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In semi-arid and arid areas, gully erosion is one of the most destructive forms of erosion and causes serious land degradation and resource destruction. Steepland gullies are widely distributed in the dry valleys of southwest China, and their formation is one of the main causes of soil erosion and the destruction of sloping farmland in the region. Previous research on the development of steepland gullies is limited, and further study is needed. In this study, 11 steepland gullies at various stages of development located in Guobu Village, Xide County, Liangshan, Sichuan Province, were selected for investigation using a digital elevation model (DEM) derived from unmanned aerial vehicle data as the primary data source. These data had a spatial resolution of 0.1 m. Fundamental parameters such as the gully length, width, depth, area, and volume were extracted from the remote sensing data. Other characteristic parameters, including the coefficient of main and tributary gullies, vertical gradient, gully elongation, and gully openness, were also investigated. The results indicate a significant linear positive correlation between the gully’s degree of openness and elongation as the gully’s length, width, and depth increase. Furthermore, the vertical gradient and coefficient of main and tributary gullies exhibit power-law relationships with these gully dimensions. The development of steepland gullies was divided into infancy, youth, maturity, and old age based on the use of the gully length as an ergodic indicator in space-for-time substitution. The morphological characteristics of these different stages were quantitatively analyzed, and a proposed mechanism for how the evolution of the gullies proceeds was developed. An empirical model of volume–length erosion was established to investigate the development process of steepland gullies in the dry valleys. It has been observed that the development law of steepland gullies is essentially consistent with the very active stage of typical gully formation, suggesting that steepland gully may represent the initial stage of gully development. The results show that these steepland gullies have their origin in high-intensity rainfall events that are accompanied by the formation of steps and drop water. The effects of gravity erosion and hydraulic erosion then cause the gullies to expand rapidly, forming gullies with a large head and a small tail before they gradually stabilize. The results of this study will help with the understanding of the formation and evolution of steepland gullies and will be of practical significance for the prevention of gully erosion and the protection of sloping farmland in the dry valley region of southwest China.

Reactive astrocytes play critical roles in the occurrence of various neurological diseases such as multiple sclerosis. Activation of astrocytes is often accompanied by a glycolysis-dominant metabolic switch. However, the role and molecular mechanism of metabolic reprogramming in activation of astrocytes have not been clarified. Here, we found that PKM2, a rate-limiting enzyme of glycolysis, displayed nuclear translocation in astrocytes of EAE (experimental autoimmune encephalomyelitis) mice, an animal model of multiple sclerosis. Prevention of PKM2 nuclear import by DASA-58 significantly reduced the activation of mice primary astrocytes, which was observed by decreased proliferation, glycolysis and secretion of inflammatory cytokines. Most importantly, we identified the ubiquitination-mediated regulation of PKM2 nuclear import by ubiquitin ligase TRIM21. TRIM21 interacted with PKM2, promoted its nuclear translocation and stimulated its nuclear activity to phosphorylate STAT3, NF-κB and interact with c-myc. Further single-cell RNA sequencing and immunofluorescence staining demonstrated that TRIM21 expression was upregulated in astrocytes of EAE. TRIM21 overexpressing in mice primary astrocytes enhanced PKM2-dependent glycolysis and proliferation, which could be reversed by DASA-58. Moreover, intracerebroventricular injection of a lentiviral vector to knockdown TRIM21 in astrocytes or intraperitoneal injection of TEPP-46, which inhibit the nuclear translocation of PKM2, effectively decreased disease severity, CNS inflammation and demyelination in EAE. Collectively, our study provides novel insights into the pathological function of nuclear glycolytic enzyme PKM2 and ubiquitination-mediated regulatory mechanism that are involved in astrocyte activation. Targeting this axis may be a potential therapeutic strategy for the treatment of astrocyte-involved neurological disease.

Fast homogenization without incipient melting is the key to designing solution heat treatment (SHT) process for single crystal superalloys. In this paper, a multicomponent phase-field model coupled with solidus temperature is developed for dynamically tracking incipient melting temperature, TIM, of alloy during SHT. The simulation process runs completely automatically only by inputting the composition information of as-cast specimen. Based on the obtained TIM-time profile, the holding temperature and the time of SHT are determined. Applying this approach to Co–30Ni–11Al–4W–1Ta–4Ti–5Cr single crystal specimen, a gradual increased TIM from 1247 °C to 1293 °C within 72,000 s is obtained, and thus a stepwise SHT process with a short time of less than 20 h is designed. The experimental verification shows that after SHT, the segregation coefficient of the slowest diffusing element W decreased from more than 2 to 1.065, the content of harmful secondary phase has decreased to below 0.1%, and no incipient melting occurs.

Objective: To establish an evaluation method for the uncertainty of high-performance liquid chromatography in the determination of sucralose in soy sauce. Methods: Testing was conducted in accordance with the national food safety standard GB 22255-2014. The content of sucralose in soy sauce was analyzed in accordance with the national metrological technical specification JJF 1059.1-2012. An uncertainty evaluation mathematical model was established to analyze the uncertainty factors during the measurement process. The uncertainty of the test results was evaluated and calculated through repeated sample measurements, standard solution purity, standard curve, glassware, weighing process, recovery rate, and testing instruments. Results: According to the confidence interval of 95%, the content of sucralose in soy sauce was (0.048±0.007) g/kg, k=2. Conclusion: The evaluation method for the uncertainty of sucralose in soy sauce by high performance liquid chromatography was established. The sources of the uncertainty of the determination results of sucralose in soy sauce were finally determined as follows: The fitting of the standard curve established by sucralose standard solution, and the recovery rate. And the proportion of various uncertainty evaluation factors in the process of determining sucralose content in soy sauce was cleared.

Background Non-invasive risk stratification for patients with endometrial carcinoma (EC) is important for developing personalised treatment plans. Our study aimed to explore the ability of quantitative MRI parameters to predict the risk stratification of EC patients based on molecular classification.Methods Fifty-three patients with histologically proven EC who underwent pelvic MRI and surgical treatment at our hospital between January 2020 and August 2022 were assessed. The tumour volume (TV) and uterine volume (UV) were estimated with the ellipsoid formula and used to calculate the tumour volume ratio (TVR). The mean apparent diffusion coefficient (ADC) of the tumour was measured on a workstation. Quantitative MRI parameters were compared among different risk groups via unpaired Student’s t-tests or Mann–Whitney’s U-tests.Results The TV and TVR were significantly different between the low- and high-risk groups (p

Abstract Bird sex chromosomes play a unique role in sex-determination, and affect the sexual morphology and behavior of bird species. Core waterbirds, a major clade of birds, share the common characteristics of being sexually monomorphic and having lower levels of inter-sexual conflict, yet their sex chromosome evolution remains poorly understood. Here, by we analyse of a chromosome-level assembly of a female crested ibis (Nipponia nippon), a typical core waterbird. We identify neo-sex chromosomes resulting from fusion of microchromosomes with ancient sex chromosomes. These fusion events likely occurred following the divergence of Threskiornithidae and Ardeidae. The neo-W chromosome of the crested ibis exhibits the characteristics of slow degradation, which is reflected in its retention of abundant gametologous genes. Neo-W chromosome genes display an apparent ovary-biased gene expression, which is largely driven by genes that are retained on the crested ibis W chromosome but lost in other bird species. These results provide new insights into the evolutionary history and expression patterns for the sex chromosomes of bird species.

This review examines the technological bottlenecks, potential solutions, and future development directions in the treatment and resource utilization of semi-coking wastewater (SCOW) in China. By comprehensively investigating the semi-coking industry and analyzing wastewater treatment research hotspots and existing projects, this study systematically explores the current status and challenges of each treatment unit, emphasizing the necessity for innovative wastewater treatment technologies that offer high efficiency, engineering feasibility, environmental friendliness, and effective resource recovery. This review highlights prospects and recommendations, including the development of novel extractants for phenol and ammonia recovery, a deeper understanding of biological enhancement mechanisms, exogenous bio-enhancement materials, and the creation of cost-effective advanced oxidation process (AOP)-based combined processes. Additionally, it underscores the potential for repurposing SCOW as a valuable resource through appropriate treatment, whether recycling for production or other applications.

