Spatiotemporal formation of the large vacuole regulated by the BIN2-VLG module is required for female gametophyte development in Arabidopsis.

In Arabidopsis thaliana, female gametophyte (FG) development is accompanied by the formation and expansion of the large vacuole in the FG; this is essential for FG expansion, nuclear polar localization, and cell fate determination. Arabidopsis VACUOLELESS GAMETOPHYTES (VLG) facilitates vesicular fusion to form large vacuole in the FG, but the regulation of VLG remains largely unknown. Here, we found that gain-of-function mutation of BRASSINOSTEROID INSENSITIVE2 (BIN2) (bin2-1) increases VLG abundance to induce the vacuole formation at stage FG1, and leads to abortion of FG. Loss-of-function mutation of BIN2 and its homologs (bin2-3 bil1 bil2) reduced VLG abundance and mimicked vlg/VLG phenotypes. Knocking down VLG in bin2-1 decreased the ratio of aberrant vacuole formation at stage FG1, whereas FG1-specific overexpression of VLG mimicked the bin2-1 phenotype. VLG partially rescued the bin2-3 bil1 bil2 phenotype, demonstrating that VLG acts downstream of BIN2. Mutation of VLG residues that are phosphorylated by BIN2 altered VLG stability and a phosphorylation mimic of VLG causes similar defects as did bin2-1. Therefore, BIN2 may function by interacting with and phosphorylating VLG in the FG to enhance its stability and abundance, thus facilitating vacuole formation. Our findings provide mechanistic insight into how the BIN2-VLG module regulates the spatiotemporal formation of the large vacuole in FG development.

PIN3 positively regulates the late initiation of ovule primordia in Arabidopsis thaliana.

Ovule initiation determines the maximum ovule number and has great impact on seed number and yield. However, the regulation of ovule initiation remains largely elusive. We previously reported that most of the ovule primordia initiate asynchronously at floral stage 9 and PINFORMED1 (PIN1) polarization and auxin distribution contributed to this process. Here, we further demonstrate that a small amount of ovule primordia initiate at floral stage 10 when the existing ovules initiated at floral stage 9 start to differentiate. Genetic analysis revealed that the absence of PIN3 function leads to the reduction in pistil size and the lack of late-initiated ovules, suggesting PIN3 promotes the late ovule initiation process and pistil growth. Physiological analysis illustrated that, unlike picloram, exogenous application of NAA can't restore these defective phenotypes, implying that PIN3-mediated polar auxin transport is required for the late ovule initiation and pistil length. qRT-PCR results indicated that the expression of SEEDSTICK (STK) is up-regulated under auxin analogues treatment while is down-regulated in pin3 mutants. Meanwhile, overexpressing STK rescues pin3 phenotypes, suggesting STK participates in PIN3-mediated late ovule initiation possibly by promoting pistil growth. Furthermore, brassinosteroid influences the late ovule initiation through positively regulating PIN3 expression. Collectively, this study demonstrates that PIN3 promotes the late ovule initiation and contributes to the extra ovule number. Our results give important clues for increasing seed number and yield of cruciferous and leguminous crops.

Synergistic effect of mesenchymal stem cell-derived extracellular vesicle and miR-137 alleviates autism-like behaviors by modulating the NF-κB pathway.

Autism spectrum disorder (ASD) is a multifaceted neurodevelopmental disorder predominant in childhood. Despite existing treatments, the benefits are still limited. This study explored the effectiveness of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) loaded with miR-137 in enhancing autism-like behaviors and mitigating neuroinflammation. Utilizing BTBR mice as an autism model, the study demonstrated that intranasal administration of MSC-miR137-EVs ameliorates autism-like behaviors and inhibits pro-inflammatory factors via the TLR4/NF-κB pathway. In vitro evaluation of LPS-activated BV2 cells revealed that MSC-miR137-EVs target the TLR4/NF-κB pathway through miR-137 inhibits proinflammatory M1 microglia. Moreover, bioinformatics analysis identified that MSC-EVs are rich in miR-146a-5p, which targets the TRAF6/NF-κB signaling pathway. In summary, the findings suggest that the integration of MSC-EVs with miR-137 may be a promising therapeutic strategy for ASD, which is worthy of clinical adoption.

