OTUB1/NDUFS2 axis promotes pancreatic tumorigenesis through protecting against mitochondrial cell death.

Pancreatic cancer is one of the most fatal cancers in the world. A growing number of studies have begun to demonstrate that mitochondria play a key role in tumorigenesis. Our previous study reveals that NDUFS2 (NADH: ubiquinone oxidoreductase core subunit S2), a core subunit of the mitochondrial respiratory chain complex I, is upregulated in Pancreatic adenocarcinoma (PAAD). However, its role in the development of PAAD remains unknown. Here, we showed that NDUFS2 played a critical role in the survival, proliferation and migration of pancreatic cancer cells by inhibiting mitochondrial cell death. Additionally, protein mass spectrometry indicated that the NDUFS2 was interacted with a deubiquitinase, OTUB1. Overexpression of OTUB1 increased NDUFS2 expression at the protein level, while knockdown of OTUB1 restored the effects in vitro. Accordingly, overexpression and knockdown of OTUB1 phenocopied those of NDUFS2 in pancreatic cancer cells, respectively. Mechanically, NDUFS2 was deubiquitinated by OTUB1 via K48-linked polyubiquitin chains, resulted in an elevated protein stability of NDUFS2. Moreover, the growth of OTUB1-overexpressed pancreatic cancer xenograft tumor was promoted in vivo, while the OTUB1-silenced pancreatic cancer xenograft tumor was inhibited in vivo. In conclusion, we revealed that OTUB1 increased the stability of NDUFS2 in PAAD by deubiquitylation and this axis plays a pivotal role in pancreatic cancer tumorigenesis and development.

The only species of Calvisia (Phasmatodea, Necrosciinae) from China, with a new synonymy and additional descriptions.

Calvisia is a colorful winged stick insect genus consisting of 6 subgenera and 44 species widely distributed in temperate and tropical Asia. C. medogensis syn. nov. was discovered in Mdog, Xizang (Tibet), China and is so far the only species recorded from China. We here propose that C. medogensis syn. nov. is a synonym of C. fuscoalata after checking type specimens of both species. New materials studied are deposited in Yunnan Agricultural University, China (YNAU).

ZBTB20 Regulates SERCA2a Activity and Myocardial Contractility Through Phospholamban.

BACKGROUND: Intracellular Ca2+ cycling determines myocardial contraction and relaxation in response to physiological demands. SERCA2a (sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 2a) is responsible for the sequestration of cytosolic Ca2+ into intracellular stores during cardiac relaxation, and its activity is reversibly inhibited by PLN (phospholamban). However, the regulatory hierarchy of SERCA2a activity remains unclear. METHODS: Cardiomyocyte-specific ZBTB20 knockout mice were generated by crossing ZBTB20flox mice with Myh6-Cre mice. Echocardiography, blood pressure measurements, Langendorff perfusion, histological analysis and immunohistochemistry, quantitative reverse transcription-PCR, Western blot analysis, electrophysiological measurements, and chromatin immunoprecipitation assay were performed to clarify the phenotype and elucidate the molecular mechanisms. RESULTS: Specific ablation of ZBTB20 in cardiomyocyte led to a significant increase in basal myocardial contractile parameters both in vivo and in vitro, accompanied by an impairment in cardiac reserve and exercise capacity. Moreover, the cardiomyocytes lacking ZBTB20 showed an increase in sarcoplasmic reticular Ca2+ content and exhibited a remarkable enhancement in both SERCA2a activity and electrically stimulated contraction. Mechanistically, PLN expression was dramatically reduced in cardiomyocytes at the mRNA and protein levels by ZBTB20 deletion or silencing, and PLN overexpression could largely restore the basal contractility in ZBTB20-deficient cardiomyocytes. CONCLUSIONS: These data point to ZBTB20 as a fine-tuning modulator of PLN expression and SERCA2a activity, thereby offering new perspective on the regulation of basal contractility in the mammalian heart.

High-Energy Composite Fuels with Improved Combustion Efficiency by Using AlH3 Embedded with Al Particles.