Impossible differential cryptanalysis is very important in the field of symmetric ciphers. Currently, there are many automatic search approaches to find impossible differentials. However, these methods have two underlying assumptions: Markov cipher assumption and key independence assumption. Actually, these two assumptions are not true in ARX ciphers, especially lightweight ones. In this paper, we study the impossible differentials in ARX cipher under weak keys for the first time. Firstly, we propose several accurate difference propagation properties on consecutive two and three modular additions. Then, these properties are applied to four typical local constructions composed of two consecutive modular additions, two modular additions with a rotation operation, xoring secret key or constant in the middle, to find impossible differentials under weak keys or special constants. What’s more, we propose a more accurate difference propagation property on three consecutive modular additions. It can be used to find impossible differentials on more complex local constructions under weak keys or special constants. In practical ciphers, these impossible differentials on local constructions can be used to find contradictions. Lastly, combining our new findings with traditional automatic search methods for impossible differentials, we propose a framework to find impossible differentials in ARX ciphers under weak keys. As applications, we apply the framework to SPECK-32/64, LEA and CHAM-64/128. As a result, we find two 8-round impossible differentials for SPECK-32/64 under 260 weak keys, and one 11-round impossible differential for LEA under 2k−1 weak keys, where k is the key size. These impossible differentials can start from any round. Furthermore, we find two 22-round impossible differentials for CHAM-64/128 under 2127 weak keys starting from certain rounds. As far as we know, all these impossible differentials are longer than previous ones.

Salicylic acid (SA) is known to be an efficient elicitor of secondary metabolism in plants. Arbutin, a characteristic phenolic glycoside found in ‘Yuluxiang’ pear (Pyrus bretschneideri Rehder × Pyrus sinkiangensis Yu), is widely used in lightening agents, in addition to cough, anti-inflammatory, and anti-microbial remedies, among other applications. However, research into the synthesis of arbutin in pear is limited. This study aimed to clarify the effect of exogenous SA on the arbutin content of pear using HPLC and investigate the mechanism for arbutin accumulation using RNA-Seq analysis. HPLC revealed that SA increased the arbutin contents of leaf, fruit, and callus in pear and demonstrated that the effect of SA is concentration and time dependent. RNA-Seq analysis of pear callus treated with or without SA revealed 380 differentially expressed genes (DEGs), 335 of which were up-regulated. According to a KEGG database analysis, the highest number of genes were annotated for phenylpropane biosynthesis. Overall, 21 DEGs were found to be involved in the synthesis of hydroquinone and UDP-glucose, which are substrates of arbutin synthesis. It is noteworthy that the expression levels of three up-regulated genes (Pbr006844.1, Pbr021064.1 and Pbr021069.1) related to hydroquinone glycosyltransferase were induced by SA and hydroquinone. Furthermore, transient overexpression of PbUGT72B1 (Pbr021069.1) increased the arbutin content in pear callus. These data explain the regulation of gene transcription associated with the promotive effect of SA on arbutin biosynthesis in pear, thus providing a theoretical foundation for enhancing the arbutin content of fruit through genetic engineering.

In this study, a pH-responsive polycaprolactone (PCL)–copper peroxide (CuO2) composite antibacterial coating was developed by suspension flame spraying. The successful synthesis of CuO2 nanoparticles and fabrication of the PCL-CuO2 composite coatings were confirmed by microstructural and chemical analysis. The composite coatings were structurally homogeneous, with the chemical properties of PCL well maintained. The acidic environment was found to effectively accelerate the dissociation of CuO2, allowing the simultaneous release of Cu2+ and H2O2. Antimicrobial tests clearly revealed the enhanced antibacterial properties of the PCL-CuO2 composite coating against both Escherichia coli and Staphylococcus aureus under acidic conditions, with a bactericidal effect of over 99.99%. This study presents a promising approach for constructing pH-responsive antimicrobial coatings for biomedical applications.

Abstract Lack of sufficient cytotoxic T lymphocytes (CD8+ T cells) infiltration and dysfunctional state of CD8+ T cells are considered enormous obstacles to antitumor immunity. Herein, we construct a synergistic nanoplatform to promote CD8+ T cell infiltration in tumors while restoring T cell function by regulating methionine metabolism and activating the STING innate immune pathway. The CRISPR/Cas9 system down-regulates the methionine transporter SLC43A2 and restricts the methionine uptake by tumor cells, thereby relieving the methionine competition pressure of T cells; simultaneously, the released nutrition metal ions activate the cGAS/STING pathway. In this work, the described nanoplatform can enhance the effect of immunotherapy in preclinical cancer models in female mice, enhancing STING pathway mediated immunity and facilitating the development of amino acid metabolic intervention-based cancer therapy.

Abstract Background Robust routine immunization schedules for pertussis-containing vaccines have been applied for years, but pertussis outbreaks remain a worldwide problem. This study aimed to investigate the association between vaccine hesitancy and pertussis in infants and children. Methods We searched PubMed, Cochrane, Web of Science, Embase, and China National Knowledge Internet for studies published between January 2012 and June 2022. This study included case–control and cohort studies that assessed the association between childhood/maternal vaccine hesitancy and odds ratios (ORs), risk ratios (RRs), and vaccine effectiveness (VE) related to pertussis in infants and children $$\le$$ ≤ 9 years old. ORs/VEs with a 95% confidence interval (CI) were calculated. Random-effects meta-analysis models were used for appropriate pooled estimates, and heterogeneity was assessed using $${I}^{2}$$ I 2 . Cumulative meta-analysis and subgroup analyses stratified by study characteristics were performed. Results Twenty-two studies were included, with a mean quality score of 7.0 (range 6.0–9.0). Infants and children with pertussis were associated with higher vaccine hesitancy to all doses (OR = 4.12 [95% CI: 3.09–5.50]). The highest OR was between children who were unvaccinated over four doses and children who were fully vaccinated (OR = 14.26 [95%CI: 7.62–26.70]); childhood vaccine delay was not statistically significantly associated with pertussis risk (OR = 1.18 [95% CI: 0.74–1.89]). Maternal vaccine hesitancy was associated with significantly higher pertussis risk in infants aged 2 and 3 months old, with higher pertussis ORs in infants $$\le$$ ≤ 2 months old (OR = 6.02 [95%CI: 4.31–8.50], OR = 5.14 [95%CI: 1.95–13.52] for infants $$\le$$ ≤ 2 and $$\le$$ ≤ 3 months old, respectively). Maternal and childhood VEs were high in reducing pertussis infection in infants and children. The administration time of maternal vaccination had little effect on VE. Conclusion Vaccine hesitancy increased pertussis risks in infants and children. Ensuring that children receive up-to-date pertussis vaccines is essential; short delays in receiving childhood vaccinations may be unimportant. Maternal vaccinations for pertussis should be encouraged.

Abstract Background The activation of CD8+ T cells and their trafficking to the skin through JAK-STAT signaling play a central role in the development of vitiligo. Thus, targeting this key disease pathway with innovative drugs is an effective strategy for treating vitiligo. Natural products isolated from medicinal herbs are a useful source of novel therapeutics. Demethylzeylasteral (T-96), extracted from Tripterygium wilfordii Hook F, possesses immunosuppressive and anti-inflammatory properties. Methods The efficacy of T-96 was tested in our mouse model of vitiligo, and the numbers of CD8+ T cells infiltration and melanocytes remaining in the epidermis were quantified using whole-mount tail staining. Immune regulation of T-96 in CD8+ T cells was evaluated using flow cytometry. Pull-down assay, mass spectrum analysis, molecular docking, knockdown and overexpression approaches were utilized to identify the target proteins of T-96 in CD8+ T cells and keratinocytes. Results Here, we found that T-96 reduced CD8+ T cell infiltration in the epidermis using whole-mount tail staining and alleviated the extent of depigmentation to a comparable degree of tofacitinib (Tofa) in our vitiligo mouse model. In vitro, T-96 decreased the proliferation, CD69 membrane expression, and IFN-γ, granzyme B, (GzmB), and perforin (PRF) levels in CD8+ T cells isolated from patients with vitiligo. Pull-down assays combined with mass spectrum analysis and molecular docking showed that T-96 interacted with JAK3 in CD8+ T cell lysates. Furthermore, T-96 reduced JAK3 and STAT5 phosphorylation following IL-2 treatment. T-96 could not further reduce IFN-γ, GzmB and PRF expression following JAK3 knockdown or inhibit increased immune effectors expression upon JAK3 overexpression. Additionally, T-96 interacted with JAK2 in IFN-γ-stimulated keratinocytes, inhibiting the activation of JAK2, decreasing the total and phosphorylated protein levels of STAT1, and reducing the production and secretion of CXCL9 and CXCL10. T-96 did not significantly inhibit STAT1 and CXCL9/10 expression following JAK2 knockdown, nor did it suppress upregulated STAT1-CXCL9/10 signaling upon JAK2 overexpression. Finally, T-96 reduced the membrane expression of CXCR3, and the culture supernatants pretreated with T-96 under IFN-γ stressed keratinocytes markedly blocked the migration of CXCR3+CD8+ T cells, similarly to Tofa in vitro. Conclusion Our findings demonstrated that T-96 might have positive therapeutic responses to vitiligo by pharmacologically inhibiting the effector functions and skin trafficking of CD8+ T cells through JAK-STAT signaling.

