Investigating shared genetic architecture between inflammatory bowel diseases and primary biliary cholangitis.

Background & Aims: Inflammatory bowel disease (IBD) is commonly associated with extraintestinal complications, including autoimmune liver disease. The co-occurrence of IBD and primary biliary cholangitis (PBC) has been increasingly observed, but the underlying relationship between these conditions remains unclear. Methods: Using summary statistics from genome-wide association studies (GWAS), we investigated the causal effects between PBC and IBD, including Crohn's disease (CD) and ulcerative colitis (UC). We also analyzed the shared genetic architecture between IBD and PBC using data from GWAS, bulk-tissue RNA sequencing, and single cell RNA sequencing, and explored potential functional genes. Result: There was a strong positive genetic correlation between PBC and IBD (linkage disequilibrium score regression: rg = 0.2249, p = 3.38 × 10-5). Cross-trait analysis yielded 10 shared-risk single nucleotide polymorphisms (SNPs), as well as nine novel SNPs, which were associated with both traits. Using Mendelian randomization, a stable causal effect was established of PBC on IBD. Genetically predicted PBC was found to have a risk effect on IBD (1.105; 95% CI: 1.058-1.15; p = 1.16 × 10-10), but not vice versa. Shared tissue-specific heritability enrichment was identified for PBC and IBD (including CD and UC) in lung, spleen, and whole-blood samples. Furthermore, shared enrichment was observed of specific cell types (T cells, B cells, and natural killer cells) and their subtypes. Nine functional genes were identified based on summary statistics-based Mendelian randomization. Conclusions: This study detected shared genetic architecture between IBD and PBC and demonstrated a stable causal relationship of genetically predicted PBC on the risk of IBD. These findings shed light on the biological basis of comorbidity between IBD and PBC, and have important implications for intervention and treatment targets of these two diseases simultaneously. Impact and Implications: The discovery of novel shared single nucleotide polymorphisms (SNPs) and functional genes provides insights into the common targets between inflammatory bowel disease (IBD) and primary biliary cholangitis (PBC), serving as a basis for new drug development and contributing to the study of disease pathogenesis. Additionally, the established significant causality and genetic correlation underscore the importance of clinical intervention in preventing the comorbidity of IBD and PBC. The enrichment of SNP heritability in specific tissues and cell types reveals the role of immune factors in the potential disease mechanisms shared between IBD and PBC. This stimulates further research on potential interventions and could lead to the development of new targets for immune-based therapies.

High-fat diet-induced obesity causes intestinal Th17/Treg imbalance that impairs the intestinal barrier and aggravates anxiety-like behavior in mice.

The prevalence of autism spectrum disorders (ASD) has been steadily increasing, and growing evidence suggests a link between high-fat diet (HFD), obesity, and ASD; however, the mechanism underlying this association remains elusive. Herein, BTBR T + tf/J (BTBR) inbred mice (a mouse ASD model) and C57Bl/6J (C57) mice were fed an HFD and normal diet (ND) for 8 weeks (groups: C57 + ND, C57 + HFD, BTBR + ND, and BTBR + HFD). Subsequently, mice underwent behavioral assessments, followed by intestinal tissues harvesting to detect expression of intestinal barrier proteins and inflammatory factors and immune cell numbers, and a correlation analysis. HFD-fed BTBR mice developed obesity, elevated blood sugar, significantly aggravated anxiety-like behaviors, impaired intestinal barrier function, intestinal inflammation with elevated CD4+IL17+ T (Th17) cells and reduced CD4+Foxp3+ T (Treg) cells, exhibiting reduced expression of proteins related to AMPK regulatory pathway (AMPK, p-AMPK, SIRT1). Correlation analysis revealed that the degree of behavioral anxiety, the degree of intestinal barrier damage, the severity of intestinal inflammation, and the degree of immune cell imbalance positively correlated with each other. Accordingly, HFD-induced obesity may cause intestinal Th17/Treg imbalance via the AMPK-SIRT1 pathway, leading to an inflammatory environment in the intestine, impairing intestinal barrier function, and ultimately aggravating anxiety-like behaviors in mice.

