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[Display omitted] • Nanoboxed HP-Co 3 O 4 @C are prepared by a MOF-involved etch-pyrolysis-oxidation strategy. • Hydroxyl radical (•OH) is the main active substance in catalytic reactions. • Peroxidase activity of HP-Co 3 O 4 @C NBs is significantly increased at different pH. • Sensitive colorimetric detections of H 2 O 2 and dopamine are established, respectively. Nanozymes are interesting alternatives to natural enzymes since they are highly stable and inexpensive. Here, we present a straightforward MOF-based etch, pyrolysis, and oxidation approach for fabricating an attractive hybrid structure comprised of extensively distributed ultrafine Co 3 O 4 hollow particles embedded in carbon nanoboxes (denoted as HP-Co 3 O 4 @C NBs), which exhibit the catalytic property of peroxidase-like nanozyme. The ultrafine size and hollow structure of Co 3 O 4 particles provide a large surface area and abundant catalytic sites of HP-Co 3 O 4 @C NBs. Mechanistic studies show that the production of reactive oxygen species (ROS) intermediates (•OH) through the decomposition of H 2 O 2 endows the peroxidase-like activity of HP-Co 3 O 4 @C NBs. 3, 3′, 5, 5′-tetramethylbenzidine (TMB) transforms into a blue oxidation product (oxTMB) in the presence of H 2 O 2 with the catalysis of HP-Co 3 O 4 @C NBs. In the existence of the reducing substance dopamine (DA), the oxidation reaction of TMB is inhibited, resulting in a marked bleaching of the blue colour. Based on these principles, we develop a colourimetric sensing platform for detecting DA with excellent sensitivity and stability. This study not only extends the application of Co-MOFs in the analytical field, but also achieves a simple, rapid (3 min), sensitive, and intuitive detection of H 2 O 2 and dopamine, which is potentially promising for real-time monitoring of biological small molecules. [ABSTRACT FROM AUTHOR]

As an oral antidiabetic agent, dichloroacetate (DCA) has been proven to improve diabetes and related complications. However, its functional role in diabetic cataract (DC) remains to be elucidated. This study was to define the role of DCA and its underlying molecular mechanism in DC in vitro and in vivo. In this study, it was shown that DCA dose-dependently ameliorated DC formation and development in DM rats. In addition, DCA significantly increased cell viability, reduced apoptosis, and inhibited EMT and oxidative stress of high glucose (HG)-treated SRA-01/04 cells in a concentration-dependent manner. Besides, it was revealed that Indoleamine 2,3-dioxygenase 1 (IDO1) expression was upregulated in lenses of DM rats and HG-treated SRA-01/04 cells, which was reversed by DCA. In addition, DCA abrogated the activation of the p38 MAPK signaling in the lenses of DM rats and HG-treated SRA-01/04 cells. Further experiments showed that IDO1 upregulation activated the p38 MAPK signaling in HG-challenged SRA-01/04 cells. Moreover, IDO1 overexpression partially reversed DCA-mediated inactivation of p38 MAPK signaling and suppression of HG-induced damage to SRA-01/04 cells. To sum up, our findings showed that DCA prevented DC-related apoptosis, EMT, and oxidative stress via inactivating IDO1-dependent p38 MAPK signaling. • DCA exerts anti-cataract effects in DM rats. • DCA promotes proliferation and represses apoptosis in HG-treated SRA-01/04 cells. • DCA mitigates EMT and oxidative stress in HG-treated SRA-01/04 cells. • DCA inhibits IDO1 expression and p38 MAPK activation in DC. • IDO1-mediated p38 MAPK activation abates the ameliorative effects of DCA on HG-induced damage to SRA-01/04 cells. [ABSTRACT FROM AUTHOR]

Drug repurposing identifies new clinical indications for existing drugs. It can be used to overcome common problems associated with cancers, such as heterogeneity and resistance to established therapies, by rapidly adapting known drugs for new treatment. In this study, we utilized a recommendation system learning model to prioritize candidate cancer drugs. We designed a drug–drug pathway functional similarity by integrating multiple genetic and epigenetic alterations such as gene expression, copy number variation (CNV), and DNA methylation. When compared with other similarities, such as SMILES chemical structures and drug targets based on the protein–protein interaction network, our approach provided better interpretable models capturing drug response mechanisms. Furthermore, our approach can achieve comparable accuracy when evaluated with other learning models based on large public datasets (CCLE and GDSC). A case study about the Erlotinib and OSI-906 (Linsitinib) indicated that they have a synergistic effect to reduce the growth rate of tumors, which is an alternative targeted therapy option for patients. Taken together, our computational method characterized drug response from the viewpoint of a multi-omics pathway and systematically predicted candidate cancer drugs with similar therapeutic effects. [ABSTRACT FROM AUTHOR]

