13 studies on brain lactate levels, which involved 322 schizophrenia patients and 324 healthy individuals as controls. 7 studies on blood lactate levels, involving 234 schizophrenia patients and 238 healthy individuals, were also included. Brain lactate levels were elevated in schizophrenia patients, both in vivo and in post-mortem studies. Nevertheless, blood lactate levels in schizophrenia patients have revealed no statistically significant difference, as compared with control individuals. CONCLUSIONS: In comparison with healthy individuals, schizophrenia patients had higher lactate levels in the brain, rather than in the blood. These findings suggest independent regulatory mechanisms of lactate levels in the brain and peripheral tissues. Abnormal lactate metabolism in the brain may be an important pathological mechanism in schizophrenia.

A naturally occurring G11S mutation in the 3C-like protease from the SARS-CoV-2 virus dramatically weakens the dimer interface.

The 3C-like protease (3CLpro ) is crucial to the replication of SARS-CoV-2, the causative agent of COVID-19, and is the target of several successful drugs including Paxlovid and Xocova. Nevertheless, the emergence of viral resistance underlines the need for alternative drug strategies. 3CLpro only functions as a homodimer, making the protein-protein interface an attractive drug target. Dimerization is partly mediated by a conserved glycine at position 11. However, some naturally occurring SARS-CoV-2 sequences contain a serine at this position, potentially disrupting the dimer. We have used concentration-dependent activity assays and mass spectrometry to show that indeed the G11S mutation reduces the stability of the dimer by 600-fold. This helps to set a quantitative benchmark for the minimum potency required of any future protein-protein interaction inhibitors targeting 3CLpro and raises interesting questions regarding how coronaviruses bearing such weakly dimerizing 3CLpro enzymes are capable of replication.

Hierarchically patterned triple-layered gelatin-based electrospun membrane functionalized by cell-specific extracellular matrix for periodontal regeneration.

OBJECTIVES: Regenerating the periodontium poses a critical challenge in oral medicine. To repair various periodontal defects, it is necessary to adopt a bio-scaffold that provides both the architecture and bioactive cues for local stem cells to migrate, reside, proliferate, and differentiate. The objective of this study is to combine a cell-specific decellularized extracellular matrix (ECM) and a biomimetic electrospinning scaffold to regenerate severely destructed periodontium. METHODS: SEM, water contact angle (WCA), live/dead staining, swelling ratio, tensile test and immune-fluorescent staining were used to define the suitable topography for certain dental stem cells seeding and culturing. Transwell assay, CCK-8, Alizarin Red staining and PCR immune-fluorescent staining were used to determine ideal cell-specific ECM for PDLSCs/BMSCs migration, viability, and oriented differentiation. A biodegradable triple-layered electrospun scaffold (TLS) was fabricated by electrospinning with aligned fibers on both surfaces and a polyporous structure in the middle. The morphology and inter-porous structure of the TLS were characterized by SEM and mercury intrusion porosimetry (MIP). The surface of the TLS was functionalized with cell-specific ECM (Bi-ECM-TLS) through decellularization of the cell sheets cultured on the scaffold. The regenerative outcome of Bi-ECM-TLS was assessed by an in-situ rat periodontal defect model. Micro-CT, HE-staining, Masson's trichome staining, Sirius Red staining and Immunofluorescent staining were used for histological analysis. RESULTS: Aligned Gelatin/PCL fibrous membrane (GPA) was most effective for both PDLSCs and BMSCs in culture with WCA around 50 degrees and better mechanical strength than the rest. MSCs favored the same type of ECM (cell-specific ECM), and their regenerative properties were effectively induced with better chemotaxis, proliferative and differentiating behaviors. TLS characterization showed that TLS possessed aligned-random-aligned structure and inter-porous structure. In a rat model of periodontal defects, the TLS functionalized by BMSC-specific ECM for bone regeneration and PDLSC-specific ECM demonstrated highest BV/TV ratio, best bone structure and ligament fiber orientation and blood vessel formation, suggesting optimal performance in regenerating both alveolar bone and periodontal ligaments over TLS, single-ECM loaded TLS and r-Bi-ECM-TLS. SIGNIFICANCE: This study highlights the importance of combining a cell-specific decellularized ECM and a biomimetic electrospinning scaffold for targeted periodontal tissue regeneration, with potential implications for periodontal tissue engineering and improved patient outcomes.

