Hyaluronic acid modified extracellular vesicles targeting hepatic stellate cells to attenuate hepatic fibrosis.

RATIONALE: Transforming growth factor-beta1 (TGF-ß1) plays a pivotal role in promoting hepatic fibrosis, pirfenidone (PFD) could inhibit TGF-ß1 signaling pathway to alleviate hepatic stellate cells (HSC) activation mediated hepatic fibrosis. The targeting delivery strategy of PFD to hepatic stellate cells is a challenge. Extracellular vesicles (EVs), cell-derived membranous particles are intraluminal nano-vesicles that play a vital role in intercellular communication, they also be considered as an ideal nano-carrier. METHODS: In this study, we developed a target strategy to deliver PFD to HSC with CD44 over-expression by EVs, hyaluronic acid (HA) modified DSPE-PEG2000 endows the active targeting ability of activated HSCs to PFD-loaded EVs. RESULTS: In both rat hepatic stellate cell line HSC-T6 and rat hepatocyte cell line BRL, HA@EVs-PFD demonstrated the capacity to down-regulate the expression of collagen-synthesis-related proteins and showed superior inhibition efficacy of HSC-T6 activation compared to free PFD. In hepatic fibrosis model, 4 weeks of HA@EVs-PFD treatment resulted in a reduction in liver collagen fibers, significant improvement in hepatic cell morphology, and amelioration of hepatic fibrosis. CONCLUSIONS: HA@EVs-PFD, as a drug delivery system that effectively targets and inhibits activated HSCs to treat hepatic fibrosis, holds promise as a potential therapeutic agent against hepatic fibrosis.

Review of sheep breeding and genetic research in Türkiye.

The livestock industry in Türkiye is vital to the country's agricultural sector and economy. In particular, sheep products are an important source of income and livelihood for many Turkish smallholder farmers in semi-arid and highland areas. Türkiye is one of the largest sheep producers in the world and its sheep production system is heavily dependent on indigenous breeds. Given the importance of the sheep industry in Türkiye, a systematic literature review on sheep breeding and genetic improvement in the country is needed for the development and optimization of sheep breeding programs using modern approaches, such as genomic selection. Therefore, we conducted a comprehensive literature review on the current characteristics of sheep populations and farms based on the most up-to-date census data and breeding and genetic studies obtained from scientific articles. The number of sheep has increased in recent years, mainly due to the state's policy of supporting livestock farming and the increase in consumer demand for sheep dairy products with high nutritional and health benefits. Most of the genetic studies on indigenous Turkish sheep have been limited to specific traits and breeds. The use of genomics was found to be incipient, with genomic analysis applied to only two major breeds for heritability or genome-wide association studies. The scope of heritability and genome-wide association studies should be expanded to include traits and breeds that have received little or no attention. It is also worth revisiting genetic diversity studies using genome-wide single nucleotide polymorphism markers. Although there was no report of genomic selection in Turkish sheep to date, genomics could contribute to overcoming the difficulties of implementing traditional pedigree-based breeding programs that require accurate pedigree recording. As indigenous sheep breeds are better adapted to the local environmental conditions, the proper use of breeding strategies will contribute to increased income, food security, and reduced environmental footprint in a sustainable manner.

sc2MeNetDrug: A computational tool to uncover inter-cell signaling targets and identify relevant drugs based on single cell RNA-seq data.

Single-cell RNA sequencing (scRNA-seq) is a powerful technology to investigate the transcriptional programs in stromal, immune, and disease cells, like tumor cells or neurons within the Alzheimer's Disease (AD) brain or tumor microenvironment (ME) or niche. Cell-cell communications within ME play important roles in disease progression and immunotherapy response and are novel and critical therapeutic targets. Though many tools of scRNA-seq analysis have been developed to investigate the heterogeneity and sub-populations of cells, few were designed for uncovering cell-cell communications of ME and predicting the potentially effective drugs to inhibit the communications. Moreover, the data analysis processes of discovering signaling communication networks and effective drugs using scRNA-seq data are complex and involve a set of critical analysis processes and external supportive data resources, which are difficult for researchers who have no strong computational background and training in scRNA-seq data analysis. To address these challenges, in this study, we developed a novel open-source computational tool, sc2MeNetDrug (https://fuhaililab.github.io/sc2MeNetDrug/). It was specifically designed using scRNA-seq data to identify cell types within disease MEs, uncover the dysfunctional signaling pathways within individual cell types and interactions among different cell types, and predict effective drugs that can potentially disrupt cell-cell signaling communications. sc2MeNetDrug provided a user-friendly graphical user interface to encapsulate the data analysis modules, which can facilitate the scRNA-seq data-based discovery of novel inter-cell signaling communications and novel therapeutic regimens.