Novel casein-derived immunomodulatory peptide PFPEVFG: Activity assessment, molecular docking, activity site and mechanism of action.

Nowadays, there is still a gap in the knowledge of the structure-activity relationship of immunomodulatory peptides. In this study, PFPEVFG was selected as a peptide with immunomodulatory activity from casein hydrolysate by virtual screening and its immunomodulatory activity was verified by the phagocytosis, proliferation, and expression of cytokines (IL-6, IL-1ß, TNF-α) and chemokines (CXCL1, CXCL2) in RAW 264.7 macrophages. Next, molecular docking and double-stranded small interfering RNA (siRNA) mutually verified that the immunomodulatory activity of PFPEVFG was mediated by TLR2/4. Furthermore, the highest occupied molecular orbital (HOMO) analysis showed that the C19 = O20 site with a HOMO contribution of 32.22988% was its active site, and the phenylalanine, where the C19 = O20 site was located, was its active amino acid. Finally, the combination of pathway inhibitors and Western blot revealed that PFPEVFG activated macrophages through the nuclear factor-κB (NF-κB) signaling pathway. In summary, this study provided a new perspective on deeply understanding the structure-activity relationship of casein-derived immunomodulatory peptides, as well as a further theoretical and technological basis for the application of immunomodulatory peptides.

Asynchrony of ovule primordia initiation in Arabidopsis.

Plant ovule initiation determines the maximum of ovule number and has a great impact on the seed number per fruit. The detailed processes of ovule initiation have not been accurately described, although two connected processes, gynoecium and ovule development, have been investigated. Here, we report that ovules initiate asynchronously. The first group of ovule primordia grows out, the placenta elongates, the boundaries of existing ovules enlarge and a new group of primordia initiates from the boundaries. The expression pattern of different marker genes during ovule development illustrates that this asynchronicity continues throughout whole ovule development. PIN-FORMED1 polar distribution and auxin response maxima correlate with ovule primordia asynchronous initiation. We have established computational modeling to show how auxin dynamics influence ovule primordia initiation. Brassinosteroid signaling positively regulates ovule number by promoting placentae size and ovule primordia initiation through strengthening auxin response. Transcriptomic analysis demonstrates numerous known regulators of ovule development and hormone signaling, and many new genes are identified that are involved in ovule development. Taken together, our results illustrate that the ovule primordia initiate asynchronously and the hormone signals are involved in the asynchrony.

Adversarial network for multi-input image restoration under strong turbulence.

Turbulence generated by random ups and downs in the refractive index of the atmosphere produces varying degrees of distortion and blurring of images in the camera. Traditional methods ignore the effect of strong turbulence on the image. This paper proposes a deep neural network to enhance image clarity under strong turbulence to handle this problem. This network is divided into two sub-networks, the generator and the discriminator, whose functions are to mitigate the effects of turbulence on the image and to determine the authenticity of the recovered image. After extensive experiments, it is proven that the present network plays a role in mitigating the image degradation problem caused by atmospheric turbulence.

DNA methylation-mediated inhibition of MGARP is involved in impaired progeny testosterone synthesis in mice exposed to DBP in utero.

The dibutyl phthalate (DBP) has been detected in fetuses and infants and can cause damage to the reproductive system in adulthood, but the exact mechanism remains unclear. Here, we aim to investigate the effects of intrauterine DBP exposure on offspring reproductive function and explore possible mechanisms. SPF C57BL/6 pregnant mice were given DBP (0.5, 5, 75 mg/kg/d) or corn oil from day 5 to day 19 by gavage. After weaning, the pups were fed a standard diet for 5 weeks. In addition, TM3 Leydig cell cultures were used to study the relevant mechanisms in vitro. The results showed that intrauterine DBP exposure could reduce sperm density and sperm motility, cause testicular tissue damage, down-regulate serum T and LH levels, and up-regulate serum FSH levels at 75 mg/kg/d. Western blot and methylation detection revealed intrauterine exposure to DBP down-regulated testosterone synthesis-related proteins StAR, P450scc, 3ß-HSD, PKA, and PKC expression, while up-regulated the levels of methyltransferase proteins expression and DNA 5-methylcytosine (5mC) in testicular tissue of mouse offspring at 75 mg/kg/d. Further detection found in utero 75 mg/kg/d DBP exposure down-regulated MGARP protein expression, and induced incomplete methylation of the MGARP gene. An in vitro analysis showed that MGARP inhibition is involved in an impaired testosterone synthesis in TM3 cells. Cell culture results suggest that MGARP down-regulation may be involved in impaired testosterone production in monobutyl phthalate-treated cells. The present study revealed that 75 mg/kg/d DBP exposure in utero resulted in testosterone synthesis disorders and reproductive function impairment in mouse offspring, and the mechanism may be related to DNA methylation-mediated down-regulation of MGARP in the testis.

