A kinesin Klp10A mediates cell cycle-dependent shuttling of Piwi between nucleus and nuage.

The piRNA pathway protects germline genomes from selfish genetic elements (e.g. transposons) through their transcript cleavage in the cytoplasm and/or their transcriptional silencing in the nucleus. Here, we describe a mechanism by which the nuclear and cytoplasmic arms of the piRNA pathway are linked. We find that during mitosis of Drosophila spermatogonia, nuclear Piwi interacts with nuage, the compartment that mediates the cytoplasmic arm of the piRNA pathway. At the end of mitosis, Piwi leaves nuage to return to the nucleus. Dissociation of Piwi from nuage occurs at the depolymerizing microtubules of the central spindle, mediated by a microtubule-depolymerizing kinesin, Klp10A. Depletion of klp10A delays the return of Piwi to the nucleus and affects piRNA production, suggesting the role of nuclear-cytoplasmic communication in piRNA biogenesis. We propose that cell cycle-dependent communication between the nuclear and cytoplasmic arms of the piRNA pathway may play a previously unappreciated role in piRNA regulation.

Heparin improves alveolarization and vascular development in hyperoxia-induced bronchopulmonary dysplasia by inhibiting neutrophil extracellular traps.

The objective of this study was to assess the role of NETs in BPD of hyperoxia-induced rat model and the effect of heparin on alveolarization and vascular development in BPD. The neonatal rats exposed to 90% oxygen continuously for 7 days to mimic BPD, meanwhile, the rats were injected by different doses of histones to evaluate the impact on lung injury. The newborn rats exposed to hyperoxia were injected by different doses of heparin (250 U/kg, 500 U/kg) or anti-H4 antibody to evaluate the effect of heparin. Histones and hyperoxia impaired alveolarization with the increase of mean linear intercept (MLI) and the decrease of radial alveolar count (RAC), decreased lung angiogenesis with the decrease expression of VEGF, and increased the expression of NETs, histones and pro-inflammatory factor. However, low dose heparin (250U/kg) administration enhanced survival, improved alveolarization and vascular development in hyperoxia-induced BPD, as well as reduced expression of NETs, histones and pro-inflammatory factor. We concluded that heparin improves alveolarization and vascularization in BPD by inhibiting NETs.

Routine blood parameters are helpful for early identification of influenza infection in children.

BACKGROUND: Routine blood parameters, such as the lymphocyte (LYM) count, platelet (PLT) count, lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), lymphocytes multiplied by platelets (LYM*PLT) and mean platelet volume-to-platelet ratio (MPV/PLT), are widely used to predict the prognosis of infectious diseases. We aimed to explore the value of these parameters in the early identification of influenza virus infection in children. METHODS: We conducted a single-center, retrospective, observational study of fever with influenza-like symptoms in pediatric outpatients from different age groups and evaluated the predictive value of various routine blood parameters measured within 48 h of the onset of fever for influenza virus infection. RESULTS: The LYM count, PLT count, LMR and LYM*PLT were lower, and the NLR and MPV/PLT were higher in children with an influenza infection (PCR-confirmed and symptomatic). The LYM count, LMR and LYM*PLT in the influenza infection group were lower in the 1- to 6-year-old subgroup, and the LMR and LYM*PLT in the influenza infection group were lower in the > 6-year-old subgroup. In the 1- to 6-year-old subgroup, the cutoff value of the LMR for predicting influenza A virus infection was 3.75, the sensitivity was 81.87%, the specificity was 84.31%, and the area under the curve (AUC) was 0.886; the cutoff value of the LMR for predicting influenza B virus infection was 3.71, the sensitivity was 73.58%, the specificity was 84.31%, and the AUC was 0.843. In the > 6-year-old subgroup, the cutoff value of the LMR for predicting influenza A virus infection was 3.05, the sensitivity was 89.27%, the specificity was 89.61%, and the AUC was 0.949; the cutoff value of the LMR for predicting influenza B virus infection was 2.88, the sensitivity was 83.19%, the specificity was 92.21%, and the AUC was 0.924. CONCLUSIONS: Routine blood tests are simple, inexpensive and easy to perform, and they are useful for the early identification of influenza virus infection in children. The LMR had the strongest predictive value for influenza virus infection in children older than 1 year, particularly in children older than 6 years with influenza A virus infection.

