Research最新文献

The wide-bandgap semiconductor material Ga₂O₃ exhibits great potential in solar-blind deep-ultraviolet (DUV) photodetection applications, including none-line-of-sight secure optical communication, fire warning, high-voltage electricity monitoring, and maritime fog dispersion navigation. However, Ga₂O₃ photodetectors have traditionally faced challenges in achieving both high responsivity and fast response time, limiting their practical application. Herein, the Ga₂O₃ solar-blind DUV photodetectors with a suspended structure have been constructed for the first time. The photodetector exhibits a high responsivity of 1.51 × 10¹⁰ A/W, a sensitive detectivity of 6.01 × 10¹⁷ Jones, a large external quantum efficiency of 7.53 × 10¹² %, and a fast rise time of 180 ms under 250-nm illumination. Notably, the photodetector achieves both high responsivity and fast response time simultaneously under ultra-weak power intensity excitation of 0.01 μW/cm². This important improvement is attributed to the reduction of interface defects, improved carrier transport, efficient carrier separation, and enhanced light absorption enabled by the suspended structure. This work provides valuable insights for designing and optimizing high-performance Ga₂O₃ solar-blind photodetectors.

Spermatogenesis is a sophisticated biological process by which spermatogonial stem cells (SSCs) undergo self-renewal and differentiation into spermatozoa. Molecular mechanisms underlying fate determinations of human SSCs by key genes and signaling pathways remain elusive. Here, we report for the first time that Yes1-associated transcriptional regulator (YAP1) is required for fate determinations of SSCs and male fertility by interacting with RAD21 and targeting NEDD4 in humans and mice. YAP1 was mainly located at cell nuclei of human SSCs. YAP1 silencing resulted in the decreases in proliferation and DNA synthesis as well as an enhancement in apoptosis of human SSCs both in vivo and in vitro. RNA sequencing and real-time polymerase chain reaction assays identified NEDD4 as a target of YAP1, and NEDD4 knockdown inhibited the proliferation of human SSCs and increased their apoptosis. Furthermore, YAP1 interacted with RAD21 to regulate NEDD4 transcription in human SSCs. Importantly, YAP1 abnormalities were found to be associated with non-obstructive azoospermia (NOA) as manifested as lower expression level of YAP1 in testicular tissues of NOA patients and YAP1 single-nucleotide variants (SNVs) in 777 NOA patients. Finally, Yap1 germline conditional knockout (cKO) mice assumed mitotic arrest, low sperm count, and motility. Collectively, these results highlight a critical role of YAP1 in determining the fate determinations of human SSCs and male infertility through the YAP1/RAD21/NEDD4 pathway. This study provides new insights into the genetic regulatory mechanisms underlying human spermatogenesis and the pathogenesis of NOA, and it offers new targets for gene therapy of male infertility.

Exposure to airborne fine particulate matter (PM_2.5) is strongly associated with poor fertility and ovarian damage. However, the mechanism underlying this remains largely unclear. Here, we found that PM_2.5 markedly impaired murine ovarian reserve, decreased hormone levels, and aggravated ovarian inflammation. Circulating interleukin-6 (IL-6) was elevated in PM_2.5-exposed mice and was further confirmed to mediate this damage by IL-6 recombinant protein intervention. PM_2.5 exposure led to increased alveolar macrophage infiltration in the lungs. However, alveolar macrophage clearance with clodronate liposomes could not fully reverse the elevated IL-6 levels and ovarian injury, suggesting that alveolar macrophages were probably not the only source of circulating IL-6. Further experiments indicated that IL-6 mainly targeted ovarian theca-interstitial cells and impaired testosterone synthesis via suppressing the peroxisome proliferator-activated receptor γ (PPARγ) pathway. In addition, apoptosis of granulosa cells and restriction of follicular growth were observed in co-cultures with IL-6-treated theca-interstitial cells, which could be further reversed by the PPARγ agonist. Moreover, IL-6-neutralizing antibodies ameliorated PM_2.5-induced ovarian damage. Notably, increased levels of circulating IL-6 were observed in premature ovarian aging patients and were inversely associated with their ovarian function. In summary, our findings offer a mechanistic explanation for PM_2.5-induced ovarian dysfunction and verify IL-6 as a biomarker and potential therapeutic target.

The vast potential of medical big data to enhance healthcare outcomes remains underutilized due to privacy concerns, which restrict cross-center data sharing and the construction of diverse, large-scale datasets. To address this challenge, we developed a deep generative model aimed at synthesizing medical data to overcome data sharing barriers, with a focus on breast ultrasound (US) image synthesis. Specifically, we introduce CoLDiT, a conditional latent diffusion model with a transformer backbone, to generate US images of breast lesions across various Breast Imaging Reporting and Data System (BI-RADS) categories. Using a training dataset of 9,705 US images from 5,243 patients across 202 hospitals with diverse US systems, CoLDiT generated breast US images without duplicating private information, as confirmed through nearest-neighbor analysis. Blinded reader studies further validated the realism of these images, with area under the receiver operating characteristic curve (AUC) scores ranging from 0.53 to 0.77. Additionally, synthetic breast US images effectively augmented the training dataset for BI-RADS classification, achieving performance comparable to that using an equal-sized training set comprising solely real images (P = 0.81 for AUC). Our findings suggest that synthetic data, such as CoLDiT-generated images, offer a viable, privacy-preserving solution to facilitate secure medical data sharing and advance the utilization of medical big data.

