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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 (CH4) and nitrous oxide (N2O) 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 CH4 and N2O per capita from municipal wastewater treatment than the poorest cities. The emitted CH4 and N2O 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.

Addressing the dual environmental challenges of dredged sludge disposal and the repurposing of industrial by-products, this study pioneers the application of Calcium Carbide Residue (CCR)-based materials for stabilizing dredged sludge in road subgrade construction. The proliferation of dredged sludge, characterized by high moisture content and pollutants, presents a significant environmental hazard, while CCR, a by-product of acetylene production, poses disposal and pollution challenges. This research endeavors to mitigate these issues by exploring the stabilization potential of CCR when mixed with dredged sludge, aiming to enhance the mechanical properties of materials used in road subgrade construction. Through comprehensive laboratory testing, including unconfined compressive strength assessments, scanning electron microscope analyses, and X-ray diffraction examinations, the study reveals the intricate physicochemical interactions between CCR and sludge. These interactions lead to notable improvements in material strength and moisture reduction, substantiating the efficacy of CCR-based binders in sludge stabilization. The CCR-based binder can make the strength of the stabilized sludge reach 215.4kPa and the water content drop to 32 %. Field tests conducted to assess real-world applicability confirm the laboratory results, demonstrating the treated material's suitability for road construction as per secondary road design criteria and its environmental safety. The research highlights the environmental and engineering benefits of using CCR-based materials for sludge stabilization, offering a sustainable solution to the challenges of dredged sludge management and industrial waste utilization. The findings represent a step forward in waste-to-resource conversion, promoting environmental sustainability in civil engineering practices.

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 (F204L and L238F), 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.

Summary: 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.

In the first wave of the COVID-19 pandemic, China provided medical assistance on an unprecedented scale. While some observers have underscored the strategic purposes of China's COVID-19 aid, referred to as “mask diplomacy,” they have yet to assess this argument against empirical evidence. We seek to examine whether China's medical aid was used as a strategic tool, or it remained reactionary and fragmented, by combining a new dataset on the global distribution of Chinese in-kind medical aid with a qualitative analysis of government and news reports during the first wave of the pandemic. Our findings show that although COVID-19 aid did have the potential to strengthen China's influence over recipients and promote Chinese knowledge of health governance, Chinese policymakers were underprepared to use aid strategically during the pandemic. The reactionary and fragmented nature of China's COVID-19 aid was reflected in its allocation, its policy-making processes, and its implementation.

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.

Optical phased arrays (OPAs) are renowned for their exceptional ability to manipulate and direct light beams, positioning them as an ideal choice for solid-state light detection and ranging (LiDAR) technologies. This review provides a comprehensive examination of the current research landscape for photonic integrated circuit (PIC)-based OPAs. It begins by addressing the critical design elements at the component level necessary for optimal functionality. This review then delves into phase calibration techniques and the overarching architecture of OPAs. It concludes by emphasizing the innovative 3-D OPA design, which stands out for its enhanced optical efficiency.

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.

Abstract 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.

ObjectiveAs 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.MethodsBoth 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.ResultsStudies 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.ConclusionsMany 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.

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.

In recent years, Apache Spark has become the de facto standard for big data processing. SparkSQL is a module offering support for relational analysis on Spark with Structured Query Language (SQL). SparkSQL provides convenient data processing interfaces. Despite its efficient optimizer, SparkSQL still suffers from the inefficiency of Spark resulting from Java virtual machine and the unnecessary data serialization and deserialization. Adopting native languages such as C++ could help to avoid such bottlenecks. Benefiting from a bare-metal runtime environment and template usage, systems with C++ interfaces usually achieve superior performance. However, the complexity of native languages also increases the required programming and debugging efforts. In this work, we present LotusSQL, an engine to provide SQL support for dataset abstraction on a native backend Lotus. We employ a convenient SQL processing framework to deal with frontend jobs. Advanced query optimization technologies are added to improve the quality of execution plans. Above the storage design and user interface of the compute engine, LotusSQL implements a set of structured dataset operations with high efficiency and integrates them with the frontend. Evaluation results show that LotusSQL achieves a speedup of up to 9× in certain queries and outperforms Spark SQL in a standard query benchmark by more than 2× on average.

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.

