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Abstract Prolactin-releasing peptide (PrRP) is an RF-amide neuropeptide that binds and activates its cognate G protein-coupled receptor, prolactin-releasing peptide receptor (PrRPR), also known as GPR10. PrRP and PrRPR are highly conserved across mammals and involved in regulating a range of physiological processes, including stress response, appetite regulation, pain modulation, cardiovascular function, and potentially reproductive functions. Here we present cryo-electron microscopy structures of PrRP-bound PrRPR coupled to Gq or Gi heterotrimer, unveiling distinct molecular determinants underlying the specific recognition of the ligand’s C-terminal RF-amide motif. We identify a conserved polar pocket that accommodates the C-terminal amide shared by RF-amide peptides. Structural comparison with neuropeptide Y receptors reveals both similarities and differences in engaging the essential RF/RY-amide motifs. Our findings demonstrate the general mechanism governing RF-amide motif recognition by PrRPR and RF-amide peptide receptors, and provide a foundation for elucidating activation mechanisms and developing selective drugs targeting this important peptide–receptor system.

Abstract Melanin-concentrating hormone (MCH) is a cyclic neuropeptide that regulates food intake, energy balance, and other physiological functions by stimulating MCHR1 and MCHR2 receptors, both of which are class A G protein-coupled receptors. MCHR1 predominately couples to inhibitory G protein, Gi/o, and MCHR2 can only couple to Gq/11. Here we present cryo-electron microscopy structures of MCH-activated MCHR1 with Gi and MCH-activated MCHR2 with Gq at the global resolutions of 3.01 Å and 2.40 Å, respectively. These structures reveal that MCH adopts a consistent cysteine-mediated hairpin loop configuration when bound to both receptors. A central arginine from the LGRVY core motif between the two cysteines of MCH penetrates deeply into the transmembrane pocket, triggering receptor activation. Integrated with mutational and functional insights, our findings elucidate the molecular underpinnings of ligand recognition and MCH receptor activation and offer a structural foundation for targeted drug design.

Abstract Background Modifying diet is crucial for diabetes and complication management. Numerous studies have shown that adjusting eating habits to align with the circadian rhythm may positively affect metabolic health. However, eating midpoint, eating duration, and their associations with diabetic kidney disease (DKD) are poorly understood. Methods The National Health and Nutrition Examination Survey (2013–2020) was examined for information on diabetes and dietary habits. From the beginning and ending times of each meal, we calculated the eating midpoint and eating duration. Urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g and/or estimated glomerular filtration rate (eGFR)

Objectives Clinically, it is very difficult to prevent pathological fracture caused by high recurrence rate of osteolytic disease of proximal femur in children. At present, there is no consensus in clinical studies of which internal fixation method can significantly reduce the probability of recurrence of pathological fracture. The study aims to research the mechanical properties of different internal fixations in the treatment of osteolytic lesions of proximal femur in children by finite element analysis, and to find out the optimal treatment. Methods Based on finite element analysis, the osteolytic disease models of the femoral neck and intertrochanter in a child (8‐year‐old, boy) were established respectively, and different internal fixation models (plate and titanium elastic intramedullary nails, TENs) were assembled. For the osteolytic lesion of the femoral neck: model A1 was assembled with a plate; model A2 with two TENs crossing the physis; model A3 with two TENs without crossing the physis. And for pertrochanteric osteolytic lesion: model B1 was assembled with a plate, model B2 with two TENs crossing the physis and model B3 with two TENs without crossing the physis. The Eccentric bearing load, torsional restraintal restraint of calcar femorale and composite load were analyzed for each models. Results When the yield strain of each model is reached, the stress concentration points are located in the proximal and distal femoral calcar. In the model of femoral neck lesions, the failure load of model A1 and model A2 are the same (1250 N), and the failure load of model A3 (980 N) is significantly lower than that of the former two; in the model of intertrochanteric lesions, the failure load of model B2 is the largest (1350 N), and the failure load of model B1 (1220 N) is lower than that of model B3 (1260 N), but both are smaller than that of model B2. Conclusion Through finite element analysis, TENs through the epiphyseal plate, is found to be the better internal fixation method for femoral neck lesions and intertrochanteric lesions under two different working conditions. The results of clinical correlation study provide new biomechanical information for orthopedic doctors to consider different treatment options for osteolytic lesions of proximal femur.

