Oxidative Cleavage of Aromatic C-O Linkages by Oxoammonium Salts.

Oxidative cleavage of aromatic C(sp2)-O bond is important to the conversion of biomass and plastic wastes into value-added chemicals. Here we put forward the oxidative cleavage of para-C-O bonds in phenolic compounds in use of oxoammonium salts as oxidant and water as the oxygen source. The mechanism is that oxoammonium cation activates water to form hydroxy-oxoammonium adduct and thus realizes the ipso-substitution of 4-alkoxyphenol, which is proved by substituent effect, isotope labelling experiments, and kinetic analysis. Furthermore, this protocol is successfully applied into the depolymerization of both lignin model compounds with α-O-5 and 4-O-5 linkages and polyphenylene oxide (PPO).

Advanced gene nanocarriers/scaffolds in nonviral-mediated delivery system for tissue regeneration and repair.

Tissue regeneration technology has been rapidly developed and widely applied in tissue engineering and repair. Compared with traditional approaches like surgical treatment, the rising gene therapy is able to have a durable effect on tissue regeneration, such as impaired bone regeneration, articular cartilage repair and cancer-resected tissue repair. Gene therapy can also facilitate the production of in situ therapeutic factors, thus minimizing the diffusion or loss of gene complexes and enabling spatiotemporally controlled release of gene products for tissue regeneration. Among different gene delivery vectors and supportive gene-activated matrices, advanced gene/drug nanocarriers attract exceptional attraction due to their tunable physiochemical properties, as well as excellent adaptive performance in gene therapy for tissue regeneration, such as bone, cartilage, blood vessel, nerve and cancer-resected tissue repair. This paper reviews the recent advances on nonviral-mediated gene delivery systems with an emphasis on the important role of advanced nanocarriers in gene therapy and tissue regeneration.

Insight into the mechanism of high hydrostatic pressure effect on inhibitory efficiency of three natural inhibitors on polyphenol oxidase.

The development of natural inhibitors of polyphenol oxidase (PPO) is crucial in the prevention of enzymatic browning in fresh foods. However, few studies have focused on the effect of subsequent sterilization on their inhibition efficiency. This study investigated the influence and mechanism of high hydrostatic pressure (HHP) on the inhibition of PPO by epigallocatechin gallate (EGCG), cyanidin-3-O-glucoside (C3G), and ferulic acid. Results showed that under the conditions of 550 MPa/30 min, the activity of EGCG-PPO decreased to 55.92%, C3G-PPO decreased to 81.80%, whereas the activity of FA-PPO remained stable. Spectroscopic experiments displayed that HHP intensified the secondary structure transformation and fluorescence quenching of PPO. Molecular dynamics simulations revealed that at 550 MPa, the surface interaction between PPO with EGCG or C3G increased, potentially leading to a reduction in their activity. In contrast, FA-PPO demonstrated conformational stability. This study can provide a reference for the future industrial application of natural inhibitors.

An angiotensin system inhibitor (losartan) potentiates antitumor efficacy of cisplatin in a murine model of non-small cell lung cancer.

Objective: Previous studies have demonstrated synergistic antitumor effects of angiotensin system inhibition (ASI) combined with cisplatin therapy in pancreatic cancer. This study examines whether or not synergistic antitumor effects occur with combination ASI and cisplatin treatment in lung cancer, and whether or not ASI-induced changes in epithelial-mesenchymal transition play a role in the mechanism of this antitumor phenomenon. Methods: A set of lung cancer cell lines representing a spectrum of epithelial to mesenchymal phenotypes were identified and characterized. Response of epithelial-mesenchymal transition markers to losartan was characterized. Cell culture models of lung cancer were next treated with losartan, cisplatin, or combination of both. Markers of epithelial-mesenchymal transition or surrogates of other signaling pathways (AKT, Stat3, and programmed death-ligand), and cell viability were quantified. Findings were confirmed in both allogenic and syngeneic in vivo murine flank tumor models. Results: Losartan treatment significantly increased E-cadherin and reduced vimentin in human lung cancer cell lines. Combination treatment with losartan and cisplatin enhanced epithelial markers, reduced mesenchymal markers, inhibited promesenchymal signaling mediators, and reduced cell viability. Findings were confirmed in vivo in a murine flank tumor model with transition from mesenchymal to epithelial phenotype and reduced tumor size following combination losartan and cisplatin treatment. Conclusions: Combination losartan and cisplatin treatment attenuates the epithelial-mesenchymal transition pathway and enhances the cytotoxic effect of chemotherapy with in vitro and in vivo models of non-small cell lung cancer. This study suggests an important role for ASI therapy in the treatment of lung cancer.

