Shaping the immune-suppressive microenvironment on tumor-associated myeloid cells through tumor-derived exosomes.

Tumor-associated myeloid cells (TAMCs) play a crucial role in orchestrating the dynamics of the tumor immune microenvironment. This heterogeneous population encompasses myeloid-derived suppressor cells, tumor-associated macrophages and dendritic cells, all of which contribute to the establishment of an immunosuppressive milieu that fosters tumor progression. Tumor-derived exosomes (TEXs), small extracellular vesicles secreted by tumor cells, have emerged as central mediators in intercellular communication within the tumor microenvironment. In this comprehensive review, we explore the intricate mechanisms through which TEXs modulate immune-suppressive effects on TAMCs and their profound implications in cancer progression. We delve into the multifaceted ways in which TEXs influence TAMC functions, subsequently affecting tumor immune evasion. Furthermore, we elucidate various therapeutic strategies aimed at targeting TEX-mediated immune suppression, with the ultimate goal of bolstering antitumor immunity.

Apoptosis dysfunction: unravelling the interplay between ZBP1 activation and viral invasion in innate immune responses.

Apoptosis plays a pivotal role in pathogen elimination and maintaining homeostasis. However, viruses have evolved strategies to evade apoptosis, enabling their persistence within the host. Z-DNA binding protein 1 (ZBP1) is a potent innate immune sensor that detects cytoplasmic nucleic acids and activates the innate immune response to clear pathogens. When apoptosis is inhibited by viral invasion, ZBP1 can be activated to compensate for the effect of apoptosis by triggering an innate immune response. This review examined the mechanisms of apoptosis inhibition and ZBP1 activation during viral invasion. The authors outlined the mechanisms of ZBP1-induced type I interferon, pyroptosis and necroptosis, as well as the crosstalk between ZBP1 and the cGAS-STING signalling pathway. Furthermore, ZBP1 can reverse the suppression of apoptotic signals induced by viruses. Intriguingly, a positive feedback loop exists in the ZBP1 signalling pathway, which intensifies the innate immune response while triggering a cytokine storm, leading to tissue and organ damage. The prudent use of ZBP1, which is a double-edged sword, has significant clinical implications for treating infections and inflammation.

Discovery of novel 4-trifluoromethyl-2-anilinoquinoline derivatives as potential anti-cancer agents targeting SGK1.

Given the critical necessity for the development of more potent anti-cancer drugs, a series of novel compounds incorporating trifluoromethyl groups within the privileged 2-anilinoquinoline scaffold was designed, synthesized, and subjected to biological evaluation through a pharmacophore hybridization strategy. Upon evaluating the in vitro anti-cancer characteristics of the target compounds, it became clear that compound 8b, which contains a (4-(piperazin-1-yl)phenyl)amino substitution at the 2-position of the quinoline skeleton, displayed superior efficacy against four cancer cell lines by inducing apoptosis and cell cycle arrest. Following research conducted in a PC3 xenograft mouse model, it was found that compound 8b exhibited significant anti-cancer efficacy while demonstrating minimal toxicity. Additionally, the analysis of a 217-kinase panel pinpointed SGK1 as a potential target for this compound class with anti-cancer capabilities. This finding was further verified through molecular docking analysis and cellular thermal shift assays. To conclude, our results emphasize that compound 8b can be used as a lead compound for the development of anti-cancer drugs that target SGK1.

P53 together with ferroptosis: a promising strategy leaving cancer cells without escape.

TP53, functioning as the keeper of the genome, assumes a pivotal function in the inhibition of tumorigenesis. Recent studies have revealed that p53 regulates ferroptosis pathways within tumor cells and is closely related to tumorigenesis. Therefore, we summarize the pathways and mechanisms by which p53 regulates ferroptosis and identify a series of upstream and downstream molecules involved in this process. Furthermore, we construct a p53-ferroptosis network centered on p53. Finally, we present the progress of drugs to prevent wild-type p53 (wtp53) degeneration and restore wtp53, highlighting the deficiencies of drug development and the prospects for p53 in cancer treatment. These findings provide novel strategies and directions for future cancer therapy.