As the “heart” of continuous caster, the flow field of mold directly affects the quality of the slab. For a billet caster, in-mold electromagnetic stirring (M-EMS), as its necessary configuration, can improve the flow field in the mold, homogenize the liquid steel temperature, improve segregation, and improve the slab quality. This paper utilized a 410 mm × 530 mm large billet caster in a factory, which is one of the largest section casters in China. Based on it, a three-dimensional numerical model was established using the ANSYS finite element software to study the influence of electromagnetic stirring on the flow field, liquid level fluctuation, and temperature field of the mold. After electromagnetic stirring was applied, the liquid steel was subjected to a radial electromagnetic force, and the liquid surface shows a rotating flow trend. The maximum tangential velocity of molten steel increases with the increase of current and decreases with the increase of frequency. When the current of electromagnetic stirring increases from 0 A to 500 A, the fluctuation of the liquid level increases from 1.21 mm to 4.35 mm. The maximum tangential velocity of the electromagnetic stirring center increases from 0.02 m∙s−1 to 0.21 m∙s−1. Electromagnetic stirring can restrain the impact of the high-temperature jet from the nozzle, move the high-temperature zone of molten steel upward, and make the temperature of molten steel more uniform. Under the action of a radial electromagnetic force, the horizontal swirl of liquid steel can inhibit the growth of the primary shell, reduce the growth rate of the shell, and reduce the thickness of the shell out of the mold by about 2.3 mm. The comprehensive analysis shows that the reasonable current of electromagnetic stirring is 400 A and the frequency is 1.5 Hz. At this time, the fluctuation of the slag level is about 2.73 mm, and the temperature field is relatively uniform.

Here, the authors report structures of corticotropin releasing factor receptor 2 (CRF2R) bound to agonist Urocortin 1 (UCN1) and coupled to G proteins G11 and Go, offering insight into the structural basis for the ability of CRF2R to couple with multiple G protein subtypes.

Abstract Background Increased serum carcinoembryonic antigen (CEA) levels are reported to be associated with various metabolic and inflammatory diseases. This study assessed whether high-normal serum CEA is related to diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes (T2D). Methods All subjects received DPN assessment based on neuropathic symptoms, neuropathic signs, and nerve conduction studies to calculate composite Z scores of nerve latency, amplitude and conduction velocity (NCV). DPN was confirmed by both at least a presentation of neuropathic symptoms/signs and an abnormal nerve conduction index. Serum CEA levels and other clinical indices were also synchronously detected. Multivariable linear regression analyses were used to determine the independent effects of serum CEA levels on nerve conduction indices, multivariable logistic regression analyses were used to determine the independent impact of CEA levels on the risk of DPN, and receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic capability of CEA levels to discriminate DPN. Results We ultimately recruited 402 eligible subjects with normal ranges of serum CEA for this study, and 25.4% (n = 102) were determined to have DPN. After adjusting for other clinical covariates, serum CEA levels were independently associated with the composite Z score for latency (β = 0.132, t = 2.330, p = 0.021), amplitude (β = − 0.164, t = − 2.838, p = 0.005) and NCV (β = − 0.210, t = − 3.662, p

Vasoactive intestinal polypeptide receptor 2 (VIP2R) is involved in immunity. Here, the authors report two cryo-EM structures of the VIP2R–Gs in complex with the endogenous peptide ligand PACAP27, revealing a unique interaction mode between PACAP27 and the receptor, stabilized by the N-terminal α-helix of VIP2R.

Abstract Background Body composition alterations may participate in the pathophysiological processes of type 2 diabetes (T2D). A sedentary lifestyle may be responsible for alterations of body composition and adverse consequences, but on which body composition of patients with T2D and to what extent the sedentary lifestyle has an effect have been poorly investigated. Methods We recruited 402 patients with T2D for this cross-sectional study. All patients received questionnaires to evaluate sedentary time and were further divided into three subgroups: low sedentary time (LST, 8 h, n = 164). Each patient underwent a dual energy X-ray absorptiometry (DXA) scan to detect body composition, which included body fat percentage (B-FAT), trunk fat percentage (T-FAT), appendicular skeletal muscle index (ASMI), lumbar spine bone mineral density (BMD) (LS-BMD), femoral neck BMD (FN-BMD), hip BMD (H-BMD) and total BMD (T-BMD). Other relevant clinical data were also collected. Results With increasing sedentary time (from the LST to HST group), B-FAT and T-FAT were notably increased, while ASMI, LS-BMD, FN-BMD, H-BMD and T-BMD were decreased (p for trend

