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The Fc-fused receptor binding domain (RBD-Fc) vaccine for SARS-CoV-2 has garnered significant attention for its capacity to provide effective and specific immune protection. However, its immunogenicity is limited, highlighting the need for improvement in clinical application. Nanoparticle delivery has been shown to be an effective method for enhancing antigen immunogenicity. In this study, we developed bivalent nanoparticle recombinant protein vaccines by assembling the RBD-Fc of SARS-CoV-2 and Fc-binding homo-oligomers o42.1 and i52.3 into octahedral and icosahedral nanoparticles. The formation of RBD-Fc nanoparticles was confirmed through structural characterization and cell binding experiments. Compared to RBD-Fc dimers, the nanoparticle vaccines induced more potent neutralizing antibodies (nAb) and stronger cellular immune responses. Therefore, using bivalent nanoparticle vaccines based on RBD-Fc presents a promising vaccination strategy against SARS-CoV-2 and offers a universal approach for enhancing the immunogenicity of Fc fusion protein vaccines., 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 © 2024 Elsevier B.V. All rights reserved.)

Wastewater treatment is an important source of non-CO 2 greenhouse gases (GHGs). However, current quantification of these GHG emissions mainly employs unit-based measurements, where emissions from individual process units are identified, leading to large uncertainties of overall emissions. Here we introduce plant-integrated measurements, where emissions from the whole plant are measured through the off-gas pipelines of the enclosed facility, to quantify methane (CH 4 ) and nitrous oxide (N 2 O) emissions from an underground municipal wastewater treatment plant (WWTP) in southern China. Our results show that the primary oxic tank contributes the largest in total CH 4 and N 2 O emissions, with an average fraction of over 80 % and over 90 %, respectively. This can be attributed to the vigorous aeration process, which facilitates the transfer of dissolved CH 4 and N 2 O from the liquid phase to the atmosphere through intensive air stripping. The plant-integrated measurements yield around 3-9 times higher emission factors of CH 4 and N 2 O than the unit-based measurements. This difference in emission accounting is attributed to both varying survey durations of the two approaches and the omission of uncertain emission sources during unit-based measurements. The comparison between these two approaches indicates that plant-integrated measurements are more applicable for emission quantification of the whole plant whereas unit-based measurements provide insights into the emission characteristics of individual process units. More plant-integrated measurements are needed in the future for more accurate emission accounting of WWTPs., 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 © 2024 Elsevier B.V. All rights reserved.)

Neuropeptide FF (NPFF) plays a critical role in various physiological processes through the activation of neuropeptide FF receptor 1 and 2 (NPFFR1 and NPFFR2). Numerous evidence has indicated that NPFF exhibits opposite opioid-modulating effects on opioid-induced analgesia after supraspinal and spinal administrations, while the detailed role of NPFFR1 and NPFFR2 remains unclear. In this study, we employed pharmacological and genetic inhibition of NPFFR to investigate the modulating roles of central NPFFR1 and NPFFR2 in opioid-induced analgesia and hyperalgesia, using a male mouse model of acute fentanyl-induced analgesia and secondary hyperalgesia. Our findings revealed that intrathecal (i.t.) injection of the nonselective NPFFR antagonist RF9 significantly enhanced fentanyl-induced analgesia, whereas intracerebroventricular (i.c.v.) injection did not show the same effect. Moreover, NPFFR2 deficient (npffr2 -/- ) mice exhibited stronger analgesic responses to fentanyl compared to wild type (WT) or NPFFR1 knockout (npffr1 -/- ) mice. Intrathecal injection of RF9 in npffr1 -/- mice also significantly enhanced fentanyl-induced analgesia. These results indicate a crucial role of spinal NPFFR2 in the enhancement of opioid analgesia. Contrastingly, hyperalgesia induced by fentanyl was markedly reversed in npffr1 -/- mice but remained unaffected in npffr2 -/- mice. Similarly, i.c.v. injection of the selective NPFFR1 antagonist RF3286 effectively prevented fentanyl-induced hyperalgesia in WT or npffr2 -/- mice. Notably, co-administration of i.c.v. RF3286 and i.t. RF9 augmented fentanyl-induced analgesia while reducing hyperalgesia. Collectively, these findings highlight the modulating effects of blocking spinal NPFFR2 and supraspinal NPFFR1 on fentanyl-induced analgesia and hyperalgesia, respectively, which shed a light on understanding the pharmacological function of NPFF system in future studies., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

DEC205 (CD205) is one of the major endocytic receptors on dendritic cells and has been widely used as a receptor target in immune therapies. It has been shown that DEC205 can recognize dead cells through keratins in a pH-dependent manner. However, the mechanism underlying the interaction between DEC205 and keratins remains unclear. Here we determine the crystal structures of an N-terminal fragment of human DEC205 (CysR∼CTLD3). The structural data show that DEC205 shares similar overall features with the other mannose receptor family members such as the mannose receptor and Endo180, but the individual domains of DEC205 in the crystal structure exhibit distinct structural features that may lead to specific ligand binding properties of the molecule. Among them, CTLD3 of DEC205 adopts a unique fold of CTLD, which may correlate with the binding of keratins. Furthermore, we examine the interaction of DEC205 with keratins by mutagenesis and biochemical assays based on the structural information and identify an XGGGX motif on keratins that can be recognized by DEC205, thereby providing insights into the interaction between DEC205 and keratins. Overall, these findings not only improve the understanding of the diverse ligand specificities of the mannose receptor family members at the molecular level but may also give clues for the interactions of keratins with their binding partners in the corresponding pathways., Competing Interests: Conflict of 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 © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The Rocahepevirus ratti hepatitis E virus genotype C1 (HEV-C1) has been documented to infect humans. However, the understanding of HEV-C1 remains constrained. This study aims to determine the prevalence and genomic characteristics of HEV-C1 in small animals in Yunnan province of southwestern China. A total of 444 liver tissues were collected from animals covering the orders Rodentia, Soricomorpha, Scandentia and Erinaceomorpha in three regions in Yunnan. Then Paslahepevirus balayani and Rocahepevirus were examined using RT-qPCR. The detection rate of Rocahepevirus was 12.95 % (36/278) in animals of order Rodentia, with 14.77 % (35/237) in Rattus tanezumi and 33.33 % (1/3) in Niviventer fulvescens. No Paslahepevirus balayani was detected. Additionally, two full-length Rocahepevirus sequences (MSE-17 and LHK-54) and thirty-three partial ORF1 sequences were amplified and determined to be HEV-C1. MSE-17 and LHK-54 shared moderate nucleotide identity (78.9 %-80.3 %) with HEV-C1 isolated in rats and humans. The HEV-C1 isolated from Niviventer fulvescens demonstrated a 100 % nucleotide identity with that from Rattus tanezumi. The rat HEV-C1 sequences isolated in our study and other Asian HEV-C1 sequences were phylogenetically distant from those isolated in North America and Europe. Furthermore, the two full-length sequences isolated in our study had less amino acid substitutions in the motifs of RNA-dependent RNA polymerase domain (F 204 L and L 238 F), compared with other Asian sequences. In summary, HEV-C1 commonly spreads in rats in Yunnan province of China. Our findings suggest a spatially associated phylogeny, and potential cross-species transmission of HEV-C1., 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 © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

With the continuous advancement of nanotechnology, nanodevices have become crucial components in computing, sensing, and energy conversion applications. The structures of nanodevices typically possess subwavelength dimensions and separations, which pose significant challenges for understanding energy transport phenomena in nanodevices. Here, on the basis of a judiciously designed thermal photonic nanodevice, we report the first measurement of near-field energy transport between two coplanar subwavelength structures over temperature bias up to ∼190 K. Our experimental results demonstrate a 20-fold enhancement in energy transfer beyond blackbody radiation. In contrast with the well-established near-field interactions between two semi-infinite bodies, the subwavelength confinements in nanodevices lead to increased polariton scattering and reduction of supporting photonic modes and, therefore, a lower energy flow at a given separation. Our work unveils exciting opportunities for the rational design of nanodevices, particularly for coplanar near-field energy transport, with important implications for the development of efficient nanodevices for energy harvesting and thermal management.

