Retinal microcirculation: A window into systemic circulation and metabolic disease.

The retinal microcirculation system constitutes a unique terminal vessel bed of the systemic circulation, and its perfusion status is directly associated with the neural function of the retina. This vascular network, essential for nourishing various layers of the retina, comprises two primary microcirculation systems: the retinal microcirculation and the choroidal microcirculation, with each system supplying blood to distinct retinal layers and maintaining the associated neural function. The blood flow of those capillaries is regulated via different mechanisms. However, a range of internal and external factors can disrupt the normal architecture and blood flow within the retinal microcirculation, leading to several retinal pathologies, including diabetic retinopathy, macular edema, and vascular occlusions. Metabolic disturbances such as hyperglycemia, hypertension, and dyslipidemia are known to modify retinal microcirculation through various pathways. These alterations are observable in chronic metabolic conditions like diabetes, coronary artery disease, and cerebral microvascular disease due to advances in non-invasive or minimally invasive retinal imaging techniques. Thus, examination of the retinal microcirculation can provide insights into the progression of numerous chronic metabolic disorders. This review discusses the anatomy, physiology and pathophysiology of the retinal microvascular system, with a particular emphasis on the connections between retinal microcirculation and systemic circulation in both healthy states and in the context of prevalent chronic metabolic diseases.

The Evolution of the Bone Turnover Marker in Patients Following Recovery from Diabetic Ketoacidosis.

The aim of the study was to investigate whether the biomarkers for bone turnover could rapidly recover during the period of diabetic ketoacidosis (DKA). Bone turnover biomarkers, including 25-hydroxyvitamin D3, N-terminal middle molecular fragment of osteocalcin (NMID), and ß-C terminal cross-linking telopeptide of type 1 collagen were evaluated using in-patient data (n=627) from Shanghai Pudong Hospital from 2018-2022. The comparison was performed between type 2 diabetes (T2D only) (n=602) and DKA (n=25), in which we checked the bone turnover markers at pre-treatment and recovery. After matching by body mass index (BMI), we found that except for 25-OH-VitD3, the age difference, indices of glucose metabolism, and bone turnover were significant between the 2 groups (p<0.05). We found only a significant restoration of NMID (p<0.001). NMID and ß-CTX, when compared with T2D, showed overt distinction between recovery and T2D (p<0.05). In addition, the investigations demonstrated a substantial difference between 25-OH-VitD3 in males and NMID in females, regardless of age (p<0.05). Multilinear regression analysis revealed that 2 hours postprandial plasma C-peptide was an independent predictor of the NMID in both pre-treatment (ß=0.58, p=0.003) and recovery (ß=0.447, p=0.025), although sex was significant in pre-treatment (ß=-0.444, p=0.020). Finally, we found that only age variation affected DKA's fasting plasma glucose level (p<0.05). The study revealed that the bone turnover of DKA is significantly different in pre-treatment and recovery; however, NMID might recover quickly if the patients received appropriate treatment. Importantly, pancreatic function plays a critical role in changing bone turnover biomarkers.

Total Synthesis, structure revision and antifungal activity of palmarumycin B8 and B7.

Palmarymycins B8 (1), its regioisomer (2) and B7 (3) were synthesized via 10-, 9-, and 11-steps in 6.5 %, 2.3 % and 0.54 % overall yields from chroman-4-one (4), 4-hydroxyindanone (12), and 2,5-dimethoxybenzaldehyde (20) as the starting materials, using benzyl protection, enol trimethylsilyl ether by TMSOTf, Rubottom oxidation and deprotection with hydrogenation under Pd/C catalyst as the key steps, respectively. Their structures were characterized by 1H, 13C NMR, COSY, HSQC, HMBC and HR-ESI-MS spectral data. The structure of palmarumycin B8 was revised from 1 to 2 based on the total synthesis, 2D NMR analysis and DFT calculation. The antifungal assay results indicated that palmarumycin B8 (1) showed moderate inhibitory activity against Phytophthora capsica. Compounds 15 and 16 exhibited excellent in vitro antifungal activities against P. capsica with EC50 values of 2.17 and 8.50 µg/mL, respectively.

Utilize multi-metabolic parameters as determinants for prediction of skeletal muscle mass quality in elderly type2 diabetic Chinese patients.