Abstract Background Plasma 1,5-anhydro-d-glucitol (1,5-AG) may be a easily accessible marker for glycemic variability under mild-to-moderate hyperglycemia. The present study was to investigate the association of 1,5-AG with peripheral nerve function and diabetic peripheral neuropathy (DPN) in patients with T2D and mild-to-moderate hyperglycemia. Methods We recruited 574 T2D patients with mild-to-moderate hyperglycemia (HbA1c

Background Type 2 diabetes mellitus (T2DM) is characterized by elevated fasting glucagon and impaired suppression of postprandial glucagon secretion, which may participate in diabetic complications. Therefore, we investigated the associations of plasma glucagon with estimated glomerular filtration rate (eGFR), albuminuria and diabetic kidney disease (DKD) in T2DM patients. Methods Fasting glucagon and postchallenge glucagon (assessed by area under the glucagon curve [AUCgla]) levels were determined during oral glucose tolerance tests. Patients with an eGFR

Abstract Background Deterioration of sleep quality has been reported to contribute to the incidence of diabetes and may be responsible for glycemic status in diabetes. The present study explored the relationship between sleep quality and glycemic variability in patients with type 2 diabetes (T2D). Methods We recruited 111 patients with T2D for this cross-sectional study. Each patient underwent flash glucose monitoring for 14 days to obtain glycemic variability parameters, such as standard deviation of glucose (SD), coefficient of variation of glucose (CV), mean amplitude of glycemic excursions (MAGE), mean of daily differences (MODD), and time in glucose range of 3.9–10 mmol/L (TIR3.9–10). After 14 days of flash glucose monitoring, each patient received a questionnaire on the Pittsburgh Sleep Quality Index (PSQI) to evaluate subjective sleep quality. HbA1c was also collected to assess average glucose. Results HbA1c was comparable among the subgroups of PSQI score tertiles. Across ascending tertiles of PSQI scores, SD, CV and MAGE were increased, while TIR3.9–10 was decreased (p for trend

BackgroundIncreased serum adenosine deaminase (ADA) levels have been shown to be involved in metabolic abnormalities and immune disequilibrium, which may in turn contribute to inflammatory diseases. This study aimed to determine whether increased serum ADA levels are related to diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes (T2D).MethodsThis study was part of a series exploring the potential risks for DPN. All patients received DPN assessment based on neuropathic symptoms, neuropathic signs, and nerve conduction studies to calculate the composite Z score of nerve latency, amplitude and conduction velocity (NCV). DPN was confirmed by both at least a presentation of neuropathic symptoms/signs and an abnormal nerve conduction index. Serum ADA levels were also synchronously detected.ResultsA total of 384 eligible patients with T2D were recruited for this study, and 24.5% (n=94) were determined to have DPN. Increases in serum ADA levels were closely associated with increases in composite Z score of latency (β=0.263, t=5.273, p

Given the accelerating depletion of iron ore resources, there is growing concern within the steel industry regarding the availability of high-phosphorus iron ore. However, it is important to note that the utilization of high-phosphorus iron ore may result in elevated phosphorus content and notable fluctuations in molten iron, thereby imposing additional challenges on the dephosphorization process in steelmaking. The most urgent issue in the process of converter steelmaking is how to achieve efficient dephosphorization. In this study, the influence of various factors on the logarithm of the phosphorus balance distribution ratio (lgLp), the logarithm of the P2O5 activity coefficient (lgγP2O5), and the logarithm of the phosphorus capacity (lgCp) were examined through thermodynamic calculations. The impact of each factor on dephosphorization was analyzed, and the optimal conditions for the dephosphorization stage of the converter were determined. Furthermore, the influence of basicity and FetO content on the form of phosphorus in the slag was analyzed using FactSage 7.2 software, and the precipitation rules of the slag phases were explored. The thermodynamic calculation results indicated that increasing the basicity of the dephosphorization slag was beneficial for dephosphorization, but it should be maintained below 3. The best dephosphorization effect was achieved when the FetO content was around 20%. The reaction temperature during the dephosphorization stage should be kept low, as the dephosphorization efficiency decreased sharply with the increasing temperature. In dephosphorization slag, Ca3(PO4)2 usually formed a solid solution with Ca2SiO4, so the form of phosphorus in the slag was mainly determined by the precipitation form and content of Ca2SiO4. The phases in the dephosphorization slag mainly consisted of a phosphorus-rich phase, an iron-rich phase, and a matrix phase. The results of scanning electron microscopy and X-ray diffraction analyses were consistent with the thermodynamic calculation results.

