ARBUSCULAR MYCORRHIZA-INDUCED KINASES AMK8 and AMK24 associate with the receptor-like kinase KINASE3 to regulate arbuscular mycorrhizal symbiosis in Lotus japonicus.

Arbuscular mycorrhizal (AM) symbiosis is a widespread, ancient mutualistic association between plants and fungi, and facilitates nutrient uptake into plants. Cell surface receptor-like kinases (RLKs) and receptor-like cytoplasmic kinases (RLCKs) play pivotal roles in transmembrane signaling, while few RLCKs are known to function in AM symbiosis. Here, we show that 27 out of 40 AM-induced kinases (AMKs) are transcriptionally upregulated by key AM transcription factors in Lotus japonicus. Nine AMKs are only conserved in AM-host lineages, among which the SPARK-RLK-encoding gene KINASE3 (KIN3) and the RLCK paralogues AMK8 and AMK24 are required for AM symbiosis. KIN3 expression is directly regulated by the AP2 transcription factor CTTC MOTIF-BINDING TRANSCRIPTION FACTOR1 (CBX1), which regulates the reciprocal exchange of nutrients in AM symbiosis, via the AW-box motif in the KIN3 promoter. Loss of function mutations in KIN3, AMK8, or AMK24 result in reduced mycorrhizal colonization in L. japonicus. AMK8 and AMK24 physically interact with KIN3. KIN3 and AMK24 are active kinases and AMK24 directly phosphorylates KIN3 in vitro. Moreover, CRISPR-Cas9-mediated mutagenesis of OsRLCK171, the sole homolog of AMK8 and AMK24 in rice (Oryza sativa), leads to diminished mycorrhization with stunted arbuscules. Overall, our results reveal a crucial role of the CBX1-driven RLK/RLCK complex in the evolutionarily conserved signaling pathway enabling arbuscule formation.

Tricarboxylic acid cycle metabolites: new players in macrophage.

Metabolic remodeling is a key feature of macrophage activation and polarization. Recent studies have demonstrated the role of tricarboxylic acid (TCA) cycle metabolites in the innate immune system. In the current review, we summarize recent advances in the metabolic reprogramming of the TCA cycle during macrophage activation and polarization and address the effects of these metabolites in modulating macrophage function. Deciphering the crosstalk between the TCA cycle and the immune response might provide novel potential targets for the intervention of immune reactions and favor the development of new strategies for the treatment of infection, inflammation, and cancer.

Mapping cerebral atrophic trajectory from amnestic mild cognitive impairment to Alzheimer's disease.

Alzheimer's disease (AD) patients suffer progressive cerebral atrophy before dementia onset. However, the region-specific atrophic processes and the influences of age and apolipoprotein E (APOE) on atrophic trajectory are still unclear. By mapping the region-specific nonlinear atrophic trajectory of whole cerebrum from amnestic mild cognitive impairment (aMCI) to AD based on longitudinal structural magnetic resonance imaging data from Alzheimer's disease Neuroimaging Initiative (ADNI) database, we unraveled a quadratic accelerated atrophic trajectory of 68 cerebral regions from aMCI to AD, especially in the superior temporal pole, caudate, and hippocampus. Besides, interaction analyses demonstrated that APOE ε4 carriers had faster atrophic rates than noncarriers in 8 regions, including the caudate, hippocampus, insula, etc.; younger patients progressed faster than older patients in 32 regions, especially for the superior temporal pole, hippocampus, and superior temporal gyrus; and 15 regions demonstrated complex interaction among age, APOE, and disease progression, including the caudate, hippocampus, etc. (P < 0.05/68, Bonferroni correction). Finally, Cox proportional hazards regression model based on the identified region-specific biomarkers could effectively predict the time to AD conversion within 10 years. In summary, cerebral atrophic trajectory mapping could help a comprehensive understanding of AD development and offer potential biomarkers for predicting AD conversion.

The risk prediction of intergenerational transmission of overweight and obesity between mothers and infants during pregnancy.

