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1.
World Neurosurg ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38986947

ABSTRACT

OBJECTIVE: This study aimed to establish a predictive nomogram model for re-collapse of fractured vertebra after posterior pedicle screw fixation in thoracolumbar fractures (TLFs). METHODS: Patients undergoing posterior pedicle screw fixation for TLFs at our hospital between January 2016 and December 2021 were retrospectively reviewed. Patients were divided into two groups according to the presence or absence of re-collapse of the fractured vertebra at the final follow-up. The predictors for fractured vertebra re-collapse were identified by univariate and multivariable logistic regression analysis, and a nomogram model was developed. The prediction performance and internal validation were established. RESULTS: A total of 224 patients were included in this study. Of these, 46 (20.5%) patients developed re-collapse of fractured vertebra. Age, thoracic and lumbar injury severity score (TLICS), screw distribution in the fractured vertebra, and anterior vertebral height compression (AVHC) ratio were associated with vertebral re-collapse. These predictors were used to construct a predictive nomogram. The area under the receiver operating characteristic curve (AUC) of the nomogram model was 0.891. The concordance index (C-index) was 0.891, and it was 0.877 with bootstrapping validation. The calibration curves and decision curve analysis (DCA)also suggested that the nomogram model had excellent predictive performances for fractured vertebra re-collapse. CONCLUSIONS: A clinical nomogram incorporating four variables was constructed to predict fractured vertebra re-collapse after posterior pedicle screw fixation for TLFs. The nomogram demonstrated good calibration and discriminative abilities, which may help clinicians to make better treatment decisions.

2.
J Genet Genomics ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-39002897

ABSTRACT

Facial morphology, a complex trait influenced by genetics, holds great significance in evolutionary research. However, due to limited fossil evidence, the facial characteristics of Neanderthals and Denisovans have remained largely unknown. In this study, we conducted a large-scale multi-ethnic meta-analysis of Genome-Wide Association Study (GWAS), including 9674 East Asians and 10,115 Europeans, quantitatively assessing 78 facial traits using 3D facial images. We identified 71 genomic loci associated with facial features, including 21 novel loci. We developed a facial polygenic score (FPS) that enables the prediction of facial features based on genetic information. Interestingly, the distribution of FPSs among populations from diverse continental groups exhibited significant correlations with observed facial features. Furthermore, we applied the FPS to predict the facial traits of seven Neanderthals and one Denisovan using ancient DNA, and aligned predictions with the fossil records. Our results suggested that Neanderthals and Denisovans likely shared similar facial features, such as a wider but shorter nose and a wider endocanthion distance. The decreased mouth width was characterized specifically in Denisovan. The integration of genomic data and facial trait analysis provides valuable insights into the evolutionary history and adaptive changes in human facial morphology.

3.
Front Genet ; 15: 1296797, 2024.
Article in English | MEDLINE | ID: mdl-39036704

ABSTRACT

Objective: Fructose-1,6-bisphosphatase deficiency (FBP1D) is a rare inborn error due to mutations in the FBP1 gene. The genetic spectrum of FBP1D in China is unknown, also nonspecific manifestations confuse disease diagnosis. We systematically estimated the FBP1D prevalence in Chinese and explored genotype-phenotype association. Methods: We collected 101 FBP1 variants from our cohort and public resources, and manually curated pathogenicity of these variants. Ninety-seven pathogenic or likely pathogenic variants were used in our cohort to estimate Chinese FBP1D prevalence by three methods: 1) carrier frequency, 2) permutation and combination, 3) Bayesian framework. Allele frequencies (AFs) of these variants in our cohort, China Metabolic Analytics Project (ChinaMAP) and gnomAD were compared to reveal the different hotspots in Chinese and other populations. Clinical and genetic information of 122 FBP1D patients from our cohort and published literature were collected to analyze the genotype-phenotypes association. Phenotypes of 68 hereditary fructose intolerance (HFI) patients from our previous study were used to compare the phenotypic differences between these two fructose metabolism diseases. Results: The estimated Chinese FBP1D prevalence was 1/1,310,034. In the Chinese population, c.490G>A and c.355G>A had significantly higher AFs than in the non-Finland European population, and c.841G>A had significantly lower AF value than in the South Asian population (all p values < 0.05). The genotype-phenotype association analyses showed that patients carrying homozygous c.841G>A were more likely to present increased urinary glycerol, carrying two CNVs (especially homozygous exon1 deletion) were often with hepatic steatosis, carrying compound heterozygous variants were usually with lethargy, and carrying homozygous variants were usually with ketosis and hepatic steatosis (all p values < 0.05). By comparing to phenotypes of HFI patients, FBP1D patients were more likely to present hypoglycemia, metabolic acidosis, and seizures (all p-value < 0.05). Conclusion: The prevalence of FBP1D in the Chinese population is extremely low. Genetic sequencing could effectively help to diagnose FBP1D.