BACKGROUND: Sarcopenia, an age-related disorder characterized by loss of skeletal muscle mass and function, is recently recognized as a complication in elderly patients with type 2 diabetes mellitus (T2DM). Skeletal muscles play a crucial role in glycemic metabolism, utilizing around 80% of blood glucose. Accordingly, we aimed to explore the relationship between glucose metabolism and muscle mass in T2DM. METHODS: We employed the AWGS 2019 criteria for diagnosing low muscle mass and 1999 World Health Organization (WHO) diabetes diagnostic standards. This study included data of 191 individuals aged 60 and above with T2DM of Shanghai Pudong Hospital from November 2021 to November 2022. Fasting C-peptide (FPCP), fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (PPG) and postprandial 2-hour C-peptide (PPCP), glycated hemoglobin A1c (HbA1c), glycated albumin (GA), serum lipids spectrum, renal and hepatic function, hemoglobin, and hormone were measured. Based on the findings of univariate analysis, logistic regression and receiver operating characteristic (ROC) curves were established. RESULTS: Participants with low muscle mass had significantly lower alanine and aspartate aminotransferase, and both FPCP and PPCP levels (P < 0.05). Compared with those without low muscle mass, low muscle mass group had significantly higher FPG, HbA1c, GA levels (P < 0.05). Body fat (BF, OR = 1.181) was an independent risk factor for low muscle mass. PPCP (OR = 0.497), BMI (OR = 0.548), and female (OR = 0.050) were identified as protective factors for low skeletal muscle. The AUC of BMI was the highest, followed by the PPCP, gender and BF (0.810, 0.675, 0.647, and 0.639, respectively), and the AUC of the combination of the above four parameters reached 0.895. CONCLUSIONS: In this cross-sectional study, BMI, Female, and PPCP associated with T2DM were protective factors for low muscle mass. BF was associated with T2DM and risk factor for low muscle mass.

Efficient gene editing in the slow-growing, non-sporulating, melanized, endophytic fungus Berkleasmium sp. Dzf12 using a CRISPR/Cas9 system.

The endophytic fungus Berkleasmium sp. Dzf12 that was isolated from Dioscorea zingiberensis, is a proficient producer of palmarumycins, which are intriguing polyketides of the spirobisnaphthalene class. These compounds displayed a wide range of bioactivities, including antibacterial, antifungal, and cytotoxic activities. However, conventional genetic manipulation of Berkleasmium sp. Dzf12 is difficult and inefficient, partially due to the slow-growing, non-sporulating, and highly pigmented behavior of this fungus. Herein, we developed a CRISPR/Cas9 system suitable for gene editing in Berkleasmium sp. Dzf12. The protoplast preparation was optimized, and the expression of Cas9 in Berkleasmium sp. Dzf12 was validated. To assess the gene disruption efficiency, a putative 1, 3, 6, 8-tetrahydroxynaphthalene synthase encoding gene, bdpks, involved in 1,8-dihydroxynaphthalene (DHN)-melanin biosynthesis, was selected as the target for gene disruption. Various endogenous sgRNA promoters were tested, and different strategies to express sgRNA were compared, resulting in the construction of an optimal system using the U6 snRNA-1 promoter as the sgRNA promoter. Successful disruption of bdpks led to a complete abolishment of the production of spirobisnaphthalenes and melanin. This work establishes a useful gene targeting disruption system for exploration of gene functions in Berkleasmium sp. Dzf12, and also provides an example for developing an efficient CRISPR/Cas9 system to the fungi that are difficult to manipulate using conventional genetic tools.

Elucidation of Palmarumycin Spirobisnaphthalene Biosynthesis Reveals a Set of Previously Unrecognized Oxidases and Reductases.

