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Excessive abdominal fat deposition negatively impacts poultry meat production and carcass yield. Identification of novel adipogenesis regulators may help improve production performance declines caused by excessive fat deposition. NUMB Endocytic Adaptor Protein (NUMB) typically functions as a cell fate determinant and plays a significant role in cell development and various diseases. Here, we found that NUMB is abundantly expressed in chicken abdominal fat depots and is induced in cultured adipocytes following adipogenic treatment. The gain- and loss-of-function experiments demonstrated that NUMB promotes the proliferation and G1/S transition of chicken adipocytes, enhances adipocyte differentiation, and increases the expression of PPARγ1 transcript. Through mRNA-seq analysis and molecular experiments, we further confirmed that NUMB inhibits the transcriptional activation of the NOTCH1 pathway and the expression of the downstream transcription factor HES1 by inducing NOTCH1 degradation. Nevertheless, the inhibition of the NOTCH1/HES1 axis alone cannot fully explain NUMB's role in adipogenesis, as NUMB also regulates the expression of multiple adipogenic transcription factors such as E2F1, EGR2, and NR4A3. Our data suggest that NUMB is a potent activator of adipogenesis and enhances our understanding of its regulatory mechanisms in chicken abdominal fat deposition., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Photocatalytic H 2 evolution technology is regarded as a promising and green route for the urgent requirement of efficient H 2 production. At present, low efficiency is a major bottleneck that limits the practical application of photocatalytic H 2 evolution. The construction of high-activity photocatalysts is highly crucial for achieving advanced hydrogen generation. Herein, a new S-scheme FeS 2 @ZnIn 2 S 4 (FeS 2 @ZIS) heterostructure as the photocatalyst was developed for enhanced photocatalytic H 2 evolution. Density function theory (DFT) calculation results strongly demonstrated that FeS 2 @ZIS generates a giant interface electric field (IEF), thus promoting the separation efficiency of photogenerated charge carriers for efficient visible-light-driven hydrogen evolution. At optimal conditions, the H 2 production rate of the 8%FeS 2 @ZIS is 5.3 and 3.6 times higher than that of the pure FeS 2 and ZIS, respectively. The experimental results further indicate that the close contact between FeS 2 and ZIS promotes the formation of the S-scheme heterojunction, where the interfacial charge transfer achieves spatial separation of charge carriers. This further broadens the light absorption range of the FeS 2 @ZIS and improves the utilization rate of photogenerated charge carriers. This work thus offers new insights that the FeS 2 -based co-catalyst can enrich the research on S-scheme heterojunction photocatalysts and improve the transfer and separation efficiency of photogenerated carriers for photocatalytic hydrogen production.

Background: Lung adenocarcinoma (LUAD) is a highly aggressive and rapidly fatal malignancy worldwide. Collagen XVII (COL17A1) has been implicated in various protumorigenic processes. However, the functions and mechanisms of COL17A1 in LUAD progression still remain elusive., Methods: COL17A1 and ubiquitin-specific protease 22 (USP22) mRNA analysis was performed by quantitative PCR, and their protein levels were detected by immunoblotting and immunohistochemistry. The functional influence was evaluated by determining cell viability, proliferation, apoptosis, invasion, migration, and ferroptosis in vitro, as well as xenograft growth in vivo. Co-immunoprecipitation (Co-IP) and IP experiments were used to examine the USP22/COL17A1 interaction and COL17A1 deubiquitination. Cycloheximide treatment was used to analyze COL17A1 protein stability., Results: COL17A1 and USP22 were upregulated in human LUAD tissues and cell lines. Functionally, COL17A1 knockdown acted for the suppression of LUAD cell growth, invasion, and migration as well as promotion of cell apoptosis and ferroptosis in vitro. COL17A1 knockdown could diminish the tumorigenicity of LUAD cells in vivo. Mechanistically, USP22 stabilized and upregulated COL17A1 by enhancing the deubiquitination of COL17A1. Additionally, reexpression of COL17A1 could reverse USP22 silencing-induced phenotype changes of LUAD cells in vitro., Conclusion: Our findings demonstrate that USP22-stabilized COL17A1 possesses oncogenic activity in LUAD. We propose that USP22 and COL17A1 would be potential targets for the establishment of therapeutic approaches against LUAD., (© 2024 The Author(s). The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

Introduction: The gut microbiota and the microbiota-gut-brain axis have gained considerable attention in recent years, emerging as key players in the mechanisms that mediate the occurrence and progression of many central nervous system-related diseases, including epilepsy. In clinical practice, one of the side effects of quinolone antibiotics is a lower seizure threshold or aggravation. However, the underlying mechanism remains unclear., Methods: We aimed to unravel the intrinsic mechanisms through 16S rRNA sequencing and serum untargeted metabolomic analysis to shed light on the effects of gut microbiota in ciprofloxacin-induced seizure susceptibility and lithium pilocarpine-induced epilepsy rat models., Results: We observed that ciprofloxacin treatment increased seizure susceptibility and caused gut dysbiosis. We also found similar changes in the gut microbiota of rats with lithium pilocarpine-induced epilepsy. Notably, the levels of Akkermansia and Bacteroides significantly increased in both the ciprofloxacin-induced seizure susceptibility and lithium pilocarpine-induced epilepsy rat models. However, Marvinbryantia, Oscillibacter , and Ruminococcaceae_NK4A214_group showed a coincidental reduction. Additionally, the serum untargeted metabolomic analysis revealed decreased levels of indole-3-propionic acid, a product of tryptophan-indole metabolism, after ciprofloxacin treatment, similar to those in the plasma of lithium pilocarpine-induced epilepsy in rats. Importantly, alterations in the gut microbiota, seizure susceptibility, and indole-3-propionic acid levels can be restored by fecal microbiota transplantation., Conclusion: In summary, our findings provide evidence that ciprofloxacin-induced seizure susceptibility is partially mediated by the gut microbiota and tryptophan-indole metabolism. These associations may play a role in epileptogenesis, and impacting the development progression and treatment outcomes of epilepsy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zou, Li, Zou, Yang, Li, Niu, Lai, Wang, Yang and Zhou.)

Due to the complex heterogeneity in different cancer types, the heterodimeric strategy has been intensively practiced to improve the effectiveness of tumor diagnostics. In this study, we developed a series of novel 18 F-labeled biotin/FAPI-conjugated heterobivalent radioligands ([ 18 F]AlF-NSFB, [ 18 F]AlF-NSFBP 2 , and [ 18 F]AlF-NSFBP 4 ), synergistically targeting both fibroblast activation protein (FAP) and biotin receptor (BR), to enhance specific tumor uptake and retention. The in vitro and in vivo biological properties of these dual-targeting tracers were evaluated, with a particular focus on positron emission tomography imaging in A549 and HT1080-FAP tumor-bearing mice. Notably, in comparison to the corresponding FAP-targeted monomer [ 18 F]AlF-NSF, biotin/FAPI-conjugated heterodimers exhibited a high uptake in tumor and prolong retention. In conclusion, as a proof-of-concept study, the findings validated the superiority of biotin/FAPI-conjugated heterodimers and the positive influence of biotin and linker on pharmacokinetics of radioligands. Within them, the bispecific [ 18 F]AlF-NSFBP 4 holds significant promise as a candidate for further clinical translational studies.

Recognizing the significance of SPECT in nuclear medicine and the pivotal role of fibroblast activation protein (FAP) in cancer diagnosis and therapy, this study focuses on the development of 99m Tc-labeled dimeric HF 2 with high tumor uptake and image contrast. The dimeric HF 2 was synthesized and radiolabeled with 99m Tc in one pot using various coligands (tricine, TPPTS, EDDA, and TPPMS) to yield [ 99m Tc]Tc-TPPTS-HF 2 , [ 99m Tc]Tc-EDDA-HF 2 , and [ 99m Tc]Tc-TPPMS-HF 2 dimers. SPECT imaging results indicated that [ 99m Tc]Tc-TPPTS-HF 2 exhibited higher tumor uptake and tumor-to-normal tissue (T/NT) ratio than [ 99m Tc]Tc-EDDA-HF 2 and [ 99m Tc]Tc-TPPMS-HF 2 . Notably, [ 99m Tc]Tc-TPPTS-HF 2 exhibited remarkable tumor accumulation and retention in HT-1080-FAP and U87-MG tumor-bearing mice, thereby surpassing the monomeric [ 99m Tc]Tc-TPPTS-HF. Moreover, [ 99m Tc]Tc-TPPTS-HF2 achieved acceptable T/NT ratios in the hepatocellular carcinoma patient-derived xenograft (HCC-PDX) model, which provided identifiable contrast and imaging quality. In conclusion, this study presents proof-of-concept research on 99m Tc-labeled FAP inhibitor dimers for the visualization of multiple tumor types. Among these candidate compounds, [ 99m Tc]Tc-TPPTS-HF 2 showed excellent clinical potential, thereby enriching the SPECT tracer toolbox.