BackgroundIncreased plasma D-dimer levels have been reported to be associated with a range of adverse health outcomes. This study aimed to determine whether plasma D-dimer is connected to diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes (T2D).MethodsThis study was part of a series exploring the potential risks for DPN. All patients were questioned for neurologic symptoms, examined for neurologic signs, and received nerve conduction studies to collect nerve action potential onset latency, amplitude, and nerve conduction velocity (NCV). Composite Z scores of latency, amplitude, and NCV were calculated. DPN was confirmed as both at least a neurologic symptom/sign and an abnormality of nerve conduction studies. Coagulation function indices, such as plasma D-dimer levels, were also synchronously detected.ResultsWe finally recruited 393 eligible patients for this study, of whom 24.7% (n = 97) were determined to have DPN. The plasma D-dimer level was found to be closely associated with the composite Z score of latency, amplitude, and NCV after adjusting for other coagulation function indices and clinical covariates (latency: β = 0.134, t = 2.299, p = 0.022; amplitude: β = –0.138, t = –2.286, p = 0.023; NCV: β = –0.139, t = –2.433, p = 0.016). Moreover, the prevalence of DPN in the first, second, third, and fourth quartiles (Q1, Q2, Q3, and Q4) of the D-dimer level was 15.2%, 15.9%, 26.4%, and 42.7%, respectively (p for trend < 0.001). The corresponding adjusted odds ratios and 95% CIs for DPN in D-dimer quartiles were 1, 0.79 (0.21–2.99), 1.75 (0.49–6.26), and 5.17 (1.38–19.42), respectively. Furthermore, the optimal cutoff value of the plasma D-dimer level to discriminate DPN was ≥0.22 mg/L (sensitivity = 67.01%, specificity = 58.78%, and Youden index = 0.26) after analysis by the receiver operating characteristic curve.ConclusionsIncreased plasma D-dimer levels may be a promising indicator for DPN in patients with T2D.

Growth hormone-releasing hormone (GHRH) controls metabolism and tissue growth through binding to the cognate receptor (GHRHR). Here authors report the structure of the human GHRHR bound to its endogenous ligand and the stimulatory G protein which reveals a characteristic hormone recognition pattern of GHRH by GHRHR.

Objective. To explore the characteristics and analyze the gut microbiota in female patients with diabetic microvascular complications (DMC). Methods. Thirty-seven female patients with type 2 diabetes mellitus (T2DM) were included in the study. These patients were divided into DM group with microvascular complications (T2DM-MC, n=17) and no microvascular complications group (T2DM-0, n=20). Patients in the microvascular group presented with the involvement of at least one of the following: kidney, retinal, or peripheral nerves. Using real-time fluorescence quantitative polymerase chain reaction, fecal samples from the two groups were tested for Bacteroides, Prevotella, Bifidobacterium spp, Lactobacillus, Faecalibacterium prausnitzii, Enterococcus spp, Eubacterium rectale, Veillonellaceae, Clostridium leptum, and Roseburia inulinivorans. Levels of fasting and 2 h postprandial blood glucose, glycosylated hemoglobin (HbA1c), lipids, and creatinine were determined to explore the correlation between gut microbiota and blood sugar. Mann–Whitney U test was used to analyze the differences between the two groups. Spearman correlation analysis was used to determine the correlation between gut microbiota and blood glucose. Multifactor logistic regression was used to analyze the risk factors for DMC. Results. The HbA1c levels in the T2DM-MC group were higher than those in the T2DM-0 group. The abundances of Bacteroides and Enterococcus spp in the T2DM-MC group were higher than that in the T2DM-0 group. The abundances of Bacteroides and Enterococcus spp in the T2DM-MC group were lower than that in the T2DM-0 group. Spearman’s correlation analysis showed that Bacteroides, Prevotella, Lactobacillus, C. leptum, and R. inulinivorans were related to the levels of HbA1c or blood glucose (p

