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Background Estimated glucose disposal rate (eGDR) is a measure of insulin sensitivity. While recent evidence suggests its role in cardiovascular risk assessment in Type 1 diabetes, its associations with cardiovascular disease (CVD), diabetic microvascular complications (DMC), and mortality across different populations remain unclear. Methods We systematically searched Medline, EMBASE, Web of Science, and the Cochrane Library up to September 1st, 2024, following PRISMA guidelines. We examined associations between eGDR and CVD, DMC (including diabetic retinopathy, nephropathy, and peripheral neuropathy), and all-cause mortality using random-effects models. Secondary analysis assessed mean eGDR levels in diabetes populations. Results Nineteen observational studies (185,810 participants) examined clinical outcomes, while 50 studies reported mean eGDR values. In patients with Type 1 diabetes (T1DM), each 1-unit (mg/kg/min) increase in eGDR was associated with lower risks of CVD (HR 0.78; 95% CI 0.69–0.87; I 2  = 68%) and all-cause mortality (HR 0.83; 95% CI 0.79–0.88; I 2  = 0%). The association between eGDR and DMC in T1DM was not statistically significant (HR 0.86; 95% CI 0.72–1.03; I 2  = 25%). In patients with Type 2 diabetes (T2DM), each 1-unit (mg/kg/min) increase in eGDR was associated with reduced all-cause mortality (HR 0.90; 95% CI 0.84–0.97; I 2  = 62%). Similarly, in the general population, each 1-unit (mg/kg/min) increase in eGDR was associated with decreased mortality risk (HR 0.88; 95% CI 0.82–0.94; I 2  = 48%). The pooled mean eGDR was higher in patients with T1DM (8.19 mg/kg/min; 95% CI 7.81–8.57; I 2  = 99%) compared to those with T2DM (7.03 mg/kg/min; 95% CI 4.89–9.17; I 2  = 100%). Conclusions Higher eGDR levels were consistently associated with lower risks of CVD and mortality in T1DM, with similar associations observed for mortality in T2DM. In the general population, higher eGDR levels were associated with reduced mortality risk. The relationship between eGDR and DMC requires further investigation, particularly in T2DM. These findings suggest eGDR's potential utility as a risk assessment tool, though its clinical application may vary across different populations.

SLC16A family members play crucial roles in tumorigenesis and tumor progression. However, the exact role of distinct members in the SLC16A family in human pancreatic cancer remains unclear. Integrated bioinformatics analysis for the identification of therapeutic targets for certain cancers based on transcriptomics, proteomics and high-throughput sequencing could help us obtain novel information and understand potential underlying molecular mechanisms. In the present study, we investigated SLC16A family members in pancreatic cancer through accumulated data from GEO (Gene Expression Omnibus), TCGA (The Cancer Genome Atlas) and other available databases. The expression profile, clinical application significance and prognostic value of the SLC16A family for patients with pancreatic cancer were explored. SLC16A1, SLC16A3 and SLC16A13 exhibited biomarker potential for prognosis, and we further identified their related genes and regulatory networks, revealing core molecular pathways that require further investigation for pancreatic cancer.

The use of fiber Bragg grating (FBG) sensors is proposed to solve the technical problem of poor sensor stability in the long-term safety monitoring of shaft lining structures. The auxiliary shaft of the Zhuxianzhuang coal mine was considered as the engineering background, and a test system implementing FBG sensors was established to monitor the long-term safety of the shaft lining structure. Indoor simulation testing revealed that the coefficient of determination (r2) between the test curves of the FBG sensor and the resistance strain gauge is greater than 0.99 in both the transverse and vertical strains. Therefore, the FBG sensor and resistance strain gauge test values are similar, and the error is small. The early warning value was obtained by calculation, according to the specific engineering geological conditions and shaft lining structure. The monitoring data obtained for the shaft lining at three test levels over more than three years reveal that the measured vertical strain value is less than the warning value, indicating that the shaft lining structure is currently in a safe state. The analysis of the monitoring data reveals that the vertical strain increment caused by the vertical additional force is approximately 0.0752 με/d. As the mine drainage progresses, the increasing vertical additional force acting on the shaft lining will compromise the safety of the shaft lining structure. Therefore, the monitoring must be enhanced to facilitate decision-making for safe shaft operation.

