AAV mediated carboxyl terminus of Hsp70 interacting protein overexpression mitigates the cognitive and pathological phenotypes of APP/PS1 mice.

JOURNAL/nrgr/04.03/01300535-202501000-00033/figure1/v/2024-05-14T021156Z/r/image-tiff The E3 ubiquitin ligase, carboxyl terminus of heat shock protein 70 (Hsp70) interacting protein (CHIP), also functions as a co-chaperone and plays a crucial role in the protein quality control system. In this study, we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer's disease. We used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse brain. CHIP overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests, reduced amyloid-ß plaques, and decreased the expression of both amyloid-ß and phosphorylated tau. CHIP also alleviated the concentration of microglia and astrocytes around plaques. In APP/PS1 mice of a younger age, CHIP overexpression promoted an increase in ADAM10 expression and inhibited ß-site APP cleaving enzyme 1, insulin degrading enzyme, and neprilysin expression. Levels of HSP70 and HSP40, which have functional relevance to CHIP, were also increased. Single nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated, which may also reflect a potential mechanism for the neuroprotective effect of CHIP. Our research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 mice. Indeed, overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer's disease.

E2F1 Facilitates the Proliferation and Stemness of Gastric Cancer Cells by Activating CDC25B Transcription and Modulating the MAPK Pathway.

Gastric cancer (GC) is a health problem that concerns people around the world. CDC25B is an essential cell cycle regulatory factor that is overexpressed in a variety of tumor cells. CDC25B plays a vital part in the progression and proliferation of malignant tumors. However, it is not yet clear that how CDC25B affects the stemness of GC cells. The study used bioinformatics to detect the expression of E2F1 and CDC25B in GC tissues and their correlation, as well as pathways enriched by CDC25B. We detected the expression of E2F1 and CDC25B in GC cell lines using quantitative reverse transcription polymerase chain reaction and tested the combination relationship between E2F1 and CDC25B using chromatin immunoprecipitation (ChIP) and dual-luciferase assays. We measured cell viability using CCK-8 assay, evaluated sphere-forming efficiency using sphere formation assay, and determined cell proliferation ability using colony formation assay. We also analyzed the expression of stemness markers and MAPK pathway-related proteins using western blot. In GC tissues and cells, CDC25B was upregulated. Silencing CDC25B could affect the MAPK pathway, thereby repressing the proliferation and stemness of GC cells. As predicted by bioinformatics, CDC25B had an upstream transcription factor, E2F1, which also had a high expression level in GC. Dual-luciferase and ChIP assays confirmed the combination relationship between the two. Rescue experiments uncovered that overexpression of CDC25B could reverse the impact induced by E2F1 knockdown on proliferation and stemness of cells. In conclusion, E2F1 could activate CDC25B transcription to regulate the MAPK pathway and enhance the proliferation and stemness of GC cells. We revealed a potential regulatory pathway of stemness of GC cells that was mediated by CDC25B, providing new ideas for improving and innovating GC treatment.

PD1/PD-L1 blockade in clear cell renal cell carcinoma: mechanistic insights, clinical efficacy, and future perspectives.

The advent of PD1/PD-L1 inhibitors has significantly transformed the therapeutic landscape for clear cell renal cell carcinoma (ccRCC). This review provides an in-depth analysis of the biological functions and regulatory mechanisms of PD1 and PD-L1 in ccRCC, emphasizing their role in tumor immune evasion. We comprehensively evaluate the clinical efficacy and safety profiles of PD1/PD-L1 inhibitors, such as Nivolumab and Pembrolizumab, through a critical examination of recent clinical trial data. Furthermore, we discuss the challenges posed by resistance mechanisms to these therapies and potential strategies to overcome them. We also explores the synergistic potential of combination therapies, integrating PD1/PD-L1 inhibitors with other immunotherapies, targeted therapies, and conventional modalities such as chemotherapy and radiotherapy. In addition, we examine emerging predictive biomarkers for response to PD1/PD-L1 blockade and biomarkers indicative of resistance, providing a foundation for personalized therapeutic approaches. Finally, we outline future research directions, highlighting the need for novel therapeutic strategies, deeper mechanistic insights, and the development of individualized treatment regimens. Our work summarizes the latest knowledge and progress in this field, aiming to provide a valuable reference for improving clinical efficacy and guiding future research on the application of PD1/PD-L1 inhibitors in ccRCC.

