A membrane-based seawater electrolyser for hydrogen generation.

Electrochemical saline water electrolysis using renewable energy as input is a highly desirable and sustainable method for the mass production of green hydrogen1-7; however, its practical viability is seriously challenged by insufficient durability because of the electrode side reactions and corrosion issues arising from the complex components of seawater. Although catalyst engineering using polyanion coatings to suppress corrosion by chloride ions or creating highly selective electrocatalysts has been extensively exploited with modest success, it is still far from satisfactory for practical applications8-14. Indirect seawater splitting by using a pre-desalination process can avoid side-reaction and corrosion problems15-21, but it requires additional energy input, making it economically less attractive. In addition, the independent bulky desalination system makes seawater electrolysis systems less flexible in terms of size. Here we propose a direct seawater electrolysis method for hydrogen production that radically addresses the side-reaction and corrosion problems. A demonstration system was stably operated at a current density of 250 milliamperes per square centimetre for over 3,200 hours under practical application conditions without failure. This strategy realizes efficient, size-flexible and scalable direct seawater electrolysis in a way similar to freshwater splitting without a notable increase in operation cost, and has high potential for practical application. Importantly, this configuration and mechanism promises further applications in simultaneous water-based effluent treatment and resource recovery and hydrogen generation in one step.

Cellular and Molecular Network Characteristics of TARM1-Related Genes in Mycobacterium tuberculosis Infections.

Tuberculosis (TB) is a global infectious threat, and the emergence of multidrug-resistant TB has become a major challenge in eradicating the disease that requires the discovery of new treatment strategies. This study aimed to elucidate the immune infiltration and molecular regulatory network of T cell-interacting activating receptors on myeloid cell 1 (TARM1)-related genes based on a bioinformatics analysis. The GSE114911 dataset was obtained from the Gene Expression Omnibus (GEO) and screened to identify 17 TARM1-related differentially expressed genes (TRDEGs). Genes interacting with the TRDEGs were analyzed using a Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. A gene set enrichment analysis (GSEA) was used to identify the biological pathways significantly associated with a Mycobacterium tuberculosis (Mtb) infection. The key genes were obtained based on Cytoscape's cytoHubba plug-in. Furthermore, protein-protein interaction (PPI) networks were analyzed through STRING, while mRNA-RNA-binding protein (RBP) and mRNA-transcription factor (TF) interaction networks were developed utilizing the StarBase v3.0 and ChIPBase databases. In addition, the diagnostic significance of key genes was evaluated via receiver operating characteristic (ROC) curves, and the immune infiltration was analyzed using an ssGSEA and MCPCounter. The key genes identified in the GSE114911 dataset were confirmed in an independent GSE139825 dataset. A total of seventeen TRDEGs and eight key genes were obtained in a differential expression analysis using the cytoHubba plug-in. Through the GO and KEGG analysis, it was found that these were involved in the NF-κB, PI3K/Akt, MAPK, and other pathways related to inflammation and energy metabolism. Furthermore, the ssGSEA and MCPCounter analysis revealed a significant rise in activated T cells and T helper cells within the Mtb infection group, which were markedly associated with these key genes. This implies their potential significance in the anti-Mtb response. In summary, our results show that TRDEGs are linked to inflammation, energy metabolism, and immune cells, offering fresh insights into the mechanisms underlying TB pathogenesis and supporting further investigation into the possible molecular roles of TARM1 in TB, as well as assisting in the identification of prospective diagnostic biomarkers.

CD4+ Effective Memory T Cell Markers GBP2 and LAG3 Are Risk Factors for PTB and COVID-19 Infection: A Study Integrating Single-Cell Expression Quantitative Trait Locus and Mendelian Randomization Analyses.