Discovery of novel 2-(trifluoromethyl)quinolin-4-amine derivatives as potent antitumor agents with microtubule polymerization inhibitory activity.

In this work, a series of 2-(trifluoromethyl)quinolin-4-amine derivatives were designed and synthesized through structural optimization strategy as a microtubule-targeted agents (MTAs) and their cytotoxicity activity against PC3, K562 and HeLa cell lines were evaluated. The half maximal inhibitory concentration (IC50) of 5e, 5f, and 5o suggested that their potency of anti-proliferative activities against HeLa cell lines were better than the combretastatin A-4. Compound 5e showed the higher anti-proliferative activity against PC3, K562 and HeLa in vitro with IC50 values of 0.49 µM, 0.08 µM and 0.01 µM, respectively. Further mechanism study indicated that the representative compound 5e was new class of tubulin inhibitors by EBI competition assay and tubulin polymerization assays, it is similar to colchicine. Immunofluorescence staining revealed that compound 5e apparently disrupted tubulin network in HeLa cells, and compound 5e arrested HeLa cells at the G2/M phase and induced cells apoptosis in a dose-dependent manner. Molecular docking results illustrated that the hydrogen bonds of represented compounds reinforced the interactions in the pocket of colchicine binding site. Preliminary results suggested that 5e deserves further research as a promising tubulin inhibitor for the development of anticancer agents.

Exosomes reveal the dual nature of radiotherapy in tumor immunology.

Radioresistance is the potential cause of cancer metastasis and recurrence. Radiation-induced changes in exosomes can partially explain the undesirable prognosis of radiotherapy (RT). Exosomes, newly discovered ways of cell communication, carry the characteristics of their origin, resulting in their diversity. Various exosomes in the tumor microenvironment exert different function in immune response. In this review, the dual effect of RT on the immune system was described, and the effect of radiotherapy on tumors via exosomes was explored. The molecules in exosomes after RT were described to play immunosuppressive and immunocompetent roles: immune-related receptors and cell signaling molecules involved in both adaptive and innate immune system were present. CD69, TIGIT, TIM-3, LAG-3 and the tumor necrosis factor (TNF) family that signal to T cells were shown to be regulated by exosomes after irradiation. The change in innate immunity-derived like receptors, Leukocyte Immunoglobin-Like Receptors (LILR) was described, as well as B7-H3, V-domain containing Ig suppressor of T cell activation (VISTA), and CD155 on tumor cells. These changed molecules inhibit and activate the immune system through different mechanisms. By analyzing the relationship between exosome-derived molecules and immunity, this review shows that radiotherapy can induce immunosuppression and immune clearance through exosomes, thereby treating tumors and improving patient prognosis.

Triple kill: DDR inhibitors, radiotherapy and immunotherapy leave cancer cells with no escape.

Radiotherapy (RT) has been widely used in the clinical treatment of cancers, but radiotherapy resistance (RR) leads to RT failure, tumor recurrence and metastasis. Many studies have been performed on the potential mechanisms behind RR, and a strong link has been found between RR and DNA damage. RT-induced DNA damage triggers a protective mechanism called the DNA damage response (DDR). DDR consists of several aspects, including the detection of DNA damage and induction of cell cycle checkpoint, DNA repair, and eventual induction of cell death. A large number of studies have shown that DDR inhibition leads to significantly enhanced sensitivity of cancer cells to RT. DDR may be an effective target for radio- and chemo-sensitization during cancer treatment. Therefore, many inhibitors of important enzymes involved in the DDR have been developed, such as PARP inhibitors, DNA-PK inhibitors, and ATM/ATR inhibitors. In addition, DNA damage also triggers the cGAS-STING signaling pathway and the ATM/ATR (CHK)/STAT pathway to induce immune infiltration and T-cell activation. This review discusses the effects of DDR pathway dysregulation on the tumor response to RT and the strategies for targeting these pathways to increase tumor susceptibility to RT. Finally, the potential for the combination treatment of radiation, DDR inhibition, and immunotherapy is described.

