Transcriptomic landscape reveals germline potential of porcine skin-derived multipotent dermal fibroblast progenitors.

According to estimations, approximately about 15% of couples worldwide suffer from infertility, in which individuals with azoospermia or oocyte abnormalities cannot be treated with assisted reproductive technology. The skin-derived stem cells (SDSCs) differentiation into primordial germ cell-like cells (PGCLCs) is one of the major breakthroughs in the field of stem cells intervention for infertility treatment in recent years. However, the cellular origin of SDSCs and their dynamic changes in transcription profile during differentiation into PGCLCs in vitro remain largely undissected. Here, the results of single-cell RNA sequencing indicated that porcine SDSCs are mainly derived from multipotent dermal fibroblast progenitors (MDFPs), which are regulated by growth factors (EGF/bFGF). Importantly, porcine SDSCs exhibit pluripotency for differentiating into three germ layers and can effectively differentiate into PGCLCs through complex transcriptional regulation involving histone modification. Moreover, this study also highlights that porcine SDSC-derived PGCLCs specification exhibit conservation with the human primordial germ cells lineage and that its proliferation is mediated by the MAPK signaling pathway. Our findings provide substantial novel insights into the field of regenerative medicine in which stem cells differentiate into germ cells in vitro, as well as potential therapeutic effects in individuals with azoospermia and/or defective oocytes.

LSM14B controls oocyte mRNA storage and stability to ensure female fertility.

Controlled mRNA storage and stability is essential for oocyte meiosis and early embryonic development. However, how to regulate mRNA storage and stability in mammalian oogenesis remains elusive. Here we showed that LSM14B, a component of membraneless compartments including P-body-like granules and mitochondria-associated ribonucleoprotein domain (MARDO) in germ cell, is indispensable for female fertility. To reveal loss of LSM14B disrupted primordial follicle assembly and caused mRNA reduction in non-growing oocytes, which was concomitant with the impaired assembly of P-body-like granules. 10× Genomics single-cell RNA-sequencing and immunostaining were performed. Meanwhile, we conducted RNA-seq analysis of GV-stage oocytes and found that Lsm14b deficiency not only impaired the maternal mRNA accumulation but also disrupted the translation in fully grown oocytes, which was closely associated with dissolution of MARDO components. Moreover, Lsm14b-deficient oocytes reassembled a pronucleus containing decondensed chromatin after extrusion of the first polar body, through compromising the activation of maturation promoting factor, while the defects were restored via WEE1/2 inhibitor. Together, our findings reveal that Lsm14b plays a pivotal role in mammalian oogenesis by specifically controlling of oocyte mRNA storage and stability.

The Method and Experiment of Detecting the Strength of Structural Components Utilizing the Distributed Strain of Sensing Optical Fibers Demodulated by OFDR.

Defects occurring during the welding process of metal structural components directly affect their overall strength, which is crucial to the load-bearing capacity and durability of the components. This signifies the importance of accurate measurement and assessment of weld strength. However, traditional non-destructive testing methods such as ultrasonic and non-contact camera inspection have certain technical limitations. In response to these issues, this paper analyzes the detection principle of weld strength, revealing that weld defects reduce the effective area of the structural bearing section and cause stress concentration around them. Through repeated experimental data analysis of samples, strain distribution data along the one-dimensional direction caused by defects such as slag inclusion and porosity were obtained. Experimental results show that this method can identify defect types in welds, including slag inclusion, porosity, and unevenness, and accurately measure the location and size of defects with a precision of 0.64 mm, achieving qualitative analysis of weld defects. Additionally, by deploying distributed optical fiber sensors (DOFS) at different vertical distances along the weld direction, the propagation law of stress induced by different types of weld defects on samples was thoroughly analyzed. This further validates the advantages of this method in weld strength detection, including high spatial resolution, high sensitivity, and non-destructive measurement.

Machine learning-based techniques for land subsidence simulation in an urban area.

