Genetic Screening of Haploid Neural Stem Cells Reveals that Nfkbia and Atp2b4 are Key Regulators of Oxidative Stress in Neural Precursors.

Neurological diseases are expected to become the leading cause of death in the next decade. Although little is known about it, the interaction between oxidative stress and inflammation is harmful to the nervous system. To find an advanced tool for neural genetics, mouse haploid neural stem cells (haNSCs) from the somite of chimeric mouse embryos at E8.5 is established. The haNSCs present a haploid neural progenitor identity for long-term culture, promising to robustly differentiate into neural subtypes and being able to form cerebral organoids efficiently. Thereafter, haNSC mutants via a high-throughput approach and screened targets of oxidative stress is generated using the specific mutant library. Deletion of Nfkbia (the top hit among the insertion mutants) reduces damage from reactive oxygen species (ROS) in NSCs exposed to H2O2. Transcriptome analysis revealed that Atp2b4 is upregulated significantly in Nfkbia-null NSCs and is probably responsible for the observed resistance. Additionally, overexpression of Atp2b4 itself can increase the survival of NSCs in the presence of H2O2, suggesting that Atp2b4 is closely involved in this resistance. Herein, a powerful haploid system is presented to study functional genetics in neural lineages, shedding light on the screening of critical genes and drugs for neurological diseases.

Peripheral nerve injury associated with JEV infection in high endemic regions, 2016-2020: a multicenter retrospective study in China.

Previously, we reported a cohort of Japanese encephalitis (JE) patients with Guillain-Barré syndrome. However, the evidence linking Japanese encephalitis virus (JEV) infection and peripheral nerve injury (PNI) remains limited, especially the epidemiology, clinical presentation, diagnosis, treatment, and outcome significantly differ from traditional JE. We performed a retrospective and multicenter study of 1626 patients with JE recorded in the surveillance system of the Chinese Center for Disease Control and Prevention, spanning the years 2016-2020. Cases were classified into type 1 and type 2 JE based on whether the JE was combined with PNI or not. A comparative analysis was conducted on demographic characteristics, clinical manifestations, imaging findings, electromyography data, laboratory results, and treatment outcomes. Among 1626 laboratory confirmed JE patients, 230 (14%) were type 2 mainly located along the Yellow River in northwest China. In addition to fever, headache, and disturbance of consciousness, type 2 patients experienced acute flaccid paralysis of the limbs, as well as severe respiratory muscle paralysis. These patients presented a greater mean length of stay in hospital (children, 22 years [range, 1-34]; adults, 25 years [range, 0-183]) and intensive care unit (children, 16 years [range, 1-30]; adults, 17 years [range, 0-102]). The mortality rate was higher in type 2 patients (36/230 [16%]) compared to type 1 (67/1396 [5%]). The clinical classification of the diagnosis of JE may play a crucial role in developing a rational treatment strategy, thereby mitigating the severity of the disease and potentially reducing disability and mortality rates among patients.

A Study on Interobserver and Intraobserver Reliability of the Huashan Radiologic Classification System for Cervical Spinal Cord Injury Without Fracture and Dislocation.

STUDY DESIGN: Observational study. OBJECTIVE: To assess the reproducibility and reliability of the system. BACKGROUND: The Huashan radiologic classification system for cervical spinal cord injury without fracture and dislocation (CSCIWFD) was recently proposed and found useful for clinical practice. PATIENTS AND METHODS: Patients diagnosed with CSCIWFD between 2015 and 2021 were recruited. Six spine surgeons from different institutions, three experienced and other inexperienced respectively, were trained as observers of the system, and these surgeons classified the recruited patients using the system. Then, 8 weeks later, they repeated the classification on the same patients in a different order. The interobserver and intraobserver agreement between the results was analyzed using percentage agreement, weighted kappa, and Cohen kappa (κ) statistics. RESULTS: A total of 60 patients were included in the analysis. Type I was the most frequent type (29 cases, 48.3%), followed by type II (13 cases, 21.7%), type III (12 cases, 20%), and type IV (6 cases, 10%). For all the observers, experienced observers, and inexperienced observers, the overall agreement percentages were 77.6% (κ = 0.78), 84.4% (κ = 0.84), and 72.8% (κ = 0.74), respectively, indicating substantial to nearly perfect interobserver reproducibility. A higher level of agreement was found for differentiating type I from other types, with the percentage agreement ranging from 87.8% to 94.4% (κ= 0.74-0.88). For distinguishing compression on the spinal cord (types I and II vs types III and IV) among the different groups of observers, the percentage agreement was 97.8% (κ = 0.94), indicating nearly perfect reproducibility. As for intraobserver agreement, the percentage agreement ranged from 86.7% to 96.7% (κ = 0.78-0.95), indicating at least substantial reliability. CONCLUSIONS: The Huashan radiologic classification system for CSCIWFD was easy to learn and apply in a clinical environment, showing excellent reproducibility and reliability. Therefore, it would be promising to apply and promote this system for the precise evaluation and personalized treatment strategy.

