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Propylene glycol (PG)-mixed steam enhanced extraction is a promising remediation technique for removing semi-volatile organic compounds (SVOCs) from the unsaturated zone. However, the mechanisms of heat and moisture transfer during PG-mixed steam injection remain unclear. In this study, a 2D experimental system was developed to enable non-invasive monitoring of the spatio-temporal distribution of temperature and degree of saturation during steam injection into porous media. Experiments were conducted to observe the migration of PG-mixed steam in horizontal and vertical planes across three varying particle sizes, while pure superheated steam injection experiments serving as a comparison. Temperature field results show that the addition of PG decreases the zone of influence during steam migration, while significantly enhancing the emergence of the superheated steam zone. The influence of particle size on the area variance of the saturated steam zone is greater than that of the superheated steam zone. The downward migration of the superheated steam front due to density different between PG vapor and air is impeded with decreasing permeability. Furthermore, saturation field results reveal that the condensed liquid within the superheated zone is a PG solution. The downward migration of condensates with high PG concentration might increase the potential risk of beneath groundwater pollution, highlighting the significance of understanding PG migration during PG-mixed steam injection., 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.)

Fluorescent proteins are indispensable tools in biological and medical research. The fluorophores are typically encoded by the primary amino acid sequence, from which a fluorescent molecular rotor structure forms upon protein folding. Here, inspired by the fluorogenic property exhibited by native fluorophores, we designed a collection of fluorogenic non-canonical amino acids that feature this molecular rotor structure-termed fluorescent molecular rotor amino acids (FMR-AAs)-akin to native fluorescent protein fluorophores. By incorporating FMR-AAs into target proteins through an expanded genetic code, we use them as encoded fluorophore analogues within a confined protein microenvironment, thus readily transforming diverse non-fluorescent proteins into artificial fluorescent proteins. We also use FMR-AAs in selected proteins as sensitive fluorescent probes for monitoring protein-protein interactions and detecting protein conformational changes in vitro and in living cells. This approach enables the generation of artificial fluorescent proteins and the development of biosensors from potentially any protein of interest with minor modifications., Competing Interests: Competing interests: T.L., L.M.H. and W.B.C. are named inventors of two related patent applications (CN 202411208715.6 and CN 202411210970.4), which were filed by Peking University. The remaining authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Pheromone-binding proteins (PBPs) are mainly responsible for binding and transporting hydrophobic pheromone molecules across the aqueous sensilla lymph to the receptor proteins. The preference of each PBP is believed to be different for each pheromone component within a single species. Significantly higher expression level of PBP1 and PBP2 in the male antennae of Spodoptera frugiperda suggesting that SfruPBP1 and SfruPBP2 might play important roles in pheromone perception. However, the preference of these two PBP to the three main pheromone components Z9-14: Ac, Z7-12: Ac and Z11-16: Ac have not been determined. In this study, a fluorescence competitive binding assay revealed that the binding intensities of SfruPBP1 and SfruPBP2 to Z9-14: Ac or Z7-12: Ac was comparable. We then used the CRISPR/Cas9 system to individually or simultaneously knock out PBP1 and PBP2 in S.frugiperda. The result of courtship behavior indicated that SfruPBP1 and SfruPBP2 were indispensable and played equal roles in perceiving the pheromones Z9-14: Ac and Z7-12: Ac for orientation, wing vibration, and hair-pencil display. Compared with Z9-14:Ac and Z7-12: Ac, Z11-16: Ac showed higher or medium binding intensities with SfruPBP1 and SfruPBP2 but played a minor role in inducing the wing vibration behavior. The results of this study are valuable for elucidating the mechanisms involved in sex pheromone perception and may facilitate the development of PBP-targeted pest control techniques., 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. Published by Elsevier Inc.)

Microorganisms symbiotic with insects, whether permanently or temporarily, play a crucial role in the nutrition, development, reproduction, defence, and metamorphosis regulation. In some Lepidoptera, oviposition-deterrent pheromones (ODPs) on egg surface were used by pregnant females to modify the behaviour of conspecifics to avoid excessive competition for limited resources. In this study, we constructed four different Spodoptera litura groups, including, OH, OA, SH, and OA, which either feed on different hosts or grow in different environments. The 16S rDNA libraries of microbes from the egg surface of the four groups were constructed and sequenced. According to alpha and beta diversity indices, the microbes in environments and diets considerably influenced the richness, diversity, and community compositions of the microbiota on egg surfaces. The quantity of the main ODP components and the corresponding oviposition-deterrent activity among four groups were significantly differed among the four groups. The result of this study revealed that altering of microbes in environments or diets considerably changed the contents of ODP and oviposition-deterrent activity. As ODPs impart oviposition-deterrent activity towards closely related species, the findings of this study suggest that we should pay more attention to the role of symbiotic microorganisms in changing the ability of insects, especially sympatric species, to occupy the optimal niche when developing novel pest-control strategies.

Historically, drug discovery and development have proven to be time-consuming and costly, with the process averaging around 15 years and costing approximately USD 2 billion to bring a new small-molecule drug to market [...].

Transforming growth factor β type 1 receptor (TGFβR1), a crucial serine-threonine kinase, is central to the TGFβ/Smad signaling pathway, governing cellular processes like growth, differentiation, apoptosis, and immune response. This pathway is closely linked to the epithelial-mesenchymal transition (EMT) process, which plays an important role in the metastasis of hepatocellular carcinoma (HCC). To date, only limited inhibitors targeting TGFβR1 have entered clinical trials, yet they encounter challenges, notably high toxicity, in clinical applications. Herein, an efficient virtual screening pipeline was developed. Eighty compounds were screened from a pool of over 17 million molecules based on docking scores and binding free energy. Four compounds were manually selected with the assistance of enhanced sampling method BPMD (binding pose metadynamics). The binding stability of these four compounds complexed with TGFβR1 was subsequently studied through long-timescale conventional molecular dynamics simulations. The three most promising compounds were subjected to in vitro bioactivity assays. Cpd272 demonstrated moderate inhibitory activity against TGFβR1, with an IC 50 value of 1.57 ± 0.33 μM. Moreover, it exhibited cytotoxic effects on human hepatocellular carcinoma cell line Bel-7402. By shedding light on the binding mode of the receptor-ligand complexes, Cpd272 was identified as a hit compound featuring a novel urea-based scaffold capable of effectively inhibiting TGFβR1.

Acetic acid is the key organic substance used to verify the authenticity of vinegar. A new method for precisely determining acetic acid δD CH3 in vinegar via gas chromatography -pyrolytic-stable isotope ratio mass spectrometry (GC-P-IRMS) was established. The δD CH3 values were obtained via calibration with a series of standards. The optimised method demonstrated a repeatability standard deviation within 3 ‰. The standard deviation of accuracy of the new method compared with that of the SNIF-NMR method was within 2.6 ‰. The synthetic acetic acid δD CH3 values was -136.7 ‰ ± 29.6 ‰, and the δD CH3 value of acetic acid in vinegar was -414.9 ‰ ± 40.5 ‰, with significant isotopic distribution characteristics. This methodology serves as a supplementary method for measuring the δD CH3 value of acetic acid in vinegar. It has advantages over other methods in terms of time, sensitivity and operability. And provides a new idea for solving the problem of analyzing substances in the presence of exchangeable groups., 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 Ltd. All rights reserved.)