Transcription factor AbrB regulates ROS generation and clearance in Bacillus licheniformis.

Oxidative damage caused by the accumulation of reactive oxygen species (ROS) is one of the main obstacles to the improvement of microbial cell growth and fermentation characteristics under adverse environments. And the antioxidant capacity of cells will increase with the cell growth. Here, we found that a transition state transcription factor AbrB related to changes in cell growth status could regulate the accumulation of ROS and antioxidant capacity in Bacillus licheniformis. The results showed that the accumulation of intracellular ROS was reduced by 23.91 % and the cell survival rates were increased by 1.77-fold under 0.5 mM H2O2 when AbrB was knocked out. We further mapped regulatory target genes of AbrB related to ROS generation or clearance based on our previously analyzed transcriptome sequencing. It proved that AbrB could promote ROS generation via upregulating the synthesis of oxidase and siderophores, and negatively regulating the synthesis of iron chelators (pulcherriminic acid, and H2S). Additionally, AbrB could inhibit ROS clearance by negatively regulating the synthesis of antioxidase (superoxide dismutase, catalase, peroxidase, thioredoxin, thioredoxin reductase) and cysteine. Those results illustrated that the inactivation of AbrB during the stationary phase, along with its control over ROS generation and clearance, might represent a vital self-protection mechanism during cell evolution. Overall, the systematic investigation of the multi-pathway regulation network of ROS generation and clearance highlights the important function of AbrB in maintaining intracellular redox balance.

Smartphone-assisted fluorescent sensor for the visualization and quantitative detection of doxycycline and L-arginine.

A novel smartphone-assisted fluorescent sensor based on europium/zirconium metal-organic framework (Eu0.5/Zr0.5-MOF) was developed for the fast and sensitive determination of doxycycline (DOX) and L-arginine (Arg). After the addition of DOX, the fluorescence of Eu0.5/Zr0.5-MOF was quenched owing to the inner filter effect (IFE). When Arg was introduced into the Eu0.5/Zr0.5-MOF@DOX complex system, the fluorescence was recovered because the interaction between Arg and Eu0.5/Zr0.5-MOF@DOX weakened the IFE. Moreover, the Eu0.5/Zr0.5-MOF produced continuous fluorescence color changes for the visual measurement of DOX and Arg. The fluorescent probe for DOX and Arg offered broad linear ranges of 0.05-80 and 0.1-60 µg/mL, respectively, with detection limits as low as 2.07 and 67.5 ng/mL. The proposed method was successfully applied to monitor DOX in eggs and Arg in human serum. This work provides a powerful platform for the real-time and visual analysis of DOX and Arg in food and biological samples.

A carrier-free, injectable, and self-assembling hydrogel based on carvacrol and glycyrrhizin exhibits high antibacterial activity and enhances healing of MRSA-infected wounds.

Inspired by glycyrrhizin's strong pharmacological activities and the directed self-assembly into hydrogels, we created a novel carrier-free, injectable hydrogel (CAR@glycygel) by combining glycyrrhizin with carvacrol (CAR), without any other chemical crosslinkers, to promote wound healing on bacteria-infected skin. CAR appeared to readily dissolve and load into CAR@glycygel. CAR@glycygel had a dense, porous, sponge structure and strong antioxidant characteristics. In vitro, it showed better antibacterial ability than free CAR. For methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus aureus, and Escherichia coli, the diameter of inhibition zone values of CAR@glycygel were 3.80 ± 0.04, 3.31 ± 0.20 and 3.12 ± 0.24 times greater, respectively, than those of free CAR. The MICs for CAR@glycygel was 156.25 µg/mL while it was 1250.00 µg/mL for free CAR to these three bacteria. Its antibacterial mechanism appeared to involve destruction of the integrity of the bacterial cell wall and biomembrane, leading to a leakage of AKP and inhibition of biofilm formation. In vivo, CAR@glycygel effectively stopped bleeding. When applied to skin wounds on rats infected with MRSA, CAR@glycygel had strong bactericidal activity and improved wound healing. The wound healing rates for CAR@glycygel were 49.59 ± 15.78 %, 93.02 ± 3.09 % and 99.02 ± 0.55 % on day 3, day 7, and day 11, respectively, which were much better than blank control and positive control groups. Mechanisms of CAR@glycygel accelerating wound healing involved facilitating epidermis remolding, promoting the growth of hair follicles, stimulating collagen deposition, mitigating inflammation, and promoting angiogenesis. Overall, CAR@glycygel showed great potential as wound dressing for infected skin wounds.

