Reconstruction of medial meniscus posterior portion deficiency in pigs with an autologous patellar tendon graft: an experimental study.

OBJECTIVE: This study was performed to investigate the effectiveness of two surgical procedures, autologous patellar tendon graft reconstruction and trans-tibial plateau pull-out repair, using a pig model. The primary focus was to assess the repair capability of medial meniscus posterior portion (MMPP) deficiency, the overall structural integrity of the meniscus, and protection of the femoral and tibial cartilage between the two surgical groups. The overall aim was to provide experimental guidelines for clinical research using these findings. METHODS: Twelve pigs were selected to establish a model of injury to the MMPP 10 mm from the insertion point of the tibial plateau. They were randomly divided into three groups of four animals each: reconstruction (autologous tendon graft reconstruction of the MMPP), pull-out repair (suture repair of the MMPP via a trans-tibial plateau bone tunnel), and control (use of a normal medial meniscus as the negative control). The animals were euthanized 12 weeks postoperatively for evaluation of the meniscus, assessment of tendon bone healing, and gross observation of knee joint cartilage. The tibial and femoral cartilage injuries were evaluated using the International Society for Cartilage Repair (ICRS) grade and Mankin score. Histological and immunohistochemical staining was conducted on the meniscus-tendon junction area, primary meniscus, and tendons. The Ishida score was used to evaluate the regenerated meniscus in the reconstruction group. Magnetic resonance imaging (MRI) was used to evaluate meniscal healing. RESULTS: All 12 pigs recovered well after surgery; all incisions healed without infection, and no obvious complications occurred. Gross observation revealed superior results in the reconstruction and pull-out repair groups compared with the control group. In the tibial cartilage, the reconstruction group had ICRS grade I injury whereas the pull-out repair and control groups had ICRS grade II and III injury, respectively. The Mankin score was significantly different between the reconstruction and control groups; histological staining showed that the structure of the regenerated meniscus in the reconstruction group was similar to that of the original meniscus. Immunohistochemical staining showed that the degree of type I and II collagen staining was similar between the regenerated meniscus and the original meniscus in the reconstruction group. The Ishida score was not significantly different between the regenerated meniscus and the normal primary meniscus in the reconstruction group. MRI showed that the MMPP in the reconstruction and pull-out repair groups had fully healed, whereas that in the control group had not healed. CONCLUSION: Autologous patellar tendon graft reconstruction of the MMPP can generate a fibrocartilage-like regenerative meniscus. Both reconstruction and pull-out repair can preserve the structural integrity of the meniscus, promote healing of the MMPP, delay meniscal degeneration, and protect the knee cartilage.

Cold-plasma activation converting conductive agent in spent Li-ion batteries to bifunctional oxygen reduction/evolution electrocatalyst for zinc-air batteries.

Considerable amount of high-value transition metals components can be recycled in spent ternary lithium-ion batteries. In this study, we utilized the conductive agent carbon black, obtained from the leaching waste resulting from the chemical recovery of spent lithium-nickel-manganese-cobalt (NCM) oxide cathode materials. This process allows us to create valuable bifunctional catalysts for the oxygen reduction reaction and oxygen evolution reaction (ORR/OER), facilitated by a facile cold plasma activation method, as a part of lithium batteries circular economy. The activated conductive agent (RCA-30) exhibited an ORR half-wave potential of 0.74 V (vs. RHE) in 0.1 mol/L KOH solution, and an OER overpotential of 360 mV at 10 mA cm-2 in 1 mol/L KOH electrolyte, owing to nitrogen doping of carbon black and activation of surface metal oxides. The complete zinc-air batteries incorporating the activated catalysts at the cathode exhibited an open circuit potential of up to 1.48 V and sustained cycling for 100 h at a current density of 5 mA cm-2. Additionally, the activated catalysts contributed to a power density of 92 mW cm-2 and a full discharge capacity of 640 mAh/g.

Decreased LDHB expression in breast tumor cells causes NK cell activation and promotes tumor progression.