Aluminum hydride (AlH3) has attracted much attention due to its potential to replace aluminum (Al) as a novel energetic material in solid propellants. In this research, ammonium perchlorate (AP) and perfluoropolyether (PFPE) as functionalized coatings and a combination of acoustic resonance and spray drying technology have been employed to prepare AlH3@Al@AP (AHAPs) and AlH3@Al@AP@PFPE (AHAPs-F) energetic composite particles. The formulations of composite propellants and modified AlH3 particles were designed and fabricated. Their thermal reactivity, reaction heat, density, vacuum stability, combustion performance, and condensed combustion products (CCPs) have been systematically investigated. The results show that the solid propellants containing AHAPs (SP13) and AHAPs-F (SP14) composites can significantly enhance the reactivity and energy output compared to conventional solid propellants with the mechanical mixture Al/AlH3 (SP12). In particular, the total heat releases of SP13 and SP14 are almost 1.2 and 1.7 times higher than those of conventional ones (SP12, 1442 J g-1), respectively. Among the AlH3-based propellants, SP14 propellants exhibit the highest reaction heat of 5887 J g-1, the most intensive flame radiation of 31.4 × 103, and the highest combustion wave temperature of 2495 °C. Moreover, the particle size distribution of CCPs from SP14 propellants is much narrower and smaller than that of SP12, resulting in higher combustion efficiency.

Neuroprotective effect of 20 (S) - Protopanaxadiol (PPD) attenuates NLRP3 inflammasome-mediated microglial pyroptosis in vascular dementia rats.

20(S)-protopanaxadiol (PPD), one of the ginsenosides from Panax ginseng, has been reported to improve performance with dementia. This study aimed to investigate the neuroprotective effect of PPD attenuating NLRP3 inflammasome-mediated microglial pyroptosis in vascular dementia (VD) rats induced by bilateral common carotid artery ligation (2-VO). Male Sprague-Dawley rats (SPF, 150-180 g, n = 10/group) were randomly divided into PPD (20, 10, 5 mg/kg, subcutaneous injection once per day for 3 weeks), model, and vehicle-sham group. It was found that PPD significantly reversed 2-VO-induced cognitive impairment by decreasing escape latency and spontaneous alternation and increasing the number of crossing platforms, showing memory-improving effects. PPD improved the pathological morphology of brain tissue in VD rats. PPD significantly reduced the cerebral infarction area and the activation of microglia in the cortex and hippocampal DG, CA1, and CA3 area. Moreover, PPD could attenuate NLRP3 inflammasome-mediated microglial pyroptosis, inhibit the positive expression of NLRP3, decrease IL-1ß, and IL-18 levels, and increase IL-10 levels in the brain cortex. PPD also significantly alleviated the neurotoxicity by decreasing the Aß and p-Tau in hippocampal DG, CA1, and CA3 areas. In addition, the levels of NLRP3, ASC, and IL-1ß in the cortex, APP, BACE1, and p-Tau in the hippocampus were significantly reduced by PPD. These results suggested that PPD hinders microglial activation to alleviate neuroinflammation of NLRP3 inflammasome and inhibits neurotoxicity of Aß deposition and Tau phosphorylation in 2-VO-induced VD rats.

Stabilization of AlH3 Crystals by the Coating of Hydrophobic PFPE and Resulted Reactivity with Ammonium Perchlorate.

Aluminum hydride (AlH3) is a promising fuel component of solid propellant, but its stabilization is still challenging. Herein, surface functionalization of hydrophobic perfluoropolyether (PFPE) followed by ammonium perchlorate (AP) coating has been implemented. In particular, AlH3@PFPE@xAP (x = 10, 30, 50, or 64.21%) composites (AHFPs) were prepared by a spray-drying technique. The PFPE-functionalized AlH3 with a hydrophobic surface shows an increased water contact angle (WCA) from 51.87° to 113.54°. Compared with pure AlH3, the initial decomposition temperatures of AHFPs were increased by 17 °C, and the decomposition properties of AP in the AHFPs were also enhanced with significantly decreased peak temperature and fairly increased energy output. Moreover, the decomposition induction time of AHFPs-30% was improved by almost 1.82 times that of raw AlH3, which indicates that the coatings of PFPE and AP could improve the stability of AlH3. The maximum flame radiation intensity of AHFPs-30% was 21.6 × 103, which is almost 7.71 times that of pure AlH3 (2.8 × 103).

Zuogui and Yougui pills improve perimenopausal syndrome regulation of apoptosis in mice.