Enzyme-linked immunosorbent assay (ELISA) is the gold standard technique for measuring protein biomarkers due to its high sensitivity, specificity, and throughput. Despite its success, continuous advancements in ELISA and immunoassay formats are crucial to meet evolving global challenges and to address new analytical needs in diverse applications. To expand the capabilities and applications of immunoassays, we introduce a novel ELISA-like assay that we call Bioluminescent-bacteria-linked immunosorbent assay (BBLISA). BBLISA is an enzyme-free assay that utilizes the inner filter effect between the bioluminescent bacteria Allivibrio fischeri and metallic nanoparticles (gold nanoparticles and gold iridium oxide nanoflowers) as molecular absorbers. Functionalizing these nanoparticles with antibodies induces their accumulation in wells upon binding to molecular targets, forming the classical immune-sandwich complex. Thanks to their ability to adsorb the light emitted by the bacteria, the nanoparticles can suppress the bioluminescence signal, allowing the rapid quantification of the target. To demonstrate the bioanalytical properties of the novel immunoassay platform, as a proof of principle, we detected two clinically relevant biomarkers (human immunoglobulin G and SARS-CoV-2 nucleoprotein) in human serum, achieving the same sensitivity and precision as the classic ELISA. We believe that BBLISA can be a promising alternative to the standard ELISA techniques, offering potential advancements in biomarker detection and analysis by combining nanomaterials with a low-cost, portable bioluminescent platform.

Objectives: Visual inspection with acetic acid (VIA) is a low-cost approach for cervical cancer screening used in most low- and middle-income countries (LMICs) but, similar to other visual tests, is subjective and requires sustained training and quality assurance. We developed, trained, and validated an artificial-intelligence-based "Automated Visual Evaluation" (AVE) tool that can be adapted to run on smartphones to assess smartphone-captured images of the cervix and identify precancerous lesions, helping augment VIA performance., Design: Prospective study., Setting: Eight public health facilities in Zambia., Participants: A total of 8204 women aged 25-55., Interventions: Cervical images captured on commonly used low-cost smartphone models were matched with key clinical information including human immunodeficiency virus (HIV) and human papillomavirus (HPV) status, plus histopathology analysis (where applicable), to develop and train an AVE algorithm and evaluate its performance for use as a primary screen and triage test for women who are HPV positive., Main Outcome Measures: Area under the receiver operating curve (AUC); sensitivity; specificity., Results: As a general population screening tool for cervical precancerous lesions, AVE identified cases of cervical precancerous and cancerous (CIN2+) lesions with high performance (AUC = 0.91, 95% confidence interval [CI] = 0.89-0.93), which translates to a sensitivity of 85% (95% CI = 81%-90%) and specificity of 86% (95% CI = 84%-88%) based on maximizing the Youden's index. This represents a considerable improvement over naked eye VIA, which as per a meta-analysis by the World Health Organization (WHO) has a sensitivity of 66% and specificity of 87%. For women living with HIV, the AUC of AVE was 0.91 (95% CI = 0.88-0.93), and among those testing positive for high-risk HPV types, the AUC was 0.87 (95% CI = 0.83-0.91)., Conclusions: These results demonstrate the feasibility of utilizing AVE on images captured using a commonly available smartphone by nurses in a screening program, and support our ongoing efforts for moving to more broadly evaluate AVE for its clinical sensitivity, specificity, feasibility, and acceptability across a wider range of settings. Limitations of this study include potential inflation of performance estimates due to verification bias (as biopsies were only obtained from participants with visible aceto-white cervical lesions) and due to this being an internal validation (the test data, while independent from that used to develop the algorithm was drawn from the same study)., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Although blue light can damage the skin to a certain extent, the pathogenesis of its damage remains still unclear. The available evidence suggests that oxidative stress may be the main cause of its damage. Lycium barbarum polysaccharide (LBP) has antioxidative effects in a variety of cells. In this paper, we investigated the protective role of LBP and its mechanism of action related to mitophagy in blue-light-damaged skin cells. The findings indicated that in HaCaT cells and mouse skin, LBP pretreatment was effective in reducing blue-light-induced apoptosis and ameliorating the elevated level of cellular autophagy/mitophagy caused by excessive blue light exposure. The markers reactive oxygen species (ROS), superoxide dismutase (SOD), and malondialdehyde (MDA) were used to assess oxidative stress. LBP could effectively inhibit blue-light-induced oxidative stress. It was also found that blue light exposure caused mitochondrial dysfunction in HaCaT cells, including increased intracellular calcium ion levels and decreased mitochondrial membrane potential. LBP pretreatment significantly relieved mitochondrial dysfunction in HaCaT cells. These findings imply that LBP pretreatment protects skin cells from damage induced by blue light irradiation and that mitophagy may be a significant factor in skin photodamage., (© 2023 American Society for Photobiology.)

Background: Chelidonium majus is a well-known traditional Chinese medicine, and has been reported of the effect in relieving cough and asthma. However, the mechanism of action is still unknown., Methods: Asthmatic SD rats were first sensitized and established through ovalbumin (OVA) motivation. Subsequently, Hematoxylin and eosin (H&E) staining, Masson's trichrome (Masson) staining, Periodic acid-Schiff (PAS) staining and inflammatory cytokines assay of interleukin (IL)-4, IL-6, IL-17 were implemented to evaluate the protective effects of Chelidonium majus on asthma. Then, the effects of Chelidonium majus and their molecular mechanisms of action on asthma were detected based on the integration of transcriptomics and metabolomics analyses., Results: After administration with Chelidonium majus, the histological injuries of inflammation, collagen deposition and mucus secretion in lungs were attenuated and the serum inflammatory cytokines perturbations were also converted. Furthermore, integrated analysis revealed that after Chelidonium majus treatment, 7 different expression genes (DEGs) (Alox15, P4ha1, Pla2g16, Pde3a, Nme1, Entpd8 and Adcy9) and 9 metabolic biomarkers (ADP, Xanthosine, Hypoxanthine, Inosine, prostaglandin E2 (PGE2), prostaglandin F2a (PGF2a), phosphatidylserine, Creatine and LysoPC (10:0)) were discovered to be connected with the enrichment metabolic pathways, including Purine metabolism, Arachidonic acid metabolism, Arginine and proline metabolism and Glycerophospholipid metabolism. The obtained metabolic biomarkers and DEGs were mainly related to energy metabolism and inflammation, and may be potential therapeutic targets., Conclusion: Chelidonium majus relieved OVA-induced asthma in rats by regulating the Alox15, P4ha1, Pla2g16, Pde3a, Nme1, Entpd8 and Adcy9 genes expression to restore the disorders in energy metabolism and inflammation., (© 2024. The Author(s).)

HER2 mutations were seen in 4% of non-small-cell lung cancer (NSCLC) patients. Most of these mutations (90%) occur as an insertion mutation within the exon 20 frame, leading to the downstream activation of the PI3K-AKT and RAS/MAPK pathways. However, no targeted therapies have yet been approved worldwide. Here a novel series of highly potent HER2 inhibitors with a pyrido[2,3,4- de ]quinazoline core were designed and developed. The derivatives with the pyrido[2,3,4- de ]quinazoline core displayed superior efficacy of antiproliferation in BaF3 cells harboring HER2insYVMA mutation compared with afatinib and neratinib. Rat studies showed that 8a and 9a with the newly developed core have good pharmacokinetic properties with an oral bioavailability of 41.7 and 42.0%, respectively. Oral administration of 4a and 10e (30 mg/kg, QD) displayed significant antitumor efficacy in an in vivo xenograft model. We proposed promising strategies for the development of HER2insYVMA mutant inhibitors in this study.

Ribonucleic acids (RNA) play active roles within cells or viruses by catalyzing biological reactions, controlling gene expression, and communicating responses to cellular signals. Rapid monitoring RNA variation has become extremely important for appropriate clinical decisions and frontier biological research. However, the most widely used method for RNA detection, nucleic acid amplification, is restricted by a mandatory temperature cycling period of ≈1 h required to reach target detection criteria. Herein, a direct detection approach via single-atom site integrated surface-enhanced Raman scattering (SERS) monitoring nucleic acid pairing reaction, can be completed within 3 min and reaches high sensitivity and extreme reproducibility for COVID-19 and two other influenza viruses' detection. The mechanism is that a single-atom site on SERS chip, enabled by positioning a single-atom oxide coordinated with a specific complementary RNA probe on chip nanostructure hotspots, can effectively bind target RNA analytes to enrich them at designed sites so that the binding reaction can be detected through Raman signal variation. This ultrafast, sensitive, and reproducible single-atom site SERS chip approach paves the route for an alternative technique of immediate RNA detection. Moreover, single-atom site SERS is a novel surface enrichment strategy for SERS active sites for other analytes at ultralow concentrations., (© 2024 Wiley-VCH GmbH.)

