High-Concentrated Binary-Salt Ether Electrolytes for High-Voltage Lithium Metal Batteries with Ni-Rich Cathode.

The incompatibility of ether electrolytes with a cathode dramatically limits its application in high-voltage Li metal batteries. Herein, we report a new highly concentrated binary salt ether-based electrolyte (HCBE, 1.25 M LiTFSI + 2.5 M LiFSI in DME) that enables stable cycling of high-voltage lithium metal batteries with the Ni-rich (NCM83, LiNi0.83Co0.12Mn0.05O2) cathode. Experimental characterizations and density functional theory (DFT) calculations reveal the special solvation structure in HCBE. A solvation structure rich in aggregates (AGGs) can effectively broaden the electrochemical window of the ether electrolyte. The anions in HCBE preferentially decompose under high voltage, forming a CEI film rich in inorganic components to protect the electrolyte from degradation. Thus, the high-energy-density Li||NCM83 cell has a capacity retention of ≈95% after 150 cycles. Significantly, the cells in HCBE have a high and stable average Coulombic efficiency of over 99.9%, much larger than that of 1 M LiPF6 + EC + EMC + DMC (99%). The result emphasizes that the anionic-driven formation of a cathode electrolyte interface (CEI) can reduce the number of interface side reactions and effectively protect the cathode. Furthermore, the Coulombic efficiency of Li||Cu using the HCBE is 98.5%, underscoring the advantages of using ether-based electrolytes. This work offers novel insights and approaches for the design of high-performance electrolytes for lithium metal batteries.

Hyperspectal imaging technology for phenotyping iron and boron deficiency in Brassica napus under greenhouse conditions.

Introduction: The micronutrient deficiency of iron and boron is a common issue affecting the growth of rapeseed (Brassica napus). In this study, a non-destructive diagnosis method for iron and boron deficiency in Brassica napus (genotype: Zhongshuang 11) using hyperspectral imaging technology was established. Methods: The recognition accuracy was compared using the Fisher Linear Discriminant Analysis (LDA) and Support Vector Machine (SVM) recognition models. Recognition results showed that Multiple Scattering Correction (MSC) could be applied for the full band hyperspectral data processing, while the LDA models presented better performance on establishing the leaf iron and boron deficiency symptom recognition than the SVM models. Results: The recognition accuracy of the training set reached 96.67%, and the recognition rate of the prediction set could be 91.67%. To improve the model accuracy, the Competitive Adaptive Reweighted Sampling algorithm (CARS) was added to construct the MSC-CARS-LDA model. 33 featured wavelengths were selected via CARS. The recognition accuracy of the MSC-CARS-LDA training set was 100%, while the recognition accuracy of the MSC-CARS-LDA prediction set was 95.00%. Discussion: This study indicates that, it is capable to identify the iron and boron deficiency in rapeseed using hyperspectral imaging technology.

mPPTMP195 nanoparticles enhance fracture recovery through HDAC4 nuclear translocation inhibition.

Delayed repair of fractures seriously impacts patients' health and significantly increases financial burdens. Consequently, there is a growing clinical demand for effective fracture treatment. While current materials used for fracture repair have partially addressed bone integrity issues, they still possess limitations. These challenges include issues associated with autologous material donor sites, intricate preparation procedures for artificial biomaterials, suboptimal biocompatibility, and extended degradation cycles, all of which are detrimental to bone regeneration. Hence, there is an urgent need to design a novel material with a straightforward preparation method that can substantially enhance bone regeneration. In this context, we developed a novel nanoparticle, mPPTMP195, to enhance the bioavailability of TMP195 for fracture treatment. Our results demonstrate that mPPTMP195 effectively promotes the differentiation of bone marrow mesenchymal stem cells into osteoblasts while inhibiting the differentiation of bone marrow mononuclear macrophages into osteoclasts. Moreover, in a mouse femur fracture model, mPPTMP195 nanoparticles exhibited superior therapeutic effects compared to free TMP195. Ultimately, our study highlights that mPPTMP195 accelerates fracture repair by preventing HDAC4 translocation from the cytoplasm to the nucleus, thereby activating the NRF2/HO-1 signaling pathway. In conclusion, our study not only proposes a new strategy for fracture treatment but also provides an efficient nano-delivery system for the widespread application of TMP195 in various other diseases.