Background: The hyperpolarization-activated cyclic nucleotide-gated cation channel (HCN1) is predominantly located in key regions associated with epilepsy, such as the neocortex and hippocampus. Under normal physiological conditions, HCN1 plays a crucial role in the excitatory and inhibitory regulation of neuronal networks. In temporal lobe epilepsy, the expression of HCN1 is decreased in the hippocampi of both animal models and patients. However, whether HCN1 expression changes during epileptogenesis preceding spontaneous seizures remains unclear., Objective: The aim of this study was to determine whether the expression of HCN1 is altered during the epileptic prodromal phase, thereby providing evidence for its role in epileptogenesis., Methods: We utilized a cobalt wire-induced rat epilepsy model to observe changes in HCN1 during epileptogenesis and epilepsy. Additionally, we also compared HCN1 alterations in epileptogenic tissues between cobalt wire- and pilocarpine-induced epilepsy rat models. Long-term video EEG recordings were used to confirm seizures development. Transcriptional changes, translation, and distribution of HCN1 were assessed using high-throughput transcriptome sequencing, total protein extraction, membrane and cytoplasmic protein fractionation, western blotting, immunohistochemistry, and immunofluorescence techniques., Results: In the cobalt wire-induced rat epilepsy model during the epileptogenesis phase, total HCN1 mRNA and protein levels were downregulated. Specifically, the membrane expression of HCN1 was decreased, whereas cytoplasmic HCN1 expression showed no significant change. The distribution of HCN1 in the distal dendrites of neurons decreased. During the epilepsy period, similar HCN1 alterations were observed in the neocortex of rats with cobalt wire-induced epilepsy and hippocampus of rats with lithium pilocarpine-induced epilepsy, including downregulation of mRNA levels, decreased total protein expression, decreased membrane expression, and decreased distal dendrite expression., Conclusions: Alterations in HCN1 expression and distribution are involved in epileptogenesis beyond their association with seizure occurrence. Similarities in HCN1 alterations observed in epileptogenesis-related tissues from different models suggest a shared pathophysiological pathway in epileptogenesis involving HCN1 dysregulation. Therefore, the upregulation of HCN1 expression in neurons, maintenance of the HCN1 membrane, and distal dendrite distribution in neurons may represent promising disease-modifying strategies in epilepsy., Competing Interests: Declaration of Competing Interest None, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Proliferative nodular formation represents a characteristic pathological feature of benign prostatic hyperplasia (BPH) and serves as the primary cause for prostate volume enlargement and consequent lower urinary tract symptoms (LUTS). Its specific mechanism is largely unknown, although several cellular processes have been reported to be involved in BPH initiation and development and highlighted the crucial role of epithelial cells in proliferative nodular formation. However, the technological limitations hinder the in vivo investigation of BPH patients., Methods: The robust cell type decomposition (RCTD) method was employed to integrate spatial transcriptomics and single cell RNA sequencing profiles, enabling the elucidation of epithelial cell alterations during nodular formation. Immunofluorescent and immunohistochemical staining was performed for verification., Results: The alterations of epithelial cells during the formation of nodules in BPH was observed, and a distinct subgroup of basal epithelial (BE) cells, referred to as BE5, was identified to play a crucial role in driving this progression through the hypoxia-induced epithelial-mesenchymal transition (EMT) signaling pathway. BE5 served as both the initiating cell during nodular formation and the transitional cell during the transformation from luminal epithelial (LE) to BE cells. A distinguishing characteristic of the BE5 cell subgroup in patients with BPH was its heightened hypoxia and upregulated expression of FOS. Histological verification results confirmed a significant association between c-Fos expression and key biological processes such as hypoxia and cell proliferation, as well as the close relationship between hypoxia and EMT in BPH tissues. Furthermore, a strong link between c-Fos expression and the progression of BPH was also been validated. Additionally, notable functional differences were observed in glandular and stromal nodules regarding BE5 cells, with BE5 in glandular nodules exhibiting enhanced capacities for EMT and cell proliferation characterized by club-like cell markers., Conclusions: This study elucidated the comprehensive landscape of epithelial cells during in vivo nodular formation in patients, thereby offering novel insights into the initiation and progression of BPH., (© 2024. The Author(s).)

The stimulator of interferon genes (STING) is pivotal in mediating STING-dependent type I interferon production, which is crucial for enhancing tumor rejection. Visualizing STING within the tumor microenvironment is valuable for STING-related treatments, yet the availability of suitable STING imaging probes is limited. In this study, we developed [ 18 F]AlF-ABI, a novel 18 F-labeled agent featuring an amidobenzimidazole core structure, for positron emission tomography (PET) imaging of STING in B16F10 and CT26 tumors. [ 18 F]AlF-ABI was synthesized with a decay-corrected radiochemical yield of 38.0 ± 7.9% and radiochemical purity exceeding 97%. The probe exhibited a nanomolar STING binding affinity ( K D = 35.6 nM). Upon administration, [ 18 F]AlF-ABI rapidly accumulated at tumor sites, demonstrating significantly higher uptake in B16F10 tumors compared to CT26 tumors, consistent with STING immunofluorescence patterns. Specificity was further validated through in vitro cell experiments and in vivo blocking PET imaging. These findings suggest that [ 18 F]AlF-ABI holds promise as an effective agent for visualizing STING in the tumor microenvironment.

The NOTCH signaling pathway plays a pivotal role in diverse developmental processes, including cell proliferation and differentiation. In this study, we investigated whether this signaling molecules also contribute to avian adipogenesis. Using previous mRNA-seq datasets, we examined the expression of 11 signaling members during avian adipocyte differentiation. We found most members are down-regulated throughout differentiation ( p < 0.05). As a representative, NOTCH1 was decreased in cultured chicken abdominal adipocytes during adipogenesis at mRNA and protein levels ( p < 0.05). Moreover, using an overexpression plasmid for NOTCH1's intracellular domain (NICD1), as well as siRNA and DAPT to activate or deplete NOTCH1 in cells, we investigated the role of NOTCH1 in avian adipogenesis. Our findings illuminate that NOTCH1 activates the expression of HES1 and SOCS3 while it decreases NR2F2 and NUMB ( p < 0.05), as well as inhibits oleic acid-induced adipocyte differentiation ( p < 0.01). We further demonstrate that HES1 , a downstream transcription factor activated by NOTCH1 , also significantly inhibits adipogenesis by suppressing PPARγ and C/EBPα ( p < 0.01). Collectively, these findings establish NOTCH1 as a negative regulator of avian adipocyte differentiation, unveiling NOTCH signaling as a potential target for regulating avian fat deposition.

Agricultural nonpoint source (NPS) pollution loss is closely related to hydrological processes. Understanding the differences in NPS pollution load loss under hydrological processes is useful for the management and prevention of NPS pollution. In this paper, hydrological and water quality data from 2016 to 2018 and monitoring data of physical and chemical indicators in 1347 field soil samples in the Shaying River Basin (SYRB) were used to analyze spatiotemporal variations in NPS pollution using the Soil and Water Assessment Tool and multifactor analysis of variance. The intensities and differences in NPS pollution losses for different soil types and land use patterns were evaluated under different hydrological zones. The annual rainfall in the SYRB decreased gradually from 1136.50 to 404.04 mm, showing a significant zoning. Areas with high loss intensities were mainly distributed in areas with steep slopes and in the 800-1000 mm rainfall zone. Cultivated land had the largest loss of NPS pollution, followed by forest land and rural residential land. Fluvo-aquic soil had the largest loss of NPS pollution, followed by cinnamon soil and lime concretion black soil. A nonlinear regression model was established for rainfall and the NPS pollution loss intensity and had a correlation coefficient of 0.60-0.99 at a 95% confidence level. Slope and rainfall were the main factors influencing the nitrogen and phosphorus losses. In the 800-1000 mm rainfall zone, the soil background nitrogen and phosphorus load was also a major factor influencing the nitrogen and phosphorus loss intensities., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Glioma is the most common primary malignant brain tumour, and survival is poor. Hirudin has anticancer pharmacological effects through suppression of glioma cell progression, but the molecular target and mechanism are poorly understood. In this study, we observed that hirudin dose- and time-dependently inhibited glioma invasion, migration and proliferation. Mechanistically, hirudin activated LC3-II but not Caspase-3 to induce the autophagic death of glioma cells by decreasing the phosphorylation of mTOR and its downstream substrates ULK1, P70S6K and 4EBP1. Furthermore, hirudin inhibited glioma growth and induced changes in autophagy in cell-derived xenograft (CDX) nude mice, with a decrease in mTOR activity and activation of LC3-II. Collectively, our results highlight a new anticancer mechanism of hirudin in which hirudin-induced inhibition of glioma progression through autophagy activation is likely achieved by inhibition of the mTOR signalling pathway, thus providing a molecular basis for hirudin as a potential and effective clinical drug for glioma therapy., (© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Purpose: Evans blue as an albumin binder has been widely used to improve pharmacokinetics and enhance tumor uptake of radioligands, including prostate-specific membrane antigen (PSMA) targeting agents. The goal of this study is to develop an optimal Evans blue-modified radiotherapeutic agent that could maximize the absolute tumor uptake and tumor absorbed dose thus the therapeutic efficacy to allow treatment of tumors even with moderate level of PSMA expression., Methods: [ 177 Lu]Lu-LNC1003 was synthesized based on PSMA-targeting agent and Evans blue. Binding affinity and PSMA targeting specificity were verified through cell uptake and competition binding assay in 22Rv1 tumor model that has moderate level of PSMA expression. SPECT/CT imaging and biodistribution studies in 22Rv1 tumor-bearing mice were performed to evaluate the preclinical pharmacokinetics. Radioligand therapy studies were conducted to systematically assess the therapeutic effect of [ 177 Lu]Lu-LNC1003., Results: LNC1003 showed high binding affinity (IC 50  = 10.77 nM) to PSMA in vitro, which was comparable with that of PSMA-617 (IC 50  = 27.49 nM) and EB-PSMA-617 (IC 50  = 7.91 nM). SPECT imaging of [ 177 Lu]Lu-LNC1003 demonstrated significantly improved tumor uptake and retention as compared with [ 177 Lu]Lu-EB-PSMA and [ 177 Lu]Lu-PSMA-617, making it suitable for prostate cancer therapy. Biodistribution studies further confirmed the remarkably higher tumor uptake of [ 177 Lu]Lu-LNC1003 (138.87 ± 26.53%ID/g) over [ 177 Lu]Lu-EB-PSMA-617 (29.89 ± 8.86%ID/g) and [ 177 Lu]Lu-PSMA-617 (4.28 ± 0.25%ID/g) at 24 h post-injection. Targeted radioligand therapy results showed noteworthy inhibition of 22Rv1 tumor growth after administration of a single dose of 18.5 MBq [ 177 Lu]Lu-LNC1003. There was no obvious antitumor effect after [ 177 Lu]Lu-PSMA-617 treatment under the same condition., Conclusion: In this study, [ 177 Lu]Lu-LNC1003 was successfully synthesized with high radiochemical purity and stability. High binding affinity and PSMA targeting specificity were identified in vitro and in vivo. With greatly enhanced tumor uptake and retention, [ 177 Lu]Lu-LNC1003 has the potential to improve therapeutic efficacy using significantly lower dosages and less cycles of 177 Lu that promises clinical translation to treat prostate cancer with various levels of PSMA expression., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The polyphosphoric acid (PPA) modified asphalt binder is a potential choice as one of the pavement materials for its excellent high-temperature performance and low cost. To further analyze the influences of temperature and load on the service life of pavement from the perspective of deformation behavior, six kinds of asphalt binders with different PPA dosages were prepared for Multiple Stress Creep and Recovery (MSCR) tests at five temperature levels. The deformation behavior is investigated by basic deformation parameters, rheological simulation, and energy parameter changes. The results show that the percent recovery (R) drops sharply while non-recoverable creep compliance (Jnr) goes up slightly with the increase in temperature. Three-element model, composed by E1, η1, and η2, can be used to describe the creep behavior. PPA-modified asphalt binder exhibits nonlinear creep behavior, and the logarithmic model can simulate recovery behavior better than the power-law model. Stored energy and dissipated energy can characterize the change of energy in the creep process under different conditions and show a significant correlation to deformation parameters. It is concluded that the elastic component of asphalt binders is increased by PPA, which is beneficial to the improvement of the deformation resistance and recovery capacity of asphalt binders. The recommended dosage of PPA is 1.5%. This investigation is conducive to a better understanding of the deformation behavior of PPA-modified asphalt binders and provides a reference for its engineering applications.