Understanding and mitigating land subsidence (LS) is critical for sustainable urban planning and infrastructure management. We introduce a comprehensive analysis of LS forecasting utilizing two advanced machine learning models: the eXtreme Gradient Boosting Regressor (XGBR) and Long Short-Term Memory (LSTM). Our findings highlight groundwater level (GWL) and building concentration (BC) as pivotal factors influencing LS. Through the use of Taylor diagram, we demonstrate a strong correlation between both XGBR and LSTM models and the subsidence data, affirming their predictive accuracy. Notably, we applied delta-rate (Δr) calculus to simulate a scenario with an 80% reduction in GWL and BC impact, revealing a potential substantial decrease in LS by 2040. This projection emphasizes the effectiveness of strategic urban and environmental policy interventions. The model performances, indicated by coefficients of determination R2 (0.90 for XGBR, 0.84 for LSTM), root-mean-squared error RMSE (0.37 for XGBR, 0.50 for LSTM), and mean-absolute-error MAE (0.34 for XGBR, 0.67 for LSTM), confirm their reliability. This research sets a precedent for incorporating dynamic environmental factors and adapting to real-time data in future studies. Our approach facilitates proactive LS management through data-driven strategies, offering valuable insights for policymakers and laying the foundation for sustainable urban development and resource management practices.

Development of a two-beveled-fiber polarized fiber-optic Raman probe coupled with a ball lens for in vivo superficial epithelial Raman measurements in endoscopy.

We report on the development of a two-beveled-fiber polarized (TBFP) fiber-optic Raman probe coupled with a ball lens for in vivo superficial epithelial Raman measurements in endoscopy. The two-beveled fibers positioned symmetrically along a ball lens, in synergy with paired parallel-polarized polarizers integrated between the fibers and the ball lens, maximize the Raman signal excitation and collection from the superficial epithelium where gastrointestinal (GI) precancer arises. Monte Carlo (MC) simulations and two-layer tissue phantom experiments show that the probe developed detects ∼90% of the Raman signal from the superficial epithelium. The suitability of the probe developed for rapid (<3 s) superficial epithelial Raman measurements is demonstrated on fresh swine esophagus, stomach, and colon tissues, followed by their differentiation with high accuracies (92.1% for esophagus [sensitivity: 89.3%, specificity: 93.2%], 94.1% for stomach [sensitivity: 86.2%, specificity: 97.2%], and 94.1% for colon [sensitivity: 93.2%, specificity: 94.7%]). The presented results suggest the great potential of the developed probe for enhancing in vivo superficial epithelial Raman measurements in endoscopy.

Single-cell RNA sequencing of the Mongolia sheep testis reveals a conserved and divergent transcriptome landscape of mammalian spermatogenesis.

Spermatogenesis is a highly coordinated and complex process, and is pivotal for transmitting genetic information between mammalian generations. In this study, we investigated the conservation, differences, and biological functions of homologous genes during spermatogenesis in Mongolia sheep, humans, cynomolgus monkey, and mice using single-cell RNA sequencing technology. We compared X chromosome meiotic inactivation events in Mongolia sheep, humans, cynomolgus monkey, and mice to uncover the concerted activity of X chromosome genes. Subsequently, we focused on the dynamics of gene expression, key biological functions, and signaling pathways at various stages of spermatogenesis in Mongolia sheep and humans. Additionally, the ligand-receptor networks of Mongolia sheep and humans in testicular somatic and germ cells at different developmental stages were mapped to reveal conserved germ cell-soma communication using single-cell resolution. These datasets provided novel information and insights to unravel the molecular regulatory mechanisms of Mongolia sheep spermatogenesis and highlight conservation in gene expression during spermatogenesis between Mongolia sheep and humans, providing a foundation for the establishment of a large mammalian disease model of male infertility.

Single-cell transcriptome landscape of ovarian cells during primordial follicle assembly in mice.

Primordial follicle assembly in the mouse occurs during perinatal ages and largely determines the ovarian reserve that will be available to support the reproductive life span. The development of primordial follicles is controlled by a complex network of interactions between oocytes and ovarian somatic cells that remain poorly understood. In the present research, using single-cell RNA sequencing performed over a time series on murine ovaries, coupled with several bioinformatics analyses, the complete dynamic genetic programs of germ and granulosa cells from E16.5 to postnatal day (PD) 3 were reported. Along with confirming the previously reported expression of genes by germ cells and granulosa cells, our analyses identified 5 distinct cell clusters associated with germ cells and 6 with granulosa cells. Consequently, several new genes expressed at significant levels at each investigated stage were assigned. By building single-cell pseudotemporal trajectories, 3 states and 1 branch point of fate transition for the germ cells were revealed, as well as for the granulosa cells. Moreover, Gene Ontology (GO) term enrichment enabled identification of the biological process most represented in germ cells and granulosa cells or common to both cell types at each specific stage, and the interactions of germ cells and granulosa cells basing on known and novel pathway were presented. Finally, by using single-cell regulatory network inference and clustering (SCENIC) algorithm, we were able to establish a network of regulons that can be postulated as likely candidates for sustaining germ cell-specific transcription programs throughout the period of investigation. Above all, this study provides the whole transcriptome landscape of ovarian cells and unearths new insights during primordial follicle assembly in mice.

