Exploring the Role of Mitochondrial Hydrogen Sulfide in Maintaining Polarity and mtDNA Integrity with a Multichannel Fluorescent Probe.

Abnormal mitochondrial state has been implicated in the pathogenesis of various diseases including neurodegenerative disorders, myopathies, cardiovascular diseases, and cancers. Assessing mitochondrial functionality can be achieved by monitoring alterations in mitochondrial polarity and mitochondrial DNA (mtDNA) integrity, which serve as valuable biomarkers. Hydrogen sulfide (H2S), a gaseous signaling molecule, plays a regulatory role in mitochondrial respiratory chain activity, ATP synthesis, and calcium ion balance, thereby influencing cellular metabolism and signal transduction. Investigating the interplay between mitochondrial H2S, polarity, and mtDNA can enhance our understanding of the underlying regulatory mechanisms involved in H2S-mediated mitochondrial functions. To address this, we designed a mitochondria-targeted multichannel fluorescent probe, HNA, capable of cascaded detection of H2S and polarity, as well as parallel detection of mtDNA. The probe exhibited a significant turn-on response to H2S, emitting at approximately 604 nm, while the product HNAP demonstrated high sensitivity to polarity within the wavelength range of 526-591 nm. Additionally, the probe was able to bind to DNA, resulting in an enhanced long-wave emission at 668 nm. Facilitated by HNA, our study provides novel insights into the role of mitochondrial H2S in maintaining mitochondrial polarity and validates its protective effect on mtDNA through antioxidative mechanisms. Overall, this work proposes a potential therapeutic strategy for modulating the inflammatory process in mitochondrial-related diseases.

Integrated profiling identifies CACNG3 as a prognostic biomarker for patients with glioma.

Gliomas are the most common malignant primary brain tumors in adults with poor prognoses. The purpose of this study is to explore CACNG3 as a prognostic factor that is closely related to the progression and survival outcome of gliomas and to provide a potential new molecular target for the diagnosis and treatment of glioma patients. CACNG3 expression and related clinical data were collected from three major databases of The Chinese Glioma Genome Atlas (CGGA), The Cancer Genome Atlas (TCGA), and Gene Expression Omnibus (GEO). The CGGA dataset was used as a training set, and TCGA and GEO datasets obtained from the GEO database were used for validation. CACNG3 was expressed at low levels in the tumor group, and the overall survival (OS) in patients with low CACNG3 expression is shorter. Furthermore, CACNG3 expression was negatively associated with glioma grades, which was confirmed in the IHC results of clinical samples. The expression level of CACNG3 in the IDH1 wide-type group, 1p/19q non-codel group, and mesenchymal subtype group was significantly reduced, and the results showed that CACNG3 could serve as a biomarker for the mesenchymal molecular subtype. In addition, the univariate and multivariate analysis verified the prognostic value of CACNG3 in predicting the OS of gliomas of all grades. The results of functional annotation and pathway enrichment analysis of differently expressed genes(DEGs), showed that CACNG3 might affect the development of glioma by interfering with synaptic transmission. Moreover, temozolomide (TMZ), commonly used in the treatment of glioma, increased CACNG3 expression in a dose and time-dependent manner. Therefore, CACNG3 plays a vital role in the occurrence and development of gliomas and can serve as a potential biomarker for targeted therapy and further investigation in the future.

The level of macrophage migration inhibitory factor is negatively correlated with the efficacy of PD-1 blockade immunotherapy combined with chemotherapy as a neoadjuvant therapy for esophageal squamous cell carcinoma.

PURPOSE: This study aimed to screen biomarkers to predict the efficacy of programmed cell death 1 (PD-1) blockade immunotherapy combined with chemotherapy as neoadjuvant therapy for esophageal squamous cell carcinoma (ESCC). METHODS: In the first stage of the study, the baseline concentrations of 40 tumor-related chemokines in the serum samples of 50 patients were measured to screen for possible biomarkers. We investigated whether the baseline concentration of the selected chemokine was related to the therapeutic outcomes and tumor microenvironment states of patients treated with the therapy. In the second stage, the reliability of the selected biomarkers was retested in 34 patients. RESULTS: The baseline concentration of macrophage migration inhibitory factor (MIF) was negatively correlated with disease-free survival (DFS) and overall survival (OS) in patients treated with the therapy. In addition, a low baseline expression level of MIF is related to a better tumor microenvironment for the treatment of ESCC. A secondary finding was that effective treatment decreased the serum concentration of MIF. CONCLUSION: Baseline MIF levels were negatively correlated with neoadjuvant therapy efficacy. Thus, MIF may serve as a predictive biomarker for this therapy. The accuracy of the prediction could be improved if the serum concentration of MIF is measured again after the patient received several weeks of treatment.