Observational studies indicate that variations in peripheral blood mononuclear cell (PBMC) subsets are associated with an increased risk of pulmonary tuberculosis (PTB) and coronavirus disease 2019 (COVID-19), but causal validation is lacking. Here, we combined single-cell expression quantitative trait locus (sc-eQTL) and two-sample mendelian randomization (MR) analyses to elucidate the causal relationship between PBMC subsets and the occurrence of PTB and COVID-19 and verified by RT-qPCR. We observed an increase in the CD4+ Effective Memory T Cell (CD4+ TEM) cluster in both PTB and COVID-19 patients according to the single-cell transcriptional landscape of PBMC. Through MR analysis using an inverse variance weighted (IVW) method, we found strong evidence of positive correlations between CD4+ TEM cell markers (GBP2, TRAV1-2, and ODF2L) and PTB, and between markers (LAG3 and SLFN5) and COVID-19, especially highlighted by lead eQTL-SNPs of GBP2 (rs2256752, p = 4.76321 × 10-15) and LAG3 (rs67706382, p = 6.16× 10-16). Similar results were observed in validation sets, and no pleiotropy was detected in sensitivity analyses including weighted median (WM), MR-Egger, MR-pleiotropy residual sum and outlier, and leave-one-out analyses (all p > 0.05). We visualized the colocalization of marker-eQTLs and markers of PTB and COVID-19 genome-wide association study (GWAS) associations. Based on CellChat analyses, monocytes communicated predominantly with CD4+ TEM cells positively expressing PTB markers (GBP2, TRAV1-2, and ODF2L) and COVID-19 markers (LAG3 and SLFN5) in both PTB and COVID-19. Our data suggest a causal effect between two key CD4+ TEM cell markers (GBP2 and LAG3) and the risk for PTB and COVID-19 infection. Our findings provide novel insights into the biological mechanism for PTB and COVID-19 infection, but future single-cell studies are necessary to further enhance understanding of this find.

Calcitonin gene-related peptide inhibits angiotensin II-induced NADPH oxidase-dependent ROS via the Src/STAT3 signalling pathway.

We had previously demonstrated that the calcitonin gene-related peptide (CGRP) suppresses the oxidative stress and vascular smooth muscle cell (VSMC) proliferation induced by vascular injury. A recent study also indicated that CGRP protects against the onset and development of angiotensin II (Ang II)-induced hypertension, vascular hypertrophy and oxidative stress. However, the mechanism behind the effects of CGRP on Ang II-induced oxidative stress is unclear. CGRP significantly suppressed the level of reactive oxygen species (ROS) generated by NADPH oxidase in Ang II-induced VSMCs. The Ang II-stimulated activation of both Src and the downstream transcription factor, STAT3, was abrogated by CGRP. However, the antioxidative effect of CGRP was lost following the expression of constitutively activated Src or STAT3. Pre-treatment with H-89 or CGRP8-37 also blocked the CGRP inhibitory effects against Ang II-induced oxidative stress. Additionally, both in vitro and in vivo analyses show that CGRP treatment inhibited Ang II-induced VSMC proliferation and hypertrophy, accompanied by a reduction in ROS generation. Collectively, these results demonstrate that CGRP exhibits its antioxidative effect by blocking the Src/STAT3 signalling pathway that is associated with Ang II-induced VSMC hypertrophy and hyperplasia.

Calcitonin gene-related peptide attenuates angiotensin II-induced ROS-dependent apoptosis in vascular smooth muscle cells by inhibiting the CaMKII/CREB signalling pathway.

Apoptosis is associated with various cardiovascular diseases. CGRP exerts a variety of effects within the cardiovascular system, and protects against the onset and development of angiotensin (Ang) II-induced vascular dysfunction and remodelling. However, it is not known whether CGRP has a direct effect on Ang II-induced apoptosis in vascular smooth muscle cells (VSMCs), and the mechanism underlying the anti-apoptotic role remains unclear. In this study, CGRP significantly suppressed reactive oxygen species (ROS) and apoptosis in Ang II-induced VSMCs. In VSMCs pre-treated with a CGRP receptor antagonist (CGRP8-37), the CGRP-mediated inhibition of Ang II-induced ROS and apoptosis was completely abolished. Moreover, pre-treatment with N-acetyl-L cysteine (NAC), an ROS scavenger, blocked the effects of CGRP on Ang II-induced apoptosis. In addition, the activation of CaMKII and the downstream transcription factor CREB stimulated by Ang II was abrogated by CGRP. Importantly, in both CGRP and NAC-treated VSMCs, CGRP failed to further attenuate CaMKII and CREB activation. The results demonstrate that CGRP attenuated Ang II-induced ROS-dependent apoptosis in VSMCs by inhibiting the CaMKII/CREB signalling pathway.