• Ni(OH) 2 nanoflowers were prepared on Ti mesh using rapid electrodeposition. • Ni(OH) 2 /Ti exhibited excellent OER catalytic activity (η 100 = 290 mV). • Flowerlike Ni 2 P/Ti showed outstanding HER performance over the full pH range. • DFT calculation confirm that Ni and P as active sites have the best |Δ G H* |. • The Ni 2 P/Ti (−) || Ni(OH) 2 /Ti (+) displayed a low voltage of 1.493 V at 10 mA cm−2. The exploration of efficient, robust and nonprecious transition metal electrocatalysts for electrochemical hydrolysis is urgently needed. Herein, we developed Ni(OH) 2 with 3D nanoflower structure on the titanium mesh by a simple electrodeposition method. The Ni(OH) 2 /Ti exhibited excellent oxygen evolution reaction performance and achieved 10 mA cm−2 at 190 mV with fast kinetics in alkaline conditions. Ni 2 P, NiS 2 and NiSe 2 were prepared by solid-phase reaction, and the 3D nanoflower increased the open structure and greatly enhanced catalytic activity. The Ni 2 P/Ti electrode required an overpotential of 52, 88 and 109 mV to reach 10 mA cm−2 for hydrogen evolution reaction in acidic, alkaline and neutral media, respectively. The results of electrochemical measurements and mechanistic studies showed that the catalytic activity of HER: Ni 2 P > NiS 2 > NiSe 2 > Ni(OH) 2. The Ni 2 P/Ti and Ni(OH) 2 /Ti electrodes were assembled into an integrated water splitting electrolytic cell. The water electrolysis device assembled with the Ni 2 P/Ti and Ni(OH) 2 /Ti electrodes only needed a low potential of 1.608 V to achieve 50 mA cm−2 in alkaline environment and was operated stably for 50 h. [ABSTRACT FROM AUTHOR]

• An effective double ligand strategy was proposed to construct catalyst precursors. • The doping of N and P can regulate the electronic structure of Co. • N from dual ligands can enhance the conductivity and stability of the catalyst. • N, P-Co 4 S 3 /NC nanospheres showed outstanding HER performance over the full pH range. In this work, N, P-Co 4 S 3 /NC nanospheres were successfully synthesized by double ligand strategy, followed by calcination and phosphating. By adjusting the radio of methimazole and 2-methylimidazole, and changing the calcination temperature, we obtained the optimal hydrogen evolution catalyst. The doping of N and P can regulate the electronic structure of Co, and further improve the electrocatalytic hydrogen production performance. Furthermore, N from dual ligands can form nitrogen-doped carbon, thus enhancing the conductivity and stability of the catalyst. The experimental results showed that N, P-Co 4 S 3 /NC exhibited good full pH activity in 0.5 M H 2 SO 4 , 1.0 M PBS and 1.0 M KOH, and the overpotentials of 163, 185 and 168 mV were required to reach the current density of 10 mA cm−2, respectively. In this study, the dual ligands strategy can propose a new path for the design and synthesis of the catalyst precursor, and N, P codoping can effectively enhance the catalyst performance. [Display omitted] [ABSTRACT FROM AUTHOR]