Climate clubs are valuable platforms for international and public-private collaboration in global climate governance; however, not all climate clubs enjoy durable support from their members. The existing literature attributes the varied fates of climate clubs to factors like legitimacy and club goods. We further argue that the norm-making function of clubs, the perceived value of club goods, and the costs of club good production collectively affect club development. We present a comparative study on two U.S.-initiated climate clubs—the Asia-Pacific Partnership on Clean Development and Climate (APP) and the Clean Energy Ministerial (CEM). While legitimacy concerns had some marginal influence on both clubs, the niche clubs occupy and the costs of club goods provision were crucial factors that influenced the two clubs’ different fates. The APP’s failure was due to its focus on norm-making and providing information-oriented assistance to the private sector. As government interest in norm-making declined, the APP’s value declined accordingly. Moreover, assistance to private sector actors was costly and less attractive to governments. In comparison, the CEM found its niche by focusing on facilitating policymaking in the clean energy sector in a cost-efficient manner. To make clubs durable, constructing an action-oriented working environment and providing value-added and low-cost services to key stakeholders are of great importance.

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*|/sinδ) than E, while E exhibited superior fatigue performance (with the reduction of up to 42.3% in |G*|·sinδ) 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 Sa 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.

This paper analyzed the effect of long period stacking ordered phases (LPSO) and aged-precipitations on corrosion behavior of Mg–6Gd–2Y–1Zn–0.3Zr magnesium alloys. As-forged alloys were subjected to aging at 225 °C for a period of 4 and 12 h such as to acquire the required microstructure. For these as-forged Mg alloys, some structures of LPSO phases were broken and replaced by fine dynamic recrystallized grains. After undergoing the aging treatment for a 4 h period, these alloys demonstrated a higher number of recrystallized grains and lesser LPSO phases. However, the 12 aging of the alloys produced the least number of LPSO phases, but produced a considerable amount of aged-precipitations on the recrystallized grains. During the period of 120 h immersion in 0.1 mol NaCl solution, the corrosion behavior of the alloys was mainly determined by the decreased volume fraction of LPSO phases and the increased volume fraction of aged-precipitations. Alloys after aging for a 12 h period, displayed the most critical corrosion rate owing to the severe micro-galvanic corrosion between high voltage aged-precipitations or LPSO phases and Mg-matrix, whereas, the alloys after aging for a 4 h period, displayed the best corrosion resistance due to the lesser volume fraction of LPSO phases. As-forged alloys with the most amount of volume fraction of LPSO phases displayed a moderate corrosion resistance.

Abstract We introduce a hyperuniform-disordered platform for the realization of near-infrared photonic devices on a silicon-on-insulator platform, demonstrating the functionality of these structures in a flexible silicon photonics integrated circuit platform unconstrained by crystalline symmetries. The designs proposed advantageously leverage the large, complete, and isotropic photonic band gaps provided by hyperuniform disordered structures. An integrated design for a compact, sub-volt, sub-fJ/bit, hyperuniform-clad, electrically controlled resonant optical modulator suitable for fabrication in the silicon photonics ecosystem is presented along with simulation results. We also report results for passive device elements, including waveguides and resonators, which are seamlessly integrated with conventional silicon-on-insulator strip waveguides and vertical couplers. We show that the hyperuniform-disordered platform enables improved compactness, enhanced energy efficiency, and better temperature stability compared to the silicon photonics devices based on rib and strip waveguides.

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 m6A 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.

Abstract 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.

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.

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.

Zero-valent metal (ZVMs)-based persulfate activation systems are extensively applied for the elimination of organic pollutants in aqueous environments. In this study, for the first time, zero-valent copper (ZVC) was employed as the peroxymonosulfate (PMS) activator for the efficient degradation of Orange G (OG). The physicochemical properties of ZVC were systematically characterized by FESEM, EDX, TEM, XRD and XPS measurements. Furthermore, the effects of catalyst loading, PMS dosage, OG concentration and inorganic anions on the ZVC/PMS system were, respectively, investigated and explicated. The formation of •OH and SO4•− in the system was verified by quenching experiments and then the possible reaction mechanism was proposed. This work can provide insight into water treatment technology based on ZVMs.

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.

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.