BACKGROUND: Overweight and obesity in mothers before pregnancy lead to overweight and obesity in their offspring, which is the main form of intergenerational transmission of overweight and obesity in early life. Many factors, especially non-genetic factors, may influence intergenerational transmission, but little prediction research has been conducted. Therefore, we analyzed the status of intergenerational transmission in maternal and infant overweight and obesity. Second, we explored the factors during the pregnancy that might affect the the intergenerational transmission; According to the two application scenarios of pregnancy screen and self-management, risk prediction models for pregnant women were carried out. METHODS: Based on a prospective birth cohort, a total of 908 mothers and offspring were followed up during early life. Follow-up visits were performed at the first trimester, second trimester, third trimester, delivery, 42 days after delivery, and 6 months and 12 months of age. The investigation methods included questionnaire survey, physical examination, biological sample collection and clinical data collection. In terms of risk prediction, univariate analysis was used to screen candidate predictors. Second, multivariable Cox proportional hazard regression models were used to determine the final selected predictors. Third, the corresponding histogram models were drawn, and then the 10-fold cross-validation methods were used for internal verification. RESULTS: Regarding intergenerational transmission of overweight and obesity between mothers and infants during pregnancy, the risk prediction model for pregnancy screen was constructed. The model established: h(t|X) = h0(t)exp.(- 0.95 × (Bachelor Degree or above) + 0.75 × (Fasting blood glucose in the second trimester) + 0.89 × (Blood pressure in the third trimester) + 0.80 × (Cholesterol in third trimester) + 0.55 × (Abdominal circumference in third trimester))., with good discrimination (AUC = 0.82) and calibration (Hosmer-Lemeshow2 = 4.17). The risk prediction model for self-management was constructed. The model established: h(t|X) = h0(t)exp. (0.98 × (Sedentary >18METs) + 0.88 × (Sleep index≥8) + 0.81 × (Unhealthy eating patterns Q3/Q4) + 0.90 × (Unhealthy eating patterns Q4/Q4) + 0.85 × (Depression)), with good discrimination (AUC = 0.75) and calibration (Hosmer-Lemeshow2 = 3.81). CONCLUSIONS: The risk predictions of intergenerational transmission of overweight and obesity between mothers and infants were performed for two populations and two application scenarios (pregnancy screening and home self-management). Further research needs to focus on infants and long-term risk prediction models.

Liraglutide attenuates type 2 diabetes mellitus-associated non-alcoholic fatty liver disease by activating AMPK/ACC signaling and inhibiting ferroptosis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most common complications of type 2 diabetes mellitus (T2DM). The pathogenesis of NAFLD involves multiple biological changes, including insulin resistance, oxidative stress, inflammation, as well as genetic and environmental factors. Liraglutide has been used to control blood sugar. But the impact of liraglutide on T2DM-associated NAFLD remains unclear. In this study, we investigated the impact and potential molecular mechanisms of inhibiting ferroptosis for liraglutide improves T2DM-associated NAFLD. METHODS: Mice were fed on high-fat-diet and injected with streptozotocin to mimic T2DM-associated NAFLD and gene expression in liver was analysed by RNA-seq. The fast blood glucose was measured during the period of liraglutide and ferrostatin-1 administration. Hematoxylin and eosin staining was used to evaluate the pathological changes in the liver. The occurrence of hepatic ferroptosis was measured by lipid peroxidation in vivo. The mechanism of liraglutide inhibition ferroptosis was investigated by in vitro cell culture. RESULTS: Liraglutide not only improved glucose metabolism, but also ameliorated tissue damage in the livers. Transcriptomic analysis indicated that liraglutide regulates lipid metabolism related signaling including AMPK and ACC. Furthermore, ferroptosis inhibitor rather than other cell death inhibitors rescued liver cell viability in the presence of high glucose. Mechanistically, liraglutide-induced activation of AMPK phosphorylated ACC, while AMPK inhibitor compound C blocked the liraglutide-mediated suppression of ferroptosis. Moreover, ferroptosis inhibitor restored liver function in T2DM mice in vivo. CONCLUSIONS: These findings indicate that liraglutide ameliorates the T2DM-associated NAFLD, which possibly through the activation of AMPK/ACC pathway and inhibition of ferroptosis.

