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An Fe–N–C/AuNP nanohybrid was combined with a glassy carbon electrode to construct a novel electrochemical sensor for rapid detection of gallic acid (GA). The sensor exhibited excellent performance to detect GA with a wide linear response range and low detection limit.

Machine learning (ML) has been universally adopted for automated decisions in a variety of fields, including recognition and classification applications, recommendation systems, natural language processing, and so on. However, in light of high expenses on training data and computing resources, recent years have witnessed a rapid increase in outsourced ML training, either partially or completely, which provides vulnerabilities for adversaries to exploit. A prime threat in training phase is called poisoning attack, where adversaries strive to subvert the behavior of machine learning systems by poisoning training data or other means of interference. Although a growing number of relevant studies have been proposed, the research among poisoning attack is still overly scattered, with each paper focusing on a particular task in a specific domain. In this survey, we summarize and categorize existing attack methods and corresponding defenses, as well as demonstrate compelling application scenarios, thus providing a unified framework to analyze poisoning attacks. Besides, we also discuss the main limitations of current works, along with the corresponding future directions to facilitate further researches. Our ultimate motivation is to provide a comprehensive and self-contained survey of this growing field of research and lay the foundation for a more standardized approach to reproducible studies.

Sorafenib has been reported to reduce blood glucose levels in diabetic and non-diabetic patients in previous retrospective studies. However, the mechanism of which the hypoglycemic effects of sorafenib is not clearly explored. In this study, we investigated the effect of sorafenib on blood glucose levels in diabetic and normal mice and explored the possible mechanism.We established a mouse model of type 2 diabetes by a high-fat diet combined with a low-dose of streptozotocin (STZ), to identify the hypoglycemic effect of sorafenib in different mice. Glucose tolerance, insulin tolerance and pyruvate tolerance tests were done after daily gavage with sorafenib to diabetic and control mice. To explore the molecular mechanism by which sorafenib regulates blood glucose levels, hepatic glucose metabolism signaling was studied by a series of in vivo and in vitro experiments.Sorafenib reduced blood glucose levels in both control and diabetic mice, particularly in the latter. The diabetic mice exhibited improved glucose and insulin tolerance after sorafenib treatment. Further studies showed that the expressions of gluconeogenesis-related enzymes, such as PCK1, G6PC and PCB, were significantly decreased upon sorafenib treatment. Mechanistically, sorafenib downregulates the expression of c-MYC downstream targets PCK1, G6PC and PCB through blocking the ERK/c-MYC signaling pathway, thereby playing its hypoglycemic effect by impairing hepatic glucose metabolism.Sorafenib reduces blood glucose levels through downregulating gluconeogenic genes, especially in diabetic mice, suggesting the patients with T2DM when treated with sorafenib need more emphasis in monitoring blood glucose to avoid unnecessary hypoglycemia.

An 8-week feeding experiment was conducted to evaluate the effect of dietary protein to lipid ratio on fish growth performance, digestive enzyme activity, body composition, serum biochemistry, immunity, and antioxidant capacity of Carassius auratus var. Pengze juveniles. Nine experimental diets were formulated in a 3 × 3 factorial design to contain three protein levels (30%, 35%, and 40%) and three lipid levels (5%, 8%, and 11%), with protein-to-energy (P/E) ratios ranging 19.2–27.1 mg/kJ and named as Diet 1 (30/5), Diet 2 (30/8), Diet 3 (30/11), Diet 4 (35/5), Diet 5 (35/8), Diet 6 (35/11), Diet 7 (40/5), Diet 8 (40/8), and Diet 9 (40/11), respectively. Each diet was randomly assigned to triplicate groups of 20 fish per cylindrical fiberglass tank. The fish fed with Diet 4 had the highest specific growth rate (SGR) among the 9 groups. The whole-body lipid content increased significantly with increasing dietary lipid levels regardless of dietary protein content ( P < 0.05 ), whereas moisture content showed an opposite trend ( P < 0.05 ). The highest values of activities of serum lysozyme (LZM) and alkaline phosphatase (AKP) were detected in the fish fed Diet 4 (35/5), whereas malondialdehyde (MDA) was lowest in the fish fed Diet 4. In addition, serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were the lowest, while high-density lipoprotein (HDL-C) and high-density lipoprotein to total cholesterol ratio (HDL-C/TC) were the highest in the Diet 4 group. The results indicate that a combination of 35.1% protein and 5.1% lipid with dietary CP/GE (mg/kJ) ratio of 24.0 is optimal for the culture of Carassius auratus var. Pengze juveniles.

