Perinatal characteristics and neonatal outcomes of singletons and twins in Chinese very preterm infants: a cohort study.

BACKGROUND: The prevalence of preterm birth has been rising, and there is a paucity of nationwide data on the perinatal characteristics and neonatal outcomes of twin deliveries of very preterm infants (VPIs) in China. This study compared the perinatal characteristics and outcomes of singletons and twins admitted to neonatal intensive care units (NICUs) in China. METHODS: The study population comprised all infants born before 32 weeks in the Chinese Neonatal Network (CHNN) between January 2019 and December 2019. Three-level and population-average generalized estimating equation (GEE)/alternating logistic regression (ALR) models were used to determine the association of twins with neonatal morbidities and the use of NICU resources. RESULTS: During the study period, there were 6634 (71.2%) singletons and 2680 (28.8%) twins, with mean birth weights of 1333.70 g and 1294.63 g, respectively. Twins were significantly more likely to be delivered by caesarean section (p < 0.01), have antenatal steroid usage (p = 0.048), have been conceived by assisted reproductive technology (ART) (p < 0.01), have a higher prevalence of maternal diabetes (p < 0.01) and be inborn (p < 0.01) than singletons. In addition, twins had a lower prevalence of small for gestational age, maternal hypertension, and primigravida mothers than singletons (all p < 0.01). After adjusting for potential confounders, twins had higher mortality rates (adjusted odds ratio [AOR] 1.28, 95% confidence interval [CI] 1.10-1.49), higher incidences of short-term composite outcomes (AOR 1.28, 95% CI 1.09-1.50), respiratory distress syndrome (RDS) (AOR 1.30, 95% CI 1.12-1.50), and bronchopulmonary dysplasia (BPD) (AOR 1.10, 95% CI 1.01-1.21), more surfactant usage (AOR 1.22, 95% CI 1.05-1.41) and prolonged hospital stays (adjusted mean ratio 1.03, 95% CI 1.00-1.06), compared to singletons. CONCLUSION: Our work suggests that twins have a greater risk of mortality, a higher incidence of RDS and BPD, more surfactant usage, and longer NICU stays than singletons among VPIs in China.

Rho GTPase Activating Protein 24 (ARHGAP24) Regulates the Anti-Cancer Activity of Sorafenib Against Breast Cancer MDA-MB-231 Cells via the Signal Transducer and Activator of Transcription 3 (STAT3) Signaling Pathway.

BACKGROUND STAT3 has emerged as a novel potential target for sorafenib, a multikinase inhibitor, in the context of cancer therapy. ARHGAP24 is a Rac-specific Rho GTPase-activating protein (Rho GAP), which can convert Rho GTPases to an inactive state. It has been proved to be an oncosuppressor protein in renal cancer. In the present study, we investigated its anti-cancer effect in breast cancer (BC). MATERIAL AND METHODS Quantitative real-time PCR (qRT-PCR) and Western blot analysis were performed to detect the expression of ARHGAP24 in clinical tissue samples. Then, BC MDA-MB-231 cells were virally transduced with ARHGAP24 silencing or overexpression lentiviral vectors in the absence or presence of sorafenib. Cell viability and metastatic ability were evaluated by using the Cell Counting Kit-8 (CCK-8) and Transwell assays. Proteins belonging to the STAT3 pathway were detected by Western blot. RESULTS ARHGAP24 decreased in BC tissues compared with the adjacent normal tissues. Forced expression of ARHGAP24 and sorafenib treatment significantly suppressed the viability, migration, and invasion of MDA-MB-231 cells. Conversely, elimination of the endogenous ARHGAP24 with shRNA promoted cell viability, migration, and invasion. The phosphorylation of STAT3 and the expression of MMP-2 and MMP-9 were attenuated by ARHGAP24 ectopic expression and sorafenib treatment. Furthermore, forced expression of ARHGAP24 significantly enhanced sorafenib-induced decrease of cell viability, migration, and invasion of MDA-MB-231 cells, while elimination of the endogenous ARHGAP24 with shRNA inhibited it. CONCLUSIONS ARHGAP24 can suppress the development of MDA-MB-231 cells via the STAT3 signaling pathway, and sorafenib inhibits cell viability, migration, invasion, and STAT3 activation in MDA-MB-231 cells through ARHGAP24.

Clinical Features of Neonates with Hydrops Fetalis.

