Integrating Transcriptomics and Proteomics to Characterize the Intestinal Responses to Cadmium Exposure Using a Piglet Model.

Cadmium (Cd) is a heavy metal element with a wide range of hazards and severe biotoxicity. Since Cd can be easily accumulated in the edible parts of plants, the exposure of humans to Cd is mainly through the intake of Cd-contaminated food. However, the intestinal responses to Cd exposure are not completely characterized. Herein, we simulated laboratory and environmental Cd exposure by feeding the piglets with CdCl2-added rice and Cd-contaminated rice (Cdcr) contained diet, as piglets show anatomical and physiological similarities to humans. Subsequent analysis of the metal element concentrations showed that exposure to the two types of Cd significantly increased Cd levels in piglets. After verifying the expression of major Cd transporters by Western blots, multi-omics further expanded the possible transporters of Cd and found Cd exposure causes wide alterations in the metabolism of piglets. Of significance, CdCl2 and Cdcr exhibited different body distribution and metabolic rewiring, and Cdcr had stronger carcinogenic and diabetes-inducing potential. Together, our results indicate that CdCl2 had a significant difference compared with Cdcr, which has important implications for a more intense study of Cd toxicity.

Molecular systematics of Pampus (Perciformes: Stromateidae) based on thousands of nuclear loci using target-gene enrichment.

Pomfret fishes of the genus Pampus are commercially important in the Indo-Pacific region, yet the phylogenetic relationships and taxonomy of Pampus remain contentious. Here, we sampled 151 specimens, representing all known species of the genus, as well as two outgroup species (two families). We collected sequences from 17,292 single-copy nuclear coding loci using target-gene enrichment and Illumina sequencing for a subset samples of P. echinogaster, P. argenteus, P. cinereus, P. liuorum, P. chinensis, P. minor, and P. punctatissimus, which were carefully examined according to their species descriptions. Concatenated gene tree and species tree analyses resulted in identical and highly supported phylogenies, in which P. argenteus was sister to P. minor in one clade and P. cinereus sister to P. chinensis and P. punctatissimus in the other clade. Phylogenetic reconstruction using sequences of cytochrome c oxidase subunit I (COI) collected by us and those retrieved from NCBI suggests extensive misidentification of Pampus species in the NCBI database. We also measured morphological characters of each species as well as observed their osteological structure using micro-CT. Both molecular and morphological results suggest that P. echinogaster is a synonym of P. argenteus, and P. liuorum is a synonym of P. cinereus. Pampus cinereus from China, Bangladesh and an uncertain origin were grouped into three clades according to their sampling localities, but we could not find decisive morphological characters to describe the "cryptic species" of P. cinereus. Finally, based on the results of the molecular analyses and morphological reexamination, we created an identification key for the genus of Pampus.

Lung function and incidence of chronic obstructive pulmonary disease after improved cooking fuels and kitchen ventilation: a 9-year prospective cohort study.

BACKGROUND: Biomass smoke is associated with the risk of chronic obstructive pulmonary disease (COPD), but few studies have elaborated approaches to reduce the risk of COPD from biomass burning. The purpose of this study was to determine whether improved cooking fuels and ventilation have effects on pulmonary function and the incidence of COPD. METHODS AND FINDINGS: A 9-y prospective cohort study was conducted among 996 eligible participants aged at least 40 y from November 1, 2002, through November 30, 2011, in 12 villages in southern China. Interventions were implemented starting in 2002 to improve kitchen ventilation (by providing support and instruction for improving biomass stoves or installing exhaust fans) and to promote the use of clean fuels (i.e., biogas) instead of biomass for cooking (by providing support and instruction for installing household biogas digesters); questionnaire interviews and spirometry tests were performed in 2005, 2008, and 2011. That the interventions improved air quality was confirmed via measurements of indoor air pollutants (i.e., SO2, CO, CO2, NO2, and particulate matter with an aerodynamic diameter of 10 µm or less) in a randomly selected subset of the participants' homes. Annual declines in lung function and COPD incidence were compared between those who took up one, both, or neither of the interventions. Use of clean fuels and improved ventilation were associated with a reduced decline in forced expiratory volume in 1 s (FEV1): decline in FEV1 was reduced by 12 ml/y (95% CI, 4 to 20 ml/y) and 13 ml/y (95% CI, 4 to 23 ml/y) in those who used clean fuels and improved ventilation, respectively, compared to those who took up neither intervention, after adjustment for confounders. The combined improvements of use of clean fuels and improved ventilation had the greatest favorable effects on the decline in FEV1, with a slowing of 16 ml/y (95% CI, 9 to 23 ml/y). The longer the duration of improved fuel use and ventilation, the greater the benefits in slowing the decline of FEV1 (p<0.05). The reduction in the risk of COPD was unequivocal after the fuel and ventilation improvements, with an odds ratio of 0.28 (95% CI, 0.11 to 0.73) for both improvements. CONCLUSIONS: Replacing biomass with biogas for cooking and improving kitchen ventilation are associated with a reduced decline in FEV1 and risk of COPD. TRIAL REGISTRATION: Chinese Clinical Trial Register ChiCTR-OCH-12002398.

