Tetrandrine activates STING/TBK1/IRF3 pathway to potentiate anti-PD-1 immunotherapy efficacy in non-small cell lung cancer.

The efficacy of PD-1 therapy in non-small cell lung cancer (NSCLC) patients remains unsatisfactory. Activating the STING pathway is a promising strategy to improve PD-1 inhibitor efficacy. Here, we found tetrandrine (TET), an anti-tumor compound extracted from a medicinal plant commonly used in traditional Chinese medicine, has the ability to inhibit NSCLC tumor growth. Mechanistically, TET induces nuclear DNA damage and increases cytosolic dsDNA, thereby activating the STING/TBK1/IRF3 pathway, which in turn promotes the tumor infiltration of dendritic cells (DCs), macrophages, as well as CD8+ T cells in mice. In vivo imaging dynamically monitored the increased activity of the STING pathway after TET treatment and predicted the activation of the tumor immune microenvironment. We further revealed that the combination of TET with αPD-1 monoclonal antibody (αPD-1 mAb) yields significant anti-cancer effects by promoting CD8+ T cell infiltration and enhancing its cell-killing effect, which in turn reduced the growth of tumors and prolonged survival of NSCLC mice. Therefore, TET effectively eliminates NSCLC cells and enhances immunotherapy efficacy through the activation of the STING pathway, and combining TET with anti-PD-1 immunotherapy deserves further exploration for applications.

Triad1 regulates the expression and distribution of EHD1 contributing to the neurite outgrowth of neurons after spinal cord injury.

Traumatic spinal cord injury is a common and severe complication after an accident. As we all know that neurite outgrowth of neurons is difficult after a spinal cord injury. Endosome system is associated with cargoes transportation and contributes in promoting the neuronal capability for neurite outgrowth. EH domain-containing protein 1 (EHD1) transports proteins through the endosome system, especially in the recycling endosomes and regulating the neurite outgrowth. In mammalian cells, the involvement of the ubiquitin-proteasome system in endosomal sorting has been well established. Two RING fingers and a DRIL (double RING finger-linked) 1 (Triad1) plays an important role in membrane trafficking and its mutant results in the wrong accumulation of receptors in endosomes and plasma membrane. In this current study, we reasonably integrated the results of the above research and investigated the regulating function of Triad1 to EHD1 following the spinal cord injury. We characterized the upregulated expression and distribution of Triad1 and EHD1 in the neurons after SCI and declared the interaction between Triad1 with EHD1 both in vitro and in vivo. Triad1 regulated the interaction between itself and the full-length or EH domain of EHD1, which influenced the neurite outgrowth of PC12 cells. Our data delineate a novel interaction between Triad1 and EHD1 that may contribute to the regulation of neurite outgrowth for neurons after the spinal cord injury.

Strategies toward High-Performance Cathode Materials for Lithium-Oxygen Batteries.

Rechargeable aprotic lithium (Li)-O2 batteries with high theoretical energy densities are regarded as promising next-generation energy storage devices and have attracted considerable interest recently. However, these batteries still suffer from many critical issues, such as low capacity, poor cycle life, and low round-trip efficiency, rendering the practical application of these batteries rather sluggish. Cathode catalysts with high oxygen reduction reaction (ORR) and evolution reaction activities are of particular importance for addressing these issues and consequently promoting the application of Li-O2 batteries. Thus, the rational design and preparation of the catalysts with high ORR activity, good electronic conductivity, and decent chemical/electrochemical stability are still challenging. In this Review, the strategies are outlined including the rational selection of catalytic species, the introduction of a 3D porous structure, the formation of functional composites, and the heteroatom doping which succeeded in the design of high-performance cathode catalysts for stable Li-O2 batteries. Perspectives on enhancing the overall electrochemical performance of Li-O2 batteries based on the optimization of the properties and reliability of each part of the battery are also made. This Review sheds some new light on the design of highly active cathode catalysts and the development of high-performance lithium-O2 batteries.

A Model to Stabilize CO2 Uptake Capacity during Carbonation-Calcination Cycles and its Case of CaO-MgO.

