Long noncoding RNA UCA1 inhibits epirubicin-induced apoptosis by activating PPARα-mediated lipid metabolism.

Metabolic reprogramming is a hallmark of cancer, and abnormal lipid metabolism is associated with drug resistance in bladder cancer cells. The long noncoding RNA (lncRNA) UCA1 is overexpressed in bladder cancer, but its functional contribution to lipid metabolism remains uncharacterized. In this study, we demonstrated that lncRNA UCA1 inhibits epirubicin-induced cell apoptosis by supporting abnormal lipid metabolism in bladder cancer cells. Mechanistically, lncRNA UCA1 promotes lipid accumulation in vitro and in vivo by upregulating PPARα mRNA and protein expression, which is mediated by miR-30a-3p. Knockdown of lncRNA UCA1 increased epirubicin-induced apoptosis via miR-30a-3p/PPARα and downstream p-AKT/p-GSK-3ß/ß-catenin signaling. Furthermore, mixed free fatty acids upregulated lncRNA UCA1 expression by promoting recruitment of the transcription factor RXRα to the lncRNA UCA1 promoter. These findings were verified in a mouse xenograft model and are consistent with the expression patterns in human bladder cancer patients. Overall, these findings establish the role of lncRNA UCA1 in lipid metabolism and bladder cancer cell resistance to epirubicin, suggesting that lncRNA UCA1 may serve as a candidate target for enhancing bladder cancer chemotherapy.

Hsa_circ_0001359 in Serum Exosomes: A Promising Marker to Predict Bronchopulmonary Dysplasia in Premature Infants.

Objective: This prospective study is to explore the role of specific circRNAs in predicting the development of bronchopulmonary dysplasia (BPD). Methods: From July 1, 2021 to December 1, 2021, peripheral blood samples were collected from 62 premature infants with gestational age (GA) ≤32 weeks on the 7th, 14th, and 28th day after birth. Then, on the 28th day, the included infants were divided into the BPD group and the non-BPD group according to the definition of BPD. Serum exosomal circRNAs from peripheral blood were identified, sequenced, and compared between the BPD and non-BPD groups at different time points. Specific differentially expressed circRNAs were further verified from another 42 enrolled premature infants (GA ≤32 weeks). The classical lung biological markers in serum were also measured simultaneously. Results: Hsa_circ_0001359 in serum exosomes showed continuous differential expression between the BPD group and the non-BPD group on the 7th, 14th, and 28th day. Compared with that, classical lung biological markers like IL-6, IL-33, KL-6, and ET-1 did not exhibit continuous differences. Moreover, the expression of hsa_circ_0001359 on day 7 had a higher predictive value in predicting BPD (area under curve:0.853, 95% CI:0.738-0.968; adjusted odds ratio:6.033, 95% CI:2.373-13.326). The calibration curve further showed the mean absolute error = 0.033, mean squared error = 0.00231, and quantile of absolute error = 0.058. Conclusion: Hsa_circ_0001359 in serum exosomes is a promising marker for predicting BPD in preterm infants with gestational age ≤32 weeks.

Inhibitory Properties of Cinnamon Bark Oil against Postharvest Pathogen Penicillium digitatum In Vitro.

Penicillium digitatum is a major postharvest pathogen that threatens the global citrus fruit industry and causes great economic losses annually. In the present study, inhibitory properties of cinnamon bark oil (CBO) against P. digitatum in vitro were investigated. Results indicated that 0.03% CBO could efficiently inhibit the spore germination, germ tube elongation, mycelial growth, colonial expansion and conidial accumulation of P. digitatum. The results of fluorescein diacetate (FDA) and MitoTraker Orange (MTO) staining also proved the suppression effects of CBO against P. digitatum. Meanwhile, CBO could inhibit green mold rots induced by P. digitatum in citrus fruit when the working concentration of CBO exceeded 0.06%. In addition, the expressions of 12 genes critical for the growth and virulence of P. digitatum were also significantly regulated under CBO stress. Through a transcriptomic analysis, a total of 1802 common differentially expressed genes (DEGs) were detected in P. digitatum after 4 h and 8 h of CBO treatment. Most of the DEG products were associated with carbohydrate, amino acid and lipid metabolism. They directly or indirectly led to the disturbance of the membrane and the generation of reactive oxygen species (ROS). Our results may deepen the understanding of antifungal properties of CBO against P. digitatum and provide the theoretical foundation to uncover the antifungal mechanism of CBO at the molecular level.