Postpartum depression (PPD) represents a important emotional disorder emerging after childbirth, characterized by its complex etiology and challenging management. Despite extensive preclinical and clinical investigations underscoring the role of estrogen fluctuations and estrogen receptor genes in PPD, the precise mechanisms underpinning this condition have remained elusive. In our present study, animal behavioral studies have elucidated a tight link between the aberrant expression of ESR2, miR-10a-5p, and BDNF in the prefrontal cortex of mice exhibiting postpartum depressive-like behavior, shedding light on the potential molecular pathways involved. Integrating bioinformatics, in vivo, and cell transfection methodologies has unraveled the intricate molecular interplay between ESR2, miR-10a-5p, and BDNF. We identified ESR2 as a negative transcription factor that down-regulates miR-10a transcription, while miR-10a-5p serves as a negative regulator that suppresses BDNF expression. This molecular triad contributes to the pathogenesis of PPD by affecting synaptic plasticity, as evidenced by alterations in synapse-related proteins (e.g., SYP, SYN, and PSD95) and glutamate receptor expression. Additionally, primary neuron culture studies have confirmed the critical roles of ESR2 and miR-10a-5p in maintaining neuronal growth and morphology. Therapeutic interventions, including stereotactic and intranasal administration of antagomir or BDNF, have demonstrated significant potential in treating PPD, highlighting the therapeutic implications of targeting the negative transcriptional and regulatory interactions between ESR2, miR-10a-5p, and BDNF. Our findings endorse the hypothesis that estrogen fluctuations and estrogen receptor gene activity are pivotal stressors and risk factors for PPD, affecting central nervous system functionality and precipitating depressive behaviors postpartum.

After myocardial infarction (MI), ventricular dilation and the microscopic passive stretching of the infarcted border zone is the meaning contributor to the continuous expansion of myocardial fibrosis. Epicardial hydrogel patches have been demonstrated to alleviate this sequela of MI in small-animal models. However, these have not been successfully translated to humans or even large animals, in part because of challenges in attaining both the greater stiffness and slower viscoelastic relaxation that mathematical models predict to be optimal for application to larger, slower-beating hearts. Here, using borate-based dynamic covalent chemistry, we develop an injectable "heart rate matched" viscoelastic gelatin (VGtn) hydrogel with a gel point tunable across the stiffnesses and frequencies that are predicted to transspecies and cross-scale cardiac repair after MI. Small-animal experiments demonstrated that, compared to heart rate mismatched patches, the heart rate matched VGtn patches inhibited ventricular bulging and attenuated stress concentrations in the myocardium after MI. In particular, the viscoelastic patch can coordinate the microscopic strain at the infarction boundary. VGtn loaded with anti-fibrotic agents further reduced myocardial damage and promoted angiogenesis in the myocardium. The tuned heart rate matched patches demonstrated similar benefits in a larger-scale and lower heart rate porcine MI model. Results suggest that heart rate matched VGtn patches may hold potential for clinical translation.

Tree shrews (TSs) possess a highly developed visual system. Here, we establish an age-related single-cell RNA sequencing atlas of retina cells from 15 TSs, covering 6 major retina cell classes and 3 glial cell types. An age effect is observed on the cell subset composition and gene expression pattern. We then verify the cell subtypes and identify specific markers in the TS retina including CA10 for bipolar cells, MEGF11 for H1 horizontal cells, and SLIT2, RUNX1, FOXP2, and SPP1 for retinal ganglion cell subpopulations. The cross-species analysis elucidates the cell type-specific transcriptional programs, different cell compositions, and cell communications. The comparisons also reveal that TS cones and subclasses of bipolar and amacrine cells exhibit the closest relationship with humans and macaques. Our results suggests that TS could be used as a better disease model to understand age-dependent cellular and genetic mechanisms of the retina, particularly for the retinal diseases associated with cones.

Achieving rubber-like stretchability in cellulose ionogels presents a substantial challenge due to the intrinsically extended chain configuration of cellulose. Inspired by the molecular configuration of natural rubber, we address this challenge by using cyanoethyl as a substitute for 1.5 hydroxyl on the D-glucose unit of cellulose. This strategy innovatively triggers the transformation of cellulose molecules into a coiled chain configuration, facilitating the creation of an ultra-stretchable ionogel free from any petrochemical polymers. The resultant ionogel demonstrates mechanical ductility comparable to that of a rubber band, achieving an elongation strain of nearly 1,000% while maintaining a tensile strength of up to 1.8 MPa and exhibiting a biomodulus akin to that of human skin, recorded at 63 kPa. Additionally, this stretchable ionogel presents skin-like self-healing behavior, favorable biocompatibility, and noteworthy thermoelectric properties, highlighted by a Seebeck coefficient of approximately 68 mV K^-1. This study delineates a feasible molecular approach for developing stretchable ionogels from biomass resources, potentially revolutionizing self-powered stretchable electronics for integration with human tissues and skin.

Redox cycling of iron plays a pivotal role in both nutrient acquisition by living organisms and the geochemical cycling of elements in aquatic environments. In nature, iron cycling is mediated by microbial Fe(II)-oxidizers and Fe(III)-reducers or through the interplay of biotic and abiotic iron transformation processes. Here, we unveil a specific iron cycling process driven by one single phototrophic species, Rhodobacter ferrooxidans SW2. It exhibits the capability to reduce Fe(III) during bacterial cultivation. A c-type cytochrome is identified with Fe(III)-reducing activity, implying the linkage of Fe(III) reduction with the electron transport system. R. ferrooxidans SW2 can mediate iron redox transformation, depending on the availability of light and/or organic substrates. Iron cycling driven by anoxygenic photoferrotrophs is proposed to exist worldwide in modern and ancient environments. Our work not only enriches the theoretical basis of iron cycling in nature but also implies multiple roles of anoxygenic photoferrotrophs in iron transformation processes.