Nowadays, capturing anthropogenic CO2 in a highly efficient and cost-effective way is one of the most challenging issues. Herein, the key parameters to stabilize CO2 uptake capacity have been studied based on four kinds of pure calcium oxides (CaO) prepared by a simple calcination method with four different calcium precursors. A simple ideal particle model was proposed to illustrate the uniform distribution of pure CaO, in which the CO2 uptake capacity is positively related with surface area of CaO particles and the stability is opposite to the distance between two CaO particles after carbonation. The adsorption capacity of the best sample with a distance of 398 nm between two CaO particles after carbonation only lost 0.344% per cycle, which is originated from the low possibility of the agglomeration between neighboring particles. On the basis of the proposed model, the composite with magnesium oxide (MgO) distributed uniformly in CaO was fabricated by a simple ball milling method, which possessed an excellent stability with a decay rate of only 3.9% over 100 carbonation-calcination cycles. In this case, MgO played as inert to increase the distance between CaO particles for agglomeration prevention.

Toward Lower Overpotential through Improved Electron Transport Property: Hierarchically Porous CoN Nanorods Prepared by Nitridation for Lithium-Oxygen Batteries.

To lower the overpotential of a lithium-oxygen battery, electron transport at the solid-to-solid interface between the discharge product Li2O2 and the cathode catalyst is of great significance. Here we propose a strategy to enhance electron transport property of the cathode catalyst by the replace of oxygen atoms in the generally used metal oxide-based catalysts with nitrogen atoms to improve electron density at Fermi energy after nitridation. Hierarchically porous CoN nanorods were obtained by thermal treatment of Co3O4 nanorods under ammonia atmosphere at 350 °C. Compared with that of the pristine Co3O4 precursor before nitridation, the overpotential of the obtained CoN cathode was significantly decreased. Moreover, specific capacity and cycling stability of the CoN nanorods were enhanced. It is assumed that the discharged products with different morphologies for Co3O4 and CoN cathodes might be closely associated with the variation in the electronic density induced by occupancy of nitrogen atoms into interstitial sites of metal lattice after nitridation. The nitridation strategy for improved electron density proposed in this work is proved to be a simple but efficient way to improve the electrochemical performance of metal oxide based cathodes for lithium-oxygen batteries.

[Risk factors for mortality in nonagenarians with femoral neck fractures undergoing joint replacement].

OBJECTIVE: To explore the risk factors for mortality in nonagenarians with femoral neck fractures and clarity the relationships between risk factors and postoperative mortality. METHODS: For this retrospective study, a total of 197 patients with consecutive isolated nonpathologic hip fractures undergoing hemiarthroplasty were recruited. There were 64 males and 133 females with an age range of 70 years or above. They were divided into three age groups: A, 70-79 years; B, 80-89 years; and C, ≥ 90 years. A retrospective chart review was conducted to compare these groups in terms of age, gender, nutritional status, blood albumin, total lymphocyte count, hemoglobin levels at admission, comorbidities, American Society of Anesthesiologists (ASA) rating of operative risk and time period between injury and surgery. RESULTS: Among them, 14 patients died within 1 year. There was one in-hospital death and 13 patients died during follow-ups. The mortality rates of groups A, B and C were (n = 3, 3.9%), (n = 5, 7.2%) and (n = 6, 24.0%). The ASA scores were III (n = 9) and IV (n = 4). And 13 patients had a preoperative blood albumin level < 35 g/L while 11 patients showed a preoperative lymphocyte count level < 1 500 cells/ml. The mortality rates were similar in groups A and B but were significantly lower than that of group C. CONCLUSION: The nonagenarians have a significantly higher mortality. And lower lymphocyte count, nonagenarian, > 2 comorbidities, high ASA score, low blood albumin level and low hemoglobin levels at admission are significant factors for assessing 1-year mortality in elders with femoral neck fractures.

Selective Shielding of the (002) Plane Enabling Vertically Oriented Zinc Plating for Dendrite-Free Zinc Anode.

