Copy number variation sequencing for the products of conception: What is the optimal testing strategy.

BACKGROUND: Copy number variation sequencing (CNV-seq) is crucial in prenatal diagnosis, but its limitations in detecting polyploidy, maternal cell contamination (MCC), and uniparental disomy (UPD) restrict its application in the analysis of products of conception (POCs). This study aimed to investigate an optimal genetic testing strategy for POCs in the era of CNV-seq. METHODS: CNV-seq and quantitative fluorescent polymerase chain reaction (QF-PCR) were performed in all 4,211 spontaneous miscarriage cases. Different testing strategies were compared and the optimal testing strategies were proposed. RESULTS: Of the 4,211 cases, 2561 (60.82%) exhibited clinically significant chromosomal abnormalities. CNV-seq alone, without QF-PCR, might misdiagnose 311 (7.39%) cases, including 278 polyploidy, 13 UPD, and 20 MCC. In 20 MCC cases identified by QF-PCR, CNV-seq successfully pinpointed the cause of miscarriage in 13 cases. Furthermore, in cases where QF-PCR suggested polyploidy, CNV-seq improved the diagnostic accuracy in 54 (1.28%) hypo/hypertriploidy cases. After comparing four different strategies, the sequential approach (initiating with CNV-seq followed by QF-PCR if necessary) emerged as advantageous, reducing approximately 70% of the cost associated with QF-PCR while maintaining result accuracy. CONCLUSIONS: We propose an initial CNV-seq followed by QF-PCR if needed-an efficient and cost-effective strategy for the genetic analysis of POCs.

Correlating the Photovoltaic Performance and Stability of the All-Small-Molecule Organic Solar Cells to Their Intermixed Phases Determined by Concentration-Dependent Ultraviolet-Visible Absorption Spectroscopy.

In addition to the donor-acceptor nano phases, the intermixed phase within the organic blends is crucial for the photovoltaic performance and stability of the bulk-heterojunction organic solar cells (OSCs). Here, the intermixed phase of a representative M-PhS:BTP-eC9 all-small-molecule organic solar cell was investigated by a concentration-dependent ultraviolet-visible (UV-vis) absorption spectroscopy method, where a shift of the absorption maximum wavelength was measured for the acceptor component with the increase of the acceptor concentration. The blend ratios of the acceptor to the donor in the intermixed phase, corresponding to the critical concentration for the formation of the acceptor nanophase (CAP), were determined to be 0.35, 0.20, and 0.15 for the as-cast, thermal annealing (TA), and the combined TA and solvent vapor annealing films. These results indicated that M-PhS and BTP-eC9 are kinetically well intermixed during spin coating, whereas TA and the following solvent annealing promote the crystallization of BTP-eC9 molecules out of the intermixed phase. The photovoltaic performance of the M-PhS:BTP-eC9 cells with different blend ratios was investigated. The formation of the BTP-eC9 nano phase in the blend film leads to stable VOC and fast increased JSC, which can be understood by the reduction of bimolecular charge recombination and the formation of electron transporting pathways within the photoactive layer. Similarly, the critical concentration for the formation of the donor phase was estimated to be 0.15 by measuring the stabilized VOC and increased JSC values of the cells with different donor blending ratios. More importantly, after a fast "burn-in" thermal degradation, the M-PhS:BTP-eC9 cell showed excellent thermal stability aging at 85 °C for over 1128 h, which is in good accordance with the unchanged intermixed phases measured by the UV-vis spectra of the annealed films. The current work demonstrates the feasibility of the spectroscopy method to investigate the intermixed phases for organic bulk-heterojunction solar cells and proves that all-small-molecule solar cells can be intrinsically very stable.

Fluorescence-coupled Micropipette Aspiration Assay to Investigate Red Blood Cell Mechanosensing.