[Genetic variant analysis of a neonate with Cornelia de Lange syndrome].

OBJECTIVE: To detect pathogenic variant in a neonate suspected for Cornelia de Lange syndrome (CdLS). METHODS: Potential mutations of CdLS-related genes (NIPBL, SMC1A, SMC3, RAD21 and HDAC8) were detected by high-throughput target region capture and next-generation sequencing. Suspected variants was verified by Sanger sequencing. RESULTS: The child was found to harbor a heterozygous splice site variant, c.6109-1G>A, of the NIPBL gene. Sanger sequencing suggested that neither parent has carried the same variant, suggesting that it was de novo. The variant was unreported by HGMD and ExAC database, and was predicted to alter an acceptor splicing site. No pathogenic variants of SMC1A, SMC3, RAD21 and HDAC8 genes were detected. CONCLUSION: The heterozygous c.6109-1G>A splicing variant of the NIPBL gene may underlie the disease in this child. Above finding has expanded the variant spectrum of the NIPBL gene.

Human ß-Defensin-2 Improves Hyperoxia-Induced Lung Structural and Functional Injury in Neonatal Rats.

BACKGROUND Bronchopulmonary dysplasia (BPD) is a major complication of extreme prematurity, characterized by alveolar simplification and pulmonary malfunction. Hyperoxia-induced lung injury in neonatal rats has been used as a model of BPD, as indicated by lung architectural change and alveolar simplification that resembles clinical feature of BPD. ß-defensin-2 (BD2) plays an important role in lung diseases by inhibiting inflammation response. However, little is known about its role in BPD. The aim of this study was to determine the effect of human BD2 (hBD2) gene on hyperoxia-induced animal model of BPD. MATERIAL AND METHODS The neonatal rats were exposed to 90% oxygen (O2) continuously for 14 days to mimic the BPD-like lung injury. These rats were then randomly assigned to the following four groups: in room air (air), in 90% O2, in 90% O2 with null adenovirus vector infection (O2+Ad), and in 90% O2 with gene therapy through adenovirus transfected hBD2 (O2+Ad-hBD2). Morphology of lungs, pulmonary function and expression of inflammatory cytokines on P7, P10, P14, and P21 were documented and compared across the 4 groups. RESULTS The overexpression of hBD2 mediated by the adenovirus vector was successfully constructed. hBD2 gene therapy increased hBD2 mRNA expression, increased radial alveolar count (RAC), lung volume and compliance, decreased mean linear intercept (MLI), tissue damping, and elastance. Furthermore, pro-inflammatory cytokines IL-1ß, IL-6, and TNF-alpha were inhibited and anti-inflammatory cytokines IL-10 was increased in the lungs of rats in O2+Ad-hBD2 group. CONCLUSIONS In hyperoxia-induced rat models of BPD, hBD2 promotes alveolarization and improves pulmonary function. The mechanism may contribute in alleviating inflammation response and inhibiting pro-inflammatory factors including IL-1ß, IL-6, and TNF-alpha.

Clinical characteristics of preterm ovarian hyperstimulation syndrome: seven cases from China and 14 cases from the literature.

Preterm ovarian hyperstimulation syndrome (POHS) is a rare condition with only a few reported cases. The objective of this study is to investigate the clinical characteristics of 21 POHS cases (seven from China and 14 from the literature). Suspected patients (n = 7) were referred for further confirmation and data on demographics, family history, clinical manifestations (edema developed in the vulva, the hypogastric site and the upper leg), serum and sonographic assessments (ovarian cyst/cysts, gonadotropins, and estradiol levels), the natural course of patients were documented. We did not observe substantial differences in clinical manifestations among POHS patients from China relative to that from the literature. Preterm female newborns developed edema in the vulva, the hypogastric site and the upper leg at 30-39+6 weeks of post-conception age (PCA) as the major clinical manifestations. The characteristic also included high gonadotropins and estradiol, and ovarian cysts. This condition can self-resolve. Clinical manifestations of POHS patients from China are similar to those from the literature. The pathognomonic signs of POHS include vulvar, hypogastric, and upper leg edema developed at 30-39+6 PCA along with high gonadotropins and E2 values and the presence of ovarian cysts in preterm female newborns and the syndrome can self-resolve.