OBJECTIVE: Abnormal metabolism is the underlying reason for breast cancer progression. Decreased lactate dehydrogenase B (LDHB) has been detected in breast cancer but the function of LDHB remains unknown. METHODS: Western blot was used to analyze LDHB expression in breast cancer cells. The impact of LDHB on tumor cell migration and invasion was determined using Transwell assays, wound healing assays, and a mouse lung metastasis model. Subcutaneous tumor formation, a natural killer (NK) cell cytotoxicity assay, and flow cytometry evaluated NK cell activation. Immunofluorescence and quantitative real-time PCR detected NK cell activation markers. Kaplan-Meier analysis evaluated the effect of immune cell infiltration on prognosis. Single-sample gene set enrichment analysis determined NK cell activation scores. A support vector machine predicted the role of LDHB in NK cell activation. RESULTS: In this study we showed that LDHB inhibits the breast cancer cell metastasis and orchestrates metabolic reprogramming within tumor cells. Our results revealed that LDHB-mediated lactic acid clearance in breast cancer cells triggers NK cell activation within the tumor microenvironment. Our findings, which were confirmed in a murine model, demonstrated that LDHB in tumor cells promotes NK cell activation and ultimately results in the eradication of malignant cells. Clinically, our study further validated that LDHB affects immune cell infiltration and function. Specifically, its expression has been linked to enhanced NK cell-mediated cytotoxicity and improved patient survival. Furthermore, we identified LDHB expression in tumors as an important predictor of NK cell activation, with strong predictive ability in some cancers. CONCLUSIONS: Our results suggest that LDHB is a promising target for activating the tumor immune microenvironment in breast cancer, where LDHB-associated lactic acid clearance leads to increased NK cell activity. This study highlights the critical role of LDHB in regulating immune responses and its potential as a therapeutic target for breast cancer.

Radix Bupleuri aqueous extract attenuates MK801-induced schizophrenia-like symptoms in mice: Participation of intestinal flora.

Schizophrenia (SCZ) is a psychotic mental disorder characterized by cognitive, behavioral, and social impairments. However, current pharmacological treatment regimens are subpar in terms of effectiveness. This study aimed to investigate the function of Radix Bupleuri aqueous extract in SCZ in mouse models. The SCZ mouse model was established by MK-801 injection and feeding of Radix Bupleuri aqueous extract or combined antibiotics. Radix Bupleuri aqueous extract significantly improved the aberrant behaviors and neuronal damage in SCZ mice, upregulated SYP and PSD-95 expression and BDNF levels in hippocampal homogenates, down-regulated DA and 5-HT levels, and suppressed microglial activation in SCZ mice. Moreover, Radix Bupleuri aqueous extract improved the integrity of the intestinal tract barrier. The 16 S rRNA sequencing of feces showed that Radix Bupleuri extract modulated the composition of gut flora. Lactobacillus abundance was decreased in SCZ mice and reversed by Radix Bupleuri aqueous extract administration which exhibited a significant negative correlation with IL-6, IL-1ß, DA, and 5-HT, and a significant positive correlation with BDNF levels in hippocampal tissues. The abundance of Parabacteroides and Alloprevotella was increased in SCZ mice. It was reversed by Radix Bupleuri aqueous extract administration, which exhibited a positive correlation with IL-6, IL-1ß, and 5-HT and a negative correlation with BDNF. In conclusion, Radix Bupleuri aqueous extract attenuates the inflammatory response in hippocampal tissues and modulates neurotransmitter levels, exerting its neuroprotective effect in SCZ. Meanwhile, the alteration of intestinal flora may be involved in this process, which is expected to be an underlying therapeutic option in treating SCZ.

Injectable Decorin/Gellan Gum Hydrogel Encapsulating Adipose-Derived Stem Cells Enhances Anti-Inflammatory Effect in Cartilage Injury via Autophagy Signaling.