Sclerostin decreases in regular swimmers after ice swimming and is associated with meteorin-like protein serum levels.

Introduction: Cold and exercise are two important stimuli affecting the secretion of osteokines and adipomyokines, which often occur simultaneously. However, few studies have investigated the changes in osteokines and adipomyokines induced by exercise during severe cold and their corresponding associations. Therefore, this study aimed to investigate the changes in sclerostin and meteorin-like (metrnl) protein before and after cold exercise (ice swimming [IS]) and observe their correlation. Methods: For this, 56 daily ice swimmers' data were included in this study. Serum sclerostin and metrnl were measured 30 min before IS and 30 min after. The fat mass, visceral fat area, fat-free mass, skeletal muscle mass, lumbar spine, and femoral neck bone mineral density of the ice swimmers were measured. Results: After IS, sclerostin exhibited significant decreases, whereas metrnl showed no significant change. In addition, the baseline level of sclerostin and the decrease in sclerostin were positively correlated with serum metrnl after adjusting for age, gender, and body composition indicators. Discussion: IS caused a significant decrease in sclerostin but did not affect metrnl. Furthermore, the associations between sclerostin and metrnl suggested a correlation between osteokines and adipomyokines; this encourages future exploration of the interconnection between bone, muscle, and fat, which will be beneficial for identifying potential common therapeutic targets for diseases such as osteoporosis, sarcopenia, and obesity.

Using Health Forum Data to Assess User Needs for mHealth App Development: A Feasibility Study on Alzheimer's Disease.

Online health forums are used by patients and caregivers as community and information resources, especially for chronic disease management, and could help determine user needs for digital health app design. This study aims to assess the feasibility of using online forum posts on Alzheimer's disease to inform user needs in mobile health application design and whether this process can be automated through text clustering methods. A total of 413 posts were analyzed manually through thematic coding and yielded three themes and nine subthemes for patient and caregiver needs. The external evaluation showed fair to substantial similarity between the automatically and manually derived labels. Four personas were developed to assess the validity of forum-generated needs. These results establish that health forum data can provide sufficient information to understand user needs. However, further refinement of the analysis process and algorithm is necessary to generalize this method to other disease conditions and types of forum data.

ATP-triggered highly sensitive probes for super-resolution mitochondrial imaging and low-dose bioimaging.

Adenosine triphosphate (ATP), mainly produced in mitochondria, plays an important role in various pathological processes such as inflammation and acute liver injury. Fluorescence imaging is a powerful tool for imaging tissue structure and function in vivo. To date, the lack of biocompatible ATP probes with bright fluorescence emission has hindered their application in basic research and clinical trials. Here, we report a method for preparing ATP probes using a ZIF-90 potting dye, which produces bright ATP probes by encapsulating a modified high fluorescence quantum yield dye into a ZIF-90 skeleton. The nanoprobe does not fluoresce due to the coating. ATP can cooperate with Zn2+ to decompose the nanoprobe structure, release the dye and restore the fluorescence. Both nanoprobes ORhBSO2@ZIF-90 and SiRhBSO2@ZIF-90 showed higher sensitivity than the reported ATP nanoprobes with detection limits of 7.56 µM and 6.6 µM, and with lower doses (10 µg mL-1) of probes for cell imaging. In addition, SiRhBSO2@ZIF-90 has also been successfully used in the liver injury model. The ZIF-90 encapsulation strategy can retain the high fluorescence quantum yield and improve the biocompatibility of the dye.

Outcome of immune checkpoint inhibitors in patients with extensive-stage small-cell lung cancer and brain metastases.

