Calycosin induces autophagy and apoptosis via Sestrin2/AMPK/mTOR in human papillary thyroid cancer cells

Calycosin, one of small molecules derived from astragalus, has anti-tumor effects in various tumors. However, the effects of calycosin on papillary thyroid cancer (PTC) remain unclear. This study aimed to explore the anti-tumor ability of calycosin on human PTC and its potential mechanisms. The B-CPAP cells were treated with calycosin, then cell proliferation, apoptosis and invasiveness were measured by CCK8 assay, flow cytometry, wound healing and transwell invasion assay, respectively. The cells were also performed by whole transcriptome microarray bioinformatics analysis. Apoptosis and autophagy-related markers or proteins were measured by qRT-PCR or western blot. Sestrin2-mediated AMPK/mTOR pathways were determined by western blot. We found that calycosin inhibited migration and invasion of B-CPAP cells and induced apoptosis (Bax/Bcl-2) and autophagy (LC3II/I, Beclin1) of B-CPAP cells. Differential expressed genes were screened between the calycosin-treated cells and control (524 genes upregulated and 328 genes downregulated). The pathway enrichment suggested that the role of calycosin in B-CPAP cells is closely related to apoptosis-related genes and p70S6 Kinase. Transmission electron microscopy found an increase in autophagosomes in calycosin-treated cells. Sestrin2 in human PTC tissues and B-CPAP cells was lower than in normal thyroid tissues and cells. And the pharmacological effects of calycosin in PTC cells were related to Sestrin2 activation, increased p-AMPK and inhibited p-mTOR and p-p70S6Kinase; these alterations were reversed when silencing Sestrin2. In conclusion, calycosin has an inhibitory effect on PTC via promoting apoptosis and autophagy through the Sestrin2/AMPK/mTOR pathway

Applications of Single-Cell Omics in Tumor Immunology

The tumor microenvironment (TME) is an ecosystem that contains various cell types, including cancer cells, immune cells, stromal cells, and many others. In the TME, cancer cells aggressively proliferate, evolve, transmigrate to the circulation system and other organs, and frequently communicate with adjacent immune cells to suppress local tumor immunity. It is essential to delineate this ecosystem’s complex cellular compositions and their dynamic intercellular interactions to understand cancer biology and tumor immunology and to benefit tumor immunotherapy. But technically, this is extremely challenging due to the high complexities of the TME. The rapid developments of single-cell techniques provide us powerful means to systemically profile the multiple omics status of the TME at a single-cell resolution, shedding light on the pathogenic mechanisms of cancers and dysfunctions of tumor immunity in an unprecedently resolution. Furthermore, more advanced techniques have been developed to simultaneously characterize multi-omics and even spatial information at the single-cell level, helping us reveal the phenotypes and functionalities of disease-specific cell populations more comprehensively. Meanwhile, the connections between single-cell data and clinical characteristics are also intensively interrogated to achieve better clinical diagnosis and prognosis. In this review, we summarize recent progress in single-cell techniques, discuss their technical advantages, limitations, and applications, particularly in tumor biology and immunology, aiming to promote the research of cancer pathogenesis, clinically relevant cancer diagnosis, prognosis, and immunotherapy design with the help of single-cell techniques

Unlocking saponin biosynthesis in soapwort

Soapwort (Saponaria officinalis) is a flowering plant from the Caryophyllaceae family with a long history of human use as a traditional source of soap. Its detergent properties are because of the production of polar compounds (saponins), of which the oleanane-based triterpenoid saponins, saponariosides A and B, are the major components. Soapwort saponins have anticancer properties and are also of interest as endosomal escape enhancers for targeted tumor therapies. Intriguingly, these saponins share common structural features with the vaccine adjuvant QS-21 and, thus, represent a potential alternative supply of saponin adjuvant precursors. Here, we sequence the S. officinalis genome and, through genome mining and combinatorial expression, identify 14 enzymes that complete the biosynthetic pathway to saponarioside B. These enzymes include a noncanonical cytosolic GH1 (glycoside hydrolase family 1) transglycosidase required for the addition of d-quinovose. Our results open avenues for accessing and engineering natural and new-to-nature pharmaceuticals, drug delivery agents and potential immunostimulants

Research on the Influence Mechanism of Outdoor Wind Environment on Indoor Smoke Exhaust Efficiency in the Super-High-Rise Tower Crown Based on Airpak Simulation

The high wind pressure and velocity of the outdoor environment make super-high-rise tower crown space distinct from general tall through space. This segregation causes the crown space to be particularly prone to smoke short-circuiting influenced by the outside wind environment if a fire occurs indoors, and causes deficient smoke exhaust efficiency in a fire. The goal of this study was to investigate the general principle regarding the effect of the outdoor wind environment on smoke exhaust efficiency of such spaces under the crown space. We measured external wind direction and wind pressure in the smoke exhaust in the tower crown and developed setting plans for the exhaust outlets and make-up air inlet. Airpak was used to create the external wind environment and compare simulations to see if smoke short-circuiting occurred. We analyzed the causes, summarized solutions that did not result in short-circuiting of smoke flow, and made adjustments. We provide an ideal plan for the setting direction and vent velocity of the make-up air inlet and exhaust outlet in the crown spaces of super-tall towers to improve the design of smoke exhaust systems in such spaces