Adipose-derived stem cells (ADSCs) are employed as a promising alternative in treating cartilage injury. Regulating the inflammatory "fingerprint" of ADSCs to improve their anti-inflammatory properties could enhance therapy efficiency. Herein, a novel injectable decorin/gellan gum hydrogel combined with ADSCs encapsulation for arthritis cartilage treatment is proposed. Decorin/gellan gum hydrogel was prepared according to the previous manufacturing protocol. The liquid-solid form transition of gellan gum hydrogel is perfectly suitable for intra-articular injection. Decorin-enriched matrix showing an immunomodulatory ability to enhance ADSCs anti-inflammatory phenotype under inflammation microenvironment by regulating autophagy signaling. This decorin/gellan gum/ADSCs hydrogel efficiently reverses interleukin-1ß-induced cellular injury in chondrocytes. Through a mono-iodoacetate-induced arthritis mice model, the synergistic therapeutic effect of this ADSCs-loaded hydrogel, including inflammation attenuation and cartilage protection, is demonstrated. These results make the decorin/gellan gum hydrogel laden with ADSCs an ideal candidate for treating inflammatory joint disorders.

Clay-Originated Two-Dimensional Holey Silica Separator for Dendrite-Free Lithium Metal Anode.

Lithium metal anode is the ultimate choice to obtain next-generation high-energy-density lithium batteries, while the dendritic lithium growth owing to the unstable lithium anode/electrolyte interface largely limits its practical application. Separator is an important component in batteries and separator engineering is believed to be a tractable and effective way to address the above issue. Separators can play the role of ion redistributors to guide the transport of lithium ions and regulate the uniform electrodeposition of Li. The electrolyte wettability, thermal shrinkage resistance, and mechanical strength are of importance for separators. Here, clay-originated two-dimensional (2D) holey amorphous silica nanosheets (ASN) to develop a low-cost and eco-friendly inorganic separator is directly adopted. The ASN-based separator has higher porosity, better electrolyte wettability, much higher thermal resistance, larger lithium transference number, and ionic conductivity compared with commercial separator. The large amounts of holes and rich surface oxygen groups on the ASN guide the uniform distribution of lithium-ion flux. Consequently, the Li//Li cell with this separator shows stable lithium plating/stripping, and the corresponding Li//LiFePO4 , Li//LiCoO2, and Li//NCM523 full cells also show high capacity, excellent rate performance, and outstanding cycling stability, which is much superior to that using the commercial separator.

Hospital spending and length of hospital stay for mental disorders in Hunan, China.

Objectives: To describe hospital spending and length of stay for mental disorders in Hunan, China. Methods: We extracted hospital care data for Hunan province from the Chinese National Health Statistics Network Reporting System. Patients with mental disorders (ICD-10 codes: F00 to F99) as the principal diagnosis and hospitalized between January 1, 2017 and December 31, 2019 were included. We retrieved information on age, sex, number of comorbidities, diagnosis, level of hospital, hospital costs, date of admission and discharge, length of stay (LOS), and method of payment of eligible participants. Spending at the provincial level, and spending and LOS at the individual level were described. Quantile regression and linear regression were conducted to investigate factors for hospital cost and LOS for major mental disorders. Results: The 2019 annual spending on mental disorders in Hunan province was 160 million US dollars, and 71.7% was paid by insurance. The annual spending on schizophrenia was 84 million dollars, contributing to a primary burden of mental disorders. The median spending for mental disorders was $1,085 per patient, and the median hospital stay was 22 days. The study identified several significant factors associated with hospital cost and LOS, including age, sex, comorbidity, and level of the hospital. In particular, a higher level of the hospital was associated with a higher hospital spending but a shorter LOS. Women with schizophrenia had a comparable hospital spending but a significantly shorter LOS than men with schizophrenia. Conclusion: Hospitalization spending for patients with mental disorders is substantial. Schizophrenia is the major burden of hospitalization for mental disorders. While patients treated at a higher level of hospital had higher spending, they stayed shorter in these hospitals.

HWJMSC-derived extracellular vesicles ameliorate IL-1ß-induced chondrocyte injury through regulation of the BMP2/RUNX2 axis via up-regulation TFRC.

