Supramolecular nanodrug targeting CDK4/6 overcomes BAG1 mediated cisplatin resistance in oral squamous cell carcinoma.

Chemoresistance to cisplatin remains a significant challenge affecting the prognosis of advanced oral squamous cell carcinoma (OSCC). However, the specific biomarkers and underlying mechanisms responsible for cisplatin resistance remain elusive. Through comprehensive bioinformatic analyses, we identified a potential biomarker, BCL2 associated athanogene-1 (BAG1), showing elevated expression in head and neck squamous cell carcinoma (HNSCC). Since OSCC represents the primary pathological type of HNSCC, we investigated BAG1 expression in human tumor tissues and cisplatin resistant OSCC cell lines, revealing that silencing BAG1 induced apoptosis in cisplatin-resistant cells both in vitro and in vivo. This effect led to impaired cell viability of cisplatin resistant OSCC cells and indicated a positive correlation between BAG1 expression and the G1/S transition during cell proliferation. Based on these insights, the administration of a CDK4/6 inhibitor in combination with cisplatin effectively overcame cisplatin resistance in OSCC through the CDK4/6-BAG1 axis. Additionally, to enable simultaneous drug delivery and enhance synergistic antitumor efficacy, we developed a novel supramolecular nanodrug LEE011-FFERGD/CDDP, which was validated in an OSCC orthotopic mouse model. In summary, our study highlights the potential of a combined administration of CDK4/6 inhibitor and cisplatin as a promising therapeutic regimen for treating advanced or cisplatin resistant OSCC.

miRNA profiling of chicken follicles during follicular development.

MicroRNAs (miRNAs) play a crucial role as transcription regulators in various aspects of follicular development, including steroidogenesis, ovulation, apoptosis, and gene regulation in poultry. However, there is a paucity of studies examining the specific impact of miRNAs on ovarian granulosa cells (GCs) across multiple grades in laying hens. Consequently, this study aims to investigate the roles of miRNAs in chicken GCs. By constructing miRNA expression profiles of GCs at 10 different time points, encompassing 4 pre-hierarchical, 5 preovulatory, and 1 postovulatory follicles stage, we identified highly expressed miRNAs involved in GC differentiation (miR-148a-3p, miR-143-3p), apoptosis (let7 family, miR-363-3p, miR-30c-5p, etc.), and autophagy (miR-128-3p, miR-21-5p). Furthermore, we discovered 48 developmentally dynamic miRNAs (DDMs) that target 295 dynamic differentially expressed genes (DDGs) associated with follicular development and selection (such as oocyte meiosis, progesterone-mediated oocyte maturation, Wnt signaling pathway, TGF-ß signaling pathway) as well as follicular regression (including autophagy and cellular senescence). These findings contribute to a more comprehensive understanding of the intricate mechanisms underlying follicle recruitment, selection, and degeneration, aiming to enhance poultry's reproductive capacity.

Hierarchical Wrinkles with Piezopotential Enhanced Surface Tribopolarity for High-Performance Self-Powered Pressure Sensor.

Achieving both high sensitivity and wide detecting range is significant for the applications of triboelectric nanogenerator-based self-powered pressure sensors (TPSs). However, most of the previous designs with high sensitivity usually struggle in a narrow pressure detection range (<30 kPa) while expanding the detection range normally sacrifices the sensitivity. To overcome this well-known obstacle, herein, piezopotential enhanced triboelectric effect realized by a rationally designed PDMS/ZnO NWs hierarchical wrinkle structure was exploited to develop a TPS (PETPS) with both high sensitivity and wide detecting range. In this PETPS design, the piezopotential derived from the deformation of ZnO NWs enhances its tribo-charge transferring ability; meanwhile, the hierarchical structure helps to establish a dynamically self-adjustable contact area. Benefiting from these advantages, the PETPS simultaneously achieves high sensitivity (0.26 nC cm-2 kPa-1 from 1 to 25 kPa, and 0.02 nC cm-2 kPa-1 from 25 to 476 kPa), fast response (46 ms), wide sensing range (1 to 476 kPa), and good stability (over 4000 cycles). In addition, the output charge density that is independent of the speed rate of driven force was adopted as the sensing signal of PETPS to replace the commonly used peak voltage/current values, enabling it more adaptive to accurately detect pressure variation in real applications.

