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The driving mechanisms of urban surface thermal environments usually differ with season. However, to date, the seasonal differences in the impacts of two-dimensional (2D) and three-dimensional (3D) building and tree morphologies on land surface temperature (LST) remain poorly understood. Additionally, there has yet to be a quantitative attempt to separate the direct effects of building and tree morphologies on LST from the indirect effects from 3D perspectives. Here, using Nanjing, China as an example, we investigated the seasonally disparate responses of LST to the 2D and 3D building and tree morphologies, by combining boosted regression trees and a structural equation model (SEM). Our findings show that the predominant factor that affects the spatial pattern of LST is the percent cover of buildings (PER_Build) in spring and summer, while the sky view factor (SVF) dominates LST variations in autumn and winter. The LST responsiveness to changes in these factors also showed a large seasonal variation. In summer, LST increased with PER_Build, and the greatest warming effect occurred when the building surface and tree canopy fractions were lower than 25% and 40%, respectively. In winter, by comparison, the variations in SVF and PER_Tree led to a larger change in LST. Further results using the SEM model suggest that LST variation is governed by more 2D building structures in spring and summer, whereas 3D building structures have a more dominant impact on LST in autumn and winter. Most of the overall impacts resulting from the 3D building and horizontal tree structures are direct throughout each season. However, the overall impacts of the 2D building structure on LST are mainly direct in spring and summer yet indirect in autumn and winter. In all seasons, the indirect impacts of 2D and 3D building structures on LST primarily originate from the horizontal and vertical tree structures, respectively. We consider that these findings can guide designing optimization strategies for urban heat mitigation for different seasons from 2D and 3D perspectives. [Display omitted] • Responses of LST to 2D/3D urban morphology indicators are analyzed across seasons. • Direct and indirect impacts of building/tree on LST are studied from 3D perspective. • Responses of LST to changes in 2D/3D morphology indicators are seasonally dependent. [ABSTRACT FROM AUTHOR]

Toy production has been increasing over the last few decades to meet the growing demands for toys across the globe, which has inevitably worsened the problem of toy waste. Given the lack of modern waste disposal facilities, rural villagers in many developing countries often discard and incinerate toy waste in backyards or riverbanks, which may release the pollutants from toys (e.g., heavy metals), contaminate the surrounding areas, and eventually threaten the health of residents. As such, this study examined the impact of improper toy waste handling on the nearby aquaculture site by measuring the contamination level of heavy metals (As, Cd, Cu, Pb, and Zn) in the sediment and seafood (crabs, shrimps, and fish). The health risk of heavy metals via seafood consumption was assessed in different groups of people (males, females, teenagers, and seniors). Results showed that the sediment and seafood at the aquaculture site were generally not contaminated with heavy metals (contamination factor and bioaccumulation factor <1). However, consuming the seafood cultured at this site, especially for crabs, could pose a health risk to humans due to As and Cd (hazard quotient > 1), irrespective of their age and gender. This risk could not be lowered by cooking, except As by boiling. Overall, we revealed that improper toy waste handling did not cause severe heavy metal pollution in the surrounding environment, but the consumption of contaminated seafood could still threaten human health. To safeguard public health, we propose that toy waste should be appropriately treated by the authorities concerned. In addition, consuming seafood with long culture periods (e.g., crabs) should be reduced to minimize the dietary intake of heavy metals and their associated health risk. [Display omitted] • Toy waste handling did not seriously contaminate the surroundings with heavy metals. • Cooking generally did not reduce the concentrations of heavy metals in seafood. • A large proportion of heavy metals in seafood could be absorbed in the human body. • Consumption of seafood cultured near toy waste handling sites could cause health risk. • The health risk was mainly driven by arsenic and cadmium in seafood. [ABSTRACT FROM AUTHOR]

