STK25: a viable therapeutic target for cancer treatments?

Serine/threonine protein kinase 25 (STK25) is a critical regulator of ectopic lipid storage, glucose and insulin homeostasis, fibrosis, and meta-inflammation. More and more studies have revealed a strong correlation between STK25 and human diseases. On the one hand, STK25 can affect glucose and fatty acid metabolism in normal cells or tumors. On the other hand, STK25 participates in autophagy, cell polarity, cell apoptosis, and cell migration by activating various signaling pathways. This article reviews the composition and function of STK25, the energy metabolism and potential drugs that may target STK25, and the research progress of STK25 in the occurrence and development of tumors, to provide a reference for the clinical treatment of tumors.

Protective Immunity against Chlamydia psittaci Lung Infection Induced by a DNA Plasmid Vaccine Carrying CPSIT_p7 Gene Inhibits Dissemination in BALB/c Mice.

Chlamydia psittaci (C. psittaci), a zoonotic pathogen, poses a potential threat to public health security and the development of animal husbandry. Vaccine-based preventative measures for infectious diseases have a promising landscape. DNA vaccines, with many advantages, have become one of the dominant candidate strategies in preventing and controlling the chlamydial infection. Our previous study showed that CPSIT_p7 protein is an effective candidate for a vaccine against C. psittaci. Thus, this study evaluated the protective immunity of pcDNA3.1(+)/CPSIT_p7 against C. psittaci infection in BALB/c mice. We found that pcDNA3.1(+)/CPSIT_p7 can induce strong humoral and cellular immune responses. The IFN-γ and IL-6 levels in the infected lungs of mice immunized with pcDNA3.1(+)/CPSIT_p7 reduced substantially. In addition, the pcDNA3.1(+)/CPSIT_p7 vaccine diminished pulmonary pathological lesions and reduced the C. psittaci load in the lungs of infected mice. It is worth noting that pcDNA3.1(+)/CPSIT_p7 suppressed C. psittaci dissemination in BALB/c mice. In a word, these results demonstrate that the pcDNA3.1(+)/CPSIT_p7 DNA vaccine has good immunogenicity and immunity protection effectiveness against C. psittaci infection in BALB/c mice, especially pulmonary infection, and provides essential practical experience and insights for the development of a DNA vaccine against chlamydial infection.

Microtubule affinity regulating kinase 4: A promising target in the pathogenesis of atherosclerosis.

Microtubule affinity regulating kinase 4 (MARK4), an important member of the serine/threonine kinase family, regulates the phosphorylation of microtubule-associated proteins and thus modulates microtubule dynamics. In human atherosclerotic lesions, the expression of MARK4 is significantly increased. Recently, accumulating evidence suggests that MARK4 exerts a proatherogenic effect via regulation of lipid metabolism (cholesterol, fatty acid, and triglyceride), inflammation, cell cycle progression and proliferation, insulin signaling, and glucose homeostasis, white adipocyte browning, and oxidative stress. In this review, we summarize the latest findings regarding the role of MARK4 in the pathogenesis of atherosclerosis to provide a rationale for future investigation and therapeutic intervention.

Heavy metal(loid)s shape the soil bacterial community and functional genes of desert grassland in a gold mining area in the semi-arid region.

Gold mining can create serious environmental problems, such as soil pollution by heavy metal (loid)s. In this study, we assessed the ecological risk of Hatu gold mining activities and synchronously investigated the bacterial community structure, distribution of soil nutrient-element cycling genes (CNPS) and heavy metal resistance genes (MRG) in adjacent desert grassland soil. The study area was above the moderate risk level, with the ecological risk index (RI) of each sampling site greater than 150. Arsenic, mercury and copper were the main pollutants. Proteobacteria, Actinobacteria and Firmicutes dominated the phyla of the bacterial communities. Species turnover rather than nestedness accounted for the significant differences in community structure among various regions in the mining area. In addition, the bioavailable heavy metal (loid)s (AHM) content had a strong correlation with beta diversity and species turnover of the bacterial community (p < 0.05). No clear difference was found in the total abundance of CNPS genes among various functional regions, but eight specific functional genes were identified from downwind grasslands with lower pollution levels. Among the MRGs, Hg MRG had the highest average total relative abundance, followed by Cu, Co/Zn/Cd and As. The mercury resistance gene subtype hgcAB was positively related to the diversity of the bacterial community, and the bacterial community of grassland soil showed congruency with the MRGs in the Hatu mining area. Total Hg (THg) showed the highest influence affecting the bacterial community, while NH4+-N had the greatest effect on CNPS genes and MRGs. These results highlighted the role of heavy metal (loid)s in shaping the bacterial community and functional genes in arid and semiarid desert grassland soil in gold mining regions.