Metabolomics profiling reveals low blood tyrosine levels as a metabolic feature of newborns from systemic lupus erythematosus pregnancies.

Introduction: Pregnancy outcomes of patients with systemic lupus erythematosus (SLE) have improved over the past four decades, leading to an increased desire for pregnancy among this cohort. However, the offspring of patients with SLE still face the risks of preterm birth, low birth weight, learning disabilities, and neurological disorders, while the causes underlying these risks remain unclear. Methods: In this study, we analyzed the blood metabolic features of neonates born to 30 SLE patients and 52 healthy control mothers by employing tandem mass spectrometry with the dual aims of identifying the etiology of metabolic features specific to infants born from mothers with SLE and providing new insights into the clinical management of such infants. Results: We found significant differences in serum metabolite levels between infants born from mothers with SLE and those born from mothers without SLE, including 15 metabolites with reduced serum levels. Further analysis revealed a disrupted tyrosine metabolism pathway in the offspring of mothers with SLE. Discussion: By constructing a composite model incorporating various factors, such as serum tyrosine levels, gestational age, and birth weight, we were able to accurately differentiate between newborns of SLE and non-SLE pregnancies. Our data reveal significant differences in serum concentrations of amino acids and acylcarnitines in newborns born to mothers with SLE. We conclude that the reduction of blood L-tyrosine levels is a feature that is characteristic of adverse neurological outcomes in infants born from mothers with SLE.

Improving the electrochemical characteristics and performance of a neutral all-iron flow battery by using the iron reduction bacteria.

At present, the all-iron redox flow batteries (RFBs) have greater application potential due to high accessibility of electrolytes compared to traditional RFBs. Meanwhile, although electroactive bacteria can accelerate the electrons transfer, their potential to improve the performance of RFBs has been overlooked. Previously, we had confirmed that ferrous-oxidizing bacteria (FeOB) could enhance the performance of an all-iron RFB, therefore we conducted several batch experiments and chronopotentiometry experiments by using the ferric-reducing bacteria (FeRB) or mixed culture (FeOB and FeRB) to demonstrate whether they have the same or stronger effects on Fe3+-DTPA/Na4[Fe(CN)6] RFB. The results showed that the experimental reactors could achieve higher charging current density and initial cathodic potential during constant voltage charging process. The electrochemical impedance spectroscopy data and cyclic voltammetry curves demonstrated that the polarization impedance increased slower and reduction peak potential of experimental groups also emerged a positive shift compared to CK. According to chronopotentiometry experiments results, the microbes could function at maximum 0.3 M, 12 mA/cm2, and also improved the charging specific capacity. Combined the SEM pictures and microbial composition analysis, the main functional electroactive FeRB were Alcaligenes, Corynebacterium and Bacillus, which indicated to have important potential in improving the performance of RFBs.

Using ferrous-oxidizing bacteria to enhance the performance of a pH neutral all-iron flow battery.

Among various redox flow batteries (RFBs), the all-iron RFBs have greater application potential due to high accessibility of electrolytes. However, the potential of microaerobic ferrous-oxidizing bacteria (FeOB) to improve the performance of RFB has been neglected. Here, several experiments were conducted using Fe2+-diethylenetriaminepentaacetic acid (DTPA)/Na3[Fe(CN)6] as a redox couple for investigating the enhanced performance by FeOB in this RFB. Results showed that the maximum current density of experimental reactors could achieve 22.56 A/m2 at 0.1 M, whereas power density could still maintain 3.42 W/m2(16.96 A/m2 and 1.58 W/m2 for control group); meantime, the polarization impedance of anode increased slower and Fe2+-DTPA oxidation peak emerged maximum 494 mV negative shift. With increased electrolyte concentration in chronopotentiometry experiments, the experimental reactor achieved higher discharging specific capacity at 0.3 M, 10 mA/cm2. Microbial composition analysis showed maximum 75% is Brucella, indicating Brucella has ferrous-oxidizing electroactivity.

