Differentiated management of ROS level in tumor and kidney to alleviate Cis-platinum induced acute kidney injury with improved efficacy.

Cisplatin (DDP) is a prevalent chemotherapeutic agent used in tumor therapy, yet DDP-induced acute kidney injury (AKI) severely limits its clinical application. Antioxidants as reactive oxygen species (ROS) scavengers can circumvent this adverse effect while leading to the decrease of efficacy to tumor. Herein, we report ultrasmall ruthenium nanoparticles (URNPs) as switchable ROS scavengers/generators to alleviate DDP-induced AKI and improve its therapeutic efficacy. In the physiological environment of the kidney, URNPs mimic multi-enzyme activities, such as superoxide dismutase and catalase, effectively protecting the renal cell and tissue by down-regulating the increased ROS level caused by DDP and alleviating AKI. Specifically, URNPs are oxidized by high levels of H2O2 in the tumor microenvironment (TME), resulting in the generation of oxygen vacancies and Ru3+/Ru4+ ions. This unique structure transformation endows URNPs to generate singlet oxygen (1O2) under laser irradiation and hydroxyl radicals (∙OH) through a Fenton-like reaction in tumor cell and tissue. The simultaneous generation of multifarious ROS effectively improves the efficacy of DDP in vitro and in vivo. This TME-responsive ROS scavenger/generator acts as an adjuvant therapeutic agent to minimize side effects and improve the efficacy of chemotherapy drugs, providing a new avenue to chemotherapy and facilitating clinical tumor therapy.

Ultraviolet attenuates centromere-mediated meiotic genome stability and alters gametophytic ploidy consistency in flowering plants.

Ultraviolet (UV) radiation influences development and genome stability in organisms; however, its impact on meiosis, a special cell division essential for the delivery of genetic information across generations in eukaryotes, has not yet been elucidated. In this study, by performing cytogenetic studies, we reported that UV radiation does not damage meiotic chromosome integrity but attenuates centromere-mediated chromosome stability and induces unreduced gametes in Arabidopsis thaliana. We showed that functional centromere-specific histone 3 (CENH3) is required for obligate crossover formation and plays a role in the protection of sister chromatid cohesion under UV stress. Moreover, we found that UV specifically alters the orientation and organization of spindles and phragmoplasts at meiosis II, resulting in meiotic restitution and unreduced gametes. We determined that UV-induced meiotic restitution does not rely on the UV Resistance Locus8-mediated UV perception and the Tapetal Development and Function1- and Aborted Microspores-dependent tapetum development, but possibly occurs via altered JASON function and downregulated Parallel Spindle1. This study provides evidence that UV radiation influences meiotic genome stability and gametophytic ploidy consistency in flowering plants.

Pioneering nanomedicine in orthopedic treatment care: a review of current research and practices.

A developing use of nanotechnology in medicine involves using nanoparticles to administer drugs, genes, biologicals, or other materials to targeted cell types, such as cancer cells. In healthcare, nanotechnology has brought about revolutionary changes in the treatment of various medical and surgical conditions, including in orthopedic. Its clinical applications in surgery range from developing surgical instruments and suture materials to enhancing imaging techniques, targeted drug delivery, visualization methods, and wound healing procedures. Notably, nanotechnology plays a significant role in preventing, diagnosing, and treating orthopedic disorders, which is crucial for patients' functional rehabilitation. The integration of nanotechnology improves standards of patient care, fuels research endeavors, facilitates clinical trials, and eventually improves the patient's quality of life. Looking ahead, nanotechnology holds promise for achieving sustained success in numerous surgical disciplines, including orthopedic surgery, in the years to come. This review aims to focus on the application of nanotechnology in orthopedic surgery, highlighting the recent development and future perspective to bridge the bridge for clinical translation.

Underlying Mechanism of Lysosomal Membrane Permeabilization in CNS Injury: A Literature Review.