Scaffold filling is a critical step in DNA assembly. Its basic task is to fill the missing genes (fragments) into an incomplete genome (scaffold) to make it similar to the reference genome. There have been a lot of work under distinct measurements in the literature of genome comparison. For genomes with gene duplications, common string partition reveals the similarity more precisely, since it constructs a one-to-one correspondence between the same segments in the two genomes. In this paper, we adopt duo-preservation as the measurement, which is the complement of common string partition, i.e., the number of duo-preservations added to the number of common strings is exactly the length of a genome. Towards a proper scaffold filling, we just focus on the increased duo-preservations. This problem is called scaffold filling to maximize increased duo-preservations (abbr. SF-MIDP). We show that SF-MIDP is solvable in linear time for a simple version where all the genes of the scaffold are matched in a block-matching, but MAX SNP-complete for the general version, and cannot be approximated within [Formula: see text]. Moreover, we present a basic approximation algorithm of factor 2, by which the optimal solution can be described in a new way, and then, improve the approximation factor to [Formula: see text] via a greedy method.

S1. Apoptosis detected by TUNEL in MDA-MB-231 cells expressing shSEMA4C or EV. S2. Sema4C cDNA re-expressed in these MDA-MB-231 siSEMA4C cells could recover cell growth and ANG and CSF secretion. S3. Expression of senescence-associated pathway proteins in MDA-MB-231 cells were examined using western blot post-transfection at the indicated time. S4. SEMA4C regulates angiogenesis. S5. The vascular integrity was detected in EV tumours and shSEMA4C tumours. S6. Sections from tumors were immunostained with anti-cd45 (white arrowhead) or F4/80(black arrow) antibody. S7. SEMA4C regulates macrophage recruitment. S8. The vascular density and macrophage area were detected in EV tumours and shSEMA4C tumours at the same weight. S9. Recombinant soluble Sema4C did not affect MDA-MB-231 proliferation and endothelial cells tube formation despite could increase macrophages migration. S10. mRNA levels of ANG and CSF were analyzed in presence of siSEMA4C RNA or sema4C cDNA in MDA-MB-231cells. S11. Expression of mRNA(A) and secreted protein(B) level of ANG and CSF-1 were detected in the MCF-7 cells overexpressing SEMA4C. S12. The growth curve and cell cycle were detected in presence of siANG in MDA-MB-231 cells.

MicroRNAs (miRNAs) are endogenous small non-coding RNAs that play critical roles in regulating plant growth and development. Here, we used Short Tandem Target Mimic (STTM) technology to generate soybean (Glycine max (L.) Merr.) miRNA knockdown lines and identify miRNAs that regulate plant height, a key agronomic trait that affects yield. STTM166 successfully silenced miR166 in soybean and upregulated the expression of miR166 target genes, such as ATHB14-LIKE. The miR166 knockdown lines (GmSTTM166) displayed a reduced plant height phenotype. Moreover, GmSTTM166 plants contained lower levels of bioactive gibberellic acid (GA3) than wild-type plants, and application of exogenous GA partially rescued the dwarf phenotype of GmSTTM166. Knockdown of miR166 altered the expression of genes involved in GA biosynthesis and catabolism. Further analysis revealed that ATHB14-LIKE directly represses transcription of the GA biosynthesis genes GmGA1 and GmGA2, while activating transcription of the GA catabolic gene GIBBERLLIN 2 OXIDASE 2 (GmGA2ox2). Collectively, these results reveal a pivotal role for miR166 in the genetic control of plant height in soybean, thereby providing invaluable insights for molecular breeding to improve soybean yield.