Prospective cohort study on tuberculosis incidence and risk factors in the elderly population of eastern China.

Background: Tuberculosis continues to be a significant public health concern in China, particularly among the elderly population. This study aimed to assess the risk factors of tuberculosis among elderly individuals in China through a cohort study, focusing on this high-risk population. Methods: The population-based census was strategically designed to cover diverse regions and demographics across the city. The survey captured demographic and lifestyle information, as well as a clinical examination. Participants were prospectively followed up over a specified duration to monitor the incidence of tuberculosis cases. Results: After a follow-up period of more than 7 years, 246 individuals developed tuberculosis, resulting in an incidence rate of 92.21 per 100,000 person-years (95 % CI 81.2-104.3). In multivariate analysis, the following factors were found to have significant associations with active tuberculosis. Increasing age correlated with a higher risk of active tuberculosis (AHR = 1.03 per 1-year increase in age, 95%CI: 1.01, 1.04, P < 0.001). Males continued to have a higher risk compared to females (HR = 2.73, 95%CI: 2.08, 3.58, P < 0.001). Individuals with a normal Body Mass Index (BMI) faced nearly three times higher risk compared to their obese counterparts (HR = 2.87, 95 % CI: 1.51, 5.46, P = 0.001). Conversely, those with an underweight BMI had a ten-fold higher risk compared to the obese group (HR = 9.89, 95 % CI: 4.92, 19.85, P < 0.001). Elderly individuals who quit smoking had a 1.35-fold increased risk compared to non-smokers (HR = 1.35, 95%CI: 1.12, 1.64, P < 0.001). Conclusions: Tuberculosis incidence among the elderly population in China remained alarmingly high. This finding emphasizes the urgent need for implementing proactive case detection measures specifically tailored to address the specific needs of this vulnerable demographic, particularly in individuals who are male, have a history of former or current smoking, and have a low BMI. Moreover, we must not underestimate the influence of former smoking on tuberculosis risk.

N-acetylcysteine protects against neurodevelopmental injuries induced by methylmercury exposure during pregnancy and lactation.

As an extremely dangerous environmental contaminant, methylmercury (MeHg) results in detrimental health effects in human brain nervous system, one of its main targets. However, as a developmental toxicant, the brain of offspring is vulnerable to MeHg during pregnancy and lactation exposure. Unfortunately, mechanisms of neurodevelopmental injuries induced by MeHg have not been fully elucidated. N-acetylcysteine (NAC) has been used for several decades as an antioxidant to antagonize oxidative stress. However, the molecular mechanisms of NAC alleviating MeHg-induced neurodevelopmental toxicity are not clear. Here, for evaluation of the dose-dependent effects of MeHg exposure on neurodevelopmental injuries of offspring, and the possible protective effects of NAC, the pregnant female mice were exposed to MeHg (4, 8, 12 mg/L, respectively) and NAC (50, 100, 150 mg/kg, respectively) from gestational day 1 (GD1) to postnatal day 21 (PND21). Our results indicated that administering MeHg caused behavioral impairment and neuronal injuries in the cerebral cortex of newborn mice. MeHg dose-dependently caused reactive oxygen species (ROS) overproduction and oxidative stress aggravation, together with expression of Nrf2, HO-1, Notch1, and p21 up-regulation, and CDK2 inhibition. NAC treatment dose-dependently antagonized MeHg-induced oxidative stress that may contribute to alleviating neurobehavioral and neurodevelopmental impairments. These results give insight into that NAC can protect against MeHg-induced neurodevelopmental toxicity by its antioxidation capacity.

