Building a Layer-Structured Aluminum/Graphene Composite with Significant Improvement in Electrical Conductivity.

Aluminum (Al) and its alloys are widely used in various fields due to their excellent physical properties. Although many efforts have been made to fabricate an Al-based composite, they usually results in a significant decrease in electrical conductivity. Herein, a special layer-structured Al/graphene (Gr)/Al composite was successfully designed and fabricated through a facile method using the ultrasonic spraying of graphene powder with alumina removal and a subsequent vacuum hot-pressing process. The as-obtained Al/Gr/Al composite presents a significantly enhanced electrical conductivity of 66% IACS, which is much higher than that of other reported Al-based composites, while it still maintains similar mechanical properties. This work provides a new strategy for the development of highly conductive Al-based composites, which would be very useful and important for practical applications.

Kaempferol Improves Exercise Performance by Regulating Glucose Uptake, Mitochondrial Biogenesis, and Protein Synthesis via PI3K/AKT and MAPK Signaling Pathways.

Kaempferol is a natural flavonoid with reported bioactivities found in many fruits, vegetables, and medicinal herbs. However, its effects on exercise performance and muscle metabolism remain inconclusive. The present study investigated kaempferol's effects on improving exercise performance and potential mechanisms in vivo and in vitro. The grip strength, exhaustive running time, and distance of mice were increased in the high-dose kaempferol group (p < 0.01). Also, kaempferol reduced fatigue-related biochemical markers and increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) related to antioxidant capacity. Kaempferol also increased the glycogen and adenosine triphosphate (ATP) content in the liver and skeletal muscle, as well as glucose in the blood. In vitro, kaempferol promoted glucose uptake, protein synthesis, and mitochondrial function and decreased oxidative stress in both 2D and 3D C2C12 myotube cultures. Moreover, kaempferol activated the PI3K/AKT and MAPK signaling pathways in the C2C12 cells. It also upregulated the key targets of glucose uptake, mitochondrial function, and protein synthesis. These findings suggest that kaempferol improves exercise performance and alleviates physical fatigue by increasing glucose uptake, mitochondrial biogenesis, and protein synthesis and by decreasing ROS. Kaempferol's molecular mechanism may be related to the regulation of the PI3K/AKT and MAPK signaling pathways.

Microvascular reperfusion of fibrinolysis followed by percutaneous coronary intervention versus primary percutaneous coronary intervention for ST-segment-elevation acute myocardial infarction.

Background: Primary percutaneous coronary intervention (PPCI) has been widely recognized as the preferred treatment for ST-segment-elevation myocardial infarction (STEMI). However, substantial numbers of STEMI patients cannot receive timely PPCI. Early fibrinolysis followed by routine percutaneous coronary intervention (FPCI) has been proposed as an effective and safe alternative for eligible patients. To date, few studies have compared FPCI with PPCI in terms of microvascular reperfusion. This study aimed to evaluate the microvascular function of FPCI and PPCI. Methods: STEMI patients at the Peking University First Hospital and Miyun Hospital were enrolled in this retrospective study between January 2015 to December 2020. Microvascular function documented by the coronary angiography-derived index of microvascular resistance (caIMR) was measured at the final angiogram after revascularization. The primary end point was the caIMR of the culprit vessels. The secondary end points were in-hospital and follow-up major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal recurrent myocardial infarction, target-vessel revascularization (TVR), and non-fatal stroke/transient ischemic attacks (TIA). Details of the adverse clinical events were obtained from telephone interviews and electronic medical record systems until January 2022. Results: In total, 496 STEMI patients were enrolled in this cross-sectional retrospective study. Of these patients, 81 underwent FPCI, and 415 underwent PPCI. At the baseline, the PPCI patients had a higher-risk profile than the FPCI patients. The time from symptom onset to reperfusion therapy was significantly shorter in the FPCI group than the PPCI group (median 3.0 vs. 4.5 hours; P<0.001). The caIMR was significantly lower in the FPCI group than the PPCI group (median 20.34 vs. 40.33; P<0.001). The median follow-up duration was 4.1 years. During the follow-up period, the rate of MACE was lower in the FPCI group than the PPCI group [7 (10.1%) vs. 82 (20.8%), P=0.048]. After propensity score matching to adjust for the imbalances at the baseline, the caIMR remained significant and the clinical outcomes did not differ significantly between the two groups. Conclusions: In eligible STEMI patients, clinically successful FPCI may be associated with better microvascular reperfusion and comparable clinical outcomes as compared with PPCI.

