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Dysregulated calcium (Ca2+) signaling pathways are associated with tumor cell death and drug resistance. In non-excitable cells, such as hepatocellular carcinoma (HCC) cells, the primary pathway for Ca2+ influx is through stromal interaction molecule 1 (STIM1)-mediated store-operated calcium entry (SOCE). Previous studies have demonstrated the involvement of STIM1-mediated SOCE in processes such as genesis, metastasis, and stem cell self-renewal of HCC. However, it remains unclear whether STIM1-mediated SOCE plays a role in developing acquired resistance to sorafenib in HCC patients. In this study, we established acquired sorafenib-resistant (SR) HCC cell lines by intermittently exposing them to increasing concentrations of sorafenib. Our results showed higher levels of STIM1 and stronger SOCE in SR cells compared with parental cells. Deleting STIM1 significantly enhanced sensitivity to sorafenib in SR cells, while overexpressing STIM1 promoted SR by activating SOCE. Mechanistically, STIM1 increased the transcription of SLC7A11 through the SOCE-CaN-NFAT pathway. Subsequently, up-regulated SLC7A11 increased glutathione synthesis, resulting in ferroptosis insensitivity and SR. Furthermore, combining the SOCE inhibitor SKF96365 with sorafenib significantly improved the sensitivity of SR cells to sorafenib both in vitro and in vivo. These findings suggest a potential strategy to overcome acquired resistance to sorafenib in HCC cells.

Abstract Carcinoembryonic antigen (CEA) is a tumor-associated antigen primarily produced by tumor cells. It has been implicated in various biological processes such as cell adhesion, proliferation, differentiation, and metastasis. Despite this, the precise molecular mechanisms through which CEA enhances tumor cell proliferation remain largely unclear. Our study demonstrates that CEA enhances the proliferation and migration of non-small cell lung cancer (NSCLC) while also inhibiting cisplatin-induced apoptosis in NSCLC cells. Treatment with CEA led to an increase in mitochondrial numbers and accumulation of lipid droplets in A549 and H1299 cells. Additionally, our findings indicate that CEA plays a role in regulating the fatty acid metabolism of NSCLC cells. Inhibiting fatty acid metabolism significantly reduced the CEA-mediated proliferation and migration of NSCLC cells. CEA influences fatty acid metabolism and the proliferation of NSCLC cells by activating the PGC-1α signaling pathway. This regulatory mechanism involves CEA increasing intracellular cAMP levels, which in turn activates PKA and upregulates PGC-1α. In NSCLC, inhibiting the PKA-PGC-1α signaling pathway reduces both fatty acid metabolism and the proliferation and migration induced by CEA, both in vitro and in vivo. These results suggest that CEA contributes to the promotion of proliferation and migration by modulating fatty acid metabolism. Targeting CEA or the PKA-PGC-1ɑ signaling pathway may offer a promising therapeutic approach for treating NSCLC.

Background While anti-programmed cell death protein-1 (PD-1) monotherapy has shown effectiveness in treating lung cancer, its response rate is limited to approximately 20%. Recent research suggests that abnormal lipid metabolism in patients with lung adenocarcinoma may hinder the efficacy of anti-PD-1 monotherapy.Methods Here, we delved into the patterns of lipid metabolism in patients with The Cancer Genome Atlas (TCGA)-lung adenocarcinoma (LUAD) and their correlation with the immune microenvironment’s cellular infiltration characteristics of the tumor. Furthermore, the lipid metabolism score (LMS) system was constructed, and based on the LMS system, we further performed screening for potential agents targeting lipid metabolism. The mechanism of MK1775 was further validated using RNA sequencing, co-culture technology, and in vivo experiments.Results We developed an LSM system and identified a potential sensitizing agent, MK1775, which targets lipid metabolism and enhances the effects of anti-PD-1 treatment. Our results demonstrate that MK1775 inhibits tumor progression by influencing lipid crosstalk between tumor cells and tumor-associated macrophages and CD8+T cells, thereby increasing the effectiveness of anti-PD-1 treatment. Further, we found that MK1775 inhibited the phosphatidylinositol 3-kinase(PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway, which on one hand downregulated FASN-mediated synthesis of fatty acids (FAs) to inhibit fatty acid oxidation of tumor-associated macrophages, and on the other hand, promoted IRF-mediated secretion of CXCL10 and CXCL11 to facilitate the infiltration of CD8+ T cells.Conclusions These findings emphasize the important role of lipid metabolism in shaping the complex tumor microenvironment. By manipulating the intricate intricacies of lipid metabolism within the tumor microenvironment, we can uncover and develop promising strategies to sensitize immunotherapy, potentially revolutionizing cancer treatment approaches.

Abstract Background Chronic kidney disease (CKD) involves a variety of pathological processes, and ferroptosis plays a vital role in CKD progression. Targeting ferroptosis is a promising strategy for the treatment of CKD. However, inhibitors of ferroptosis have not been used in the clinical treatment of CKD. Vitexin is a natural flavonoid with many biological activities and protective effects against various diseases. However, whether vitexin can prevent the progression of CKD is not known. Methods In vivo, the effect of vitexin on CKD was evaluated by using mouse models of unilateral ureteral obstruction (UUO) and unilateral ischemia–reperfusion (UIR). Western blotting, Sirius red staining and transmission electron microscopy were used to analyze renal tubular injury, interstitial fibrosis, and inflammation in the kidneys of UUO and UIR mice. In vitro, CCK8 assays and lipid peroxidation assays were performed to analyze cell viability and lipid peroxidation in human renal tubular epithelial cells (HK2 cells) induced by erastin. The activation of renal fibroblasts (NRK-49 F cells) was also analyzed. Additionally, an in-silico protein-drug docking model and coimmunoprecipitation were performed to determine the direct substrate of vitexin. Results In vivo, vitexin treatment significantly ameliorated renal tubular injury, interstitial fibrosis, and inflammation in the kidneys of UUO and UIR mice. Additionally, our results showed that vitexin significantly attenuated UUO- and UIR-induced ferroptosis in renal tubular epithelial cells by upregulating glutathione peroxidase 4 (GPX4) protein levels and inhibiting lipid peroxidation in mouse kidneys. In vitro, treatment with vitexin inhibited erastin-induced ferroptosis in HK2 cells. Moreover, vitexin inhibited the expression of collagen I and α-SMA (alpha-smooth muscle actin) in NRK-49 F cells induced by the supernatant of erastin-treated HK2 cells. Mechanistically, our results suggested that vitexin could activate the NRF2/heme oxygenase-1 (HO-1) pathway by inhibiting the KEAP1- and ubiquitination-mediated degradation of NRF2, thereby increasing the expression of GPX4, and further inhibiting lipid peroxidation and ferroptosis. Additionally, knockout of NRF2 greatly inhibited the antiferroptotic effects of vitexin. Conclusions Taken together, our results indicate that vitexin can protect against renal tubular epithelial cell ferroptosis in CKD by activating the KEAP1/NRF2/HO-1 pathway and is a promising drug to treat CKD.