Screening candidate genes for fruit size based on QTL-seq in Chinese jujube.

Introduction: Fruit size is an important economic trait affecting jujube fruit quality, which has always been the focus of marker-assisted breeding of jujube traits. However, despite a large number of studies have been carried out, the mechanism and key genes regulating jujube fruit size are mostly unknown. Methods: In this study, we used a new analysis method Quantitative Trait Loci sequencing (QTL-seq) (bulked segregant analysis) to screen the parents 'Yuhong' and 'Jiaocheng 5' with significant phenotypic differences and mixed offspring group with extreme traits of large fruit and small fruit, respectively, and, then, DNA mixed pool sequencing was carried out to further shortening the QTL candidate interval for fruit size trait and excavated candidate genes for controlling fruit size. Results: The candidate intervals related to jujube fruit size were mainly located on chromosomes 1, 5, and 10, and the frequency of chromosome 1 was the highest. Based on the QTL-seq results, the annotation results of ANNOVAR were extracted from 424 SNPs (single-nucleotide polymorphisms) and 164 InDels (insertion-deletion), from which 40 candidate genes were selected, and 37 annotated candidate genes were found in the jujube genome. Four genes (LOC107428904, LOC107415626, LOC125420708, and LOC107418290) that are associated with fruit size growth and development were identified by functional annotation of the genes in NCBI (National Center for Biotechnology Information). The genes can provide a basis for further exploration and identification on genes regulating jujube fruit size. Discussion: In summary, the data obtained in this study revealed that QTL intervals and candidate genes for fruit size at the genomic level provide valuable resources for future functional studies and jujube breeding.

Genomic dynamics of the Lower Yellow River Valley since the Early Neolithic.

The Yellow River Delta played a vital role in the development of the Neolithic civilization of China. However, the population history of this region from the Neolithic transitions to the present remains poorly understood due to the lack of ancient human genomes. This especially holds for key Neolithic transitions and tumultuous turnovers of dynastic history. Here, we report genome-wide data from 69 individuals dating to 5,410-1,345 years before present (BP) at 0.008 to 2.49× coverages, along with 325 present-day individuals collected from 16 cities across Shandong. During the Middle to Late Dawenkou period, we observed a significant influx of ancestry from Neolithic Yellow River farmers in central China and some southern Chinese ancestry that mixed with local hunter-gatherers in Shandong. The genetic heritage of the Shandong Longshan people was found to be most closely linked to the Dawenkou culture. During the Shang to Zhou Dynasties, there was evidence of genetic admixture of local Longshan populations with migrants from the Central Plain. After the Qin to Han Dynasties, the genetic composition of the region began to resemble that of modern Shandong populations. Our genetic findings suggest that the middle Yellow River Basin farmers played a role in shaping the genetic affinity of neighboring populations in northern China during the Middle to Late Neolithic period. Additionally, our findings indicate that the genetic diversity in the Shandong region during the Zhou Dynasty may be linked with their complex ethnicities.

[Wood smoke condensate had weak proliferation and strong necrotic effects on human airway smooth muscle cells].