OBJECTIVE: The objective of this study was to evaluate the clinical characteristics of neonates with hydrops fetalis to improve recognition of the disease. PATIENTS AND METHODS: The clinical data of 10 neonates with hydrops fetalis were retrospectively studied. Prenatal characteristics, causes, clinical features, and prognosis were explored. RESULTS: Eight neonates presenting abnormal nonstress test suffered from severe neonatal asphyxia at birth and were resuscitated by endotracheal intubation. Nine had skin edema, eight had pleural effusions with one unilateral and seven bilateral. Six had ascites, eight had polyhydramnios, one had multiple malformations and one had chromosome abnormalities. One survived and nine died. Six died due to resuscitation failure in delivery room, two died due to giving up after 1 day and one died due to the treatment failure after 6 months. Causes of hydrops fetalis were a congenital diaphragmatic hemangioma, recurrent atrial premature beats, genetic syndrome suspicious, Down syndrome, congenital pulmonary lymphangiectasia, anemia, paroxysmal supraventricular tachycardia, placental chorioangioma, and idiopathic edema. CONCLUSION: The prognosis varied because of different etiologies of hydrops fetalis. Severe cases frequently had skin edema and high rate of asphyxia at birth and difficult resuscitation. Timely intrauterine interventions were helpful for successful resuscitation. A well-prepared resuscitation team and the effectiveness of resuscitation could correlate to increasing survival rate.

Mitochondrial dysfunction in some triple-negative breast cancer cell lines: role of mTOR pathway and therapeutic potential.

INTRODUCTION: Triple-negative breast cancer (TNBC) is a subtype of highly malignant breast cancer with poor prognosis. TNBC is not amenable to endocrine therapy and often exhibit resistance to current chemotherapeutic agents, therefore, further understanding of the biological properties of these cancer cells and development of effective therapeutic approaches are urgently needed. METHODS: We first investigated the metabolic alterations in TNBC cells in comparison with other subtypes of breast cancer cells using molecular and metabolic analyses. We further demonstrated that targeting these alterations using specific inhibitors and siRNA approach could render TNBC cells more sensitive to cell death compared to other breast cancer subtypes. RESULTS: We found that TNBC cells compared to estrogen receptor (ER) positive cells possess special metabolic characteristics manifested by high glucose uptake, increased lactate production, and low mitochondrial respiration which is correlated with attenuation of mTOR pathway and decreased expression of p70S6K. Re-expression of p70S6K in TNBC cells reverses their glycolytic phenotype to an active oxidative phosphorylation (OXPHOS) state, while knockdown of p70S6K in ER positive cells leads to suppression of mitochondrial OXPHOS. Furthermore, lower OXPHOS activity in TNBC cells renders them highly dependent on glycolysis and the inhibition of glycolysis is highly effective in targeting TNBC cells despite their resistance to other anticancer agents. CONCLUSIONS: Our study shows that TNBC cells have profound metabolic alterations characterized by decreased mitochondrial respiration and increased glycolysis. Due to their impaired mitochondrial function, TNBC cells are highly sensitive to glycolytic inhibition, suggesting that such metabolic intervention may be an effective therapeutic strategy for this subtype of breast cancer cells.

A p-block dopant enables energy-efficient hydrogen production from biomass.

Herein, we develop innovative p-block Bi-doped Co3O4 nanoflakes (Bi-Co3O4 NFAs) on nickel foam, which exhibit excellent electrocatalytic activity for both glucose oxidation (GOR) and H2 evolution reactions (HER). The two-electrode GOR-HER electrolyzer using Bi-Co3O4 NFAs as both the cathode and anode shows a remarkable reduced operation voltage of 1.48 V at 10 mA cm-2, superior to the 1.66 V of the OER-HER electrolyzer, demonstrating promising potential for advanced H2 production featuring energy saving and simultaneously produced value-added chemicals.

S-Block Metal Mg-Mediated Co─N─C as Efficient Oxygen Electrocatalyst for Durable and Temperature-Adapted Zn-Air Batteries.

