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Abstract Doxorubicin (DOX) is an important chemotherapeutic agent for the treatment of hematologic tumors and breast carcinoma. However, its clinical application is limited owing to severe cardiotoxicity. Pyroptosis is a form of programmed cell death linked to DOX-induced cardiotoxicity. Bone mesenchymal stem cell–derived exosomes (BMSC-Exos) and endothelial progenitor cells-derived exosomes (EPC-Exos) have a protective role in the myocardium. Here we found that BMSC-Exos could improve DOX-induced cardiotoxicity by inhibiting pyroptosis, but EPC-Exos couldn’t. Compared with EPCs-Exo, BMSC-Exo-overexpressing lncRNA GHET1 more effectively suppressed pyroptosis, protecting against DOX-induced cardiotoxicity. Further studies showed that lncRNA GHET1 effectively decreased the expression of Nod-like receptor protein 3 (NLRP3), which plays a vital role in pyroptosis by binding to IGF2 mRNA-binding protein 1 (IGF2BP1), a non-catalytic posttranscriptional enhancer of NLRP3 mRNA. In summary, lncRNA GHET1 released by BMSC-Exo ameliorated DOX-induced pyroptosis by targeting IGF2BP1 to reduce posttranscriptional stabilization of NLRP3.

In seismic exploration, complex seismic wave fields comprising reflected waves, scattered waves, and other phenomena are formed due to the intricate nature of underground structures. Traditional imaging methods typically focus solely on the reflected wave field, disregarding the scattered wave field. This limitation hampers accurate imaging of small-scale structures and impedes the identification of complex structures. To address this challenge and achieve precise imaging of small-scale structures, it is crucial to separate from the scattered waves from the seismic wave field. Among the various wave field separation algorithms, filtering-based methods have shown promising results in accurately extracting scattered waves and enhancing imaging resolution. This study explores and summarizes different methods for seismic scattered wave separation based on filtering techniques. By reviewing the research findings of both domestic and international scholars in the field of filtering-based scattered wave separation, the study provides an overview of the progress made and compares and analyzes the separation effects of each method. Additionally, considering the advancements in deep learning within the realm of artificial intelligence, the future development direction of filtering-based scattered wave separation is also envisioned.

This study applied the cycle-consistent generative adversarial network method to the denoising of shallow profile data to realize intelligent denoising. This could help resolve the problem of noise and low resolution of shallow profile data. To do this, the cycle generative adversarial network with special symmetric generation countermeasure network cycle mechanism and "cycle consistency loss" was selected. We improved the performance of the network learning and training by optimizing the network structure. Next, based on the optimized shallow profile sample set training network, random noise was removed from the shallow profile data and the signal-to-noise ratio of the data was improved. The effectiveness and adaptability of this method for denoising shallow profile data were verified by trial calculations of experimental and actual data and by comparison with the traditional band-pass filtering method.

Abstract Doxorubicin (DOX) has a wide antitumor spectrum, but its adverse cardiotoxicity may lead to heart failure. Urotensin II (UII) is the most potent vasoconstrictor in mammals. It plays a role by activating the UII receptor (UT), the orphan G protein-coupled receptor (GPR14), collectively referred to as the UII/UT system. In the new version of "Chinese expert consensus on cardiac rehabilitation of chronic heart failure," it is pointed out that exercise rehabilitation is the cornerstone of cardiac rehabilitation. In this study, in vitro and in vivo assessments were performed using DOX-treated H9C2 cells and rats. It was found that the UT antagonist Urantide and exercise training improved DOX-induced cardiac insufficiency, reduced DOX-induced cardiomyocyte apoptosis, improved the structural disorder of myocardial fibers, and inhibited DOX-induced myocardial fibrosis. Further studies showed that Urantide alleviated DOX-induced cardiotoxicity by downregulating the expression levels of the p38 mitogen-activated protein kinase signaling pathway.

Monitoring the aging process in vivo is challenging. Here the authors generate a Glb1 +/m‒Glb1-2A-mCherry (GAC) reporter mouse model, where the GAC signal is consistently correlated with established biomarkers of cellular senescence, cardiac hypertrophy and shortened lifespan, which may prove helpful for studies developing anti-aging interventions.