Micropipette aspiration assays have long been a cornerstone for the investigation of live-cell mechanics, offering insights into cellular responses to mechanical stress. This paper details an innovative adaptation of the fluorescence-coupled micropipette aspiration (fMPA) assay. The fMPA assay introduces the capability to administer precise mechanical forces while concurrently monitoring the live-cell mechanotransduction processes mediated by ion channels. The sophisticated setup incorporates a precision-engineered borosilicate glass micropipette connected to a finely regulated water reservoir and pneumatic aspiration system, facilitating controlled pressure application with increments as refined as ± 1 mmHg. A significant enhancement is the integration of epi-fluorescence imaging, allowing for the simultaneous observation and quantification of cell morphological changes and intracellular calcium fluxes during aspiration. The fMPA assay, through its synergistic combination of epi-fluorescence imaging with micropipette aspiration, sets a new standard for the study of cell mechanosensing within mechanically challenging environments. This multifaceted approach is adaptable to various experimental setups, providing critical insights into the single-cell mechanosensing mechanisms.

Endoplasmic Reticulum Protein 72 Regulates Integrin Mac-1 Activity to Influence Neutrophil Recruitment.

BACKGROUND: Integrins mediate the adhesion, crawling, and migration of neutrophils during vascular inflammation. Thiol exchange is important in the regulation of integrin functions. ERp72 (endoplasmic reticulum-resident protein 72) is a member of the thiol isomerase family responsible for the catalysis of disulfide rearrangement. However, the role of ERp72 in the regulation of Mac-1 (integrin αMß2) on neutrophils remains elusive. METHODS: Intravital microscopy of the cremaster microcirculation was performed to determine in vivo neutrophil movement. Static adhesion, flow chamber, and flow cytometry were used to evaluate in vitro integrin functions. Confocal fluorescent microscopy and coimmunoprecipitation were utilized to characterize the interactions between ERp72 and Mac-1 on neutrophil surface. Cell-impermeable probes and mass spectrometry were used to label reactive thiols and identify target disulfide bonds during redox exchange. Biomembrane force probe was performed to quantitatively measure the binding affinity of Mac-1. A murine model of acute lung injury induced by lipopolysaccharide was utilized to evaluate neutrophil-associated vasculopathy. RESULTS: ERp72-deficient neutrophils exhibited increased rolling but decreased adhesion/crawling on inflamed venules in vivo and defective static adhesion in vitro. The defect was due to defective activation of integrin Mac-1 but not LFA-1 (lymphocyte function-associated antigen-1) using blocking or epitope-specific antibodies. ERp72 interacted with Mac-1 in lipid rafts on neutrophil surface leading to the reduction of the C654-C711 disulfide bond in the αM subunit that is critical for Mac-1 activation. Recombinant ERp72, via its catalytic motifs, increased the binding affinity of Mac-1 with ICAM-1 (intercellular adhesion molecule-1) and rescued the defective adhesion of ERp72-deficient neutrophils both in vitro and in vivo. Deletion of ERp72 in the bone marrow inhibited neutrophil infiltration, ameliorated tissue damage, and increased survival during murine acute lung injury. CONCLUSIONS: Extracellular ERp72 regulates integrin Mac-1 activity by catalyzing disulfide rearrangement on the αM subunit and may be a novel target for the treatment of neutrophil-associated vasculopathy.

Biallelic variants in RBM42 cause a multisystem disorder with neurological, facial, cardiac, and musculoskeletal involvement.

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.

Heterogeneity of prostate-specific membrane antigen (PSMA) and PSMA-ligand uptake detection combining autoradiography and postoperative pathology in primary prostate cancer.

BACKGROUND: Targeting prostate-specific membrane antigen (PSMA) has been highly successful for imaging and treatment of prostate cancer. However, heterogeneity in immunohistochemistry indicates limitations in the effect of imaging and radionuclide therapy of multifocal disease. 99mTc-PSMA-I&S is a γ-emitting probe, which can be used for intraoperative lesion detection and postsurgical autoradiography (ARG). We aimed to study its intraprostatic distribution and compared it with (immuno)-histopathology. RESULTS: Seventeen patients who underwent RGS between 11/2018 and 01/2020 with a total of 4660 grids were included in the preliminary analysis. Marked intratumor and intra-patient heterogeneity of PSMA expression was detected, and PSMA negative foci were observed in all samples (100%). Heterogeneous intra-patient PSMA-ligand uptake was observed, and no significant correlation was present between the degree of heterogeneity of PSMA expression and PSMA-ligand uptake. Higher PSMA-ligand uptake was observed in GS ≥ 8 than GS < 8 (p < 0.001). The appearance of Gleason Pattern (GP) 4 was strongly associated with higher uptake (coefficient: 0.43, p < 0.001), while GP 5 also affected the uptake (coefficient: 0.07, p < 0.001). CONCLUSION: PSMA expression and PSMA-ligand uptake show marked heterogeneity. Prostate carcinoma with GP 4 showed significantly higher uptake compared with non-neoplastic prostate tissue. Our analyses extend the scope of applications of radiolabeled PSMA-ligands to ARG for identifying high-grade disease and using its signal as a noninvasive biomarker in prostate cancer.

