ABSTRACT
Superconducting phase transitions in two dimensions lie beyond the description of the Ginzburg-Landau symmetry-breaking paradigm for three-dimensional superconductors. They are Berezinskii-Kosterlitz-Thouless (BKT) transitions of paired-electron condensate driven by the unbinding of topological excitations, i.e. vortices. The recently discovered monolayers of layered high-transition-temperature ([Formula: see text]) cuprate superconductor Bi2Sr2CaCu2O8+δ (Bi2212) meant that this 2D superconductor promised to be ideal for the study of unconventional superconductivity. But inhomogeneity posed challenges for distinguishing BKT physics from charge correlations in this material. Here, we utilize the phase sensitivity of scanning superconducting quantum interference device microscopy susceptometry to image the local magnetic response of underdoped Bi2212 from the monolayer to the bulk throughout its phase transition. The monolayer segregates into domains with independent phases at elevated temperatures below [Formula: see text]. Within a single domain, we find that the susceptibility oscillates with flux between diamagnetism and paramagnetism in a Fraunhofer-like pattern up to [Formula: see text]. The finite modulation period, as well as the broadening of the peaks when approaching [Formula: see text] from below, suggests well-defined vortices that are increasingly screened by the dissociation of vortex-antivortex plasma through a BKT transition. In the multilayers, the susceptibility oscillation differs in a small temperature regime below [Formula: see text], consistent with a dimensional crossover led by interlayer coupling. Serving as strong evidence for BKT transition in the bulk, we observe a sharp jump in phase stiffness and paramagnetism at small fields just below [Formula: see text]. These results unify the superconducting phase transitions from the monolayer to the bulk underdoped Bi2212, and can be collectively referred to as the BKT transition with interlayer coupling.
ABSTRACT
Viruses are crucial in shaping soil microbial functions and ecosystems. However, studies on soil viromes have been limited in both spatial scale and biome coverage. Here we present a comprehensive synthesis of soil virome biogeographic patterns using the Global Soil Virome dataset (GSV) wherein we analysed 1,824 soil metagenomes worldwide, uncovering 80,750 partial genomes of DNA viruses, 96.7% of which are taxonomically unassigned. The biogeography of soil viral diversity and community structure varies across different biomes. Interestingly, the diversity of viruses does not align with microbial diversity and contrasts with it by showing low diversity in forest and shrubland soils. Soil texture and moisture conditions are further corroborated as key factors affecting diversity by our predicted soil viral diversity atlas, revealing higher diversity in humid and subhumid regions. In addition, the binomial degree distribution pattern suggests a random co-occurrence pattern of soil viruses. These findings are essential for elucidating soil viral ecology and for the comprehensive incorporation of viruses into soil ecosystem models.
Subject(s)
Soil , Viruses , Soil/chemistry , Ecosystem , Virome , Soil Microbiology , Ecology , Viruses/geneticsABSTRACT
The discoveries of ferromagnetism down to the atomically thin limit in van der Waals (vdW) crystals by mechanical exfoliation have enriched the family of magnetic thin films [C. Gong et al., Nature 546, 265-269 (2017) and B. Huang et al., Nature 546, 270-273 (2017)]. However, compared to the study of traditional magnetic thin films by physical deposition methods, the toolbox of the vdW crystals based on mechanical exfoliation and transfer suffers from low yield and ambient corrosion problem and now is facing new challenges to study magnetism. For example, the formation of magnetic superlattice is difficult in vdW crystals, which limits the study of the interlayer interaction in vdW crystals [M. Gibertini, M. Koperski, A. F. Morpurgo, K. S. Novoselov, Nat. Nanotechnol. 14, 408-419 (2019)]. Here, we report a strategy of interlayer engineering of the magnetic vdW crystal Fe3GeTe2 (FGT) by intercalating quaternary ammonium cations into the vdW spacing. Both three-dimensional (3D) vdW superlattice and two-dimensional (2D) vdW monolayer can be formed by using this method based on the amount of intercalant. On the one hand, the FGT superlattice shows a strong 3D critical behavior with a decreased coercivity and increased domain wall size, attributed to the co-engineering of the anisotropy, exchange interaction, and electron doping by intercalation. On the other hand, the 2D vdW few layers obtained by over-intercalation are capped with organic molecules from the bulk crystal, which not only enhances the ferromagnetic transition temperature (TC), but also substantially protects the thin samples from degradation, thus allowing the preparation of large-scale FGT ink in ambient environment.
