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Hong-Peng Chen,1,2,* Xiao-Yan Wang,1,* Xiao-Yan Pan,1 Wang-Wang Hu,1 Shu-Ting Cai,1 Kiran Joshi,3 Lie-Hua Deng,1,2 Daqing Ma3 1Department of Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, People’s Republic of China; 2Zhanjiang Key Laboratory of Organ Injury and Protection and Translational Medicine, Zhanjiang, Guangdong, People’s Republic of China; 3Division of Anesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London, UK*These authors contributed equally to this workCorrespondence: Lie-Hua Deng; Daqing MaDepartment of Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, ChinaEmail glinson@126.com; d.ma@imperial.ac.ukIntroduction: Because of its high morbidity and mortality, sepsis remains the leading cause of death in the ICU. Microparticles (MP) have been largely studied as potential diagnostic or prognostic markers in various diseases including sepsis.Objective: The biological and clinical relevance of neutrophil-derived microparticles (NDMPs) within the MP population remains unclear. The objective of this study was to elucidate the relationship between plasma NDMPs and the prognosis of patients with sepsis and/or septic shock.Methods: The study was designed as an observational, noninterventional clinical study. The cohort for this study included 40 sepsis and 40 septic shock patients together with 10 healthy controls admitted to the Intensive Care Unit (ICU) and the Health Surveillance Center in the Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China, from January to November 2018, respectively. The degree of critical disease for sepsis and septic shock was evaluated, with data analyses conducted from 2018 to 2019.Results: On days 1, 3 and 5 post-admission a series of data including plasma NDMP levels, patient demographics, TNF-α levels, IL-6 levels, sTREM-1 levels, and the sepsis severity score measurements were collected. A survival curve was plotted against levels of plasma NDMPs. Levels of NDMPs were observed to be higher in the septic shock patients than in the sepsis patients on days 1, 3, and 5 post-ICU admission (p < 0.05). NDMP levels were significantly increased in sepsis and septic shock patients with a parallel increase in pro-inflammatory mediators and sepsis severity score (p < 0.05) as well as mortality.Conclusion: Our data suggest that NDMPs may be a biomarker of sepsis severity and mortality although its implications on sepsis prognosis warrant further study.Keywords: sepsis, septic shock, cell-derived microparticles, biomarker, prognosis

Organic aerosols (OA) in Pasadena are characterized using multiple measurements from the California Research at the Nexus of Air Quality and Climate Change (CalNex) campaign. Five OA components are identified using positive matrix factorization including hydrocarbon-like OA (HOA) and two types of oxygenated OA (OOA). The Pasadena OA elemental composition when plotted as H:C versus O:C follows a line less steep than that observed for Riverside, CA. The OOA components from both locations follow a common line, however, indicating similar secondary organic aerosol (SOA) oxidation chemistry at the two sites such as fragmentation reactions leading to acid formation. In addition to the similar evolution of elemental composition, the dependence of SOA concentration on photochemical age displays quantitatively the same trends across several North American urban sites. First, the OA/ΔCO values for Pasadena increase with photochemical age exhibiting a slope identical to or slightly higher than those for Mexico City and the northeastern United States. Second, the ratios of OOA to odd-oxygen (a photochemical oxidation marker) for Pasadena, Mexico City, and Riverside are similar, suggesting a proportional relationship between SOA and odd-oxygen formation rates. Weekly cycles of the OA components are examined as well. HOA exhibits lower concentrations on Sundays versus weekdays, and the decrease in HOA matches that predicted for primary vehicle emissions using fuel sales data, traffic counts, and vehicle emission ratios. OOA does not display a weekly cycle - after accounting for differences in photochemical aging - which suggests the dominance of gasoline emissions in SOA formation under the assumption that most urban SOA precursors are from motor vehicles. © 2013. Her Majesty the Queen in Right of Canada. American Geophysical Union.

Hydrogen is an essential energy resource, playing a pivotal role in advancing a sustainable future. Electrolysis of seawater shows great potential for large-scale hydrogen production but encounters challenges such as electrode corrosion caused by chlorine evolution. Herein, a durable CoCO 3 /CoFe layered double hydroxide (LDH) electrocatalyst is presented for alkaline seawater oxidation, showcasing resistance to corrosion and stable operation exceeding 1,000 h at a high current density of 1 A cm -2 . The results indicate that CoCO 3 within the electrocatalyst undergoes conversion into CoOOH and releases CO 3 2- during electrolysis. The incorporation of CO 3 2- within its layers and the anchoring of the electrocatalyst's surface prevent the adverse adsorption of chloride ions, enhancing resistance to chloride ion corrosion, thereby protecting the active sites of the electrocatalyst effectively., (© 2024 Wiley‐VCH GmbH.)

Nebulized inhalation administration refers to the dispersion of drugs into small droplets suspended in the gas through a nebulized device, which are deposited in the respiratory tract by inhalation, to achieve the local therapeutic effect of the respiratory tract. Compared with other drug delivery methods, nebulized inhalation has the advantages of fast effect, high local drug concentration, less dosage, convenient application and less systemic adverse reactions, and has become one of the main drug delivery methods for the treatment of respiratory diseases. In this review, we first discuss the characteristics of nebulized inhalation, including its principles and influencing factors. Next, we compare the advantages and disadvantages of different types of nebulizers. Finally, we explore the clinical applications and recent research developments of nebulized inhalation therapy. By delving into these aspects, we aim to gain a deeper understanding of its pivotal role in contemporary medical treatment.

In the rapidly evolving field of life sciences and biomedicine, detecting low-abundance biomolecules, and ultraweak biosignals presents significant challenges. This has spurred a rapid development of analytical techniques aiming for increased sensitivity and specificity. These advancements, including signal amplification strategies and the integration of biorecognition events, mark a transformative era in bioanalytical precision and accuracy. A prominent method among these innovations is immuno-rolling circle amplification (immuno-RCA) technology, which effectively combines immunoassays with signal amplification via RCA. This process starts when a targeted biomolecule, such as a protein or cell, binds to an immobilized antibody or probe on a substrate. The introduction of a circular DNA template triggers RCA, leading to exponential amplification and significantly enhanced signal intensity, thus the target molecule is detectable and quantifiable even at the single-molecule level. This review provides an overview of the biosensing strategy and extensive practical applications of immuno-RCA in detecting biomarkers. Furthermore, it scrutinizes the limitations inherent to these sensors and sets forth expectations for their future trajectory. This review serves as a valuable reference for advancing immuno-RCA in various domains, such as diagnostics, biomarker discovery, and molecular imaging., (© 2024 Wiley‐VCH GmbH.)