Articular osteochondral injury is a common and frequently occurring disease in orthopedics that is caused by aging, disease, and trauma. The cytokine interleukin-1ß (IL-1ß) is a crucial mediator of the inflammatory response, which exacerbates damage during chronic disease and acute tissue injury. Human Wharton's jelly mesenchymal stem cell (HWJMSC) extracellular vesicles (HWJMSC-EVs) have been shown to promote cartilage regeneration. The study aimed to investigate the influence and mechanisms of HWJMSC-EVs on the viability, apoptosis, and cell cycle of IL-1ß-induced chondrocytes. HWJMSC-EVs were isolated by Ribo™ Exosome Isolation Reagent kit. Nanoparticle tracking analysis was used to determine the size and concentration of HWJMSC-EVs. We characterized HWJMSC-EVs by western blot and transmission electron microscope. The differentiation, viability, and protein level of chondrocytes were measured by Alcian blue staining, Cell Counting Kit-8, and western blot, respectively. Flow cytometer was used to determine apoptosis and cell cycle of chondrocytes. The results showed that HWJMSCs relieved IL-1ß-induced chondrocyte injury by inhibiting apoptosis and elevating viability and cell cycle of chondrocyte, which was reversed with exosome inhibitor (GW4869). HWJMSC-EVs were successfully extracted and proven to be uptake by chondrocytes. HWJMSC-EVs ameliorate IL-1ß-induced chondrocyte injury by inhibiting cell apoptosis and elevating viability and cycle of cell, but these effects were effectively reversed by knockdown of transferrin receptor (TFRC). Notably, using bone morphogenetic protein 2 (BMP2) pathway agonist and inhibitor suggested that HWJMSC-EVs ameliorate IL-1ß-induced chondrocyte injury through activating the BMP2 pathway via up-regulation TFRC. Furthermore, over-expression of runt-related transcription factor 2 (RUNX2) reversed the effects of BMP2 pathway inhibitor promotion of IL-1ß-induced chondrocyte injury. These results suggested that HWJMSC-EVs ameliorate IL-1ß-induced chondrocyte injury by regulating the BMP2/RUNX2 axis via up-regulation TFRC. HWJMSC-EVs may play a new insight for early medical interventions in patients with articular osteochondral injury.

Granulocyte-macrophage colony-stimulating factor suppresses induction of type I interferon in infants with severe pneumonia.

BACKGROUND: The underlying mechanisms for infantile bronchopneumonia development remain unknown. METHODS: Peripheral blood mononuclear cell (PBMCs) and serum derived from severe and mild infantile bronchopneumonia were obtained, and the expression of various molecules was detected with enzyme-linked immunosorbent assay and quantitative PCR. Such molecules were also detected in granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced bone marrow-derived NFκB2-/- dendritic cells (DCs) or NIK SMI1 (NF-κB-inducing kinase inhibitor) administrated DCs. RESULTS: The relative mRNA expression levels of type I interferons (IFNs) (IFN-α4, IFN-ß), Th17 cell-associated markers (interleukin-17A, retinoic-acid-receptor-related orphan nuclear receptor gamma, and GM-CSF), and non-canonical NF-κB member (NFκB2) were significantly up-regulated in PBMCs and DCs derived from infantile bronchopneumonia compared with healthy controls. However, compared with Th17 cell-associated markers and non-canonical NF-κB molecules, the expression of IFN-α4 and IFN-ß was significantly inhibited in severe infantile bronchopneumonia compared with mild infantile bronchopneumonia. The relative protein expression of the above molecules also showed a similar expression pattern in the PBMCs or serum. NF-κB2 knockout or NIK SMI1 administration could reverse the diminished expression of IFN-ß in GM-CSF-induced bone marrow-derived DCs. CONCLUSIONS: GM-CSF-dependent non-canonical NF-κB pathway-mediated inhibition of type I IFNs production in DCs contributes to the development of severe bronchopneumonia in infant. IMPACT: Granulocyte-macrophage colony-stimulating factor-dependent non-canonical NF-κB pathway-mediated inhibition of type I IFNs production in dendritic cells is critical for the development of infantile bronchopneumonia. Our findings reveal a possible mechanism underlying the development of severe infantile bronchopneumonia. The results could provide therapeutic molecular target for the treatment of such disease.

Mechanochemical Preparation of Edge-Selectively justify Hydroxylated Graphene Nanosheets Using Persulfate via a Sulfate Radical-Mediated Process.