Purpose: To determine the prognostic value of tumour contour irregularity degree (CID) in surgical strategy options for T1bN0M0 renal cell carcinoma (RCC)., Materials and Methods: We performed a retrospective multi-institutional review of 489 patients with T1bN0M0 RCC treated between January 2009 and June 2019. Cox regression and Kaplan-Meier analyses were performed to analyse the impact of CID on disease-free survival (DFS)., Results: The median follow-up time was 55 months (interquartile range, 40-81 months) for 55 (11.2 %) patients with metastasis or recurrence. Logistic analysis indicated that CID was associated with World Health Organization/International Society of Urological Pathology (WHO/ISUP) grades III-IV (odds ratio, 1.015; 95 % confidence interval [CI], 1.008-1.023; p < 0.001). After being classified into high CID (≥50 %) and low CID (<50 %) groups, those with a high CID showed a significantly higher ratio of WHO/IUSP grades III-IV (74/277 [26.7 %] vs 25/212 [11.8 %]) and shorter DFS than the low CID group (p < 0.001). Multivariable Cox regression showed that partial nephrectomy (PN; hazard ratio [HR], 1.889; 95 % CI, 1.020-3.499; p = 0.043), high CID (HR, 6.685; 95 % CI, 2.776-16.100; p < 0.001), and WHO/ISUP grade III-IV (HR, 1.950; 95 % CI, 1.100-3.458; p = 0.022) were independent prognostic factors for DFS. The Kaplan-Meier plot showed that PN had a DFS rate comparable to that of radical nephrectomy (RN; p = 0.994). In the low CID group, patients who underwent PN showed comparable DFS to those who underwent RN (p = 0.903). Furthermore, patients with a high CID tended to have worse DFS in the PN versus RN group (p = 0.044). Multivariable Cox regression showed that PN (HR, 2.049; 95 % CI, 1.065-3.942; p = 0.032) and WHO/ISUP grade III-IV (HR, 2.148; 95 % CI, 1.189-3.881; p = 0.011) were independent prognostic factors of DFS in the high CID group., Conclusions: CID is a reliable preoperative parameter which is positively correlated with WHO/ISUP grade and can help with surgical decision-making in patients with T1bN0M0 RCC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Angiogenesis is an essential physiological process in the growth and metastasis of primary tumors. Ca 2+ signaling is crucial for tumor angiogenesis. The purpose of this study was to detect the potential role of Ca 2+ permeable transient receptor potential vanilloid-3 (TRPV3) in the angiogenesis of non-small cell lung cancer (NSCLC)., Methods: Small interfering RNA was used to down-regulate TRPV3 expression in A549 cells. A laser scanning confocal microscope was used to examine intracellular calcium concentration ([Ca 2+ ]i). Human umbilical vein endothelial cells (HUVECs) tube formation and migration assay, Western blot, MTT and ELISA were performed to detect the potential mechanisms of TRPV3 in tumor angiogenesis. A mouse tumor xenograft model was performed to expound the effects of TRPV3 on tumor cell growth., Results: Inhibition of TRPV3 reduced [Ca 2+ ]i and protein expressions of VEGF and HIF-1α in A549 cells. Moreover, HIF-1α depletion decreased the secretion and expression of VEGF. Depletion of TRPV3 inhibited HUVECs proliferation, tube formation and migration induced by conditioned medium. And TRPV3 inhibition could decrease the volume of xenograft tumors and MVD of CD34 + cells. The expression levels of HIF-1α, VEGF and p-CaMKП in the xenograft tumors in RuR and siTRPV3 groups was reduced., Conclusions: TRPV3 calcium channel protein may play a key role in NSCLC angiogenesis. TRPV3 could promote the angiogenesis through HIF-1α-VEGF signaling pathway. Targeting TRPV3 channel protein by novel approaches would be useful for reversing NSCLC angiogenesis., Competing Interests: Competing interests All the authors declared that there is no conflict of interest in this work., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Angioimmunoblastic T-cell lymphoma (AITL), a type of malignant lymphoma with unique genomic aberrations, significant clinicopathological features, and poor prognosis, is characterized by immune system dysregulation. Recent sequencing studies have identified recurrent mutations and interactions in tet methylcytosine dioxygenase 2 ( TET2 ), ras homology family member A ( RHOA ), DNA methyltransferase 3 alpha ( DNMT3A ), and mitochondrial isocitrate dehydrogenase II ( IDH2 ). Notably, since B-cell lymphomas are frequently observed along with AITL, this review first summarizes its controversial mechanisms based on traditional and recent views. Epigenetic regulation represented by TET2 plays an increasingly important role in understanding the multi-step and multi-lineage tumorigenesis of AITL, providing new research directions and treatment strategies for patients with AITL. Here, we review the latest advances in our understanding of AITL and highlight relevant issues that have yet to be addressed in clinical practice.

Background: Tuberous root formation and development is a complex process in sweet potato, which is regulated by multiple genes and environmental factors. However, the regulatory mechanism of tuberous root development is unclear., Results: In this study, the transcriptome of fibrous roots (R0) and tuberous roots in three developmental stages (Rl, R2, R3) were analyzed in two sweet potato varieties, GJS-8 and XGH. A total of 22,914 and 24,446 differentially expressed genes (DEGs) were identified in GJS-8 and XGH respectively, 15,920 differential genes were shared by GJS-8 and XGH. KEGG pathway enrichment analysis showed that the DEGs shared by GJS-8 and XGH were mainly involved in "plant hormone signal transduction" "starch and sucrose metabolism" and "MAPK signal transduction". Trihelix transcription factor (Tai6.25300) was found to be closely related to tuberous root enlargement by the comprehensive analysis of these DEGs and weighted gene co-expression network analysis (WGCNA)., Conclusion: A hypothetical model of genetic regulatory network for tuberous root development of sweet potato is proposed, which emphasizes that some specific signal transduction pathways like "plant hormone signal transduction" "Ca 2+ signal" "MAPK signal transduction" and metabolic processes including "starch and sucrose metabolism" and "cell cycle and cell wall metabolism" are related to tuberous root development in sweet potato. These results provide new insights into the molecular mechanism of tuberous root development in sweet potato., (© 2022. The Author(s).)