Characteristics and functions of DNA N(6)-methyladenine in embryonic chicken muscle development.

DNA N(6)-methyladenine (DNA-6mA) is a new epigenetic mark in eukaryotes, the distribution and functions of which in genomic DNA remain unknown. Although recent studies have suggested that 6mA is present in multiple model organisms and is dynamically regulated during development, the genomic features of 6mA in avian species have yet to be elucidated. 6mA immunoprecipitation sequencing approach was used to analysis the distribution and function of 6mA in the muscle genomic DNA during embryonic chicken development. 6mA immunoprecipitation sequencing was combined with transcriptomic sequencing to reveal the role of 6mA in the regulation of gene expression and to explore possible pathways by which 6mA is involved in muscle development. We here provide evidence that 6mA modification exists widely throughout the chicken genome, and show preliminary data regarding genome-wide distribution of this epigenetic mark. Gene expression was shown to be inhibited by 6mA modification in promoter regions. In addition, the promoters of some genes related to development were modified by 6mA, indicating that 6mA may be involved in embryonic chicken development. Furthermore, 6mA may participate in muscle development and immune function by regulating HSPB8 and OASL expression. Our study improves our understanding of the distribution and function of 6mA modification in higher organisms and provide new information about differences between mammals and other vertebrates. These findings demonstrate an epigenetic role for 6mA in gene expression and potential involvement in chicken muscle development. Furthermore, the results suggest a potential epigenetic role for 6mA in avian embryonic development.

Integrated Transcriptome Analysis Reveals mRNA-miRNA Pathway Crosstalk in Roman Laying Hens' Immune Organs Induced by AFB1.

Aflatoxin B1 (AFB1) is a widely distributed contaminant in moldy corn, rice, soybean, and oil crops. Many studies have revealed its adverse effects, such as carcinogenicity, immunotoxicity, and hepatotoxicity, on the health of humans and animals. To investigate the immunotoxic effects on chicken immune organs induced by AFB1, we integrated RNA and small-RNA sequencing data of the spleen and the bursa of Fabricius to elucidate the response of the differentially expressed transcriptional profiles and related pathways. AFB1 consumption negatively influenced egg quality, but no obvious organ damage was observed compared to that of the control group. We identified 3918 upregulated and 2415 downregulated genes in the spleen and 231 upregulated and 65 downregulated genes in the bursa of Fabricius. We confirmed that several core genes related to immune and metabolic pathways were activated by AFB1. Furthermore, 42 and 19 differentially expressed miRNAs were found in the spleen and the bursa of Fabricius, respectively. Differentially expressed genes and target genes of differentially expressed miRNAs were mainly associated with cancer progression and immune response. The predicted mRNA-miRNA pathway network illustrated the potential regulatory mechanisms. The present study identified the transcriptional profiles and revealed potential mRNA-miRNA pathway crosstalk. This genetic regulatory network will facilitate the understanding of the immunotoxicity mechanisms of chicken immune organs induced by high concentrations of AFB1.

Gene expression profiles of specific chicken skeletal muscles.

The chicken provides large amounts of protein for the human diet and is also used as a model organism for biomedical research. Increasing meat production is an important goal in the poultry industry and skeletal muscles have highly diverse origins, shapes, metabolic features, and physical functions. Previous gene expression atlases have largely ignored the differences among diverse types of skeletal muscles; therefore, comprehensive transcriptional maps of all skeletal muscles are needed to improve meat production traits. In this study, we sequenced 58 samples from 10 different skeletal muscles of 42-day-old White Plymouth Rock chickens. We also measured myofiber diameter and generated myofiber-type datasets of these 10 tissues. We generated 418.4 Gb high-quality bulk RNA-Seq data from four or six biological replicates of each skeletal muscle (four replicates from extraocular samples) (approximately 7.4 Gb per sample). This dataset provides valuable information for understanding the muscle fiber characteristics of White Plymouth Rock chickens. Furthermore, our data can be used as a model for heterogeneity analysis between tissues with similar properties.

Dynamic Changes in the Gut Microbial Community and Function during Broiler Growth.