A novel transformer-based DL model enhanced by position-sensitive attention and gated hierarchical LSTM for aero-engine RUL prediction.

Accurate prediction of remaining useful life (RUL) for aircraft engines is essential for proactive maintenance and safety assurance. However, existing methods such as physics-based models, classical recurrent neural networks, and convolutional neural networks face limitations in capturing long-term dependencies and modeling complex degradation patterns. In this study, we propose a novel deep-learning model based on the Transformer architecture to address these limitations. Specifically, to address the issue of insensitivity to local context in the attention mechanism employed by the Transformer encoder, we introduce a position-sensitive self-attention (PSA) unit to enhance the model's ability to incorporate local context by attending to the positional relationships of the input data at each time step. Additionally, a gated hierarchical long short-term memory network (GHLSTM) is designed to perform regression prediction at different time scales on the latent features, thereby improving the accuracy of RUL estimation for mechanical equipment. Experiments on the C-MAPSS dataset demonstrate that the proposed model outperforms existing methods in RUL prediction, showcasing its effectiveness in modeling complex degradation patterns and long-term dependencies.

Tuning the End Alkyl Chain of the Ether Solvent to Stabilize the Electrode/Electrolyte Interfaces in the NCM-Li Battery.

Lithium metal batteries (LMBs) combined with a high-voltage nickel-rich cathode show great potential in meeting the growing need for high energy density. The lack of advanced electrolytes has been a major obstacle in the commercialization of high-voltage lithium metal batteries (LMBs), as these electrolytes need to effectively support both a stable lithium metal anode (LMA) and a high-voltage cathode (>4 V vs Li+/Li). In this work, by extending the two terminal methyl groups in DIGDME and TEGDME to n-butyl groups, we design a new weakly solvating electrolyte (2 M LIFSI+TEGDBE) that enables the stable cycling of NMC83 (LiNi0.83Co0.12Mn0.05O2) cathodes. The NMC83 cell exhibits a high and stable Coulombic efficiency (CE) of over 99%, as well as capacity retention of approximately 99.8% after 100 cycles at 0.3 C. X-ray photoelectron spectroscopy analysis (XPS) and high-resolution transmission electron microscope (HRTEM) images revealed that the anion species decomposed first, resulting in the formation of a cathode-electrolyte interface (CEI) film predominantly consisting of decomposition products from the anions on the positive electrode surface. This work links the functional group of solvents with the solvation structure and electrochemical performance of ether-based electrolytes, providing a distinctive sight to design advanced electrolytes for high-energy-density LMBs.

Mitigating heavy metal accumulation in tobacco: Strategies, mechanisms, and global initiatives.

The threat of heavy metal (HM) pollution looms large over plant growth and human health, with tobacco emerging as a highly vulnerable plant due to its exceptional absorption capacity. The widespread cultivation of tobacco intensifies these concerns, posing increased risks to human health as HMs become more pervasive in tobacco-growing soils globally. The absorption of these metals not only impedes tobacco growth and quality but also amplifies health hazards through smoking. Implementing proactive strategies to minimize HM absorption in tobacco is of paramount importance. Various approaches, encompassing chemical immobilization, transgenic modification, agronomic adjustments, and microbial interventions, have proven effective in curbing HM accumulation and mitigating associated adverse effects. However, a comprehensive review elucidating these control strategies and their mechanisms remains notably absent. This paper seeks to fill this void by examining the deleterious effects of HM exposure on tobacco plants and human health through tobacco consumption. Additionally, it provides a thorough exploration of the mechanisms responsible for reducing HM content in tobacco. The review consolidates and synthesizes recent domestic and international initiatives aimed at mitigating HM content in tobacco, delivering a comprehensive overview of their current status, benefits, and limitations.