Construction and identification of lncRNA/circRNA-coregulated ceRNA networks in gemcitabine-resistant bladder carcinoma.

OBJECTIVES: To explore the regulatory networks that underlie the development of chemoresistance in bladder cancer. METHODS: We analyzed profiles of differentially expressed long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), microRNAs (miRNAs) and messenger RNA (mRNAs) in gemcitabine-resistant/sensitive bladder cancer cells using next-generation sequencing data. RESULTS: Hundreds of differentially expressed lncRNAs and miRNAs and thousands of circRNAs and mRNAs were identified. Bioinformatics analysis revealed the chromosomal localizations, classification and coexpression of mRNAs, as well as candidates for cis and trans regulation by lncRNAs. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of differentially expressed mRNAs and circRNAs indicated important functional roles of coregulated RNAs, thus establishing competing endogenous RNA (ceRNA) and protein-protein interactions networks that may underlie chemoresistance in bladder cancer. We demonstrated that lncRNA LINP1 can act as a ceRNA by inhibiting miR-193a-5p to increase TP73 expression; and that lncRNA ESRG and hsa_circ_0075881 can simultaneously bind miR-324-3p to increase ST6GAL1 expression. Modulation of ceRNA network components using ablation and overexpression approaches contributed to gemcitabine resistance in bladder cancer cells. CONCLUSIONS: These results elucidate mechanisms by which lncRNAs and circRNAs coregulate the development of bladder cancer cell resistance to gemcitabine, thus laying the foundation for future research to identify biomarkers and disease targets.

An Intraoperative Sub-Anesthetic Dose of Esketamine on Postoperative Depressive Symptoms in Perimenopausal Women with Breast Cancer Undergoing Modified Radical Mastectomy: Protocol for a Randomized, Triple-Blinded, Controlled Trial.

Background: Depressive symptoms are common among perimenopausal women with breast cancer having modified radical mastectomy. Esketamine exerts antidepressant effects. This study aims to assess whether an intraoperative sub-anesthetic dose of esketamine prevents postoperative depressive symptoms in these patients. Methods: In this randomized, triple-blinded, placebo-controlled trial, we will enroll 130 perimenopausal women (aged 45-60 years) with breast cancer undergoing unilateral modified radical mastectomy. Patients will be randomly assigned with a 1:1 ratio to receive either esketamine (0.25 mg/kg i.v.) or normal saline after anesthesia induction and before skin incision. The primary outcome is the incidence of depressive symptoms at day 30 postoperatively, assessed using the Beck's Depression Inventory (BDI). Secondary outcomes include incidence of depressive symptoms and BDI scores at day 1, 3, and 180 postoperatively, anxiety symptoms and scores at day 1, 3, 30, and 180 postoperatively, pain intensity and quality of recovery at day 1 and 2 postoperatively, nausea and vomiting within 48 hours postoperatively, length of postoperative hospital stay, and cancer-specific outcomes. Data will be analyzed in the modified intention-to-treat population. Discussion: This is the first trial to evaluate the effects of a sub-anesthetic dose of esketamine on depressive symptoms in perimenopausal women after modified radical mastectomy. The results of this study will help to improve their mental health and recovery after breast cancer surgery. Trial Registration: Chinese Clinical Trial Registry (ChiCTR2200064348).

The RNA polymerase II subunit B (RPB2) functions as a growth regulator in human glioblastoma.