Melatonin alleviates necrotizing enterocolitis by reducing bile acid levels through the SIRT1/FXR signalling axis.

Bile acids (BAs) have increasingly been implicated in the onset and progression of necrotizing enterocolitis (NEC); multiple findings have demonstrated their ability to induce damage to the intestinal epithelium, thereby exacerbating disease severity. Although we previously showed that melatonin was able to treat NEC by correcting the Treg/Th17 imbalance, the modulatory effect of melatonin on BAs remains unclear. In this study, we conducted transcriptome analysis on intestinal tissues from patients with NEC and validated these findings. Subsequently, we treated mice with melatonin alone or in combination with an agonist/inhibitor of Sirtuin 1 (SIRT1) to assess faecal and serum BA levels, the expression levels of BA transporters and regulators, and the extent of intestinal injury. Our transcriptome results indicated dysregulation of BA metabolism and abnormal expression of BA transporters in patients with NEC, which were also observed in our NEC mouse model. Furthermore, exogenous BAs were found to aggravate NEC severity in mice. Notably, melatonin effectively restored the aberrant expression of BA transporters, such as apical membrane sodium-dependent bile acid transporters (ASBT), ileal bile acid-binding protein (IBABP), and organic solute transporter-alpha (OST-α), by upregulating SIRT1 expression while reducing farnesoid X receptor (FXR) acetylation, consequently leading to decreased serum and faecal BA levels and mitigated NEC severity. Thus, we propose a potential mechanism through which melatonin reduces BA levels via the SIRT1/FXR signalling axis in an NEC mouse model. Collectively, these results highlight that melatonin holds promise for reducing BA levels and represents a promising therapeutic strategy for treating NEC.

High-dimensional mass cytometry reveals systemic and local immune signatures in necrotizing enterocolitis.

Objective: Patients with necrotizing enterocolitis display severe gastrointestinal complications of prematurity, but the mechanism driving this clinical profile remains unknown. We used mass cytometry time-of-flight to characterize and compare immune cell populations in the blood and intestine tissue from patients with and without (controls) necrotizing enterocolitis at single-cell resolution. Methods: We completed a deep mapping of the immune system of the peripheral blood mononuclear cells and intestinal mucosa tissue using mass cytometry to evaluate immune cell types, which revealed global immune dysregulation characteristics underlying necrotizing enterocolitis. Results: Compared with controls, natural killer cells display signs of heightened activation and increased cytotoxic potential in the peripheral blood and mucosa of patients with necrotizing enterocolitis. Furthermore, CD4+ T effector memory cells, non-classical monocytes, active dendritic cells, and neutrophils were specifically enriched in the mucosa, suggesting trafficking from the periphery to areas of inflammation. Moreover, we mapped the systemic and local distinct immune signatures suggesting patterns of cell localization in necrotizing enterocolitis. Conclusion: We used mass cytometry time-of-flight technology to identify immune cell populations specific to the peripheral blood and intestinal mucosa tissue from patients with necrotizing enterocolitis and controls. This information might be used to develop precise diagnosis and therapies that target specific cell populations in patients with necrotizing enterocolitis.

Congenital scrub typhus: a case report and literature review.