Asprosin in the Paraventricular Nucleus Induces Sympathetic Activation and Pressor Responses via cAMP-Dependent ROS Production.

Asprosin is a newly discovered adipokine that is involved in regulating metabolism. Sympathetic overactivity contributes to the pathogenesis of several cardiovascular diseases. The paraventricular nucleus (PVN) of the hypothalamus plays a crucial role in the regulation of sympathetic outflow and blood pressure. This study was designed to determine the roles and underlying mechanisms of asprosin in the PVN in regulating sympathetic outflow and blood pressure. Experiments were carried out in male adult SD rats under anesthesia. Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP), and heart rate (HR) were recorded, and PVN microinjections were performed bilaterally. Asprosin mRNA and protein expressions were high in the PVN. The high asprosin expression in the PVN was involved in both the parvocellular and magnocellular regions according to immunohistochemical analysis. Microinjection of asprosin into the PVN produced dose-related increases in RSNA, MAP, and HR, which were abolished by superoxide scavenger tempol, antioxidant N-acetylcysteine (NAC), and NADPH oxidase inhibitor apocynin. The asprosin promoted superoxide production and increased NADPH oxidase activity in the PVN. Furthermore, it increased the cAMP level, adenylyl cyclase (AC) activity, and protein kinase A (PKA) activity in the PVN. The roles of asprosin in increasing RSNA, MAP, and HR were prevented by pretreatment with AC inhibitor SQ22536 or PKA inhibitor H89 in the PVN. Microinjection of cAMP analog db-cAMP into the PVN played similar roles with asprosin in increasing the RSNA, MAP, and HR, but failed to further augment the effects of asprosin. Pretreatment with PVN microinjection of SQ22536 or H89 abolished the roles of asprosin in increasing superoxide production and NADPH oxidase activity in the PVN. These results indicated that asprosin in the PVN increased the sympathetic outflow, blood pressure, and heart rate via cAMP-PKA signaling-mediated NADPH oxidase activation and the subsequent superoxide production.

Ovule initiation: the essential step controlling offspring number in Arabidopsis.

Seed is the offspring of angiosperms. Plants produce large numbers of seeds to ensure effective reproduction and survival in varying environments. Ovule is a fundamentally important organ and is the precursor of the seed. In Arabidopsis and other plants characterized by multi-ovulate ovaries, ovule initiation determines the maximal ovule number, thus greatly affecting seed number per fruit and seed yield. Investigating the regulatory mechanism of ovule initiation has both scientific and economic significance. However, the genetic and molecular basis underlying ovule initiation remains unclear due to technological limitations. Very recently, rules governing the multiple ovules initiation from one placenta have been identified, the individual functions and crosstalk of phytohormones in regulating ovule initiation have been further characterized, and new regulators of ovule boundary are reported, therefore expanding the understanding of this field. In this review, we present an overview of current knowledge in ovule initiation and summarize the significance of ovule initiation in regulating the number of plant offspring, as well as raise insights for the future study in this field that provide potential routes for the improvement of crop yield.

Interaction of brassinosteroid and cytokinin promotes ovule initiation and increases seed number per silique in Arabidopsis.