CAFs and T cells interplay: The emergence of a new arena in cancer combat.

The interaction between the immune system and the tumor matrix has a huge impact on the progression and treatment of cancer. This paper summarizes and discusses the crosstalk between T cells and cancer-associated fibroblasts (CAFs). CAFs can also produce inhibitors that counteract the function of T cells and promote tumor immune escape, while T cells can also engage in complex two-way interactions with CAFs through direct cell contact, the exchange of soluble factors such as cytokines, and the remodeling of the extracellular matrix. Precise targeted intervention can effectively reverse tumor-promoting crosstalk between T cells and CAFs, improve anti-tumor immune response, and provide a new perspective for cancer treatment. Therefore, it is important to deeply understand the mechanism of crosstalk between T cells and CAFs. This review aims to outline the underlying mechanisms of these interactions and discuss potential therapeutic strategies that may become fundamental tools in the treatment of cancer, especially hard-to-cure cancers.

Multigenerational Adaptation Can Enhance the Pathogen Resistance of Plants via Changes in Rhizosphere Microbial Community Assembly.

Plants withstand pathogen attacks by recruiting beneficial bacteria to the rhizosphere and passing their legacy on to the next generation. However, the underlying mechanisms involved in this process remain unclear. In our study, we combined microbiomic and transcriptomic analyses to reveal how the rhizosphere microbiome assembled through multiple generations and defense-related genes expressed in Arabidopsis thaliana under pathogen attack stress. Our results showed that continuous exposure to the pathogen Pseudomonas syringae pv tomato DC3000 led to improved growth and increased disease resistance in a third generation of rps2 mutant Arabidopsis thaliana. It could be attributed to the enrichment of specific rhizosphere bacteria, such as Bacillus and Bacteroides. Pathways associated with plant immunity and growth in A. thaliana, such as MAPK signaling pathways, phytohormone signal transduction, ABC transporter proteins, and flavonoid biosynthesis, were activated under the influence of rhizosphere bacterial communities. Our findings provide a scientific basis for explaining the relationship between beneficial microbes and defense-related gene expression. Understanding microbial communities and the mechanisms involved in plant responses to disease can contribute to better plant management and reduction of pesticide use.

Spatiotemporal fate of nanocarriers-embedded dissolving microneedles: the impact of needle dissolving rate.

OBJECTIVE: Dissolving microneedles (DMNs) have shown great potential for transdermal drug delivery due to their excellent skin-penetrating ability and combination with nanocarriers (NCs) can realize targeted drug delivery. The objective of this study was to investigate the impact of microneedle dissolving rate on the in vivo fate of NC-loaded DMNs, which would facilitate the clinical translation of such systems. METHODS: Solid lipid nanoparticles (SLNs) were selected as the model NC for loading in DMNs, which were labeled by P4 probes with aggregation-quenching properties. Sodium hyaluronate acid (HA) and chitosan (CS), with different aqueous dissolving rates, were chosen as model tip materials. The effects of needle dissolving rate on the in vivo fate of NC-loaded DMNs was investigated by tracking the distribution of fluorescence signals after transdermal exposure. RESULTS: P4 SLNs achieved a deeper diffusion depth of 180 µm in DMN-HA with a faster dissolution rate, while the diffusion depth in DMN-CS with a slower dissolution rate was lower (140 µm). The in vivo experiments demonstrated that P4 SLNs had a T1/2 value of 12.14 h in DMN-HA, whilst a longer retention time was found in DMN-CS, with a T1/2 of 13.12 h. CONCLUSIONS: This study confirmed that the in vivo diffusion rate of NC-loaded DMNs was determined by the dissolving rate of DMNs materials and provided valuable guidance for the design and development of NC-loaded DMNs in the future.

