Spermatogenesis, an elaborate and male-specific process in adult testes by which a number of spermatozoa are produced constantly for male fertility, relies on spermatogonial stem cells (SSCs). As a ...sub-population of undifferentiated spermatogonia, SSCs are capable of both self-renewal (to maintain sufficient quantities) and differentiation into mature spermatozoa. SSCs are able to convert to pluripotent stem cells during in vitro culture, thus they could function as substitutes for human embryonic stem cells without ethical issues. In addition, this process does not require exogenous transcription factors necessary to produce induced-pluripotent stem cells from somatic cells. Moreover, combining genetic engineering with germ cell transplantation would greatly facilitate the generation of transgenic animals. Since germ cell transplantation into infertile recipient testes was first established in 1994, in vivo and in vitro study and manipulation of SSCs in rodent testes have been progressing at a staggering rate. By contrast, their counterparts in domestic animals, despite the failure to reach a comparable level, still burgeoned and showed striking advances. This review outlines the recent progressions of characterization, isolation, in vitro propagation, and transplantation of spermatogonia/SSCs from domestic animals, thereby shedding light on future exploration of these cells with high value, as well as contributing to the development of reproductive technology for large animals.
Aims. To assess the maresin 1 (MaR1) contents in type 2 diabetic patients with or without diabetic foot ulcer and to analyze the association of MaR1 concentrations with several metabolism-related ...parameters. Methods. Plasma MaR1 concentrations were analyzed in 96 subjects with normal glucose tolerant (NC, n=43), type 2 diabetes (T2DM, n=40), or diabetic foot ulcer (DFU, n=13). The intravenous glucose tolerance test (IVGTT) and biochemical parameters were measured in all participants. Results. Plasma MaR1 concentrations were significant decreased in type 2 diabetes patient with or without DFU compared with NC (both P<0.001) and were lowest in DFU patients among these 3 groups. (DFU vs. T2DM, P<0.05). Plasma MaR1 concentrations were negatively correlated with BMI, waist circumference (Wc), waist hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), LDL-c, FPG, 2hPG, HbA1c, and homeostasis model assessment for insulin resistance (HOMA-IR) (all P<0.05) and were positively correlated with HDL-c, acute insulin response (AIR), area under the curve of the first-phase (0-10 min) insulin secretion (AUC), and homeostasis model assessment for beta-cell function (HOMA-β) (all P<0.05). After adjusting for age and sex, Wc, WHR, TG, FPG, 2hPG, HbA1c, HOMA-IR, AIR, AUC, and HOMA-β remain statistically significant (all P<0.05). Conclusions. Plasma MaR1 concentration were decreased in T2DM with or without DFUs and were the lowest in DFU patients. The decreased plasma MaR1 strongly associated with obesity, impaired glucose and lipid metabolism, reduced first-phase of glucose-stimulated insulin secretion, and enhanced insulin resistance.
Rapid and specific antibody testing is crucial for improved understanding, control, and treatment of COVID-19 pathogenesis. Herein, we describe and apply a rapid, sensitive, and accurate virus ...neutralization assay for SARS-CoV-2 antibodies. The assay is based on an HIV-1 lentiviral vector that contains a secreted intron Gaussia luciferase (Gluc) or secreted nano-luciferase reporter cassette, pseudotyped with the SARS-CoV-2 spike (S) glycoprotein, and is validated with a plaque-reduction assay using an authentic, infectious SARS-CoV-2 strain. The assay was used to evaluate SARS-CoV-2 antibodies in serum from individuals with a broad range of COVID-19 symptoms; patients included those in the intensive care unit (ICU), health care workers (HCWs), and convalescent plasma donors. The highest neutralizing antibody titers were observed among ICU patients, followed by general hospitalized patients, HCWs, and convalescent plasma donors. Our study highlights a wide phenotypic variation in human antibody responses against SARS-CoV-2 and demonstrates the efficacy of a potentially novel lentivirus pseudotype assay for high-throughput serological surveys of neutralizing antibody titers in large cohorts.
