This study aimed to investigate the structural and metabolic changes in cumulus cells of underweight women and their effects on oocyte maturation and fertilization. The cytoplasmic ultrastructure was analyzed by electron microscopy, mitochondrial membrane potential by immunofluorescence, and mitochondrial DNA copy number by relative quantitative polymerase chain reaction. The expression of various proteins including the oxidative stress-derived product 4-hydroxynonenal (4-HNE) and autophagy and apoptosis markers such as Vps34, Atg-5, Beclin 1, Lc3-I, II, Bax, and Bcl-2 was assessed and compared between groups. Oocyte maturation and fertilization rates were lower in underweight women (P < 0.05), who presented with cumulus cells showing abnormal mitochondrial morphology and increased cell autophagy. Compared with the mitochondrial DNA copies of the control group, those of the underweight group increased but not significantly. The mitochondrial membrane potential was similar between the groups (P = 0.8). Vps34, Atg-5, Lc3-II, Bax, and Bcl-2 expression and 4-HNE levels were higher in the underweight group compared with the control group (P < 0.01); however, the Bax/Bcl-2 ratio was lower in the underweight group compared with the control group (P = 0.031). Additionally, Beclin 1 protein levels were higher in the underweight group compared with the control group but without statistical significance. In conclusion, malnutrition and other conditions in underweight women may adversely affect ovulation, and the development, and fertilization of oocytes resulting from changes to the intracellular structure of cumulus cells and metabolic processes. These changes may lead to reduced fertility or unsatisfactory reproduction outcomes in women.

The objective of this study was to understand and measure epigenetic changes associated with the occurrence of CHDs by utilizing the discordant monozygotic twin model. A unique set of monozygotic twins discordant for double-outlet right ventricles (DORVs) was used for this multiomics study. The cardiac and muscle tissue samples from the twins were subjected to whole genome sequencing, whole genome bisulfite sequencing, RNA-sequencing and liquid chromatography-tandem mass spectrometry analysis. Sporadic DORV cases and control fetuses were used for validation. Global hypomethylation status was observed in heart tissue samples from the affected twins. Among 36,228 differentially methylated regions (DMRs), 1097 DMRs involving 1039 genes were located in promoter regions. A total of 419 genes, and lncRNA–mRNA pairs involved 30 genes, and 62 proteins were significantly differentially expressed. Multiple omics integrative analysis revealed that five genes, including BGN, COL1A1, COL3A1, FBLN5, and FLAN, and three pathways, including ECM-receptor interaction, focal adhesion and TGF-β signaling pathway, exhibited differences at all three levels. This study demonstrates a multiomics profile of discordant twins and explores the possible mechanism of DORV development. Global hypomethylation might be associated with the risk of CHDs. Specific genes and specific pathways, particularly those involving ECM–receptor interaction, focal adhesion and TGF–β signaling, might be involved in the occurrence of CHDs.

One of the most common harmful mites in edible fungi is Histiostoma feroniarum Dufour (Acaridida: Histiostomatidae), a fungivorous astigmatid mite that feeds on hyphae and fruiting bodies, thereby transmitting pathogens. This study examined the effects of seven constant temperatures and 10 types of mushrooms on the growth and development of H. feroniarum, as well as its host preference. Developmental time for the total immature stages was significantly affected by the type of mushroom species, ranging from 4.3 ± 0.4 days (reared on Pleurotus eryngii var. tuoliensis Mou at 28°C) to 17.1 ± 2.3 days (reared on Auricularia polytricha Sacc. at 19°C). The temperature was a major factor in the formation of facultative heteromorphic deutonymphs (hypopi). The mite entered the hypopus stage when the temperature dropped to 16°C or rose above 31°C. The growth and development of this mite were significantly influenced by the type of species and variety of mushrooms. Moreover, the fungivorous astigmatid mite preferred to feed on the ‘Wuxiang No. 1’ strain of Lentinula edodes (Berk.) Pegler and the ‘Gaowenxiu’ strain of P. pulmonarius (Fr.) Quél., with a shorter development period compared with that of feeding on other strains. These results therefore quantify the effect of host type and temperature on fungivorous astigmatid mite growth and development rates, and provide a reference for applying mushroom cultivar resistance to biological pest control.

This paper studies the open-loop equilibrium strategies for a class of non-zero-sum reinsurance–investment stochastic differential games between two insurers with a state-dependent mean expectation in the incomplete market. Both insurers are able to purchase proportional reinsurance contracts and invest their wealth in a risk-free asset and a risky asset whose price is modeled by a general stochastic volatility model. The surplus processes of two insurers are driven by two standard Brownian motions. The objective for each insurer is to find the equilibrium investment and reinsurance strategies to balance the expected return and variance of relative terminal wealth. Incorporating the forward backward stochastic differential equations (FBSDEs), we derive the sufficient conditions and obtain the general solutions of equilibrium controls for two insurers. Furthermore, we apply our theoretical results to two special stochastic volatility models (Hull–White model and Heston model). Numerical examples are also provided to illustrate our results.