The cyclic peptide c[d-Lys 2 , Asp 5 ]-DN-9 has recently been identified as a multifunctional opioid/neuropeptide FF receptor agonist, displaying potent analgesic activity with reduced side effects. This study utilized Tyr-c[d-Lys-Gly-Phe-Asp]-d-Pro-NH 2 ( 0 ), a cyclic hexapeptide derived from the opioid pharmacophore of c[d-Lys 2 , Asp 5 ]-DN-9, as a chemical template. We designed, synthesized, and characterized 22 analogs of 0 with a single amino acid substitution to investigate its structure-activity relationship. Most of these cyclic hexapeptide analogs exhibited multifunctional activity at μ and δ opioid receptors (MOR and DOR, respectively) and produced antinociceptive effects following subcutaneous administration. The lead compound analog 15 showed potent agonistic activities at the MOR, κ opioid receptor (KOR), and DOR in vitro and produced a strong and long-lasting analgesic effect through peripheral MOR and KOR in the tail-flick test. Further biological evaluation identified that analog 15 did not cause significant side effects such as tolerance, withdrawal, or reward liability.

Our previous study reported the multifunctional agonist for opioid and neuropeptide FF receptors DN-9, along with its cyclic peptide analogues c[ D -Cys 2 , Cys 5 ]-DN-9 and c[ D -Lys 2 , Asp 5 ]-DN-9. These analogues demonstrated potent antinociceptive effects with reduced opioid-related side effects. To develop more stable and effective analgesics, we designed, synthesized, and evaluated seven hydrocarbon-stapled cyclic peptides based on DN-9. In vitro calcium mobilization assays revealed that most of the stapled peptides, except 3 , displayed multifunctional agonistic activities at opioid and neuropeptide FF receptors. Subcutaneous administration of all stapled peptides resulted in effective and long-lasting antinociceptive activities lasting up to 360 min. Among these stapled peptides, 1a and 1b emerged as the optimized compounds, producing potent central antinociception following subcutaneous, intracerebroventricular, and oral administrations. Additionally, subcutaneous administration of 1a and 1b caused nontolerance antinociception, with limited occurrence of constipation and addiction. Furthermore, 1a was selected as the final optimized compound due to its wider safety window compared to 1b .

CircRNAs are implicated in colorectal cancer (CRC) development and progression. Protein O-fucosyltransferase 1 (POFUT1) plays an oncogenic role via activating Notch1 signaling in CRC. However, the roles of circPOFUT1, which is originated from POFUT1, have not been investigated. Our study showed circPOFUT1 was highly expressed in CRC tissues and cells. CircPOFUT1 enhanced the proliferation, migration and invasion of CRC cells, and promoted tumor growth and liver metastasis in vivo . It also reinforced stemness and chemoresistance of CRC cells. Mechanistically, circPOFUT1 regulated the function of E2F7 via sponging miR-653-5p, thereby transcriptionally inducing WDR66 expression and further promoting metastasis in CRC. On the other hand, circPOFUT1 promoted stemness and chemoresistance of CRC cells via stabilizing BMI1 in an IGF2BP1-dependent manner. In conclusion, circPOFUT1 fosters CRC metastasis and chemoresistance via decoying miR-653-5p/E2F7/WDR66 axis and stabilizing BMI1., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

Introduction: Ticagrelor is extensively utilized for the treatment of acute coronary syndromes (ACS), but its platelet aggregation inhibitory effects can potentially result in tissue bleeding, posing a serious risk to patients' lives. Methods: In this study, we developed highly sensitive full length anti-ticagrelor Quenchbodies (Q-bodies) for fast monitoring of ticagrelor both in solution and serum for the first time. Ticagrelor coupled with N- hydroxysuccinimide (Ticagrelor-NHS) ester was also designed and synthesized for interaction and biological activity detection. Results: Both ATTO-labeled MEDI2452 (2452A) Q-body and TAMRA-labeled IgG 152 (152T) Q-body demonstrated efficient detection of ticagrelor and its active metabolite (TAM). The 2452A Q-body exhibited a broader detection range, while the 152T Q-body displayed a lower limit of detection (LOD). Under physiological conditions (Ticagrelor:TAM, 3:1), the concentration of ticagrelor was further measured, yielding LOD values of 4.65 pg/mL and 2.75 pg/mL for the two Q-bodies, with half-maximal effect concentrations of 8.15 ng/mL and 3.0 ng/mL, respectively. Discussion: Compared with traditional liquid chromatography-mass spectrometry (LC-MS) methods, anti-ticagrelor Q-bodies have higher sensitivity and detection speed. It enabled the completion of analysis within 3 min, facilitating rapid preoperative detection of blood drug concentration in ACS to determine the feasibility of surgery and mitigate the risk of intraoperative and postoperative hemorrhage. The swift detection of ticagrelor holds promise for enhancing individualized drug administration, preventing adverse reactions, and providing preoperative guidance., 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 © 2023 Zhang, Cheng, Gao, Zou, Xiao, Li, Li, Yu and Dong.)

Wastewater treatment is an important source of greenhouse gases (GHGs). Yet large uncertainties remain in the quantification of GHG emissions from municipal wastewater treatment plants (MWWTPs) in China. A high-resolution and technology-specific emission inventory is still lacking to support mitigation strategies of MWWTPs. Here we develop a plant-level and technology-based MWWTP emission inventory for China covering 8703 plants and 19 treatment technology categories by compiling and harmonizing the most up-to-date facility-level databases. China's methane (CH 4 ) and nitrous oxide (N 2 O) emissions from MWWTPs in 2020 are estimated to be 150.6 Gg and 22.0 Gg, respectively, with the uncertainty range of -30% to 37% and -30% to 26% at 95% confidence interval. We find an emission inequality across cities, with the richest cities emitting two times more CH 4 and N 2 O per capita from municipal wastewater treatment than the poorest cities. The emitted CH 4 and N 2 O are dominated by Anaerobic/Anoxic/Oxic-, Sequencing Batch Reactor-, Oxidation Ditch-, and Anoxic/Oxic-based MWWTPs of less than 20 years old. Considering the relatively young age structure of China's MWWTPs, the committed emissions highlight the importance of reducing on-site GHG emissions by optimization of operating conditions and innovation management. The emission differences among our estimates, previous studies, and the Intergovernmental Panel on Climate Change guidelines are largely attributed to the uncertainties in emission factors, implying the urgent need for more plant-integrated measurements to improve the accuracy of emission accounting., Competing Interests: 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., (© 2023 The Authors.)

