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The precisely manipulated π–π stacking of the hybrid catalyst favors the specific prediction of the ORR active sites, which are the iron atoms in the form of natural Fe-N 4 that bind preferentially to the oxygen. [Display omitted] Metal macrocycles with well-defined molecular structures are ideal platforms for the in-depth study of electrochemical oxygen reduction reaction (ORR). Structural integrity of metal macrocycles is vital but remain challenging since the commonly used high-temperature pyrolysis would cause severe structure damage and unidentifiable active sites. Herein, we propose a pyrolysis-free strategy to precisely manipulate the exfoliated 2D iron polyphthalocyanine (FePPc) anchored on reduced graphene oxide (rGO) via π–π stacking using facile high-energy ball milling. A delocalized electron shift caused by π–π interaction is firstly found to be the mechanism of facilitating the remarkable ORR activity of this hybrid catalyst. The optimal FePPc@rGO-HE achieves superior half-wave potential (0.90 V) than 20 % Pt/C. This study offers a new insight in designing stable and high-performance metal macrocycle catalysts with well-defined active sites. [ABSTRACT FROM AUTHOR]

Bifunctional catalyst was prepared by one-step pyrolysis of trimetallic ZIF. The obtained catalyst showed excellent charge–discharge stability in rechargeable Zn-air battery. • A facile and effect strategy is proposed for the synthesis of catalyst precursor. • This strategy reduces the adverse effects of the pyrolysis process on the catalyst. • The coexistence of Co NPs and CoFe-N x improves the ORR/OER activity. • The catalyst displays excellent durability as a cathode for Zn-air battery. Searching for high active, low cost and durable catalysts for oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) remains challenge in developing metal-air battery cathodes. Herein, we proposed a novel bifunctional catalyst derived from the pyrolysis of Co/Fe/Zn trimetallic zeolitic imidazolite framework. The obtained Co@CoFe 0.01 N C catalyst displays desirable activity for both ORR and OER (E 1/2 = 0.844 V, E j=10 = 1.654 V). The Zn-air battery equipped with Co@CoFe 0.01 N C catalyst on the cathode exhibits a high peak power density of 174.1 mW cm−2, which is much superior than that of commercial 20% Pt/C (87.6 mW cm−2). Significantly, the designed Co@CoFe 0.01 N C presents an outstanding stability for over 100 h in rechargeable Zn-air battery. [ABSTRACT FROM AUTHOR]

Abstract CircRNAs are reported to be implicated in the development of lung cancer. This study focused on assessing the expression, functions and molecular mechanism of circPUM1 in lung adenocarcinoma. Here, it showed that circPUM1 is significantly upregulated in both lung adenocarcinoma cell lines and tissues. Furthermore, silencing of circPUM1 impaired the proliferation, migration and invasion ability, and increased apoptosis in A549 cells. Nevertheless, overexpression of circPUM1 in SPC-A1 cells has the opposite effect. Silencing of circPUM1 inhibits the tumorigenesis in nude mice. Mechanistically, circPUM1 could sponge miR-326 and promote the expression of its downstream proteins Cyclin D1 and Bcl-2. In summary, this present study revealed that circPUM1 functions as an oncogene to promote the tumorigenesis of lung adenocarcinoma through circPUM1/miR-326/Cyclin D1 and Bcl-2 axis. This indicates that circPUM1 may act as a potential therapeutic target for lung adenocarcinoma. Highlights • Upregulation of circPUM1 in lung adenocarcinoma cell lines and tissues. • Silencing of circPUM1 inhibits the proliferation, migration, invasion and inhibited apoptosis in vitro, and vice versa. • CircPUM1 sponges miR-326 to upregulate Cyclin D1 and Bcl-2 expression to promote tumorigenesis. [ABSTRACT FROM AUTHOR]

Antibiotics, which are hardly removed from polluted water by conventional water-treatment technologies, adsorption has been deemed as one of the efficient and promising method to resolve the problems of antibiotics pollution. Herein, we reported a synthesis of filtration separable hollow nanostructured silicas (HNSs) with efficient click functionalization property for antibiotics adsorption. The clickable HNSs were synthesized by the co-condensation and assembling of tetramethoxysilane (TMOS) and 3-azidopropyltrimethoxysilane (AzPTMS) around F127 single micelle template. Alkynyl compounds such as phenylacetylene (Ph), propargyl alcohol (PA), 1-heptyne (Hep), and 2-butyne-1,4-diol (BD) have been linked to the materials through click reaction with high efficiency. Antibiotic adsorption results reveal that functional groups play an important role in adsorption properties of adsorbents and phenyl was found to be the optimal functional group due to the π–π stacking effect. Excellent adsorption capacity and recyclability indicate that the clickable hollow nanostructured silicas exhibit potential application for antibiotics removal. [ABSTRACT FROM AUTHOR]