Lysosomes play a crucial role in various intracellular pathways as their final destination. Various stressors, whether mild or severe, can induce lysosomal membrane permeabilization (LMP), resulting in the release of lysosomal enzymes into the cytoplasm. LMP not only plays a pivotal role in various cellular events but also significantly contributes to programmed cell death (PCD). Previous research has demonstrated the participation of LMP in central nervous system (CNS) injuries, including traumatic brain injury (TBI), spinal cord injury (SCI), subarachnoid hemorrhage (SAH), and hypoxic-ischemic encephalopathy (HIE). However, the mechanisms underlying LMP in CNS injuries are poorly understood. The occurrence of LMP leads to the activation of inflammatory pathways, increased levels of oxidative stress, and PCD. Herein, we present a comprehensive overview of the latest findings regarding LMP and highlight its functions in cellular events and PCDs (lysosome-dependent cell death, apoptosis, pyroptosis, ferroptosis, and autophagy). In addition, we consolidate the most recent insights into LMP in CNS injury by summarizing and exploring the latest advances. We also review potential therapeutic strategies that aim to preserve LMP or inhibit the release of enzymes from lysosomes to alleviate the consequences of LMP in CNS injury. A better understanding of the role that LMP plays in CNS injury may facilitate the development of strategic treatment options for CNS injury.

Single Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis.

Rationale: Fibrotic hypersensitivity pneumonitis is a debilitating interstitial lung disease driven by incompletely understood immune mechanisms. Objectives: To elucidate immune aberrations in fibrotic hypersensitivity pneumonitis in single-cell resolution. Methods: Single-cell 5' RNA sequencing was conducted on peripheral blood mononuclear cells and bronchoalveolar lavage cells obtained from 45 patients with fibrotic hypersensitivity pneumonitis, 63 idiopathic pulmonary fibrosis, 4 non-fibrotic hypersensitivity pneumonitis, and 36 healthy controls in the United States and Mexico. Analyses included differential gene expression (Seurat), transcription factor activity imputation (DoRothEA-VIPER), and trajectory analyses (Monocle3/Velocyto-scVelo-CellRank). Measurements and Main Results: Overall, 501,534 peripheral blood mononuclear cells from 110 patients and controls and 88,336 bronchoalveolar lavage cells from 19 patients were profiled. Compared to controls, fibrotic hypersensitivity pneumonitis has elevated classical monocytes (adjusted-p=2.5e-3) and are enriched in CCL3hi/CCL4hi and S100Ahi classical monocytes (adjusted-p<2.2e-16). Trajectory analyses demonstrate that S100Ahi classical monocytes differentiate into SPP1hi lung macrophages associated with fibrosis. Compared to both controls and idiopathic pulmonary fibrosis, fibrotic hypersensitivity pneumonitis patient cells are significantly enriched in GZMhi cytotoxic T cells. These cells exhibit transcription factor activities indicative of TGFß and TNFα/NFκB pathways. These results are publicly available at https://ildimmunecellatlas.org. Conclusions: Single-cell transcriptomics of fibrotic hypersensitivity pneumonitis patients uncovered novel immune perturbations, including previously undescribed increases in GZMhi cytotoxic CD4+ and CD8+ T cells - reflecting this disease's unique inflammatory T-cell driven nature - as well as increased S100Ahi and CCL3hi/CCL4hi classical monocytes also observed in idiopathic pulmonary fibrosis. Both cell populations may guide the development of new biomarkers and therapeutic interventions.

Neuregulin-1, a member of the epidermal growth factor family, mitigates STING-mediated pyroptosis and necroptosis in ischaemic flaps.