Spirobisnaphthalenes (SBNs) are a class of highly oxygenated, fungal bisnaphthalenes containing a unique spiroketal bridge, that displayed diverse bioactivities. Among the reported SBNs, palmarumycins are the major type, which are precursors for the other type of SBNs structurally. However, the biosynthesis of SBNs is unclear. In this study, we elucidated the biosynthesis of palmarumycins, using gene disruption, heterologous expression, and substrate feeding experiments. The biosynthetic gene cluster for palmarumycins was identified to be distant from the polyketide synthase gene cluster, and included two cytochrome P450s (PalA and PalB), and one short chain dehydrogenase/reductase (PalC) encoding genes as key structural genes. PalA is an unusual, multifunctional P450 that catalyzes the oxidative dimerization of 1,8-dihydroxynaphthalene to generate the spiroketal linkage and 2,3-epoxy group. Chemical synthesis of key intermediate and in vitro biochemical assays proved that the oxidative dimerization proceeded via a binaphthyl ether. PalB installs the C-5 hydroxy group, widely found in SBNs. PalC catalyzes 1-keto reduction, the reverse 1-dehydrogenation, and 2,3-epoxide reduction. Moreover, an FAD-dependent oxidoreductase, encoded by palD, which locates outside the cluster, functions as a 1-dehydrogenase. These results provided the first genetic and biochemical evidence for the biosynthesis of palmarumycin SBNs.

Diphenyl Ether Derivative Rhexocerins and Rhexocercosporins from the Endophytic Fungus Rhexocercosporidium sp. Dzf14 Active against Gram-Positive Bacteria with Multidrug-Resistance.

Ten new diphenyl ether polyketides, including rhexocerins A-D (1-4) and rhexocercosporins A-F (5-10), together with three known congeners (11-13), were isolated from the endophytic fungus Rhexocercosporidium sp. Dzf14 obtained from Dioscorea zingiberensis. Their structures were elucidated by analysis of NMR and HRESIMS data, and their absolute configurations were determined by quantum chemical ECD calculations and X-ray crystallography. Compounds 1-4 featured an unprecedented tetracyclic carbon skeleton (6/7/5/6). Among them, compounds 1 and 5-9 showed antibacterial activities against methicillin-resistant S. aureus T144 and vancomycin-resistant E. faecalis 10.

A Genome-Wide Comparison of Rice False Smut Fungus Villosiclava virens Albino Strain LN02 Reveals the Genetic Diversity of Secondary Metabolites and the Cause of Albinism.

Rice false smut (RFS) caused by Villosiclava virens (anamorph: Ustilaginoidea virens) has become one of the most destructive fungal diseases to decrease the yield and quality of rice grains. An albino strain LN02 was isolated from the white RFS balls collected in the Liaoning Province of China in 2019. The strain LN02 was considered as a natural albino mutant of V. virens by analyzing its phenotypes, internal transcribed spacer (ITS) conserved sequence, and biosynthesis gene clusters (BGCs) for secondary metabolites. The total assembled genome of strain LN02 was 38.81 Mb, which was comprised of seven nuclear chromosomes and one mitochondrial genome with an N50 value of 6,326,845 bp and 9339 protein-encoding genes. In addition, the genome of strain LN02 encoded 19 gene clusters for biosynthesis of secondary metabolites mainly including polyketides, terpenoids and non-ribosomal peptides (NRPs). Four sorbicillinoid metabolites were isolated from the cultures of strain LN02. It was found that the polyketide synthase (PKS)-encoding gene uspks1 for ustilaginoidin biosynthesis in strain LN02 was inactivated due to the deletion of four bases in the promoter sequence of uvpks1. The normal uvpks1 complementary mutant of strain LN02 could restore the ability to synthesize ustilaginoidins. It demonstrated that deficiency of ustilaginoidin biosynthesis is the cause of albinism for RFS albino strain LN02, and V. virens should be a non-melanin-producing fungus. This study further confirmed strain LN02 as a white phenotype mutant of V. virens. The albino strain LN02 will have a great potential in the development and application of secondary metabolites. The physiological and ecological functions of ustilaginoidins in RFS fungus are needed for further investigation.

Spatial-temporal evaluation of urban resilience in the Yangtze River Delta from the perspective of the coupling coordination degree.

Scientific evaluation of urban resilience will help to improve the ability of self-prevention and self-recovery when facing internal and external pressure. However, existing studies are on basis of the overall perspective of the urban resilience evaluation index system to measure urban resilience, often ignoring the coupling and coordination degree among indicators. Therefore, an empirical analysis is developed, which is used to measure the urban resilience of eight cities in the Yangtze River Delta urban agglomeration from 2010 to 2019 from the perspective of coupling coordination degree based on the urban resilience evaluation index system. The empirical results show that (1) In time, the eight cities' resilience fluctuated dynamically and varied to different degrees. It presents the spatial distribution characteristics of "high in the center and low in the periphery" in space. (2) In time, the coupling coordination degree in the eight cities fluctuated slightly. The spatial distribution pattern of "high in the center and low in the periphery" was formed in terms of space. (3) There is a long-term stable relationship between urban resilience and the coupling coordination degree among all indicators. In a certain sense, the higher the coupling coordination degree is, the higher the urban resilience is. These results can improve urban resilience to some extent and make cities more resilient in the future collaborative development process, and provide a way to evaluate urban resilience at different spatial-temporal scales.