Background Doxorubicin (DOX) , a common and powerful anthracycline antitumor agent, has been widely used in the treatment of various tumors, especially solid tumors. However, its strong cardiotoxicity-induced irreversible cardiomyopathy and congestive heart failure limit its clinical application. Yellow Wine Polyphenols Compounds (YWPC) are polyphenols extracted from Shaoxing yellow rice wine which have anti-inflammatory and antioxidant activities, and can alleviate DOX-induced myocardial injury, but the mechanism of actions is still unclear. Objective To explore the mechanism of YWPC reducing DOX-induced myocardial injury via in vitro and in vivo experiments. Methods SD rats were used for an in vivo experiment and divided into four groups: control group (intervened with normal saline) , YWPC group (intervened with YWPC and normal saline) , DOX group (intervened with DOX and normal saline for establishing a DOX-induced myocardial injury model) and DOX+YWPC group (intervened with DOX, YWPC and normal saline for observing the myocardial protective effect of YWPC in a DOX-induced myocardial injury model) . When the experiment ended, all rats were sacrificed and cardiac tissues were taken out for examining myocardial fiber morphology using Masson's trichrome staining, myocardial cell apoptosis using TUNEL assay, pathological changes using immunohistochemical assay, and levels of proteins (Bcl-2 and Bax) involved in apoptosis as well as expression level of SIRT3 using Western blotting. And the serum lactate dehydrogenase (LDH) was also measured. Cardiomyocyte H9C2 cells of rats were used for an in vitro experiment and divided into five groups: control group, YWPC group (intervened with YWPC and normal saline) , DOX group (intervened with DOX for establishing a DOX-induced myocardial injury model within 24 hours) and three DOX+YWPC (1 mg/L, 10 mg/L, 100 mg/L) groups〔first intervened with DOX for establishing a DOX-induced myocardial injury model within 24 hours, then with YWPC for observing the myocardial protective effect of three concentrations of YWPC (1 mg/L, 10 mg/L, 100 mg/L) , respectively〕. Viability of H9C2 cells was measured by CCK-8 assay. Apoptosis, and SIRT3 expressed in H9C2 cells were measured by Western blotting. Then another batch of the same H9C2 cells were took and divided into control group, DOX group, DOX+YWPC group, DOX+3-TYP group and DOX+YWPC+3-TYP group, and SIRT3 inhibitor 3-TYP was used to inhibit the activity of SIRT3 protein in the latter two groups. Then apoptosis level and SIRT3 protein expressed in H9C2 cells were detected by Western blotting for further assessing the effect of SIRT3 in reducing DOX-induced myocardial injury. Results In vivo experiment: (1) Under the microscope, Masson's trichrome-stained myocardial fibers of rats in DOX group were disordered and intersected with a large number of blue collagen fibers. The myocardial texture of DOX+YWPC group was partially restored with decreased blue collagen fibers. DOX group had higher proportion of collagen fibers distributed in cardiovascular tissues, and higher serum LDH than control and DOX+YWPC groups (P0.05) . Conclusion DOX-induced myocardial injury in in vitro and in vivo experiments with rats may be alleviated by YWPC via improving the expression level of SIRT3, and the effect may be reduced if the expression level of SIRT3 protein is inhibited.

Random noise adversely affects the signal-to-noise ratio of complex seismic signals in complex surface conditions and media. The primary challenges related to processing seismic data have always been reducing the random noise and increasing the signal-to-noise ratio. In this study, we propose an improved cycle-consistent generative adversarial network (CycleGAN) seismic random noise suppression method. First, the generator replaces the original cycle-consistent generative adversarial network generator network structure with the Unet structure combined with the Resnet structure in order to increase the diversity of seismic data feature extraction and decrease the loss of seismic data details. Second, in order to improve the network’s stability, the feature extraction effect, the event texture preservation effect, and the signal-to-noise ratio, the Least Square GAN (LSGAN) square difference loss is used in place of the conventional generative adversarial network cross-entropy loss. The feasibility of the proposed method was confirmed using model and real seismic data, both of which demonstrated that the improved cycle-consistent generative adversarial network method effectively suppressed random noise in seismic data. In addition, the denoising effect was superior to both the widely used FX deconvolution denoising method and original cycle-consistent generative adversarial network denoising method.