ABSTRACT
The use of oxidoreductase nanozymes to regulate reactive oxygen species (ROS) has gradually emerged in periodontology treatments. However, current nanozymes for treating periodontitis eliminate ROS extensively and non-specifically, ignoring the physiological functions of ROS under normal conditions, which may result in uncontrolled side effects. Herein, using the MIL-47(V)-F (MVF) nanozyme, which mimics the function of glutathione peroxidase (GPx), it is proposed that ROS can be properly regulated by specifically eliminating H2 O2 , the most prominent ROS. Through H2 O2 elimination, MVF contributes to limiting inflammation, regulating immune microenvironment, and promoting periodontal regeneration. Moreover, MVF stimulates osteogenic differentiation of periodontal stem cells directly, further promoting regeneration due to the vanadium in MVF. Mechanistically, MVF regulates ROS by activating the nuclear factor erythroid 2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) pathway and promotes osteogenic differentiation directly through the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway. A promising periodontitis therapy strategy is presented using GPx-mimicking nanozymes through their triple effects of antioxidation, immunomodulation, and bone remodeling regulation, making nanozymes an excellent tool for developing precision medicine.
Subject(s)
Periodontitis , Signal Transduction , Humans , Reactive Oxygen Species/metabolism , Oxidative Stress , Glutathione Peroxidase/metabolism , Glutathione Peroxidase/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Osteogenesis , NF-E2-Related Factor 2/metabolism , NF-E2-Related Factor 2/pharmacology , Bone Regeneration , Periodontitis/drug therapyABSTRACT
Pesticides represent one of the largest intentional inputs of potentially hazardous compounds into agricultural soils. However, as an important vegetable producing country, surveys on pesticide residues in soils of vegetable production areas are scarce in China. This study presented the occurrence, spatial distribution, correlation between vegetable types and pesticides, and ecological risk evaluation of 94 current-use pesticides in 184 soil samples from vegetable production areas of Zhejiang province (China). The ecological risks of pesticides to soil biota were evaluated with toxicity exposure ratios (TERs) and risk quotient (RQ). The pesticide concentrations varied largely from below the limit of quantification to 20703.06 µg/kg (chlorpyrifos). The situation of pesticide residues in Jiaxing is more serious than in other cities. Soils in the vegetable areas are highly diverse in pesticide combinations. Eisenia fetida suffered exposure risk from multiple pesticides. The risk posed by chlorpyrifos, which exhibited the highest RQs at all scenarios, was worrisome. Only a few pesticides accounted for the overall risk of a city, while the other pesticides make little or zero contribution. This work will guide the appropriate use of pesticides and manage soil ecological risks, achieving green agricultural production.