Uncontrolled growth of Zn dendrites hinders the future development of aqueous Zn-ion batteries. Despite that the (100) plane possesses better zincophilic ability and fast kinetics, dendrites are generally suppressed via (002) plane-oriented Zn deposition in previous reports; the ordered (100) plane-dominant Zn deposition, especially under high current density has not yet been realized. Herein, vertically-oriented Zn plating with preferential growth of (100) plane is reported using disodium lauryl phosphate (DLP) as an electrolyte additive. DLP is preferentially anchored on the Zn (002) crystal plane via the polar phosphate group, then the deposition of Zn atoms on the (002) plane is retarded by the long alkyl chain, finally promoting the preferred growth of the (100) plane. This unique growth pattern results in ultrastable Zn plating/stripping at a super-high current density of 50 mA cm-2 , with a cumulative capacity of 8500 mAh cm-2 . The Zn//Zn symmetric cell also cycles steadily for 700 h with a large areal capacity of 10 mAh cm-2 at a current density of 10 mA cm-2 . This study provides new insights into the realization of dendrite-free Zn anodes by crystal plane modulation.

STING agonist-based hydrogel enhances immune activation in synergy with radiofrequency ablation for hepatocellular carcinoma treatment.

Immunosuppression caused by incomplete radiofrequency ablation (iRFA) is a crucial factor affecting the effectiveness of RFA for solid tumors. However, little is known about the changes iRFA induces in the tumor immune microenvironment (TIME) of hepatocellular carcinoma (HCC), the primary application area for RFA. In this study, we found iRFA promotes a suppressive TIME in residual HCC tumors, characterized by M2 macrophage polarization, inhibited antigen presentation by dendritic cells (DCs), and reduced infiltration of cytotoxic T lymphocytes (CTLs). Interestingly, the STING agonist MSA-2 was able to reorganize M2-like tumor-promoting macrophages into M1-like anti-tumor states and enhance antigen presentation by DCs. To optimize the therapeutic effect of MSA-2, we used a calcium ion (Ca2+) responsive sodium alginate (ALG) as a carrier, forming an injectable hydrogel named ALG@MSA-2. This hydrogel can change from liquid to gel, maintaining continuous drug release in situ. Our results suggested that ALG@MSA-2 effectively activated anti-tumor immunity, as manifested by increased M1-like macrophage polarization, enhanced antigen presentation by DCs, increased CTL infiltration, and inhibited residual tumor growth. ALG@MSA-2 also resulted in a complete regression of contralateral tumors and widespread liver metastases in vivo. In addition, the excellent biosafety of ALG@MSA-2 was also proved by blood biochemical analysis and body weight changes in mice. In summary, this study demonstrated that the immune cascade of ALG@MSA-2 mediated the STING pathway activation and promoted a favorable TIME which might provide novel insights for the RFA treatment of HCC.

Solid-State Electrolyte for Lithium-Air Batteries: A Review.

Traditional lithium-air batteries (LABs) have been seriously affected by cycle performance and safety issues due to many problems such as the volatility and leakage of liquid organic electrolyte, the generation of interface byproducts, and short circuits caused by the penetration of anode lithium dendrite, which has hindered its commercial application and development. In recent years, the emergence of solid-state electrolytes (SSEs) for LABs well alleviated the above problems. SSEs can prevent moisture, oxygen, and other contaminants from reaching the lithium metal anode, and their inherent performance can solve the generation of lithium dendrites, making them potential candidates for the development of high energy density and safety LABs. This paper mainly reviews the research progress of SSEs for LABs, the challenges and opportunities for synthesis and characterization, and future strategies are addressed.

FGF21 prevents neuronal cell ferroptosis after spinal cord injury by activating the FGFR1/ß-Klotho pathway.