Heralded quantum multiplexing entanglement between stationary qubits via distribution of high-dimensional optical entanglement.

Quantum entanglement between pairs of remote quantum memories (QMs) is a prerequisite for realizing many applications in quantum networks. Here, we present a heralded protocol for the parallel creation of quantum entanglement among multiple pairs of QMs placed in spatially separated nodes, where each QM, encoding a stationary qubit, couples to an optical cavity and deterministically interacts with single photons. Our protocol utilizes an entangled photon pair encoded in the high-dimensional time-bin degree of freedom to simultaneously entangle multiple QM pairs, and is efficient in terms of reducing the time consumption and photon loss during transmission. Furthermore, our approach can be extended to simultaneously support spatial-temporal multiplexing, as its success is heralded by the detection of single photons. These distinguishing features make our protocol particularly useful for long-distance quantum communication and large-scale quantum networks.

ApoSEVs-Mediated Modulation of Versatile Target Cells Promotes Diabetic Wound Healing: Unveiling a Promising Strategy.

Background: Diabetic chronic wounds present a formidable challenge in clinical management, lacking effective treatment options. Mesenchymal stem cell (MSC) transplantation has emerged as a promising therapy for tissue repair and regeneration. However, transplanted MSCs often undergo rapid apoptosis, giving rise to heterogeneous extracellular vesicles (EVs), including apoptotic bodies (apoBDs) and apoptotic small extracellular vesicles (apoSEVs). The potential stimulatory role of these EVs in diabetic wound healing remains unknown. Methods: In this study, we investigated the effects of apoSEVs derived from adipose-derived mesenchymal/stromal cells (ADSCs) on the recovery of diabetic wounds by modulating the function of versatile target cells. First, we characterized the apoSEVs and apoBDs derived from apoptotic ADSCs. Subsequently, we evaluated the effects of apoSEVs and apoBDs on macrophages, endothelial cells, and fibroblasts, three essential cell types in wound healing, under high-glucose conditions. Furthermore, we developed a gelatin methacryloyl (GelMA) hydrogel for the sustained release of apoSEVs and investigated its therapeutic effects on wound healing in type 2 diabetic mice in vivo. Results: apoSEVs facilitated the polarization of M1 phenotype macrophages to M2 phenotype, promoted proliferation, migration, and tube formation of endothelial cells, and enhanced fibroblast proliferation and migration. However, apoBDs failed to improve the function of endothelial cells and fibroblasts. In vivo, the apoSEVs-loaded GelMA effectively promoted wound healing by facilitating collagen fiber deposition, angiogenesis, and immune regulation. Conclusion: Our study elucidates the beneficial effects of apoSEVs on wound recovery in diabetes and introduces a novel strategy for diabetic wound treatment based on apoSEVs.

An 8-year follow-up of IgG4-related skin disease presented with generalized ALHE-like eruptions: successful treatment of glucocorticoid and cyclophosphamide.

Immunoglobulin gamma (IgG) type 4-related disease (IgG4-RD) is a chronic immunologic systemic disorder that could affect multiple organs, which may cause irreversible organ damage or even death. Skin involvement is rare and associated especially with systemic disease. The dermatologist must be equipped to recognize IgG4-RD to prevent delayed identification and treatment. This case reports a very rare case of IgG4-related skin disease (IgG4-RSD) presenting with a generalized angiolymphoid hyperplasia with eosinophilia (ALHE)-like lesions in a middle-aged male patient with no other organ involvement. He was treated with oral glucocorticoid and cyclophosphamide, which resulted in complete remission. No relapse and disease progression were seen with a follow-up for 8 years.

Hydrochemistry, quality, and integrated health risk assessments of groundwater in the Huaibei Plain, China.

Groundwater is an essential freshwater resource utilized in industry, agriculture, and daily life. In the Huaibei Plain (HBP), where groundwater significantly influences socio-economic development, information about its quality, hydrochemistry, and related health risks remains limited. We conducted a comprehensive groundwater sampling in the HBP and examined its rock characteristics, water quality index (WQI), and potential health risks. The results revealed that the primary factors shaping groundwater hydrochemistry were rock dissolution and weathering, cation exchange, and anthropogenic activities. WQI assessment indicated that only 73% of the groundwaters is potable, as Fe2+, Mn2+, NO3-, and F- contents in the water could pose non-carcinogenic hazards to humans. Children were more susceptible to these health risks through oral ingestion than adults. Uncertainty analysis indicated that the probabilities of non-carcinogenic risk were approximately 57% and 31% for children and adults, respectively. Sensitivity analysis further identified fluoride as the primary factor influencing non-carcinogenic risks, indicating that reducing fluoride contamination should be prioritized in future groundwater management in the HBP.