Micro/nanospherical lens photolithography (SLPL) constitutes an efficient and precise micro/nanofabrication methodology. It offers advantages over traditional nanolithography approaches, such as cost-effectiveness and ease of implementation. By using micrometer-sized microspheres, SLPL enables the preparation of subwavelength scale features. This technique has gained attention due to its potential applications. However, the SLPL process has a notable limitation in that it mostly produces simple pattern shapes, mainly consisting of circular arrays. There has been a lack of theoretical analysis regarding the possible shapes that can be created. In our experiments, we successfully prepared annular and ring-with-hole pattern shapes. To address this limitation, we applied the Mie scattering theory to systematically analyze and summarize the various patterns that can be obtained through the SLPL process. We also proposed methods to predict and obtain different patterns. This theoretical analysis enhances the understanding of SLPL and expands its potential applications, making it a valuable area for further research.

This study aimed to investigate the levels of 12 sulfonamide antibiotics in freshwater fish species obtained from three cities in northeastern China (Harbin, Changchun, and Shenyang). The analysis was conducted using HPLC-MS/MS to accurately quantify the antibiotic concentrations in the fish samples. The results showed that the average levels of sulfonamide antibiotics in fish samples from Harbin, Changchun, and Shenyang were 1.83 ng/g ww, 0.98 ng/g ww, and 1.60 ng/g ww, respectively. Sulfamethoxazole displayed the highest levels and detection rates in all three cities, whereas sulphapyridine exhibited the lowest concentrations in all the fish samples. The levels of sulfonamide antibiotic residues in the different fish species varied widely among the cities, and the highest level of antibiotic residues was found in the muscle of carnivorous fish. The results from a health risk evaluation on the consumption of these fish indicated that the risk from long-term antibiotic exposure to local residents from the intake of the sampled fish was small and not sufficient to pose a significant health risk to consumers.

Circular RNAs (circRNAs) are covalently closed RNA structures that play multiple roles in tumorigenesis and progression. Compared with exon‒intron circRNAs, the biological functions and implications of intergenic circRNAs in human cancer are still poorly understood. Here, we performed circRNA microarray analysis and identified an intergenic circRNA, circ_0007379 , that was significantly downregulated in patients with colorectal cancer (CRC). The biogenesis of circ_0007379 was mediated by reverse complementary matches (RCMs) and was negatively regulated by the RNA helicase DHX9. Functionally, circ_0007379 suppressed CRC cell growth and metastasis in cell culture as well as in patient-derived organoid and xenograft models. Mechanistically, circ_0007379 acted as a scaffold to facilitate the processing of both pri-miR-320a and pre-miR-320a in a KSRP-dependent manner, leading to miR-320a maturation and subsequent repression of transcription factor RUNX1 expression. Thus, our findings establish a previously unrecognized function of circRNA in inhibiting CRC progression., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Viruses invade susceptible cells through a complex mechanism before injecting their genetic material into them. This causes direct damage to the host cell, as well as resulting in disease in the corresponding system. Echovirus type 30 (E30) is a member of the Enterovirus B group and has recently been reported to cause central nervous system (CNS) disorders, leading to viral encephalitis and viral meningitis in children. In this review, we aim to help in improving the understanding of the mechanisms of CNS diseases caused by E30 for the subsequent development of relevant drugs and vaccines., 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 © 2023 Liang, Chen, Wang, Yu, Zhang and Liu.)

Objective: As one of the cancers that seriously threatens women's health, ovarian cancer has a high morbidity and mortality rate. Surgery and chemotherapy are the basic treatment strategies for ovarian cancer, and chemotherapy resistance is a significant factor in affecting the prognosis, survival cycle, and recurrence of ovarian cancer. This article aims to analyze articles about ovarian cancer and drug resistance via bibliometric software, offering new ideas and directions for researchers in this field., Methods: Both Citespace and Vosviewer are bibliometric software on the Java platform. Articles were collected on ovarian cancer and drug resistance in the Web of Science Core Collection database from 2013 to 2022. The countries, institutions, journals, authors, keywords, and references were analyzed, and the development status of this field was indicated from multiple perspectives., Results: Studies on ovarian cancer and drug resistance generally showed an increasing trend from 2013 to 2022. The People's Republic of China and Chinese institutions contributed more to this field. Gynecologic Oncology published the most articles, and the journal with the most citations was Cancer Research . Li Li was the author with the most publications, and Siegel RL was the author with the most citations. Through burst detection, it can be found that the research hotspots in this field mainly focused on the in-depth exploration of the drug resistance mechanism of ovarian cancer and the progress of PARP inhibitors and bevacizumab in the treatment of ovarian cancer., Conclusions: Many studies on the mechanism of drug resistance in ovarian cancer have been discovered; however, the deeper mechanism remains to be explored. Compared with traditional chemotherapy drugs, PARP inhibitors and bevacizumab have shown better efficacy, but PARP inhibitors have initially shown drug resistance. The future direction of this field should be to overcome the resistance of existing drugs and actively develop new ones., 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 © 2023 Liu, Ma, Zhang, Li, Yu, Choe, Ding, Zhang and Zhang.)

Background: The pentose phosphate pathway (PPP) is an important mechanism by which tumour cells resist stressful environments and maintain malignant proliferation. However, the mechanism by which the PPP regulates these processes in colorectal cancer (CRC) remains elusive., Methods: Closely related PPP genes were obtained from the TCGA and GEO databases. The effect of ATP13A2 on CRC cell proliferation was evaluated by performing in vitro assays. The connection between the PPP and ATP13A2 was explored by assessing proliferation and antioxidative stress. The molecular mechanism by which ATP13A2 regulates the PPP was investigated using chromatin immunoprecipitation and dual luciferase experiments. The clinical therapeutic potential of ATP13A2 was explored using patient-derived xenograft (PDX), patient-derived organoid (PDO) and AOM/DSS models., Findings: We identified ATP13A2 as a novel PPP-related gene. ATP13A2 deficiency inhibited CRC growth and PPP activity, as manifested by a decrease in the levels of PPP products and an increase in reactive oxygen species levels, whereas ATP13A2 overexpression induced the opposite effect. Mechanistically, ATP13A2 regulated the PPP mainly by affecting phosphogluconate dehydrogenase (PGD) mRNA expression. Subsequent studies showed that ATP13A2 overexpression promoted TFEB nuclear localization by inhibiting the phosphorylation of TFEB, thereby enhancing the transcription of PGD and ultimately affecting the activity of the PPP. Finally, ATP13A2 knockdown inhibited CRC growth in PDO and PDX models. ATP13A2 - / - mice had a lower CRC growth capacity than ATP13A2 +/+ in the AOM/DSS model.Our findings revealed that ATP13A2 overexpression-driven dephosphorylation of TFEB promotes PPP activation by increasing PGD transcription, suggesting that ATP13A2 may serve as a potential target for CRC therapy., (© 2023 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Oxpecker, the homolog of Rhino/HP1D, exclusively expressed in Drosophila ovaries, belongs to the Heterochromatin Protein 1 family, as does Rhino. Rhi recognizes piRNA clusters enriched with the heterochromatin marker H3K9me3 via its N-terminal chromodomain and recruits Deadlock via its C-terminal chromoshadow domain, further recruits Moonshiner, a paralog of the TATA box-binding protein-related factor 2 large subunits, to promote transcription of piRNA precursors, thereby protecting the genome. Despite Oxp possessing only the chromodomain, its loss leads to the upregulation of transposons in the female germline. In this study, we solved the crystal structure of the Oxp chromodomain in complex with the histone H3K9me3 peptide. As the Oxp chromodomain dimerizes, two H3K9me3 peptides bind to the Oxp chromodomain in an antiparallel manner. ITC experiments and site-directed mutagenesis experiments showed that E44 determines Oxp's five-fold stronger binding ability to H3K9me3 than that of Rhi. In addition, we found that Oxp and Rhi can form a heterodimer, which may shed light on the molecular mechanism by which Oxp regulates transposon silencing in the absence of CSD., 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 © 2023 Elsevier Inc. All rights reserved.)