Two-cell-like (2C-like) embryonic stem cells (ESCs) are a small group of ESCs that spontaneously express zygotic genome activation (ZGA) genes and repeats, such as Zscan4 and murine endogenous retrovirus with leucine (MERVL), and are specifically expressed in 2-cell-stage mouse embryos. Although numerous types of treatment and agents elevate the transition of ESCs to 2C-like ESCs, Dux serves as a critical factor in this transition by increasing the expression of Zscan4 and MERVL directly. However, the loss of Dux did not impair the birth of mice, suggesting that Dux may not be the primary transitioning factor in fertilized embryos. It has been reported that for 2-cell embryos derived from somatic cell nuclear transfer (SCNT) and whose expression of ZGA genes and repeats was aberrant, Dux improved the reprogramming efficiency by correcting aberrant H3K9ac modification via its C-terminal domain. We confirmed that the overexpression of full-length Dux mRNA in SCNT embryos improved the efficiency of preimplantation development (62.16% vs. 41.26% with respect to controls) and also increased the expression of Zscan4 and MERVL. Furthermore, we found that the N-terminal double homeodomains of Dux were indispensable for Dux localization and function. The intermediate region was essential for MERVL and Zscan4 activation, and the C-terminal domain was important for elevating level of H3K27ac. Mutant Dux mRNA containing N-terminal double homeodomains with the intermediate region or the C-terminal domain also improved the preimplantation development of SCNT embryos. This is the first report focusing on distinguishing functional domains of Dux in embryos derived from SCNT. Graphical Abstract

The study of human brain physiology, including cellular interactions in normal and disease conditions, has been a challenge due to its complexity and unavailability. Induced pluripotent stem cell (iPSC) study is indispensable in the study of the pathophysiology of neurological disorders. Nevertheless, monolayer systems lack the cytoarchitecture necessary for cellular interactions and neurological disease modeling. Brain organoids generated from human pluripotent stem cells supply an ideal environment to model both cellular interactions and pathophysiology of the human brain. This review article discusses the composition and interactions among neural lineage and non-central nervous system cell types in brain organoids, current studies, and future perspectives in brain organoid research. Ultimately, the promise of brain organoids is to unveil previously inaccessible features of neurobiology that emerge from complex cellular interactions and to improve our mechanistic understanding of neural development and diseases. Graphical abstract

Induced pluripotent stem cells (iPSCs) are mainly characterized by their unlimited proliferation abilities and potential to develop into almost any cell type. The creation of this technology has been of great interest to many scientific fields, especially regenerative biology. However, concerns about the safety of iPSC application in transplantation have arisen due to the tumorigenic and immunogenic properties of iPSCs. This review will briefly introduce the developing history of somatic reprogramming and applications of iPSC technology in regenerative medicine. In addition, the review will highlight two challenges to the efficient usage of iPSCs and the underlying mechanisms of these challenges. Finally, the review will discuss the expanding application of iPSC technology in cancer immunotherapy as a potential cancer vaccine and its advantages in auxiliary treatment compared with oncofetal antigen-based and embryonic stem cell (ESC)-based vaccines.

The Proto-Tethys Ocean has played a significant role in the geological history of Earth. However, ongoing debates persist regarding the timing and polarity of its early subduction. Volcanic rocks associated with iron deposits in the Bulunkuole Complex, West Kunlun Orogen, offer insights into both the complex’s formation age and Proto-Tethys evolution. This study presents newly obtained zircon U–Pb age data (~536 Ma) along with comprehensive whole-rock major and trace element and Sr–Nd–Hf isotope analyses of these volcanic rocks. Our dataset implies that the Bulunkuole Complex partly formed in the early Paleozoic rather than entirely in the Paleoproterozoic, as previously suggested. Geochemically, the volcanic rocks exhibit enrichments in large ion lithophile elements and light rare earth elements, along with depletions in high-field strength elements. They also display elevated initial 87Sr/86Sr values (0.71093, 0.72025) and negative εNd(t) values (−5.13, −6.18), classifying them as continental arc volcanic rocks. These geochemical fingerprints, complemented by zircon εHf(t) values (−12.7 to −1.6), indicate that the parental magmas of the volcanic rocks were produced by partial melting of the lithospheric mantle wedge, which had been metasomatized by subducted sediment-derived melts. The available data, in conjunction with previously published findings, strongly suggest that the Proto-Tethys Ocean subducted southward prior to approximately 536 Ma due to the assembly of Gondwana. Subsequent slab rollback may have resulted in a crustal thinning of 9–25 km during 536–514 Ma. Further shifts in subduction dynamics led to the transition from high-angle subduction to either normal or low-angle subduction, facilitating the formation of a thicker crust ranging from 39 to 70 km between 514 and 448 Ma. This study, therefore, provides valuable insights into the early evolution of the Proto-Tethys Ocean and contributes significantly to our understanding of the tectonic history of the West Kunlun Orogen.