Analysis of genetic testing in fetuses with congenital heart disease of single atria and/or single ventricle in a Chinese prenatal cohort.

OBJECTIVE: This study aimed to investigate the genetic etiologies of fetuses with single atria and/or ventricle (SA or/and SV) using different genetic detection methods in a Chinese prenatal cohort. METHODS: In this retrospective study, the various genetic results of 44 fetuses with SA and/or SV were analyzed. All 44 cases were tested by chromosomal microarray analysis (CMA) and karyotyping simultaneously, and 8 underwent whole exome sequencing (WES). Data on the pregnancy outcomes and neonatal prognoses were collected from medical records and postnatal follow-up. RESULTS: The whole cohort of 44 fetuses included 14 SA cases (31.8%), 12 SV cases (27.3%), and 18 SA and SV cases (40.9%). A total of 9 pathogenic genetic results were detected by conventional karyotyping, CMA and trio-WES, indicating an overall detection rate of 20.5% (9/44). Six pathogenic chromosomal abnormalities were identified by CMA among the 44 cases, showing a detection rate of 13.6% (6/44). Two microdeletions being missed by karyotyping were diagnosed by CMA, showing an additional diagnostic yield of 4.5% for CMA in present cohort(2/44). Three pathogenic variants in two fetuses were identified by WES, indicating an incremental diagnostic yield of 4.5%(2/44) for WES in fetuses with SA or/and SV. CONCLUSION: In this study, WES achieved an additional diagnostic yield of 4.5% in fetuses with SA or/and SV. WES is valuable for fetal prognosis assessment and could add diagnostic value for fetuses with SA and/or SV when CMA is negative. It would be a valuable technique for the identification of underlying pathogenic variants in prenatal cohorts.

Biomembrane force probe (BFP): Design, advancements, and recent applications to live-cell mechanobiology.

Mechanical forces play a vital role in biological processes at molecular and cellular levels, significantly impacting various diseases such as cancer, cardiovascular disease, and COVID-19. Recent advancements in dynamic force spectroscopy (DFS) techniques have enabled the application and measurement of forces and displacements with high resolutions, providing crucial insights into the mechanical pathways underlying these diseases. Among DFS techniques, the biomembrane force probe (BFP) stands out for its ability to measure bond kinetics and cellular mechanosensing with pico-newton and nano-meter resolutions. Here, a comprehensive overview of the classical BFP-DFS setup is presented and key advancements are emphasized, including the development of dual biomembrane force probe (dBFP) and fluorescence biomembrane force probe (fBFP). BFP-DFS allows us to investigate dynamic bond behaviors on living cells and significantly enhances the understanding of specific ligand-receptor axes mediated cell mechanosensing. The contributions of BFP-DFS to the fields of cancer biology, thrombosis, and inflammation are delved into, exploring its potential to elucidate novel therapeutic discoveries. Furthermore, future BFP upgrades aimed at improving output and feasibility are anticipated, emphasizing its growing importance in the field of cell mechanobiology. Although BFP-DFS remains a niche research modality, its impact on the expanding field of cell mechanobiology is immense.

Association of epidural analgesia during labor and early postpartum urinary incontinence among women delivered vaginally: a propensity score matched retrospective cohort study.