Background Myeloid-derived suppressor cells (MDSCs) are crucial mediators of tumor-associated immune suppression. Targeting the accumulation and activation of MDSCs has been recognized as a promising approach to enhance the effectiveness of immunotherapies for different types of cancer.Methods The MC38 and B16 tumor-bearing mouse models were established to investigate the role of Fgl2 during tumor progression. Fgl2 and FcγRIIB-deficient mice, adoptive cell transfer, RNA-sequencing and flow cytometry analysis were used to assess the role of Fgl2 on immunosuppressive activity and differentiation of MDSCs.Results Here, we show that fibrinogen-like protein 2 (Fgl2) regulates the differentiation and immunosuppressive functions of MDSCs. The absence of Fgl2 leads to an increase in antitumor CD8+ T-cell responses and a decrease in granulocytic MDSC accumulation. The regulation mechanism involves Fgl2 modulating cholesterol metabolism, which promotes the accumulation of MDSCs and immunosuppression through the production of reactive oxygen species and activation of XBP1 signaling. Inhibition of Fgl2 or cholesterol metabolism in MDSCs reduces their immunosuppressive activity and enhances differentiation. Targeting Fgl2 could potentially enhance the therapeutic efficacy of anti-PD-1 antibody in immunotherapy.Conclusion These results suggest that Fgl2 plays a role in promoting immune suppression by modulating cholesterol metabolism and targeting Fgl2 combined with PD-1 checkpoint blockade provides a promising therapeutic strategy for antitumor therapy.

Annexin A2 (Anxa2) is a calcium (Ca2+)-regulated phospholipid binding protein composed of a variable N-terminus and a conserved core domain. This protein has been widely found in many tissues and fluids, including tubule cells, glomerular epithelial cells, renal vessels, and urine. In acute kidney injury, the expression level of this protein is markedly elevated in response to acute stress. Moreover, Anxa2 is a novel biomarker and potential therapeutic target with prognostic value in chronic kidney disease. In addition, Anxa2 is associated not only with clear-cell renal cell carcinoma differentiation but also the formation of calcium-related nephrolithiasis. In this review, we discuss the characteristics and functions of Anxa2 and focus on recent reports on the role of Anxa2 in the kidney, which may be useful for future research.

The many-banded krait, Bungarus multicinctus, has been recorded as the animal resource of JinQianBaiHuaShe in the Chinese Pharmacopoeia. Characterization of its venoms classified chief phyla of modern animal neurotoxins. However, the evolutionary origin and diversification of its neurotoxins as well as biosynthesis of its active compounds remain largely unknown due to the lack of its high-quality genome. Here, we present the 1.58 Gbp genome of B. multicinctus assembled into 18 chromosomes with contig/scaffold N50 of 7.53 Mbp/149.8 Mbp. Major bungarotoxin-coding genes were clustered within genome by family and found to be associated with ancient local duplications. The truncation of glycosylphosphatidylinositol anchor in the 3′-terminal of a LY6E paralog released modern three-finger toxins (3FTxs) from membrane tethering before the Colubroidea divergence. Subsequent expansion and mutations diversified and recruited these 3FTxs. After the cobra/krait divergence, the modern unit-B of β-bungarotoxin emerged with an extra cysteine residue. A subsequent point substitution in unit-A enabled the β-bungarotoxin covalent linkage. The B. multicinctus gene expression, chromatin topological organization, and histone modification characteristics were featured by transcriptome, proteome, chromatin conformation capture sequencing, and ChIP-seq. The results highlighted that venom production was under a sophisticated regulation. Our findings provide new insights into snake neurotoxin research, meanwhile will facilitate antivenom development, toxin-driven drug discovery and the quality control of JinQianBaiHuaShe.

In recent years, the clinical impact of intestinal microbiota–kidney interaction has been emerging. Experimental evidence highlighted a bidirectional evolutionary correlation between intestinal microbiota and kidney diseases. Nonetheless, acute kidney injury (AKI) is still a global public health concern associated with high morbidity, mortality, healthcare costs, and limited efficient therapy. Several studies on the intestinal microbiome have improved the knowledge and treatment of AKI. Therefore, the present review outlines the concept of the gut–kidney axis and data about intestinal microbiota dysbiosis in AKI to improve the understanding of the mechanisms of the intestinal microbiome on the modification of kidney function and response to kidney injury. We also introduced the future directions and research areas, emphasizing the intervention approaches and recent research advances of intestinal microbiota dysbiosis during AKI, thereby providing a new perspective for future clinical trials.