Ovule initiation is a key step that strongly influences ovule number and seed yield. Notably, mutants with enhanced brassinosteroid (BR) and cytokinin (CK) signaling produce more ovules and have a higher seed number per silique (SNS) than wild-type plants. Here, we crossed BR- and CK-related mutants to test whether these phytohormones function together in ovule initiation. We determined that simultaneously enhancing BR and CK contents led to higher ovule and seed numbers than enhancing BR or CK separately, and BR and CK enhanced each other. Further, the BR-response transcription factor BZR1 directly interacted with the CK-response transcription factor ARABIDOPSIS RESPONSE REGULATOR1 (ARR1). Treatments with BR or BR plus CK strengthened this interaction and subsequent ARR1 targeting and induction of downstream genes to promote ovule initiation. Enhanced CK signaling partially rescued the reduced SNS phenotype of BR-deficient/insensitive mutants whereas enhanced BR signaling failed to rescue the low SNS of CK-deficient mutants, suggesting that BR regulates ovule initiation and SNS through CK-mediated and -independent pathways. Our study thus reveals that interaction between BR and CK promotes ovule initiation and increases seed number, providing important clues for increasing the seed yield of dicot crops.

Transparent HfO x -based memristor with robust flexibility and synapse characteristics by interfacial control of oxygen vacancies movement.

Hafnium oxides (HfO x ) based flexible memristors were fabricated on polyethylene naphtholate (PEN) substrates to simulate a variety of bio-synapse functions. By optimizing the manufacturing conditions of electrode and active films, it is proved that the TiN/HfO x /W/ITO/PEN bilayer device has robust flexibility and can still be modulated after 2000 times of bending. The memristor device exhibits better symmetrical and linear characteristics with excellent uniformity at lower programming power consumption (∼38 µW). In addition, the essential synaptic behaviors have further been achieved in the devices, including the transition from short-term plasticity to long-term plasticity and spike time-dependent plasticity. Through the analysis of I-V curves and XPS data, a switching mechanism based on HfO x /W interface boundary drift is constructed. It is revealed that the redox reaction caused by W intercalation can effectively regulate the content of oxygen vacancy in HfO x . At the same time, bias-induced interfacial reactions will regulate the movement of oxygen vacancies, which emulates bio-synapse functions and improves the electrical properties of the device.

Two tonoplast proton pumps function in Arabidopsis embryo development.

Two types of tonoplast proton pumps, H+ -pyrophosphatase (V-PPase) and the H+ -ATPase (V-ATPase), establish the proton gradient that powers molecular traffic across the tonoplast thereby facilitating turgor regulation and nutrient homeostasis. However, how proton pumps regulate development remains unclear. In this study, we investigated the function of two types of proton pumps in Arabidopsis embryo development and pattern formation. While disruption of either V-PPase or V-ATPase had no obvious effect on plant embryo development, knocking out both resulted in severe defects in embryo pattern formation from the early stage. While the first division in wild-type zygote was asymmetrical, a nearly symmetrical division occurred in the mutant, followed by abnormal pattern formation at all stages of embryo development. The embryonic defects were accompanied by dramatic differences in vacuole morphology and distribution, as well as disturbed localisation of PIN1. The development of mutant cotyledons and root, and the auxin response of mutant seedlings supported the hypothesis that mutants lacking tonoplast proton pumps were defective in auxin transport and distribution. Taking together, we proposed that two tonoplast proton pumps are required for vacuole morphology and PIN1 localisation, thereby controlling vacuole and auxin-related developmental processes in Arabidopsis embryos and seedlings.

Identification of the urine and serum metabolomics signature of gout.

OBJECTIVE: Gout is the most common inflammatory arthritis and the worldwide incidence is increasing. By revealing the metabolic alterations in serum and urine of gout patients, the first aim of our study was to discover novel molecular biomarkers allowing for early diagnosis. We also aimed to investigate the underlying pathogenic pathways. METHODS: Serum and urine samples from gout patients (n = 30) and age-matched healthy controls (n = 30) were analysed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) to screen the differential metabolites and construct a diagnostic model. Next, the model was verified and optimized in the second validation cohort (n = 100). The pathways were illustrated to understand the underlying pathogenesis of gout. RESULTS: In general, serum metabolomics demonstrated a clearer distinction than urine metabolomics. In the discovery cohort, 40 differential serum metabolites were identified that could distinguish gout patients from healthy controls. Among them, eight serum metabolites were verified in the validation cohort. Through regression analysis, the final model consisted of three serum metabolites-pyroglutamic acid, 2-methylbutyryl carnitine and Phe-Phe-that presented optimal diagnostic power. The three proposed metabolites produced an area under the curve of 0.956 (95% CI 0.911, 1.000). Additionally, the proposed metabolic pathways were primarily involved in purine metabolism, branched-chain amino acids (BCAAs) metabolism, the tricarboxylic acid cycle, synthesis and degradation of ketone bodies, bile secretion and arachidonic acid metabolism. CONCLUSION: The metabolomics signatures could serve as an efficient tool for early diagnosis and provide novel insights into the pathogenesis of gout.