Run-up speed and jumping ground reaction force of male elite gymnasts on vault in China.

Background: A high run-up speed and a big jumping ground reaction force are crucial to perform difficult movements and improving the quality of movement performance in the competition vault. However, the relationship between performance in the competition vault and run-up speeds, as well as jumping ground reaction force, still needs to be discovered in detail. Objective: We aimed to investigate the interrelations between different run-up speeds and jumping ground reaction force, and to explore the different requirements of performing different vault styles as well as difficult movements on run-up speed and jumping ground reaction force. Methods: The data, including vaulting run-up speed and jumping ground reaction force of 30 Chinese male elite gymnasts of performance testing, were analyzed. Descriptive statistics and Binary logistic regression analysis were used for statistical analysis. Results: There was no significant difference in the pedaling run-up speed between the Front handspring types and Cartwheel types (p > 0.05). The comparison between interval run-up speeds revealed that the last 5 m run-up speeds were faster during the 25 m run-up distance, and 30 m sprint speed was strongly associated with the 25 m vaulting run-up speed of Handspring and Cartwheel (r = 0.81, p < 0.01). There are significant differences in the jumping ground reaction force of different types and difficult movements (p < 0.01). When the D-score is greater than 4.6, the jumping ground reaction force will increase significantly. Jumping ground reaction force was strongly correlated with 25 m run-up speed (r = 0.715, p < 0.01), last 5 m run-up speed (r = 0.718, p < 0.01), and 30 m sprint speed (r = 0.704, p < 0.01) respectively, but not significantly associated with last 10-5 m run-up speed as well as before the last 10 m run-up speed (p > 0.05). Conclusions: The special requirement for run-up speed and jumping ground reaction force may vary as the difficult vault. Moreover, the optimization of interval run-up speeds and improvement of the 25 m run-up speed may contribute to the bigger jumping ground reaction force and increase the potential to perform more difficult Handspring/Cartwheel vaults. The topic may merit an interventional study to optimize run-up rhythm and improve lower limb strength for achieving higher run-up speeds and bigger jumping ground reaction force within the limited run-up distance to perform more difficult vaults for male elite gymnasts in China.

Adaptive design of mRNA-loaded extracellular vesicles for targeted immunotherapy of cancer.

The recent success of mRNA therapeutics against pathogenic infections has increased interest in their use for other human diseases including cancer. However, the precise delivery of the genetic cargo to cells and tissues of interest remains challenging. Here, we show an adaptive strategy that enables the docking of different targeting ligands onto the surface of mRNA-loaded small extracellular vesicles (sEVs). This is achieved by using a microfluidic electroporation approach in which a combination of nano- and milli-second pulses produces large amounts of IFN-γ mRNA-loaded sEVs with CD64 overexpressed on their surface. The CD64 molecule serves as an adaptor to dock targeting ligands, such as anti-CD71 and anti-programmed cell death-ligand 1 (PD-L1) antibodies. The resulting immunogenic sEVs (imsEV) preferentially target glioblastoma cells and generate potent antitumour activities in vivo, including against tumours intrinsically resistant to immunotherapy. Together, these results provide an adaptive approach to engineering mRNA-loaded sEVs with targeting functionality and pave the way for their adoption in cancer immunotherapy applications.

[Status of infant and young child feeding in China in 2016-2017].