HIV/HBV coinfection: understanding the complex interactions and their impact on spontaneous HBV clearance, chronic liver damage, cirrhosis, and hepatocellular carcinoma.

Compared to either HIV or hepatitis B virus (HBV) monoinfected individuals, HIV/HBV-coinfected individuals have a decreased probability of spontaneous HBV clearance and a greater risk of developing chronic liver damage and a faster progression to cirrhosis and hepatocellular carcinoma. This manuscript attempts to provide a comprehensive review of the landscape of current HIV/HBV coinfection research with a focus on the intricate interactions between these two viruses. Our review will help understand the disease dynamics of HIV/HBV coinfection and has important implications for designing public health strategies.

16S full-length gene sequencing analysis of intestinal flora in breast cancer patients in Hainan Province.

Breast cancer has become the number one cancer in the world, and intestinal flora may be closely linked to it. Geographic location also has an important impact on human intestinal flora. We conducted the first study on the intestinal flora of breast cancer patients and non-breast cancer patients in a tropical region - Hainan Province in China. At the same time, Pacbio platform based on third-generation sequencing was used for the first time to conduct 16S full-length sequencing of fecal microorganism DNA. We completed the species diversity analysis and differential species analysis of the intestinal flora between the two groups, inferred their functional genetic composition and performed functional difference analysis. There were statistically significant differences in alpha diversity between the two groups in Hainan Province. By species composition difference analysis, at the phylum level, Bacteroidales (P = 0.006) and Firmicutes (P = 0.002) was differed between the two groups, and at the genus level, 17 breast cancer-related differential species such as Bacteroides were screened. According to the five grouping methods including ER level, PR level, HER2 status, Ki67 index and histological grade of breast cancer patients, 4, 1, 9, 6, 5 differential microbiota were screened out respectively, which were in total 25 (P < 0.05 for all subgroups) . The functional prediction and difference analysis revealed two functional metabolisms with significant differences between the two groups of microbes (P < 0.05). These results suggest that breast cancer is associated with changes in the composition and function of intestinal flora. These microflora and functional differences may become biomarkers or new targets for diagnosis and treatment of breast cancer.

Low Expression of BIRC5-206 Promotes Cancer Progression in Nasopharyngeal Carcinoma via Enhancing Expression of Stem Cell Markers.

OBJECTIVE: Survivin is highly expressed in various malignant tumor cells and positively related to poor prognosis and drug resistance. This study aimed to explore the role of non-coding splice variant of Survivin, BIRC5-206 (ENST00000589892.1) in the progression of nasopharyngeal carcinoma (NPC), a malignant tumor that highly occurs in the southern region of China. METHODS: shRNA was used to knockdown BIRC5-206 mRNA level in CNE-2 and HOPNE-1 cells. Then, cell death, migration, invasion and clone formation ability of CNE-2 and HOPNE-1 cells were detected by flow cytometry, scratch-healing experiments, transwell invasion assay and clone formation assay, respectively. CD44+ and CD133+ positive cells were determined via Flow cytometry. Oct4, Nanog and SOX2 protein levels in CNE-2 and HOPNE-1 cells were measured by Western blot. RESULTS: BIRC5-206 decreased significantly in NPC cell lines. Silencing of BIRC5-206 suppressed the apoptosis, facilitated the migration, invasion and proliferation of both HONE1 and CNE-2 cells. In addition, knockdown of BIRC5-206 significantly promoted the expression cancer stem cell marker (CD44 and CD133) and pluripotency markers (Oct4, Sox2 and Nanog). CONCLUSIONS: BIRC5-206 might facilitate NPC tumor progression by inducing the transformation of NPC cells to cancer stem cells.