Supplementary Figure from Integrative Genomic Profiling Uncovers Therapeutic Targets of Acral Melanoma in Asian Populations

Purpose:Tumor repopulation is known as a major cause of treatment failure and/or tumor recurrence after radiotherapy. The underlying mechanism remains unclear. Our previous study demonstrated that irradiated apoptotic cells mediated tumor repopulation, in which caspase-3 played an important role. Herein, we investigated downstream effectors of caspase-3 involved in this process.Experimental Design:A dominant-negative protein kinase Cδ (DN_PKCδ) mutant that could not be cleaved by caspase-3 and therefore could not be activated by irradiation-induced apoptosis was constructed. DN_PKCδ stably transduced tumor cells were compared with wild-type tumor cells for their growth stimulation effects in in vitro and in vivo tumor repopulation models. Downstream effectors of caspase-3 and PKCδ were investigated. The role of PKCδ was further verified in human colorectal tumor specimens.Results:Inactivation of caspase-3 or caspase-7 attenuated tumor repopulation and weakened PKCδ cleavage. Both DN_PKCδ and PKCδ inhibitors restrained tumor repopulation both in vitro and in vivo. Phosphorylated Akt was attenuated in caspase-3–, caspase-7–, or PKCδ-inactivated tumor cells. Furthermore, expression of vascular endothelial growth factor (VEGF)-A but not hypoxia-inducible factor 1α (HIF1α) was decreased in PKCδ- or Akt-inactivated tumor cells. In addition, inhibition of p-Akt, HIF1α, VEGF-A, or VEGF-A receptor reduced tumor repopulation significantly. Finally, increased nuclear translocation of PKCδ in colorectal tumor specimens was associated with worse patient prognosis.Conclusions:The caspase-3/PKCδ/Akt/VEGF-A axis is involved in tumor repopulation and could be exploited as a potential target to enhance the efficacy of radiotherapy.

Supplementary Figures and Tables. // Figure S1, Survival fractions. Figure S2, Linearity of bioluminescence signals vs. Fluc-GFP-labeled tumor cell numbers. Figure S3, Cisplatin-induced dying tumor cells stimulated living tumor cell growth. Figure S4, DN_PKCÎ' (K378A) stably transduced HT-29 cells showed less growth stimulation effect when compared with wild-type HT-29 cells. Figure S5, A specific HIF1α inhibitor PX-478 2HCl remarkably suppressed the reporter cell growth on irradiated feeder cells. // Table S1, Summary of clinical characteristics in 68 patients of colorectal cancer.

Purpose:Acral melanoma is the major subtype of melanoma seen in Asian patients with melanoma and is featured by its insidious onset and poor prognosis. The genomic study that elucidates driving mutational events is fundamental to the development of gene-targeted therapy. However, research on genomic profiles of acral melanoma in Asian patients is still sparse.Experimental Design:We carried out whole-exome sequencing (WES) on 60 acral melanoma lesions (with 55 primary samples involved), targeted deep sequencing in a validation cohort of 48 cases, RNA sequencing in 37 acral melanoma samples (all from the 60 undergoing WES), and FISH in 233 acral melanoma specimens (54 of the 60 undergoing WES included). All the specimens were derived from Asian populations.Results:BRAF, NRAS, and KIT were discerned as significantly mutated genes (SMG) in acral melanoma. The detected COSMIC signature 3 related to DNA damage repair, along with the high genomic instability score, implied corresponding pathogenesis of acral melanoma. Moreover, the copy number gains of EP300 were associated with the response of acral melanoma to targeted therapy of A485 (a p300 inhibitor) and immune checkpoint blockade treatment. In addition, the temporal order in mutational processes of the samples was reconstructed, and copy-number alterations were identified as early mutational events.Conclusions:Our study provided a detailed view of genomic instability, potential therapeutic targets, and intratumoral heterogeneity of acral melanoma, which might fuel the development of personalized strategies for treating acral melanoma in Asian populations.