Focal adhesion and actin orientation regulated by cellular geometry determine stem cell differentiation via mechanotransduction.

Tuning cell adhesion geometry can affect cytoskeleton organization and the distribution of cytoskeleton forces, which play critical roles in controlling cell functions. To elucidate the geometrical relationship with cytoskeleton force distribution, it is necessary to control cell morphology. In this study, a series of dextral vortex micropatterns were prepared to precisely control cell morphology for investigating the influence of the curvature degree of adhesion curves on intracellular force distribution and stem cell differentiation at a sub-cellular level. Peripherial actin filaments of micropatterned cells were assembled along the adhesion curves and showed different orientations, filament thicknesses and densities. Focal adhesion and cytoskeleton force distribution were dependent on the curvature degree. Intracellular force distribution was also regulated by adhesion curves. The cytoskeleton and force distribution affected the osteogenic differentiation of mesenchymal stem cells through a YAP/TAZ-mediated mechanotransduction process. Thus, regulation of cell adhesion curvature, especially at cytoskeletal filament level, is critical for cell function manipulation. STATEMENT OF SIGNIFICANCE: In this study, a series of dextral micro-vortexes were prepared and used for the culture of human mesenchymal stem cells (hMSCs) to precisely control adhesive curvatures (0°, 30°, 60°, and 90°). The single MSCs on the micropatterns had the same size and shape but showed distinct focal adhesion (FA) and cytoskeleton orientations. Cellular nanomechanics were observed to be correlated with the curvature degrees, subsequently influencing nuclear morphological features. As a consequence, the localization of the mechanotransduction sensor and activator-YAP/TAZ was affected, influencing osteogenic differentiation. The results revealed the pivotal role of adhesive curvatures in the manipulation of stem cell differentiation via the machanotransduction process, which has rarely been investigated.

HIV coinfection exacerbates HBV-induced liver fibrogenesis through a HIF-1α- and TGF-ß1-dependent pathway.