Nitrate_dependent suberization regulates cadmium uptake and accumulation in maize.

In this study, effect of nitrate-dependent suberization in maize root on cadmium (Cd) uptake and accumulation was investigated. Suberization in maize roots was significantly lower in plants grown with a high nitrate supply compared with low nitrate. This decrease was seen in the total amount of suberin, in which the aliphatic suberin amount was significantly decreased, whereas no difference in aromatic suberin content between different N-treatments. RNA-sequencing showed that suberin biosynthesis genes were upregulated in low nitrate treatment, which correlated well with the increased suberin content. Bioimaging and xylem sap analysis showed that reduced exodermal and endodermal suberization in roots of plants grown under high nitrate promoted radial Cd transport along the crown root. The enhanced suberization in crown roots of plants grown in low nitrate restricted the radial transport of Cd from epidermis to cortex via decreased accessibility to Cd related transporters at the plasmalemma. Also, under low nitrate supply, the Cd transport gene ZmNramp5 was upregulated in the crown root, which may enhance Cd uptake by root tip where exodermis and endodermis were not fully suberized. These results suggest that high nitrate supply enhances Cd uptake and radial transport in maize roots by reducing exodermal and endodermal suberization.

Alfuzosin ameliorates diabetes by boosting PGK1 activity in diabetic mice.

AIMS: Diabetes mellitus (DM) has become a global problem, causing a huge economic burden. The purpose of this study is to find a new potential method and mechanism for the treatment of DM. MAIN METHODS: The oxidation, glycation and insulin resistance cell models were built to screen the potential anti-diabetic chemicals. Then the DM mice were induced by the combination of high-fat diet (HFD) and intraperitoneal injection of streptozotocin (50 mg/kg) for five days. The alfuzosin (1.2 mg/kg) was administered by intraperitoneal injection once daily for sequential 12 weeks. Fasting blood glucose, blood lipid, oxidative stress and key markers of glucose metabolism were detected. PGK1/AKT/GLUT4 pathway related proteins were analyzed by Western blot. KEY FINDINGS: Alfuzosin ameliorated oxidative stress, glycative stress and insulin resistance in HepG2 cells. Further, in a high-fat diet/streptozotocin (HFD/STZ)-induced diabetic mouse model, alfuzosin reduced fasting blood glucose, improved insulin sensitivity. Mechanically, alfuzosin activated PGK1 directly to stimulate the protein kinase B (AKT) signaling pathway, thus facilitating glucose uptake as well as improving insulin resistance. SIGNIFICANCE: The present finding has shed a new light on the treatment of DM and provides validation for PGK1 as a therapeutic target for DM.

FTY720 Attenuates LPS-Induced Inflammatory Bone Loss by Inhibiting Osteoclastogenesis via the NF-κB and HDAC4/ATF Pathways.

Osteoclast (OC) abnormalities lead to many osteolytic diseases, such as osteoporosis, inflammatory bone erosion, and tumor-induced osteolysis. Exploring effective strategies to remediate OCs dysregulation is essential. FTY720, also known as fingolimod, has been approved for the treatment of multiple sclerosis and has anti-inflammatory and immunosuppressive effects. Here, we found that FTY720 inhibited osteoclastogenesis and OC function by inhibiting nuclear factor kappa-B (NF-κB) signaling. Interestingly, we also found that FTY720 inhibited osteoclastogenesis by upregulating histone deacetylase 4 (HDAC4) expression levels and downregulating activating transcription factor 4 (ATF4) expression levels. In vivo, FTY720 treatment prevented lipopolysaccharide- (LPS-) induced calvarial osteolysis and significantly reduced the number of tartrate-resistant acid phosphatase- (TRAP-) positive OCs. Taken together, these results demonstrate that FTY720 can inhibit osteoclastogenesis and ameliorate inflammation-induced bone loss. Which may provide evidence of a new therapeutic target for skeletal diseases caused by OC abnormalities.