Sequence Requirements for miR-424-5p Regulating and Function in Cancers.

MiRNAs (microRNAs) are the most abundant family of small noncoding RNAs in mammalian cells. Increasing evidence shows that miRNAs are crucial regulators of individual development and cell homeostasis by controlling various biological processes. Therefore, miRNA dysfunction can lead to human diseases, especially in cancers with high morbidity and mortality worldwide. MiRNAs play different roles in these processes. In recent years, studies have found that miR-424-5p is closely related to the occurrence, development, prognosis and treatment of tumors. This review discusses how miR-424-5p plays a role in different kinds of cancers from different stages of tumors, including its roles in (i) promoting or inhibiting tumorigenesis, (ii) regulating tumor development in the tumor microenvironment and (iii) participating in cancer chemotherapy. This review provides a deep discussion of the latest findings on miR-424-5p and its importance in cancer, as well as a mechanistic analysis of the role of miR-424-5p in various tissues through target gene verification and pathway analysis.

Genome Sequence of Fusarium oxysporum f. sp. conglutinans, the Etiological Agent of Cabbage Fusarium Wilt.

Fusarium oxysporum f. sp. conglutinans is the causal agent of Fusarium wilt of cabbage (Brassica oleracea var. capitata L.), which results in severe yield loss. Here, we report a high-quality genome sequence of a race 1 strain (IVC-1) of F. oxysporum f. sp. conglutinans, which was assembled using a combination of PacBio long-read and Illumina short-read sequences. The assembled IVC-1 genome has a total size of 71.18 Mb, with a contig N50 length of 4.59 Mb, and encodes 23,374 predicted protein-coding genes. The high-quality genome of IVC-1 provides a valuable resource for facilitating our understanding of F. oxysporum f. sp. conglutinans-cabbage interaction.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

The impact of COVID-19 on the Chinese stock market: Sentimental or substantial?

We investigate the impact of COVID-19 on Chinese stock market by an event study and examine the effect of individual investor sentiment on returns. The pandemic has an overall negative effect on stock market during the post-event window, which can't be explained by real losses. Results show a stronger positive correlation between individual investor sentiment and stock returns than usual. The impact on individual investor sentiment on stock returns is more significant for enterprises with high PB, PE and CMV, low net asset, and low institutional shareholding. Only 7 industries related to pharmacy, digitalization, and agriculture are boosted.

What investors say is what the market says: measuring China's real investor sentiment.

This paper describes a novel approach to measure individual investor sentiment using text-based analysis of millions of posts extracted from Chinese financial online forums. We describe how we built a database of more than 200 million stock posts from online financial forums, created GubaLex, a sentiment dictionary consisting of 48,878 words to allow sentiment analysis, and how we developed GubaSenti, an individual investor sentiment index for the stock market in China. This allowed (1) the first systemic measurement of individual investor sentiment in China; (2) an approach to text-based analysis that reflects investor sentiment about millions of posts about stocks listed in Guba; (3) a way to flexibly measure investor sentiment of a single stock, a sector or an industry and the whole market; and (4) made this possible for daily, weekly, monthly, quarterly, and yearly time periods. We also examine the relationship of the sentiment proxy and stock returns and compare it with two typical BW metrics in China. Empirical results show that GubaSenti correlates better with market performance than BW metrics in China and can be used to predict market changes in the short term.

Effects of daphnetin on the autophagy signaling pathway of fibroblast-like synoviocytes in rats with collagen-induced arthritis (CIA) induced by TNF-α.