Previous studies indicated per- and poly-fluoroalkyl substances (PFAS) were related to uric acid and hyperuricemia risk, but evidence for the exposure-response (E-R) curves and combined effect of PFAS mixture is limited. Moreover, the potential mediation effect of kidney function was not assessed. Hence, we conducted a national cross-sectional study involving 13,979 US adults in NHANES 2003–2018 to examine the associations of serum PFAS with uric acid and hyperuricemia risk, and the mediation effects of kidney function. Generalized linear models and E-R curves showed positive associations of individual PFAS with uric acid and hyperuricemia risk, and nearly linear E-R curves indicated no safe threshold for PFAS. Weighted quantile sum regression found positive associations of PFAS mixture with uric acid and hyperuricemia risk, and PFOA was the dominant contributor to the adverse effect of PFAS on uric acid and hyperuricemia risk. Causal mediation analysis indicated significant mediation effects of kidney function decline in the associations of PFAS with uric acid and hyperuricemia risk, with the mediated proportion ranging from 19 % to 57 %. Our findings suggested that PFAS, especially PFOA, may cause increased uric acid and hyperuricemia risk increase even at low levels, and kidney function decline plays a crucial mediation effect. [Display omitted] • PFAS had nearly linear E-R with uric acid and hyperuricemia without safe threshold. • Combined effect of PFAS mixture on higher uric acid and hyperuricemia was observed. • PFOA was the dominant PFAS compound with increased uric acid and hyperuricemia risk. • Kidney function decline causally mediated the adverse effects of PFAS on uric acid. [ABSTRACT FROM AUTHOR]

• Seasonal and diurnal SUHI (SUHI sea and SUHI diu) dynamics were studied globally. • Both SUHI sea and SUHI diu dynamics showed six typical patterns. • SUHI sea dynamics relate to climate during the day and rural land cover type at night. • SUHI diu dynamics are regulated by the urban-rural contrast in vegetation and albedo. Knowledge of the temporally continuous dynamics of seasonal and diurnal surface urban heat islands (SUHIs) as well as their underlying determinants is crucial to better understand their variations at multiple time scales. Owing to the orbital limitation of satellites, previous studies primarily focused on SUHI dynamics at limited time-nodes, either in a diurnal or seasonal cycle. However, a joint investigation of the continuous dynamics of seasonal and diurnal SUHIs (hereafter referred to as SUHI sea and SUHI diu) remains lacking. The comprehensive taxonomy of the patterns of continuous SUHI sea and SUHI diu dynamics across global cities is also not clear. Using satellite-derived land surface temperature (LST) data, we investigated the prevalent patterns of continuous SUHI sea and SUHI diu dynamics across global cities by combining annual and diurnal temperature cycle models and the k -means clustering algorithm. Our results showed that: (1) Both SUHI sea and SUHI diu dynamics exhibited six typical patterns including, single-peak type (SPT), single-valley type (SVT), peak-valley type (PVT) , valley-peak type (VPT), two-peak type (TPT), and two-valley type (TVT). (2) The daytime SUHI sea dynamics pattern was closely related to the background climate, with SPT and PVT mainly occurring in cities located in the warm temperate and snow zones, SVT and VPT in the arid zone, and TPT and TVT in the equatorial zone. In contrast, the nighttime SUHI sea dynamics pattern depended more on rural land cover type, with SPT, PVT, and TPT mostly occurring in cities surrounded by barren lands with high albedo and SVT, VPT, and TVT in cities surrounded by dense vegetation with low albedo. We also find a significant negative relationship between daytime SUHI sea dynamics and urban-rural contrast in vegetation and between nighttime SUHI sea dynamics and urban-rural contrast in albedo across cities. (3) For SUHI diu dynamics, SPT, PVT, and TVT were mainly located in cities with higher vegetation coverage in rural than in urban areas, while SVT, VPT, and TPT were in cities with higher vegetation coverage in urban areas. The SUHI diu dynamics were found to be synthetically affected by the urban-rural contrast in vegetation and albedo. We consider these findings to be beneficial for deepening the understanding of SUHI dynamics at various time scales. [ABSTRACT FROM AUTHOR]