Tomato zonate spot virus (TZSV), a member of the genus orthotospovirus, causes severe damage to vegetables and ornamental crops in southwest China. The NSs protein is an RNA silencing suppressor in various orthotospovirus like TZSV, but its mechanism and role in virus infection are poorly understood. Here, we observed that an NSs-GFP fusion protein was transiently expressed on the plasma membrane and Golgi bodies in Nicotiana benthamiana plants. The TZSV NSs gene was silenced and infiltrated into N. benthamiana and N. tabacum cv. K326. RT-qPCR and Indirect enzyme-linked immunosorbent assay (ID-ELISA) showed that the transcription and the protein expression of the NSs gene were inhibited by more than 90.00%, and the symptoms on silenced plants were alleviated. We also found that the expression of the Zingipain-2-like gene significantly decreased when the NSs gene was silenced, resulting in co-localization of the NSs-GFP and the Zingipain-2-like-mCherry fusion protein. The findings of this study provide new insights into the mechanism of silencing suppression by NSs, as well as its effect on systemic virus infection, and also support the theory of disease resistance breeding and control and prevention of TZSV in the field.

Background: To assess the effectiveness of the nurse-led individualised self-care model on myocardial infarction (MI) patients with diabetes. Methods: A total of 120 MI patients were enrolled from May 2020 to December 2021. The intervention group received the nurse-led individualised self-care model (n = 60), whereas the control group only received routine health education (n = 60). The Myocardial Infarction Dimensional Assessment Scale (MIDAS), Coronary Heart Disease Self-Management Behavior Scale (CSMS), Self-Rated Abilities for Health Practices (SRAHP) scale, General Self-Efficacy Scale (GSES), Hospital Anxiety and Depression Scale (HADS), blood glucose and nursing satisfaction in both groups were observed and recorded. Results: The six MIDAS subscales except for insecurity, and all dimensions of the CSMS, SRAHP, GSES and HADS scores, of the intervention group were significantly improved compared to those of the control group (p < 0.05). Compared with the control group (5.69 ± 1.43 mmol/L), the intervention group showed a decrease in the serum levels of fasting blood glucose (4.83 ± 1.57 mmol/L; p < 0.01). Conclusions: Our pilot study provides preliminary evidence supporting the feasibility of implementing nurse-led individualised self-care, suggesting its preliminary effects in improving health-related quality of life, self-care ability, health behaviours, self-efficacy, social support and nursing satisfaction among MI patients with diabetes. However, considering the unblinded and pilot nature of this study, these positive results should be interpreted with caution. Clinical Trial Registration: OSF Registration number: DOI 10.17605/OSF.IO/DVW95 (https://archive.org/details/osf-registrations-dvw95-v1).

Objectives To review the experience at our center with elastic stable titanium flexible intramedullary nails (ESIN) for pediatric femoral shaft unstable fractures. Methods From January 2015 to January 2017, 56 consecutive patients with femur shaft fractures were treated in our hospital. History and radiologic parameters were retrospectively reviewed. The inclusion criteria were: femur shaft fractures treated by ESIN or locking compressing plates (LCP); more than 2 years’ follow‐up care; and complete clinical information. A total of 51 patients were included according to the criteria: 16 girls and 35 boys. Ages at operation averaged 5.9 ± 2.8 years. Outcome: anteroposterior (AP) and lateral X‐ray radiographs were performed every 2 weeks before the fracture healing, every 3 months until 1 year, then once a year after the surgery. Clinical examinations were recorded for any clinical deformity, hardware prominence, pain, and infection. ESIN were applied in either a retrograde or an antegrade fashion for 29 patients. For 22 patients, LCP were implanted. For the remaining 5 cases, instruments other than ESIN and LCP were applied. Results The average follow‐up time was 29 months (range, 24–37 months). The average operation time was 78.2 min (range, 25–155 mins). The average blood loss in surgery was 69.6 mL (range, 3–700 mL). The average healing of fracture time was 2.2 month (range, 1–6 months). The average removal of implants time was 7.8 months (range, 3–20 months). The average expense for index operation was CNY 31 100 (CNY 17 500–142 200). Comminution grades were strongly correlated with time to fracture union (P