Gut Microbiota in Tibetan Herdsmen Reflects the Degree of Urbanization

Urbanization is associated with shifts in human lifestyles, thus possibly influencing the diversity, interaction and assembly of gut microbiota. However, the question regarding how human gut microbiota adapts to varying lifestyles remains elusive. To understand the relationship between gut microbiota and urbanization, we compared the diversity, interaction and assembly of gut microbial communities of herdsmen from three regions with different levels of urbanization, namely traditional herdsmen (TH), semi-urban herdsmen (SUH) and urban herdsmen (UH). The relative abundance of Prevotella decreased with the degree of urbanization (from TH to UH), whereas that of Bacteroides, Faecalibacterium, and Blautia showed an opposite trend. Although the alpha diversity measures (observed OTUs and phylogenetic diversity) of gut microbiota were unaffected by urbanization, the beta diversity (Jaccard or Bray-Curtis distances) was significantly influenced by urbanization. Metagenome prediction revealed that the gene functions associated with metabolism (i.e., carbohydrate and lipid metabolism) had significant differences between TH and UH. Network analysis showed that the modularity increased with the degree of urbanization, indicating a high extent of niche differentiation in UH. Meanwhile the trend of network density was opposite, indicating a more complex network in TH. Notably, the relative importance of environmental filtering that governed the community assembly increased with the degree of urbanization, which indicated that deterministic factors (e.g , low-fiber diet) play more important roles than stochastic factors (e.g., stochastic dispersal) in shaping the gut microbiota. A quantification of ecological processes showed a stronger signal of variable selection in UH than TH, implying that different selective pressures cause divergent gut community compositions due to urban lifestyles. Our results suggest that beta diversity, network interactions and ecological processes of gut microbiota may reflect the degree of urbanization, and highlight the adaptation of human gut microbiota to lifestyle changes

An On-Chip Silicon Photonics Thermometer with Milli-Kelvin Resolution

Photonic-based thermometers have been attracting intense research interest as a potential alternative to traditional electrical thermometers due to their physical and chemical stability and immunity to electromagnetic interference. However, due to the high requirements for the stability of the laser source, the existing studies on resolution are only theoretical predictions and do not include real-measured results. In this paper, we report on the fabrication and characterization of an on-chip silicon whispering-gallery-mode (WGM) ring resonator thermometer. The strip grating and the ring structure were fabricated on the silicon-on-insulator (SOI) substrate by two-step etching. The quality-factor (Q-factor), temperature sensitivity, and measurement range of the packaged device were 21,400, 42 pm/K, and 150 K, respectively. The real-measured temperature resolution of 2.9 mK was achieved by virtue of the power and polarization stabilization of the laser source

Unmasking the silent culprit: recurrent exercise-induced acute kidney injury in a Chinese adolescent with renal hypouricemia

Primary renal hypouricemia (RHUC) is a rare autosomal recessive disorder with a mean duration of end-stage acute kidney injury (EIAKI) of 14 days. The pathogenesis of EIAKI in patients with RHUC remains unclear. Several hypotheses have been proposed, including those related to the renal vasoconvulsive effect and the elevating effect of xanthine oxidase (XO). The effect of xanthine oxidase (XO) is most often observed following strenuous anaerobic exercise, which is frequently accompanied by low back pain, nausea, and acute kidney injury (AKI). Consequently, we postulate that EIAKI could be prevented by avoiding strenuous exercise, thus preventing the onset and recurrence of EIAKI. In this paper, we present a case of recurrent EIAKI in a patient with RHUC and a mutation in the SLC2A9 gene

Image-Based Crack Detection Method for FPSO Module Support

Floating Production Storage and Offloading (FPSO) is essential offshore equipment for developing offshore oil and gas. Due to the complex sea conditions, FPSOs will be subjected to long-term alternate loads under some circumstances. Thus, it is inevitable that small cracks occur in the upper part of the module pier. Those cracks may influence the structure’s safety evaluation. Therefore, this paper proposes a method for the FPSO module to support crack identification based on the PSPNet model. The main idea is to introduce an attention mechanism into the model with Mobilenetv2 as the backbone of the PSPNet, which can fuse multiple feature maps and increase context information. The detail feature loss caused by multiple convolutions and compressions in the original model was solved by applying the proposed method. Moreover, the attention mechanism is introduced to enhance the extraction of adequate information and suppress invalid information. The mPA value and MIoU value of the improved model increased by 2.4% and 1.8%, respectively, through verification on FPSO datasets

The regulatory network for the G1/S transition in Saccharomyces cerevisiae promotes the understanding of cancer developmental mechanisms

The G1/S transition is crucial for regulating the initiation of cell division and is highly conserved across eukaryotes. This phase of the cell cycle involves intricate transcriptional controls that are essential for understanding cell proliferation dynamics. The G1/S transition integrates diverse intracellular and extracellular signals, including growth factors and cell sizes. Saccharomyces cerevisiae, an important model organism, plays an integral role in unveiling the regulatory mechanisms of the G1/S transition. Recent studies on the G1/S transition in both yeast and vertebrates have demonstrated a direct correlation between dysregulation of the G1/S transition and the development of cancer. This review explores the G1/S transition regulatory network and its association with cancer formation, providing a theoretical foundation for future research in fundamental cell cycle dynamics and cancer