Metagenomic binning and assembled genome analysis revealed the distinct composition of resistome and mobilome in the Ili River.

Rivers play an important role in receiving and transporting the resistome among different environmental compartments. However, the difference in resistome and mobilome between the water and sediment and their underlying mechanisms were still poorly understood. In this study, the Ili River, an important water source in the arid area of Central Asia, was selected as the studied target. The comprehensive profile of resistome and mobilome and their host in water and sediment were studied based on metagenomic binning and assembled genome (MAG) analysis. The relative abundance of resistome and mobilome in sediment were 28.0 - 67.8 × /Gb and 46.5 - 121.1 × /Gb, respectively, which were significantly higher than those in water (23.1 - 52.8 ×/Gb and 25.3 - 67.7 ×/Gb). Multidrug and macrolides-lincosamides-streptogramin (MLS) resistance genes were the main ARG types in both water and sediment from relative abundance. Transposases dominated the relative abundance of mobilome, followed by insert elements and integrases. Strong correlations were found between the relative abundance of resistome and mobilome (r > 0.6 and p < 0.01) in both water and sediment, indicating the mobilome played an important role in the propagation of resistome in the Ili River. The main hosts for multidrug resistance genes via MAG analysis differed in water (Alphaproteobacteria and Gammaproteobacteria) and sediment (Gammaproteobacteria). Distinct compositions of resistome and mobilome existed between water and sediment in the Ili River. Specificity-occupancy analysis of the differential resistome and mobilome showed that occurrence frequencies and habitat selections of the differential ARGs shaped the resistome of water and sediment. In contrast, habitat was the main driver that shaped the mobilome in the Ili River.

Monocular Depth Estimation with Self-Supervised Learning for Vineyard Unmanned Agricultural Vehicle.

To find an economical solution to infer the depth of the surrounding environment of unmanned agricultural vehicles (UAV), a lightweight depth estimation model called MonoDA based on a convolutional neural network is proposed. A series of sequential frames from monocular videos are used to train the model. The model is composed of two subnetworks-the depth estimation subnetwork and the pose estimation subnetwork. The former is a modified version of U-Net that reduces the number of bridges, while the latter takes EfficientNet-B0 as its backbone network to extract the features of sequential frames and predict the pose transformation relations between the frames. The self-supervised strategy is adopted during the training, which means the depth information labels of frames are not needed. Instead, the adjacent frames in the image sequence and the reprojection relation of the pose are used to train the model. Subnetworks' outputs (depth map and pose relation) are used to reconstruct the input frame, then a self-supervised loss between the reconstructed input and the original input is calculated. Finally, the loss is employed to update the parameters of the two subnetworks through the backward pass. Several experiments are conducted to evaluate the model's performance, and the results show that MonoDA has competitive accuracy over the KITTI raw dataset as well as our vineyard dataset. Besides, our method also possessed the advantage of non-sensitivity to color. On the computing platform of our UAV's environment perceptual system NVIDIA JETSON TX2, the model could run at 18.92 FPS. To sum up, our approach provides an economical solution for depth estimation by using monocular cameras, which achieves a good trade-off between accuracy and speed and can be used as a novel auxiliary depth detection paradigm for UAVs.

Evaluation of a tandem Chlamydia psittaci Pgp3 multiepitope peptide vaccine against a pulmonary chlamydial challenge in mice.