Recombinant protein expression and purification are crucial in modern life sciences research. A fluorescent immunosensor termed Quenchbody (Q-body) was developed for real-time monitoring of FLAG-fused protein expression. Detection results showed that the limit of detection of the 3 × FLAG peptide detected by the TAMRA-labeled anti-FLAG Q-body was as low as 3.1 nM, with a half-maximal effective concentration of 21.4 nM. Furthermore, the anti-FLAG Q-body was used for detecting different proteins fused with a FLAG-tag at the N- or C-terminal. Subsequently, the constructed Q-body was used to monitor the real-time fermentation process of single-strand DNA-binding protein in Escherichia coli. Unlike previously reported Q-bodies that widely used Fab or scFv, the present study used a full-length anti-FLAG IgG for the first time. Owing to its excellent detection speed and sensitivity, the FLAG Q-body immunosensor has the potential to quantify and monitor target recombinant proteins in multiple biological processes in real-time., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background : L-carnitine supplementation has been utilized against glucolipid metabolism disruption. However, to the best of our knowledge, no meta-analysis process has analyzed the effects of L-carnitine supplementation on insulin resistance, fasting blood glucose, lipid metabolism, and liver enzyme levels in adults. Methods : Through the analysis and screening of 12 221 studies, 15 studies were selected from eligible trials for meta-analysis. Meta-analysis was performed in a random effect model with heterogeneity determined by I 2 , and subgroup analyses were used to further identify the source of heterogeneity. Result : The results showed significant effects of L-carnitine on FBG (MD = -4.94 mg dL -1 , 95% CI: -7.07 to -2.82), insulin (MD = -0.99 μU mL -1 , 95% CI: -1.41 to -0.56), HOMA-IR (MD = -0.58, 95% CI: -0.77 to -0.38), TG (MD = -11.22 mg dL -1 , 95% CI: -19.21 to -3.22), TC (MD = -6.45 mg dL -1 , 95% CI: -9.95 to -2.95, LDLc (MD = -8.28 mg dL -1 , 95% CI: -11.08 to -5.47), and ALT (MD = -19.71 IU L -1 , 95% CI: -36.45 to -2.96). However, no significant effect of L-carnitine supplementation was observed in HDLc (MD = -0.77 mg dL -1 , 95% CI: -0.10 to -1.63) or AST (MD = -11.05 IU L -1 , 95% CI: -23.08 to 0.99). The duration of carnitine supplementation was negatively associated with mean differences in FBG, as assessed by meta-regression. Conclusion : The current meta-analysis revealed that L-carnitine may have favorable effects on glucolipid profile, especially insulin, FBG, HOMA-IR, TG, TC, LDLc, and ALT levels.

The most commonly used opioid analgesics are limited by their severe side-effects in the clinical treatment of pain. Preliminary reports indicate that the combination of classical opioids and N/OFQ receptor (NOP) ligands may be an effective strategy to reduce unwanted side-effects and improve antinociception. But the interaction of these two receptor ligands in pain regulation at the peripheral level remains unclear. In this study, the antinociception of a designed amide analogue of the mu opioid receptor (MOP) peptide agonist DAMGO, DAMGO-NH 2 , and its antinociceptive interaction with the peripherally limited NOP peptide agonist NOP01 was investigated in two mouse models of formalin pain. Our results showed that DAMGO-NH 2 acted as a MOP agonist in in vitro functional assays. Moreover, local subcutaneous or intraplantar injection of DAMGO-NH 2 exerted dose-related antinociception in both phases of the formalin orofacial and intraplantar pain, which could be mediated by the classical opioid receptor. Peripheral but not central pretreatment with the peripherally restricted opioid antagonist naloxone methiodide inhibited local DAMGO-NH 2 -induced antinociception, supporting the involvement of the peripheral opioid receptor in local DAMGO-NH 2 -induced antinociception. Furthermore, co-administration of the inactive doses of DAMGO-NH 2 and NOP01 produced effective antinociception. More importantly, isobolographic analysis indicates that the combination of DAMGO-NH 2 and NOP01 elicited supra-additive antinociception in these two models of formalin pain. In addition, the combination of DAMGO-NH 2 and NOP01 did not change motor function of mice in rotarod test. In conclusion, these data suggest that peripheral DAMGO-NH 2 and particularly its combination therapy with NOP01 may be effective for pain management., Competing Interests: Declarations of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The traditional photonic integrated circuit (PIC) inherits the mature CMOS fabrication process from the electronic integrated circuit (IC) industry. However, this process also limits the PIC structure to a single-waveguide-layer configuration. In this work, we explore the possibility of the multi-waveguide-layer PIC by proposing and demonstrating a 3D optical phased array (OPA) device, with the light exiting from the edge of the device, based on multi-layer Si 3 N 4 /SiO 2 stacks. This device is in a multi-waveguide-layer configuration at every single position of the device. This configuration offers the possibility of using edge couplers at both the input and the emitting ends to achieve broadband high efficiency, and its uniqueness provides the potential for a more extended detection range in the lidar application. The device has been studied by numerical simulation, and proof-of-concept samples have been fabricated and tested.

The rheological properties of warm-mix recycled asphalt binders are critical to enhancing design quality and interpreting the performance mechanisms of the corresponding mixtures. This study investigated the rheological behavior of warm-mix recycled asphalt binders with high percentages of RAP binder. The effects of two warm-mix additives [wax-based Sasobit (S) and surfactant-based Evotherm-M1 (E)], a rejuvenating aging [ZGSB (Z)], four RAP binder contents (0%, 30%, 50% and 70%), and three aging states (unaged, short-term aged and long-term aged) were evaluated in detail using the dynamic shear rheometer (DSR), bending beam rheometer (BBR) and Brookfield rotational viscometer tests as well as conventional performance tests over the whole range of temperatures. The results showed that the rejuvenating agent Z effectively alleviated the aging effect of the RAP binder; however, it could hardly eliminate entirely this negative impact, especially at higher RAP binder contents. The addition of S remarkably lowered the apparent viscosity of the warm-mix recycled binders by up to 35.0%, whereas E had little influence on the binder viscosity due to its surfactant nature. Besides, S performed much better in improving rutting resistance (with the increase of up to 411.3% in | G *|/sin δ ) than E, while E exhibited superior fatigue performance (with the reduction of up to 42.3% in | G *|·sin δ ) to that of S. In terms of the thermal cracking resistance, E had very slight influence and S even yielded an adverse impact (with the increase of up to 70.2% in S a and the decrease of up to 34.1% in m-value). Further, S broadened the ranges of pavement service temperatures by about 12 °C, whereas E almost did not change the PG grades of the binders. Finally, regarding the characteristics of viscoelastic master curves, S considerably improved the dynamic modulus and lowered the phase angle of the binders over a wide range of frequencies and temperatures but led to the failure of the time-temperature superposition principle due to its thermorheologically complex nature. Nevertheless, in this regard, the effect of E was found very mild.