OBJECTIVE: To investigate the effect of wood smoke condensate (WSC) on proliferation and necrosis of human airway smooth muscle cells (HASMCs). METHODS: Primary cultured HASMCs between passage 2 and 8 were divided into 3 groups: a control group, a WSC group and a cigarette smoke condensate (CSC) group. The viability of cells was examined by the CCK8 assays. The ratio of cellular proliferative stage (S phase) and cell cycle index were examined by fluorescent-labeled thymidine analogue uptake assays and flow cytometry. The expression of cyclin D1 was detected by quantitative reverse transcriptase polymerase chain reaction (Q-PCR) and Western blot. Cell apoptosis and necrosis were observed by the annexin-V and PI staining. Statistical analysis was performed by using the One-way ANOVA and LSD-t test. RESULTS: Cell viability reached peak at WSC 1 mg/L[(126 ± 12)%] and at CSC 10 mg/L exposure level [(142 ± 11) %] respectively. While at WSC 10 mg/L and CSC 60 mg/L exposure levels, cell viability decreased significantly to 86% and 76%, respectively, as compared with that of the blank control group[(100 ± 0)%] (q = 3.63- 9.33, P < 0.05). In the WSC 1 mg/L group, the cell proliferation ratio and the expression of cyclin D1 protein were (124 ± 20)% and 1.31 ± 0.64, respectively, the differences being significant as compared with the blank control group [(100 ± 0)%, 1.0 ± 0.0] (q = 5.85, 5.91, P < 0.05), while the expression of cyclin D1 mRNA and the percentage of S+G2M phase were 1.18 ± 0.21 and (103 ± 4)%, respectively, not significantly different as compared to the control group [(100 ± 0)%, 1.0 ± 0.0], (q = 1.16, 2.05, P > 0.05). In the CSC 10 mg/L group, the above-mentioned values were (204 ± 45)%, 1.80 ± 0.25, (140 ± 6)%, 1.48 ± 0.2, respectively, which were significantly higher than those in the blank control group (q = 5.38-16.51, P < 0.05) and in the WSC group (q = 3.33-15.35, P < 0.05). However, when HASMCs were exposed to WSC 10 mg/L, the cell death ratio was (13.39 ± 0.15)%, higher than that of the blank control group [(1.57 ± 0.41)%] and the CSC group [(6.61 ± 1.91)%] (q = 18.03, 10.34, P < 0.05). Apoptosis ratio in the CSC 40 mg/L group was [(61.8 ± 10.6)%], higher than that of the blank control group [(0.0 ± 0.0)%] and the WSC group [(1.7 ± 0.4)%] (q = 17.44, 16.95, P < 0.05). CONCLUSIONS: Exposure to WSC caused a weak proliferation of HASMCs, but resulted in cell necrosis instead of apoptosis at high doses. There was a slight difference in cell effects between the WSC group and the CSC group.

Research advances of molecular docking and molecular dynamic simulation in recognizing interaction between muscle proteins and exogenous additives.

During storage and processing, muscle proteins, e.g. myosin and myoglobin, will inevitably undergo degeneration, which is thus accompanied by quality deterioration of muscle foods. Some exogenous additives have been widely used to interact with muscle proteins to stabilize the quality of muscle foods. Molecular docking and molecular dynamics simulation (MDS) are regarded as promising tools for recognizing dynamic molecular information at atomic level. Molecular docking and MDS can explore chemical bonds, specific binding sites, spatial structure changes, and binding energy between additives and muscle proteins. Development and workflow of molecular docking and MDS are systematically summarized in this review. Roles of molecular simulations are, for the first time, comprehensively discussed in recognizing the interaction details between muscle proteins and exogenous additives aimed for stabilizing color, texture, flavor, and other properties of muscle foods. Finally, research directions of molecular docking and MDS for improving the qualities of muscle foods are discussed.

Construction of a highly saturated genetic map and identification of quantitative trait loci for leaf traits in jujube.