Objectives: Visual inspection with acetic acid (VIA) is a low-cost approach for cervical cancer screening used in most low- and middle-income countries (LMICs) but, similar to other visual tests like histopathology, is subjective and requires sustained training and quality assurance. We developed, trained, and validated an artificial-intelligence-based "Automated Visual Evaluation" (AVE) tool that can be adapted to run on smartphones to assess smartphone-captured images of the cervix and identify precancerous lesions, helping augment performance of VIA., Design: Prospective study., Setting: Eight public health facilities in Zambia., Participants: 8,204 women aged 25-55., Interventions: Cervical images captured on commonly used low-cost smartphone models were matched with key clinical information including human immunodeficiency virus (HIV) and human papillomavirus (HPV) status, plus histopathology analysis (where applicable), to develop and train an AVE algorithm and evaluate its performance for use as a primary screen and triage test for women who are HPV positive., Main Outcome Measures: Area under the receiver operating curve (AUC); sensitivity; specificity., Results: As a general population screening for cervical precancerous lesions, AVE identified cases of cervical precancerous and cancerous (CIN2+) lesions with high performance (AUC = 0.91, 95% confidence interval [CI] = 0.89 to 0.93), which translates to a sensitivity of 85% (95% CI = 81% to 90%) and specificity of 86% (95% CI = 84% to 88%) based on maximizing the Youden's index. This represents a considerable improvement over VIA, which a meta-analysis by the World Health Organization (WHO) estimates to have sensitivity of 66% and specificity of 87%. For women living with HIV, the AUC of AVE was 0.91 (95% CI = 0.88 to 0.93), and among those testing positive for high-risk HPV types, the AUC was 0.87 (95% CI = 0.83 to 0.91)., Conclusions: These results demonstrate the feasibility of utilizing AVE on images captured using a commonly available smartphone by screening nurses and support our transition to clinical evaluation of AVE's sensitivity, specificity, feasibility, and acceptability across a broader range of settings. The performance of the algorithm as reported may be inflated, as biopsies were obtained only from study participants with visible aceto-white cervical lesions, which can lead to verification bias; and the images and data sets used for testing of the model, although "unseen" by the algorithm during training, were acquired from the same set of patients and devices, limiting the study to that of an internal validation of the AVE algorithm.

O-Aminophenol (OAP) is widely used in various industries, but it can have severe negative impacts on both the environment and human health. Herein, we reported the development of hemicyanine boronic acid (HBA) for the fluorescent detection of OAP. The reaction of HBA with OAP produced a strong fluorescence emission at 675 nm because of the generation of tricyclic borate ester hemicyanine (TBEH). The detection was very rapid, sensitive and specific. The detection had a linear range 0.1 - 10.0 µM in ethanol with a detection limit of 60 nM in water and ethanol. The accuracy and precision of our results were successfully verified via HPLC analysis. Our study offers a valuable tool for the facile and efficient detection of OAP, with practical applications in environmental and health management., 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 B.V. All rights reserved.)

The high structural homology of histone deacetylases 6 and 8 (HDAC6/8) poses a challenge in achieving isoform selectivity and has resulted in adverse side effects due to pan-inhibition in clinical applications. Additionally, the rational design of dual-target inhibitors, centered on HDAC6/8, demands a profound understanding of their selectivity mechanisms. Addressing the urgent need for enhanced specificity in the development of inhibitors targeting specific isoforms, we elucidate the mechanism underpinning the selective inhibition of HDAC6/8 inhibitors through in-silico strategies. The hydrogen bonding interaction with Asp101 and Tyr306 is a key factor that enables compound 12b to selectively inhibit HDAC8. Its favorable spatial orientation places the Cap group of 12b between Tyr306 and Tyr100, resulting in an overall L-shaped conformation. These two factors significantly contribute to the selective inhibitory activity of 12b against HDAC8. The zinc binding group (ZBG) of compound NN-390 forms a hydrogen bond with His610, a key residue of HDAC6, facilitating stable chelation with zinc ions. In addition, the Cap group of NN-390 interacts with Phe620 and Phe680 via van der Waals forces, leading to an overall Y-shaped conformation. The aforementioned factors are the main reasons for the selective inhibition of HDAC6 by NN-390 . Furthermore, whether the Cap group is in the para or meta-position will influence the selective inhibition of either HDAC6 or HDAC8. We believe these clues can offer valuable insights for the rational design of selective inhibitors targeting HDAC6/8 and pave the way for rational design of dual-target HDAC6/8-based inhibitors.Communicated by Ramaswamy H. Sarma.

Chemosensory proteins (CSPs) are highly efficient carry tools to bind and deliver hydrophobic compounds, which play an important role in the chemosensory process in insects. The diamondback moth, Plutella xylostella L. (Lepidoptera: Plutellidae), is a cosmopolitan pest that attacks cruciferous crops. However, the detailed physiological functions of CSPs in P. xylostella remain limited to date. Here, we identified a typical CSP, named PxylCSP18, in P. xylostella and investigated its expression patterns and binding properties of volatiles. PxylCSP18 was highly expressed in antennae and head (without antennae), and the expression level in the male antennae of P. xylostella was obviously higher than that in the female antennae. Moreover, PxylCSP18 has a relatively broad binding spectrum. Fluorescence competitive binding assays showed that PxylCSP18 had strong binding abilities with 14 plant volatiles (Ki < 10 μM) that were repellent or attractive to P. xylostella. Notably, PxylCSP18 had no significant binding affinity to (Z)-11-hexadecenal, (Z)-11-hexadecenyl acetate, and (Z)-11-hexadecenyl alcolol, which are the pheromone components of P. xylostella. The attractive effects of trans-2-hexen-1-ol and isopropyl isothiocyanate to male adults and the attractive effects of isopropyl isothiocyanate and the repellent effects of linalool to female adults were significantly decreased after knocked down the expression of PxylCSP18. Our results revealed that PxylCSP18 might play an important role in host plant detection, avoidance of unsuitable hosts, and selection of oviposition sites; however, it does not participate in mating behavior. Overall, these results extended our knowledge on the CSP-related functions, which provided insightful information about CSP-targeted insecticides., (© The Author(s) 2024. Published by Oxford University Press on behalf of Entomological Society of America.)

Beauvericin (BEA), a naturally occurring cyclic peptide with good pharmacological activity, has been widely explored in anticancer research. Although BEA is toxic, studies have demonstrated its antioxidant activity. However, to date, the antioxidant mechanisms of BEA remain unclear. Herein, we conducted a comprehensive and detailed study of the antioxidant mechanism of BEA using an untargeted metabolomics approach, subsequently validating the results. BEA concentrations of 0.5 and 1 μM significantly inhibited H 2 O 2 -induced oxidative stress (OS), decreased reactive oxygen species levels in PC-12 cells, and restored the mitochondrial membrane potential. Untargeted metabolomics indicated that BEA was primarily involved in lipid-related metabolism, suggesting its role in resisting OS in PC-12 cells by participating in lipid metabolism. BEA combated OS damage by increasing phosphatidylcholine, phosphatidylethanolamine, and sphingolipid levels. In the current study, BEA upregulated proteins related to the PI3K/AKT/mTOR pathway, thereby promoting cell survival. These findings support the antioxidant activity of BEA at low concentrations, warranting further research into its pharmacological effects., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Limited studies have evaluated the burden of inflammatory bowel disease (IBD) in China. We aimed to estimate the incidence of IBD including ulcerative colitis (UC) and Crohn's disease (CD) in urban China., Methods: The national urban incidence in 2016 was calculated based on urban basic medical insurance from 2012 to 2016 in China by using a 4-year washout period. The incidence in Yinzhou District estimated from the Yinzhou electronic health care record database was used to test the accuracy of the results from insurance data., Results: A total of 95,555 patients with IBD were identified. The incidence in 2016 was 10.04 (95% confidence interval, 6.95-13.71) per 100,000 person-years. The incidence rates of both UC and CD were higher among males than among females. There was a sharp increase in UC incidence before the age of 30 years and stabilization in later years (50-79 years old), whereas CD incidence peaked at 30 to 34 years old and experienced decline subsequently. The incidence of UC was much greater than that of CD, with a UC-to-CD incidence ratio of 12.61. The results from the Yinzhou database confirmed these results., Conclusions: This study is the first to draw a portrait of the distribution of IBD in urban China. The difference in IBD incidence between urban China and other countries suggests an association between the IBD burden and industrialization process. The accelerating urbanization and industrialization process in China, a country with a population of 1.4 billion people, will likely increase the burden of IBD., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Peroxynitrite (ONOO - ) is a crucial reactive oxygen species that plays a vital role in cellular signal transduction and homeostatic regulation. Determining and visualizing peroxynitrite accurately in biological systems is important for understanding its roles in physiological and pathological activity. Among the various detection methods, fluorescent probe-based spectroscopic detection offers real-time and minimally invasive detection, high sensitivity and selectivity, and easy structural and property modification. This review categorizes fluorescent probes by their fluorophore structures, highlighting their chemical structures, recognition mechanisms, and response behaviors in detail. We hope that this review could help trigger novel ideas for potential medical diagnostic applications of peroxynitrite-related molecular diseases.