The HCMV (human cytomegalovirus) encodes numerous proteins which function to evade the immune response, which allows the virus to replicate. Exploring the mechanisms of HCMV immune escape helps to find the strategy to inhibit HCMV replicate. CD8+ T cells play a critical role in the immune response to viral pathogens. However, the mechanisms of HCMV to evade the attack by CD8+ T cells remain largely unknown. Viral CXCL1 (vCXCL1) is the production of HCMV UL146 gene. Here, we found that vCXCL1 promoted the resistance of hepatic cells to CD8+ T cells. vCXCL1 increased the levels of PD-L1 protein expression and mRNA expression. VCXCL1 enhanced the binding of STAT3 transcription factor to the promoter of PD-L1 and increased the activity of PD-L1 promoter. Furthermore, down-regulation of PD-L1 reduced the effects of vCXCL1 on the resistance of hepatic cells to CD8+ T cells. Taken together, vCXCL1 promotes the resistance of hepatic cells to CD8+ T cells through up-regulation of PD-L1. This finding might provide a new mechanism of HCMV immune escape. • vCXCL1 promotes the immune escape of hepatic cells. • vCXCL1 promotes the transcription of PD-L1 though activation of STAT3 phosphorylation. • vCXCL1 protects hepatic cells from CD8+ T cells through up-regulation of PD-L1. [ABSTRACT FROM AUTHOR]

The relationship between alcohol dehydrogenase (ADH) and liver fibrosis has been studied, but the mechanism of ADH involvement in liver fibrosis remains unclear. The aim of the present study was to explore the role of ADHI, the classical liver ADH, in hepatic stellate cell (HSC) activation and the effect of 4-methylpyrazole (4-MP), an ADH inhibitor, on liver fibrosis induced by carbon tetrachloride (CCl 4) in mice. The results showed that overexpression of ADHI significantly increases proliferation, migration, adhesion and invasion rates of HSC-T6 cells as compared with controls. When HSC-T6 cells were activated by ethanol, TGF-β1 or LPS, the expression of ADHI was elevated significantly (P < 0.05). Overexpression of ADHI significantly increased the levels of COL1A1 and α-SMA, markers of HSC activation. Moreover, the expression of COL1A1 and α-SMA was decreased significantly by transfection of ADHI siRNA (P < 0.01). In a liver fibrosis mouse model ADH activity increased significantly and was highest in the 3rd week. The activity of ADH in the liver was correlated with its activity in the serum (P < 0.05). 4-MP significantly decreased ADH activity and ameliorated liver injury, and ADH activity was positively correlated with the Ishak score of liver fibrosis. In conclusion, ADHI plays an important role in the activation of HSC, and inhibition of ADH ameliorates liver fibrosis in mice. [Display omitted] • Overexpression of ADHI significantly increases proliferation, migration and invasion rates of HSC-T6 cells. • The expression of ADHI was elevated significantly in HSC-T6 cells after activated by ethanol, TGF-β1 or LPS. • 4-MP, an inhibitor of ADH, significantly decreased ADH activity and ameliorated liver fibrosis in mice induced by CCl4. [ABSTRACT FROM AUTHOR]

Atemoya is prone to soft ripening and cracking and has a short storage life at room temperature in summer and autumn in China. To better understand the mechanisms involved in fruit ripening and cracking, the effects of five temperature and humidity treatments (28 °C + 50%, 28 °C + 70%, 28 °C + 95%, 32 °C + 95%, 15 °C + 95%) were evaluated, and transcriptome analysis of the fruits was performed under storage conditions (stored for 0, 2, 4, and 6 days at 28 and 15 °C) in this study. The transcriptome results revealed that starch and sucrose metabolism was the most enriched KEGG pathway, including 485 DEGs. Compared with the 28 °C + 95% and 28 °C + 70% treatments, which accelerated the fruit ripening and cracking, low-temperature storage (15 °C + 95%) inhibited the expression of starch hydrolase genes such as GWD, LSF2, BAM3, BAM9, ISA3, and DPE2 , decreased the activities of BAM and DBE, increased the concentrations of sucrose and trehalose, slowed down the conversion rate of the starch to soluble sugar, decreased the RWC of the pulp, and effectively delayed ripening and cracking. These results provide a physiology and molecular foundation for explaining fruit softening and cracking and extending the shelf life of atemoya. • Low-temperature and high-humidity delay atemoya fruit ripening and cracking. • Starch and sucrose metabolism is the key pathway involved in atemoya fruit ripening. • GWD , BAM3 , ISA3 and DPE2 are the main starch degradation enzyme genes. [ABSTRACT FROM AUTHOR]