The appearance quality grading of walnut kernels is extremely important in the deep processing of walnuts. Foreign body pollution in food is also a challenging problem that has been troubling food companies. Therefore, it is necessary to propose an efficient and non-destructive detection method for walnut kernels and their endogenous foreign bodies. To improve the quality and safety of walnut deep-processed products, this paper proposes an improved detection model based on the original YOLO V5. The improved model achieves a reduction in memory consumption by 38% and computational workload by 34%. Additionally, it increases the average precision of the model by 1.1% and improves CPU speed by 52%. When compared to other lightweight networks, our model demonstrates optimal overall performance. Moreover, our algorithm significantly enhances the precision of detecting small targets and target selection, as compared to the original model.By reducing the input image size of the model, it is able to meet the requirements of real-time detection of walnut kernels and their endogenous foreign bodies on the edge device Raspberry Pi. This provides a technical reference for the non-destructive detection of food quality and its endogenous foreign bodies. • YOLO V5; lightweight model; walnut kernels;endogenous foreign body;raspberry [ABSTRACT FROM AUTHOR]

Urbanization experiences different speeds and forms under diverse development stages across the globe. However, urbanization-induced impacts on long-term surface urban heat island intensity (I s) trends across global cities and the regulators of such impacts remain understudied Here we estimate interannual trends in daytime I s (i.e., urban-rural differences in surface temperatures) across 511 major cities for 1985–2020 using annual averages calculated using reconstructed land surface temperature data derived from >250,000 Landsat thermal images. Our study reveals that the global mean I s growth rate is 0.156 °C/decade. We further examine I s change associated with per 1% impervious land growth (denoted as β) in each city throughout the research period and during different periods. The global mean β is 0.018 ± 0.025 °C/% (mean ± 1 standard deviation) for the whole period, with greater values in humid than in arid climates; and the β may change during different periods, e.g., it has more than tripled when urban impervious land exceeds 30%, indicating the spatiotemporally divergent impacts of urbanization on I s trends across global cities. The spatial variations in β across global cities are well correlated with rural vegetation abundance and precipitation but not with urban population. Among these three factors, rural vegetation abundance possesses the greatest standardized regression coefficient of partial least-squares model, signifying the critical role of biome background in regulating β. The finding implies that future urbanization over densely vegetated regions should be more carefully and strategically planned due to the greater urbanization-induced surface warming effect. • Landsat land surface temperatures across global 511 cities were reconstructed. • Global surface urban heat island trends since the 1980s were analyzed. • Urbanization-induced impacts on surface urban heat island trends were evaluated. • Urbanization-induced impacts are greater in cities with humid climates. • Rural vegetation abundance regulates urbanization-induced impacts. [ABSTRACT FROM AUTHOR]