BACKGROUND: Although epidural analgesia is considered the gold standard for pain relief during labor and is safe for maternity and fetus, the association between the epidural analgesia and pelvic floor disorders remains unclear. Thus we estimate the association between epidural analgesia and early postpartum urinary incontinence (UI). METHODS: A propensity score-matched retrospective cohort study was conducted at a university-affiliated hospital in Shanghai, China. Primiparous women with term, singleton, and vaginal delivery between December 2020 and February 2022 were included. UI was self-reported by maternity at 42 to 60 days postpartum and was classified by International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF). Using logistic regression models, the associations between epidural analgesia and early postpartum UI were assessed. RESULTS: Among 5190 participants, 3709 (71.5%) choose epidural anesthesia during labor. Analysis of the propensity-matched cohort (including 1447 maternal pairs) showed epidural anesthesia during labor was independently associated with UI in early postpartum period (aOR 1.50, 95% CI 1.24-1.81). This association was mainly contributed to stress UI (aOR 1.38, 95% CI 1.12-1.71) rather than urge UI (aOR 1.45, 95% CI 0.99-2.15) and mixed UI (aOR 1.52, 95% CI 0.95-2.45). Furthermore, we observed that the association between epidural anesthesia and UI was more pronounced among older women (≥ 35 y) and women with macrosomia (infant weight ≥ 4000 g), compared with their counterparts (both P for interaction < 0.01). After further analysis excluding the women with UI during pregnancy, the results remained largely consistent with the main analysis. CONCLUSIONS: The findings support that epidural anesthesia was associated with SUI in the early postpartum period.

Noninvasive Evaluation of Fetal Zygosity in Twin Pregnancies Involving a Binary Analysis of Single-Nucleotide Polymorphisms.

Twin pregnancy constitutes significant risks for maternal and fetal health, which is usually detected by ultrasound examination at early gestation. However, the imaging-based approach may not accurately identify all twins confounded by practical or clinical variables. The analysis of fetal cell-free DNA in noninvasive prenatal screening assays can completement the ultrasound method for twin detection, which differentiates fraternal or identical twins based on their distinct genotypes. Here, a new noninvasive prenatal screening employing high-coverage next-generation sequencing for targeted nucleotide polymorphisms was developed for detection of zygosity and determination of fetal fraction in twin pregnancies. This method utilizes a binary analysis of both the number and allelic fraction of fetus-specific single-nucleotide polymorphisms to infer the zygosity. In 323 samples collected from 215 singleton, 90 dizygotic, and 18 monozygotic twin pregnancies, all 90 dizygotic twins were correctly detected, with a 100% sensitivity and a 100% specificity. In addition, this method can detect complex pregnancies, such as egg donors, contamination, and twins with complete hydatidiform mole. The fetus-specific fetal fraction change was monitored in nine dizygotic twin pregnancies, which demonstrated highly variable dynamics of fetal cell-free DNA turnover up to 7 weeks after twin reduction. Overall, this study provides a new noninvasive prenatal screening strategy for the accurate identification of twin zygosity and quantification of fetal fraction, which has important clinical implications for the management of twin pregnancies.

Can uterine artery pulsatility index predict fetal chromosomal abnormality in early pregnancy loss? A retrospective cohort study.

BACKGROUND: Early pregnancy loss (EPL) or spontaneous loss of an intrauterine pregnancy within the first trimester occurs commonly worldwide. It is useful to predict the possibility of fetal chromosomal abnormalities using other cheap and easily available markers. OBJECTIVE: This study aimed to evaluate whether the uterine artery pulsatility index (UtA-PI) can predict fetal chromosomal abnormality in early pregnancy loss (EPL). METHODS: This was a retrospective cohort study including 148 women who underwent dilation and curettage for missed abortion. The UtA-PI was measured and evaluated by transvaginal ultrasound. Abnormal UtA-PI was identified through the mean of left and right UA-PI ≥ 90th percentiles of the relevant values for the corresponding gestational age. Copy number variation sequencing (CNV-seq) was performed on EPL cases without maternal cell contamination. RESULTS: 107 (72.3%) cases were classified with normal UtA-PI, while 41 (27.7%) cases were classified with abnormal UtA-PI. The fetal chromosomal abnormality rate was significantly higher in cases with normal UtA-PI than in those with abnormal UtA-PI (67.3% vs 22.0%, P = 7.1 × 10-7). Compared to cases with abnormal UtA-PI, the risk of fetal chromosomal abnormalities in cases with normal UtA-PI increased with an odds ratio of 7.3 (95% confidence interval [CI]: 3.2‒17.0, P = 4 × 10-7). The predictive value of normal UtA-PI alone for fetal chromosomal abnormalities was shown to have an area under the curve of 0.67‒0.71 in our population. CONCLUSION: The UtA-PI seems to be lower and less likely to be elevated in EPL with fetal chromosomal abnormalities compared to those without aneuploidies. We suggest that UtA-PI should be examined in all EPL patients.

