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Ethnopharmacological Relevance: Cholestatic liver disease (CLD) is a disease characterized by cholestasis. Farnesoid X receptor (FXR) is a nuclear receptor that maintains homeostasis in bile acid metabolism. Studies have shown that gut microbiota interfered with the FXR pathway. Modulation of FXR to inhibit cholestasis has become a key measure in the treatment of CLD. In traditional folk medicine, Desmodium styracifolium (Osb.) Merr. was used as a primary treatment for gallstones, gonorrhea, jaundice, cholecystitis and other diseases. Modern pharmacological studies had also found that the herb has anti-calculus, anti-inflammatory, antioxidant, diuretic and liver damage. Therefore, we speculated that Desmodium styracifolium (Osb.) Merr. extracts (DME) could alleviate CLD through the FXR pathway and might be associated with the gut microbiota. However, studies of DME alleviating CLD through the FXR pathway have not been reported., Aim of Study: To study the effect and mechanism of DME in relieving CLD through in vivo and in vitro experiments., Materials and Methods: First, mice were administrated with alpha-naphthyl isothiocyanate (ANIT) to establish a CLD model in vivo. Meanwhile, HepG2 cells were induced by lithocholic acid (LCA) to establish the CLD model in vitro. To evaluate the therapeutic effect of DME on CLD mice, hematoxylin-eosin (HE) staining, and biochemical indicators were performed. The prototype of the blood components in mice serum was detected by ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). 16S rDNA sequencing was used to analyze the gut microbiota. Finally, the protein and mRNA expression of the FXR pathway in mice liver tissues or HepG2 cells were detected by Western blot, qRT-PCR, or immunofluorescence., Results: Pathological testing and biochemical indexes showed that DME significantly reduced serum ALT, AST, ALP, TBIL, DBIL, TBA and liver TBA levels, and attenuated liver tissue injury, necrosis and jaundice in CLD mice. In addition, MetagenomeSeq analysis of gut microbiota showed that DME significantly up-regulated the abundance of Parvibacter, down-regulated the abundance of Paenalcaligenes, and regulated bile acid homeostasis. In terms of mRNA expression, DME significantly upregulated the mRNA levels of Nr1h4, Abcb11, Cyp7a1 and Slc10a1. Meanwhile, in terms of protein expression, DME significantly up-regulated the protein expression levels of FXR, BSEP, CYP7A1 and NTCP, which regulated bile acid homeostasis. Finally, the molecular docking results showed that the components of DME, such as Lumichrome, Daidzein and Folic acid, all had good binding ability with FXR, and the surface plasmon resonance (SPR) results also showed that both Lumichrome and Daidzein had a relatively high affinity with FXR., Conclusion: DME alleviated CLD through the FXR pathway, and the mechanisms might be associated with the gut microbiota., 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.)

Zwitterionic peptides, as a type of peptide composed of charged residues, are electrically neutral, which combine the advantages of zwitterionic materials and biological peptides, exhibiting hydrophilicity and programmable properties. As attractive candidates for resisting nonspecific adsorption of biomacromolecules and microorganisms, zwitterionic peptides have been applied in materials science, biomedicine, and biochemistry over the past decade. In this review, the development of zwitterionic peptides has been systematically outlined and analyzed, including their mechanisms, structure-function relationships, and design strategies. Furthermore, this review emphasizes and discusses their recent applications for developing functional coatings, biosensors, drug delivery systems, and engineering proteins. Finally, future research perspectives and challenges of zwitterionic peptides are also prospected and discussed. This review is intended to provide clarity and insight into the design and applications of zwitterionic peptides.