BACKGROUND & AIMS: Persons with chronic HBV infection coinfected with HIV experience accelerated progression of liver fibrosis compared to those with HBV monoinfection. We aimed to determine whether HIV and its proteins promote HBV-induced liver fibrosis in HIV/HBV-coinfected cell culture models through HIF-1α and TGF-ß1 signaling. METHODS: The HBV-positive supernatant, purified HBV viral particles, HIV-positive supernatant, or HIV viral particles were directly incubated with cell lines or primary hepatocytes, hepatic stellate cells, and macrophages in mono or 3D spheroid coculture models. Cells were incubated with recombinant cytokines and HIV proteins including gp120. HBV sub-genomic constructs were transfected into NTCP-HepG2 cells. We also evaluated the effects of inhibitor of HIF-1α and HIV gp120 in a HBV carrier mouse model that was generated via hydrodynamic injection of the pAAV/HBV1.2 plasmid into the tail vein of wild-type C57BL/6 mice. RESULTS: We found that HIV and HIV gp120, through engagement with CCR5 and CXCR4 coreceptors, activate AKT and ERK signaling and subsequently upregulate hypoxia-inducible factor-1α (HIF-1α) to increase HBV-induced transforming growth factor-ß1 (TGF-ß1) and profibrogenic gene expression in hepatocytes and hepatic stellate cells. HIV gp120 exacerbates HBV X protein-mediated HIF-1α expression and liver fibrogenesis, which can be alleviated by inhibiting HIF-1α. Conversely, TGF-ß1 upregulates HIF-1α expression and HBV-induced liver fibrogenesis through the SMAD signaling pathway. HIF-1α small-interfering RNA transfection or the HIF-1α inhibitor (acriflavine) blocked HIV-, HBV-, and TGF-ß1-induced fibrogenesis. CONCLUSIONS: Our findings suggest that HIV coinfection exacerbates HBV-induced liver fibrogenesis through enhancement of the positive feedback between HIF-1α and TGF-ß1 via CCR5/CXCR4. HIF-1α represents a novel target for antifibrotic therapeutic development in HBV/HIV coinfection. IMPACT AND IMPLICATIONS: HIV coinfection accelerates the progression of liver fibrosis compared to HBV monoinfection, even among patients with successful suppression of viral load, and there is no sufficient treatment for this disease process. In this study, we found that HIV viral particles and specifically HIV gp120 promote HBV-induced hepatic fibrogenesis via enhancement of the positive feedback between HIF-1α and TGF-ß1, which can be ameliorated by inhibition of HIF-1α. These findings suggest that targeting the HIF-1α pathway can reduce liver fibrogenesis in patients with HIV and HBV coinfection.

Association between CT-based adipose variables, preoperative blood biochemical indicators and pathological T stage of clear cell renal cell carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC) is corelated with tumor-associated material (TAM), coagulation system and adipocyte tissue, but the relationships between them have been inconsistent. Our study aimed to explore the cut-off intervals of variables that are non-linearly related to ccRCC pathological T stage for providing clues to understand these discrepancies, and to effectively preoperative risk stratification. Methods: This retrospective analysis included 218 ccRCC patients with a clear pathological T stage between January 1st, 2014, and November 30th, 2021. The patients were categorized into two cohorts based on their pathological T stage: low T stage (T1 and T2) and high T stage (T3 and T4). Abdominal and perirenal fat variables were measured based on preoperative CT images. Blood biochemical indexes from the last time before surgery were also collected. The generalized sum model was used to identify cut-off intervals for nonlinear variables. Results: In specific intervals, fibrinogen levels (FIB) (2.63-4.06 g/L) and platelet (PLT) counts (>200.34 × 109/L) were significantly positively correlated with T stage, while PLT counts (<200.34 × 109/L) were significantly negatively correlated with T stage. Additionally, tumor-associated material exhibited varying degrees of positive correlation with T stage at different cut-off intervals (cut-off value: 90.556 U/mL). Conclusion: Preoperative PLT, FIB and TAM are nonlinearly related to pathological T stage. This study is the first to provide specific cut-off intervals for preoperative variables that are nonlinearly related to ccRCC T stage. These intervals can aid in the risk stratification of ccRCC patients before surgery, allowing for developing a more personalized treatment planning.

Comparison of the mid-term clinical efficacy of different fixtaion methods combined with oblique lumbar interbody fusion in treating lumbar degenerative diseases.