OBJECTIVE: To examine, dissect, and understand the molecular mechanisms and combinatorial effects of Zuogui (, ZGP) and Yougui pills (, YGP) in 4-vinyl cyclohexene diepoxide (4-VCD)-induced Perimenopausal syndrome (PMS). METHODS: Using the 4-VCD-induced PMS mouse model, uterine and ovary index were measured, and serum sex steroidal hormone levels were evaluated after treatment with ZGP, YGP, ZGP + YGP, estradiol valerate (EV), and Gengnian An (gengnianan, GNA). Histopathological examinations, ingredient-target network predictions, western blotting, and real-time quantitative polymerase chain reaction (RT-qPCR) analyses were performed to ascertain the possible pharmacological effects and molecular mechanisms of ZYP and YGP. RESULTS: Treatment with ZGP and YGP remarkably improves estrous cyclicity and prevents pathological damage to the uterus. Also, altered sex hormones, including AMH, E2, FSH, LH, P, and T, were restored to normal levels after ZGP and YGP administration. Ingredient-target network analysis showed that the 5 ingredients common to the ZGP and YGP formula modulate 53 targets shared with PMS. Pathway-enrichment analysis further predicted that ZGY and YGP likely regulate of apoptosis and other essential pathways during PMS. In-vivo studies showed that ZGP and YGP suppress PMS modulating apoptosis through decreasing Caspase-3 and Bcl-2-associated X (Bax) levels and increasing B-cell lymphoma-2 (Bcl-2)/Bax and Bcl-2 levels. Importantly, ZGP + YGP treatment modulation effects were somewhat or significantly better compared to ZGP or YGP alone treatment. CONCLUSION: ZGP and YGP represent novel anti-PMS agents whose effects involve restoring altered hormonal levels, protecting the uterus, and regulating apoptosis.

Trends in prevalence and all-cause mortality of metabolic dysfunction-associated fatty liver disease among adults in the past three decades: Results from the NHANES study.

BACKGROUND: Given the escalating epidemic of obesity and diabetes coupled with redefined diagnostic criteria, it is critical to identify the prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD). We sought to determine the prevalence and mortality outcomes of MAFLD subtypes based on diagnostic criteria in the USA over the past three decades. METHODS: Eleven cycles of the National Health and Nutrition Examination Surveys (NHANES; 1988-1994 and 1999-2020) were used, and 72,224 participants were included. MAFLD was defined according to the 2020 International Expert Consensus. Based on diagnostic criteria and risk factors, MAFLD was categorized into seven subtypes: type 1 (obesity subtype), 2 (metabolic unhealthy subtype), 3 (diabetes subtype), 4 (metabolic unhealthy non-diabetes subtype), 5 (obesity and diabetes subtype), 6 (metabolic unhealthy non-obesity subtype), and 7 (mixed subtype). RESULTS: Over the study period, the estimated prevalence of MAFLD increased significantly from 22% in 1988-1994 to 36% in 2017-2020. The prevalence of Type 4 was the highest, followed by that of Type 7, whereas other types were low and almost unchanged over time. Individuals with MAFLD had 19% and 38% increased mortality risks from all causes and cardiovascular disease, respectively. Among them, the metabolically unhealthy participants with normal weight demonstrated a 116% higher risk for all-cause mortality [hazard ratio (HR): 2.16, 95% CI: 1.52-3.08] and a 222% higher risk for cardiovascular mortality (HR: 3.22, 95% CI: 1.72-6.04). Interestingly, stratification and interaction analyses demonstrated a significant impact of metabolic parameters on the relationship between MAFLD and all-cause mortality. CONCLUSIONS: In conclusion, our study identified an increase in MAFLD prevalence and a significant association between metabolic derangements in MAFLD and all-cause or cardiovascular mortality.