Subject(s)
Chlorpyrifos , Pesticide Residues , Pesticides , Soil Pollutants , Pesticides/toxicity , Pesticides/analysis , Pesticide Residues/toxicity , Pesticide Residues/analysis , Soil/chemistry , Vegetables , Environmental Monitoring , Risk Assessment , Soil Pollutants/toxicity , Soil Pollutants/analysisABSTRACT
Periodontitis is an inflammatory disorder which leads to the defect of tooth-supporting tissue, especially in alveolar bone. During this process, the polarization behavior of macrophages affects immune inflammation and bone regeneration in which reactive oxygen species (ROS) play an essential role. ROS level should be regulated to the physiological level to protect stem cells from the inflammatory immune microenvironment. Our previous study constructed a ROS-responsive nanoplatform (Pssl-NAC), which possessed ROS-responsive antioxidative effect and could be potentially applied in periodontitis. However, the connection among bone regeneration, inflammation and oxidative stress remained in osteoimmune regulation is not clear. To further investigate the mechanism of the way how Pssl-NAC works in the treatment of periodontitis would be meaningful. Here, we investigated the effect of PssL-NAC in the regulation of the osteoimmune microenvironment through macrophage polarization. Results show PssL-NAC regulated the macrophage polarization direction in an inflammatory environment by maintaining an appropriate level of intracellular ROS, in which the MAPK/NFκB phosphorylation pathway is particularly important. In the macrophage-human periodontal ligament stem cells (hPDLSCs) co-culture system, PssL-NAC treatment significantly enhanced the osteogenic differentiation of hPDLSCs. In vivo experiment further confirmed the M2-like macrophages increased in the periodontal tissue of rats, and the expression of iNOS and p65 decreased after PssL-NAC treatment. In conclusion, PssL-NAC regulates the osteoimmune microenvironment and protects stem cells from oxidative stress injury for bone regeneration, which provides a strategy for the treatment of periodontitis.
ABSTRACT
The occurrence of superconductivity in proximity to various strongly correlated phases of matter has drawn extensive focus on their normal state properties, to develop an understanding of the state from which superconductivity emerges1-4. The recent finding of superconductivity in layered nickelates raises similar interests5-8. However, transport measurements of doped infinite-layer nickelate thin films have been hampered by materials limitations of these metastable compounds: in particular, a high density of extended defects9-11. Here, by moving to a substrate (LaAlO3)0.3(Sr2TaAlO6)0.7 that better stabilizes the growth and reduction conditions, we can synthesize the doping series of Nd1-xSrxNiO2 essentially free from extended defects. In their absence, the normal state resistivity shows a low-temperature upturn in the underdoped regime, linear behaviour near optimal doping and quadratic temperature dependence for overdoping. This is phenomenologically similar to the copper oxides2,12 despite key distinctions-namely, the absence of an insulating parent compound5,6,9,10, multiband electronic structure13,14 and a Mott-Hubbard orbital alignment rather than the charge-transfer insulator of the copper oxides15,16. We further observe an enhancement of superconductivity, both in terms of transition temperature and range of doping. These results indicate a convergence in the electronic properties of both superconducting families as the scale of disorder in the nickelates is reduced.
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Organochlorine pesticides (OCPs) are organic pollutants that are persistent and undegradable in the environment. To investigate their residual concentrations, spatial and temporal distributions, and the relationship with the crops planted, 12 individual OCPs in 687 soil samples from Jiangsu, Zhejiang and Jiangxi provinces of southeast China were examined. The detection frequencies of OCPs in the studied areas were 1.89%-64.9%. The concentrations of dichloro-diphenyl-trichloroethanes (DDTs), hexachlorocyclohexanes (HCHs), and endosulfans ranged from 0.01 to 5659 µg/kg, 0.03-3.58 µg/kg, and 0.05-3235 µg/kg, respectively. Jiangsu was mainly contaminated by p,p'-DDT, p,p'-DDD and endosulfan sulfate, Zhejiang was more polluted by OCPs except δ-HCH, and Jiangxi was more vulnerable to the contamination of OCPs except o,p'-DDE. The partial least-squares discrimination analysis (PLS-DA) model with RX2 36.3-36.8% revealed that compounds with similar chemical properties tended to appear in the same year and month. All crop lands were polluted by DDTs and Endosulfans. The highest concentrations of DDTs and Endosulfans were found in citrus and vegetable fields, respectively. This study offers new insight into the layout and partitioning of OCPs in agricultural land and into insecticide management on public health and ecological safety.
