A new charge transfer pathway in the MoSe2-WSe2 heterostructure under the conditions of B-excitons being resonantly pumped.

Most transition metal dichalcogenide (TMD) heterostructures (HSs) exhibit a type II band alignment, leading to a charge transfer process accompanied by the transfer of spin-valley polarization and spontaneous formation of interlayer excitons. This unique band structure facilitates achieving a longer exciton lifetime and extended spin-valley polarization lifetime. However, the mechanism of charge transfer in type II TMD HSs is not fully comprehended. Here, the ultrafast charge transfer process is studied in MoSe2-WSe2 HS via valley-solved broadband pump-probe spectroscopy. Under the conditions of B-excitons of WSe2 and MoSe2 being resonantly pumped, a new charge transfer pathway through the higher energy state associated with the B-exciton is found. Meanwhile, the holes (electrons) in the WSe2 (MoSe2) layer of MoSe2-WSe2 HS produce obvious spin-valley polarization even under the condition of B-exciton of WSe2 (MoSe2) being resonantly pumped, and the lifetime can reach tens of ps, which is in stark contrast to the absence of A-exciton spin-valley polarization in monolayer WSe2 (MoSe2) under the same pumping condition. The results deepen the insight into the charge transfer process in type II TMD HSs and show the great potential of TMD HSs in the application of spin-valley electronics devices.

Assessing the application of barbed sutures in comparison to conventional sutures for surgical applications: a global systematic review and meta-analysis of preclinical animal studies.

BACKGROUND: Following an initiative published by Lancet in 2002 and an IDEAL-D framework, the value of preclinical animal studies has garnered increasing attention in recent research. Numerous preclinical animal experiments tried to generate evidence to guide the development of barbed sutures. However, discernible drawbacks and incongruities in outcomes have emerged between clinical and preclinical animal studies. Therefore, this meta-analysis aimed to review the preclinical animal experiments comparing barbed sutures with conventional sutures. We hope to facilitate clinical translation of barbed sutures by evaluating effectiveness, safety, and physical properties/reliability. MATERIALS AND METHODS: A systematic search of PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov was conducted to identify controlled preclinical animal experiments comparing barbed sutures with conventional sutures. The risk of bias was assessed using SYRCLE. GRADE approach was used to evaluate evidence quality. Revman was applied to analyze all the data. Subgroup, sensitivity, and meta-regression analyses were also performed. RESULTS: A total of 55 articles were eligible with low to moderate quality, including 1937 samples from 10 different animal species across 25 surgical procedures. Barbed suture exhibited a significant reduction in suture time, limited change in Cross-Sectional Area (CSA), and decreased instances of tissue disruption (all P ＜0.05). Subgroup analyses, considering both clinical and research significance, indicated that barbed sutures might cause more specific adverse events and demonstrate suboptimal performance of physical properties/reliability. Meta-regression suggested that heterogeneity resulted from variations in studies and animal models. CONCLUSION: Although barbed suture demonstrated superiority in numerous surgeries for time efficiency, its safety and physical properties/reliability might be influenced by diverse preclinical models, sutures' brand, surgeries, and anatomical sites. Further evaluation, based on standardized and well-designed animal experiments, is essential for medical device development and applications in human beings.

Baohuoside I suppresses the NLRP3 inflammasome activation via targeting GPER to fight against Parkinson's disease.