Background: Ensuring the survival of the distal end of a random flap during hypoperfusion (ischaemia) is difficult in clinical practice. Effective prevention of programmed cell death is a potential strategy for inhibiting ischaemic flap necrosis. The activation of stimulator of interferon genes (STING) pathway promotes inflammation and leads to cell death. The epidermal growth factor family member neuregulin-1 (NRG1) reduces cell death by activating the protein kinase B (AKT) signalling pathway. Moreover, AKT signalling negatively regulates STING activity. We aimed to verify the efficacy of NRG1 injection in protecting against flap necrosis. Additionally, we investigated whether NRG1 effectively enhances ischemic flap survival by inhibiting pyroptosis and necroptosis through STING suppression. Methods: A random-pattern skin flap model was generated on the backs of C57BL/6 mice. The skin flap survival area was determined. The blood supply and vascular network of the flap was assessed by laser Doppler blood flow analysis. Cluster of differentiation 34 immunohistochemistry (IHC) and haematoxylin and eosin (H&E) staining of the flap sections revealed microvessels. Transcriptome sequencing analysis revealed the mechanism by which NRG1 promotes the survival of ischaemic flaps. The levels of angiogenesis, oxidative stress, necroptosis, pyroptosis and indicators associated with signalling pathways in flaps were examined by IHC, immunofluorescence and Western blotting. Packaging adeno-associated virus (AAV) was used to activate STING in flaps. Results: NRG1 promoted the survival of ischaemic flaps. An increased subcutaneous vascular network and neovascularization were found in ischaemic flaps after the application of NRG1. Transcriptomic gene ontology enrichment analysis and protein level detection indicated that necroptosis, pyroptosis and STING activity were reduced in the NRG1 group. The phosphorylation of AKT and forkhead box O3a (FOXO3a) were increased after NRG1 treatment. The increased expression of STING in flaps induced by AAV reversed the therapeutic effect of NRG1. The ability of NRG1 to phosphorylate AKT-FOXO3a, inhibit STING and promote flap survival was abolished after the application of the AKT inhibitor MK2206. Conclusions: NRG1 inhibits pyroptosis and necroptosis by activating the AKT-FOXO3a signalling pathway to suppress STING activation and promote ischaemic flap survival.

State-level population estimates of sexual minority adolescents in the United States: A predictive modeling study.

PURPOSE: The Youth Risk Behavior Survey (YRBS) among high school students includes standard questions about sexual identity and sex of sexual contacts, but these questions are not consistently included in every state that conducts the survey. This study aimed to develop and apply a method to predict state-level proportions of high school students identifying as lesbian, gay, or bisexual (LGB) or reporting any same-sex sexual contacts in those states that did not include these questions in their 2017 YRBS. METHODS: We used state-level high school YRBS data from 2013, 2015, and 2017. We defined two primary outcomes relating to self-reported LGB identity and reported same-sex sexual contacts. We developed machine learning models to predict the two outcomes based on other YRBS variables, and comparing different modeling approaches. We used a leave-one-out cross-validation approach and report results from best-performing models. RESULTS: Modern ensemble models outperformed traditional linear models at predicting state-level proportions for the two outcomes, and we identified prediction methods that performed well across different years and prediction tasks. Predicted proportions of respondents reporting LGB identity in states that did not include direct measurement ranged between 9.4% and 12.9%. Predicted proportions of respondents reporting any same-sex contacts, where not directly observed, ranged between 7.0% and 10.4%. CONCLUSION: Comparable population estimates of sexual minority adolescents can raise awareness among state policy makers and the public about what proportion of youth may be exposed to disparate health risks and outcomes associated with sexual minority status. This information can help decision makers in public health and education agencies design, implement and evaluate community and school interventions to improve the health of LGB youth.

Porous organic polymers assisted aptamer signal amplification for enhanced photoeletrochemical detection of MUC1.

Mucin1 (MUC1) is an extensively glycosylated transmembrane protein that is widely distributed and overexpressed on the surface of cancer cells, playing an important role in tumor occurrence and metastasis. Therefore, highly sensitive detection of MUC1 is of great significance for early diagnosis, treatment monitoring, and prognosis of cancer. Here, an ultra-sensitive photoelectrochemical (PEC) sensing platform was developed based on an aptamer amplification strategy for highly selective and sensitive detection of MUC1 overexpressed in serum and on cancer cell surfaces. The sensing platform utilized copper phthalocyanine to fabricate porous organic polymers (CuPc POPs), and was effectively integrated with g-C3N4/MXene to form a ternary heterojunction material (g-C3N4/MXene/CuPc POPs). This material effectively improved electron transfer capability, significantly enhanced light utilization, and greatly enhanced photoelectric conversion efficiency, resulting in a dramatic increase in photocurrent response. MUC1 aptamer 1 was immobilized on a chitosan-modified photoelectrode for the selective capture of MUC1 or MCF-7 cancer cells. When the target substance was present, MUC1 aptamer 2 labeled with methylene blue (MB) was specifically adsorbed on the electrode surface, leading to enhanced photocurrent. The concentration of MUC1 directly correlated with the number of MB molecules attracted to the electrode surface, establishing a linear relationship between photocurrent intensity and MUC1 concentration. The PEC biosensor exhibited excellent sensitivity for MUC1 detection with a wide detection range from 1 × 10-7 to 10 ng/mL and a detection limit of 8.1 ag/mL. The detection range for MCF-7 cells was from 2 × 101 to 2 × 106 cells/mL, with the capability for detecting single MCF-7 cells. The aptamer amplification strategy significantly enhanced PEC performance, and open up a promising platform to establish high selectivity, stability, and ultrasensitive analytical techniques.

