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BackgroundEstimated pulse wave velocity (ePWV), which measures vascular aging, is an independent predictor of cardiovascular death. Nevertheless, the relationship between ePWV and all-cause mortality among patients suffering from non-traumatic subarachnoid hemorrhages (NSAH) remains obscure. Consequently, the objective of this study is to ascertain whether ePWV exerts influence on the prognosis of individuals afflicted with NSAH.MethodsThrough the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, 644 eligible participants were included. The Kaplan–Meier survival curve method was employed to assess the disparity in survival status between the low and high ePWV cohorts. The Cox proportional hazard model was employed to investigate the association between ePWV and inpatient mortality among critically ill patients diagnosed with NSAH. The Restricted Cubic Spline (RCS) model was employed to examine the dose–response correlation. Subsequently, multivariate Cox regression analysis was performed to identify independent prognostic factors. Lastly, the impact of ePWV on inpatient mortality across various subgroups was evaluated through stratified analysis.ResultsParticipants were categorized into two groups, delineated by their ePWV levels: a low ePWV level group and a high ePWV level group. Survival analysis unveiled that individuals with high ePWV exhibited a diminished survival rate compared to their counterparts with low ePWV. Following adjustment, low ePWV was significantly linked with a reduced risk of inpatient mortality among patients with NSAH (HR = 0.54, 95% CI = 0.32–0.89, p = 0.016). Simultaneously, analysis employing the RCS model further substantiated a linear escalation in the risk of inpatient mortality with increasing ePWV values.ConclusionElevated ePWV levels have been identified as an independent risk factor for the rise in inpatient mortality among NSAH patients and as a significant predictor of the clinical outcome of NSAH.

Abstract Sharing of genetic elements among different pathogens and commensals inhabiting same hosts and environments has significant implications for antimicrobial resistance (AMR), especially in settings with high antimicrobial exposure. We analysed 661 Escherichia coli and Salmonella enterica isolates collected within and across hosts and environments, in 10 Chinese chicken farms over 2.5 years using data-mining methods. Most isolates within same hosts possessed the same clinically relevant AMR-carrying mobile genetic elements (plasmids: 70.6%, transposons: 78%), which also showed recent common evolution. Supervised machine learning classifiers revealed known and novel AMR-associated mutations and genes underlying resistance to 28 antimicrobials, primarily associated with resistance in E. coli and susceptibility in S. enterica. Many were essential and affected same metabolic processes in both species, albeit with varying degrees of phylogenetic penetration. Multi-modal strategies are crucial to investigate the interplay of mobilome, resistance and metabolism in cohabiting bacteria, especially in ecological settings where community-driven resistance selection occurs.

Abstract Background Clostridium butyricum (CB) is a probiotic that can regulate intestinal microbial composition and improve meat quality. Rumen protected fat (RPF) has been shown to increase the dietary energy density and provide essential fatty acids. However, it is still unknown whether dietary supplementation with CB and RPF exerts beneficial effects on growth performance and nutritional value of goat meat. This study aimed to investigate the effects of dietary CB and RPF supplementation on growth performance, meat quality, oxidative stability, and meat nutritional value of finishing goats. Thirty-two goats (initial body weight, 20.5 ± 0.82 kg) were used in a completely randomized block design with a 2 RPF supplementation (0 vs. 30 g/d) × 2 CB supplementation (0 vs. 1.0 g/d) factorial treatment arrangement. The experiment included a 14-d adaptation and 70-d data and sample collection period. The goats were fed a diet consisted of 400 g/kg peanut seedling and 600 g/kg corn-based concentrate (dry matter basis). Result Interaction between CB and RPF was rarely observed on the variables measured, except that shear force was reduced (P

Abstract Background Gastric cancer patients harboring a TP53 mutation exhibit a more aggressive and chemoresistant phenotype. Unfortunately, efforts to identify the vulnerabilities to overcome these aggressive malignancies have made minimal progress in recent years. Therefore, there is an urgent need to explore the novel therapeutic strategies for this subclass. Histone methylation modulators are critical epigenetic targets for cancer therapies that help maintain the malignancies of cancers harboring TP53 mutations and senescence evasion. Triggering senescence is now considered to benefit multiple cancer therapies. Furthermore, senescence-based “one-two punch” therapy was validated in clinical trials. Therefore, we hypothesized that screening epigenetic modulators might help identify a novel vulnerability to trigger senescence in gastric cancer harboring TP53 mutations. Results We developed a novel efficient approach to identify senescence inducers by sequentially treating cells with drug candidates and senolytic agents. Based on this, we demonstrated that QC6352 (a selective KDM4C inhibitor) efficiently triggered cellular senescence in gastric cancer harboring TP53 mutations. More importantly, the “one-two punch’ therapy consisting of QC6352 and SSK1 eliminates tumor cells harboring TP53 mutations. This finding highlights a potential therapeutic strategy for the aggressive subgroup of gastric cancer. Besides, the functions of QC6352 were totally unknown. We demonstrated that QC6352 might possess far more powerful anti-tumor capacities compared to the traditional genotoxic drugs, 5-Fu and Oxaliplatin. Conclusions This initial investigation to identify a senescence inducer revealed that QC6352 triggers senescence in gastric cancer cells harboring TP53 mutations by regulating the SP1/CDK2 axis through suppressing KDM4C. QC6352 and senolytic agent-SSK1 represent a novel ‘one-two punch’ therapeutic strategy for the more malignant gastric cancer subtypes.

Porcine epidemic diarrhea virus (PEDV) causes porcine epidemic diarrhea (PED), a highly infectious disease, which has resulted in huge economic losses for the pig industry. To date, the pathogenic and immune response mechanism was not particularly clear. The purpose of this study was to investigate the pathogenic and immune responses of pigs infected with PEDV.In this study, 12 Min pigs were randomly selected without taking colostrum. At 3 days old, eight piglets were infected with 1 mL of PEDV solution (10 TCID50/ml), and the remaining four piglets were handled by 1 mL of 0.9% normal saline. Within the age of 7 days old, four piglets died and were considered as the death group. Correspondingly, four alive individuals were classified into the resistance group. Tissues of the duodenum, jejunum, ileum, colon, cecum, and rectum of piglets in the three groups were collected to measure the PEDV content. Additionally, the jejunum was used for the measurements and analyses of Hematoxylin-eosinstaining (HE), immunohistochemical sections, and transcriptomics. The phenotypes of Min piglets infected with PEDV showed that the viral copy numbers and jejunal damage had significant differences between the death and resistance groups. We also observed the transcriptome of the jejunum, and the differentially expressed (DE) analysis observed 6,585 DE protein-coding genes (PCGs), 3,188 DE long non-coding RNAs (lncRNAs), and 350 DE microRNAs (miRNAs), which were mainly involved in immune response and metabolic pathways. Furthermore, the specific expressed molecules for each group were identified, and 97 PCGs,108 lncRNAs, and 51 miRNAs were included in the ceRNA-regulated networks. By weighted gene co-expression network analysis (WGCNA) and transcription factor (TF) prediction, 27 significant modules and 32 significant motifs (E-value < 0.05) annotated with 519 TFs were detected. Of these TFs, 53 were DE PCGs. In summary, the promising key PCGs, lncRNAs, and miRNAs related to the pathogenic and immunological response of pigs infected with PEDV were detected and provided new insights into the pathogenesis of PEDV.