Locally Saturated Ether-Based Electrolytes With Oxidative Stability For Li Metal Batteries Based on Li-Rich Cathodes.

Li metal batteries applying Li-rich, Mn-rich (LMR) layered oxide cathodes present an opportunity to achieve high-energy density at reduced cell cost. However, the intense oxidizing and reducing potentials associated with LMR cathodes and Li anodes present considerable design challenges for prospective electrolytes. Herein, we demonstrate that, somewhat surprisingly, a properly designed localized-high-concentration electrolyte (LHCE) based on ether solvents is capable of providing reversible performance for Li||LMR cells. Specifically, the oxidative stability of the LHCE was found to heavily rely on the ratio between salt and solvating solvent, where local-saturation was necessary to stabilize performance. Through molecular dynamics (MD) simulations, this behavior was found to be a result of aggregated solvation structures of Li+/anion pairs. This LHCE system was found to produce significantly improved LMR cycling (95.8% capacity retention after 100 cycles) relative to a carbonate control as a result of improved cathode-electrolyte interphase (CEI) chemistry from X-ray photoelectron spectroscopy (XPS), and cryogenic transmission electron microscopy (cryo-TEM). Leveraging this stability, 4 mAh cm-2 LMR||2× Li full cells were demonstrated, retaining 87% capacity after 80 cycles in LHCE, whereas the control electrolyte produced rapid failure. This work uncovers the benefits, design requirements, and performance origins of LHCE electrolytes for high-voltage Li||LMR batteries.

The outer membrane protein Tp92 of Treponema pallidum delays human neutrophil apoptosis via the ERK, PI3K/Akt, and NF-κB pathways.

Syphilis is a persistent sexually transmitted disease caused by infiltration of the elusive pathogen Treponema pallidum. Despite the prevalence of human polymorphonuclear neutrophils (hPMNs) within cutaneous lesions, which are characteristic of incipient syphilis, their role in T. pallidum infection remains unclear. Tp92 is the only T. pallidum helical outer membrane protein that exhibits structural features similar to those of outer membrane proteins in other gram-negative bacteria. However, the functional mechanism of this protein in immune cells remains unclear. Neutrophils are short-lived cells that undergo innate apoptosis in response to external stimuli that typically influence this process. In this study, we determined that Tp92 impedes the activation of procaspase-3 via the ERK MAPK, PI3K/Akt, and NF-κB signaling pathways, consequently suppressing caspase-3 activity within hPMNs, and thereby preventing hPMNs apoptosis. Furthermore, Tp92 could also modulate hPMNs apoptosis by enhancing the expression of the anti-apoptotic protein Mcl-1, stimulating IL-8 secretion, and preserving the mitochondrial membrane potential. These findings provide valuable insights into the molecular mechanisms underlying T. pallidum infection and suggest potential therapeutic targets for syphilis treatment.

Phthalate acid esters and polycyclic aromatic hydrocarbons concentrations with their determining factors among Chinese pregnant women: A focus on dietary patterns.