Chlamydia psittaci is the pathogen of psittacosis, and it has emerged as a significant public health threat. Because most infections are easily overlooked, a vaccine is recognized as the best solution to control the spread of C. psittaci. Our previous study showed that Pgp3 protein is efficacious as a subunit vaccine while not the best candidate due to the negative effects. Thus, in this study, we tested the ability of a tandem epitope vaccine candidate designated SP based on Pgp3-dominant epitopes to induce protective immunity against pulmonary chlamydial infection. BALB/c mice were intraperitoneally inoculated with multiepitope peptide antigens followed by intranasal infection with C. psittaci. We found that the multiepitope peptide antigens induced strong humoral and cellular immune responses with high Th1-related (IFN-γ and IL-2) and proinflammatory (IL-6) cytokine levels. Meanwhile, the pathogen burden and inflammatory infiltration were significantly reduced in lungs of SP-immunized mice after chlamydial challenge. In addition, the IFN-γ and IL-6 secretion levels in the infected lungs were substantially reduced. Overall, our findings demonstrate that the peptide vaccine SP plays a significant role with good immunogenicity and protective efficacy against C. psittaci lung infection in BALB/c mice, providing important insights towards understanding the potential of peptide vaccines as new vaccine antigens for inducing protective immunity against chlamydial infection.

Apelin-13 inhibits lipoprotein lipase expression via the APJ/PKCα/miR-361-5p signaling pathway in THP-1 macrophage-derived foam cells.

Atherosclerotic lesions are characterized by the accumulation of abundant lipids and chronic inflammation. Previous researches have indicated that macrophage-derived lipoprotein lipase (LPL) promotes atherosclerosis progression by accelerating lipid accumulation and pro-inflammatory cytokine secretion. Although apelin-13 has been regarded as an atheroprotective factor, it remains unclear whether it can regulate the expression of LPL. The aim of this study was to explore the effects of apelin-13 on the expression of LPL and the underlying mechanism in THP-1 macrophage-derived foam cells. Apelin-13 significantly decreased cellular levels of total cholesterol, free cholesterol, and cholesterol ester at the concentrations of 10 and 100 nM. ELISA analysis confirmed that treatment with apelin-13 reduced pro-inflammatory cytokine secretion, such as interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and tumor necrosis factor-alpha (TNF-α). It was also found that apelin-13 inhibited the expression of LPL as revealed by western blot and real-time PCR analyses. Bioinformatics analyses and dual-luciferase reporter assay indicated that miR-361-5p directly downregulated the expression of LPL by targeting the 3'UTR of LPL. In addition, apelin-13 + miR-361-5p mimic significantly downregulated the expression of LPL in cells. Finally, we demonstrated that apelin-13 downregulated the expression of LPL through activating the activity of PKCα. Taken together, our results showed that apelin-13 downregulated the expression of LPL via activating the APJ/PKCα/miR-361-5p signaling pathway in THP-1 macrophage-derived foam cells, leading to inhibition of lipid accumulation and pro-inflammatory cytokine secretion. Therefore, our studies provide important new insight into the inhibition of lipid accumulation and pro-inflammatory cytokine secretion by apelin-13, and highlight apelin-13 as a promising therapeutic target in atherosclerosis.

PSI showed higher tolerance to Sb(V) than PSII due to stimulation of cyclic electron flow around PSI.

The knowledge of the effects of Sb(V) on the physiological characteristics of cyanobacteria was still limited. In the present study, responses of photosystem I and II (PSI and PSII), cyclic electron flow (CEF), and interphotosystem electron transport of Microcystis aeruginosa to 5-100 mg/l Sb(V) were synchronously measured using the Dual-PAM-100. 5 mg/l Sb (V) significantly inhibited PSII activity, but had no significant effects on PSI activity. At higher concentrations of Sb(V), the quantum yield and electron transport of PSI were less affected compared to PSII. The ratio of Y(II)/Y(I) significantly decreased with increasing Sb(V) concentration. It decreased from 0.7 for control to 0.4 for 100 mg/l Sb(V)-treated cells, indicating that the change of the distribution of quantum yields between two photosystems and more serious inhibition of PSII under stress of Sb(V) compared to PSI. CEF was activated associated with the inhibition of linear electron flow after exposure to Sb(V). The contribution of Y(CEF) to the quantum yield and activity of PSI increased with increasing Sb(V) concentrations. The cyclic electron transport rate made a significant contribution to electron transport rate of PSI, especially at high Sb(V) concentration (100 mg/l) and high illumination (above 555 µmol photons/m(2)/s). The stimulation of CEF was essential for the higher tolerance of PSI than PSII to Sb(V).