Background: This study aimed to analyze the clinical course of a newborn with congenital scrub typhus caused by vertical transmission and explore early diagnosis and treatment strategies. The clinical data of the neonate were retrospectively analyzed and the related literature was reviewed. Case presentation: The newborn was a full-term one, with a good Apgar score at birth. The neonate had apnea at 3 h of life, requiring NICU care and IV antibiotics (piperacillin) for suspected sepsis. An examination revealed hepatosplenomegaly. Blood tests revealed anemia and thrombocytopenia and a chest x-ray showed patchy inflammation. On the second day of life, he developed a fever. On the third day of life, he required mechanical ventilation because his condition worsened after he presented with dyspnea, hypotension, depressed sensorium, and other signs of sepsis. Importantly, the neonate's mother had a history of scrub typhus at 31+ weeks of gestation. While the blood culture result was still pending, high-throughput sequencing of blood and cerebrospinal fluid was performed. To address the suspected scrub typhus infection, oral azithromycin dry suspension was added to the treatment regimen. High-throughput sequencing results on the 5th day of life confirmed a significant presence of 16SrRNA sequences in the blood, suggesting an Orientia tsutsugamushi infection. The neonate steadily recovered and was discharged 16 days after hospitalization. The neonate was followed up for 9 months, and the outcome was favorable with normal growth and development. Conclusions: This article reports a case of congenital Orientia tsutsugamushi infection, a rare condition caused by vertical transmission. Our review of the literature, combined with the presented case, brings the total number of documented congenital scrub typhus cases caused by vertical transmission to eight. Regrettably, one patient from this group unexpectedly died on the 10th day of hospitalization, resulting in a mortality rate of 12.5% (1/8). The special transmission mode and clinical manifestations of this disease will serve as an alert to doctors for timely diagnosis and treatment. Because of the non-specific clinical manifestations of congenital scrub typhus, limited understanding, low index of suspicion among clinicians, and a lack of diagnostic facilities, scrub typhus is seriously underdiagnosed in pregnant women, fetuses, and neonates.

Gastric peroral endoscopic pyloromyotomy for the treatment of congenital hypertrophic pyloric stricture in an infant with a self-made bite block.

Gastric per-oral endoscopic myotomy (G-POEM) is reported to be a promising treatment for refractory gastroparesis, on the other hand, it is also an effective treatment for congenital hypertrophic pyloric stenosis (CHPS). Here, we want to report a case in which G-POEM was performed in an infant with CHPS.

Discrimination of blood metabolomics profiles in neonates with idiopathic polyhydramnios.

This study aimed to compare the blood metabolic status of neonates with idiopathic polyhydramnios (IPH) and those with normal amniotic fluid, and to explore the relationship between IPH and fetal health. Blood metabolites of 32 patients with IPH and 32 normal controls admitted to the Sixth Affiliated Hospital of Sun Yat-sen University between January 2017 and December 2022 were analyzed using liquid chromatography-mass spectrometry (LC-MS/MS). Orthogonal partial least squares discriminant analysis (OPLS-DA) and metabolite enrichment analyses were performed to identify the differential metabolites and metabolic pathways. There was a significant difference in the blood metabolism between newborns with IPH and those with normal amniotic fluid. Six discriminant metabolites were identified: glutamate, serine, asparagine, aspartic acid, homocysteine, and phenylalanine. Differential metabolites were mainly enriched in two pathways: aminoacyl-tRNA biosynthesis, and alanine, aspartate, and glutamate metabolism. CONCLUSIONS: This study is the first to investigate metabolomic profiles in newborns with IPH and examine the correlation between IPH and fetal health. Differential metabolites and pathways may affect amino acid synthesis and the nervous system. Continuous attention to the development of the nervous system in children with IPH is necessary. WHAT IS KNOWN: • There is an increased risk of adverse pregnancy outcomes with IPH, such as perinatal death, neonatal asphyxia, neonatal intensive care admission, cesarean section rates, and postpartum hemorrhage. • Children with a history of IPH have a higher proportion of defects than the general population, particularly central nervous system problems, neuromuscular disorders, and other malformations. WHAT IS NEW: • In neonates with IPH, six differential metabolites were identified with significant differences and good AUC values using LC-MS/MS analysis: glutamic acid, serine, asparagine, aspartic acid, homocysteine, and phenylalanine, which were mainly enriched in two metabolic pathways: aminoacyl-tRNA biosynthesis and alanine, aspartate, and glutamate metabolism. • These differential metabolites and pathways may affect amino acid synthesis and development of the nervous system in neonates with IPH.

Increased acylcarnitine ratio indices in newborn screening for carnitine-acylcarnitine translocase deficiency shows increased sensitivity and reduced false-positivity.