Nanozymes have demonstrated significant potential as promising alternatives to natural enzymes in biomedical applications. However, their lower catalytic activity compared to that of natural enzymes has limited their practical utility. Addressing this challenge necessitates the development of innovative enzymatic systems capable of achieving specific activity levels of natural enzymes. In this study, we focus on enhancing the catalytic performance of nanozymes by introducing Ru atoms into the single-atom-thick A layer of the V 2 SnC MAX phase, resulting in the formation of V 2 (Sn 0.8 Ru 0.2 )C with Ru single-atom sites. The V 2 (Sn 0.8 Ru 0.2 )C MAX phase demonstrated an exceptional peroxidase-like specific activity of up to 1792.6 U mg -1 , surpassing the specific activity of a previously reported horseradish peroxidase (HRP). Through X-ray photoelectron spectroscopy (XPS) and density functional theory (DFT) investigations, it has been revealed that both the V 2 C atom layers and single-atom-thick Sn readily accept a negative charge from Ru, leading to a reduction of the energy barrier for H 2 O 2 adsorption. This discovery has enabled the successful application of V 2 (Sn 0.8 Ru 0.2 )C in the development of a lateral flow immunoassay for heart failure biomarkers, achieving a detection sensitivity of 4 pg mL -1 . Additionally, V 2 (Sn 0.8 Ru 0.2 )C demonstrated exceptional broad-spectrum antibacterial efficacy. This study lays the groundwork for the precise design of MAX phase-based nanozymes with high specific activity, offering a viable alternative to natural enzymes for various applications.

Rationale: Intracranial atherosclerotic stenosis (ICAS) represents a prevalent global cause of stroke, posing a notably higher risk of stroke recurrence than other stroke etiologies. Herein, we report a case of a 39-year-old male patient diagnosed with ICAS, treated through an integrated approach incorporating Chinese and Western medicine with significant efficacy and satisfied clinical safety., Patient Concerns: This patient presented with 1 transient ischemic attack and prolonged headache, dizziness and poor sleep quality. In addition, the patient refused to undergo surgery due to the high cost and postoperative risks., Diagnoses: Diagnostic methods used to identify ICAS include conventional cerebral angiography, magnetic resonance angiography (MRA), CT angiography (CTA), transcranial Doppler ultrasound (TCD), and High-Resolution Magnetic resonance imaging. Considering the cost and risks associated with conventional angiography, noninvasive imaging has emerged as the method of choice for diagnosing ICAS. After a series of noninvasive examinations (CTA, TCD, and HR-MRI), the patient was diagnosed with ICAS., Interventions: The western medical regimen includes antiplatelet coagulation, blood pressure control, lipid regulation, plaque stabilization, and lifestyle modifications such as exercise, weight loss, and adherence to low-salt, low-fat diets. Complementing this, traditional Chinese medicine (TCM) treatment was guided by the principle of strengthening the spleen, resolving dampness, nourishing blood and harmonizing ying, resolving blood stasis and clearing collaterals. This involved the administration oral Chinese medicine such as modified Shenling Baizhu powder and modified Si Wu decoction., Outcomes: The efficacy of the treatment was assessed by evaluating the degree of luminal stenosis and peak systolic blood flow velocity in the M1 segment of the left middle cerebral artery (MCA) before and after the intervention. Encouragingly, posttreatment results demonstrated the disappearance of the plaque in the left MCA-M1 segment, with no significant lumen stenosis observed. Moreover, a notable and smooth reduction in blood flow velocity was achieved in the left MCA, indicating positive outcomes from the integrated traditional Chinese and Western medicine approach., Conclusion: This case report shows that a combination of traditional Chinese and Western medicine is safe and effective in the treatment of ICAS and is worthy of promotion in the clinic., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Skeletal muscle (SKM) is the largest organ in mammalian body and it can repair damages by using the residential myogenic stem cells (MuSC), but this repairing capacity reduces with age and in some genetic muscular dystrophy. Under these circumstances, artificial amplification of autologous MuSC in vitro might be necessary to repair the damaged SKM. The amplification of MuSC is highly dependent on myogenic signals, such as sonic hedgehog (Shh), Wnt3a, and fibroblast growth factors, so formulating an optimum myogenic kit composed of specific myogenic signals might increase the proliferation and differentiation of MuSC efficiently. In this study, various myogenic signals have been tested on C2C12 myoblasts and primary MuSC, and a myogenic kit consists of insulin, lithium chloride, T 3 , and retinoic acid has been formulated, and we found it significantly increased the fusion index and MHC expression level of both C2C12 and MuSC myotubes. A novel bioreactor providing cyclic stretching (CS) and electrical stimulation (ES) has been fabricated to enhance the myogenic differentiation of both C2C12 and MuSC. We further found that coating the bioreactor substratum with collagen gave the best effect on proliferation and differentiation of MuSC. Furthermore, combining the collagen coating and physical stimuli (CS + ES) in the bioreactor can generate more proliferative primary MuSC cells. Our results have demonstrated that the combination of myogenic kit and bioreactor can provide environment for efficient MuSC proliferation and differentiation. These MuSC and mature myotubes amplified in the bioreactor might be useful for clinical grafting into damaged SKM in the future., (© 2024 Wiley Periodicals LLC.)

Each year, millions of new cancer cases and cancer-related deaths underscore the urgent need for effective, affordable screening methods. Circulating tumor cells (CTCs), which derived from tumors and shedding into bloodstream, are considered promising biomarkers for liquid biopsy due to their unique biological significance and the substantial volume of supporting research. Among many advanced CTCs detection methods, electrochemical sensing is rapidly developing due to their high selectivity, high sensitivity, low cost, and rapid detection capability, well meeting the growing demand for non-invasive liquid biopsy. This review focuses on the entire procedure of detecting CTCs using electrochemical cytosensors, starting from sample preparation, detailing bio-recognition elements for capturing CTCs, highlighting design strategies of cytosensor, and discussing the prospects and challenges of electrochemical cytosensor applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The exploration of noble metal-free nanoarrays as high-activity catalytic electrodes for glucose biosensing holds great significance. Herein, we propose a Ni nanoparticle-decorated TiO 2 nanoribbon array on a titanium plate (Ni@TiO 2 /TP) as an effective non-enzymatic glucose biosensing electrode. The as-prepared Ni@TiO 2 /TP electrode demonstrates rapid glucose response, a wide linear response range (1 μM to 1 mM), a low detection limit (0.08 μM, S/N = 3), and high sensitivity (10 060 and 3940 μA mM -1 cm -2 ), with good mechanical flexibility and stability. Moreover, it proves efficient in glucose biosensing in real human blood serum and cell culture fluid. Thus, it is highly promising for practical applications.

The ion-sensitive field effect transistor (ISFET) has emerged as a crucial sensor device, owing to its numerous benefits such as label-free operation, miniaturization, high sensitivity, and rapid response time. Currently, ISFET technology excels in detecting ions, nucleic acids, proteins, and cellular components, with widespread applications in early disease screening, condition monitoring, and drug analysis. Recent advancements in sensing techniques, coupled with breakthroughs in nanomaterials and microelectronics, have significantly improved sensor performance. These developments are steering ISFETs toward a promising future characterized by enhanced sensitivity, seamless integration, and multifaceted detection capabilities. This review explores the structure and operational principles of ISFETs, highlighting recent research in ISFET biosensors for biomarker detection. It also examines the limitations of these sensors, proposes potential solutions, and anticipates their future trajectory. This review aims to provide a valuable reference for advancing ISFETs in the field of biomarker measurement.