A LATS2 and ALKBH5 positive feedback loop supports their oncogenic roles.

N(6)-methyladenosine (m6A) critically regulates RNA dynamics in various biological processes. The m6A demethylase ALKBH5 promotes tumorigenesis of glioblastoma, while the intricate web that orchestrates its regulation remains enigmatic. Here, we discover that cell density affects ALKBH5 subcellular localization and m6A dynamics. Mechanistically, ALKBH5 is phosphorylated by the large tumor suppressor kinase 2 (LATS2), preventing its nuclear export and enhancing protein stability. Furthermore, phosphorylated ALKBH5 reciprocally erases m6A from LATS2 mRNA, thereby stabilizing this transcript. Unexpectedly, LATS2 depletion suppresses glioblastoma stem cell self-renewal independent of yes-associated protein activation. Additionally, deficiency in either LATS2 or ALKBH5 phosphorylation impedes tumor progression in mouse xenograft models. Moreover, high levels of LATS2 expression and ALKBH5 phosphorylation are associated with tumor malignancy in patients with gliomas. Collectively, our study unveils an oncogenic positive feedback loop between LATS2 and ALKBH5, revealing a non-canonical branch of the Hippo pathway for RNA processing and suggesting potential anti-cancer interventions.

Electronic structures and quantum capacitance of twisted bilayer graphene with defects based on three-band tight-binding model.

Twisted bilayer graphene (tBLG) with C vacancies would greatly improve the density of states (DOS) around the Fermi level (EF) and quantum capacitance; however, the single-band tight-binding model only considering pz orbitals cannot accurately capture the low-energy physics of tBLG with C vacancies. In this work, a three-band tight-binding model containing three p orbitals of C atoms is proposed to explore the modulation mechanism of C vacancies on the DOS and quantum capacitance of tBLG. We first obtain the hopping integral parameters of the three-band tight-binding model, and then explore the electronic structures and the quantum capacitance of tBLG at a twisting angle of θ = 1.47° under different C vacancy concentrations. The impurity states contributed by C atoms with dangling bonds located around the EF and the interlayer hopping interaction could induce band splitting of the impurity states. Therefore, compared with the quantum capacitance of pristine tBLG (∼18.82 µF cm-2) at zero bias, the quantum capacitance is improved to ∼172.76 µF cm-2 at zero bias, and the working window with relatively large quantum capacitance in the low-voltage range is broadened in tBLG with C vacancies due to the enhanced DOS around the EF. Moreover, the quantum capacitance of tBLG is further increased at zero bias with an increase of the C vacancy concentration induced by more impurity states. These findings not only provide a suitable multi-band tight-binding model to describe tBLG with C vacancies but also offer theoretical insight for designing electrode candidates for low-power consumption devices with improved quantum capacitance.

Chirality-selective topological magnon phase transition induced by interplay of anisotropic exchange interactions in honeycomb ferromagnet.