AK7-deficiency reversal inhibits ccRCC progression and boosts anti-PD1 immunotherapy sensitivity.

Clear cell renal cell carcinoma (ccRCC) is a common kidney cancer with subtle early symptoms, high recurrence rates, and low sensitivity to traditional treatments like radiotherapy and chemotherapy. Identifying novel therapeutic targets is critical. The expression level of adenylate kinases 7 (AK7) in ccRCC was examined by the TCGAportal and UALCAN databases. The effect of AK7 on proliferation, invasion and migration of ccRCC cell lines was evaluated by cell assay. The correlation between AK7 expression and prognosis, as well as its direct relationship with immunotherapy efficacy, was analyzed using CANCERTOOL and Kaplan-Meier plotter data. Moreover, the TISIDB database was used to study the relationship between AK7 and immune markers. The effect of overexpressed AK7 combined with PD1 monoclonal antibody on ccRCC was evaluated in animal experiments. The results showed that low level of AK7 expression was observed in ccRCC tissues. The expression of AK7 can regulate the proliferation, invasion, and migration of human ccRCC cell lines. The level of AK7 expression was associated with OS of ccRCC patients. This was potentially due to the negative connection between AK7 expression and CD8+ T cell depletion, indicating that immunotherapy might be less effective in individuals with low AK7 expression. Conversely, augmenting AK7 demonstrated an enhanced effectiveness of anti-PD1 therapy. The findings of our research strongly indicated that AK7 could serve as both a prognostic indicator and therapeutic target for patients with ccRCC. Moreover, the overexpression of AK7 combined with anti-PD1 held promising potential as a therapeutic approach for treating ccRCC.

Enhanced Pressure Response of Edge-Deposited Graphene Nanomechanical Resonators.

Nanomechanical resonators made of suspended graphene exhibit high sensitivity to pressure changes. Nevertheless, the graphene resonator pressure performance is affected owing to the gas permeation problem between the graphene film and the substrate. Therefore, we prepared edge-deposited graphene resonators by focused ion beam (FIB) deposition of SiO2, and their gas leakage velocities and pressure-sensing ability were demonstrated. In this paper, we characterize the pressure-sensing response and gas leakage velocities of graphene membranes using an all-optical actuation system. The gas leakage velocities of graphene resonators with diameters of 10, 20, and 40 µm are reduced by 5.0 × 106, 2.0 × 107, and 8.1 × 107 atoms/s, respectively, which demonstrates that the edge deposition structure can reduce the gas leakage of the resonator. Furthermore, the pressure-sensing performance of three graphene resonators with different diameters was evaluated, and their average pressure sensitivities were calculated to be 3.4, 2.4, and 1.9 kHz/kPa, with the largest full-range hysteresis errors of 0.6, 0.7, and 1.0%, respectively. The temperature stabilities of the three sizes of resonators in the temperature range of 300-400 K are 0.016, 0.015, and 0.016%/K, and the maximum resonance frequency drift over 1 h is 0.0058, 0.0048, and 0.0112%, respectively. This work has great significance for the improvement of gas leakage velocity characterization of graphene membrane and graphene resonant pressure sensor performance optimization.

Comparative study of acute and chronic pain after inflatable videoasisted MediastinoscopicTranshiatal esophagectomy and minimally invasive McKeown Esophagectomy:A propensity score matching analysis.