Temporal and spatial variations in river water quality and the factors influencing such variations are important basis and prerequisites for identifying pollution sources and improving river water environment. Monthly data for 22 indicators at 485 surface water quality (SWQ) monitoring sites (46,560 groups) in the Huaihe River Basin (HRB) from 2011 to 2018 were analyzed. This paper assessed temporal and spatial changes in SWQ in the HRB and identified the main factors influencing the changes and each factor's contribution to the changes. The five-day biological oxygen demand, permanganate index, fluoride, ammonium nitrogen, and total phosphorus were the main pollutants. Spatial cluster analysis indicated that the HRB could be divided by SWQ into areas I-IV from light to heavy pollution. Areas I and IV were nitrogen and phosphorus nutrients pollution, and areas II and III were heavy metals and organic pollution. Area IV (poor SWQ) locates mainly north of the Huaihe mainstream with annual average rainfall ≤ 640 mm. SWQ in the HRB has been improving for two decades, with an inflection point in 2015 between 2011 and 2018, and rainfall change is an important factor for the inflection point. The urbanization rate, industrial water consumption, and rainfall were the key factors influencing SWQ changes in the watershed with significant hydrological zonation, with urbanization rate and rainfall increased, industrial water consumption decreased, the SWQ was gradually improved. The key factors contributing to SWQ changes in the future will be the sewage treatment rate and rainfall changes caused by natural variations., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aqueous-phase oxygen evolution reaction (OER) is the bottleneck of water splitting. The formation of the O-O bond involves the generation of paramagnetic oxygen molecules from the diamagnetic hydroxides. The spin configurations might play an important role in aqueous-phase molecular electrocatalysis. However, spintronic electrocatalysis is almost an uncultivated land for the exploration of the oxygen molecular catalysis process. Herein, we present a novel magnetic Fe III site spin-splitting strategy, wherein the electronic structure and spin states of the Fe III sites are effectively induced and optimized by the Jahn-Teller effect of Cu 2+ . The theoretical calculations and operando attenuated total reflectance-infrared Fourier transform infrared (ATR FT-IR) reveal the facilitation for the O-O bond formation, which accelerates the production of O 2 from OH - and improves the OER activity. The Cu 1 -Ni 6 Fe 2 -LDH catalyst exhibits a low overpotential of 210 mV at 10 mA cm -2 and a low Tafel slope (33.7 mV dec -1 ), better than those of the initial Cu 0 -Ni 6 Fe 2 -LDHs (278 mV, 101.6 mV dec -1 ). With the Cu 2+ regulation, we have realized the transformation of NiFe-LDHs from ferrimagnets to ferromagnets and showcase that the OER performance of Cu-NiFe-LDHs significantly increases compared with that of NiFe-LDHs under the effect of a magnetic field for the first time. The magnetic-field-assisted Cu 1 -Ni 6 Fe 2 -LDHs provide an ultralow overpotential of 180 mV at 10 mA cm -2 , which is currently one of the best OER performances. The combination of the magnetic field and spin configuration provides new principles for the development of high-performance catalysts and understandings of the catalytic mechanism from the spintronic level.

The cell cycle machinery controls cell proliferation and the dysregulation of the cell cycle lies at the heart of carcinogenesis. Thus, exploring the unknown regulators involved in the cell cycle not only contribute to better understanding of cell proliferation but also provide substantial improvement to cancer therapy. In this study, we identified that the expression of methyltransferase METTL3 was upregulated in the M phase. Overexpression of METTL3 facilitated cell cycle progression, induced cell proliferation in vitro and enhanced tumorigenicity in vivo , while knockdown of METTL3 reversed these processes. METTL3 induced CDC25B mRNA m 6 A modification in the M phase, which accelerated the translation of CDC25B mRNA through YTHDF1-dependent m 6 A modification. Clinical data analysis showed that METTL3 and CDC25B were highly expressed in cervical cancer. Our work reveals that a new mechanism regulates cell cycle progression through the METTL3/m 6 A/CDC25B pathway, which provides insight into the critical roles of m 6 A methylation in the cell cycle., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Purpose: To explore the predictive value of renal tumor contour irregular degree (CID) in pathological T3a upstaging of clinical T1 renal cell carcinoma (RCC)., Materials and Methods: We performed a retrospective multi-institutional review of 1,487 patients with clinical T1N0M0 RCC between January 2009 and June 2019. Kaplan-Meier survival curve and Cox regressions were used to analyze the prognostic factors of disease-free survival (DFS). Logistic regressions were performed to determine predictors of pathological T3a upstaging in clinical T1 RCC., Results: Among 1,487 patients with cT1 RCC, 96 (6.5%) were pathological T3a upstaging. Multivariable logistic regression analysis showed that age (odds ratio [OR] = 1.022, 95% confidence interval [CI] = 1.001-1.042, P = 0.036), tumor maximum diameter(OR = 1.242, 95% CI = 1.042--1.480, P = 0.015) and CID (OR = 1.067, 95% CI = 1.051-1.083, P < 0.001) were independent predictors of pathological T3a upstaging. The area under the curve (AUC) of the prediction model that included the CID was 0.846, while the AUC of the prediction model that did not include CID was only 0.741, the difference was statistically significant (P < 0.001). Kaplan-Meier survival curve showed that patients with pathological T3a upstaging had significantly worse DFS than patients without pathological T3a upstaging (P < 0.001). Multivariable Cox analysis showed that pathological T3a upstaging (HR = 1.836, 95% CI = 1.013-3.329, P = 0.002) is an independent prognostic factor for DFS in patients with cT1N0M0 RCC., Conclusions: The predictive model of CID combined with tumor maximum diameter and age significantly improved the ability to predict pathological T3a upstaging in clinical T1 RCC, compared with the prediction model of tumor maximum diameter combined with age. The predictive model of CID combined with tumor maximum diameter and age may be applicable to patients considering partial vs. radical nephrectomy., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: Limited literature exists on primary external auditory canal (EAC) cholesteatoma (EACC). Here, we focus on the clinical features of this rare disease, especially the invasive patterns of lesion progression, through a large population study and present simple and practical staging., Methods: In all, 276 patients (male 99; female 177; mean age 41.3 ± 21 years; ears 301) with primary EACC were retrospectively analyzed. Stage I indicated EACC without bony lesions, stage II indicated invasion confined within EAC, stage III indicated invasion beyond the EAC involving mastoid air cells or tympanic cavity, but within the temporal bone, and stage IV indicated invasion beyond the temporal bone., Results: In all, 41, 219, 40, and 1 ear with Stage I, II, III, and IV lesions were found, respectively. Common clinical symptoms were hearing loss (237 ears, 78.7%), otalgia (221 ears, 73.4%), and otorrhea (85 ears, 28.2%). The mean air conduction and air-bone gaps were 45.4 ± 17.9 dB HL and 24.6 ± 15 dB HL, respectively. EACCs were found to invade in all directions of the EAC, with the inferior wall (224 ears, 74.4%) > posterior wall (207 ears, 68.8%) > anterior wall (186 ears, 61.8%) > superior wall (86 ears, 28.6%) invasion; multiwall invasions (207 ears) were common; however, inward invasions into the tympanic cavity were rare., Conclusion: Primary EACCs occurred mostly in women and often unilaterally invaded multiple bony walls in the lower half of the EAC. The present staging reflects the patterns and severity of lesion progression and may be beneficial in treatment planning., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Two-dimensional MXene with high conductivity has metastable Ti atoms and inert functional groups on the surface, greatly limiting application in surface-related electrocatalytic reactions. A surface-functionalized nitrogen-doped two-dimensional TiO 2 /Ti 3 C 2 T x heterojunction (N-TiO 2 /Ti 3 C 2 T x ) was fabricated theoretically, with high conductivity and optimized electrocatalytic active sites. Based on the conductive substrate of Ti 3 C 2 T x , the heterojunction remained metallic and efficiently accelerated the transfer of Li + and electrons in the electrode. More importantly, the precise regulation of active sites in the N-TiO 2 /Ti 3 C 2 T x heterojunction optimized the adsorption for LiO 2 and Li 2 O 2 , facilitating the sluggish kinetics with a lowest theoretical overpotential in both the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). Employed as an electrocatalyst in a Li-oxygen battery (Li-O 2 battery), it demonstrated a high specific capacity of 15 298 mAh g -1 and a superior cyclability with more than 200 cycles at 500 mA g -1 , as well as the swiftly reduced overpotential. Furthermore, combined with the in situ differential electrochemical mass spectrometry, ex situ Raman spectra, and SEM tests, the N-TiO 2 /Ti 3 C 2 T x heterojunction electrode presented a superior stability and reduced side reaction along with the high performance toward the ORR and OER. It provides an efficient insight for the design of high-performance electrocatalysts for metal-oxygen batteries.

Ferroptosis has been implicated in the therapeutic responses of various types of tumors. Cyclophosphamide (CTX), one of the most successful antitumor agents, is widely used to treat both hematopoietic and solid tumors. In this study, we revealed the ferroptosis pathway targeted by CTX treatment in tumor cells and clarified its mechanisms. Cell viability was remarkably suppressed by CTX, accompanied by the accumulation of intracellular iron and reactive oxygen species (ROS), reduced glutathione levels, deformed mitochondria and a loss of the mitochondrial membrane potential. These effects were impeded by the ferroptosis inhibitors ferrostatin-1 (Fer1) and deferoxamine (DFO). Moreover, CTX treatment obviously upregulated nuclear factor E2 related factor 2 (NRF2) and heme oxygenase-1 (HMOX-1) expression. Additionally, the HMOX-1 inducer Hemin notably enhanced CTX-mediated tumor inhibition in vitro and in vivo through a mechanism that involved interfering with the ferroptosis process. Therefore, our findings indicated ferroptosis induction by CTX through the activation of the NRF2/HMOX-1 pathway, which might provide a potential strategy for tumor chemotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shi, Hou, Li, Zhou and Du.)