Spinal cord injury (SCI) is a kind of traumatic nervous system disease caused by neuronal death, causing symptoms like sensory, motor, and autonomic nerve dysfunction. The recovery of neurological function has always been a intractable problem that has greatly distressed individuals and society. Although the involvement of iron-dependent lipid peroxidation leading to nerve cell ferroptosis in SCI progression has been reported, the underlying mechanisms remain unaddressed. Thus, this study aimed to investigate the potential of recombinant human FGF21 (rhFGF21) in inhibiting ferroptosis of nerve cells and improving limb function after SCI, along with its underlying mechanisms. In vivo animal model showed that FGFR1, p-FGFR1, and ß-Klotho protein gradually increased over time after injury, reaching a peak on the third day. Moreover, rhFGF21 treatment significantly reduced ACSL4, increased GPX4 expression, reduced iron deposition, and inhibited ferroptosis. Meanwhile, rhFGF21 decreased cell apoptosis following acute spinal cord damage. In contrast, FGFR1 inhibitor PD173074 partially reversed the rhFGF21-induced therapeutic effects. Overall, this work revealed that rhFGF21 activates the FGFR1/ß-Klotho pathway to decrease ferroptosis of nerve cells, suggesting that FGF21 could be a new therapeutic target for SCI neurological rehabilitation.

Carbon Tube-Based Cathode for Li-CO2 Batteries: A Review.

Metal-air batteries are considered the research, development, and application direction of electrochemical devices in the future because of their high theoretical energy density. Among them, lithium-carbon dioxide (Li-CO2) batteries can capture, fix, and transform the greenhouse gas carbon dioxide while storing energy efficiently, which is an effective technique to achieve "carbon neutrality". However, the current research on this battery system is still in the initial stage, the selection of key materials such as electrodes and electrolytes still need to be optimized, and the actual reaction path needs to be studied. Carbon tube-based composites have been widely used in this energy storage system due to their excellent electrical conductivity and ability to construct unique spatial structures containing various catalyst loads. In this review, the basic principle of Li-CO2 batteries and the research progress of carbon tube-based composite cathode materials were introduced, the preparation and evaluation strategies together with the existing problems were described, and the future development direction of carbon tube-based materials in Li-CO2 batteries was proposed.

Solid-State Electrolytes for Lithium-Sulfur Batteries: Challenges, Progress, and Strategies.

Lithium-sulfur batteries (LSBs) represent a promising next-generation energy storage system, with advantages such as high specific capacity (1675 mAh g-1), abundant resources, low price, and ecological friendliness. During the application of liquid electrolytes, the flammability of organic electrolytes, and the dissolution/shuttle of polysulfide seriously damage the safety and the cycle life of lithium-sulfur batteries. Replacing a liquid electrolyte with a solid one is a good solution, while the higher mechanical strength of solid-state electrolytes (SSEs) has an inhibitory effect on the growth of lithium dendrites. However, the lower ionic conductivity, poor interfacial contact, and relatively narrow electrochemical window of solid-state electrolytes limit the commercialization of solid-state lithium-sulfur batteries (SSLSBs). This review describes the research progress in LSBs and the challenges faced by SSEs, which are classified as polymer electrolytes, inorganic solid electrolytes, and composite electrolytes. The advantages, as well as the disadvantages of various types of electrolytes, the common coping strategies to improve performance, and future development trends, are systematically described.

Nanofibrous Cathode Catalysts with MoC Nanoparticles Embedded in N-Rich Carbon Shells for Low-Overpotential Li-CO2 Batteries.

Li-CO2 batteries with high theoretical energy densities are recognized as next-generation energy storage devices for addressing the range anxiety and environmental issues encountered in the field of electric transportation. However, cathode catalysts with unsatisfactory activity toward CO2 absorption and reduction/evolution reactions hinder the development of Li-CO2 batteries with desired specific capacities and sufficient cycle numbers. In this work, a multifunctional nanofibrous cathode catalyst that integrates N-rich carbon shells embedded with molybdenum carbide nanoparticles and multiwalled carbon nanotube cores was designed and prepared. The N-rich carbon shell could strengthen the absorption capacity of CO2 and Li2CO3. The molybdenum carbide nanoparticles would improve the catalytic activity of both CO2 reduction and evolution reactions. The carbon nanotube cores would provide an efficient network for electron transportation. The synergistic effect of the cathode catalysts enhances the electrochemical performance of Li-CO2 batteries. A high cycling stability of more than 150 cycles at a current density of 250 mA g-1 with a cutoff capacity of 1000 mAh g-1 and a charge/discharge overpotential of less than 1.5 V is achieved. This work provides a feasible strategy for the design of a high-performance cathode catalyst for lithium-air batteries.