Effect of miR-22 Targeting FMNL2 on Cell Migration and Apoptosis in Childhood Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of miR-22 targeting formin-like protein 2 (FMNL2) on the migration and apoptosis of childhood acute myeloid leukemia (AML) cells.@*METHOD@#Peripheral blood samples from 11 children with AML, 10 children with immune thrombocytopenia, human AML cell lines TF-1a, HL-60, THP-1 and human bone marrow stromal cells HS-5 were used as the research objects. UniCel DxH 800 automatic hematology analyzer detected platelet count, hemoglobin, and white blood cell count in peripheral blood samples, and RT-qPCR detected miR-22 expression in peripheral blood samples and AML cells. HL-60 cells were transfected with LipofectamineTM 2000 kit, the experiments were divided into seven groups: blank (no cells transfected), miR-NC, miR-22 mimics, si-NC, si-FMNL2 , miR-22 mimics+OE-NC and miR-22 mimics+OE-FMNL2 . RT-qPCR was used to detect the expression of miR-22 in each group. Transwell was used to detect cell migration. Flow cytometry was used to detect cell apoptosis. Dual-luciferase reporter gene detection experiments verified the targeting relationship between miR-22 and FMNL2 . Western blot was used to detect the expression of FMNL2 protein.@*RESULTS@#Compared with the control group, the number of leukocytes in the peripheral blood of children with AML was significantly increased (P <0.001), while the concentration of hemoglobin and the number of platelets were significantly decreased P <0.001). The expression level of miR-22 in peripheral blood of children with AML was significantly lower than that in control group (P <0.001). Compared with HS-5 cells, the expression levels of miR-22 in TF-1a, HL-60, and THP-1 cells were significantly decreased (P <0.05), and in HL-60 cells was the lowest. Therefore, HL-60 cells were selected for subsequent experiments. Up-regulation of miR-22 or silencing of FMNL2 could reduce the number of migrating cells and increase apoptosis rate (P <0.05). MiR-22 targeted and negatively regulated the expression of FMNL2 . FMNL2 overexpression reversed the effects of up-regulated miR-22 on migration and apoptosis of HL-60 cells.@*CONCLUSION@#MiR-22 can inhibit the migration and promote apoptosis of HL-60 cells by down regulating the expression of FMNL2 .

Molecular Studies of Relationships and Identifications Among Insects of the Subfamily Panchaetothripinae (Thysanoptera, Thripidae).

The Panchaetothripinae comprises 42 genera and 146 species of leaf-feeding thrips, some of which are horticultural pests. We examined representatives of the 18 genera that include most of these pests. For species delimitation, we used DNA barcoding to produce171 sequences for 40 morphospecies. Most species were found to be monophyletic, although cryptic diversity was evident in 8 presumptive species. A multilocus molecular phylogenetic assessment was based on one mitochondrial (COI) and three nuclear loci (EF-1α, ITS2, and 28S) from 132 specimens (18 genera and 33 species), representing all genera and ~82% of species in China. Maximum likelihood (ML) and Bayesian inference (BI) confirmed monophyly of each genus with strong support. Monophyly of tribes Panchaetothripini and Monilothripini were refuted, but the well supported tribe Tryphactothripini was confirmed. Rhipiphorothrips was recovered as a sister to the remainder of the genera of Panchaetothripinae combined. Both analyses revealed two major clades. Clade A comprised the majority of the genera, including tribe Tryphactothripini. Clade B included only four genera of which two, Helionothrips and Caliothrips, are particularly species rich. The relationships of some genera remain unresolved.

Analysis of Risk Factors for Coronary Artery Lesion in Children with Kawasaki Disease.

OBJECTIVE: To determine the frequency of coronary artery lesion (CAL) in children with Kawasaki disease (KD) and to analyse the related risk factors of CAL and the predictive value of risk factors for CAL. STUDY DESIGN: A descriptive study. PLACE AND DURATION OF STUDY: Department of Pediatrics, People's Hospital of Linquan County, Anhui Province, China, from January 2019 to January 2022. METHODOLOGY: Clinical data of 71 children with KD were retrospectively analysed, including 31 in the CAL group and 40 in the non-CAL group. The age, gender, days of fever, blood routine, plasma N-terminal B-type natriuretic peptide (NT-proBNP), and Kobayashi score were registered as independent variables of all the children, and the presence or absence of CAL was used as the dependent variable. All the independent variables were subjected to univariate analysis between the groups, and those with significance in univariate analysis were further subjected to unconditional binary logistic regression analysis. A receiver operating curve (ROC) was drawn to analyse the predictive power and optimal cut-off value of related risk factors for CAL. RESULTS: On univariate analysis, age, NT-proBNP and Kobayashi's score were closely related to CAL (all p<0.05). Multivariate analysis showed that NT-proBNP and Kobayashi scores were independent risk factors for CAL in children with KD. ROC curve analysis showed that the area under the curve (AUC) of NT-proBNP and Kobayashi scores were 0.771 and 0.732, respectively, at optimal critical values of 543.12 ng/L and 7.50 points, respectively. CONCLUSION: The frequency of CAL in children with KD is high. NT-proBNP and Kobayashi scores are independent risk factors for the occurrence of CAL in children with KD, and they have good predictive performance for the diagnosis of CAL. KEY WORDS: Kawasaki disease, Children, Coronary artery lesion, Risk factors, Kobayashi score, NT-pro BNP.