A variety of distinct anisotropic exchange interactions commonly exist in one magnetic material due to complex crystal, magnetic and orbital symmetries. Here we investigate the effects of multiple anisotropic exchange interactions on topological magnon in a honeycomb ferromagnet, and find a chirality-selective topological magnon phase transition induced by a complicated interplay of Dzyaloshinsky-Moriya interaction and pseudo-dipolar interaction, accompanied by the bulk gap close and reopen with chiral inversion. Moreover, this novel topological phase transition involves band inversion at high symmetry pointsKandK', which can be regarded as a pseudo-orbital reversal, i.e. magnon valley degree of freedom, implying a new manipulation corresponding to a sign change of the magnon thermal Hall conductivity. Indeed, it can be realized in 4dor 5dcorrelated materials with both spin-orbit coupling and orbital localized states, such as iridates and ruthenates,etc.This novel regulation may have potential applications on magnon devices and topological magnonics.

Metformin rejuvenates Nap1l2-impaired immunomodulation of bone marrow mesenchymal stem cells via metabolic reprogramming.

Ageing and cell senescence of mesenchymal stem cells (MSCs) limited their immunomodulation properties and therapeutic application. We previously reported that nucleosome assembly protein 1-like 2 (Nap1l2) contributes to MSCs senescence and osteogenic differentiation. Here, we sought to evaluate whether Nap1l2 impairs the immunomodulatory properties of MSCs and find a way to rescue the deficient properties. We demonstrated that metformin could rescue the impaired migration properties and T cell regulation properties of OE-Nap1l2 BMSCs. Moreover, metformin could improve the impaired therapeutic efficacy of OE-Nap1l2 BMSCs in the treatment of colitis and experimental autoimmune encephalomyelitis in mice. Mechanistically, metformin was capable of upregulating the activation of AMPK, synthesis of l-arginine and expression of inducible nitric oxide synthase in OE-Nap1l2 BMSCs, leading to an increasing level of nitric oxide. This study indicated that Nap1l2 negatively regulated the immunomodulatory properties of BMSCs and that the impaired functions could be rescued by metformin pretreatment via metabolic reprogramming. This strategy might serve as a practical therapeutic option to rescue impaired MSCs functions for further application.

Protein crotonylation promotes osteogenic differentiation of periodontal ligament stem cells via the PI3K-AKT pathway.

Posttranslational modifications are crucial regulatory mechanisms for cellular differentiation and organismal development. Acylation modification is one of the main posttranslational modifications that play a pivotal role in regulating the osteogenic differentiation of mesenchymal stem cells and is a focal point of research in bone tissue regeneration. However, its mechanism remains incompletely understood. This article aims to investigate the impact of protein crotonylation on osteogenic differentiation in periodontal ligament stem cells (PDLSCs) and elucidate its underlying mechanisms. Western blot analysis identified that the modification level of acetylation, crotonylation and succinylation were significantly upregulated after osteogenic induction of PDLSCs. Subsequently, sodium crotonate (NaCr) was added to the medium and acyl-CoA synthetase short-chain family member 2 (ACSS2) was knocked down by short hairpin RNA plasmids to regulate the total level of protein crotonylation. The results indicated that treatment with NaCr promoted the expression of osteogenic differentiation-related factors in PDLSCs, whereas silencing ACSS2 had the opposite effect. In addition, mass spectrometry analysis was used to investigate the comprehensive analysis of proteome-wide crotonylation in PDLSCs under osteogenic differentiation. The analysis revealed that the level of protein crotonylation related to the PI3K-AKT signaling pathway was significantly upregulated in PDLSCs after osteogenic induction. Treatment with NaCr and silencing ACSS2 affected the activation of the PI3K-AKT signaling pathway. Collectively, our study demonstrates that protein crotonylation promotes osteogenic differentiation of PDLSCs via the PI3K-AKT pathway, providing a novel targeting therapeutic approach for bone tissue regeneration.

High-temperature magnetically topological candidate material Mn3Bi2Te6.

The Mn-Bi-Te family displaying magnetism and non-trivial topological properties has received extensive attention. Here, we predict that the antiferromagnetic structure of Mn3Bi2Te6with three MnTe layers is energetically stable and the magnetic energy difference of Mn-Mn is enhanced four times compared with that in the single MnTe layer of MnBi2Te4. The predicted Néel transition point is raised to 102.5 K, surpassing the temperature of liquid nitrogen. The topological properties show that with the variation of the MnTe layer from a single layer to three layers, the system transforms from a non-trivial topological phase to a trivial topological phase. Interestingly, the ferromagnetic state of Mn3Bi2Te6is a topological semimetal and it exhibits a topological transition from trivial to non-trivial induced by the magnetic transition. Our results enrich the Mn-Bi-Te family system, offer a new platform for studying topological phase transitions, and pave a new way to improve the working temperature of magnetically topological devices.