Objectives: Brain metastases (BMs) are common in extensive-stage small-cell lung cancer (SCLC) and are underrepresented in pivotal clinical trials that demonstrate the efficacy of immune checkpoint inhibitors (ICIs). We conducted a retrospective analysis to assess the role of ICIs in BM lesions in less selected patients. Materials and methods: Patients with histologically confirmed extensive-stage SCLC who were treated with ICIs were included in this study. Objective response rates (ORRs) were compared between the with-BM and without-BM groups. Kaplan-Meier analysis and the log-rank test were used to evaluate and compare progression-free survival (PFS). The intracranial progression rate was estimated using the Fine-Gray competing risks model. Results: A total of 133 patients were included, 45 of whom started ICI treatment with BMs. In the whole cohort, the overall ORR was not significantly different for patients with and without BMs (p = 0.856). The median progression-free survival for patients with and without BMs was 6.43 months (95% CI: 4.70-8.17) and 4.37 months (95% CI: 3.71-5.04), respectively (p =0.054). In multivariate analysis, BM status was not associated with poorer PFS (p = 0.101). Our data showed that different failure patterns occurred between groups, with 7 patients (8.0%) without BM and 7 patients (15.6%) with BM having intracranial-only failure as the first site progression. The cumulative incidences of brain metastases at 6 and 12 months were 15.0% and 32.9% in the without-BM group and 46.2% and 59.0% in the BM group, respectively (Gray's p<0.0001). Conclusions: Although patients with BMs had a higher intracranial progression rate than patients without BMs, the presence of BMs was not significantly associated with a poorer ORR and PFS with ICI treatment in multivariate analysis.

Factors for incidence risk and prognosis of synchronous brain metastases in pulmonary large cell carcinoma patients: a population-based study.

BACKGROUND: Patients with pulmonary large cell carcinoma (LCC) have a high incidence of synchronous brain metastases (SBM) and a poor prognosis. Our study was to evaluate the predictive and prognostic value of the clinical characteristics of pulmonary LCC patients with SBM at initial diagnosis by utilizing the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: LCC patients, diagnosed from 2010 to 2019, were identified from the latest SEER database which was released in April 2022. Logistic regression and Cox regression were used to identify the predictive and prognostic factors for LCC patients with SBM. Propensity score matching (PSM) and Kaplan-Meier analyses were applied to assess different therapy modalities. RESULTS: A total of 1375 LCC patients were enrolled in this study and 216 (15.7%) of them had SBM at the initial diagnosis. The median overall survival (OS) of LCC patients with SBM was 4 months. Multivariate Cox regression identified age 60-79 (OR 0.57; 95% CI 0.41-0.78; p < 0.001), age ≥ 80 (OR 0.23; 95% CI 0.12-0.45; p < 0.001) and bone metastases (OR 1.75; 95% CI 1.22-2.51; p < 0.001) as significant independent predictors for developing SBM. Multivariable Cox regression revealed that age 60-79, T stage, bone metastases and chemotherapy were independent prognostic factor for OS. The surgery combined with chemotherapy and radiotherapy group, in which all patients were N0 stage and had no other site-specific metastases, exhibited the best median OS of 15 months. CONCLUSIONS: LCC patients with age < 60 or bone metastases were more likely to have SBM at initial diagnosis. Age, T stage, bone metastases and chemotherapy were independent prognostic factors for OS of LCC patients with SBM. Highly selected patients might achieve the best survival benefit from surgery combined with chemotherapy and radiotherapy.

Rechallenge of immunotherapy beyond progression in patients with extensive-stage small-cell lung cancer.