Abstract Background Diabetic complications may be associated with impaired time-dependent glycemic control. Therefore, long-term glycemic variability, assessed by variations in haemoglobin A1c (HbA1c), may be a potential risk factor for microvascular complications, such as diabetic peripheral neuropathy (DPN). We investigated the association of HbA1c variability with DPN in patients with type 2 diabetes. Methods In this cross-sectional study, 563 type 2 diabetic patients who had been screened for DPN and undergone quarterly HbA1c measurements during the year preceding enrolment were recruited. DPN was confirmed in patients displaying both clinical manifestations of neuropathy and abnormalities in a nerve conduction evaluation. HbA1c variability was assessed by the coefficient of variation of HbA1c (CV-HbA1c), and the mean of HbA1c (M-HbA1c) was calculated. In addition, medical history and clinical data were collected. Results Among the recruited patients, 18.1% (n = 102) were found to have DPN, and these patients also presented with a higher CV-HbA1c than the patients without DPN (p

The inner cell mass of the pre-implantation blastocyst consists of the epiblast and hypoblast from which embryonic stem cells (ESCs) and extra-embryonic endoderm (XEN) stem cells, respectively, can be derived. Importantly, each stem cell type retains the defining properties and lineage restriction of its in vivo tissue origin. We have developed a novel approach for deriving porcine XEN (pXEN) cells via culturing the blastocysts with a chemical cocktail culture system. The pXEN cells were positive for XEN markers, including Gata4, Gata6, Sox17, and Sall4, but not for pluripotent markers Oct4, Sox2, and Nanog. The pXEN cells also retained the ability to undergo visceral endoderm (VE) and parietal endoderm (PE) differentiation in vitro. The maintenance of pXEN required FGF/MEK+TGFβ signaling pathways. The pXEN cells showed a stable phenotype through more than 50 passages in culture and could be established repeatedly from blastocysts or converted from the naïve-like ESCs established in our lab. These cells provide a new tool for exploring the pathways of porcine embryo development and differentiation and providing further reference to the establishment of porcine ESCs with potency of germline chimerism and gamete development.

The development of highly thermally conductive composites with excellent electrical insulation has attracted extensive attention, which is of great significance to solve the increasingly severe heat concentration issue of electronic equipment. Herein, we report a new strategy to prepare boron nitride nanosheets (BNNSs) via an ion-assisted liquid-phase exfoliation method. Then, silver nanoparticle (AgNP) modified BNNS (BNNS@Ag) was obtained by in situ reduction properties. The exfoliation yield of BNNS was approximately 50% via the ion-assisted liquid-phase exfoliation method. Subsequently, aramid nanofiber (ANF)/BNNS@Ag composites were prepared by vacuum filtration. Owing to the “brick-and-mortar” structure formed inside the composite and the adhesion of AgNP, the interfacial thermal resistance was effectively reduced. Therefore, the in-plane thermal conductivity of ANF/BNNS@Ag composites was as high as 11.51 W m−1 K−1, which was 233.27% higher than that of pure ANF (3.45 W m−1 K−1). The addition of BNNS@Ag maintained tensile properties (tensile strength of 129.14 MPa). Moreover, the ANF/BNNS@Ag films also had good dielectric properties and the dielectric constant was below 2.5 (103 Hz). Hence, the ANF/BNNS@Ag composite shows excellent thermal management performance, and the electrical insulation and mechanical properties of the matrix are retained, indicating its potential application prospects in high pressure and high temperature application environments.

Abstract Background Reduced insulin sensitivity not only contributes to the pathogenesis of type 2 diabetes but is also linked to multiple metabolic risk factors and cardiovascular diseases (CVD). A prolonged heart rate-corrected QT interval (QTc interval) is related to ventricular arrhythmias and CVD mortality and exhibits a high prevalence among type 2 diabetes patients. The aim of the study was to investigate the relationship between insulin sensitivity and the QTc interval in patients with type 2 diabetes. Methods This cross-sectional observational study recruited 2927 patients with type 2 diabetes who visited the Affiliated Haian Hospital and Second Affiliated Hospital of Nantong University. The insulin sensitivity index (Matsuda index, ISIMatsuda) derived from 75-g OGTT and other metabolic risk factors were examined in all patients. The QTc interval was estimated using a resting 12-lead electrocardiogram, and an interval longer than 440 ms was considered abnormally prolonged. Results The QTc interval was significantly and negatively correlated with the ISIMatsuda (r = −0.296, p