Subject(s)
Hydrocarbons, Chlorinated , Pesticides , Soil Pollutants , Soil/chemistry , Soil Pollutants/analysis , Environmental Monitoring , Pesticides/analysis , Hydrocarbons, Chlorinated/analysis , DDT/analysis , Dichlorodiphenyl Dichloroethylene , Trichloroethanes/analysis , ChinaABSTRACT
Background: To explore the prognostic risk factors of 30-day death in patients with traumatic lower limb fracture (TLLF) complicated with acute pulmonary embolism (APE). Methods: 295 consecutive TLLF patients diagnosed as APE according to pulmonary artery CT angiography, hospitalized in our hospital from January 2017 to December 2021, were included in this study. Patients were divided into nonsurvival group and survival group according to 30-day follow-up results. After adjusting age, sex, and all the clinical variables with P values of <0.2 with backward stepwise method (likelihood ratio), multivariate Cox regression analysis was used to analyze risk factors of 30 days all-cause death in TLLF patients with APE. The area under curve (AUC) calculated by receiver operating characteristic curve (ROC) and the incremental model were used to determine the prognostic potential of identified risk factors. Results: 29 patients died during 30-day follow-up. Simplified pulmonary embolism severity index (sPESI) score ≥1 (P < 0.05), Wells score ≥7 (P < 0.01), and pulmonary hypertension (P < 0.01) were associated with higher risk, while anticoagulant therapy (P < 0.01) was associated with lower risk of all-cause death during 30 days follow-up in APE patients. Compared with sPESI score, Wells score plus pulmonary hypertension produced better predictive efficacy. Prognostic value of sPESI score could be enhanced by adding Wells score, pulmonary hypertension, and anticoagulant therapy to the predicting models. Conclusions: Wells score ≥7 and pulmonary hypertension are independent predictive risk factors of 30-day all-cause death in TLLF patients with APE.
Subject(s)
Hominidae , Hypertension, Pulmonary , Pulmonary Embolism , Humans , Animals , Prognosis , Retrospective Studies , Pulmonary Embolism/complications , Pulmonary Embolism/diagnostic imaging , Risk Factors , Acute Disease , Anticoagulants , Lower Extremity , Severity of Illness Index , Risk Assessment , ROC CurveABSTRACT
Hepatocellular carcinoma (HCC) is a malignant type of liver cancer that poses severe threat to human health worldwide. Aerobic glycolysis is a hallmark of HCC and facilitates its progression. Solute carrier family 10 member 1 (SLC10A1) and long intergenic non-protein coding RNA 659 (LINC00659) were detected to be downregulated in HCC cells, yet their potential functions underlying HCC progression remained unidentified. In the current work, colony formation and transwell assays were used to detect HCC cells (HepG2 and HuH-7) proliferation and migration in vitro study. The quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assays were used for gene/protein expression determination. Seahorse assay was performed for aerobic glycolysis assessment. RNA immunoprecipitation (RIP) and RNA pull-down assays were conducted for detection of the molecular interaction between LINC00659 and SLC10A1. The results showed that overexpressed SLC10A1 significantly suppressed the proliferation, migration, and aerobic glycolysis in HCC cells. Mechanical experiments further demonstrated that LINC00659 positively regulated SLC10A1 expression in HCC cells by recruiting fused protein in sarcoma (FUS). Our work elucidated that LINC00659 inhibited HCC progression and aerobic glycolysis via the FUS/SLC10A1 axis, revealing a novel lncRNA-RNA-binding protein-mRNA network in HCC, which might provide potential therapeutic targets for HCC.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , MicroRNAs , RNA, Long Noncoding , Humans , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , MicroRNAs/genetics , Cell Line, Tumor , Proteins/genetics , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Glycolysis , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Cell Movement/genetics , RNA-Binding Protein FUS/genetics , RNA-Binding Protein FUS/metabolismABSTRACT
Although humans and animals are usually exposed to combinations of toxic substances, little is known about the interactive toxicity of mycotoxins and farm chemicals. Therefore, we can not precisely evaluate the health risks of combined exposure. In the present work, using different approaches, we examined the toxic impacts of zearalenone and trifloxystrobin on zebrafish (Danio rerio). Our findings showed that the lethal toxicity of zearalenone to embryonic fish with a 10-day LC50 of 0.59 mg L-1 was lower than trifloxystrobin (0.037 mg L-1). Besides, the mixture of zearalenone and trifloxystrobin triggered acute synergetic toxicity to embryonic fish. Moreover, the contents of CAT, CYP450, and VTG were distinctly altered in most single and combined exposures. Transcriptional levels of 23 genes involved in the oxidative response, apoptosis, immune, and endocrine systems were determined. Our results implied that eight genes (cas9, apaf-1, bcl-2, il-8, trb, vtg1, erß1, and tg) displayed greater changes when exposed to the mixture of zearalenone and trifloxystrobin compared with the corresponding individual chemicals. Our findings indicated that performing the risk assessment based on the combined impact rather than the individual dosage response of these chemicals was more accurate. Nevertheless, further investigations are still necessary to reveal the modes of action of mycotoxin and pesticide combinations and alleviate their effects on human health.