BACKGROUND: To compare the mid-term follow-up clinical efficacy among three treatment approaches for lumbar degenerative diseases (LDD): standalone oblique lumbar interbody fusion (SF), oblique lumbar interbody fusion combined with lateral screw fixation (LF), and oblique lumbar interbody fusion combined with posterior screw fixation (PF). METHOD: This retrospective study included a total of 71 cases of single level LDD that underwent OLIF in Hospital of Chengdu University of Traditional Chinese Medicine were retrospectively collected between March 2016 and September 2017. Patients were divided into three groups: 24 cases in the SF group, 24 cases in the LF group and 23 cases in the PF group. Various parameters, such as operation time, hospitalization time, and complications, were recorded. The fusion condition was assessed at last follow up. Clinical outcomes were evaluated using the Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) from pre-operation to 5 years post-surgery. RESULTS: Significantly lower mean operation time and hospitalization time were observed in the SF and LF groups compared to the PF group (p < .05). However, no significant difference in fusion rate was found among the three groups. Regarding clinical outcomes, there was no statistically significant difference in VAS scores between the three groups during all follow-up periods. At the 6th month and 1st year after surgery, the SF and LF groups had significantly lower Oswestry Disability Index (ODI) scores compared to the PF group (p < .05). There was no significant difference in perioperative complication rates among the three groups (p > .05). In the LF group, one case of instrument displacement and urethra injury were reported, while in the SF, LF, and PF groups, 10, 9, and 3 cases of cage subsidence were reported, respectively. CONCLUSION: The study findings suggest that oblique lumbar interbody fusion (OLIF) is a safe and effective treatment for mid-term management of lumbar degenerative diseases (LDD). Compared to the posterior screw fixation (PF) group, both the standalone OLIF (SF) and OLIF combined with lateral screw fixation (LF) groups showed advantages in terms of reduced operation time, shorter hospitalization, and faster symptom alleviation in the short-term. However, OLIF combined with PF demonstrated comparable symptom relief in the mid-term and had the additional benefit of lower cage subsidence rates while improving fusion rates as well.

Chiral Cell Nanomechanics Originated in Clockwise/Counterclockwise Biofunctional Microarrays to Govern the Nuclear Mechanotransduction of Mesenchymal Stem Cells.

Cell chirality is extremely important for the evolution of cell morphogenesis to manipulate cell performance due to left-right asymmetry. Although chiral micro- and nanoscale biomaterials have been developed to regulate cell functions, how cell chirality affects cell nanomechanics to command nuclear mechanotransduction was ambiguous. In this study, chiral engineered microcircle arrays were prepared by photosensitive cross-linking synthesis on cell culture plates to control the clockwise/counterclockwise geometric topology of stem cells. Asymmetric focal adhesion and cytoskeleton structures could induce chiral cell nanomechanics measured by atomic force microscopy (AFM) nanoindentation in left-/right-handed stem cells. Cell nanomechanics could be enhanced when the construction of mature focal adhesion and the assembly of actin and myosin cytoskeletons were well organized in chiral engineered stem cells. Curvature angles had a negative effect on cell nanomechanics, while cell chirality did not change cytoskeletal mechanics. The biased cytoskeleton tension would engender different nuclear mechanotransductions by yes-associated protein (YAP) evaluation. The chiral stimuli were delivered into the nuclei to oversee nuclear behaviors. A strong cell modulus could activate high nuclear DNA synthesis activity by mechanotransduction. The results will bring the possibility of understanding the interplay of chiral cell nanomechanics and mechanotransduction in nanomedicines and biomaterials.

A systematic review and meta-analysis of risk factors for reoperation after degenerative lumbar spondylolisthesis surgery.

BACKGROUND: Considering the high reoperation rate in degenerative lumbar spondylolisthesis (DLS) patients undergoing lumbar surgeries and controversial results on the risk factors for the reoperation, we performed a systematic review and meta-analysis to explore the reoperation rate and risk factors for the reoperation in DLS patients undergoing lumbar surgeries. METHODS: Literature search was conducted from inception to October 28, 2022 in Pubmed, Embase, Cochrane Library, and Web of Science. Odds ratio (OR) was used as the effect index for the categorical data, and effect size was expressed as 95% confidence interval (CI). Heterogeneity test was performed for each outcome effect size, and subgroup analysis was performed based on study design, patients, surgery types, follow-up time, and quality of studies to explore the source of heterogeneity. Results of all outcomes were examined by sensitivity analysis. Publication bias was assessed using Begg test, and adjusted using trim-and-fill analysis. RESULTS: A total of 39 cohort studies (27 retrospective cohort studies and 12 prospective cohort studies) were finally included in this systematic review and meta-analysis. The overall results showed a 10% (95%CI: 8%-12%) of reoperation rate in DLS patients undergoing lumbar surgeries. In surgery types subgroup, the reoperation rate was 11% (95%CI: 9%-13%) for decompression, 10% (95%CI: 7%-12%) for fusion, and 9% (95%CI: 5%-13%) for decompression and fusion. An increased risk of reoperation was found in patients with obesity (OR = 1.91, 95%CI: 1.04-3.51), diabetes (OR = 2.01, 95%CI: 1.43-2.82), and smoking (OR = 1.51, 95%CI: 1.23-1.84). CONCLUSIONS: We found a 10% of reoperation rate in DLS patients after lumbar surgeries. Obesity, diabetes, and smoking were risk factors for the reoperation.

