Hydrogen sulfide alleviates heart failure with preserved ejection fraction in mice by targeting mitochondrial abnormalities via PGC-1α.

AIM: Increasing evidence has proposed that mitochondrial abnormalities may be an important factor contributing to the development of heart failure with preserved ejection fraction (HFpEF). Hydrogen sulfide (H2S) has been suggested to play a pivotal role in regulating mitochondrial function. Therefore, the present study was designed to explore the protective effect of H2S on mitochondrial dysfunction in a multifactorial mouse model of HFpEF. METHODS: Wild type, 8-week-old, male C57BL/6J mice or cardiomyocyte specific-Cse (Cystathionine γ-lyase, a major H2S-producing enzyme) knockout mice (CSEcko) were given high-fat diet (HFD) and l-NAME (an inhibitor of constitutive nitric oxide synthases) or standardized chow. After 4 weeks, mice were randomly administered with NaHS (a conventional H2S donor), ZLN005 (a potent transcriptional activator of PGC-1α) or vehicle. After additional 4 weeks, echocardiogram and mitochondrial function were evaluated. Expression of PGC-1α, NRF1 and TFAM in cardiomyocytes was assayed by Western blot. RESULTS: Challenging with HFD and l-NAME in mice not only caused HFpEF but also inhibited the production of endogenous H2S in a time-dependent manner. Meanwhile the expression of PGC-1α and mitochondrial function in cardiomyocytes were impaired. Supplementation with NaHS not only upregulated the expression of PGC-1α, NRF1 and TFAM in cardiomyocytes but also restored mitochondrial function and ultrastructure, conferring an obvious improvement in cardiac diastolic function. In contrast, cardiac deletion of CSE gene aggravated the inhibition of PGC-1α-NRF1-TFAM pathway, mitochondrial abnormalities and diastolic dysfunction. The deleterious effect observed in CSEcko HFpEF mice was partially counteracted by pre-treatment with ZLN005 or supplementation with NaHS. CONCLUSION: Our findings have demonstrated that H2S ameliorates left ventricular diastolic dysfunction by restoring mitochondrial abnormalities via upregulating PGC-1α and its downstream targets NRF1 and TFAM, suggesting the therapeutic potential of H2S supplementation in multifactorial HFpEF.

The risk factors for Group B Streptococcus colonization during pregnancy and influences of intrapartum antibiotic prophylaxis on maternal and neonatal outcomes.

BACKGROUND: Group B Streptococcus (GBS), also referred as Streptococcus agalactiae, is one of the leading causes of life-threatening invasive diseases such as bacteremia, meningitis, pneumonia and urinary tract infection in pregnant women and neonates. Rates of GBS colonization vary by regions, but large-sample studies on maternal GBS status are limited in southern China. As a result, the prevalence of GBS among pregnant women and its associated risk factors and the efficacy of intrapartum antibiotic prophylaxis (IAP) intervention in preventing adverse pregnancy and neonatal outcomes remain poorly understood in southern China. METHODS: To fill this gap, we retrospectively analyzed demographic and obstetrical data of pregnant women who have undergone GBS screening and delivered between 2016 and 2018 in Xiamen, China. A total of 43,822 pregnant women were enrolled and only a few GBS-positive women did not receive IAP administration. Possible risk factors for GBS colonization were assayed by univariate and multivariate logistic regression analysis. Generalized linear regression model was applicated to analyze whether IAP is one of the impact factors of the hospital length of stay of the target women. RESULTS: The overall GBS colonization rate was 13.47% (5902/43,822). Although women > 35 years old (P = 0.0363) and women with diabetes mellitus (DM, P = 0.001) had a higher prevalence of GBS colonization, the interaction between ages and GBS colonization was not statistically significant in Logistic Regression analysis (adjusted OR = 1.0014; 95% CI, 0.9950, 1.0077). The rate of multiple births was significantly dropped in GBS-positive group than that of GBS-negative group (P = 0.0145), with no significant difference in the rate of fetal reduction (P = 0.3304). Additionally, the modes of delivery and the incidences of abortion, premature delivery, premature rupture of membranes, abnormal amniotic fluid and puerperal infection were not significantly different between the two groups. The hospitalization stays of the subjects were not influenced by GBS infection. As for neonatal outcomes, the cases of fetal death in maternal GBS-positive group did not statistically differ from that in maternal GBS-negative group. CONCLUSION: Our data identified that pregnant women with DM are at high risk of GBS infection and IAP is highly effective in prevention of adverse pregnancy and neonatal outcomes. This stressed the necessity of universal screening of maternal GBS status and IAP administration to the target population in China, and women with DM should be considered as priorities.