The anaerobic baffled reactor (ABR) is an anaerobic bioreactor that uses baffles to separate the working area into multiple reaction zones. The ABR-microbial fuel cell (MFC) reactor was constructed by embedding MFC in each reaction zone of the ABR. Its degradation of azo dye type (acid mordant red) wastewater and microbial power generation performance were investigated. For different electrode area ratios, the best enhanced treatment and electrical energy output of the coupled system was achieved with an anode/cathode area ratio of 1:1. Compared with the electrode area ratio of 2:1 and 1:2, the power density increased by 82.5% and 80.6%, and the Coulomb efficiency increased by 133.3% and 64.7%. In addition, the best enhanced treatment of printing and dyeing wastewater was achieved by ABR-MFC at 1:1. At a dye concentration of 200 mg/L and a sucrose concentration of 1000 mg/L, the coupled system obtained a COD removal of 92.85% and a chromaticity removal of 96.2%, which achieved a relative COD and chromaticity removal improvement of 1.82% and 2.64%, respectively, relative to the ABR. Scanning electron microscopy (SEM) observation of the electrodes at 1:1 revealed that more microorganisms were attached to the anode surface of the coupled system, the particle size of the granular sludge within the system was larger, and the UV scanning pattern showed lower dye concentration in the water. In conclusion, the microbial fuel cell enhanced anaerobic treatment of dyeing wastewater was the most effective when the electrode area ratio was 1:1, and the best electrical energy output was obtained at the same time. ABR-MFC provides a new idea for the enhanced treatment of dyeing wastewater and electrical energy production., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The tobacco-rice rotation cropping (TRRC) is an ecologically friendly system that can both alleviate soil nicotine pollution and decrease the brown planthopper (BPH, Nilaparvata lugens Stål) fitness on rice. However, few studies on this green and effective rotational cropping system have been reported. In particular, the underlying mechanisms of TRRC on the significant reduction of field pest population at the molecular level is still unknown., Results: Field investigation showed that BPH population decreased significantly in TRRC than in rice-rice successive cropping (RRSC) field. In addition, the short neuropeptide F (NlsNPF) and its receptor NlA7 of BPH had half-times lower levels in the TRRC field. Behavioral bioassay indicated a 1.93-fold increase in the number of salivary flanges of the dsNlsNPF group, while BPH fitness parameters, such as honeydew, weight gain, and mortality decreased significantly. Dopamine (DA) content in BPH decreased by ~11.1% under the influence of nicotine, and its presence increased the expression levels of NlsNPF and NlA7. Exogenous DA application eliminated the inhibitory effects of nicotine on BPH feeding and restored the fitness levels of its parameters. Independent application of either a mixture of dsNlsNPF with a nanocarrier or nicotine to the normal rice field revealed that the latter could produce better effects in combination with dsRNA., Conclusion: These findings confirmed that DA regulated NlsNPF to inhibit the BPH feeding behavior in TRRC. The results not only provided novel findings on the mechanism of pest-host interactions, but also presented new method for integrated pest management. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Thermal desorption technology can effectively remediate fuels-contaminated clayey soil. However, the microscopic mechanism for the contaminant desorption on clay is still unclear, especially with the existence of water on clay surfaces. In this study, a combination method including TGA experiments, multi-phase and multi-component kinetic models, and MD simulation was proposed to reveal the thermal desorption mechanism of n-dodecane in unsaturated clay. Results showed that the thermal desorption behavior of the free nonaqueous phase liquid (NAPL) and the adsorbed phase of n-dodecane or water could be identified by the multi-phase and multi-component kinetic models based on the desorption process rate obtained by thermogravimetric analysis (TGA) experiments. The activation energy of the NAPL phase (49-69.9 kJ/mol) was lower than the adsorbed phase (90 kJ/mol). The activation energy of the NAPL phase had the same linear relationship with its mass on kaolinite and montmorillonite, while adsorbed phase only existed on the kaolinite surface. MD simulation showed that water demonstrated competitive adsorption with n-dodecane on montmorillonite surfaces and prevented the formation of the adsorbed phase while having little influence on the n-dodecane adsorption on kaolinite surface, which agrees well with the kinetic analysis of the TGA experiments. With the combination of macroscopic experimental analysis and microscopic molecular simulation, it can be concluded that the mass of the NAPL phase limited the desorption behavior, while the interaction between the clay mineral surface and n-dodecane was the key factor that dominated the thermal desorption behavior of the adsorbed phase. The presented results provide new insight into the desorption mechanism of hydrocarbon on clay minerals, which is of significance for the design of thermal desorption remediation., 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 Ltd. All rights reserved.)

Despite the widespread theranostic utilization of cyanine dyes (Cy7), their synthetic method is still limited with pyridine or cyclohexanone derivatives as starting materials. Herein, we report the synthesis of Cy7 from furfural derivatives. First, a one-pot reaction strategy is developed to solve the unstable problem of the Stenhouse salts. Second, a stepwise condensation strategy is exploited to regioselectively synthesize asymmetrical Cy7. The methodology possesses advantages, such as easy handling, high yield, wide substrate scopes, and good functional group tolerance.

Graphene-based materials are of interest in electrochemical biosensing due to their unique properties, such as high surface areas, unique electrochemical properties, and biocompatibility. However, the scalable production of graphene electrodes remains a challenge; it is typically slow, expensive, and inefficient. Herein, we reported a simple, fast, and maskless method for large-scale, low-cost reduced graphene oxide electrode fabrication; using direct writing (laser scribing and inkjet printing) coupled with a stamp-transferring method. In this process, graphene oxide is simultaneously reduced and patterned with a laser, before being press-stamped onto polyester sheets. The transferred electrodes were characterized by SEM, XPS, Raman, and electrochemical methods. The biosensing utility of the electrodes was demonstrated by developing an electrochemical test for Escherichia coli. These biosensors exhibited a wide dynamic range (917-2.1 × 10 7 CFU/mL) of low limits of detection (283 CFU/mL) using just 5 μL of sample. The test was also verified in spiked artificial urine, and the sensor was integrated into a portable wireless system driven and measured by a smartphone. This work demonstrates the potential to use these biosensors for real-world, point-of-care applications. Hypothetically, the devices are suitable for the detection of other pathogenic bacteria.