BACKGROUND: Accumulating evidence indicates the crucial role of microglia-mediated inflammation and the NLR family pyrin domain containing 3 (NLRP3) inflammasome-mediated pyroptosis in the pathogenesis of Parkinson's disease (PD). Baohuoside I, a natural flavonoid extracted from Herba Epimedii, has been shown to possess anti-inflammatory effects, but its potential neuroprotective effects and mechanism against PD have not been documented. STUDY DESIGN AND METHODS: The anti-inflammatory effects of Baohuoside I were evaluated by LPS-induced BV2 cells or primary microglia isolated from wide type or G protein-coupled estrogen receptor (GPER) gene knockout mice. The underlying mechanism related to GPER-mediated NLRP3 inflammasome inhibition was further explored using LPS-induced GPER+/+ or GPER-/- mouse models of PD. The neuroprotective effects of Baohuoside I were detected through western blot analysis, real-time PCR, molecular docking, mouse behavioral tests, immunofluorescence, and immunohistochemistry. RESULTS: Baohuoside I significantly alleviated LPS-induced neuroinflammation by inhibiting the activation of NF-κB signal and the increase of pyroptosis levels as evidenced by the downregulated expression of pyroptosis-related proteins (NLRP3, ASC, pro-Caspase-1, IL-1ß) in microglia cells. Intragastric administration of Baohuoside I protected against LPS-induced motor dysfunction and loss of dopaminergic neurons, reduced pro-inflammatory cytokines expressions, and inhibited microglial (Iba-1) and astrocyte (GFAP) activation in the nigrostriatal pathway in LPS-induced mouse model of PD. Pretreatment with GPER antagonist G15 in microglia cells or GPER gene deletion in mice significantly blocked the inhibitory effects of Baohuoside I on LPS-induced neuroinflammation and activation of the NLRP3/ASC/Caspase-1 pathway. Molecular docking further indicated that Baohuoside I might bind to GPER directly with a binding energy of -10.4 kcal/mol. CONCLUSION: Baohuoside I provides neuroprotective effects against PD by inhibiting the activation of the NF-κB signal and NLRP3/ASC/Caspase-1 pathway. The molecular target for its anti-inflammatory effects is proved to be GPER in the PD mouse model. Baohuoside I may be a valuable anti-neuroinflammatory agent and a drug with well-defined target for the treatment of PD.

Diallyl disulfide induces DNA damage and growth inhibition in colorectal cancer cells by promoting POU2F1 ubiquitination.

Previous studies have demonstrated that diallyl disulfide (DADS) exhibits potent anti-tumor activity. However, the pharmacological actions of DADS in inhibiting the growth of colorectal cancer (CRC) cells have not been clarified. Herein, we show that DADS treatment impairs the activation of the pentose phosphate pathway (PPP) to decrease PRPP (5-phosphate ribose-1-pyrophosphate) production, enhancing DNA damage and cell apoptosis, and inhibiting the growth of CRC cells. Mechanistically, DADS treatment promoted POU2F1 K48-linked ubiquitination and degradation by attenuating the PI3K/AKT signaling to up-regulate TRIM21 expression in CRC cells. Evidently, TRIM21 interacted with POU2F1, and induced the K272 ubiquitination of POU2F1. The effects of DADS on the enhanced K272 ubiquitination of POU2F1, the PPP flux, PRPP production, DNA damage and cell apoptosis as well as the growth of CRC tumors in vivo were significantly mitigated by TRIM21 silencing or activating the PI3K signaling in CRC cells. Conversely, the effects of DADS were enhanced by TRIM21 over-expression or inhibiting the PI3K/AKT signaling in CRC cells. Collectively, our findings reveal a novel mechanism by which DADS suppresses the growth of CRC by promoting POU2F1 ubiquitination, and may aid in design of novel therapeutic intervention of CRC.

Effectiveness and safety of knotless barbed sutures in cosmetic surgery: A systematic review and meta-analysis.

BACKGROUND: The barbed suture, which can eliminate knot tying and accelerate the placement of sutures, is an innovative type of suture, whereas the benefits of cosmetic surgeries (CS) are controversial. This study aimed to comprehensively evaluate the effectiveness and safety of barbed sutures in CS. METHOD: PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov were searched for English studies comparing the use of barbed with conventional sutures in CS up to October 2020. The updated Cochrane risk-of-bias tool (ROB2.0) and Newcastle-Ottawa Scale (NOS) were utilized to evaluate the risk of bias. Subgroup analysis was performed according to study designs and barbed suture types. RESULTS: A total of 14 studies, including 5 randomized controlled trials and 9 cohort studies, were included (risk of bias: moderate to low), representing 2259 patients. The barbed suture was identified to reduce suture time (mean difference [MD]=-6.18, 95% confidence interval [CI]: -8.75 to -3.60, P < 0.00001) and operative time (MD=-10.80, 95% CI: -20.83 to -0.76, P = 0.03) without increasing the hospital stays and total postoperative complications (most were Clavien I and IIIa). No significant difference was detected for incisional infection, delayed wound healing, and hematoma; however, increasing incidence of wound dehiscence (odds ratio [OR]=1.60, 95% CI: 1.09-2.34, P = 0.02) and suture extrusion (OR=3.97, 95%CI: 1.96-8.04, P = 0.0001) were found, particularly in the unidirectional barbed suture subgroup. Barbed sutures might also help CS advance and reduce seroma formation. CONCLUSION: The barbed suture was effective in CS; however, its safety needs to be cautiously interpreted as it might be related to more wound dehiscence and suture extrusion despite similar total postoperative complications with conventional sutures. This study might provide important references for decision-makers and clinicians, though further evidence of randomized design, larger sample size, longer follow-up, and standardized rating approaches are warranted.