Efficient utilization of agricultural wastes and reduction of chemical fertilizer inputs are crucial for sustainable development of agriculture. Plant growth promoting rhizobacteria (PGPR) are widely used as biofertilizers to partially replace chemical fertilizers in agricultural production. The functional performance of PGPR strains is closely related to their root colonization capacity. Some organic acids from root exudates can recruit PGPR to colonize the root. In this study, agricultural organic wastes such as mushroom bran and tobacco waste materials were used to produce organic acids through the hypoxic hydrolysis process. The hydrolysis conditions were optimized to maximize the production of a mixture of complex organic acids from the hypoxic hydrolysis of these materials, employing both single-factor and orthogonal experimental methods. The diluted hydrolysates were tested for their effects on the rhizosphere colonization of the PGPR strain Bacillus amyloliquefaciens SQR9 using fluorogenic quantitative PCR in greenhouse pot experiments. The results demonstrated that hypoxic hydrolysates from tobacco waste and mushroom bran significantly enhanced the colonization of SQR9 in the maize rhizosphere. Specifically, a 2000-fold dilution of tobacco waste hydrolysate yielded the most effective result, while a 5000-fold dilution of mushroom bran hydrolysate provided the best outcome. All treatments combining these hydrolysates with SQR9 significantly increased maize stem dry weight, indicating that with appropriate treatment, such as anaerobic fermentation, these agricultural organic wastes can serve as synergistic agents of microbial fertilizers, contributing to agricultural sustainability., 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 © 2024 Xu, Wang, Wang, Tian, Yue, Li, Wang, Zhang and Zhang.)

Atomically thin transition metal dichalcogenides (TMDs) with ambient stable exciton resonances have emerged as an ideal material platform for exciton-polaritons. In particular, the strong coupling between excitons in TMDs and optical resonances in anisotropic photonic nanostructures can form exciton-polaritons with polarization selectivity, which offers a new degree of freedom for the manipulation of the light-matter interaction. In this work, we present the experimental demonstration of polarization-controlled exciton-polaritons in tungsten disulfide (WS 2 ) strongly coupled with polarization singularities in the momentum space of low-symmetry photonic crystal (PhC) nanostructures. The utilization of polarization singularities can not only effectively modulate the polarization states of exciton-polaritons in the momentum space but also facilitate or suppress their far field coupling capabilities by tuning the in-plane momentum. Our results provide new strategies for creating polarization-selective exciton-polaritons.

Owing to their strong exciton effects and valley polarization properties, monolayer transition-metal dichalcogenides (1L TMDs) have unfolded the prospects of spin-polarized light-emitting devices. However, the wavefront control of exciton emission, which is critical to generate structured optical fields, remains elusive. In this work, the experimental demonstration of spin-locked vortex emission from monolayer Tungsten Disulfide (1L WS 2 ) integrated with Silicon Nitride (SiN x ) PhC slabs is presented. The symmetry-protected bound states in the continuum (BIC) in the SiN x PhC slabs engender azimuthal polarization field distribution in the momentum space with a topological singularity in the center of the Brillouin zone, which imposes the resonantly enhanced WS 2 exciton emission with a spin-correlated spiral phase front by taking advantage of the winding topologies of resonances with the assistance of geometric phase scheme. As a result, exciton emission from 1L WS 2 exhibits helical wavefront and doughnut-shaped intensity beam profile in the momentum space with topological charges locked to the spins of light. This strategy on spin-dependent excitonic vortex emission may offer the unparalleled capability of valley-polarized structured light generation for 1L TMDs., (© 2024 Wiley‐VCH GmbH.)

Litter and root decomposition is an important source of soil organic matter and nutrients. To ascertain the contribution of litter and root to natural grassland nutrients in rocky desertification areas, from March 2017 to January 2018, the continuous soil column method, collector method, and litter decomposition method were used to study the soil nutrients, litter and root biomass, decomposition, and nutrient release of potential, moderate, and severe rocky desertification grasslands, as well as their responses to rocky desertification. The results showed that the litter and root decomposition rate showed a trend of being first fast and then slow, and the decomposition rate of litter and root was greater than 50% after 300 days. The annual litter decomposition rates of potential, moderate, and severe rocky desertification grasslands were 69.98%, 62.14%, and 49.79%, respectively, and the annual decomposition rates of root were 73.64%, 67.61%, and 64.09%, respectively. With a deepening degree of rocky desertification, the litter and root decomposition rate decreased. The decomposition coefficients, k , of litter in potential, moderate, and severe rocky desertification grasslands were 1.128, 0.896, and 0.668, respectively, and the decomposition coefficients, k , of root were 1.152, 1.018, and 0.987, respectively. The nutrient release processes of litter and root were different, and the release mode ultimately manifests as "release". In rocky desertification grasslands, the organic carbon (OC), total nitrogen (TN), total phosphorus (TP), and total potassium (TK) released by litter and root decomposition were 18.93-263.03 g·m -2 ·yr -1 , 1.79-5.59 g·m -2 ·yr -1 , 0.18-0.47 g·m -2 ·yr -1 , and 0.66-3.70 g·m -2 ·yr -1 , respectively. The contribution of root to soil nutrients was greater than that of litter. The degree of rocky desertification was negatively correlated with the biomass, decomposition rate, and nutrient return amount of litter and root. The results of this study provide direct field evidence and illustrate the contribution of litter and root decomposition in rocky desertification grasslands to soil nutrients.