The production of water-dispersed graphene with low defects remains a challenge. The dry ball milling of graphite with additives produces edge-selectively functionalized graphene. However, the "inert" additives require a long milling time and cause inevitable in-plane defects. Here, the mechanochemical reaction of graphite with persulfate solved the above drawback and produced edge-selectively hydroxylated graphene (EHG) nanosheets through a 2 h ball-milling and a subsequent 0.5 h sonication. The mechanochemical cleavage of persulfate yielded SO4 ⋅- to spontaneously oxidize graphite to form the carbon radical cations selectively at edges, followed by hydroxylation with water of moisture. Because the O-O bond dissociation energy of persulfate is 20 % of the graphitic C-C bond, the rather low milling energy allowed the hydroxylation of graphite at edges with nearly no in-plane defects. The obtained EHG showed high water-dispersibility and excellent photothermal and electrochemical properties, thereby opening up a new door to fabricate graphene-based composites.

Artesunate, a new antimalarial clinical drug, exhibits potent anti-AML activity by targeting the ROS/Bim and TFRC/Fe2+ pathways.

BACKGROUND AND PURPOSE: Artesunate, approved by the Food and Drug Administration in 2020 as a new treatment for severe malaria, also shows anti-tumour activity against acute myeloid leukaemia (AML). However, the underlying molecular mechanism(s) of artesunate-induced apoptosis and differentiation of AML is not clearly elucidated. EXPERIMENTAL APPROACH: The biological effects of artesunate on AML were explored in vitro, using cells from AML patients and leukaemia cell lines, and in vivo, using female C57BL/6 or nude nu/nu BALB/c mice. Underlying mechanisms in vitro were examined with the Trypan blue dye exclusion assay, western blotting and flow cytometry. Effects of artesunate in C57BL/6 mice intravenously injected with murine AML cells (C1498-GFP) were assessed by numbers of AML cells and by survival. KEY RESULTS: In vitro, artesunate promoted apoptosis and differentiation in both leukaemia cell lines and patient-derived primary leukaemia cells. Mechanistically, artesunate promoted cell apoptosis by triggering reactive oxygen species (ROS) production and increasing expression of the pro-apoptotic protein Bim. Interestingly, transferrin receptor 1 (TFRC)-mediated regulation of intracellular iron homeostasis also played an essential role in AML cell differentiation induced by artesunate. In vivo, artesunate slowed AML progression and prolonged survival in a mouse leukaemia model. Notably, artesunate displayed no apparent toxicity towards healthy haematopoietic stem cells, bone marrow mononuclear cells or experimental animals. CONCLUSION AND IMPLICATIONS: Artesunate is a safe agent with significant anti-leukaemia effects in mice and may serve as a promising chemotherapeutic strategy for patients with AML, based on two different mechanisms, targeting the ROS/Bim and the TFRC/Fe2+ pathways.

Association between abnormal plasma metabolism and brain atrophy in alcohol-dependent patients.

Objective: In this study, we aimed to characterize the plasma metabolic profiles of brain atrophy and alcohol dependence (s) and to identify the underlying pathogenesis of brain atrophy related to alcohol dependence. Methods: We acquired the plasma samples of alcohol-dependent patients and performed non-targeted metabolomic profiling analysis to identify alterations of key metabolites in the plasma of BA-ADPs. Machine learning algorithms and bioinformatic analysis were also used to identify predictive biomarkers and investigate their possible roles in brain atrophy related to alcohol dependence. Results: A total of 26 plasma metabolites were significantly altered in the BA-ADPs group when compared with a group featuring alcohol-dependent patients without brain atrophy (NBA-ADPs). Nine of these differential metabolites were further identified as potential biomarkers for BA-ADPs. Receiver operating characteristic curves demonstrated that these potential biomarkers exhibited good sensitivity and specificity for distinguishing BA-ADPs from NBA-ADPs. Moreover, metabolic pathway analysis suggested that glycerophospholipid metabolism may be highly involved in the pathogenesis of alcohol-induced brain atrophy. Conclusion: This plasma metabolomic study provides a valuable resource for enhancing our understanding of alcohol-induced brain atrophy and offers potential targets for therapeutic intervention.

Synthesis and biological evaluation of novel all-hydrocarbon cross-linked aza-stapled peptides.