The Role of Polaronic States on the Spin Dynamics in Solution-Processed Two-Dimensional Layered Perovskite with Different Layer Thickness.

2D lead halide perovskites (LHPs) show strong excitonic and spin-orbit coupling effects, generating a facile spin injection. Besides, they possess a polaron character due to the soft crystal lattice, which can prolong the spin lifetime, making them favorable materials for spintronic applications. Here, the spin dynamics of 2D PEA2 PbI4 (MAPbI3 )n -l thin films with different layers by temperature- and pump fluence-dependent circularly polarization-resolved transient absorption (TA) measurements is studied. These results indicate that the spin depolarization mechanism is gradually converted from the Maialle-Silva-Sham (MSS) mechanism to the polaronic states protection mechanism with the layer number increasing from = 1 to 3, which is determined by the interplay between the strength of Coulomb exchange interaction and the strength of polaronic effect. While for ≥ 4, the Elliot-Yafet (EY) impurities mechanism is proposed, in which the formed polaronic states with free charge carriers no longer play the protective role.

Exosomal cargos-mediated metabolic reprogramming in tumor microenvironment.

Metabolic reprogramming is one of the hallmarks of cancer. As nutrients are scarce in the tumor microenvironment (TME), tumor cells adopt multiple metabolic adaptations to meet their growth requirements. Metabolic reprogramming is not only present in tumor cells, but exosomal cargos mediates intercellular communication between tumor cells and non-tumor cells in the TME, inducing metabolic remodeling to create an outpost of microvascular enrichment and immune escape. Here, we highlight the composition and characteristics of TME, meanwhile summarize the components of exosomal cargos and their corresponding sorting mode. Functionally, these exosomal cargos-mediated metabolic reprogramming improves the "soil" for tumor growth and metastasis. Moreover, we discuss the abnormal tumor metabolism targeted by exosomal cargos and its potential antitumor therapy. In conclusion, this review updates the current role of exosomal cargos in TME metabolic reprogramming and enriches the future application scenarios of exosomes.

The role of tripartite motif-containing 28 in cancer progression and its therapeutic potentials.

Tripartite motif-containing 28 (TRIM28) belongs to tripartite motif (TRIM) family. TRIM28 not only binds and degrades its downstream target, but also acts as a transcription co-factor to inhibit gene expression. More and more studies have shown that TRIM28 plays a vital role in tumor genesis and progression. Here, we reviewed the role of TRIM28 in tumor proliferation, migration, invasion and cell death. Moreover, we also summarized the important role of TRIM28 in tumor stemness sustainability and immune regulation. Because of the importance of TRIM28 in tumors, TIRM28 may be a candidate target for anti-tumor therapy and play an important role in tumor diagnosis and treatment in the future.

Epimedin B exerts neuroprotective effect against MPTP-induced mouse model of Parkinson's disease: GPER as a potential target.

Mitochondrial dysfunction and oxidative stress play important roles in the neuropathogenesis of Parkinson's disease (PD). Epimedin B, the second highest active ingredient in the flavonoids of Herba Epimedii, has been proven effective in treating osteoporosis and oxaliplatin-induced peripheral neuropathy. The present study aims to investigate the neuroprotective effects of Epimedin B in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP)-induced mouse model of PD, and the involvement of G protein-coupled estrogen receptor (GPER)-mediated anti-apoptosis as well as anti-endoplasmic reticulum stress. Molecular docking revealed that Epimedin B could directly bind to GPER at the same site as GPER agonist G1 and the binding energy was - 7.3 kcal/mol. Epimedin B treatment ameliorated MPTP-induced motor dysfunction and alleviated the decreased contents of DA with its metabolites in the striatum and the loss of tyrosine hydroxylase-immunoreactive (TH-IR) neurons in the substantial nigra pars compacta (SNpc). Epimedin B treatment markedly prevented MPTP-induced changes in apoptosis-related protein Bcl-2 and Bax as well as endoplasmic reticulum stress-related protein glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP). Pharmacological blockade with GPER antagonist G15 could antagonize these neuroprotective effects of Epimedin B on the nigrostriatal system. Moreover, the anti-apoptosis and anti-endoplasmic reticulum stress effects of Epimedin B against MPTP toxicity were significantly reduced in GPER knockout (GPER-/-) mice. The present study provides the first evidence that Epimedin B can protect against MPTP-induced PD mice model. GPER may be a potential target for the neuroprotective effect of Epimedin B against PD.