Factors associated with higher falling risk in elderly diabetic patients with lacunar stroke.

PURPOSE: The aim of this study is to explore the factors associated with the fall risk in type 2 diabetes (T2D) patients with a lacunar stroke. MATERIALS AND METHODS: We compiled data of 146 T2D patients (mean age 68 years), including the Morse fall scale data (MFS), nutrition score, self-care scale, laboratory data, and data from continuous glucose monitoring system (CGMS) from 2019 to 2021 in Shanghai Pudong Hospital. Thereby, we evaluated the associations between MFS and other clinical parameters. RESULTS: The analyses showed that there were significantly increased size and numbers of lacunar infarction (p < 0.05). Furthermore, the greater risk group had an older mean age (p < 0.05), and significant decreased estimated glomerular filtration rate (eGFR), total triglyceride (TG), while increased microalbuminuria, magnesium, lipoprotein A (LP(a)), anti-thyroid peroxidase antibody (TPOAb) (p < 0.05). However, the time in range (TIR) was very comparable (p > 0.05). The correlational study revealed the higher score of MFS was associated with the age (r = 0.41), number of lacunar infarction (r = 0.18), nutrition score (r = 0.20), self-care score (r = - 0.43), serum creatine level (r = 0.19), eGFR (r = - 0.26) (p < 0.05). The total numbers of lacunar infarction were associated with age (r = 0.36), eGFR (r = - 0.40), homocysteine level (r = 0.33) (p < 0.05). CONCLUSIONS: Age, nutrition, self-care ability, and renal function are all critical factors associated with the risk of fall in T2D with lacunar infarction. The age, eGFR, and homocysteine are closely associated with lacunar infarction, suggesting that in T2D, evaluation of kidney dysfunction, homocysteine level in the elderly can predict lacunar infarcts and falls.

CircLDLR acts as a sponge for miR-667-5p to regulate SIRT1 expression in non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver (NAFLD) is a complex metabolic disease characterized by fatty degeneration of hepatocytes. Circular RNAs (circRNAs) have been reported to be essential for (NAFLD progression. The potential mechanism of circRNA low-density lipoprotein receptor (circLDLR) in the NAFLD was investigated in this study. METHODS: Hepatocyte (Hepa1-6) cells treated with oleic acid/palmitic acid (OA/PA) were used as the in vitro NAFLD model, and C57BL/6 mice fed with high-fat diet (HFD) were used as the in vivo NAFLD model. The circLDLR, LDLR, and miR-667-5p expression were measured by quantitative real-time polymerase chain reaction (qRT-PCR), while the protein levels of Light Chain Microtubule-Associated Protein 3 (LC3) and Sequestosome-1(p62) was examined by western blot. The circLDLR location was confirmed using RNA fluorescence in situ hybridization. Oil red O staining was carried out to measure lipid deposition in cells. The secreted levels of triglyceride (TG) and total cholesterol (TC) were detected through Enzymatic. The existence of the circLDLR/miR-667-5p/sirtuin 1 (SIRT1) regulatory axis was validated by applying the dual-luciferase reporter assay. RESULTS: The circLDLR expression showed a prominent down-regulation in OA/PA-treated Hepa1-6 cells, whereas the LDLR expression was up-regulated. Overexpression of circLDLR significantly attenuated lipid droplet accumulation in NAFLD models in vitro/vivo, reduced TG, TC, and p62 levels, and increased LC3-II levels and the amount of the green fluorescent protein (GFP)-LC3 puncta in cells. CircLDLR and SIRT1 are common targets of miR-667-5p to inhibit the TG and TC and promote the autophagy pathway. SIRT1 knockdown reversed the effects of circLDLR overexpression. CONCLUSIONS: CircLDLR alleviated the development of NAFLD by inducing autophagic flux while modulating the miR-667-5p/SIRT1 axis reversed its effects, suggesting that targeting circLDLR/miR-667-5p/SIRT1 axis may be a promising therapeutic strategy for NAFLD.