Abstract A classic problem in preservation is the microbes can grow in low-moisture foods. In this paper, the water sorption, and thermodynamic properties of glucose/WPI solid matrices were measured, while their molecular mobility was analyzed and associated with the microbial growth of D. Hansenii at various a w and 30 °C. Although the sorption isotherms, T g , and relaxation processes of studied matrices were affected by a w and WPI, the microbial growth showed highly dependent on water mobility rather than a w . Hence, we introduced water usability (U w ), derived from the mobility difference between system-involved water and liquid pure water explicating from the classical thermodynamic viewpoint, to describe the dynamic changes of water mobility in glucose/WPI matrices. Despite to a w , the yeast growth rate was enhanced at high U w matrices concomitantly with a rapid cell doubling time. Therefore, the proposed U w provides a better understanding of the water relationships of microorganisms in food preservation.

To systematically explore land use/cover change (LUCC) trends and driving mechanisms at the large watershed scale under the background of climate change and rapid urbanization. Taking the lower reaches of the Yangtze River (LRYR) as the research object, based on the land use remote sensing monitoring data from 1980 to 2020, the spatial and temporal evolution characteristics of LUCC in LRYR were analyzed by adopting the methods of land use dynamics degree (LUDD) and hotspot analysis and used geospatial detectors to quantitatively assess the intensity of the role of the land use change drivers in the LRYR. The results show that: 1) The land-use types in LRYR were dominated by arable land and woodland, accounting for more than 70% of the total area. During the study period, the construction land area increased by 11,835 km2, and became the third largest land-use type in LRYR after 2010 and formed a typical urban contiguous zone along the route from Nanjing to Shanghai. 2) The land use degree comprehensive index (LUDCI) in LRYR at each stage is 270.91, 270.88, 272.22, 272.72, 274.00, 275.57, 276.93 and 280.37, respectively. LUCC in LRYR has become more dramatic, and there is significant spatial heterogeneity. Shanghai has always been a hot area of LUCC and Huangshan and Chizhou are cold spots of LUCC. 3) The driving mechanism of LUCC in LRYR can be divided into three stages. In these three stages, secondary industry output value, precipitation, and elevation are always important factors affecting LUCC. The interaction between driving factors is significant. The strongest interaction is the output value of the secondary industry ∩ precipitation, the interaction reaches above 0.6. The research results are of great significance for promoting the sustainable development of land use in this region.

Summary: Background: The impact of previous vaccination on protective immunity, duration, and immune imprinting in the context of BA.5-XBB.1.9.1 reinfection remains unknown. Methods: Based on a 2-year longitudinal cohort from vaccination, BA.5 infection and XBB reinfection, several immune effectors, including neutralizing antibodies (Nabs), antibody-dependent cellular cytotoxicity (ADCC), virus-specific T cell immunity were measured to investigate the impact of previous vaccination on host immunity induced by BA.5 breakthrough infection and BA.5-XBB.1.9.1 reinfection. Findings: In absence of BA.5 Nabs, plasma collected 3 months after receiving three doses of inactivated vaccine (I-I-I) showed high ADCC that protected hACE2-K18 mice from fatality and significantly reduced viral load in the lungs and brain upon BA.5 challenge, compared to plasma collected 12 months after I-I-I. Nabs against XBB.1.9.1 induced by BA.5 breakthrough infection were low at day 14 and decreased to a GMT of 10 at 4 months and 28% (9/32) had GMT ≤4, among whom 67% (6/9) were reinfected with XBB.1.9.1 within 1 month. However, 63% (20/32) were not reinfected with XBB.1.9.1 at 5 months post BA.5 infection. Interestingly, XBB.1.9.1 reinfection increased Nabs against XBB.1.9.1 by 24.5-fold at 14 days post-reinfection, which was much higher than that against BA.5 (7.3-fold) and WT (4.5-fold), indicating an immune imprinting shifting from WT to XBB antigenic side. Interpretation: Overall, I-I-I can provide protection against BA.5 infection and elicit rapid immune response upon BA.5 infection. Furthermore, BA.5 breakthrough infection effectively protects against XBB.1.9.1 lasting more than 5 months, and XBB.1.9.1 reinfection results in immune imprinting shifting from WT antigen induced by previous vaccination to the new XBB.1.9.1 antigen. These findings strongly suggest that future vaccines should target variant strain antigens, replacing prototype strain antigens. Funding: This study was supported by R&D Program of Guangzhou National Laboratory (SRPG23-005), National Key Research and Development Program of China (2022YFC2604104, 2019YFC0810900), S&T Program of Guangzhou Laboratory (SRPG22-006), and National Natural Science Foundation of China (81971485, 82271801, 81970038), Emergency Key Program of Guangzhou Laboratory (EKPG21-30-3), Zhongnanshan Medical Foundation of Guangdong Province (ZNSA-2020013), and State Key Laboratory of Respiratory Disease (J19112006202304).

Abstract Life science studies involving clustered regularly interspaced short palindromic repeat (CRISPR) editing generally apply the best-performing guide RNA (gRNA) for a gene of interest. Computational models are combined with massive experimental quantification on synthetic gRNA-target libraries to accurately predict gRNA activity and mutational patterns. However, the measurements are inconsistent between studies due to differences in the designs of the gRNA-target pair constructs, and there has not yet been an integrated investigation that concurrently focuses on multiple facets of gRNA capacity. In this study, we analyzed the DNA double-strand break (DSB)-induced repair outcomes and measured SpCas9/gRNA activities at both matched and mismatched locations using 926,476 gRNAs covering 19,111 protein-coding genes and 20,268 non-coding genes. We developed machine learning models to forecast the on-target cleavage efficiency (AIdit_ON), off-target cleavage specificity (AIdit_OFF), and mutational profiles (AIdit_DSB) of SpCas9/gRNA from a uniformly collected and processed dataset by deep sampling and massively quantifying gRNA capabilities in K562 cells. Each of these models exhibited superlative performance in predicting SpCas9/gRNA activities on independent datasets when benchmarked with previous models. A previous unknown parameter was also empirically determined regarding the “sweet spot” in the size of datasets used to establish an effective model to predict gRNA capabilities at a manageable experimental scale. In addition, we observed cell type-specific mutational profiles and were able to link nucleotidylexotransferase as the key factor driving these outcomes. These massive datasets and deep learning algorithms have been implemented into the user-friendly web service http://crispr-aidit.com to evaluate and rank gRNAs for life science studies.

Porcine neutrophil elastase (PPE) has been demonstrated to have a histone H1 isoform dependent anti-tumour effect. Here, the authors develop a biomimetic nanoplatform combining PPE and elevated histone H1 release induced by porphyrin nuclear localisation signal peptide and demonstrate its efficacy in preclinical cancer models.

Three pectin fractions (water-soluble fraction (WSF), chelator-soluble fraction (CSF), and sodium carbonate-soluble fraction (NSF)) were obtained from Chinese dwarf cherry (Cerasus humilis) fruits. All of them were branched low methoxylated pectins with an amorphous or partially nanocrystalline nature and eight neutral monosaccharides (arabinose and galactose were most abundant). WSF, CSF and NSF had a degree of methylation (DM) of 35.82 %, 14.85 % and 7.13 %, uronic acid (UA) content of 76.02 %, 83.71 % and 69.01 %, and total protein content of 2.4 %, 2.1 % and 8.8 %, respectively. Their molecular weights were 340.31, 330.16 and 141.31 kg/mol, respectively (analyzed by gel permeation chromatography (GPC)). WSF, CSF and NSF exhibited good rheological, thermal, emulsifying, emulsion-stabilizing, water-adsorbing, oil-binding, cholesterol-binding and antioxidant properties. NSF had the highest emulsifying, emulsion stabilizing, water-/oil-/cholesterol-binding and antioxidant capacities, followed by CSF. NSF had the highest viscosity (406.77 mPa·s), flowability, and resistance to heat-induced changes/damage, which may be related to its lowest polydispersity index, DM and UA content and highest protein content. The three pectin fractions with desirable characteristics can be used as food additives/ingredients and dietary supplements.