BACKGROUND: Pregnant women are susceptible to adverse health effects associated with phthalate acid esters (PAEs) and polycyclic aromatic hydrocarbons (PAHs), and diet is a significant exposure source. Little is known about the contributions of dietary patterns during pregnancy to the exposure variability of these environmental contaminants. OBJECTIVES: To identify dietary patterns in relation to PAEs and PAHs exposure in the Chinese pregnant population. METHODS: Dietary data and urinary concentrations of environmental pollutants were obtained from 1190 pregnant women in the Tongji Birth Cohort (TJBC). PAEs and PAHs were measured in spot urine samples. Food intake was assessed using a food-frequency questionnaire. Dietary patterns were constructed by principal component analysis (PCA). Through PCA, we also extracted three chemical mixture scores that represent different co-exposure patterns of PAEs and PAHs. Multiple linear regression models were adopted to identify predictors of PAEs and PAHs exposure. RESULTS: Four dietary patterns were identified by PCA that explained 44.9 % of the total variance of food intake. We found egg-dairy products pattern, whole grain-tuber crop pattern, and meat-aquatic products pattern were positively associated with specific pollutants exposure. In contrast, fruit-nut-vegetable pattern was negatively correlated with PAEs and PAHs exposure. Every SD increase in this pattern score was associated with 14.36 % reduced mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) (95 % CI: -24.50 ~ -2.96, p-trend = 0.01), 10.86 % reduced 2-hydroxynaphthalene (2-OHNap) (95 % CI: -20.07 ~ -0.60, p-trend = 0.04), 19.35 % reduced 9-hydroxyphenanthrene (9-OHPhe) (95 % CI: -34.49 ~ -0.70, p-trend = 0.01), and 8.33 % reduced scores of PAHs group (95 % CI: -15.97 ~ -0.10, p-trend = 0.02). In addition, disposable tableware usage and passive smoking were suggested as potentially modifiable sources of PAEs and PAHs exposure, respectively. CONCLUSION: Adhering to egg-dairy products pattern, whole grain-tuber crop pattern, and meat-aquatic products pattern may be related to increased PAEs and PAHs exposure, while following fruit-nut-vegetable pattern seems to correlate with a lower burden of such exposure.

Introduction of long non-coding RNAs to regulate autophagy-associated therapy resistance in cancer.

Autophagy is a lysosomal degradation pathway that depends on various evolutionarily conserved autophagy-related genes (ATGs). Dysregulation of autophagy plays an important role in the occurrence and development of cancer. Chemotherapy, targeted therapy, radiotherapy, and immunotherapy are important treatment options for cancer, which can significantly improve the survival rate of cancer patients. However, the occurrence of therapy resistance results in therapeutic failure and poor prognosis of cancer. Accumulating studies have found that long non-coding RNAs (lncRNAs) are well known as crucial regulators to control autophagy through regulating ATGs and autophagy-associated signaling pathways, including the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, ultimately mediating chemoresistance and radioresistance. Taken together, this review systematically summarizes and elucidates the pivotal role of lncRNAs in cancer chemoresistance and radioresistance via regulating autophagy. Understanding the specific mechanism of which may provide autophagy-related therapeutic targets for cancer in the future.

Analysis of furan and its major furan derivatives in coffee products on the Chinese market using HS-GC-MS and the estimated exposure of the Chinese population.

The current study analysed concentrations of furan and its derivatives in coffee products commercially available in China based on an improved headspace gas chromatography-mass spectrometry (HS-GC-MS) method and estimated health risks. A total of 101 samples of coffee products on the Chinese market was analysed. Furan (98%, ND-6569 µg/kg) and 2-methylfuran (100%, 2-29639 µg/kg) were the compounds with the highest concentrations and detection rates in coffee products. The mean dietary exposure of Chinese consumers to furan and the sum of furan, 2-methylfuran and 3-methylfuran in coffee products was 0.09 and 0.46 µg/kg bw/day, respectively. For the neoplastic effects of furan, the margin of exposure (MOE) was 14,556 for the mean dietary exposure of consumers. For the non-neoplastic effects of furan, MOEs were 711 and 139 for furan and the sum of furan, 2-methylfuran and 3-methylfuran, respectively. Overall, a health concern is indicated for coffee consumers with MOEs below 10000.

LncRNA BC200/miR-150-5p/MYB positive feedback loop promotes the malignant proliferation of myelodysplastic syndrome.

Myelodysplastic syndrome (MDS) is a group of heterogeneous hematologic malignancies with a risk of transformation to acute myeloid leukemia. Understanding the molecular mechanisms of the specific roles of long noncoding RNAs (lncRNAs) in MDS would create novel ways to identify diagnostic and therapeutic targets. The lncRNA BC200 is upregulated and acts as an oncogene in various cancers; however, its expression, clinical significance, and roles in MDS remain unclear. Here, we found that BC200 was highly expressed in MDS patients compared with normal individuals. Knockdown of BC200 inhibited MDS cell proliferation, colony formation, and cell cycle progression in vitro and suppressed the growth and invasiveness of MDS cells in vivo. Mechanistic investigations revealed that BC200 functioned as a miRNA sponge to positively regulate the expression of MYB through sponging miR-150-5p and subsequently promoted malignant proliferation of MDS cells. Conversely, we found that BC200 was a direct transcriptional target of MYB, and knockdown of MYB abolished the oncogenic effect of BC200/miR-150-5p. Taken together, our results revealed that the BC200/miR-150-5p/MYB positive feedback loop promoted the proliferation of MDS cells and is expected to be a potential biomarker and therapeutic target in MDS.