A pilot study on biological characteristics of human CD24(+) stem cells from the apical papilla.

BACKGROUND/PURPOSE: CD24 is a specific cell surface marker for undifferentiated dental stem cells from apical papilla (SCAPs) seen only during root development, before the tooth emerges through gum. But the comprehensive role of CD24 in the SCAPs is unclear. This study aims to clarify the exact roles of CD24 in SCAPs. MATERIALS AND METHODS: SCAPs were divided into CD24 (+)-SCAPs (high percentage CD24) and CD24 (-)-SCAPs (low percentage CD24) via flow cytometry. The proliferation, migration and osteogenic/adipogenic differentiation of the two groups were detected, RT-PCR was performed to detect the expression of osteogenic/adipogenic related genes and thegene expression were analyzed. RESULTS: The proliferative and migratory ability of CD24 (-)-SCAPs were significantly stronger than that of CD24 (+)-SCAPs. Although, the mineralization process and the osteogenic genes expression were not significantly difference in the two groups. Both CD24 (+)-SCAPs and CD24 (-)-SCAPs differentiated into adipocytes. The adipogenic differentiation in CD24 (+)-SCAPs was better than that in CD24 (-)-SCAPs, after 3 weeks of adipogenic induction. However, the expression of adipogenic related gene, PPAR γ2 mRNA in CD24 (+)-SCAPs was lower than that in CD24 (-)-SCAPs after 1 week of adipogenic induction. But the trend changed for the opposite after 3 weeks. CONCLUSION: The study proposes that CD24 has a regulatory effect on the adipogenic differentiation of SCAPs, and this may be attained by targeting the PPAR γ2 mRNA. Concurrently, it was found that CD24 plays an inhibitory role in the proliferation and migration of SCAPs, which may minimize the manifestation of diseases caused by an abnormal cell growth.

The zinc finger and BTB domain containing protein ZBTB20 regulates plasma triglyceride metabolism by repressing lipoprotein lipase gene transcription in hepatocytes.

BACKGROUND AND AIMS: Lipoprotein lipase (LPL) is responsible for the lipolytic processing of triglyceride-rich lipoproteins, the deficiency of which causes severe hypertriglyceridemia. Liver LPL expression is high in suckling rodents but relatively low at adulthood. However, the regulatory mechanism and functional significance of liver LPL expression are incompletely understood. We have established the zinc finger protein ZBTB20 as a critical factor for hepatic lipogenesis. Here, we evaluated the role of ZBTB20 in regulating liver Lpl gene transcription and plasma triglyceride metabolism. APPROACH AND RESULTS: Hepatocyte-specific inactivation of ZBTB20 in mice led to a remarkable increase in LPL expression at the mRNA and protein levels in adult liver, in which LPL protein was mainly localized onto sinusoidal epithelial cells and Kupffer cells. As a result, the LPL activity in postheparin plasma was substantially increased, and postprandial plasma triglyceride clearance was significantly enhanced, whereas plasma triglyceride levels were decreased. The dysregulated liver LPL expression and low plasma triglyceride levels in ZBTB20-deficient mice were normalized by inactivating hepatic LPL expression. ZBTB20 deficiency protected the mice against high-fat diet-induced hyperlipidemia without causing excessive triglyceride accumulation in the liver. Chromatin immunoprecipitation and gel-shift assay studies revealed that ZBTB20 binds to the LPL promoter in the liver. A luciferase reporter assay revealed that ZBTB20 inhibits the transcriptional activity of LPL promoter. The regulation of LPL expression by ZBTB20 is liver-specific under physiological conditions. CONCLUSIONS: Liver ZBTB20 serves as a key regulator of LPL expression and plasma triglyceride metabolism and could be a therapeutic target for hypertriglyceridemia.