Objective: The short-term quality of life of patients can be enhanced by performing Inflatable Video-Assisted Mediastinoscopic Transhiatal Esophagectomy (IVMTE). Nevertheless, there is limited research on how it impacts postoperative acute and chronic pain in individuals diagnosed with esophageal cancer.Hence, this research aimed to examine the impact of IVMTE and minimally invasive Mckeown esophagectomy (MIME) on the occurrence of acute and chronic pain following surgery in individuals diagnosed with esophageal cancer. Methods: A retrospective, propensity score matching analysis was adopted. In total, 133 patients with esophageal cancer who underwent IVMTE and MIME between January 2020 and December 2021 were part of the study. Among them, 38 patients underwent IVMTE and 95 patients underwent MIME. Following the propensity score matching analysis, 36 patients were included in each group. Patients' postoperative pain was evaluated using the numerical rating scale (NRS). Results: The IVMTE group (Group A) had significantly reduced operation time and intraoperative blood loss compared to the MIME group (Group B) (P < 0.05). NRS scores on the 1st, 2nd, 3rd, and 7th days after surgery, as well as on the 3rd and 6th months post-surgery, were notably reduced in the IVMTE group (Group A) compared to the MIME group (Group B) (P < 0.05). Univariate and multivariate analysis showed that chronic pain occurred postoperative 3rd months was related to the operation methods (P < 0.05). Univariate analysis showed that chronic pain occurred postoperative 6th months was related to the operation time, postoperative 14th days NRS scores and operation methods (P < 0.05). Multivariate analysis showed that chronic pain occurred postoperative 6th months was related to the operation methods (P < 0.05). Conclusion: The results showed that the operation methods were the main risk factors for postoperative chronic pain. The compared with MIME, IVMTE can further reduce the acute and chronic pain of patients with esophageal cancer.

91-month follow-up of solitary punctate chorioretinitis in a Chinese patient.

BACKGROUND: Solitary Punctate Chorioretinitis (SPC) is a recently identified form of punctate inner choroidopathy (PIC) characterized by a single lesion in the fovea of the macula. Previous studies with a maximum follow-up of 48 months were insufficient. Our review uncovered a case sustained for 91 months. CASE PRESENTATION: A 28-year-old young woman experienced with sudden visual loss in her right eye. Comprehensive examinations, including assessment of best-corrected visual acuity (BCVA), slit-lamp biomicroscopy, noncontact tonometry, fundus fluorescein angiography (FFA), fundus autofluorescence (FAF), optical coherence tomography angiography (OCTA), perimetry, and microperimetry, were conducted. Over 91 months, the lesion slightly enlarged, remained yellow-white and punctate, and stayed in the central macula of the posterior pole. OCT images depicted subsidence in the inner nuclear layer (INL), the outer plexiform layer (OPL), photoreceptor layer, and disruption of the external limiting membrane (ELM), ellipsoid zone, and retinal pigment epithelium (RPE)/Bruch's membrane complex. Retinal herniation, focal choroidal excavation (FCE), and abnormal vessels in the choriocapillaris were noted. At the slab of the choriocapillaris, OCTA demonstrated that the lesion resembled a linear vascular structure, distinct from the structure of normal choriocapillaris. This confirmed the lesion as an abnormal vascular formation. FAF revealed a punctate hypo-autofluorescence lesion and abnormal hyper-autofluorescence near the optic disc and macula. FFA demonstrated a punctate hyper-fluorescent lesion inferotemporal to the fovea. The vascular structure remained stable without fluid exudation on OCT images, hence anti-vascular endothelial growth factor (anti-VEGF) treatment was not administered. Visual acuity improved from counting fingers to 0.07 in 52 days, reached 0.6 after 15 months, remained at 0.6 from 56 to 80 months, and returned to 0.8 after 91 months, although accompanied by local scotomas. The lesion pattern slightly enlarged without scarring. CONCLUSIONS: Throughout long-term follow-up, we had long suspected the presence of choroidal neovascularization (CNV) and found the FCE in the last visit. Eventually, we concluded that SPC could potentially constitute a distinct subtype of PIC. The patient received no treatment, and vision recovered to 0.8. If CNV is suspected in SPC, anti-VEGF treatment may not be necessary without activity on OCT, but close monitoring is essential.

Global, regional, and national burden of female cancers in women of child-bearing age, 1990-2021: analysis of data from the global burden of disease study 2021.