Role of Hepatocyte- and Macrophage-Specific PPARγ in Hepatotoxicity Induced by Diethylhexyl Phthalate in Mice.

BACKGROUND: Phthalates may disturb metabolic homeostasis in the liver by interfering with the peroxisome proliferator-activated receptors (PPARs). However, the role of hepatic macrophages in the lipid metabolic dysregulation induced by diethylhexyl phthalate (DEHP) remains unclear. OBJECTIVES: We aimed to evaluate the respective role of hepatocyte- and macrophage-specific PPARγ in the hepatotoxicity induced by DEHP. METHODS: Wild-type (WT), hepatocyte-specific PPARγ knockout (Hep-KO), and macrophage-specific PPAR knockout (Mac-KO) mice were administered DEHP (625mg/kg body weight) by daily gavage for 28 d, followed by hepatotoxicity examination and macrophage analysis. RNA sequencing and lipid metabolomic analysis were used to characterize the molecular changes in mouse liver. Mouse bone marrow-derived macrophages (BMDMs) and human monocytic THP-1 cell-derived macrophages were used to investigate the mechanistic regulation of macrophages' polarization by DEHP and mono(2-ethylhexyl) phthalate (MEHP). RESULTS: The levels of hepatic steatosis and triglyceride were significantly higher in the mice treated with DEHP compared with the control mice in the WT and Hep-KO model. Lipid accumulation induced by DEHP was notably attenuated in the Mac-KO mice, but M2-polarization of hepatic macrophages in the Mac-KO mice was significantly higher compared with the WT mice under DEHP treatment. The M2-polarization of BMDMs and human macrophages was suppressed by DEHP and MEHP. Transcriptomic and lipidomic data suggested lower levels of lipid biosynthesis, fatty acid oxidation, and oxidative phosphorylation in the Mac-KO mice compared with the WT and Hep-KO mice under DEHP treatment. CONCLUSIONS: Our data suggested that the orchestrated activation of PPARα and PPARγ by MEHP may reprogram hepatic macrophages' polarization, thereby affecting lipid homeostasis in the mouse liver. Although this conclusion was based on studies conducted in mice and in vitro, these findings may aid in elucidating the health effect of environmental phthalate exposure. https://doi.org/10.1289/EHP9373.

Intricate crosstalk between MYB and noncoding RNAs in cancer.

MYB is often overexpressed in malignant tumors and plays a carcinogenic role in the initiation and development of cancer. Deletion of the MYB regulatory C-terminal domain may be a driving mutation leading to tumorigenesis, therefore, different tumor mechanisms produce similar MYB proteins. As MYB is a transcription factor, priority has been given to identifying the genes that it regulates. All previous attention has been focused on protein-coding genes. However, an increasing number of studies have suggested that MYB can affect the complexity of cancer progression by regulating tumor-associated noncoding RNAs (ncRNAs), such as microRNAs, long-non-coding RNAs and circular RNAs. ncRNAs can regulate the expression of numerous downstream genes at the transcription, RNA processing and translation levels, thereby having various biological functions. Additionally, ncRNAs play important roles in regulating MYB expression. This review focuses on the intricate crosstalk between oncogenic MYB and ncRNAs, which play a pivotal role in tumorigenesis, including proliferation, apoptosis, angiogenesis, metastasis, senescence and drug resistance. In addition, we discuss therapeutic strategies for crosstalk between MYB and ncRNAs to prevent the occurrence and development of cancer.

Analysis on the effect of intravenous anesthesia with dexmedetomidine and propofol combined with seaweed polysaccharides on hemodynamics and analgesia in pregnant females undergoing painless induced abortion.