In the quest to enhance Zn-air batteries (ZABs) for operating across a wide spectrum of temperatures, synthesizing robust oxygen electrocatalysts is paramount. Conventional strategies focusing on orbital hybridization of d-d and p-d aim to moderate the excessive interaction between the d-band of the transition metal active site and oxygen intermediate, yet often yield suboptimal performance. Herein, an innovative s-block metal modulation is reported to refine the electronic structure and catalytic behavior of Co─NC catalysts. Employing density functional theory (DFT) calculations, it is revealed that incorporating Mg markedly depresses the d-band center of Co sites, thereby fine-tuning the adsorption energy of the oxygen reduction reaction (ORR) intermediate. Consequently, the Mg-modified Co─NC catalyst (MgCo─NC) unveils remarkable intrinsic ORR activity with a significantly reduced activation energy (Ea) of 10.0 kJ mol-1, outstripping the performance of both Co─NC (17.6 kJ mol-1), benchmark Pt/C (15.9 kJ mol-1), and many recent reports. Moreover, ZABs outfitted with the finely tuned Mg0.1Co0.9─NC realize a formidable power density of 157.0 mW cm-2, paired with an extremely long cycle life of 1700 h, and an exceptionally minimal voltage gap decay rate of 0.006 mV h-1. Further, the Mg0.1Co0.9─NC-based flexible ZAB presents a mere 2% specific capacity degradation when the temperature fluctuates from 25 to -20 °C, underscoring its robustness and suitability for practical deployment in diverse environmental conditions.

Research trends in chemogenetics for neuroscience in recent 14 years: A bibliometric study in CiteSpace.

BACKGROUND: Chemogenetics has been widely adopted in Neuroscience. Neuroscience has become a hot research topic for scientists. Therefore, the purpose of this study is to explore the current status and trends in the global application of chemogenetics in neuroscience over the last 14 years via CiteSpace. METHODS: Publications related to chemogenetics in neuroscience were retrieved from the Science Citation Index-Extended Web of Science from 2008 to 2021. We used CiteSpace to analyze publications, citations, cited journals, countries, institutions, authors, cited authors, cited references, and keywords. RESULTS: A total of 947 records were retrieved from 2008 to 2021 on February 21, 2022. The number and rate of publications and citations increased significantly. Journal of Neuroscience was the most cited journal, and BRAIN RES BULL ranked first in the centrality of cited journals. The United States of America (USA) had the highest number of publications among the countries. Takashi Minamoto was the most prolific author and Armbruster BN ranked the first among authors cited. The first article in the frequency ranking of the references cited was published by Roth BL. The keyword of "nucleus accumben (NAc)" had the highest frequency. The top 3 keywords with the strongest citation bursts include "transgenic mice," "cancer," and "blood-brain barrier." CONCLUSION: The period 2008 to 2021 has seen a marked increase in research on chemogenetics in neuroscience. The application of chemogenetics is indispensable for research in the field of neuroscience. This bibliometrics study provides the current situation and trend in chemogenetic methods in neuroscience in recent 14 years, which may help researchers to identify the hot topics and frontiers for future studies in this field.

Tunable Heterogeneous FeCo Alloy-Mo0.82N Bifunctional Electrocatalysts for Temperature-Adapted Zn-Air Batteries.

The practical applications of temperature-tolerant Zn-air batteries (ZABs) rely on highly active and stable bifunctional catalysts that accelerate cathodic oxygen reduction (ORR) and oxygen evolution (OER) reactions. Herein, we successfully integrated fascinating transition metal nitrides and FeCo alloys through a simple coordination assembly and pyrolysis process. Importantly, the alloy-to-nitride ratio in the heterogeneous catalyst can be carefully regulated through the subsequent etching process. Moreover, the composition-dependent ORR/OER performance of the FeCo-Mo0.82N catalysts was revealed. Aqueous ZABs using the optimized FeCo-Mo0.82N-60 as a cathode exhibit a high peak power density of 149.7 mW cm-2 and an impressive stability of 600 h with a low charge-discharge voltage gap decay rate of 0.025 mV h-1, which exceeds those of most of recent reports. Furthermore, the FeCo-Mo0.82N-60-based flexible ZABs display a small specific capacity degradation (3%) from 40 to -10 °C, demonstrating excellent temperature tolerance.

Gallic acid inhibits osteoclastogenesis and prevents ovariectomy-induced bone loss.