Sulfathiazole treats type 2 diabetes by restoring metabolism through activating CYP19A1.

Globally, diabetes mellitus has been a major epidemic bringing metabolic and endocrine disorders. Currently, 1 in 11 adults suffers from diabetes mellitus, among the patients >90% contract type 2 diabetes mellitus (T2DM). Therefore, it is urgent to develop new drugs that effectively prevent and treat type 2 diabetes through new targets. With high-throughput screening, we found that sulfathiazole decreased the blood glucose and improved glucose metabolism in T2DM mice. Notably, we discovered that sulfathiazole treated T2DM by activating CYP19A1 protein to synthesize estrogen. Collectively, sulfathiazole along with CYP19A1 target bring new promise for the better therapy of T2DM.

Quinacrine attenuates diet-induced obesity by inhibiting adipogenesis via activation of AMPK signaling.

Obesity, a global epidemic chronic metabolic disease, urgently demands novel therapies. As an antimalarial drug, quinacrine has not been reported for its anti-obesity effect to our knowledge. This study aimed to explore the ability of quinacrine to attenuate obesity. In an in vitro adipogenic model, quinacrine exhibited an outstanding suppression on adipogenesis of 3T3-L1 cells, mainly by activating the AMPK (Adenosine 5'-monophosphate (AMP)-activated protein kinase) signaling pathway to regulate preadipocytes differentiation and lipid accumulation. In addition, C57BL/6N female mice were fed with high-fat diet and high-fructose water for 14 weeks to establish an obesity model, followed by oral administration of quinacrine or orlistat. After 9 weeks of treatment, quinacrine significantly reduced the body weight and energy intake, ameliorated the impaired glucose tolerance and restored the homeostasis of serum lipids. Also, quinacrine improved lipid profile and optimized the expression of AMPK signaling pathway related proteins in livers and adipose tissues of obese mice. Quinacrine reverses obesity through activating AMPK phosphorylation to down-regulate adipogenesis, along with lowering the risk of type 2 diabetes and atherosclerosis. It should be a novel application for the treatment of obesity and its associated diseases.

Primaquine activates Keratin 7 to treat diabetes and its complications.

Background: The global prevalence of type 2 diabetes mellitus (T2DM) raises the rates of its complications, such as diabetic nephropathy and cardiovascular diseases. To conquer the complications, new strategies to reverse the deterioration of T2DM are urgently needed. In this project, we aimed to examine the hypoglycemic effect of primaquine and explore its specific target. Methods: In vitro T2DM insulin resistance model was built in HepG2 cells to screen the potential anti-diabetic chemicals. On the other hand, the potential protein targets were explored by molecular docking. Accordingly, we chose C57BL/6 N mice to establish T2DM model to verify the effect of the chemicals on anti-hyperglycemia and diabetic complications. Results: By targeting the Keratin 7 (K7) to activate EGFR/Akt glucose metabolism signaling pathway, primaquine poses a potent hypoglycemic effect. The level of acetyl-CoA is enhanced markedly, supporting that primaquine upregulates the aerobic glycolysis. Moreover, primaquine ameliorates kidney function by reducing the secretion of urinary proteins and creatinine, especially for the urea nitrogen which is significantly decreased compared to no-treatment T2DM mice. Notably, primaquine restores the level of plasma low-density lipoprotein cholesterol (LDL-C) nearly to normal, minimizing the incidence of cardiovascular diseases. Conclusions: We find that primaquine may reverse the dysregulated metabolism to prevent diabetic complications by stimulating EGFR/Akt signaling axis, shedding new light on the therapy of T2DM. Graphical abstract: Insulin resistance is characterized by reduced p-Akt and glucose metabolism, dominated by anaerobic glycolysis. Primaquine activates the complex made of K7 and EGFR, further stimulating Akt phosphorylation. Then, p-Akt promotes the aerobic glucose metabolism and upregulates Ac-CoA to mobilize TCA cycle, improving insulin sensitivity. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-01135-8.