Unraveling schizophrenia replicable functional connectivity disruption patterns across sites.

Functional connectivity (FC) disruption is a remarkable characteristic of schizophrenia. However, heterogeneous patterns reported across sites severely hindered its clinical generalization. Based on qualified nodal-based FC of 340 schizophrenia patients (SZ) and 348 normal controls (NC) acquired from seven different scanners, this study compared four commonly used site-effect correction methods in removing the site-related heterogeneities, and then tried to cluster the abnormal FCs into several replicable and independent disrupted subnets across sites, related them to clinical symptoms, and evaluated their potentials in schizophrenia classification. Among the four site-related heterogeneity correction methods, ComBat harmonization (F1 score: 0.806 ± 0.145) achieved the overall best balance between sensitivity and false discovery rate in unraveling the aberrant FCs of schizophrenia in the local and public data sets. Hierarchical clustering analysis identified three replicable FC disruption subnets across the local and public data sets: hypo-connectivity within sensory areas (Net1), hypo-connectivity within thalamus, striatum, and ventral attention network (Net2), and hyper-connectivity between thalamus and sensory processing system (Net3). Notably, the derived composite FC within Net1 was negatively correlated with hostility and disorientation in the public validation set (p < .05). Finally, the three subnet-specific composite FCs (Best area under the receiver operating characteristic curve [AUC] = 0.728) can robustly and meaningfully discriminate the SZ from NC with comparable performance with the full identified FCs features (best AUC = 0.765) in the out-of-sample public data set (Z = -1.583, p = .114). In conclusion, ComBat harmonization was most robust in detecting aberrant connectivity for schizophrenia. Besides, the three subnet-specific composite FC measures might be replicable neuroimaging markers for schizophrenia.

Carbon Quantum Dot/Chitosan-Derived Hydrogels with Photo-stress-pH Multiresponsiveness for Wearable Sensors.

In recent years, hydrogels have attracted extensive attention in smart sensing owing to their biocompatibility and high elasticity. However, it is still a challenge to develop hydrogels with excellent multiple responsiveness for smart wearable sensors. In this paper, a facile synthesis of carbon quantum dots (CQDs)-doped cross-linked chitosan quaternary/carboxymethylcellulose hydrogels (CCCDs) is presented. Designing of dual network hydrogels decorated with CQDs provides abundant crosslinking and improves the mechanical properties of the hydrogels. The hydrogel-based strain sensor exhibits excellent sensitivity (gauge factor: 9.88), linearity (R2 : 0.97), stretchable ability (stress: 0.67 MPa; strain: 404%), good cyclicity, and durability. The luminescent properties are endowed by the CQDs further broaden the application of hydrogels for realizing flexible electronics. More interestingly, the strain sensor based on CCCDs hydrogel demonstrates photo responsiveness (ΔR/R0 ≈20%) and pH responsiveness (pH range ≈4-7) performance. CCCDs hydrogels can be used for gesture recognition and light sensing switch. As a proof-of-concept, a smart wearable sensor is designed for monitoring human activities and detecting pH variation in human sweat during exercise. This study reveals new possibilities for further applications in wearable health monitoring.

Pharmacokinetics and tissue distribution of five bioactive components in the Corydalis yanhusuo total alkaloids transdermal patch following Shenque acupoint application in rats assessed by ultra-performance liquid chromatography-tandem mass spectrometry.