Waned vaccine-induced immunity and emerging severe acute respiratory syndrome coronavirus 2 variants with potential for immune escape pose a major threat to the coronavirus disease (COVID-19) pandemic. Here, we showed that humoral immunity components, including anti-S + N, anti-RBD IgG, and neutralizing antibodies (NAbs), gradually waned and decreased the neutralizing capacity against emerging Omicron variants at 3 and 6 months after two inactivated COVID-19 vaccinations. We evaluated two boosting strategies with either a third dose of inactivated vaccine (homologous, I-I-I) or a recombinant subunit vaccine (heterologous, I-I-S). Both strategies induced the production of high levels of NAbs with a broad neutralizing capacity and longer retention. Interestingly, I-I-S induced 3.5-fold to 6.8-fold higher NAb titres than I-I-I, with a broader neutralizing capacity against six variants of concern, including Omicron. Further immunological analysis revealed that the two immunization strategies differ considerably, not only in the magnitude of total NAbs produced, but also in the composite pattern of NAbs and the population of virus-specific CD4+ T cells produced. Additionally, in some cases, heterologous boosted immunity induced the production of more effective epitopes than natural infection. The level of I-I-S-induced NAbs decreased to 48% and 18% at 1 and 3 months after booster vaccination, respectively. Overall, our data provide important evidence for vaccination strategies based on available vaccines and may help guide future global vaccination plans.

The rapid widespread Omicron subvariant BA.5 of SARS-CoV-2 has become a potential imminent pandemic threat, but available vaccines lack high efficacy against this subvariant. Thus, it is urgent to find highly protective vaccination strategies within available SARS-CoV-2 vaccines. Here, by using a SARS-CoV-2 pseudovirus neutralization assay, we demonstrated that the aerosol inhalation of adenoviral vector COVID-19 vaccine after two dose of inactivated vaccine (I-I-Ad5) led to higher levels of neutralizing antibodies against D614G strain (2041.00[95% CI, 1243.00–3351.00] vs 249.00[149.10–415.70]), Omicron BA.2 (467.10[231.00–944.40] vs 72.21[39.31–132.70]), BA.2.12.1(348.5[180.3–673.4] vs 53.17[31.29–90.37]), BA.2.13 (410.40[190.70–883.3] vs 48.48[27.87–84.32]), and BA.5 (442.40 vs 56.08[35.14–89.51]) than three inactivated vaccine doses (I-I-I). Additionally, the level of neutralizing antibodies against BA.5 induced by I-I-Ad5 was 2.41-fold higher than those boosted by a third dose of RBD subunit vaccine (I-I-S) (p = 0.1308). The conventional virus neutralizing assay confirmed that I-I-Ad5 induced higher titre of neutralizing antibodies than I-I-I (116.80[84.51–161.5] vs 4.40[4.00–4.83]). In addition, I-I-Ad5 induced higher, but later, anti-RBD IgG and IgA in plasma than I-I-I. Our study verified that mucosal immunization with aerosol inhalation of adenoviral vector COVID-19 vaccine may be an effective strategy to control the probable wave of BA.5 pandemic in addition to two inactivated vaccines.

HPV vaccine uptake remains low in China, especially among girls. Recently, China has initiated a pilot program on HPV immunization for girls 9–14. From November to December 2021, a cross-sectional study was conducted among parents of girls 9–14 in China through a web-based anonymous online questionnaire survey. Descriptive epidemiological analysis was used to analyze parental acceptability. Hierarchical regression analysis and structural equation modeling were to determine associated factors. A total of 5623 participants were included in the analysis. 21.2% girls had received HPV vaccine, and 94.3% parents intended to receive vaccination for their daughters, the Kappa values between them was −0.016. 31.9% of vaccinated mothers had received HPV vaccine for their daughters, vaccination history had a positive impact on behavior (β = 0.048). Attitude (β = 0.186), subjective norms (β = 0.148) and perceived behavioral control (β = 0.648) had a positive impact on intention. Vaccination intention mediated the relationships between attitude (β = 0.044), subjective norms (β = 0.035), and perceived behavioral control (β = 0.154) with behavior. There is a gap between vaccination intention and behavior in parents of girls 9–14. Perceived behavior control had a strong association on HPV vaccination behavior.

There were some ecological and environmental problems in limestone soil in the karst peak-cluster depression in Pingguo City of Guangxi, such as the destruction of soil structure, soil acidification and soil fertility decline, and these problems were closely related to soil organic matter. The soil in this site was classified as Cambisols. Therefore, this project took soil under five major land uses (grassland, afforestation, sugarcane field, corn field and pitaya field) in the karst area of Guangxi as the research object. The contents and molecular structure properties of humic acids, fulvic acids and humins in soils were studied by solid-state 13C nuclear magnetic resonance spectroscopy and elemental composition. From the perspective of the chemical structure of humic substances, the differences in the quantity and structural characteristics of humic acids, fulvic acids and humins in different land uses were revealed. The results showed that the organic carbon content of both afforestation (34.83 g kg−1) and natural restored grassland (31.67 g kg−1) were significantly higher than that of sugarcane field (17.60 g kg−1), corn field (16.35 g kg−1) and pitaya field (14.31 g kg−1) (p < 0.05). The contents of three humic fractions in grassland were relatively high, and the contents of three humic fractions in sugarcane field were relatively low (p < 0.05). The structural characteristics of humic substances showed that the protein components of the three humic fractions in the afforestation were high, indicating that the humic substances in the afforestation contained more unstable components. The Alkyl C/O-alkyl C and Hydrophobic C/hydrophilic C ratios of the three humic fractions of corn field were high, indicating high stability and maturity in humic substances in corn field.

In this paper, the separation and purification of jellyfish polypeptide with Angiotensin-I converting enzyme (ACE) inhibitory activity by macroporous adsorption resin was studied from the perspective of molecular polarity. The enzymatic hydrolysates of jellyfish were taken as the research object, and three different types of macroporous resin HP20SS, SP20SS and SP207 were used to isolate and purify the ACE inhibitory peptide of jellyfish. The ACE inhibitory rate was used as the evaluation index, and the separation and purification process of ACE inhibitory peptide was screened. The results showed that HP20SS macroporous resin was the best for the separation and purification of ACE inhibitory peptide. Under the conditions of 10.0 mg/mL of hydrolysate, 2.0 BV/h of sample loading, 3 h of standing adsorption, 70% ethanol solution of eluent, 1.0 mL/min of eluent, after enrichment, the molecular weight of ACE inhibitory peptide was 2.65×103 Da, the purity was 89.16%, and the inhibition rate was up to 92.18%, the IC50 value was 1.02 mg/mL. The average recovery was 94.76% and RSD was 0.63% after three parallel tests. Comprehensive analysis showed that HP20SS macroporous resin had a good separation and purification effect on the ACE inhibitory peptide of jellyfish, and the process was reasonable and feasible with good reproducibility.