Transcription factors are frequently aberrantly reactivated in various cancers, including colorectal cancer (CRC). However, as a transcription factor, the role of GMEB2 in cancer is still unclear, and further studies are needed. Here, we aimed to identify the function and mechanism of GMEB2 in regulating the malignant progression of CRC. GMEB2 was found to be highly expressed in online data analyses. We demonstrated that GMEB2 was markedly upregulated at both the mRNA and protein levels in CRC cells and tissues. GMEB2 knockdown inhibited CRC cell growth in vitro and in vivo. Mechanistically, as a transcription factor, GMEB2 transactivated the ADRM1 promoter to increase its transcription. Rescue experiments showed that ADRM1 downregulation partially reversed the promoting effects of GMEB2 on CRC growth in vitro. Moreover, the GMEB2/ADRM1 axis induced nuclear translocation of NF-κB, thus activating NF-κB signalling. Finally, we further revealed that YTHDF1 recognized and bound to the m 6 A site on GMEB2 mRNA, which enhanced its stability. Taken together, our findings reveal the crucial role and regulatory mechanism of GMEB2 in CRC for the first time and provide a novel potential therapeutic target for CRC therapy.

Mounting evidence indicates that the neuropeptide FF (NPFF) system is involved in the side effects of opioid usage, including antinociceptive tolerance, hyperalgesia, abuse, constipation, and respiratory depression. Our group recently discovered that the multitarget opioid/NPFF receptor agonist DN-9 exhibits peripheral antinociceptive activity. To improve its metabolic stability, antinociceptive potency, and duration, in this study, we designed and synthesized a novel cyclic disulfide analogue of DN-9, OFP011, and examined its bioactivity through in vitro cyclic adenosine monophosphate (cAMP) functional assays and in vivo behavioral experiments. OFP011 exhibited multifunctional agonistic effects at the μ-opioid and the NPFF 1 and NPFF 2 receptors and partial agonistic effects at the δ- and κ-opioid in vitro , as determined via the cAMP functional assays. Pharmacokinetic and pharmacological experiments revealed improvement in its blood-brain barrier permeability after systemic administration. In addition, subcutaneous OFP011 exhibited potent and long-lasting antinociceptive activity via the central μ- and κ-opioid receptors, as observed in different physiological and pathological pain models. At the highest antinociceptive doses, subcutaneous OFP011 exhibited limited tolerance, gastrointestinal transit, motor coordination, addiction, reward, and respiration depression. Notably, OFP011 exhibited potent oral antinociceptive activities in mouse models of acute, inflammatory, and neuropathic pain. These results suggest that the multifunctional opioid/NPFF receptor agonists with improved blood-brain barrier penetration are a promising strategy for long-term treatment of moderate to severe nociceptive and pathological pain with fewer side effects.

Background: The gut microbiota is known to be associated with the regulation of many neurological diseases and behaviors, including chronic pain. However, it is unclear whether the gut microbiota is critical to the itch sensation. In this study, we investigated the effects of gut microbiota depletion on acute itch., Methods: First, an antibiotic cocktail was orally administered to deplete the gut microbiota in male C57BL/6 mice. Then, pruritogens were intradermally injected to induce acute itch behavior. In addition, antibiotic-treated mice received transplantation of fecal microbiota from untreated mice, followed by tests for acute itch. The changes in c-Fos expression in trigeminal ganglia (TG) neurons were also investigated by immunofluorescence staining., Results: Our results indicated that chronic antibiotic treatment significantly reduced the diversity and richness of the gut microbiota of mice. Compared to vehicle-treated mice, antibiotic-treated mice showed reductions in acute itch behavior induced by compound 48/80, chloroquine (CQ), and serotonin (5-HT), respectively. Moreover, repositioning of microbiota reversed the reductions in acute itch behavior in antibiotic-treated mice. In addition, immunofluorescence staining revealed that antibiotic-treated mice displayed decreased c-Fos expression in ipsilateral TG compared to controls., Conclusions: Our study, for the first time, discovered that antibiotic-induced gut microbiota depletion could reduce acute itch behavior, which may be connected with decreased TG neuronal activity., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Bacterial skin infections cause a variety of common skin diseases that require drugs that are safer than antibiotics and have fewer side effects. However, for evaluating skin disease drugs, human skin tissue in vitro constructed traditionally on Transwell has inefficient screening ability because of its fragile barrier function. With mechanical forces and dynamic flow, the organ-on-a-chip system became an innovative, automatic, and modular way to construct pathological models and analyze effective pharmaceutical ingredients in vitro . In this research, we integrated skin extracellular matrix and skin cells into a microfluidic chip to construct a biomimetic "interface-controlled-skin-on-chip" system (IC-SoC), which constructed a stable air-liquid interface (ALI) and necessary mechanical signals for the development of human skin equivalents. The results demonstrated that in the microfluidic system with a flowing microenvironment and ALI, the skin tissue formed in vitro could differentiate into more mature tissue morphological structures and improve barrier function. Then, following exposing the skin surface on the IC-SoC to the stimulation of Propionibacterium acnes ( P.acnes ) and SLS (sodium lauryl sulfate), the barrier function decreased, as well as inflammatory factors such as IL-1α, IL-8, and PEG2 increased in the medium channel of the IC-SoC. After this pathological skin model was treated with dexamethasone and polyphyllin H, the results showed that polyphyllin H had a significant repair effect on the skin barrier and a significant inhibition effect on the release of inflammation-related cytokines, and the effects were more prominent than dexamethasone. This automated microfluidic system delivers an efficient tissue model for toxicological applications and drug evaluation for bacterial-infected damaged skin instead of animals., 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 Quan, Weng, Li, An, Yang, Yu, Ma and Wang.)

Keratins are one of the major components of cytoskeletal network and assemble into fibrous structures named intermediate filaments (IFs), which are important for maintaining the mechanical properties of cells and tissues. Over the past decades, evidence has shown that the functions of keratins go beyond providing mechanical support for cells, they interact with multiple cellular components and are widely involved in the pathways of cell proliferation, differentiation, motility and death. However, the structural details of keratins and IFs are largely missing and many questions remain regarding the mechanisms of keratin assembly and recognition. Here we briefly review the current structural models and assembly of keratins as well as the interactions of keratins with the binding partners, which may provide a structural view for understanding the mechanisms of keratins in the biological activities and the related diseases., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

MicroRNAs (miRNAs) and their target genes have been shown to play an important role in gastric cancer but have not been fully clarified. Therefore, our goal was to identify the key miRNA-mRNA regulatory network in gastric cancer by utilizing a variety of bioinformatics analyses and experiments. A total of 242 miRNAs and 1080 genes were screened from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively. Then, survival-related differentially expressed miRNAs and their differentially expressed target genes were screened. Twenty hub genes were identified from their protein-protein interaction network. After weighted gene co-expression network analysis was conducted, we selected miR-137-3p and its target gene, COL5A1, for further research. We found that miR-137-3p was significantly downregulated and that overexpression of miR-137-3p suppressed the proliferation, invasion, and migration of gastric cancer cells. Furthermore, we found that its target gene, COL5A1, could regulate the expression of another hub gene, FSTL1, by sponging miR-137-3p, which was confirmed by dual-luciferase reporter assays. Knockdown of COL5A1 inhibited the proliferation, invasion, and migration of gastric cancer cells, which could be rescued by the miR-137-3p inhibitor or overexpression of FSTL1. Ultimately, bioinformatics analyses showed that the expression of FSTL1 was highly correlated with immune infiltration.