Adipose mesenchymal stem cells-derived exosomes attenuated hyperoxia-induced lung injury in neonatal rats via inhibiting the NF-κB signaling pathway.

OBJECTIVE: Bronchopulmonary dysplasia (BPD) is the most common chronic morbidity in extremely preterm infants. Mesenchymal stem cells-derived exosomes (MSC-Exos) therapies have shown prospects in animal models of BPD. Our study aimed to evaluate the effect of adipose mesenchymal stem cells-derived exosomes (AMSC-Exos) on BPD and the role of the NF-κB signaling pathway in this process. METHODS: The AMSCs were extracted and AMSC-Exos were isolated by ultracentrifugation method. Newborn rats were exposed to hyperoxia (90% O2) continuously for 7 days to establish a BPD model. The rats were treated with AMSC-Exos by intratracheal administration on postnatal day 4 (P4). Pulmonary morphology, pulmonary vasculature, inflammatory factors, and NF-κB were assessed. Hyperoxia-induced primary type II alveolar epithelial cells (AECIIs) and AMSC-Exos treatment with or without a pan-NF-κB inhibitor (PDTC) were established to explore the potential mechanism. RESULTS: Hyperoxia-exposed rats showed alveolar simplification with decreased radial alveolar count and increased mean linear intercept, low CD31, and vascular endothelial growth factor expression, reduced microvessel density, increased the expression of TNF-α, IL-1ß, and IL-6 and decreased the expression of IL-10, and induced NF-κB phosphorylation. AMSC-Exos protected the neonatal lung from the hyperoxia-induced arrest of alveolar and vascular development, alleviated inflammation, and inhibited NF-κB phosphorylation. Hyperoxia decreased viability, increased apoptosis, enhanced inflammation, and induced NF-κB phosphorylation of AECIIs but improved by AMSC-Exos, PDTC, or AMSC-Exos+PDTC. The effect of AMSC-Exos+PDTC in AECIIs was the same as AMSC-Exos, but more notable than PDTC alone. CONCLUSION: AMSC-Exos attenuated the hyperoxia-induced lung injury in neonatal rats by inhibiting the NF-κB signaling pathway partly.

Photosensitizer-incorporated quadruplex DNA-gated nanovechicles for light-triggered, targeted dual drug delivery to cancer cells.

A novel light-operated vehicle for targeted intracellular drug delivery is constructed using photosensitizer-incorporated G-quadruplex DNA-capped mesoporous silica nanoparticles. Upon light irradiation, the photosensitizer generates ROS, causing the DNA capping to be cleaved and allowing cargo to be released. Importantly, this platform makes it possible to develop a drug-carrier system for the synergistic combination of chemotherapy and PDT for cancer treatment with spatial/temporal control. Furthermore, the introducing of targeting ligands further improves tumor targeting efficiency. The excellent biocompatibility, cell-specific intracellular drug delivery, and cellular uptake properties set up the basis for future biomedical application that require in vivo controlled, targeted drug delivery.

Stimuli-responsive controlled-release system using quadruplex DNA-capped silica nanocontainers.

A novel proton-fueled molecular gate-like delivery system has been constructed for controlled cargo release using i-motif quadruplex DNA as caps onto pore outlets of mesoporous silica nanoparticles. Start from simple conformation changes, the i-motif DNA cap can open and close the pore system in smart response to pH stimulus. Importantly, the opening/closing and delivery protocol is highly reversible and a partial cargo delivery can be easily controlled at will. A pH-switchable nanoreactor has also been developed to validate the potential of our system for on-demand molecular transport. This proof of concept might open the door to a new generation of carrier materials and could also provide a general route to use other functional nucleic acids/peptide nucleic acids as capping agents in the fields of versatile controlled delivery nanodevices.

Transfer RNA-derived small RNAs (tsRNAs) sequencing revealed a differential expression landscape of tsRNAs between glioblastoma and low-grade glioma.