Background: Carnitine-acylcarnitine translocase (CACT) deficiency is a rare autosomal recessive metabolic disorder of mitochondrial long-chain fatty acid oxidation. Newborn screening via tandem mass spectrometry (MS/MS) technology enables early diagnosis. However, previous analyses of MS/MS data of patients showed that some results were misdiagnosed because they did not show typical acylcarnitine profiles of CACT deficiency. This study aimed to identify additional indices to assist the diagnosis of CACT deficiency. Methods: To evaluate the acylcarnitine profile and the acylcarnitine ratios of individuals with CACT deficiency, the MS/MS data of 15 patients diagnosed via genetic testing were retrospectively analysed. The sensitivity and false-positive rates of primary acylcarnitine markers and ratio indices were validated using the data from 28,261 newborns and 53 false-positive cases. Additionally, the MS/MS data of 20 newborns carrying the c.199-10T>G mutation in SLC25A20 and 40 normal controls were compared to verify whether the carriers had abnormal acylcarnitine concentrations. Results: The acylcarnitine profiles from 15 patients were classified into three categories using C12, C14, C16, C18, C16:1, C18:1, and C18:2 as the primary diagnostic markers. The first category represented a typical profile (P1-P6). The second category for patients P7 and P8 showed a significant decrease in the C0 level and a normal concentration of long-chain acylcarnitines. The third category for patients P9-P15 showed the presence of interfering acylcarnitines. The second and third categories may have been misdiagnosed. An acylcarnitine ratio analysis showed that C14/C3, C16/C2, C16/C3, C18/C3, C16:1/C3, and C16:1-OH/C3 were significantly increased in all 15 patients. The verification of 28,261 newborn screening results showed that the false-positive rate of ratios, except for (C16 + C18)/C0, was lower than that of acylcarnitine indices (0.02-0.08% vs. 0.16-0.88%). None of the single long-chain acylcarnitines could separate patients from the false-positive cases; however, all ratios produced good discrimination between the two groups. Conclusions: Based on the primary acylcarnitine markers alone, CACT deficiency can be misdiagnosed in newborn screening. The ratios of the primary markers (C16 + C18:1)/C2, C16/C2, C16:1/C3, and C16:1-OH/C3 can facilitate the diagnosis of CACT deficiency, thereby increasing sensitivity and reducing false-positivity.

Maternal melatonin supplementation shapes gut microbiota and protects against inflammation in early life.

BACKGROUND: Gut microbiota colonization is critical for immune education and nutrient metabolism. Research shows that melatonin has beneficial effects as a therapy for many diseases via modulating gut dysbiosis. However, it is unclear whether melatonin alters gut microbiota colonization in early life. METHODS: In the experimental group (Mel), mice were intraperitoneally injected with melatonin at 10 mg/kg body weight for embryonic days 14-16 and received drinking water containing 0.4 mg/mL melatonin until 28 days postpartum. In the control group (Ctrl), mice were injected with the same volume of 2.5% ethanol in saline and provided with standard water. Two more groups were created by treating neonatal mice with 20 mg/kg lipopolysaccharide (LPS) to induce inflammation, resulting in the groups Ctrl + LPS and Mel + LPS, respectively. We examined the gut microbiota of the neonatal mice in the Ctrl and Mel group on Days 7, 14, 21, and 28 post-birth. On Day 14, melatonin and short-chain fatty acids (SCFAs) concentrations were measured in the Ctrl and Mel group and the mice were treated with LPS to be evaluated for intestinal injury and inflammatory response 15 h post treatment. According to the result of the SCFAs concentrations, some neonatal mice were intraperitoneally injected with 500 mg/kg sodium butyrate (SB) from Days 11-13, intraperitoneally injected with 20 mg/kg LPS on Day 14, and then euthanized by carbon dioxide inhalation the next morning. Intestinal injury and inflammatory responses were evaluated in the Ctrl + LPS and SB + LPS groups, respectively. RESULTS: By Day 14, it was evident that maternal melatonin supplementation significantly increased the relative abundance of Firmicutes in the ileal [61.03 (35.35 - 76.18) % vs. 98.02 (86.61 - 99.01) %, P = 0.003] and colonic [73.88 (69.77 - 85.99) % vs. 96.16 (94.57 - 96.34) %, P = 0.04] microbiota, the concentration of melatonin (0.79 ± 0.49 ng/ml vs. 6.11 ± 3.48 ng/ml, P = 0.008) in the gut lumen, and the fecal butyric acid (12.91 ± 5.74 µg/g vs. 23.58 ± 10.71 µg/g, P = 0.026) concentration of neonatal mice. Melatonin supplementation, and sodium butyrate treatment markedly alleviated intestinal injury and decreased inflammatory factors in neonatal mice. CONCLUSION: This study suggests that maternal melatonin supplementation can shape the gut microbiota and metabolism of offspring under normal physiological conditions and protect them against LPS-induced inflammation in early life.