4.
Sci Rep ; 14(1): 14345, 2024 06 21.
Article in English | MEDLINE | ID: mdl-38906930

ABSTRACT

The causal relationship between Packed red blood cell (RBC) transfusion and necrotizing enterocolitis (NEC) remains uncertain. This study aims to provide an exploration of transfusion and NEC in very preterm infants. Using data from the Chinese Neonatal Network cohort study between 2019 and 2021, the analysis focused on very preterm infants (with a birth weight of < 1500 g or a gestational age of < 32 weeks) who developed NEC after receiving transfusions. The time interval between the prior transfusion and NEC was analyzed. An uneven distribution of the time interval implies an association of transfusion and NEC. Additionally, multivariable logistic analysis was conducted to detect the prognosis of defined transfusion-associated NEC(TANEC). Of the 16,494 infants received RBC transfusions, NEC was noted in 1281 (7.7%) cases, including 409 occurred after transfusion. Notably, 36.4% (149/409) of post-transfusion NEC occurred within 2 days after transfusion. The time interval distribution showed a non-normal pattern (Shapiro-Wilk test, W = 0.513, P < 0.001), indicating a possible link between transfusion and NEC. TANEC was defined as NEC occurred within 2 days after transfusion. Infants with TANEC had a higher incidence of death (adjusted OR 1.69; 95% CI 1.08 to 2.64), severe bronchopulmonary dysplasia (adjusted OR 2.03; 95% CI 1.41 to 2.91) and late-onset sepsis (adjusted OR 2.06; 95% CI 1.37 to 3.09) compared with infants without NEC after transfusion. Unevenly high number of NEC cases after RBC transfusions implies transfusion is associated with NEC. TANEC is associated with a poor prognosis. Further research is warranted to enhance our understanding of TANEC.


Subject(s)
Enterocolitis, Necrotizing , Erythrocyte Transfusion , Humans , Enterocolitis, Necrotizing/etiology , Enterocolitis, Necrotizing/epidemiology , Erythrocyte Transfusion/adverse effects , Infant, Newborn , Male , Female , Infant, Premature , Gestational Age , Infant, Very Low Birth Weight , Prognosis , Infant, Premature, Diseases/therapy , Infant, Premature, Diseases/etiology , Infant, Premature, Diseases/epidemiology , Incidence , Infant , Risk Factors , China/epidemiology
5.
J Nutr Biochem ; 131: 109678, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38844080

ABSTRACT

The solute carrier family 25 member 1 (Slc25a1)-dependent mitochondrial citrate shuttle is responsible for exporting citrate from the mitochondria to the cytoplasm for supporting lipid biosynthesis and protein acetylation. Previous studies on Slc25a1 concentrated on pathological models. However, the importance of Slc25a1 in maintaining metabolic homeostasis under normal nutritional conditions remains poorly understood. Here, we investigated the mechanism of mitochondrial citrate shuttle in maintaining lipid metabolism homeostasis in male Nile tilapia (Oreochromis niloticus). To achieve the objective, we blocked the mitochondrial citrate shuttle by inhibiting Slc25a1 under normal nutritional conditions. Slc25a1 inhibition was established by feeding Nile tilapia with 250 mg/kg 1,2,3-benzenetricarboxylic acid hydrate for 6 weeks or intraperitoneal injecting them with dsRNA to knockdown slc25a1b for 7 days. The Nile tilapia with Slc25a1 inhibition exhibited an obesity-like phenotype accompanied by fat deposition, liver damage and hyperglycemia. Moreover, Slc25a1 inhibition decreased hepatic citrate-derived acetyl-CoA, but increased hepatic triglyceride levels. Furthermore, Slc25a1 inhibition replenished cytoplasmic acetyl-CoA through enhanced acetate pathway, which led to hepatic triglycerides accumulation. However, acetate-derived acetyl-CoA caused by hepatic Slc25a1 inhibition did not activate de novo lipogenesis, but rather modified protein acetylation. In addition, hepatic Slc25a1 inhibition enhanced fatty acids esterification through acetate-derived acetyl-CoA, which increased Lipin1 acetylation and its protein stability. Collectively, our results illustrate that inhibiting mitochondrial citrate shuttle triggers lipid anabolic remodeling and results in lipid accumulation, indicating the importance of mitochondrial citrate shuttle in maintaining lipid metabolism homeostasis.

