Carboxymethyl chitosan-methacrylic acid gelatin hydrogel for wound healing and vascular regeneration.

At present, wound dressings in clinical applications are primarily used for superficial skin wounds.However these dressings have significant limitations, including poor biocompatibility and limited ability to promote wound healing. To address this issue, t this study used aldehyde polyethylene glycol as the cross-linking agent to design a carboxymethyl chitosan-methacrylic acid gelatin hydrogel with enhanced biocompatibility, which can promote wound healing and angiogenesis.The CSDG hydrogel exhibites acid sensitivity, with a swelling ratio of up to 300%. Additionally, it exhibited excellent resistance to external stress, withstanding pressures of up to 160 kPa and self-deformation of 80%. Compared to commercially available chitosan wound gels, the CSDG hydrogel demonstrates excellent biocompatibility, antibacterial properties, and hemostatic ability. Both in vitro and in vivo results showed that the CSDG hydrogel accelerated blood vessel regeneration by upregulating the expression of CD31, IL-6, FGF, and VEGF, thereby promoting rapid healing of wounds. In conclusion, this study successfully prepared the CSDG hydrogel wound dressings, providing a new approach and method for the development of hydrogel dressings based on natural macromolecules. .

Development and evaluation of a new luciferase immunosorbent assay to detect GII.6 norovirus-specific IgG in different domestic and wild animals.

Noroviruses (NoVs) are the leading viral pathogens globally causing acute gastroenteritis (AGE) in humans, posing a significant global health threat and economic burden. Recent investigations revealed that human NoVs had been detected in different animals, which raises concerns about whether NoVs are potential zoonotic diseases. This study developed a novel luciferase immunosorbent assay (LISA) to detect GII.6 NoV IgG based on P protein of VP1. The LISA showed high specificity (99.20%) and sensitivity (92.00%) with 4-16 times more sensitivity compared with an ELISA. NoV-LISA was reproducible with human serum regarding the inter- and intra-assay coefficient of variance values. Potential cross-reactivity was also evaluated using mice serum immunized by other antigens, which showed that NoV-LISA could differentiate GII.6 NoV from rotavirus and various genotypes of NoV. Specific GII.6 NoV IgG was widely detected in different domestic and wild animals, including dogs, pigs, bats, rats, and home shrews, with various IgG-positive rates ranging from 2.5 to 74.4%. In conclusion, our newly developed NoV-LISA assay is suitable for NoV-specific IgG detection in humans and animals. The wide distribution of IgG antibodies against human NoV indicates potential zoonotic transmission between humans and animals.

Serological surveillance of GI norovirus reveals persistence of blockade antibody in a Jidong community-based prospective cohort, 2014-2018.

Introduction: Herd immunity against norovirus (NoV) is poorly understood in terms of its serological properties and vaccine designs. The precise neutralizing serological features of genotype I (GI) NoV have not been studied. Methods: To expand insights on vaccine design and herd immunity of NoVs, seroprevalence and seroincidence of NoV genotypes GI.2, GI.3, and GI.9 were determined using blockade antibodies based on a 5-year longitudinal serosurveillance among 449 residents in Jidong community. Results: Correlation between human histo-blood group antigens (HBGAs) and GI NoV, and dynamic and persistency of antibodies were also analyzed. Seroprevalence of GI.2, GI.3, and GI.9 NoV were 15.1%-18.0%, 35.0%-38.8%, and 17.6%-22.0%; seroincidences were 10.0, 21.0, and 11.0 per 100.0 person-year from 2014 to 2018, respectively. Blockade antibodies positive to GI.2 and GI.3 NoV were significantly associated with HBGA phenotypes, including blood types A, B (excluding GI.3), and O+; Lewis phenotypes Leb+/Ley+ and Lea+b+/Lex+y+; and secretors. The overall decay rate of anti-GI.2 antibody was -5.9%/year (95% CI: -7.1% to -4.8%/year), which was significantly faster than that of GI.3 [-3.6%/year (95% CI: -4.6% to -2.6%/year)] and GI.9 strains [-4.0%/year (95% CI: -4.7% to -3.3%/year)]. The duration of anti-GI.2, GI.3, and GI.9 NoV antibodies estimated by generalized linear model (GLM) was approximately 2.3, 4.2, and 4.8 years, respectively. Discussion: In conclusion, enhanced community surveillance of GI NoV is needed, and even one-shot vaccine may provide coast-efficient health benefits against GI NoV infection.