CRISPR/Cas9-Mediated CtBP1 Gene Editing Enhances Chemosensitivity and Inhibits Metastatic Potential in Esophageal Squamous Cell Carcinoma Cells.

Innovative therapeutic strategies for esophageal squamous cell carcinoma (ESCC) are urgently required due to the limited effectiveness of standard chemotherapies. C-Terminal Binding Protein 1 (CtBP1) has been implicated in various cancers, including ESCC. However, the precise expression patterns and functional roles of CtBP1 in ESCC remain inadequately characterized. In this study, we aimed to investigate CtBP1 expression and its role in the resistance of ESCC to paclitaxel, an effective chemotherapeutic agent. Western blotting and immunofluorescence were applied to assess CtBP1 expression in the TE-1 and KYSE-50 cell lines. We observed the marked expression of CtBP1, which was associated with enhanced proliferation, invasion, and metastasis in these cell lines. Further, we successfully generated paclitaxel resistant ESCC cell lines and conducted cell viability assays. We employed the CRISPR/Cas9 genome editing system to disable the CtBP1 gene in ESCC cell lines. Through the analysis of the drug dose-response curve, we assessed the sensitivity of these cell lines in different treatment groups. Remarkably, CtBP1-disabled cell lines displayed not only improved sensitivity but also a remarkable inhibition of proliferation, invasion, and metastasis. This demonstrates that CtBP1 may promote ESCC cell malignancy and confer paclitaxel resistance. In summary, our study opens a promising avenue for targeted therapies, revealing the potential of CtBP1 inhibition to enhance the effectiveness of paclitaxel treatment for the personalized management of ESCC.

Fatigue strength and life prediction of lower limb venous stents under three-stage loading conditions.

After the implantation of lower limb artery stents, the complex loading conditions imposed on the limb can lead to fatigue failure, which may induce inflammation and restenosis. To investigate the effect of multi-axial loading conditions on the fatigue performance of stents, five stents, namely APsolute Pro (APbott Vascular, USA), Complete SE (Medtronic, USA), Protégé EverFlex (PE3, USA), Pulsar-35 (Biotronik, Germany), and E-luminexx-B (Bard, USA), were analyzed based on the finite element method (FEM). Besides, their fatigue strength was determined under three levels of loading conditions, including tension-bending-torsion and compression-bending-torsion. Based on that, the fatigue life of these stents was predicted. The results showed that based on the nominal stress method, tension-bending-torsion loading had a more significant impact on the fatigue life of stents than compression-bending-torsion loading. Besides, two different types of initial cracks were analyzed by the fracture mechanics method. The results suggested that both the initial crack and the external load were the main causes of stent fatigue fractures. Compared with the loading nature, the influence of the initial crack on stent fatigue life was more significant. Under the same loading condition, the APsolute Pro stent had the longest fatigue life, while the E-luminexx-B stent had the shortest. Moreover, the mechanism of stent fatigue failure was revealed by exploring the fatigue performance and life prediction of stents under complex loading conditions. These findings have important implications for improving the structural design of stents and their clinical selection.

Computational and biophysical methods for the discovery and optimization of covalent drugs.

Drugs that act by covalently attaching to their targets have been used to treat human diseases for over a hundred years. However, the deliberate design of covalent drugs was discouraged due to concerns of toxicity and off-target effects. Recent successes in covalent drug discovery have sparked fresh interest in this field. New screening and testing methods aimed at covalent inhibitors can play pivotal roles in facilitating the discovery process. This feature article focuses on computational and biophysical advances originating from our labs over the past decade and how these approaches have contributed to the design of prolyl oligopeptidase (POP) and SARS-CoV-2 3CLpro covalent inhibitors.

BMI-1 activates hepatic stellate cells to promote the epithelial-mesenchymal transition of colorectal cancer cells.