Herbicidal effects of harmaline from Peganum harmala on photosynthesis of Chlorella pyrenoidosa: probed by chlorophyll fluorescence and thermoluminescence.

The herbicidal effects of harmaline extracted from Peganum harmala seed on cell growth and photosynthesis of green algae Chlorella pyrenoidosa were investigated using chlorophyll a fluorescence and thermoluminescence techniques. Exposure to harmaline inhibited cell growth, pigments contents and oxygen evolution of C. pyrenoidosa. Oxygen evolution was more sensitive to harmaline toxicity than cell growth or the whole photosystem II (PSII) activity, maybe it was the first target site of harmaline. The JIP-test parameters showed that harmaline inhibited the donor side of PSII. Harmaline decreased photochemical efficiency and electron transport flow of PSII but increased the energy dissipation. The charge recombination was also affected by harmaline. Amplitude of the fast phase decreased and the slow phase increased at the highest level of harmaline. Electron transfer from QA(-) to QB was inhibited and backward electron transport flow from QA(-) to oxygen evolution complex was enhanced at 10 µg mL(-1) harmaline. Exposure to 10 µg mL(-1) harmaline caused appearance of C band in thermoluminescence. Exposure to 5 µg mL(-1) harmaline inhibited the formation of proton gradient. The highest concentration of harmaline treatment inhibited S3QB(-) charge recombination but promoted formation of QA(-)YD(+) charge pairs. P. harmala harmaline may be a promising herbicide because of its inhibition of cell growth, pigments synthesis, oxygen evolution and PSII activities.

Progress in Research on CNPY2 in Diseases.

Canopy FGF signaling regulator 2 (CNPY2) is a novel angiogenic growth factor. In recent years, increasing evidence highlights that CNPY2 has important functions in health and disease. Many new blood vessels need to be formed to meet the nutrient supply in the process of tumor growth. CNPY2 can participate in the development of tumors by promoting angiogenesis. CNPY2 also enhances neurite outgrowth in neurologic diseases and promotes cell proliferation and tissue repair, thereby improving cardiac function in cardiovascular diseases. Regrettably, there are few studies on CNPY2 in various diseases. At the same time, its biological function and molecular mechanism in the process and development of disease are still unclear. This paper reviews the recent studies on CNPY2 in cervical cancer, renal cell carcinoma, prostate cancer, colorectal cancer, lung cancer, gastric cancer, hepatocellular carcinoma, cerebral ischemia-reperfusion injury, spinal cord ischemia-reperfusion injury, Parkinson's disease, ischemic heart disease, myocardial ischemiareperfusion injury, myocardial infarction, heart failure, and non-alcoholic fatty liver disease. The biological function and molecular mechanism of CNPY2 in these diseases have been summarized in this paper. Many drugs that play protective roles in tumors, cardiovascular diseases, non-alcoholic fatty liver disease, and neurologic diseases by targeting CNPY2, have also been summarized in this paper. In addition, the paper also details the biological functions and roles of canopy FGF signaling regulator 1 (CNPY1), canopy FGF signaling regulator 3 (CNPY3), canopy FGF signaling regulator 4 (CNPY4), and canopy FGF signaling regulator 5 (CNPY5). The mechanism and function of CNPY2 should be continued to study in order to accelerate disease prevention in the future.

Bioremediation of uranium enriched coal fly ash based on microbially induced calcite precipitation.