Starting with our previously reported work, a novel series of 3,4-dihydro-2H-[1,4]oxazino[2,3-f]quinazolin-derivatives were designed, synthesized and evaluated as potent EGFR tyrosine kinase inhibitors. All of the compounds showed significant inhibitory activities against EGFR wt kinase (IC 50  ≤ 937.7 nM). Among them, compound 7j demonstrated the most potent inhibitory activity toward EGFR wt tyrosine kinase with IC 50 value of 25.69 nM and showed good antiproliferative activities against NCI-H1563 and H1975 cells. The median cytotoxic concentration (CC 50 ) showed that most of the tested compounds displayed almost no cytotoxicity in vitro against 16HBE cells. In view of the reported compounds activity, the structure deserves further optimization as cancer treatment agents., 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 © 2022. Published by Elsevier Ltd.)

Shale gas has become one of the important contributors to the global energy supply. The declining pattern of the gas production rate with time from an unconventional gas reservoir is due to the depletion of shale gas stored in the nanovoids of the shale formation. However, there are only limited ways to predict the variation of the gas production rate with time from an unconventional gas reservoir. This is due to the multiple transport mechanisms of gas in nano-scale pores and changes in shale gas permeability with pressures in nano-scale pores, which is impacted by the pore structure of the shale. In this study, the permeability-pressure (K-p) relationship for different shales (Eagle Ford, Haynesville, Longmaxi and Opalinus) were determined using an equivalent anisotropic pore network model (PNM). This PNM has REV-scale shale gas flow in randomly generated nanovoids and their connection in the shale matrix, and the multiphase flow of shale gas including viscous flow, slip flow and Knudsen diffusion. These predicted K-p correlations were then used in a finite element model (FEM) to predict the variation of the gas production rate with time (flux-time curves) at the macroscale. The simulation results show that the flux-time curves can be simplified to two linear segments in logarithmic coordinates, which are influenced by the fracture length and initial gas pressure. The predicted results using the PNM-FEM were validated by comparing them with the reported field test data. The method described in this study can be used to upscale the gas transport process from micro- to macroscale, which can provide a predictive tool for the gas production in shales., (© 2023. The Author(s).)

The mobility of nano zero-valent iron (nZVI) will greatly affect its practical application as a remediation material for contaminated groundwater. One-dimensional (1D) column tests are commonly used in previous work to study its migration behavior, but the two-dimensional (2D) test is still very limited. This study reports a novel research system to study the 2D transport and retention behavior of colloids and solutes, which includes a 2D model test setup and the corresponding image analysis method. The transport behaviors of methyl orange (MO), nZVI, and phosphate-loaded nZVI (PnZVI) are studied using this system. The results show that the research system can reasonably describe the tempo-spatial concentration distribution of colloids and solutes. After phosphate adsorption, the mobility of nZVI is enhanced due to the increase in negative surface charge, which implies a potential environmental risk of nZVI to facilitate contaminant transport. The migration of PnZVI is not significantly influenced by its density, which is faster than MO in the longitudinal direction. The range of the plume of PnZVI in the longitudinal direction is larger than that of MO, which implies that PnZVI has a stronger longitudinal dispersion than MO.

A method was developed for the determination of 10 organic acids in liquor, yellow rice wine, and dry red wine by ion chromatography-triple quadrupole mass spectrometry (IC-MS/MS). First, the liquor samples were diluted with deionized water, degassed with nitrogen, and analyzed by IC-MS/MS. Then, the yellow rice wine and dry red wine samples were purified with different solid-phase extraction cartridges. Finally, the GCB solid-phase extraction cartridge was selected for purification, diluted with deionized water, and analyzed by IC-MS/MS. The samples were separated using a Dionex IonPac AS11-HC anion analysis column with high capacity and strong hydrophilicity, with an KOH aqueous solution as the eluent, which was produced by an automatic generator for gradient elution. After being suppressed using a suppressor, the eluent was injected directly into the electrospray ionization tandem mass spectrometry (ESI-MS/MS), ionized in negative ion mode, detected in multiple reaction monitoring (MRM) mode, and quantified using an external standard method. Oxalic acid, fumaric acid, maleic acid, malic acid, tartaric acid, citric acid, quinic acid, and aconitic acid showed good linear relationships in the range of 0.05-2 mg/L. Succinic acid and lactic acid showed good linearities in the range of 0.05-5 mg/L and 0.05-10 mg/L, respectively. The correlation coefficients ( r 2 ) were >0.99. The limits of detection (LODs) and limits of quantification (LOQs) were 1.0-8.0 μg/L and 3.5-26.5 μg/L, respectively. The average recoveries ranged from 83.0% to 112.1%, and the relative standard deviations (RSDs) were <9.1% in spiked samples at three levels. The proposed method allowed easy pretreatment without using organic solvents or derivatization processing. Overall, the proposed method is accurate, rapid, sensitive, and it is suitable for the qualitative and quantitative analyses of the 10 organic acids in three wine samples. Moreover, it can be used for the determination of flavor and quality of alcoholic products.

Objectives: Conventional approaches for patients with nonerosive gastroesophageal reflux disease (NERD) were not satisfactory. This study aimed to evaluate the effectiveness and mechanisms of Chinese herbal medicine Hewei Jiangni Decoction (HWJND) as a novel and promising regimen for NERD., Methods: A total of 128 patients with NERD were randomly assigned to the Treatment group and Control group. The patients from the Treatment group were administered HWJND (81 g) plus dummy omeprazole (20 mg) daily for 8 weeks, and the others were given dummy HWJND granules (81 g) plus omeprazole (20 mg). The clinical efficacy was assessed using the gastroesophageal reflux disease questionnaire (GERD-Q) scale, patient reported outcomes (PRO) scale, and short form health survey 36 (SF-36) scale at week 4. Moreover, its pharmacological and molecular mechanisms were elucidated based on network pharmacology and molecular docking., Results: Due to case shedding and other reasons, 109 patients, including 56 in the Treatment group and 53 in the Control group completed this study. Our results showed that HWJND significantly improved heartburn, regurgitation, epigastric pain, nausea, and sleep disturbance, which led to a significant reduction of GERD-Q scores in NERD patients. In addition, PRO scores of NERD patients with HWJND administration were improved, and sufficient relief of physical role, body pain, general health, social function, and mental health on the SF-36 scale was also observed in patients after HWJND treatment. We further showed that the curative effect of HWJND was close to that of omeprazole, except for the better improvement of general health and social function. What's more, the main active ingredients of HWJND included quercetin, beta-sitosterol, naringenin, baicalein, and kaempferol were retrieved, and the protective effects of HWJND against NERD may be closely related to targets such as TNF, IL6, IL1B, MMP9, CXCL8, and EGFR, which were mainly enriched in IL-17 signaling pathway and TNF signaling pathway., Conclusion: Our findings demonstrate that HWJND is noninferior to oral omeprazole for the treatment of patients with NERD, plays a therapeutic role through multiple targets and diverse pathways, and holds promise for complementary and alternative therapy for the treatment of NERD. This trial is registered with http://www.chictr.org.cn, Chinese Clinical Trials Registry [ChiCTR2200055960]., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Feng Li et al.)

Background: Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating disease caused by intracranial aneurysm (IA) rupture. Lysyl oxidase ( LOX ) family genes ( LOX-like [LOXL] 1-4 ) have roles in collagen cross-linking in the extracellular matrix (ECM) and may be associated with IA rupture. We aimed to explore the association between LOX polymorphisms and the risk of aSAH., Methods: This case-control study included 2 cohorts: 133 single ruptured and 115 unruptured IA patients, and 65 multiple ruptured and 71 unruptured IA patients. Genotyping of 27 single nucleotide polymorphisms (SNPs) in LOX was performed. Logistic regression analysis was performed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of the SNPs of LOX and the risk of aSAH., Results: LOX rs1800449 and LOXL4 rs3793692 were positively associated with the risk of single IA rupture in the recessive model (OR =5.66, 2.06; 95% CI =1.22-26.24, 1.11-3.82, respectively) and LOX rs10519694 demonstrated a protective effect on single IA rupture (dominant model: OR =0.42, 95% CI =0.21-0.83; recessive model: OR =0.16, 95% CI =0.04-0.65; additive model: OR =0.46, 95% CI =0.28-0.78). LOXL1 rs2165241, LOXL2 rs1063582, and LOXL3 rs17010021 showed risk effects on multiple IAs rupture. LOXL3 rs17010022 showed a protective effect on multiple IAs ruptures (dominant model: OR =0.41, 95% CI =0.21-0.82; additive model: OR =0.51, 95% CI =0.30-0.85)., Conclusions: LOX and LOXL4 may be susceptibility genes for single IA rupture, whereas LOXL1 - 3 may have a role in susceptibility to multiple IAs ruptures in the Chinese population, suggesting that LOX family genes may be associated with aSAH., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-3484/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

This manuscript aims at raising the attention of the scientific community to the need for better characterised bioreceptors for fast development of point-of-care diagnostic devices able to support mass frequency testing. Particularly, we present the difficulties encountered in finding suitable antibodies for the development of a lateral flow assay for detecting the nucleoprotein of SARS-CoV-2.