BACKGROUND: Activated hepatic stellate cells (aHSCs) are the major source of cancer-associated fibroblasts in the liver. Although the crosstalk between aHSCs and colorectal cancer (CRC) cells supports liver metastasis (LM), the mechanisms are largely unknown. AIM: To explore the role of BMI-1, a polycomb group protein family member, which is highly expressed in LM, and the interaction between aHSCs and CRC cells in promoting CRC liver metastasis (CRLM). METHODS: Immunohistochemistry was carried out to examine BMI-1 expression in LM and matched liver specimens of CRC. The expression levels of BMI-1 in mouse liver during CRLM (0, 7, 14, 21, and 28 d) were detected by Western blotting (WB) and the quantitative polymerase chain reaction (qPCR) assay. We overexpressed BMI-1 in HSCs (LX2) by lentivirus infection and tested the molecular markers of aHSCs by WB, qPCR, and the immunofluorescence assay. CRC cells (HCT116 and DLD1) were cultured in HSC-conditioned medium (LX2 NC CM or LX2 BMI-1 CM). CM-induced CRC cell proliferation, migration, epithelial-mesenchymal transition (EMT) phenotype, and transforming growth factor beta (TGF-ß)/SMAD pathway changes were investigated in vitro. A mouse subcutaneous xenotransplantation tumor model was established by co-implantation of HSCs (LX2 NC or LX2 BMI-1) and CRC cells to investigate the effects of HSCs on tumor growth and the EMT phenotype in vivo. RESULTS: Positive of BMI-1 expression in the liver of CRLM patients was 77.8%. The expression level of BMI-1 continued to increase during CRLM in mouse liver cells. LX2 overexpressed BMI-1 was activated, accompanied by increased expression level of alpha smooth muscle actin, fibronectin, TGF-ß1, matrix metalloproteinases, and interleukin 6. CRC cells cultured in BMI-1 CM exhibited enhanced proliferation and migration ability, EMT phenotype and activation of the TGF-ß/SMAD pathway. In addition, the TGF-ßR inhibitor SB-505124 diminished the effect of BMI-1 CM on SMAD2/3 phosphorylation in CRC cells. Furthermore, BMI-1 overexpressed LX2 HSCs promoted tumor growth and the EMT phenotype in vivo. CONCLUSION: High expression of BMI-1 in liver cells is associated with CRLM progression. BMI-1 activates HSCs to secrete factors to form a prometastatic environment in the liver, and aHSCs promote proliferation, migration, and the EMT in CRC cells partially through the TGF-ß/SMAD pathway.

Insight into pyrolysis mechanism of plastic waste with C-O/C-N bonds in the backbone.

Pyrolysis is an important method for efficiently recovering plastic monomers, fuels and chemicals from plastic waste. The depolymerization of the backbone structure of plastic waste is a key step of the pyrolysis process. Currently, researches on the pyrolysis mechanism of plastics with C-O/C-N bonds in the backbone are still not sufficiently in-depth and also lack systematic and comprehensive investigation. Therefore, this study for the first time comprehensively investigated both macroscopic and microscopic pyrolysis processes of plastics with C-O/C-N bonds in the backbone, and evaluated the difficulty of breaking different backbone linkages via bond dissociation energy (BDE) obtained by density functional theory (DFT) calculations to deeply reveal the pyrolysis mechanism. The results indicated that polyethylene terephthalate (PET) had a higher initial pyrolysis temperature and its thermal stability was slightly stronger than nylon 6. The backbone of PET was mainly decomposed via the cleavage of Cα-O on the alkyl side, while the degradation of nylon 6 backbone began with NH2 groups at the end of the backbone. The pyrolysis products of PET were mainly derived from the small molecular fragments, which were generated by the degradation of the backbone through the cleavage of CO bonds or CC bonds, while the pyrolysis products of nylon 6 were always dominated by caprolactam. In addition, based on the results of DFT calculations, it could be inferred that the cleavage of CC bond in PET backbone and the cleavage of its adjacent Cα-O were most likely to occur, which followed a competitive reaction mechanism. However, in pyrolysis of nylon 6, the conversion to caprolactam was mainly via the concerted reaction of amide CN bonds. Compared with the concerted cleavage of amide CN bond, the cleavage of CC bond in the backbone of nylon 6 was not predominant.