Osteoporosis is a common metabolic bone disease with a rapidly increasing prevalence, characterized by massive bone loss because of excessive osteoclast formation. Gallic acid (GA), a phenolic acid isolated from Cornus officinalis, has anti-inflammatory and anti-oxidant effects, but its effect on osteoclast formation has not been confirmed. In our study, we demonstrated that GA significantly inhibited RANKL-induced osteoclast formation and function of osteoclast in bone marrow monocytes (BMMs) and RAW264.7 cells in a dose-dependent manner without cytotoxicity. For molecular mechanisms, GA repressed osteoclastogenesis by blocking Akt, ERK, and JNK pathways, and suppressed osteoclastogenesis-related marker expression, including nuclear factor of the activated T-cell cytoplasmic 1 (NFATc1), c-Fos, and cathepsin K (CTSK). In addition, we further assessed the effect of GA in an ovariectomized mouse model, which indicated that GA has a notable effect on preventing bone loss. In conclusion, GA exerts notable effects in inhibiting osteoclastogenesis and preventing ovariectomy-induced bone loss, suggesting that GA is a potential agent in osteoporosis treatment.

Afferent and efferent projections of the rostral anterior cingulate cortex in young and middle-aged mice.

Research shows that across life, the incidence of mental illness is highest in the young. In the context of the COVID-19 pandemic, mental health issues of the young in particular have received global attention. The rostral anterior cingulate cortex (rACC) plays an important role in psychiatric disorders and chronic pain-psychiatric comorbidities. However, it remains unknown whether or how the afferent and efferent circuits of the rACC change with aging. In this study, we microinjected a retrograde tracer virus and an anterograde trans-monosynaptic virus into the rACC of young and middle-aged mice (both male and female), and systematically and quantitatively analyzed the whole-brain afferent and efferent connections of rACC at different ages and sexes. Notably, in young and middle-aged mice, afferents of the rACC belong to four groups of brain structures arising mainly from the amygdala [mainly basolateral amygdaloid nucleus (BLA)] and cerebral cortex (mainly orbital cortex), with a small part originating from the basal forebrain and thalamus. In contrast, efferents of the rACC belong to four groups of brain structures mainly projecting to the thalamus (mainly ventral anterior-lateral/ventromedial thalamic nucleus (VAL/VM)], with a very small part projecting to the amygdala, basal forebrain, and cerebral cortex. Compared with young mice, the BLA-rACC circuit in middle-aged mice (male and female) did not change significantly, while the rACC-VAL/VM circuit in middle-aged mice (male and female) decreased significantly. In conclusion, this study comprehensively analyzed the input-output neural projections of rACC in mice of different ages and sexes and provided preliminary evidence for further targeted research.

[Correlation between blood T-cell receptor rearrangement excision circles levels and severe infection in children with acute lymphoblastic leukemia].

OBJECTIVE: This study quantitatively examined signal joint T-cell receptor rearrangement excision circles (sjTRECs) levels in peripheral blood of children with acute lymphoblastic leukemia (ALL) at different stages in order to evaluate the role of sjTRECs in predicting severe infection postchemotherapy. METHODS: sjTRECs levels in peripheral blood were measured by fluorescent quantitation-polymerase chain reaction in 30 children with newly diagnosed ALL, 36 children with ALL who accepted chemotherapy but were not infected, 30 children with ALL who had severe infection after chemotherapy, and 50 normal children. RESULTS: Blood sjTRECs levels in the normal group (394 ± 270 copies/103 MNC) were significantly higher than those in the other three groups (P<0.05). Blood sjTRECs levels in the chemotherapy group without infection (96 ± 78 copies/103 MNC) were significantly lower than those in the newly diagnosed ALL group (210 ± 219 copies/103 MNC) (P<0.05). The chemotherapy group with severe infection showed the lowest blood sjTRECs levels (48 ± 40 copies/103 MNC) in the four groups. CONCLUSIONS: The measurement of blood sjTRECs levels might be helpful for predicting the occurrence of severe infection postchemotherapy in children with ALL.

Ultrasound performed shortly after birth can predict the respiratory support needs of late preterm and term infants: A diagnostic accuracy study.