Odd-chain FAs (OCFAs) are present in very low level at nearly 1% of total FAs in human plasma, and thus, their functions were usually ignored. Recent epidemiological studies have shown that OCFAs are inversely associated with a variety of disease risks. However, the contribution of OCFAs incorporated into complex lipids remains elusive. Here, we developed a targeted odd-chain fatty acyl-containing lipidomics method based on equivalent carbon number and retention time prediction. The method displayed good reproducibility and robustness as shown by peak width at half height within 0.7 min and coefficient of variation under 20%. A total number of 776 lipid species with odd-chain fatty acyl residues could be detected in the ESI mode of reverse-phase LC-MS, of which 309 lipids were further validated using multiple reaction monitoring transitions. Using this method, we quantified odd-chain fatty acyl-containing lipidome in tissues from 12 colon cancer patients, revealing the remodeling of triacylglycerol. The dynamics of odd-chain fatty acyl lipids were further consolidated by the association with genomic and proteomic features of altered catabolism of branched-chain amino acids and triacylglycerol endogenous synthesis in colon cancer. This lipidomics approach will be applicable for screening of dysregulated odd-chain fatty acyl lipids, which enriches and improves the methods for diagnosis and prognosis evaluation of cancer using lipidomics.

Abstract Human activities such as urbanization often has negative affects wildlife. However, urbanization can also be beneficial to some animals by providing suitable microhabitats. To test the impact of urbanization on cold-blooded animals, we first conducted a snake survey at a national nature reserve (Xianghai natural reserve) and an adjacent tourist bird park (Red-crowned Crane Park). We show high presence of Elaphe dione in the tourist park even with high human activities and predator population (the endangered, red-crowned crane, Grus japonensis). We then radio-tracked 20 individuals of E. dione, set seven camera traps, and recorded the temperature of the snakes and artificial structures in Crane Park to document their space use, activity, and thermal preference, respectively. Our results show E. dione preferred to use artificial facilities to shelter from their predators and for thermoregulation. The high number of rats from the camera traps indicate abundant prey items. Overall, E. dione appears to be adapted to modified habitats and may expand population size at the current study site.

Street trees extraction and further acquisition of their property information is one of the current research hotspots, which can be applied in various urban management. For the processing task of automated identification of tree points from large-scale point clouds in urban road scenes, we propose an improved RandLA-Net network that takes into account both extraction accuracy and complexity. The method can eliminate the problem of insufficient feature extraction and more redundancy within the RandLA-Net model, and achieve efficient recognition of the street trees. As an application of street tree recognition results, we studied the accurate calculation method of street tree shading area and designed a density-based iterative $\alpha $ -shape algorithm. The method effectively solves the problems of large density differences among different point sets and overestimation of shading area caused by the existing convex hull algorithms’ unrefined contour reconstruction, and improves the calculation accuracy of the canopy shading area. Experiments on the Paris-Lille-3D dataset show that the improved RandLA-Net network improves the IoU of three classes by 3.19%~6.46% and reduces the model complexity by 1.4% compared to the original model. The density-based iterative $\alpha $ -shape algorithm achieves more refined contour reconstruction and solves the overestimation of shading area by 26% and 9% due to the other two convex hull algorithms. Its ability to effectively calculate accurate shading area was confirmed.

Abstract Comprehensive research on rural–urban disparities in the association of hyperuricaemia (HUA) with cardiovascular disease (CVD) in China, especially among minority groups, is limited. We explored the HUA-CVD relationship between rural and urban areas within ethnic Chinese groups. We included Dong, Miao, and Bouyei adults in Southwest China from the China Multi-Ethnic Cohort Study. Multivariable logistic regression models were used to assess the relationship between HUA and CVD in both residences. We performed stratified analyses by sex and age. The study population included 16,618 people (37.48% Dong, 30.00% Miao, and 32.52% Bouyei) without a reduced estimated glomerular filtration rate. We identified 476 (188 Dong, 119 Miao, and 169 Bouyei) and 175 (62 Dong, 77 Miao, and 36 Bouyei) CVD cases in rural and urban areas. Compared to urban residents, an at least 49% increased CVD risk (adjusted OR 1.49, 95%CI 1.06–2.08 for the Dong ethnic group; 1.55, 1.07–2.25 for the Bouyei ethnic group) and a 1.65-fold elevated coronary heart disease risk (1.65, 1.03–2.64) related to HUA was present in rural residents. Moreover, HUA was positively associated with increased risk of CVD and coronary heart disease in rural women (2.05, 1.26–3.31; 2.11, 1.19–3.75) and rural older adults (1.83, 1.22–2.75; 2.32, 1.39–3.87) among the Bouyei ethnic group, respectively. We found rural elderly individuals with HUA among the Dong ethnic group had a 52% elevated risk of CVD (1.52, 1.05–2.21); furthermore, an at least 79% increased risk of stroke related to HUA was observed in women (2.24, 1.09–4.62) and elderly people (1.79, 1.02–3.13) in rural areas among the Dong ethnic group. But a positive association was not found among the Miao ethnic group. Screening early-onset HUA patients may be helpful for the control and prevention of CVD in rural residents, especially for women and older adults living in a rural community, among the Dong and Bouyei ethnic groups in China.

Abstract Background Bungarus multicinctus, from which a classical Chinese medicine is produced, is known as the most venomous land snake in the world, but the chromatin organization and transcription factor activity during venom replenishment progress have not been explored yet. This study aimed to determine the roles of chromatin structure in toxin activity via bioinformatics and experimental validation. Methods Chromosome conformation capture (Hi-C) analysis was used to examine interactions among chromosomes and identify different scales of chromatin during envenomation in B. multicinctus. Correlations between epigenetic modifications and chromatin structure were verified through ChIP-seq analysis. RNA-seq was used to validate the influence of variation in chromatin structure and gene expression levels on venom production and regulation. Results Our results suggested that intra-chromosomal interactions are more intense than inter-chromosomal interactions among the control group, 3-day group of venom glands and muscles. Through this, we found that compartmental transition was correlated with chromatin interactions. Interestingly, the up-regulated genes in more compartmental switch regions reflect the function of toxin activity. Topologically associated domain (TAD) boundaries enriched with histone modifications are associated with different distributions of genes and the expression levels. Toxin-coding genes in the same loop are highly expressed, implying that the importance of epigenetic regulation during envenomination. On a smaller scale, the epigenetic markers affect transcriptional regulation by controlling the recruitment/inhibition of transcription initiation complexes. Conclusions Chromatin structure and epigenetic modifications could play a vital status role in the mechanisms of venom regulation in B. multicinctus.