Supplementary Data from Integrative Genomic Profiling Uncovers Therapeutic Targets of Acral Melanoma in Asian Populations

Background Aberrant epigenetic remodeling events contribute to progression and metastasis of breast cancer (Bca). The specific mechanims that epigenetic factors rely on to mediate tumor aggressiveness remain unclear. We aimed to elucidate the roles of epigenetic protein PHF6 in breast tumorigenesis. Methods Published datasets and tissue samples with PHF6 staining were used to investigate the clinical relevance of PHF6 in Bca. CCK-8, clony formation assays were used to assess cell growth capacity. Cell migration and invasion abilities were measured by Transwell assay. The gene mRNA and protein levels were measured by quantitative real-time PCR and western blot. Chromatin immunoprecipitation (ChIP)-qPCR assays were used to investigate transcriptional relationships among genes. The Co-immunoprecipitation (Co-IP) assay was used to validate interactions between proteins. The CRISPR/Cas9 editing technology was used to construct double HIF knockout (HIF-DKO) cells. The subcutaneous xenograft model and orthotopic implantation tumor model were used to asess in vivo tumor growth. Results In this study, we utilized MTT assay to screen that PHF6 is required for Bca growth. PHF6 promotes Bca proliferation and migration. By analyzing The Cancer Genome Atlas breast cancer (TCGA-Bca) cohort, we found that PHF6 was significantly higher in tumor versus normal tissues. Mechanistically, PHF6 physically interacts with HIF-1α and HIF-2α to potentiate HIF-driven transcriptional events to initiate breast tumorigenesis. HIF-DKO abolished PHF6-mediated breast tumor growth, and PHF6 deficiency in turn impaired HIF transcriptional effects. Besides, hypoxia could also rely on YAP activation, but not HIF, to sustain PHF6 expressions in Bca cells. In addition, PHF6 recuits BPTF to mediate epigenetic remodeling to augment HIF transcriptional activity. Targeting PHF6 or BPTF inhibitor (AU1) is effective in mice models. Lastly, PHF6 correlated with HIF target gene expression in human breast tumors, which is an independent prognostic regulator. Conclusions Collectively, this study identified PHF6 as a prognostic epigenetic regulator for Bca, functioning as a HIF coactivator. The fundamental mechanisms underlying YAP/PHF6/HIF axis in breast tumors endowed novel epigenegtic targets for Bca treatment.

Objective: To determine the changes in serum bone metabolism indexes and ultrasonic bone mineral density (BMD) in patients with diabetic nephropathy at different stages, and their effects on diabetic renal microvascular complications. Methods: This is a clinical comparative study. One hundred twenty two diabetic patients admitted to the Baoding No.1 Central Hospital from January 2020 to March 2022 were selected as subjects and divided into three groups according to their actual condition: the simple diabetes (Group-A, 40 cases), diabetic nephropathy with micro urinary protein (Group-B, 40 cases) and diabetic nephropathy with massive proteinuria (Group-C, 42 cases). Another 36 healthy subjects were selected as the control group. Differences in serum bone metabolism indexes and ultrasound BMD levels were compared. Results: Twenty five hydroxy-vitamin D, BGP, T-PINP and ultrasound BMD levels in the control group were > Group-A > Group-B > Group-C, PTH and β-CTX in the control group were < Group-A < Group-B < Group-C, statistically significant differences (p