Dynamic Prognostic Score to Predict Survival in East Asian Elderly Populations with Dysphagia.

INTRODUCTION: Dysphagia is a common disorder in older adults, leading to severe complications, including aspiration pneumonia, dehydration, malnutrition, weight loss, and even death. However, no prognostic model has been developed to predict the prognosis of older adults with dysphagia. METHODS: Data from patients with dysphagia at a single center were retrospectively reviewed between 2014 and 2017. All data were obtained from the Dryad Digital Repository. The least absolute shrinkage and selection operator regression model was used to select potentially relevant features. Multiple Cox proportional hazard analysis was used to develop a model based on the training set. RESULTS: The nomogram comprised age, sex, percutaneous endoscopic gastrostomy, chronic heart failure, total lymphocyte count, daily calorie intake, and severe pneumonia, which provided favorable calibration and discrimination in the training dataset, with AUCs for the 1-year, 2-year, and 3-year survival predictions of 0.833, 0.871, and 0.886, respectively. Furthermore, it showed acceptable discrimination in the validation cohort, with AUCs for the 1-year, 2-year, and 3-year survival predictions of 0.884, 0.834, and 0.782, respectively. Moreover, the decision curve analysis results revealed that the nomogram was clinically beneficial. CONCLUSION: A nomogram, combining seven demographic and clinical factors, provided an excellent preoperative prediction of survival probability in older individuals with dysphagia. This predictive model can be used as a reference to assist clinicians in making clinical decisions.

Neuronal Nitric Oxide Synthase in Nucleus Accumbens Specifically Mediates Susceptibility to Social Defeat Stress through Cyclin-Dependent Kinase 5.

Stress-induced depression is common worldwide. NAc, a "reward" center, is recently reported to be critical to confer the susceptibility to chronic social defeat stress (CSDS) and the depression-related outcome. However, the underlying molecular mechanisms have not been well characterized. In this study, we induced depression-like behaviors with CSDS and chronic mild stress in male mice to mimic social and environmental factors, respectively, and observed animal behaviors with social interaction test, tail suspension test, and sucrose preference test. To determine the role of neuronal nitric oxide synthase (nNOS) and its product nitric oxide (NO), we used brain region-specifically nNOS overexpression and stereotaxic injection of NO inhibitor or donor. Moreover, the downstream molecular cyclin-dependent kinase 5 (CDK5) was explored by conditional KO and gene mutation. We demonstrate that nNOS-implicated mechanisms in NAc shell (NAcSh), including increased cell number, increased protein expression levels, and increased specific enzyme activity, contribute the susceptibility to social defeat and the following depression-like behaviors. NAcSh nNOS does not directly respond to chronic mild stress but facilitates the depression-like behaviors. The increased NAcSh nNOS expression after CSDS leads to the social avoidance and depression-like behaviors in defeated mice, which is dependent on the nNOS enzyme activity and NO production. Moreover, we identify the downstream signal in NAcSh. S-nitrosylation of CDK5 by NO contributes to enhanced CDK5 activity, leading to depression-related behaviors in susceptible mice. Therefore, NAcSh nNOS mediates susceptibility to social defeat stress and the depression-like behaviors through CDK5.SIGNIFICANCE STATEMENT Stress-induced depression is common worldwide, and chronic exposure to social and psychological stressors is important cause of human depression. Our study conducted with chronic social defeat stress mice models demonstrates that nNOS in NAcSh is crucial to regulate the susceptibility to social defeat stress and the following depression-like behaviors, indicating NAcSh nNOS as the responding molecule to social factors of depression. Moreover, we discover the downstream mechanism of NAcSh nNOS in mediating the susceptibility is NO and S-nitrosylation of CDK5. Thus, NAcSh nNOS mediates susceptibility to social defeat stress through CDK5 is a potential mechanism for depression, which may interpret how the brain transduces social stress exposure into depression.

