Programmed death of cardiomyocytes in cardiovascular disease and new therapeutic approaches.

Cardiovascular diseases (CVDs) have a complex pathogenesis and pose a major threat to human health. Cardiomyocytes have a low regenerative capacity, and their death is a key factor in the morbidity and mortality of many CVDs. Cardiomyocyte death can be regulated by specific signaling pathways known as programmed cell death (PCD), including apoptosis, necroptosis, autophagy, pyroptosis, and ferroptosis, etc. Abnormalities in PCD can lead to the development of a variety of cardiovascular diseases, and there are also molecular-level interconnections between different PCD pathways under the same cardiovascular disease model. Currently, the link between programmed cell death in cardiomyocytes and cardiovascular disease is not fully understood. This review describes the molecular mechanisms of programmed death and the impact of cardiomyocyte death on cardiovascular disease development. Emphasis is placed on a summary of drugs and potential therapeutic approaches that can be used to treat cardiovascular disease by targeting and blocking programmed cell death in cardiomyocytes.

Socioeconomic support, quality of life, and prognosis of frailty among the older adults.

Background: Although socioeconomic support is recommended for frailty management, its association with the prognosis of frailty is unclear. Methods: Using data from participants aged ≥65 years in the Chinese Longitudinal Healthy Longevity Survey (2008-2018), the associations between socioeconomic support (source of income, medical insurance, community support, living status), onset of prefrailty/frailty, and worsening of prefrailty, were analyzed using multinominal logistic regression models. The associations between self-reported low quality of life (QoL) and reversion of prefrailty/frailty were analyzed using multivariate logistic regression models. Associations with mortality risk were analyzed using Cox proportional hazard regression models. Results: A total of 13,859 participants (mean age: 85.8 ± 11.1 years) containing 2056 centenarians were included. Financial dependence was a risk factor for low QoL among prefrail/frail individuals, but not among robust individuals. Having commercial or other insurance, and receiving social support from the community were protective factors for low QoL among prefrail/frail individuals and for the worsening of prefrailty. Continuing to work was a risk factor for low QoL, but a protective factor for worsening of prefrailty. A negative association between continuing to work and mortality existed in prefrail individuals aged <85 years and ≥85 years. Living alone was a risk factor for low QoL, but was not significantly associated with frailty prognosis. Conclusions: Prefrail and frail individuals were vulnerable to changes in socioeconomic support and more sensitive to it compared with robust individuals. Preferential policies regarding financial support, social support, and medical insurance should be developed for individuals with frailty.

Smad2/3/4 complex could undergo liquid liquid phase separation and induce apoptosis through TAT in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) represents one of the most significant causes of mortality due to cancer-related deaths. It has been previously reported that the TGF-ß signaling pathway may be associated with tumor progression. However, the relationship between TGF-ß signaling pathway and HCC remains to be further elucidated. The objective of our research was to investigate the impact of TGF-ß signaling pathway on HCC progression as well as the potential regulatory mechanism involved. METHODS: We conducted a series of bioinformatics analyses to screen and filter the most relevant hub genes associated with HCC. E. coli was utilized to express recombinant protein, and the Ni-NTA column was employed for purification of the target protein. Liquid liquid phase separation (LLPS) of protein in vitro, and fluorescent recovery after photobleaching (FRAP) were utilized to verify whether the target proteins had the ability to drive force LLPS. Western blot and quantitative real-time polymerase chain reaction (qPCR) were utilized to assess gene expression levels. Transcription factor binding sites of DNA were identified by chromatin immunoprecipitation (CHIP) qPCR. Flow cytometry was employed to examine cell apoptosis. Knockdown of target genes was achieved through shRNA. Cell Counting Kit-8 (CCK-8), colony formation assays, and nude mice tumor transplantation were utilized to test cell proliferation ability in vitro and in vivo. RESULTS: We found that Smad2/3/4 complex could regulate tyrosine aminotransferase (TAT) expression, and this regulation could relate to LLPS. CHIP qPCR results showed that the key targeted DNA binding site of Smad2/3/4 complex in TAT promoter region is -1032 to -1182. In addition. CCK-8, colony formation, and nude mice tumor transplantation assays showed that Smad2/3/4 complex could repress cell proliferation through TAT. Flow cytometry assay results showed that Smad2/3/4 complex could increase the apoptosis of hepatoma cells. Western blot results showed that Smad2/3/4 complex would active caspase-9 through TAT, which uncovered the mechanism of Smad2/3/4 complex inducing hepatoma cell apoptosis. CONCLUSION: This study proved that Smad2/3/4 complex could undergo LLPS to active TAT transcription, then active caspase-9 to induce hepatoma cell apoptosis in inhibiting HCC progress. The research further elucidate the relationship between TGF-ß signaling pathway and HCC, which contributes to discover the mechanism of HCC development.

Research on dense object detection methods in congested environments of urban streets and roads based on DCYOLO.