Background: Rechallenge of immunotherapy beyond progression (RIBP) has been demonstrably effective in a variety of cancers. Our study aims to investigate the efficacy of RIBP in small-cell lung cancer (SCLC) patients under real-world conditions. Methods: SCLC patients who experienced progressive disease after receiving programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) inhibitors combined with chemotherapy from January 2017 to October 2021 were enrolled. The study population was divided into two groups: the RIBP group and the discontinuation of immunotherapy beyond progression (DIBP) group. Inverse propensity score weighting (IPSW) method was used to balance the clinical baseline characteristics. The short-term and long-term efficacy of the two groups was compared. Results: 100 SCLC patients were included in this study. There were 45 patients in the RIBP group and 55 patients in the DIBP group. The disease control rate (DCR) and the proportion of durable clinical benefit (DCB) were significantly higher in the RIBP group (DCR: 79.7% vs. 55.7%, p = 0.027; DCB: 40.7 vs. 20.7%, p = 0.025) after weighting. The median progressive-free survival (PFS) in the RIBP group was significantly longer than the DIBP group in the total population (mPFS: 4.8 vs. 2.4 months, p = 0.002), while there was no significant difference in overall survival (OS) of the two groups (mOS: 17.4 vs. 8.0 months, p = 0.098). In the weighted first-line initial immunotherapy subgroup, PFS and OS were significantly improved in the RIBP group (mPFS: 4.5 vs. 2.8 months, p = 0.017; mOS: 11.6 vs. 5.4 months, p = 0.028). After weighting, the RIBP group had a significantly longer PFS than the DIBP group in the SD/PD response to the initial immunotherapy subgroup (mPFS: 6.8 vs. 1.8 months, p = 0.026). Conclusion: Rechallenge of PD-1/PD-L1 inhibitors could bring benefits to SCLC patients, especially in the first-line initial immunotherapy subgroup or SD/PD response to the initial immunotherapy subgroup.

Design strategy for an analyte-compensated fluorescent probe to reduce its toxicity.

During biological detection, the toxicity caused by probes to living organisms is neglected. In this study, an analyte-compensated fluorescent probe (NP-SN3) was constructed for the detection of H2S. Through experiments with HepG2 cells and zebrafish embryos and larvae, the NP-SN3 probe showed no significant difference in imaging performance compared with the traditional probe (NP-N3) but exhibited lower detection-induced toxicity in the imaging of liver fibrosis in activated HSC-T6 cells. During the development of zebrafish embryos and continuous administration in rats, NP-SN3 showed a lower death rate, higher hatchability and lower malformation in zebrafish embryos and milder pathological symptoms in stained rat tissues.

First-line PD-1/PD-L1 inhibitors plus chemotherapy versus bevacizumab plus chemotherapy for advanced non-squamous non-small cell lung cancer: A Bayesian network meta-analysis of randomized controlled trials.

Chemotherapy in combination with immune checkpoint inhibitor (ICI) or bevacizumab has demonstrated a superior effect for non-squamous non-small cell lung cancer (NS-NSCLC). There are still few randomized controlled trials (RCTs) investigating the differences between ICI plus chemotherapy (ICI-chemotherapy) and bevacizumab plus chemotherapy (Bev-chemotherapy) in first-line treatment of NS-NSCLC. We identified RCTs in databases and conference abstracts presented at international conferences by Sep 1, 2021. Bayesian network meta-analysis was performed using randomized effect consistency model to estimate hazard ratio (HR) and odds ratio (OR). The outcomes included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and grade ≥ 3 treatment-related adverse events (TRAEs). Fifteen RCTs (17 articles) of 6561 advanced NS-NSCLC patients receiving ICI-chemotherapy, Bev-chemotherapy, or chemotherapy at first-line were eligible for analysis. NMA results showed that first-line ICI-chemotherapy prolonged OS (HR 0.79, 0.66-0.94) in patients with advanced NS-NSCLC compared with Bev-chemotherapy, while no differences were in PFS, ORR, and grade ≥ 3 TRAEs (p > 0.05). Ranking plots suggested that ICI-chemotherapy had the most probability to offer the best OS (probability 0.993), PFS (probability 0.658), and ORR (probability 0.565), and Bev-chemotherapy had the most risks of grade ≥ 3 TRAEs (probability 0.833). Therefore, our findings showed that first-line ICI-chemotherapy was associated with better OS than Bev-chemotherapy in patients with advanced NS-NSCLC, and more clinical trials are warranted to confirm these results.

Fabrication of self-assembled peptide nanoparticles for in vitro assessment of cell apoptosis pathway and in vivo therapeutic efficacy.