UvSorA and UvSorB Involved in Sorbicillinoid Biosynthesis Contribute to Fungal Development, Stress Response and Phytotoxicity in Ustilaginoidea virens.

Ustilaginoidea virens (teleomorph: Villosiclava virens) is an important fungal pathogen that causes a devastating rice disease. It can produce mycotoxins including sorbicillinoids. The biosynthesis and biological functions of sorbicillinoids have not been reported in U. virens. In this study, we identified a sorbicillinoid biosynthetic gene cluster in which two polyketide synthase genes UvSorA and UvSorB were responsible for sorbicillinoid biosynthesis in U. virens. In ∆UvSorA and ∆UvSorB mutants, the mycelial growth, sporulation and hyphal hydrophobicity were increased dramatically, while the resistances to osmotic pressure, metal cations, and fungicides were reduced. Both phytotoxic activity of rice germinated seeds and cell wall integrity were also reduced. Furthermore, mycelia and cell walls of ∆UvSorA and ∆UvSorB mutants showed alterations of microscopic and submicroscopic structures. In addition, feeding experiment showed that sorbicillinoids could restore mycelial growth, sporulation, and cell wall integrity in ∆UvSorA and ∆UvSorB mutants. The results demonstrated that both UvSorA and UvSorB were responsible for sorbicillinoid biosynthesis in U. virens, and contributed to development (mycelial growth, sporulation, and cell wall integrity), stress responses, and phytotoxicity through sorbicillinoid mediation. It provides an insight into further investigation of biological functions and biosynthesis of sorbicillinoids.

A very preterm infant born to mother of mirror syndrome secondary to fetomaternal hemorrhage: a case report.

BACKGROUND: Mirror syndrome (MS) is defined as maternal edema with fetal hydrops and placental edema with different etiologies, such as rhesus isoimmunization and twin-twin transfusion syndrome. Herein, we showcased a unique MS case secondary to fetomaternal hemorrhage (FMH). CASE PRESENTATION: A 32-year-old gravida 2 para 0 woman diagnosed with fetal hydrops was admitted to our hospital. Maternal laboratory tests revealed anemia, slightly increased creatinine and uric acid levels, hypoproteinemia, and significantly increased alpha-fetoprotein and hemoglobin-F levels. Therefore, FMH was diagnosed initially. Two days after admission, the woman had unexpectedly progressive anasarca and started to feel chest distress, palpitations, lethargy, and oliguria, and MS was suspected. An emergency cesarean section was performed to terminate the pregnancy. The maternal clinical symptoms and laboratory tests rapidly improved after delivery. A very preterm infant with a 2080-g birthweight at 31 weeks gestation survived after emergency cesarean section, active resuscitation, emergency blood transfusion, abdominocentesis, and advanced life support. CONCLUSIONS: FMH could develop into MS, providing new insights into the etiology of MS. Once MS is diagnosed, emergency cesarean section might be an alternative treatment. The very preterm infant survived with a favorable long-term outcome, and a well-trained perinatal work team is needed for such cases.

Consensus-Based Linguistic Distribution Large-Scale Group Decision Making Using Statistical Inference and Regret Theory.

Large-scale group decision-making (LSGDM) deals with complex decision- making problems which involve a large number of decision makers (DMs). Such a complex scenario leads to uncertain contexts in which DMs elicit their knowledge using linguistic information that can be modelled using different representations. However, current processes for solving LSGDM problems commonly neglect a key concept in many real-world decision-making problems, such as DMs' regret aversion psychological behavior. Therefore, this paper introduces a novel consensus based linguistic distribution LSGDM (CLDLSGDM) approach based on a statistical inference principle that considers DMs' regret aversion psychological characteristics using regret theory and which aims at obtaining agreed solutions. Specifically, the CLDLSGDM approach applies the statistical inference principle to the consensual information obtained in the consensus process, in order to derive the weights of DMs and attributes using the consensus matrix and adjusted decision-making matrices to solve the decision-making problem. Afterwards, by using regret theory, the comprehensive perceived utility values of alternatives are derived and their ranking determined. Finally, a performance evaluation of public hospitals in China is given as an example in order to illustrate the implementation of the designed method. The stability and advantages of the designed method are analyzed by a sensitivity and a comparative analysis.