Background: Widespread neuropathic pain usually affects a wide range of body areas and inflicts huge suffering on patients. However, little is known about how it happens and effective therapeutic interventions are lacking., Methods: Widespread neuropathic pain was induced by partial infraorbital nerve transection (p-IONX) and evaluated by measuring nociceptive thresholds. In vivo/vitro electrophysiology were used to evaluate neuronal activity. Virus tracing strategies, combined with optogenetics and chemogenetics, were used to clarify the role of remodeling circuit in widespread neuropathic pain., Results: We found that in mice receiving p-IONX, along with pain sensitization spreading from the orofacial area to distal body parts, glutamatergic neurons in the ventral posteromedial nucleus of the thalamus (VPM Glu ) were hyperactive and more responsive to stimulations applied to the hind paw or tail. Tracing experiments revealed that a remodeling was induced by p-IONX in the afferent circuitry of VPM Glu , notably evidenced by more projections from glutamatergic neurons in the dorsal column nuclei (DCN Glu ). Moreover, VPM Glu receiving afferents from the DCN extended projections further to glutamatergic neurons in the posterior insular cortex (pIC). Selective inhibition of the terminals of DCN Glu in the VPM, the soma of VPM Glu or the terminals of VPM Glu in the pIC all alleviated trigeminal and widespread neuropathic pain., Conclusion: These results demonstrate that hyperactive VPM Glu recruit new afferents from the DCN and relay the extra-cephalic input to the pIC after p-IONX, thus hold a key position in trigeminal neuropathic pain and its spreading. This study provides novel insights into the circuit mechanism and preclinical evidence for potential therapeutic targets of widespread neuropathic pain., (© 2024. The Author(s).)

Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer (mCRC), but the prognosis remains poor. This phase 3 trial (ClinicalTrials.gov: NCT03950154) assessed the efficacy and adverse events (AEs) of the combination of PD-1 blockade-activated DC-CIK (PD1-T) cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC. A total of 202 participants were enrolled and randomly assigned in a 1:1 ratio to receive either first-line XELOX plus bevacizumab (the control group, n = 102) or the same regimen plus autologous PD1-T cell immunotherapy (the immunotherapy group, n = 100) every 21 days for up to 6 cycles, followed by maintenance treatment with capecitabine and bevacizumab. The main endpoint of the trial was progression-free survival (PFS). The median follow-up was 19.5 months. Median PFS was 14.8 months (95% CI, 11.6-18.0) for the immunotherapy group compared with 9.9 months (8.0-11.8) for the control group (hazard ratio [HR], 0.60 [95% CI, 0.40-0.88]; p = 0.009). Median overall survival (OS) was not reached for the immunotherapy group and 25.6 months (95% CI, 18.3-32.8) for the control group (HR, 0.57 [95% CI, 0.33-0.98]; p = 0.043). Grade 3 or higher AEs occurred in 20.0% of patients in the immunotherapy group and 23.5% in the control groups, with no toxicity-associated deaths reported. The addition of PD1-T cells to first-line XELOX plus bevacizumab demonstrates significant clinical improvement of PFS and OS with well tolerability in patients with previously untreated mCRC., (© 2024. The Author(s).)

Microglia regulate synaptic function in various ways, including the microglial displacement of the surrounding GABAergic synapses, which provides important neuroprotection from certain diseases. However, the physiological role and underlying mechanisms of microglial synaptic displacement remain unclear. In this study, we observed that microglia exhibited heterogeneity during the displacement of GABAergic synapses surrounding neuronal soma in different cortical regions under physiological conditions. Through three-dimensional reconstruction, in vitro co-culture, two-photon calcium imaging, and local field potentials recording, we found that IL-1β negatively modulated microglial synaptic displacement to coordinate regional heterogeneity in the motor cortex, which impacted the homeostasis of the neural network and improved motor learning ability. We used the Cre-Loxp system and found that IL-1R1 on glutamatergic neurons, rather than that on microglia or GABAergic neurons, mediated the negative effect of IL-1β on synaptic displacement. This study demonstrates that IL-1β is critical for the regional heterogeneity of synaptic displacement by coordinating different actions of neurons and microglia via IL-1R1, which impacts both neural network homeostasis and motor learning ability. It provides a theoretical basis for elucidating the physiological role and mechanism of microglial displacement of GABAergic synapses., (© 2024. The Author(s).)

Microglia play a crucial role in interacting with neuronal synapses and modulating synaptic plasticity. This function is particularly significant during postnatal development, as microglia are responsible for removing excessive synapses to prevent neurodevelopmental deficits. Dysregulation of microglial synaptic function has been well-documented in various pathological conditions, notably Alzheimer's disease and multiple sclerosis. The recent application of RNA sequencing has provided a powerful and unbiased means to decipher spatial and temporal microglial heterogeneity. By identifying microglia with varying gene expression profiles, researchers have defined multiple subgroups of microglia associated with specific pathological states, including disease-associated microglia, interferon-responsive microglia, proliferating microglia, and inflamed microglia in multiple sclerosis, among others. However, the functional roles of these distinct subgroups remain inadequately characterized. This review aims to refine our current understanding of the potential roles of heterogeneous microglia in regulating synaptic plasticity and their implications for various brain disorders, drawing from recent sequencing research and functional studies. This knowledge may aid in the identification of pathogenetic biomarkers and potential factors contributing to pathogenesis, shedding new light on the discovery of novel drug targets. The field of sequencing-based data mining is evolving toward a multi-omics approach. With advances in viral tools for precise microglial regulation and the development of brain organoid models, we are poised to elucidate the functional roles of microglial subgroups detected through sequencing analysis, ultimately identifying valuable therapeutic targets., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The pursuit of stable and efficient electrocatalysts toward seawater oxidation is of great interest, yet it poses considerable challenges. Herein, the utilization of Cr-doped CoFe-layered double hydroxide nanosheet array is reported on nickel-foam (Cr-CoFe-LDH/NF) as an efficient electrocatalyst for oxygen evolution reaction in alkaline seawater. The Cr-CoFe-LDH/NF catalyst can achieve current densities of 500 and 1000 mA cm  -2 with remarkably low overpotentials of only 334 and 369 mV, respectively. Furthermore, it maintains at least 100 h stability when operated at 500 mA cm -2 ., (© 2023 Wiley‐VCH GmbH.)