A PDA-Functionalized 3D Lung Scaffold Bioplatform to Construct Complicated Breast Tumor Microenvironment for Anticancer Drug Screening and Immunotherapy.

2D cell culture occupies an important place in cancer progression and drug discovery research. However, it limitedly models the "true biology" of tumors in vivo. 3D tumor culture systems can better mimic tumor characteristics for anticancer drug discovery but still maintain great challenges. Herein, polydopamine (PDA)-modified decellularized lung scaffolds are designed and can serve as a functional biosystem to study tumor progression and anticancer drug screening, as well as mimic the tumor microenvironment. PDA-modified scaffolds with strong hydrophilicity and excellent cell compatibility can promote cell growth and proliferation. After 96 h treatment with 5-FU, cisplatin, and DOX, higher survival rates in PDA-modified scaffolds are observed compared to nonmodified scaffolds and 2D systems. The E-cadhesion formation, HIF-1α-mediated senescence decrease, and tumor stemness enhancement can drive drug resistance and antitumor drug screening of breast cancer cells. Moreover, there is a higher survival rate of CD45+ /CD3+ /CD4+ /CD8+ T cells in PDA-modified scaffolds for potential cancer immunotherapy drug screening. This PDA-modified tumor bioplatform will supply some promising information for studying tumor progression, overcoming tumor resistance, and screening tumor immunotherapy drugs.

HIGF-Net: Hierarchical information-guided fusion network for polyp segmentation based on transformer and convolution feature learning.

Polyp segmentation plays a role in image analysis during colonoscopy screening, thus improving the diagnostic efficiency of early colorectal cancer. However, due to the variable shape and size characteristics of polyps, small difference between lesion area and background, and interference of image acquisition conditions, existing segmentation methods have the phenomenon of missing polyp and rough boundary division. To overcome the above challenges, we propose a multi-level fusion network called HIGF-Net, which uses hierarchical guidance strategy to aggregate rich information to produce reliable segmentation results. Specifically, our HIGF-Net excavates deep global semantic information and shallow local spatial features of images together with Transformer encoder and CNN encoder. Then, Double-stream structure is used to transmit polyp shape properties between feature layers at different depths. The module calibrates the position and shape of polyps in different sizes to improve the model's efficient use of the rich polyp features. In addition, Separate Refinement module refines the polyp profile in the uncertain region to highlight the difference between the polyp and the background. Finally, in order to adapt to diverse collection environments, Hierarchical Pyramid Fusion module merges the features of multiple layers with different representational capabilities. We evaluate the learning and generalization abilities of HIGF-Net on five datasets using six evaluation metrics, including Kvasir-SEG, CVC-ClinicDB, ETIS, CVC-300, and CVC-ColonDB. Experimental results show that the proposed model is effective in polyp feature mining and lesion identification, and its segmentation performance is better than ten excellent models.

Display of CCL21 on cancer cell membrane through genetic modification using a pH low insertion peptide.