Near-infrared fluorescent (NIRF) dye-coupled self-assembled RGD-linked proapoptotic peptide nanoparticles have been synthesized with spherical shape and size ~ 30-40 nm diameters. The peptide sequence was coupled with cyanine 5.5 probe as NIRF-dye to introduce optical imaging properties and pH-dependent method was used to design Cy5.5 coupled self-assembled peptide nanoparticles (f-SAPNs). This nanoprobe has the ability to target αvß3-integrin receptor overexpressed on cancer cell's surface with improved internalization capabilities into the mitochondria. The in situ study showed that this peptide sequence has potential to disrupt the mitochondrial membrane efficiently, activating the Caspase-3 enzyme, and ultimately induces cell apoptosis. It has been observed from in vitro study that the degree of apoptosis for f-SAPNs was increased from 25.6% to 96.3%, while decreased degree of necrosis from 51.7% to 0.2% compared with its parent peptide analog (Cy5.5-c[RGDKLAK]; f-CP) occurs. Further investigations revealed that these f-SAPNs showed high uptake in U87MG glioblastoma cells in comparison with PC-3 prostate cancer cells. Moreover, in vivo therapeutic studies represented the prominent decrease in the size of tumor tissue treated with f-CP and f-SAPNs (201 ± 13 mm3 and 104 ± 6 mm3, respectively) compared with untreated tumor tissues (366 ± 18 mm3). These outcomes highlighted the specificity, and efficacy of f-SAPNs toward αvß3-integrin expressing tumor tissue in vivo and suggested that these novel designed f-SAPNs may serve as a potential theranostic drug for brain tumor glioblastoma multiforme. The pH-sensitive method gives NIRF dye-coupled self-assembled peptide nanoparticle (f-SAPNs), enables the tunable synthesis of spherical nanoparticles with high stability towards proteolysis, improved biocompatibility, and promising therapeutic efficacy.

A novel fluorescent probe with large Stokes shift for accurate detection of HOCl in mitochondria and its imaging application.

Hypochlorous acid (HOCl), mainly generated in mitochondria, plays a critical role in various physiological processes. To better understand the role and function of HOCl in mitochondria, herein, we present the design and synthesis of a Mito-QL reporter for probing the HOCl within mitochondria without other interference generated in living cells. Through the combination of TICT/ICT mechanisms, probe Mito-QL, with large stokes shift (203 nm) and low background fluorescence, exhibited excellent sensitivity (900-fold fluorescence enhancement) and selectivity towards HOCl (LOD = 2.4 nM). The co-location experiments confirmed that probe Mito-QL can firstly localize in the mitochondria and then react with HOCl in mitochondria. Also, the probe is capable of imaging endogenous and exogenous HOCl even the generation of HOCl during the ferroptosis of cells, which is beneficial for more efficient application in biological imaging.

A water-soluble near-infrared fluorescent probe for monitoring change of hydrogen sulfide during cell damage and repair process.

As a signal molecule involved in autophagy, hydrogen sulfide (H2S) is considered to be essential in the development and treatment of diseases. In order to clarify the complex role of H2S in organism and the participation of H2S in disease process, it is urgently needed to visualize the dynamics of H2S. In this contribution, a water-soluble near-infrared (695 nm emission) self-immolative fluorescent probe CySO3N3 was constructed for H2S detection. The ability of self-immolative strategy to detect H2S was verified to increase the metabolic capacity and reduce the toxicity of probe. This probe can not only be used to detect H2S in living cell and mice, but also shows great potential in detecting H2S changes to monitor cell self-repair during inflammation and myocardial injury.

Hybridization of tumor homing and mitochondria-targeting peptide domains to design novel dual-imaging self-assembled peptide nanoparticles for theranostic applications.

A novel hybridized dual-targeting peptide-based nanoprobe was successfully designed by using the cyclic heptapeptide. This peptide has Arg-Gly-Asp-Lys-Leu-Ala-Lys sequence, in which the RGD homing motif and KALK mitochondria-targeting motif were linked via amide bond. The designed peptide probe was further modified through covalent linkage to induce dual-imaging functionality, and self-assembled to form spherical nanoparticles. The novel Cy5.5-SAPD-99mTc nanoparticles were tested for in vitro cytotoxicity, cellular uptake, and apoptosis-inducing functionalities. The cellular internalization, enhanced cytotoxicity and selective receptor binding capabilities against U87MG cells, excellent dual-imaging potential, improved apoptosis-inducing feature by damaging mitochondria, and in vivo preclinical investigations suggested that our newly designed novel hybridized peptide-based dual-imaging nanoparticles may serve as an admirable theranostic probe to treat brain tumor glioblastoma multiforme. This study describes the development of dual-targeting self-assembled peptide nanoparticles followed by modifications using NIRF dye and radiolabeled with 99mTc for dual-imaging and enhanced therapeutic efficacy against brain tumor.