Background: The global status of women's health is underestimated, particularly the burden on women of child-bearing age (WCBA). We aim to investigate the pattern and trend of female cancers among WCBA from 1990 to 2021. Methods: We retrieved data from the Global Burden of Disease Study (GBD) 2021 on the incidence and disability-adjusted life-years (DALYs) of four major female cancers (breast, cervical, uterine, and ovarian cancer) among WCBA (15-49 years) in 204 countries and territories from 1990 to 2021. Estimated annual percentage changes (EAPC) in the age-standardised incidence and DALY rates of female cancers, by age and socio-demographic index (SDI), were calculated to quantify the temporal trends. Spearman correlation analysis was used to examine the correlation between age-standardised rates and SDI. Findings: In 2021, an estimated 1,013,475 new cases of overall female cancers were reported globally, with a significant increase in age-standardised incidence rate (EAPC 0.16%), and a decrease in age-standardised DALY rate (-0.73%) from 1990 to 2021. Annual increase trends of age-standardised incidence rate were observed in all cancers, except for that in cervical cancer. Contrary, the age-standardised DALY rate decreased in all cancers. Breast and cervical cancers were prevalent among WCBA worldwide, followed by ovarian and uterine cancers, with regional disparities in the burden of four female cancers. In addition, the age-standardised incidence rates of breast, ovarian, and uterine cancers basically showed a consistent upward trend with increasing SDI, while both the age-standardised incidence and DALY rates in cervical cancer exhibited downward trends with SDI. Age-specific rates of female cancers increased with age in 2021, with the most significant changes observed in younger age groups, except for uterine cancer. Interpretation: The rising global incidence of female cancers, coupled with regional variations in DALYs, underscores the urgent need for innovative prevention and healthcare strategies to mitigate the burden among WCBA worldwide. Funding: This study was supported by the Science Foundation for Young Scholars of Sichuan Provincial People's Hospital (NO. 2022QN44 and NO. 2022QN18); the Key R&D Projects of Sichuan Provincial Department of Science and Technology (NO. 2023YFS0196); the National Natural Science Foundation of China (No. 82303701).

Surveillance of fluoroquinolones resistance in rifampicin-susceptible tuberculosis in eastern China with whole-genome sequencing-based approach.

Background: Leveraging well-established DNA-level drug resistance mechanisms, whole-genome sequencing (WGS) has emerged as a valuable methodology for predicting drug resistance. As the most effective second-line anti-tuberculosis (anti-TB) drugs, fluoroquinoloness (FQs) are generally used to treat multidrug-resistant tuberculosis (MDR-TB, defined as being resistant to resistant to rifampicin and isoniazid) or rifampicin-resistant tuberculosis (RR-TB). However, FQs are also commonly used in the management of other bacterial infections. There are few published data on the rates of FQs resistance among rifampicin-susceptible TB. The prevalence of FQs resistance among TB patients who are rifampicin-susceptible has not been studied in Zhejiang Province, China. The goal of this study was to provide a baseline characterization of the prevalence of FQs resistance, particularly among rifampicin-susceptible TB in Zhejiang Province, China. Methods: Based on WGS, we have investigated the prevalence of FQs resistance among rifampicin-susceptible TB in Zhejiang Province. All pulmonary TB patients with positive cultures who were identified in Zhejiang area during TB drug resistance surveillance from 2018 to 2019 have enrolled in this population-based retrospective study. Results: The rate of FQs resistance was 4.6% (32/698) among TB, 4.0% (27/676) among rifampicin-susceptible TB, and 22.7% (5/22) among RR-TB. According to WGS, strains that differ within 12 single-nucleotide polymorphisms (SNPs) were considered to be transmission of FQ-resistant strains. Specifically, 3.7% (1/27) of FQs resistance was caused by the transmission of FQs-resistant strains among the rifampicin-susceptible TB and 40.7% (11/27) of FQs resistance was identified as hetero-resistance. Conclusion: The prevalence of FQs resistance among TB patients who were rifampicin-susceptible was severe in Zhejiang. The emergence of FQs resistance in TB isolates that are rifampicin-susceptible was mainly caused by the selection of drug-resistant strains. In order to prevent the emergence of FQs resistance, the WGS-based surveillance system for TB should be urgently established, and clinical awareness of the responsible use of FQs for respiratory infections should be enhanced.

Coordination engineering for iron-based hexacyanoferrate as a high-stability cathode for sodium-ion batteries.