ABSTRACT Hepatitis E virus (HEV) is a zoonotic pathogen that is widespread worldwide. At present, most enzyme-linked immunosorbent assay (ELISA) kits only detect antibodies against human HEV. In this study, a nanobody-horseradish peroxidase (HRP) fusion protein-based competitive ELISA (cELISA) with more convenience and spectral characteristics for HEV antibody detection was developed and used to detect HEV IgG in various species. First, 6 anti-swine HEV capsid protein nanobodies were screened using phage display technology from an immunized Bactrian camel. Then, HEV-Nb67-HRP fusions were expressed and used as a probe for developing a cELISA. The cutoff value of the cELISA was 17.8%, and there was no cross-reaction with other anti-swine virus antibodies, suggesting that the cELISA had good specificity. The intra-assay and interassay coefficients of variation (CVs) were 1.33 to 5.06% and 1.52 to 6.84%, respectively. The cELISA and Western blot showed a higher coincidence rate (97.14%, kappa value = 0.927) than cELISA and indirect ELISA (95.00%, kappa value = 0.876) in clinical swine serum samples. Finally, the seroprevalence of HEV IgG in humans, pigs, rabbits, cows, and goats was 30.67%, 19.26%, 8.75%, 27.59%, and 18.08%, respectively, suggesting that cELISA may have a broader scale for mammalian HEV antibody detection. These results suggest that the newly developed cELISA was rapid, low-cost, reliable, and useful for the serological evaluation of current HEV. IMPORTANCE HEV is thought to be a zoonotic infection and is widespread worldwide; it is beneficial to establish a more convenient and spectral method for HEV antibody detection. In this study, a convenient, time-saving, reproducible, highly sensitive, specific, and novel nanobody-based cELISA was developed and can be used to detect IgG antibodies against mammalian HEV. It provides a new technique for serological evaluation and ELISA-based diagnosis of HEV infection.

Candida albicans is a clinically significant opportunistic fungus that is generally treated with antifungal drugs such as itraconazole and fluconazole. However, the recent emergence of fungal resistance has made treatment increasingly difficult. Therefore, novel antifungal treatment methods are urgently required. Hexanol ethosome photodynamic therapy (HE-PDT) is a method that uses photosensitizers (PS), such as hexanol ethosome, to exert antifungal effects, and can be used to treat resistant fungal strains. However, due to the high dose of PS required for antifungal treatment, excess photosensitizers may remain. Furthermore, once exposed to light, normal tissues or cells are damaged after photodynamic therapy, which limits the clinical application of HE-PDT. Therefore, improving the efficacy without increasing the dose is the key to this treatment. In this study, the antifungal effect of copper sulfate combined with HE-PDT was investigated, and its mechanism was explored. The results suggested that exogenous copper sulfate significantly increased the antifungal effect of HE-PDT by enhancing the rate of C. albicans inhibition, increasing reactive oxygen species (ROS) accumulation, increasing the rate of apoptosis, and altering the mitochondrial membrane potential (MMP) and ATP concentration, which is related to the downregulation of apoptosis-inducing factor (AIF1) expression. In conclusion, copper sulfate combined with photodynamic therapy significantly inhibited the activity of C. albicans by inducing apoptosis. The combined approach reported herein provides new insights for future antifungal therapy.

Abstract Background Hepatitis E virus (HEV) genotypes 3 and 4 are zoonotic. In this study, HEV infection in laboratory Bama miniature pigs in Sichuan Province of China was investigated. Firstly, one hundred rectal swabs were collected for HEV RNA testing, and chose positive samples for sequence analysis. Concurrently, for pathogenicity study, six healthy Bama miniature pigs were randomly divided into two groups of 3 pigs each. A total of 500 μL of HEV stock (positive fecal samples identified in this study) was inoculated intravenously into each pig in the experimental group, and the three pigs in the other group served as negative controls. Serum and fecal samples were collected at 1 to 10 weeks post-inoculation (wpi) for alanine aminotransferase (ALT) levels, anti-HEV antibodies and HEV RNA detection, respectively. During necropsies, liver lesions and HEV antigen in liver were observed at 10 wpi. Results The rate of fecal sample HEV RNA-positivity was 12% (12/100). Sequence comparisons indicated that partial ORF1 and ORF2 gene sequences of this isolate shared highest identities with corresponding sequences of genotype 4a HEV isolates (81.4%-96.1% and 89.9%-97.1%, respectively). Phylogenetic tree analysis further demonstrated that sequences of this isolate clustered together with sub-genotype 4a HEV isolate sequences. Experimentally, the pathogenicity of Bama miniature pigs infected with this isolate exhibited viremia, fecal virus shedding, seroconversion, ALT level increasing, liver lesions and HEV antigen in liver. Conclusions This is the first study to confirm that HEV is currently circulating in laboratory Bama miniature pigs in China and this isolate can successfully infect Bama miniature pigs experimentally. More importantly, this study suggested HEV screening of laboratory pigs should be conducted to prevent research personnel from acquiring zoonotic HEV infections.

ABSTRACT: Avian hepatitis E virus (avian HEV) increases poultry mortality and decreases egg production, leading to huge economic losses worldwide. However, there is no effective serological test for avian HEV. Researchers previously created a testing platform using the nanobody (Nb)-horseradish peroxidase (HRP) fusion protein as an ultrasensitive probe to develop competitive ELISA (cELISA) to detect antibodies against different animal viruses. In this study, a rapid and reliable cELISA was developed to test for antibodies against avian HEV using the same platform. Six anti-avian HEV capsid protein nanobodies were selected from an immunized Bactrian camel using phage display technology. The avian HEV-Nb49-HRP fusion protein was expressed and used as a probe for developing a cELISA assay to test for avian HEV antibodies. The cut-off value of the developed cELISA was 22.0%. There was no cross-reaction with other anti-avian virus antibodies, suggesting that the cELISA had good specificity. The coefficients of variation were 0.91% to 4.21% (intra-assay) and 1.52% to 6.35% (inter-assay). Both cELISA and indirect ELISA showed a consistency of 86.7% (kappa = 0.738) for clinical chicken serum samples, and coincidence between cELISA and Western blot was 96.0% (kappa = 0.919). The epitope recognized by Nb49 was located in aa 593-604 of the avian HEV capsid protein, and the peptide (TFPS) in aa 601-604 was essential for binding. The novel cELISA is a saving cost, rapid, useful, and reliable assay for the serological investigation of avian HEV. More importantly, the peptide TFPS may be crucial to immunodominant antigen composition and protection.