6.
Children (Basel) ; 11(6)2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38929259

ABSTRACT

The objective of this study was to assess the relationship of ACS with neonatal outcomes among very preterm infants born to mothers with clinical chorioamnionitis in China. This was a multicenter retrospective cohort study. Study participants included infants born at <32 weeks' gestation with clinical chorioamnionitis and registered in the Chinese Neonatal Network from 1 January 2019 to 31 December 2020. Infants were divided into two groups: any amount of ACS or no administration of ACS. Multivariable generalized linear models using generalized estimating equations were used to assess the association between ACS and neonatal outcomes among the study population. We identified 2193 infants eligible for this study; 1966 (89.6%) infants had received ACS therapy, and 227 (10.4%) had not received any ACS therapy. Among very preterm infants born to mothers with clinical chorioamnionitis, any ACS usage was significantly associated with decreased risks of early death (aRR 0.56, 95% CI 0.32, 0.99) and severe ROP (aRR 0.51, 95% CI 0.28, 0.93) after adjustment for maternal hypertension, gestational age at birth, Caesarean section, being inborn, and administration of systemic antibiotics to the mother within 24 h before birth. In addition, out of the 2193 infants, the placentas of 1931 infants underwent pathological examination with recorded results. Subsequently, 1490 of these cases (77.2%) were diagnosed with histological chorioamnionitis. In 1490 cases of histologic chorioamnionitis, any ACS usage was significantly related to decreased risks of overall mortality (aRR 0.52, 95% CI 0.31, 0.87), severe ROP (aRR 0.47, 95% CI 0.25, 0.97), and respiratory distress syndrome (aRR 0.52, 95% CI 0.31, 0.87). We concluded that any ACS was associated with reduced risks for neonatal early death and severe ROP among very preterm infants born to mothers with clinical chorioamnionitis.

7.
JAMA Netw Open ; 7(6): e2418831, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38935376

ABSTRACT

Importance: The overutilization of antibiotics in very preterm infants (VPIs) at low risk of early-onset sepsis (EOS) is associated with increased mortality and morbidities. Nevertheless, the association of early antibiotic exposure with bronchopulmonary dysplasia (BPD) remains equivocal. Objective: To evaluate the association of varying durations and types of early antibiotic exposure with the incidence of BPD in VPIs at low risk of EOS. Design, Setting, and Participants: This national multicenter cohort study utilized data from the Chinese Neonatal Network (CHNN) which prospectively collected data from January 1, 2019, to December 31, 2021. VPIs less than 32 weeks' gestational age or with birth weight less than 1500 g at low risk of EOS, defined as those born via cesarean delivery, without labor or rupture of membranes, and no clinical evidence of chorioamnionitis, were included. Data analysis was conducted from October 2022 to December 2023. Exposure: Early antibiotic exposure was defined as the total number of calendar days antibiotics were administered within the first week of life, which were further categorized as no exposure, 1 to 4 days of exposure, and 5 to 7 days of exposure. Main Outcomes and Measures: The primary outcome was the composite of moderate to severe BPD or mortality at 36 weeks' post menstrual age (PMA). Logistic regression was employed to assess factors associated with BPD or mortality using 2 different models. Results: Of the 27 176 VPIs included in the CHNN during the study period (14 874 male [54.7%] and 12 302 female [45.3%]), 6510 (23.9%; 3373 male [51.8%] and 3137 female [48.2.%]) were categorized as low risk for EOS. Among them, 1324 (20.3%) had no antibiotic exposure, 1134 (17.4%) received 1 to 4 days of antibiotics treatment, and 4052 (62.2%) received 5 to 7 days of antibiotics treatment. Of the 5186 VPIs who received antibiotics, 4098 (79.0%) received broad-spectrum antibiotics, 888 (17.1%) received narrow-spectrum antibiotics, and 200 (3.9%) received antifungals or other antibiotics. Prolonged exposure (5-7 days) was associated with increased likelihood of moderate to severe BPD or death (adjusted odds ratio [aOR], 1.23; 95% CI, 1.01-1.50). The use of broad-spectrum antibiotics (1-7 days) was also associated with a higher risk of moderate to severe BPD or death (aOR, 1.27; 95% CI, 1.04-1.55). Conclusions and Relevance: In this cohort study of VPIs at low risk for EOS, exposure to prolonged or broad-spectrum antibiotics was associated with increased risk of developing moderate to severe BPD or mortality. These findings suggest that VPIs exposed to prolonged or broad-spectrum antibiotics early in life should be monitored for adverse outcomes.