OBJECTIVE: To describe the feeding status and related factors of infant and young child aged 6-23 months in China. METHODS: Data was from the China Nutrition and Health Surveillance among 0-17 Years Old Children and Lactating Women in 2016-2017, and 20 423 children aged 6-23 months were involved in 275 surveillance sites from 31 provinces(autonomous regions and municipalities). The introduction of solid, semi-solid or soft foods, minimum dietary diversity, minimum meal frequency were analyzed with WHO and UNICEF 2021 updated infant and young child feeding indicators. Data analyses were conducted using the complex weight based on national census from National Bureau of Statistics in 2010. Rao-Scott Chi-square was used test for statistical difference. RESULTS: The percentage of infants 6-8 months of age who consumed solid, semi-solid or soft foods was 83.2%(95%CI 80.5%-85.9%) in 2016-2017. No significant difference were observed between boys and girls; there was significant difference in different areas(Rao-Scott χ~2=30.85, P<0.01), it was 90.3% in medium and small cities, and reached 75.0% even in poor rural areas. The proportions of children aged 6-23 months meeting minimum dietary diversity(MDD) was 60.6%(95%CI 58.1%-63.1%). It was 71.1% in medium and small cities, and 50.5% in poor rural areas. Except for breast milk, the percentage of eggs(34.4%) and legumes(19.0%) consumption was low, the percentage of grains, vitamin A-rich fruits or vegetables consumption was 89.7%(95%CI 88.4%-91.1%). The percentage of consuming egg and/or flesh food was 76.4%(95%CI 74.2%-78.7%). The percentage of zero vegetables or fruits consumption was 9.1%(95%CI 7.8%-10.4%). The proportions of children aged 6-23 months meeting minimum meal frequency(MMF) was 72.4%(95%CI 70.1%-74.7%). It was over 70% in large cities, medium and small cities, general rural areas; and 60.2% in poor rural areas. The proportions of children aged 6-23 months meeting minimum acceptable diet was 43.4%(95%CI 40.7%-46.1%), it was over 50% in urban areas, and less than 40% in rural areas, 30.1% in poor rural areas. No consistent differences were observed between boys and girls for all 3 indicators(MDD, MMF and MAD), and there was significant difference in different areas and various months of age(P<0.01). CONCLUSION: There was no gender difference in the feeding status of children aged 6-23 months in China, the complementary feeding was relatively timely, and the minimum dietary diversity and meal frequency of children were relatively ideal, but the minimum acceptable diet of children in poor rural areas was poor.

Research progress of diabetic retinopathy and gut microecology.

According to the prediction of the International Diabetes Federation, global diabetes mellitus (DM) patients will reach 783.2 million in 2045. The increasing incidence of DM has led to a global epidemic of diabetic retinopathy (DR). DR is a common microvascular complication of DM, which has a significant impact on the vision of working-age people and is one of the main causes of blindness worldwide. Substantial research has highlighted that microangiopathy and chronic low-grade inflammation are widespread in the retina of DR. Meanwhile, with the introduction of the gut-retina axis, it has also been found that DR is associated with gut microecological disorders. The disordered structure of the GM and the destruction of the gut barrier result in the release of abnormal GM flora metabolites into the blood circulation. In addition, this process induced alterations in the expression of various cytokines and proteins, which further modulate the inflammatory microenvironment, vascular damage, oxidative stress, and immune levels within the retina. Such alterations led to the development of DR. In this review, we discuss the corresponding alterations in the structure of the GM flora and its metabolites in DR, with a more detailed focus on the mechanism of gut microecology in DR. Finally, we summarize the potential therapeutic approaches of DM/DR, mainly regulating the disturbed gut microecology to restore the homeostatic level, to provide a new perspective on the prevention, monitoring, and treatment of DR.

Novel heterozygous mutations of SLC12A3 gene in a Chinese pedigree with Gitelman syndrome: A care-compliant case report.