Integrated optical phased array (OPA) devices have been widely studied as a solution for solid-state light detection and ranging technology in the autonomous driving application. In this work, a phase-combining unit (PCU) is proposed and studied. With a given number (N) of phase shifters, instead of the general N (phase shifters) to N (emitters) control, the PCU can enable an N to 2N-1 control, which efficiently suppresses the aliasing effect. The theoretical analysis, numerical simulation, and experimental proof-of-concept have been completed in this work. The results show that a maximum suppression of 92.54% can be achieved for the grating lobes in simulation, and an average 53.76% is tested for one grating lobe in the experiment. In conclusion, the PCU can be used as a universal aliasing suppression unit on many types of integrated OPA devices.

Photoactive metal-organic frameworks, MIL-100(Fe), with controllable thickness are coated on plasmonic Ag/AgCl nanowire, for boosting visible light photodegradation of rhodamine B and tetracycline hydrochloride. The morphology and composition of the obtained nano-heterostructure were investigated in detail by SEM imaging, TEM imaging, XRD patterns, FT-IR spectra, N 2 adsorption-desorption curves and TGA patterns. Photoelectric performance test suggested that a Z-scheme photocatalysis system for efficient transfer of photogenerated charge carriers was established between MIL-100(Fe) and plasmonic Ag/AgCl nanowire., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Scavenger receptor class A (SR-A) proteins are type II transmembrane glycoproteins that form homotrimers on the cell surface. This family has five known members (SCARA1 to 5, or SR-A1 to A5) that recognize a variety of ligands and are involved in multiple biological pathways. Previous reports have shown that some SR-A family members can bind modified low-density lipoproteins (LDLs); however, the mechanisms of the interactions between the SR-A members and these lipoproteins are not fully understood. Here, we systematically characterize the recognition of SR-A receptors with lipoproteins and report that SCARA1 (SR-A1, CD204), MARCO (SCARA2), and SCARA5 recognize acetylated or oxidized LDL and very-low-density lipoprotein in a Ca 2+ -dependent manner through their C-terminal scavenger receptor cysteine-rich (SRCR) domains. These interactions occur specifically between the SRCR domains and the modified apolipoprotein B component of the lipoproteins, suggesting that they might share a similar mechanism for lipoprotein recognition. Meanwhile, SCARA4, a SR-A member with a carbohydrate recognition domain instead of the SRCR domain at the C terminus, shows low affinity for modified LDL and very-low-density lipoprotein but binds in a Ca 2+ -independent manner. SCARA3, which does not have a globular domain at the C terminus, was found to have no detectable binding with these lipoproteins. Taken together, these results provide mechanistic insights into the interactions between SR-A family members and lipoproteins that may help us understand the roles of SR-A receptors in lipid transport and related diseases such as atherosclerosis., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

HCV cell-culture system uses hepatoma-derived cell lines for efficient virus propagation. Tumor cells cultured in glucose undergo active aerobic glycolysis, but switch to oxidative phosphorylation for energy production when cultured in galactose. Here, we investigated whether modulation of glycolysis in hepatocytes affects HCV infection. We showed HCV release, but not entry, genome replication or virion assembly, is significantly blocked when cells are cultured in galactose, leading to accumulation of intracellular infectious virions within multivesicular body (MVB). Blockade of the MVB-lysosome fusion or treatment with pro-inflammatory cytokines promotes HCV release in galactose. Furthermore, we found this glycometabolic regulation of HCV release is mediated by MAPK-p38 phosphorylation. Finally, we showed HCV cell-to-cell transmission is not affected by glycometabolism, suggesting that HCV cell-to-supernatant release and cell-to-cell transmission are two mechanistically distinct pathways. In summary, we demonstrated glycometabolism regulates the efficiency and route of HCV release. We proposed HCV may exploit the metabolic state in hepatocytes to favor its spread through the cell-to-cell transmission in vivo to evade immune response., Competing Interests: The authors have declared that no competing interests exist.

Background: Isorhapontigenin (ISO) has been shown to have antioxidant activity. This study aimed to investigate the antioxidant effects of ISO on cerebral ischemia/reperfusion (I/R) injury and its possible molecular mechanisms., Methods: Focal cerebral ischemia-reperfusion injury (MCAO/R) model and primary cortical neurons were established an oxygen-glucose deprivation (OGD / R) injury model. After 24 hr of reperfusion, the neurological deficits of the rats were analyzed and HE staining was performed, and the infarct volume was calculated by TTC staining. In addition, the reactive oxygen species (ROS) in rat brain tissue, the content of 4-Hydroxynonenal (4-HNE), and 8-hydroxy2deoxyguanosine (8-OHdG) were detected. Neuronal cell viability was determined by MTT assay. Western blot analysis was determined for protein expression., Results: ISO treatment significantly improved neurological scores, reduced infarct volume, necrotic neurons, ROS production, 4-HNE, and 8-OHdG levels. At the same time, ISO significantly increased the expression of Nrf2 and HO-1. The neuroprotective effects of ISO can be eliminated by knocking down Nrf2 and HO-1. In addition, knockdown of the PKCε blocked ISO-induced nuclear Nfr2, HO-1 expression., Conclusion: ISO protected against oxidative damage induced by brain I/R, and its neuroprotective mechanism may be related to the PKCε/Nrf2/HO-1 pathway., (© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Two-dimensional nanolayers have found increasingly widespread applications in modern flexible electronic devices. Their adhesion with neighbouring layers can significantly affect the mechanical stability and the reliability of those devices. However, the measurement of such adhesion has been a great challenge. In this work, we develop a new and simple methodology to measure the interfacial adhesion between a mica nanolayer (MNL) and a single-layer graphene (SLG) supported by a SiO 2 substrate. The method is based on the well-known Obreimoff method but integrated with innovative nanomanipulation and profile measuring approaches. Our study shows that the adhesion energy of MNLs on the SLG/SiO 2 substrate system is considerably lower than that on the SiO 2 substrate alone. Quantitative analyses reveal that the wrinkles formed on the SLG can considerably lower the adhesion. This outcome is of technological value as the adhesion maybe tailored by controlling the wrinkle formation in the graphene layer in a flexible electronic device.