The urban street is a congested environment that contains a large number of occluded and size-differentiated objects. Aiming at the problems of the loss of the target to be detected and low detection accuracy resulting from this situation, a newly improved algorithm, based on YOLOv4, DCYOLO is proposed. Firstly, a Difference sensitive network (DSN) is introduced to extract the edge features of objects from the original image. Then, assign the edge features back to increase the edge intensity of the object in the original image and ultimately improve the detection performance. Secondly, the feature fusion module (CFFB) based on context information is introduced to realize the cross-scale fusion of shallow fine-grained features and deep-level features, to strengthen the cross-scale semantic information fusion of feature maps and eventually improve the performance of object detection. At last, in the network prediction part, the SIOU loss function replaces the original CIOU loss function to improve the convergence speed and accuracy of object detection. The experiments based on MS COCO 2017 and self-made datasets show that, compared with the YOLOv4, the detection accuracy of DCYOLO models is greatly improved with an increase of 9.1 percentage points in AP and 10.4 percentage points in APs. Compared with YOLOv5x and Faster R-CNN, DCYOLO shows higher accuracy and better detection performance. The experiment result proves that the DCYOLO algorithm can adapt to the dense object detection requirements in the congested environment of urban streets.

Phosphorus Addition Reduces Seedling Growth and Survival for the Arbuscular Mycorrhizal Tree Cinnamomum camphora (Lauraceae) and Ectomycorrhizal Tree Castanopsis sclerophylla (Fagaceae) in Fragmented Forests in Eastern China.

Global changes in nutrient deposition rates and habitat fragmentation are likely to have profound effects on plant communities, particularly in the nutrient-limited systems of the tropics and subtropics. However, it remains unclear how increased phosphorus (P) supply affects seedling growth in P-deficient subtropical fragmented forests. To explore this, we applied P to 11 islands in a subtropical Chinese archipelago and examined the results in combination with a contemporary greenhouse experiment to test the influence of P addition on seedling growth and survival. We measured the growth (i.e., base area) and mortality rate of seedlings for one arbuscular mycorrhizal (AM) and one ectomycorrhizal (EcM) tree species separately and calculated their relative growth rate and mortality when compared with P addition and control treatment on each island. We also measured three functional traits and the biomass of seedlings in the greenhouse experiment. Results showed that P addition significantly increased the mortality of AM and EcM seedlings and reduced the growth rate of EcM seedlings. The relative growth rate of AM seedlings, but not EcM seedlings, significantly decreased as the island area decreased, suggesting that P addition could promote the relative growth rate of AM seedlings on larger islands. The greenhouse experiment showed that P addition could reduce the specific root length of AM and EcM seedlings and reduce the aboveground and total biomass of seedlings, indicating that P addition may affect the resource acquisition of seedlings, thereby affecting their survival and growth. Our study reveals the synergistic influence of habitat fragmentation and P deposition, which may affect the regeneration of forest communities and biodiversity maintenance in fragmented habitats.

Natural Products and Gastric Cancer: Cellular Mechanisms and Effects to Change Cancer Progression.

Gastric cancer is a severe malignant tumor with high morbidity and mortality, which seriously affects people's health. At present, the most common treatment for gastric cancer is chemotherapy. However, chemotherapy is very harmful to the human body, and some of the injuries caused by chemotherapy are irreversible. Natural products have low toxicity and anti-cancer activity, so they are currently widely studied at present. Natural products are a large variety of compounds naturally found in fruits, vegetables, spices, and medicinal plants. It is reported that natural products have different anti-cancer properties. This review has summarized the study of natural products in inducing gastric cancer cell apoptosis, inhibiting gastric cancer cell metastasis, and inhibiting gastric cancer cell proliferation. The relevant references on gastric cancer and natural products were obtained from scientific databases, including Pub- Med, Web of Science, and Science Direct. This paper records dozens of natural products with anti-gastric tumor activity and describes the potential living anti-cancer chemical compounds, their element targets, and their underlying mechanism. This review may lay the foundation for future researchers to treat gastric cancer.

LRF-WiVi: A WiFi and Visual Indoor Localization Method Based on Low-Rank Fusion.

In this paper, a WiFi and visual fingerprint localization model based on low-rank fusion (LRF-WiVi) is proposed, which makes full use of the complementarity of heterogeneous signals by modeling both the signal-specific actions and interaction of location information in the two signals end-to-end. Firstly, two feature extraction subnetworks are designed to extract the feature vectors containing location information of WiFi channel state information (CSI) and multi-directional visual images respectively. Then, the low-rank fusion module efficiently aggregates the specific actions and interactions of the two feature vectors while maintaining low computational complexity. The fusion features obtained are used for position estimation; In addition, for the CSI feature extraction subnetwork, we designed a novel construction method of CSI time-frequency characteristic map and a double-branch CNN structure to extract features. LRF-WiVi jointly learns the parameters of each module under the guidance of the same loss function, making the whole model more consistent with the goal of fusion localization. Extensive experiments are conducted in a complex laboratory and an open hall to verify the superior performance of LRF-WiVi in utilizing WiFi and visual signal complementarity. The results show that our method achieves more advanced positioning performance than other methods in both scenarios.