Urban vegetation, a harbinger of future global vegetation change, is controlled by complex urban environments. The urban-rural gradient in vegetation greenness trends and their responses to biogeochemical drivers (e.g. elevated atmospheric CO 2 concentration and climate warming) and land-cover changes, however, remain unclear. Here we used satellite-derived enhanced vegetation index to examine the greenness trends for 1500-plus cities in China for 2000–2019. We developed a conceptual framework to differentiate between the contributions of four key drivers to the greenness trends: two biogeochemical drivers, a background biogeochemical driver (BBD) and an urban biogeochemical driver (UBD), and two drivers of land-cover changes, urban expansion or densification (UED) and urban green recovery (UGR). We find that the greening trends gradually decreased from urban cores to urban new towns and then to browning trends in urban fringes. The significant greening in urban cores was mainly contributed by BBD (25.6%) and UBD (52.3%). While the minor greening in urban new towns was contributed by both BBD (33.1%) and UBD (24.1%) and weakened by UED (−39.7%). The UED (−64.4%) dominated the browning in urban fringes. These results suggest that biogeochemical drivers and land-cover changes jointly regulated the urban-rural gradient in greenness trends, which contributes to the assessment of future global vegetation change driven by complex environmental changes. • The urban-rural gradient in greenness trends and its drivers were analyzed. • The urban-rural gradient in greenness trends is vividly featured by a 'V-shape'. • Biogeochemical drivers and land-cover changes jointly regulate the 'V-shape'. • Urban biogeochemical drivers lead to the significant greening in urban cores. • Urban expansion or densification dominates the browning in urban fringes. [ABSTRACT FROM AUTHOR]

[Display omitted] • Prenatal PFOA and PFOS exposures were adversely associated with communication domains of infants at 6 months of age. • PFHxS and 6:2Cl-PFESA were associated with poor scores of communication domain at 6 months. • PFOA, PFOS, and PFHxS can affect the communication domain's trajectory in infancy. • Boys were more sensitive to PFOA, PFOS, and PFHxS than girls. • The impacts of PFAS mixtures were greater than effects induced by individual PFAS. Epidemiological data on the effects of perfluoroalkyl and polyfluoroalkyl substances (PFAS) on infant neurodevelopment trajectories are far from being sufficiently addressed. In this study, 1285 mother–child pairs were recruited during 2016–2017. A high-performance liquid chromatography-triple quadrupole mass spectrometer was used to measure 16 PFAS levels in cord serum. Ages and Stages Questionnaires were used to examine children's neurodevelopment at 2, 6, 12, and 24 months of age. Group-based trajectory models were applied to derive the neurodevelopmental trajectories. Children with relatively low scores from 2 to 24 months were classified into a low-score group and were used as a risk group in each domain. Multiple linear regression, logistic regression, and quantile-based g-computation were performed to assess associations of single or mixture PFAS exposures with neurodevelopment and trajectories. Perfluorooctane sulphonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulfonic acid (PFHxS), and 6:2 chlorinated polyfluorooctane ether sulfonate (6:2Cl-PFESA) were detected in over 90 % samples. PFOA had the highest concentration (median: 4.61 μg/L). Each ln-unit (μg/L) increase of PFAS (e.g., PFOA, PFOS, PFHxS, 6:2Cl-PFESA) was associated with poor scores of communication domain at 6 months, with the effect size ranging from −0.69 to −0.44. PFOS (OR: 1.14, (1.03, 1.26), PFDA (OR:1.08, (1.02, 1.15)), PFHxS (OR:1.31, (1.12, 1.56)), and 6:2Cl-PFESA (OR:1.08, (1.00, 1.16)) were associated with an increased risk of being in the low-score group in the early childhood communication domain's trajectory. Each mixture quartile increment was associated with a 1.60 (−2.76, −0.45) decrease in communication domain scores of 6-month-old infants, and the mixture effect was mainly attributed to PFOS. Each mixture quartile increase was associated with a 1.23-fold (1.03, 1.46) risk of being in the low-score group of the communication domain, and the mixture effect was mainly attributed to PFOS. In conclusion, PFAS and their mixtures might adversely affect childhood neurodevelopment. The gender-specific associations existed in the above associations. [ABSTRACT FROM AUTHOR]