Under-five mortality in Sierra Leone and possible associated factors: evidence from the 2019 Demographic and Health Survey.

High under-five mortality rate remains one of the public health challenges, especially in Sub-Saharan Africa, accounting for more than half of all global cases. Sierra Leone was and is still one of the countries with the highest under-five mortality rate. Using the latest 2019 Sierra Leone Demographic and Health Survey data, we investigated factors associated with under-five mortality in Sierra Leone. A total of 9771 mothers aged 15-49 years in the country were interviewed and included in the analysis. The dependent variable is child status (dead = 1; alive = 0). A total of 871 (9%) children died before their fifth birthday. The maternal age of 20-24 years [adjusted odds ratios (AOR) = 0.46; 95% confidence interval (CI) = 0.33-0.64; P < 0.001] up to 40-44 years (AOR = 0.43; CI = 0.27-0.7; P = 0.001), currently breastfeeding (AOR = 0.20; CI = 0.17-0.24; P < 0.001), maternal media exposure and usage of reading newspapers/magazines less than once a week (AOR = 0.48; CI = 0.28-0.85; P = 0.011) were more likely to enhance child survivability through their fifth birthday. Also, the child sex being female (AOR = 0.68; CI = 0.59-0.79) was more likely to survive under-five mortality compared to their male counterpart. On the other hand, mothers who listened to radio at least once a week (AOR = 1.31; CI = 1.08-1.59; P = 0.007) watched television less than once a week (AOR = 1.48; CI = 1.16-1.90), had two (AOR = 3.4, CI = 2.78-4.16; P < 0.001) or three and above birth (AOR = 8.11; CI = 6.07-10.83; P < 0.001) in five years, had multiple birth children (AOR = 1.41; CI = 1.08-1.86) and very small-sized child at birth (AOR= 1.95; CI = 1.41-2.70) were more likely to lose their children below the age of 5 years. The factors contributing to under-five mortality in Sierra Leone are critical to ensuring child survival and improving maternal health. Breastfeeding, maternal age, media exposure, child's sex, multiple birth type, very small-sized child and the total number of births in 5 years were significant drivers of under-five mortality. The result affirms the need for attention to be focused on enhancing the survival rate of under-five children in Sierra Leone.

miR-152-mediated MKK7 downregulation is attenuated by MYCNOS in ovarian adenocarcinoma.

MYCN opposite strand (MYCNOS) acts as an oncogenic long non-coding RNA in liver cancer. However, its role in other cancer types is unknown. The aim of the present study was to investigate the function of MYCNOS in ovarian adenocarcinoma (OA). MYCNOS expression in OA was determined using reverse transcription-quantitative PCR (RT-qPCR), and its prognostic value for OA was evaluated in a 5-year follow-up study. The predicted interaction between MYCNOS and microRNA (miR)-152 was confirmed using a dual luciferase reporter assay. The association between MYCNOS and miR-152 was also analyzed in overexpression experiments. The effects of MYCNOS and miR-152 on mitogen-activated protein kinase kinase 7 (MKK7) expression were explored using RT-qPCR and western blotting. Cell proliferation was analyzed using a Cell Counting Kit-8 assay. MYCNOS expression was found to be upregulated in OA and predicted poor survival. In addition, MYCNOS was predicted to interact with miR-152, and a dual luciferase assay confirmed this interaction. However, MYCNOS and miR-152 overexpression did not affect their mutual expression levels. MYCNOS overexpression upregulated MKK7, a target of miR-152. Cell proliferation increased following simultaneous MYCNOS and MKK7 overexpression, but was reduced following miR-152 overexpression. Moreover, MYCNOS overexpression attenuated the effects of miR-152 overexpression. In conclusion, MYCNOS may act by sponging miR-152 to upregulate MKK7 expression in OA, thereby promoting cell proliferation.