Subject(s)
Mycotoxins , Water Pollutants, Chemical , Zearalenone , Animals , Humans , Zearalenone/toxicity , Zebrafish/metabolism , Larva , Mycotoxins/metabolism , Gene Expression , Water Pollutants, Chemical/toxicityABSTRACT
Fertilization has become one of the most important ways to recycle perishable waste. In order to reveal the effect of the nutrient of the perishable waste primary products on the market and the possible impact of their application, 136 perishable waste primary products were sampled in nine cities in Zhejiang province, China. The result shows that these products have high nutrient content (average nutrient content was 5.00%). However, the conductivity (7.19 mS/cm) total soluble salt content (12.07%), and grease content (5.99%) were too high. The excessive salt and grease may cause harm to soil and crops, and become the main limiting factors for the fertilizer utilization of perishable waste. Heavy metal content of most of the samples met current commercial organic fertilizer standards, except that lead and chromium content of some samples exceeded the limit standard. Toluene, ethylbenzene, m & p-xylene were generally detected in the samples. These toxic and harmful substances have brought risks to the safe use of perishable waste into fertilizers.
Subject(s)
Metals, Heavy , Waste Products , Fertilizers/analysis , Soil/chemistry , Risk Assessment , Crops, Agricultural , Metals, Heavy/analysisABSTRACT
BACKGROUND: It has been observed previously that chronic methamphetamine (METH) administration could upregulate neuropeptide Y (NPY) expression and promote atherosclerotic formation in apolipoprotein E knockout (ApoE-/-) mice fed with a normal cholesterol or high diet and NPY might be involved in the pathogenesis of METH-induced atherogenic effects through NPY Y1 receptor pathway. Vulnerable coronary atherosclerotic plaque (VP) is a critical pathological finding responsible for the acute coronary syndrome (ACS). In this study, we explored whether METH abuse could aggravate the formation of VP in ApoE-/- mice fed with high cholesterol diet. OBJECTIVE: The purpose of this study was to observe if chronic METH administration could aggravate vulnerable plaque (VP) formation in ApoE-/- mice fed with a high-cholesterol diet. METHODS: Male ApoE-/- mice fed with a high-cholesterol diet were intraperitoneally injected with normal saline (NS) or 8 mg/kg/day METH (M8) for 24 weeks. Body weight was monitored from baseline to 24 weeks at 2 weeks intervals. After 24 weeks of treatment, plasma lipid variables were measured. Movat's staining and immunohistochemical staining were performed on frozen sections of the aortic roots to calculate VP percentage and intraplaque hemorrhage (IPH) percentage and detect expression of NPY, vascular endothelial growth factor (VEGF), and CD31. In vitro, the expressions of Y2R, VEGF, and CD31 were detected by immunofluorescence staining in aortic endothelial cells incubated with PBS, 100µM METH, 10nmol NPY, or 100µM METH plus 10nmol NPY for 12 hours. RESULTS: The CD31 positive area, percentage of IPH, VP, and the expressions of NPY and VEGF were significantly increased in the M8 group than in the NS group. In vitro, the expressions of Y2R, VEGF, and CD31 were significantly increased in the METH+NPY group than in the PBS, METH, and NPY groups and these effects could be blunted by treatment with a Y2R antagonist or DPPIV inhibitor. CONCLUSION: Chronic METH administration could aggravate VP in ApoE-/- mice fed with a high-cholesterol diet, possibly through upregulating vascular NPY and VEGF expression and promoting angiogenesis and vessel rupture in atherosclerotic plaques. Our findings indicated that increased VP formation might contribute to the development of acute coronary syndrome post-chronic METH abuse by activating DPPIV/NPY/Y2R pathway.