Previous research indicated that fine particulate matter (PM 2.5 ) exposure affected both offspring neurodevelopment and the colonization of gut microbiota (GM), while the underlying mechanism remained unclear. Our study aimed to evaluate the impacts of prenatal PM 2.5 exposure on child cognitive development and investigate the role of neonatal GM colonization in the association. Based on the Shanghai Maternal-Child Pairs Cohort, 361 maternal-child pairs were recruited. Prenatal PM 2.5 exposure concentrations were estimated using a high-spatial-resolution prediction model, and child neurodevelopment was assessed by the Ages and Stages Questionnaire. Multivariable linear regression models, logistic regression models, linear discriminant analysis effect size, and random forest model were applied to explore the associations among PM 2.5 exposure, GM colonization, and children's neurodevelopment. The present study revealed a negative correlation between PM 2.5 exposure throughout pregnancy and child neurodevelopment. Prenatal PM 2.5 exposure was associated with an increased risk of suspected developmental delay (SDD) (OR = 1.683, 95% CI: 1.138, 2.489) in infants aged 2 months. Additionally, potential operational taxonomic unit markers were identified for PM 2.5 -related neurotoxicity, demonstrating promising classification potential for early SDD screening (AUC = 71.27%). Prenatal PM 2.5 exposure might disrupt the composition, richness, and evenness of meconium GM, thereby influencing cognitive development and the occurrence of SDD in offspring. Seven PM 2.5 -related genera, Ruminococcus gnavus group , Romboutsia , Burkholderiaceae Caballeronia Paraburkholderia , Blautia , Alistipes , Parabacteroides , and Bacteroides , were validated as correlated with prenatal PM 2.5 exposure and the occurrence of SDD. Moreover, alterations of GM related to PM 2.5 exposure and SDD might be accompanied by changes in functional pathways of amino acid, lipid, and vitamin metabolism as indicated by differentially enriched species in the Kyoto Encyclopedia of Genes and Genomes., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Co-published by Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, and American Chemical Society.)

Background: Epidemiological studies addressing the combined effects of exposure to chemical mixtures at different stages of pregnancy on birth size are scarce., Objective: To evaluate the association between prenatal exposure to chemical mixtures and birth size., Methods: Our previous study repeatedly measured the urinary concentrations of 34 chemical substances among 743 pregnant women and identified three distinct clusters of exposed population and six dominant principal components of exposed chemicals in each trimester. In this study, we assessed the associations of these exposure profiles with birth weight, birth length, and ponderal index using multivariable linear regression., Results: We found that compared with women in cluster 1 (lower urinary chemical concentrations), women in cluster 2 (higher urinary concentrations of metals, benzothiazole, benzotriazole, and some phenols), and women in cluster 3 (higher urinary concentrations of phthalates) were more likely to give birth to children with higher birth length [0.23 cm (95% CI: -0.03, 0.49); 0.29 cm (95%CI: 0.03, 0.54), respectively]. This association was observed only in 1st trimester. In addition, prenatal exposure to PC3 (higher benzophenones loading) was associated with reduced birth length across pregnancy [-0.07 cm (95% CI: -0.18, 0.03) in 1st and 2nd trimester; -0.13 cm (95% CI: -0.24, -0.03) in 3rd trimester]. Exposure to PC6 (higher thallium and BPA loading in 2nd trimester) was associated with increased birth length [0.15 cm (95% CI: 0.05, 0.26)]. Compared with other outcomes, associations of both clusters and PCs with birth length were stronger, and these associations were more pronounced in boys., Impact Statement: Exposure to multiple chemicals simultaneously, the actual exposure situation of pregnant women, was associated with birth size, indicating that chemical mixtures should be taken more seriously when studying the health effects of pollutants., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Given the high prevalence of avian leukosis