RATIONALE: The diagnosis of Gentleman syndrome (GS) is usually delayed because the clinical symptoms are easily mistaken. PATIENT CONCERNS: A 19-year-old male patient was referred to endocrinology due to intermittent twitch of extremities for approximately 7 years. DIAGNOSES: The diagnosis of GS was made based on the laboratory and gene detection results. We identified 2 new variants in the SLC12A3 gene [c.857 A > C (exon7) and c.2089_2095del (exon17)] in his Asian family. INTERVENTIONS: The patient received the treatment of potassium chloride sustained release tablets, potassium magnesium aspartate and spironolactone. After given potassium supplement through enema, his serum potassium level was corrected to normal. OUTCOMES: The electrolyte imbalance including hypokalemia and hypomagnesemia were improved with a remission of the clinical manifestations. But the patient's condition still could not remain stable for his irregular oral potassium supplementation during the follow-up of nearly 3 months. LESSONS: Our finding broadens the variant spectrum of SLC12A3 and contributes to a more quickly genetic counseling. As a result, when a patient presents with persistent, unspecified, and inadequately treated hypokalemia, tests for GS should indeed be considered. For suspected cases of GS, genetic testing should always be considered in the diagnosis.

Autologous humanized PDX modeling for immuno-oncology recapitulates features of the human tumor microenvironment.

BACKGROUND: Interactions between immune and tumor cells are critical to determining cancer progression and response. In addition, preclinical prediction of immune-related drug efficacy is limited by interspecies differences between human and mouse, as well as inter-person germline and somatic variation. To address these gaps, we developed an autologous system that models the tumor microenvironment (TME) from individual patients with solid tumors. METHOD: With patient-derived bone marrow hematopoietic stem and progenitor cells (HSPCs), we engrafted a patient's hematopoietic system in MISTRG6 mice, followed by transfer of patient-derived xenograft (PDX) tissue, providing a fully genetically matched model to recapitulate the individual's TME. We used this system to prospectively study tumor-immune interactions in patients with solid tumor. RESULTS: Autologous PDX mice generated innate and adaptive immune populations; these cells populated the TME; and tumors from autologously engrafted mice grew larger than tumors from non-engrafted littermate controls. Single-cell transcriptomics revealed a prominent vascular endothelial growth factor A (VEGFA) signature in TME myeloid cells, and inhibition of human VEGF-A abrogated enhanced growth. CONCLUSIONS: Humanization of the interleukin 6 locus in MISTRG6 mice enhances HSPC engraftment, making it feasible to model tumor-immune interactions in an autologous manner from a bedside bone marrow aspirate. The TME from these autologous tumors display hallmarks of the human TME including innate and adaptive immune activation and provide a platform for preclinical drug testing.

An atlas of regulatory elements in chicken: A resource for chicken genetics and genomics.

A comprehensive characterization of regulatory elements in the chicken genome across tissues will have substantial impacts on both fundamental and applied research. Here, we systematically identified and characterized regulatory elements in the chicken genome by integrating 377 genome-wide sequencing datasets from 23 adult tissues. In total, we annotated 1.57 million regulatory elements, representing 15 distinct chromatin states, and predicted about 1.2 million enhancer-gene pairs and 7662 super-enhancers. This functional annotation of the chicken genome should have wide utility on identifying regulatory elements accounting for gene regulation underlying domestication, selection, and complex trait regulation, which we explored. In short, this comprehensive atlas of regulatory elements provides the scientific community with a valuable resource for chicken genetics and genomics.

Evaluating metabolic and genomic data for predicting grain traits under high night temperature stress in rice.

The asymmetric increase in average nighttime temperatures relative to increase in average daytime temperatures due to climate change is decreasing grain yield and quality in rice. Therefore, a better genome-level understanding of the impact of higher night temperature stress on the weight of individual grains is essential for future development of more resilient rice. We investigated the utility of metabolites obtained from grains to classify high night temperature (HNT) conditions of genotypes, and metabolites and single-nucleotide polymorphisms (SNPs) to predict grain length, width, and perimeter phenotypes using a rice diversity panel. We found that the metabolic profiles of rice genotypes alone could be used to classify control and HNT conditions with high accuracy using random forest or extreme gradient boosting. Best linear unbiased prediction and BayesC showed greater metabolic prediction performance than machine learning models for grain-size phenotypes. Metabolic prediction was most effective for grain width, resulting in the highest prediction performance. Genomic prediction performed better than metabolic prediction. Integrating metabolites and genomics simultaneously in a prediction model slightly improved prediction performance. We did not observe a difference in prediction between the control and HNT conditions. Several metabolites were identified as auxiliary phenotypes that could be used to enhance the multi-trait genomic prediction of grain-size phenotypes. Our results showed that, in addition to SNPs, metabolites collected from grains offer rich information to perform predictive analyses, including classification modeling of HNT responses and regression modeling of grain-size-related phenotypes in rice.