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor with a poor prognosis. The growth of GBM cells depends on the core transcriptional apparatus, thus rendering RNA polymerase (RNA pol) complex as a candidate therapeutic target. The RNA pol II subunit B (POLR2B) gene encodes the second largest subunit of the RNA pol II (RPB2); however, its genomic status and function in GBM remain unclear. Certain GBM data sets in cBioPortal were used for investigating the genomic status and expression of POLR2B in GBM. The function of RPB2 was analyzed following knockdown of POLR2B expression by shRNA in GBM cells. The cell counting kit-8 assay and PI staining were used for cell proliferation and cell cycle analysis. A xenograft mouse model was established to analyze the function of RPB2 in vivo. RNA sequencing was performed to analyze the RPB2-regulated genes. GO and GSEA analyses were applied to investigate the RPB2-regulated gene function and associated pathways. In the present study, the genomic alteration and overexpression of the POLR2B gene was described in glioblastoma. The data indicated that knockdown of POLR2B expression suppressed tumor cell growth of glioblastoma in vitro and in vivo. The analysis further demonstrated the identification of the RPB2-regulated gene sets and highlighted the DNA damage-inducible transcript 4 gene as the downstream target of the POLR2B gene. The present study provides evidence indicating that RPB2 functions as a growth regulator in glioblastoma and could be used as a potential therapeutic target for the treatment of this disease.

Adipose-derived stem cell exosomes ameliorate traumatic brain injury through the NLRP3 signaling pathway.

The exosomes of mesenchymal stem cells have immunoregulatory properties and can effectively mitigate secondary neuroinflammation due to traumatic brain injury (TBI). In this study, we found that adipose-derived stem cell exosomes (ADSCs-Exo) could reduce the inflammatory response after traumatic brain injury by reducing NLRP3 inflammasome secretion by microglial. ADSCs-Exo were monitored by Western blot and electron microscopy. An in-vitro lipopolysaccharide (LPS)-caused primary microglia model and a TBI rat model were constructed. Functional recovery was examined using the modified neurological severity score and foot fault tests. Inflammasome inactivation in LPS-stimulated microglial, ADSCs-Exo can reduce the secretion of interleukin (IL)-1ß, IL-6 and tumor necrosis factor α. Compared with PBS-processed controls, the sensorimotor functional recovery was significantly improved by exosome treatment after injury at 14-35 days. Additionally, NLRP3 inflammasome was stimulated within 24 h after TBI. ADSCs-Exo application led to remarkable down-expression of NLRP3 and caspase-1. ADSCs-Exo can ameliorate LPS-induced inflammatory activation by reducing microglial pro-inflammatory cytokines. Moreover, the neuroprotective effect of ADSCs-Exo may be partially attributed to the inhibition thereof on the formation of NLRP3-mediated inflammasome. Such findings imply a potential function of ADSCs-Exo in treating TBI.

Dose pulmonary hemorrhage increase the risk of bronchopulmonary dysplasia in very low birth weight infants?

OBJECTIVE: To evaluate the association between pulmonary hemorrhage and bronchopulmonary dysplasia (BPD) in very low birth weight infants (VLBWIs). METHODS: The study participants were all VLBW newborns admitted from January 1, 2019 to December 31, 2021. The BPD subjects finally included were VLBWIs who survived until the diagnosis was established. This study was divided into pulmonary hemorrhage group (PH group, n = 35) and non-pulmonary hemorrhage group (Non-PH group, n = 190). RESULTS: By univariate analysis it was found that premature rupture of membranes, tracheal intubation in the delivery room, duration of mechanical ventilation, course of invasive ventilation (≥3 courses), pulmonary surfactant (>1 dose), medically and surgically treated patent ductus arteriosus, grade III-IV RDS, early onset sepsis, BPD and moderate to severe BPD showed significant differences between groups (p < .05). By Multivariate analysis, pulmonary hemorrhage did not increase the risks of BPD and moderate to severe BPD (adjusted OR for BPD = 1.710, 95% CI 0.581-5.039; adjusted OR for moderate to severe BPD = 2.401, 95% CI 0.736-7.834). CONCLUSION: It suggests that pulmonary hemorrhage is not associated with the development of BPD and moderate to severe BPD in VLBWIs.

Effectiveness and safety of rectal dexibuprofen versus oral ibuprofen for closure of patent ductus arteriosus in preterm infants with gestational age<34 weeks: A pilot study.