Abstract. Background:. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a global pandemic that has resulted in millions of casualties. Although researchers have reported the existence of neutralizing antibodies and viral T cell immunity against SARS-CoV-2, little is known about the presence of antibody-dependent cellular cytotoxicity (ADCC) and its role in combating SARS-CoV-2 infection. Methods:. Nineteen acute COVID-19 patients at the First Affiliated Hospital of Guangzhou Medical University from January to February, 2020 and 55 recovery COVID-19 patients at the Second Peoples Hospital of Changde City from February, 2020 to February, 2021 were recruited in this study. Longitudinal plasma samples were collected. A virus-specific ADCC assay was performed to study the COVID-19 plasma samples. The correlations between ADCC and total IgG titer, including anti-RBD, anti-N, and neutralizing antibody titer were analyzed. Results:. A high level of ADCC with 0.86% of IFN-γ+CD107a+ NK cells induced by anti RBD antibodies and with 0.54% of IFN-γ+CD107a+ NK cells induced by anti N antibodies was observed. This activity peaked at 3 weeks after disease onset with 1.16% and 0.63% of IFN-γ+CD107a+ NK cells induced by anti RBD and anti N antibodies respectively, declined to 0.32% and 0.32% of IFN-γ+CD107a+ NK cells respectively after more than 2 months, and persisted for 12 months after disease onset. The ADCC did not aggravate the severity of COVID-19 in terms of sequential organ failure assessment, although ADCC decreased with the age of COVID-19 patients. Interestingly, ADCC response is not correlated with neutralizing antibody titer or total IgG titers against S protein RBD and N protein in acute patients. ADCC in recovered patients showed a significant correlation with anti RBD IgG titer (R2 = 0.33, P

Background: Understanding the transmissibility and pathogenicity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial for control policies, but evidence remains limited. Methods: We presented a systematic and meta-analytic summary concerning the transmissibility and pathogenicity of COVID-19. Results: A total of 105 studies were identified, with 35042 infected cases and 897912 close contacts. 48.6% (51/105) of studies on secondary transmissions were from China. We estimated a total SIR of 7.8% (95% confidence interval [CI], 6.8%−8.8%), SAR of 6.6% (95% CI, 5.7%−7.5%), and symptomatic infection ratio of 86.9% (95%CI, 83.9%−89.9%) with a disease series interval of 5.84 (95%CI, 4.92–6.94) days. Household contacts had a higher risk of both symptomatic and asymptomatic infection, and transmission was driven between index cases and second-generation cases, with little transmission occurring in second-to-later-generation cases (SIR, 12.4% vs. 3.6%). The symptomatic infection ratio was not significantly different in terms of infection time, generation, type of contact, and index cases. Conclusions: Our results suggest a higher risk of infection among household contacts. Transmissibility decreased with generations during the intervention. Pathogenicity of SARS-CoV-2 varied among territories, but didn’t change over time. Strict isolation and medical observation measures should be implemented.

The physical properties of small molecular sugars, such as monosaccharides and oligosaccharides, are important to determine the processibility, storage stability, safety and nutritional value of sugar-rich foods. Temporal-spatial property, as a new parameter to describe the mobility of molecules or groups included in sugars when experiencing phase transition, has been proved to be related with the quality deterioration and the diffuse-limited reaction of sugar-rich foods. Therefore, a comprehensive understanding of the temporal-spatial property can provide a novel idea and technical means to guarantee the deep processing of small molecular sugars as well as to develop and construct the functional structure of sugar-rich foods. In this review, the origins of temporal-spatial property and its latest practical studies are reviewed. This review aims to provide a theoretical reserve for the development of temporal-spatial property and emphasised on the characterization quantity of such property based on thermodynamic approach—Strength value. Meanwhile, the potential applications of the above parameter in moisture-proof, anti-crystallization, and the controlling of diffusive-limited reactions on sugar-rich foods are discussed. The main conclusions we summarized are of guiding significance for the improvement of the processability and storage stability on sugar-rich food.

Abstract Vitiligo is a cutaneous depigmenting autoimmune disease caused by the extensive destruction of epidermal melanocytes. Convincing data has defined a critical role for oxidative stress in the pathogenesis of vitiligo. Oxeiptosis is a caspase-independent cell death modality that was reportedly triggered by oxidative stress and operative in pathogen clearance. However, whether oxeiptosis exists in oxidative stress-induced melanocytes demise in vitiligo remains undetermined. In the present study, we initially found that other cell death modalities might exist in addition to the well-recognized apoptosis and necroptosis in H2O2-treated melanocytes. Furthermore, AIFM1 was found to be dephosphorylated at Ser116 in oxidative stress-induced melanocytes death, which was specific to oxeiptosis. Moreover, KEAP1 and PGAM5, upstream of the AIFM1 in oxeiptosis, were found to operate in melanocytic death. Subsequently, the KEAP1-PGAM5-AIFM1 signaling pathway was proved to be involved in oxidative stress-triggered melanocytes demise through the depletion of KEAP1 and PGAM5. Altogether, our study indicated that oxeiptosis might occur in melanocytes death under oxidative stress and contribute to the pathogenesis of vitiligo.

BackgroundOlder adults are particularly at risk from infectious diseases, including serve complications, hospitalization, and death. ObjectiveThis study aimed to explore the drivers of vaccine hesitancy among older adults based on the “3Cs” (confidence, complacency, and convenience) framework, where socioeconomic status and vaccination history played the role of moderators. MethodsA cross-sectional questionnaire survey was conducted in Jiangsu Province, China, between June 1 and July 20, 2021. Older adults (aged ≥60 years) were recruited using a stratified sampling method. Vaccine hesitancy was influenced by the 3Cs in the model. Socioeconomic status and vaccination history processed through the item parceling method were used to moderate associations between the 3Cs and hesitancy. Hierarchical regression analyses and structural equation modeling were used to test the validity of the new framework. We performed 5000 trials of bootstrapping to calculate the 95% CI of the pathway’s coefficients. ResultsA total of 1341 older adults participated. The mean age was 71.3 (SD 5.4) years, and 44.7% (599/1341) of participants were men. Confidence (b=0.967; 95% CI 0.759-1.201; P=.002), convenience (b=0.458; 95% CI 0.333-0.590; P=.002), and less complacency (b=0.301; 95% CI 0.187-0.408; P=.002) were positively associated with less vaccine hesitancy. Socioeconomic status weakened the positive effect of low complacency (b=–0.065; P=.03) on low vaccine hesitancy. COVID-19 vaccination history negatively moderated the positive association between confidence (b=–0.071; P=.02) and lower vaccine hesitancy. ConclusionsOur study identified that confidence was the more influential dimension in reducing vaccine hesitancy among older adults. COVID-19 vaccination history, as well as confidence, had a positive association with less vaccine hesitancy and could weaken the role of confidence in vaccine hesitancy. Socioeconomic status had a substitution relationship with less complacency, which suggested a competitive positive association between them on less vaccine hesitancy.

Litter decomposition is the main process that affects nutrient cycling and carbon budgets in mixed forests. However, knowledge of the response of the soil microbial processes to the mixed-litter decomposition of fresh leaf, semi-decomposed leaf and fine root is limited. Thus, a laboratory microcosm experiment was performed to explore the mixed-litter effects of fresh leaf, semi-decomposed leaf and fine root on the soil enzyme activity and microbial community in an evergreen broadleaf karst forest in Southwest China. Fresh leaf litter, semi-decomposed litter and fine root in the Parakmeria nitida and Dayaoshania cotinifolia forests, which are unique protective species and dominant species in the evergreen broadleaf forest, were decomposed alone and in all possible combinations, respectively. Our results showed that the mass loss of fresh leaf litter in three mixed-litter treatment was significantly higher than that in two mixed-litter treatment in the P. nitida and D. cotinifolia forests. Mass loss of fine root in the single litter treatment was significantly lower in the P. nitida forest and higher in the D. cotinifolia forest compared to that in the other litter treatments. There were insignificant differences in the activities of β-glucosidase (BG) and leucine aminopeptidase (LAP) between control and mixed-litter treatment in the P. nitida forest and between control and single litter treatment in the D. cotinifolia forest. The N-acetyl-β-D-glucosaminidase (NAG) activity was significantly increased by the single litter decomposition of fresh leaf and fine root and three mixed-litter decomposition in the P. nitida and D. cotinifolia forests. The activity of acid phospomonoesterase (AP) in the decomposition of fresh leaf litter was lower in the P. nitida forest and higher in the D. cotinifolia forest compared to that in control. The most dominant soil bacteria were Proteobacteria in the P. nitida forest and were Actinobacteria and Proteobacteria in the D. cotinifolia forest. Shannon, Chao1, ACE and PD indexes in the mixed-litter decomposition of fresh leaf and semi-decomposition litter were higher than that in control in P. nitida forest. There were insignificant differences in observed species and indexes of Chao1, ACE and PD between litter treatments in the D. cotinifolia forest. Richness of mixed-litter significantly affected mass loss, soil enzyme activity and microbial diversity in the P. nitida forest. Litter N concentration and the presence of fresh leaf litter were significantly correlated with the mass loss and soil enzyme activity in the P. nitida and D. cotinifolia forests. These results indicated that the presence of fresh leaf litter showed a non-negligible influence on mixed-litter decomposition and soil enzyme activity, which might be partly explained by litter initial quality in the P. nitida and D. cotinifolia forests.