Increasing evidence indicates that the gut microbiota contributes to the occurrence and development of metabolic diseases. However, little is known about the effects of commonly used antidiabetic ...agents on the gut microbiota. In this study, we investigated the roles of dipeptidyl peptidase-4 inhibitors (DPP-4i) and α-glucosidase inhibitor in modulating the gut microbiota.
16S-rDNA sequencing was performed to analyse the effects of DPP-4i and acarbose on the gut microbiota in mice fed a high-fat diet (HFD). Fecal microbiota transplantation (FMT) from type 2 diabetes patients to germ-free mice was performed to investigate the contribution of the altered microbiome to antidiabetic effects of the drugs. Fecal metabolomics was also analysed by untargeted and targeted GC–MS systems.
Although DPP-4i and α-glucosidase inhibitor both altered the gut microbial composition, only the microbiome modulation of DPP-4i contributed to its hypoglycemic effect. Specifically, the changes of 68.6% genera induced by HFD were rescued by DPP-4i. FMT showed that the DPP-4i-altered microbiome improved glucose tolerance in colonized mice, while acarbose did not. Moreover, DPP-4i increased the abundance of Bacteroidetes, and also promoted a functional shift in the gut microbiome, especially increasing the production of succinate.
Our findings demonstrate an important effect of DPP-4i on the gut microbiota, revealing a new hypoglycemic mechanism and an additional benefit of it. Furthermore, modulating the microbial composition, and the functional shift arising from changes in the microbiome, might be a potential strategy for improving glucose homeostasis.
This work was supported by grants from the National Natural Science Foundation of China (No. 81700757, No. 81471039, No. 81700714 and No. 81770434), the National Key R&D Program of China (No. 2017YFC1309602, No. 2016YFC1101100, No. 2017YFD0500503 and No. 2017YFD0501001), and the Natural Science Foundation of Chongqing (No. cstc2014jcyjjq10006, No. cstc2016jcyjA0093 and No. cstc2016jcyjA0518).
High myopia (HM) is defined as a refractive error worse than -6.00 diopter (D). This study aims to update the phenotypic and genotypic landscape of nonsyndromic HM and to establish a biological link ...between the phenotypic traits and genetic deficiencies.
A cross-sectional study involving 731 participants varying in refractive error, axial length (AL), age, myopic retinopathy, and visual impairment. The phenotypic traits were analyzed by four ophthalmologists while mutational screening was performed in eight autosomal causative genes. Finally, we assessed the clinical relevance of identified mutations under the guidance of the American College of Medical Genetics and Genomics.
The relationship between refractive error and AL varied in four different age groups ranging from 3- to 85-years old. In adult groups older than 21 years, 1-mm increase in AL conferred 10.84% higher risk of pathologic retinopathy (Category ≥2) as well as 7.35% higher risk of low vision (best-corrected visual acuities <0.3) with P values < 0.001. The prevalence rates of pathologic retinopathy and low vision both showed a nonlinear positive correlation with age. Forty-five patients were confirmed to harbor pathogenic mutations, including 20 novel mutations. These mutations enriched the mutational pool of nonsyndromic HM to 1.5 times its previous size and enabled a statistically significant analysis of the genotype-phenotype correlation. Finally, SLC39A5, CCDC111, BSG, and P4HA2 were more relevant to eye elongation, while ZNF644, SCO2, and LEPREL1 appeared more relevant to refracting media.
Our findings shed light on how multiple HM-related phenotypes are associated with each other and their link with gene variants.
Abstract
Background
Pulmonary arterial hypertension is a major cause of death in systemic lupus erythematosus, but there are no tools specialized for predicting survival in systemic lupus ...erythematosus-associated pulmonary arterial hypertension.
Research question
To develop a practical model for predicting long-term prognosis in patients with systemic lupus erythematosus-associated pulmonary arterial hypertension.