virus subgroup K (ALV-K) in chickens in China, the positive rate of ALV-K in local chickens in Henan province was investigated, and the genetic region encoding the glycoprotein gp85 of isolates from positive chickens was analyzed. The positive rate of ALV-K in local chickens in Henan was found to be 87.2% (41/47). Phylogenetic analysis of gp85 sequences revealed six clusters that differed in their host range regions (hr1 and hr2) and variable regions (vr1, vr2, and vr3). Evidence of recombination of hr1, hr2, vr1, vr2, and vr3 was observed between the different clusters. The isolate HN23LS02 appears to have obtained its hr1 and hr2 regions from separate lineages via recombination but without having a significant affect on the replication capacity of the virus., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Indoor microorganisms impact asthma and allergic rhinitis (AR), but the associated microbial taxa often vary extensively due to climate and geographical variations. To provide more consistent environmental assessments, new perspectives on microbial exposure for asthma and AR are needed. Home dust from 97 cases (32 asthma alone, 37 AR alone, 28 comorbidity) and 52 age- and gender-matched controls in Shanghai, China, were analyzed using high-throughput shotgun metagenomic sequencing and liquid chromatography-mass spectrometry. Homes of healthy children were enriched with environmental microbes, including Paracoccus , Pseudomonas , and Psychrobacter , and metabolites like keto acids, indoles, pyridines, and flavonoids (astragalin, hesperidin) (False Discovery Rate < 0.05). A neural network co-occurrence probability analysis revealed that environmental microorganisms were involved in producing these keto acids, indoles, and pyridines. Conversely, homes of diseased children were enriched with mycotoxins and synthetic chemicals, including herbicides, insecticides, and food/cosmetic additives. Using a random forest model, characteristic metabolites and microorganisms in Shanghai homes were used to classify high and low prevalence of asthma/AR in an independent dataset in Malaysian schools (N = 1290). Indoor metabolites achieved an average accuracy of 74.9% and 77.1% in differentiating schools with high and low prevalence of asthma and AR, respectively, whereas indoor microorganisms only achieved 51.0% and 59.5%, respectively. These results suggest that indoor metabolites and chemicals rather than indoor microbiome are potentially superior environmental indicators for childhood asthma and AR. This study extends the traditional risk assessment focusing on allergens or air pollutants in childhood asthma and AR, thereby revealing potential novel intervention strategies for these diseases., (© 2023 The Author(s).)

Competing Interests: The authors declare no competing interests.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy that harbors mutations in homologous recombination-repair (HR-repair) proteins in 20%-25% of cases. Defects in HR impart a specific vulnerability to poly ADP ribose polymerase inhibitors and platinum-containing chemotherapy in tumor cells. However, not all patients who receive these therapies respond, and many who initially respond ultimately develop resistance. Inactivation of the HR pathway is associated with the overexpression of polymerase theta (Polθ, or POLQ). This key enzyme regulates the microhomology-mediated end-joining (MMEJ) pathway of double-strand break (DSB) repair. Using human and murine HR-deficient PDAC models, we found that POLQ knockdown is synthetically lethal in combination with mutations in HR genes such as BRCA1 and BRCA2 and the DNA damage repair gene ATM. Further, POLQ knockdown enhances cytosolic micronuclei formation and activates signaling of cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING), leading to enhanced infiltration of activated CD8+ T cells in BRCA2-deficient PDAC tumors in vivo. Overall, POLQ, a key mediator in the MMEJ pathway, is critical for DSB repair in BRCA2-deficient PDAC. Its inhibition represents a synthetic lethal approach to blocking tumor growth while concurrently activating the cGAS-STING signaling pathway to enhance tumor immune infiltration, highlighting what we believe to be a new role for POLQ in the tumor immune environment.