This study evaluated different varicella vaccination strategies in Jiangsu province, China. A decision-tree Markov model was used to evaluate the cost effectiveness of various varicella vaccination strategies for children, including direct and selective vaccination (serotesting pre-vaccination). A cohort of one-year-old children was followed through 60 one-year Markov cycles. The parameter estimation was based on field work, the literature, and statistical yearbooks. We calculated the incremental cost-utility ratio (ICUR) using the saved quality-adjusted life year (QALY). One-way and probability sensitivity analyses were performed to assess uncertainty. Among 100,000 cohort members, one-dose and two-dose direct vaccination averted 8061 and 10,701 varicella cases, respectively, compared with no vaccination. Furthermore, compared with no vaccination, one-dose and two-dose direct vaccination saved one QALY at the ICUR of USD 21,401.33 and USD 35,420.81, respectively, at less than three times the per capita gross domestic product (USD 47,626.86) of Jiangsu. The ICURs of the one-dose and two-dose selective strategies versus no vaccination were USD 42,623.62 and USD 51,406.35 per QALY gained, respectively. The cost effectiveness results were most sensitive to the QALY loss of outpatients and vaccine prices. Thus, in Jiangsu, one-dose and two-dose direct varicella vaccination in children could be cost effective at the willingness to pay threshold of three times provincial GDP per capita from a societal perspective. The findings were sensitive to the vaccine price and health utility of varicella cases.

This study aimed to estimate the disease burden and health-related quality of life (HRQOL) among patients with severe hand, foot, and mouth disease (HFMD) in Jiangsu Province, China. We analyzed the surveillance data of HFMD cases in Jiangsu Province from 2009 to 2020. Moreover, a cross-sectional study was conducted in Nanjing and Suzhou, China, between January 2017 and May 2018. Patients with severe HFMD and their parents were recruited from selected hospitals. Questionnaires and hospital management systems were used to collect data on direct economic burden. The HRQOL of children was assessed using the TNO-AZL Preschool Quality of Life (TAPQOL) scale. A total of 1,348,737 confirmed cases of HFMD were reported to the NNDRS in Jiangsu province during 2009–2020. Of these, 9,622 were severe cases, with 62 (.64%) of these being fatal. From January 2017 to May 2018, data was collected from 362 severe HFMD cases using a structured questionnaire. The median per capita direct economic burden was RMB 16142.88, and was associated with the region and length of hospital stay (P

The common carbamate insecticide aldicarb is considered one of the most acutely toxic pesticides. Herein, rational design was used to synthesize two haptens with spacers of different carbon chain lengths. The haptens were then used to immunize mice. The antibodies obtained were evaluated systematically, and a colloidal gold immunochromatographic strip was developed based on an anti-aldicarb monoclonal antibody. The 50% inhibition concentration and linear range of anti-aldicarb monoclonal antibody immunized with Hapten 1 were 0.432 ng/mL and 0.106–1.757 ng/mL, respectively. The cross-reactivities for analogs of aldicarb were all

BackgroundEpstein–Barr virus (EBV)–related hemophagocytic lymphohistiocytosis (HLH) is an abnormal inflammation caused by EBV infection, which has high mortality during induction therapy.ObjectivesThis study is aimed to build a model to predict the risk of death during induction therapy.MethodsThe patients with EBV-HLH admitted from January 2015 to December 2018 were retrospectively reviewed. The primary outcome was death during induction therapy. The interval from receiving therapy to death or the end of induction therapy was the observing time. The patients admitted from January 2015 to December 2017 were assigned to the primary group, and the patients admitted from January to December 2018 were assigned to the validation group.ResultsWe included 234 patients with EBV-HLH, of whom 65 (27.4%) died during induction therapy. The middle observing time was 25 days. On the basis of the primary group, the multivariate Cox analysis demonstrated age >18 years, blood urea nitrogen, procalcitonin >2 µg/L, serum CD25, and EBV-DNA in peripheral blood mononuclear cell as the risk factors of death during induction therapy. We developed a nomogram integrating the above factors with high predictive accuracy (c-statistic, 0.86) and stratified all patients into the high-risk and the low-risk groups. On the basis of the validation group, the high-risk patients had a higher risk of death (hazard ratio, 4.93; P = 0.012). In the subgroup analysis based on patients receiving etoposide-based strategy, the mortality in high-risk and low-risk patients was 43.9 and 3.1 per 100 person-weeks, respectively.ConclusionWe developed a nomogram for risk stratification of patients with EBV-HLH receiving induction therapy.

BackgroundPromoting vaccination and eliminating vaccine hesitancy are key measures for controlling vaccine-preventable diseases. ObjectiveWe aimed to understand the beliefs surrounding and drivers of vaccination behavior, and their relationships with and influence on vaccination intention and practices. MethodsWe conducted a web-based survey in 31 provinces in mainland China from May 24, 2021 to June 15, 2021, with questions pertaining to vaccination in 5 dimensions: attitude, subjective norms, perceived behavioral control, intention, and behavior. We performed hierarchical regression analysis and structural equation modeling based on the theory of planned behavior—in which, the variables attitude, subjective norms, and intention each affect the variable intention; the variable intention mediates the relationships of attitude and subjective norms with behavior, and the variable perceived behavioral control moderates the strength of this mediation—to test the validity of the theoretical framework. ResultsA total of 9924 participants, aged 18 to 59 years, were included in this study. Vaccination intention mediated the relationships of attitude and subjective norms with vaccination behavior. The indirect effect of attitude on vaccination behavior was 0.164 and that of subjective norms was 0.255, and the difference was statistically significant (P

Abstract Conductive and degradable nanofibrous scaffolds have great potential in promoting cell growth, proliferation, and differentiation under an external electric field. Although the issue of inferior electrical conductivity in body fluids still exists, polyaniline (PANI)-based degradable nanofibers can promote cell adhesion, growth, and proliferation. To investigate whether the effect is caused by the PANI morphology, we selected three inorganic acids as dopants in the process of PANI in situ oxidative polymerization: hydrochloric acid, sulfuric acid, and perchloric acid. The obtained polyaniline/polylactic acid (PANI/PLA) composite nanofibers were characterized via SEM, FTIR, and XPS analysis, and we confirmed that the PLA nanofibers were successfully coated by PANI without any change to the porous structure of the PLA nanofibers. The in vitro mechanical properties and degradability indicated that the oxidation of acid dopants should be considered and that it was likely to have a higher oxidation degradation effect on PLA nanofibers. The contact angle test demonstrated that PANI/PLA composite nanofibers with different surface morphologies have good wettability, implying that they meet the requirements of bone tissue engineering scaffolds. The surface roughness and cell viability demonstrated that different PANI morphologies on the surface can promote cell proliferation. The higher the surface roughness of the PANI, the better the biocompatibility. Consequently, the regulated surface morphology of PANI/PLA composite nanofibers via different acids doping has positive effect on biocompatibility in tissue engineering.

Peroxisome proliferator-activated receptor γ (PPARγ) has 2 protein isoforms (PPARγ1 and PPARγ2) generated by alternative promoter usage and alternative splicing. However, their functional uniqueness and similarity remain unclear. In the study, we investigated the effects of lentivirus-mediated overexpression of PPARγ1 and PPARγ2 on proliferation, apoptosis, and differentiation of the immortalized chicken preadipocytes. Cell Counting Kit–8 assay showed PPARγ1 and PPARγ2 overexpression markedly suppressed cell proliferation, and fluorescence activated cell sorting analysis showed that PPARγ1 and PPARγ2 overexpression caused cell cycle arrest at G0/G1 phase. Cell death detection ELISA analysis showed both PPARγ1 and PPARγ2 overexpression induced cell apoptosis. Oil red O staining and gene expression analysis showed both PPARγ1 and PPARγ2 overexpression promoted preadipocyte differentiation. In the presence of PPARγ ligand, rosiglitazone, PPARγ2 overexpression was more potent in inducing apoptosis, promoting adipogenesis, and suppressing cell proliferation than PPARγ1 overexpression. We further explored the molecular basis for their functional differences. Reporter gene assay showed that under ligand conditions, PPARγ2 overexpression resulted in 1.68-fold increase in transcription activity compared with PPARγ1. Electrophoretic mobility shift assay showed both PPARγ1 and PPARγ2 could bind to PPAR response element (PPRE) as heterodimer with retinoid X receptor alpha, and by comparison, PPARγ2 had a higher affinity for PPRE than PPARγ1. Reporter gene assay showed expression PPARγ1 and PPARγ2 similarly induced fatty acid synthase and adipocyte fatty acid–binding protein promoter activity but differentially induced lipoprotein lipase and perilipin 1 promoter activities. Coimmunoprecipitation analysis showed that PPARγ1 and PPARγ2 interacted similarly with the coactivators, Tat-interacting protein 60. Taken together, our results demonstrate that PPARγ1 and PPARγ2 differentially regulate preadipocyte proliferation, apoptosis, and differentiation as a result of their distinct and overlapping molecular functions.