This study attempted to investigate the effect of intravenous anesthesia with dexmedetomidine and propofol combined with seaweed polysaccharides on painless induced abortion. A total of 82 pregnant females were divided into study group and reference group. The subjects in the study group took seaweed polysaccharides orally before surgery and received intravenous anesthesia with dexmedetomidine and propofol, while the subjects in the reference group received intravenous anesthesia with sufentanil combined with propofol. The onset time of anesthesia in the reference group was significantly shorter than that in the study group (P<0.001) and both recovery time and the dosage of propofol in the study group were significantly lower than those in the reference group (P<0.001). The values of MAP and HR at T3 and T4, clinical analgesia effective rate, ramsay sedation scores and incidence of adverse reactions of the subjects in study group was significantly better than those indexes of the subjects in reference group (P<0.05). The intravenous anesthesia with dexmedetomidine and propofol combined with seaweed polysaccharides is a promising strategy for painless induced abortion, which is worthy of application and popularization in clinical practice.

Cu-Doped-ZnO Nanocrystals Induce Hepatocyte Autophagy by Oxidative Stress Pathway.

As a novel nanomaterial for cancer therapy and antibacterial agent, Cu-doped-ZnO nanocrystals (CZON) has aroused concern recently, but the toxicity of CZON has received little attention. Results of hematology analysis and blood biochemical assay showed that a 50 mg/kg dosage induced the increase in white blood cells count and that the concentration of alanine aminotransferase (ALT), superoxide dismutase (SOD), catalase (CAT), and Malonaldehyde (MDA) in the serum, liver, and lungs of the CZON group varied significantly from the control mice. Histopathological examinations results showed inflammation and congestion in the liver and lung after a single injection of CZON at 50 mg/kg. A transmission electron microscope (TEM) result manifested the autolysosome of hepatocyte of mice which received CZON at 50 mg/kg. The significant increase in LC3-II and decrease in p62 of hepatocyte in vivo could be seen in Western blot. These results indicated that CZON had the ability to induce autophagy of hepatocyte. The further researches of mechanism of autophagy revealed that CZON could produce hydroxyl radicals measured by erythrocyte sedimentation rate (ESR). The result of bio-distribution of CZON in vivo, investigated by ICP-OES, indicated that CZON mainly accumulated in the liver and two spleen organs. These results suggested that CZON can induce dose-dependent toxicity and autophagy by inducing oxidative stress in major organs. In summary, we investigated the acute toxicity and biological distribution after the intravenous administration of CZON. The results of body weight, histomorphology, hematology, and blood biochemical tests showed that CZON had a dose-dependent effect on the health of mice after a single injection. These results indicated that CZON could induce oxidative damage of the liver and lung by producing hydroxyl radicals at the higher dose.

TB@PLGA Nanoparticles for Photodynamic/Photothermal Combined Cancer Therapy with Single Near-Infrared Irradiation.

BACKGROUND: Phototherapy has significant potential as an effective treatment for cancer. However, the application of a multifunctional nanoplatform for photodynamic therapy (PDT) and photothermal therapy (PTT) at a single excitation wavelength remains a challenge. MATERIALS AND METHODS: The double emulsion solvent evaporation method was used to prepare toluidine blue@poly lactic-co-glycolic acid (TB@PLGA) nanoparticles (NPs). The biocompatibility of TB@PLGA NPs was evaluated, and a 660 nm luminescence was used as the light source. The photothermal effect, photothermal stability, and singlet oxygen yield of NPs in an aqueous solution verified the feasibility of NPs as a PTT/PDT synergistic therapy drug. RESULTS: TB@PLGA NPs were successfully prepared and characterized. In vitro experiments demonstrated that TB@PLGA NPs can cause massive necrosis of tumor cells and induce apoptosis through a photodynamic mechanism under 660 nm laser irradiation. The TB@PLGA NPs also achieved optimal tumor inhibition effect in vivo. CONCLUSION: The TB@PLGA NPs prepared in this study were applied as a dual-mode phototherapeutic agent under single laser irradiation. Both in vitro and in vivo experiments demonstrated the good potential of PTT/PDT for tumor inhibitors.

MicroRNA-155 influences cell damage in ischemic stroke via TLR4/MYD88 signaling pathway.