Sulfur-driven autotrophic denitrification (S0dAD) was employed to remove residual nitrogen from the biological effluent of landfill leachate after partial nitrification and denitrification pretreatment. The performance of S0dAD were assessed with various NO x −-N (NO 2 −-N and NO 3 −-N) loadings over a 185-day operational period. The results demonstrated that a notable NO x −-N removal efficiency of 97.8 ± 2.0% was achieved under nitrogen removal rates of 0.12 ± 0.02 kg N/(m3· d), leading to total nitrogen concentrations of 8.6 ± 3.8 mg/L in the effluent. Batch experiments revealed competitive utilization of nitrogenous electron acceptors, with NO 2 −-N demonstrating 2–4 times higher denitrification rates than NO 3 −-N under coexistence conditions. Genus-level microbial community identified that Thiobacillus and Sulfurovum was highly enriched with as key denitrifying bacteria in the S0dAD system. These findings provide insights for advanced nitrogen removal coupling S0dAD with partial nitrification and denitrification process for landfill leachate treatment. • NO x −-N removal efficiency of 97.8 ± 2.0% was achieved via S0dAD under HRT of 0.90 d. • Effluent TN of 8.6 ± 3.8 mg/L was achieved with NRR of 0.12 ± 0.02 kg N/(m3·d). • NO 2 −-N showed 2–4 times higher denitrification rates than NO 3 −-N under coexistence. • S0dAD contributed to over 85% of total NO x −-N removal. • Thiobacillus and Sulfurovum was highly enriched in the S0dAD system. [ABSTRACT FROM AUTHOR]

The urgent concerns of controlling water body eutrophication and the alleviating phosphorus shortage have led to an urgent need for action. The removal of phosphate from polluted waters and its reuse are essential for the prevention of eutrophication and for the sustainable utilization of phosphate resources. In this study, modified attapulgite with different Ca:Mg molar ratios was synthesized to facilitate the recovery of phosphate, with subsequent use of soil fertilizer. Ca–Mg modified attapulgite with the optimal ratio (ACM-5:3) exhibited an exceptional adsorption quality, achieving a maximum adsorption capacity of 63.2 mg/g. The pseudo-second-order model and Langmuir model could well describe the adsorption kinetics and isotherms, respectively. The adsorption mechanism analyses suggested that the interaction between ACM-5:3 and phosphate depended mainly on ion exchange and electrostatic attraction. Moreover, phosphate-laden-ACM-5:3 demonstrated a significant potential as a phosphorus-releasing fertilizer. It could promote corn growth by ensuring a continuous supply of phosphorus and minimizing phosphorus runoff losses. The above results suggested that ACM-5:3 was a potential adsorbent for efficient phosphate removal and recovery. [Display omitted] • Ca–Mg modified attapulgite was prepared using the co-precipitation method. • The maximum adsorption capacity of ACM-5:3 was 63.2 mg/g. • Phosphate-laden-ACM-5:3 was directly used as a slow-release phosphorus fertilizer. • Efficient recovery and reuse of phosphates was achieved. [ABSTRACT FROM AUTHOR]

Abstract Cryptophthalmos is a rare congenital disorder characterized by ocular dysplasia with eyelid malformation. Complete cryptophthalmos is characterized by the presence of continuous skin from the forehead over the eyes and onto the cheek, along with complete fusion of the eyelids. In the present study, we characterized the clinical manifestations of three patients with isolated bilateral cryptophthalmos. These patients shared the same c.6499C > T missense mutation in the FRAS1-related extracellular matrix protein 2 (FREM2) gene, while each individual presented an additional nonsense mutation in the same gene (Patient #1, c.2206C > T; Patient #2, c.5309G > A; and Patient #3, c.4063C > T). Then, we used CRISPR/Cas9 to generate mice carrying Frem2 R725X/R2156W compound heterozygous mutations, and showed that these mice recapitulated the human isolated cryptophthalmos phenotype. We detected FREM2 expression in the outer plexiform layer of the retina for the first time in the cryptophthalmic eyes, and the levels were comparable to the wild-type mice. Moreover, a set of different expressed genes that may contribute secondarily to the phenotypes were identified by performing RNA sequencing (RNA-seq) of the fetal Frem2 mutant mice. Our findings extend the spectrum of FREM2 mutations, and provide insights into opportunities for the prenatal diagnosis of isolated cryptophthalmos. Furthermore, our work highlights the importance of the FREM2 protein during the development of eyelids and the anterior segment of the eyeballs, establishes a suitable animal model for studying epithelial reopening during eyelid development and serves as a valuable reference for further mechanistic studies of the pathogenesis of isolated cryptophthalmos. Highlights • Novel compound heterozygous mutations of FREM2 in three patients with rare bilateral cryptophthalmos. • Recapitulates this complete cryptophthalmos phenotype in Frem2R725X/R2156W mutant mice on a C57BL/6 background. • The first description of FREM2 expression in the retina was completed. • Data source for a set of genes which may contribute secondarily to the phenotypes. • Evidence for FREM2 playing a critical role during the development of eyelids and the anterior segment of the eyeballs. FREM2 playing a critical role during the development of eyelids and the anterior segment of the eyeballs. [ABSTRACT FROM AUTHOR]