This pilot study aimed to explore the effectiveness and safety of dexibuprofen suppository in the treatment of PDA in preterm infants. Preterm infants with gestational age <34 weeks and color Doppler echocardiographic evidence of hemodynamically significant PDA (hs PDA) with systemic hypoperfusion was intended to be included into this study since January 2020. As of January 1, 2021, this trial had recruited 87 preterm infants who met the inclusion criteria. Neonates were admitted into hospital within 1 hour after birth and were randomly assigned into two groups. Group one included 44 preterm newborns administered with oral ibuprofen. Group two included 43 preterm newborns administered with dexibuprofen suppository. This preliminary study showed that rectal dexibuprofen and oral ibuprofen were both effective for the closure of PDA, and the closure rate of dexibuprofen suppository was comparable to that of oral ibuprofen after the 1st and 2nd courses of treatment. In addition, rectal dexibuprofen did not increase the incidence of adverse outcomes, including bronchopulmonary dysplasia, intraventricular hemorrhage, sepsis, and necrotising enterocolitis. This pilot study showed dexibuprofen suppository is as effective and safe as oral ibuprofen; yet, better designed, muticenter controlled studies are still needed.

RNA sequencing and bioinformatics analysis of circular RNAs in asphyxial newborns with acute kidney injury.

As one kind of novel noncoding RNA, circular RNAs (circRNAs) are involved in different biological processes. Although growing evidences have supported the important role of circRNAs in renal diseases, the mechanism remains unclear in neonatal acute kidney injury (AKI). High-throughput sequencing analysis was used to investigate the expression of circRNAs between hypoxia-induced AKI neonates and controls. Bioinformatics analysis was conducted to predict the function of differentially expressed circRNAs. Finally, the differentially expressed circRNAs were screened and determined by quantitative real-time PCR (qPCR). (1) A total of 296 differentially expressed circRNAs were identified (Fold change >2 and p < 0.05). Of them, 184 circRNAs were markedly upregulated, and 112 were significantly downregulated in the AKI group. (2) The pathway analysis showed that ubiquitin-mediated proteolysis, renal cell carcinoma, Jak-STAT, and HIF-1 signaling pathways participated in AKI. (3) Top five upregulated and five downregulated circRNAs with higher fold changes were selected for qPCR validation. Hsa_circ_0008898 (Fold Change = 5.48, p = 0.0376) and hsa_circ_0005519 (Fold Change = 4.65, p = 0.0071) were significantly upregulated, while hsa_circ_0132279 (Fold Change = -4.47, p = 0.0008), hsa_circ_0112327 (Fold Change = -4.26, p = 0.0048), and hsa_circ_0017647 (Fold Change = -4.15, p = 0.0313) were significantly downregulated in asphyxia-induced AKI group compared with the control group. This study could contribute to future research on neonatal AKI and facilitate the identification of novel therapeutic targets.

Methylmercury promotes oxidative stress and autophagy in rat cerebral cortex: Involvement of PI3K/AKT/mTOR or AMPK/TSC2/mTOR pathways and attenuation by N-acetyl-L-cysteine.

Methylmercury (MeHg) is a potent neurotoxicant that could induce oxidative stress and autophagy. However, the underlying mechanisms through which MeHg affects the central nervous system have not been fully elucidated, and little has been known of the interaction between oxidative stress and autophagy. Therefore, rats were administrated with different MeHg concentrations to evaluate the neurotoxic effects and autophagy in cerebral cortex. Moreover, we have investigated the neuroprotective role of N-acetyl-L-cysteine (NAC) against MeHg-induced neurotoxicity in order to estimate the regulation effects of oxidative stress on autophagy. A total of 64 rats, 40 of which were randomly divided into control and MeHg-treated (4, 8 and 12 µ mol/kg) groups. The remaining 24 rats were divided into control, NAC control (1 mmol/kg), 12 µ mol/kg MeHg, and NAC pretreatment. Administration of 12 µ mol/kg MeHg significantly increased behavioral and pathological abnormalities, and autophagy levels. In addition, the oxidative stress levels increased, together with abnormal expression of autophagy-related molecules. Pretreatment with NAC significantly prevented MeHg-induced oxidative stress and PI3K/AKT/mTOR or AMPK/TSC2/mTOR-mediated autophagy. In conclusion, the present study suggested that oxidative stress can regulate autophagy through PI3K/AKT/mTOR or AMPK/TSC2/mTOR pathways. This study provides a theoretical basis for the study and treatment of MeHg-induced neurotoxicity.