Inherited autosomal dominant gain-of-function (GOF) mutations of signal transducer and activator of transcription 1 (STAT1) cause a wide range of symptoms affecting multiple systems, including chronic mucocutaneous candidiasis (CMC), infections, and autoimmune disorders. We describe a rare case of STAT1 mutation with recurrent CMC, lung infections, and anemia. According to the whole-exome sequencing (WES), the patient was genetically mutated in STAT1 GOF (c.854A>G, p.Q285R), and bone marrow biopsy suggested pure red cell aplasia (PRCA). As a functional verification, STAT1 levels and phosphorylation (p-STAT1) of peripheral blood mononuclear cells (PBMCs) following IFN-γ stimulation in STAT1 GOF patient was higher than in the healthy control. Combination therapy of blood transfusion, antimicrobials, intravenous immunoglobulin, methylprednisolone, and the Janus Kinase (JAK) specific inhibitor ruxolitinib was used during treatment of patients. The patient also received a hematopoietic stem cell transplant (HSCT) to help with infections and anemia. This is the first reported case of STAT1 GOF disease complicated with PRCA. This complication might be attributed to immune disorders caused by STAT1 GOF. Furthermore, ruxolitinib may be a viable therapeutic option before HSCT to improve disease management.

Background: Podocyte injury contributes to progressive glomerulosclerosis. Previously, we demonstrated the important role of the NLR family pyrin domain containing 3 (NLRP3) inflammasome in mediating the podocyte injury induced by aldosterone. Silent mating type information regulation 2 homolog 1 (SIRT1) is an NAD+-dependent deacetylase that is associated with the regulation of cellular inflammation. However, whether the activation of the NLRP3 inflammasome in podocytes is regulated by SIRT1, and the mechanism involved, remains unknown. Methods: In this study, we detected SIRT1 expression in patients with podocyte disease and performed an aldosterone infusion model in podocyte-specific Sirt1 knockout mice. In cultured podocytes, we used plasmids to overexpress SIRT1 and treated the podocyte with aldosterone. Results: SIRT1 was significantly decreased in the glomeruli of patients with podocyte disease. Sirt1-deficient mice showed significant urinary albumin excretion after aldosterone infusion, and the severity of the glomerular injury was significantly greater in podocyte-specific Sirt1 knockout mice than in the wild-type mice. Moreover, podocyte conditional Sirt1 knockout aggravated NLRP3 inflammasome activation and mitochondrial dysfunction (MtD). In vitro, overexpression of SIRT1 inhibited NLRP3 activation, protected against MtD and podocyte injury. Conclusion: Taken together, these findings revealed a novel regulatory mechanism of the NLRP3 inflammasome by SIRT1 by promoting mitochondrial function, which provides some potential targets for the treatment of glomerular diseases.

Mobile videos contain a large amount of data, where the information interesting to the user can either be discrete or distributed. This paper introduces a method for fusing 3D geographic information systems (GIS) and video image textures. For the dynamic fusion of video in 3DGIS where the position and pose angle of the filming device change moment by moment, it integrates GIS 3D visualization, pose resolution and motion interpolation, and proposes a projection texture mapping method for constructing a dynamic depth camera to achieve dynamic fusion. In this paper, the accuracy and time efficiency of different systems of gradient descent and complementary filtering algorithms are analyzed mainly by quantitative analysis method, and the effect of dynamic fusion is analyzed by the playback delay and rendering frame rate of video on 3DGIS as indicators. The experimental results show that the gradient descent method under the Aerial Attitude Reference System (AHRS) is more suitable for the solution of smartphone attitude, and can control the root mean square error of attitude solution within 2°; the delay of video playback on 3DGIS is within 29 ms, and the rendering frame rate is 34.9 fps, which meets the requirements of the minimum resolution of human eyes.

According to the WORLD Disabled Persons federation (WPF), there are a large number of disabled people in the world, accounting for over 400 million in the Asia-Pacific region alone. This paper discusses the application of the Internet of Things technology in the rehabilitation of special populations, aiming at achieving high allocation of resources without changing personnel allocation, realizing innovation to improve economic benefits without changing personnel allocation, and rationally optimizing resource allocation to achieve maximum. Firstly, we give an overview of the Internet of Things technology and its application, and introduce the sensor, RFID, embedded system and other technologies. Then, we discuss the application of Internet of Things technology in the rehabilitation of disabled people, from the rehabilitation needs of disabled people and the application of Internet of Things technology in the field of rehabilitation. Then, from the statistical analysis of the application of Internet of Things technology in the rehabilitation field in the past 10 years, we obtained the shortcomings of the application of Internet of Things technology in the rehabilitation field and some space for further exploration. Finally, we believe that the application of Internet of Things technology to the rehabilitation management of persons with disabilities will be a breakthrough in the rehabilitation management of persons with disabilities, and have important reference value for the rehabilitation management of persons with disabilities worldwide. We also hope that understanding, respecting, caring and helping people with disabilities will increasingly become a global consensus and action.