Ginsenosides are the main bioactive constituents of Panax species, which are biosynthesized by glycosylation at C3-OH and/or C20-OH of protopanaxadiol (PPD), C6-OH and/or C20-OH of protopanaxatriol (PPT). The C12-glycosylated ginsenosides have scarcely been identified from Panax species. The C12-glycosylated ginsenosides produced from PPD by chemical semi-synthesis have been reported to exhibit higher cytotoxicity than the natural ginsenosides. However, the chemical semi-synthesis approach is not practical due to its complexity and high cost. In our study, a new UDP-glycosyltransferase UGT109A1 was identified from Bacillus subtilis . This enzyme transferred a glucose moiety to C3-OH and C20-OH of dammarenediol-II (DM), C3-OH and C12-OH of PPD and PPT respectively to produce the unnatural ginsenosides 3 β-O -Glc-DM, 3 β ,20 S- Di -O -Glc-DM, 3 β ,12 β -Di- O -Glc-PPD and 3 β ,12 β -Di- O -Glc-PPT. Among these unnatural ginsenosides, 3 β ,12 β- Di -O -Glc-PPT is a new compound which has never been reported before. The anti-cancer activities of these unnatural ginsenosides were evaluated in vitro and in vivo . 3 β ,12 β -Di- O -Glc-PPD exhibited higher anti-lung cancer activity than Rg3, which is the most active natural ginsenoside against lung cancer. Finally, we constructed metabolically engineered yeasts to produce 3 β ,12 β -Di- O -Glc-PPD by introducing the genes encoding B. subtilis UGT109A1, Panax ginseng dammarenediol-II synthase (DS), P. ginseng cytochrome P450-type protopanaxadiol synthase (PPDS) together with Arabidopsis thaliana NADPH-cytochrome P450 reductase (ATR1) into Saccharomyces cerevisiae INVSc1. The yield of 3 β ,12 β -Di- O -Glc-PPD was increased from 6.17 mg/L to 9.05 mg/L by overexpressing tHMG1. Thus, this study has established an alternative route to produce the unnatural ginsenoside 3 β ,12 β -Di- O -Glc-PPD by synthetic biology strategies, which provides a promising candidate for anti-cancer drug discovery. [ABSTRACT FROM AUTHOR]

Multi-branch feature aggregation has recently been introduced and shows superior performance for speaker verification. It is often implemented via simple operations, such as element-wise addition or concatenation, but this might lead to suboptimal results. In this paper, we propose a novel multi-branch feature aggregation method based on multiple weighting (MBFA-MW), which adaptively learns attention weights for each branch to extract discriminative information that is beneficial to speaker verification. This method contains two weighting strategies, point attention and channel attention. Point attention learns a point-wise weight to emphasize salient local information from the time–frequency domain, and channel attention learns a channel-wise weight to enhance the correlation between the key information and the channel from the frequency domain. Combining the time–frequency domain and the frequency domain, the two strategies complement each other and extract informational features from multiple branch. In addition, we compared different multi-branch feature aggregation methods in the same environment. Experimental results on the datasets of Voxceleb and Cnceleb show the proposed method achieves performance improvements compared to other multi-branch feature aggregation methods and other mainstream methods. • Multi-branch feature aggregation method based on multiple weighting learns attention weights for each branch. • Point attention and channel attention aggregate multi-branch features. • These two strategies complement each other and extract informational features. [ABSTRACT FROM AUTHOR]