Novel therapeutic strategies for breast cancer are urgently needed due to the sustained development of drug resistance and tumor recurrence. Trivalent arsenic derivative (arsenite, AsIII) has been reported to induce cytotoxicity in breast cancer cells. We recently demonstrated that AsIII 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 AsIII 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 AsIII 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 AsIII 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 AsIII 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 AsIII in combination with Tetra for patients with different types of breast cancer.

Hepatitis C virus (HCV) is a member of Hepacivirus and belongs to the family of Flaviviridae. HCV infects millions of people worldwide and may lead to cirrhosis and hepatocellular carcinoma. HCV envelope proteins, E1 and E2, play critical roles in viral cell entry and act as major epitopes for neutralizing antibodies. However, unlike other known flaviviruses, it has been challenging to study HCV envelope proteins E1E2 in the past decades as the in vitro expressed E1E2 heterodimers are usually of poor quality, making the structural and functional characterization difficult. Here we express the ectodomains of HCV E1E2 heterodimer with either an Fc-tag or a de novo designed heterodimeric tag and are able to isolate soluble E1E2 heterodimer suitable for functional and structural studies. Then we characterize the E1E2 heterodimer by electron microscopy and model the structure by the coevolution based modeling strategy with Rosetta, revealing the potential interactions between E1 and E2. Moreover, the E1E2 heterodimer is applied to examine the interactions with the known HCV receptors, neutralizing antibodies as well as the inhibition of HCV infection, confirming the functionality of the E1E2 heterodimer and the binding profiles of E1E2 with the cellular receptors. Therefore, the expressed E1E2 heterodimer would be a valuable target for both viral studies and vaccination against HCV.

There exists a correlation in the flow movement between the front and back bends of a continuous bend, and the change in the transition section configuration influences this correlation. In this paper, laboratory experiments were conducted to systematically measure the three-dimensional velocity in a continuous bend with different width/depth ratios of the transition section. Based on this work, the flow movement characteristics of a continuous bend were analysed, including the circulation structure, circulation intensity and Turbulent Kinetic Energy (TKE). The flow movement correlation between the front and back bends of the continuous bend was also analysed. The influence of the width/depth ratio of the transition section on the correlation of the flow movement of the front and back bends and their relationship with discharge were explored. This research could help to elucidate the development and evolution laws of the continuous bend and provide theoretical support for flow movement, flood routing, sediment transport and riverbed evolution. It is found that in addition to the circulation structure and intensity, the TKE of the front and back bends of the continuous bend also shows a strong correlation. With increasing discharge, the correlation between the front and back bends increases, and the larger the discharge is, the greater the influence of the same amplitude of variation in the discharge on the correlation. At the same time, the larger the discharge is, the greater the influence of the same amplitude of variation in the width/depth ratio of the transition section on the correlation of the front and back bends. When the discharge is constant, the correlation between the front and back bends decreases with the decrease in the width/depth ratio of the transition section, and the smaller the width/depth ratio, the greater the influence of the same amplitude of variation in the width/depth ratio on the correlation. There is no linear relationship between the amplitudes of variation in both the discharge and width/depth ratio and the corresponding amplitude of variation in the correlation. With increasing discharge, the amplitude of variation in the correlation caused by the same amplitude of the variation in discharge slightly increases. However, there is an exponential relationship between the amplitude of variation in the width/depth ratio and the corresponding correlation. The influence of the width/depth ratio on the correlation is clearly greater than that of the discharge.

In the present work, we perform experiments and molecular dynamics simulations to elucidate the underlying deformation mechanisms of single crystalline copper under the load-controlled multi-passes nanoscratching using a triangular pyramidal probe. The correlation of microscopic deformation behavior of the material with macroscopically-observed machining results is revealed. Moreover, the influence of crystallographic orientation on the nanoscratching of single crystalline copper is examined. Our simulation results indicate that the plastic deformation of single crystalline Cu under the nanoscratching is exclusively governed by dislocation mechanisms. However, there is no glissile dislocation structure formed due to the probe oscillation under the load-controlled mode. Both experiments and MD simulations demonstrate that the machined surface morphologies in terms of groove depth and surface pile-up exhibit strong crystallographic orientation dependence, because of different geometries of activated slip planes cutting with free surfaces and strain hardening abilities associated with different crystallographic orientations.