Iron-based hexacyanoferrate (Fe-HCF) are promising cathode materials for sodium-ion batteries (SIBs) due to their unique open-channel structure that facilitates fast ion transport and framework stability. However, practical implementation of SIBs has been hindered by low initial Coulombic efficiency (ICE), poor rate performance, and short lifespan. Herein, we report a coordination engineering to synthesize sodium-rich Fe-HCF as cathodes for SIBs through a uniquely designed 10-kg-scale chemical reactor. Our study systematically investigated the relationship between coordination surroundings and the electrochemical behavior. Building on this understanding, the cathode delivered a reversible capacity of 99.3 mAh g-1 at 5 C (1 C = 100 mA g-1), exceptional rate capability (51 mAh g-1 even at 100 C), long lifespan (over 15,000 times at 50 C), and a high ICE of 92.7%. A full cell comprising the Fe-HCF cathode and hard carbon (HC) anode exhibited an impressive cyclic stability with a high-capacity retention rate of 98.3% over 1,000 cycles. Meanwhile, this material can be readily scaled to the practical levels of yield. The findings underscore the potential of Fe-HCF as cathodes for SIBs and highlight the significance of controlling nucleation and morphology through coordination engineering for a sustainable energy storage system.

High-efficient M-NC single-atom catalysts for catalytic ozonation in water purification: Performance and mechanisms.

Heterogeneous catalytic ozonation (HCO) holds promise in water purification but suffers from limited accessible metal sites, metal leaching, and unclear structure-activity relationships. This work reported M-NC (M=Co, Ni, Fe, and Mn) single-atom catalysts (SACs) with high atomic efficiency and minimal metal release. The new HCO systems, especially the Co-based system, exhibited impressive performance in various refractory contaminant removal, involving various reactive species generation, such as •OHads, •OHfree, *O, and 1O2. For sulfamethoxazole removal, the normalized kobs for Co-NC, Ni-NC, Fe-NC, and Mn-NC were determined as 13.53, 3.94, 3.55, and 4.13 min-1·mMmetal-1·g·m-2 correspondingly, attributed to the abundant acid sites, faster electron transfer, and lower energy required for O3 decomposition and conversion. The metal atoms and hydroxyl groups, individually serving as Lewis and Bronsted acid sites (LAS and BAS), were the primary centers for •OH generation and O3 adsorption. The relationships between active sites and both O3 utilization and •OH generation were found. LAS and BAS were responsible for O3 adsorption, while strong LAS facilitated O3 conversion into •OH. Theoretical calculations revealed the catalytic mechanisms involved O3→ *O→ *OO→ O3•-→ •OH. This work highlights the significance of SAC design for HCO and advances the understanding of atomic-level HCO behavior.

NIR-II Light-Powered Core-Shell Prodrug Nanomotors Enhance Cancer Therapy through Synergistic Oxidative Stress-Photothermo Modulation.

Near-infrared-II (NIR-II) photothermal therapy is emerging as a cutting-edge modality for tumor ablation due to its good biosafety, high penetration ability and spatiotemporal controllability. Despite efforts, establishing a link between cellular metabolic regulation and photothermal performance is still promising in synergistic cancer therapy. Herein, we developed a core-shell semiconducting polymer@metal-phenolic network (SP@GFP) nanomotor by assembling diphenol-terminated cisplatin prodrug ligand (cPt-DA) and iron (III) (Fe3+) through metal coordination on SP particles in the presence of GOx and DSPE-PEG-cRGD, for NIR-II-propelled self-propulsion and synergistic cancer therapy. Remotely driving the SP@GFP nanomotor with an NIR-II laser through a thermophoresis mechanism would allow for in-depth penetration and accumulation. The synergistic photothermal effect and continuous Fe2+-mediated ROS generation of SP@GFP nanomotor could activate photothermal, chemotherapeutic effects and ferroptosis pathway for cancer cells through reshaping cellular metabolic pathways (HSP and GPX4). By combining the concepts of chemotherapeutic prodrugs, catalytic ROS generation, photothermal response and cellular metabolic regulation, the NIR-II laser-controlled core-shell SP@GFP nanomotor displayed improved outcomes for enhanced cancer therapy through synergistic oxidative stress-photothermo modulation. STATEMENT OF SIGNIFICANCE: •A NIR-II-powered core-shell SP@GFP prodrug nanomotor was constructed through metal coordination assembly for enhanced cancer therapy; •NIR-II laser propelled the propulsion of SP@GFP nanomotor through thermophoresis mechanism for in depth penetration and accumulation. •Therapeutic outcomes were improved through synergistic modulating oxidative stress and photothermal performance.

Inflammatory microenvironment of moderate pulpitis enhances the osteo-/odontogenic potential of dental pulp stem cells by autophagy.