Subject(s)
Anti-Bacterial Agents , Bronchopulmonary Dysplasia , Humans , Bronchopulmonary Dysplasia/epidemiology , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/therapeutic use , Infant, Newborn , Female , Male , Infant, Premature , Sepsis/epidemiology , China/epidemiology , Cohort Studies , Risk Factors , Incidence , Gestational Age , Infant, Very Low Birth Weight
8.
BMC Pediatr ; 24(1): 394, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38877528

ABSTRACT

BACKGROUND: The occurrence of severe intraventricular hemorrhage (sIVH) was high in the very preterm infants (VPIs) in China. The management strategies significantly contributed to the occurrence of sIVH in VPIs. However, the status of the perinatal strategies associated with sIVH for VPIs was rarely described across the multiple neonatal intensive care units (NICUs) in China. We aim to investigate the characteristics of the perinatal strategies associated with sIVH for VPIs across the multiple NICUs in China. METHODS: This was a retrospective analysis of data from a prospective cohort of Chinese Neonatal Network (CHNN) dataset, enrolling infants born at 24+0-31+6 from 2019 to 2021. Eleven perinatal practices performed within the first 3 days of life were investigated including antenatal corticosteroids use, antenatal magnesium sulphate therapy, intubation at birth, placental transfusion, need for advanced resuscitation, initial inhaled gas of 100% FiO2 in delivery room, initial invasive respiratory support, surfactant and caffeine administration, early enteral feeding, and inotropes use. The performances of these practices across the multiple NICUs were investigated using the standard deviations of differences between expected probabilities and observations. The occurrence of sIVH were compared among the NICUs. RESULTS: A total of 24,226 infants from 55 NICUs with a mean (SD) gestational age of 29.5 (1.76) and mean (SD) birthweight of 1.31(0.32) were included. sIVH was detected in 5.1% of VPIs. The rate of the antenatal corticosteroids, MgSO4 therapy, and caffeine was 80.0%, 56.4%, and 31.5%, respectively. We observed significant relationships between sIVH and intubation at birth (AOR 1.52, 95% CI 1.13 to 1.75) and initial invasive respiratory support (AOR 2.47, 95% CI 2.15 to 2.83). The lower occurrence of sIVH (4.8%) was observed corresponding with the highest utility of standard antenatal care, the lowest utility of invasive practices, and early enteral feeding administration. CONCLUSIONS: The current evidence-based practices were not performed in each VPI as expected among the studied Chinese NICUs. The higher utility of the invasive practices could be related to the occurrence of sIVH.


Subject(s)
Cerebral Intraventricular Hemorrhage , Intensive Care Units, Neonatal , Female , Humans , Infant, Newborn , Male , Adrenal Cortex Hormones/therapeutic use , Cerebral Intraventricular Hemorrhage/epidemiology , China/epidemiology , East Asian People , Infant, Extremely Premature , Infant, Premature , Infant, Premature, Diseases/epidemiology , Perinatal Care/methods , Retrospective Studies
9.
J Hazard Mater ; 474: 134782, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-38824781

ABSTRACT

For a plastic syringe, a stopper at the end of plunger is usually made of polydimethylsiloxane (PDMS, and co-ingredients). To reduce friction and prevent leakage between the stopper and barrel, short chain polymer of liquid PDMS is also used as lubricant. Consequently, an injection process can release solid PDMS debris from the stopper and barrel, and liquid PDMS droplets from the lubricant, both of which are confirmed herein as solid and liquid micro(nano)plastics. From molecular spectrum perspective to directly visualise those micro(nano)plastics, Raman imaging was employed to analyse hundreds-to-thousands of spectra (hyper spectrum or hyperspectral matrix) and significantly enhance signal-to-noise ratio. From morphology perspective to provide high resolution of image, scanning electron microscopy (SEM) was engaged to cross-check with Raman images and increase assignment / quantification certainty. The weak Raman imaging signal of nanoplastics was extracted using image deconvolution algorithm to remove the background noise and average the signal variation. To increase the result's representativeness and avoid quantification bias, multiple syringes were tested and multiple areas were randomly scanned toward statistical results. It was estimated that thousands of microplastics and millions of nanoplastics of solid/liquid PDMS might be injected when using a plastic syringe of 1 mL. Overall, Raman imaging (along with algorithm and SEM) can be helpful for further research on micro(nano)plastics, and it should be cautious to use plastic syringe due to the increasing concern on the emerging contamination of not only solid but also liquid micro(nano)plastics.