NK cells play a role in various cancers, but their role in head and neck squamous cell carcinoma (HNSCC) still needs to be explored. All public data are obtained from the Cancer Genome Atlas Program (TCGA) database. All analysis was performed using specific packages in R software. In our study, we quantified the immune microenvironment of HNSCC through multiple algorithms. Next, we identified NK cell-associated genes by quantifying NK cells, including SSNA1, TRIR, PAXX, DPP7, WDR34, EZR, PHLDA1 and ELOVL1. Then, we explored the single-cell expression pattern of these genes in the HNSCC microenvironment. Univariate Cox regression analysis indicated that the EZR, PHLDA1 and ELOVL1 were related to the prognosis of HNSCC patients. Following this, we selected EZR for further analysis. Our results showed that the patients with high EZR expression might have a poor prognosis and worse clinical features. Biological enrichment analysis showed that EZR is associated with many oncogenic pathways and a higher tumour stemness index. Meanwhile, we found that EZR can remodel the immune microenvironment of HNSCC. Moreover, we noticed that EZR could affect the immunotherapy and specific drug sensitivity, making it an underlying clinical target. In summary, our results can improve the understanding of NK cell in HNSCC. Meanwhile, we identified EZR as the underlying clinical target of HNSCC., (© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

A multifunctional bioreactor was fabricated in this study to investigate the facilitation efficiency of electrical and mechanical stimulations on myogenic differentiation. This bioreactor consisted of a highly stretchable conductive membrane prepared by depositing polypyrrole (PPy) on a flexible polydimethylsiloxane (PDMS) film. The tensile deformation of the PPy/PDMS membrane can be tuned by adjusting the channel depth. In addition, PPy/PDMS maintained its electrical conductivity under continuous cyclic stretching in the strain range of 6.5%-13% for 24 h. This device can be used to individually or simultaneously perform cyclic stretching and electrical stimulation. The results of single stimulation showed that either cyclic stretching or electrical stimulation upregulated myogenic gene expression and promoted myotube formation, where electrical stimulation improved better than cyclic stretching. However, only cyclic stretching can align C2C12 cells perpendicular to the stretching direction, and electrical stimulation did not affect cell morphology. Myosin heavy chain (MHC) immunostaining demonstrated that oriented cells under cyclic stretching resulted in parallel myotubes. The combination of these two stimuli exhibited synergetic effects on both myogenic gene regulation and myotube formation, and the incorporated electrical field did not affect the orientation effect of the cyclic stretching. These results suggested that these two treatments likely influenced cells through different pathways. Overall, the simultaneous application of cyclic stretching and electrical stimulation preserved both stimuli's advantages, so myo-differentiation can be highly improved to obtain abundant parallel myotubes, suggesting that our developed multifunctional bioreactor should benefit muscle tissue engineering applications., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)

The study was conducted to assess medical staffs' fear of receiving the fourth dose of the Coronavirus disease 2019 (COVID-19) vaccine. From December 17, 2022, to January 31, 2023, an online survey was conducted to assess the fear among medical staffs regarding the administration of the fourth dose of the COVID-19 vaccine. The participants were exclusively drawn from a tertiary grade hospital in Taizhou. Out of the 1, 832 medical staffs invited to participate in the questionnaire, a total of 613 (33.5%) provided valid responses for subsequent analysis. Among them, 81 (13.8%) expressed fear of receiving the fourth dose of COVID-19. The fear was significantly influenced by these factors: the presence of serious food/drug allergic reactions (OR = 3.84, 95% CI: 1.40-10.52), received booster COVID-19 vaccine (OR = 0.20, 95% CI: 0.11-0.35), opinion on vaccination requirement (OR = 0.20, 95% CI: 0.11-0.35), viewpoint (OR = 0.23, 95% CI: 0.12-0.44) with scores ≥10, and positive attitude toward vaccination (OR = 0.21, 95% CI: 0.13-0.35). Our study revealed that a subset of medical staffs still harbor apprehension toward receiving the fourth dose of the new COVID-19 vaccine. Factors influencing this fear encompass allergic reactions, booster COVID-19 vaccine, as well as opinion, viewpoint, and attitude toward vaccination. Educating medical staffs on these factors may help mitigate their fear.

Electrochemical CO 2 reduction into value-added chemicals represents an attractive and promising approach to capitalize on the abundant CO 2 present in the atmosphere. This reaction, however, is hampered by low energy efficiency and selectivity owing to competition from hydrogen evolution reaction and multiple-electron transfer processes. Therefore, there is a pressing need to develop efficient yet cost-effective electrocatalysts to facilitate practical applications. Sn-based electrocatalysts have gained increasing attention in this active field due to their outstanding merits such as abundance, non-toxicity, and environmental friendliness. This review provides a comprehensive overview of recent advances in Sn-based catalysts for the CO 2 reduction reaction (CO 2 RR), beginning with a brief introduction to the CO 2 RR mechanism. Subsequently, the CO 2 RR performance of various Sn-based catalysts with different structures is discussed. The article concludes by addressing the existing challenges and offering personal perspectives on the future prospects in this exciting research area.

Purpose: To compare the differences in peripheral blood inflammatory indices between patients with neovascular age-related macular degeneration (nAMD) and haemorrhagic polypoidal choroidal vasculopathy (PCV)., Methods: Retrospective, best corrected visual acuity (BCVA), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR), were analysed across the nAMD, PCV and normal control (NCG) groups of patients. The ratios' cut-off values for nAMD were calculated., Results: nAMD had a significantly longer duration and better BCVA than PCV (all P < .05). The NLR, MLR and PLR were significantly higher in nAMD than in PCV and NCG (all P < .01), no significant differences between PCV and NCG (all P > .05). The ROC curve analysis revealed that the cut-off values for NLR and MLR were 1.98 and 0.24, respectively, for nAMD., Conclusion: NLR, MLR and PLR are significantly high in patients with nAMD. The ability of these inflammatory indicators to distinguish nAMD and PCV is unclear.

Zoledronic acid (ZOL) is a potent antiresorptive agent that increases bone mineral density (BMD) and reduces fracture risk in postmenopausal osteoporosis (PMOP). The anti-osteoporotic effect of ZOL is determined by annual BMD measurement. In most cases, bone turnover markers function as early indicators of therapeutic response, but they fail to reflect long-term effects. We used untargeted metabolomics to characterize time-dependent metabolic shifts in response to ZOL and to screen potential therapeutic markers. In addition, bone marrow RNA-seq was performed to support plasma metabolic profiling. Sixty rats were assigned to sham-operated group (SHAM, n = 21) and ovariectomy group (OVX, n = 39) and received sham operation or bilateral ovariectomy, respectively. After modeling and verification, rats in the OVX group were further divided into normal saline group (NS, n = 15) and ZOL group (ZA, n = 18). Three doses of 100 μg/kg ZOL were administrated to the ZA group every 2 weeks to simulate 3-year ZOL therapy in PMOP. An equal volume of saline was administered to the SHAM and NS groups. Plasma samples were collected at five time points for metabolic profiling. At the end of the study, selected rats were euthanatized for bone marrow RNA-seq. A total number of 163 compound were identified as differential metabolites between the ZA and NS groups, including mevalonate, a critical molecule in target pathway of ZOL. In addition, prolyl hydroxyproline (PHP), leucyl hydroxyproline (LHP), 4-vinylphenol sulfate (4-VPS) were identified as differential metabolites throughout the study. Moreover, 4-VPS negatively correlated with increased vertebral BMD after ZOL administration as time-series analysis revealed. Bone marrow RNA-seq showed that the PI3K-AKT signaling pathway was significantly associated with ZOL-mediated changes in expression (adjusted-p = 0.018). In conclusion, mevalonate, PHP, LHP, and 4-VPS are candidate therapeutic markers of ZOL. The pharmacological effect of ZOL likely occurs through inhibition of the PI3K-AKT signaling pathway., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Wang, Ren, Wei, Hu, Gu, Zhang, Yu and Wang.)