Characteristics of Adenosine-to-Inosine RNA editing-based subtypes and novel risk score for the prognosis and drug sensitivity in stomach adenocarcinoma.

Stomach adenocarcinoma (STAD) is always characterized by high mortality and poor prognosis with drug resistance and recrudescence due to individual genetic heterogeneity. Adenosine-to-Inosine RNA editing (ATIRE) has been reported associated with multiple tumors but the potential connection between ATIRE-related signatures and STAD remains unclear. In this study, we comprehensively elevated the genetic characteristics of ATIRE in STAD patients and first screened five vital survival-related ATIRE sites to identify a novel ATIRE-Risk score. Based on the risk scores, we further divided the patients into two different subtypes with diverse clinical characteristics and immune landscapes including immune cell infiltration (ICI), tumor microenvironment (TME), and immune checkpoint expression analysis. The low-risk subgroups, associated with better survival prognosis, were characterized by activated immune-cells, higher immune scores in TME, and down-expression of immunotherapy checkpoints. Moreover, different expressional genes (DEGs) between the above subtypes were further identified and the activation of immune-related pathways were found in low-risk patients. The stratified survival analysis further indicated patients with low-risk and high-tumor mutation burden (TMB) exhibited the best prognosis outcomes, implying the role of TMB and ATIRE-Risk scores was synergistic for the prognosis of STAD. Interestingly, anti-tumor chemotherapeutic drugs all exhibited lower IC50 values in low-risk subgroups, suggesting these patients might obtain a better curative response from the combined chemotherapy of STAD. Finally, combined with classical clinical features and ATIRE-Risk scores, we successfully established a promising nomogram system to accurately predict the 1/3/5-years survival ratio of STAD and this model was also estimated with high diagnostic efficiency and stable C-index with calibration curves. These significant ATIRE sites are promising to be further explored and might serve as a novel therapeutic target for STAD treatment.

Relative vaccine effectiveness against Delta and Omicron COVID-19 after homologous inactivated vaccine boosting: a retrospective cohort study.

ObjectiveTwo COVID-19 outbreaks occurred in Henan province in early 2022-one was a Delta variant outbreak and the other was an Omicron variant outbreak. COVID-19 vaccines used at the time of the outbreak were inactivated, 91.8%; protein subunit, 7.5%; and adenovirus5-vectored, 0.7% vaccines. The outbreaks provided an opportunity to evaluate variant-specific breakthrough infection rates and relative protective effectiveness of homologous inactivated COVID-19 vaccine booster doses against symptomatic infection and pneumonia. DESIGN: Retrospective cohort study METHODS: We evaluated relative vaccine effectiveness (rVE) with a retrospective cohort study of close contacts of infected individuals using a time-dependent Cox regression model. Demographic and epidemiologic data were obtained from the local Centers for Disease Control and Prevention; clinical and laboratory data were obtained from COVID-19-designated hospitals. Vaccination histories were obtained from the national COVID-19 vaccination dataset. All data were linked by national identification number. RESULTS: Among 784 SARS-CoV-2 infections, 379 (48.3%) were caused by Delta and 405 (51.7%) were caused by Omicron, with breakthrough rates of 9.9% and 17.8%, respectively. Breakthrough rates among boosted individuals were 8.1% and 4.9%. Compared with subjects who received primary vaccination series ≥180 days before infection, Cox regression modelling showed that homologous inactivated booster vaccination was statistically significantly associated with protection from symptomatic infection caused by Omicron (rVE 59%; 95% CI 13% to 80%) and pneumonia caused by Delta (rVE 62%; 95% CI 34% to 77%) and Omicron (rVE 87%; 95% CI 3% to 98%). CONCLUSIONS: COVID-19 vaccination in China provided good protection against symptomatic COVID-19 and COVID-19 pneumonia caused by Delta and Omicron variants. Protection declined 6 months after primary series vaccination but was restored by homologous inactivated booster doses given 6 months after the primary series.