ABSTRACT
OBJECTIVES: Human-derived pulp stem cells play key roles during dentinogenesis. Erythropoietin is reportedly involved in osteoblastogenesis and facilitates bone formation. However, the mechanism is still unknown. This research was to study the potential of erythropoietin in enhancing odontoblastic differentiation of human-derived pulp stem cells and to determine the underlying mechanism. METHODS: The human-derived pulp stem cells were treated with erythropoietin, EphB4 inhibitor, and MAPK inhibitors, and the odontoblastic differentiation was measured by ALP staining, ALP activity assay, alizarin red S staining, and their quantitative analysis, and RT-qPCR of DSPP, DMP1, OCN, and RUNX2. The direct pulp capping model was established to evaluate the formation of tertiary dentin after treatment with erythropoietin. Western blot assay was conducted to assess relevant protein expressions in the phosphorylated EphB4 and MAPK pathway. RESULTS: The results showed that erythropoietin promoted odontoblastic differentiation of human-derived pulp stem cells at 20 U/ml. Erythropoietin induced tertiary dentin formation in vivo. The potential mechanism of this was upregulating phosphorylated EphB4 and phosphorylated MAPK; furthermore, this effect could be decreased by EphB4 inhibitors, which inhibited MAPK phosphorylation. Blockage of MAPK pathways attenuated human-derived pulp stem cells' odontoblastic differentiation, suggesting that MAPK pathways are involved. CONCLUSION: Erythropoietin induced tertiary dentin formation in vivo. And erythropoietin enhanced human-derived pulp stem cells' odontoblastic differentiation via the EphB4-mediated MAPK signaling pathway.
Subject(s)
Erythropoietin , Signal Transduction , Humans , MAP Kinase Signaling System , Cell Differentiation , Odontoblasts , Dental Pulp , Erythropoietin/pharmacology , Erythropoietin/metabolism , Stem Cells , Cells, CulturedABSTRACT
Rapid global industrialization has resulted in widespread cadmium contamination in agricultural soils and products. A considerable proportion of rice consumers are exposed to Cd levels above the provisional safe intake limit, raising widespread environmental concerns on risk management. Therefore, a generalized approach is urgently needed to enable correct evaluation and early warning of cadmium contaminants in rice products. Combining big data and computer science together, this study developed a system named "SMART Cd Early Warning", which integrated 4 modules including genotype-to-phenotype (G2P) modelling, high-throughput sequencing, G2P prediction and rice Cd contamination risk assessment, for rice cadmium accumulation early warning. This system can rapidly assess the risk of rice cadmium accumulation by genotyping leaves at seeding stage. The parameters including statistical methods, population size, training population-testing population ratio, SNP density were assessed to ensure G2P model exhibited superior performance in terms of prediction precision (up to 0.76 ± 0.003) and computing efficiency (within 2 h). In field trials of cadmium-contaminated farmlands in Wenling and Fuyang city, Zhejiang Province, "SMART Cd Early Warning" exhibited superior capability for identification risk rice varieties, suggesting a potential of "SMART Cd Early-Warning system" in OsGCd risk assessment and early warning in the age of smart.