BACKGROUND: Glioblastomas (GBMs) are the most lethal brain cancer with a median survival rate of fewer than 15 months. Both clinical and biological features of GBMs are largely different from those of low-grade gliomas (LGs), but the reasons for this intratumoral heterogeneity are not entirely clear. Transfer RNA (tRNA)-derived small RNAs (tsRNAs) were derived from tRNA precursors and mature tRNA, referring to the specific cleavage of tRNAs by dicer and angiogenin (ANG) in particular cells or tissues or under certain conditions such as stress and hypoxia. With the characteristics of wide expression and high stability, tsRNAs could be used as favorable biomarkers for diagnosis, treatment, and prognosis prediction of the tumor, viral infection, neurological as well as other systemic diseases. In this study, we have compared the differential expressed tsRNAs between GBMs and LGs, so as to investigate the possible pathogenic molecules and provide references for discovering novel nucleic acid drugs in future studies. METHODS: Fresh tumor tissues of patients that were diagnosed as GBMs (4 cases) and LGs (5 cases) at the First Affiliated Hospital of Wenzhou Medical University from 2019.05 to 2021.01 were collected. The tsRNAs' levels were analyzed and compared through high-throughput sequencing, candidate tsRNAs were chosen according to the expression level, and the expression of the candidate tsRNAs was validated through qPCR. Finally, the potential targets were imputed using the Miranda and TargetScan databases, and possible biological functions of the differentially expressed (DE) tsRNAs' targets were enriched based on GO and KEGG databases. RESULTS: A total of 4 GBMs and 5 LGs patients were enrolled in the current study. High-throughput sequencing showed that 186 tsRNAs were expressed in two groups, over them, 43 tsRNAs were unique to GBMs, and 24 tsRNAs were unique to LGs. A total of 9 tsRNAs were selected as candidate tsRNAs according to the tsRNA expression level, among which 6 tsRNAs were highly expressed in GBMs and 3 tsRNAs were low expressed in GBMs. qPCR verification further demonstrated that 5 tsRNAs were significantly up-regulated and 1 tsRNA was significantly down-regulated in GBMs: tRF-1-32-chrM.Lys-TTT (p=0.00118), tiRNA-1-33-Gly-GCC-1 (p=0.00203), tiRNA-1-33-Gly-CCC-1 (p=0.00460), tRF-1-31-His-GTG-1 (p=0.00819), tiRNA-1-33-Gly-GCC-2-M3 (p=0.01032), and tiRNA-1-34-Lys-CTT-1-M2 (p=0.03569). Enrichment analysis of the qPCR verified DE tsRNAs showed that the 5 up-regulated tsRNAs seemed to be associated with axon guidance, pluripotent stem cells regulation, nucleotide excision repair, Hippo signaling pathway, and cancer-related pathways, while the down-regulated tsRNA (tRF-1-32-chrM.Lys-TTT) was associated with oocyte meiosis and renin secretion. CONCLUSION: The tsRNAs were differentially expressed in tumor tissues between GBMs and LGs, especially tRF-1-32-chrM.Lys-TTT, tiRNA-1-33-Gly-GCC-1, tiRNA-1-33-Gly-CCC-1, tRF-1-31-His-GTG-1, tiRNA-1-33-Gly-GCC-2-M3, and tiRNA-1-34-Lys-CTT-1-M2. These tsRNAs seemed to be associated with nucleotide excision repair, Hippo signaling, and cancer-related pathways. This may be the main reason for the differences in clinical characteristics between GBMs and LGs, which may provide a certain theoretical basis for further functional research and development of related nucleic acid drugs. CONCLUSION: The tsRNAs were differentially expressed in tumor tissues between GBMs and LGs, especially tRF-1-32-chrM.Lys-TTT, tiRNA-1-33-Gly-GCC-1, tiRNA-1-33-Gly-CCC-1, tRF-1-31-His-GTG-1, tiRNA-1-33-Gly-GCC-2-M3, and tiRNA-1-34-Lys-CTT-1-M2. These tsRNAs seemed to be associated with nucleotide excision repair, Hippo signaling, and cancer-related pathways. This may be the main reason for the differences in clinical characteristics between GBMs and LGs, which may provide a certain theoretical basis for further functional research and development of related nucleic acid drugs.