Daphnetin (DAP), an active ingredient extracted from Daphne odora, has pharmacological effects such as anti-inflammatory, antioxidation and anti-tumor properties. The current study aims to investigate the relationship between the anti-rheumatoid effect of DAP and the inhibition of both the PI3K/AKT/mTOR and autophagy signaling pathways. DAP inhibited the proliferation of CIA-FLS in a dose-dependent manner and induce apoptosis, accelerated the G1/G0 phase and inhibited the S phase. DAP reduced the phosphorylation of AKT and mTOR and the expression of Atg5, Beclin-1 and LC3-II/LC3-I in CIA-FLS induced by TNF-α. DAP also reduced the inflammatory response in CIA-FLS induced by TNF-α by inhibiting the cytokine expression of TNF-α, IL-6, TGF-ß, IL-17, and INF-γ and promoting IL-10 expression. Overall, DAP inhibited the proliferation of CIA-FLS by down-regulating the PI3K/AKT/mTOR signaling pathway and inhibited autophagy in order to induces apoptosis, which may be potential therapeutic approach in treatment of RA.

Daphnetin induces apoptosis in fibroblast-like synoviocytes from collagen-induced arthritic rats mainly via the mitochondrial pathway.

Rheumatoid arthritis (RA) is a chronic, symmetric, systemic autoimmune disease. Because insufficient apoptosis of fibroblast-like synoviocytes (FLS) is an important characteristic of RA, promoting apoptosis is considered a potential therapeutic tool for treating RA. We have previously found that daphnetin (7,8-dihydroxycoumarin, DAP) has a pro-apoptotic effect on fibroblast-like synoviocytes from collagen-induced arthritis (CIA) rats. In the present study, we further investigated the mechanisms of DAP-induced apoptosis in CIA-FLS. CIA-FLS were incubated with DAP for 48 h in the presence or absence of caspase inhibitors, including inhibitors of caspase-3, caspase-8, or caspase-9 or a pan-caspase inhibitor; then, a series of experiments were performed to evaluate the mechanisms of DAP-induced apoptosis. Our results showed that DAP markedly decreased cell viability and induced the apoptosis of CIA-FLS along with typical morphological and ultrastructural changes; moreover, DAP increased FasL, cytochrome c (Cyt-c), Bax, caspase-3, caspase-8, and caspase-9 mRNA expression and Bax, caspase-3, caspase-8, and caspase-9 protein expression. In contrast, DAP decreased Bcl-2 mRNA and protein expression and promoted the release of Cyt-c from the mitochondria into the cytosol; these effects were attenuated to varying degrees by pre-treatment with caspase inhibitors, especially with caspase-3 or caspase-9 inhibitors or a pan-caspase inhibitor. In conclusion, the current findings demonstrate that the DAP-induced apoptosis of CIA-FLS occurred mainly via a caspase-dependent pathway, in particular the mitochondrial pathway, and that the Bax/Bcl-2 ratio was involved in this process. Thus, DAP may be a potential therapeutic agent for RA.

Fli-1 Activation through Targeted Promoter Activity Regulation Using a Novel 3', 5'-diprenylated Chalcone Inhibits Growth and Metastasis of Prostate Cancer Cells.

The friend leukemia integration 1 (Fli-1) gene is involved in the expression control of key genes in multiple pathogenic/physiological processes, including cell growth, differentiation, and apoptosis; this implies that Fli-1 is a strong candidate for drug development. In our previous study, a 3',5'-diprenylated chalcone, (E)-1-(2-hydroxy-4-methoxy-3,5-diprenyl) phenyl-3-(3-pyridinyl)-propene-1-one (C10), was identified as a novel anti-prostate cancer (PCa) agent. Here, we investigated the molecular mechanisms underlying the anti-cancer effects of C10 on the growth, metastasis, and invasion of PC3 cells in vitro. Our results show that C10 exhibited a strong inhibitory effect on proliferation and metastasis of PC3 cells via several cellular and flow cytometric analyses. Further mechanism studies revealed that C10 likely serves as an Fli-1 agonist for regulating the expression of Fli-1 target genes including phosphatidylinositol 3-kinase (P110), murine double minute2 (MDM2), B-cell lymphoma-2 (Bcl-2), Src homology-2 domain-containing inositol 5-phosphatase 1 (SHIP-1), and globin transcription factor-1 (Gata-1) as well as the phosphorylation of extracellular-regulated protein kinases 1 (ERK1). Further, we confirmed that C10 can regulate the expressions of vascular endothelial growth factor 1 (VEGF-1), transforming growth factor-ß2 (TGF-ß2), intercellular cell adhesion molecule-1 (ICAM-1), p53, and matrix metalloproteinase 1 (MMP-1) genes associated with tumor apoptosis, migration, and invasion. Thus, C10 exhibits stronger anticancer activity with novel molecular targets and regulatory molecular mechanisms, indicating its great potency for development as a novel targeted anticancer drug.