Circular RNA expression profiles and features in NAFLD mice: a study using RNA-seq data.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is primarily characterized by the hepatic cholesterol accumulation. Circular RNA (circRNA), one of noncoding RNA, involves in many liver diseases progression. However, no recent studies on circRNA expression profiles in NAFLD have been reported previously. METHODS: A NAFLD mouse model was constructed by providing high-fat diet (HFD) for 32 weeks. The circRNAs expression profile in normal mice and NAFLD mice were determined using high-output RNA sequencing method and bioinformatics methods, while the differentially expressed circRNAs were confirmed using Sanger sequencing and qRT-PCR. The circRNA-miRNA network was also predicted. The biological functions of circRNAs were annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). RESULTS: The results demonstrated the successful construction of NAFLD mice model by immunohistology and serology assay. In total, 93 dysregulated circRNAs were observed, including 57 upregulated circRNAs and 36 downregulated circRNAs, in the NAFLD group. The circRNA-miRNA network revealed the complex interaction between circRNAs and its potential miRNA targets in NAFLD. The characteristic of tissue-specific expression in circRNA was demonstrated. The differentially expressed circRNAs with important biological function were also annotated using GO and KEGG. Both DDAH1 and VAV3 genes were found to be associated with the NAFLD development. CONCLUSIONS: Taken together, this study demonstrated the circRNAs expression profile and features in NAFLD, which may provide potential biological markers for the pathogenesis of NAFLD.

Ustiloxin A is Produced Early in Experimental Ustilaginoidea virens Infection and Affects Transcription in Rice.

Ustiloxin is a kind of 13-membered cyclic peptides found in mature rice false smut generated by Ustilaginoidea virens infecting rice spikelet. So far, six kinds of ustiloxins have been identified from false smut balls (FSBs) in which ustiloxin A is the main component. The toxins can not only inhibit the growth of rice, wheat, and corn, but also poison people and animals. However, so far, there have been few studies of the content of ustiloxin except that in mature FSB. The effect of ustiloxins on the process of infection has not been clarified. In this study, the technique of artificial inoculation coupled with UPLC-ESI-MS was introduced to investigate the content of ustiloxins in the course of infection. The initial formation time of ustiloxin A, B, C, D, F, and G was no later than 5, 5, 9, 7, 7, and 9 days post inoculation (dpi) prior to FSB's formation, respectively. The content of ustiloxin A per spikelet was increased rapidly from 6.0 ng at 5 dpi to 14,157.1 ng at 25 dpi. Meanwhile, the content of ustiloxin A per dry weight (DW) of the FSBs also peaked at 1321.2 µg/g at 25 dpi. Interestingly, both the contents of ustiloxin A per dry weight and per spikelet were significantly reduced from 25 to 30 dpi. Transcriptome sequencing revealed that a total of 146 transcripts (103 upregulated and 43 downregulated) were significantly changed in rice spikelets after 3-h acute exposure to 100 ng ustiloxin A. In addition, several of the significantly altered genes were validated by RT-qPCR.

Shifting diets and the rise of male-biased inequality on the Central Plains of China during Eastern Zhou.

Farming domesticated millets, tending pigs, and hunting constituted the core of human subsistence strategies during Neolithic Yangshao (5000-2900 BC). Introduction of wheat and barley as well as the addition of domesticated herbivores during the Late Neolithic (∼2600-1900 BC) led to restructuring of ancient Chinese subsistence strategies. This study documents a dietary shift from indigenous millets to the newly introduced cereals in northcentral China during the Bronze Age Eastern Zhou Dynasty (771-221 BC) based on stable isotope analysis of human and animal bone samples. Our results show that this change affected females to a greater degree than males. We find that consumption of the newly introduced cereals was associated with less consumption of animal products and a higher rate of skeletal stress markers among females. We hypothesized that the observed separation of dietary signatures between males and females marks the rise of male-biased inequality in early China. We test this hypothesis by comparing Eastern Zhou human skeletal data with those from Neolithic Yangshao archaeological contexts. We find no evidence of male-female inequality in early farming communities. The presence of male-biased inequality in Eastern Zhou society is supported by increased body height difference between the sexes as well as the greater wealth of male burials.