Genome-Wide Identification of Petunia HSF Genes and Potential Function of PhHSF19 in Benzenoid/Phenylpropanoid Biosynthesis.

Volatile benzenoids/phenylpropanoids are the main flower scent compounds in petunia (Petunia hybrida). Heat shock factors (HSFs), well known as the main regulator of heat stress response, have been found to be involved in the biosynthesis of benzenoid/phenylpropanoid and other secondary metabolites. In order to figure out the potential function of HSFs in the regulation of floral scent in petunia, we systematically identified the genome-wide petunia HSF genes and analyzed their expression and then the interaction between the key petunia HSF gene with target gene involved in benzenoid/phenylpropanoid biosynthesis. The results revealed that 34 HSF gene family members were obtained in petunia, and most petunia HSFs contained one intron. The phylogenetic analysis showed that 23 petunia HSFs were grouped into the largest subfamily HSFA, while only two petunia HSFs were in HSFC subfamily. The DBD domain and NLS motif were well conserved in most petunia HSFs. Most petunia HSF genes' promoters contained STRE motifs, the highest number of cis-acting element. PhHSF19 is highly expressed in petal tubes, followed by peduncles and petal limbs. During flower development, the expression level of PhHSF19 was dramatically higher at earlier flower opening stages than that at the bud stage, suggesting that PhHSF19 may have potential roles in regulating benzenoid/phenylpropanoid biosynthesis. The expression pattern of PhHSF19 is positively related with PhPAL2, which catalyzes the first committed step in the phenylpropanoid pathway. In addition, there are three STRE elements in the promoter of PhPAL2. PhHSF19 was proven to positively regulate the expression of PhPAL2 according to the yeast one hybrid and dual luciferase assays. These results lay a theoretical foundation for further studies of the regulation of HSFs on plant flower scent biosynthesis.

Clinical effectiveness of the Eruption Guidance Appliances in treating malocclusion in the mixed dentition: A systematic review and meta-analysis.

AIM: To evaluate the clinical effectiveness of the eruption guidance appliances (EGAs) in treating malocclusion in the early mixed dentition. DESIGN: Electronic databases were comprehensively searched for the eligibility literature of the EGA treatment for a period spanning from the earliest available date in each database up to July 2021. Randomized controlled trials, controlled clinical trials, and prospective and retrospective cohort studies were included in the present review. The quality of clinical trials was assessed according to the Cochrane Collaboration's tools (RoB2.0 and ROBINS-I), whereas cohort studies were based on the Newcastle-Ottawa Scale (NOS). The data were gathered and synthesized with the Stata software (version 12). RESULTS: The screen yielded 436 articles, of which 17 papers were potentially eligible, and 7 articles from 3 studies (1 RCT, 1 CCT, and 1 PCS) were qualified for the final review and analysis. The meta-analysis showed both favorable dentoalveolar and skeletal changes in short term. Both overjet and overbite had a significant decrease after treatment (MD = -2.38 mm, 95% CI: -2.82 to -1.94, p < .001, and MD = -2.43 mm, 95% CI: -3.52 to -1.35, p < .001, respectively), and SNB increased significantly by 0.73 degrees (95% CI: 0.17-1.28, p = .01). After the retention period, however, overbite had a significant increase of 0.88mm, which indicated the occurrence of a relapse (95% CI: 0.60-1.16, p < .001). CONCLUSIONS: According to the existing evidence, the EGA treatment is effectively correcting overjet and overbite in the early mixed dentition in short term; furthermore, high-quality and long-term studies are warranted to determine its long-term effectiveness.

CYCLIC NUCLEOTIDE-GATED ION CHANNELs 14 and 16 Promote Tolerance to Heat and Chilling in Rice.