The purpose of this study was to evaluate the pharmacokinetics and tissue distribution of the Corydalis yanhusuo total alkaloids transdermal patch (CTTP) following Shenque acupoint application in rats. The concentrations of corydaline, tetrahydropalmatine, tetrahydrocolumbamine, protopine, and dehydrocorydaline in rat plasma and various tissues were simultaneously detected by ultra-performance liquid chromatography-tandem mass spectrometry after Shenque acupoint administration of CTTP. Plasma, heart, liver, spleen, lung, and kidney tissue samples were collected at specific times and separated by gradient elution on an ACQUITY UPLC HSS T3 column (1.8 µm, 100 mm × 2.1 mm) with a mobile phase of 0.01% formic acid aqueous solution and acetonitrile-0.01% formic acid. The methodological results showed that the selectivity, linear range, accuracy, precision, stability, matrix effect, and extraction recovery of the established method met the requirements of biological sample analysis. The results indicated that CTTP following Shenque acupoint administration rapidly delivered adequate drug into rat blood and maintained an effective plasma level for a significantly longer time than non-acupoint administration. Furthermore, CTTP effectively reached the liver through Shenque acupoint administration and showed tissue selectivity. The data obtained could provide a prospect for the treatment of chronic pain with CTTP following Shenque acupoint application.

Temperature-Stress Bimodal Sensing Conductive Hydrogel-Liquid Metal by Facile Synthesis for Smart Wearable Sensor.

Conductive hydrogels have attracted great attention due to their promising applications in wearable sensors. However, developing conductive hydrogels with excellent sensor properties and multiple stimuli responsiveness for smart wearable devices is still a challenge. This paper presents a facile synthetic method of a crosslinked chitosan quaternary ammonium salt and liquid metal (CHACC-LM) composite hydrogel with temperature-stress bimodal sensing for smart wearable sensor. LM as liquid fillers toughen the hydrogel matrix (stress: 1.11 MPa) and enhance the hydrogel extensibility (strain: 233%). The CHACC-LM hydrogel exhibits conductivity , excellent antibacterial properties (> 99%), an electrical self-healing property, and strain sensitivity (GF = 1.6). In addition, the CHACC-LM hydrogel can be used as wearable flexible sensors with the ability of monitoring human activities directly and the distinguished ability of discerning subtle motions (handwriting). It also shows sensitivity in the external environment such as low temperature, thermal response, and water solution. Importantly, the composite hydrogel simultaneous response to different stress and temperature stimuli. Furthermore, the CHACC-LM hydrogel can be used for gesture recognition and to control the manipulator in human-computer interaction. All these properties provide a great scope for researchers to achieve practical advances in smart wearable sensors.

Characterization of diterpene metabolism in rats with ingestion of seed products from Euphorbia lathyris L. (Semen Euphorbiae and Semen Euphorbiae Pulveratum) using UHPLC-Q-Exactive MS.

Previous pharmacological studies have indicated that diterpenoids are the primary effective chemical cluster in the seeds of Euphorbia lathyris L. The seed products are used in traditional Chinese medicine in the forms of Semen Euphorbiae (SE) and Semen Euphorbiae Pulveratum (SEP). However, the metabolism of the plant's diterpenoids has not been well elucidated, which means that the in vivo metabolite products have not been identified. The current study screened the physiological metabolites of six diterpenes [Euphorbia factor L1 (L1), L2 (L2), L3 (L3), L7a (L7a), L7b (L7b), and L8 (L8)] in feces and urine of rats after oral administration of SE and SEP using UHPLC-Q-Exactive MS. A total of 22 metabolites were detected in feces and 8 in urine, indicating that the major elimination route of diterpenoids is via the colon. Hydrolysis, methylation, and glucuronidation served as the primary metabolic pathways of these diterpenoids. In sum, this study contributed to the elucidation of new metabolites and metabolic pathways of SE and SEP, and the new chemical identities can be used to guide further pharmacokinetic studies.

Vagus nerve stimulated by microbiota-derived hydrogen sulfide mediates the regulation of berberine on microglia in transient middle cerebral artery occlusion rats.