Cerebral ischemic stroke (CIS) is extremely harmful, and its treatment should be underpinned by understanding its pathogenic mechanism. This study was designed to determine the involvement of miR-155 in CIS development via the TLR4/MyD88 signaling pathway. First, we quantified serum miR-155 in patients with CIS and healthy individuals, and found high expression of miR-155 in such patients and a decrease in it in the patients after therapy (P < 0.05). Serum miR-155 demonstrated a favorable function in predicting the development and prognosis of CIS (P < 0.001). We also conducted a mouse assay, and found that knocking out miR-155 can improve the neurological function of mice and suppress protein TLR4 and MyD88 (all P < 0.05). Finally, we carried out a cell assay, and found enhancement in the activity of SH-SY5Y cells, decrease in their apoptosis, and protein TLR4 and MyD88 in them after suppression of miR-155 (all P < 0.05). Furthermore, we also found complete reverse by TLR4/MyD88 pathway inhibitor on the influence of increasing miR-155 on cells (P > 0.05). Therefore, with an increase in cases with CIS, miR-155 takes a part in the development of cell damage by activating TLR4/MyD88, and it is probably the key to diagnosing and treating CIS.

High Li-Ion Conductivity Artificial Interface Enabled by Li-Grafted Graphene Oxide for Stable Li Metal Pouch Cell.

The fragile electrolyte/Li interface is responsible for the long-lasting consumption of Li resources and fast failure of Li metal batteries. The polymer artificial interface with high mechanical flexibility is a promising candidate to maintain the stability of the electrolyte/Li interface; however, sluggish Li-ion transportation of the conventional polymer interface hinders the application. In this work, Li-functionalized graphene oxide (GO-ADP-Li3), which is synthesized by covalent grafting of adenosine 5'-diphosphate lithium on GO nanosheets, is used as a functional additive to improve the Li-ion conductivity of the polymer artificial interface based on PVDF-HFP/LiTFSI. The enhanced Li-ion conductivity is contributed by accelerated Li-ion hopping at the surface between polymer chains and functionalized GO as well as the reduced crystallization degree of PVDF-HFP by this novel additive. The use of this modified polymer as an artificial interface on Li foil enables highly reversible Li stripping/plating and a high capacity retention of 78.4% after 150 cycles for a 0.2 A h Li metal pouch cell (Li/NCM811, strictly following practical conditions). This Li-grafted strategy on GO sheets provides an alternative for designing a compatible electrolyte/Li interface for practical Li metal batteries.

Analysis of ceRNA networks and identification of potential drug targets for drug-resistant leukemia cell K562/ADR.

BACKGROUND: Drug resistance is the main obstacle in the treatment of leukemia. As a member of the competitive endogenous RNA (ceRNA) mechanism, underlying roles of lncRNA are rarely reported in drug-resistant leukemia cells. METHODS: The gene expression profiles of lncRNAs and mRNAs in doxorubicin-resistant K562/ADR and sensitive K562 cells were established by RNA sequencing (RNA-seq). Expression of differentially expressed lncRNAs (DElncRNAs) and DEmRNAs was validated by qRT-PCR. The potential biological functions of DElncRNAs targets were identified by GO and KEGG pathway enrichment analyses, and the lncRNA-miRNA-mRNA ceRNA network was further constructed. K562/ADR cells were transfected with CCDC26 and LINC01515 siRNAs to detect the mRNA levels of GLRX5 and DICER1, respectively. The cell survival rate after transfection was detected by CCK-8 assay. RESULTS: The ceRNA network was composed of 409 lncRNA-miRNA pairs and 306 miRNA-mRNA pairs based on 67 DElncRNAs, 58 DEmiRNAs and 192 DEmRNAs. Knockdown of CCDC26 and LINC01515 increased the sensitivity of K562/ADR cells to doxorubicin and significantly reduced the half-maximal inhibitory concentration (IC50) of doxorubicin. Furthermore, knockdown of GLRX5 and DICER1 increased the sensitivity of K562/ADR cells to doxorubicin and significantly reduced the IC50 of doxorubicin. CONCLUSIONS: The ceRNA regulatory networks may play important roles in drug resistance of leukemia cells. CCDC26/miR-140-5p/GLRX5 and LINC01515/miR-425-5p/DICER1 may be potential targets for drug resistance in K562/ADR cells. This study provides a promising strategy to overcome drug resistance and deepens the understanding of the ceRNA regulatory mechanism related to drug resistance in CML cells.