Calcium signaling has been postulated to be critical for both heat and chilling tolerance in plants, but its molecular mechanisms are not fully understood. Here, we investigated the function of two closely related cyclic nucleotide-gated ion channel (CNGC) proteins, OsCNGC14 and OsCNGC16, in temperature-stress tolerance in rice (Oryza sativa) by examining their loss-of-function mutants generated by genome editing. Under both heat and chilling stress, both the cngc14 and cngc16 mutants displayed reduced survival rates, higher accumulation levels of hydrogen peroxide, and increased cell death. In the cngc16 mutant, the extent to which some genes were induced and repressed in response to heat stress was altered and some Heat Shock factor (HSF) and Heat Shock Protein (HSP) genes were slightly more induced compared to the wild type. Furthermore, the loss of either OsCNGC14 or OsCNGC16 reduced or abolished cytosolic calcium signals induced by either heat or chilling stress. Therefore, OsCNGC14 and OsCNGC16 are required for heat and chilling tolerance and are modulators of calcium signals in response to temperature stress. In addition, loss of their homologs AtCNGC2 and AtCNGC4 in Arabidopsis (Arabidopsis thaliana) also led to compromised tolerance of low temperature. Thus, this study indicates a critical role of CNGC genes in both chilling and heat tolerance in plants, suggesting a potential overlap in calcium signaling in response to high- and low-temperature stress.

The 5-year overall survival of cervical cancer in stage IIIC-r was little different to stage I and II: a retrospective analysis from a single center.

BACKGROUND: The 2018 International Federation of Gynecology and Obstetrics (FIGO) staging guideline for cervical cancer includes stage IIIC recognized by preoperative radiology (IIIC-r) to state there are lymph nodes metastases (LNM) identified by imaging tools. We aim to explore the reasonability and limitations of stage IIIC-r and try to explore the potential reasons. METHODS: Electronic medical records were used to identify patients with cervical cancer. According to the new staging guidelines, patients were reclassified and assigned into five cohorts: stage I, stage II, stage IIIC-r, LNM confirmed by pathology (IIIC-p) and LNM detected by radiology and confirmed by pathology (IIIC r + p). Five-year overall survivals were estimated for each cohort. The diagnosis accuracy of computed tomography (CT), magnetic resonance imaging (MRI) and diameter of detected lymph nodes were also evaluated. RESULTS: A total of 619 patients were identified. The mean follow-up months were 65 months (95% CI 64.43-65.77) for all patients. By comparison, the 5-year overall survival rates were not statistically different (p = 0.21) among stage IIIC-r, stage I and stage II. While, the rates were both statistical different (p<0.001) among stage IIIC-p, IIIC r + p and stage I and stage II. The sensitivities of CT and MRI in detecting LNM preoperatively were 51.2 and 48.8%. The mean maximum diameter of pelvic lymph nodes detected by CT cohort was 1.2 cm in IIIC-r cohort, and was 1.3 cm in IIIC r + p cohort. While, the mean maximum diameter of pelvic lymph nodes detected by MRI was 1.2 cm in IIIC-r cohort, and was 1.48 cm in IIIC r + p cohort. When the diagnosis efficacy of the diameter of pelvic lymph nodes in detecting LNM were evaluated, the area under the receiver operating characteristic curve (ROC curve) was 0.58 (p = 0.05). CONCLUSIONS: It seems that the FIGO 2018 staging guideline for cervical cancer is likely to has certain limitations for the classification of those with LNM. CT or MRI, however, has limitations on detecting LNM. It would be better to use more accurate imaging tools to identify LNM in the clinical practices.

A novel method for automatic pharmacological evaluation of sucrose preference change in depression mice.

Sucrose preference test (SPT) is a most frequently applied method for measuring anhedonia, a core symptom of depression, in rodents. However, the method of SPT still remains problematic mainly due to the primitive, irregular, and inaccurate various types of home-made equipment in laboratories, causing imprecise, inconsistent, and variable results. To overcome this issue, we devised a novel method for automatic detection of anhedonia in mice using an electronic apparatus with its program for automated detecting the behavior of drinking of mice instead of manual weighing the water bottles. In this system, the liquid surface of the bottles was monitored electronically by infrared monitoring elements which were assembled beside the plane of the water surface and the information of times and duration of each drinking was collected to the principal machine. A corresponding computer program was written and installed in a computer connected to the principal machine for outputting and analyzing the data. This new method, based on the automated system, was sensitive, reliable, and adaptable for evaluation of stress- or drug-induced anhedonia, as well as taste preference and effects of addictive drugs. Extensive application of this automated apparatus for SPT would greatly improve and standardize the behavioral assessment method of anhedonia, being instrumental in novel antidepressant screening and depression researching.

Surgical Approach and Use of Uterine Manipulator Are Not Associated with LVSI in Surgery for Early-stage Cervical Cancer.