Abstract Triple negative (TN) breast cancer is a subtype of breast cancer which is difficult for early detection and the prognosis is poor. In this paper, 910 benign and 934 malignant (110 TN and 824 NTN) B-mode breast ultrasound images were collected. A Resnet50 deep convolutional neural network was fine-tuned. The results showed that the averaged area under the receiver operating characteristic curve (AUC) of discriminating malignant from benign ones were 0.9789 (benign vs. TN), 0.9689 (benign vs. NTN). To discriminate TN from NTN breast cancer, the AUC was 0.9000, the accuracy was 88.89%, the sensitivity was 87.5%, and the specificity was 90.00%. It showed that the computer-aided system based on DCNN is expected to be a promising noninvasive clinical tool for ultrasound diagnosis of TN breast cancer.

ABSTRACT Substantial drug resistance afforded by Candida albicans biofilms results in ineffective treatment with conventional drugs and persistent infection. Our previous study showed that hexyl-aminolevulinate ethosomes (HAL-ES) act against C. albicans biofilms and weaken their drug resistance and pathogenicity; however, the mechanism involved remains unclear. Here, we systematically evaluated the effects and mechanisms of HAL-ES on biofilm formation and drug resistance. We found that, in addition to mediating antifungal photodynamic therapy, HAL-ES inhibited the early, developmental, and mature stages of biofilm formation compared with fluconazole, HAL, or ES. Notably, adhesion and hyphal formation were significantly inhibited by postdrug effects even after brief exposure (2 h) to HAL-ES. Its therapeutic effect in vivo also has been demonstrated in cutaneous candidiasis. RNA sequencing and quantitative PCR showed that HAL-ES inhibited ribosome biogenesis by disrupting zinc homeostasis in C. albicans, thereby reducing the translation process during protein synthesis. Furthermore, HAL-ES downregulated the expression of multidrug resistance genes and increased fluconazole susceptibility in C. albicans. Our findings provide a novel and efficient method for the treatment of biofilm resistance in C. albicans infection as well as a basis for the application of HAL-ES. We also describe a new strategy for the treatment of biofilm-related infections via zinc restriction. IMPORTANCE Candida albicans is the most prevalent fungal species of the human microbiota. The medical impact of C. albicans on its human host depends on its ability to form biofilms. The intrinsic resistance conferred by biofilms to conventional antifungal drugs makes biofilm-based infections a significant clinical challenge. In this study, we demonstrate the attenuating effect of HAL-ES on C. albicans biofilm formation and drug resistance. Furthermore, we propose that HAL-ES inhibits protein translation by disrupting zinc homeostasis in C. albicans. This study not only provides a novel and effective therapeutic strategy against C. albicans biofilm but also proposes a new strategy to resolve C. albicans biofilm infection by disrupting zinc homeostasis.

Hepatitis E virus (HEV) is thought to be a zoonotic pathogen that causes serious economic loss and threatens human health. However, there is a lack of efficient antiviral strategies. As a more promising tool for antiviral therapy, nanobodies (also named single-domain antibodies, sdAbs) exhibit higher specificity and affinity than traditional antibodies. In this study, nanobody anti-genotype four HEV open reading frame 2 (ORF2) was screened using phage display technology, and two nanobodies (nb14 and nb53) with high affinity were prokaryotically expressed. They were identified to block HEV ORF2 virus like particle (VLP) sp239 (aa 368–606) absorbing HepG2 cells in vitro. With the previously built animal model, the detection indicators of fecal shedding, viremia, seroconversion, alanine aminotransferase (ALT) levels, and liver lesions showed that nb14 could completely protect rabbits from swine HEV infection, and nb53 partially blocked swine HEV infection in rabbits. Collectively, these results revealed that nb14, with its anti-HEV neutralizing activity, may be developed as an antiviral drug for HEV.

Biofilm formation is a fundamental part of life cycles of bacteria which affects various aspects of bacterial-host interactions including the development of drug resistance and chronic infections. In clinical settings, biofilm-related infections are becoming increasingly difficult to treat due to tolerance to antibiotics. Bacterial biofilm formation is regulated by different external and internal factors, among which quorum sensing (QS) signals and nucleotide-based second messengers play important roles. In recent years, different kinds of anti-biofilm agents have been discovered, among which are the Chinese herbal medicines (CHMs). CHMs or traditional Chinese medicines have long been utilized to combat various diseases around the world and many of them have the ability to inhibit, impair or decrease bacterial biofilm formation either through regulation of bacterial QS system or nucleotide-based second messengers. In this review, we describe the research progresses of different chemical classes of CHMs on the regulation of bacterial biofilm formation. Though the molecular mechanisms on the regulation of bacterial biofilm formation by CHMs have not been fully understood and there are still a lot of work that need to be performed, these studies contribute to the development of effective biofilm inhibitors and will provide a novel treatment strategy to control biofilm-related infections.

Background: Ischemic stroke, the most common stroke type, has threatened human life and health. Currently, intravenous thrombolysis and endovascular thrombectomy are the mainstream treatment methods, but they may cause cerebral ischemia-reperfusion injury (CIRI), which aggravates brain injury. Consequently, it is worthwhile to start with a study of CIRI mechanism to identify better prevention and treatment methods. Applying single-cell RNA sequencing (scRNA-seq) technology to further understand the biological functions of various cell types in CIRI will facilitate the intervention of CIRI. Methods: This study aimed to establish a rat middle cerebral artery occlusion (MCAO) model to simulate cerebral ischemia-reperfusion, perform enzymatic hydrolysis, and suspend cerebral cortex tissue edema. Single-cell transcriptome sequencing was used, combined with cluster analysis, t-distributed stochastic neighbor embedding (t-SNE) visualization, and other bioinformatics methods to distinguish cell subgroups while using gene ontology (GO) function enrichment and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment to reveal the biological function of each cell subgroup. Results: We identified 21 brain clusters with cell type-specific gene expression patterns and cell subpopulations, as well as 42 marker genes representing different cell subpopulations. The number of cells in clusters 0–3 increased significantly in MCAO group compared to that in the sham group, and nine-cell subpopulations exhibited remarkable differences in the number of genes. Subsequently, GO and KEGG analyses were performed on the top 40 differentially expressed genes (DEGs) in the six cell subpopulations with significant differences. These results indicate that biological processes and signaling pathways are involved in different cell subpopulations. Conclusions: ScRNA-seq revealed the diversity of cell differentiation and the unique information of cell subpopulations in the cortex of rats with acute ischemic stroke, providing novel insight into the pathological process and drug discovery in stroke.

In this study, based on the EM-DAT (The Emergency Events Database) database, disaster assessment for the “Belt and Road” region was carried out in relation to the $${\rm{SD}}{{\rm{G}}_{13.1.1}}$$ indicator of the Sustainable Development Goals (SDGs) agenda launched in 2015. A new method for diagnosing trends in the $${\rm{SD}}{{\rm{G}}_{13.1.1}}$$ indicators based on the Theil-Sen median method is proposed. In addition, using the data available in the EM-DAT, an overview of disaster records is used to quantify disasters for a total of 73 countries. The disaster trends for the period 2015‒2019 were found to demonstrate the following. (1) As a result of geological and climate conditions, Asia and Africa are high-risk disaster areas and disasters have caused considerable economic losses and affected the populations in developing and underdeveloped countries in these regions. (2) The clear positive value of $$\Delta {\rm{s}}13.1.1$$ found for China reflects the country’s encouraging achievements in disaster prevention and mitigation. (3) The value of $${\rm{SD}}{{\rm{G}}_{13.1.1}}$$ was observed to be increasing in South Asia, northwest Africa and South Africa, with the increase in India and Mauritania being the most serious. The new method proposed in this paper allows the real trend in the $${\rm{SD}}{{\rm{G}}_{13.1.1}}$$ indicator in various countries to be derived and provides critical intelligence support for international disaster risk reduction plans and sustainable development goals.