Abdominal wall hernia repair: from prosthetic meshes to smart materials.

Hernia reconstruction is one of the most frequently practiced surgical procedures worldwide. Plastic surgery plays a pivotal role in reestablishing desired abdominal wall structure and function without the drawbacks traditionally associated with general surgery as excessive tension, postoperative pain, poor repair outcomes, and frequent recurrence. Surgical meshes have been the preferential choice for abdominal wall hernia repair to achieve the physical integrity and equivalent components of musculofascial layers. Despite the relevant progress in recent years, there are still unsolved challenges in surgical mesh design and complication settlement. This review provides a systemic summary of the hernia surgical mesh development deeply related to abdominal wall hernia pathology and classification. Commercial meshes, the first-generation prosthetic materials, and the most commonly used repair materials in the clinic are described in detail, addressing constrain side effects and rational strategies to establish characteristics of ideal hernia repair meshes. The engineered prosthetics are defined as a transit to the biomimetic smart hernia repair scaffolds with specific advantages and disadvantages, including hydrogel scaffolds, electrospinning membranes, and three-dimensional patches. Lastly, this review critically outlines the future research direction for successful hernia repair solutions by combing state-of-the-art techniques and materials.

Band splitting and enhanced charge density wave modulation in Mn-implanted CsV3Sb5.

Kagome metal CsV3Sb5 has attracted unprecedented attention due to the charge density wave (CDW), Z2 topological surface states and unconventional superconductivity. However, how the paramagnetic bulk CsV3Sb5 interacts with magnetic doping is rarely explored. Here we report a Mn-doped CsV3Sb5 single crystal successfully achieved by ion implantation, which exhibits obvious band splitting and enhanced CDW modulation via angle-resolved photoemission spectroscopy (ARPES). The band splitting is anisotropic and occurs in the entire Brillouin region. We observed a Dirac cone gap at the K point but it closed at 135 K ± 5 K, much higher than the bulk value of ∼94 K, suggesting enhanced CDW modulation. According to the facts of the transferred spectral weight to the Fermi level and weak antiferromagnetic order at low temperature, we ascribe the enhanced CDW to the polariton excitation and Kondo shielding effect. Our study not only offers a simple method to realize deep doping in bulk materials, but also provides an ideal platform to explore the coupling between exotic quantum states in CsV3Sb5.

The association between the interdelivery interval and early postpartum urinary incontinence in women who had consecutive vaginal deliveries: a retrospective cohort study.

Background: Urinary incontinence (UI) is associated with obstetric-related factors; however, the association between the timing of deliveries and UI remains unclear. We examined the association between the interdelivery interval (IDI) and early postpartum UI. Methods: This retrospective cohort study included 2,492 parous women who had consecutive singleton, full-term, and vaginal deliveries. UI was self-reported by the participants from 42 to 60 days postpartum and was classified using the International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form. The IDI was measured as the number of months between 2 consecutive live births, and the participants were divided into 4 groups based on the IDI quartiles. The associations between the IDI and early postpartum UI were assessed using multiple logistic regression models. Results: The median [interquartile range] IDI for the entire cohort was 62 [40-90] months at the baseline. In general, the restricted cubic splines showed a U-shaped curve association between the IDI and the incidence of early postpartum UI. After fully adjusting for potential confounders, a longer IDI was associated with a lower adjusted odds ratio (aOR) of postpartum UI. Among the 4 groups, the Quartile 3 IDI group had the lowest aOR [aORQuartile 1-Quartile 2: 0.48 (95% CI: 0.36-0.63); aORQuartile 1-Quartile 3: 0.37 (95% CI: 0.27-0.49); aORQuartile 1-Quartile 4: 0.40 (95% CI: 0.28-0.57); the P value for the trend was <0.001). The association between the IDI and UI was more pronounced in the younger women (<35 years old) and the women with a pre-pregnancy body mass index of <25 kg/m2 (the P values for both interactions were <0.01). Conclusions: We found that the IDI was independently associated with the incidence of early postpartum UI in parous women. IDI ≥41 months was associated with a lower risk of postpartum UI compared to IDI <41 months.