Design, synthesis and biological evaluation of novel pteridinone derivatives possessing a hydrazone moiety as potent PLK1 inhibitors.

A series of novel pteridinone derivatives possessing a hydrazone moiety were designed, synthesized and evaluated for their biological activity. Most of the synthesized compounds demonstrated moderate to excellent activity against A549, HCT116 and PC-3 cancer cell lines. In particular, compound L19 exhibited the most potent antiproliferative effects on three cell lines with IC50 values of 3.23 µM, 4.36 µM and 8.20 µM, respectively. In kinase assays, the compound L19 also showed potent inhibition activity toward PLK1 with % inhibition values of 75.1. Further mechanism studies revealed that compound L19 significantly inhibited proliferation of HCT-116 cell lines, induced a great decrease in mitochondrial membrane potential resulting in apoptosis of cancer cells, inhibited the migration of tumor cells, and arrested G1 phase of HCT116 cells.

Total synthesis and structural revision of (+)-uprolide G acetate.

The first, asymmetric total synthesis of the proposed structure of (+)-uprolide G acetate (UGA) is reported, and the spectral properties of the synthetic compound clearly differed from those reported for natural UGA. On the basis of comprehensive analysis of the NMR data, two possible structures for the natural UGA were proposed and their total synthesis achieved, thus leading to the identification and confirmation of the correct structure and absolute configuration of the natural UGA. This synthesis was enabled by development of a novel synthetic strategy, which revolved around three key cyclization reactions: an Achmatowicz rearrangement, Sharpless asymmetric dihydroxylation/lactonization, and ring-closing metathesis. These synthetic studies pave the way for further studies on this class of structurally unusual cytotoxic cembranolides.

LINC00665 target let-7i/HMGA1 promotes the proliferation and invasion of hepatoma cells.

OBJECTIVES: Our group previously found that LINC00665 was upregulated in hepatocellular carcinoma (HCC) tissues through database analysis; however, the potential molecular mechanism of LINC00665 in HCC progression still needs further study. METHODS: qRTPCR was performed to determine the differential expression of LINC00665 and let-7i in HCC cells. Dual-luciferase reporter assays were performed to analyze the interaction of LINC00665 and let-7i. CCK-8 assays, scratch assays, Transwell invasion assays, qRTPCR and western blotting were performed to determine the regulatory mechanism of LINC00665/let-7i/HMGA1 in HCC cells. RESULTS: LINC00665 was upregulated in HCC cells compared with normal hepatocytes. A potential binding site between LINC00665 and let-7i was confirmed by dual-luciferase reporter assay. In HCC cells, inhibition of LINC00665 significantly reduced cell proliferation, migration and invasion ability via the let-7i/HMGA1 signaling axis. CONCLUSION: LINC00665 promotes the proliferation and invasion of HCC cells via the let-7i/HMGA1 signaling axis.

M2 macrophage exosome-derived lncRNA AK083884 protects mice from CVB3-induced viral myocarditis through regulating PKM2/HIF-1α axis mediated metabolic reprogramming of macrophages.

Viral myocarditis (VM) is a clinically common inflammatory disease. Accumulating literature has indicated that M2 macrophages protect mice from Coxsackievirus B3 (CVB3)-induced VM. However, mechanisms that underlie M2 macrophages alleviating myocardial inflammation remain largely undefined. We found that M2 macrophage-derived exosomes (M2-Exo) can effectively attenuate VM. The long non-coding RNA (lncRNA) AK083884 in M2-Exo was found to be involved in the regulation of macrophage polarization by exosome lncRNA sequencing combined with in vitro functional assays. M2-Exo-derived AK083884 promotes macrophage M2 polarization and protects mice from CVB3-induced VM. Furthermore, we identified pyruvate kinase M2 (PKM2) as a protein target binding to AK083884 and found that PKM2 knockdown could promote macrophages to polarize to M2 phenotype. Intriguingly, functional assay revealed that downregulation of AK083884 promotes metabolic reprogramming in macrophages. In addition, co-immunoprecipitation was performed to reveal AK083884 could interact with PKM2 and inhibition of AK083884 can facilitate the binding of PKM2 and HIF-1α. Collectively, our findings uncovered an important role of M2-Exo-derived AK083884 in the regulation of macrophage polarization through metabolic reprogramming, identified a new participant in the development of VM and provided a potential clinically important therapeutic target.