Comparison of chemiluminescence microparticle immunoassay, indirect immunofluorescence assay, linear immunoassay and multiple microbead immunoassay detecting autoantibodies in systemic lupus erythematosus.

The aim of study was to detect antinuclear antibodies (ANA) using indirect immunofluorescence assay (IIFA), linear immunoassay (LIA), chemiluminescence microparticle immunoassay (CMIA), multiple microbead immunoassay (MBI) and to compare these four methods in the performance of diagnosing systemic lupus erythematosus (SLE). Serum ANA were detected in 147 SLE cases and 42 healthy controls (HCs). The sensitivity, specificity, accuracy, positive predictive value and agreement, the area under the curve of four methods in diagnosing were calculated. Finally, a diagnostic model through logistic regression was constructed. The sensitivity of CMIA and IIFA in diagnosing SLE was 89.08% and 89.12%, higher than other two methods (P < .01), while highest specificity lied in CMIA (95.24%) and LIA (95.24%). The accuracy was highest in CMIA (91.01%), and lowest in LIA (83.07%). CMIA and the other three methods had good agreement, especially with LIA (κ = .798, 95% CI, 0.708-0.88). ANA-IIFA (OR = 1.016, P < .001) and anti-SSA antibodies (OR = 1.017, P = .043) were finally included in the SLE diagnostic model, with AUC value of 0.964 (95% CI, 0.936-0.991). SLE patients exhibited 14 various ANA patterns, especially AC-1, AC-4, and AC-5. Antibodies against SSA and dsDNA were mostly seen with AC-1 and AC-4 patterns, while antibodies against RNP, Sm, SSA, dsDNA, nucleosome and PO were most frequently observed with AC-5 pattern in SLE. CMIA method is a reliable screening test for detections of antibodies related to SLE. Using ANA-IIFA and anti-SSA antibodies by CMIA can discriminate SLE patients from HCs effectively.

The comparison of dyslipidemia and serum uric acid in patients with gout and asymptomatic hyperuricemia: a cross-sectional study.

BACKGROUND: Dyslipidemia often concurs with hyperuricemia. Our study was to discover different lipid levels of gout and asymptomatic hyperuricemia and the predictors of sUA (serum uric acid) levels. METHODS: A cross-sectional study was performed to collect demographic, clinical variables, comorbidities and laboratory testing in patients with gout and asymptomatic hyperuricemia. Group comparison was performed with Student's t-test or Mann Whitney U test for continuous variables and chi-squared tests for categorical variables (Fisher's exact test where appropriate) and to screen potential risk factors. Correlation of sUA levels with demographic and biochemical variables were performed by using correlation analysis. The variable with s p-value less than 0.20 during the group comparison or clinical relevance was introduced into the stepwise multiple regression model. RESULTS: Six hundred fifty-three patients with gout and 63 patients with asymptomatic hyperuricemia (> 420 µmol/L in male and > 360 µmol/L in female) were enrolled, including 553 (84.7%) males. The mean age was 47.8 ± 16.0 years old. Elevated total cholesterol (TC) was observed in 173 (26.5%) cases with gout. Increased triglycerides (TG) and low-density lipoprotein (LDL-C) levels were observed in 242 (37.1%) cases and 270 (41.3%) cases with gout, individually. In contrast, elevated TC, TG and LDL-C levels were observed in 10 (15.9%) cases, 30 (47.6%) cases and 22 (34.9%) cases with hyperuricemia, individually. Significant differences were found in age, serum creatine, TC and erythrocyte sedimentation rate (ESR) between gout and asymptomatic hyperuricemia groups (p < 0.05). In patients with asymptomatic hyperuricemia, 12 (19.0%) patients had hypertension and 5 (7.9%) suffered from coronary heart diseases. Male (B = -112.7, p < 0.001), high-density lipoprotein (HDL-C) (B = -60.797, p = 0.013), body mass index (BMI) (B = 5.168, p = 0.024), age (B = -3.475, p = 0.006), age of hyperuricemia onset (B = 2.683, p = 0.032), and serum creatine (B = 0.534, p < 0.001) were predictors of sUA levels in gout patients (adjusted R2 = 28.7%). CONCLUSIONS: Dyslipidemia is more commonly seen in patients with gout, compared to asymptomatic hyperuricemia. HDL-C is a protective predictor of sUA levels in gout.