Multi-environment analysis enhances genomic prediction accuracy of agronomic traits in sesame.

Introduction: Sesame is an ancient oilseed crop containing many valuable nutritional components. The demand for sesame seeds and their products has recently increased worldwide, making it necessary to enhance the development of high-yielding cultivars. One approach to enhance genetic gain in breeding programs is genomic selection. However, studies on genomic selection and genomic prediction in sesame have yet to be conducted. Methods: In this study, we performed genomic prediction for agronomic traits using the phenotypes and genotypes of a sesame diversity panel grown under Mediterranean climatic conditions over two growing seasons. We aimed to assess prediction accuracy for nine important agronomic traits in sesame using single- and multi-environment analyses. Results: In single-environment analysis, genomic best linear unbiased prediction, BayesB, BayesC, and reproducing kernel Hilbert spaces models showed no substantial differences. The average prediction accuracy of the nine traits across these models ranged from 0.39 to 0.79 for both growing seasons. In the multi-environment analysis, the marker-by-environment interaction model, which decomposed the marker effects into components shared across environments and environment-specific deviations, improved the prediction accuracies for all traits by 15%-58% compared to the single-environment model, particularly when borrowing information from other environments was made possible. Discussion: Our results showed that single-environment analysis produced moderate-to-high genomic prediction accuracy for agronomic traits in sesame. The multi-environment analysis further enhanced this accuracy by exploiting marker-by-environment interaction. We concluded that genomic prediction using multi-environmental trial data could improve efforts for breeding cultivars adapted to the semi-arid Mediterranean climate.

Human Milk Oligosaccharides Are Associated with Lactation Stage and Lewis Phenotype in a Chinese Population.

BACKGROUND: Human milk oligosaccharides (HMOs) are the third most abundant component of human milk. Various factors may affect the concentration of HMOs, such as the lactation period, Lewis blood type, and the maternal secretor gene status. OBJECTIVES: The purpose of this study is to investigate factors associated with HMO concentrations in Chinese populations. METHODS: A sub-sample of 481 was randomly selected from a large cross-sectional study in China (n = 6481) conducted in eight provinces (Beijing, Heilongjiang, Shanghai, Yunnan, Gansu, Guangdong, Zhejiang, and Shandong) between 2011 and 2013. HMO concentrations were determined by a high-throughput UPLC-MRM method. Various factors were collected through face-to-face interviews. Anthropometric measurement was conducted by trained staff. RESULTS: Median total HMO concentration was 13.6 g/L, 10.7 g/L, and 6.0 g/L for colostrum, transitional milk, and mature milk, respectively. HMO concentration decreased significantly as the lactation period increased (p < 0.0001). There were significant differences of average total HMO concentration between secretor mothers and non-secretor mothers (secretor 11.3 g/L vs. non-secretor 5.8 g/L, p < 0.0001). There were significant differences of average total HMO concentrations among three Lewis blood types (p = 0.003). Comparing with the concentration of total oligosaccharides of Le+ (a-b+), average of total oligosaccharides concentrations increased by 3.9 (Le+ (a+b-), p = 0.004) and 1.1 g/L (Le- (a-b-), p = 0.049). The volume of breast milk expressed and the province the mother came from affected the concentration of total oligosaccharides (all p < 0.0001). Maternal BMI (p = 0.151), age (p = 0.630), prematurity (p = 0.850), mode of delivery (p = 0.486), infants' gender (p = 0.685), maternal education level (p = 0.989), maternal occupation (p = 0.568), maternal allergic history (p = 0.370), maternal anemia (p = 0.625), pregnancy-induced hypertension (p = 0.739), gestational diabetes (p = 0.514), and parity (p = 0.098) were not significantly correlated with the concentration of milk oligosaccharides. The concentrations of 2'-fucosyllactose (2'-FL), lacto-N-neotetraose (LNnT), sialyllacto-N-tetraose c (LSTc), lacto-N-fucopentaose I (LNFP-I), disialylated lacto-N-tetraose (DSLNT), difucosyl-para-lacto-N-neohexaose (DFpLNnH), difucosyl-lacto-N-hexaose (DFLNH[a]), and 3-sialyllactose (3'-SL) showed a gradual downward trend, while the concentration of 3-fucosyllactose (3-FL) showed a gradual upward trend among three lactation stages (p < 0.05). CONCLUSIONS: The concentration of HMOs changes throughout lactation, and it varies between different HMOs. HMO concentrations differed between lactation stage, maternal secretor gene status, Lewis blood type, volume of breast milk expressed, and the province the mother came from. Prematurity, mode of delivery, parity, infants' gender, and maternal characteristics did not affect the HMO concentration. Geographical region may be not associated with HMOs concentration in human milk. There may be a mechanism for co-regulation of the secretion of some of the oligosaccharides such as 2'FL vs. 3FL, 2'FL vs. LNnT, and lacto-N-tetraose (LNT).