Dielectric phase gradient metasurfaces have emerged as promising candidates to shrink bulky optical elements to subwavelength thickness scale based on dielectric meta-atoms. These meta-atoms strongly interact with light, thus offering excellent phase manipulation of incident light. However, to fulfill 2π phase control using meta-atoms, the metasurface thickness, to date, is limited to the order of 10 2 nm. Here, we present the thickness scaling down of phase gradient metasurfaces to <λ/20 by using excitonic van der Waals metasurfaces. High-refractive-index enabled by exciton resonances and symmetry-breaking nanostructures in the patterned layered tungsten disulfide (WS 2 ) corporately enable quasibound states in the continuum in WS 2 metasurfaces, which consequently yield complete phase regulation of 2π with the thickness down to 35 nm. To illustrate the concept, we have experimentally demonstrated beam steering, focusing, and holographic display using WS 2 metasurfaces. We envision our results unveiling new venues for ultimate thin phase gradient metasurfaces.

Conjugation to a carrier protein is essential to give rise to the antigenicity of hapten. Three carrier proteins e.g. KLH (Keyhole Limpet hemocyanin), BSA (bovine serum albumin), and OVA (Ovalbumin) were used mostly. KLH is advantageous to the others, majorly owing to its strong immunogenicity and limited usage in other biological assays. However, the cost of obtaining Keyhole Limpet is high and the solubility of KLH is not as well as the other carriers, especially after hapten conjugation. Here, we extracted the shrimp hemocyanin (SHC) from Litopenaeus vannamei (L. vannamei), which is a commonly sea product worldwide. The high pure SHC could be acquired by two-step purification, with a production yield of > 1 g proteins (98% pure) per 1 kg shrimp. Compared to KLH, the peptide-SHC conjugates exhibit higher solubility after hapten conjugation. Meanwhile, compared with KLH, SHC induces comparable antibody production efficiency in mammals, with or without conjugation. Furthermore, rabbit polyclonal antibodies or mouse monoclonal antibodies were generated by immunizing SHC-peptide conjugates, and the subsequent antibodies were confirmed to be used in western blot, immunofluorescence and immunohistochemistry. Therefore, we demonstrated that SHC may be used as a substitute for KLH in future antibody and vaccine development., (© 2024. The Author(s).)

Atomically thin transition metal dichalcogenides (TMDS) offer a promising route to the scaling down of optoelectronic devices to the ultimate thickness limit. But the weak light-matter interaction caused by their atomically thin nature makes them inevitably rely on external photonic structures to enhance optical absorption. Here, we report chiral absorption enhancement in atomically thin tungsten diselenide (WSe 2 ) using chiral resonances in photonic crystal (PhC) nanostructures patterned directly in WSe 2 itself. We show that the quality factors (Q factors) of the resonances grow exponentially as the PhC thickness approaches atomic limit. As such, the strong interaction of high Q factor photonic resonance with the coexisting exciton resonance in WSe 2 results into self-coupled exciton-polaritons. By balancing the light coupling and absorption rates, the incident light can critically couple to chiral resonances in WSe 2 PhC exciton-polaritons, leading to the theoretically limited 50% optical absorptance with over 84% circular dichroism (CD).