PurposeDiabetic heart failure (DHF) or cardiomyopathy is a common complication of diabetes; however, the underlying mechanism is not clear. In the present study, the authors searched for differentially expressed genes associated with DHF and the molecular types of immune cells based on bioinformatics.MethodsThe RNA expression dataset of DHF was obtained from the NCBI Gene Expression Omnibus (GEO) database. After preprocessing the data, the differentially expressed genes (DEGs) between the DHF group and the non-diabetic heart failure (NHF) group were screened and intersected with immune-related genes (IRGs) in the ImmPort database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the DAVID tool. The ssGSEA algorithm was used to evaluate immune infiltration of the heart tissue in each group. In addition, the protein-protein interaction (PPI) network and miRNA-mRNA network were constructed using the STRING online website and Cytoscape program. Finally, validation analysis was performed using animal models.ResultsEight immune-related core genes were identified. GO and KEGG showed that core genes were mainly enriched in angiogenesis and cytokine-cytokine receptor interaction. Immune infiltration results showed that activated dendritic cells, central memory CD4 T cells, central memory CD8 T cells, myeloid-derived suppressor cells (MDSCs), neutrophils, and regulatory T cells may be involved in DHF. Neutrophils may play a key role in the pathogenesis of HF in diabetes.ConclusionImmune-related core genes and immune infiltrating cells provide a new perspective on the pathogenesis of DHF.

BackgroundChronic endoplasmic reticulum stress (ERS) plays a crucial role in cardiovascular diseases. Thus, it can be considered a therapeutic target for these diseases. In this study, poly (D,L-lactic acid) (PDLLA) nanoparticle-eluting stents loaded with tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor, was fabricated to assess their ability to reduce endothelial cell apoptosis and promote re-endothelialization after stent implantation.Materials and methodsPDLLA nanoparticles loaded with TUDCA were prepared via the emulsification-solvent evaporation method. The cumulative release rates of TUDCA were measured in vitro via high-performance liquid chromatography. The carotid arteries of rabbits were subsequently implanted with stents in vivo. The rabbits were then sacrificed after 4 weeks for scanning electron microscopy. Meanwhile, TUDCA concentration in the homogenate of the peripheral blood and distal vascular tissue after stent implantation was measured. The effect of TUDCA on ERS, apoptosis, and human umbilical vein endothelial cell (HUVEC) function was investigated in vitro by performing cell migration assay, wound healing assay, cell proliferation assays, endoplasmic reticulum (ER)-specific fluorescence staining, immunofluorescence, and western blotting.ResultsTUDCA nanoparticles were released slowly over 28 days. In addition, TUDCA-eluting stents enhanced re-endothelialization and accelerated the recovery of endotheliocytes in vivo. ERS and apoptosis significantly increased in H2O2-treated HUVECs in vitro. Meanwhile, TUDCA reduced apoptosis and improved function by inhibiting ERS in H2O2-treated HUVECs. Decreased rates of apoptosis and ERS were observed after silencing XBP-1s in H2O2-treated HUVECs.ConclusionTUDCA can inhibit apoptosis and promote re-endothelialization after stent implantation by inhibiting IRE/XBP1s-related ERS. These results indicate the potential therapeutic application of TUDCA as a drug-coated stent.

The combination of intermittent fasting and chemotherapy can improve the response to treatment. Here, the authors show that SIRT7 activation is required to inactivate Akt during intermittent fasting and that the combination of intermittent fasting and inhibitors that block the Erk pathway can improve efficacy of treatment.

Exponential sums over Galois rings have many applications in coding theory, cryptography and algebraic combinatorics. In this article, we employ additive characters and multiplicative characters over Galois rings to present two classes of codebooks, and prove that these codebooks asymptotically achieve the Welch bound. In addition, the resulting codebooks have new parameters.

Codebooks with low coherence have extensive applications in many fileds such as code division multiple access (CDMA) communication systems, MIMO communications, compressed sensing and so on. In this paper, based on additive characters over finite fields, we propose a construction of optimal codebook with respect to the Levenshtein bound and verify that it is a new construction. By shortening the length of the optimal codebooks, we present a construction of codebooks asymptotically meeting the Levenshtein bound. To the best of our knowledge, the parameters of the asymptotically optimal codebooks are new.