Chinese jujube (Ziziphus jujuba Mill.), a member of the genus Ziziphus, which comes under the family Rhamnaceae, is the most important species in terms of its economic, ecological, and social benefits. To dissect the loci associated with important phenotypical traits and analyze their genetic and genomic information in jujube, a whole-genome resequencing (WGR) based highly saturated genetic map was constructed using an F1 hybrid population of 140 progeny individuals derived from the cross of 'JMS2' × 'Jiaocheng 5'. The average sequencing depth of the parents was 14.09× and that of the progeny was 2.62×, and the average comparison efficiency between the sample and the reference genome was 97.09%. Three sets of genetic maps were constructed for a female parent, a male parent, and integrated. A total of 8,684 markers, including 8,158 SNP and 526 InDel markers, were evenly distributed across all 12 linkage groups (LGs) in the integrated map, spanning 1,713.22 cM with an average marker interval of 0.2 cM. In terms of marker number and density, this is the most saturated genetic map of jujube to date, nearly doubling that of the best ones previously reported. Based on this genetic map and phenotype data from 2019 to 2021, 31 leaf trait QTLs were identified in the linkage groups (LG1, 15; LG3, 1; LG5, 8; LG7, 4; LG8, 1, and LG11, 2), including 17 major QTLs. There were 4, 8, 14, and 5 QTLs that contributed to leaf length, leaf width, leaf shape index, and leaf area, respectively. Six QTLs clusters were detected on LG1 (8.05 cM-9.52 cM; 13.12 cM-13.99 cM; 123.84 cM-126.09 cM), LG5 (50.58 cM-50.86 cM; 80.10 cM-81.76 cM) and LG11 (35.98 cM-48.62 cM). Eight candidate genes were identified within the QTLs cluster regions. Annotation information showed that 4 genes (LOC107418196, LOC107418241, LOC107417968, and LOC112492570) in these QTLs are related to cell division and cell wall integrity. This research will provide a valuable tool for further QTL analysis, candidate gene identification, map-based gene cloning, comparative mapping, and marker-assisted selection (MAS) in jujube.

Salubrinal Enhances Cancer Cell Death during Glucose Deprivation through the Upregulation of xCT and Mitochondrial Oxidative Stress.

Cancer cells have the metabolic flexibility to adapt to heterogeneous tumor microenvironments. The integrated stress response (ISR) regulates the cellular adaptation response during nutrient stress. However, the issue of how the ISR regulates metabolic flexibility is still poorly understood. In this study, we activated the ISR using salubrinal in cancer cells and found that salubrinal repressed cell growth, colony formation, and migration but did not induce cell death in a glucose-containing condition. Under a glucose-deprivation condition, salubrinal induced cell death and increased the levels of mitochondrial reactive oxygen species (ROS). We found that these effects of salubrinal and glucose deprivation were associated with the upregulation of xCT (SLC7A11), which functions as an antiporter of cystine and glutamate and maintains the level of glutathione to maintain redox homeostasis. The upregulation of xCT did not protect cells from oxidative stress-mediated cell death but promoted it during glucose deprivation. In addition, the supplementation of ROS scavenger N-acetylcysteine and the maintenance of intracellular levels of amino acids via sulfasalazine (xCT inhibitor) or dimethyl-α-ketoglutarate decreased the levels of mitochondrial ROS and protected cells from death. Our results suggested that salubrinal enhances cancer cell death during glucose deprivation through the upregulation of xCT and mitochondrial oxidative stress.

Ampelopsins A and C Induce Apoptosis and Metastasis through Downregulating AxL, TYRO3, and FYN Expressions in MDA-MB-231 Breast Cancer Cells.

Ampelopsins A and C are resveratrol oligostilbenes whose role in cancer development remains unknown. This study evaluated the antimetastatic and apoptosis-inducing properties of ampelopsins A and C in MDA-MB-231 cells. The IC50 values of ampelopsins A and C against MDA-MB-231 cells at 72 h were 38.75 ± 4.61 and 2.71 ± 0.21 µM, respectively. However, at 24 h, ampelopsins A and C decreased cell metastasis significantly. Among the 71 proteins present on the human phosphoreceptor tyrosin kinase array, ampelopsin C decreased the phosphorylated protein level of AXL, Dtk (TYRO3), EphA2, EphA6, Fyn, Hck, and SRMS. Additionally, antiproliferation effects of ampelopsin C were enhanced when combined with luteolin and chrysin compared to either two or a single agent in MDA-MB-231 cells. Overall, ampelopsins A and C extracted from Vitis thunbergii are both novel antimetastatic agents and potential therapeutic targets in patients with breast cancer.

Test-retest and inter-rater reliability for the Comprehensive Developmental Inventory for Infants and Toddlers diagnostic and screening tests.