The structure and fractal characteristics of nanopores of high-rank coal were investigated using an approach that integrates N₂ adsorption and field emission scanning electron microscopy (FE-SEM). The results indicated that the high-rank coal of the Shanxi Formation has a complex pore-fracture network composed of organic matter pores, mineral-related pores, and microfractures. The pore type of high-rank coal tends to be complicated, and the main pore types are inkbottle pores and open pores, which are more conducive to methane enrichment. The R o ,max has a negative relationship with the total pore volume. In addition, the ash and inertinite contents show a positive correlation with the average pore size (APS), while the fixed carbon content exhibits a negative relationship with the APS. The pore structure of high-rank coal is controlled not only by the degree of metamorphism but also by coal composition, which leads to the variation in pore structure becoming more complicated. With the increase in coal metamorphism, high-rank coal with high amounts of fixed carbon content generally possesses a higher irregularity in pore structure. No obvious relationship was observed between D ₂ and the coal components, which indicates that the pore structure, ash content, moisture content and other factors controlled by the metamorphism of coal have different effects on D ₂ that lead to this inapparent relationship. A negative relationship exists between adsorption volume and D 1 , which indicates that the high irregularity of the pore structure is not conducive to methane absorption and that no obvious correlation exists between the adsorption volume and D ₂. In the high-rank coal, the high D 1 value represents the complexity and heterogeneity of the pore structure and represents a low adsorption affinity for methane molecules; in addition, D ₂ has no effect on the methane adsorption capacity.

Background: Breast cancer has become one of the most common malignant tumors in women owing to its increasing incidence each year. Clinical studies have shown that Cinnamomum cassia (L.) J. Presl (cinnamon) has a positive influence on the prevention and treatment of breast cancer. Aim: We aimed to screen the potential targets of cinnamon in the treatment of breast cancer through network pharmacology and explore its potential therapeutic mechanism through cell experiments. Methods: We used the TCMSP, TCM Database @ Taiwan, and TCMID websites and established the active ingredient and target database of cinnamon. Thereafter, we used the GeneCards and OMIM databases to establish a breast cancer-related target database, which matched the cinnamon target database. Based on the matching results, the STRING database was used to analyze the interaction between the targets, and the biological information annotation database was used to analyze the biological process of the target (gene ontology) and the pathway enrichment of Kyoto Encyclopedia of Genes and Genomes (KEGG). After establishing the layout of the analysis, we used Cytoscape 3.6.0 software for network analysis. Finally, the cell experiment was used to verify the anti-breast cancer effect of cinnamaldehyde. Results: Our research showed that the main components of cinnamon, including cinnamaldehyde, can play a role in the treatment of breast cancer through 59 possible important targets. Subsequently, enrichment analysis by gene ontology and Kyoto Encyclopedia of Genes and Genomes showed that 83 cell biological processes and 37 pathways were associated with breast cancer ( p < 0.05), including the peroxisome proliferator-activated receptor and PI3K-Akt pathway, which are closely related to tumor cell apoptosis. In vitro cell verification experiments showed that cinnamaldehyde can significantly inhibit cell proliferation, change cell morphology, inhibit cell migration and invasion ability, and promote cell apoptosis. Conclusion: Our results showed that cinnamaldehyde is a potential novel drug for the treatment and prevention of breast cancer., 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 © 2020 Liu, An, Wan, Yu, Fan and Pei.)

Accumulation of evidence has indicated a close relationship between alternative splicing (AS) and gastric cancer (GC), whereas systematic analyses of the differentially expressed AS events (DEAS) between GC and normal tissues are lacking. RNA-Seq data and the corresponding clinical information were downloaded from TCGA GC cohort. The percent spliced-in (PSI) value calculated in the GC tissues and normal tissues was employed to quantify the DEAS. Further, survival-associated DEAS and DEAS signatures were identified by univariate and multivariate cox regression analyses. To evaluate the association between DEAS and patients' clinical features, Kaplan-Meier analysis, receiver operator characteristic (ROC) curve, Cox proportional regression and nomograms incorporating the DEAS signatures were performed. DEAS and their splicing networks were finally analyzed by bioinformatics methods. In addition, we use the method of random grouping to divide the samples into the training group and the test group. The final results of the two groups are consistent. After strict filtering, a total of 44,935 AS events were identified, among which 11,141 DEAS were preliminarily screened from 5032 genes. A total of 454 DEAS was associated with OS, and 872 DEAS were associated with DFS. The final prognostic signatures were constructed from the survival-associated DEAS with an area under the receiver operating characteristic (ROC) curve (AUC) greater than 0.6. Only ES in ABI1 was simultaneously associated with OS and DFS. Finally, we identified the splicing correlation network between the prognostic splicing factors (SF) and DEAS in GC. Our study provided a systematic portrait of survival-associated DEAS in GC and uncovered splicing networks that are valuable in deciphering the underlying mechanisms of AS in GC., (Copyright © 2020 Lin, Yu, Zhang, Chen, Li and Zhao.)

Scavenger receptors are a superfamily of membrane-bound receptors that recognize both self and nonself targets. Scavenger receptor class A (SR-A) has five known members (SCARA1 to -5 or SR-A1 to -A5), which are type II transmembrane proteins that form homotrimers on the cell surface. SR-A members recognize various ligands and are involved in multiple biological pathways. Among them, SCARA5 can function as a ferritin receptor; however, the interaction between SCARA5 and ferritin has not been fully characterized. Here, we determine the crystal structures of the C-terminal scavenger receptor cysteine-rich (SRCR) domain of both human and mouse SCARA5 at 1.7 and 2.5 Å resolution, respectively, revealing three Ca 2+ -binding sites on the surface. Using biochemical assays, we show that the SRCR domain of SCARA5 recognizes ferritin in a Ca 2+ -dependent manner, and both L- and H-ferritin can be recognized by SCARA5 through the SRCR domain. Furthermore, the potential binding region of SCARA5 on the surface of ferritin is explored by mutagenesis studies. We also examine the interactions of ferritin with other SR-A members and find that SCARA1 (SR-A1, CD204) and MARCO (SR-A2, SCARA2), which are highly expressed on macrophages, also interact with ferritin. By contrast, SCARA3 and SCARA4, the two SR-A members without the SRCR domain, have no detectable binding with ferritin. Overall, these results provide a mechanistic view regarding the interactions between the SR-A members and ferritin that may help to understand the regulation of ferritin homeostasis by scavenger receptors., Competing Interests: Conflict of interest—The authors declare that they have no conflicts of interest with the contents of this article., (© 2020 Yu et al.)

In view of the current high cost of graphene, the corn flour with rich sources was selected as the raw material to prepare nano-graphene by the hydrazine hydrate (Hummers) redox method. The elements, structure, and morphology of the obtained corn graphene (CG) were studied by the organic element analysis, X-ray photoelectron spectroscopy, X-ray diffraction, Raman spectroscopy, atomic force microscopy, and transmission electron microscopy. It was found that the carbon content of CG was increased by 37.8% from 57.4% (corn flour) to 95.2% (CG). There was a diffraction peak of graphene on the (002) crystal surface at 23.08°. The D and G peaks of the Raman test were present, and the I D / I G of the peak intensity ratio was 1.19. The lattice distance of the CG sample was larger than that of the commercial graphene (GE), the CG was about three layers with a layer spacing of 1.21 nm, and the CG was thinner than the GE, which proved that the obtained CG was the nano-graphene., Competing Interests: The authors declare no competing financial interest., (© 2020 The Authors. Published by American Chemical Society.)