Spaceflight presents a series of physiological and pathological challenges to astronauts resulting from ionizing radiation, microgravity, isolation, and other spaceflight hazards. These risks cause a series of aging-related diseases associated with increased oxidative stress and mitochondria dysfunction. The skin contains many autofluorescent substances, such as nicotinamide adenine dinucleotide phosphate (NAD(P)H), keratin, melanin, elastin, and collagen, which reflect physiological and pathological changes in vivo . In this study, we used a portable handheld two-photon microscope to conduct high-resolution in vivo skin imaging on volunteers during 15 days of head-down bed rest. The two-photon microscope, equipped with a flexible handheld scanning head, was used to measure two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) images of the left forearm, left front chest, and forehead of volunteers. Changes in TPEF, SHG, and the extended SHG-to-AF(TPEF) aging index of the dermis (SAAID) were measured. It was found that TPEF intensity increased during bed rest and was restored to normal levels after recovery. Meanwhile, SHG increased slightly during bed rest, and the skin aging index increased. Moreover, we found the skin TPEF signals of the left forearm were significantly negatively associated with the oxidative stress marker malondialdehyde (MDA) and DNA damage marker 8-hydroxy-2'-desoxyguanosine (8-OHdG) values of subjects during head-down bed rest. Meanwhile, the SHG signals were also significantly negatively correlated with MDA and 8-OHDG. A significant negative correlation between the extended SAAID of the left chest and serum antioxidant superoxide dismutase (SOD) levels was also found. These results demonstrate that skin autofluorescence signals can reflect changes in human oxidant status. This study provides evidence for in-orbit monitoring of changes in human stress using a portable handheld two-photon microscope for skin imaging., Competing Interests: Authors YH and QF were employed by the company Beijing Transcend Vivoscope Bio-Technology Co. Ltd. The remaining 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 Wang, Zhen, Wang, Wu, Hu, Fu, Li, Xin, Song, Li, Ren, Feng, Cheng, Wang, Hu, Ling and Li.)

Naphthalene, as one of the representative polycyclic aromatic hydrocarbons, widely exists in contaminated sites and is a potential threat to human health due to its high mobility in soil. The interaction between naphthalene and clay minerals is of great significance to the environmental behavior of naphthalene and the design of remediation technology. In this study, montmorillonite and kaolinite were selected as representative clay minerals. Naphthalene adsorption behavior on mineral surfaces and water-wet kaolinite surfaces was investigated using molecular dynamics (MD) simulation. The interaction energy was calculated to represent the interaction between naphthalene and soil fractions, and the relative concentration and density distribution of naphthalene was analyzed to describe the distribution of naphthalene on the clay surfaces. The self-diffusion coefficient of naphthalene was obtained to represent its mobility under different water content. The electron density calculation was performed to reveal the different adsorption behavior of naphthalene on different surfaces of kaolinite. The simulation results show that montmorillonite had a stronger interaction with naphthalene due to larger electrostatic interaction energy compared to kaolinite, and naphthalene distributed more intensively on the montmorillonite surface. With regards to kaolinite, naphthalene tended to be absorbed on the alumina octahedral surface rather than the silicon tetrahedral surface due to the weak hydron bond interaction. The results indicate that water impeded the adsorption of naphthalene, and the optimal initial thickness of water film, which was 10 Å, was put forward for the application of thermal remediation technology. Furthermore, the average interaction energies between water and mineral surfaces largely depended on the water content, and the competitive adsorption between water and naphthalene only occurred under absorbed and bound water conditions. Overall, the knowledge of naphthalene-soil fractions interaction gained in this study is critical to the understanding of the environmental behavior of naphthalene and the reference for remediation technology.

Wu-tou decoction has been used as a traditional Chinese medicine prescription for thousands of years. It comprises five herbs, namely Radix Aconiti Preparata, Ephedrae Herba, Astragali Radix, Glycyrrhiza Radix, and Paeoniae Radix Alba. In addition, the original prescription contains honey, but in modern research, the existence of honey is commonly ignored. The aim was to investigate the effect of absorption in rats after oral wu-tou decoction with or without honey. In this research, a rapid and sensitive UPLC-MS/MS method was investigated for the quantitative analysis of ephedrine, pseudoephedrine, paeoniflorin, calycosin-7-glucoside, glycyrrhizic acid, liquiritin, and benzoylmesaconine in rat plasma after single and continuous oral decoctions. The results of the pharmacokinetic parameters showed that C max , CL/F, AUC 0-t , and AUC 0-∞ in the honey group were significantly increased than those in the non-honey group except for ephedrine and pseudoephedrine. The same trend was observed regardless of single or continuous oral administrations. Research studies showed that honey could promote the absorption of some effective components in wu-tou decoction in rats, enhance bioavailability, and provide a theoretical basis for the scientific and rational compatibility of the original prescription., (© 2022 John Wiley & Sons, Ltd.)

Background: Abnormal Cu(II) ions levels may affect many biological functions, and it is of great importance to detect Cu(II) ions in organisms., Methods: Herein, we report a near-infrared (NIR) fluorescent probe EtRh-N-NH 2 for the detection of Cu(II). In the probe structure, a rhodamine core was used, and a hydrazine group was employed as the responsive site. Results & Conlusions: EtRh-N-NH 2 displayed sensitive, specific and fast response upon Cu(II) with excellent linear relationship between the concentration and fluorescence emission intensity in 0-1 μM range. The releasing EtRh-COOH exhibited 762 nm of emission wavelength with a 75 nm of Stokes shift., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s). Published by IMR Press.)

The quantitative detection of different molecular targets is of utmost importance for a variety of human activities, ranging from healthcare to environmental studies. Bioanalytical methods have been developed to solve this and to achieve the quantification of multiple targets from small volume samples. Generally, they can be divided into two different classes: point of care (PoC) and laboratory-based approaches. The former is rapid, low-cost, and user-friendly; however, the majority of the tests are semiquantitative, lacking in specificity and sensitivity. On the contrary, laboratory-based approaches provide high sensitivity and specificity, but the bulkiness of experimental instruments and complicated protocols hamper their use in resource-limited settings. In response, here we propose a smartphone-based device able to support laboratory-based optical techniques directly at the point of care. Specifically, we designed and fabricated a portable microplate reader that supports colorimetric, fluorescence, luminescence, and turbidity analyses. To demonstrate the potential of the device, we characterized its analytical performance by detecting a variety of relevant molecular targets (ranging from antibodies, toxins, drugs, and classic fluorophore dyes) and we showed how the estimated results are comparable to those obtained from a commercial microplate reader. Thanks to its low cost (<$300), portability (27 cm [length] × 18 cm [width] × 7 cm [height]), commercially available components, and open-source-based system, we believe it represents a valid approach to bring high-precision laboratory-based analysis at the point of care.