Subject(s)
Oryza , Soil Pollutants , Cadmium/analysis , Soil Pollutants/analysis , Soil , Risk AssessmentABSTRACT
BACKGROUND: To observe the effect and mechanism of alpha-adrenergic receptor inhibitor phentolamine (PTL) in a rabbit model of acute pulmonary embolism (APE) combined with shock. METHODS: Twenty-four New Zealand rabbits were randomly divided into sham operation group (S group, n = 8), model group (M group, n = 8) and PTL group (n = 8), the model of APE combined with shock was established. Mean pulmonary arterial pressure (MPAP), peripheral mean arterial pressure (MAP) and pulmonary circulation time were evaluated. The expression levels of α1 receptor, α2 receptor and their downstream molecules in pulmonary embolism (PE) and non-pulmonary embolism (non-PE) regions lung tissues were detected and compared, respectively. RESULTS: In M group, α receptor-related signaling pathways were significantly activated in both PE and non-PE areas as expressed by up-regulated α1, α2 receptor and phospholipase C (PLC); the expression level of phosphorylated protein kinase A (p-PKA) was significantly down-regulated; myosin light chain kinase (MLCK) and α-smooth muscle actin (α-SMA) levels were up-regulated. PTL treatment significantly improved pulmonary as well as systemic circulation failure: decreased MPAP, restored blood flow in non-PE area, shortened pulmonary circulation time, increased MAP, and restored the circulation failure. PTL induced significantly down-regulated expression of α1 receptor and its downstream molecule PLC in both PE and non-PE area, the expression level of α2 receptor was also down-regulated, the expression level of p-PKA was significantly up-regulated. PTL treatment can inhibit both α1 and α2 receptor-related signaling pathways in whole lung tissues, and inhibit Ca2+ signaling pathways. The expression level of MLCK and α-SMA were significantly down-regulated. Compared with PE area, the changes of expression levels of α receptor and its downstream molecules were more significant in the non-PE region. CONCLUSION: In this model of APE combined with shock, the sympathetic nerve activity was enhanced in the whole lung, α1 and α2 receptor and their downstream signaling activation might mediate blood flow failure in the whole lung. PTL treatment can effectively restore pulmonary blood flow in non-PE area and improve pulmonary as well as systemic circulation failure possibly through down-regulating α1 and α2 receptor and their downstream signaling pathways.
Subject(s)
Hominidae , Pulmonary Embolism , Shock , Animals , Rabbits , Phentolamine/pharmacology , Pulmonary Embolism/complications , Pulmonary Embolism/drug therapy , Receptors, Adrenergic, alphaABSTRACT
Cervical cancer is one of the women-associated tumors that affects numerous people yearly. It is the fourth most common malignancy in women worldwide. Following early diagnosis, this cancer can be cured mainly by traditional methods such as surgery, tumor resection, and chemotherapy; nonetheless, it becomes more challenging to treat in advanced and metastatic stages. With the advent of novel treatments such as angiogenesis inhibitors or immuno-checkpoint blockers in recent years, the survival rate of patients with advanced cervical cancer has significantly increased. However, it has not yet reached a satisfactory level. It has been revealed that human papillomavirus (HPV) infection is responsible for more than 90% of cervical cancer cases. However, evidence revealed that monotherapy with anti-HPV vaccines such as ISA101 could not affect tumor growth and progression in patients with HPV-induced cervical cancer. Therefore, combining ISA101 and immune checkpoint blockers or other immunotherapeutic approaches may be more robust and effective than monotherapy with ISA101 or immune checkpoint blockers for treating cervical cancer. This review summarizes the ISA101 properties, advantages and disadvantages. Furthermore, various conducted combination therapies with ISA101 and the effectiveness and challenges of this treatment have been discussed.