Coal fly ash (CFA) is an essential raw material in brickmaking industry worldwide. There are some coal mines with a relatively high content of uranium (U) in the Xinjiang region of China that are yet understudied. The CFA from these coal mines poses substantial environmental risks due to the concentrated uranium amount after coal burning. In this paper, we demonstrated a calcifying ureolytic bacterium Halomonas sp. SBC20 for its biocementation of U in CFA based on microbially induced calcite precipitation (MICP). Rectangle-shaped CFA bricks were made from CFA using bacterial cells, and an electric testing machine tested their compressive strength. U distribution pattern and immobility against rainfall runoff were carefully examined by a five-stage U sequential extraction method and a leaching column test. The microstructural changes in CFA bricks were characterized by FTIR and SEM-EDS methods. The results showed that the compressive strength of CFA bricks after being cultivated by bacterial cells increased considerably compared to control specimens. U mobility was significantly decreased in the exchangeable fraction, while the U content was markedly increased in the carbonate-bound fraction after biocementation. Much less U was released in the leaching column test after the treatment with bacterial cells. The FTIR and SEM-EDX methods confirmed the formation of carbonate precipitates and the incorporation of U into the calcite surfaces, obstructing the release of U into the surrounding environments. The technology provides an effective and economical treatment of U-contaminated CFA, which comes from coal mines with high uranium content in the Xinjiang region, even globally.

Mini-review: research and progress of oxeiptosis in diseases.

Oxeiptosis is a novel cell death pathway that was introduced in 2018. As a form of regulated cell death, it operates independently of caspases and is induced by ROS. Distinguished from other cell death pathways such as apoptosis, necroptosis, pyroptosis, and ferroptosis, oxeiptosis features unique damage causes pivotal genes, and signaling pathways (KEAP1/PGAM5/AIFM1). Emerging studies indicate that oxeiptosis plays a significant role in the progression of various diseases and its regulation could serve as a promising therapeutic target. However, the precise molecular mechanisms underlying oxeiptosis remain to be fully elucidated. In this mini-review, we systematically summarize the latest developments in oxeiptosis-related diseases while detailing the molecular mechanisms and regulatory networks of oxeiptosis. These insights offer a foundation for a deeper understanding of oxeiptosis.

The roles of E2F7 in cancer: Current knowledge and future prospects.

Background: E2F7 is a recently discovered member of the E2F family. Investigating the function and mechanism of E2F7 in the growth of tumors is significant for the clinical diagnosis and therapy of these malignancies. Objective: The purpose of this review is to provide theoretical basis for the diagnosis and treatment of malignant tumors by exploring E2F7. Methods: The relevant information was collected through the PubMed database using keyword searches "E2F7" and "cancer". Results: On the one hand, E2F7 plays an essential role in embryonic development, angiogenesis, and the nervous system. On the other hand, E2F7 is also linked to the occurrence and growth of various malignant tumors. Conclusion: E2F7 has potential as a therapeutic target in future cancer treatments.

Ophiopogonin D: review of pharmacological activity.

Background: Ophiopogon D is an important natural organic compound in Ophiopogon japonicus, which often has significant biological activity. Purpose: The purpose of this review is to systemically summarize and discuss the pharmacological activity and underlying mechanisms of OP-D in recent years. Method: PubMed and Web of Science were searched with the keywords:"Ophiopogon japonicus", "Ophiopogon D" "pharmacology", and "pharmacokinetics". There was no restriction on the publication year, and the last search was conducted on 1 Jan 2024. Results: Emerging evidence suggests that OP-D possess numerous pharmacological activities, including bone protection, cardiovascular protection, immune regulation, anti-cancer, anti-atherosclerosis, anti-inflammatory and anti-NAFLD. Conclusion: OP-D has a potential value in the prevention and treatment of many diseases. We hope that this review will contribute to therapeutic development and future studies of OP-D.

Necrostatin-1: a promising compound for neurological disorders.

Necrostatin-1, a small molecular alkaloid, was identified as an inhibitor of necroptosis in 2005. Investigating the fundamental mechanism of Necrostatin-1 and its role in various diseases is of great significance for scientific and clinical research. Accumulating evidence suggests that Necrostatin-1 plays a crucial role in numerous neurological disorders. This review aims to provide a comprehensive overview of the potential functions of Necrostatin-1 in various neurological disorders, offering valuable insights for future research.

Dauricine: Review of Pharmacological Activity.