Novel all-hydrocarbon cross-linked aza-stapled peptides were designed and synthesized for the first time by ring-closing metathesis between two aza-alkenylglycine residues. Three aza-stapled peptidic analogues based on the peptide dual inhibitor of p53-MDM2/MDMX interactions were synthesized and screened for biological activities. Among the three aza-stapled peptides, aSPDI-411 displayed increased anti-tumor activity, binding affinities to both MDM2 and MDMX, and cell membrane permeability compared to its linear peptide counterpart.

Acacetin protects against depression-associated dry eye disease by regulating ubiquitination of NLRP3 through gp78 signal.

Dry eye disease (DED) is a multifactorial syndrome that commonly occurs with depression. However, therapies targeting depression-related dry eye disease are rare. In the current study, we studied the beneficial effect of a natural flavone, acacetin, in depression-associated dry eye disease by utilizing the chronic unpredictable mild stress (CUMS) depression model. Our data showed that acacetin improved the depressive behaviors in sucrose preference test (SPT), tail suspension test (TST) and forced swim test (FST); relieved the dry eye symptoms including corneal epithelial impairments, tear production decrease and goblet cell loss in CUMS mice. Acacetin also inhibited NOD-like receptor protein 3 (NLRP3) inflammasome expression levels and suppressed inflammatory responses via enhancing glycoprotein 78 (gp78)/Insulin induced gene-1 (Insig-1)-controlled NLRP3 ubiquitination in CUMS mice. Furthermore, knockdown of gp78 compromised acacetin-conferred protective efficacy in depression-related dry eye disease. In summary, our findings indicated that acacetin exerts beneficial effect in depression-associated dry eye disease, which is tightly related to gp78-mediated NLRP3 ubiquitination.

Low expression of INHB co-receptor TGFBR3 in connection with metastasis and immune infiltration in lung adenocarcinoma.

OBJECTIVE: Inhibin B (INHB) is one of the TGF-ß superfamily member, consisting of α (INHA) and ßB (INHBB) subunits. Studies have found that TGF-ß receptor 3 (TGFBR3) binds to a convex α subunit on the surface of INHB, and enhances the binding affinity of activin receptor type-2 (ACVR2A/B) to INHß subunit. This study tried to evaluate the roles of INHB subunits and its receptors (INHA, ACVR2A, ACVR2B, INHBB, TGFBR3) as prognostic biomarkers and therapeutic targets for the effective treatment of lung adenocarcinoma (LUAD). METHODS: We analyzed INHB subunits and its receptors' expression and the influence of LUAD from Oncomine, GEPIA, HCMDB, CancerSEA, TIMER databases and so on. Then, 41 cases of cancer tissue and 41 cases of adjacent epithelium were detected in LUAD patients by immunohistochemistry. RESULTS: INHA, ACVR2A, ACVR2B, INHBB were up-regulated while TGFBR3 was down-regulated in LUAD. INHA, ACVR2A and TGFBR3 were found to be strongly associated with high-grade malignancies and advanced TNM, only TGFBR3 expression was negatively correlated with LUAD metastasis probably mainly through cell adhesion molecules and the PI3K-Akt signaling pathway, univariate and multivariate analysis suggested that overall survival was lower in LUAD cases with low TGFBR3 levels. Further analysis revealed that low TGFBR3 expression was related to reduced infiltration of immune cells into the LUAD, promoting metastasis of LUAD cells. TGFBR3 expression negatively correlates with lymphatic metastasis and clinical stage in patients with LUAD. CONCLUSION: TGFBR3 could be a potential new metastatic biomarker for LUAD, with potential application as a prognostic marker and for immunotherapy of LUAD.

In situ construction of FeCo alloy nanoparticles embedded in nitrogen-doped bamboo-like carbon nanotubes as a bifunctional electrocatalyst for Zn-air batteries.