Autophagy is an essential cellular mechanism that degrades cytoplasmic proteins and organelles to recycle their components. Moreover, autophagy is essential for preimplantation development in mammals. Here we show that autophagy is also important for reprogramming in somatic cell nuclear transfer (SCNT). Our data indicate that unlike fertilized oocytes, autophagy is not triggered in SCNT embryos during 6 hours of activation. Mechanistically, the inhibited autophagic induction during SCNT activation is due to the cytochalasin B (CB) caused depolymerization of actin filaments. In this study, we induced autophagy during SCNT activation by rapamycin and pp242, which could restore the expected level of autophagy and significantly enhance the development of SCNT embryos to the blastocyst stage when compared with the control (68.5% and 68.7% vs. 41.5%, P  < 0.05). Furthermore, the treatment of rapamycin and pp242 accelerates active DNA demethylation indicated by the conversion of 5 mC to 5 hmC and treatment of rapamycin improves degradation of maternal mRNA as well. Thus, our findings reveal that autophagy is important for development of SCNT embryos and inhibited autophagic induction during SCNT activation might be one of the serious causes of low efficiency of SCNT.

The Hatu gold deposit is the largest historical gold producer of the West Junggar, western China, with an Au reserve of about 62 t. The orebodies were controlled by NE-, EW-, and NW-trending subsidiary faults associated with the Anqi fault. This deposit exhibits characteristics typical of a fault-controlled lode system, and the orebodies consist of auriferous quartz veins and altered wall rocks within Early Carboniferous volcano-sedimentary rocks. Three stages of mineralization have been identified in the Hatu gold deposit: the early pyrite-albite-quartz stage, the middle polymetallic sulfides-ankerite-quartz stage, and late quartz-calcite stage. The sulfur isotopic values of pyrite and arsenopyrite vary in a narrow range from − 0.8‰ to 1.3‰ and an average of 0.4‰, the near-zero δ 34 S values implicate the thorough homogenization of the sulfur isotopes during the metamorphic dehydration of the Early Carboniferous volcano-sedimentary rocks. Lead isotopic results of pyrite and arsenopyrite ( 206 Pb/ 204 Pb = 17.889–18.447, 207 Pb/ 204 Pb = 15.492–15.571, 208 Pb/ 204 Pb = 37.802–38.113) are clustered between orogenic and mantle/upper crust lines, indicating that the lead was mainly sourced from the hostrocks within the Early Carboniferous Tailegula Formation. The characteristics of S and Pb isotopes suggest that the ore-forming metals of the Hatu orogenic gold deposit are of metamorphogenic origin, associated with the continental collision between the Yili-Kazakhstan and Siberian plates during the Late Carboniferous.

Patient-specific induced pluripotent stem cells (iPSCs) have the potential to be useful in the treatment of human diseases. While prior studies have reported multiple methods to generate iPSCs, DNA methylation continues to limit the totipotency and reprogramming efficiency of iPSCs. Here, we first show the competency of embryonic germ cells (EGCs) as a reprogramming catalyst capable of effectively promoting reprogramming induced by four defined factors, including Oct4, Sox2, Klf4 and c-Myc. Combining EGC extracts with these four factors resulted in formation of more embryonic stem cell-like colonies than did factors alone. Notably, expression of imprinted genes was higher with combined induction than with factors alone. Moreover, iPSCs derived from the combined inductors tended to have more global hypomethylation. Our research not only provides evidence that EGC extracts could activate DNA demethylation and reprogram imprinted genes, but also establishes a new way to enhance reprogramming of iPSCs, which remains a critical safety concern for potential use of iPSCs in regenerative medicine.