Regulatory role of long non-coding RNA UCA1 in signaling pathways and its clinical applications.

Long non-coding RNA metastasis-associated urothelial carcinoma associated 1 (UCA1) plays a pivotal role in various human diseases. Its gene expression is regulated by several factors, including transcription factors, chromatin remodeling and epigenetic modification. UCA1 is involved in the regulation of the PI3K/AKT, Wnt/ß-catenin, MAPK, NF-κB and JAK/STAT signaling pathways, affecting a series of cellular biological functions, such as cell proliferation, apoptosis, migration, invasion and tumor drug resistance. Furthermore, UCA1 is used as a novel potential biomarker for disease diagnosis and prognosis, as well as a target for clinical gene therapy. The present review systematically summarizes and elucidates the mechanisms of upstream transcriptional regulation of UCA1, the regulatory role of UCA1 in multiple signaling pathways in the occurrence and development of several diseases, and its potential applications in clinical treatment.

Cellular senescence and hematological malignancies: From pathogenesis to therapeutics.

Cellular senescence constitutes a permanent state of cell cycle arrest in proliferative cells induced by different stresses. The exploration of tumor pathogenesis and therapies has been a research hotspot in recent years. Cellular senescence is a significant mechanism to prevent the proliferation of potential tumor cells, but it can also promote tumor growth. Increasing evidence suggests that cellular senescence is involved in the pathogenesis and development of hematological malignancies, including leukemia, myelodysplastic syndrome (MDS) and multiple myeloma (MM). Cellular senescence is associated with functional decline of hematopoietic stem cells (HSCs) and increased risk of hematological malignancies. Moreover, the bone marrow (BM) microenvironment has a crucial regulatory effect in the process of these diseases. The senescence-associated secretory phenotype (SASP) in the BM microenvironment establishes a protumor environment that supports the proliferation and survival of tumor cells. Therefore, a series of therapeutic strategies targeting cellular senescence have been gradually developed, including the induction of cellular senescence and elimination of senescent cells. This review systematically summarizes the emerging information describing the roles of cellular senescence in tumorigenesis and potential clinical applications, which may be beneficial for designing rational therapeutic strategies for various hematopoietic malignancies.

Dietary exposure of general Chinese population to fatty acid esters of 3-monochloropropane-1, 2-diol (3-MCPD) from edible oils and oil-containing foods.

Edible oils and oil-containing foods have been regarded as the main source of 3-monochloropropane-1, 2-diol (3-MCPD) esters. A total of 3,847 individual food samples were collected in China to carry out 3-MCPD fatty acid esters analysis. The samples comprising edible oils, fried foods and bakery foods from 31 Chinese provinces, municipalities and autonomous regions were obtained from the national food contaminant information system during 2015-2017. The dietary exposure and potential risks associated with the consumption of 3-MPCD esters from edible oils and oil-containing foods were estimated using a semi-probabilistic assessment model. Concentrations of 3-MCPD fatty acid esters in food samples were detected by gas chromatography-mass spectrometry (GC-MS). The mean levels of 3-MCPD fatty acid esters in edible oils, fried foods and bakery foods were 0.862, 0.249 and 0.145 mg/kg, respectively. The range of mean dietary intakes of 3-MCPD esters in different subpopulation groups (classified by gender and age) was from 0.586 to 1.539 µg/kg bw/day, which were all lower than 2 µg/kg bw/day - the tolerable daily intake (TDI) established by the European Food Safety Authority (EFSA). The range of dietary intake of 3-MCPD esters in high consumers (95th percentile) in each group was from 1.511 to 4.027 µg/kg bw/day, which accounted for 75.6% to 201.4% of the TDI. The 3-MCPD esters exposure level of 3.5% of the total Chinese population exceeded the TDI. The findings indicate that the potential health risks caused by dietary 3-MCPD esters from edible oils and oil-containing foods were of low concern for most of the Chinese population. However, the exposure risk of the consumers with excessive edible oil consumption calls for attention.