Sequential detection of H2S and HOBr with a novel lysosome-targetable fluorescent probe and its application in biological imaging.

Understanding the complex relationship between active small molecules is of great significance in various physiological processes. Herein, we present the design and synthesis of a sequential responsive Lysosome-Naphthalene imide-Azido (lyso-NP-N3) reporter for probing the H2S and HOBr within organelle (lysosome) in living cells. Probe lyso-NP-N3 exhibited high selectivity and sensitivity towards H2S (LOD = 23.5 nM) and HOBr (LOD = 254 nM). Additionally, lyso-NP-N3 possessed an excellent lysosome targeting ability and was utilized to visualize the exogenous/endogenous H2S and HOBr in RAW 264.7, Hela and HepG2 cells. Facilitated by this sequentially activated mechanism, the probe was successfully applied to confirm that the reported scavenger of HOBr, N-acetyl-L-cysteine (NAC) mainly relied on its metabolite H2S to eliminate excess HOBr, thereby playing the role of cell regulation and protection. These results establish the crosstalk between H2S and HOBr in lysosome and provide a promising tool to study metabolite interactions.

Response of Bone Metabolism Markers to Ice Swimming in Regular Practitioners.

Objective: Both exercise and cold exposure cause physiological stress and they often occur in combination. However, the effects of exercise during severe cold on variation in bone metabolism in humans have remained elusive. The aim of this study was to investigate the variations in circulating bone metabolism markers after ice swimming (IS). Methods: Eighty-seven women and men aged 42-84 years old were recruited to perform regular IS activities. Serum parathyroid hormone (PTH), total calcium (Ca2+), total phosphorus (Pi), total magnesium (Mg2+), N-terminal osteocalcin (N-MID), total propeptide of procollagen 1 (TPINP), and C-terminal telopeptide of type 1 collagen (ß-CTX) were measured 30 min before and 30 min after IS. Bone mineral content (BMC) and bone mineral density (BMD) were assessed at lumbar spine 1-4 (L1-L4) and femoral neck (FN). The IS habits were obtained from questionnaires and the 10-year probability of osteoporotic fracture was calculated using the FRAX® tool with and without a BMD value of the FN. Results: There were significant increases in PTH (median, 40.120-51.540 pg/mL), Ca2+ (median, 2.330-2.400 mmol/L), and Pi (median, 1.100-1.340 mmol/L) and significant decreases in TPINP (median, 38.190-36.610 ng/mL) and ß-CTX (median, 0.185-0.171 ng/mL), while there was a trend for increased serum Mg2+ (P = 0.058) but no significant change in N-MID (P = 0.933) after IS in all subjects. The increases in the proportions of cases of hyperparathyroidemia, hypercalcemia, and hyperphosphatemia in those performing IS were statistically significant. The baseline levels and the changes of bone metabolism markers had associations with osteoporosis and bone status, but these may be age and sex dependent. Finally, there were significant correlations among the bone metabolism markers. Conclusion: IS caused significant alterations in bone metabolic markers, specifically, increases in PTH, Ca2+ and Pi should raise concerns about potential cardiovascular health risks in severe cold exercise. Additionally, a divergence between PTH elevation and a decline in bone turnover, which shown a special change of bone metabolism after IS and may suggest potential therapeutic implications of cold exercise in PTH and bone metabolic disorders.

Resveratrol modulates Toxoplasma gondii infection induced liver injury by intervening in the HMGB1/TLR4/NF-κB signaling pathway.