Analysis of antinuclear antibody titers and patterns by using HEp-2 and primate liver tissue substrate indirect immunofluorescence assay in patients with systemic autoimmune rheumatic diseases.

BACKGROUND: Indirect immunofluorescence assay (IIFA) is viewed as a preliminary standard to assess antinuclear antibodies (ANAs). Our aim was to explore ANA positivity rate, titers, and patterns in patients with systemic autoimmune rheumatic diseases (SARD), including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), primary Sjögren's syndrome (pSS), systemic sclerosis (SSc), and mixed connective tissue disease (MCTD), compared with healthy controls (HC). METHODS: Assess antinuclear antibody titers and patterns were retrospectively identified and compared by IIFA using human epithelial cells (HEp-2) and primate liver tissue substrate according to international consensus in SARD. Serum complement 3 (C3), C4, and immunoglobulin G were compared among subgroups with different ANA titers. The positive predictive values (PPV) for different ANA titers were calculated. RESULTS: There were a total of 3510 samples, including 2034 SLE, 973 RA, 155 SSc, 309 pSS, and 39 MCTD cases. There was no difference in age between HC and SARD, excluding RA. ANA positivity rate in SARD and HC was 78.7% and 12.2%, respectively. A titer of ≥1:320 revealed a PPV of 84.0% in SARD. SLE patients with ANA titers ≥1:320 had significantly lower levels of C3 and C4. AC-4 (31.2%) was the major pattern in patients with SARD, followed by AC-5 (23.9%) and AC-1 (18.8%). SLE mostly presented with AC-4 (30.3%). Several mixed patterns provided a significant hint for SSc and SLE. The major pattern in HC was AC-2 (12.2%). CONCLUSIONS: Assess antinuclear antibody positivity, titers, and patterns display differences in various SARD, contributing to the classification of SARD.

Helios but not CD226, TIGIT and Foxp3 is a Potential Marker for CD4+ Treg Cells in Patients with Rheumatoid Arthritis.

BACKGROUND/AIMS: Rheumatoid arthritis (RA) is a progressive, chronic, even disabling systemic autoimmune disease. Imbalance between pathogenic immune cells and immunosuppressive cells is associated with the pathogenesis and development of RA and other autoimmune diseases. As Foxp3 is also expressed on activated CD4+ cells in the presence of inflammation, the identification of Treg cells in patients with RA remains a challenge. METHODS: Comprehensive analyses were carried out by Flow cytometry. Expression of Helios, CD226, T cell immunoreceptor with Ig and ITIM domains clinical samples and healthy controls. RESULTS: We have systemically examined three potential markers, Helios, CD226 and TIGIT, that are possibly related to Treg identification, and found that Helios expression on CD4+Foxp3+cells was decreased and negatively correlated with the disease activity of RA patients, while CD226 and TIGIT both showed elevated expression levels in CD4+Foxp3+cells in RA patients and they were not associated with disease activity of RA patients. CONCLUSION: Taken together, our findings indicate that CD4+CD25hiCD127low/-Foxp3+Helios+ may represent the real Treg cell population in patients with RA.

A meta-analysis of serum osteocalcin level in postmenopausal osteoporotic women compared to controls.