Emerging half metal electrides in manganese oxyarsenide hydrides LaMnAsO1-xHx.

In the paper, we report that the hydrides LaMnAsO1-xHxcan serve as a switchable half-metal electride which combines the dual properties of half metals and electrides. Using density functional theory calculations, it is found that this hydride compounds exhibit a novel magnetic structure in which magnetic electrides arising from the excess electrons induced by the H dopants coexist with local-moment antiferromagnetism of the Mn spin lattice. While the reported sizable negative magnetoresistance and ferromagnetism are merely contributed by the spin polarization of excess electrons, this material mimics the behavior of a switchable half-metal electride because the completely spin polarization of excess electrons is easily achieved by controlling the concentration of conductive electrons or H dopants. These effects look very promising for continuing the rapid pace of spintronics application.

O-GlcNAcylation Regulates Centrosome Behavior and Cell Polarity to Reduce Pulmonary Fibrosis and Maintain the Epithelial Phenotype.

O-GlcNAcylation functions as a cellular nutrient and stress sensor and participates in almost all cellular processes. However, it remains unclear whether O-GlcNAcylation plays a role in the establishment and maintenance of cell polarity, because mice lacking O-GlcNAc transferase (OGT) are embryonically lethal. Here, a mild Ogt knockout mouse model is constructed and the important role of O-GlcNAcylation in establishing and maintaining cell polarity is demonstrated. Ogt knockout leads to severe pulmonary fibrosis and dramatically promotes epithelial-to-mesenchymal transition. Mechanistic studies reveal that OGT interacts with pericentriolar material 1 (PCM1) and centrosomal protein 131 (CEP131), components of centriolar satellites required for anchoring microtubules to the centrosome. These data further show that O-GlcNAcylation of PCM1 and CEP131 promotes their centrosomal localization through phase separation. Decrease in O-GlcNAcylation prevents PCM1 and CEP131 from localizing to the centrosome, instead dispersing these proteins throughout the cell and impairing the microtubule-centrosome interaction to disrupt centrosome positioning and cell polarity. These findings identify a previously unrecognized role for protein O-GlcNAcylation in establishing and maintaining cell polarity with important implications for the pathogenesis of pulmonary fibrosis.

Periodontitis and NAFLD-related diseases: A bidirectional two-sample Mendelian randomization study.

BACKGROUND: Epidemiological studies have shown an association between periodontitis and nonalcoholic fatty liver disease (NAFLD)-related diseases. However, a causal relationship between these two diseases remains unclear. To examine the causal relationship between these two diseases, we conducted a bidirectional two-sample Mendelian randomization (MR) analysis using genetic markers as proxies. METHODS: Statistical summary was obtained from a large genome-wide association study (GWAS) on NAFLD (N = 342,499), nonalcoholic steatohepatitis (NASH, N = 342,499), fibrosis (N = 339,081), cirrhosis (N = 342,499), fibrosis/cirrhosis (N = 334,553), and periodontitis (N = 34,615) in the European ancestry. The inverse variance weighted (IVW) method was used as the main method to estimate the bidirectional association. Sensitivity analysis was performed to evaluate the rigidity of the results. RESULTS: Limited evidence indicated positive causal associations between genetically predicted NAFLD and periodontitis (IVW odds ratio [OR], 1.094; 95% confidence interval [CI], 1.006-1.189; p = 0.036) and between cirrhosis and periodontitis (IVW OR, 1.138; 95% CI, 1.001-1.294; p = 0.048). However, the opposite trend did not indicate a causative effect of periodontitis on NAFLD-related diseases. The sensitivity analysis revealed no obvious pleiotropy or heterogeneity. CONCLUSIONS: Our MR analysis provides new evidence in favor of the moderate causal impact of NAFLD on periodontitis. The causal effects of periodontitis on NAFLD-related diseases warrant further investigation.