High ion barrier hydrogel with excellent toughness achieved by directional structures.

Owing to their nontoxicity, environmental friendliness, and high biocompatibility, physically cross-linked hydrogels have become popular research materials; however, their high water content and high free volume, along with the weak bonding interactions inherent to ordinary physically cross-linked hydrogels, limit their application in fields such as flexible devices, packaging materials, and substance transport regulation. Here, a structural barrier approach based on directional freezing-assisted salting out was proposed, and the directional structure significantly enhanced the barrier performance of the hydrogel. When the direction of substance diffusion was perpendicular to the pore channel structure of the directional freezing-PVA hydrogel (DFPVA), the Cl- transmission rate was 57.2% for the uniform freezing-PVA hydrogel (UFPVA). By adjusting the concentration of the salting-out solution and the salting-out time, the crystallinity and crystal domain size of the hydrogel could be further changed, optimizing and regulating the barrier performance of the hydrogel, with the best Cl- unit permeability being 36.02 mg mm per cm2 per day. Additionally, DFPVA had excellent mechanical properties (stress of 6.47 ± 1.04 MPa, strain of 625.85 ± 61.58%, toughness of 25.77 ± 3.72 MPa). Due to the barrier and mechanical properties of the direct structure, DFPVA is suitable as a drug carrier for slow drug release in vitro.

Global prevalence of Borrelia burgdorferi and Anaplasma phagocytophilum coinfection in Ixodes tick populations: protocol for a systematic review and meta-analysis.

INTRODUCTION: Ixodes ticks are pivotal in transmitting diseases like Lyme disease and human granulocytic anaplasmosis, caused by Borrelia burgdorferi and Anaplasma phagocytophilum, respectively. These pathogens not only affect humans through single or multiple tick bites but also pose risks to animal hosts, leading to potential coinfections. Despite regional studies indicating significant prevalence, their global coinfection data remain sparse. This study aims to bridge this gap through a systematic review and meta-analysis of B. burgdorferi and A. phagocytophilum coinfections in Ixodes ticks worldwide. Addressing data limitations and study variability, it seeks to provide a nuanced understanding of coinfection patterns, their epidemiological implications and inform targeted prevention strategies. METHODS AND ANALYSIS: Following Preferred Reporting Items for Systematic Review and Meta-analysis Protocols 2015 guidelines and PROSPERO registration, this study will undertake a thorough database search without constraints on language or publication date, using standardised screening and data extraction protocols. The quality and bias of studies will be evaluated using Joanna Briggs Institute tools. In the statistical analysis phase, conducted in R, we will initially determine the use of fixed or random-effects models based on the assessment of data heterogeneity. This choice will guide the framework for subsequent analyses. Within the selected model's framework, we will perform subgroup analyses and meta-regression to investigate the effects of various factors, ensuring that each step is tailored to the initial model selection to maintain analytical consistency. ETHICS AND DISSEMINATION: As this study does not involve clinical research or data collection from subjects, ethical approval is not required. We will uphold ethical standards in synthesising and reporting data. Study outcomes will be published in peer-reviewed journals, communicating findings to the scientific community and contributing to the understanding of Ixodes tickborne diseases. PROSPERO REGISTRATION NUMBER: CRD42023449735.

Unraveling electronic origins for boosting thermoelectric performance of p-type (Bi,Sb)2Te3.

P-type Bi2-xSbxTe3 compounds are crucial for thermoelectric applications at room temperature, with Bi0.5Sb1.5Te3 demonstrating superior performance, attributed to its maximum density-of-states effective mass (m*). However, the underlying electronic origin remains obscure, impeding further performance optimization. Herein, we synthesized high-quality Bi2-xSbxTe3 (00 l) films and performed comprehensive angle-resolved photoemission spectroscopy (ARPES) measurements and band structure calculations to shed light on the electronic structures. ARPES results directly evidenced that the band convergence along the [Formula: see text]-[Formula: see text] direction contributes to the maximum m* of Bi0.5Sb1.5Te3. Moreover, strategic manipulation of intrinsic defects optimized the hole density of Bi0.5Sb1.5Te3, allowing the extra valence band along [Formula: see text]-[Formula: see text] to contribute to the electrical transport. The synergy of the above two aspects documented the electronic origins of the Bi0.5Sb1.5Te3's superior performance that resulted in an extraordinary power factor of ~5.5 milliwatts per meter per square kelvin. The study offers valuable guidance for further performance optimization of p-type Bi2-xSbxTe3.