Methods
A prognostic model was developed from a multicenter, longitudinal national cohort of consecutively evaluated patients with systemic lupus erythematosus-associated pulmonary arterial hypertension. The study was conducted between November 2006 and February 2020. All-cause death was defined as the endpoint. Cox regression and least absolute shrinkage and selection operators were used to fit the model. Internal validation of the model was assessed by discrimination and calibration using bootstrapping.
Results
Of 310 patients included in the study, 81 (26.1%) died within a median follow-up of 5.94 years (interquartile range 4.67–7.46). The final prognostic model included eight variables: modified World Health Organization functional class, 6-min walking distance, pulmonary vascular resistance, estimated glomerular filtration rate, thrombocytopenia, mild interstitial lung disease, N-terminal pro-brain natriuretic peptide/brain natriuretic peptide level, and direct bilirubin level. A 5-year death probability predictive algorithm was established and validated using the C-index (0.77) and a satisfactory calibration curve. Risk stratification was performed based on the predicted probability to improve clinical decision-making.
Conclusions
This new risk stratification model for systemic lupus erythematosus-associated pulmonary arterial hypertension may provide individualized prognostic probability using readily obtained clinical risk factors. External validation is required to demonstrate the accuracy of this model's predictions in diverse patient populations.
To accurately and quantitatively reveal the physical mechanism underlying the formation of microstructure during coaxial powder-fed laser cladding, a three-dimensional comprehensive model, coupling ...laser-powder interaction, temperature field, and flow field, is developed to identify the effects of multiphysics on microstructure characteristics. The high-speed camera and numerical simulation are employed to characterize the powder distribution, which is converted into the corresponding cladding layer growth rate and applied to solve the temperature rise and flow behavior of the molten pool. The energy conservation equation and the Navier-Stokes equation are applied to describe the physical field government, and the free surface motion of metallic liquid is tracked utilizing the Level Set method. The comprehensive model accurately visualizes the molten pool hydrodynamic behavior and temperature field distribution during laser cladding. In addition, the experimental results are combined to analyze the formation mechanism of microstructure. The direction and magnitude of forces acting on the metallic liquid in the flow field (such as surface tension, Marangoni force, recoil pressure) intuitively explain the formation of circulation in the molten pool, ultimately reflected in the grain growth direction. The evolution of cooling rates in the molten pool indicates that the specific location and varied temperature field dominates the grain type and size of the cladding layer, which contributes to the planar crystal, cellular crystal, columnar dendrite, equiaxed dendrite and equiaxed crystal from bottom to top.
Remnants of the Proto-Tethys are mainly preserved in the region between south of the North China-Tarim Block and north of Qiangtang-Sibumasu/Baoshan Blocks. Magmatic-metallogenic events related to ...the Proto-Tethyan subductions were rarely reported, and the subduction history and polarity of the Proto-Tethyan are still under debate. Here, we presented new data of zircon UPb ages, whole-rock Sr–Nd–Pb isotopes, major and trace elements and zircon Hf isotopes for the volcanic rocks in the northeastern Altyn Mountains. Information of over 14 volcanic-hosted deposits/prospects in the region has been compiled. These volcanic ore hosts consist mainly of basaltic andesite, andesite, dacite and rhyolite rocks. The andesite and rhyolite rocks are newly zircon UPb dated to be Late Cambrian-Early Ordovician (andesite: 490.5 ± 5.2 Ma; rhyolite: 492.6 ± 2.9 Ma and 491.6 ± 5.6 Ma), representing the timing of volcanism and VMS (Volcanogenic Massive Sulfide) mineralization. All the volcanic rocks belong to the high-K calc-alkaline and shoshonite series: the andesite rocks from the Kaladawan area in north of the region display arc geochemical affinities and contain (87Sr/86Sr)i (0.7082–0.7083) and εNd(t) (−9.7 to −7.6), indicating that they were likely formed by partial melting of the mantle wedge with subducted sediment inputs. The rhyolite rocks from the Kaladaban area in south of the region are characterized by high SiO2 (64.46–78.55 wt%), low alkali (Na2O + K2O, 3.46–7.17 wt%), and contain (87Sr/86Sr)i (0.7063–0.7095), εNd(t) (−6.6 to −1.5), and zircon εHf(t) (−5.5 to 5.4), indicating that they were likely derived from partial melting of the lower crust with depleted mantle inputs. Rock assemblage and geochemistry suggest that volcanic rocks in the northeastern Altyn Mountains may have formed in a continental arc setting. Their spatial distributions with respect to the ophiolites in the region suggest that the subduction was likely south-dipping. This subduction-related arc magmatism may have formed the many important VMS and porphyry–skarn deposits in the region.