Amelioration of neuroinflammation via modulating microglia is a promising approach for cerebral ischemia therapy. The aim of the present study was to explore gut-brain axis signals in berberine-modulating microglia polarization following cerebral ischemia. The potential pathway was determined through analyzing the activation of the vagus nerve, hydrogen sulfide (H2 S) metabolism, and cysteine persulfides of transient receptor potential vanilloid 1 (TRPV1) receptor. The cerebral microenvironment feature was explored with a metabolomics assay. The data indicated that berberine ameliorated behavioral deficiency in transient middle cerebral artery occlusion rats through modulating microglia polarization and neuroinflammation depending on microbiota. Enhanced vagus nerve activity following berberine treatment was blocked by antibiotic cocktails, capsazepine, or sodium molybdate, respectively. Berberine-induced H2 S production was responsible for vagus nerve stimulation achieved through assimilatory and dissimilatory sulfate reduction with increased synthetic enzymes. Sulfation of the TRPV1 receptor resulted in vagus nerve activation and promoted the c-fos and ChAT in the nucleus tractus solitaries with berberine. Sphingolipid metabolism is the primary metabolic characteristic with berberine in the cerebral cortex, hippocampus, and cerebral spinal fluid disrupted by antibiotics. Berberine, in conclusion, modulates microglia polarization in a microbiota-dependent manner. H2 S stimulates the vagus nerve through TRPV1 is responsible for the berberine-induced gut-brain axis signal transmission. Sphingolipid metabolism might mediate the neuroinflammation amelioration following vagus afferent fiber activation.

A Low-Latency Divider Design for Embedded Processors.

Division is generally regarded as a low-frequency, high-latency operation in integer operations. Division is also the operation that stalls the processor pipeline most frequently. In order to improve the overall performance of embedded processors, a low-delay divider for embedded processors was designed. Based on the non-restoring algorithm, the divider uses a compound adder to execute addition and subtraction simultaneously and reduces the iteration path delay. By shifting the operands to align the most effective bits, the divider dynamically adjusts the number of iteration cycles to reduce the average number of cycles in the division process. The divider design was simulated by Modelsim and implemented on a FPGA board for verification. Synthesized in a Semiconductor Manufacturing International Corporation (SMIC) 65 nm Low Leakage process, the achieved frequency of the design was up to 500 MHz and the area cost was 5670.36 µm2. Compared with other dividers, the proposed divider design can reduce the delay of single iteration by up to 45.3%, save the average number of iteration cycles by 20-50%, and save the area by 23.3-86.1%. Compared with other dividers implemented on FPGA, it saves LUTs by 36.47-59.6% and FFs by 67-84.28%, runs 2-6.36 times faster. Therefore, the proposed design is suitable for embedded processors that require low power consumption, low resource consumption, and high performance.

The Integration of Metabolomics and Transcriptomics Provides New Insights for the Identification of Genes Key to Auxin Synthesis at Different Growth Stages of Maize.

As a staple food crop, maize is widely cultivated worldwide. Sex differentiation and kernel development are regulated by auxin, but the mechanism regulating its synthesis remains unclear. This study explored the influence of the growth stage of maize on the secondary metabolite accumulation and gene expression associated with auxin synthesis. Transcriptomics and metabonomics were used to investigate the changes in secondary metabolite accumulation and gene expression in maize leaves at the jointing, tasseling, and pollen-release stages of plant growth. In total, 1221 differentially accumulated metabolites (DAMs) and 4843 differentially expressed genes (DEGs) were screened. KEGG pathway enrichment analyses of the DEGs and DAMs revealed that plant hormone signal transduction, tryptophan metabolism, and phenylpropanoid biosynthesis were highly enriched. We summarized the key genes and regulatory effects of the tryptophan-dependent auxin biosynthesis pathways, giving new insights into this type of biosynthesis. Potential MSTRG.11063 and MSTRG.35270 and MSTRG.21978 genes in auxin synthesis pathways were obtained. A weighted gene co-expression network analysis identified five candidate genes, namely TSB (Zm00001d046676 and Zm00001d049610), IGS (Zm00001d020008), AUX2 (Zm00001d006283), TAR (Zm00001d039691), and YUC (Zm00001d025005 and Zm00001d008255), which were important in the biosynthesis of both tryptophan and auxin. This study provides new insights for understanding the regulatory mechanism of auxin synthesis in maize.