Purpose: Membrane associated ubiquitin ligase MARCH2 majorly involves in inflammation response and protein trafficking. However, its comprehensive role in hepatocellular carcinoma (HCC) is largely unknown., Methods: Firstly, multiple bioinformatic analyses were applied to determine MARCH2 mRNA level, its expression comparison in diverse molecular and immune subtypes, and diagnostic value in HCC. Subsequently, RNA-seq, real-time quantitative PCR, immunohistochemistry and cell proliferation assay are used to explore the epithelial-mesenchymal transition (EMT) and proliferation by gene-silencing or overexpressing in cultured HCC cells or in vivo xenograft. Moreover, dual luciferase reporter assay and immunoblotting are delved into verify the transcription factor that activating MARCH2 promoter., Results: Multiple bioinformatic analyses demonstrate that MARCH2 is upregulated in multiple cancer types and exhibits startling diagnostic value as well as distinct molecular and immune subtypes in HCC. RNA-seq analysis reveals MARCH2 may promote EMT, cell proliferation and migration in HepG2 cells. Furthermore, overexpression of MARCH2 triggers EMT and significantly enhances HCC cell migration, proliferation and colony formation in a ligase activity-dependent manner. Additionally, above observations are validated in the HepG2 mice xenografts. For up-stream mechanism, transcription factor KLF15 is highly expressed in HCC and activates MARCH2 expression., Conclusion: KLF15 activated MARCH2 triggers EMT and serves as a fascinating biomarker for precise diagnosis of HCC. Consequently, MARCH2 emerges as a promising candidate for target therapy in cancer management., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Curcumin demonstrated therapeutic potential for cancer. However, its medical application is limited due to low solubility, poor stability and low absorption rate. Here, we used the mussel-inspired functional protein (MPKE) to fabricate the curcumin-carrying nanoparticle (Cur-MPKE) for encapsulating and delivering curcumin. The protein MPKE is composed of the mussel module and zwitterionic peptide. The Dopa group bonding characteristic of the mussel module was leveraged for the self-assembly of nanoparticles, while the superhydrophilic property of the zwitterionic peptide was utilized to enhance the stability of nanoparticles. As expected, MPKE and Cur are tightly bound through hydrogen bonds and dynamic imide bonds to form nanoparticles. Cur-MPKE showed improved solubility and stability in aqueous solutions as well as excellent biocompatibility. Besides, Cur-MPKE also exhibited pH-triggered release and enhanced uptake of curcumin by tumor cells, promoting the antioxidant activity and antitumor effect of curcumin. Moreover, systemic experiments of Cur-MPKE to rats demonstrated that Cur-MPKE significantly inhibited tumor tissue growth and proliferation without causing obvious systemic toxicity. This work provides a new strategy for fabricating the delivery system of curcumin with improved stability, sustainability and bioavailability., 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.)

The formation of high-quality Chinese medicinal materials is a micro-evolutionary process of multiple genes involving quantitative inheritance under environmental stress. Atractylodes lancea is a traditionally used medicinal plant in China that is broadly distributed and possesses a considerable amount of essential oils. However, to date, limited research has been conducted to characterize the genetics and metabolites of A. lancea shaped by natural variation. Hence, we assembled a high-quality genome of A. lancea , featuring a contig N50 of 1.18 Mb. We further integrated population resequencing of A. lancea and conducted analyses to characterize its genetic diversity, population evolution, and rewiring of volatile metabolites. The natural variation effect exerted significant pressure on A. lancea from different geographic locations, resulting in genetic differentiation among three groups. Correlation analysis of metabolites in A. lancea revealed significant natural variations of terpenoids, heterocyclic compounds, ketones, and esters. We also found that 427 metabolites displayed noteworthy divergence due to directional selection. Additionally, our genome-wide association studies on the metabolome for medicinal quality traits identified several candidate genes, such as AlZFP706 and AlAAHY1 , exhibiting significant correlations with atractylodin and hinesol levels, respectively. Overall, this study provides an intricate genomic resource for A. lancea , thereby expanding our understanding of the effect of natural variation on metabolites and facilitating the genetic improvement of its medicinal properties., Competing Interests: The authors declare that there are no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nanjing Agricultural University.)