The use of the mean computed-tomography value to predict the invasiveness of ground-glass nodules: A meta-analysis.

The invasiveness of ground-glass nodules (GGNs) is difficult to characterize through morphological examination. Multiple studies have independently detected a close relationship between mean computed tomography value and invasiveness of GGNs, however, their relative diagnostic accuracy is uncertain. Here, we performed a meta-analysis to validate whether the mean computed tomography value can predict the invasiveness of GGNs. Briefly, we searched the Web of Science, Embase, PubMed, Cochrane, Google Scholar, CNKI, VIP, Wanfang and SinoMed databases. The sensitivity, specificity, 95% confidence interval (CI), symmetric receiver operating characteristic curve (SROC curve) and the area under curve (AUC) were obtained using STATA 16.0 to evaluate the predictive value of the mean computed tomography value for GGNs. The presence of heterogeneity was assessed using fixed effects sensitivity analysis and I2 statistics. We used the Deek's funnel plot to evaluate the possibility of publication bias. Thirteen studies encompassing 1564 GGNs were included in our meta-analysis. Six of these studies revealed that using the mean computed tomography value for the diagnosis of pre-invasive and invasive lesions had a sensitivity and specificity of 0.75 (95% CI: 0.61-0.85) and 0.81 (95% CI: 0.74-0.86), respectively. The optimal critical value was -557 Hu. Later, eight studies were examined for the use of the mean CT value for patients with minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC); the results showed that the sensitivity was 0.78 (95% CI: 0.66-0.86) and the specificity was 0.81 (95% CI: 0.68-0.89), and the optimal critical value was -484 Hu. Therefore, the mean computed tomography value assessed via CT scan could be a significant predictor of the invasiveness of GGNs as well as a good surgical treatment guide in patients diagnosed with lung cancer. PROSPERO REGISTRATION NUMBER: CRD42020177125.

Adipose Stem Cells Derived Exosomes Alleviate Bronchopulmonary Dysplasia and Regulate Autophagy in Neonatal Rats.

BACKGROUND: Mesenchymal stem cell-derived exosomes (MSC-Exos) therapies have shown prospects in preclinical models of pathologies relevant to neonatal medicine, such as bronchopulmonary dysplasia (BPD). Adipose-derived stem cells (ADSCs) have been recognized as one of the most promising stem cell sources. Autophagy plays a key role in regulating intracellular conditions, maintaining cell growth and development, and participating in the pathogenesis of BPD. OBJECTIVES: To investigate the potential therapeutic role of ADSC-Exos on BPD and to illustrate the role of autophagy in this process. METHOD: ADSC-Exos was isolated from media conditioned of ADSCs by ultracentrifugation and characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting (WB). Newborn rats were exposed to hyperoxia (90% O2) to mimic BPD, treated with ADSC-Exos by intratracheal or intravenous administration on postnatal day 4 (P4) and returned to room air on P7 until P14. Treated animals and appropriate controls were harvested on P7 and P14 for assessment of pulmonary parameters. RESULTS: Hyperoxia-exposed rats were presented with pronounced alveolar simplification with decreased radial alveolar count (RAC) and increased mean linear intercept (MLI), impaired vascular development with low vascular endothelial growth factor (VEGF) and CD31 expression, and stimulated inflammation with increased expression of TNF-α, IL-1ß, and IL-6, and decreased expression of IL-10. Meanwhile, the rats with hyperoxia exposure blocked autophagic flux with lower levels of Beclin1, LC3B, LC3BII/I ratio and higher levels of p62. ADSC-Exos administration protected the neonatal lung tissues from the hyperoxia-induced arrest of alveolar and vascular development, reduced inflammation, and facilitated autophagy. Intratracheal administration was more efficacious than intravenous administration. CONCLUSION: The intratracheal administration of ADSC-Exos significantly improved alveolarization and pulmonary vascularization arrest in hyperoxia-induced BPD, which was associated with facilitating autophagy in part.