Dynamic changes of the gut microbial colonization in preterm infants with different time points after birth.

Risks associated with preterm birth are unevenly distributed across all gestations. At earlier gestational ages, complications such as necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) conditions are significantly more common and are associated with a shift in the composition of the gut microbiome. Conventional bacterial culture techniques demonstrate that the colonization of the gut microbiota of preterm infants differs significantly from that of healthy-term infants. The current study aimed to investigate the impact of preterm infancy on the dynamic changes of fecal microbiota in preterm infants at different time points (1, 7, 14, 21, 28, and 42 days) after birth. We selected 12 preterm infants hospitalized in the Sixth Affiliated Hospital of Sun Yat-sen University from January 2017 to December 2017. A total of 130 fecal specimens from preterm infants were analyzed using 16S rRNA gene sequencing. We found that the colonization process of fecal microbiota in preterm infants is highly dynamic at different time points after birth, i.e., Exiguobacterium, Acinetobacter, and Citrobacter showed a declining abundance pattern with the advancement of age, while the bacterial groups of Enterococcus (Klebsiella and Escherichia coli) gradually grew and became the main microbiota during the development of fecal microbiota in preterm infants at the age of 42 days. Furthermore, the colonization of intestinal Bifidobacteria in preterm infants was relatively late and did not rapidly become the predominant microbiota. Moreover, the results also showed the presence of Chryseobacterium bacterial group, whose colonization was different in different time point groups. Conclusively, our findings deepen our comprehension and offer new perspectives on targeting particular bacteria in the treatment of preterm infants at different time points after birth.

Identification and verification of feature biomarkers associated with immune cells in neonatal sepsis.

BACKGROUND: Neonatal sepsis (NS), a life-threatening condition, is characterized by organ dysfunction and is the most common cause of neonatal death. However, the pathogenesis of NS is unclear and the clinical inflammatory markers currently used are not ideal for diagnosis of NS. Thus, exploring the link between immune responses in NS pathogenesis, elucidating the molecular mechanisms involved, and identifying potential therapeutic targets is of great significance in clinical practice. Herein, our study aimed to explore immune-related genes in NS and identify potential diagnostic biomarkers. Datasets for patients with NS and healthy controls were downloaded from the GEO database; GSE69686 and GSE25504 were used as the analysis and validation datasets, respectively. Differentially expressed genes (DEGs) were identified and Gene Set Enrichment Analysis (GSEA) was performed to determine their biological functions. Composition of immune cells was determined and immune-related genes (IRGs) between the two clusters were identified and their metabolic pathways were determined. Key genes with correlation coefficient > 0.5 and p < 0.05 were selected as screening biomarkers. Logistic regression models were constructed based on the selected biomarkers, and the diagnostic models were validated. RESULTS: Fifty-two DEGs were identified, and GSEA indicated involvement in acute inflammatory response, bacterial detection, and regulation of macrophage activation. Most infiltrating immune cells, including activated CD8 + T cells, were significantly different in patients with NS compared to the healthy controls. Fifty-four IRGs were identified, and GSEA indicated involvement in immune response and macrophage activation and regulation of T cell activation. Diagnostic models of DEGs containing five genes (PROS1, TDRD9, RETN, LOC728401, and METTL7B) and IRG with one gene (NSUN7) constructed using LASSO algorithm were validated using the GPL6947 and GPL13667 subset datasets, respectively. The IRG model outperformed the DEG model. Additionally, statistical analysis suggested that risk scores may be related to gestational age and birth weight, regardless of sex. CONCLUSIONS: We identified six IRGs as potential diagnostic biomarkers for NS and developed diagnostic models for NS. Our findings provide a new perspective for future research on NS pathogenesis.