AIM: This study investigated the effects of the inflammatory microenvironment of moderate pulpitis on biological properties of human dental pulp stem cells (DPSCs) and further explored the mechanism involved in osteo-/odontogenic induction of the inflammatory microenvironment. METHODOLOGY: Healthy DPSCs (hDPSCs) and inflammatory DPSCs (iDPSCs) were isolated from human-impacted third molars free of caries and clinically diagnosed with moderate pulpitis, respectively. Healthy DPSCs were treated with lipopolysaccharides (LPS) to mimic iDPSCs in vitro. The surface markers expressed on hDPSCs and iDPSCs were detected by flow cytometry. A CCK-8 assay was performed to determine cell proliferation. Flow cytometric analysis was used to evaluate cell apoptosis. The osteo-/odontogenic differentiation of DPSCs was evaluated by western blot, alkaline phosphatase staining, and Alizarin Red S staining. The functions of the genes of differentially expressed mRNAs of hDPSCs and iDPSCs were analysed using gene set enrichment analysis. Transmission electron microscopy and western blot were used to evaluate the autophagy changes of LPS-treated DPSCs. RESULTS: Compared with hDPSCs, iDPSCs showed no significant difference in proliferative capacity but had stronger osteo-/odontogenic potential. In addition, the mRNAs differentially expressed between iDPSCs and hDPSCs were considerably enriched in autophagosome formation and assembly-related molecules. In vitro mechanism studies further found that low concentrations of LPS could upregulate DPSC autophagy-related protein expression and autophagosome formation and promote its odontogenic/osteogenic differentiation, whereas the inhibition of DPSC autophagy led to the weakening of the odontogenic/osteogenic differentiation induced by LPS. CONCLUSIONS: This explorative study showed that DPSCs isolated from teeth with moderate pulpitis possessed higher osteo-/odontogenic differentiation capacity, and the mechanism involved was related to the inflammatory microenvironment-mediated autophagy of DPSCs. This helps to better understand the repair potential of inflamed dental pulp and provides the biological basis for pulp preservation and hard tissue formation in minimally invasive endodontics.

Arthroscopic medial patellofemoral ligament reconstruction with polyethylene suture combined with medial retinaculum plication for the treatment of acute patellar dislocation in young and middle-aged patients with a follow-up of at least 2 years.

PURPOSE: The purpose of this study was to propose a surgical technique for arthroscopic medial patellofemoral ligament (MPFL) reconstruction with polyethylene suture combined with medial retinaculum plication and to evaluate the efficacy of this surgical technique in the treatment of acute patellar dislocation. METHODS: Clinical data of patients with acute patellar dislocations treated with arthroscopic MPFL reconstruction with polyethylene tape (FiberTape) combined with medial support band compression were analyzed retrospectively from January 2018 to January 2021. The mean age of the patients was 25.15 ± 4.66 years; the mean follow-up time was 27.5 (24-36) months. Clinical evaluation consisted of apprehension test results, patellar extrapolation test results, Lysholm score, Kujala score, and IKDC score, the Patellar lateral shift distance and patellar tilt angle (PTA) measured by CT scan. RESULTS: All patients had no recurrent patellar dislocation or subluxation after surgery, and the apprehension test was negative. In all patients, the Kujala score (36.0 ± 9.9 vs. 98.2 ± 3.1), the IKDC score (48.6 ± 7.0 vs. 90.6 ± 4.4) and the Lysholm score (32.8 ± 10.4 vs. 96.7 ± 3.1) had improved at the 24-month follow up (P < 0.05). In addition, PTA was significantly lower at the 12-month follow-up and 24-giving-month follow-up compared to the preoperative period (P < 0.05, Table 2). The patellar lateral shift distance decreased from 14.94 ± 6.11 mm preoperatively to 3.00 ± 1.40 mm (12-month follow up) and 3.26 ± 1.37 mm (24-month follow up), respectively. CONCLUSION: Arthroscopic MPFL reconstruction with polyethylene suture combined with medial retinaculum plication is a safe and reliable surgical technique for the treatment of acute patellar dislocation in young and middle-aged patients. LEVEL OF EVIDENCE: Level III, Therapeutic Study.