Variability in Cardiometabolic and Inflammatory Parameters and Cognitive Decline.

INTRODUCTION: The relationship between variability in cardiometabolic and inflammatory parameters and cognitive changes is unknown. This study investigates the association of visit-to-visit variability in BMI, mean arterial pressure, total cholesterol, triglycerides, HbA1c, high-sensitivity C-reactive protein, ferritin, and fibrinogen with cognitive decline. METHODS: This population-based cohort study included 2,260 individuals (mean age=63.0 [SD=7.5] years) free of cognitive diseases who underwent ≥3 clinical measurements from 2004 to 2019. Variability was expressed as variability independent of the mean across visits. Participants were divided on the basis of quartiles of variability score, a scoring system generated to explore the composite effect of parameter variability (range=0-24), where 0 points were assigned for Quartile 1, 1 point was assigned for Quartile 2, 2 points were assigned for Quartile 3, and 3 points were assigned for Quartile 4, each for the variability of 8 parameters measured as variability independent of the mean. Linear mixed models evaluated the longitudinal associations with cognitive decline in memory and verbal fluency. All analyses were conducted in 2020-2021. RESULTS: Higher BMI, mean arterial pressure, total cholesterol, HbA1c, and ferritin variability were linearly associated with cognitive decline irrespective of their mean values. In addition, participants in the highest quartile of variability score had a significantly worse cognitive decline rate in memory (-0.0224 points/year, 95% CI= -0.0319, -0.0129) and verbal fluency (-0.0088 points/year, 95% CI= -0.0168, -0.0008) than those in the lowest quartile. CONCLUSIONS: A higher variability in cardiometabolic and inflammatory parameters was significantly associated with cognitive decline. Stabilizing these parameters may serve as a target to preserve cognitive functioning.

Serological surveillance of noroviruses in a community-based prospective cohort: a study protocol.

INTRODUCTION: Noroviruses are the leading cause of viral acute gastroenteritis affecting all age groups. Since 2014, the previous rarely reported GII.P17-GII.17 and recombinant GII.P16-GII.2 norovirus emerged, replacing GII.4 predominant genotype, causing increased outbreaks in China and other countries. Meanwhile, GII.4/2012 Sydney strain has re-emerged as the dominant variant in many places in 2015-2018. The role of herd immunity as the driving force during these new emerging or re-emerging noroviruses is poorly defined. Serological surveillance studies on community-based prospective cohort on norovirus are highly needed. METHODS AND ANALYSES: This study will include 1000 out of 9798 participants aged 18 years and above from Caofeidian district, Tangshan city, northern China. Baseline data on sociodemographic characteristics and blood samples were collected in 2013-2014. Blood collection will be replicated annually throughout the cohort until 2023. Saliva samples were also collected in 2016. The seroprevalence and seroincidence of blockade antibodies against norovirus genotypes of GII.P17-GII.17, GII.P16-GII.2, the re-emerged GII.4/2012 and potential novel pandemic variants will be evaluated by ELISA. Associations between genotype blockade antibodies and sociodemographic factors and human histo-blood group antigens will be evaluated using univariate and multivariate analysis. The dynamics of herd immunity duration will be estimated in this longitudinal surveillance. ETHICS AND DISSEMINATION: The study has been approved by the Ethical Committees of the Staff Hospital of Jidong oil-field of China National Petroleum Corporation. This study will provide insight into the seroprevalence and seroincidence of noroviruses, and their relationships with sociodemographic characteristics and genetic susceptibility. It will also explain herd immunity of the emerged and re-emerged genotypes or variants. The study will further enable an understanding of the mechanism driving the replacement of norovirus genotypes. Research findings will be disseminated in peer-reviewed journals and at scientific meetings.

Characterization of Antigenic Relatedness Among GI Norovirus Genotypes Using Serum Samples From Norovirus-Infected Patients and Mouse Sera.