Molecular dynamics study on thermal conductance between a nanotip and a substrate under vertical forces and horizontal sliding.

The heat transfer between a nanotip and its substrate is extremely complex but is a key factor in determining the measurement accuracy in tip-assisted nanomanufacturing and thermometry. In this work, the heat transfer from the nanotip to the substrate during sliding is investigated using molecular dynamics simulations. Interfacial interaction and bond formation are analyzed during the sliding process. The results show that the increase of vertical force would greatly improve the interface thermal conductance between the nanotip and the substrate. It is found that more bonds are formed and there are larger contact areas at the interface. In addition, we found that the thermal conductivity of the nanotip is another obstacle for heat transfer between the tip and substrate and it is greatly limited by the nanotip diameter near contact which is close to or even smaller than the phonon mean free path. Meanwhile, the dynamic formation and breakage of the covalent bonds during the sliding could gradually smoothen the tip apex and enhance the thermal transport at the interface. This work provides guidance for the thermal design of a nanotip-substrate system for nanoscale thermal transport measurements.

Melatonin promotes the proliferation of primordial germ cell-like cells derived from porcine skin-derived stem cells: A mechanistic analysis.

In vitro differentiation of stem cells into functional gametes remains of great interest in the biomedical field. Skin-derived stem cells (SDSCs) are an adult stem cells that provides a wide range of clinical applications without inherent ethical restrictions. In this paper, porcine SDSCs were successfully differentiated into primordial germ cell-like cells (PGCLCs) in conditioned media. The PGCLCs were characterized in terms of cell morphology, marker gene expression, and epigenetic properties. Furthermore, we also found that 25 µM melatonin (MLT) significantly increased the proliferation of the SDSC-derived PGCLCs while acting through the MLT receptor type 1 (MT1). RNA-seq results found the mitogen-activated protein kinase (MAPK) signaling pathway was more active when PGCLCs were cultured with MLT. Moreover, the effect of MLT was attenuated by the use of S26131 (MT1 antagonist), crenolanib (platelet-derived growth factor receptor inhibitor), U0126 (mitogen-activated protein kinase kinase inhibitor), or CCG-1423 (serum response factor transcription inhibitor), suggesting that MLT promotes the proliferation processes through the MAPK pathway. Taken together, this study highlights the role of MLT in promoting PGCLCs proliferation. Importantly, this study provides a suitable in vitro model for use in translational studies and could help to answer numerous remaining questions related to germ cell physiology.

Applications of machine learning in computational nanotechnology.

Machine learning (ML) has gained extensive attention in recent years due to its powerful data analysis capabilities. It has been successfully applied to many fields and helped the researchers to achieve several major theoretical and applied breakthroughs. Some of the notable applications in the field of computational nanotechnology are ML potentials, property prediction, and material discovery. This review summarizes the state-of-the-art research progress in these three fields. ML potentials bridge the efficiency versus accuracy gap between density functional calculations and classical molecular dynamics. For property predictions, ML provides a robust method that eliminates the need for repetitive calculations for different simulation setups. Material design and drug discovery assisted by ML greatly reduce the capital and time investment by orders of magnitude. In this perspective, several common ML potentials and ML models are first introduced. Using these state-of-the-art models, developments in property predictions and material discovery are overviewed. Finally, this paper was concluded with an outlook on future directions of data-driven research activities in computational nanotechnology.

Anisotropic thermal transport in twisted bilayer graphene.