Surface enhanced Raman scattering (SERS) is a rapid and nondestructive technique that is capable of detecting and identifying chemical or biological compounds. Sensitive SERS quantification is vital for practical applications, particularly for portable detection of biomolecules such as amino acids and nucleotides. However, few approaches can achieve sensitive and quantitative Raman detection of these most fundamental components in biology. Herein, a noble-metal-free single-atom site on a chip strategy was applied to modify single tungsten atom oxide on a lead halide perovskite, which provides sensitive SERS quantification for various analytes, including rhodamine, tyrosine and cytosine. The single-atom site on a chip can enable quantitative linear SERS responses of rhodamine (10 -6 -1 mmol L -1 ), tyrosine (0.06-1 mmol L -1 ) and cytosine (0.2-45 mmol L -1 ), respectively, which all achieve record-high enhancement factors among plasmonic-free semiconductors. The experimental test and theoretical simulation both reveal that the enhanced mechanism can be ascribed to the controllable single-atom site, which can not only trap photoinduced electrons from the perovskite substrate but also enhance the highly efficient and quantitative charge transfer to analytes. Furthermore, the label-free strategy of single-atom sites on a chip can be applied in a portable Raman platform to obtain a sensitivity similar to that on a benchtop instrument, which can be readily extended to various biomolecules for low-cost, widely demanded and more precise point-of-care testing or in-vitro detection., Electronic Supplementary Material: Supplementary material is available for this article at 10.1007/s40843-022-1968-5 and is accessible for authorized users., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (© Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2022.)

The COVID-19 pandemic made clear how our society requires quickly available tools to address emerging healthcare issues. Diagnostic assays and devices are used every day to screen for COVID-19 positive patients, with the aim to decide the appropriate treatment and containment measures. In this context, we would have expected to see the use of the most recent diagnostic technologies worldwide, including the advanced ones such as nano-biosensors capable to provide faster, more sensitive, cheaper, and high-throughput results than the standard polymerase chain reaction and lateral flow assays. Here we discuss why that has not been the case and why all the exciting diagnostic strategies published on a daily basis in peer-reviewed journals are not yet successful in reaching the market and being implemented in the clinical practice.

Hydraulic fracturing is widely applied for economical gas production from shale reservoirs. Still, the swelling of the clay micro/nano pores due to retained fluid from hydraulic fracturing causes a gradual reduction of gas production. Four different gas-bearing shale samples with different mineralogical characteristics were investigated to study the expected shale swelling and reduction in gas permeability due to hydraulic fracturing. To simulate shale softening, these shale samples were immersed in deionized (DI) water heated to 100 °C temperature and subjected to 8 MPa pressure in a laboratory reactor for 72 hours to simulate shale softening. The low-temperature nitrogen adsorption and density measurements were performed on the original and treated shale to determine the changes in micro and nano pore structure. The micro and nano pore structures changed, and the porosity decreased after shale treatment. The porosity decreased by 4% for clayey shale, while for well-cemented shale the porosity only decreased by 0.52%. The findings showed that the initial mineralogical composition of shale plays a significant role in the change of micro and nano pores and the pore structure alteration due to retained fluid from hydraulic fracturing. A pore network model is used to simulate the permeability of shale used in this study. To define pore structure properties, specific factors such as porosity, pore size, pore throat distribution, and coordination number were used. Furthermore, the anisotropy characteristics of shale were integrated into the model via a coordination number ratio. Finally, the change in permeability due to shale softening was determined and compared with untreated with the progress of shale softening. The simulation showed that the permeability of Longmaxi shale could decrease from 3.82E-16 m2 to 4.71E-17 m 2 after treatment., (© 2021. The Author(s).)

Background: Accumulating evidence demonstrates that tRFs (tRNA-derived small RNA fragments) and tiRNAs (tRNA-derived stress-induced RNA), an emerging category of regulatory RNA molecules derived from transfer RNAs (tRNAs), are dysregulated in in various human cancer types and play crucial roles. However, their roles and mechanisms in hepatocellular carcinoma (HCC) and liver cancer stem cells (LCSCs) are still unknown., Methods: The expression of glycine tRNA-derived fragment (Gly-tRF) was measured by qRT-PCR. Flow cytometric analysis and sphere formation assays were used to determine the properties of LCSCs. Transwell assays and scratch wound assays were performed to detect HCC cell migration. Western blotting was conducted to evaluate the abundance change of Epithelial-mesenchymal transition (EMT)-related proteins. Dual luciferase reporter assays and signalling pathway analysis were performed to explore the underlying mechanism of Gly-tRF functions., Results: Gly-tRF was highly expressed in HCC cell lines and tumour tissues. Gly-tRF mimic increased the LCSC subpopulation proportion and LCSC-like cell properties. Gly-tRF mimic promoted HCC cell migration and EMT. Loss of Gly-tRF inhibited HCC cell migration and EMT. Mechanistically, Gly-tRF decreased the level of NDFIP2 mRNA by binding to the NDFIP2 mRNA 3' UTR. Importantly, overexpression of NDFIP2 weakened the promotive effects of Gly-tRF on LCSC-like cell sphere formation and HCC cell migration. Signalling pathway analysis showed that Gly-tRF increased the abundance of phosphorylated AKT., Conclusions: Gly-tRF enhances LCSC-like cell properties and promotes EMT by targeting NDFIP2 and activating the AKT signalling pathway. Gly-tRF plays tumor-promoting role in HCC and may lead to a potential therapeutic target for HCC., (© 2021. The Author(s).)

In this study, the antitoxicity performance of the traditional anaerobic baffled reactor (ABR) and the newly constructed membraneless anaerobic baffled reactor coupled with microbial fuel cell (ABR-MFC) was compared for the treatment of simulated printing and dyeing wastewater under the same hydraulic residence time. The sludge performances of ABR-MFC and ABR were evaluated on the dye removal rate, extracellular polymer (EPS) content, sludge particle size, methane yield, and the surface morphology of granular sludge. It was found that the maximum power density of the ABR-MFC reactor reached 1226.43 mW/m 3 , indicating that the coupled system has a good power generation capacity. The concentration of the EPS in the ABR-MFC reactor was about 3 times that in the ABR, which could be the result of the larger average particle size of sludge in the ABR-MFC reactor than in the ABR. The dye removal rate of the ABR-MFC reactor (91.71%) was higher than that of the ABR (1.49%). The methane production and microbial species in the ABR-MFC system were higher than those in the ABR. Overall, the MFC embedded in the ABR can effectively increase the resistance of the reactor, promote the formation of granular sludge, and improve the performance of the reactor for wastewater treatment., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Aim: The role of TMEM176A methylation in lung cancer and its therapeutic application remains unclear. Materials and methods: Nine lung cancer cell lines and 123 cases of cancer tissue samples were employed. Results: TMEM176A was methylated in 53.66% of primary lung cancer. Restoration of TMEM176A expression induced cell apoptosis and G2/M phase arrest, and inhibited colony formation, cell proliferation, migration and invasion. TMEM176A suppressed H1299 cell xenograft growth in mice. Methylation of TMEM176A activated ERK signaling and sensitized H1299 and H23 cells to AZD0156, an ATM inhibitor. Conclusion: The expression of TMEM176A is regulated by promoter region methylation. Methylation of TMEM176A is a potential lung cancer diagnostic marker and a novel synthetic lethal therapeutic marker for AZD0156.