BackgroundIt was reported that one in four parents were hesitant about vaccinating their children in China. Previous studies have revealed a declining trend in the vaccine willingness rate in China. There is a need to monitor the level of parental vaccine hesitancy toward routine childhood vaccination and hesitancy toward the COVID-19 vaccine during the ongoing COVID-19 pandemic. ObjectiveThis study aims to assess changes in trends of parental attitudes toward routine childhood vaccines and COVID-19 vaccinations across different time periods in China. MethodsThree waves of cross-sectional surveys were conducted on parents residing in Wuxi City in Jiangsu Province, China from September to October 2020, February to March 2021, and May to June 2021. Participants were recruited from immunization clinics. Chi-square tests were used to compare the results of the three surveys, controlling for sociodemographic factors. Binary and multivariable logistic regression analysis was used to examine factors related to parental vaccine hesitancy and COVID-19 vaccine willingness. ResultsOverall, 2881, 1038, and 1183 participants were included in the survey’s three waves. Using the Vaccine Hesitancy Scale, 7.8% (225/2881), 15.1% (157/1038), and 5.5% (65/1183) of parents showed hesitancy to childhood vaccination (P

Abstract Background Sarcomatoid carcinoma (SC) is a malignant tumour composed of spindle cells. The incidence of SC is low, especially in the uterus. The imaging features of uterine sarcomatoid carcinoma (USC) are rarely reported. We report a case of USC and discuss the dynamic contrast-enhanced MR (DCE-MR) and PET/CT findings. Case presentation A 69-year-old woman presented to the Department of Gynaecology with vaginal bleeding. Ultrasound examination discovered a heterogeneous mass in the cervix. Then, MRI examination of the pelvis was performed. On T2-weighted images, the uterus was replaced by an ill defined and diffuse lesion with inhomogeneous intensity. On T1-weighted images, the lesion appeared with signal hypointensity and was heterogeneously enhanced with contrast material. Additionally, enlarged lymph nodes were found in the pelvic cavity. PET/CT demonstrated high uptake in the region of the uterus and pelvic lymph nodes, which was consistent with MRI findings. The radiologists diagnosed the patient with malignant uterine lesions. The patient underwent hysterectomy and bilateral adnexectomy with pelvic lymph node dissection. Then, systemic radiotherapy and chemotherapy were performed. USC with lymph node metastasis was diagnosed with the help of immuno-histochemical analysis. There was no treatment related complication and no evidence of tumour recurrence at the postoperative 6-month follow-up. Conclusion MRI and PET/CT features are sufficient to indicate the malignant nature of a USC, but they are not pathognomonic.

Vitiligo is a depigmented skin disorder caused by a variety of factors, including autoimmune, metabolic disturbance or their combined effect, etc. Non-targeted metabolomic analyses have denoted that dysregulated fatty acids metabolic pathways are involved in the pathogenesis of vitiligo. However, the exact category of fatty acids that participate in vitiligo development and how they functionally affect CD8+ T cells remain undefined. We aimed to determine the difference in specific fatty acids among vitiligo patients and healthy individuals and to investigate their association with clinical features in patients with vitiligo. Serum levels of fatty acids in 48 vitiligo patients and 28 healthy individuals were quantified by performing ultra-performance liquid chromatography-tandem mass spectrometry. Univariate and multivariate analyses were carried out to evaluate the significance of differences. Moreover, flow cytometry was used to explore the effect of indicated fatty acids on the function of CD8+ T cells derived from patients with vitiligo. We demonstrated that serological level of alpha-linolenic acid (ALA) was markedly upregulated, while that of arachidonic acid (ARA), arachidic acid (AA) and behenic acid were significantly downregulated in patients with vitiligo. Moreover, ALA levels were positively associated with vitiligo area scoring index (VASI) and ARA was a probable biomarker for vitiligo. We also revealed that supplementation with ARA or nordihydroguaiaretic acid (NDGA) could suppress the function of CD8+ T cells. Our results showed that vitiligo serum has disorder-specific phenotype profiles of fatty acids described by dysregulated metabolism of polyunsaturated fatty acids. Supplementation with ARA or NDGA might promote vitiligo treatment. These findings provide novel insights into vitiligo pathogenesis that might add to therapeutic options.

Evidence for the validity and reliability of the World Health Organization’s 10-item vaccine hesitancy scale (VHS) in different settings is not sufficient, especially for criteria validity. This study aimed to assess the validity and reliability of the VHS using child vaccination data in China. A cross-sectional survey was performed with parents of 19–48-month-old children at six vaccination clinics in Wuxi City between September and October 2020. The VHS was revised to category A (expanded program on immunization, EPI) VHS and category B (Non-EPI) VHS. Factor analysis was used to confirm the latent domain and to assess the model structure. The average variance extracted (AVE) was calculated to assess convergent validity, and Cronbach’s α and composite reliability (CR) were used to determine internal consistency. The association between VHS scores and children’s vaccination status was examined to assess criteria validity using logistic regression. The survey response rate was 75.3% (n = 802). Two factors were identified, explaining 64.60% and 63.34% of the common variance in categories A and B VHS, respectively. The Cronbach’s α of > 0.7 and CR of >0.7 in the scale indicated the VHS has acceptable internal consistency. The AVE values indicated that convergent validity was not ideal for the VHS. There were no statistically significant associations between VHS scores and vaccination status, indicating that the criterion validity was not ideal. The VHS needs improvement before becoming a standard survey tool.

Background Vaccine hesitancy was listed as one of the top 10 issues threatening global health in 2019. The objectives of this study were to (a) use an extended protection motivation theory (PMT) with an added trust component to identify predictors of vaccine hesitancy and (b) explore the predictive ability of vaccine hesitancy on vaccination behavior. Methods We conducted an online questionnaire from February 9 to April 9, 2021, in China. The target population was Chinese residents aged 18 and over. A total of 14,236 responses were received. Structural equation modeling was used to test the extended PMT model hypotheses. Results A total of 10,379 participants were finally included in this study, of whom 52.0% showed hesitancy toward vaccination. 2854 (27.5%) participants reported that they got flu shots in the past year, and 2561 (24.7%) participants were vaccinated against COVID-19. 2857 (27.5%) participants engaged in healthcare occupation. The model explained 85.7% variance of vaccine hesitancy. Self-efficacy was the strongest predictor, negatively associated with vaccine hesitancy (β = −0.584; p

This study aimed to assess the cost-effectiveness of various public health measures in dealing with coronavirus disease 2019 (COVID-19) in China. A stochastic agent-based model was used to simulate the progress of the COVID-19 outbreak in scenario I (imported one case) and scenario II (imported four cases) with a series of public health measures. The main outcomes included the avoided infections and incremental cost-effectiveness ratios (ICERs). Sensitivity analyses were performed to assess uncertainty. The results indicated that isolation-and-quarantine averted the COVID-19 outbreak at the lowest ICERs. The joint strategy of personal protection and isolation-and-quarantine averted one more case than only isolation-and-quarantine with additional costs. The effectiveness of isolation-and-quarantine decreased with lowering quarantine probability and increasing delay time. The strategy that included community containment would be cost-effective when the number of imported cases was >65, or the delay time of the quarantine was more than 5 days, or the quarantine probability was below 25%, based on current assumptions. In conclusion, isolation-and-quarantine was the most cost-effective intervention. However, personal protection combined with isolation-and-quarantine was the optimal strategy for averting more cases. The community containment could be more cost-effective as the efficiency of isolation-and-quarantine drops and the imported cases increases.