10.
Nat Immunol ; 25(6): 969-980, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38831104

ABSTRACT

Rare genetic variants in toll-like receptor 7 (TLR7) are known to cause lupus in humans and mice. UNC93B1 is a transmembrane protein that regulates TLR7 localization into endosomes. In the present study, we identify two new variants in UNC93B1 (T314A, located proximally to the TLR7 transmembrane domain, and V117L) in a cohort of east Asian patients with childhood-onset systemic lupus erythematosus. The V117L variant was associated with increased expression of type I interferons and NF-κB-dependent cytokines in patient plasma and immortalized B cells. THP-1 cells expressing the variant UNC93B1 alleles exhibited exaggerated responses to stimulation of TLR7/-8, but not TLR3 or TLR9, which could be inhibited by targeting the downstream signaling molecules, IRAK1/-4. Heterozygous mice expressing the orthologous Unc93b1V117L variant developed a spontaneous lupus-like disease that was more severe in homozygotes and again hyperresponsive to TLR7 stimulation. Together, this work formally identifies genetic variants in UNC93B1 that can predispose to childhood-onset systemic lupus erythematosus.


Subject(s)
Genetic Predisposition to Disease , Lupus Erythematosus, Systemic , Toll-Like Receptor 7 , Lupus Erythematosus, Systemic/genetics , Humans , Animals , Toll-Like Receptor 7/genetics , Toll-Like Receptor 7/metabolism , Mice , Child , Female , Membrane Transport Proteins/genetics , Membrane Transport Proteins/metabolism , Male , Age of Onset , Genetic Variation , NF-kappa B/metabolism , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Adolescent , THP-1 Cells , Interferon Type I/metabolism
11.
Cancer Med ; 13(11): e7389, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38864475

ABSTRACT

BACKGROUND: Ion channels play an important role in tumorigenesis and progression of cervical cancer. Multiple long non-coding RNA genes are widely involved in ion channel-related signaling regulation. However, the association and potential clinical application of lncRNAs in the prognosis of cervical cancer are still poorly explored. METHODS: Thirteen patients with cervical cancer were enrolled in current study. Whole transcriptome (involving both mRNAs and lncRNAs) sequencing was performed on fresh tumor and adjacent normal tissues that were surgically resected from patients. A comprehensive cervical cancer-specific lncRNA landscape was obtained by our custom pipeline. Then, a prognostic scoring model of ion-channel-related lncRNAs was established by regression algorithms. The performance of the predictive model as well as its association with the clinical characteristics and tumor microenvironment (TME) status were further evaluated. RESULTS: To comprehensively identify cervical cancer-specific lncRNAs, we sequenced 26 samples of cervical cancer patients and integrated the transcriptomic results. We built a custom analysis pipeline to improve the accuracy of lncRNA identification and functional annotation and obtained 18,482 novel lncRNAs in cervical cancer. Then, 159 ion channel- and tumorigenesis-related (ICTR-) lncRNAs were identified. Based on nine ICTR-lncRNAs, we also established a prognostic scoring model and validated its accuracy and robustness in assessing the prognosis of patients with cervical cancer. Besides, the TME was characterized, and we found that B cells, activated CD8+ T, and tertiary lymphoid structures were significantly associated with ICTR-lncRNAs signature scores. CONCLUSION: We provided a thorough landscape of cervical cancer-specific lncRNAs. Through integrative analyses, we identified ion-channel-related lncRNAs and established a predictive model for assessing the prognosis of patients with cervical cancer. Meanwhile, we characterized its association with TME status. This study improved our knowledge of the prominent roles of lncRNAs in regulating ion channel in cervical cancer.