During the entire growth process, gut microbiota continues to change and has a certain impact on the performance of broilers. Here, we used 16S rRNA gene sequencing to explore the dynamic changes in the fecal bacterial communities and functions in 120 broilers from 4 to 16 weeks of age. We found that the main phyla (Firmicutes, Fusobacteria, Proteobacteria, and Bacteroides) accounted for more than 93.5% of the total bacteria in the feces. The alpha diversity of the fecal microbiota showed a downward trend with time, and the beta diversity showed significant differences at various time points. Then, the study on the differences of microbiota between high-weight (HW) and low-weight (LW) broilers showed that there were differences in the diversity and composition of microbiota between high- and low-weight broilers. Furthermore, we identified 22 genera that may be related to the weight change of broilers. The analysis of flora function reveals their changes in metabolism, genetic information processing, and environmental information processing. Finally, combined with microbial function and cecal transcriptome results, we speculated that microorganisms may affect the immune level and energy metabolism level of broilers through their own carbohydrate metabolism and lipid metabolism and then affect body weight (BW). Our results will help to expand our understanding of intestinal microbiota and provide guidance for the production of high-quality broilers. IMPORTANCE The intestinal microbiota has a certain impact on the performance of broilers. However, the change of intestinal microbiota after 4 weeks of age is not clear, and the mechanism of the effect of microorganisms on the weight change of broilers needs more exploration. After 4 weeks of age, the alpha diversity of microorganisms in broiler feces decreased, and the dominant bacteria were Firmicutes, Fusobacteria, Proteobacteria, and Bacteroides. There were differences in microbiota diversity and composition between high- and low-weight broilers. Intestinal microorganisms may affect the immune level and energy metabolism level of broilers through their own carbohydrate metabolism and lipid metabolism and then affect the body weight. The results are helpful to increase the understanding of intestinal microbiota and provide reference for the production of high-quality broilers.

Coaxial Spring-Like Stretchable Triboelectric Nanogenerator Toward Personal Healthcare Monitoring.

Stretchable triboelectric nanogenerators have attracted increasing interests in the field of Internet of Things and sensor network. Therefore, great efforts have been made to realize the stretchability of electronic devices via elaborated material configurations and ingenious device designs. In this work, a flexible and stretchable TENG is developed with a coaxial spring-like structure. The unique structure allows it to generate electrical energy for different degrees of stretching deformations. Its output demonstrates good response to the strain and frequency of the mechanical deformation. At the same time, it exhibits excellent stability and washability. The TENG can be worn on the human fingers, elbow, and knee to monitor the body activities. Furthermore, a self-powered temperature sensor system is fabricated by integrating the TENG with a temperature sensor to identify the operating ambient temperature in real time. A combination of this flexible and stretchable TENG with body motions and a temperature sensor brings a novel insight into wearable functional electronics and user-friendly health monitoring, which has an important basic research significance and practical application value in biometric systems.

Multi-Omics Analysis After Vaginal Administration of Bacteroides fragilis in Chickens.

The reproductive tract of chickens is an important organ for egg formation. The vagina is in close contact with the external environment, which may lead to the invasion of a variety of pathogenic bacteria, affect the internal and external quality of eggs, and even increase mortality and cause economic loss. In recent years, probiotics as a substitute for antibiotics have brought economic benefits in livestock and poultry production. In the present study, we investigated the effects of vaginal administration of Bacteroides fragilis on the cloacal microbiota, vaginal transcriptome and metabolomics of chickens and evaluated the beneficial potential of B. fragilis. The results showed that B. fragilis treatment could affect the microbial composition of the cloaca. Transcriptome analysis found that the immune-related genes CCN3, HAS2, and RICTOR were upregulated, that the inflammatory genes EDNRB, TOX, and NKX2-3 were downregulated, and that DEGs were also enriched in the regulation of the inflammatory response, cellular metabolism, and synaptic response pathways. In addition, the differential metabolites were mainly related to steroid hormone biosynthesis, unsaturated fatty acid biosynthesis, and arachidonic acid metabolism, and we identified associations between specific differential metabolites and genes. Overall, this study provides a theoretical basis for the application of B. fragilis as a potential probiotic in livestock and poultry production.

A Fully Self-Healing Piezoelectric Nanogenerator for Self-Powered Pressure Sensing Electronic Skin.