Melanoma is the most lethal type of skin cancer, originating from the malignant transformation of melanocyte. While the development of targeted therapy and immunotherapy has gained revolutionary advances in potentiating the therapeutic effect, the prognosis of patients with melanoma is still suboptimal. During tumor progression, melanoma frequently encounters stress from both endogenous and exogenous sources in tumor microenvironment. SIRT7 is a nuclear-localized deacetylase of which the activity is highly dependent on intracellular nicotinamide adenine dinucleotide (NAD+), with versatile biological functions in maintaining cell homeostasis. Nevertheless, whether SIRT7 regulates tumor cell biology and tumor immunology in melanoma under stressful tumor microenvironment remains elusive. Herein, we reported that SIRT7 orchestrates melanoma progression by simultaneously promoting tumor cell survival and immune evasion via the activation of unfolded protein response. We first identified that SIRT7 expression was the most significantly increased one in sirtuins family upon stress. Then, we proved that the deficiency of SIRT7 potentiated tumor cell death under stress in vitro and suppressed melanoma growth in vivo. Mechanistically, SIRT7 selectively activated the IRE1α-XBP1 axis to potentiate the pro-survival ERK signal pathway and the secretion of tumor-promoting cytokines. SIRT7 directly de-acetylated SMAD4 to antagonize the TGF-β-SMAD4 signal, which relieved the transcriptional repression on IRE1α and induced the activation of the IRE1α-XBP1 axis. Moreover, SIRT7 up-regulation eradicated anti-tumor immunity by promoting PD-L1 expression via the IRE1α-XBP1 axis. Additionally, the synergized therapeutic effect of SIRT7 suppression and anti-PD-1 immune checkpoint blockade was also investigated. Taken together, SIRT7 can be employed as a promising target to restrain tumor growth and increase the effect of melanoma immunotherapy.

It is exceedingly desired yet challenging to steer the photocatalytic overall CO2 reduction reaction (CRR) toward high-value liquid products, especially multicarbon products like ethanol. Numerous attempts have been reported such as developing new materials, cocatalyst engineering, etc. Here, we find that by just curling the superhydrophobic Cu2O to create an enclosed Cu2O hollow structure, the selectivity of ethanol (59.59%) is impressively elevated by ~ 9 times higher than that without the enclosed hollow structure. Further investigations indicate that the superhydrophobic hollow structure can efficiently repel water out and thus create an enclosed gas storage space, enabling the high concentration of CO2 molecules. With such a strategy, an impressive ethanol generation rate of 996.18 µmol g− 1 h− 1 is achieved. The mechanism is also investigated based on theoretical calculations and corresponding characterizations. This strategy provides a geometry-modulated method with high compatibility, which is promising to develop more efficient photocatalysts for multicarbon production combined with other traditional methods.

Prognostic nutritional index has been found to be related to the clinical outcomes of patients with cancer. However, its role in myelodysplastic syndromes (MDS) patients is unclear. We aimed to assess the value of nutritional status in predicting the prognosis of MDS patients.Totally 121 MDS patients were analyzed retrospectively. The prognostic nutritional index (PNI) was used to assess nutritional status of the patients. The bio-informatics tool X-tile was used to define the threshold, and accordingly patients were divided into PNIThe PNIPNI would be a simple and immediately available tool for predicting the prognosis of MDS.

Purpose: Acral melanoma is the major subtype of melanoma seen in Asian patients with melanoma and is featured by its insidious onset and poor prognosis. The genomic study that elucidates driving mutational events is fundamental to the development of gene-targeted therapy. However, research on genomic profiles of acral melanoma in Asian patients is still sparse. Experimental Design: We carried out whole-exome sequencing (WES) on 60 acral melanoma lesions (with 55 primary samples involved), targeted deep sequencing in a validation cohort of 48 cases, RNA sequencing in 37 acral melanoma samples (all from the 60 undergoing WES), and FISH in 233 acral melanoma specimens (54 of the 60 undergoing WES included). All the specimens were derived from Asian populations. Results: BRAF, NRAS, and KIT were discerned as significantly mutated genes (SMG) in acral melanoma. The detected COSMIC signature 3 related to DNA damage repair, along with the high genomic instability score, implied corresponding pathogenesis of acral melanoma. Moreover, the copy number gains of EP300 were associated with the response of acral melanoma to targeted therapy of A485 (a p300 inhibitor) and immune checkpoint blockade treatment. In addition, the temporal order in mutational processes of the samples was reconstructed, and copy-number alterations were identified as early mutational events. Conclusions: Our study provided a detailed view of genomic instability, potential therapeutic targets, and intratumoral heterogeneity of acral melanoma, which might fuel the development of personalized strategies for treating acral melanoma in Asian populations.