Renal denervation inhibits the renin-angiotensin-aldosterone system in spontaneously hypertensive rats.

This study was conducted to explore the effect of renal denervation (RDN) on the renin-angiotensin-aldosterone system (RAAS) in spontaneously hypertensive rats (SHRs). Our experimental rats were randomly divided into the RDN group conducted by painting 10% phenol on the bilateral renal nerves (RDNX), the shamoperation group simply painting with saline (Sham), and the normotension control group (WKY) following all the animal blood and tissues of kidney, hypothalamus, and adrenal gland collected and examined 2 weeks after RDN operation. We found that the aldosterone (ALD) levels in serum and tissues all decreased in the RDNX group compared with the Sham group (p < .05). Meantime, the expression of angiotensin II type1 receptor (AT1R) mRNA also exhibited significantly reduced by 2.22-fold in the RDNX group compared to the Sham group identical to the expression of AT1R protein in the renal cortex and outer stripe of the outer medulla (OSOM) subjected to denervation surgery, which manifested the lower ATIR protein expression than the Sham group (p < .05). Besides, the expression of angiotensin II (Ang II) protein in the cortex , OSOM, and inner stripe of the outer medulla were all attenuated by RDN in comparison with the Sham group (p < .05). RDN reduced intrarenal RAAS and circulating RAAS to lower blood pressure and repair renal function.

[Neuroprotective effect of cinnamaldehyde in MPTP-induced mouse model of subacute Parkinson's disease].

This paper aims to explore the neuroprotective effect of cinnamaldehyde(CA) in mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced subacute Parkinson's disease(PD) and the mechanism. To be specific, male C57 BL/6 mice(n=72, SPF) were randomized into control group, model group, positive control(madopar 0.1 mg·g~(-1)) group, and low-dose, me-dium-dose, and high-dose CA groups(0.15, 0.30, 0.60 mg·g~(-1)). MPTP(intraperitoneal injection, 0.03 mg·g~(-1), once a day for 5 days) was used to induce subacute PD in mice except for the control group. The administration began from the day of modeling and lasted 19 days. On the 0 th, 12 th, and 19 th day, the open field test, pole test, and rotarod test were carried out. After the tests, the mice were killed and brains were separated. In addition, the organ index was measured. The number of cells in substantia nigra(SN) in the midbrain of MPTP-induced PD model mice was detected based on hematoxylin and eosin(HE) staining. The levels of tyrosine hydroxylase(TH)-and α-synuclein(α-Syn)-positive cells in SN were determined by immunohistochemical staining, and the protein levels of TH and α-Syn in SN by Western blot. The results showed that the MPTP-stimulated mice had abnormal behaviors such as erect hair, arched back, rigidity of the tail, slow movement, and tremor, decreased number of crossings and rearing, increased frequency of urination and defecation, longer time of pole climbing, and shorter time of staying on the rotating rod. In addition, the mice showed obvious damage of neurons in the SN and reduced neuron cells in irregular arrangement with some shrinking. In addition, the average optical density of TH in SN decreased and that of α-Syn increased. All these suggested the successful modeling. CA displayed obvious therapeutic effect on the PD mice, as manifested by the increased number of crossings and rearing, decreased frequency of urination and defecation, shorter time of climbing pole, longer time of staying on the rotating rod, and more neuron cells in the SN with a few pykno-tic cells. Moreover, CA significantly alleviated the decrease of TH and the overexpression of α-Syn in SN. As a result, the MPTP-induced injury of dopaminergic neurons was alleviated. The performance of 0.3 mg·g~(-1) CA was the best. This study is expected to lay a scientific basis for the development of CA products.

Clinical treatment outcomes and their changes in extremely preterm twins: a multicenter retrospective study in Guangdong Province, China / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China.@*METHODS@#A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups.@*RESULTS@#Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05).@*CONCLUSIONS@#There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.

Association of Cholecystectomy With Liver Fibrosis and Cirrhosis Among Adults in the USA: A Population-Based Propensity Score-Matched Study.