Mixed multiple oxidation states CoMoO 4 nanowires (electrocatalysts) with tunable intrinsic oxygen vacancies were fabricated. CoMoO 4 with proper oxygen vacancy can be employed to construct a Li-air battery with a high capacity and stable cyclability. This is possible because CoMoO 4 contains surface oxygen vacancies, which result in the unit of CoMo bond, that is important for electrocatalysts used in Li-air batteries. Both the experimental and theoretical results demonstrate that the surface oxygen vacancies containing CoMoO 4 nanowires have a higher electrocatalytic activity. This shows that the highly efficient electrocatalysts used for Li-air batteries were designed to modify the redox properties of the mixed metal oxide in the catalytic active sites. This successful material design led to an improved strategy for high oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) activities based on the fast formation and extinction of ORR products., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Several studies have focused on the high potential effects of probiotics on the reproductive system. However, there is a paucity of information regarding the ameliorative intracellular roles of indigenous Iranian yogurt-extracted/cultured probiotics on animals' reproductive health suffering from obesity and/or fatty liver disease, such as non-alcoholic fatty liver disease (NAFLD). For this purpose, simultaneously with the consumption of D-fructose (200 g/1000 mL water, induction of NAFLD model), all pubertal animals were also gavaged every day for 63 consecutive days with extracted probiotics, including 1 × 10 9  CFU/mL of Lactobacillus acidophilus (LA), Bifidobacterium spp. (BIF), Bacillus coagulans (BC), Lactobacillus rhamnosus (LR), and a mixture form (LA + BIF + BC + LR). At the end of the ninth week, the indices of epididymal sperm, and oxidative stress, as well as histopathological changes, were assessed. The results show that NAFLD could induce robust oxidative stress, highlighted as considerable increments in ROS level, TBARS content, total oxidized protein levels, along with severe decrements in reduced glutathione reservoirs, total antioxidant capacity in the hepatic and testicular tissues, as well as testicular and hepatic histopathological alterations. Moreover, a significant decrease in the percentage of sperm progressive motility, sperm count, and membrane integrity along with an increment in the percentage of sperm abnormality was detected in NAFLD animals. The observed adverse effects were significantly reversed upon probiotics treatment, especially in the group challenged with a mixture of all probiotics. Taken together, these findings indicate that the indigenous yogurt-isolated/cultured probiotics had a high potential antioxidant activity and the ameliorative effect against reprotoxicity and blood biochemical alterations induced by the NAFLD model. Highlights: 1. Reproductive indices could be reversely affected by xenobiotics and diseases. 2. NAFLD and cholestasis considerably affect the reproductive system in both genders. 3. NAFLD induced hepatic and testicular oxidative stress (OS). 4. NAFLD induced histopathological alterations and spermatotoxicity through OS. 5. The adverse effects were significantly reversed upon exposure to probiotics., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We investigated the roles of rootstocks in Cu accumulation and tolerance in Malus plants by grafting 'Hanfu' (HF) scions onto M. baccata (Mb) and M. prunifolia (Mp) rootstocks, which have different Cu tolerances. The grafts were exposed to basal or excess Cu for 20 d. Excess Cu-treated HF/Mb had less biomass, and pronounced root architecture deformation and leaf ultrastructure damage than excess Cu-challenged HF/Mp. Root Cu concentrations and bio-concentration factor (BCF) were higher in HF/Mp than HF/Mb, whereas HF/Mb had higher stem and leaf Cu concentrations than HF/Mp. Excess Cu lowered root and aerial tissue BCF and translocation factor (T f ) in all plants; however, T f was markedly higher in HF/Mb than in HF/Mp. The subcellular distribution of Cu in the roots and leaves indicated that excess Cu treatments increased Cu fixation in the root cell walls, which decreased Cu mobility. Compared to HF/Mb, HF/Mp sequestered more Cu in its root cell walls and less Cu in leaf plastids, nuclei, and mitochondria. Moreover, HF/Mp roots and leaves had higher concentrations of water-insoluble Cu compounds than HF/Mb, which reduced Cu mobility and toxicity. Fourier transform infrared spectroscopy analysis showed that the carboxyl, hydroxyl and acylamino groups of the cellulose, hemicellulose, pectin and proteins were the main Cu binding sites in the root cell walls. Excess Cu-induced superoxide anion and malondialdehyde were 28.6% and 5.1% lower, but soluble phenolics, ascorbate and glutathione were 10.5%, 41.9% and 17.7% higher in HF/Mp than HF/Mb leaves. Compared with HF/Mb, certain genes involved in Cu transport were downregulated, while other genes involved in detoxification were upregulated in HF/Mp roots and leaves. Our results show that Mp inhibited Cu translocation and mitigated Cu toxicity in Malus scions by regulating Cu mobility, antioxidant defense mechanisms, and transcription of key genes involved in Cu translocation and detoxification., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Chemosensory proteins (CSPs) play important roles in chemical communication, but their precise physiological functions are still unclear. Cylas formicarius is the most serious pest attacking sweet potato around the world. At present, there is no effective way to control this pest., Results: Our results showed that CforCSP1, 5 and 6 genes were highly expressed in the antennae of both sexes of C. formicarius. In addition, results from a fluorescence competitive binding assay showed that the CforCSP1, 5 and 6 proteins had high binding affinities for 17 plant volatiles including eight host plant volatiles. This indicated that the three proteins may be involved in the detection of host plant volatiles. Furthermore, results from four-arm olfactometer bioassays showed that there was a significant tendency for C. formicarius to be attracted to eucalyptol, β-carotene, benzaldehyde, vanillin and phenethyl alcohol, while it was repelled by β-ionone. Finally, the levels of expression of the three CforCSPs in C. formicarius were successfully inhibited by RNA interference (RNAi). Behavioral experiments showed that CforCSP1, 5 and 6-deficient C. formicarius were partly anosmic to β-cyclocitral, benzaldehyde, octyl aldehyde, and β-ionone and exhibited a reduced ability to locate the host plant volatiles β-carotene and vanillin., Conclusion: Our data suggest that CforCSP1, 5 and 6 likely are involved in the chemical communication between C. formicarius and host plant volatiles, which may play pivotal roles in oviposition and feeding site preferences. More importantly, these results could provide information for the development of monitoring and push-pull strategies for the control of C. formicarius. © 2021 Society of Chemical Industry., (© 2021 Society of Chemical Industry.)