Analysis of Patient-Reported Outcomes After Breast Reconstruction: A Retrospective Study.

OBJECTIVE: This study aimed to investigate the effects of surgical timing, procedure, and age, on complication rates, health-related quality of life, and postoperative satisfaction, in patients who underwent breast reconstruction. METHODS: The data of 80 patients who underwent breast reconstruction surgery between August 2004 and June 2018 were reviewed. Patients were grouped according to surgical timing, procedure, and age. The evaluation indicators included complications and BREAST-Q scores. The statistical methods used included the Mann-Whitney U test and analyses of variance and covariance. RESULTS: The incidence of complications was 15.0% (12/80). The complication rates were similar in each group ( P > 0.05). The postsurgical scores of patient satisfaction with breast, psychosocial well-being, and sexual well-being were higher than the presurgical scores ( P < 0.05). The postoperative psychosocial and sexual well-being scores of patients in the immediate group were higher than those in the delayed group ( P < 0.05). The satisfaction with the outcome in the abdominal flap group was higher than that in the other group, whereas the sexual well-being score of the abdominal flap group was lower than that of the other group ( P < 0.05). The scores of the postoperative physical well-being of the chest and abdomen in the younger group were higher than that in the older group ( P < 0.05). CONCLUSIONS: Breast reconstruction can significantly improve patients' health-related quality of life and satisfaction. Immediate breast reconstruction can reduce the adverse psychological and physical effects that breast loss exerts on patients, leading to better postoperative satisfaction. Patients who underwent breast reconstruction with abdominal flaps had higher postoperative satisfaction. Breast reconstruction in elderly patients was associated with considerable postoperative satisfaction.

[Breast milk intake of Chinese infants aged 0-5 months in 2019-2021].