Prolonged heart rate-corrected QT(QTc) interval is related to ventricular arrhythmia and cardiovascular mortality, with considerably high prevalence of type 2 diabetes. Additionally, long-term glycaemic variability could be a significant risk factor for diabetic complications in addition to chronic hyperglycaemia. We compared the associations of long-term glycaemic variability versus sustained chronic hyperglycaemia with the QTc interval among type 2 diabetes patients.In this cross-sectional study, 2904 type 2 diabetes patients were recruited who had undergone at least four fasting plasma glucose (FPG) and 2-hour postprandial plasma glucose (PPG) measurements (at least once for every 3 months, respectively) during the preceding year. Long-term glycaemic variabilities of FPG and 2-hour PPG were assessed by their standard deviations (SD-FPG and SD-PPG, respectively), and chronic fasting and postprandial hyperglycaemia were assessed by their means (M-FPG and M-PPG, respectively). HbA1c was also determined upon enrolment to assess current overall glycaemic control. QTc interval was estimated from resting 12-lead electrocardiograms, and more than 440 ms was considered abnormally prolonged.Patients with prolonged QTc interval (≥440 ms) had greater M-FPG, M-PPG, SD-PPG and HbA1c than those with normal QTc interval but comparable SD-FPG. QTc interval was correlated with M-FPG, M-PPG, SD-PPG and HbA1c (r = 0.133, 0.153, 0.245 and 0.207, respectively, p = 0.000) but not with SD-FPG (r = 0.024, p = 0.189). After adjusting for metabolic risk factors via multiple linear regression analysis, SD-PPG, M-PPG and HbA1c (t = 12.16, 2.69 and 10.16, respectively, p = 0.000) were the major independent contributors to the increased QTc interval. The proportion of prolonged QTc interval increased significantly from 10.9% to 14.2% to 26.6% for the first (T1) to second (T2) to third (T3) tertiles of SD-PPG. After adjusting via multiple logistic regression analysis, the odd ratios of prolonged QTc interval of the T2 and T3 versus the T1 of SD-PPG were 1.15 (95% CI, 0.82-1.60) and 2.62 (1.92-3.57), respectively.Increased long-term variability of PPG is a strong independent risk factor for prolonged QTc interval in type 2 diabetes patients, in addition to long-term postprandial hyperglycaemia and current HbA1c.

Tadpoles of two sympatric anurans, Bufo gargarizans Cantor, 1842 and Rana zhenhaiensis Ye, Fei & Matsui, 1995, were used as model organisms to examine the effects of different levels of tail loss on swimming performance and survival. On average, B. gargarizans tadpoles were shorter and had smaller tails and body mass than R. zhenhaiensis. After 75% tail loss, the survival rate of experimental and control B. gargarizans tadpoles, and of experimental tadpoles of the two species, differed significantly; the number of tadpoles surviving a complete impairment of their swimming ability did not differ between B. gargarizans and R. zhenhaiensis. After 50% tail loss, the swimming performance (swimming speed, maximum distance and number of stops) of the two species was significantly affected. However, the adverse influence of tail loss on the swimming speed of B. gargarizans tadpoles was greater compared to R. zhenhaiensis tadpoles. Our data indicates that a 50% tail loss results in swimming costs for B. gargarizans and R. zhenhaiensis tadpoles, and that 75% tail loss decreases the survival rate of B. gargarizans tadpoles. Therefore, we conclude that tadpoles of different species and with the same degree of tail loss use distinctive strategies to improve individual fitness in the face of predator pressure.

The insulin-pancreatic acinar axis may play a major role in pancreatic function. Amylase is an exocrine enzyme that is produced by pancreatic acinar cells, and low serum amylase levels may be associated with endocrine diseases, such as metabolic syndrome and diabetes. We hypothesized that low serum amylase levels may be associated with impaired islet β cell function in type 2 diabetes. Therefore, we investigated the relationship between the serum amylase levels and islet β cell function in patients with early type 2 diabetes.The cross-sectional study recruited 2327 patients with a mean of 1.71±1.62 years since their diagnosis of type 2 diabetes, and all participants were treated with lifestyle intervention alone. Serum amylase levels, the 75-g oral glucose tolerance test (OGTT) and metabolic risk factors were examined in all participants. The insulin sensitivity index (Matsuda index, ISIMatsuda) and insulin secretion index (ratio of total area-under-the-insulin-curve to glucose-curve, AUCins/glu) were derived from the OGTT. Integrated islet β cell function was assessed by the Insulin Secretion-Sensitivity Index-2 (ISSI-2) (ISIMatsuda multiplied by AUCins/glu).Serum amylase levels in the normal range were significantly correlated with ISIMatsuda, AUCins/glu and ISSI-2 (r = 0.203, 0.246 and 0.413, respectively, p