ObjectivePrimary hypomagnesemia with secondary hypocalcemia (HSH) is caused by loss-of-function mutations in the TRPM6 gene encoding the epithelial magnesium channel. It is characterized by hypomagnesemia and secondary hypocalcemia associated with neurological symptoms. Here, we aimed to investigate the genetic defects of the TRPM6 gene found in a girl from China.MethodsThe genomic DNA of the proband and the parents was extracted for whole-exome sequencing. Sanger sequencing was further performed to validate the candidate variants. Subsequently, the TRPM6 gene deletion was verified by quantitative PCR (qPCR) experiment. The effect of the variant on mRNA splicing was analyzed through a minigene splice assay and reverse transcription PCR (RT-PCR) in vitro.ResultsThe proband presented with the symptoms of generalized seizures, tetany, and muscle spasms, which were refractory to anticonvulsant treatment. Phenotypic data indicated that the patient had hypomagnesemia, poor parathyroid hormone response, and resultant hypocalcemia. The trio whole-exome sequencing identified that the proband carried compound heterozygous variants in the TRPM6 gene, a paternally derived exon 6 deletion, and a maternally derived splicing variant (c.1638+7T>C) in exon 14. The minigene splice assay confirmed that the c.1638+7T>C variant resulted in exon 14 skipping, which caused the alteration of TRPM6 mRNA splicing.ConclusionOur results support that the compound heterozygous variants in TRPM6 are responsible for HSH in this patient. A novel pathogenic splicing variant (c.1638+7T>C) in the intron 14 disturbs the normal TRPM6 mRNA splicing, suggesting that the non-classical splice variant plays a critical role in HSH. This variant is essential for future effective genetic diagnosis.

Abstract Background Ovarian cancer is the most lethal gynecologic cancer. Chemoresistance, especially platinum-resistance, is closely related to metastasis of ovarian cancer, however, the molecular basis by which links chemoresistance and metastasis remains vague. Disordered arachidonic acid (AA) metabolism has been shown to play an important role in the advanced ovarian cancer. This study aimed to explore the underlying mechanism involving eicosanoid metabolism that controlling chemoresistance and metastasis of ovarian cancer. Methods Cisplatin (DDP)-resistant SKOV3 (SKOV3-R) cells were constantly induced. Ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was performed to determine the AA metabolism in SKOV3 and SKOV3-R cells. Half maximal inhibitory concentration (IC50) and percentage of cell viability were tested using cell counting kit 8 (CCK-8). Realtime quantitative PCR (qPCR) and immunohistochemistry (IHC) were used to evaluate indicated genes and proteins respectively. Bioinformatic analysis and chromatin immunoprecipitation (ChIP) were performed to predict and identify the co-transcription factor of interest genes. Tumor growth and metastasis in the liver were assessed with nude mice by subcutaneously injection of SKOV3-R cells. Results SKOV3-R cells expressed higher multidrug resistance-associated proteins (MRPs) MRP1 and MRP4. They showed enhanced metastatic ability and produced increased AA-derived eicosanoids. Mechanistically, MRPs, epithelial mesenchymal transition (EMT) markers Snail and Slug, as well as key enzymes involved in AA-metabolism including 12-lipoxygenase (12LOX) were transcribed by the mutual transcription factor SP1 which was consistently upregulated in SKOV3-R cells. Inhibition of SP1 or 12LOX sensitized SKOV3-R cells to DDP and impaired metastasis in vitro and in vivo. Conclusion Our results reveal that SP1-12LOX axis signaling plays a key role in DDP-resistance and metastasis, which provide a new therapeutic target for ovarian cancer.

Background and Purpose: Breast cancer survivors have an increased cardiovascular risk, and vascular calcification is the pathological basis of cardiovascular disease. Some factors that affect the progression of thoracic aortic calcification (TAC) in survivors are unclear, and this study aims to explore the relationship between dexamethasone or radiotherapy and the progression of TAC in survivors.Materials and Methods: This study included 189 female patients with breast cancer, and they were divided into the progression and non-progression TAC groups. Radiation or dexamethasone doses, and related laboratory parameters were collected.Results: The cumulative dose of dexamethasone was higher [40 (10–180) mg versus 180 (80–270) mg, p < 0.001], and the cycle was longer [4 (1–6) cycles versus 6 (4–8) cycles, p < 0.001] in the non-progression TAC group. The cumulative dose (r = −0.303, p < 0.001) and cycle (r = −0.357, p < 0.001) of dexamethasone were negatively correlated with the level of increased TAC Agatston scores in survivors. Logistic regression analysis showed that dexamethasone was a protective factor for the progression of TAC (p = 0.029, odds ratio = 0.263, 95% confidence interval = 0.08–0.872). However, there wasn’t significant relationship between radiotherapy, radiation dose, follow-up time and the progression of TAC (all p > 0.05). In addition, aorta volume was positively correlated with the level of increased TAC Agatston scores in intensity modulated radiation therapy (r = 0.460, p < 0.001).Conclusion: Dexamethasone is associated with a lower risk of the progression of TAC in breast cancer survivors, and there’s no correlation between radiotherapy and progression of TAC, but the aorta volume may be a predictor of the severity of progression of TAC.

Pulse Train (PT) control is a nonlinear voltage regulation method with favorable characteristics of quick response time and simple structure. In this paper, a PT-based feedback control strategy is proposed for stabilizing the output voltage of two-stage wireless power transfer (WPT) systems. Low-frequency voltage oscillations can be observed in PT controlled front-stage power converters, which significantly degrades the output power quality of the WPT system. To solve this problem, by using feedback variables sampled from both output sides of a power converter and WPT, a capacitor current and output voltage feedback PT (CC&OV-PT) controlled two-stage WPT system is further devised in this paper. A discrete time model of the two-stage WPT system is established, and the performance of low-frequency voltage oscillations suppression for the double-side feedback CC&OV-PT controlled WPT system is analyzed. Simulation and experimental verification have been conducted, both of which show that the CC&OV-PT controlled WPT system achieves fast response with effective low-frequency oscillation suppression.