Functional characterization of a gamma-glutamyl phosphate reductase ProA in proline biosynthesis and promoting expression of type three secretion system in Ralstonia solanacearum.

Ralstonia solanacearum RSc2741 has been predicted as a gamma-glutamyl phosphate reductase ProA catalyzing the second reaction of proline formation from glutamate. Here, we experimentally demonstrated that proA mutants were proline auxotrophs that failed to grow in a minimal medium, and supplementary proline, but not glutamate, fully restored the diminished growth, confirming that ProA is responsible for the biosynthesis of proline from glutamate in R. solanacearum. ProA was previously identified as one of the candidates regulating the expression of genes for type three secretion system (T3SS), one of the essential pathogenicity determinants of R. solanacearum. Supplementary proline significantly enhanced the T3SS expression both in vitro and in planta, indicating that proline is a novel inducer of the T3SS expression. Deletion of proA substantially impaired the T3SS expression both in vitro and in planta even under proline-supplemented conditions, indicating that ProA plays additional roles apart from proline biosynthesis in promoting the expression of the T3SS genes. It was further revealed that the involvement of ProA in the T3SS expression was mediated through the pathway of PrhG-HrpB. Both the proA mutants and the wild-type strain grew in the intercellular spaces of tobacco leaves, while their ability to invade and colonize tobacco xylem vessels was substantially impaired, which was about a 1-day delay for proA mutants to successfully invade xylem vessels and was about one order of magnitude less than the wild-type strain to proliferate to the maximum densities in xylem vessels. It thus resulted in substantially impaired virulence of proA mutants toward host tobacco plants. The impaired abilities of proA mutants to invade and colonize xylem vessels were not due to possible proline insufficiency in the rhizosphere soil or inside the plants. All taken together, these results extend novel insights into the understanding of the biological function of ProA and sophisticated regulation of the T3SS and pathogenicity in R. solanacearum.

Thromboxane-Prostanoid Receptor Signaling Drives Persistent Fibroblast Activation in Pulmonary Fibrosis.

Rationale: Although persistent fibroblast activation is a hallmark of idiopathic pulmonary fibrosis (IPF), mechanisms regulating persistent fibroblast activation in the lungs have not been fully elucidated. Objectives: On the basis of our observation that lung fibroblasts express TBXA2R (thromboxane-prostanoid receptor) during fibrosis, we investigated the role of TBXA2R signaling in fibrotic remodeling. Methods: We identified TBXA2R expression in lungs of patients with IPF and mice and studied primary mouse and human lung fibroblasts to determine the impact of TBXA2R signaling on fibroblast activation. We used TBXA2R-deficient mice and small-molecule inhibitors to investigate TBXA2R signaling in preclinical lung fibrosis models. Measurements and Main Results: TBXA2R expression was upregulated in fibroblasts in the lungs of patients with IPF and in mouse lungs during experimental lung fibrosis. Genetic deletion of TBXA2R, but not inhibition of thromboxane synthase, protected mice from bleomycin-induced lung fibrosis, thereby suggesting that an alternative ligand activates profibrotic TBXA2R signaling. In contrast to thromboxane, F2-isoprostanes, which are nonenzymatic products of arachidonic acid induced by reactive oxygen species, were persistently elevated during fibrosis. F2-isoprostanes induced TBXA2R signaling in fibroblasts and mediated a myofibroblast activation profile due, at least in part, to potentiation of TGF-ß (transforming growth factor-ß) signaling. In vivo treatment with the TBXA2R antagonist ifetroban reduced profibrotic signaling in the lungs, protected mice from lung fibrosis in three preclinical models (bleomycin, Hermansky-Pudlak mice, and radiation-induced fibrosis), and markedly enhanced fibrotic resolution after bleomycin treatment. Conclusions: TBXA2R links oxidative stress to fibroblast activation during lung fibrosis. TBXA2R antagonists could have utility in treating pulmonary fibrosis.