The current status of various preclinical therapeutic approaches for tendon repair.

Tendons are fibroblastic structures that link muscle and bone. There are two kinds of tendon injuries, including acute and chronic. Each form of injury or deterioration can result in significant pain and loss of tendon function. The recovery of tendon damage is a complex and time-consuming recovery process. Depending on the anatomical location of the tendon tissue, the clinical outcomes are not the same. The healing of the wound process is divided into three stages that overlap: inflammation, proliferation, and tissue remodeling. Furthermore, the curing tendon has a high re-tear rate. Faced with the challenges, tendon injury management is still a clinical issue that must be resolved as soon as possible. Several newer directions and breakthroughs in tendon recovery have emerged in recent years. This article describes tendon injury and summarizes recent advances in tendon recovery, along with stem cell therapy, gene therapy, Platelet-rich plasma remedy, growth factors, drug treatment, and tissue engineering. Despite the recent fast-growing research in tendon recovery treatment, still, none of them translated to the clinical setting. This review provides a detailed overview of tendon injuries and potential preclinical approaches for treating tendon injuries.

MLLT6/ATF2 axis restrains breast cancer progression by driving DDIT3/4 expression.

Epigenetic deregulation is strongly associated with tumour progression. The identification of natural tumour suppressors to overcome cancer metastasis is urgent for cancer therapy. We investigate whether myeloid/lymphoid or mixed-lineage leukaemia translocated (MLLT) family members contribute to breast cancer progression and found that high MLLT6 expression predicted a better prognosis and that gradually decreased MLLT6 expression was accompanied by breast cancer malignancy. MLLT6 was downregulated by hypoxia-induced enrichment of DNMT1 at the MLLT6 promoter. The results of in vitro functional experiments indicated that MLLT6 depletion promoted colony formation and cell migration, probably by hampering apoptosis. RNA profiling revealed that the apoptotic pathway was downregulated following stable knockdown of MLLT6. DNA damage-inducible transcript 3/4 (DDIT3/4) were among the top 10 downregulated genes and may have expression patterns similar to that of MLLT6. Restoring DDIT3/4 expression in cells with MLLT6 depletion blocked colony formation and cell migration and attenuated the successful colonization of breast cancer cells in vivo. We also determined that the transcription factor activating transcription factor 2 (ATF2) is a binding partner of MLLT6 and participates in the MLLT6/ATF2 axis, which was reinforced by inhibition of AKT signalling, in turn inducing DDIT3/4 expression by establishing an active chromatin structure at the DDIT3/4 gene promoters. Because MLLT6 promotes breast cancer cell apoptosis by inducing DDIT3/4 expression during metastasis, it could be a novel tumour suppressor. Implications: Control of MLLT6 expression via inhibition of PI3K/AKT kinase activity is a potential therapeutic approach for the management of metastatic breast cancer.

[Analysis of the factors influencing prognosis of the adult in-hospital cardiac arrest].