CCL21, a secondary lymphoid tissue chemokine, plays an important role in generating an effective anti-tumor immune response. In this study, a genetically modified CCL21 was developed by inserting a pH low insertion peptide to establish a CCL21-rich microenvironment for tumors. The fusion tag thioredoxin (Trx) was designed and fused at the N-terminal of the recombinant protein to protect it from being irrevocably misfolded in microbial host cells. The prokaryotic expression vector pET32a-CCL21-pHLIP was constructed and successfully expressed in E. coli BL21 (DE3) with a soluble expression form and a molecular weight of ~35 kDa. The induction conditions were optimized to obtain an extremely high yield of 6.7 mg target protein from 31.1 mg total protein. The 6xHis tagged Trx-CCL21-pHLIP was purified using Ni-NTA resin, and it was confirmed using SDS-PAGE and Western blot analyses. Consequently, the Trx-CCL21-pHLIP protein was successfully displayed on the cancer cell surface in a weak acidic microenvironment and showed the same ability as CCL21 in recruiting CCR7-positive cells. Additionally, the CCL21 fusion protein with or without Trx tag showed similar functions. Therefore, the study implies the feasibility of directing a modular genetic method for the development of protein-based drugs.

Training to be a spinal endoscopic surgeon: What matters?

Objective: Spinal endoscopic surgery has been promoted rapidly in the past decade, attracting an increasing number of young, dedicated surgeons. However, it has long been denounced for its long learning curve as a factor impeding the development of this state-of-the-art technique. The aim of the present study was to discover what really matters in the educational process of becoming a spinal endoscopic surgeon. Methods: An online survey consisting of 14 compulsory questions was distributed in April and May 2022 through the First Chinese Spinal Endoscopic Surgeons Skills Competition. Reminders were sent to increase response rates. Results: Of the 893 emails that were sent, we received 637 responses. A total of 375 (76.7%) surgeons most frequently used endoscopic techniques in their practices. Regardless of their different backgrounds, 284 (75.7%) surgeons thought it would be necessary for a young spinal endoscopic surgeon to perform 300 cases independently in order to become proficient, followed by 500 (n=43, 11.5%), 100 (n=40, 10.7%), and 1,000 (n=8, 2.1%) cases. According to the surgeons, the most difficult aspect of mastering the endoscopic technique is a disparate surgical view (n=255, 68%), followed by adaption to new instruments (n=86, 22.9%) and hand-eye coordination (n=34, 9.1%). The most helpful training method for helping the spinal endoscopic surgeons of younger generations improve is operating on simulation models or cadaver courses (n=216, 57.6%), followed by online or offline theoretical courses (n=67, 17.9%), acquiring opportunities during surgeries (n=51, 13.6%), and frequently participating in surgeries as an assistant (n=41, 10.9%). Conclusion: From the perspective of surgeons, to be skilled in spinal endoscopic surgery means overcoming a steep learning curve. However, training systems should be given more attention to make them more accessible to younger surgeons so they can work on simulation models or take cadaver courses.

Near-Infrared Photoresponsive Nanotransducers for Precise Regulation of Gene Expression.

Regulation of gene expression is conducive to understanding the physiological roles of specific genes and provides therapeutic potentials, which however still remains a great challenge. Nonviral carriers have some advantages for gene delivery compared to traditional physical delivery strategies, but they often fail to control the delivery of genes in targeting regions, and thus lead to off-target side effects. Although endogenous biochemical signal-responsive carriers have been used to improve the transfection efficiency, their selectivity and specificity are still poor because of the coexistence of biochemical signals in both normal tissues and disease sites. In contrast, light-responsive carriers can be adopted to precisely control gene transgenic behaviors at the specified locations and time, thus reducing the off-target gene editing at nontarget positions. Particularly, the near-infrared (NIR) light has better tissue penetration depth and lower phototoxicity than ultraviolet and visible light sources, showing great promise for intracellular gene expression regulation. In this review, we summarize the recent progress of NIR photoresponsive nanotransducers for precision regulation of gene expression. These nanotransducers can achieve controlled gene expression via three different mechanisms (photothermal activation, photodynamic regulation, and NIR photoconversion) to allow various applications, such as gene therapy of cancer, which will be discussed in detail. A conclusion and discussion of the challenges and outlook will be given at the end of this review.