Adenosine 2A receptor contributes to the facilitation of post-infectious irritable bowel syndrome by γδ T cells via the PKA/CREB/NF-κB signaling pathway.

BACKGROUND: Immunological dysfunction-induced low-grade inflammation is regarded as one of the predominant pathogenetic mechanisms in post-infectious irritable bowel syndrome (PI-IBS). γδ T cells play a crucial role in innate and adaptive immunity. Adenosine receptors expressed on the surface of γδ T cells participate in intestinal inflammation and immunity regulation. AIM: To investigate the role of γδ T cell regulated by adenosine 2A receptor (A2AR) in PI-IBS. METHODS: The PI-IBS mouse model has been established with Trichinella spiralis (T. spiralis) infection. The intestinal A2AR and A2AR in γδ T cells were detected by immunohistochemistry, and the inflammatory cytokines were measured by western blot. The role of A2AR on the isolated γδ T cells, including proliferation, apoptosis, and cytokine production, were evaluated in vitro. Their A2AR expression was measured by western blot and reverse transcription polymerase chain reaction (RT-PCR). The animals were administered with A2AR agonist, or A2AR antagonist. Besides, γδ T cells were also injected back into the animals, and the parameters described above were examined, as well as the clinical features. Furthermore, the A2AR-associated signaling pathway molecules were assessed by western blot and RT-PCR. RESULTS: PI-IBS mice exhibited elevated ATP content and A2AR expression (P < 0.05), and suppression of A2AR enhanced PI-IBS clinical characteristics, indicated by the abdominal withdrawal reflex and colon transportation test. PI-IBS was associated with an increase in intestinal T cells, and cytokine levels of interleukin-1 (IL-1), IL-6, IL-17A, and interferon-α (IFN-α). Also, γδ T cells expressed A2AR in vitro and generated IL-1, IL-6, IL-17A, and IFN-α, which can be controlled by A2AR agonist and antagonist. Mechanistic studies demonstrated that the A2AR antagonist improved the function of γδ T cells through the PKA/CREB/NF-κB signaling pathway. CONCLUSION: Our results revealed that A2AR contributes to the facilitation of PI-IBS by regulating the function of γδ T cells via the PKA/CREB/NF-κB signaling pathway.

Maize transcription factor ZmNAC2 enhances osmotic stress tolerance in transgenic Arabidopsis.

Osmotic stress seriously limits crop yield and quality. Among plant-specific transcription factors families, the NAC family of transcription factors is extensively involved in various growth, development and stress responses. Here we identified a maize NAC family transcription factor ZmNAC2 with inducible gene expression in response to osmotic stress. The subcellular localization showed that it was localized in the nucleus and overexpression of ZmNAC2 in Arabidopsis significantly promoted seed germination and elevated cotyledon greening under osmotic stress. ZmNAC2 also enhanced stomatal closure and decreased water loss in transgenic Arabidopsis. Overexpression of ZmNAC2 activated ROS scavenging and the transgenic lines accumulated less MDA and developed more lateral roots with drought or mannitol treatment. Further RNA-seq and qRT-PCR analysis showed that ZmNAC2 up-regulated a number of genes related to osmotic stress resistance, as well as plant hormone signaling genes. All together, ZmNAC2 enhances osmotic stress tolerance by regulating multiple physiological processes and molecular mechanisms, and exhibits potential as the target gene in crop breeding to increase osmotic stress resistance.

Establishment and validation of a simple nomogram for predicting early postpartum stress urinary incontinence among women with vaginal delivery: a retrospective study.