STUDY OBJECTIVE: In 2018, the Laparoscopic Approach to Cervical Cancer trial reported that patients undergoing minimally invasive surgery for cervical cancer (CC) had poorer outcomes than patients undergoing open surgery. Several hypotheses have been made to explain the results. We aimed to investigate whether laparoscopic procedures and use of a uterine manipulator increase the risk of lymphovascular space invasion (LVSI) in early-stage CC. DESIGN: A retrospective study. SETTING: A Chinese women's and children's hospital. PATIENTS: Patients with early-stage CC who underwent radical hysterectomy in West China Second University Hospital between April 2019 and May 2020. INTERVENTIONS: Laparoscopic surgery (with uterine manipulator and uterine manipulator-free) and open surgery. MEASUREMENTS AND MAIN RESULTS: A total of 979 patients diagnosed with CC were registered in West China Second University Hospital for surgical treatment. Of these, 525 patients underwent laparoscopic surgery and 454 patients underwent open surgery. In total, 735 patients with early-stage cancer underwent radical hysterectomy and pelvic lymphadenectomy, including 357 by laparoscopic surgery and 378 by open surgery. For those who underwent radical hysterectomy and pelvic lymphadenectomy, the incidence of LVSI was 48.41% and 47.34% in laparoscopic and open groups, respectively (p = .771). After 1:1 propensity score matching with age, International Federation of Gynecology and Obstetrics stage, pathology, and tumor size, the incidence of LVSI was 45.54% and 51.79% in laparoscopic and open groups, respectively (p = .186). Subdividing the laparoscopic group into uterine manipulator and uterine manipulator-free groups, the incidence of LVSI was 45.22% and 48.35%, respectively (p = .580). After propensity score matching with age, International Federation of Gynecology and Obstetrics stage, pathology, and tumor size, the incidence of LVSI was 45.78% and 55.42% in these 2 groups, respectively (p = .214). Multiple factor analysis revealed that lymph node metastasis and deep stromal invasion were associated with LVSI (p value <.05 in both groups). CONCLUSION: The surgical approach and use of a uterine manipulator are not associated with LVSI in surgery for early-stage CC. Lymph node metastasis and deep stromal invasion are associated with LVSI.

Sarcoidosis: a state of the art review from the Thoracic Society of Australia and New Zealand.

Sarcoidosis is a systemic disease of unknown aetiology, characterised by non-caseating granulomatous inflammation. It most commonly manifests in the lungs and intrathoracic lymph nodes but can affect any organ. This summary of an educational resource provided by the Thoracic Society of Australia and New Zealand outlines the current understanding of sarcoidosis and highlights the need for further research. Our knowledge of the aetiology and immunopathogenesis of sarcoidosis remains incomplete. The enigma of sarcoidosis lies in its immunological paradox of type 1 T helper cell-dominated local inflammation co-existing with T regulatory-induced peripheral anergy. Although specific aetiological agents have not been identified, mounting evidence suggests that environmental and microbial antigens may trigger sarcoidosis. Genome-wide association studies have identified candidate genes conferring susceptibility and gene expression analyses have provided insights into cytokine dysregulation leading to inflammation. Sarcoidosis remains a diagnosis of exclusion based on histological evidence of non-caseating granulomas with compatible clinical and radiological findings. In recent years, endobronchial ultrasound-guided transbronchial needle aspiration of mediastinal lymph nodes has facilitated the diagnosis, and whole body positron emission tomography scanning has improved localisation of disease. No single biomarker is adequately sensitive and specific for detecting and monitoring disease activity. Most patients do not require treatment; when indicated, corticosteroids remain the initial standard of care, despite their adverse side effect profile. Other drugs with fewer side effects may be a better long term choice (eg, methotrexate, hydroxychloroquine, azathioprine, mycophenolate), while tumour necrosis factor-α inhibitors are a treatment option for patients with refractory disease.

Salubrinal protects human skin fibroblasts against UVB-induced cell death by blocking endoplasmic reticulum (ER) stress and regulating calcium homeostasis.