[Pulmonary hemorrhage in very low birth weight infants: risk factors and clinical outcome]. / æžä½Žå‡ºç”Ÿä½“é‡å„¿å‘ç”Ÿè‚ºå‡ºè¡€çš„å±é™©å› ç´ åŠå ¶ä¸´åºŠè½¬å½’.

OBJECTIVES: To investigate the risk factors for pulmonary hemorrhage and its clinical outcome in very low birth weight infants (VLBWIs). METHODS: The medical data were collected from all live VLBWIs (gestational age <35 weeks) who were admitted to Jiangsu Women and Children Health Hospital and Children's Hospital of Nanjing Medical University between January 1, 2020 and December 31, 2021. Based on inclusion and exclusion criteria, 574 VLBWIs were included in the study, with 44 VLBWIs in the pulmonary hemorrhage group and 530 VLBWIs in the non-pulmonary hemorrhage group. The clinical data were compared between the two groups. A multivariate logistic regression analysis was used to identify the risk factors for pulmonary hemorrhage. RESULTS: There were significant differences between the two groups in maternal age, rate of positive-pressure ventilation for resuscitation, rate of tracheal intubation for resuscitation, and minimum body temperature within 1 hour after birth (P<0.05). The pulmonary hemorrhage group had a higher proportion of VLBWIs with grade Ⅲ-Ⅳ respiratory distress syndrome or early-onset sepsis than the non-pulmonary hemorrhage group (P<0.05). The pulmonary hemorrhage group also had a higher proportion of VLBWIs with a capillary refilling time of >3 seconds within 1 hour after birth and with the maximum positive end-expiratory pressure (PEEP) of <5 cmH2O within 24 hours after birth (P<0.05). The multivariate regression analysis showed that maternal age of 30-<35 years (OR=0.115, P<0.05) was a protective factor against pulmonary hemorrhage, while a lower temperature (<34°C) within 1 hour after birth, the maximum PEEP of <5 cm H2O within 24 hours after birth, and early-onset sepsis were risk factors for pulmonary hemorrhage (OR=11.609, 11.118, and 20.661, respectively; P<0.05). For all VLBWIs, the pulmonary hemorrhage group had a longer duration of invasive ventilation and a higher mortality rate than the non-pulmonary hemorrhage group (P<0.05); for the survival VLBWIs, the pulmonary hemorrhage group had a higher incidence rate of bronchopulmonary dysplasia than the non-pulmonary hemorrhage group (P<0.05). CONCLUSIONS: Maintaining the stability of temperature, giving appropriate PEEP, and identifying sepsis as early as possible can reduce the incidence rate of pulmonary hemorrhage, thereby helping to reduce the incidence of bronchopulmonary dysplasia and mortality in VLBWIs.

DLGAP1-AS2 promotes human colorectal cancer progression through trans-activation of Myc.