Peculiarity of the Mechanism of Early Stages of Photo-Oxidative Degradation of Linear Low-Density Polyethylene Films in the Presence of Ferric Stearate.

Ferric stearate (FeSt3) is very efficient in accelerating polyethylene (PE) degradation, but there is a lack of exploration of its role in accelerating the early stages of polyethylene photo-oxidative degradation. This study aimed to investigate the effect of FeSt3 on the photo-oxidative degradation of PE films, especially in the early stages of photo-oxidative degradation. The results show that FeSt3 not only promotes the oxidative degradation of PE but also contributes significantly to the early behavior of photo-oxidative degradation. Moreover, the results of the density functional theory (DFT) calculations proved that the C-H in the FeSt3 ligand was more easily dissociated compared with the PE matrix. The generated H radicals participate in the coupling reaction of the primary alkyl macro radicals leading to the molecular weight reduction, thus significantly increasing the initial rate of molecular weight reduction of PE. Meanwhile, the transfer reaction of the dissociation-generated C-centered radicals induced the PE matrix to produce more secondary alkyl macroradicals, which shortened the time to enter the oxidative degradation stage. This finding reveals the mechanism by which FeSt3 promotes the degradation of PE at the early stage of photo-oxidative degradation. It provides guiding significance for the in-depth study of the early degradation behavior in photo-oxidative degradation on polyolefin/FeSt3 films.

Effects of exercise training on neurological recovery, TGF-ß1, HIF-1α, and Nogo-NgR signaling pathways after spinal cord injury in rats.

OBJECTIVE: To evaluate the effects of exercise training on neurological recovery, Growth Transforming Factor-ß1 (TGF-ß1), Hypoxia Inducible Factor-1α (HIF-1α), and Nogo-NgR signaling pathways after spinal cord injury in rats. METHODS: Forty-eight male Sprague-Dawley rats were randomly divided into four groups: normal group, sham-operated group, model group, and training group. The rat spinal cord injury model was established using Allen's method, and the training group received exercise training on the 8th day postoperatively. The Basso, Beattie and Bresnahan (BBB) score, modified Tarlow score, and inclined plane test scores were compared in each group before injury and 1, 7, 14, 21 and 28 days after injury. RESULTS: The BBB score and modified Tarlow score of the model group and the training group were 0 at the first day after the injury, and gradually increased on the seventh day onwards (p < 0.05). The BBB score and modified Tarlow score of the training group were higher than those of the model group at the 14th, 21st and 28th day (p < 0.05). The angles of the inclined plate at multiple time points after injury were lower in the model group and the training group than in the normal group and the sham-operated group (p < 0.05); The angles of the inclined plate at the 14th, 21st and 28th day after injury were higher in the training group than in the model group (p < 0.05). CONCLUSION: The mechanism of exercise training may be connected to the inhibition of the Nogo-NgR signaling pathway to promote neuronal growth.

Role of Lanthanides and Bilayer Fe2As2 in the Electronic Properties of RbLn2Fe4As4O2 (Ln = Gd, Tb, and Dy) Superconductors.

The superconducting transition temperatures (Tc) of RbGd2Fe4As4O2, RbTb2Fe4As4O2, and RbDy2Fe4As4O2 are 35 K, 34.7 K, and 34.3 K without doping, respectively. For the first time, we have studied the high-temperature nonmagnetic state and the low-temperature magnetic ground state of 12442 materials, RbTb2Fe4As4O2 and RbDy2Fe4As4O2, using first principles calculations and comparing them with RbGd2Fe4As4O2. We also performed a detailed study of the effects of lanthanides and bilayer Fe2As2. We predict that the ground state of RbLn2Fe4As4O2 (Ln = Gd, Tb, and Dy) is spin-density-wave-type, in-plane, striped antiferromagnets, and the magnetic moment around each Fe atom is about 2 µB. We also found that the structural differences caused by the simple ionic radius have little effect on the properties of these three materials. Different lanthanide elements themselves play a major role in the electronic properties of the materials. It can be confirmed that the effect of Gd on RbLn2Fe4As4O2 is indeed different from that of Tb and Dy, and the presence of Gd is more conducive to interlayer electron transfer. This means that Gd can transfer more electrons from the GdO layer to the FeAs layer compared to Tb and Dy. Therefore, RbGd2Fe4As4O2 has a stronger internal coupling strength of the bilayer Fe2As2 layer. This can explain why the Tc of RbGd2Fe4As4O2 is slightly higher than that of RbTb2Fe4As4O2 and RbDy2Fe4As4O2.