A biomimetic double network hydrogel ameliorates renal fibrosis and promotes renal regeneration.

Acute kidney injury (AKI) and chronic kidney disease (CKD) are serious global public health issues. Both interconnect closely, and AKI-CKD transition significantly increases the morbidity of CKD and inevitably progresses to end stage renal disease. However, with the current drug delivery system it is hard to achieve precise delivery and apply it to clinical practice due to the local fibrotic milieu of the AKI-CKD transition procedure. Consequently, new treatment options to halt or even reverse AKI-CKD transition are urgently needed. Curcumin and Ac-SDKP were proved to be capable of ameliorating renal injury and restoring renal biological function. However, due to the water-insolubility, poor absorption and ease of degradation features, their utilization based on traditional drug delivery systems was still confined to the laboratory. A new approach for the targeted delivery of curcumin and Ac-SDKP into kidneys is needed. Hydrogels, owing to their capability of targeted-drug delivery and bio-favorable nature, emerge as a promising resolution. Herein, we developed a bioinspired double network hydrogel scaffold loaded with curcumin and N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) to explore the feasibility of drug-loaded hydrogels for treatment of AKI-CKD transition. This double network hydrogel (GCS) was prepared based on gelatin and curcumin-zinc with polydopamine (DOPA) coating and then immobilized with Ac-SDKP on the surface. The prepared hydrogels possessed appropriate porosity, suitable mechanical properties, and excellent biocompatibility. In vitro, the GCS hydrogel was demonstrated to be pro-angiogenic, anti-oxidative and anti-fibrotic. In vivo, after the GCS hydrogel was implanted into partially nephrectomized rat kidneys, local renal fibrosis was observed to be improved significantly, and neo-blood vessels and neonatal renal tubules appeared around the implanted area. We speculated that the GCS hydrogel could ameliorate renal fibrosis and injury significantly and stimulate regeneration in situ. Taken together, this study demonstrated the promising potential of this bioinspired hydrogel scaffold for renal injury repair and renal regeneration.

Exosomal miR-205-5p enhances angiogenesis and nasopharyngeal carcinoma metastasis by targeting desmocollin-2.

The aim of this study was to investigate whether and how exosomal miR-205-5p regulated angiogenesis and nasopharyngeal carcinoma (NPC) metastasis. We found that up-regulated serum exosomal miR-205-5p levels were associated with NPC progression and worse overall survival of NPC patients. miR-205-5p over-expression significantly increased tube formation, wound healing, migration and invasion of NPC cells, and lung metastasis of NPC tumors, whereas miR-205-5p inhibition had opposite effects. Exosomal miR-205-5p from NPC cells promoted the migration, tube formation, and microvessel density (MVD) of HUVECs in vitro and in vivo. Furthermore, bioinformatics-, luciferase reporter-, and biotinylated miR-205-5p-based pull-down assays indicated that miR-205-5p directly bound to the 3' UTR of desmocollin-2 (DSC2). Exosomal miR-205-5p targeted DSC2 to enhance the EGFR/ERK signaling and MMP2/MMP9 expression, promoting angiogenesis and NPC metastasis, which was abrogated by DSC2 over-expression. Finally, the levels of miR-205-5p transcripts were positively correlated with MVD but negatively with DSC2 expression in NPC tissues, and patients with miR-205high/DSC2low NPC had worse overall survival. In conclusion, exosomal miR-205-5p promotes angiogenesis and NPC metastasis by targeting DSC2 to enhance EGFR/ERK signaling and MMP expression. This exosomal/miR-205-5p/EGFR/ERK axis may be a new therapeutic target for intervention of NPC metastasis.