OBJECTIVE: To describe the breast milk intake of infants aged 0-5 months in China and its trends, and to analyze the effects of feeding mode, gender and regions on breast milk intake. METHODS: Data were extracted from Ministry of Science and Technology's basic resource survey project "China's 0-18-year-old children's nutrition and health system survey and application" project. Caregivers were face to face interviewed to collect the basic information of infants. Weighing method was used to measure 24 hourly breast milk intake of infants aged 0-5 months in China. The rank sum test was used to compare the differences in breast milk intake between groups, the Spearman rank sum test was used to analyze the trend of breast milk intake with increasing age, and the general linear regression model was used to analyze the effects of gender and region on breast milk intake. RESULTS: The mean breast milk intake of exclusively breastfed infants aged 0-5 months was 800.1 g/d, ranging from 696.4 to 937.7 g/d. Breast milk intake increased with age and remained stable at 5 months(ß=29.6, P=0.009). There was a statistically significant difference in breast milk intake among infants in different month age groups(χ~2=17.96, P=0.003). Infants aged 0-5 months who are exclusively breastfed were fed 8 times in 24 hours, the breast milk intake per each time is 103.4-152.5 g, the duration of each feeding is 20.4-24.6 min, and the breast milk intake per minute is 4.4-7.0 g. Except for 5 months of age, there was no gender difference in the 24-hour breast milk intake of exclusively breastfed infants aged 0 to 4 months(P>0.05). Except for 4-month-old exclusively breastfed infants, there was no regional differences in the breast milk intake of others(t=-4.25, P<0.001). In the mixed feeding group, breast milk + complementary feeding group and breast milk + formula powder + complementary feeding group, the breast milk intake of infants aged 0-5 months were 341.1-496.7 g, 239.1-742.7 g and 90.0-508.0 g, respectively. CONCLUSION: In 2019-2021, infants aged 0-5 months in China Breast milk intake increased with age, and remained stable at 5 months. The breast milk intake of infants aged 0-5 months in different regions or genders is similar except for individual months. The introduction of formula or complementary food directly affects the intake of breast milk in infants.

Proteins in Tumor-Derived Plasma Extracellular Vesicles Indicate Tumor Origin.

Cancer-derived extracellular vesicles (EVs) promote tumorigenesis, premetastatic niche formation, and metastasis via their protein cargo. However, the proteins packaged by patient tumors into EVs cannot be determined in vivo because of the presence of EVs derived from other tissues. We therefore developed a cross-species proteomic method to quantify the human tumor-derived proteome of plasma EVs produced by patient-derived xenografts of four cancer types. Proteomic profiling revealed individualized packaging of novel protein cargo, and machine learning accurately classified the type of the underlying tumor.

Willingness to pay for and willingness to vaccinate with the COVID-19 vaccine booster dose in China.

Objective: The present study aims to assess the willingness to pay (WTP) for and willingness to vaccinate (WTV) with the Coronavirus (COVID-19) vaccine booster dose in China when the pandemic is under adequate control and the majority of the population is vaccinated. This study is also to identify significant factors associated with the WTP. Methods: This was a cross-sectional study on adults with no past or present COVID-19 infection. An online questionnaire was distributed to collect data on vaccination status, quarantine experience, and factors related to health beliefs on vaccination. The WTV was assessed through the vaccination preference. The WTP was examined by payment scale (PS) and iterative bidding game (IBG) administered in random order. Three IBG algorithms with different starting-price were presented randomly. The average WTP of PS and IBG were analyzed as primary outcomes using univariate and multivariate analyses. Multivariate ordered logistic regression was performed to identify significant factors for the WTP. Results: The survey recruited 543 participants with a mean age of 32 years and 57.80% being female. The WTV rate was 86.74%, while 94.66% of participants completed full-schedule or enhanced vaccination. The mean WTP was CNY 149 (±CNY 197) and the median WTP was CNY 80. Regarding significant factors for the WTP, urban residents were 57% more likely (95% CI: 1.11-2.22) to pay for a high-priced vaccine than rural residents. Respondents who completed full-schedule vaccination were 46% more likely (95% CI: 1.03-2.07) to pay for a high-priced vaccine than those who completed enhanced vaccination. Respondents with a low household income of CNY 40k or lower were 62% less likely (95% CI: 0.21-0.66) to pay for a high-priced vaccine than those with a middle household income of CNY 110k-210k. Other significant factors associated with the WTP included the perceived benefit of vaccination and peer environmental pressure in the health belief model. Conclusion: The WTV with the COVID-19 vaccine booster dose was high in China. The WTP was influenced by the place of residence, vaccination status, household income, perceived benefit of vaccination, and environmental peer pressure. Study findings can inform policymakers to better design vaccination programs and financial schemes involving out-of-pocket payments.

A New Distance Stereotest by Autostereoscopic Display Using an Eye-Tracking Method.