Levels of heavy metals and polybrominated diphenyl ethers (PBDEs) were determined in fishes sampled in Jilin Songhua Lake, China. Concentrations and congener profiles of these contaminants varied by fish type. The highest concentrations of Zn, Cu, Mn, and Cd were found in three omnivorous fish (Carassius carassius, Hypomesus olidus, and Hemiculter leucisculus). The highest concentrations of Ni, Cr, and Hg were found in Silurus asotus and Hemibarbus maculatus which are two kinds of carnivorous fish. The minimum total concentration of the seven PBDEs of fish was 0.093 ng/g wet weight (ww) in Ctenopharyngodon idellus, while the maximum, 0.342 ng/g ww, was detected in Aristichthys nobilis. Of all the congeners, BDE 28 and 47 were dominant. The estimated daily intake (EDI) of these metals and PBDEs via consuming the fishes was estimated to be 1.159-10.121 μg/kg bw/day and 0.046-0.597 ng/kg bw/day, respectively. The total hazard quotients (THQs) of both types of pollutants were far below 1, indicating that the health risks of these pollutants were low for the people who consumed the fish species from the Songhua Lake.

The long noncoding RNA (lncRNA) LUCAT1 was recently reported to be upregulated and to play an essential role in multiple cancer types, especially colorectal cancer (CRC), but the molecular mechanisms of LUCAT1 in CRC are mostly unreported. Here, a systematic analysis of LUACT1 expression is performed with data from TCGA database and clinic CRC samples. LUCAT1 is identified as a putative oncogene, which is significantly upregulated in CRC and is associated with poor prognosis. Loss of LUCAT1 restricts CRC proliferative capacities in vitro and in vivo. Mechanically, NCL is identified as the protein binding partner of LUCAT1 by using chromatin isolation by RNA purification coupled with mass spectrometry (ChIRP-MS) and RNA immunoprecipitation assays. We also show that NCL directly binds to LUCAT1 via its putative G-quadruplex-forming regions from nucleotides 717 to 746. The interaction between LUCAT1 and NCL interferes NCL-mediated inhibition of MYC and promote the expression of MYC. Cells lacking LUCAT1 show a decreased MYC expression, and NCL knockdown rescue LUCAT1 depletion-induced inhibition of CRC cell proliferation and MYC expression. Our results suggest that LUCAT1 plays a critical role in CRC cell proliferation by inhibiting the function of NCL via its G-quadruplex structure and may serve as a new prognostic biomarker and effective therapeutic target for CRC.

Single-layered, double-layered, and triple-layered Pt nanoparticles with a well-defined arrangement were encapsulated inside metal-organic frameworks (MOFs) to investigate the catalytic performance influenced by the progressive increasing of Pt nanoparticles inside MOFs; the results show that the catalytic activity of the Pt-MOF hybrid catalysts increases progressively with the progressive increasing of the Pt nanoparticles inside MOFs. Progressive increasing of Pt nanoparticles with a multiple-layered manner inside MOFs provides a new route for designing well-organized hybrid catalysts of noble metal nanoparticles and MOFs with enhanced catalytic activity.

The evolution of retained species during the whole methanol-to-olefins process was revealed with the aid of GC-MS, thermogravimetric analysis (TG) and density functional theory (DFT) calculations. Precise routes for the transformation of retained methylbenzenes to methylnaphthalenes were proposed, based on the direct capture of three possible organic intermediates, to explain the catalyst deactivation procedure.

Novel therapeutic strategies for breast cancer are urgently needed due to the sustained development of drug resistance and tumor recurrence. Trivalent arsenic derivative (arsenite, As III ) has been reported to induce cytotoxicity in breast cancer cells. We recently demonstrated that As III plus tetrandrine (Tetra), a Chinese plant-derived alkaloid, exerted potent antitumor activity against human breast cancer cells, however, the underlying mechanisms for their action have not been well defined. In order to provide fundamental insights for understanding the action of As III plus Tetra, the effects of the combined regimen on two breast cancer cell lines T47D and MDA-MB-231 were evaluated. Compared to T47D cells, MDA-MB-231 cells were much more susceptible to the synergistic cytotoxic effects of As III and Tetra. Besides the induction of apoptotic/necrotic cell death, S-phase arrest and autophagic cell death were also observed in MDA-MB-231 cells. Exposure of MDA-MB-231 cells to As III and Tetra caused the activation of MAPKs. Cytotoxicity of the combined regimen in MDA-MB-231 cell was significantly abrogated by SP600125, a potent c-Jun N-terminal kinase (JNK) inhibitor. However, similar abrogation was not caused by p38 and ERK inhibitors. The addition of either autophagy inhibitors (3-methyladenine or wortmannin) or SP600125 corrected the combined regimen-triggered S-phase arrest, whereas had little effect on the apoptosis/necrosis induction in the cells. Surprisingly, SP600125NC, a negative control for SP600125, significantly strengthened S-phase arrest and the cytotoxicity induced by the combined regimen. The addition of SP600125 did not alter autophagy induction. In conclusion, the cytotoxicity of As III combined with Tetra was attributed to the induction of S-phase arrest, apoptotic/necrotic and autophagic cell death. The enhanced cytotoxicity of the two drugs by SP600125NC might be explained by its capability to strengthen S-phase arrest. Our results suggested that JNK and autophagy independently contributed to the cytotoxicity via modulating cell cycle progression. The study further provides fundamental insights for the development of As III in combination with Tetra for patients with different types of breast cancer., (Copyright © 2020 Yu, Yuan, Li, Kiyomi, Kikuchi, Hayashi, Hu, Okazaki, Sugiura, Hirano, Fan, Pei and Takagi.)

Modulated synthesis and isoreticular expansion of Th-MOFs enable the stepwise construction of hierarchical complexes in which porosity and functionality can be fine-tuned, affording new Th-MOFs with a record high void space (74.0%), the largest surface area (3396.5 m2 g-1) among thorium materials, and excellent adsorption capacities toward radioactive iodine.

Natural rubber (NR) nanocomposites were prepared by filling cornmeal graphene (CGE) to improve its mechanical properties and thermal properties, and CGE was modified with coupling agents to improve its dispersion in NR. The mechanical properties, wear resistance, thermal stability, and morphology of CGE/NR nanocomposites were studied. The results showed that when NR was 100 phr (parts per hundred rubbers), the CGE was 0.02 phr, and the coupling agent KH590 was 2 phr, the thermal stability and mechanical properties of the CGE/NR nanocomposites were the best. Compared with NR, the thermal conductivity of the nanocomposites increased by 6.0 mW/g, and the decomposition temperature increased by 37 °C. The mechanical properties and wear resistance of KH590-CGE/NR nanocomposites were the best, and compared with NR, the tensile strength, elongation at break, and wear resistance of KH590-CGE/NR nanocomposites increased by 16, 14, and 17%, respectively. The compatibility and dispersion of KH590-CGE/NR nanocomposites were the best., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Although metamaterials or metasurfaces consisting of patterned subwavelength structures have been widely employed for thermal emission control, the collective behavior of the emitter array in a metasurface still remains unclear. Here, based on the quasinormal mode theory, we derive a new scale law to elucidate the far-field thermal emission from a metasurface composed of densely packed plasmonic nanoemitters. The tight binding method is used to approximate the collective resonant mode of the emitter array. Because of in-phase near-field interaction, the thermal radiation from a single emitter in a metasurface is suppressed by its adjacent emitters. We find that the overall far-field thermal radiation from a metasurface can be either positively or negatively correlated with the packing density of the emitters, depending on the mode properties of the single emitter. This new scale law thus serves as a general guideline for designing metasurfaces with desired thermal emission properties.