INTRODUCTION: Lip language is one of the most important communication methods in social life for people with hearing impairment and impaired expression ability. This communication method relies on visual recognition to understand the meaning expressed in communication. OBJECTIVES: In order to improve the accuracy of this natural language recognition, we propose six-layer optimized convolutional neural network for lip recognition. METHODS: The calculation method of the convolutional layer in the CNN model is used, and two pooling methods are compared: the maximum pooling operation and the average pooling operation to analyse the most important feature data in the picture. In order to reduce the simulation in the model training process, the closing rate has been optimized by introducing Dropout technology. RESULTS: It shows that the recognition accuracy rate based on the six-layer convolutional neural network can reach 85.74% on average. This method can effectively recognize lip language. CONCLUSION: We propose a six-layer optimized convolutional neural network method for lip language recognition, and the identification of lip language features of this method is better than 3D+ DenseNet +1 × 1 Conv +resBi-LSTM, 3D+CNN, ConvNet+2 -256-LSTM+VGG-16 three advanced methods.

INTRODUCTION: "Inverse light" is the experience of visually impaired people an immersive gaming experience, reducing the blind of the difficulties in life and study, etc., to bring players to experience the real life scene, the hearing, sight, touch, fully integrated into the game, let the players from the Angle of view of the blind, rational view of the nowadays social existence of accessibility issues, It also analyses several important issues, such as fun, playability, education in games, etc. This paper will elaborate the connotation of educational games and gamified learning, the source of creativity, and the design and implementation of games. OBJECTIVES: In order to raise the public's attention to the visually impaired people and strengthen quality education, mobile games are combined with the inconveniences that the visually impaired people encounter in life to arouse the players' thinking and call on people to be more patient and helpful to the visually impaired. METHODS: This game is mainly based on the black screen effect. In the case of limited vision, the direction is judged by clicking, holding down, sliding and other keys as well as the background sound effect, so as to bypass the obstacles. Finally, through the level, the background and animation in the game are designed with Photoshop, and the modeling is completed with 3DMAX. Microsoft Visual Studio was used to write C# scripts, and Unity was used for scene construction and overall coordination. RESULTS: The experiment proves that the game can analyse the current situation of quality education very well and combine quality education with games. The system framework of the game has clear logic, moderate operation difficulty, and appropriate sounds are used to simulate visually impaired people, which increases the immersive sense of the game. At the same time, the problem of boring game and easy loss of players is solved, and the win-win effect of education and playability of the game is realized. CONCLUSION: " Inverse light " game from the design ideas, game development framework, difficulty and other aspects of the analysis, has a very good reflection, and the game interface design is exquisite, has a certain level of art, can meetthe experience of visually impaired people's feelings of the original intention of game development.

Herbgenomics is an emerging field of traditional Chinese medicine (TCM) research and development. By combining TCM research with genomics, herbgenomics can help to establish the scientific validity of TCM and bring it into wider usage within the field of medicine. Salvia Linn. (S. Linn.) is a large genus of Labiatae that includes important medicinal plants. In this herbgenomics study, the complete chloroplast (cp) genomes of two Salvia spp.—namely, S. przewalskii and S. bulleyana, which are used as a surrogate for S. miltiorrhiza—were sequenced and compared with those of two other reported Salvia spp.—namely, S. miltiorrhiza and S. japonica. The genome organization, gene number, type, and repeat sequences were compared. The annotation results showed that both Salvia plants contain 114 unique genes, including 80 protein-coding, 30 transfer RNA (tRNA), and four ribosomal RNA (rRNA) genes. Repeat sequence analysis revealed 21 forward and 22 palindromic sequences in both Salvia cp genomes, and 17 and 21 tandem repeats in S. przewalskii and S. bulleyana, respectively. A synteny comparison of the Salvia spp. cp genomes showed a high degree of sequence similarity in the coding regions and a relatively high divergence of the intergenic spacers. Pairwise alignment and single-nucleotide polymorphism (SNP) analyses found some candidate fragments to identify Salvia spp., such as the intergenic region of the trnV–ndhC, trnQ–rps16, atpI–atpH, psbA–ycf3, ycf1, rpoC2, ndhF, matK, rpoB, rpoA, and accD genes. All of the results—including the repeat sequences and SNP sites, the inverted repeat (IR) region border, and the phylogenetic analysis—showed that S. przewalskii and S. bulleyana are extremely similar from a genetic standpoint. The cp genome sequences of the two Salvia spp. reported here will pave the way for breeding, species identification, phylogenetic evolution, and cp genetic engineering studies of Salvia medicinal plants. Keywords: Salvia, Chloroplast genome, Comparative analysis

Background: To contain the pandemic of COVID-19, China has implemented a series of public health interventions that impacted the tuberculosis control substantially, but these impacts may vary greatly depending on the severity of the local COVID-19 epidemic. The impact of COVID-19 on TB control in Ningxia Hui Autonomous Region is little known.Methods: Based on the national TB Information Management System (TBIMS), this study accessed the actual impact of COVID-19 on TB by comparing TB notifications, pre-treatment delays, and clinical characteristics of TB cases between 2020 COVID-19 period and 2017–2019 baseline. The data were divided into three periods based on the response started to fight against COVID-19 in Ningxia Hui Autonomous Region, including the control period (10 weeks before the pandemic), intensive period (10 weeks during the Ningxia Hui Autonomous Region lockdown), and regular (10 additional weeks after Ningxia Hui Autonomous Region reopen).Results: TB notification dropped sharply in the first week of the intensive period but took significantly longer to return to the previous level in 2020 compared with the 2017–2019 baseline. Totally, the TB notification rates decreased by more than 60% in the intensive period of COVID-19 compared with the average level of 2017–2019. The sputum smear-positive rate of TB patients diagnosed in intensive period of COVID-19 was significantly higher than that in the corresponding periods of 2017–2019 (P < 0.001). The rate of cavity on X-ray inspection of TB cases diagnosed in the intensive period of COVID-19 was significantly higher than that in period 2 of 2017–2019 (23.5 vs. 15.4%, P = 0.004). The patients' delay in the intensive period was significantly longer than that before the pandemic (P = 0.047).Conclusions: The TB notification in Ningxia was impacted dramatically by the pandemic of COVID-19. To compensate for the large numbers of missed diagnosis as well as delayed diagnosis during the intensive period of COVID-19, an urgent restoration of normal TB services, and further emphasis on enhanced active case finding and scale-up of household contact tracing and screening for TB-related symptoms or manifestation, will be essential.