In-situ direct seawater electrolysis using floating platform in ocean with uncontrollable wave motion.

Direct hydrogen production from inexhaustible seawater using abundant offshore wind power offers a promising pathway for achieving a sustainable energy industry and fuel economy. Various direct seawater electrolysis methods have been demonstrated to be effective at the laboratory scale. However, larger-scale in situ demonstrations that are completely free of corrosion and side reactions in fluctuating oceans are lacking. Here, fluctuating conditions of the ocean were considered for the first time, and seawater electrolysis in wave motion environment was achieved. We present the successful scaling of a floating seawater electrolysis system that employed wind power in Xinghua Bay and the integration of a 1.2 Nm3 h-1-scale pilot system. Stable electrolysis operation was achieved for over 240 h with an electrolytic energy consumption of 5 kWh Nm-3 H2 and a high purity (>99.9%) of hydrogen under fluctuating ocean conditions (0~0.9 m wave height, 0~15 m s-1 wind speed), which is comparable to that during onshore water electrolysis. The concentration of impurity ions in the electrolyte was low and stable over a long period of time under complex and changing scenarios. We identified the technological challenges and performances of the key system components and examined the future outlook for this emerging technology.

Targeting SOX13 inhibits assembly of respiratory chain supercomplexes to overcome ferroptosis resistance in gastric cancer.

Therapeutic resistance represents a bottleneck to treatment in advanced gastric cancer (GC). Ferroptosis is an iron-dependent form of non-apoptotic cell death and is associated with anti-cancer therapeutic efficacy. Further investigations are required to clarify the underlying mechanisms. Ferroptosis-resistant GC cell lines are constructed. Dysregulated mRNAs between ferroptosis-resistant and parental cell lines are identified. The expression of SOX13/SCAF1 is manipulated in GC cell lines where relevant biological and molecular analyses are performed. Molecular docking and computational screening are performed to screen potential inhibitors of SOX13. We show that SOX13 boosts protein remodeling of electron transport chain (ETC) complexes by directly transactivating SCAF1. This leads to increased supercomplexes (SCs) assembly, mitochondrial respiration, mitochondrial energetics and chemo- and immune-resistance. Zanamivir, reverts the ferroptosis-resistant phenotype via directly targeting SOX13 and promoting TRIM25-mediated ubiquitination and degradation of SOX13. Here we show, SOX13/SCAF1 are important in ferroptosis-resistance, and targeting SOX13 with zanamivir has therapeutic potential.

On-line preconcentration and determination of sulfadiazine in food samples using surface molecularly imprinted polymer coating by capillary electrophoresis.

In this study, on-line preconcentration and selective determination of the trace sulfadiazine (SDZ) existing in milk and hen egg white samples were realized by the capillary electrophoresis using molecularly imprinted polymer (MIP) coated capillary. The capillary coated with MIP was firstly prepared through the surface imprinted techniques, using SDZ as template molecule and dopamine as function monomer and crosslinker, and then amine-terminated poly(2-methyl-2-oxazoline) (PMOXA-NH2) was introduced onto polydopamine layer to reduce the non-specific adsorption. Successful preparation of SDZ-MIP-PMOXA coating was verified by zeta potential, as well as water contact angle. The SDZ-MIP-PMOXA coated capillary performed well on-line preconcentration of SDZ and the obtained peak area of SDZ was 46 times higher than that one obtained in bare capillary using the same procedure. Then the proposed on-line preconcentration method was fully validated and displayed good linear behavior in the concentration from 5.0 to 100.0 ng/mL, with the limit of detection was low to 1.5 ng/mL; and this method presented excellent accuracy and robustness. The prepared SDZ-MIP-PMOXA coated capillary also showed high selectivity with the imprinting factor of 5.85 and good repeatability during five consecutive runs with the relative standard deviation value of peak area was 1.6%. At last, the application of the prepared SDZ-MIP-PMOXA coated capillary in the detection of SDZ in spiked food samples was investigated, and good recoveries of 98.7-109.3% were obtained.