The rational design and exploration of low-cost, highly efficient, and robust bifunctional oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) electrocatalysts are essential for the application of zinc-air batteries. Herein, a novel highly active and stable oxygen electrode catalyst is designed based on in situ construction of FeCo alloy nanoparticles embedded in nitrogen-doped carbon nanotubes (FeCo/N-CNTs-800) with a bamboo-like structure. The unique architecture of bamboo-like nanotubes, the large surface area with abundant mesoporous structure, and the strong coupling interactions between the encapsulated alloy nanoparticle core and the nitrogen-doped graphitic carbon shell synergistically enhance the electrocatalytic activity. As a result, FeCo/N-CNTs-800 exhibits remarkable ORR (with a half-wave potential of 0.891 V in 0.1 M KOH) and OER (with an overpotential of 359 mV to deliver 10 mA cm-2 in 1 M KOH) performance, respectively. More impressively, an assembled zinc-air battery with the bifunctional FeCo/N-CNTs-800 catalyst as the air electrode demonstrates a large power density of 200.4 mW cm-2 and robust cycling performance over 445 h compared to precious-metal catalysts Pt/C∥IrO2. Thus, the electrocatalyst presented in this work holds great potential as an air cathode for practical applications of zinc-air batteries.

Solid Carbon Spheres with Interconnected Open Pore Channels Enabling High-Efficient Polysulfide Conversion for High-Rate Lithium-Sulfur Batteries.

Hollow carbon spheres or core-sheath porous carbon spheres have been widely used in the S cathode of lithium-sulfur batteries. However, the sphere shells or the pore walls may block the free transport of active species to a certain extent and may have a negative influence on the effective accommodation of elemental sulfur. Herein, solid but porous carbon spheres (PNCS) with large porosity and high specific surface area are developed, which enable high sulfur loading and ample cathode/electrolyte contact area, and the interconnected open pore channels significantly shorten the ion/electron transport pathways. Together with high-conducting nitrogen-doped graphene (NG), facilitated polysulfide conversion kinetics is realized in the as-assembled Li-S batteries, which deliver a high initial discharge capacity of 1445 mAh g-1 at 0.2 C, excellent rate capability of 872 mAh g-1 at 4 C, and low capacity decay of 0.047% per cycle for 500 cycles at 1 C. Even under high sulfur loading of 5.5 mg cm-2 and low electrolyte/sulfur (E/S) ratio of 5 µL mg-1, the Li-S batteries still display high specific capacities of 896 mAh g-1 and 4.96 mAh cm-2. The real application of PNCS/NG is also demonstrated by the corresponding Li-S pouch cells showing high discharging capacity and stable open circuit voltage. This work exhibits the promising application of the solid carbon spheres as the S host for effectively addressing the polysulfide shuttle and propelling the development of high-performance Li-S batteries.

Ursolic acid enhances the antitumor effects of sorafenib associated with Mcl-1-related apoptosis and SLC7A11-dependent ferroptosis in human cancer.

As a broad-spectrum oral small molecule inhibitor targeting multikinase, sorafenib is currently approved for the clinical treatment of several types of cancer as a single agent. A considerable number of clinical trial results have indicated that combination therapies involving sorafenib have been shown to improve treatment efficacy and may lead to novel therapeutic applications. Ursolic acid (UA), a natural pentacyclic triterpene compound extracted from a great variety of traditional medicinal plants and most fruits and vegetables, exhibits a wide range of therapeutic potential, including against cancer, diabetes, brain disease, liver disease, cardiovascular diseases, and sarcopenia. In the present study, we investigated the antitumor effects of sorafenib in combination with ursolic acid and found that the two agents displayed significant synergistic antitumor activity in in vitro and in vivo tumor xenograft models. Sorafenib/UA induced selective apoptotic death and ferroptosis in various cancer cells by evoking a dramatic accumulation of intracellular lipid reactive oxygen species (ROS). Mechanistically, the combination treatment promoted Mcl-1 degradation, which regulates apoptosis. However, decreasing the protein level of SLC7A11 plays a critical role in sorafenib/UA-induced cell ferroptosis. Therefore, these results suggest that the synergistic antitumor effects of sorafenib combined with ursolic acid may involve the induction of Mcl-1-related apoptosis and SLC7A11-dependent ferroptosis. Our findings may offer a novel effective therapeutic strategy for tumor treatment.

HDL-Associated Lipoproteins: Potential Prognostic Biomarkers for Gram-Negative Sepsis.