Pregnancy is a complex biological process. The establishment and maintenance of foetal–maternal interface are pivotal events. Decidual immune cells and inflammatory cytokines play indispensable roles in the foetal–maternal interface. The disfunction of decidual immune cells leads to adverse pregnancy outcome. Tumour necrosis factor (TNF)-α, a common inflammatory cytokine, has critical roles in different stages of normal pregnancy process. However, the relationship between the disorder of TNF-α and adverse pregnancy outcomes, including preeclampsia (PE), intrauterine growth restriction (IUGR), spontaneous abortion (SA), preterm birth and so on, is still indefinite. In this review, we thoroughly reviewed the effect of TNF-α disorder on pathological conditions. Moreover, we summarized the reports about the adverse pregnancy outcomes (PE, IUGR, SA and preterm birth) of using anti-TNF-α drugs (infliximab, etanercept and adalimumab, certolizumab and golimumab) currently in the clinical studies. Overall, IUGR, SA and preterm birth are the most common adverse pregnancy outcomes of anti-TNF-α drugs. Our review may provide insight for the immunological treatment of pregnancy-related complication, and help practitioners make informed decisions based on the current evidences.

The most important issue for the clinical application of sarcopenic obesity (SO) is the lack of a consensus definition. The aim of the present study was to determine the best measurement for SO by estimating the association between various definitions and the risk of falls and metabolic syndrome (MS). We studied a community of 765 adults aged 65 years and older in 2015–2017. Sarcopenia obesity was measured by sarcopenia (defined by low muscle mass with either low handgrip strength or low gait speed or both) plus obesity (defined by waist circumference, body fat percentage and BMI). The MS was defined according to the National Cholesterol Education Program ATP III. Logistic regression models were constructed to examine the relationships between sarcopenia obesity and risk of fall and MS. In the analysis of the fall risk with SO defined by waist circumference, the participants with non-sarcopenia/non-obesity were treated as the reference group. The OR to fall in participants with SO was 10·16 (95 % CI 2·71, 38·13) after adjusting for confounding covariates. In the analysis of the risk of the MS between participants with individual components of sarcopenia coupled with obesity defined by waist circumference, the risk was statistically significant for low gait speed (OR: 7·19; 95 % CI 3·61, 14·30) and low grip strength (OR: 9·19; 95 % CI 5·00, 16·91). A combination of low grip strength and abdominal obesity for identifying SO may be a more precise and practical method for predicting target populations with unfavourable health risks, such as falls risk and MS.

We investigated the effects of botulinum toxin on gait in Parkinson’s disease (PD) patients with foot dystonia. Six patients underwent onabotulinum toxin A injection and were assessed by Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS), visual analog scale (VAS) of pain, Timed Up and Go (TUG), Berg Balance Test (BBT), and 3D gait analysis at baseline, 1 month, and 3 months. BFMDRS (p = 0.002), VAS (p = 0.024), TUG (p = 0.028), and BBT (p = 0.034) were improved. Foot pressures at Toe 1 (p = 0.028) and Midfoot (p = 0.018) were reduced, indicating botulinum toxin’s effects in alleviating the dystonia severity and pain and improving foot pressures during walking in PD.

The FNDC5 gene encodes the fibronectin type III domain-containing protein 5 that is a membrane protein mainly expressed in skeletal muscle, and the FNDC5 rs3480 polymorphism may be associated with liver disease severity in non-alcoholic fatty liver disease (NAFLD). We investigated the influence of the FNDC5 rs3480 polymorphism on the relationship between sarcopenia and the histological severity of NAFLD. A total of 370 adult individuals with biopsy-proven NAFLD were studied. The association between the key exposure sarcopenia and the outcome liver histological severity was investigated by binary logistic regression. Stratified analyses were undertaken to examine the impact of FNDC5 rs3480 polymorphism on the association between sarcopenia and the severity of NAFLD histology. Patients with sarcopenia had more severe histological grades of steatosis and a higher prevalence of significant fibrosis and definite non-alcoholic steatohepatitis than those without sarcopenia. There was a significant association between sarcopenia and significant fibrosis (adjusted OR 2·79, 95 % CI 1·31, 5·95, P = 0·008), independent of established risk factors and potential confounders. Among patients with sarcopenia, significant fibrosis occurred more frequently in the rs3480 AA genotype carriers than in those carrying the FNDC5 rs3480 G genotype (43·8 v. 17·2 %, P = 0·031). In the association between sarcopenia and liver fibrosis, there was a significant interaction between the FNDC5 genotype and sarcopenia status (P value for interaction = 0·006). Sarcopenia is independently associated with significant liver fibrosis, and the FNDC5 rs3480 G variant influences the association between sarcopenia and liver fibrosis in patients with biopsy-proven NAFLD.