Recent advances in the functional explorations of nuclear microRNAs.

Approximately 22 nucleotide-long non-coding small RNAs (ncRNAs) play crucial roles in physiological and pathological activities, including microRNAs (miRNAs). Long ncRNAs often stay in the cytoplasm, modulating post-transcriptional gene expression. Briefly, miRNA binds with the target mRNA and builds a miRNA-induced silencing complex to silence the transcripts or prevent their translation. Interestingly, data from recent animal and plant studies suggested that mature miRNAs are present in the nucleus, where they regulate transcriptionally whether genes are activated or silenced. This significantly broadens the functional range of miRNAs. Here, we reviewed and summarized studies on the functions of nuclear miRNAs to better understand the modulatory networks associated with nuclear miRNAs.

[Viral myocarditis serum exosome-derived miR-320 promotes the apoptosis of mouse cardiomyocytes by inhibiting AKT/mTOR pathway and targeting phosphatidylinositol 3-kinase regulatory subunit 1 (Pik3r1)].

Objective To investigate the effect of viral myocarditis serum exosomal miR-320 on apoptosis of cardiomyocytes and its mechanism. Methods The model of viral myocarditis mice was established by intraperitoneal injection of Coxsackie virus B3. Serum exosomes were extracted by serum exosome extraction kit and co-cultured with cardiomyocytes. The uptake of exosomes by cardiomyocytes was detected by laser confocal microscopy. Cardiomyocytes were transfected with miR-320 inhibitor or mimic, and the expression level of miR-320 was detected by real-time quantitative PCR. Flow cytometry was used to detect cardiomyocyte apoptosis rate, and the expression levels of B cell lymphoma 2 (Bcl2) and Bcl2-related X protein (BAX) were tested by Western blot analysis. The prediction of miR-320 target genes and GO and KEGG enrichment analysis were tested by online database. The relationship between miR-320 and its target gene phosphoinositide-3-kinase regulatory subunit 1(Pik3r1) was examined by luciferase reporter gene. The effect of miR-320 on AKT/mTOR pathway protein was detected by Western blot analysis. Results Viral myocarditis serum exosomes promoted cardiomyocyte apoptosis, and increased the level of BAX while the level of Bcl2 was decreased. miR-320 was significantly up-regulated in myocardial tissue of viral myocarditis mice, and both pri-miR-320 and mature of miR-320 were up-regulated greatly in cardiomyocytes. The level of miR-320 in cardiomyocytes treated with viral myocarditis serum exosomes was significantly up-regulated, while transfection of miR-320 inhibitor counteracted miR-320 overexpression and reduced apoptosis rate caused by exosomes. Pik3r1 is the target gene of miR-320, and its overexpression reversed cardiomyocyte apoptosis induced by miR-320 up-regulation. The overexpression of miR-320 inhibited AKT/mTOR pathway activation. Conclusion Viral myocarditis serum exosome-derived miR-320 promotes apoptosis of mouse cardiomyocytes by inhibiting AKT/mTOR pathway by targeting Pik3r1.

DNAJB4 promotes triple-negative breast cancer cell apoptosis via activation of the Hippo signaling pathway.

INTRODUCTION: Triple-negative breast cancer (TNBC) is currently the most malignant subtype of breast cancer without effective targeted therapies. DNAJB4 (Dnaj heat shock protein family (Hsp40) member B4) is a member of the human heat shock protein family (Hsp40). The clinical significance of DNAJB4 in breast cancer has been reported in our previous study. However, the biological function of DNAJB4 in TNBC cell apoptosis remains unclear to date. METHODS: The expression of DNAJB4 in normal breast cells, breast cancer cells, four-paired TNBC tissues, and adjacent noncancerous tissues was quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assay. The role of DNAJB4 in TNBC cell apoptosis was investigated using a number of gain- and loss-of-function in vitro and in vivo assays. The underlying molecular mechanisms in TNBC cell apoptosis were elucidated via Western blot assay. RESULTS: DNAJB4 expression was significantly downregulated in TNBC tissues and cell lines. DNAJB4 knockdown inhibited TNBC cell apoptosis and promoted tumorigenicity in vitro and in vivo, but DNAJB4 overexpression resulted in the opposite. Mechanically, DNAJB4 knockdown inhibited TNBC cell apoptosis through suppression of the Hippo signaling pathway, and the result was reversed after DNAJB4 overexpression. CONCLUSIONS: DNAJB4 promotes TNBC cell apoptosis by activating the Hippo signaling pathway. Therefore, DNAJB4 may act as a prognostic biomarker and therapeutic target for TNBC.