As an important way of converting mechanical energy into electric energy, a piezoelectric nanogenerator (PENG) has been widely applied in energy harvesting as well as self-powered sensors in recent years. However, its robustness and durability are still severely challenged by frequent and inevitable mechanical impacts in real application environments. Herein, a fully self-healing PENG (FS-PENG) as a self-powered pressure sensing electronic skin is reported. The self-healing piezoelectric composite and self-healing Ag NW electrode fabricated through mixing piezoelectric PZT particles and conductive Ag NWs into self-healing polydimethylsiloxane (H-PDMS) are assembled into the sandwich structure FS-PENG. The FS-PENG could not only effectively convert external stimulation into electrical signals with a linear response to the pressure but also retain the excellent self-healing and stable sensing property after multiple cycles of cutting and self-healing process. Moreover, a self-healing pressure sensor array composed of 9 FS-PENGs was attached on the back of the human hand to mimic the human skin, and accurate monitoring of the spatial position distribution and magnitude of the pressure was successfully realized.

Hierarchical Particle-In-Quasicavity Architecture for Ultratrace In Situ Raman Sensing and Its Application in Real-Time Monitoring of Toxic Pollutants.

Unstable detection environment is one of the biggest interferences for in situ surface-enhanced Raman spectroscopy (SERS) using in real-time monitoring of toxic pollutants, leading to unreliable results. To address this problem, we have designed and prepared a cavity-based particle-in-quasicavity (PIQC) architecture composed of hierarchical ZnO/Ag nanosheets and nanoprotrusions for improving the in situ SERS performance under a liquid environment. Benefitting from the special cascaded optical field mode, the PIQC ZnO/Ag exhibits excellent in situ SERS detectability, with 10-18 M of limit of detection for rhodamine 6G and 12.8% of signal relative standard deviation value. Furthermore, by means of a microfluidic chip, this PIQC structure is proved to have the quantitative analysis feasibility and realizes real-time monitoring of the 3,3',4,4'-tetrachlorobiphenyl, a representative global environmental hazard, under the flowing environment. The strategy in this paper provides a brand new idea to promote the application of in situ SERS in contaminant monitoring and is also instructive for light control in other optical fields.

Pretreatment of Diabetic Adipose-derived Stem Cells with mitoTEMPO Reverses their Defective Proangiogenic Function in Diabetic Mice with Critical Limb Ischemia.

Adipose-derived stem cells (ADSCs) have the ability to migrate to injury sites and facilitate tissue repair by promoting angiogenesis. However, the therapeutic effect of ADSCs from patients with diabetes is impaired due to oxidative stress. Given that diabetes is a group of metabolic disorders and mitochondria are a major source of reactive oxygen species (ROS), it is possible that mitochondrial ROS plays an important role in the induction of diabetic ADSC (dADSC) dysfunction. ADSCs isolated from diabetic mice were treated with mitoTEMPO, a mitochondrial ROS scavenger, or TEMPO, a universal ROS scavenger, for three passages. The results showed that pretreatment with mitoTEMPO increased the proliferation, multidifferentiation potential, and the migration and proangiogenic capacities of dADSCs to levels similar to those of ADSCs from control mice, whereas pretreatment with TEMPO showed only minor effects. Mechanistically, mitoTEMPO pretreatment enhanced the mitochondrial antioxidant capacity of dADSCs, and knockdown of superoxide dismutase reduced the restored mitochondrial antioxidant capacity and attenuated the proangiogenic effects induced by mitoTEMPO pretreatment. In addition, mitoTEMPO pretreatment improved the survival of dADSCs in diabetic mice with critical limb ischemia, showing protective effects similar to those of control ADSCs. Pretreatment of dADSCs with mitoTEMPO decreased limb injury and improved angiogenesis in diabetic mice with critical limb ischemia. These findings suggested that short-term pretreatment of dADSCs with a mitochondrial ROS scavenger restored their normal functions, which may be an effective strategy for improving the therapeutic effects of ADSC-based therapies in patients with diabetes.

High stability luminophores: fluorescent CsPbX3 (X = Cl, Br and I) nanofiber prepared by one-step electrospinning method.

The novel fluorescent nanofiber membranes of CsPbX3 (FNMs/CPX, X = Cl, Br, I) with a wide photoluminescence range from 405 nm to 675 nm are fabricated by a one-step electrospinning method in this paper. Owing to the polymer cladding, these FNMs/CPX show much better thermal and humid stability compared to the common CsPbX3 particles, and the corresponding white light-emitting diode prepared by them also exhibits excellent optical properties. Without adopting any complicated processes, this method opens up a brand new way for the perovskite materials using in lighting and display fields.