Significance: Heart failure, a disease with extremely high incidence, is closely associated with inflammation and oxidative stress. The Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway plays an important role in the occurrence and development of heart failure. Recent advances: Previous studies have shown that TLR4/NF-κB causes heart failure by inducing oxidative stress and inflammation; damaging the endothelia; promoting fibrosis; and inducing myocardial hypertrophy, apoptosis, pyroptosis, and autophagy. Critical issues: Understanding the pathogenesis of heart failure is essential for the treatment of this disease. In this review, we outline the mechanisms underlying TLR4/NF-κB pathway-mediated heart failure and discuss drugs that alleviate heart failure by regulating the TLR4/NF-κB pathway. Future directions: During TLR4/NF-κB overactivation, interventions targeting specific receptor antagonists may effectively alleviate heart failure, thus providing a basis for the development of new anti-heart failure drugs.

Background: Recent studies have revealed that a novel selective sodium-glucose cotransporter 1 (SGLT1) inhibiton has shown beneficial effects in cardiovascular diseases. However, the question of whether SGLT1 inhibition influences diabetic cardiomyopathy (DCM) remains unanswered. In this study, we investigated the influence and underlying mechanism of SGLTI inhibition on DCM.Methods: SGLT1 levels were measured in diabetic patients with similar conditions who visited our hospital from January to December 2019. Wistar male rats (n = 50) were divided into five groups: control, diabetes induced by streptozotocin infusion, and diabetes treated with 0.5, 1.0, or 1.5 mg/kg mizagliflozin via stomach gavage for 12 weeks. H9C2 cardiomyocytes were treated with mizagliflozin and then exposed to a high glucose concentration (30 mmol/L). TUNEL assays were performed, and bcl2, bax, p-p38, p-Erk, p-JNK and caspase-3 levels were measured. We used siRNA and an SGLT1 overexpression plasmid to detect the effects of SGLT1.Results: SGLT1 levels were significantly elevated in DCM patients, and receiver operating characteristic (ROC) curve analysis identified SGLT1 as influencing DCM. The area under the curve (AUC) was 0.705 (p < 0.05), with 65.8% sensitivity, and 62.2% specificity. SGLT1 inhibition appeared to attenuate apoptosis in DCM via the JNK and p38 pathway.Conclusion: SGLT1 can be used as a marker for the diagnosis of DCM, and SGLT1 inhibition can attenuate apoptosis, thereby suppressing DCM development via the JNK and p38 pathway.

Doxorubicin (DOX) is well-known for its potent antitumor activity but limited by its multiple and serious adverse effects. A major adverse effect is acute cardiotoxicity; yet, its mechanism has not been elucidated. Fucoidan is a multifunctional and nontoxic polysaccharide that is widely studied because of its favorable biological activities and safety. Hence, we proposed that fucoidan may play a protective role in DOX-induced acute cardiotoxicity without causing additional side effects. Sprague-Dawley rats were injected intraperitoneally with a single high dose of DOX to induce acute cardiac injury. Fucoidan was administered orally before DOX injection and AG490, a JAK2 inhibitor, was applied to verify the participation of the JAK2/STAT3 pathway. In vitro, H9C2 cells were treated with the same drugs at different concentrations and intervention times. in vivo and in vitro results demonstrated that DOX administration induced myocardial damage accompanied by acceleratory apoptosis and deficient autophagy in heart tissues or cells, which could be significantly improved by fucoidan supplement. AG490 partly abolished the cardioprotective effects of fucoidan, suggesting the involvement of JAK2 signaling. Additionally, western blotting revealed DOX-induced JAK2/STAT3 pathway activation, which was enhanced by fucoidan and weaken by AG490. Hence, fucoidan exerted a favorable effect on DOX-induced cardiotoxicity by enhancing autophagy and suppressing apoptosis in a JAK2/STAT3-dependent manner, which may provide a promising and novel therapeutic strategy against negative chemotherapy-induced effects.

The DNA damage response (DDR) is a highly orchestrated process but how double-strand DNA breaks (DSBs) are initially recognized is unclear. Here, we show that polymerized SIRT6 deacetylase recognizes DSBs and potentiates the DDR in human and mouse cells. First, SIRT1 deacetylates SIRT6 at residue K33, which is important for SIRT6 polymerization and mobilization toward DSBs. Then, K33-deacetylated SIRT6 anchors to γH2AX, allowing its retention on and subsequent remodeling of local chromatin. We show that a K33R mutation that mimics hypoacetylated SIRT6 can rescue defective DNA repair as a result of SIRT1 deficiency in cultured cells. These data highlight the synergistic action between SIRTs in the spatiotemporal regulation of the DDR and DNA repair in humans and mice.