The cholestatic liver injury could occur in response to a variety of diseases or xenobiotics. Although cholestasis primarily affects liver function, it has been well-known that other organs such as the kidney could be influenced in cholestatic patients. Severe cholestasis could lead to tissue fibrosis and organ failure. Unfortunately, there is no specific therapeutic option against cholestasis-induced organ injury. Hence, finding the mechanism of organ injury during cholestasis could lead to therapeutic options against this complication. The accumulation of potentially cytotoxic compounds such as hydrophobic bile acids is the most suspected mechanism involved in the pathogenesis of cholestasis-induced organ injury. A plethora of evidence indicates a role for the inflammatory response in the pathogenesis of several human diseases. Here, the role of nuclear factor-kB (NFkB)-mediated inflammatory response is investigated in an animal model of cholestasis. Bile duct ligated (BDL) animals were treated with sulfasalazine (SSLZ, 10 and 100 mg/kg, i.p) as a potent inhibitor of NFkB signaling. The NFkB proteins family activity in the liver and kidney, serum and tissue levels of pro-inflammatory cytokines, tissue biomarkers of oxidative stress, serum markers of organ injury, and the liver and kidney histopathological alterations and fibrotic changes. The oxidative stress-mediated inflammatory-related indices were monitored in the kidney and liver at scheduled time intervals (3, 7, and 14 days after BDL operation). Significant increase in serum and urine markers of organ injury, besides changes in biomarkers of oxidative stress and tissue histopathology, were evident in the liver and kidney of BDL animals. The activity of NFkB proteins (p65, p50, p52, c-Rel, and RelB) was significantly increased in the liver and kidney of cholestatic animals. Serum and tissue levels of pro-inflammatory cytokines (IL-1β, IL-2, IL-6, IL-7, IL-12, IL-17, IL-18, IL-23, TNF-α, and INF-γ) were also higher than sham-operated animals. Moreover, TGF- β, α-SMA, and tissue fibrosis (Trichrome stain) were evident in cholestatic animals' liver and kidneys. It was found that SSLZ (10 and 100 mg/kg/day, i.p) alleviated cholestasis-induced hepatic and renal injury. The effect of SSLZ on NFkB signaling and suppression of pro-inflammatory cytokines could play a significant role in its protective role in cholestasis. Based on these data, NFkB signaling could receive special attention to develop therapeutic options to blunt cholestasis-induced organ injury., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To explore and analyze the effect and indication of hormone replacement therapy（HRT） in perimenopausal women with chronic tinnitus. Methods: The perimenopausal women with chronic tinnitus were divided into mild group and moderate to severe group according to Kupperman score of menopause, and then were divided into treatment group and untreated group according to whether they received MHT treatment or not. The serum 5-HT level, tinnitus handicap inventory （THI） and Pittsburgh sleep quality index （PSQI） were compared before and after treatment. Results: In moderate to severe perimenopausal tinnitus, the serum 5-HT level, THI and PSQI in the treatment group were statistically different before and after treatment（ P <0.05）, and no significant difference was found in the untreated group. In mild perimenopausal tinnitus, there was no significant difference in 5-HT levels, THI and PSQI between the treated group and the untreated group before and after treatment. The 5-HT levels were correlated with THI. The lower the 5-HT level was, the more severe tinnitus was. Conclusion: HRT is helpful in the treatment of perimenopausal chronic tinnitus, especially in moderate to severe perimenopausal patients, and is recommended for clinical use., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Cholestasis is a severe clinical complication that severely damages the liver. Kidneys are also the most affected extrahepatic organs in cholestasis. The pivotal role of oxidative stress has been mentioned in the pathogenesis of cholestasis-induced organ injury. The activation of the nuclear factor-E2-related factor 2 (Nrf2) pathway is involved in response to oxidative stress. The current study was designed to evaluate the potential role of Nrf2 signaling activation in preventing bile acids-induced toxicity in the liver and kidney. Dimethyl fumarate was used as a robust activator of Nrf2 signaling. Rats underwent bile duct ligation surgery and were treated with dimethyl fumarate (10 and 40 mg/kg). Severe oxidative stress was evident in the liver and kidney of cholestatic animals ( P  < 0.05). On the other hand, the expression and activity of Nrf2 and downstream genes were time-dependently decreased ( P  < 0.05). Moreover, significant mitochondrial depolarization, decreased ATP levels, and mitochondrial permeabilization were detected in bile duct-ligated rats ( P  < 0.05). Histopathological alterations included liver necrosis, fibrosis, inflammation and kidney interstitial inflammation, and cast formation. It was found that dimethyl fumarate significantly decreased hepatic and renal injury in cholestatic animals ( P  < 0.05). Based on these data, the activation of the cellular antioxidant response could serve as an efficient therapeutic option for managing cholestasis-induced organ injury., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Caoyuanwang Baijiu (CYW), a mild-flavor style Baijiu (MSB), is popular in northern China. However, there is a lack of studies reporting its aroma-active components. The aroma compounds of five CYW samples were analyzed using gas chromatography-olfactory-mass spectrometry coupled with aroma extraction dilution analysis. Fifty-five aroma-active compounds were identified in CYW, of which 27 had odor activity values ≥ 1. Reconstituted models successfully simulated the aroma profiles of CYW. The omission tests elucidated that β-damascenone, dimethyl trisulfide, ethyl pentanoate, butanoic acid, ethyl acetate, 3-methylbutanal, ethyl lactate, hexanoic acid, γ-nonalactone, 3-hydroxy-2-butanone, ethyl butanoate, 1-propanol, 4-(ethoxymethyl)-2-methoxy-phenol, and vanillin were key odorants in CYW. The addition test confirmed the significant influence of dimethyl trisulfide on Chen-aroma note. Nine key odorants were identified as the differential quality-markers, and 85.71% key odorants were predicted using the partial least square regression (PLSR) analysis, indicating the applicability of PLSR in selecting the target compounds for omission tests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Universal screening of congenital cytomegalovirus (cCMV) infection is important for monitoring and intervention during critical stages of speech and language development. This study aimed to explore the optimal detection strategy for cCMV infection screening., Methods: Serum samples from pregnant women and saliva and urine samples from their newborns were collected for the anti-CMV IgG and CMV DNA PCR tests, respectively. The sensitivity, specificity, and predictive values as well as the likelihood ratios of 12 potential screening strategies for cCMV infection, based on tests for saliva, urine, and their combination, were evaluated., Findings: A total of 6729 pregnant women were enrolled, and the seroprevalence was 98.1%. Among 6350 newborns that were followed up, 49 were defined as having cCMV infection. In the screening test, the CMV DNA positivity rate remained similar from day 0 to day 5, increased slowly from day 6 to day 13, and became high in newborns beyond 13 days of birth. In the confirmatory testing, the positive rates increased significantly beyond day 21. For the 49 newborns with cCMV infection, the proportion of agreement between saliva and urine testing was poor. Upon evaluating alternative screening strategies, using saliva and urine screening with saliva and urine confirmation as the reference strategy, saliva screening with saliva and urine confirmation showed good diagnostic accuracy and feasibility, with sensitivity, specificity, positive predictive and negative predictive values of 85.7%, 100.0%, 100.0% and 99.9%, respectively., Interpretation: In populations with high seroprevalence, saliva screening with saliva and urine confirmation might be an alternative strategy for screening cCMV infections. The suggested timeframes for screening and confirmation are within 13 (ideally 5) and 21 (ideally 13) days of birth, respectively., Funding: National Natural Science Foundation of China, National Science and Technology Major Project of China and Merck & Co., Inc., Kenilworth, New Jersey, U.S.A., Competing Interests: Jun Zhang received grant from Merck & Co., Inc. during the conduct of the study. All other authors declare no competing interests., (© 2021 The Author(s). Published by Elsevier Ltd.)

Cholestasis is a clinical complication with different etiologies. The liver is the primary organ influenced in cholestasis. Renal injury is also a severe clinical complication in cholestatic/cirrhotic patients. Several studies mentioned the importance of oxidative stress and mitochondrial impairment as two mechanistically interrelated events in cholestasis-induced organ injury. Apoptosis-inducing factor (AIF) is a flavoprotein located in the inner mitochondrial membrane. This molecule is involved in a distinct pathway of cell death. The current study aimed to evaluate the role of AIF in the pathophysiology of cholestasis-associated hepatic and renal injury. Bile duct ligation (BDL) was used as an animal model of cholestasis. Serum, urine, and tissue samples were collected at scheduled time intervals (3, 7, 14, and 28 days after BDL surgery). Tissues' AIF mRNA levels, as well as serum, urine, and tissue activity of AIF, were measured. Moreover, markers of DNA fragmentation and apoptosis were assessed in the liver and kidney of cholestatic animals. A significant increase in liver and kidney AIF mRNA levels, in addition to increased AIF activity in the liver, kidney, serum, and urine, was detected in BDL rats. DNA fragmentation and apoptosis were raised in the liver and kidney of cholestatic animals, especially at the early stage of the disease. The apoptotic mode of cell death in the liver and kidney was connected to a higher AIF level. These data mention the importance of AIF in the pathogenesis of cholestasis-induced organ injury, especially at the early stage of this disease. Mitochondrial release of apoptosis-inducing factor (AIF) seems to play a pathogenic role in cholestasis-associated hepatic and renal injury. AIF release is directly connected to oxidative stress and mitochondrial impairment in cholestatic animals.

This study aims to investigate the effects of commercial probiotic supplementation in water on the performance parameters, carcass traits, immune function, and antioxidant capacity of broiler chicks. In the experiment, 120 Arbor Acres (AA) broilers (60 male and 60 female) were randomly allocated into four groups (G) - G1: basal diet and G2, G3, and G4: basal diet with 1% Lactobacillus casei , 1% L. acidophilus , and 1% Bifidobacterium in the water, lasting 42 days. The experimental results revealed that probiotic additives produced positive impacts on body weight, average daily feed intake (ADFI), and average daily weight gain for female chicks, whereas these probiotics significantly reduced ADFI and the feed conversion ratio of male chicks ( P < 0.05). Probiotics efficiently improved eviscerated yield and breast yield while reducing the abdominal fat ( P < 0.05) for the male broiler chicks. A marked increase was observed in the weight of the spleen, bursa of Fabricius, and thymus in the treatment group ( P < 0.05). Besides, probiotics produced a significant effect on the concentrations of immune-related proteins ( P < 0.05) and markedly increased the concentrations of antioxidase and digestive enzymes when compared with the control ( P < 0.05). The addition of probiotics dramatically reduced the total counts of Escherichia coli and Salmonella and increased the quantity of Lactobacilli ( P < 0.05). The results of the present study demonstrated an increase in growth performance, carcass traits, immune function, gut microbial population, and antioxidant capacity by supplementing 1% probiotics ( L. casei , L. acidophilus , and Bifidobacterium ) in the water for broilers., Competing Interests: Conflict of interest: The authors state no conflict of interest., (© 2021 Lihuan Zhang et al., published by De Gruyter.)

Background: The sweet potato weevil, Cylas formicarius, is the most serious pest of sweet potato worldwide. The molecular mechanism of sex pheromone recognition in C. formicarius has not been reported. Odorant-binding proteins (OBPs) play a critical role in selectively binding and transporting pheromones or other odors to the surface of olfactory receptor neurons through the aqueous sensillar lymph, therefore the function of sweet potato OBPs is worth studying., Results: Herein, the CforOBP1-3 genes encoding three classical OBPs were cloned in C. formicarius by reverse transcription-polymerase chain reaction. Phylogenetic analysis showed that CforOBP1-3 were homologous genes, but the relationship between CforOBP2 and CforOBP3 was closest among the three genes. In addition, real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assays demonstrated that the expression of CforOBP1 was higher in the antennae and legs of female and male insects, while CforOBP2 and CforOBP3 were mainly expressed in the antennae of male insects. The fluorescent competitive binding assay results indicated that CforOBP1-3 had strong binding affinities to sex pheromones and other tested ligands. Finally, the mRNA expression of CforOBP1-3 was successfully inhibited by RNA interference, and in vivo behavioral experiments showed that CforOBP1-3-deficient C. formicarius was partly anosmic and lost some of its ability to locate sex pheromones and host plant volatiles., Conclusion: These results suggested that CforOBP1 was shown to be involved in the process of weevils feeding and finding sweet potato, and CforOBP2-3 were mainly involved in the mating behavior of adult male weevils., (© 2020 Society of Chemical Industry.)