The aim of this study was to investigate the gas production (GP), dry matter disappearance (DMD), fermentation parameters, and rumen microbiota in response to Clostridium butyricum (CB) supplementation in batch culture using a high forage substrate. The doses of CB were supplemented at 0 (Control), 0.5 × 106, 1 × 106, and 2 × 106 CFU/bottle, respectively, at either media pH 6.0 or pH 6.6. The 16S rRNA gene sequencing was used to detect the microbiota of fermentation culture in control and 1 × 106 CFU/bottle after 24 h of incubation. The results showed that the GP (p

An experiment was conducted to investigate the influences of supplemental lysophospholipids (LPL) on the growth performance, nutrient digestibility, and fecal bacterial profile, and short-chain fatty acids (SCFAs) of beef cattle. Thirty-six Angus beef cattle [565 ± 10.25 kg body weight (BW)] were grouped by BW and age, and randomly allocated to 1 of 3 treatment groups: (1) control (CON, basal diet); (2) LLPL [CON supplemented with 0.5 g/kg LPL, dry matter (DM) basis]; and (3) HLPL (CON supplemented with 0.75 g/kg, DM basis). The Angus cattle were fed a total mixed ration that consisted of 25% roughage and 75% concentrate (dry matter [DM] basis). The results reveal that LPL inclusion linearly increased the average daily gain (P = 0.02) and the feed efficiency (ADG/feed intake, P = 0.02), while quadratically increasing the final weight (P = 0.02) of the beef cattle. Compared with CON, the total tract digestibilities of DM (P < 0.01), ether extract (P = 0.04) and crude protein (P < 0.01) were increased with LPL supplementation. At the phylum-level, the relative abundance of Firmicutes (P = 0.05) and ratio of Firmicutes: Bacteroidetes (P = 0.04) were linearly increased, while the relative abundances of Bacteroidetes (P = 0.04) and Proteobacteria (P < 0.01) were linearly decreased with increasing LPL inclusion. At the genus-level, the relative abundances of Clostridium (P < 0.01) and Roseburia (P < 0.01) were quadratically increased, and the relative abundances of Ruminococcus was linearly increased (P < 0.01) with LPL supplementation. Additionally, increasing the dose of LPL in diets linearly increased the molar proportion of butyrate (P < 0.01) and total SCFAs (P = 0.01) concentrations. A conclusion was drawn that, as a promising feed additive, LPL promoted growth performance and nutrient digestibility, which may be associated with the change of fecal microbiome and SCFAs.

In order to avoid the irritation of metformin hydrochloride to the stomach and realize its release in the intestine, with metformin hydrochloride as the main drug and chitosan/sodium alginate as the composite support, the optimal formulation and preparation technology of metformin hydrochloride loaded pH-sensitive hydrogel microspheres were selected, and the pH-sensitivity and in vitro drug release characteristics were investigated. The formulation and process were optimized by single factor test and orthogonal test. The morphology was characterized by SEM. The entrapment efficiency and drug-loaded amount were determined by UV. The release degree was studied by rotating basket method. The results show that the optimized prescription is as following: chitosan and sodium alginate with a total concentration of 2%(mass-volume ratio), mass ratio of sodium alginate to chitosan =1∶1, mass ratio of drug to sodium alginate=2∶5, and 3.5% CaCl2(mass-volume ratio). The cumulative release rate is less than 4% in artificial gastric juice within 6 h, and up to 96.4% in artificial intestinal juice within 6 h. The formulation and process are stable and reliable, and the hydrogel microspheres have high mechanical strength, good biodegradability and stability. So it is a new metformin hydrochloride delivery system.

Cerebral ischemia and the subsequent cerebral ischemia-reperfusion (I/R) injury usually result in neuronal impairment with serious disabilities. Although neural stem cell (NSC) transplantation can help with functional recovery after stroke, due to the improper cellular milieu after brain injury, direct NSC transplantation will result low cell survival rates and differentiation efficiency into neurons. Here a conductive hybrid hydrogel based on gelatin methacryloyl (GelMA) and poly(3,4-ethylenedioxythiophene): poly (styrene sulfonate) (PEDOT:PSS) was created as a NSC niche for the treatment of cerebral I/R injury. GelMA/PEDOT:PSS hybrid hydrogel promoted the development of NSCs into neurons. GelMA/PEDOT:PSS hydrogel along with NSCs could enhance neuronal activity and minimize apoptosis when co-cultured with oxygen-glucose deprivation/reperfusion (OGD/R) neurons. Furthermore, after 7 days of implantation, GelMA/PEDOT:PSS/NSCs on the infarcted brain of rats subjected to reperfusion injury after middle cerebral artery occlusion (MCAO) was verified to attenuate inflammatory responses. These findings show that the conductive GelMA/PEDOT:PSS hybrid hydrogel could regulate NSC development and act as promising cell niches for the treatment of cerebral I/R injury.

Propolis has been widely used in foods and health care products to prevent diseases due to its various and prominent biological activities. Caffeic acid phenethyl ester(CAPE) is the main active component of propolis, which has been widely studied for its various pharmacological effects such as antioxidation, anti-inflammation, antitumor, antibacterial activities, immunovegularion, and so on. The content of CAPE is very low in nature, and the traditional extraction method of CAPE is time-consuming and costly, so efficient and mass preparation for CAPE has become a research hotspot. The CAPE with high purity can be obtained by ultrasonic extraction. Knoevenagel condensation reaction can be applied to its industrial production with high yield. Based on the analysis of the latest progress in extraction and separation, synthetic methods, pharmacological activity, and other aspects of CAPE, the research status of CAPE was reviewed, and the development prospect and the research trend of CAPE were provided, which are to explore the preparation method with high practicability and generality and relatively simple operation, and to conduct in-depth and detailed research on the mechanism of CAPE.