Obstetric and Perinatal Outcomes After Assisted Reproductive Technology in Women With Cesarean Scar.

INTRODUCTION: Assisted reproductive technology (ART) and previous Cesarean section (CS) are independently associated with the risk of adverse obstetric and perinatal outcomes in general. Few studies have focused on the association between adverse obstetric and perinatal outcomes and ART used in the high-risk population of women with previous CS. MATERIALS AND METHODS: A retrospective cohort study including 14,099 women with a previous delivery and a subsequent delivery between April 2014 and April 2020 was conducted at our hospital. We assessed the risk of adverse obstetric and perinatal outcomes in pregnancies conceived by ART in women with previous CS, using log-binomial regression models. RESULTS: In women with previous CS, ART singleton pregnancies were associated with an increased risk of maternal complications, such as pregnancy complications, placental anomalies of implantation, postpartum hemorrhage, and preterm birth (PTB), as compared to spontaneously conceived pregnancies. The implementation of ART and previous CS interacted in a synergistic manner to increase the likelihood of the placenta accreta spectrum in women with singleton pregnancies [adjusted relative risk (aRR) 5.30, 95% confidence interval (CI) 4.01-7.00; relative risk due to interaction: 1.41, 95%CI 0.07-2.75]. In women with previous CS who underwent ART, women with singletons conceived through intracytoplasmic sperm injection were at increased risk of velamentous placenta (aRR 2.46, 95%CI 1.35-4.48) compared with those with singletons conceived through in vitro fertilization (IVF), whereas women with singletons conceived through cleavage-stage embryo transfer (ET) were at increased risk of gestational diabetes mellitus (GDM) (aRR 1.74, 95%CI 1.16-2.60) than those with singletons conceived through blastocyst-stage ET. CONCLUSION: Pregnancies conceived through ART were at increased risk for adverse obstetric and perinatal outcomes in women who had previously delivered by CS, particularly for placental anomalies of implantation. In women with previous CS undergoing ART, IVF and blastocyst-stage ET may be a relatively safe treatment.

Centrosome-centric view of asymmetric stem cell division.

The centrosome is a unique organelle: the semi-conservative nature of its duplication generates an inherent asymmetry between 'mother' and 'daughter' centrosomes, which differ in their age. This asymmetry has captivated many cell biologists, but its meaning has remained enigmatic. In the last two decades, many stem cell types have been shown to display stereotypical inheritance of either the mother or daughter centrosome. These observations have led to speculation that the mother and daughter centrosomes bear distinct information, contributing to differential cell fates during asymmetric cell divisions. This review summarizes recent progress and discusses how centrosome asymmetry may promote asymmetric fates during stem cell divisions.

Alstrom syndrome gene is a stem-cell-specific regulator of centriole duplication in the Drosophila testis.

Asymmetrically dividing stem cells often show asymmetric behavior of the mother versus daughter centrosomes, whereby the self-renewing stem cell selectively inherits the mother or daughter centrosome. Although the asymmetric centrosome behavior is widely conserved, its biological significance remains largely unclear. Here, we show that Alms1a, a Drosophila homolog of the human ciliopathy gene Alstrom syndrome, is enriched on the mother centrosome in Drosophila male germline stem cells (GSCs). Depletion of alms1a in GSCs, but not in differentiating germ cells, results in rapid loss of centrosomes due to a failure in daughter centriole duplication, suggesting that Alms1a has a stem-cell-specific function in centrosome duplication. Alms1a interacts with Sak/Plk4, a critical regulator of centriole duplication, more strongly at the GSC mother centrosome, further supporting Alms1a's unique role in GSCs. Our results begin to reveal the unique regulation of stem cell centrosomes that may contribute to asymmetric stem cell divisions.

Low-Dose Vitamin D Protects Hyperoxia-Induced Bronchopulmonary Dysplasia by Inhibiting Neutrophil Extracellular Traps.