[A summary of research progress on intelligent information processing methods for pregnant women's remote monitoring].

The monitoring of pregnant women is very important. It plays an important role in reducing fetal mortality, ensuring the safety of perinatal mother and fetus, preventing premature delivery and pregnancy accidents. At present, regular examination is the mainstream method for pregnant women's monitoring, but the means of examination out of hospital is scarce, and the equipment of hospital monitoring is expensive and the operation is complex. Using intelligent information technology (such as machine learning algorithm) can analyze the physiological signals of pregnant women, so as to realize the early detection and accident warning for mother and fetus, and achieve the purpose of high-quality monitoring out of hospital. However, at present, there are not enough public research reports related to the intelligent processing methods of out-of-hospital monitoring for pregnant women, so this paper takes the out-of-hospital monitoring for pregnant women as the research background, summarizes the public research reports of intelligent processing methods, analyzes the advantages and disadvantages of the existing research methods, points out the possible problems, and expounds the future development trend, which could provide reference for future related researches.

[A partition bagging ensemble learning algorithm for Parkinson's speech data mining].

Methods for achieving diagnosis of Parkinson's disease (PD) based on speech data mining have been proven effective in recent years. However, due to factors such as the degree of disease of the data collection subjects and the collection equipment and environment, there are different categories of sample aliasing in the sample space of the acquired data set. Samples in the aliased area are difficult to be identified effectively, which seriously affects the classification accuracy of the algorithm. In order to solve this problem, a partition bagging ensemble learning is proposed in this article, which measures the aliasing degree of the sample by designing the the ratio of sample centroid distance metrics and divides the training set into multiple subsets. And then the method of transfer training of misclassified samples is used to adjust the results of subset partitioning. Finally, the optimized weights of each sub-classifier are used to integrate the test results. The experimental results show that the classification accuracy of the proposed method is significantly improved on two public datasets and the increasement of mean accuracy is up to 25.44%. This method not only effectively improves the classification accuracy of PD speech dataset, but also increases the sample utilization rate, providing a new idea for the diagnosis of PD.

Ultra-thin and broadband tunable metamaterial graphene absorber.

A broadband tunable metamaterial graphene absorber is investigated in this paper. The unit cell of the proposed metamaterial graphene absorber is composed of four patch resonators. By tuning the chemical potential of graphene and the geometric size of each patch, the simulated total reflectivity is less than -10 dB from 22.02 to 36.61 THz and with the total thickness of 0.76 um (only 0.09λ at the lowest frequency). The analysis of the surface current, magnetic field and power flow distributions has been performed to better understand the absorption mechanism. Moreover, this proposed absorber achieves its bandwidth tunable characteristics through a voltage biasing of the graphene's Fremi level. This proposed metamaterial graphene absorber (MGA) could be used as smart absorbers, photovoltaic devices and tunable sensors.

Localized instance fusion of MRI data of Alzheimer's disease for classification based on instance transfer ensemble learning.