Abstract Background The gamma-type phospholipase A2 inhibitor (PLIγ) is a natural protein commonly found in snake serum, which can neutralize pathophysiological effects of snake venom phospholipases A2. Therefore, this protein is a potential candidate to the development of a novel antivenom. To the best of our knowledge, there is no antibody currently available for PLIγ identification and characterization. Methods Bioinformatics prediction of epitope using DNAStar software was performed based on the sequence of Sinonatrix annularis PLIγ (SaPLIγ). The best epitope 151CPVLRLSNRTHEANRNDLIKVA172 was chosen and synthesized, and then conjugated to keyhole limpet hemocyanin and bovine serum albumin for use as an immunogen and plate-coating antigen, respectively. Results Eighteen IgG anti-PLIγ mAb hybridoma cell strains were obtained, and all the mAbs had positive interaction with recombinant His6-PLIγ and natural SaPLIγ. Moreover, the mAb from 10E9 strain was also successfully used for the immunodetection of other snake serum PLIγs. cDNA sequence alignment of those PLIγs from different snake species showed that their epitope segments were highly homologous. Conclusions The successful preparation of anti-PLIγmAb is significant for further investigation on the relationship between the structure and function of PLIγs, as well as the interaction between PLIγs and PLA2s.

Applications supporting various multimedia data in wireless multimedia sensor networks (WMSNs) have specific QoS requirements on bandwidth, delay, and/or packet loss. Perception of applications' QoS requirements and detection of link states are indispensable for the design of QoS-aware routing mechanism. Software defined networking (SDN) is suitable for the purpose since it provides visibility of network resources and programmable interfaces. OpenFlow is the most recognized realization of SDN. We propose a QoS-aware routing mechanism for OpenFlow-enabled WMSNs. The mechanism consists of a framework and routing algorithms on SDN controller. The framework includes two functions: detection of link states among OpenFlow-enabled nodes and determination of flow's QoS requirements. The routing algorithms are achieved in two steps. First, the SDN controller seeks the feasible paths that satisfy QoS requirements of a flow. If there is no path which satisfies the required QoS, the path will be decided by the proposed algorithms depending on flow types: delay-sensitive, bandwidth-sensitive, and best-effort traffic. We conducted experiments on a SDN testbed to evaluate our mechanism and compared the results with conventional routing protocols. The results show that proposed routing mechanism increases the throughput by 43% for video data and reduces the delay by more than 30% for audio data.

Snake venom is a complex cocktail of toxins which induces a series of clinical and pathophysiological manifestations in victims, including severe local tissue damage and systemic alterations. Deinagkistrodon acutus (D. acutus) ranks among the “big four” life-threatening venomous species in China, whose venom possesses strong myotoxicity and hematotoxicity that often lead to permanent disability or muscle atrophy. Varespladib, an inhibitor of mammalian phospholipase A2 (PLA2), has been recently reproposed as an effective antidote against snakebite envenomation. The present study aimed at evaluating the protective role of varespladib on muscle regeneration in envenomed mice. Mice were grouped and subjected to inoculation with D. acutus venom or a mixture of venom and varespladib or control vehicle in the gastrocnemius muscle. Local injuries including hemorrhage, myonecrosis, ulceration, and systemic damages including general dysfunction, visceral failure, and inflammatory responses were observed at 1, 3, 7, 14, and 21 days. The results indicated that most of the muscle myonecrosis and hemorrhage were alleviated by varespladib. Besides, the pretreated mice recovered rapidly with lesser atrophy and muscle fibrosis. In conclusion, the findings of the present study suggested that varespladib is an effective antidote that could neutralize D. acutus venom and allow for earlier and improved rehabilitation outcome.

In mobile SCTP, a mobile terminal has two or more network interfaces and vertical handover occurs when it moves from one network to another. The delay due to the handover process and the slow-start phase of SCTP's congestion control after handover cause substantial performance degradation. If the mobile node goes back and forth frequently, excessive handovers occur and data transmission quality deteriorates. In order to provide the required level of QoS for on-going application, the frequency of handovers should be kept minimized. In this paper, we propose a transport layer handover mechanism using the mobile SCTP. We take the QoS requirements of application as the major criterion in deciding path switching. In our mechanism, the mobile node in overlapping area does not perform handover if the current network metrics satisfy the QoS requirements of on-going application. Both analytic evaluation and simulation results show that the proposed mechanism significantly improves the throughput by suppressing unnecessary handovers. Our research results can also be applied to distributed mobile sensor networks.