OBJECTIVE: To explore the factors influencing prognosis of patients with in-hospital cardiac arrest (IHCA). METHODS: A retrospective observational study was conducted. The clinical data of patients who developed IHCA and underwent cardiopulmonary resuscitation (CPR) at the Second Xiangya Hospital of Central South University from January 1, 2016, to December 31, 2022 were analyzed. The patients' information, including gender, age, medical history, pre-cardiac arrest related parameters [1-hour pre-cardiac arrest neurological function, 24-hour pre-cardiac arrest hemoglobin (Hb) levels, 1-hour pre-cardiac arrest vital signs], initial CPR-related factors (implementation time and location, initial rhythm, ventilation method, defibrillation and resuscitation drugs) as well as restoration of spontaneous circulation (ROSC) related parameters (vital signs at ROSC and 1 hour after ROSC, 24-hour post-cardiac arrest Hb, and IHCA events), were collected through the hospital's electronic medical record system. The clinical data were compared between ROSC and non-ROSC patients as well as between patients with favorable neurological function [cerebral performance category (CPC) grades 1-2] and unfavorable neurological function (CPC grades 3-5) at 28 days. The factors with statistical significance in univariate analysis and clinical significance were enrolled in a binary multivariate Logistic regression model to analyze the influencing factors of ROSC and neurological function at 28 days after ROSC. The predictive value of factors influencing neurological function at 28 days was assessed using receiver operator characteristic curve (ROC curve). RESULTS: A total of 277 IHCA-CPR patients were enrolled, of which 230 achieved ROSC (83.0%) and 47 were not achieved (17.0%). Compared with non-ROSC patients, ROSC patients had lower prevalence of cerebrovascular disease history and proportion of adrenaline usage, but a higher proportion of initial shockable rhythms. In the multivariate Logistic regression analysis, it was found that using a bag-mask ventilation+endotracheal intubation (compared with a bag-mask ventilation alone) was beneficial for achieving ROSC in IHCA-CPR patients [odds ratio (OR) = 2.895, 95% confidence interval (95%CI) was 1.204-6.962, P = 0.018], while a initial non-shockable rhythm was not conducive to achieving ROSC in IHCA-CPR patients (OR = 0.349, 95%CI was 0.147-0.831, P = 0.017). Among the 230 ROSC patients, 42 had good neurological function at 28 days (18.3%), and 188 had poor neurological function (81.7%). Compared with the patients with good neurological function, the patients with the poor neurological function were older and had a higher prevalence of 1-hour pre-cardiac arrest neurological dysfunction and low perfusion, initial non-shockable rhythms, endotracheal intubation, and usage of adrenaline, vasopressors and sodium bicarbonate, a lower proportion of defibrillation and antiarrhythmic medication usage as well as lower 24-hour post-cardiac arrest Hb levels. The multivariate Logistic regression analysis revealed that female (OR = 6.449, 95%CI was 1.837-22.642, P = 0.004), older age (OR = 1.054, 95%CI was 1.017-1.093, P = 0.004), 1-hour pre-cardiac arrest neurological dysfunction (OR = 25.044, 95%CI was 2.737-229.169, P = 0.004), 1-hour pre-cardiac arrest low perfusion (OR = 3.880, 95%CI was 1.306-11.524, P = 0.028), endotracheal intubation (compared with a bag-mask ventilation; OR = 8.712, 95%CI was 1.402-54.141, P = 0.020) and face mask+endotracheal intubation during CPR (compared with a bag-mask ventilation; OR = 11.089, 95%CI was 3.482-35.320, P = 0.000), IHCA events > 1 time (OR = 4.221, 95%CI was 1.249-14.226, P = 0.020) were positively associated with poor neurological function at 28 days, which were independent risk factors those were not conducive to 28-day neurological function recovery after ROSC in IHCA-CPR patients. In contrast, usage of antiarrhythmic medication (OR = 0.345, 95%CI was 0.134-0.890, P = 0.028) and 24-hour post-cardiac arrest Hb (OR = 0.983, 95%CI was 0.966-0.999, P = 0.043) were negatively associated with poor neurological function at 28 days, which were protective factors those were beneficial for the recovery of neurological function. ROC curve analysis showed that the area under the ROC curve (AUC) of 24-hour post-cardiac arrest Hb for predicting poor neurological function at 28 days after ROSC in IHCA-CPR patients was 0.659 (95%CI was 0.577-0.742), with a cut-off value of 99.5 g/L (sensitivity was 76.2%, specificity was 57.8%). CONCLUSIONS: Defibrillation and tracheal intubation during CPR are crucial for IHCA patients. It was also observed that patients with low Hb (< 99.5 g/L should be of high concern), older age, 1-hour pre-cardiac arrest neurological function and hypoperfusion, and IHCA events > 1 time were significantly related to unfavorable neurological outcome in adult resuscitated patients with IHCA.

Current developments and future perspectives of nanotechnology in orthopedic implants: an updated review.