Studies have suggested an association between metabolic and cerebrocardiovascular diseases and major depressive disorder (MDD). However, the risk of metabolic and cerebrocardiovascular diseases in the unaffected siblings of patients with MDD remains uncertain. Using the Taiwan National Health Insurance Research Database, 22,438 unaffected siblings of patients with MDD and 89,752 age-/sex-matched controls were selected and followed up from 1996 to the end of 2011. Individuals who developed metabolic and cerebrocardiovascular diseases during the follow-up period were identified. Compared with the controls, the unaffected siblings of patients with MDD had a higher prevalence of metabolic diseases, such as hypertension (5.0% vs. 4.5%, p = 0.007), dyslipidemia (5.6% vs. 4.8%, p < 0.001), and obesity (1.7% vs. 1.5%, p = 0.028), and cerebrocardiovascular diseases, such as ischemic stroke (0.6% vs. 0.4%, p < 0.005) and ischemic heart disease (2.1% vs. 1.7%, p < 0.001). Logistic regression analyses revealed that the unaffected siblings of patients with MDD were more likely to develop hypertension, dyslipidemia, ischemic stroke, and ischemic heart diseases during the follow-up period than the controls. Our study revealed a familial coaggregation between MDD and metabolic and cerebrocardiovascular diseases. Additional studies are required to investigate the shared pathophysiology of MDD and metabolic and cerebrocardiovascular diseases.

The Wulian complex is located on the northern margin of the Sulu orogenic belt, and was formed by collision between the North China Craton (NCC) to the north and South China Craton (SCC) to the south. It consists of the metasedimentary Wulian Group, gneissic granite and meta-diorite. The U–Pb analyses for the detrital zircons from the Wulian Group exhibit one predominant age population of 2600–2400 Ma with a peak at c. 2.5 Ga and several secondary age populations of > 3000, 3000–2800, 2800–2600, 2200–2000, 1900–1800, 1500–1300 and 1250–950 Ma; some metamorphic zircons have metamorphic ages of c. 2.7, 2.55–2.45, 2.1–2.0 and 1.95–1.80 Ga, which are consistent with magmatic-metamorphic events in the SCC. Additionally, the Wulian Group was intruded by the gneissic granite and meta-diorite at c. 0.76 Ga, attributed to Neoproterozoic syn-rifting bimodal magmatic activity in the SCC and derived from partial melting of Archaean continental crust and depleted mantle, respectively. The Wulian Group therefore has tectonic affinity to the SCC and was mainly sourced from the SCC. The detrital zircons have positive and negative ϵHf(t) values, indicating that their source rocks were derived from reworking of both ancient and juvenile crustal rocks. The major early Precambrian crustal growth took place during c. 3.4–2.5 Ga with a dominant peak at 2.96 Ga and several secondary peaks at 3.27, 2.74 and 2.52 Ga. The two oldest zircons with ages of 3307 and 3347 Ma record the recycling of ancient continental crust (> 3.35 Ga) and crustal growth prior to c. 3.95 Ga in the SCC.

Emerging evidence has been revealed that high fat diet (HFD) correlate with insulin resistance (IR) which could be induced by endoplasmic reticulum stress (ERS). Recently, obesity or HFD induced nonalcoholic fatty liver disease (NAFLD) could promote alteration of iron metabolism. Disorder of iron metabolism have been linked to unnormal metabolism of glucose and lipid. Herein, we investigated the effect of impaired iron homeostasis on hepatic IR, focusing on ferritinophagy. Male C57/6J mice were administered with HFD (60% energy from fat) or LFD (10% energy from fat) for 10 weeks (n = 10), and Palmitic acid (PA)-insulin treated HepG2 cells were also established. Hepatic IR as evidenced by increased hepatic steatosis and decreased of p-AKT (48%, p < 0.0005), p-GSK-3β (34%, p < 0.05) in the liver of HFD mice. In addition, decreased iron level and expression NCOA4, as well as increased up-regulation of IRE1α and EIF2α were observed in HFD liver. By using desferrioxamine (DFO) and ferric ammonium citrate (FAC), we examined iron level on IRE1α and EIF2α. And glucose uptake assay shown that FAC supplementation, and ERS inhibitors of 4-PBA and STF could improve the glucose uptake of HepG2 cells in the presence of PA. Furthermore, we evaluated the glucose uptake of HepG2 cells incubated with adenovirus which mediated overexpression of NCOA4, FAC, 4-PBA (ERS inhibitor) or STF (IRE1 inhibitor). Taken together, deficiency of iron induced by impaired ferritinophagy induced hepatic IR, partly by aggravating hepatic ERS, especially IRE1 signal pathway in vivo and vitro. These findings provide evidence and new insight for therapeutic strategy of iron deficiency in NAFLD.