Recently, twisted bilayer graphene (TBLG) has attracted enormous attention owing to its peculiar electronic properties. In this work, the anisotropic thermal conductivity of TBLG is comprehensively investigated. It is reported that interlayer twisting can be a practical approach for thermal transport regulation with high accuracy. A strong non-monotonic correlation between anisotropic thermal conductivity and twisting angles is revealed. Extensive phonon behavior analyses reveal the physical mechanism. The anisotropic thermal transport in TBLG is explained by the calculated phonon density of states (PDOS). Meanwhile, the phonon spectra and phonon relaxation times extracted from spectral energy density (SED) profiles explain the decreasing trend of thermal conductivity with increasing twisting angles. The increase in thermal conductivity is attributed to the combined effects of twist and anisotropy. The reported anisotropic thermal conductivity is important to the thermal modulation and our analyses provide a valuable complement to the phonon studies of TBLG.

Dissecting the initiation of female meiosis in the mouse at single-cell resolution.

Meiosis is one of the most finely orchestrated events during gametogenesis with distinct developmental patterns in males and females. However, the molecular mechanisms involved in this process remain not well known. Here, we report detailed transcriptome analyses of cell populations present in the mouse female gonadal ridges (E11.5) and the embryonic ovaries from E12.5 to E14.5 using single-cell RNA sequencing (scRNA seq). These periods correspond with the initiation and progression of meiosis throughout the first stage of prophase I. We identified 13 transcriptionally distinct cell populations and 7 transcriptionally distinct germ cell subclusters that correspond to mitotic (3 clusters) and meiotic (4 clusters) germ cells. By analysing cluster-specific gene expression profiles, we found four cell clusters correspond to different cell stages en route to meiosis and characterized their detailed transcriptome dynamics. Our scRNA seq analysis here represents a new important resource for deciphering the molecular pathways driving female meiosis initiation.

Full-spectrum thermal analysis in twisted bilayer graphene.

It has been recently reported that a magic angle, i.e. 1.1°, exists in twisted bilayer graphene which could lead to intrinsic unconventional superconductivity. Variations of the twisting angle between different graphene layers could lead to altered electronic band structures, which results in the peculiar superconductivity phenomenon. The effects of twisting angles on different properties of bilayer graphene need to be comprehensively investigated in order to fully understand its mechanism. In this work, classical molecular dynamics simulations are performed to calculate the interfacial thermal resistance (R) at twisting angles from 0° to 359°. Due to the symmetric structures of the honeycomb lattice, only angles from 0° to 60° are needed but the full spectrum is explored to generate the complete picture of R with θ. It was reported that the interfacial thermal resistance changes periodically with the twisting angle, with the smallest R values at every 60° starting from 0° and the largest values at every 60° starting from 30°. The phonon density of states and radial distribution functions are calculated to explain the predicted results. The effects of temperature and single- and bi-direction tensile strains on the calculated interfacial thermal resistance are also studied. The results in this work contribute to the fundamental understanding of the thermal properties in twisted bilayer graphene and provide reasonable guidelines to its applications in thermal management devices.

An Efficient and Stable MoS2 /Zn0.5 Cd0.5 S Nanocatalyst for Photocatalytic Hydrogen Evolution.

Photocatalytic hydrogen evolution by water splitting is highly important for the application of hydrogen energy and the replacement of fossil fuel by solar energy, which needs the development of efficient catalysts with long-term catalytic stability under light irradiation in aqueous solution. Herein, Zn0.5 Cd0.5 S solid solution was synthesized by a metal-organic framework-templated strategy and then loaded with MoS2 by a hydrothermal method to fabricate a MoS2 /Zn0.5 Cd0.5 S heterojunction for photocatalytic hydrogen evolution. The composition of MoS2 /Zn0.5 Cd0.5 S was fine-tuned to obtain the optimized 5 wt % MoS2 /Zn0.5 Cd0.5 S heterojunction, which showed a superior hydrogen evolution rate of 23.80 mmol h-1 g-1 and steady photocatalytic stability over 25 h. The photocatalytic performance is due to the appropriate composition and the formation of an intimate interface between MoS2 and Zn0.5 Cd0.5 S, which endows the photocatalyst with high light-harvesting ability and effective separation of photogenerated carriers.

Streptomyces apocyni sp. nov., an endogenous actinomycete isolated from Apocynum venetum.