[Blood metabolites in preterm infants with retinopathy of prematurity based on tandem mass spectrometry: a preliminary study]. / åŸºäºŽè´¨è°±æŠ€æœ¯çš„æ—©äº§å„¿è§†ç½‘è†œç— è¡€ä»£è°¢äº§ç‰©çš„åˆæ­¥ç ”ç©¶.

OBJECTIVES: To study new biomarkers for the early diagnosis of retinopathy of prematurity (ROP) by analyzing the differences in blood metabolites based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) and metabolomics. METHODS: Dried blood spots were collected from 21 infants with ROP (ROP group) and 21 infants without ROP (non-ROP group) who were hospitalized in the Sixth Affiliated Hospital of Sun Yat-sen University from January 2013 to December 2016. LC-MS/MS was used to measure the metabolites, and orthogonal partial least squares-discriminant analysis was used to search for differentially expressed metabolites and biomarkers. RESULTS: There was a significant difference in blood metabolic profiles between the ROP and non-ROP groups. The pattern recognition analysis, Score-plot, and weight analysis obtained 10 amino acids with a relatively large difference. Further statistical analysis showed that the ROP group had significant increases in blood levels of glutamic acid, leucine, aspartic acid, ornithine, and glycine compared with the non-ROP group (P<0.05). The receiver operating characteristic curve analysis showed that glutamic acid and ornithine had the highest value in diagnosing ROP. CONCLUSIONS: Blood metabolites in preterm infants with ROP are different from those without ROP. Glutamic acid and ornithine are the metabolic markers for diagnosing ROP. LC-MS/MS combined with metabolomics analysis has a potential application value in the early identification and diagnosis of ROP.

Bempedoic acid, an ATP citrate lyase inhibitor, reduces intimal hyperplasia via activation of AMPKα signaling pathway.

BACKGROUND: One of the common pathophysiological basis of atherosclerosis is intimal hyperplasia. ATP citrate lyase (ACLY) has been reported as a promising therapeutic target for treatment of dyslipidemia and atherosclerosis. However, the role of ACLY in intimal hyperplasia has yet to be clarified. METHODS: The current investigation studies the molecular effects of ACLY and bempedoic acid, an ACLY inhibitor, on platelet-derived growth factor (PDGF)-induced primary human aortic smooth muscle cells (HASMCs) proliferation in vitro and on femoral arterial wire-injured neointimal hyperplasia in mouse in vivo. The role of ACLY in intimal hyperplasia was further investigated in mice treated with bempedoic acid. Cell proliferation was measured by CCK8 and BrdU assays. We explored further mechanisms using western blot, qPCR and immunofluorescence. RESULTS: We found that ACLY was significantly increased in dedifferentiated VSMC in vitro and vivo. Bempedoic acid which can inhibit ACLY expression effectively blocked PDGF-induced VSMC proliferation and dedifferentiation by activating AMPK/ACC signaling pathway. Moreover, bempedoic acid also attenuated VSMC proliferation and inhibited VSMC dedifferentiation in the wire-injured mouse femoral arteries, resulting in reduced neointima formation. CONCLUSIONS: We demonstrates that bempedoic acid reduces ACLY expression to restrain VSMC proliferation and dedifferentiation by activating AMPK/ACC signaling pathway, which may provide a potential therapeutic strategy for diseases associated with intimal hyperplasia including restenosis and atherosclerosis.