The hypoglycemia associated autonomic failure triggered by exercise in the patients with "brittle" diabetes and the strategy for prevention.

Exercise is a fundamental component of diabetes management. However, choosing inappropriate type or timing of exercise is associated with mild or severe hypoglycemia either during exercise or several hours after exercise. Several studies have shown that impaired counterregulatory responses triggers hypoglycemia. Therefore, in this investigation, we explored the appropriate intensity and time of exercise in patients with diabetes. The mechanisms of counterregulatory responses and hypoglycemia associated autonomic failure (HAAF), as well as the strategies for preventing episodes of hypoglycemia after exercise were also investigated. In this study, we obtained the following results: 1) High intensity interval exercise is more suitable for diabetic patients. 2) Morning exercise reduces nocturnal hypoglycemia risks compared with midday, afternoon and evening exercise. 3) Hypoglycemia can be prevented by dietary approach, reduction or suspension of insulin dose, use of mini dose glucagon, caffeine, mitigation methods, prediction algorithm, autonomic feedback controlled close-loop insulin delivery, real time continuous glucose monitoring. Based on these results we concluded that exercise may cause severe hypoglycemia or induce blunted response in patients with diabetes. For Diabetes Mellitus (DM) patients, the intensity and time of exercise influence the occurrence of hypoglycemia. This review summarizes the clinical characteristics of different types of exercises and time of exercise that can be potentially used to educate and guide patients regarding the role of exercise in standard of care.

The impact of neuropsychiatric disease on fetal growth: a case-control study.

PURPOSE: To determine the impact of depression, epilepsy and drug abuse during pregnancy on delivery and fetal outcome. Due to the worldwide increasing prevalence of neurological and psychiatric diseases and drug abuse, the number of affected pregnant women is increasing. METHODS: A large-scale retrospective case-control analysis of pregnancies affected by depression, epilepsy or drug abuse with and without medication was conducted in two German perinatal centres between 2013 and 2017. The case group consisted of 706 pregnant women who had a diagnosis of depression, epilepsy or drug abuse vs. 12,574 pregnant women without neuropsychiatric diagnosis (control group). The analysis included the rate of intrauterine growth restriction, birth weight and length, neonatal head circumference. RESULTS: Significant differences in the subgroups were found in the parameters intrauterine growth restriction, birth weight, length and head circumference. Women with epilepsy were affected less often than women with depression and substance abuse. Major differences were found in the group of women with substance abuse. Negative associations were found within the non-pharmacologically managed disease group itself compared to women exposed to medication. CONCLUSION: The present results demonstrated a negative association between maternal neurological or psychiatric disease and pregnancy outcome in the examined parameters. However, the non-pharmacologically treated maternal disease was identified as a risk factor itself.

A composite consisting of sulfo-functionalized magnetic graphene and mesoporous silica for extraction of metformin and glimepiride prior to their determination by liquid chromatography tandem mass spectrometry.

A new sorbent was synthesized for restricted-access matrix solid phase extraction (RAM-SPE) of the diabetes drugs metformin (MET) and glimepiride (Glim). Mesoporous silica layers were placed on Fe3O4-magnetized graphene modified with sulfo-functionalized pore walls (denoted as magG@mSiO2-SO3H composites). The composites have a large specific surface (173 m2·g-1), appropriate pore sizes (typically 3.7 nm), and sulfo-functionalized pore walls. Magnetic separation can be accomplished within 10 s. The unique properties of the composites allow both MET and Glim to be selectively and quickly extracted from plasma sample. Following magnetic separation and elution by 50% aqueous acetonitrile with 4% ammonium solution, the two drugs were quantified by LC-MS/MS analysis. The assay has high selectivity, good linearity (2.5-4000 ng•mL-1 for MET and 0.02-1600 ng•mL-1 for Glim), a low detection limit (as low as 60 pg•mL-1 for MET and 1 pg•mL-1 for Glim), excellent recovery (above 92.2%), and good precision (RSDs <12%). The method was successfully applied in a pharmacokinetic study in beagle dogs. Graphical abstract Schematic representation of the synthesis of sulfo-functionalized magnetic graphene/mesoporous silica composites, giving a material of type magG@mSiO2-SO3H. Results showed its great potential as a feasible and alternative adsorbent for the selective extraction of MET and Glim from complicated biological samples.