A novel actinomycete, designated strain TRM 66233T, was isolated from Apocynum venetum L. collected from the Xinjiang Uygur Autonomous Region of China and characterized using a polyphasic taxonomic approach. Phylogenetic analysis based on 16S rRNA gene sequences affiliated strain TRM 66233T with the genus Streptomyces. Strain TRM 66233T showed a high similarity value to Streptomyces bikiniensis NRRL B-1049T (98.07 %) based on the 16S rRNA gene phylogenetic tree. The whole-cell sugar pattern of TRM 66233T consisted of glucose, galactose, mannose and ribose. The predominant menaquinones were MK-9(H2), MK-9(H6), MK-9(H8) and MK-9(H10). The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and four unidentified lipids. The major fatty acids were iso-C15 : 0, anteiso-C15 : 0, iso-C16 : 0, C16 : 0 and iso-C17 : 0. The G+C content of the DNA was 70.35 mol%. The DNA-DNA relatedness and average nucleotide identity values as well as evolutionary distances based on multilocus (atpD, gyrB, recA, rpoB and trpB) sequences between strain TRM 66233T and closely related type strains were significantly lower than the recommended threshold values. The whole-genome average nucleotide identity and digital DNA-DNA hybridization values between strain TRM 66233T and S. bikiniensis NRRL B-1049T were 78.86 and 23.2 %, respectively. On the basis of evidence from this polyphasic study, strain TRM 66233T should represent a novel species of the genus Streptomyces, for which the name Streptomyces apocyni sp. nov. is proposed. The type strain is TRM 66233T (=CCTCC AA 2019056T=LMG 31559T).

Small regulatory polypeptide of amino acid response negatively relates to poor prognosis and controls hepatocellular carcinoma progression via regulating microRNA-5581-3p/human cardiolipin synthase 1.

Hepatocellular carcinoma (HCC) is one of the most common malignancies with extremely high rates of occurrence and death. Long noncoding RNAs (lncRNAs) have been increasingly revealed to participate in tumorigenesis and development of multiple human cancers, including HCC. LINC00961 is a novel lncRNA which has been uncovered as a tumor suppressor in lung cancer and glioma. However, the role of LINC00961 in HCC has never been probed yet. Herein, we revealed a marked downregulation of LINC00961 in HCC tissues and cell lines. Correlation of low LINC00961 expression with poor outcomes in patients with HCC suggested LINC00961 as an independent predictor for HCC prognosis. Functionally, LINC00961 overexpression obviously inhibited cell proliferation, migration, and invasion in HCC cells. Mechanistically, LINC00961 regulated cardiolipin synthase 1 (CRLS1) expression via sponging miR-5581-3p. Importantly, both miR-5581-3p upregulation and CRLS1 inhibition led to an acceleration in cellular processes in HCC cells. At length, the rescue assays suggested that LINC00961 functioned in HCC through the miR-5581-3p/CRLS1 axis. On the whole, our findings disclosed that LINC00961 played a suppressive role in HCC progression via modulating miR-5581-3p/CRLS1, thus providing a potentially effective target for the prognosis and treatment of patients with HCC.

Metagenomic analysis of gut microbiota alteration in a mouse model exposed to mycotoxin deoxynivalenol.

As one of the most prevalent contaminants in animal and human food, the deleterious effects of trichothecene mycotoxin deoxynivalenol (DON) warrant extensive investigation. Here, to assess the effects of DON exposure to the populations of gut microbiota, four-weeks-old mice were exposed to different doses (1.0 and 5.0 mg/kg) of DON every two days for 14 days. The contents of the cecum were then collected for DNA extraction and metagenomic shotgun sequencing, in order to detect alterations of the gut microbiota. We found that the average body weight and daily gain in the high dose DON treated group decreased. Metagenomic analysis demonstrated that the relative abundance of Firmicutes in the low and Bacteroidetes in the high dose groups increased compared to that in the untreated control group. Moreover, using gene calling and functional annotation, we found that large numbers of biosynthesis and degradation dependent populations were altered. As a result, metabolism pathways including sphingolipid, protein digestion/absorption, and lipoic acid pathways in the high dose DON exposed group dramatically fluctuated in comparison to the control and low dose groups. In addition, metagenomic binning identified ten microbiota genome drafts, with high levels of completeness, that further explain the DON-induced intestinal toxicity. Our findings suggested that DON exposure significantly impacted the microbiota community in the mouse, causing biosynthesis and degradation damage and metabolism pathway disorders.