The occurrence of excitotoxic damage caused by cerebral ischemia-reperfusion (I/R) injury is closely linked to a decrease in central inhibitory function, in which the concentration of chloride inside the cells ([Cl-] i ) plays a crucial role. The outflow and inflow of [Cl-] i are controlled by KCC2 and NKCC1, which are cellular cotransporters for K+/Cl- and Na+/K+/Cl-, respectively. NKCC1/KCC2 is regulated by upstream regulators such as SPAK and OSR1, whose activity is influenced by I/R. Sevoflurane is the most commonly used and controversial general anesthetic. To elucidate the impact of sevoflurane on cerebral ischemia-reperfusion (I/R) injury and its underlying mechanism, we investigated its influence on cognitive function and the mechanism of action utilizing a rat model of I/R. By activating the kinase Spak/OSR1, we discovered that I/R damage enhanced the function of NKCC1 and inhibited the function of KCC2, which triggered an imbalance of [Cl-]i concentration, leading to neurological dysfunction and cognitive dysfunction. At the beginning of reperfusion, administration of 1.3 MAC sevoflurane for 3 h increased activation of Spak/OSR1 kinases on day 7 post-perfusion, resulting in an additional dysregulation of NKCC1 and KCC2 activity, which disappeared on day 14. Administration of Closantel, a Spak/OSR1 kinase inhibitor, to animals treated with sevoflurane reverses the additional stimulation. The research revealed that sevoflurane modified the functioning of NKCC1 and KCC2, resulting in cognitive decline by activating Spak/OSR1 kinase. However, this issue could be resolved by inhibiting Spak/OSR1. The research revealed that sevoflurane transiently alters the function of NKCC1 and KCC2, resulting in exacerbating cognitive decline. However, this can be fixed by suppressing Spak/OSR1., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Minimizing the emission of arsenic (As) is one of the urgent problems during co-gasification of Shenmu coal (SM) and sewage sludge (SS). The intrinsic mechanism of As retention was obtained by analyzing the effect of different SM addition ratios on the As form transformation during co-gasification at 1000 °C under CO 2 atmosphere. The results showed that the addition of SM effectively promoted the enrichment of As in the co-gasified residues. Especially, the best As retention rate of 65.71% was achieved with the 70 wt% addition ratio of SM. The addition of SM promoted the adsorption and chemical oxidation of As(III) to the less toxic As(V) through the coupling of Ca and Fe compounds in the co-gasified residues. XRD and XPS results indicated that Fe 2 O 3 adsorbed As 2 O 3 (g) after partial conversion to Fe 3 O 4 by the Boudouard reaction, while part of As 2 O 3 was oxidized to As 2 O 5 by lattice oxygen. Finally, the generated As 2 O 5 was successively trapped by CaO and Fe 2 O 3 to form stable Ca 3 (AsO 4 ) 2 and FeAsO 4 . HRTEM and TEM analysis comprehensively proved that As(III) was stabilized by the lattice cage of CaAl 2 Si 2 O 8 . In conclusion, the co-oxidation of Ca and Fe compounds and lattice stabilization simultaneously played a crucial role in the retention of As 2 O 3 (g) during co-gasification., 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.)

Atractylodes lancea is a perennial herb whose rhizome (AR) is a valuable traditional Chinese medicine with immense market demand. The cultivation of Atractylodes lancea faces outbreaks of root rot and deterioration in herb quality due to complex causes. Here, we investigated the effects of Trichoderma spp., well-known biocontrol agents and plant-growth-promoters, on ARs. We isolated Trichoderma strains from healthy ARs collected in different habitats and selected three T . harzianum strains (Th2, Th3 and Th4) with the strongest antagonizing effects on root rot pathogens ( Fusarium spp.). We inoculated geo-authentic A . lancea plantlets with Th2, Th3 and Th4 and measured the biomass and quality of 70-day-old ARs. Th2 and Th3 promoted root rot resistance of A . lancea . Th2, Th3 and Th4 all boosted AR quality: the concentration of the four major medicinal compounds in ARs (atractylon, atractylodin, hinesol and β-eudesmol) each increased 1.6- to 18.2-fold. Meanwhile, however, the yield of ARs decreased by 0.58- to 0.27-fold. Overall, Th3 dramatically increased the quality of ARs at a relatively low cost, namely lower yield, showing great potential for practical application. Our results showed selectivity between A. lancea and allochthonous Trichoderma isolates, indicating the importance of selecting specific microbial patches for herb cultivation.