In this study, four types of soybean products with different processing methods (soybean meal 1 and soybean meal 2, extruded soybean meal, fermented soybean meal and extruded soybean) were used to examine the effect of fermentation and extrusion on molecular structures of protein and carbohydrate. Extrusion and fermentation significantly decreased (P < 0.05) the values of related protein spectral intensities (height and area of amide and secondary structure) and the biggest reduction was found in extruded soybean compared to soybean meal 1 and soybean meal 2. Compared with extruded soybean meal, the area ratio of amide I to amide II and the height ratio of α-helix to β sheet in extruded soybean were significantly reduced (P < 0.05), and there was no difference in these spectral values between extruded and fermented soybean. Extrusion and fermentation significantly decreased (P < 0.05) the values of carbohydrate spectral intensities, including structural carbohydrate (STCHO) and cellulosic compounds (CELC) and total carbohydrate (CHO), compared to soybean meal 2. The ratio of α-helix to β-sheet was positively related to the DM of soybean degradability in the rumen (P < 0.05, r = 0.590), so was A-CELC to A-STCHO (P < 0.05, r = 0.747). A positive relationship was found between CP degradability in the rumen and the area ratios of amide I and amide II, CELC to CHO, and STCHO to CHO. Spectral intensity of CHO area was negatively associated with neutral detergent fibre (NDF) and acid detergent fibre (ADF) degradability in the rumen. The study indicated that extrusion and fermentation could alter the molecular structure of protein and carbohydrate and the degradation characteristics of soybean products in the rumen.

ObjectiveThis paper used meta-regression to analyze the heterogenous factors contributing to the prevalence rate of mental health symptoms of the general and frontline healthcare workers (HCWs) in China under the COVID-19 crisis.MethodWe systematically searched PubMed, Embase, Web of Science, and Medrxiv and pooled data using random-effects meta-analyses to estimate the prevalence rates, and ran meta-regression to tease out the key sources of the heterogeneity.ResultsThe meta-regression results uncovered several predictors of the heterogeneity in prevalence rates among published studies, including severity (e.g., above severe vs. above moderate, p < 0.01; above moderate vs. above mild, p < 0.01), type of mental symptoms (PTSD vs. anxiety, p = 0.04), population (frontline vs. general HCWs, p < 0.01), sampling location (Wuhan vs. Non-Wuhan, p = 0.04), and study quality (p = 0.04).ConclusionThe meta-regression findings provide evidence on the factors contributing to the prevalence rate of mental health symptoms of the general and frontline healthcare workers (HCWs) to guide future research and evidence-based medicine in several specific directions.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=220592, identifier: CRD42020220592.

Changes in a large-scale glacial lake area directly reflect the regional glacier status and climate changes. However, long time series of glacial lake dataset and comprehensive investigation of the spatiotemporal changes in the glacial lake area in the whole High Mountain Asia (HMA) region remained elusive. Satellite remote sensing provides an indispensable way for dynamic monitoring of glacial lakes over large regions. But glacial lakes are quite small and discretely distributed, and the extraction of glacial lakes is usually influenced by clouds, snow/ice cover, and terrain shadows; thus, there is a lack of an automatic method to continuously monitor the dynamic changes of glacial lakes in a large scale. In this paper, we developed a per-pixel composited method named the “multitemporal mean NDWI composite” to automatically extract the glacial lake area in HMA from 1990 to 2020 using time-series Landsat data. There were 19,294 glacial lakes covering a total area of 1471.85±366.42 km2 in 1990, and 22,646 glacial lakes with an area of 1729.08±461.31 km2 in 2020. It is noted that the glacial lake area in the whole HMA region expanded by 0.58±0.21%/a over the past three decades, with high spatiotemporal heterogeneity. The glacial lake area increased at a consistent speed over time. The fastest expansion was in East Kun Lun at an average rate of 2.01±0.54%/a, while in the Pamir and Hengduan Shan, they show slow increases with rates of 0.33±0.08%/a and 0.39±0.01%/a, respectively, during 1990–2020. The greatest increase in lake area occurred at 5000-5200 m a.s.l., which increased by about 45 km2 (~25%). We conclude that the temperature rise and glacier thinning are the leading factors of glacial lake expansion in HMA, and precipitation is the main source of lake water increase in West Kun Lun. Using the proposed method, a large amount of Landsat images from successive years of melting seasons can be fully utilized to obtain a pixel-level composited cloud-free and solid snow/ice-free glacial lake map. The uncertainties from supraglacial ponds and glacial meltwater were also estimated to improve the reliability and comparability of glacial lake area changes among different regions. This study provides important technical and data support for regional climate changes, glacier hydrology, and disaster analysis.

This study was conducted to evaluate the effect of dietary supplementation with lysophospholipids (LPLs) on the growth performance, nutrient digestibility, nitrogen utilization, and blood metabolites of finishing beef cattle. In total, 40 Angus beef bulls were blocked for body weight (447 ± 9.64 kg) and age (420 ± 6.1 days) and randomly assigned to one of four treatments (10 beef cattle per treatment): (1) control (CON; basal diet); (2) LLPL (CON supplemented with 0.012% dietary LPL, dry matter (DM) basis); (3) MLPL (CON supplemented with 0.024% dietary LPL, DM basis); and (4) HLPL (CON supplemented with 0.048% dietary LPLs, DM basis). The results showed that dietary supplementation with LPLs linearly increased the average daily gain (p < 0.01), digestibility of DM (p < 0.01), crude protein (p < 0.01), and ether extract (p < 0.01) and decreased the feed conversion ratio (p < 0.01). A linear increase in N retention (p = 0.01) and a decrease in urinary (p = 0.04) and fecal N (p = 0.02) levels were observed with increasing the supplemental doses of LPLs. Bulls fed LPLs showed a linear increase in glutathione peroxidase (p = 0.04) and hepatic lipase (p < 0.01) activity and a decrease in cholesterol (p < 0.01), triglyceride (p < 0.01), and malondialdehyde (p < 0.01) levels. In conclusion, supplementation with LPLs has the potential to improve the growth performance, nutrient digestibility, and antioxidant status of beef cattle.

The triangular ridged surface can improve the grip reliability of products, but the sharp edge of triangular ridge induces sharp and uncomfortable feeling. To study the effect of edge shape (sharp, round, and flat shape) of triangular ridges on brain activity during touching, electroencephalograph (EEG) signals during tactile perception were evaluated using event-related potentials (ERP) and non-linear analysis methods. The results showed that the early component of P100 and P200, and the late component of P300 were successfully induced during perceiving the ridged texture. The edge shape features affect the electrical activity of brain during the tactile perceptions. The sharp shape feature evoked fast P100 latency and high P100 amplitude. The flat texture with complex (sharp and flat) shape feature evoked fast P200 latency, high P200 amplitude and RQA parameters. Both of the sharp shape and complex shape feature tended to evoke high peak amplitude of P300. The large-scale structures of recurrence plots (RPs) and recurrence quantification analysis (RQA) parameters can visually and quantitatively characterize the evolution regulation of the dynamic behavior of EEG system along with the tactile process. This study proved that RPs and RQA were protential methods for the feature extraction and state recognition of EEG during tactile perception of textured surface. This research contributes to optimize surface tactile characteristics on products, especially effective surface textures design for good grip.