Background and Aims: Cholecystectomy is the "gold standard" for treating diseases of the gallbladder. In addition, non-alcoholic fatty liver disease (NAFLD), liver fibrosis or cirrhosis, are major causes of morbidity and mortality across the world. However, the association between cholecystectomy and these diseases is still unclear. We assessed the association among US adults and examined the possible risk factors. Methods: This cross-sectional study used data from 2017 to 2018 National Health and Nutrition Examination Survey, a population-based nationally representative sample of US. Liver fibrosis and cirrhosis were defined by median stiffness, which was assessed by transient elastography. Furthermore, patients who had undergone cholecystectomy were identified based on the questionnaire. In addition, Propensity Score Matching (PSM, 1:1) was performed based on gender, age, body mass index (BMI) and diabetes. Results: Of the 4,497 included participants, cholecystectomy was associated with 60.0% higher risk of liver fibrosis (OR:1.600;95% CI:1.278-2.002), and 73.3% higher risk of liver cirrhosis (OR:1.733, 95% CI:1.076-2.792). After PSM based on age, gender, BMI group and history of diabetes, cholecystectomy was associated with 139.3% higher risk of liver fibrosis (OR: 2.393;95% CI: 1.738-3.297), and 228.7% higher risk of liver cirrhosis (OR: 3.287, 95% CI: 1.496-7.218). Conclusions: The present study showed that cholecystectomy is positively associated with liver fibrosis and cirrhosis in US adults. The discovery of these risk factors therefore provides new insights on the prevention of NAFLD, liver fibrosis, and cirrhosis.

Fructose and metabolic diseases: too much to be good.

ABSTRACT: Excessive consumption of fructose, the sweetest of all naturally occurring carbohydrates, has been linked to worldwide epidemics of metabolic diseases in humans, and it is considered an independent risk factor for cardiovascular diseases. We provide an overview about the features of fructose metabolism, as well as potential mechanisms by which excessive fructose intake is associated with the pathogenesis of metabolic diseases both in humans and rodents. To accomplish this aim, we focus on illuminating the cellular and molecular mechanisms of fructose metabolism as well as its signaling effects on metabolic and cardiovascular homeostasis in health and disease, highlighting the role of carbohydrate-responsive element-binding protein in regulating fructose metabolism.

1,2,4-Trimethoxybenzene selectively inhibits NLRP3 inflammasome activation and attenuates experimental autoimmune encephalomyelitis.

NOD-like receptor (NLR) family pyrin domain-containing-3 (NLRP3) inflammasome is implicated in inflammation-associated diseases such as multiple sclerosis, Parkinson's disease, and stroke. Targeting the NLRP3 inflammasome is beneficial to these diseases, but few NLRP3 inflammasome-selective inhibitors are identified to date. Essential oils (EOs) are liquid mixtures of volatile and low molecular-weight organic compounds extracted from aromatic plants, which show various pharmacological activities, including antibacterial, antifungal, antiviral, antioxidant, and anti-inflammatory properties. In this study we screened active ingredients from essential oils, and identified 1,2,4-trimethoxybenzene (1,2,4-TTB) as a selective NLRP3 inflammasome inhibitor. We showed that 1,2,4-TTB (1 mM) markedly suppressed nigericin- or ATP-induced NLRP3 inflammasome activation, thus decreased caspase-1 activation and IL-1ß secretion in immortalized murine bone marrow-derived macrophages (iBMDMs) and in primary mouse microglia. Moreover, 1,2,4-TTB specifically inhibited the activation of NLRP3 inflammasome without affecting absent in melanoma 2 (AIM2) inflammasome activation. We further demonstrated that 1,2,4-TTB inhibited oligomerization of the apoptosis-associated speck-like protein containing a CARD (ASC) and protein-protein interaction between NLRP3 and ASC, thus blocking NLRP3 inflammasome assembly in iBMDMs and in primary mouse macrophages. In mice with experimental autoimmune encephalomyelitis (EAE), administration of 1,2,4-TTB (200 mg · kg-1 · d-1, i.g. for 17 days) significantly ameliorated EAE progression and demyelination. In conclusion, our results demonstrate that 1,2,4-TTB is an NLRP3 inflammasome inhibitor and attenuates the clinical symptom and inflammation of EAE, suggesting that 1,2,4-TTB is a potential candidate compound for treating NLRP3 inflammasome-driven diseases, such as multiple sclerosis.