Background: Dauricine is an important natural organic compound in Menispermum dauricum, which often has significant biological activity. Purpose: The purpose of this review is to systemically summarize and discuss the pharmacological activity and underlying mechanisms of dauricine in recent years. Methods: Web of Science (121 articles) and PubMed databases (97 articles) were used to search for articles related to "dauricine" published from 2000 to 2024. Meanwhile, we classified the pharmacological activity of dauricine by screening these articles. Results: Emerging evidence suggests that dauricine possesses numerous pharmacological activities, including neuroprotection, anti-cancer, anti-arrhythmia, anti-inflammatory and anti-diabetes. Conclusion: Dauricine has a potential value in the treatment of many diseases. We hope that this review will contribute to therapeutic development and future studies of dauricine.

The role and mechanism of various trace elements in atherosclerosis.

Atherosclerosis is a slow and complex disease that involves various factors, including lipid metabolism disorders, oxygen-free radical production, inflammatory cell infiltration, platelet adhesion and aggregation, and local thrombosis. Trace elements play a crucial role in human health. Many trace elements, especially metallic ones, not only maintain the normal functions of organs but also participate in basic metabolic processes. The latest studies have revealed a close correlation between trace elements and the occurrence and progression of atherosclerosis. The imbalance of these trace elements can induce atherosclerosis or accelerate its progression through various mechanisms, which poses a significant threat to human health. Therefore, exploring the specific mechanism of trace elements on atherosclerosis is highly significant. In this review, we summarized the roles and mechanisms of iron, copper, zinc, magnesium, and selenium homeostasis and imbalance in atherosclerosis development, in order to identify novel targets and therapeutic strategies for treating atherosclerosis.

Mechanism of efferocytosis in atherosclerosis.

Atherosclerosis (AS) is a chronic inflammatory vascular disease that occurs in the intima of large and medium-sized arteries with the immune system's involvement. It is a common pathological basis for high morbidity and mortality of cardiovascular diseases. Abnormal proliferation of apoptotic cells and necrotic cells leads to AS plaque expansion, necrotic core formation, and rupture. In the early stage of AS, macrophages exert an efferocytosis effect to engulf and degrade apoptotic, dead, damaged, or senescent cells by efferocytosis, thus enabling the regulation of the organism. In the early stage of AS, macrophages rely on this effect to slow down the process of AS. However, in the advanced stage of AS, the efferocytosis of macrophages within the plaque is impaired, which leads to the inability of macrophages to promptly remove the apoptotic cells (ACs) from the organism promptly, causing exacerbation of AS. Moreover, upregulation of CD47 expression in AS plaques also protects ACs from phagocytosis by macrophages, resulting in a large amount of residual ACs in the plaque, further expanding the necrotic core. In this review, we discussed the molecular mechanisms involved in the process of efferocytosis and how efferocytosis is impaired and regulated during AS, hoping to provide new insights for treating AS.

Feasibility of using wire-guided needle-knife electrocautery for refractory biliary and pancreatic strictures.

BACKGROUND: Endoscopic management of biliary or pancreatic strictures by stent insertion is well established. However, some high-grade strictures are refractory to dilation and stent placement with conventional methods. OBJECTIVE: To evaluate the safety and efficacy of the wire-guided electrotomy technique in dilating stiff biliary and/or pancreatic stenoses when ordinary methods failed. DESIGN: Retrospective analysis of a prospective database. SETTING: Tertiary referral university hospital. PATIENTS: This study involved 279 patients with biliary or pancreatic strictures who underwent ERCP for stenting. INTERVENTION: After conventional dilation failed, wire-guided needle-knife electrocautery was attempted to facilitate insertion of the dilating devices and eventually endoprosthesis. MAIN OUTCOME MEASUREMENTS: The successful treatment and drainage of biliary or pancreatic strictures. RESULTS: With wire-guided needle-knife cauterization, the success rate of stricture dilatation increased from 95.7% (267 of 279 patients) to 98.9% (276 of 279 patients). Dilation of stenoses was successful in 9 of 10 patients (90%) by using electrocautery with the wire-guided needle-knife technique. Postprocedure adverse events included self-limited bleeding, mild acute pancreatitis, hyperamylasemia, cholangitis, and biliary perforation. No procedure-related death occurred. LIMITATIONS: Retrospective, single-center study and small sample size. CONCLUSIONS: Wire-guided needle-knife electroincision appears to be effective for traversing refractory biliary or pancreatic strictures and can be considered as an alternative approach to conventional methods. However, the safety of such a technique needs to be further evaluated.