BACKGROUND: Reliability information for the Comprehensive Developmental Inventory for Infants and Toddlers diagnostic (CDIITDT) and screening tests (CDIITST) is inadequate. AIM: To assess the test-retest and inter-rater reliability of the CDIITDT and CDIITST. STUDY DESIGN: A repeated measures design was selected. SUBJECTS: Non-disabled term (n=15; mean age 8.4+/-1.6 months) and preterm infants (n=16; mean age 9.3+/-2.9 months), and children with developmental disabilities (n=15; mean age 24.7+/-11.8 months) were recruited. A single rater assessed the children twice in 3 days to examine the test-retest reliability; and a second rater observed and scored performance while the same rater conducted the first assessment for the inter-rater reliability analysis. OUTCOME MEASURES: The raw score, developmental age (DA) and developmental quotient (DQ)/Z score for the six subtests, two motor subdomains and the whole test were used as outcome measures for the CDIITDT and CDIITST. RESULTS: The test-retest reliabilities for the CDIITDT were rated good for the three pediatric groups (ICC 0.76-1.00), with the exception of moderate ratings for the self-help subtest for the term infants and for the social, self-help and fine-motor DQs for the preterm group. The CDIITDT inter-rater reliabilities were good for the three groups (ICC 0.76-1.00), with the exception of only moderate reliability for the cognitive DQs for the preterm infants. The reliabilities for the whole CDIITST for the three groups were high (ICC 0.93-1.00). CONCLUSION: The reliabilities for the whole CDIITDT and its various subtests and the whole CDIITST are acceptable for clinical use.

ICF-CY code set for infants with early delay and disabilities (EDD Code Set) for interdisciplinary assessment: a global experts survey.

PURPOSE: Comprehensive description of functioning is important in providing early intervention services for infants with developmental delay/disabilities (DD). A code set of the International Classification of Functioning, Disability and Health: Children and Youth Version (ICF-CY) could facilitate the practical use of the ICF-CY in team evaluation. The purpose of this study was to derive an ICF-CY code set for infants under three years of age with early delay and disabilities (EDD Code Set) for initial team evaluation. METHODS: The EDD Code Set based on the ICF-CY was developed on the basis of a Delphi survey of international professionals experienced in implementing the ICF-CY and professionals in early intervention service system in Taiwan. RESULTS: Twenty-five professionals completed the Delphi survey. A total of 82 ICF-CY second-level categories were identified for the EDD Code Set, including 28 categories from the domain Activities and Participation, 29 from body functions, 10 from body structures and 15 from environmental factors. CONCLUSIONS: The EDD Code Set of 82 ICF-CY categories could be useful in multidisciplinary team evaluations to describe functioning of infants younger than three years of age with DD, in a holistic manner. Future validation of the EDD Code Set and examination of its clinical utility are needed. IMPLICATIONS FOR REHABILITATION: The EDD Code Set with 82 essential ICF-CY categories could be useful in the initial team evaluation as a common language to describe functioning of infants less than three years of age with developmental delay/disabilities, with a more holistic view. The EDD Code Set including essential categories in activities and participation, body functions, body structures and environmental factors could be used to create a functional profile for each infant with special needs and to clarify the interaction of child and environment accounting for the child's functioning.

Linkage of ICF-CY codes with environmental factors in studies of developmental outcomes of infants and toddlers with or at risk for motor delays.

PURPOSE: Environmental variables have been explored in studies of the development of young children with motor delays. Linking environmental variables to the International Classification of Functioning, Disability and Health - Children and Youth (ICF-CY), environmental factors (EFs) categories can provide a common language for documenting their contribution to developmental outcomes. This review of studies aimed to (1) link EFs for developmental outcomes in infants with or at risk for motor delays to ICF-CY categories and (2) synthesize the influences of EFs (with ICF-CY linkage) on developmental outcomes. METHOD: A systematic literature search was performed of multiple databases. After applying selection criteria, environmental variables in 28 articles were linked to ICF-CY categories and underwent qualitative synthesis. RESULTS: Results indicated that physical environmental variables could be linked successfully to ICF-CY EFs categories, but not social environmental variables. Multiple environmental variables were associated with motor and other developmental outcomes. CONCLUSION: Difficulties in linking social factors to ICF-CY categories indicate that additional EFs codes may need to be considered in the ICF-CY revision processes. The review provides empirical data on relationships between EFs and developmental outcomes in children with or at risk for motor delay.