Experiments were conducted to evaluate the effects of an aflatoxin B1 (AFB1)-contaminated diet treated with ammonia on the diet detoxification and growth performance, nutrient digestibility, nitrogen utilization, and blood metabolites in sheep. Twenty-four female mutton sheep with an initial body weight of 50 ± 2.5 kg were randomly assigned to one of three groups: (1) control diet (C); (2) aflatoxin diet (T; control diet supplemented with 75 μg of AFB1/kg of dry matter); and (3) ammoniated diet (AT; ammoniated aflatoxin diet). The results showed decreases (p < 0.05) in average daily feed intake, nutrient digestibility of dry matter, crude protein and ether extract, and retained nitrogen, and an increase (p < 0.05) in urine nitrogen excretion in sheep fed diet T compared with those fed the other diets. In comparison to C and AT, feeding T decreased (p < 0.05) the concentrations of total protein, immunoglobulin A, immunoglobulin G, immunoglobulin M, superoxide dismutase, and total antioxidants and increased (p < 0.05) the concentrations of alanine amino transferase, malondialdehyde, and interleukin-6. In summary, ammonia treatment has the potential to decrease the concentration of AFB1 and alleviate the adverse effects of AFB1.

Background: Cerebral ischemia–reperfusion (I/R) injury can lead to severe dysfunction, and its treatment is difficult. It is reported that nucleotide-binding domain and leucine-rich repeat family protein 3 (NLRP3) inflammasome-mediated cell pyroptosis is an important part of cerebral I/R injury and the activation of autophagy can inhibit pyroptosis in some tissue injury. Our previous study found that the protective effects of bone marrow mesenchymal stem cells (BMSCs) in cerebral I/R injury may be associated with the regulation of autophagy. Recent studies have demonstrated that exosomes secreted from BMSCs (BMSC-Exos) may play an essential role in the effective biological performance of BMSCs and the protective mechanism of BMSC-Exos is associated with the activation of autophagy and the remission of inflammation, but it has not been reported in studies of cerebral I/R injury. We aimed to investigate the effects of BMSC-Exos on cerebral I/R injury and determine if the mechanism is associated with the regulation of pyroptosis and autophagic flux.Method: PC12 cells were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) to induce cerebral I/R in vitro and were cocultured with BMSC-Exos. Cell viability was determined with CCK-8 and lactate dehydrogenase (LDH) detection kits. Scanning electron microscopy (SEM), Hoechst 33342/propidium iodide (PI) double staining, 2′,7′-dichlorodihydrofluorescein diacetate assay, immunofluorescence, Western blot, and Enzyme-linked immunosorbent assay (ELISA) were used to detect cell pyroptosis. Furthermore, transmission electron microscopy (TEM), GFP-RFP-LC3 adenovirus transfection, and Western blot were used to detect autophagic flux and its influence on pyroptosis. Finally, coimmunoprecipitation was used to detect the binding interaction between NLRP3 and LC3.Results: BMSC-Exos increased cell viability in OGD/R. The inhibitory effect of BMSC-Exos on pyroptosis was comparable to the NLRP3 inhibitor MCC950 and was reversed by NLRP3 overexpression. Furthermore, BMSC-Exos promoted autophagic flux through the AMP-activated kinase (AMPK)/mammalian target of the rapamycin pathway, whereas chloroquine, AMPK silencing, and compound C blocked the inhibitory effect on pyroptosis.Conclusions: BMSC-Exos can protect PC12 cells against OGD/R injury via attenuation of NLRP3 inflammasome-mediated pyroptosis by promoting AMPK-dependent autophagic flux.

This paper investigates how the government can develop subsidies or tax policies to incent power plants to effectively carry out carbon capture to reduce carbon emissions. According to the government’s incentive model for carbon capture power plants, the regulation mechanism is developed when government controls carbon emission. When regional or national carbon emission quota is tense, significant effect can be obtained when regulators make regulations to take off low efficiency power plants. In addition, it is verified that the regulators should not blindly pursue a reduction in carbon emissions regardless of the cost. Therefore, regulators need to pay more attention to control the costs of carbon capture equipment and technology. Finally, by parametric and numerical analyses, the conditions of the power plant to maximize corporate surplus are further studied.

Glacial lakes are highly sensitive indicators of global climate change. The accurate extraction of glacial lakes from image data is of great importance to the evaluation of the hydrological environment in high mountain regions. This paper demonstrates a systematic approach—TSCV (threshold and simplified C-V)—that integrates the advantages of the threshold segmentation method and the active contour model to improve the effect of glacial lake extraction, by overcoming the problems involved in the efficient extraction of small, overlooked glacial lakes and in the removal of some mountain shadows. Three typical areas of glacial lake development in High Asia were selected for glacial lake extraction from Landsat-8 imagery and the results were then compared with those obtained using the threshold segmentation method and the fuzzy clustering method (FCM). The values of the kappa coefficient (KC) and average extraction accuracy (AEA) shows that the TSCV (KC = 0.895, AEA = 0.739) performed superior than other two methods, especially for the small glacial lakes, but also that the threshold segmentation method (KC = 0.869, AEA = 0.631) requires the least time and that the FCM (KC = 871, AEA = 0.663) has the lowest commission error. Our findings lead to a new approach to improve the accuracy of glacial lake extraction in situation where a large proportion of the lakes are small and with a potential for automated glacial lake mapping in rugged mountain areas at a large scale.

This paper presents a micromachined silicon resonant accelerometer based on electrostatic active damping control, which can improve the shock response performance of the accelerometer. In the accelerometer, an electrostatic active damping structure and damping control circuit are designed to improve the equivalent damping coefficient of the system. System-level Simulink modeling and simulation of the accelerometer with an electrostatic active damping closed-loop control link were carried out. The simulation results indicate that the system can quickly return to normal output without an obvious vibration process after the shock. The fabricated and packaged accelerometer was connected to an external test circuit for shock performance testing. The stabilization time of the accelerometer after a 100 g, 3–5 ms half-sine shock was reduced from 19.8 to 5.6 s through use of the damping control. Furthermore, the change in deviation before and after the shock without damping control was 0.8197 mg, whereas it was 0.1715 mg with damping control. The experimental results demonstrate that the electrostatic active damping control can effectively improve the dynamic performance of the micromachined silicon resonant accelerometer.

This study designed an in-plane resonant micro-accelerometer based on electrostatic stiffness. The accelerometer adopts a one-piece proof mass structure; two double-folded beam resonators are symmetrically distributed inside the proof mass, and only one displacement is introduced under the action of acceleration, which reduces the influence of processing errors on the performance of the accelerometer. The two resonators form a differential structure that can diminish the impact of common-mode errors. This accelerometer realizes the separation of the introduction of electrostatic stiffness and the detection of resonant frequency, which is conducive to the decoupling of accelerometer signals. An improved differential evolution algorithm was developed to optimize the scale factor of the accelerometer. Through the final elimination principle, excellent individuals are preserved, and the most suitable parameters are allocated to the surviving individuals to stimulate the offspring to find the globally optimal ability. The algorithm not only maintains the global optimality but also reduces the computational complexity of the algorithm and deterministically realizes the optimization of the accelerometer scale factor. The electrostatic stiffness resonant micro-accelerometer was fabricated by deep dry silicon-on-glass (DDSOG) technology. The unloaded resonant frequency of the accelerometer resonant beam was between 24 and 26 kHz, and the scale factor of the packaged accelerometer was between 54 and 59 Hz/g. The average error between the optimization result and the actual scale factor was 7.03%. The experimental results verified the rationality of the structural design.