Postoperative bone graft migration into the thecal sac and shifting down to the lower level after an endoscopic lumbar interbody fusion: a case report.

BACKGROUND: Postoperative bone graft migration (PBGM) is a fairly rare spinal postoperative complication. Its occurrence after endoscopic surgery has rarely been reported in the literature so far. This is a case report of a 52-year-old male occurring PBGM into the thecal sac in the 8th days after an endoscopic lumbar interbody fusion (ELIF), which can make surgeons more minded with such serious rare complication after BGM. CASE PRESENTATION: A 52-year-old male patient, underwent a L4-5 ELIF, presented with an acute radiculopathy on right leg and urinary incontinence in the 8th postoperative day. An emergency lumbar Computed Tomography(CT scan) and Magnetic Resonance Imaging (MRI) demonstrated bone graft migration into the thecal sac at the L4-5 level, and shifting down to the lower level. The revision surgery was performed at once successfully. Finally, the patient got well managed before discharge. CONCLUSION: Supported by this case report, we believe that PBGM into the thecal sac is a rare but horrible complication of ELIF. However, too much volume of bone graft and its posterior placement are more prone to developing this complication. Finally, we are not sure that the outcome presented in this study will be repeated in future cases.

Molecular Self-Assembled Ether-Based Polyrotaxane Solid Electrolyte for Lithium Metal Batteries.

Poly(ethylene oxide) has been widely investigated as a potential separator for solid-state lithium metal batteries. However, its applications were significantly restricted by low ionic conductivity and a narrow electrochemical stability window (<4.0 V vs Li/Li+) at room temperature. Herein, a novel molecular self-assembled ether-based polyrotaxane electrolyte was designed using different functional units and prepared by threading cyclic 18-crown ether-6 (18C6) to linear poly(ethylene glycol) (PEG) via intermolecular hydrogen bond and terminating with hexamethylene diisocyanate trimer (HDIt), which was strongly confirmed by local structure-sensitive solid/liquid-state nuclear magnetic resonance (NMR) techniques. The designed electrolyte has shown an obviously increased room-temperature ionic conductivity of 3.48 × 10-4 S cm-1 compared to 1.12 × 10-5 S cm-1 without assembling polyrotaxane functional units, contributing to the enhanced cycling stability of batteries with both LiFePO4 and LiNi0.8Co0.15Al0.05O2 cathode materials. This advanced molecular self-assembled strategy provides a new paradigm in designing solid polymer electrolytes with demanded performance for lithium metal batteries.

RNF20 deletion causes inflammation in model of sepsis through the NLRP3 activation.

Aim: Sepsis is an extremely complex, threatening and difficult-to-treat disease, which can occur at any age and under any underlying disease. RNF20 regulate NF-kappaB (NF-κB) signaling pathway and the transcription of inflammatory factors of target genes. Therefore, it is of great significance to study the function of RNF20 in the clinical treatment of sepsis and its underlying mechanisms.Methods: C57BL/6 mice were subjected to cecal ligation and puncture (CLP) surgery. THP-1 cells were induced with Lipopolysaccharide for 4 h.Results: RNF20 gene, mRNA expression and protein expression were reduced in patients with sepsis and mice with sepsis. Based on RNF20 deletion (RNF20-/-) mice, these were found to be increased inflammation reactions in RNF20-/- mice. However, the RNF20 human protein reduced inflammation reactions in mice with sepsis. In vitro model of sepsis, over-expression of RNF20 inhibited inflammation reactions by inducing Vitamin D Receptor (VDR), while down-regulation of RNF20 promoted inflammation reactions through the suppression of VDR. RNF20 protein was interlinked with VDR protein, and VDR protein was also interlinked with NLRP3. Furthermore, VDR promoted NLRP3 ubiquitination and reduced NLRP3 function in vitro model of sepsis.Conclusion: These studies demonstrate that RNF20 suppressed inflammation reactions in models with sepsis through NLRP3 inflammasome and NLRP3 ubiquitination by activating VDR.