BACKGROUND: The therapeutic properties of Hippophae rhamnoides L. were known in Ancient Greece and in Tibetan and Mongolian medicine, which commonly used it for the treatment of heart ailments, rheumatism, and brain disorders. Modern studies have indicated that Hippophae rhamnoides L. polysaccharide (HRP) can improve cognitive impairment in mice with Alzheimer's disease (AD) but the specific mechanisms of the protective effect of HRP have not been elucidated fully. RESULTS: Our results showed that Hippophae rhamnoides L. polysaccharide I (HRPI) improved pathological behaviors related to memory and cognition, and reduced 1Beta‐amyloid (Aβ) peptide deposition and neuronal cell necrosis. Pretreatment with Hippophae rhamnoides L. polysaccharide I (HRPI) also decreased the level of Toll‐like receptor 4 (TLR4) and Myeloid differentiation factor 88 (MyD88), and reduced the release of inflammatory factors Tumor necrosis factor alpha (TNFα) and interleukin 6 (IL‐6) in the brains of mice with AD. Treatment with HRPI also suppressed the expression level of Recombinant Kelch Like ECH Associated Protein 1 (KEAP1), and increased the levels of Nuclear factor erythroid 2‐Related Factor 2 (Nrf2), antioxidant enzymes Superoxide dismutase (SOD) and Glutathione peroxidase (GSH‐Px) in the brains of AD mice. CONCLUSIONS: On the whole, these findings revealed that HRPI could improve the learning and memory ability and attenuate pathologic impairment in AD mice, and the underlying mechanisms may involve mediating oxidative stress and inflammation, possibly through the regulation of the Keap1/Nrf2 and TLR4/MyD88 signaling pathways. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

SnO 2 nanoparticles (NPs) have been widely employed as electron transport layers (ETLs) in planar n-i-p perovskite solar cells (PSCs). Perfect SnO 2 ETL/perovskite interface plays a key role in high efficiency PSCs, however, the main issues caused by the self-aggregation of the SnO 2 NPs and the interface recombination limit the further improvement of device performance. Here, l -carnitine hydrochloride (L-ch) zwitterion with multiple functional groups has been incorporated into SnO 2 NP solution for high-efficiency PSCs. The results demonstrate that the unique coordination complexes assembled between L-ch zwitterion and SnO 2 NPs can inhibit the aggregation of SnO 2 NPs, benefiting for the formation of more compact film with reduced roughness. Simultaneously, the L-ch zwitterion can adjust the electronic properties of SnO 2 and promote the carrier transport between perovskite and SnO 2 ETL with well aligned energy level. Moreover, the -COO- and –N+ (CH 3) 3 groups can passivate uncoordinated Pb2+ and MA vacancies defects in the perovskite film, respectively. Therefore, by using SnO 2 /L-ch as the ETL, the efficiency of champion MAPbI 3 PSCs can be increased from 18.77% to 20.56%, with reduced hysteresis and improved stability. A novel multifunctional L-ch zwitterion is introduced to inhibit the aggregation of SnO 2 NPs and passivate interfacial defects in PSCs. [Display omitted] • A novel L-ch zwitterion with multiple functional groups is introduced into SnO 2 nanoparticles (NPs). • The unique coordination complexes can inhibit the aggregation of SnO 2 NPs, benefiting for the formation of compact film. • The L-ch can adjust the electronic properties of SnO 2 and promote the carrier transport with well aligned energy level. • The -COO- and –N+(CH 3) 3 groups can passivate uncoordinated Pb2+ and MA vacancies defects, respectively. [ABSTRACT FROM AUTHOR]

The therapeutic properties of Hippophae rhamnoides L. were already known in ancient Greece as well as in Tibetan and Mongolian medicine. Modern studies have indicated that Hippophae rhamnoides L. fermentation liquid protected against alcoholic fatty liver disease (AFLD). However, the underlying mechanism of Hippophae rhamnoides L. flavonoids extract (HLF) treating AFLD remains elusive. This study aimed to investigate the hepatoprotective effect of HLF in mice with AFLD and the interaction between AFLD and gut microbiota. Chemical constituents of HLF were analyzed by Liquid Chromatography-Ion Trap-ESI-Mass Spectrometry. The Hepatoprotective effect of HLF was evaluated in mice with AFLD induced by alcohol (six groups, n = 10) daily at doses of 0.1, 0.2, and 0.4 g/kg for 30 consecutive days. At the end of experiment, mice were sacrificed and the liver, serum and feces were harvested for analysis. The liver histological changes were observed by H&E staining and oil red O staining. Moreover, the alterations of fecal microflora were detected by 16S rRNA gene sequencing. The inflammatory related genes were determined by qRT-PCR and western blotting respectively. The results showed that the oral administration of HLF remarkably alleviated hepatic lipid accumulation by decreasing the levels of ALT, AST, TG and TC. The levels of TNF-α, TGF-β, and IL-6 were also reduced after treatment with HLF. Meanwhile, the protein and mRNA expression of NF-kB p65, MAPK p38 and TAK-1 in the liver of mice with AFLD were all reduced by HLF compared with model group. Furthermore, the 16S rRNA gene sequencing analysis demonstrated that HLF treatment can help restore the imbalance of intestinal microbial ecosystem and reverse the changes in Fimicutes/Bacterodietes , Clostridiales, Lachnospiraceae, S24-7, and Prevotella in mice with AFLD. HLF can effectively ameliorate liver injury in mice with AFLD, and regulate the composition of gut microbiota. Its regulatory mechanism may be related to TAK1/p38MAPK/p65NF-κB pathway. This study may provide novel insights into the mechanism of HLF on AFLD and a basis for promising clinical usage. [Display omitted] [ABSTRACT FROM AUTHOR]