PURPOSE: To determine the levels of serum HDL-associated apolipoproteins (apoM and apoC) and HDL-binding receptor (scavenger receptor BI, SR-BI) in patients with gram-negative bacteria sepsis (G-sepsis) and to evaluate the value of lipoproteins in the diagnosis, severity and prognosis of G-sepsis. PATIENTS AND METHODS: A total of 128 patients with sepsis, 40 patients with system inflammatory reaction syndrome (SIRS) and 40 healthy subjects were enrolled in the Second People's Hospital of Hunan Province from September 2019 to September 2020. The levels and the correlation of lipoproteins were detected and dynamically monitored by enzyme-linked adsorption method, ROC curve for the diagnostic, severity and prognostic value of lipoproteins in G-sepsis. RESULTS: The levels of serum HDL-associated lipoproteins in patients with G-sepsis were significantly decreased (P < 0.05), and the ROC curve showed that HDL-C, SR-BI, apoM and apoC had cut-off values of 0.915 mmol/L, 122.100 pg/mL, 102.400 ug/mL and 17.55 mg/mL, respectively, for the diagnosis of G-sepsis, with the sensitivity was 85.56%, 97.78%, 93.33% and 73.03%, and the specificity was 95.0%, 82.50%, 61.54% and 82.50%, respectively. There was a correlation between HDL-associated apolipoproteins. Changes in serum HDL-associated lipoproteins were more obvious in shock group than classic inflammation indicators, such as PCT, IL-6 and CRP. They showed a trend change on day 3, with the levels of SR-BI and apoC changing 2-3 times, and the sensitivity of HDL-C, SR-BI, apoM and apoC for the diagnosis of G-septic shock were 32.43%, 72.97%, 65.75%, and 43.24%, and specificity of 94.34%, 81.13%, 83.07%, and 86.79%, respectively. The AUC, sensitivity and specificity of apoM combined with SR-BI were improved. CONCLUSION: HDL-associated lipoproteins were correlated with bacterial-infected types, and serum levels of HDL-associated lipoproteins can be used as potential biomarkers for early diagnosis and progress of G-sepsis. ApoM combined with SR-BI could improve the sensitivity and specificity of prognosis assessment.

Chaihu Longgu Muli Decoction relieving temporal lobe epilepsy in rats by inhibiting TLR4 signaling pathway through miR-146a-3p and miR-146a-5p / 数字中医药（英文）

@#Objective To explore the effect and mechanism of Chaihu Longgu Muli Decoction (柴胡龙骨牡蛎汤, CHLGMLD) in rats with temporal lobe epilepsy (TLE). Methods A total of 80 Sprague-Dawley (SD) male rats were randomized into control (CON), model (MOD), carbamazepine (CBZ, 0.1 g/kg), CHLGMLD low dose (CHLGMLD-L, 12.5 g/kg), and high dose (CHLGMLD-H, 25 g/kg) groups, with 16 rats in each group. TLE rat models were established in the four groups with the use of lithium-pilocarpine except for the CON group. After the successful establishment of TLE models, all drugs were administered through gavage, and distilled water was given to rats in the CON and MOD groups for four weeks. The frequency and duration of seizures before and after treatment were recorded for the evaluation of the alleviation degree. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of miR-146a-3p and miR-146a-5p. The expression levels of toll-like receptor 4 (TLR4), interleukin-1 receptor-associated kinase 1 (IRAK1), tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6), TAK1-binding protein (TAB), nuclear factor-kappa B (NF-κB), and interleukin-1 beta (IL-1β) in hippocampus were tested by immunofluorescence assay. Correlation analysis between the above factors and expressions of miR-146a-3p and miR-146a-5p were performed separately. Results CHLGMLD decreased the frequency (P < 0.05) and duration (P < 0.01) of seizures in rats. CHLGMLD down-regulated the expression levels of miR-146a-5p and miR-146a-3p (P < 0.05), and inhibited the expression levels of TLR4, IRAK1, TRAF6, TAB, NF-κB, and IL-1β (P < 0.01). The correlation analysis revealed that the expression levels of TLR4, IRAK1, TRAF6, TAB, NF-κB, and IL-1β were positively correlated with the expression levels of miR-146a-3p and miR-146a-5p detected by qRT-PCR, respectively (P < 0.01). Conclusion CHLGMLD can inhibite the TLR4 signaling pathway by lowering the expression levels of miR-146a-3p and miR-146a-5p to alleviate hippocampal dentate gyrus inflammation in TLE rats, thus relieving seizures.