Subject(s)
Gene Expression Regulation, Neoplastic , Ion Channels , RNA, Long Noncoding , Tumor Microenvironment , Uterine Cervical Neoplasms , Humans , RNA, Long Noncoding/genetics , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/mortality , Female , Prognosis , Ion Channels/genetics , Ion Channels/metabolism , Tumor Microenvironment/genetics , Biomarkers, Tumor/genetics , Gene Expression Profiling , Middle Aged , Transcriptome
12.
Heliyon ; 10(11): e31742, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38845994

ABSTRACT

This review aims to explore the current application of Cranial Ultrasound Screening (CUS) in the diagnosis and treatment of brain diseases in extremely preterm infants. It also discusses the potential role of emerging ultrasound-derived technologies such as Super Microvascular Structure Imaging (SMI), Shear Wave Elastography (SWE), Ultrafast Doppler Ultrasound (UfD), and 3D ventricular volume assessment and automated segmentation techniques in clinical practice. A systematic search of medical databases was conducted using the keywords "(preterm OR extremely preterm OR extremely low birth weight) AND (ultrasound OR ultrasound imaging) AND (neurodevelopment OR brain development OR brain diseases OR brain injury OR neuro*)" to identify relevant literature. The titles, abstracts, and full texts of the identified articles were carefully reviewed to determine their relevance to the research topic. CUS offers unique advantages in early screening and monitoring of brain diseases in extremely preterm infants, as it can be performed at the bedside without the need for anesthesia or special monitoring. This technique facilitates early detection and intervention of conditions such as intraventricular hemorrhage, white matter injury, hydrocephalus, and hypoxic-ischemic injury in critically ill preterm infants. Continuous refinement of the screening and follow-up processes provides reliable clinical decision-making support for healthcare professionals and parents. Emerging ultrasound technologies, such as SWE, SMI, and UfD, are being explored to provide more accurate and in-depth understanding of brain diseases in extremely preterm infants. SWE has demonstrated its effectiveness in assessing the elasticity of neonatal brain tissue, aiding in the localization and quantification of potential brain injuries. SMI can successfully identify microvascular structures in the brain, offering a new perspective on neurologic diseases. UfD provides a high-sensitivity and quantitative imaging method for the prevention and treatment of neonatal brain diseases by detecting subtle changes in red blood cell movement and accurately assessing the status and progression of brain diseases. CUS and its emerging technologies have significant applications in the diagnosis and treatment of brain diseases in extremely preterm infants. Future research aims to address current technical challenges, optimize and enhance the clinical decision-making capabilities related to brain development, and improve the prevention and treatment outcomes of brain diseases in extremely preterm infants.

13.
Materials (Basel) ; 17(10)2024 May 09.
Article in English | MEDLINE | ID: mdl-38793293

ABSTRACT

The quality of Ti alloy casing is crucial for the safe and stable operation of aero engines. However, the fluctuation of key process parameters during the investment casting process of titanium alloy casings has a significant influence on the volume and number of porosity defects, and this influence cannot be effectively suppressed at present. Therefore, this paper proposes a strategy to control the influence of process parameters on shrinkage volume and number. This study constructed multiple regression prediction models and neural network prediction models of porosity volume and number for a ZTC4 casing by simulating the gravity investment casting process. The results show that the multiple regression prediction model and neural network prediction model of shrinkage cavity total volume have an accuracy of over 99%. The accuracy of the neural network prediction model is higher than that of the multiple regression model, and the neural network model realizes the accurate prediction of shrinkage defect volume and defect number through pouring temperature, pouring time, and mold shell temperature. The sensitivity degree of casing defects to key process parameters, from high to low, is as follows: pouring temperature, pouring time, and mold temperature. Further optimizing the key process parameter window reduces the influence of process parameter fluctuation on the volume and number of porosity defects in casing castings. This study provides a reference for actual production control process parameters to reduce shrinkage cavity and loose defects.

14.
iScience ; 27(6): 109869, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38799568

ABSTRACT

The core of telomerase consists of the protein subunit telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC). So far, the role of TERC in cancer development has remained elusive. Here, we found TERC expression elevated in non-small cell lung cancer (NSCLC) tissues, which was associated with disease progression and poor prognosis in patients. Using NSCLC cell lines and xenograft models, we showed that knockdown of TERC caused cell cycle arrest, and inhibition of cell proliferation and migration. Mechanistically, TERC was exported to the cytoplasm by nuclear RNA export factor 1 (NXF1), where it mediated the interaction of TERT with other telomerase subunits. Depletion of TERC hindered the assembly and subsequent nuclear localization of the telomerase complex, preventing TERT from functioning in telomere maintenance and transcription regulation. Our findings suggest that TERC is a potential biomarker for NSCLC diagnosis and prognosis and can be a target for NSCLC treatment.