Graphical abstract The UC luminescence propertiesand mechanism are analyzed under excitation of 1064 nm and 1550 nm for the first time. The UC luminescence mechanism of the samples excited by 1064 nm laser is shown in Fig. 1(a) and (b). The results show that the intense green emission at 541 nm and 548 nm originates from the 4F 9/2 →4I 15/2 transition of Ho3+ ions and the 4S 3/2 →4I 15/2 transition of Er3+ ions. The weak green emission at 523 nm derives from the 2H 11/2 →4I 15/2 transition of Er3+ ions and the weak red emission at 653 nm and 667 nm originates from the 5F 5 →5I 8 transition of Ho3+ ions and the 4F 9/2 →4I 15/2 transition of Er3+ ions. The UC luminescence mechanism of the samples excited by 1064 nm laser is shown in Fig. 1(c) and (d). The results present that the green emission at 546 nm derives from the 5F 4 (5S 2 )→5I 8 transition of Ho3+ ions and the 4S 3/2 →4I 15/2 transition of Er3+ ions. On the other hand, the weak red emission at 653 nm and 667 nm derives from the 5F 5 →5I 8 transition of Ho3+ ions and the 4F 9/2 →4I 15/2 transition of Er3+ ions. (a) Energy level diagram for Ho3+, Er3+ and Yb3+ ions excited by 1064 nm. (b) Scheme of cross-relaxation between Ho3+ and Er3+ ions. (c) Energy level diagram for Ho3+, Er3+ and Yb3+ ions excited by 1550 nm. (d) Scheme of cross-relaxation between Ho3+ and Er3+ ions. Highlights • In this paper, PbF 2 : Ho3+, Er3+, Yb3+ phosphors are prepared by a high-temperature solid-state method for the first time. • The crystal structure of the as-prepared phosphors is refined. • The upconversion luminescence properties and mechanism of the as-prepared phosphors are analyzed under excitation of 1064 nm, 1550 nm for the first time. Abstract In this paper, PbF 2 : Ho3+, Er3+, Yb3+ phosphors are prepared by a high-temperature solid-state method. The crystal structure acquired by X ray powder diffractometer shows that the resultant phosphor is a pure cubic PbF 2 crystal. The upconversion (UC) emission spectra of samples are performed by a fluorescence spectrophotometer coupled with lasers of 980 nm, 1064 nm and 1550 nm, presenting the green emission in the range of 541∼548 nm and red emission in the range of 653–667 nm, corresponding to the excitation path: Ho3+: 4F 9/2 →4I 15/2 , Er3+: 4S 3/2 →4I 15/2 , Er3+: 4F 9/2 →4I 15/2 and Ho3+: 5F 5 →5I 8. Finally, the UC luminescence mechanism is analyzed under excitation of different wavelengths. The result shows that the phosphors have a promising prospect for application in anti-counterfeiting technologies and solar cell field. [ABSTRACT FROM AUTHOR]

Homeobox C8 (HOXC8) is a transcription factor that has been reported as a potential driver oncogene in several tumors and involved in the regulation of many cancer-related proteins. In this study, we investigated the expression and role of HOXC8 in ovarian cancer. Western blot and immunohistochemistry analyses were performed to detect the expression of HOXC8. Kaplan-Meier curve showed that high expression of HOXC8 was related to poor prognosis of patients with epithelial ovarian cancer (EOC). Starvation and refeeding assay were used to assess cell cycle, suggesting that HOXC8 played a critical role in EOC cell proliferation. HOXC8 depletion by small interfering RNA inhibited cell proliferation, migration, and induced apoptosis in EOC cells. Moreover, HOXC8 knockdown increased the expression of ZAC1. Owing to the overexpression of HOXC8, our findings implied that HOXC8 is involved in the progression of EOC and could be a potential therapeutical approach of EOC. [ABSTRACT FROM AUTHOR]