BACKGROUND: Stress urinary incontinence (SUI) is a common public health issue that negatively impacts the quality of life for women worldwide, of which early detection and rehabilitation are consequently pivotal. The aim of this study is to establish a simple nomogram for identifying women at risk of postpartum SUI. METHODS: A retrospective study was conducted in a tertiary specialized hospital in Shanghai, China. The study included only women with singleton, full-term, and vaginal deliveries. 2,441 women who delivered from July 2019 to November 2019 were included in the training cohort, and 610 women who delivered from January 2022 to February 2022 were included in the validation cohort. SUI was determined by the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF). Univariate and multifactorial logistical regression were used to identify independent risk factors for postpartum SUI and further construct the nomogram accordingly. Based on concordance statistics (C-statistics), calibration curves, and decision curve analyses, we evaluated the performance of the nomogram in the training cohort and the validation cohort. In addition, the model was validated internally in the training cohort through cross-validation. RESULTS: There were no significant statistically differences in important baseline data such as age, pre-pregnancy BMI, and parity between the training and validation cohorts. SUI was observed in 431 (17.6%) and 125 (20.5%) women in the training and validation cohorts, respectively. According to the regression analysis, age, parity, second stage of labor, infant weight, and forceps delivery were included in the nomogram. The nomogram had a C-statistic of 0.80 (95% confidence interval [CI] 0.74-0.85) for predicting SUI. C-statistics were stable in both internally cross-validated training cohort (mean 0.81) and validation cohort (0.83 [95% CI 0.79-0.87]). The nomogram's calibration curve was near the ideal diagonal line. Additionally, the model exhibited a positive net benefit from the decision curve analysis. CONCLUSION: We have created a nomogram that can be utilized to quantify the risk of postpartum SUI for women with vaginal delivery. The model might contribute to predicting early postpartum SUI, thereby facilitating the management of SUI.

Influence of Different Obstetric Factors on Early Postpartum Pelvic Floor Function in Primiparas After Vaginal Delivery.

Purpose: This study sought to explore the obstetric factors affecting early postpartum pelvic floor function of primiparas after vaginal delivery. Patients and Methods: We included 3362 primiparas who underwent postpartum re-examination in International Peace Maternity and Child Health Hospital at 42-60 days after delivery. The Glazer Protocol was used to evaluate their pelvic floor function, and univariate and multivariate logistic regression analyses were performed to identify obstetric factors that might affect it. Results: Forceps-assisted delivery significantly increased the risk of the decline in fast- and slow-twitch muscle strength in the early postpartum period when compared with natural vaginal delivery (P < 0.05). Women with a pre-pregnancy body mass index (BMI) of ≥18.5 kg/m2 had a decreased risk of decline in fast-twitch muscle strength than those with a pre-pregnancy BMI of <18.5 kg/m2 (P < 0.05). Women who had a pre-pregnancy BMI of 24.0 to <28.0 kg/m2 bore a decreased risk of decline in slow-twitch muscle strength than those with a pre-pregnancy BMI of <18.5 kg/m2 (P < 0.05). The risk of decline in fast-twitch muscle strength and slow-twitch muscle in women with anemia during pregnancy was significantly increased (P < 0.05); women with second-stage labors of >2 h had an increased risk of fast-twitch and slow-twitch muscle strength decline than those with <2 h (P < 0.05). Conclusion: Both pre-pregnancy underweight and obesity may cause impairment of early postpartum pelvic floor function. Forceps delivery, anemia during pregnancy, and the length of second stage of labor are independent factors leading to pelvic floor function impairment.

Accommodating population differences when validating risk prediction models.

Validation of risk prediction models in independent data provides a more rigorous assessment of model performance than internal assessment, for example, done by cross-validation in the data used for model development. However, several differences between the populations that gave rise to the training and the validation data can lead to seemingly poor performance of a risk model. In this paper we formalize the notions of "similarity" or "relatedness" of the training and validation data, and define reproducibility and transportability. We address the impact of different distributions of model predictors and differences in verifying the disease status or outcome on measures of calibration, accuracy and discrimination of a model. When individual level information from both the training and validation data sets is available, we propose and study weighted versions of the validation metrics that adjust for differences in the risk factor distributions and in outcome verification between the training and validation data to provide a more comprehensive assessment of model performance. We provide conditions on the risk model and the populations that gave rise to the training and validation data that ensure a model's reproducibility or transportability, and show how to check these conditions using weighted and unweighted performance measures. We illustrate the method by developing and validating a model that predicts the risk of developing prostate cancer using data from two large prostate cancer screening trials.