BACKGROUND: Diagnosis of Alzheimer's disease (AD) is very important, and MRI is an effective imaging mode of Alzheimer's disease. There are many existing studies on the diagnosis of Alzheimer's disease based on MRI data. However, there are no studies on the transfer learning between different datasets (including different subjects), thereby improving the sample size of target dataset indirectly. METHODS: Therefore, a new framework method is proposed in this paper to solve this problem. First, gravity transfer is used to transfer the source domain data closer to the target data set. Secondly, the best deviation between the transferred source domain samples and the target domain samples is searched by instance transfer learning algorithm (ITL) based on wrapper mode, thereby obtaining optimal transferred domain samples. Finally, the optimal transferred domain samples and the target domain training samples are combined for classification. If the source data and the target data have different features, a feature growing algorithm is proposed to solve this problem. RESULTS: The experimental results show that the proposed method is effective regardless of different kernel functions, different number of samples and different parameters. Besides, the transferred source domain samples by ITL algorithm can enlarge the target domain training samples and assist to improve the classification accuracy significantly. CONCLUSIONS: Therefore, the study can enlarge the samples of AD by instance transfer learning, thereby being helpful for the small sample problems of AD. Since the proposed algorithm is a framework algorithm, the study is heuristics to the relevant researchers.

Targeted-gene silencing of BRAF to interrupt BRAF/MEK/ERK pathway synergized photothermal therapeutics for melanoma using a novel FA-GNR-siBRAF nanosystem.

Melanoma is significantly associated with mutant BRAF gene, a suitable target for siRNA-based anti-melanoma therapy. However, a tumor-specific delivery system is a major hurdle for clinical applications. Here, we developed a novel nano-carrier, FA-GNR-siBRAF for safe topical application, which consists of folic acid (FA) as the tumor-targeting moiety, golden nanorods (GNR) providing photothermal capability to kill tumor cells under laser irradiation, and siRNA specifically silencing BRAF (siBRAF). The in vitro and in vivo results revealed that FA-GNR-siBRAF displayed high transfection rates, and subsequently induced remarkable gene knockdown of BRAF, resulting in suppression of melanoma growth due to the interruption of the MEK/ERK pathway. Combinatorial photothermal effects and BRAF knockdown by FA-GNR-siBRAF effectively killed tumor cells through apoptosis, with enhanced efficiency than individual treatments. Therefore, the FA-GNR-siBRAF simultaneously induced BRAF gene silencing and photothermal effects which achieved synergistic efficacy in the treatment of melanoma, paving a new path for developing clinical treatment methods for melanoma.

A Novel Adaptive Modulation Based on Nondata-Aided Error Vector Magnitude in Non-Line-Of-Sight Condition of Wireless Sensor Network.

The high demand for multimedia applications in environmental monitoring, invasion detection, and disaster aid has led to the rise of wireless sensor network (WSN). With the increase of reliability and diversity of information streams, the higher requirements on throughput and quality of service (QoS) have been put forward in data transmission between two sensor nodes. However, lower spectral efficiency becomes a bottleneck in non-line-of-sight (NLOS) transmission of WSN. This paper proposes a novel nondata-aided error vector magnitude based adaptive modulation (NDA-EVM-AM) to solve the problem. NDA-EVM is considered as a new metric to evaluate the quality of NLOS link for adaptive modulation in WSN. By modeling the NLOS scenario as the η - µ fading channel, a closed-form expression for the NDA-EVM of multilevel quadrature amplitude modulation (MQAM) signals over the η - µ fading channel is derived, and the relationship between SER and NDA-EVM is also formulated. Based on these results, NDA-EVM state machine is designed for adaptation strategy. The algorithmic complexity of NDA-EVM-AM is analyzed and the outage capacity of NDA-EVM-AM in an NLOS scenario is also given. The performances of NDA-EVM-AM are compared by simulation, and the results show that NDA-EVM-AM is an effective technique to be used in the NLOS scenarios of WSN. This technique can accurately reflect the channel variations and efficiently adjust modulation order to better match the channel conditions, hence, obtaining better performance in average spectral efficiency.