Introduction: To retrospectively evaluate the safety and efficacy of computed tomography (CT)-guided iodine-125 ( 125 I) seed implantation for patients with abdominal incision metastases from colorectal cancer., Materials and Methods: Data of patients with abdominal incision metastases of colorectal cancer from November 2010 to October 2020 were retrospectively reviewed. Each incisional metastasis was percutaneously treated with 125 I seed implantation under CT guidance. Follow-up contrast-enhanced CT was reviewed, and the outcomes were evaluated in terms of objective response rate, complications, and overall survival., Results: A total of 17 patients were enrolled in this study. The median follow-up was 18 months (range, 2.7-22.1 months). At 3, 6, 12, and 18 months after the treatment, objective response rate was 52.9%, 63.6%, 33.3%, and 0%, respectively. A small amount of local hematoma occurred in two patients and resolved spontaneously without any treatment. Two patients experienced a minor displacement of radioactive seeds with no related symptoms. Severe complications, such as massive bleeding and radiation injury, were not observed. No ≥ grade 3 adverse events were identified. By the end of follow-up, 14 patients died of multiple hematogenous metastases. The one-year overall survival rate was 41.6%, and the median overall survival was 8.6 months., Conclusion: CT-guided 125 I seed implantation brachytherapy is safe and feasible for patients with abdominal incision metastases from colorectal cancer., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The study aimed to determine the willingness of medical staff to have their children vaccinated with a COVID-19 booster in Taizhou, China. From March 21 to April 19, 2022, an online questionnaire survey was conducted to assess the willingness of medical staff to vaccinate their children with a booster dose of the COVID-19 vaccine. Of the 1,252 medical staff in a tertiary grade hospital in Taizhou who were invited to answer the structured questionnaire, 514 (41.1%) samples had valid information for further data analysis. Four hundred thirty-seven medical staff (85.0%) were willing to have their children receive vaccine boosters. After adjustments for confounding factors, the opinion ('Do you think your child needs a booster vaccination against COVID-19?') (yes vs. no, OR = 6.91, 95% CI: 3.29-14.54), the viewpoint ('What are your thoughts the effectiveness of COVID-19 vaccine boosters for children?' (≥12 vs. <12, OR = 13.81, 95% CI: 4.03-), and the attitude ('Your attitude to whether your child is boosting the Covid-19 vaccine?') (yes vs. no, OR = 4.66, 95% CI: 2.30-9.44) were significantly associated with their willingness to have their children receive a COVID-19 vaccine booster. A moderate percentage of the respondents expressed willingness to have their children receive booster vaccines. The findings implied that factors affecting medical staffs' willingness to vaccinate their children with a COVID-19 vaccine booster included viewpoint, opinion, and attitudes.

Progressive ischemic stroke (PIS) is featured by progressive neurological dysfunction after ischemia. Ischemia-evoked neuroinflammation is implicated in the progressive brain injury after cerebral ischemia, while Caspase-1, an active component of inflammasome, exaggerates ischemic brain injury. Current Caspase-1 inhibitors are inadequate in safety and druggability. Here, we investigated the efficacy of CZL80, a novel Caspase-1 inhibitor, in mice with PIS. Mice and Caspase-1 -/- mice were subjected to photothrombotic (PT)-induced cerebral ischemia. CZL80 (10, 30 mg·kg -1 ·d -1 , i.p.) was administered for one week after PT onset. The transient and the progressive neurological dysfunction (as foot faults in the grid-walking task and forelimb symmetry in the cylinder task) was assessed on Day1 and Day4-7, respectively, after PT onset. Treatment with CZL80 (30 mg/kg) during Day1-7 significantly reduced the progressive, but not the transient neurological dysfunction. Furthermore, we showed that CZL80 administered on Day4-7, when the progressive neurological dysfunction occurred, produced significant beneficial effects against PIS, suggesting an extended therapeutic time-window. CZL80 administration could improve the neurological function even as late as Day43 after PT. In Caspase-1 -/- mice with PIS, the beneficial effects of CZL80 were abolished. We found that Caspase-1 was upregulated during Day4-7 after PT and predominantly located in activated microglia, which was coincided with the progressive neurological deficits, and attenuated by CZL80. We showed that CZL80 administration did not reduce the infarct volume, but significantly suppressed microglia activation in the peri-infarct cortex, suggesting the involvement of microglial inflammasome in the pathology of PIS. Taken together, this study demonstrates that Caspase-1 is required for the progressive neurological dysfunction in PIS. CZL80 is a promising drug to promote the neurological recovery in PIS by inhibiting Caspase-1 within a long therapeutic time-window., (© 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Our previous study showed that H 3 receptor antagonists reduced neuronal apoptosis and cerebral infarction in the acute stage after cerebral ischemia, but through an action independent of activation of histaminergic neurons. Because enhanced angiogenesis facilitates neurogenesis and neurological recovery after ischemic stroke, we herein investigated whether antagonism of H 3 R promoted angiogenesis after brain ischemia. Photothrombotic stroke was induced in mice. We showed that administration of H 3 R antagonist thioperamide (THIO, 10 mg·kg -1 ·d -1 , i.p., from D1 after cerebral ischemia) significantly improved angiogenesis assessed on D14, and attenuated neurological defects on D28 after cerebral ischemia. Compared with wild-type mice, Hrh3 -/- mice displayed more blood vessels in the ischemic boundary zone on D14, and THIO administration did not promote angiogenesis in these knockout mice. THIO-promoted angiogenesis in mice was reversed by i.c.v. injection of H 3 R agonist immepip, but not by H 1 and H 2 receptor antagonists, histidine decarboxylase inhibitor α-fluoromethylhistidine, or histidine decarboxylase gene knockout (HDC -/- ), suggesting that THIO-promoted angiogenesis was independent of activation of histaminergic neurons. In vascular endothelial cells (bEnd.3), THIO (10 -9 -10 -7  M) dose-dependently facilitated cell migration and tube formation after oxygen glucose deprivation (OGD), and H 3 R knockdown caused similar effects. We further revealed that H 3 R antagonism reduced the interaction between H 3 R and Annexin A2, while knockdown of Annexin A2 abrogated THIO-promoted angiogenesis in bEnd.3 cells after OGD. Annexin A2-overexpressing mice displayed more blood vessels in the ischemic boundary zone, which was reversed by i.c.v. injection of immepip. In conclusion, this study demonstrates that H 3 R antagonism promotes angiogenesis after cerebral ischemia, which is independent of activation of histaminergic neurons, but related to the H 3 R on vascular endothelial cells and its interaction with Annexin A2. Thus, H 3 R antagonists might be promising drug candidates to improve angiogenesis and neurological recovery after ischemic stroke., (© 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Purpose: This study aimed to establish the multienzyme isothermal rapid amplification with a lateral flow dipstick (MIRA-LFD) assay and evaluate its performance in detection of A. baumannii in spiked blood specimens., Methods: The study was divided into two stages: a pilot study to establish the methodology and a clinical validation study to evaluate its performance. In the first step, we designed primers specific to detect A. baumannii , optimized the MIRA-LFD assay and analyzed its performance regarding limits of detection, reproducibility, specificity, and efficiency of detection using real-time PCR method. In the second step, we obtained 50 spiked blood isolates and detected these pathogens by MIRA-LFD assay. The MIRA-LFD time was 15 min from DNA sample amplification to complete pathogen detection., Results: The developed MIRA-LFD assay displayed a detection limit of 6 CFU/mL for detecting A. baumannii , which was significantly better than that of real-time PCR method, and no cross-reactivity was observed in other non- A. baumannii studied. The results obtained with 50 spiked blood isolates suggested that the developed MIRA-LFD assay had high specificity and sensitivity for identifying A. baumannii ., Conclusions: This study demonstrates that the established MIRA-LFD assay is time-saving, more effective and sensitive, which may become a powerful tool for rapid and reliable diagnosis of bloodstream infection caused by A. baumannii in primary hospitals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hu, He, Guo and Li.)