Toxoplasma gondii (T. gondii) is an obligate intracellular parasite that can cause liver diseases in the host, including hepatitis and hepatomegaly. High mobility group box 1 (HMGB1) is the main inflammatory mediator causing cell injury or necrosis. HMGB1 binds to toll like receptor 4 (TLR4), then activates the nuclear factor-κB (NF-κB) signaling pathway, which promotes the release of inflammatory factors. Our previous studies showed that HMGB1 mediated TLR4/NF-κB signaling pathway plays an important role in liver injury induced by T. gondii infection. Resveratrol (RSV) is a small polyphenol, which has anti-inflammatory, anti-cancer, anti-T. gondii effect. However, the effect of RSV on liver injury caused by T. gondii infection is unclear. This study used the RH strain tachyzoites of T. gondii to infect murine liver line, NCTC-1469 cells to establish an in vitro model and acute infection of mice for the in vivo model to explore the protective effect of RSV on liver injury induced by T. gondii infection. The results showed that RSV inhibited the proliferation of T. gondii in the liver, reduced the alanine aminotransferase/aspartate aminotransferase levels and pathological liver damage. Additionally, RSV inhibited the production of tumor necrosis factor-α, inducible nitric oxide synthase and HMGB1 by interfering with the TLR4/NF-κB signaling pathway. These results indicate that RSV can protect liver injury caused by T. gondii infection by intervening in the HMGB1/TLR4/NF-κB signaling pathway. This study will provide a theoretical basis for RSV treatment of T. gondii infection induced liver injury.

A feasible self-assembled near-infrared fluorescence sensor for acid phosphatase detection and cell imaging.

The single signal amplification strategy is significant for detecting various disease biomarkers but is restricted by its limited accuracy. The multi-signal and multi-mode methods have overcome this deficiency. Acid phosphatase (ACP) is an important intracellular enzyme but one-step cell imaging material-based probes are scarce for ACP. Herein, we designed a one-step self-assembled polymer probe using neutral red (NR), modified-(pyridoxal-5'-phosphate (PLP)) and Eu3+. The polymer exhibited non-emission and excellent stability. Upon the catalytic hydrolysis reaction of ACP, the polymer exhibited two strong fluorescence signals at 373 nm and 613 nm and an appreciable decline of absorbance at 395 nm. The probe has excellent selectivity and higher sensitivity with a limit of detection as low as 0.02 mU mL-1. It possesses favorable biocompatibility and has been successfully used to detect and image intracellular ACP in several living cells.

Handgrip strength is positively associated with bone mineral density in middle and aged adults: results from NHANES 2013-2014.

Few studies have examined the association between handgrip strength and BMD in specific subgroups. Therefore, we examined the associations of handgrip strength with BMD aged ≥ 40 years and found that handgrip strength is associated with BMD which is independent of BMI, physical activity, and other potential confounders. PURPOSE: Previous studies have revealed that handgrip strength is a measure of muscular fitness and is associated with fracture and bone mineral density (BMD) in adolescents and adults, with conflicting results. In addition, few studies have examined the association between handgrip strength in predefined subgroups such as sex, age, and physical activity in a whole population. METHODS: We examined the associations of handgrip strength with BMD in 2720 adults (1359 men and 1361 women) aged ≥ 40 years (mean age, 58.6 ± 11.8 years) from the National Health and Nutrition Examination Survey (NHANES) 2013-2014. NHANES collects data via household interviews and direct standardized physical examinations conducted in specially equipped mobile examination centers. The date of final data collection was 2014 and the present data analysis was conducted in January to February 2020. RESULTS: Handgrip strength was significantly associated with total femur (r = 0.482, P < 0.001) and femoral neck BMD (r = 0.427, P < 0.001) among all participants, respectively. After adjustment for age, sex, race, body mass index (BMI), physical activity, smoking, history of diabetes, history of hypertension, and history of high cholesterol, each unit (1 SD) of BMI-adjusted handgrip strength was positively associated with 0.026 g/cm2 increase in total femur BMD (P < 0.001) and 0.027 g/cm2 increase in femoral neck BMD (P < 0.001). There was a significant increasing trend in total femur and femoral BMD as handgrip strength increased from the lowest quartile to the highest quartile (P for trend < 0.001). For subgroup analysis, there were no significant interaction effects of handgrip strength with BMD between predefined subgroups (all P > 0.05). CONCLUSIONS: High level of handgrip strength is associated with increased BMD. The association is independent of BMI, physical activity, and other potential confounders.