Inhibitory effect of lingonberry extract on HepG2 cell proliferation, apoptosis, migration, and invasion.

Lingonberry (Vaccinium vitis-idaea L.) extract contains various active ingredients with strong inhibitory effects on cancer cell growth. HepG2 cells were treated with various concentrations of lingonberry extract, cell inhibition rate was measured by CCK-8 assay, and apoptosis rate by annexin-propidium iodide double-staining assay. The cell cycle was analyzed by flow cytometry, and cell migration and invasion by transwell assay. Real-time reverse transcription-PCR and western blotting were employed to analyze the expression of C-X-C motif chemokine ligand 3 (CXCL3). Ki-67, TUNEL, and transwell assays were used to verify the relationship between CXCL3 expression and cell proliferation, apoptosis, migration, and invasion. The composition of lingonberry extract was: 37.58% cyanidin-3-O-glucoside, 10.96% kaempferol 3-O-arabinoside, 4.52% epicatechin, 4.35% chlorogenic acid, 3.83% catechinic acid, 1.54% isoquercitrin, 1.05% 4-hydroxycinnamon acid, 1.03% cyanidin chloride, 0.85% 2,3-dihydroxybenzoic acid, 0.55% quercetin, 0.36% D-(-)-quininic acid, 0.96% caffeic acid, 0.16% ferulic acid, 0.12% oleanolic acid, and 0.03% ursolic acid. Lingonberry extract inhibited the proliferation of HepG2 cells in a dose-dependent manner. After 48 h exposure to 100 µg/mL extract the inhibition rate and IC50 were 80.89±6.05% and 22.62 µg/mL, respectively. Lingonberry extract promoted late apoptosis in HepG2 cells and arrested the cell cycle at G2/M and S phases. Lingonberry extract also promoted the apoptosis of HepG2 cancer cells, inhibiting their proliferation, migration, and invasion by regulating the expression of CXCL3. This study offers new insight into the antihepatoma activity of lingonberry extract and provides a basis for the development of pilot antitumor drugs.

Efficacy and safety of anlotinib in patients with unresectable or metastatic bone sarcoma: A retrospective multiple institution study.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) such as cabozantinib, regorafenib have demonstrated encouraging activity in prolonging progression-free survival (PFS) in several bone sarcoma entities in prospective clinical trials. This retrospective study aims to analyze the safety and efficacy of anlotinib, a novel multi-target TKI, in patients with locally unresectable or metastatic bone sarcoma at three institutions. METHODS: Patients with advanced bone sarcoma administered anlotinib 12 mg once daily, 2 weeks on/1 week off, from June 2018 to June 2020, until disease progression or intolerance of treatment. The primary endpoints were objective response rate (ORR) and PFS. RESULTS: Forty-eight patients were analyzed: 27 have osteosarcoma, 9 have chondrosarcoma, 8 have Ewing's sarcoma, and 3 have chordoma. The median age was 24 years (range, 16-68 years), and the median number of prior regimens was 1 (range, 0-4). Until the final follow-up, five patients obtained a partial response and while 24 achieved stable disease. The ORR in all patients was 10.4%, and the median PFS was 4.6 months, with a progression-free rate (PFR) at 3 months and 6 months of 72.9% and 35.4%, respectively. The ORR and median PFS varied much among tumor subtypes. The most frequent grade 3-4 adverse events (AEs) were pneumothorax, hand-foot syndrome, cholesterol elevation, hypertriglyceridemia, and fatigue. No patients died from anlotinib-related AEs during the study period. CONCLUSIONS: Anlotinib may show promising antitumor activity in unresectable or metastatic bone sarcoma. The ORR and median PFS of anlotnib are similar to those of other targeted drugs in different subtypes of sarcomas. The AEs were generally mild and tolerated well. Further studies of anlotinib in selected subtypes of bone sarcoma are needed.