Segetoside I is a plant-derived bisdesmosidic saponin from Vaccaria segetalis (Neck) with reported anticancer activities. This development has raised an interest in the therapeutic potential of segetoside I. Here, we report the in vitro and in vivo antitumor activities of segetoside I against some selected cancer cell lines (HepG2, human hepatoma; H 22 , mouse hepatoma; MCF-7, breast cancer; U251, gliocoma; BGC, HGC & SGC, gastric cancinoma; Lovo-1,colon cancer). MTT bioassay analysis showed that HepG2 cells were the most sensitive to segetoside I compared with other cancer cell lines, with lower toxicity in healthy mouse embryonic fibroblast cells. Segetoside I pretreatment of HepG2 resulted in apoptotic induction, dose-dependent DNA fragmentation, inhibition of cell migration, up-regulation of Bax and down-regulation of Bcl-2, which indicated that an apoptotic signaling event could have been initiated. The segetoside I also suppressed hepato-tumour growth in mice with virtually no cytotoxicity and prolonged animal survival, making it a strong oncology drug agent. These findings showed that segetoside I exhibited its antitumor activity via apoptotic induction and significantly support the possible application of the antitumor agent as a potential chemotherapeutic candidate worthy of further investigations. [ABSTRACT FROM AUTHOR]

tRNA-derived small RNAs (tsRNAs) participate in several biological processes, including carcinogenesis. The correlations between tsRNAs and human cancers are attracting substantial attention. Nevertheless, the involvement of tsRNAs in laryngeal squamous cell carcinoma (LSCC) progression remains unclear. We constructed tsRNAs expression profiles in LSCC and adjacent normal tissues by next-generation sequencing. Interestingly, we identified a specific 5′-tiRNA fragment (tRF-33-Q1Q89P9L842205) that was significantly downregulated and was closely associated with lymph node metastasis and advanced stages of LSCC. Importantly, we found that tRF-33-Q1Q89P9L842205 suppressed cell growth, proliferation, migration, invasion and induced apoptosis in LSCC by directly silencing phosphoinositide 3-kinase catalytic subunit (PIK3CD). We speculated that tRF-33-Q1Q89P9L842205 is a potential diagnostic biomarker for LSCC and acts as a tumor suppressor by directly targeting PIK3CD. • Construction of tsRNA expression profiles in LSCC based on next-generation sequencing. • tRF-33-Q1Q89P9L842205 was downregulated and associated with metastasis in LSCC. • tRF-33-Q1Q89P9L842205 inhibits proliferation and migration of LSCC. • PIK3CD is one of the target genes of tRF-33-Q1Q89P9L842205. [ABSTRACT FROM AUTHOR]

Compared with lithium-ion batteries, sodium-ion batteries possess the advantages of low cost and high energy density. The research and development of the positive, negative and electrolyte materials of sodium-ion batteries is of great significance to develop sodium-ion energy storage devices. The sodium superionic conductor (NASICON) with a stoichiometric ratio of Na 3 Sc 2 P 3 O 12 (NSP) has a variety of crystal types, namely α-, β- and γ-phase. Different crystal structures exhibit different ion transport characteristics, resulting in the varied ionic conductivity and other electrochemical performance. The effect of different crystalline-type Na 3 Sc 2 P 3 O 12 (α-Na 3 Sc 2 P 3 O 12 , β-Na 3.5 Sc 2 P 2.5 Si 0.5 O 12 and γ-Na 4 Sc 2 P 2 SiO 12) fillers on gel polymer electrolytes (GPE) was investigated in detail. Due to the difference in the adsorption capacity of the gel electrolyte added three types of crystalline-type fillers and the difference in the conductivity of fillers, the composite gel electrolytes exhibited various performances. The optimal gel electrolyte with 7 ​% γ-Na 4 Sc 2 P 2 SiO 12 filler delivers the optimal conductivity as high as 2.783 ​× ​10−3 ​S ​cm−1. The optimal performance of Na 3 V 2 (PO 4) 3 /C| GPE |Na cell shows that the first discharge specific capacity was 92.3 mAh g−1 with a capacity retention rate of 98.18% after 100 cycles. Different crystalline-type sodium conductive filler (α-Na 3 Sc 2 P 3 O 12 , β-Na 3.5 Sc 2 P 2.5 Si 0.5 O 12 and γ-Na 4 Sc 2 P 2 SiO 12) modified GPEs membranes with enhanced ionic conductivity were fabricated and the application performances in sodium ions batteries (SIBs) were demonstrated. [Display omitted] • Sodium conductive Na 3 Sc 2 P 3 O 12 filler with three types of crystal phases modified GPEs were fabricated. • Ionic conductivity of GPEs was enhanced with the presence of Na 3 Sc 2 P 3 O 12 filler. • Na 3 Sc 2 P 3 O 12 filler decreased the crystallinity and enlarged the porosity of GPEs. • GPEs membranes delivered competitive electrochemical performances applied in SIBs. [ABSTRACT FROM AUTHOR]