Characterizing diversity and the antigenic relatedness of norovirus remains a primary focus in understanding its biological properties and vaccine designs. The precise antigenic and serological features of GI genotypes have not been studied. The study represented an investigation on a gastroenteritis outbreak related to GI.3 norovirus and the three most detected GI genotypes, GI.2 (belonging to immunotype B), GI.3 and GI.9 (belonging to immunotype C), were selected to characterize their phylogenetic relationship, HBGA binding profiles and antigenic relatedness within (intra-immunotype), and between (inter-immunotypes) genotypes using mouse sera and patient's serum samples from the GI.3 related outbreak. Wide HBGA binding profiles and evolution of binding affinity were observed in the three GI genotypes studied. A low specific blockade antibody to GI.3 in the population generated the pool of susceptible individuals and supported virus spread in the outbreak. We found strong blockade immune response in homologous strains, moderate intra-immunotype blockade but weak inter-immunotypes blockade in humans following GI.3 norovirus infections. These findings further support the immunotypes grouping and will be valuable for optimizing the design of norovirus vaccine.

H19 Rises in Gastric Cancer and Exerts a Tumor-Promoting Function via miR-138/E2F2 Axis.

PURPOSE: The aim of this paper was to investigate H19 expression in gastric cancer (GC) and its effects on the biological behavior of gastric cancer cells (GCCs), and at exploring its potential mechanism. METHODS: H19 expression in the patients' tissues and serum was detected, and the correlation of the expression with the patients' pathological data and survival rate was analyzed. Overexpression or inhibitory vectors of H19, microRNA-138 (miR-138) and E2F2 were constructed and transfected into GCCs to observe their effects on the cells' proliferation, invasion and apoptosis. RESULTS: H19 rose in GC and was higher in GC patients with a tumor size ≥5 cm, high stages (III+IV) and lymph node metastasis. High H19 expression was associated with the poorer survival rate of the patients, so serum H19 had a certain diagnostic value for GC. H19 knockdown could inhibit GCCs to proliferate and invade and induce their apoptosis. miR-138 can be used as the target gene of H19, and E2F2 can be negatively regulated by this miR, so miR-138 knockdown or E2F2 upregulation can weaken GCCs' biological behavior changes that were caused by H19 knockdown. CONCLUSION: H19 can be used as a biological indicator for diagnosing GC and predicting patients' poor prognosis. Additionally, it promotes GCCs to proliferate and invade through miR-138/E2F2 axis.

Early prediction of noninvasive ventilation failure in COPD patients: derivation, internal validation, and external validation of a simple risk score.

BACKGROUND: Early identification of noninvasive ventilation (NIV) failure is a promising strategy for reducing mortality in chronic obstructive pulmonary disease (COPD) patients. However, a risk-scoring system is lacking. METHODS: To develop a scale to predict NIV failure, 500 COPD patients were enrolled in a derivation cohort. Heart rate, acidosis (assessed by pH), consciousness (assessed by Glasgow coma score), oxygenation, and respiratory rate (HACOR) were entered into the scoring system. Another two groups of 323 and 395 patients were enrolled to internally and externally validate the scale, respectively. NIV failure was defined as intubation or death during NIV. RESULTS: Using HACOR score collected at 1-2 h of NIV to predict NIV failure, the area under the receiver operating characteristic curves (AUC) was 0.90, 0.89, and 0.71 for the derivation, internal-validation, and external-validation cohorts, respectively. For the prediction of early NIV failure in these three cohorts, the AUC was 0.91, 0.96, and 0.83, respectively. In all patients with HACOR score > 5, the NIV failure rate was 50.2%. In these patients, early intubation (< 48 h) was associated with decreased hospital mortality (unadjusted odds ratio = 0.15, 95% confidence interval 0.05-0.39, p < 0.01). CONCLUSIONS: HACOR scores exhibited good predictive power for NIV failure in COPD patients, particularly for the prediction of early NIV failure (< 48 h). In high-risk patients, early intubation was associated with decreased hospital mortality.

[The efficacy of autocatalytic casapse-3 driven by human telomerase reverse transcriptase promoter on human ovarian carcinoma].