Glacial lake extraction is essential for studying the response of glacial lakes to climate change and assessing the risks of glacial lake outburst floods. Most methods for glacial lake extraction are based on either optical images or synthetic aperture radar (SAR) images. Although deep learning methods can extract features of optical and SAR images well, efficiently fusing two modality features for glacial lake extraction with high accuracy is challenging. In this study, to make full use of the spectral characteristics of optical images and the geometric characteristics of SAR images, we propose an atrous convolution fusion network (ACFNet) to extract glacial lakes based on Landsat 8 optical images and Sentinel-1 SAR images. ACFNet adequately fuses high-level features of optical and SAR data in different receptive fields using atrous convolution. Compared with four fusion models in which data fusion occurs at the input, encoder, decoder, and output stages, two classical semantic segmentation models (SegNet and DeepLabV3+), and a recently proposed model based on U-Net, our model achieves the best results with an intersection-over-union of 0.8278. The experiments show that fully extracting the characteristics of optical and SAR data and appropriately fusing them are vital steps in a network’s performance of glacial lake extraction.

Remote sensing is a powerful tool that provides flexibility and scalability for monitoring and investigating glacial lakes in High Mountain Asia (HMA). However, existing methods for mapping glacial lakes are designed based on a combination of several spectral features and ancillary data (such as the digital elevation model, DEM) to highlight the lake extent and suppress background information. These methods, however, suffer from either the inevitable requirement of post-processing work or the high costs of additional data acquisition. Signifying a key advancement in the deep learning models, a generative adversarial network (GAN) can capture multi-level features and learn the mapping rules in source and target domains using a minimax game between a generator and discriminator. This provides a new and feasible way to conduct large-scale glacial lake mapping. In this work, a complete glacial lake dataset was first created, containing approximately 4600 patches of Landsat-8 OLI images edited in three ways—random cropping, density cropping, and uniform cropping. Then, a GAN model for glacial lake mapping (GAN-GL) was constructed. The GAN-GL consists of two parts—a generator that incorporates a water attention module and an image segmentation module to produce the glacial lake masks, and a discriminator which employs the ResNet-152 backbone to ascertain whether a given pixel belonged to a glacial lake. The model was evaluated using the created glacial lake dataset, delivering a good performance, with an F1 score of 92.17% and IoU of 86.34%. Moreover, compared to the mapping results derived from the global–local iterative segmentation algorithm and random forest for the entire Eastern Himalayas, our proposed model was superior regarding the segmentation of glacial lakes under complex and diverse environmental conditions, in terms of accuracy (precision = 93.19%) and segmentation efficiency. Our model was also very good at detecting small glacial lakes without assistance from ancillary data or human intervention.

The current glacial lake datasets in the High Mountain Asia (HMA) region still need to be improved because their boundary divisions in the land–water transition zone are not precisely delineate, and also some very small glacial lakes have been lost due to their mixed reflectance with backgrounds. In addition, most studies have only focused on the changes in the area of a glacial lake as a whole, but do not involve the actual changes of per pixel on its boundary and the potential controlling factors. In this research, we produced more accurate and complete maps of glacial lake extent in the HMA in 2008, 2012, and 2016 with consistent time intervals using Landsat satellite images and the Google Earth Engine (GEE) cloud computing platform, and further studied the formation, distribution, and dynamics of the glacial lakes. In total, 17,016 and 21,249 glacial lakes were detected in 2008 and 2016, respectively, covering an area of 1420.15 ± 232.76 km2 and 1577.38 ± 288.82 km2; the lakes were mainly located at altitudes between 4400 m and 5600 m. The annual areal expansion rate was approximately 1.38% from 2008 to 2016. To explore the cause of the rapid expansion of individual glacial lakes, we investigated their long-term expansion rates by measuring changes in shoreline positions. The results show that glacial lakes are expanding rapidly in areas close to glaciers and had a high expansion rate of larger than 20 m/yr from 2008 to 2016. Glacial lakes in the Himalayas showed the highest expansion rate of more than 2 m/yr, followed by the Karakoram Mountains (1.61 m/yr) and the Tianshan Mountains (1.52 m/yr). The accelerating rate of glacier ice and snow melting caused by global warming is the primary contributor to glacial lake growth. These results may provide information that will help in the understanding of detailed lake dynamics and the mechanism, and also facilitate the scientific recognition of the potential hazards associated with glacial lakes in this region.

Glacial lake outburst floods (GLOFs) are among the most serious natural hazards in high mountain regions in the last several decades. The recent global warming has caused dramatic glacial lake changes and increased potential GLOF risk, particularly in Tibet Plateau (TP). Thus there is a pressing need to understand area and spatial distribution of glacial lakes at a large scale. Current efforts about glacial lake mapping in TP region is limited by spurious detections in the heterogeneous backgrounds. The nonlocal active contour algorithm, which takes full consideration of the regional heterogeneity in image, has been effectively applied in the field of medical image segmentation, but has not been tested at large scale of glaciated area yet. Moreover, the improved radiometric resolution and geographic coverage from Landsat 8 provides an opportunity to map glacial lakes. This study evaluated the potential of Landsat 8 images on annual glacial lake mapping in TP region which was characterized by various complex water conditions. The Google Earth Engine based cloud computing effectively facilitated the processing of a complete time series of Landsat 8 imagery from 2015 (156 path/rows and approximately 3580 scenes). Characteristics of glacial lake distribution were analyzed from aspects of size classes and elevation. Our results demonstrate that these strategies and methods automatically produce highly reliable glacial lake extents across the entire TP region, and are potentially applicable to other large-scale glacial lake mapping projects.

The purpose of this study was to improve the bioavailability of carbamazepine (CBZ), a poorly water-soluble antiepileptic drug, via modified-release amorphous solid dispersions (mr-ASD) by a thin film freezing (TFF) process. Three types of CBZ-mr-ASD with immediate-, delayed-, and controlled-release properties were successfully prepared with HPMC E3 (hydrophilic), L100-55 (enteric), and cellulose acetate (CA, lipophilic), defined as CBZ-ir-ASD, CBZ-dr-ASD, and CBZ-cr-ASD, respectively. A dry granulation method was used to prepare CBZ-mr-ASD capsule formulations. Various characterization techniques were applied to evaluate the physicochemical properties of CBZ-mr-ASD and the related capsules. The drug remained in an amorphous state when encapsulated within CBZ-mr-ASD, and the capsule formulation progress did not affect the performance of the dispersions. In dissolution tests, the preparations and the corresponding dosage forms similarly showed typical immediate-, delayed-, and controlled-release properties depending on the solubility of the polymers. Moreover, single-dose 24 h pharmacokinetic studies in rats indicated that CBZ-mr-ASD significantly enhanced the oral absorption of CBZ compared to that of crude CBZ. Increased oral absorption of CBZ was observed, especially in the CBZ-dr-ASD formulation, which showed a better pharmacokinetic profile than that of crude CBZ with 2.63- and 3.17-fold improved bioavailability of the drug and its main active metabolite carbamazepine 10,11-epoxide (CBZ-E).