Well-ordered mesoporous Fe2O3/C composites as high performance anode materials for sodium-ion batteries.

Sodium-ion batteries have attracted considerable attention in recent years. In order to promote the practical application of sodium-ion batteries, the electrochemical performances, such as specific capacity, reversibility, and rate capability of the anode materials, should be further improved. In this work, a Fe2O3/C composite with a well-ordered mesoporous structure is prepared via a facile co-impregnation method by using mesoporous silica SBA-15 as a hard template. When used as an anode material for sodium-ion batteries, the well-ordered mesoporous structure ensures fast mass transport kinetics. The presence of nano-sized Fe2O3 particles confined within the carbon walls significantly enhances the specific capacity of the composite. The carbon walls in the composite act not only as an active material contributing to the specific capacity, but also as a conductive matrix improving the cycling stability of Fe2O3 nanoparticles. As a result, the well-ordered mesoporous Fe2O3/C composite exhibits high specific capacity, excellent cycleability, and high rate capability. It is proposed that this simple co-impregnation method is applicable for the preparation of well-ordered mesoporous transition oxide/carbon composite electrode materials for high performance sodium-ion and lithium-ion batteries.

Hydroquinone Resin Induced Carbon Nanotubes on Ni Foam As Binder-Free Cathode for Li-O2 Batteries.

In this work, hydroquinone resin was used to grow carbon nanotubes directly on Ni foam. The composites were obtained via a simple carbonization method, which avoids using the explosive gaseous carbon precursors that are usually applied in the chemical vapor deposition method. When evaluated as cathode for Li-O2 batteries, the binder-free structure showed enhanced ORR/OER activities, thus giving a high rate capability (12690 mAh g(-1) at 200 mA g(-1) and 3999 mAh g(-1) at 2000 mA g(-1)) and outstanding long-term cycling stability (capacity limited 2000 mAh g(-1), 110 cycles at 200 mA g(-1)). The excellent battery performance provides new insights into designing a low-cost and high-efficiency cathode for Li-O2 batteries.

Co3O4-based binder-free cathodes for lithium-oxygen batteries with improved cycling stability.

A novel binder-free electrode for lithium-oxygen batteries has been prepared by electrodepositing a Co3O4 layer onto a pretreated TiO2 fiber mesh, formed on nickel foam by an electrospinning method. The Co3O4 depositing layer is composed of Co3O4 nanoflakes, forming a uniform flower-like porous structure. The Co3O4 nanoflakes within the depositing layer provide a large amount of catalytic active sites for oxygen evolution and reduction reactions. The three-dimensional porous network of the Co3O4 depositing layer can not only facilitate the transportation of ions and electrolyte within the electrode, but also provide plenty of space to accommodate Li2O2 species formed during the discharge process. The Co3O4 spheres embedded in the TiO2 fiber mesh, formed by the treatment of a suspension of cobaltammine precipitate, function as anchors to prevent the detachment of the Co3O4 layer from the current collector, resulting in excellent structural and cycling stability. Only a slight specific capacity decay is observed at full discharge/charge after 80 cycles. This work demonstrates the important factors in the preparation of binder-free cathodes for high performance lithium-oxygen batteries.

Hierarchical 3D TiO2@Fe2O3 nanoframework arrays as high-performance anode materials.

Hierarchical 3D TiO2@Fe2O3 nanoframework arrays grown on a Ti substrate are synthesized via a facile hydrothermal reaction. As the synergetic effect of this hybrid material, the TiO2@Fe2O3 electrode shows superior rate capability and cycling performance to bare TiO2 and Fe2O3 electrodes.

Incorporation of heterostructured Sn/SnO nanoparticles in crumpled nitrogen-doped graphene nanosheets for application as anodes in lithium-ion batteries.

Sn/SnO nanoparticles are incorporated in crumpled nitrogen-doped graphene nanosheets by a simple melting diffusion method. The resulting composite exhibits large specific capacity, excellent cycling stability and high rate capability as an anode for lithium-ion batteries.