Overexpression of ZmSRG7 Improves Drought and Salt Tolerance in Maize (Zea mays L.).

Osmotic stress caused by drought and high salinity is the key factor limiting plant growth. However, its underlying molecular regulatory mechanism remains unclear. In this study, we found the stress-related gene Zm00001d019704 (ZmSRG7) based on transcriptome sequencing results previously obtained in the laboratory and determined its biological function in maize. We found that ZmSRG7 was significantly expressed in both roots and leaves under 10% PEG6000 or 150 mM NaCl. Subcellular localization showed that the gene was localized in the nucleus. The germination rate and root length of the ZmSRG7 overexpressing lines were significantly increased under drought or salt stress compared with the control. However, after drought stress, the survival rate and relative water content of maize were increased, while the water loss rate was slowed down. Under salt stress, the Na+ concentration and Na+: K+ ratio of maize was increased. In addition, the contents of antioxidant enzymes and proline in maize under drought or salt stress were higher than those in the control, while the contents of MDA, H2O2 and O2- were lower than those in the control. The results showed that the ZmSRG7 gene played its biological function by regulating the ROS signaling pathway. An interaction between ZmSRG7 and the Zmdhn1 protein was found using a yeast two-hybrid experiment. These results suggest that the ZmSRG7 gene can improve maize tolerance to drought or salt by regulating hydrogen peroxide homeostasis.

Association of gestational diabetes mellitus with offspring weight status across infancy: a prospective birth cohort study in China.

BACKGROUND: The association between gestational diabetes mellitus (GDM) and childhood body weight remains controversial, and additional study is needed, especially in Asian populations. METHODS: This prospective study investigated the association between maternal glucose concentration, and GDM status and infant body weight from birth to 12 months of age. Linear mixed effects (LME) models and multiple linear regression were used to assess the longitudinal association of GDM with infant growth measured by weight-for-length z-scores (WFLZ), weight-for-age z-scores (WFAZ), and length-for-age z-scores (LFAZ) at birth, 1, 3, 6, 8, and 12 months of age. RESULTS: Offspring born to mothers with GDM had higher WFLZ [ß: 0.26 SD units (95% CI: 0.13-0.40)] across infancy than those of mothers without GDM. When stratified analysis by maternal pre-pregnancy body mass index (BMI) status, the association was pronounced in normal-weight [ß:0.28 SD units (95% CI: 0.11-0.45)] and overweight/obese women [ß: 0.34 SD units (95% CI: 0.09-0.58)] but not in underweight women (P for interaction < 0.05). Multiple linear regression found that the effect estimate of GDM on infant WFLZ was highest at birth [ß: 0.36 SD units (95% CI: 0.11-0.61)], remained significant at 1 [ß: 0.22 SD units (95% CI: 0.03-0.41)] and 3 [ß:0.19 SD units (95% CI: 0.01-0.37)] months of age and decreased across infancy. Maternal GDM status was not associated with infant WFAZ or LFAZ. CONCLUSIONS: Maternal GDM status was associated with infant WFLZ, but not WFAZ or LFAZ. The association between GDM status and offspring WFLZ was more pronounced in early infancy or in normal-weight and overweight/obese women. Increased public health efforts to prevent GDM in normal-weight and overweight/obese pre-pregnancy mothers are recommended to control offspring overweight or obesity.

Bidirectional association of neurodevelopment with growth: a prospective cohort study.