Background: Associations of air pollution with anxiety and depression were found in previous studies. However, whether air pollution exposure during pregnancy contributes to prenatal anxiety and depression or not is under-investigated. In this study, we aimed to analyze associations between fine particulate matter (PM 2.5 ) exposure with anxiety and depression during pregnancy and to explore the critical window of PM 2.5 exposure., Methods: This study was based on the Shanghai Maternal-Child Pairs Cohort (Shanghai MCPC). We used a gap-filling random forest model to estimate PM 2.5 exposure concentration during pregnancy of each participant. The Self-Rating Anxiety Scale (SAS) and the Center for Epidemiological Survey-Depression Scale (CES-D) were used to quantify the anxiety and depression levels in late pregnancy. Covariate information was obtained from medical records and questionnaires. We performed generalized linear regression and logistic regression models to assess the association and the critical window., Results: Totally 3731 pregnant women were included, with the age of 28.85 ± 3.97 years old. Anxiety and depression rates were 10.8 % and 11.5 % respectively, according to the cut-off value of SAS and CES-D. Generalized linear regression results showed that the increase of PM 2.5 concentration in three stages (gestational 0-13 weeks, 0-26 weeks, 0-36 weeks) was related to the increase of scale score. The PM 2.5 concentration in 0-13 weeks could increase the risk of anxiety and depression by approximately 23 % and 25 %, respectively. And the gestational weeks 4th-13th were the suspicious critical window of PM 2.5 exposure., Conclusion: The increased risk of anxiety or depression was related to PM 2.5 exposure during pregnancy, especially early pregnancy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To explore the genetic etiology of a patient with primary infertility and repeated failure of assisted reproductive technology., Methods: Peripheral blood samples of the patient and her husband were collected for the extraction of genomic DNA and clinical exome sequencing. Candidate variants were verified by Sanger sequencing., Results: The patient was found to harbor compound heterozygous variants of the PATL2 gene, namely c.223-14&#95;223-2del and c.1369G>T (p.G457*). Sanger sequencing has verified that they were respectively inherited from her father and mother. The patient was diagnosed with oocyte maturation defect type 4., Conclusion: Oocyte maturation arrest due to mutations of the PATL2 gene can result in primary female infertility. Discovery of the novel c.1369G>T (p.G457*) variant has expanded the spectrum of pathogenic variants of the PATL2 gene.

Impaired glucose-stimulated insulin secretion (GSIS) is a hallmark of type-2 diabetes. However, cellular signaling machineries that control GSIS remain incompletely understood. Here, we report that β-klotho (KLB), a single-pass transmembrane protein known as a co-receptor for fibroblast growth factor 21 (FGF21), fine tunes GSIS via modulation of glycolysis in pancreatic β-cells independent of the actions of FGF21. β-cell-specific deletion of Klb but not Fgf21 deletion causes defective GSIS and glucose intolerance in mice and defective GSIS in islets of type-2 diabetic mice is mitigated by adenovirus-mediated restoration of KLB. Mechanistically, KLB interacts with and stabilizes the cytokine receptor subunit GP130 by blockage of ubiquitin-dependent lysosomal degradation, thereby facilitating interleukin-6-evoked STAT3-HIF1α signaling, which in turn transactivates a cluster of glycolytic genes for adenosine triphosphate production and GSIS. The defective glycolysis and GSIS in Klb-deficient islets are rescued by adenovirus-mediated replenishment of STAT3 or HIF1α. Thus, KLB functions as a key cell-surface regulator of GSIS by coupling the GP130 receptor signaling to glucose catabolism in β-cells and represents a promising therapeutic target for diabetes., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: To establish a non-invasive method for beta-thalassemia by detecting parental CD41-42 mutation in cell-free DNA derived from maternal plasma with droplet digital PCR (ddPCR)., Methods: Beta-actin gene and beta-thalassemia gene CD41-42 mutation were respectively set as the reference and target sequences. A novel method was established based on Bio-Rad ddPCR technique with specific primers and TaqMan probes for the two genes. The accuracy, sensitivity and detective linearity range of the developed method were evaluated by detection of the target gene gradient concentration samples. The applicability was also evaluated by testing 20 maternal plasma samples., Results: The ddPCR method could accurately detect the beta-thalassemia CD41-42 mutation in cell-free DNA derived from maternal plasma. Within the target sequence concentration ratio of 5.00%-0.50%, the relative errors were all < 0.05, the linear regression equation was Y=1.0101-X-0.0071 and R 2 =0.9994. The results of 20 maternal plasma cell-free DNA samples were all consistent with those of the follow-up testing., Conclusion: A ddPCR method for detecting parental CD41-42 mutation in cell-free DNA from maternal plasma was developed. The method is simple, rapid, accurate, and can be applied for non-invasive prenatal diagnosis for couples simultaneously carrying the CD41-42 mutation.