FFAs display pleiotropic functions in human diseases. Short-chain FAs (SCFAs), medium-chain FAs, and long-chain FAs are derived from different origins, and precise quantification of these FFAs is critical for revealing their roles in biological processes. However, accessing stable isotope-labeled internal standards is difficult, and different chain lengths of FFAs challenge the chromatographic coverage. Here, we developed a metabolomics strategy to analyze FFAs based on isotope-free LC-MS-multiple reaction monitoring integrated with dual derivatization. Samples and dual derivatization internal standards were synthesized using 2-dimethylaminoethylamine or dansyl hydrazine as a “light” label and N,N-diethyl ethylene diamine or N,N-diethyldansulfonyl hydrazide as a “heavy” label under mild and efficient reaction conditions. General multiple reaction monitoring parameters were designed to analyze these FFAs. The limit of detection of SCFAs varied from 0.5 to 3 nM. Furthermore, we show that this approach exhibits good linearity (R2 = 0.99374–0.99929), there is no serious substrate interference, and no quench steps are required, confirming the feasibility and reliability of the method. Using this method, we successfully quantified 15 types of SCFAs in fecal samples from hepatocellular carcinoma patients and healthy individuals; among these, propionate, butyrate, isobutyrate, and 2-methylbutyrate were significantly decreased in the hepatocellular carcinoma group compared with the healthy control group. These results indicate that the integrated LC-MS metabolomics with isotope-free and dual derivatization is an efficient approach for quantifying FFAs, which may be useful for identifying lipid biomarkers of cancer.

Background/Aims: This study aimed to explore the metabololipidome in mice upon cupping treatment. Methods: A nude mouse model mimicking the cupping treatment in humans was established by administrating four cupping sets on the back skin for 15 minutes. UPLC-MS/ MS was performed to determine the PUFA metabolome in mice skin and blood before and after cupping treatment. The significantly changed lipids were administered in macrophages to assess the production of pro-inflammatory cytokines IL-6 and TNF-α by ELISA. Results: The anti-inflammatory lipids, e.g. PGE1, 5,6-EET, 14,15-EET, 10S,17S-DiHDoHE, 17R-RvD1, RvD5 and 14S-HDoHE were significantly increased while pro-inflammatory lipids, e.g. 12-HETE and TXB2 were deceased in the skin or plasma post cupping treatment. Cupping treatment reversed the LPS-stimulated IL-6 and TNF-α expression in mouse peritoneal exudates. Moreover, 5,6-EET, PGE1 decreased the level of TNF-α, while 5,6-EET, 5,6-DHET downregulated IL-6 production in macrophages. Importantly, 14,15-EET and 14S-HDoHE inhibited both IL-6 and TNF-α induced by lipopolysaccharide (LPS). 17-RvD1, RvD5 and PGE1 significantly reduced the LPS-initiated TNF-α, while TXB2 and 12-HETE further upregulated the LPS-enhanced IL-6 and TNF-α expression in macrophages. Conclusion: Our results reveal the identities of anti-inflammatory versus pro-inflammatory metabolipidome and suggest the potential therapeutic mechanism of cupping treatment.

Abstract Background The development of male- or female-specific phenotypes in squamates is typically controlled by either temperature-dependent sex determination (TSD) or chromosome-based genetic sex determination (GSD). However, while sex determination is a major switch in individual phenotypic development, it is unknownhow evolutionary transitions between GSD and TSD might impact on the evolution of squamate phenotypes, particularly the fast-evolving and diverse genitalia. Here, we take the unique opportunity of studying the impact of both sex determination mechanisms on the embryological development of the central bearded dragon (Pogona vitticeps). This is possible because of the transitional sex determination system of this species, in which genetically male individuals reverse sex at high incubation temperatures. This can trigger the evolutionary transition of GSD to TSD in a single generation, making P. vitticeps an ideal model organism for comparing the effects of both sex determination processes in the same species. Results We conducted four incubation experiments on 265 P. vitticeps eggs, covering two temperature regimes (“normal” at 28 °C and “sex reversing” at 36 °C) and the two maternal sexual genotypes (concordant ZW females or sex-reversed ZZ females). From this, we provide the first detailed staging system for the species, with a focus on genital and limb development. This was augmented by a new sex chromosome identification methodology for P. vitticeps that is non-destructive to the embryo. We found a strong correlation between embryo age and embryo stage. Aside from faster growth in 36 °C treatments, body and external genital development was entirely unperturbed by temperature, sex reversal or maternal sexual genotype. Unexpectedly, all females developed hemipenes (the genital phenotype of adult male P. vitticeps), which regress close to hatching. Conclusions The tight correlation between embryo age and embryo stage allows the precise targeting of specific developmental periods in the emerging field of molecular research on P. vitticeps. The stability of genital development in all treatments suggests that the two sex-determining mechanisms have little impact on genital evolution, despite their known role in triggering genital development. Hemipenis retention in developing female P. vitticeps, together with frequent occurrences of hemipenis-like structures during development in other squamate species, raises the possibility of a bias towards hemipenis formation in the ancestral developmental programme for squamate genitalia.

A compact and wideband directional circularly polarized (CP) antenna is presented in this paper. The antenna adopts four distributed micropatches as the radiation structure to realize directional radiation and wideband potential, and a low-loss sequentially rotated feeding network is utilized to provide CP excitation. Because of the good impedance matching between the proposed radiation structure and the feeding network, the antenna obtains wide bandwidths in both impedance and axial ratio (AR), and high efficiency is also achieved in the wide band. A prototype of the antenna is fabricated to validate the proposed method. The antenna's dimensions are 0.418λ0 × 0.418λ0 × 0.064λ0 (λ0 is the free-space wavelength at the center frequency of operating band). The impedance bandwidth for VSWR ≤ 2 reaches 42.9% (1.457 ~ 2.253 GHz), and the CP bandwidth for AR ≤ 3 dB reaches 22.8% (1.67 ~ 2.10 GHz). In the overlapped band, the radiation efficiency is more than 96.5%, and the gains are greater than 4.8 dBic.