Arsenic (As) exerts a wide range of adverse effects on biological systems, including the reproductive organs in males and females. However, the mechanisms of As-induced reproductive toxicity are mostly obscure. Recently, we showed that autophagy is an essential route for As 2 O 3 -induced reprotoxicity through the hypothalamic-pituitary-gonadal-sperm (HPG-S) axis in pubertal and matured F1-male mice. However, the role of autophagy in As 2 O 3 - induced ovarian toxicity is mostly unknown. Hence, this study aimed to elucidate the role of oxidative stress, mitochondrial impairment, and autophagic processes in the ovary of As-exposed female mice. For this purpose, mature female mice were challenged with 0, low (0.2), medium (2), and high (20 ppm) As 2 O 3 from 35-days before mating till weaning their pups, and the F1- females from weaning until maturity. Then, all the mice were sacrificed, and oxidative stress parameters, mitochondrial indices, electron microscopic evaluation of the ovaries, expression of autophagic-related genes and proteins, and autophagosome formation were assessed. It was shown that medium and high As 2 O 3 doses were a potent inducer of oxidative stress, mitochondrial dysfunction, and autophagy in the ovary of F1-generation. A dose-dependent increment in the gene expression of PDK 1 , PI3K, TSC2, AMPK, ULK1, ATG13, Beclin1, ATG12, ATG5, LC3, P62, ATG3, ATG7, and p62, as well as protein expression of Beclin1, and LC3- I, II, was evident in the ovaries of the As-treated animals. Moreover, a dose-dependent decrease in the expression of mTOR and Bcl-2 genes, and mTOR protein was detected with increasing doses of As, suggesting that As treatment-induced autophagy. Along with a dose-dependent increase in the number of MDC-labeled autophagic vacuoles, transmission electron microscopy also confirmed more autophagosomes and injured mitochondria in medium and high As 2 O 3 doses groups. As 2 O 3 also negatively affected the mean body weight, litter size, organ coefficient, and stereological indices in female mice. Finally, in physiological conditions, arsenic trioxide (As 2 O 3 ) leads to an increased level of autophagy in the oocyte when many oocytes were being lost. These findings indicated that an imbalance in the oxidant-antioxidant system, mitochondrial impairment, and the autophagic process, through inhibition of mTOR, dependent and independent pathways, and Bcl-2, as well as activation of AMPK/PI3K/Beclin1/LC3 routes, could play a pivotal role in As-induced reproductive toxicity through ovarian dysfunction in females., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: External auditory canal (EAC) cholesteatoma (EACC) is rare and its treatment for different lesions has not yet been standardized. Objective: This study aimed to explore the clinical features of EACC with bone erosion, and to assess the curative effect of initial complete cholesteatoma debridement (ICCD). Material and methods: Clinical characteristics and prognosis of 41 ears were analyzed retrospectively. Results: The bone erosion of the EAC was most commonly affected on the posterior wall (37 ears), next by the inferior wall (34 ears), the anterior wall (30 ears) and the superior wall (23 ears). Hearing loss (36 ears) was the most common symptom, followed by otalgia (33 ears), otorrhea (18 ears), tinnitus (11 ears) and pruritus (3 ears). The hearing impairment of mean air conduction and air-bone gaps were improved from 39.2 dB to 22.7 dB, and 23.5 dB to 7.1 dB after the ICCD procedure, respectively. Four ears presented recurrence during the follow-up time and accepted a revision-debridement. Conclusion and significance: The ICCD might be applicable in the treatment of patients in the early stages and with non-extensive bone defect; however, close and long-term surveillance is essential and serial debridement is probable.

To understand the roles of Malus rootstock, scion, and their interaction in Cd accumulation and tolerance, four scion/rootstock combinations consisting of the apple cultivars "Hanfu" (HF) and "Fuji" (FJ) grafted onto M. baccata (Mb) or M. micromalus "qingzhoulinqin" (Mm) rootstocks differing in relative Cd tolerance were exposed either to 0 µM or 50 µM CdCl 2 for 18 d. Cd accumulation and tolerance in grafted Malus plants varied within rootstock, scion, and rootstock-scion interaction. Cd-induced decreases in photosynthesis, photosynthetic pigment level, and biomass were lower for HF grafted onto Mb than those for HF grafted onto Mm. Reductions in growth and photosynthetic rate were always the lowest for HF/Mb. Cd concentration, bioconcentration factor (BCF), and translocation factor ( T f ) were always comparatively higher in HF and FJ grafted onto rootstock Mm than in HF and FJ grafted on Mb, respectively. When HF and FJ were grafted onto the same rootstock, the root Cd concentrations were always higher in HF than FJ, whereas the shoot Cd concentrations displayed the opposite trend. The shoot Cd concentrations and T f were lower for HF/Mb than the other scion/rootstock combinations. Rootstock, scion, and rootstock-scion interaction also affected subcellular Cd distribution. Immobilization of Cd in the root cell walls may be a primary Cd mobility and toxicity reduction strategy in Malus . The rootstock and scion also had statistically significant influences on ROS level and antioxidant activity. Cd induced more severe oxidative stress in HF and FJ grafted onto Mm than it did in HF and FJ grafted onto Mb. Compared with FJ, HF had lower foliar O 2 - , root H 2 O 2 , and root and leaf MDA levels, but higher ROS-scavenging capacity. The rootstock, scion, and rootstock-scion interaction affected the mRNA transcript levels of several genes involved in Cd uptake, transport, and detoxification including HA7 , FRO2-like , NRAMP1 , NRAMP3 , HMA4 , MT2 , NAS1 , and ABCC1 . Hence, the responses of grafted Malu s plants to Cd toxicity vary with rootstock, scion, and rootstock-scion interaction., (Copyright © 2020 He, Zhou, Wan, Zhuang, Li, Qin and Lyu.)

Previous studies have suggested that prostate-specific antigen (PSA) plays a role in the etiology of prostate cancer (PCa), and that polymorphisms of KLK3 may be associated with PCa. However, these results were conflicting. Therefore, we performed a meta-analysis to illuminate this problem. We searched the PubMed and Web of Science databases. Ten single nucleotide polymorphisms (SNPs) were involved in this meta-analysis. The pooled results showed that the minor alleles of rs1058205, rs2735839, rs174776, rs17632542, rs266849, rs266878, and rs2569735 were significantly associated with PCa. Compared to genotypes of the common homozygotes, the heterozygous genotypes of rs1058205, rs2735839, rs174776, rs17632542, rs266849, and rs266878 were significantly associated with PCa, as well as the homozygous genotypes of rs1058205, rs2735839, rs17632542, rs266878, rs266876, and rs2569735. Only rs2735839 was involved in the Gleason score (GS). The pooled results showed that when compared with GS ≥ 8 PCa, the A-allele was the protective factor for GS < 7 PCa. It was also a protective factor for GS ≥ 4+3 when compared to GS ≤ 3+4 PCa. A strong association was observed between PCa and rs1058205, rs2735839, rs266882, rs174776, rs17632542, rs266849, rs266878, rs266876, rs1058274, and rs2569735. The G-allele of rs2735839 was a risk factor for GS < 7 PCa when compared with the GS ≥ 8 PCa, as well as for the GS ≥ 4+3 when compared to the GS ≤ 3+4 PCa. Therefore, these SNPs may be valuable as biomarkers for PCa in the future.

NiFe layered double hydroxides (LDHs) have been denoted as benchmark non-noble-metal electrocatalysts for the oxygen evolution reaction (OER). However, for laminates of NiFe LDHs, the edge sites are active, but the basal plane is inert, leading to underutilization as catalysts for the OER. Herein, for the first time, light and electron-deficient Li ions are intercalated into the basal plane of NiFe LDHs. The results of theoretical calculations and experiments both showed that electrons would be transferred from near Ni 2+ to the surroundings of Li + , resulting in electron-deficient properties of the Ni sites, which would function as "electron-hungry" sites, to enhance surface adsorption of electron-rich oxygen-containing groups, which would enhance the effective activity for the OER. As demonstrated by the catalytic performance, the Li-NiFe LDH electrodes showed an ultralow overpotential of only 298 mV at 50 mA cm -2 , which was lower than that of 347 mV for initial NiFe LDHs and lower than that of 373 mV for RuO 2 . Reasonable intercalation adjustment effectively activates laminated Ni 2+ sites and constructs the electron-deficient structure to enhance its electrocatalytic activity, which sheds light on the functional treatment of catalytic materials., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