Pregnane X receptor (PXR) deficiency protects against spinal cord injury by activating NRF2/HO-1 pathway.

INTRODUCTION: As a devastating neurological disease, spinal cord injury (SCI) results in severe tissue loss and neurological dysfunction. Pregnane X receptor (PXR) is a ligand-activated nuclear receptor with a major regulatory role in xenobiotic and endobiotic metabolism and recently has been implicated in the central nervous system. In the present study, we aimed to investigate the role and mechanism of PXR in SCI. METHODS: The clip-compressive SCI model was performed in male wild-type C57BL/6 (PXR+/+ ) and PXR-knockout (PXR-/- ) mice. The N2a H2 O2 -induced injury model mimicked the pathological process of SCI in vitro. Pregnenolone 16α-carbonitrile (PCN), a mouse-specific PXR agonist, was used to activate PXR in vivo and in vitro. The siRNA was applied to knock down the PXR expression in vitro. Transcriptome sequencing analysis was performed to discover the relevant mechanism, and the NRF2 inhibitor ML385 was used to validate the involvement of PXR in influencing the NRF2/HO-1 pathway in the SCI process. RESULTS: The expression of PXR decreased after SCI and reached a minimum on the third day. In vivo, PXR knockout significantly improved the motor function of mice after SCI, meanwhile, inhibited apoptosis, inflammation, and oxidative stress induced by SCI. On the contrary, activation of PXR by PCN negatively influenced the recovery of SCI. Mechanistically, transcriptome sequencing analysis revealed that PXR activation downregulated the mRNA level of heme oxygenase-1 (HO-1) after SCI. We further verified that PXR deficiency activated the NRF2/HO-1 pathway and PXR activation inhibited this pathway in vitro. CONCLUSION: PXR is involved in the recovery of motor function after SCI by regulating NRF2/HO-1 pathway.

Copper-Mediated Deconstructive Ring Cleavage of Cyclic Thioethers with Boron Compounds.

The deconstructive ring cleavage of cyclic thioethers is achieved through a Chan-Lam type process with boron compounds. The sequential hydroboration/ring cleavage process from alkynes offered a new route to the preparation of vinyl sulfides based on the developed conditions. Further exploration has demonstrated the versatility of nucleophiles, delivering various functionalized sulfides featuring linear frameworks.

Protective effect of rosmarinic acid-rich extract from Trichodesma khasianum Clarke against microbiota dysbiosis in high-fat diet-fed obese mice.

Hypertrophy of adipose tissues and dysbiosis are hallmarks of obesity. Although drugs are applied for obesity treatment, side effects limit their use. The anti-obesity capacity of rosmarinic acid (RA) has been documented. Trichodesma khasianum Clarke is an edible RA-rich plant grown in Taiwan. Our previous study found that an 80 % ethanol extract of T. khasianum Clarke leaves (80EETC) ameliorates gastric mucosal damage through its anti-inflammatory, antioxidant, and microbiota modulation abilities. However, the anti-obesity effect of 80EETC remains unclear. Therefore, the objective of this study was to explore the protective effects of low-dose 80EETC (125 mg/kg b.w., 80EETCL) or high-dose 80EETC (250 mg/kg b.w., 80EETCH) on obesity development through gut microbiota modulation in high-fat diet (HFD)-induced C57BL/6 mice. The results showed a high RA content (89.2 ± 7.4 mg/g) in 80EETC. 80EETC administration significantly decreased body weight, body fat ratio, serum lipid levels (TC, TG, and LDL-C), adipose tissue accumulation, malondialdehyde (MDA), and tumor necrosis factor-α (TNF-α) in HFD-fed mice. Furthermore, supplementation with 80EETC reduced the Firmicutes/Bacteroidetes ratio and enhanced the relative abundance of gut microbiota (p_Bacteroidetes, f_Lactobacillus, f_Muribaculaceae, f_Prevotellaceae, g_Lactobacillus, g_Prevotellaceae_NK3B31_group, g_Ruminococcaceae_UCG-013, and g_Ruminococcaceae_UCG-014), which negatively correlated with obesity-related factors such as body weight, energy intake, fat accumulation in adipose tissue, TC, TG, LDL, and MDA. In conclusion, RA-rich 80EETC had a protective effect against obesity development and it has potential in healthy food applications.