Orthopedic implants are the most commonly used fracture fixation devices for facilitating the growth and development of incipient bone and treating bone diseases and defects. However, most orthopedic implants suffer from various drawbacks and complications, including bacterial adhesion, poor cell proliferation, and limited resistance to corrosion. One of the major drawbacks of currently available orthopedic implants is their inadequate osseointegration at the tissue-implant interface. This leads to loosening as a result of immunological rejection, wear debris formation, low mechanical fixation, and implant-related infections. Nanotechnology holds the promise to offer a wide range of innovative technologies for use in translational orthopedic research. Nanomaterials have great potential for use in orthopedic applications due to their exceptional tribological qualities, high resistance to wear and tear, ability to maintain drug release, capacity for osseointegration, and capability to regenerate tissue. Furthermore, nanostructured materials possess the ability to mimic the features and hierarchical structure of native bones. They facilitate cell proliferation, decrease the rate of infection, and prevent biofilm formation, among other diverse functions. The emergence of nanostructured polymers, metals, ceramics, and carbon materials has enabled novel approaches in orthopaedic research. This review provides a concise overview of nanotechnology-based biomaterials utilized in orthopedics, encompassing metallic and nonmetallic nanomaterials. A further overview is provided regarding the biomedical applications of nanotechnology-based biomaterials, including their application in orthopedics for drug delivery systems and bone tissue engineering to facilitate scaffold preparation, surface modification of implantable materials to improve their osteointegration properties, and treatment of musculoskeletal infections. Hence, this review article offers a contemporary overview of the current applications of nanotechnology in orthopedic implants and bone tissue engineering, as well as its prospective future applications.

Biochar dose-dependent impacts on soil bacterial and fungal diversity across the globe.

Biochar, a widely used material for soil amendment, has been found to offer numerous advantages in improving soil properties and the habitats for soil microorganisms. However, there is still a lack of global perspectives on the influence of various levels of biochar addition on soil microbial diversity and primary components. Thus, in our study, we performed a global meta-analysis of studies to determine how different doses of biochar affect soil total carbon (C), nitrogen (N), pH, alpha- and beta-diversity, and the major phyla of both bacterial and fungal communities. Our results revealed that biochar significantly increased soil pH by 4 %, soil total C and N by 68 % and 22 %, respectively, in which the positive effects increased with biochar doses. Moreover, biochar promoted soil bacterial richness and evenness by 3-8 % at the biochar concentrations of 1-5 % (w/w), while dramatically shifting bacterial beta-diversity at the doses of >2 % (w/w). Specifically, biochar exhibited significantly positive effects on bacterial phyla of Acidobacteria, Bacteroidetes, Gemmatimonadetes, and Proteobacteria, especially Deltaproteobacteria and Gammaproteobacteria, by 4-10 % depending on the concentrations. On the contrary, the bacterial phylum of Verrucomicrobia and fungal phylum of Basidiomycota showed significant negative responses to biochar by -8 % and -24 %, respectively. Therefore, our meta-analysis provides theoretical support for the development of optimized agricultural management practices by emphasizing biochar application dosing.

Apoptotic Bodies Derived from Fibroblast-Like Cells in Subcutaneous Connective Tissue Inhibit Ferroptosis in Ischaemic Flaps via the miR-339-5p/KEAP1/Nrf2 Axis.

Preventing and treating avascular necrosis at the distal end of the flaps are critical to surgery success, but current treatments are not ideal. A recent study shows that apoptotic bodies (ABs) generated near the site of apoptosis can be taken up and promote cell proliferation. The study reveals that ABs derived from fibroblast-like cells in the subcutaneous connective tissue (FSCT cells) of skin flaps promoted ischaemic flap survival. It is also found that ABs inhibited cell death and oxidative stress and promoted M1-to-M2 polarization in macrophages. Transcriptome sequencing and protein level testing demonstrated that ABs promoted ischaemic flap survival in endothelial cells and macrophages by inhibiting ferroptosis via the KEAP1-Nrf2 axis. Furthermore, microRNA (miR) sequencing data and in vitro and in vivo experiments demonstrated that ABs inhibited KEAP1 by delivering miR-339-5p to exert therapeutic effects. In conclusion, FSCT cell-derived ABs inhibited ferroptosis, promoted the macrophage M1-to-M2 transition via the miR-339-5p/KEAP1/Nrf2 axis and promoted ischaemic flap survival. These results provide a potential therapeutic strategy to promote ischaemic flap survival by administering ABs.

Manganese Dioxide-Based Nanomaterials for Medical Applications.