To examine the potential roles of melatonin in cadmium (Cd) uptake, accumulation and detoxification in Malus plants, we exposed two different apple rootstocks varying greatly in Cd uptake and accumulation to either 0 or 30 μM Cd together with 0 or 100 μM melatonin. Cadmium stress stimulated endogenous melatonin production to a greater extent in the Cd-tolerant Malus baccata Borkh. than in the Cd-susceptible Malus micromalus 'qingzhoulinqin'. Melatonin application attenuated Cd-induced reductions in growth, photosynthesis and enzyme activity, as well as reactive oxygen species (ROS) and malondialdehyde accumulation. Melatonin treatment more effectively restored photosynthesis, photosynthetic pigments and biomass in Cd-challenged M. micromalus 'qingzhoulinqin' than in Cd-stressed M. baccata. Exogenous melatonin lowered root Cd2+ uptake, reduced leaf Cd accumulation, decreased Cd translocation factors and increased root, stem and leaf melatonin contents in both Cd-exposed rootstocks. Melatonin application increased both antioxidant concentrations and enzyme activities to scavenge Cd-induced ROS. Exogenous melatonin treatment altered the mRNA levels of several genes regulating Cd uptake, transport and detoxification including HA7, NRAMP1, NRAMP3, HMA4, PCR2, NAS1, MT2, ABCC1 and MHX. Taken together, these results suggest that exogenous melatonin reduced aerial parts Cd accumulation and mitigated Cd toxicity in Malus plants, probably due to the melatonin-mediated Cd allocation in tissues, and induction of antioxidant defense system and transcriptionally regulated key genes involved in detoxification., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The development of high-performance, low-cost, and long-lasting electrocatalysts for both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) is urgently needed for effective electrochemical water splitting. In the present study, an engineering process was employed to prepare "Lewis base-hungry" amorphous-crystalline nickel borate-nickel sulfide (Ni 3 (BO 3 ) 2 -Ni 3 S 2 ) heterostructures, which exhibited unprecedentedly high electrocatalytic activity toward both OER and HER in alkaline media. The optimal Ni 3 (BO 3 ) 2 -Ni 3 S 2 /nickel foam (Ni 3 (BO 3 ) 2 -Ni 3 S 2 /NF) electrode displayed an ultralow overpotential of only -92 and +217 mV to reach the current density of 10 mA cm -2 for HER and OER, respectively. When the Ni 3 (BO 3 ) 2 -Ni 3 S 2 /NF electrode was used as both the anode and cathode for overall water splitting, a low cell voltage of 1.49 V was needed to achieve the current density of 10 mA cm -2 , which was superior to the performance of most noble metal-free electrocatalysts. Results from density functional theory calculations showed that the Lewis base-hungry sites in the heterostructures effectively enhanced the chemisorption of hydrogen and oxygen intermediates, a critical step in HER and OER electrocatalysis. Results from this study highlight the significance of rational design and engineering of heterostructured materials for the development of high-efficiency electrocatalysts.

Background: NAC transcription factors play important roles in the regulation of plant growth, development, abiotic and biotic stress responses. The transcriptional level of MdNAC s in different tissues and under various biotic and abiotic stress treatments was determined to provide a solid foundation for studying the function of MdNAC s., Methods: Thirty-two full-length cDNA sequences of Md NAC s were isolated by homologous comparison and RT-PCR confirmation, and the obtained cDNA sequences and the deduced amino acid sequences were analyzed with bioinformatics methods. The prediction of subcellular locations of MdNAC proteins was performed using CELLO v.2.5, PSORT, and SoftBerry ProtComp 9.0. Expression levels of MdNAC s were detected in 16 different tissues using an array. Expression patterns of MdNAC s were detected in response to Alternaria alternata apple pathotype (AAAP) infection using RNA-seq, and the expression of MdNAC s was analyzed under NaCl and mannitol treatments using RT-qPCR., Results: The sequencing results produced 32 cDNAs (designated as MdNAC24-39 , MdNAC54-65, and MdNAC67-70 with GenBank accession No. MG099861-MG099876, MG099891-MG099902, and MG099904-MG099907, respectively). Phylogenetic analysis revealed that MdNAC34 belonged to the ATAF group, MdNAC63 belonged to the AtNAC3 group, MdNAC24, MdNAC26-30, MdNAC32-33, MdNAC35, MdNAC37-39, MdNAC56-57, MdNAC59-62, MdNAC64-65, and MdNAC67-70 belonged to the NAM group, and MdNAC25, MdNAC36, MdNAC54-55, and MdNAC58 belonged to the VND group. Predictions of subcellular localization showed that MdNAC24-27, MdNAC29-30, MdNAC33-37, MdNAC39, MdNAC54-65, and MdNAC67-70 proteins were located in the nucleus, MdNAC28 proteins were located in the cytoplasm, MdNAC31-32 proteins were located in the nucleus and cytoplasm, and MdNAC38 proteins were located in the nucleus and plasma membrane. Array results indicated that 32 MdNACs were expressed in all examined tissues at various expression levels. RNA-seq results showed that expression levels of MdNAC26-28 , MdNAC33-34 , MdNAC60 , MdNAC62-65, and MdNAC68 were induced, but MdNAC24 , MdNAC32, and MdNAC58 were down-regulated in response to AAAP infection. Under salt treatment, MdNAC24 , MdNAC27 , MdNAC29 , MdNAC34 , MdNAC37 , MdNAC39 , MdNAC54 , MdNAC59, and MdNAC63 transcription levels were induced. Under mannitol treatment, MdNAC32 and MdNAC54 transcription levels were induced, but MdNAC24 , MdNAC28 , MdNAC30 , MdNAC33 , MdNAC35 , MdNAC37 , MdNAC55 , MdNAC56 , MdNAC58, and MdNAC59 were down-regulated. Taken together, the results indicated that the cloned MdNAC genes were expressed constitutively in all examined tissues. These genes were up-regulated or down-regulated in response to AAAP infection and to salt or mannitol, which suggested they may be involved in the regulation of growth, development, and stress response in apple., Competing Interests: The authors declare there are no competing interests., (©2020 Li et al.)

Purpose: Some chemotherapeutics have been shown to induce both the release of damage-associated molecular patterns (DAMPs) and the production of type I interferon (IFN-I), leading to immunogenic cell death (ICD). However, the standard chemotherapy drug for glioma, temozolomide (TMZ), cannot induce ICD as it cannot activate IFN-I signaling. Moreover, inefficient delivery of immunostimulants across the blood-brain barrier (BBB) is the main obstacle to overcome in order to induce local immune responses in the brain., Methods: A new oligonucleotide nanoformulation (Au@PP)/poly(I:C)) was constructed by coating gold nanoparticles (AuNPs) with methoxypolyethylene glycol (mPEG)-detachable (d)-polyethyleneimine (PEI) (Au@PP) followed by inducing the formation of electrostatic interactions with polyinosinic-polycytidylic acid (poly(I:C)). Intracranial GL261 tumor-bearing C57BL/6 mice were used to explore the therapeutic outcomes of Au@PP/poly(I:C) plus TMZ in vivo. The anti-tumor immune response in the brain induced by this treatment was analyzed by RNA sequencing and immunohistochemical analyses., Results: Au@PP/poly(I:C) induced IFN-I production after endocytosis into glioma cells in vitro. Additionally, Au@PP/poly(I:C) was efficiently accumulated in the glioma tissue after intranasal administration, which allowed the nanoformulation to enter the brain while bypassing the BBB. Furthermore, Au@PP/poly(I:C) plus TMZ significantly improved the overall survival of the tumor-bearing mice compared with group TMZ only. RNA sequencing and immunohistochemical analyses revealed efficient immune response activation and T lymphocyte infiltration in the Au@PP/poly(I:C) plus TMZ group., Conclusion: This study demonstrates that intranasal administration of Au@PP/poly(I:C) combined with TMZ induces ICD, thereby stimulating an in situ immune response to inhibit glioma growth., Competing Interests: The authors declare that they have no conflicts of interest in this work., (© 2020 Yin et al.)

Efficient energy management for the solid rocket is very important to exhaust excess energy and to meet the various terminal constraints. Based on the online planning of the velocity capability curve, a Double-arcs Energy Management (DAEM) guidance algorithm is proposed in this paper. In the DAEM, the velocity capability curve is designed with two tangential arcs. By using the elegant geometric characteristic of the arcs, the closed-loop guidance problem is transformed as a problem of solving a system of nonlinear equations about the parameters (radius and center position) of the two arcs, and the nonlinear equations can be solved in real time. The main advantages of this algorithm are that the height increment constraint, which is difficult to be satisfied in traditional energy management methods, can be satisfied theoretically, and the convergence of the solution of the DAEM is quadratic. The effectiveness and advantages of the proposed DAEM algorithm are demonstrated by simulations and comparisons with other energy management algorithms., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 ISA. Published by Elsevier Ltd. All rights reserved.)

Background: Pigmentation development, is a complex process regulated by many transcription factors during development. With the development of the RNA sequencing (RNA-seq), non-coding RNAs, such as miRNAs, lncRNAs, and circRNAs, are found to play an important role in the function detection of related regulation factors. In this study, we provided the expression profiles and development of ncRNAs related to melanocyte and skin development in mice with black coat color skin and mice with white coat color skin during embryonic day 15 (E15) and postnatal day 7 (P7). The expression profiles of different ncRNAs were detected via RNA-seq and also confirmed by the quantitative real-time PCR (qRT-PCR) method. GO and KEGG used to analyze the function the related target genes., Results: We identified an extensive catalogue of 206 and 183 differently expressed miRNAs, 600 and 800 differently expressed lncRNAs, and 50 and 54 differently expressed circRNAs, respectively. GO terms and pathway analysis showed the target genes of differentially expressed miRNA and lncRNA. The host genes of circRNA were mainly enriched in cellular process, single organism process. The target genes of miRNAs were mainly enriched in chromatin binding and calcium ion binding in the nucleus. The function of genes related to lncRNAs are post translation modification. The competing endogenous RNA (ceRNA) network of lncRNAs and circRNAs displays a complex interaction between ncRNA and mRNA related to skin development, such as Tcf4, Gnas, and Gpnms related to melanocyte development., Conclusions: The ceRNA network of lncRNA and circRNA displays a complex interaction between ncRNA and mRNA related to skin development and melanocyte development. The embryonic and postnatal development of skin provide a reference for further studies on the development mechanisms of ncRNA during pigmentation.