ObjectivesTo explore the clinical value of subendometrial enhancement (SEE), irregular thin-layered peritumoral early enhancement (ITLPE) and focal irregular peritumoral early enhancement (FIPE) on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for myometrial invasion in patients with low-risk endometrial carcinoma.MethodsSeventy-seven patients with low-risk endometrial carcinoma who preoperatively underwent DCE-MRI were included. Two radiologists independently evaluated and recorded the occurrences of SEE, ITLPE and FIPE on DCE-MRI in all patients. Interobserver agreement was calculated between the two radiologists, and the relationships between SEE, ITLPE, FIPE, and myometrial invasion were analyzed based on histologic findings. For statistically significant findings, the sensitivity and specificity were calculated, and the differences in myometrial invasion evaluations were analyzed. For those with no statistical significance, images were compared with the histopathologic sections.ResultsInter-observer agreement was good (k = 0.80; 95%CI, 0.577–0.955) for SEE, and very good (k = 0.88; 95%CI, 0.761–0.972) (k = 0.86; 95%CI, 0.739–0.973) for ITLPE and FIPE. After consensus, SEE was identified in 12/77 (15.6%) patients; ITLPE and FIPE were found in 53/77 (68.8%) and 30/77 (39.0%) patients, respectively. SEE and ITLPE were significantly correlated with myometrial infiltration (P = 0.000), but FIPE were not (P = 0.725).The sensitivity and specificity of SEE and ITLPE for myometrial invasion in patients with low-risk endometrial carcinoma were 95.0 and 52.9%, and 85.0 and 88.0%, respectively. The area under the curve (AUC) of SEE and ITLPE for myometrial invasion were 0.740 (95%CI, 0.584–0.896), and 0.866 (95%CI, 0.763–0.970), respectively. The sensitivity and specificity were statistically different between SEE and ITLPE for the detection of myometrial invasion (P = 0.031, 0.016). According to the comparison between FIPE and histopathologic findings, the irregular endomyometrial junction was found in 30/77 (38.9%) cases, 24/30 (80.0%) with myometrial infiltration and 6/30 (20.0%) cases without myometrial infiltration.ConclusionsFIPE was the irregular endomyometrial junction. It can be found in patients with or without myometrial infiltration and may lead to the overestimation of myometrial invasion by SEE on DCE-MRI. ITLPE presented high diagnostic performance and specificity for myometrial invasion in patients with low-risk endometrial carcinoma.

As vane inlet temperatures and turbine loadings are increasing, the aerodynamic and thermal management for the endwalls of gas turbines have received increased attention. Non-axisymmetric endwalls are becoming popular due to their proficient capabilities to modify the secondary flow fields and to change the film cooling performance on the endwalls. In this study, by considering the interaction between mainstream and purge flow based on non-axisymmetric endwall contouring, the numerical research model used in the present research was established. Based on the validated numerical method, the influence of the non-axisymmetric endwall contouring on the film-cooling effectiveness and aerodynamic characteristics was studied. Furthermore, the effect of different inclination angles on the film-cooling performance of the contoured endwalls was also investigated. The results indicate that for the high-load turbine vane used in this research, various types of non-axisymmetric endwall contouring can alter the aero-dynamic characteristics and cooling performance simultaneously. By inhibiting the secondary flows, non-axisymmetric endwall contouring can reduce the total cascade pressure loss coefficient by 0.305%. In addition, non-axisymmetric endwall contouring can significantly enhance the effective coverage area of purge flow up to 28.29%, and the endwall near the suction side can achieve better cooling performance. Finally, non-axisymmetric endwall contouring can improve the protective effect of large-angle purge flow.

Abstract Intestinal epithelium functions as a barrier to protect multicellular organisms from the outside world. It consists of epithelial cells closely connected by intercellular junctions, selective gates which control paracellular diffusion of solutes, ions and macromolecules across the epithelium and keep out pathogens. Rotavirus is one of the major enteric viruses causing severe diarrhea in humans and animals. It specifically infects the enterocytes on villi of small intestines. The polarity of rotavirus replication in their target enterocytes and the role of intestinal epithelial integrity were examined in the present study. Treatment with EGTA, a drug that chelates calcium and disrupts the intercellular junctions, (i) significantly enhanced the infection of rotavirus in primary enterocytes, (ii) increased the binding of rotavirus to enterocytes, but (iii) considerably blocked internalization of rotavirus. After internalization, rotavirus was resistant to EGTA treatment. To investigate the polarity of rotavirus infection, the primary enterocytes were cultured in a transwell system and infected with rotavirus at either the apical or the basolateral surface. Rotavirus preferentially infected enterocytes at the basolateral surface. Restriction of infection through apical inoculation was overcome by EGTA treatment. Overall, our findings demonstrate that integrity of the intestinal epithelium is crucial in the host’s innate defense against rotavirus infection. In addition, the intercellular receptor is located basolaterally and disruption of intercellular junctions facilitates the binding of rotavirus to their receptor at the basolateral surface.

Background: 6-Mercaptopurine (6-MP) is the cornerstone of current antileukemia regimen and contributes greatly to improve the survival of pediatric acute lymphoblastic leukemia (ALL) patients. However, 6-MP dose-related toxicities limit its application. TPMT, NUDT15, and ITPA are pharmacogenetic markers predicting 6-MP-related toxicities, but their genetic polymorphisms differ from those of ethnic populations. In Yunnan province, a multiethnic region of China, we had no genetic data to predict 6-MP toxicities. In this study, we evaluated the most common variants involved in 6-MP metabolism—TPMT*3C (rs1142345), NUDT15 c.415C>T (rs116855232), and ITPA c.94C>A (rs1127354) variants—in our cohort of pediatric ALL patients.Methods: A total of 149 pediatric ALL patients in the Affiliated Children's Hospital of Kunming Medical University (Yunnan Children's Medical Center) from 2017 to 2019 were enrolled in this retrospective study. We assessed the TPMT*3C (rs1142345), NUDT15 c.415C>T (rs116855232), and ITPA c.94C>A (rs1127354) frequencies and evaluated association between genotypes and 6-MP toxicities, 6-MP dose, and event-free survival (EFS) in these ALL patients.Results: The allele frequencies of TPMT*3C (rs1142345), NUDT15 c.415C>T (rs116855232), and ITPA c.94C>A (rs1127354) were 1.34%, 14.43%, and 18.79%, respectively. Only NUDT15 c.415C>T (rs116855232) was strongly associated with 6-MP toxicity and 6-MP tolerable dose. NUDT15 c.415C>T was related to leukopenia, p = 0.008, OR = 2.743 (95% CI: 1.305–5.768). The T allele was significantly correlated with 6-MP tolerable dose, dose of NUDT15 c.415C>T wild genotype CC 39.80 ± 1.32 mg/m2, heterozygotes CT 35.20 ± 2.29 mg/m2, and homozygotes TT 18.95 ± 3.95 mg/m2. 6-MP tolerable dose between CC and TT had a significant difference, p = 0.009. Between CC and CT, and CT and TT, they had no significant difference. EFS showed no significant difference among NUDT15 c.415C>T genotypes.Conclusion:NUDT15 c.415C>T (rs116855232) was an optimal predictor for 6-MP toxicity and tolerable dose in pediatric ALL patients from Yunnan province, a multiethnic region in China, and would play an important role in precise therapy for ALL.

Exploring the health risks of diseases attributed to PM2.5 and SO2 exposure and analyzing the differences in their distribution over emissions can provide useful insights for decision-makers to reduce premature mortality due to PM2.5 and SO2 exposure. This study used exposure-response functions, health risk inequality curve (HRICU, based on Lorenz curve), and the health risk inequality coefficient (HRICO, based on Gini coefficient) to estimate population health risks of PM2.5 and SO2 exposure in China from 2013 to 2017 based on a full-coverage, high-precision PM2.5 and SO2 concentration and emission dataset. The inequality in the distribution of premature mortality was explored in terms of pollutant emissions. The results showed that (1) premature mortalities from cardiovascular disease (CVD) and respiratory disease (RD) due to PM2.5 and SO2 exposure decreased by 21% and 54%, respectively, from 2013 to 2017. (2) At a national scale, the HRICO value for the distribution of PM2.5 and SO2 health risks on emissions were lower than 0.10 and 0.20, respectively. (3) More than 20% of provinces had HRICO values above 0.1 for PM2.5 or SO2. The provinces near the national borders generally had higher HRICO for PM2.5, while the province with the most severe inequity in the distribution of SO2 health risks on emissions appeared in Xinjiang Uygur Autonomous Region, Ningxia Hui Autonomous Region, and Hainan Province.