Manganese dioxide (MnO2) nanomaterials can react with trace hydrogen peroxide (H2O2) to produce paramagnetic manganese (Mn2+) and oxygen (O2), which can be used for magnetic resonance imaging and alleviate the hypoxic environment of tumors, respectively. MnO2 nanomaterials also can oxidize glutathione (GSH) to produce oxidized glutathione (GSSG) to break the balance of intracellular redox reactions. As a consequence of the sensitivity of the tumor microenvironment to MnO2-based nanomaterials, these materials can be used as multifunctional diagnostic and therapeutic platforms for tumor imaging and treatment. Importantly, when MnO2 nanomaterials are implanted along with other therapeutics, synergetic tumor therapy can be achieved. In addition to tumor treatment, MnO2-based nanomaterials display promising prospects for tissue repair, organ protection, and the treatment of other diseases. Herein, we provide a thorough review of recent progress in the use of MnO2-based nanomaterials for biomedical applications, which may be helpful for the design and clinical translation of next-generation MnO2 nanomaterials.

Simulated in vitro infant digestion and lipidomic analysis to explore how the milk fat globule membrane modulates fat digestion.

We hypothesized that the addition of milk fat globule membranes (MFGMs) to infant formula would improve its lipolysis, making it more similar to human milk (HM) and superior to commercial infant formula (CIF) in fat digestion. Therefore, we prepared two model infant formulas (MIFs) by adding MFGMs to dairy ingredients in different ways and compared their fat digestion behavior with those of HM and CIF. MFGMs were added alone (MIF1) and with other milk-based materials (MIF2) before homogenization. The addition of MFGMs reduced the flocculation of lipids and proteins in the gastric phase and promoted lipolysis in the intestine phase. The amount of free fatty acids released followed the order of HM > MIF1 > CIF ≥ MIF2. After digestion, the number of different glyceride species between each sample and HM reached 64 (MIF1), 73 (MIF2), 67 (CIF1), and 72 (CIF2). In conclusion, the fat digestion of MIF1 had the highest similarity with HM.

GeSe ovonic threshold switch: the impact of functional layer thickness and device size.

Three-dimensional phase change memory (3D PCM), possessing fast-speed, high-density and nonvolatility, has been successfully commercialized as storage class memory. A complete PCM device is composed of a memory cell and an associated ovonic threshold switch (OTS) device, which effectively resolves the leakage current issue in the crossbar array. The OTS materials are chalcogenide glasses consisting of chalcogens such as Te, Se and S as central elements, represented by GeTe6, GeSe and GeS. Among them, GeSe-based OTS materials are widely utilized in commercial 3D PCM, their scalability, however, has not been thoroughly investigated. Here, we explore the miniaturization of GeSe OTS selector, including functional layer thickness scalability and device size scalability. The threshold switching voltage of the GeSe OTS device almost lineally decreases with the thinning of the thickness, whereas it hardly changes with the device size. This indicates that the threshold switching behavior is triggered by the electric field, and the threshold switching field of the GeSe OTS selector is approximately 105 V/µm, regardless of the change in film thickness or device size. Systematically analyzing the threshold switching field of Ge-S and Ge-Te OTSs, we find that the threshold switching field of the OTS device is larger than 75 V/µm, significantly higher than PCM devices (8.1-56 V/µm), such as traditional Ge2Sb2Te5, Ag-In-Sb-Te, etc. Moreover, the required electric field is highly correlated with the optical bandgap. Our findings not only serve to optimize GeSe-based OTS device, but also may pave the approach for exploring OTS materials in chalcogenide alloys.

Assessment of the methodological, recommendation and reporting quality of global guidelines for neck pain and synthesis of evidence and recommendations: a systematic review protocol.