Display omitted
•The Kaladawan ore-hosting volcanic rocks yielded zircon UPb age of 492.6–490.5 Ma.•The volcanics have geochemical characters similar to typical arc igneous rocks.•The south-dipping subduction of Proto-Tethys Ocean formed a continental island arc.
While adult mammalian skeletal muscle is stable due to its post‐mitotic nature, muscle regeneration is still essential throughout life for maintaining functional fitness. During certain diseases, ...such as the modern pandemics of obesity and diabetes, the regeneration process becomes impaired, which leads to the loss of muscle function and contributes to the global burden of these diseases. However, the underlying mechanisms of the impairment are not well defined. Here, we identify mGPDH as a critical regulator of skeletal muscle regeneration. Specifically, it regulates myogenic markers and myoblast differentiation by controlling mitochondrial biogenesis via CaMKKβ/AMPK. mGPDH−/− attenuated skeletal muscle regeneration in vitro and in vivo, while mGPDH overexpression ameliorated dystrophic pathology in mdx mice. Moreover, in patients and animal models of obesity and diabetes, mGPDH expression in skeletal muscle was reduced, further suggesting a direct correlation between its abundance and muscular regeneration capability. Rescuing mGPDH expression in obese and diabetic mice led to a significant improvement in their muscle regeneration. Our study provides a potential therapeutic target for skeletal muscle regeneration impairment during obesity and diabetes.
Synopsis
mGPDH is here identified as an important regulator of muscle differentiation and regeneration. Activation of the mGPDH/AMPK/mitochondrial biogenesis pathway provides a new strategy for improving muscle frailty. Direct targeting of mGPDH may also have therapeutic benefits for obesity and diabetes.
mGPDH improves skeletal muscle regeneration by promoting myoblast differentiation.
mGPDH promotes myoblast differentiation via CaMKKβ/AMPK control of mitochondrial biogenesis.
mGPDH expression was reduced in skeletal muscle obtained from patients and animal models of obesity and diabetes.
Rescuing mGPDH deficiency improves skeletal muscle regeneration during these pathological processes.
mGPDH is here identified as an important regulator of muscle differentiation and regeneration. Activation of the mGPDH/AMPK/mitochondrial biogenesis pathway provides a new strategy for improving muscle frailty. Direct targeting of mGPDH may also have therapeutic benefits for obesity and diabetes.
This study is to develop a method for isolation, identification, and quantitative determination of dammarane-type triterpene saponins in the Panax notoginseng fruits (PNF). The saponins were isolated ...by a serious of chromatographic methods, and their structures were elucidated on the basis of spectroscopic evidence and comparison with those of literature reports. Quantitative assay was performed on an ultra-performance liquid chromatography-UV (UPLC-UV) method. As a result, 22 saponins were isolated from the extract of PNF, among them, compound 1 was a new saponin, named as malonylgypenoside IX, compounds 3-10, and 14-18 were isolated from the PNF for the first time. As to quantitative analysis, the calibration curves showed good linearity (r > 0.998) within the concentration range, and the method validation provided good reproducibility and sensitivity for the quantification of eight major saponins with precision and accuracy of less than 3.0%.
PDF