The role of UVB in skin photo damages has been widely reported. Overexposure to UVB will induce severe DNA damages in epidermal cells and cause most cytotoxic symptoms. In the present study, we tested the potential activity of salubrinal, a selective inhibitor of Eukaryotic Initiation Factor 2 (eIF2) -alpha phosphatase, against UV-induced skin cell damages. We first exposed human fibroblasts to UVB radiation and evaluated the cytosolic Ca2+ level as well as the induction of ER stress. We found that UVB radiation induced the depletion of ER Ca2+ and increased the expression of ER stress marker including phosphorylated PERK, CHOP, and phosphorylated IRE1α. We then determined the effects of salubrinal in skin cell death induced by UVB radiation. We observed that cells pre-treated with salubrinal had a higher survival rate compared to cells treated with UVB alone. Pre-treatment with salubrinal successfully re-established the ER function and Ca2+ homeostasis. Our results suggest that salubrinal can be a potential therapeutic agents used in preventing photoaging and photo damages.

31 P magnetic resonance fingerprinting for rapid quantification of creatine kinase reaction rate in vivo.

The purpose of this work was to develop a 31 P spectroscopic magnetic resonance fingerprinting (MRF) method for fast quantification of the chemical exchange rate between phosphocreatine (PCr) and adenosine triphosphate (ATP) via creatine kinase (CK). A 31 P MRF sequence (CK-MRF) was developed to quantify the forward rate constant of ATP synthesis via CK ( kfCK), the T1 relaxation time of PCr ( T1PCr), and the PCr-to-ATP concentration ratio ( MRPCr). The CK-MRF sequence used a balanced steady-state free precession (bSSFP)-type excitation with ramped flip angles and a unique saturation scheme sensitive to the exchange between PCr and γATP. Parameter estimation was accomplished by matching the acquired signals to a dictionary generated using the Bloch-McConnell equation. Simulation studies were performed to examine the susceptibility of the CK-MRF method to several potential error sources. The accuracy of nonlocalized CK-MRF measurements before and after an ischemia-reperfusion (IR) protocol was compared with the magnetization transfer (MT-MRS) method in rat hindlimb at 9.4 T (n = 14). The reproducibility of CK-MRF was also assessed by comparing CK-MRF measurements with both MT-MRS (n = 17) and four angle saturation transfer (FAST) (n = 7). Simulation results showed that CK-MRF quantification of kfCK was robust, with less than 5% error in the presence of model inaccuracies including dictionary resolution, metabolite T2 values, inorganic phosphate metabolism, and B1 miscalibration. Estimation of kfCK by CK-MRF (0.38 ± 0.02 s-1 at baseline and 0.42 ± 0.03 s-1 post-IR) showed strong agreement with MT-MRS (0.39 ± 0.03 s-1 at baseline and 0.44 ± 0.04 s-1 post-IR). kfCK estimation was also similar between CK-MRF and FAST (0.38 ± 0.02 s-1 for CK-MRF and 0.38 ± 0.11 s-1 for FAST). The coefficient of variation from 20 s CK-MRF quantification of kfCK was 42% of that by 150 s MT-MRS acquisition and was 12% of that by 20 s FAST acquisition. This study demonstrates the potential of a 31 P spectroscopic MRF framework for rapid, accurate and reproducible quantification of chemical exchange rate of CK in vivo.

Effects of sialidase NEU1 siRNA on proliferation, apoptosis, and invasion in human ovarian cancer.

Ovarian cancer is one of the most common malignancies encountered in the world. In ovarian cancer tissues of patients, NEU1 was expressed in a higher level than that in adjacent normal tissues. In this research, we aimed to elucidate the role of NEU1 siRNA on proliferation, apoptosis, and invasion of OVCAR3 and SKOV3 cells which expressed NEU1 notably. By cell viability assay and flow cytometry method, we found that NEU1 siRNA effectively inhibited the cancer proliferation, arrested cells cycle at G0/G1 phase, and induced apoptosis when compared to the Mock group. Result of transwell assay showed that invasion of cells in OVCAR3 and SKOV3 treated with NEU1 siRNA were suppressed significantly. Gene set enrichment analysis showed that lysosome and oxidative phosphorylation related signal pathway were associated with the NEU1 expression. In addition, Western blot revealed that expressions of Cln3 and Cln5 were depressed, and ATP5B and ATP5J expressions were also reduced. In conclusion, NEU1 siRNA can effectively inhibit proliferation, apoptosis, and invasion of human ovarian cancer cells by targeting lysosome and oxidative phosphorylation signaling, which can serve as a new target ovarian cancer treatment.