Excessive sea turtle nest predation is a problem for conservation management of sea turtle populations. This study assessed predation on nests of the endangered loggerhead sea turtle (Caretta caretta) at Wreck Rock beach adjacent to Deepwater National Park in Southeast Queensland, Australia after a control program for feral foxes was instigated. The presence of predators on the nesting dune was evaluated by tracking plots (2 × 1 m) every 100 m along the dune front. There were 21 (2014–2015) and 41 (2015–2016) plots established along the dune, and these were monitored for predator tracks daily over three consecutive months in both nesting seasons. Predator activities at nests were also recorded by the presence of tracks on top of nests until hatchlings emerged. In addition, camera traps were set to record the predator activity around selected nests. The tracks of the fox (Vulpes vulpes) and goanna (Varanus spp) were found on tracking plots. Tracking plots, nest tracks and camera traps indicated goanna abundance varied strongly between years. Goannas were widely distributed along the beach and had a Passive Activity Index (PAI) (0.31 in 2014–2015 and 0.16 in 2015–2016) approximately seven times higher than that of foxes (PAI 0.04 in 2014–2015 and 0.02 in 2015–2016). Five hundred and twenty goanna nest visitation events were recorded by tracks but no fox tracks were found at turtle nests. Camera trap data indicated that yellow-spotted goannas (Varanus panoptes) appeared at loggerhead turtle nests more frequently than lace monitors (V. varius) did, and further that lace monitors only predated nests previously opened by yellow-spotted goannas. No foxes were recorded at nests with camera traps. This study suggests that large male yellow-spotted goannas are the major predator of sea turtle nests at the Wreck Rock beach nesting aggregation and that goanna activity varies between years.

Research on Chinese Sign Language (CSL) provides convenience and support for individuals with hearing impairments to communicate and integrate into society. This article reviews the relevant literature on Chinese Sign Language Recognition (CSLR) in the past 20 years. Hidden Markov Models (HMM), Support Vector Machines (SVM), and Dynamic Time Warping (DTW) were found to be the most commonly employed technologies among traditional identificationmethods. Benefiting from the rapid development of computer vision and artificial intelligence technology, Convolutional Neural Networks (CNN), 3D-CNN, YOLO, Capsule Network (CapsNet) and various deep neural networks have sprung up. Deep Neural Networks (DNNs) and their derived models are integral tomodern artificial intelligence recognitionmethods. In addition, technologies thatwerewidely used in the early days have also been integrated and applied to specific hybrid models and customized identification methods. Sign language data collection includes acquiring data from data gloves, data sensors (such as Kinect, LeapMotion, etc.), and high-definition photography.Meanwhile, facial expression recognition, complex background processing, and 3D sign language recognition have also attracted research interests among scholars. Due to the uniqueness and complexity of Chinese sign language, accuracy, robustness, real-time performance, and user independence are significant challenges for future sign language recognition research. Additionally, suitable datasets and evaluation criteria are also worth pursuing. [ABSTRACT FROM AUTHOR]

Object: The benefits of low-dose esketamine for painless gastrointestinal endoscopy remain unclear. As such, the present study aimed to investigate the efficacy and safety of low-dose esketamine for this procedure. Methods: Seven common databases were searched for clinical studies investigating low-dose esketamine for painless gastrointestinal endoscopy. Subsequently, a meta-analysis was performed to synthesize and analyze the data extracted from studies fulfilling the inclusion criteria. Results: Meta-analysis revealed that, compared with propofol, low-dose esketamine in combination with propofol significantly reduced recovery time by 0.56 min (mean difference [MD] -0.56%, 95% confidence interval (CI) -1.08 to -0.05, p = 0.03), induction time by 9.84 s (MD -9.84, 95% CI -12.93 to -6.75, p < 0.00001), propofol dosage by 51.05 mg (MD -51.05, 95% CI -81.53 to -20.57, p = 0.01), and increased mean arterial pressure by 6.23 mmHg (MD 6.23, 95% CI 1.37 to 11.08, p = 0.01). Meanwhile, low-dose esketamine reduced injection pain by 63% (relative risk [RR] 0.37, 95% CI 0.28 to 0.49, p < 0.00001), involuntary movements by 40% (RR 0.60, 95% Cl 0.42 to 0.85, p < 0.005), choking by 42% (RR 0.58, 95% Cl 0.38 to 0.88, p = 0.01), bradycardia by 68% (RR 0.32, 95% Cl 0.18 to 0.58, p = 0.0002), hypotension by 71% (RR 0.29, 95% Cl 0.21 to 0.40, p < 0.00001), respiratory depression by 63% (RR 0.37, 95% 0.26 to 0.51, p < 0.00001), additional cases of propofol by 53% (RR 0.47, 95% Cl 0.29 to 0.77, p = 0.002), and increased hypertension by 1000% (RR 11.00, 95% Cl 1.45 to 83.28, p = 0.02). Therewere no significant differences in mean heart rate, mean oximetry saturation, delirium, dizziness, vomiting, tachycardia, and hypoxemia. Subgroup analyses revealed that, compared with other dose groups, 0.25 mg/kg esketamine afforded additional benefits in recovery and induction time, mean arterial pressure, involuntary movements, hypoxemia, identified as the optimal dose within the dosage ranges examined. However, caution should be exercised when administering this drug to patients with inadequate preoperative blood pressure control. and respiratory depression. Conclusion: Low-dose esketamine was found to be safe and effective for providing anesthesia during gastrointestinal endoscopy, with 0.25 mg/kg identified as the optimal dose within the dosage ranges examined. However, caution should be exercised when administering this drug to patients with inadequate preoperative blood pressure control. [ABSTRACT FROM AUTHOR]