In this study, we compared the physicochemical properties and starch structures of hybrid rice varieties with similar apparent amylose content but different taste values. In addition to the apparent amylose content, gel permeation chromatography analysis showed that the higher proportions of amylopectin short chains and relatively lower proportions of amylopectin long chains, which could lead to higher peak viscosity and breakdown value, as well as a softer and stickier texture of cooked rice, were the key factors in determining the eating quality of hybrid rice. High-performance anion-exchange chromatography analyses showed that the proportion of amylopectin short chains (degree of polymerization 6-10) and intermediate chains (degree of polymerization 13-24), which might affect the gelatinisation enthalpy and crystallinity, also contributed greatly to the eating quality of hybrid rice. Moreover, this study indicated that a greater diversity of forms and sizes of starch granules might influence the eating quality of hybrid rice., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: Intracranial aneurysms (IA) comprise a multifactorial disease with unclear physiological mechanisms. The lysyl oxidase ( LOX ) family genes ( LOX , LOX-like 1-4 ) plays important roles in extracellular matrix (ECM) reconstruction and has been investigated in terms of susceptibility to IA in a few populations. We aimed to determine whether polymorphisms in LOX family genes are associated with susceptibility to IA in a Chinese population., Methods: This case-control study included 384 patients with IA and 384 healthy individuals without IA (controls). We genotyped 27 single nucleotide polymorphisms (SNPs) of LOX family genes using the Sequenom MassARRAY ® platform. These SNPs were adjusted for known risk factors and then, odds ratios (OR) and 95% confidence intervals (CI) were evaluated using binary logistic regression analysis., Results: The result showed that LOX rs10519694 was associated with the risk of IA in recessive (OR, 3.88; 95% CI, 1.12-13.47) and additive (OR, 1.56; 95%CI, 1.05-2.34) models. Stratified analyses illustrated that LOX rs10519694 was associated with the risk of single IA in the recessive (OR, 3.95; 95%CI, 1.04-15.11) and additive (OR, 1.64; 95%CI, 1.04-2.56) models. The LOXL2 rs1010156 polymorphism was associated with multiple IA in the dominant model (OR, 1.92; 95%CI, 1.02-3.62). No associations were observed between SNPs of LOXL1 , LOXL3 , and LOXL4 and risk of IA., Conclusion: LOX and LOXL2 polymorphisms were associated with risk of single IA and multiple IA in a Chinese population, suggesting potential roles of these genes in IA. The effects of these genes on IA require further investigation., 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 © 2021 Luo, Hu, Li, Liu, Hu, Dong, Liao, Zhou, Xu, Liu, Li, Yuan, Jiang and Yan.)

The development of embryo sacs is crucial for seed production in plants, but the genetic basis regulating the meiotic crossover formation in the macrospore and microspore mother cells remains largely unclear. Here, we report the characterization of a spontaneous rice female sterile variation 1 mutant (fsv1) that showed severe embryo sacs abortion with low seed-setting rate. Through map-based cloning and functional analyses, we isolated the causal gene of fsv1, OsMLH3 encoding a MutL-homolog 3 protein, an ortholog of HvMLH3 in barley and AtMLH3 in Arabidopsis. OsMLH3 and OsMLH1 (MutL-homolog 1) interact to form a heterodimer (MutLγ) to promote crossover formation in the macrospore and microspore mother cells and development of functional megaspore during meiosis, defective OsMLH3 or OsMLH1 in fsv1 and CRISPR/Cas9-based knockout lines results in reduced type I crossover and bivalent frequency. The fsv1 and OsMLH3-knockout lines are valuable germplasms for development of female sterile restorer lines for mechanized seed production of hybrid rice., (© 2021 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

Water is the most important ingredient of life. Water fecal pollution threatens water quality worldwide and has direct detrimental effects on human health and the global economy. Nowadays, assessment of water fecal pollution relies on time-consuming techniques that often require well-trained personnel and highly-equipped laboratories. Therefore, faster, cheaper, and easily-used systems are needed to in situ monitor water fecal pollution. Herein, we have developed colorimetric lateral flow strips (LFS) able to detect and quantify Escherichia coli species in tap, river, and sewage water samples as an indicator of fecal pollution. The combination of LFS with a simple water filtration unit and a commercially available colorimetric reader enhanced the assay sensitivity and enabled more accurate quantification of bacteria concentration down to 104 CFU mL-1 in 10 minutes, yielding recovery percentages between 80% and 90% for all water samples analyzed. Overall, this system allows for monitoring and assessing water quality based on E. coli species as a standard microbiological indicator of fecal pollution. Furthermore, we have developed a novel bioluminescent, bacteria-based method to quickly characterize the performance of a great variety of LFS materials. This new method allows evaluating the flow rate of big analytes such as bacteria through the LFS materials, as a suggestive means for selecting the appropriate materials for fabricating LFS targeting big analytes (≈2 μm). As a whole, the proposed approach can accelerate and reduce the costs of water quality monitoring and pave the way for further improvement of fecal pollution detection systems.

Epidermal growth factor receptor (EGFR) is the most attractive target for drug research in non-small cell lung cancer (NSCLC). The first-generation EGFR tyrosine kinase inhibitors (TKIs) Gefetinib and Elotinib showed good clinical efficacy on lung adenocarcinoma tumors, but almost all patients developed resistance to these inhibitors over time. Quinazoline and quinoline derivatives are common targeted inhibitors of EGFR kinase, and their structural optimization is an important direction for the development of effective targeted anticancer drugs. Based on these facts, a series of heterocyclic 2,3-dihydro-[1,4]dioxino[2,3-f]quinazoline derivatives have been designed and synthesized and their structures were confirmed by spectral analyses. The cytotoxic activity of the newly synthesized compounds was evaluated against the human kidney epithelial T293 cell line, normal lung cell lines WI-38, non-small cell lung cancer A549 and NCI-H157 cell lines using MTT. The tested compounds showed an evident anticancer activity against the tested cell lines, especially compound 13c, which was the most potent anticancer agent with half maximal inhibitory concentrations (IC 50 ) between 8.82 and 10.24 μM. Docking study showed that compound 13b could be nicely bound to the ATP binding pocket of EGFR. In addition, the inhibitory activity of the target compounds against epidermal growth factor receptor tyrosine kinase (EGFR-TK) was evaluated. Results indicated the ability of the target compounds to inhibit EGFR-TK with half maximal inhibitory concentrations (IC 50 ) in the range of 10.29 nM to 652.3 nM. In view of the reported compound activity, the structure deserves further optimization as cancer treatment agents., (Copyright © 2021. Published by Elsevier Inc.)

The permeability of shale is a significant and important design parameter for shale gas extraction. The shale gas permeability is usually obtained based on Darcy flow using standard laboratory permeability tests done on core samples, that do not account for different transport mechanisms at high pressures and anisotropic effects in shales due to nano-scale pore structure. In this study, the permeability of shale is predicted using a pore network model. The characteristics of pore structure can be described by specific parameters, including porosity, pore body and pore throat sizes and distributions and coordination numbers. The anisotropy was incorporated into the model using a coordination number ratio, and an algorithm that was developed for connections of pores in the shale formation. By predicting hydraulic connectivity and comparing it with several high-pressure permeability tests, the proposed three-dimensional pore network model was verified. Results show that the prediction from the anisotropic pore network model is closer to the test results than that based on the isotropic pore network model. The predicted permeability values from numerical simulation using anisotropic pore network model for four shales from Qaidam Basin, China are quite similar to those measured from laboratory tests. This study confirmed that the developed anisotropic three-dimensional pore network model could reasonably represent the natural gas flow in the actual shale formation so that it can be used as a prediction tool.

Recently, many bioluminescence-based applications have arisen in several fields, such as biosensing, bioimaging, molecular biology, and human health diagnosis. Among all bioluminescent organisms, Aliivibrio fischeri (A. fischeri) is a bioluminescent bacterium used to carry out water toxicity assays since the late 1970s. Since then, several commercial A. fischeri-based products have been launched to the market, as these bacteria are considered as a gold standard for water toxicity assessment worldwide. However, the aforementioned commercial products rely on expensive equipment, requiring several reagents and working steps, as well as high-trained personnel to perform the assays and analyze the output data. For these reasons, in this work, we have developed for the first time a mobile-phone-based sensing platform for water toxicity assessment in just 5 min using two widespread pesticides as model analytes. To accomplish this, we have established new methodologies to enhance the bioluminescent signal of A. fischeri based on the bacterial culture in a solid media and/or using graphene oxide. Finally, we have addressed the biocompatibility of graphene oxide to A. fischeri, boosting the sensitivity of the toxicity assays and the bacterial growth of the lyophilized bacterial cultures for more user-friendly storage., (Copyright © 2020 Elsevier B.V. All rights reserved.)