Objectives: This research aimed to present a novel glasses-free distance random-dot stereotest system (GFDRDSS) using an eye-tracking method. Methods: A single-view autostereoscopic display applying a backlight control system combined with an eye-tracking method and the corresponding random-dot stereotest software were developed to create a GFDRDSS with a viewing distance of 5 m. The stereoacuity of 12 subjects with normal eye position was evaluated using the Randot Stereotest, Stereoscopic Test Charts vol. 3 (Yan's Charts), Distance Randot® Stereotest, and GFDRDSS. Results: The GFDRDSS could provide distinct and stable glasses-free stereoscopic perception even while the subject was moving their head. It could evaluate binocular disparities of 40-2,400 arcsec. Eleven subjects with normal near visual acuity had fine near stereovision (20-60 arcsec) using the Randot stereotest and Yan's Charts. Under refractive correction, 10 subjects had fine stereovision (≤60 arcsec) using the GFDRDSS at a distance of 5 m, and 9 had fine stereovision using the Distance Randot® Stereotest at 3 m. Other subjects described the 100 arcsec-level stereograms correctly. The results exhibited a concordance of stereoacuity within one degrade between the two distance stereotests. Conclusion: The proposed GFDRDSS can alternately project a couple of random-dot stereograms to the subjects' eyes and provide a glasses-free distance stereotest, which showed good concordance with the Distance Randot® Stereotest. More data are needed for statistical studies.

Development of high-throughput UPLC-MS/MS using multiple reaction monitoring for quantitation of complex human milk oligosaccharides and application to large population survey of secretor status and Lewis blood group.

Human milk oligosaccharides (HMOs) have attracted increasing attention due to the emerging evidence of their positive roles for infant's health. A high-throughput method for absolute quantitation of the complex HMOs including multiple isomeric structures is important but very challenging, due to the highly divers nature and wide variation in content of HMOs from different individuals. Here we used UPLC-MS-MRM in the negative-ion mode for accurate quantitation of 23 complex HMOs in just 15 min. The selected oligosaccharides are in their native forms and include neutral and sialylated, fucosylated and non-fucosylated, linear and branched, and secretor and Lewis phenotype indicators. The well validated method with good sensitivity, recovery and reproducibility was then applied to a large population quantitative survey of 251 Chinese mothers from five different ethnic groups (Han, Zhuang, Hui, Mongolian and Tibetan) living in different geographical regions for their secretor's status and Lewis phenotypes.

[Gestational weight gain and associated factors of Chinese women in the second and third trimester of pregnancy in 2015].

OBJECTIVE: To describe gestational weight gain status of pregnant women in China, and to explore potential factors related to gestational weight gain of pregnant women in the 2 nd and 3 rd trimester in 2015. METHODS: Participants were from Chinese National Nutrition and Health Surveillance in 2012 and in 2015. Using a multi-stage stratified cluster random sampling method, a total of 8512 pregnant women were recruited in 2015. A standard questionnaire was used to collect general information and pre-pregnancy weight. Body weight and height of pregnant women were measured using a unified weighing scale and stadiometer. RESULTS: In 2015, the prevalences of underweight, normal weight, overweight and obesity in pre-pregnancy were 16.0%, 66.0%, 14.9%, 3.1% according to Chinese BMI standard, respectively. In the 2 nd trimester, the prevalences of inadequate gestational weight gain, appropriate gestational weight gain and excess gestational weight gain were 14.6%, 27.2% and 58.2% based on IOM gestational weight gain standard, respectively. In the 3 rd trimester, the prevalences of inadequate gestational weight gain, appropriate gestational weight gain and excess gestational weight gain were 12.7%, 31.5%, 55.8% based on IOM gestational weight gain standard, respectively. The odds of excess gestational weight gain was 1.53(95%CI 1.19-1.99) in the second trimester, and 2.05(95% CI 1.59-2.63) in the third trimester for overweight women, compared to normal weight women during pre-pregnancy. The prevalence of excess gestational weight gain showed an increasing trend in both urban and rural areas, which was not related to pregnant women's age and education. Second parity might be a protective factor for appropriate weight gain in late pregnancy. CONCLUSION: Compared to 2012, the prevalence of underweight before pregnancy and inadequate gestaional weight gain decreased in 2015. By contrast, the prevalence of overweight, obesity and excess gestational weight gain showed an upward trend.