BACKGROUND: Late preterm and term infants may develop respiratory issues with severe outcomes. Early identification of these diseases shortly after infants' birth can improve their management. Lung ultrasound (LUS) has been used to diagnose neonatal respiratory diseases. However, few LUS methods have been reported to predict the need for respiratory support, the basis of infant respiratory diseases management. METHODS: We conducted a prospective diagnostic accuracy study following the Standards for the Reporting of Diagnostic Accuracy Studies guidelines at a tertiary academic hospital between 2019 and 2020. A total of 310 late preterm and term infants with mild respiratory symptoms were enrolled. The LUS assessment was performed for each participant at one of the following times: 0.5, 1.0, 2.0, or 4.0 h after birth. Predictive reliability was tested by receiver operating characteristic curve analysis. The main outcome was the need for any respiratory support determined according to international guidelines. RESULTS: Seventy-four infants needed respiratory support, and 236 were healthy according to a 3-day follow-up confirmation. Six LUS imaging patterns were found. Two "high-risk" patterns were strongly correlated with respiratory support needs (area under the curve [AUC] = 0.95; 95% confidence interval [CI]: 0.92-0.98, p < .001). The optimal cut-off value for "high-risk" patterns was 2 (sensitivity = 87.8% and specificity = 91.1%). The predictive value of LUS was greater than that of a symptom-based method (the Acute Care of at-Risk Newborns assessment score) (AUCs' p < .01). CONCLUSIONS: LUS can be used to predict the need for respiratory support in late preterm and term infants and is more reliable than tools based on respiratory symptoms.

The Impact of COVID-19 on Clinical Trial Execution at the Dana-Farber Cancer Institute.

Interventions designed to limit the spread of coronavirus disease 2019 (COVID-19) are having profound effects on the delivery of health care, but data showing the impact on oncology clinical trial enrollment, treatment, and monitoring are limited. We prospectively tracked relevant data from oncology clinical trials at Dana-Farber Cancer Institute from January 1, 2018, to June 30, 2020, including the number of open trials, new patient enrollments, in-person and virtual patient visits, dispensed investigational infusions, dispensed or shipped oral investigational agents, research biopsies, and blood samples. We ascertained why patients came off trials and determined on-site clinical research staffing levels. We used 2-sided Wilcoxon rank sum tests to assess the statistical significance of the reported changes. Nearly all patients on interventional treatment trials were maintained, and new enrollments continued at just under one-half the prepandemic rate. The median number of investigational prescriptions shipped to patients increased from 0 to 74 (range = 22-107) per week from March to June 2020. The median number of telemedicine appointments increased from 0 to 107 (range = 33-267) per week from March to June 2020. Research biopsies and blood collections decreased dramatically after Dana-Farber Cancer Institute implemented COVID-19-related policies in March 2020. The number of research nurses and clinical research coordinators on site also decreased after March 2020. Substantial changes were required to safely continue clinical research during the pandemic, yet we observed no increases in serious adverse events or major violations related to drug dosing. Lessons learned from adapting research practices during COVID-19 can inform industry sponsors and governmental agencies to consider altering practices to increase operational efficiency and convenience for patients.

N,S-Codoped hierarchical porous carbon spheres embedded with cobalt nanoparticles as efficient bifunctional oxygen electrocatalysts for rechargeable zinc-air batteries.

Rational design and fabrication of cost-effective, efficient bifunctional electrocatalysts is fundamentally important for the air cathode of metal-air batteries. Herein, a Co(ii) ion-driven self-assembly strategy is described for the synthesis of cobalt-based nanostructured transition metal compounds (Co-NTMCs) embedded in nitrogen and sulfur codoped hierarchical porous carbon submicrospheres (Co-NTMCs@NSC), where condensation of thiourea-ethylenediamine-formaldehyde resin (TEFR) is induced by Co(ii) ions which is simultaneously assembled with polydopamine to form a multifunctional precursor through coordinated interaction. The resulting Co-NTMCs@NSC sample comprises abundant hierarchical porous textures, a high content of active cobalt species including the nanoparticles of Co, Co3O4 and amorphous CoSx, and a considerable amount of defective structures. These characteristics lead to remarkable oxygen electrocatalytic activities, with a half-wave potential of +0.833 V vs. RHE, which is comparable to that of commercial Pt/C for the oxygen reduction reaction (ORR), and a lower overpotential of 284 mV than RuO2 at 10 mA·cm-2 for the oxygen evolution reaction (OER) in alkaline media. Furthermore, its operational stability is also much higher than that of commercial RuO2 and Pt/C catalysts. When used as a breathing air electrode for Zn-air batteries, Co-NTMCs@NSC shows a higher open-circuit voltage (1.509 V), higher discharge power density (262 mW cm-2) and better charge-discharge reversibility than commercial Pt/C. The results from the present work suggest that controlled assembly of functional polymers may be exploited for the preparation of doped carbon/metal nanoparticle nanocomposites as viable, high-performance catalysts for electrochemical energy technologies.