INTRODUCTION: Neck pain is a global health problem that can cause severe disability and a huge medical burden. Clinical practice guideline (CPG) is an important basis for clinical diagnosis and treatment. A high-quality CPG plays a significant role in clinical practice. However, the quality of the CPGs for neck pain lacks comprehensive assessment. This protocol aims to evaluate the methodological, recommendation, reporting quality of global CPGs for neck pain and identify key recommendations and gaps that limit evidence-based practice. METHOD: CPGs from January 2013 to November 2023 will be identified through a systematic search on 13 scientific databases (PubMed, Cochrane Library, Embase, etc) and 7 online guideline repositories. Six reviewers will independently evaluate the quality of CPGs for neck pain by using the Appraisal of Guidelines for Research and Evaluation, the Appraisal of Guidelines Research and Evaluation-Recommendations Excellence and the Reporting Items for Practice Guidelines in Healthcare tools. Intraclass correlation coefficient will be used to test the consistency of the assessment. We will identify the distribution of evidence and recommendations in each evidence-based CPGs for neck pain and regrade the level of evidence and strength of recommendations by adopting the commonly used Grading of Recommendations, Assessment, Development and Evaluations system. The key recommendations based on high-quality evidence will be summarised. In addition, we will categorise CPGs by different characteristics and conduct a subgroup analysis of the results of assessment. ETHICS AND DISSEMINATION: No subjects will be involved in this systematic review, so there is no need for ethical approval. The finding of this review will be summarised as a paper for publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023417717.

Effects of reverse osmosis membrane replacement of pure water system on clinical chemistry and immunoassay in clinical laboratory.

Introduction: Reverse osmosis (RO) membrane, key component of water-purifying equipment, is often stored in protection fluid containing substances such as glycerol, which may contaminate the water at replacement. This study aims to explore the effects of RO membrane replacement on clinical chemistry and immunoassay, particularly triglyceride (TG), providing reference for managing test interference caused by RO membrane replacement. Materials and methods: The RO membrane of water-purifying equipment A, which provided water to C16000 biochemistry analyzer (Abbott Laboratories, Abbott Park, USA) and E801 electrochemiluminescence analyzer (Roche, Basel, Switzerland), was replaced. Water resistivity was recorded, and quality control (QC) tests were performed on C16000 and E801. Moreover, TG was measured in 29 of selected serum samples on C16000 at 0.5h and 10.5h after RO membrane replacement and on reference biochemistry analyzer BS2000M (Mindray Biomedical Electronics Co., Shenzhen, China), which was connected to water-purifying equipment B without RO membrane replacement. Finally, blank, calibrator 1 and calibrator 2 of TG reagent were measured on C16000 before and at 0.5h, 2.5h and 10.5h after RO membrane replacement. All statistical analyses of data were done using GraphPad Prism (GraphPad Software Inc., San Diego, USA), and a value of P < 0.05 was considered statistically significant. Results: After RO membrane replacement, all QC results of clinical chemistry and immune tests passed except TG that showed positive bias of 536% and 371% at two levels, respectively. Moreover, TG results of the same serum samples were significantly higher at 0.5h than 10.5h after RO membrane replacement. Meanwhile, there was worse agreement and correlation of TG results between C16000 and BS2000M at 0.5h than 10.5h after replacement. Furthermore, the absorbance of TG blank, calibrator 1 and calibrator 2 was significantly higher at 0.5h and 2.5h after replacement than before replacement, and the absorbance gradually returned to normal value at 10.5h after replacement. Conclusions: Replacement of RO membrane could cause significant interference to TG test while have no effects on other laboratory tests performed in the study, which may be due to glycerol contamination. Our data provides important reference for management of test interference caused by RO membrane replacement. Clinical laboratory should observe the effects of RO membrane replacement on laboratory tests through both water quality monitoring and QC detection.

Current advancements in therapeutic approaches in orthopedic surgery: a review of recent trends.

Recent advancements in orthopedic surgery have greatly improved the management of musculoskeletal disorders and injuries. This review discusses the latest therapeutic approaches that have emerged in orthopedics. We examine the use of regenerative medicine, including stem cell therapy and platelet-rich plasma (PRP) injections, to accelerate healing and promote tissue regeneration. Additionally, we explore the application of robotic-assisted surgery, which provides greater precision and accuracy during surgical procedures. We also delve into the emergence of personalized medicine, which tailors treatments to individual patients based on their unique genetic and environmental factors. Furthermore, we discuss telemedicine and remote patient monitoring as methods for improving patient outcomes and reducing healthcare costs. Finally, we examine the growing interest in using artificial intelligence and machine learning in orthopedics, particularly in diagnosis and treatment planning. Overall, these advancements in therapeutic approaches have significantly improved patient outcomes, reduced recovery times, and enhanced the overall quality of care in orthopedic surgery.