Cleaning and Disinfecting Oval-Shaped Root Canals: Ex Vivo Evaluation of Three Rotary Instrumentation Systems with Passive Ultrasonic Irrigation.

Background and Objectives: Successful root canal treatment depends on the thorough removal of biofilms through chemomechanical preparation. This study aimed to investigate and compare the cleaning and disinfecting efficiency of oval-shaped root canals using XP-endo Shaper (XPS), ProTaper Next (PTN), and HyFlex CM (HCM) in combination with passive ultrasonic irrigation (PUI). Materials and Methods: Ninety extracted teeth were contaminated and randomly divided into three groups: XPS, PTN, and HCM. Each group was assigned to three subgroups: subgroup A (sterile saline), subgroup B (3% sodium hypochlorite and 17% ethylenediaminetetraacetic acid), and subgroup C (3% sodium hypochlorite, 17% ethylenediaminetetraacetic acid, and PUI). Bacterial sampling was conducted both from baseline samples and samples after chemomechanical preparation. Scanning electron microscopy (SEM) was used to evaluate the residue bacterial biofilms, hard tissue debris, and smear layers on the buccolingual walls of oval-shaped root canals. Results: When combined with sterile saline, XPS demonstrated a higher reduction of bacterial counts and was more effective in eradicating Enterococcus faecalis in the middle third of the canals compared to the other instruments (p < 0.05). Additionally, when used with antimicrobial irrigants, XPS was more effective in disinfecting the coronal third of the canals than the other instruments (p < 0.05). Furthermore, XPS reduced hard tissue debris more effectively in the middle third of canals than in the apical third (p < 0.05). Conclusions: XPS outperforms PTN and HCM in disinfecting oval-shaped root canals. Despite the fact that combining XPS and PUI improves cleaning and disinfecting, removing hard tissue debris from the critical apical area remains challenging.

Role of Doping Effect and Chemical Pressure Effect Introduced by Alkali Metal Substitution on 1144 Iron-Based Superconductors.

CaAFe4As4 with A = K, Rb, and Cs are close to the doped 122 system, and the parent material can reach a superconducting transition temperature of 31-36 K without doping. To study the role of alkali metals, we investigated the induced hole doping and chemical pressure effects as a result of the introduction of alkali metals using density-functional-based methods. These two effects can affect the superconducting transition temperature by changing the number of electrons and the structure of the FeAs conductive layer, respectively. Our study shows that the dxz and dyz orbitals, which are degenerate in CaFe2As2, become nondegenerate in CaAFe4As4 due to two nonequivalent arsenic atoms (As1 and As2). The unusual oblate ellipsoid hole pocket at Γ point in CaAFe4As4 results from a divalent cation Ca2+ replaced by a monovalent cation A+. It shows one of the main differences in fermiology compared to a particular form of CaFe2As2 with reduced 1144 symmetry, due to the enhancement of As2-Fe hybridization. The unusual band appears in CaFe2As2 (1144) and gradually disappears in the change of K to Cs. Further analysis shows that this band is contributed by As1 and has strong dispersion perpendicular to the FeAs layer, suggesting that it is related to the peculiar van Hove singularity below the Fermi level. In addition, various aspects of CaFe2As2 (1144) and CaAFe4As4 in the ground state are discussed in terms of the influence of hole doping and chemical pressure.

CYLD inhibits osteoclastogenesis to ameliorate alveolar bone loss in mice with periodontitis.