[Analysis of clinical characteristics and genetic variant in a child with Nicolaides-Baraitser syndrome due to maternal mosaicism].

OBJECTIVE: To carry out genetic testing for a child featuring global developmental delay, abnormal liver function, congenital heart disease, and brain malformation. METHODS: Peripheral blood samples of the child and his parents were collected for the extraction of genomic DNA and trio-whole exome sequencing. Candidate variant was verified by Sanger sequencing. RESULTS: Genetic testing revealed that the child has harbored a heterozygous c.2002G>T (p.Glu668Ter) variant of the SMARCA2 gene, which was predicted to be likely pathogenic by bioinformatic analysis. His mother was found to be a low-percentage mosaic for the same variant, with a ratio of 0.054 (246/4549). CONCLUSION: The child was diagnosed with Nicolaides-Baraitser syndrome resulting from maternal mosaicism for the SMARCA2 gene variant.

[Research methods and progress on the reduction effects of vehicle emission pollutants by street canyon greening.] / è¡—è°·ç»¿åŒ–æ¶ˆå‡æœºåŠ¨è½¦æŽ’æ”¾æ±¡æŸ“ç‰©çš„ç ”ç©¶æ–¹æ³•ä¸Žè¿›å±•.

With the development of high-density and high-rise buildings on both sides of the street, widespread attention has been paid to the applicability of the traditional greening model of 'the more trees, the better atmospheric environment' in dealing with air pollution in urban street canyons. Clarifying the characteristics of street canyons greening and its planting design pattern on the reduction of emission pollutants by vehicles is an important prerequisite for the improvement of air quality in the street canyons. Based on literature review, we compared the applicability and limitations of the three methods, including field observation, wind tunnel test, and numerical simulation. We further analyzed the effects of roadside trees and hedges on the dispersion and deposition of air pollutants, and put forward a framework of adaptive greening design for air quality improvement. Finally, we proposed that future studies should address the creation of graphic languages for roadside greening design, the development of technical guidelines for evaluating the exposure of air pollution, and the optimization of parameterization schemes for the physical processes of greening effect in computational fluid dynamics models. Overall, our review could provide ideas and reference for the subsequent research.

Decreased Polymorphonuclear Myeloid-Derived Suppressor Cells and ROS Production Correlated Closely with Bronchopulmonary Dysplasia in Preterm Infants.

Background: Bronchopulmonary dysplasia (BPD) is one of the most serious complications in premature infants. Myeloid-derived suppressor cells (MDSCs) have been indicated to promote immune tolerance and induce anti-inflammatory responses during the neonatal stage. However, the role of MDSCs in BPD has not been completely expounded. Methods: 130 cases of newborns were collected from six tertiary hospitals in Guangzhou from August 2019 to June 2022. They were divided into BPD group, non-BPD preterm infants group, and term infants group according to gestational age and presence of BPD. The peripheral blood was collected and used to analyze the proportion, phenotypic, and function of MDSCs at 3 to 7 days and 8 to 14 days after birth, respectively. Results: We indicated that the number of both MDSCs in premature infants is reduced, and the number of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in peripheral blood of BPD infants was significantly lower than that of non-BPD infants under 34 weeks of gestational age (P < 0.05). Furthermore, PMN-MDSCs from peripheral blood of patients presented inhibitory effect on proliferation of CD4+T and CD8+T cells in each group. However, PMN-MDSCs from BPD group had obviously weaker inhibitory effect on proliferation of CD4+T and CD8+T cells than that from non-BPD preterm infants group. In addition, we demonstrated that the expression of NADPH oxidase (Nox2) and reactive oxygen species (ROS) in PMN-MDSCs of BPD children was significantly lower than that in non-BPD preterm infants, suggesting that ROS pathway was affected in BPD in premature infants. Conclusion: This study preliminarily revealed the role of PMN-MDSCs in the pathogenesis of BPD in premature infants. The specific immune regulation mechanism of PMN-MDSCs in BPD will provide new ideas and strategies for clinical prevention and treatment of BPD in premature infants.