15.
Vox Sang ; 119(6): 572-580, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38622920

ABSTRACT

BACKGROUND AND OBJECTIVES: National-level data on the incidence of red blood cell (RBC) transfusions and outcomes among very preterm infants (VPIs) are lacking in China. This study aims to describe the use and variation of RBC transfusion among VPIs in China. MATERIALS AND METHODS: This cohort study was conducted among 70 tertiary hospitals participating in the Chinese Neonatal Network (CHNN) from 2019 to 2020 across China. All VPIs admitted to the CHNN neonatal intensive care units (NICUs) were included. RESULTS: A total of 13,447 VPIs were enrolled, of whom 7026 (52.2%) received ≥1 RBC transfusions. The mean number of transfusions per infant was 2 (interquartile range [IQR] 1-4 times) and the median age at first transfusion was 15 days (IQR 3-27 days). The transfusion rate was higher in critically ill infants compared with non-critically ill infants (70.5% vs. 39.3%). The transfusion rate varied widely (13.5%-95.0%) between different NICUs. The prevalence of death, severe intra-ventricular haemorrhage, necrotizing enterocolitis (NEC) or spontaneous intestinal perforation (SIP), sepsis, bronchopulmonary dysplasia (BPD), severe retinopathy of prematurity (ROP) and cystic periventricular leukomalacia (cPVL) was significantly higher in the transfused group. Among non-critically ill infants, RBC transfusion was independently associated with BPD, severe ROP and cPVL. CONCLUSION: Our study, providing the first baseline data on RBC transfusions among VPIs in China, shows an alarmingly high RBC transfusion rate with significant site variations. There is an urgent need for national guidelines on RBC transfusions for VPIs in China.


Subject(s)
Erythrocyte Transfusion , Humans , China/epidemiology , Infant, Newborn , Male , Female , Intensive Care Units, Neonatal , Infant , Infant, Premature , Cohort Studies , Infant, Extremely Premature
16.
Nat Prod Res ; : 1-9, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38623908

ABSTRACT

Two novel neolignans, piperkadsurenin A (1) and kadsurenin N (2), along with six known neolignans (3-8) and two lignans (9-10) were isolated from the stems of Piper kadsura (Choisy) Ohwi. Extensive spectroscopic data interpretation and ECD calculations were used to identify the structures of the new compounds 1 and 2. Especially, compound 1 represents the first example of neolignan with cyclopenta[b]pyran framework. The anti-inflammatory efficacy of compounds 1-10 in vitro was systematically assessed through NO production inhibitory assay. Compounds 3 and 7 significantly inhibited LPS-induced NO generation in RAW 264.7 cells, with IC50 values of 34.29 ± 0.82 and 47.5 ± 5.81 µM, respectively.

17.
Angew Chem Int Ed Engl ; 63(24): e202403263, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38657031

ABSTRACT

Hierarchical self-assembly represents a powerful strategy for the fabrication of functional materials across various length scales. However, achieving precise formation of functional hierarchical assemblies remains a significant challenge and requires a profound understanding of molecular assembly interactions. In this study, we present a molecular-level understanding of the hierarchical assembly of sequence-defined peptoids into multidimensional functional materials, including twisted nanotube bundles serving as a highly efficient artificial light harvesting system. By employing synchrotron-based powder X-ray diffraction and analyzing single crystal structures of model compounds, we elucidated the molecular packing and mechanisms underlying the assembly of peptoids into multidimensional nanostructures. Our findings demonstrate that incorporating aromatic functional groups, such as tetraphenyl ethylene (TPE), at the termini of assembling peptoid sequences promotes the formation of twisted bundles of nanotubes and nanosheets, thus enabling the creation of a highly efficient artificial light harvesting system. This research exemplifies the potential of leveraging sequence-defined synthetic polymers to translate microscopic molecular structures into macroscopic assemblies. It holds promise for the development of functional materials with precisely controlled hierarchical structures and designed functions.


Subject(s)
Peptoids , Peptoids/chemistry , Peptoids/chemical synthesis , Nanostructures/chemistry , Nanotubes/chemistry , Models, Molecular , Particle Size
18.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(3): 321-324, 2024 Mar 15.
Article in Chinese | MEDLINE | ID: mdl-38557387

ABSTRACT

The male patient, one day old, was admitted to the hospital due to hypoglycemia accompanied by apnea appearing six hours after birth. The patient had transient hypoglycemia early after birth, and acute heart failure suddenly occurred on the eighth day after birth. Laboratory tests showed significantly reduced levels of adrenocorticotropic hormone and cortisol, and pituitary magnetic resonance imaging was normal. Genetic testing results showed that the patient had probably pathogenic compound heterozygous mutations of the TBX19 gene (c.917-2A>G+c.608C>T), inherited respectively from the parents. The patient was conclusively diagnosed with congenital isolated adrenocorticotropic hormone deficiency caused by mutation of the TBX19 gene. Upon initiating hydrocortisone replacement therapy, cardiac function rapidly returned to normal. After being discharged, the patient continued with the hydrocortisone replacement therapy. By the 18-month follow-up, the patient was growing and developing well. In neonates, unexplained acute heart failure requires caution for possible endocrine hereditary metabolic diseases, and timely cortisol testing and genetic testing should be conducted.