BACKGROUND: Circulatory osteocalcin (OC) has been widely used as a biomarker to indicate bone turnover status in postmenopausal osteoporosis (PMO). However, the change of serum OC (sOC) level in PMO cases compared to postmenopausal controls remains controversial. METHODS: We searched the online database of PubMed and Cochrane Library. A meta-analysis of case-control studies was performed to compare the pooled sOC level between PMO patients and postmenopausal controls. Subgroup analysis according to potential confounding factors (different OC molecules and regions of the study population) was also performed. RESULTS: Ten case-control studies with 1577 postmenopausal women were included in this meta analysis. We found no significant difference in the pooled sOC level [mean difference (MD) = 1.84, 95% confidence interval (CI): (- 1.49, 5.16), p = 0.28] between PMO patients and controls. Subgroup analysis also revealed no significant difference in intact OC [MD = 1.76, 95%CI: (- 1.71, 5.23), p = 0.32] or N-terminal mid-fragment of the OC molecule [MD = 0.67, 95%(- 5.83, 7.18), p = 0.84] between groups. For different regions, no significant difference in sOC was found in Asian population between cases and controls [MD = -0.06, 95%(- 6.02, 5.89), p = 0.98], while the pooled sOC level was significantly higher in European PMO cases than controls [MD = 3.15, 95%(0.90, 5.39), p = 0.006]. CONCLUSIONS: Our analysis revealed no significant difference in sOC level between PMO cases and controls according to all the current eligible studies. OC molecules are quite heterogeneous in the circulation and can be influenced by glucose metabolism. Therefore, sOC is currently not a good indicator for the high bone turnover status in PMO. More trials with standardized methodologies for the evaluation of circulatory OC are awaited to update our current findings.

Metabolomic analysis of pathways related to rice grain chalkiness by a notched-belly mutant with high occurrence of white-belly grains.

BACKGROUND: Grain chalkiness is a highly undesirable trait deleterious to rice appearance and milling quality. The physiological and molecular foundation of chalkiness formation is still partially understood, because of the complex interactions between multiple genes and growing environments. RESULTS: We report the untargeted metabolomic analysis of grains from a notched-belly mutant (DY1102) with high percentage of white-belly, which predominantly occurs in the bottom part proximal to the embryo. Metabolites in developing grains were profiled on the composite platforms of UPLC/MS/MS and GC/MS. Sampling times were 5, 10, 15, and 20 days after anthesis, the critical time points for chalkiness formation. A total of 214 metabolites were identified, covering most of the central metabolic pathways and partial secondary pathways including amino acids, carbohydrates, lipids, cofactors, peptides, nucleotides, phytohormones, and secondary metabolites. A comparison of the bottom chalky part and the upper translucent part of developing grains of DY1102 resulted in 180 metabolites related to chalkiness formation. CONCLUSIONS: Generally, in comparison to the translucent upper part, the chalky endosperm had lower levels of metabolites regarding carbon and nitrogen metabolism for synthesis of storage starch and protein, which was accompanied by perturbation of pathways participating in scavenging of reactive oxygen species, osmorugulation, cell wall synthesis, and mineral ion homeostasis. Based on these results, metabolic mechanism of chalkiness formation is discussed, with the role of embryo highlighted.

Rapid focus map surveying for whole slide imaging with continuous sample motion.

Whole slide imaging (WSI) has recently been cleared for primary diagnosis in the U.S. A critical challenge of WSI is to perform accurate focusing in high speed. Traditional systems create a focus map prior to scanning. For each focus point on the map, a sample needs to be static in the x-y plane, and axial scanning is needed to maximize the contrast. Here we report a novel focus map surveying method for WSI. In this method, we illuminate the sample with two LEDs and recover the focus points based on 1D autocorrelation analysis. The reported method requires no axial scanning, no additional camera and lens, works for stained and transparent samples, and allows continuous sample motion in the surveying process. By using a 20× objective lens, we demonstrate a mean focusing error of ∼0.08 µm in the static mode and ∼0.17 µm in the continuous motion mode. The reported method may provide a turnkey solution for most existing WSI systems due to its simplicity, robustness, accuracy, and high speed. It may also standardize the imaging performance of WSI systems for digital pathology and find other applications in high-content microscopy, such as time-lapse live-cell imaging.