Background and Objective: As bronchopulmonary dysplasia (BPD) can lead to considerable mortality and morbidity, this disease is the focus of attention in neonatology. Vitamin D (VD), which has anti-inflammatory properties and promotes lung growth, may have a therapeutic effect on BPD. The overexpression of neutrophil extracellular traps (NETs) has been demonstrated to be involved in the pathogenesis of BPD in our previous study. This study aimed to elucidate the effect of VD on BPD and the role of NETs in this process. Methods: Newborn rats were exposed to 90% oxygen continuously for 7 days to mimic BPD, and rats under hyperoxia were injected with 1,25(OH)2D3 at different doses (0.5 ng/g, 3 ng/g). Alveolarization, pulmonary vascular development, inflammatory cytokines and NETs were assessed. Results: Hyperoxia increased mortality, decreased body weight, impaired alveolarization with a decrease in radial alveolar count (RAC) and an increase in mean linear intercept (MLI), and impaired vascular development with low vascular endothelial growth factor (VEGF) expression. Meanwhile, hyperoxia enhanced expression of the proinflammatory factors TNF-α, IL-1ß, and IL-6, and elevated NETs in lung tissues and plasma. Low-dose VD (0.5 ng/g) administration increased the survival rate, attenuated developmental retardation, improved alveolarization, and pulmonary vascular development in hyperoxia-induced BPD, and reduced the expression of proinflammatory factors and NETs. However, high-dose VD (3 ng/g) treatment did not attenuate lung injury or NETs significantly, and even led to more severe developmental retardation and a higher mortality rate. Conclusions: Low-dose VD increased the survival rate, attenuated developmental retardation, and improved alveolarization and pulmonary vascularization arrest in hyperoxia-induced BPD partially by inhibiting NETs.

Germline stem cell homeostasis.

In many species, germline stem cells (GSCs) function to sustain gametogenesis throughout the life of organismal life span. As the source of gametes, the only cell type that can pass the genetic information to the next generation, GSCs play a fundamental role in maximizing the quantity of gametes that animals produce, while ensuring their highest quality. GSCs are maintained by the signals from their niches, and germ cells that exited the niche undergo differentiation to generate functional gametes. GSC population is sustained by a multitude of mechanisms such as asymmetric stem cell divisions and dedifferentiation of partially differentiated germ cells. In this review, we summarize the mechanisms that maintain GSC homeostasis to ensure life-long production of functional gametes.

High Neutrophil-to-Lymphocyte Ratio Is an Early Predictor of Bronchopulmonary Dysplasia.

Background and Objective: Bronchopulmonary dysplasia (BPD) is a common complication in preterm infants; predicting the degree of BPD at an early life stage is difficult. Inflammation is a crucial risk factor for BPD pathogenesis, and the neutrophil-to-lymphocyte ratio (NLR) is a potential systemic inflammatory biomarker. We aimed to assess the predictive value of the NLR for BPD. Methods: We carried out a retrospective, single-center, observational study of neonates with gestational ages (GAs) <32 weeks and assessed the association between the NLR and BPD. Results: The study population included 296 preterm infants with BPD (n = 144) or without BPD (n = 152). Among the infants, 75 (25.3%) had mild BPD, 37 (12.5%) had moderate BPD, and 32 (10.8%) had severe BPD. The BPD group had a higher NLR at birth and at 72 h than the non-BPD group. The NLR cutoff value at 72 h for the prediction of BPD was 3.035 (sensitivity = 0.519, specificity = 0.964), and the area under the curve (AUC) was 0.714. The NLR cutoff value at 72 h for predicting severe BPD was 3.105 (sensitivity = 0.607, specificity = 0.819), with an AUC of 0.756. At the NLR cutoff value at 72 for the prediction of BPD, the AUCs were 0.640 and 0.970 in the preterm infants with EOS and congenital pneumonia, respectively. Conclusions: The NLR is an inexpensive, accessible and convenient tool; an increase in the NLR at 72 h could be an early predictor of BPD, especially severe BPD. Additionally, the NLR at 72 h could be a predictor of BPD in preterm infants with intrauterine infections.

A simple and sensitive colorimetric pH meter based on DNA conformational switch and gold nanoparticle aggregation.

A simple and rapid colorimetric pH meter has been developed based on the conformational switch of i-motif DNA and non-crosslinking AuNP aggregation, the average accuracy of the nano-meter was found to be +/-0.04 pH unit across the physiological operating range.