Acyclovir alleviates insulin resistance via activating PKM1 in diabetic mice.

AIMS: Diabetes mellitus (DM) is a major global health threat characterized by insulin resistance. A new tactic to ameliorate insulin resistance, thereby reversing the exacerbation of DM, is urgently needed. The work is aiming to provide a new strategy for DM treatment as well as to identify new targets. MAIN METHODS: C57BL/6 N mice were raised with high-fat diet (HFD) and infused with streptozotocin (STZ) to induce diabetes. The blood glucose, serum insulin, blood lipid and oxidative stress were detected. In vitro insulin resistance model experiment has been made to examine the molecular mechanisms underlying anti-diabetic effect of potential active chemicals in human hepatocellular carcinoma cells (HepG2). KEY FINDINGS: Acyclovir, an antiviral nucleotide analog, alleviates insulin resistance by reducing blood lipids as well as oxidative stress and elevating insulin sensitivity on diabetic mice, which is in accord with results in the insulin resistance model of HepG2 cells. Mechanically, acyclovir stimulates pyruvate kinase M1 (PKM1) directly to activate adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/Sirtuin1 (SIRT1) signaling pathway, thus improving insulin resistance. SIGNIFICANCE: The present study supports that acyclovir should be translated to remedy DM, and PKM1 might be a valuable target to develop new medicines.

TTN-AS1 accelerates the growth and migration of nasopharyngeal carcinoma cells via targeting miR-876-5p/NETO2.

Nasopharyngeal carcinoma (NPC) is one of the most predominant cancers occurring in China with high morbidity. Lately, large quantities of long non-coding RNAs (lncRNAs) have been highlighted to regulate the biological activities in multiple tumors, including NPC. Our study centered on whether TTN-AS1 was involved in NPC and how it modulated the progression of NPC. Here, qRT-PCR data uncovered that TTN-AS1 expression was conspicuously high in NPC cells. Based on the results of functional assays, TTN-AS1 silence hampered the proliferative, migratory, and invasive abilities but stimulated the apoptotic capability of NPC cells. After a series of mechanism assays, TTN-AS1 was found to competitively bind with miR-876-5p and recruit UPF1 to enhance NETO2 expression. In addition, TTN-AS1 could be transcriptionally activated by YY1 in NPC cells. It was also found that miR-876-5p overexpression or NETO2 downregulation had inhibitory effects on cell proliferation, migration, and invasion in NPC. Moreover, NETO2 upregulation could restore the suppressive impacts of TTN-AS1 depletion on NPC cell and tumor growth. In conclusion, YY1-activated TTN-AS1 interacted with both miR-876-5p and UPF1 to upregulate NETO2, thus strengthening NPC cell malignant behaviors, which might provide more useful information for people to develop effective NPC treatments.

Malignancies in people living with HIV.

Almost 40 years have passed since the first case of what is known as AIDS was documented. In these 40 years, AIDS has always been a research challenge and hot spot. Researchers and scientists have made tremendous progress in basic and clinical research on HIV. In particular, the widespread use of antiretroviral therapy (ART) has made it less of a deadly disease today and more of a manageable one. In the post- ART era when ART can significantly improve the immunity of people living with HIV (PLWH) and extend their life, the incidence of non-AIDS-defined cancers is greatly increased. Factors related to immunosuppression do not seem to explain this problem sufficiently. This suggests that besides immunosuppression, there are other mechanisms that may also contribute to the increased incidence of cancer in PLWH. Here, we summarized and discussed four possible mechanisms for the increased incidence of cancers in PLWH: immunosuppression, oncogenic viral infection, chronic infection, inflammatory damage, and the direct impact of HIV.