BACKGROUND: The study aims to use the cross-lagged model and utilize data from the Born in Shenyang Cohort Study to characterize the bidirectional associations of the term-born infants' neurodevelopment in five domains and physical growth in early life. METHOD: This study consists of 688 mother-child dyads from the Born in Shenyang Cohort Study. Infants' anthropometric (weight and length) and development in neurological outcomes (Gesell Development Scale) were measured at the age of 6 and 12 months. Cross-lagged analyses and multiple linear regression analyses were used to explore the longitudinal relationships in both directions. RESULTS: In terms of longitudinal studies, the inverse associations between infants' two skills (gross motor and social behavior) at the age of 6 months with BMI Z -scores at the age of 12 months (gross motor: aß = - 0.20, 95% CI: - 0.31 to- 0.09; social behavior: aß = - 0.23, 95% CI: - 0.33 to- 0.13) were found. Conversely, a higher infant Z -scored BMI at the age of 6 months predicted a lower gross motor at the age of 12 months (aß = - 0.08, 95% CI: - 0.12 to- 0.04). In cross-lagged analyses, an adverse association in both directions between gross motor and Z -scored BMI was observed. CONCLUSION: We found bidirectional relationships between infants' neurodevelopment of gross motor with physical growth and suggested the term-born infants, who are on the edge of the developmental danger, should not be overlooked.

A novel association of CCDC80 with gestational diabetes mellitus in pregnant women: a propensity score analysis from a case-control study.

BACKGROUND: Gestational diabetes mellitus (GDM) is a growing global epidemic. Our study aims to confirm the association between circulatory coiled-coil domain-containing 80 (CCDC80) in pregnant women with GDM, to investigate the discriminatory power of CCDC80 on GDM, and to explore the relationships between this molecular level and clinical cardiometabolic parameters. METHODS: A 1:2 matched case-control study with 61 GDM patients and 122 controls was conducted using a propensity score matching protocol. All participants were screened from a multicenter prospective pre-birth cohort: Born in Shenyang Cohort Study (BISCS). During 24 and 28 weeks of gestation, follow-up individuals underwent an oral glucose tolerance test (OGTT) and blood sampling for cardiometabolic characterization. RESULTS: Following propensity score matching adjustment for clinical variables, including maternal age, gestational age, body mass index, SBP and DBP, plasma CCDC80 levels were significantly decreased in patients with GDM when compared with controls (0.25 ± 0.10 vs. 0.31 ± 0.12 ng/ml, P = 0.003). Conditional multi-logistic regression analyses after adjustments for potential confounding factors revealed that CCDC80 was a strong and independent protective factor for GDM (ORs < 1). In addition, the results of the ROC analysis indicated the CCDC80 exhibited the capability to identify pregnant women with GDM (AUC = 0.633). Finally, multivariate regression analyses showed that CCDC80 levels were positively associated with AST, monoamine oxidase, complement C1q, LDL-C, apolipoprotein A1and B, and negatively associated with blood glucose levels at 1 h post- OGTT. CONCLUSIONS: Biomarker CCDC80 could be of great value for the development of prediction, diagnosis and therapeutic strategies against GDM in pregnant women.

Surface plasmon resonance biosensor using hydrogel-AuNP supramolecular spheres for determination of prostate cancer-derived exosomes.

Based on the hydrogel-AuNP supramolecular sphere (H-Au), a label-free and real-time surface plasmon resonance imaging biosensor has been developed for highly sensitive and specific determination of prostate cancer cell-derived exosomes. After integrating the signal amplification effect of the mass cumulative hydrogel and the LSPR effect of AuNPs with high specific aptamer, the SPRi biosensor for exosome detection exhibited a wide linear range from 1.00 × 105 to 1.00 × 107 particles/mL with a limit of detection of 1.00 × 105 particles/mL. Most importantly, with a strong correlation between the SPRi signal and the t-PSA value measured by the clinical chemiluminescence immunoassay, this biosensor displayed excellent practicability for human serum analysis, which exhibits great potential applications in disease diagnosis and bioanalysis. Prostate cancer has been one of the most threatening diseases in human life and health nowadays. In particular, as cancer metastasizes, it is more likely to cause fracture, paraplegia, and even fatal consequences. However, the predominant t-PSA test needs further improvement for the deficiencies of limited specificity and sensitivity, which is prone to false positive. As one of the noninvasive markers of liquid biopsies, exosome has the potential to be a substitute for t-PSA, which can provide specific and predictive information in disease diagnosis and prognosis. Herein, based on the hydrogel-AuNP supramolecular sphere (H-Au), a label-free and real-time surface plasmon resonance biosensor has been developed for highly sensitive and specific detection of prostate cancer cell-derived exosomes. After integrating the signal amplification effect of mass cumulative hydrogel and LSPR effect of AuNPs with high specific aptamer, this developed SPRi biosensor for exosome detection exhibited a wide linear range from 1.00 × 105 to 1.00 × 107 particles/mL with a limit of detection down to 1.00 × 105 particles/mL. Most importantly, with a strong correlation between the SPRi signal and the t-PSA value measured by the clinical chemiluminescence immunoassay, this biosensor displayed excellent practicability in human serum, which exhibited great potential applications in disease diagnosis and bioanalysis.