Substantial evidence suggests that non-coding RNA plays a vital role in human cancer, especially long non-coding RNA (lncRNA) with a length greater than 200nt. Herein, we found a lncRNA facilitating human colorectal cancer (CRC) progression. DLGAP1-AS2 was significantly increased in CRC tissues and cell lines. Knockdown of DLGAP1-AS2 inhibited CRC cell proliferation, migration, invasion in vitro, and tumor growth in vivo. The subcellular localization of DLGAP1-AS2 was translocated from the cytoplasm of normal cells to the nucleus of CRC cells due to reduced levels of N6-methyladenosine (m6A) modification. Further, through the screening of a series of signal pathways, we found that Myc pathway was involved in the effect of DLGAP1-AS2. Silencing of DLGAP1-AS2 markedly reduced Myc mRNA and protein levels. Blockade of Myc effectively abolished the enhanced aggressive behaviors of CRC cells caused by DLGAP1-AS2 overexpression. Mechanistically, DLGAP1-AS2 directly bound CTCF, a well-known transcriptional repressor of Myc, resulting in reduced binding of CTCF on Myc promoter and activating Myc transcription. The second hairpin structure of DLGAP1-AS2 was critical for the interaction between DLGAP1-AS2 and CTCF in the nucleus. Taken together, our study reveals the oncogenic regulatory axis of DLGAP1-AS2/CTCF/Myc in CRC, implying a promising targeted therapy for clinical application.

Integrative analyses identify HIF-1α as a potential protective role with immune cell infiltration in adamantinomatous craniopharyngioma.

Craniopharyngiomas (CPs) are histologically benign tumors located in the sellar-suprasellar region. Although the transcriptome development in recent years have deepened our knowledge to the tumorigenesis process of adamantinomatous craniopharyngioma (ACP), the peritumoral immune infiltration of tumor is still not well understood. In this study, weighted gene coexpression network analysis (WGCNA) was applied to identify different gene modules based on clinical characteristics and gene expression, and then, the protein-protein interaction (PPI) network with the Cytohubba plug-in were performed to screen pivotal genes. In addition, immune cell infiltration (ICI) analysis was used to evaluate the immune microenvironment of ACP patients. In total, 8,568 differential expression genes were identified based on our datasets and two microarray profiles from the public database. The functional enrichment analysis revealed that upregulated genes were mainly enriched in immune-related pathways while downregulated genes were shown in the hormone and transduction of signaling pathways. The WGCNA investigated the most relevant modules, and 1,858 hub genes was detected, from which the PPI network identified 14 pivotal genes, and the Hypoxia-inducible factor 1-alpha (HIF-1α) pathway including four critical genes may be involved in the development of ACP. Moreover, naïve CD4+ and CD8+ T cells were decreased while specific subtypes of T cells were significantly increased in ACP patients according to ICI analysis. Validation by immunofluorescence staining revealed a higher expression of HIF-1α in ACP (ACP vs. control) and adult-subtype (adult vs. children), suggesting a possible state of immune system activation. Notably, children with low HIF-1α scores were related to the hypothalamus involvement and hydrocephalus symptoms. In this study, we successfully identified HIF-1α as a key role in the tumorigenesis and development of ACP through comprehensive integrated analyses and systematically investigated the potential relationship with immune cells in ACP. The results may provide valuable resources for understanding the underlying mechanisms of ACP and strengthen HIF-1α as a potential immunotherapeutic target in clinical application.

Soy oil and SPI based-oleogels structuring with glycerol monolaurate by emulsion-templated approach: Preparation, characterization and potential application.

In this study, soybean oil-based oleogels were prepared using soy-protein isolate (SPI) and glycerol monolaurate (GML) in an emulsion-template approach. The rheological, texture, microstructure, and oil-retention properties of the obtained oleogels were analyzed. Results showed that the soy oil-based oleogel prepared with 6 wt% GML exhibited high oil loss, low-hardness, and needle-like morphology compared to the soy-oil/SPI-based oleogel. On the other hand, soy oil-based /SPI-based oleogels structured by 3 or 6 wt% GML presented moderate thermal-stability and lowest oil loss than those prepared without GML. Furthermore, SPI-based oleogel containing 6 wt% GML showed highest free fatty acids release (62.07%) with significantly improved elastic modulus and apparent viscosity. Additionally, the obtained oleogels displayed the occurrence of van der Waals interactions and intermolecular hydrogen bonds, presenting enhanced thermal stability. These results contribute to a better understanding of oleogelation-based emulsions for formulating trans-free and low-saturated foodstuffs with desired physical and functional properties.