It is known that psychological stress affects reproduction in women, but it is unknown whether the effect is by impairing implantation. Although studies suggest that long periods of auditory or restraint stress may inhibit implantation in rats and mice, the exact stage of pregnancy at which stress impairs implantation is unclear. Furthermore, whether stress impairs implantation by decreasing the heparin-binding epidermal growth factor-like growth factor (HB-EGF), estrogen and/or progesterone and whether by acting on embryos or on the uterus need further investigations. In this study, a 24-h restraint stress was initiated at 15:30 of day 3 (regimen 1) or at 07:30 (regimen 2) or 15:30 of day 4 (regimen 3) of pregnancy (vaginal plug = day 1) to observe effects of restraint stress applied at different peri-implantation stages on implantation. Among the three regimens, whereas regimens 1 and 3 affected neither term pregnancy nor litter size, regimen 2 reduced both. Further observations indicated that regimen 2 of restraint stress also delayed blastocyst hatching and the attachment reaction, decreased serum concentrations of progesterone and estradiol, and down regulated the expression of HB-EGF in both the endometrium and blastocysts. Taken together, the results suggested that restraint stress inhibited mouse implantation in a temporal window-dependent manner and by impairing blastocyst activation and hatching and uterine receptivity via down-regulating HB-EGF, estrogen and progesterone. Thus, the stress applied within the implantation window impaired implantation by acting on both embryos and the uterus.

Although the predatory stress experimental protocol is considered more psychological than the restraint protocol, it has rarely been used to study the effect of psychological stress on reproduction. Few studies exist on the direct effect of psychological stress to a female on developmental competence of her oocytes, and the direct effect of predatory maternal stress on oocytes has not been reported. In this study, a predatory stress system was first established for mice with cats as predators. Beginning 24 h after injection of equine chorionic gonadotropin, female mice were subjected to predatory stress for 24 h. Evaluation of mouse responses showed that the predatory stress system that we established increased anxiety-like behaviors and plasma cortisol concentrations significantly and continuously while not affecting food and water intake of the mice. In vitro experiments showed that whereas oocyte maturation and Sr(2+) activation or fertilization were unaffected by maternal predatory stress, rate of blastocyst formation and number of cells per blastocyst decreased significantly in stressed mice compared to non-stressed controls. In vivo embryo development indicated that both the number of blastocysts recovered per donor mouse and the average number of young per recipient after embryo transfer of blastocysts with similar cell counts were significantly lower in stressed than in unstressed donor mice. It is concluded that the predatory stress system we established was both effective and durative to induce mouse stress responses. Furthermore, predatory stress applied during the oocyte pre-maturation stage significantly impaired oocyte developmental potential while exerting no measurable impact on nuclear maturation, suggesting that cytoplasmic maturation of mouse oocytes was more vulnerable to maternal stress than nuclear maturation.

Somatostatin receptor 5 (SSTR5) is an important G protein--coupled receptor and drug target for neuroendocrine tumors and pituitary disorders. This study presents two high-resolution cryogenicelectron microscope structures of the SSTR5-Gi complexes bound to the cyclic neuropeptide agonists, cortistatin-17 (CST17) and octreotide, with resolutions of 2.7 Å and 2.9 Å, respectively. The structures reveal that binding of these peptides causes rearrangement of a "hydrophobic lock", consisting of residues from transmembrane helices TM3 and TM6. This rearrangement triggers outward movement of TM6, enabling Gαi protein engagement and receptor activation. In addition to hydrophobic interactions, CST17 forms conserved polar contacts similar to somatostatin-14 binding to SSTR2, while further structural and functional analysis shows that extracellular loops differently recognize CST17 and octreotide. These insights elucidate agonist selectivity and activation mechanisms of SSTR5, providing valuable guidance for structure-based drug development targeting this therapeutically relevant receptor. [ABSTRACT FROM AUTHOR]