OBJECTIVE: To construct recombinant adenoviral vector expressing autocatalysis caspase-3 driven by human telomerase reverse transcriptase promoter (hTERTp), and investigate its antitumor effect on ovarian cancer in vitro and in vivo. METHODS: Recombinant adenovirus expressing autocatalytic caspase-3 (rev-csapase-3) driven by hTERTp, AdHT-rev-casp3, was constructed. Ad-rev-casp3 expressing rev-caspase-3 driven by cytomegalovirus promoter (CMVp) was used as a positive control. hTERT positive human ovarian cancer cells of the line AO and hTERT-negative human umbilical venous endothelial cells (HUVECs) were cultured and transfected with AdHT-rev-casp3, Ad-rev-casp3, or Ad-EGFG expressing enhanced green fluorescent protein as control group. Western blotting, Cell Counting Kit (CCK-8), flow cytometry, and TUNEL were used to detect the expression of p17, active subunit of caspase-3, and p85, a poly ADP-ribose polymerase (PARP) cleavage fragment, and they were also used to measure the cell survival rate and apoptotic rate. Western blotting was used to detect the expression of active caspase-3 and its substrate PARP in the AO cells and HUVECs. Twenty nude BALB/c mice were inoculated subcutaneously with AO cells to establish subcutaneous tumor models, when the tumor grew to the volume of 150 mm3 the rats were divided into 4 equal groups to undergo intra-tumor injection of AdHT-rev-casp3, Ad-rev-casp3, Ad-EGFG, and phosphate-buffered saline (PBS) respectively, the survival rate tumor inhibition rate was observed, 72 days later the mice were killed with their livers and tumors taken out, and Western blotting was used to detect the expression of active caspase-3. Another 40 mice underwent intraperitoneal injection of AO cells to establish intraperitoneal transplanted tumor models, 21 days later the rats were divided into 4 equal groups to be injected intraperitoneally with AdHT-rev-casp3, Ad-rev-casp3, Ad-EGFG, or PBS, the survival rate was observed, and the blood levels of alanine transaminase (ALT) and aspartate transaminase (AST) were detected. RESULTS: Following the administration of AdHT-rev-casp3, active caspase-3 protein was significantly expressed, and the levels of p17 and p85 expressions were significantly elevated in AO cells, while no expressions of p17 and p85 was observed in HUVEC. In contrast, both AO and HUVEC expressed high levels of p17 and p85 protein after administrations of Ad-rev-casp3. AdHT-rev-casp3 dose-dependently killed the hTERT positive AO cells, however, showed no killing effect on the hTERT-negative HUVEC cells; whereas Ad-rev-casp3 was cytotoxic independent of the hTERT status of the cells. The killing effect of Ad-rev-casp3 was stronger than that of AdHT-rev-casp3. Treated with AdHT-rev-cap3 the expression levels of the caspase-3 fragment p17 and PARP cleavage fragment p85 of the AO cells were significantly higher than those before the treatment, however, the expression levels of p17 and p85 were both weaker than those of the AO cells treated with Ad-rev-casp-3. Though treated with AdHT-rev-casp-3, there was still no remarkable expression of p17 and p85 in the HUVECs, however, rather high protein expression levels of p17 and p85 was shown. After treatment with AdHT-rev-casp3 remarkable expression of active caspase-3 was seen in the tumor collected from the mouse body, but not in the liver; however, high caspase-3 expression level was shown in both the liver and tumor after the treatment of Ad-rev-casp-3. 53 days after treatment the tumor suppression rate of the AdHT-rev-casp3 and ad-rev-casp-3 groups were 60% and 70% respectively, both significantly higher than that of the control group. The survival rates of the mice treated with AdHT-rev-casp3 and Ad-rev-casp-3 were both significantly longer than that of the PBS group; however the survival rate of the Ad-rev-casp-3 group was longer than that of the AdHT-rev-casp3 group. The serum ALT and AST levels were not significantly elevated in the AdHT-rev-casp3-treated mice, whereas 7-9-times that before treatment in the Ad-rev-casp3-treated mice. CONCLUSION: Recombinant adenovirus AdHT-rev-casp3 expressing rev-caspase-3 driven by hTERTp effectively causes cell apoptosis targeting tumor, significantly suppresses tumor growth and prolongs the mouse survival duration, with mild liver toxicity.