Improving ovarian cancer imaging with LHRH-NBs: an experimental study.

PURPOSE: Our previous study used freeze-drying and biotin-avidin binding methods and obtained nontargeted nanobubbles (N-NBs) and ovarian cancer-targeting nanobubbles (LHRH-NBs, luteinizing hormone-releasing hormone nanobubbles). Our study also identified the physical and chemical properties of these two contrast agents, and validated the targeting ability and underlying mechanisms of LHRH-NBs in vitro. The present study investigated the imaging of N-NBs and LHRH-NBs in nude mice and their binding with tissues. METHODS: The nude mice models of xenografts were divided into three groups, N-NB, LHRH-NB, and SonoVue. These contrast agents were injected via the caudal vein to observe the imaging of ovarian cancer. Fluorescence microscope was used to observe the penetration of N-NBs and LHRH-NBs through the vascular endothelial gaps. Immunofluorescence was used to observe the penetration of N-NBs and LHRH-NBs through vascular endothelial gaps and binding to the tumor cells. RESULTS: The imaging intensity and duration were not significantly different between N-NBs and LHRH-NBs. The imaging intensity in the N-NB and LHRH-NB groups was not significantly different compared with the SonoVue group; however, the imaging duration in the N-NB and LHRH-NB groups was significantly longer than in the SonoVue group (P < 0.001). Both N-NBs and LHRH-NBs penetrated through the vascular endothelial gaps. After penetrating through the vascular endothelial gapes, LHRH-NBs could target and bind to the tumor cells. CONCLUSIONS: N-NBs and LHRH-NBs are of good imaging effectiveness and relatively long imaging duration. LHRH-NB is a potent contrast agent for imaging ovarian cancer, while achieving targeted delivery of drugs to the site of ovarian cancer.

Ethane-bridged periodic mesoporous organosilicas functionalized with high loadings of carboxylic acid groups: synthesis, bifunctionalization, and fabrication of metal nanoparticles.

Well-ordered periodic mesoporous organosilicas (PMOs) functionalized with high contents of carboxylic acid (COOH) groups, up to 85 mol % based on silica, were synthesized by co-condensation of 1,2-bis(triethoxysilyl)ethane (BTEE) and carboxyethylsilanetriol sodium salt (CES) under acidic conditions by using alkyl poly(oxyethylene) surfactant Brij 76 as a structure-directing agent. A variety of techniques including powder X-ray diffraction (XRD), nitrogen adsorption/desorption, Fourier-transformed infrared (FTIR), transmission electron microscopy (TEM), (13) C- and (29) Si solid-state nuclear magnetic resonance (NMR) were used to characterize the products. The materials thus obtained were used as an effective support to synthesize metal nanoparticles (Ag and Pt) within the channel of 2D hexagonal mesostructure of PMOs. The size and distribution of the nanoparticles were observed to be highly dependent on the interaction between the carboxylic acid functionalized group and the metal precursors. The size of Pt nanoparticles reduced from 3.6 to 2.5 nm and that of Ag nanoparticles reduced from 5.3 to 3.4 nm with the increase in the COOH loading from 10 to 50 %.

Effective multifocus image fusion based on HVS and BP neural network.

The aim of multifocus image fusion is to fuse the images taken from the same scene with different focuses to obtain a resultant image with all objects in focus. In this paper, a novel multifocus image fusion method based on human visual system (HVS) and back propagation (BP) neural network is presented. Three features which reflect the clarity of a pixel are firstly extracted and used to train a BP neural network to determine which pixel is clearer. The clearer pixels are then used to construct the initial fused image. Thirdly, the focused regions are detected by measuring the similarity between the source images and the initial fused image followed by morphological opening and closing operations. Finally, the final fused image is obtained by a fusion rule for those focused regions. Experimental results show that the proposed method can provide better performance and outperform several existing popular fusion methods in terms of both objective and subjective evaluations.

Dual-tree complex wavelet transform and image block residual-based multi-focus image fusion in visual sensor networks.