VRK1 is a member of the vaccinia-related kinase (VRK) family of serine/threonine protein kinases, which is known to play multiple roles in cellular proliferation, cell cycle regulation and carcinogenesis. However, the expression and physiological significance of VRK1 in hepatocellular carcinoma (HCC) remain unclear. In this study, we aimed to investigate the potential role of VRK1 in the development and progression of HCC. Western blot and immunohistochemical analysis revealed that VRK1 was highly expressed in HCC tissues and cell lines, compared with adjacent nontumorous tissues and LO2 normal hepatocytes. Meanwhile, clinicopathological analysis showed that VRK1 was significantly associated with AJCC stage, Ki-67 and a poor prognosis in HCC specimens. Univariate and multivariate analysis showed that VRK1 could serve as an independent prognostic indicator of HCC patients’ survival. Furthermore, we found that VRK1 was lowly expressed in serum-starved Huh7 cells, and was progressively increased after serum-refeeding. Finally, flow cytometry, CCK-8 and colony formation assay indicated that the depletion of VRK1 could retard cell cycle progression and reduce cells proliferation in HCC cells. On the basis of these findings, we conclude that VRK1 may be a candidate prognostic biomarker as well as a potential therapeutical target of HCC. [ABSTRACT FROM AUTHOR]

PFTK1, also known as PFTAIRE1, CDK14, is a novel member of Cdc2-related serine/threonine protein kinases. Recent studies show that PFTK1 is highly expressed in several malignant tumors such as hepatocellular carcinoma, esophageal cancer, breast cancer, and involved in regulation of cell cycle, tumors proliferation, migration, and invasion that further influence the prognosis of tumors. However, the expression and physiological significance of PFTK1 in gastric cancer remain unclear. In this study, we analyzed the expression and clinical significance of PFTK1 by Western blot in 8 paired fresh gastric cancer tissues, nontumorous gastric mucosal tissues and immunohistochemistry on 161 paraffinembedded slices. High PFTK1 expression was correlated with the tumor grade, lymph node invasion as well as Ki-67. Through Cell Counting Kit (CCK)-8 assay, flow cytometry, colony formation, wound healing and transwell assays, the vitro studies demonstrated that PFTK1 overexpression promoted proliferation, migration and invasion of gastric cancer cells, while PFTK1 knockdown led to the opposite results. Our findings for the first time supported that PFTK1 might play an important role in the regulation of gastric cancer proliferation, migration and would provide a novel promising therapeutic strategy against human gastric cancer. [ABSTRACT FROM AUTHOR]

Background: Individualized drug response prediction is vital for achieving personalized treatment of cancer and moving precision medicine forward. Large-scale multi-omics profiles provide unprecedented opportunities for precision cancer therapy.Methods: In this study, we propose a pipeline to identify subpathway signatures for anticancer drug response of individuals by integrating the comprehensive contributions of multiple genetic and epigenetic (gene expression, copy number variation and DNA methylation) alterations.Results: Totally, 46 subpathway signatures associated with individual responses to different anticancer drugs were identified based on five cancer-drug response datasets. We have validated the reliability of subpathway signatures in two independent datasets. Furthermore, we also demonstrated these multi-omics subpathway signatures could significantly improve the performance of anticancer drug response prediction. In-depth analysis of these 46 subpathway signatures uncovered the essential roles of three omics types and the functional associations underlying different anticancer drug responses. Patient stratification based on subpathway signatures involved in anticancer drug response identified subtypes with different clinical outcomes, implying their potential roles as prognostic biomarkers. In addition, a landscape of subpathways associated with cellular responses to 191 anticancer drugs from CellMiner was provided and the mechanism similarity of drug action was accurately unclosed based on these subpathways. Finally, we constructed a user-friendly web interface-CancerDAP ( http://bio-bigdata.hrbmu.edu.cn/CancerDAP/ ) available to explore 2751 subpathways relevant with 191 anticancer drugs response.Conclusions: Taken together, our study identified and systematically characterized subpathway signatures for individualized anticancer drug response prediction, which may promote the precise treatment of cancer and the study for molecular mechanisms of drug actions. [ABSTRACT FROM AUTHOR]