ABSTRACT
Formulations from nanotechnology platform promote therapeutic drug delivery and offer various advantages such as biocompatibility, non-inflammatory effects, high therapeutic output, biodegradability, non-toxicity, and biocompatibility in comparison with free drug delivery. Due to inherent shortcomings of conventional drug delivery to cancerous tissues, alternative nanotechnological-based approaches have been developed for such ailments. Ovarian cancer is the leading gynecological cancer with higher mortality rates due to its reoccurrence and late diagnosis. In recent years, the field of medical nanotechnology has witnessed significant progress in addressing existing problems and improving the diagnosis and therapy of various diseases including cancer. Nevertheless, the literature and current reviews on nanotechnology are mainly focused on its applications in other cancers or diseases. In this review, we focused on the nanoscale drug delivery systems for ovarian cancer targeted therapy and diagnosis, and different nanocarriers systems including dendrimers, nanoparticles, liposomes, nanocapsules, and nanomicelles for ovarian cancer have been discussed. In comparison to non-functionalized counterparts of nanoformulations, the therapeutic potential and preferential targeting of ovarian cancer through ligand functionalized nanoformulations' development has been reviewed. Furthermore, numerous biomarkers such as prostatic, mucin 1, CA-125, apoptosis repeat baculoviral inhibitor-5, human epididymis protein-4, and e-cadherin have been identified and elucidated in this review for the assessment of ovarian cancer. Nanomaterial biosensor-based tumor markers and their various types for ovarian cancer diagnosis are explained in this article. In association, different nanocarrier approaches for the ovarian cancer therapy have also been underpinned. To ensure ovarian cancer control and efficient detection, there is an urgent need for faster and less costly medical tools in the arena of oncology.
Subject(s)
Dendrimers , Nanocapsules , Nanoparticles , Ovarian Neoplasms , Female , Humans , Cadherins/therapeutic use , Carcinoma, Ovarian Epithelial/drug therapy , Drug Delivery Systems , Ligands , Liposomes , Nanotechnology , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/drug therapyABSTRACT
Soil acidification often occurs when the concentration of ammonium (NH4 +) in soil rises, such as that observed in farmland. Both soil acidification and excess NH4 + have serious adverse effects on crop growth and food production. However, we still do not know which of these two inhibitors has a greater impact on the growth of crops, and the degree of their inhibitory effect on crop growth have not been accurately evaluated. 31 wheat cultivars originating in various areas of China were planted under 5 mM sole NH4 + (ammonium nitrogen, AN) or nitrate nitrogen in combined with two pH levels resembling acidified conditions (5.0 and 6.5). The results showed that the shoots and roots biomass were severely reduced by AN in both and these reduction effects were strengthened by a low medium pH. The concentration of free NH4 + and amino acids, the glutamine synthetase activity were significantly higher, but the total soluble sugar content was reduced under NH4 + conditions, and the glutamine synthetase activity was reduced by a low medium pH. Cultivar variance was responsible for the largest proportion of the total variance in plant dry weight, leaf area, nodal root number, total root length and root volume; the nitrogen (N) form explains most of the variation in N and C metabolism; the effects of pH were the greatest for plant height and root average diameter. So, soil acidification and excess NH4 + would cause different degrees of inhibition effects on different plant tissues. The findings are expected to be useful for applying effective strategies for reducing NH4 + stress in the field.
ABSTRACT
Ovarian cancer (OC) is one of the most common cancers in women, with a high mortality rate and very few available and effective treatments. Evidence shows that immunotherapy in OC has not been very successful because immune checkpoint blockers have not achieved satisfactory clinical outcomes. On the other hand, as one of the effective treatment approaches, chimeric antigen receptor T-cell (CAR T-cell) therapy has gained a moral position, especially in blood malignancies. Although in solid tumors, CAR T-cell therapy faces various complications and challenges. One of these challenges is selecting the appropriate tumor antigen targeted by CAR T cells, making the selection difficult due to the expression of antigens by tumor cells and normal cells. In addition, the rate of tumor antigen expression and CAR T-cell access to the desired antigen and proper stimulation of CAR T cells can be other important points in antigen selection. This review summarized common tumor antigens and the challenges of selecting them in CAR T cells therapy of OC.