Fiber optic method for obtaining the peak reflected pressure of shock waves.

Most of fiber-optic pressure sensors used in shock wave measurements are based on deformations of sensing elements. These approaches result in low dynamic pressure ranges for these sensors used in the air. A novel fiber-optic method based on the relationship between pressure and the acceleration of a diaphragm is proposed to obtain peak reflected pressure of shock waves in the air. The optical sensor is designed with a thin circular diaphragm as the sensing element, and the Fabry-Perot optical interferometry is used to detect the acceleration of the diaphragm. Shock tube and explosive-blast experiments prove that the proposed fiber optic method is feasible and has the advantages of no calibration, high precision and fast response time. The proposed fiber-optic pressure method has potential in practical applications for shock wave measurements.

miRNA-338-3p/CDK4 signaling pathway suppressed hepatic stellate cell activation and proliferation.

BACKGROUND: Activated hepatic stellate cell (HSC) is the main fibrogenic cell type in the injured liver. miRNA plays an important role in activation and proliferation of HSC. METHODS: Our previous study examined the expression profiles of microRNAs in quiescent and activated HSC. Real-time PCR and western blot were used to detect the expression of Collagen type I (Col 1) and Alpha-Smooth Muscle Actin (α-SMA). CCK-8 and Edu assay was used to measure the proliferation rate of HSC. Luciferase reporter gene assay was used to tested the binding between miR-338-3p and Cyclin-dependent kinase 4 (CDK4). RESULTS: We found overexpression of miR-338-3p could inhibit Col 1 and α-SMA, two major HSC activation markers, whereas miR-338-3p inhibitor could promote them. Besides, miR-338-3p overexpression could suppress the growth rate of HSC. Further, we found that CDK4, a pleiotropic signaling protein, was a direct target gene of miR-338-3p. Moreover, we found that overexpression of CDK4 could block the effects of miR-338-3p. CONCLUSIONS: We found miR-338-3p is an anti-fibrotic miRNA which inhibits cell activation and proliferation. Our findings suggest that miR-338-3p/CDK4 signaling pathway participates in the regulation of HSC activation and growth and may act as a novel target for further anti-fibrotic therapy.

Land management policy shift influenced seasonal variation of erosion-induced nitrogen and phosphorus outputs from intensive agricultural catchment.

A shift in policy to intensive agricultural production and land management often leads to excessive fertilizer application and accelerated erosion with consequent detrimental effects to water bodies. We investigated the impact of that shift by quantifying the spatial and temporal change in sediment sources and associated total nitrogen (TN) and total phosphorus (TP) pollutants output loads in an intensive agricultural catchment in North China across one year (November 2021-November 2022). We describe the implications of this work for intensive agriculture elsewhere in China and other countries. Seasonal sediment source apportionment was estimated at the catchment outlet using Berillium-7 (7Be) combined with compound-specific stable isotope (CSSI) signatures from sources and sediments. Diagnostic 'fingerprints' in MixSIAR were used to discriminate sediment sources between forest and crop farmland converted from forest (F + C(F)), crop farmland (C), and vegetable farmland (V). Our study identified F + C(F) as the dominant sediment source (mean 55.24 ± 2.91 %), intermediate on V (mean 30.06 ± 2.20 %), and least on C (mean 14.70 ± 2.13 %). Sedimentation ranged from 37.98 ± 3.02 to 89.60 ± 12.68 t·ha-1·event-1 and coincided with shifted land use policy and rainfall distribution. The TN and TP in sediment were both mainly derived from F + C(F) (averaged 22.27 ± 4.26 t·event-1 and 11.62 ± 2.28 t·event-1) and least from V (averaged 1.63 ± 0.29 and 2.09 ± 0.33 t·event-1). Despite being a significant sediment source, V contributed little sediment TN and TP input for eutrophication. Our findings imply that F + C(F) are diffuse sources of catchment pollution over the short term. These results describe the successful use of CSSI and 7Be to cost-effectively quantify the seasonal variation of sediment TN and TP loads from land-use-specific sources in the catchment under shifting land management policy in China with potential for use elsewhere. These findings enable soil conservation strategies and land management practices optimized for implementing targeted pollutant abatement initiatives in intensive agriculture in China and elsewhere.