Introduction: Parental vaccine-hesitancy can lead to delays or refusal to vaccinate children despite the availability of vaccines. This is a population-based, cross-sectional study investigating whether parents in China are hesitant to vaccinate their children with a COVID-19 vaccine booster., Methods: Parents in Taizhou, China, responded to a self-reported online questionnaire on their hesitancy to vaccinate their children with a COVID-19 vaccine booster. Of the 1252 parents who were invited to answer the structured questionnaire, 514 (41.1%) samples had valid data for data analysis., Results: A total of 41.8% of participants were hesitant to give their children a COVID-19 vaccine booster. After adjusting for confounders, parental gender (female vs. male parent, OR=0.56 95% CI: 0.32-0.87), parental opinion (yes vs. no, OR=0.17, 95% CI: 0.09-0.30), parental attitudes (yes vs. no, OR=0.28, 95% CI: 0.16-0.50), the presence of people around them who are generally hesitant to receive COVID-19 booster vaccines for children (yes vs. no, OR=0.14, 95%CI: 0.08-0.23), the individual hesitancy of people around them to administer booster COVID-19 vaccines to children (yes vs. no, OR=0.02, 95%CI: 0.02-0.22), and parents' hesitancy to receive a booster vaccine for their children showed significant correlation. The disparity of factors related to booster vaccine-hesitancy for children between fathers and mothers was also found., Conclusions: We found that a moderate proportion of parents reported that they were hesitant to give their children a COVID-19 vaccine booster. The results suggest that an in-depth, dynamic assessment and further health education planning are necessary to reduce Chinese parents' hesitancy to vaccinate their children., Competing Interests: Disclosure of interest The authors have no proprietary interest in any aspect of this study., (Copyright © 2022. Published by Elsevier Ltd.)

Chronic cerebral hypoperfusion can cause progressive demyelination as well as ischemic vascular dementia, however no effective treatments are available. Here, based on magnetic resonance imaging studies of patients with white matter damage, we found that this damage is associated with disorganized cortical structure. In a mouse model, optogenetic activation of glutamatergic neurons in the somatosensory cortex significantly promoted oligodendrocyte progenitor cell (OPC) proliferation, remyelination in the corpus callosum, and recovery of cognitive ability after cerebral hypoperfusion. The therapeutic effect of such stimulation was restricted to the upper layers of the cortex, but also spanned a wide time window after ischemia. Mechanistically, enhancement of glutamatergic neuron-OPC functional synaptic connections is required to achieve the protection effect of activating cortical glutamatergic neurons. Additionally, skin stroking, an easier method to translate into clinical practice, activated the somatosensory cortex, thereby promoting OPC proliferation, remyelination and cognitive recovery following cerebral hypoperfusion. In summary, we demonstrated that activating glutamatergic neurons in the somatosensory cortex promotes the proliferation of OPCs and remyelination to recover cognitive function after chronic cerebral hypoperfusion. It should be noted that this activation may provide new approaches for treating ischemic vascular dementia via the precise regulation of glutamatergic neuron-OPC circuits., Competing Interests: The authors declare that they have no conflicts of interest in this work., (© 2022 The Authors. Publishing Services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

Background: Whether neuroinflammation causes comorbid mood disorders in neuropathic pain remains elusive. Here we investigated the role of high mobility group box 1 protein (HMGB1), a proinflammatory cytokine, in the medial prefrontal cortex (mPFC) in anxiety comorbidity of neuropathic pain., Methods: Neuropathic pain was induced by partial transection of the infraorbital nerve (p-IONX) or partial sciatic nerve ligation (PSL) in mice and evaluated by measuring nociceptive thresholds to mechanical and heat stimulation. Anxiety-like behaviors were assessed by elevated plus maze, light dark box and open field tests. Aversive or anti-aversive effect was detected by conditioned place preference test. Neuronal activity was evaluated by single-unit and patch clamp recordings. The contribution of mPFC pyramidal neurons to anxiety was further examined by selectively inhibiting them by optogenetics. HMGB1 expression was measured by immunohistochemistry and western blotting. Antagonism of HMGB1 was achieved by injecting anti-HMGB1 monoclonal antibody (mAb) intracerebrally or intraperitoneally., Results: Anxiety-like behaviors were presented earlier after p-IONX than after PSL. HMGB1 expression was upregulated in the mPFC temporally in parallel to anxiety onset, rather than in other regions associated with anxiety. The upregulation of HMGB1 expression and its translocation from the nucleus to cytoplasm in the mPFC occurred predominantly in neurons and were accompanied with activation of microglia and astrocytes. Infusion of anti-HMGB1 mAb into the mPFC during the early and late phases after either p-IONX or PSL alleviated anxiety-like behaviors and aversion without changing pain sensitization, while local infusion of exogenous ds-HMGB1, the proinflammatory form of HMGB1, into the mPFC induced anxiety and aversion but not pain sensitization in naïve mice. In addition to reversing established pain sensitization and anxiety simultaneously, intraperitoneal injection of anti-HMGB1 mAb reduced HMGB1 upregulation and suppressed the hyperexcitability of layer 2/3 pyramidal neurons in the mPFC after p-IONX. Moreover, optogenetic inhibition of mPFC pyramidal neurons alleviated anxiety in p-IONX mice., Conclusion: These results demonstrate that HMGB1 in the mPFC drives and maintains anxiety comorbidity in neuropathic pain by increasing the excitability of layer 2/3 pyramidal neurons, and justify antagonism of HMGB1, e.g., neutralization by mAb, as a promising therapeutic strategy for neuropathic pain with anxiety comorbidity., (© 2022. The Author(s).)