Periodontitis is a chronic immune inflammatory disease that can lead to the destruction and loss of the tooth-supporting apparatus. During this process, the balance between bone absorption mediated by osteoclasts and bone formation mediated by osteoblasts is damaged. Consistent with previous studies, we observed that depletion of cylindromatosis (CYLD) resulted in an osteoporotic bone phenotype. However, the effect of CYLD deficiency on periodontitis is undetermined. Here, we investigated whether CYLD affects periodontal tissue homeostasis in experimental periodontitis in Cyld knockout (KO) mice, and we explored the underlying mechanisms. Interestingly, we discovered significant alveolar bone density loss and severely reduced alveolar bone height in Cyld KO mice with experimentally induced periodontitis. We observed increased osteoclast number and activity in both the femurs and alveolar bones, accompanied by the downregulation of osteogenesis genes and upregulation of osteoclastogenesis genes of alveolar bones in ligatured Cyld KO mice. Taken together, our findings demonstrate that the deletion of CYLD in mice plays a vital role in the pathogenesis of periodontal bone loss and suggest that CYLD might exert an ameliorative effect on periodontal inflammatory responses.

Mesoporous Gold Film with Surface Sulfur Modification to Enable Dendrite-Free Lithium Plating/Stripping for Long-Life Lithium Metal Anodes.

The formation of a lithiophilic phase is an effective method to inhibit the growth of lithium dendrites and obtain high-performance Li metal anodes (LMAs). Nonetheless, previous studies have overlooked the underlying mechanistic studies that modulate the structure of the lithiophilic phase as well as lithiophilicity. A self-supporting sulfur-modified mesoporous gold film on nickel foam (SMGF@NF) for LMAs is created with mesoporous structure, which can provide sufficient active sites for uniform lithium deposition. The synergistic promotion of lithiophilic gold and sulfur leads to uniform lithium nucleation and induces consistent lithium removal during lithium stripping. The doping of S promotes the decomposition of bistrifluoromethanesulfonimide lithium salt to generate lithium fluorde, thus forming a more stable solid electrolyte interface. Combining the multifaceted advantages of SMGF@NF, its lithium-plated electrode can achieve ultralong cycle life in symmetrical batteries (over 1000 h at 0.5 mA cm-2 and 1 mAh cm-2 ) and ultralow overpotential (≈10 mV). Meanwhile, the Li-SMGF@NF||LiFePO4 full cell achieves a high cycling performance and rate capability (92.4% capacity retention after 1000 cycles at 5 C). The study probes into the composite electrode surface composition and structure, revealing the mechanism of high-performance LMAs.

Melatonin activates mitochondrial unfolded protein response to preserve osteogenic potential of senescent BMSCs via upregulating PDI-6.

Bone marrow stromal cells (BMSCs) possess the capability to differentiate into osteogenic or adipogenic lineages. With aging, BMSCs suffer from mitochondrial dysfunction and undergo senescence, favoring adipogenesis at the expense of osteoblastogenesis. It leads to decreased bone formation and contributes to senile osteoporosis (SOP). In the current study, RNA-seq analysis unveiled that senescent BMSCs from mice exhibited a significant suppression in the expression of the protein disulfide isomerase PDI-6, an important regulator of mitochondrial unfolded protein response (UPRmt) as well as maintenance of mitochondrial homeostasis. Overexpression of PDI-6 in senescent BMSCs partially rescued mitochondrial function and enhanced osteogenic differentiation. In contrast, osteoblastogenesis of BMSCs remarkably deteriorated under the condition of PDI-6 silencing. Furthermore, melatonin, an endocrine hormone, effectively enhanced PDI-6 expression and repaired injured mitochondria, and the effect of melatonin on PDI-6 expression was melatonin receptor dependent. We further identified that PDI-6 was a downstream effector of Wnt/ß-catenin pathway, as the inhibitor of Wnt3A/TCF signaling, Wnt-C59, inhibited PDI-6 expression. Potential ß-catenin-TCF/LEF binding sites on the promoter of PDI-6 gene were also validated by chromatin immunoprecipitation (ChIP) assay. Thus, our study suggests that PDI-6 is a pharmacological target of melatonin for the intervention of age-related osteoporosis via mitigating mitochondrial dysfunction in senescent BMSCs.