Subject(s)
Adrenal Insufficiency , Heart Failure , Hypoglycemia , Infant, Newborn , Humans , Male , Hydrocortisone/therapeutic use , Hypoglycemia/etiology , Adrenal Insufficiency/congenital , Adrenal Insufficiency/diagnosis , Adrenal Insufficiency/genetics , Heart Failure/etiology , Heart Failure/genetics , Adrenocorticotropic Hormone
19.
Ann Clin Microbiol Antimicrob ; 23(1): 33, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38622723

ABSTRACT

BACKGROUND: Antimicrobial resistance (AMR) is a major threat to children's health, particularly in respiratory infections. Accurate identification of pathogens and AMR is crucial for targeted antibiotic treatment. Metagenomic next-generation sequencing (mNGS) shows promise in directly detecting microorganisms and resistance genes in clinical samples. However, the accuracy of AMR prediction through mNGS testing needs further investigation for practical clinical decision-making. METHODS: We aimed to evaluate the performance of mNGS in predicting AMR for severe pneumonia in pediatric patients. We conducted a retrospective analysis at a tertiary hospital from May 2022 to May 2023. Simultaneous mNGS and culture were performed on bronchoalveolar lavage fluid samples obtained from pediatric patients with severe pneumonia. By comparing the results of mNGS detection of microorganisms and antibiotic resistance genes with those of culture, sensitivity, specificity, positive predictive value, and negative predictive value were calculated. RESULTS: mNGS detected bacterial in 71.7% cases (86/120), significantly higher than culture (58/120, 48.3%). Compared to culture, mNGS demonstrated a sensitivity of 96.6% and a specificity of 51.6% in detecting pathogenic microorganisms. Phenotypic susceptibility testing (PST) of 19 antibiotics revealed significant variations in antibiotics resistance rates among different bacteria. Sensitivity prediction of mNGS for carbapenem resistance was higher than penicillins and cephalosporin (67.74% vs. 28.57%, 46.15%), while specificity showed no significant difference (85.71%, 75.00%, 75.00%). mNGS also showed a high sensitivity of 94.74% in predicting carbapenem resistance in Acinetobacter baumannii. CONCLUSIONS: mNGS exhibits variable predictive performance among different pathogens and antibiotics, indicating its potential as a supplementary tool to conventional PST. However, mNGS currently cannot replace conventional PST.


Subject(s)
Anti-Bacterial Agents , Pneumonia , Humans , Child , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Retrospective Studies , Drug Resistance, Bacterial/genetics , High-Throughput Nucleotide Sequencing , Carbapenems , Sensitivity and Specificity , Bronchoalveolar Lavage Fluid
20.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(4): 403-409, 2024 Apr 15.
Article in Chinese | MEDLINE | ID: mdl-38660905

ABSTRACT

Further evidence is needed to explore the impact of high-altitude environments on the neurologic function of neonates. Non-invasive techniques such as cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography can provide data on cerebral oxygenation and brain electrical activity. This study will conduct multiple cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography monitoring sessions at various time points within the first 3 days postpartum for healthy full-term neonates at different altitudes. The obtained data on cerebral oxygenation and brain electrical activity will be compared between different altitudes, and corresponding reference ranges will be established. The study involves 6 participating centers in the Chinese High Altitude Neonatal Medicine Alliance, with altitude gradients divided into 4 categories: 800 m, 1 900 m, 2 400 m, and 3 500 m, with an anticipated sample size of 170 neonates per altitude gradient. This multicenter prospective cohort study aims to provide evidence supporting the impact of high-altitude environments on early brain function and metabolism in neonates.


Subject(s)
Altitude , Brain , Electroencephalography , Oxygen , Humans , Infant, Newborn , Brain/metabolism , Oxygen/metabolism , Spectroscopy, Near-Infrared , Prospective Studies
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