We developed a composite wound dressing that provides multifunctional wound care. Alginate and polycaprolactone (PCL) were coelectrospun as composite fibers. Highly absorbent alginate provided a moist environment for wounds and PCL increased cell adhesion. Silver nanoparticles embedded in PCL fibers for long-term release inhibited the growth of microorganisms. In addition, plasmid DNA encoding platelet-derived growth factor-B (PDGF-B) were complexed with polyethylenimine (PEI) to form cationic nanoparticles which were then adsorbed on anionic alginate fibers through electrostatic interaction. As wound cells adhered to composite fibers, they were in situ transfected to express PDGF-B continuously. Moreover, calcium ions in alginate fibers were released into the wound site through ion exchange to accelerate hemostasis. Wound healing experiments demonstrated that PDGF-B gene-loaded composite fibers accelerated wound closure and promoted collagen formation. We expect this comprehensive study offers an ideal multifunctional solution to facilitate wound healing., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The duration of beta-blocker therapy in patients without heart failure (HF) or left ventricular systolic dysfunction after acute myocardial infarction (AMI) is unclear., Hypothesis: Continuous beta-blocker therapy is associated with an improved prognosis., Methods: This is a prospective, multicenter, cohort study. One thousand four hundred and eighty-three patients eventually met the inclusion criteria. The study groups included the continuous beta-blocker therapy group (lasted ≥6 months) and the discontinuous beta-blocker therapy group (consisting of the no-beta-blocker therapy group and the beta-blocker therapy <6 months group). The inverse probability treatment weighting was used to control confounding factors. The study tried to learn the role of continuous beta-blocker therapy on outcomes. The median duration of follow-up was 13.0 months. The primary outcomes were cardiac death and major adverse cardiovascular events (MACE). The secondary outcomes were all-cause death, stroke, unstable angina, rehospitalization for HF, and recurrent myocardial infarction (MI)., Results: Compared with discontinuous beta-blocker therapy, continuous beta-blocker therapy was associated with a reduced risk of unstable angina, recurrent MI, and MACE (hazard ratio [HR]: 0.51; 95% CI: 0.32-0.82; p = 0.006); but this association was not available for cardiac death (HR: 0.57; 95% CI: 0.24-1.36; p = 0.206). When compared to the subgroups of no-beta-blocker therapy and beta-blocker therapy <6 months, respectively, continuous beta-blocker therapy was still observed to be associated with a reduced risk of unstable angina, recurrent MI, and MACE., Conclusions: Continuous beta-blocker therapy was associated with a reduced risk of unstable angina or recurrent MI or MACE in patients without HF or left ventricular systolic dysfunction after AMI., (© 2022 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Isoprene is the most abundant precursor of global secondary organic aerosol (SOA). The epoxide pathway plays a critical role in isoprene SOA (iSOA) formation, in which isoprene epoxydiols (IEPOX) and/or hydroxymethyl-methyl-α-lactone (HMML) can react with nucleophilic sulfate and water producing isoprene-derived organosulfates (iOSs) and oxygen-containing tracers (iOTs), respectively. This process is complicated and highly influenced by anthropogenic emissions, especially in the polluted urban atmospheres. In this study, we took a 1-year measurement of the paired iOSs and iOTs formed through the IEPOX and HMML pathways at the three urban sites from northern to southern China. The annual average concentrations of iSOA products at the three sites ranged from 14.6 to 36.5 ng m -3 . We found that the nucleophilic-addition reaction of isoprene epoxides with water dominated over that with sulfate in the polluted urban air. A simple set of reaction rate constant could not fully describe iOS and iOT formation everywhere. We also found that the IEPOX pathway was dominant over the HMML pathway over urban regions. Using the kinetic data of IEPOX to estimate the reaction parameters of HMML will cause significant underestimation in the importance of HMML pathway. All these findings provide insights into iSOA formation over polluted areas.

Lung adenocarcinoma (LUAD) is a major subtype of non-small-cell lung cancer, which is the leading cause of cancer death worldwide. The histone H3K36 methyltransferase SETD2 has been reported to be frequently mutated or deleted in types of human cancer. However, the functions of SETD2 in tumor growth and metastasis in LUAD has not been well illustrated. Here, we found that SETD2 was significantly downregulated in human lung cancer and greatly impaired proliferation, migration, and invasion in vitro and in vivo. Furthermore, we found that SETD2 overexpression significantly attenuated the epithelial-mesenchymal transition (EMT) of LUAD cells. RNA-seq analysis identified differentially expressed transcripts that showed an elevated level of interleukin 8 (IL-8) in STED2-knockdown LUAD cells, which was further verified using qPCR, western blot, and promoter luciferase report assay. Mechanically, SETD2-mediated H3K36me3 prevented assembly of Stat1 on the IL-8 promoter and contributed to the inhibition of tumorigenesis in LUAD. Our findings highlight the suppressive role of SETD2/H3K36me3 in cell proliferation, migration, invasion, and EMT during LUAD carcinogenesis, via regulation of the STAT1-IL-8 signaling pathway. Therefore, our studies on the molecular mechanism of SETD2 will advance our understanding of epigenetic dysregulation at LUAD progression., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Purposes: In order to investigate the association between serum periostin levels and the variation of its encoding gene POSTN and the prevalence of vertebral fractures and bone mineral density (BMD) in Chinese postmenopausal women, an association study was performed., Materials and Methods: 385 postmenopausal women were recruited. For participants without a history of vertebral fracture, lateral X-rays of the spine covering the fourth thoracic spine to the fifth lumbar spine were performed to detect any asymptomatic vertebral fractures. Ten tag-single nucleotide polymorphisms (SNP) of POSTN were genotyped. Serum periostin levels, biochemical parameters, and BMD were measured individually., Results: rs9603226 was significantly associated with vertebral fractures. Compared to allele G, the minor allele A carriers of rs9603226 had a 1.722-fold higher prevalence of vertebral fracture ( p = 0.037). rs3923854 was significantly associated with the serum periostin level. G/G genotype of rs3923854 had a higher serum periostin level than C/C and C/G (67.26 ± 19.90 ng/mL vs. 54.57 ± 21.44 ng/mL and 54.34 ± 18.23 ng/mL). Furthermore, there was a negative correlation between the serum level of periostin and BMD at trochanter and total hip., Conclusion: Our study suggested that genetic variation of POSTN could be a predicting factor for the risk of vertebral fractures. The serum level of periostin could be a potential biochemical parameter for osteoporosis in Chinese postmenopausal women.