Association of sleep quality during pregnancy with stress and depression: a prospective birth cohort study in China.

BACKGROUND: The sleep quality of pregnant women in the third trimester is related to mental health. However, there is still a lack of large-scale cohort research exploring this relationship in the second trimester. Thus, we assessed the associations of sleep quality during the second trimester with antenatal stress and antenatal and postnatal depression. METHODS: We examined 1152 pregnant women from a prospective cohort study in China to assess the associations of sleep quality in the second trimester with antenatal stress, antenatal depression, and postnatal depression. We used linear regression models and logistic regression models to examine the associations of sleep quality (Pittsburgh Sleep Quality Index [PSQI]) during pregnancy with perinatal stress (Pregnancy Pressure Scale [PPS]) and depression (Edinburgh Postnatal Depression Scale [EPDS]) status. We further assessed the relationship in groups divided according to maternal age. RESULTS: PSQI scores were positively associated with antenatal PPS scores (ß: 1.52, 95% confidence interval [CI]: 1.28, 1.76), antenatal EPDS scores (ß: 0.68, 95% CI: 0.58, 0.78), and postpartum EPDS scores (ß: 0.51, 95% CI: 0.38, 0.64). Poor sleep quality (PSQI scores ≥5) was associated with antenatal stress status (odds ratio [OR]: 2.60, 95% CI: 1.79, 3.77), antenatal depression status (OR: 3.42, 95% CI: 2.48, 4.72), and postpartum depression status (OR: 2.40, 95% CI: 1.58, 3.64) after adjusting maternal age, BMI, gestational age, smoking, educational level, annual household income and social support. The association of poor sleep quality (PSQI scores ≥5) in the second trimester with postnatal depression status was significant among women more than or equal to 30 years old (OR: 4.12, 95% CI: 2.18, 7.78) but not among women less than 30 years old after adjusting covariates above. CONCLUSION: Poor sleep quality in the second trimester among Chinese pregnant women is associated with stress and depression symptoms. Strategies to boost sleep quality should be considered during prenatal health care to improve women's mental health status.

A highly sensitive SPRi biosensing strategy for simultaneous detection of multiplex miRNAs based on strand displacement amplification and AuNP signal enhancement.

Herein, a dual channel surface plasmon resonance imaging (SPRi) biosensor has been developed for the simultaneous and highly sensitive detection of multiplex miRNAs based on strand displacement amplification (SDA) and DNA-functionalized AuNP signal enhancement. In the presence of target miRNAs (miR-21 or miR-192), the miRNAs could specifically hybridize with the corresponding hairpin probes (H) and initiate the SDA, resulting in massive triggers. Subsequently, the two parts of the released triggers could hybridize with capture probes (CP) and DNA-functionalized AuNPs, assembling DNA sandwiches with great mass on the chip surface. A significantly amplified SPR signal readout was achieved. This established biosensing method was capable of simultaneously detecting multiplex miRNAs with a limit of detection down to 0.15 pM for miR-21 and 0.22 pM for miR-192. This method exhibited good specificity and acceptable reproducibility. Moreover, the developed method was applied to the determination of target miRNAs in a complex matrix. Thus, this developed SPRi biosensing method may present a potential alternative tool for miRNA detection in biomedical research and clinical diagnosis.