The in vitro and in vivo antioxidant activities of six flavonoids with similar structures, including epicatechin (EC), epigallocatechin (EGC), procyanidin B2 (P), quercetin (Q), taxifolin (T), and rutin (R) were compared. The structures of the six flavonoids and their scavenging activities for 2,2-diphenyl-1-picrylhydrazyl (DPPH•) and 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+) radicals were closely related. The flavonoids decreased serum contents of malondialdehyde (MDA) and nitric oxide (NO), and increased serum total antioxidative capacity (T-AOC), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) levels to different degrees in d-galactose-treated mice. The changes in mRNA expression of liver GSH-Px1, CAT, SOD1, and SOD2 by d-galactose were dissimilarly restored by the six flavonoids. Moreover, the six flavonoids differentially prevented the inflammatory response caused by oxidative stress by inhibiting interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α levels, and restoring IL-10 levels. These six flavonoids from two subclasses revealed the following antioxidant capability: P > EC, EGC > EC, Q > T, Q > R. Our results indicate that (1) the pyrogallol, dimerization, and C2=C3 double bonds of flavonoids enhanced antioxidant activity and (2) the C3 glycosylation of flavonoids attenuated antioxidant capacity.

Genotype 4 hepatitis E virus (HEV) is a zoonotic pathogen transmitted to humans through food and water. Previously, three genotype 4 swine HEV ORF2 peptides (407EPTV410, 410VKLYTS415, and 458PSRPF462) were identified as epitopes of virus-neutralizing monoclonal antibodies that partially blocked rabbit infection with swine HEV. Here, individual and tandem fused peptides were synthesized, conjugated to keyhole limpet hemocyanin (KLH), then evaluated for immunoprotection of rabbits against swine HEV infection. Forty New Zealand White rabbits were randomly assigned to eight groups; groups 1 thru 5 received three immunizations with EPTV-KLH, VKLYTS-KLH, PSRPF-KLH, EPTVKLYTS-KLH, or EPTVKLYTSPSRPF-KLH, respectively; group 6 received truncated swine HEV ORF2 protein (sp239), and group 7 received phosphate-buffered saline. After an intravenous swine HEV challenge, all group 7 rabbits exhibited viremia and fecal virus shedding by 2–4 weeks post challenge (wpc), seroconversion by 4–9 wpc, elevated alanine aminotransferase (ALT) at 2 wpc, and severe liver lymphocytic venous periphlebitis. Only 1–2 rabbits/group in groups 1–4 exhibited delayed viremia, fecal shedding, seroconversion, increased ALT levels, and slight liver lymphocytic venous periphlebitis; groups 5–6 showed no pathogenic effects. Collectively, these results demonstrate that immunization with a polypeptide containing three genotype 4 HEV ORF2 neutralizing epitopes completely protected rabbits against swine HEV infection.

The objective of this study was to prepare curcumin-loaded mixed Soluplus/TPGS micelles (Cur-TPGS-PMs) for oral administration. The Cur-TPGS-PMs showed a mean size of 65.54 ± 2.57 nm, drug encapsulation efficiency over 85%, and drug loading of 8.17%. The Cur-TPGS-PMs were found to be stable in various pH media (pH 1.2 for 2 h, pH 6.8 for 2 h, and pH 7.4 for 6 h). The X-ray diffraction (XRD) patterns illustrated that curcumin was in the amorphous or molecular state within PMs. The In vitro release test indicated that Cur-TPGS-PMs possessed a significant sustained-release property. The cell viability in MCF-7 cells was found to be relatively lower in Cur-TPGS-PM-treated cells as compared to free Cur-treated cells. CLSM imaging revealed that mixed micelles were efficiently absorbed into the cytoplasm region of MCF-7 cells. Therefore, Cur-TPGS-PMs could have the significant value for the chronic breast cancer therapy.

To prepare a stable complex of doxycycline (Doxy) and hydroxypropy-β-cyclodextrin (HP-β-CD) for ophthalmic delivery, the optimum formulation and preparation conditions were investigated using response surface methodology (RSM), artificial neural network (ANN) and support vector machine (SVM) modeling. The molar ratios of HP-β-CD/Doxy and Mg2+/Doxy, inclusion time and temperature were selected as independent variables (X1–X4) and inclusion efficiency and stability of the Doxy-HP-β-CD complex were selected as dependent (response) variables (Y1 and Y2). The optimal formulation predicted by genetic algorithm (GA) combined with the models was characterized by microscopy and nuclear magnetic resonance spectrometry, and the stability of Doxy in the complex was evaluated. The highest values of Y1 and Y2 were obtained using an ANN model combined with GA which predicted the values of X1–X4 to be 4, 10.8, 12 h and 25 °C, respectively. The modeling and optimization results indicated that a feed-forward back-propagation ANN with one hidden layer and 10 hidden units showed better fitting to both responses compared to the RSM and SVM models. GA proved to be an efficient tool in multi-objective optimization of a pharmaceutical formulation.

This study aims to understand the level of contraceptive knowledge and attitudes towards contraception, and then to explore the association between the contraceptive behavior and unintended pregnancy in unmarried female university students in China. A cross-sectional study was conducted of university students in 49 universities across 7 cities in China from September 2007 to January 2008. We distributed 74,800 questionnaires, of which 69,842 were returned. In this paper, the data from 35,383 unmarried female university students were analyzed. The prevalence of sexual intercourse in unmarried female university students was 10.2%. The prevalence of unintended pregnancy in those sexually active female university students, was 31.8%. Among students with pregnancy, 53.5% experienced two or more pregnancies. 28.3% of the students with sexual intercourse reported that they always adopted contraceptive methods, and of those 82.9% chose to use male condoms. The majority (83.9%) of students with unintended pregnancy chose to terminate the latest pregnancy by surgical abortion or medical abortion. The contraceptive knowledge level of students who experienced unintended pregnancy was lower than those who did not. In China, about one third of unmarried female students with sexual intercourse experience unintended pregnancy. A variety of contraceptive methods are adopted, but the frequency of contraceptive use is low. Most of unmarried female students who experienced unintended pregnancy would choose to terminate the pregnancy with surgical or medical abortion. University students, especially the ones who have experienced unintended pregnancy, lack contraceptive and reproductive health knowledge.

This paper investigates two different architectures of a 5th order electro-mechanical sigma-delta modulator: a feed-forward (FF) architecture and a multiple-feedback (MF) architecture. And a comparison was performed in terms of stability and noise shaping ability, sensitivities to parameter variances due to fabrication tolerances and loop gain, and nonlinearity in feedback force. Both architectures were modeled in Simulink and investigated at system level. The results show that: a) both architectures are stable and achieve the similar noise floor level of -170dB within 250Hz in the ideal condition; b) both architectures have good ability in fabrication tolerance; c) the performance of the MF architecture will degrade heavily with the loop gain decreasing and become unstable if the loop gain beyond one optimal value, while the FF architecture is insensitive; d) the FF architecture controls the proof mass well and achieves better SNDR, whereas the MF has a 56dB degradation in consideration of nonlinearity in feedback force.