Burkholderia thailandensis is a clinically underestimated conditional pathogen in the genus Burkholderia , the pathogenicity of the infection caused by B. thailandensis remains poorly understood. According to previous studies, Type-VI secretion system (T6SS) is a protein secreting device widely existing in Gram-negative bacilli. Valine-glycine repeat protein G (VgrG) is not only an important component of T6SS, but also a virulence factor of many Gram-negative bacilli. In one of our previous studies, a unique T6SS vgrG gene ( vgrG2 gene) was present in a virulent B. thailandensis strain BPM (BPM), but not in the relatively avirulent B. thailandensis strain E264 (E264). Meanwhile, transcriptome analysis of BPM and E264 showed that the vgrG2 gene was strongly expressed in BPM, but not in E264. Therefore, we identified the function of the vgrG2 gene by constructing the mutant and complemented strains in this study. In vitro , the vgrG2 gene was observed to be involved in the interactions with host cells. The animal model experiment showed that the deletion of vgrG2 gene significantly led to the decrease in the lethality of BPM and impaired its ability to trigger host immune response. In conclusion, our study provides a new perspective for studying the pathogenicity of B. thailandensis and lays the foundation for discovering the potential T6SS effectors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Hu, Qu, Li, Xiang, Jiang, Luo, He, Jin and Shi.)

White matter injury is the major pathological alteration of subcortical ischemic vascular dementia (SIVD) caused by chronic cerebral hypoperfusion. It is characterized by progressive demyelination, apoptosis of oligodendrocytes and microglial activation, which leads to impairment of cognitive function. Triptolide exhibits a variety of pharmacological activities including anti-inflammation, immunosuppression and antitumor, etc. In this study, we investigated the effects of triptolide on white matter injury and cognitive impairments in mice with chronic cerebral hypoperfusion induced by the right unilateral common carotid artery occlusion (rUCCAO). We showed that triptolide administration alleviated the demyelination, axonal injury, and oligodendrocyte loss in the mice. Triptolide also improved cognitive function in novel object recognition test and Morris water maze test. In primary oligodendrocytes following oxygen-glucose deprivation (OGD), application of triptolide (0.001-0.1 nM) exerted concentration-dependent protection. We revealed that the protective effect of triptolide resulted from its inhibition of oligodendrocyte apoptosis via increasing the phosphorylation of the Src/Akt/GSK3β pathway. Moreover, triptolide suppressed microglial activation and proinflammatory cytokines expression after chronic cerebral hypoperfusion in mice and in BV2 microglial cells following OGD, which also contributing to its alleviation of white matter injury. Importantly, mice received triptolide at the dose of 20 μg·kg -1 ·d -1 did not show hepatotoxicity and nephrotoxicity even after chronic treatment. Thus, our results highlight that triptolide alleviates whiter matter injury induced by chronic cerebral hypoperfusion through direct protection against oligodendrocyte apoptosis and indirect protection by inhibition of microglial inflammation. Triptolide may have novel indication in clinic such as the treatment of chronic cerebral hypoperfusion-induced SIVD., (© 2021. The Author(s), under exclusive licence to CPS and SIMM.)

Backgroud: Recently, monitoring the vital-sign with the noncontact method is a popular technology., Objective: In this work, we present a fully pulse radar system including front-end sensing and back-end data processing. A series of ultra-wide band sensing pulses is generated and radiated to detect the subject's chest vibration which in turn obtains the required vital-sign signals., Methods: An artificial plywood with 3 centimeter thickness is placed between a transmitting/receiving antenna of the radar and subject to demonstrate the characteristic of noncontact sensing. The firmware and digital signal processing are also presented in this paper to optimize physiological data quality., Results: The experimental results show that the continuous heart rate and breathing rate can be monitored by this customized system radar module., Conclusion: A fully customized ultra-wide band radar for vital-sign application is presented. The radar system plan with wall parameter is also incorporated into the design consideration to meet the FCC requirement and SNR.

Ischemic white matter damage (WMD) is increasingly being considered as one of the major causes of neurological disorders in older adults and preterm infants. The functional consequences of WMD triggers a progressive cognitive decline and dementia particularly in patients with ischemic cerebrovascular diseases. Despite the major stride made in the pathogenesis mechanisms of ischemic WMD in the last century, effective medications are still not available. So, there is an urgent need to explore a promising approach to slow the progression or modify its pathological course. In this review, we discussed the animal models, the pathological mechanisms and the potential therapeutic agents for ischemic WMD. The development in the studies of anti-oxidants, free radical scavengers, anti-inflammatory or anti-apoptotic agents and neurotrophic factors in ischemic WMD were summarized. The agents which either alleviate oligodendrocyte damage or promote its proliferation or differentiation may have potential value for the treatment of ischemic WMD. Moreover, drugs with multifaceted protective activities or a wide therapeutic window may be optimal for clinical translation., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: In the rankings of cancer mortality and incidence worldwide, colorectal cancer ranks fourth and the third, respectively. Circular RNA hsa&#95;circ&#95;0136666 (hsa&#95;circ&#95;0136666) is reported to participate in the growth of colorectal cancer. However, the mechanism by which hsa&#95;circ&#95;0136666 regulates the tumorigenesis of colorectal cancer needs to be further explored. In this study, we report here the role of hsa&#95;circ&#95;0136666 in the aberrant activation of Treg cells and immune evasion of tumor cells, providing a new strategy for the treatment of colorectal cancer., Methods: Western blotting assay and qRT-PCR assay were used to determine protein and mRNA expression levels. Dual-luciferase reporter assay was used to evaluate the targeted regulatory relationship. RNA immunoprecipitation was used to detect RNA binding. Colony formation assay was utilized to measure the cell proliferation. Flow cytometry was used to assess cell apoptosis. Xenograft model was setup to evaluate tumor growth., Results: The results showed that hsa&#95;circ&#95;0136666 and PD-L1 was increased in colorectal cancer cells while miR-497 was decreased in colorectal cancer cells when compared with normal colon epithelial cell line. Hsa&#95;circ&#95;0136666 was demonstrated to directly target miR-497, which also regulated PD-L1 by binding to its 3'UTR. Further mechanistic studies identified that hsa&#95;circ&#95;0136666 controlled cell proliferation and apoptosis via targeting miR-497 and regulating PD-L1 expression. Of note, hsa&#95;circ&#95;0136666 stimulated Treg cells mediated by miR-497/PD-L1 axis and its downstream signal pathway in Treg cells. Finally, hsa&#95;circ&#95;0136666 was found to accelerate the tumor growth in vivo., Conclusions: Our findings demonstrated that hsa&#95;circ&#95;0136666 promoted the expression of PD-L1 by inhibiting miR-497 level in colorectal cancer, thus inducing the activation of Treg cells and leading to the immune escape of tumor, providing a novel mechanistic insight into the pathogenesis of colorectal cancer., (Copyright © 2021. Published by Elsevier Inc.)