This paper presents a novel framework for the fusion of multi-focus images explicitly designed for visual sensor network (VSN) environments. Multi-scale based fusion methods can often obtain fused images with good visual effect. However, because of the defects of the fusion rules, it is almost impossible to completely avoid the loss of useful information in the thus obtained fused images. The proposed fusion scheme can be divided into two processes: initial fusion and final fusion. The initial fusion is based on a dual-tree complex wavelet transform (DTCWT). The Sum-Modified-Laplacian (SML)-based visual contrast and SML are employed to fuse the low- and high-frequency coefficients, respectively, and an initial composited image is obtained. In the final fusion process, the image block residuals technique and consistency verification are used to detect the focusing areas and then a decision map is obtained. The map is used to guide how to achieve the final fused image. The performance of the proposed method was extensively tested on a number of multi-focus images, including no-referenced images, referenced images, and images with different noise levels. The experimental results clearly indicate that the proposed method outperformed various state-of-the-art fusion methods, in terms of both subjective and objective evaluations, and is more suitable for VSNs.

Neutrophil lncRNA ZNF100-6:2 is a potential diagnostic marker for active pulmonary tuberculosis.

Active pulmonary tuberculosis (PTB) poses challenges in rapid diagnosis within complex clinical conditions. Given the close association between neutrophils and tuberculosis, we explored differentially expressed long non-coding RNAs (lncRNAs) in neutrophils as potential molecular markers for diagnosing active PTB. We employed a gene microarray to screen for lncRNA alterations in neutrophil samples from three patients with active PTB and three healthy controls. The results revealed differential expression of 1457 lncRNAs between the two groups, with 916 lncRNAs upregulated and 541 lncRNAs down-regulated in tuberculosis patients. Subsequent validation tests demonstrated down-regulation of lncRNA ZNF100-6:2 in patients with active PTB, which was restored following anti-tuberculosis treatment. Our findings further indicated a high diagnostic potential for lncRNA ZNF100-6:2, as evidenced by an area under the receiver operating characteristic (ROC) curve of 0.9796 (95% confidence interval: 0.9479 to 1.000; P < 0.0001). This study proposes lncRNA ZNF100-6:2 as a promising and novel diagnostic biomarker for active PTB.

Hydrogen sulfide protects cardiomyocytes from doxorubicin-induced ferroptosis through the SLC7A11/GSH/GPx4 pathway by Keap1 S-sulfhydration and Nrf2 activation.

Recent studies have demonstrated that ferroptosis, a novel form of nonapoptotic regulated cell death plays an important role in doxorubicin (DOX)-induced cardiotoxicity (DoIC). Hydrogen sulfide (H2S) is emerging as the third important gaseous mediator in cardiovascular system. However, whether H2S has an effect on DOX-induced ferroptosis remains unknown. Here, we found that DOX not only triggered cardiomyocyte ferroptosis but also significantly inhibited the synthesis of endogenous H2S in the murine model of chronic DoIC. Application of NaHS, an H2S donor obviously activated the SLC7A11/GSH/GPx4 antioxidant pathway and thus alleviated DOX-induced ferroptosis and cardiac injury in mice. In contrast, cardiac-specific knockout of cystathionine γ-lyase gene (Cse) in mice (Csef/f/Cre+) to abolish the cardiac synthesis of endogenous H2S evidently exacerbated DOX-induced ferroptosis and cardiac dysfunction. A further suppression of SLC7A11/GSH/GPx4 pathway was obtained in Csef/f/Cre+ mice with DoIC, as compared to Csef/f/Cre- mice with DoIC. The aggravation caused by cardiac-specific Cse deficiency was remarkably rescued by exogenous supplementation of NaHS. Moreover, in DOX-stimulated H9c2 cardiomyocytes, pretreatment with NaHS dose-dependently enhanced the activity of SLC7A11/GSH/GPx4 pathway and subsequently mitigated ferroptosis and mitochondrial impairment. On the contrary, transfection with Cse siRNA in DOX-stimulated H9c2 cardiomyocytes markedly inhibited SLC7A11/GSH/GPx4 pathway, thus leading to aggravated ferroptosis and more damage to mitochondrial structure and function. In addition, the protective effect of NaHS on DOX-induced ferroptosis was closely related to the S-sulfhydrated Keap1, which in turn promoted nuclear translocation of Nrf2 and the transcription of SLC7A11 and GPx4. In conclusion, our findings suggest that H2S may exert protective effect on DoIC by inhibiting DOX-induced ferroptosis via Keap1/Nrf2-dependent SLC7A11/GSH/GPx4 antioxidant pathway.