Purpose: The objective of this paper is to offer a thorough examination of the clinical presentations, etiology, and treatment strategies associated with perivascular epithelioid cell tumors (PEComas)., Methods: This retrospective study examined the comprehensive archival data of PEComa cases diagnosed at Beijing Hospital from 2015 to 2023. The pathology slides of all patients were thoroughly reassessed by two experienced pathologists. A thorough retrospective analysis was undertaken, incorporating clinicopathological data including gender, age at diagnosis, initial clinical manifestations, signs, disease onset site, tumor markers, imaging findings, therapeutic modalities, pathological features, immunohistochemical profiles, treatment responses, and prognostic indicators. Patients were evaluated for disease severity according to established pathological classification criteria and were followed up until the designated analysis cut-off date. In instances where patients were unable to be monitored on-site, they were contacted via telephone for postoperative follow-up inquiries., Results: This study included 11 patients with ages ranging from 17 to 66 years old, presenting with the disease in multiple anatomical sites, including the retroperitoneum (2/11), liver (4/11), kidney (4/11), lung (1/11), and broad ligament of the uterus (1/11). Most patients presented with non-specific clinical symptoms and were subsequently diagnosed with space-occupying lesions upon physical examination. The tumor demonstrated progressive growth and enlargement, which could result in compression of neighboring organs. Preoperative imaging alone is insufficient for a definitive diagnosis of PEComa, but MRI can provide an initial evaluation of the tumor's potential malignancy. Molecular marker testing specific to PEComa, such as HMB-45 (90.0%), SMA (81.8%), Melan-A (90.9%), vimentin (90.9%), and Desmin (36.3%), was conducted on all patients. No adjuvant therapies were administered postoperatively. Upon analysis, no instances of relapse at the primary site or the development of new tumors at other sites were observed. Regular imaging reviews of three patients with malignant PEComa post-surgery showed no evidence of recurrence., Conclusions: The clinical presentation, tumor biomarkers, and imaging characteristics of PEComa lack specificity, necessitating dependence on pathology and immunohistochemistry for precise diagnosis. The mainstay of treatment consists of surgical resection, with patients typically experiencing a favorable prognosis., (© 2024. The Author(s).)

This study aimed to explore the role of the two-component system Bae SR in the mechanism of drug resistance in carbapenem-resistant A. baumannii (CRAB) using molecular docking and real-time polymerase chain reaction (PCR). The two-component system Bae SR of Acinetobacter baumannii was subjected to molecular docking with imipenem, meropenem, and levofloxacin. Antibacterial assays and fluorescence quantitative PCR were used to explore protein-ligand interactions and molecular biological resistance mechanisms related to CRAB. The analysis of the two-component system in A. baumannii revealed that imipenem exhibited the highest docking energy in Bae S at - 5.81 kcal/mol, while the docking energy for meropenem was - 4.92 kcal/mol. For Bae R, imipenem had a maximum docking energy of - 4.28 kcal/mol, compared with - 4.60 kcal/mol for meropenem. The highest binding energies for Bae S-levofloxacin and Bae R-levofloxacin were - 3.60 and - 3.65 kcal/mol, respectively. All imipenem-resistant strains had minimum inhibitory concentration (MIC) values of 16 µg/mL, whereas levofloxacin-resistant strains had MIC values of 8 µg/mL. The time-sterilization curve showed a significant decrease in bacterial colony numbers at 2 h under the action of 8 µg/mL imipenem, indicating antibacterial effects. In contrast, levofloxacin did not exhibit any antibacterial activity. Fluorescence quantitative PCR results revealed significantly increased relative expression levels of bae S and bae R genes in the CRAB group, which were 2 and 1.5 times higher than those in the CSAB group, respectively, with statistically significant differences. Molecular docking in this study found that the combination of Bae SR and carbapenem antibiotics (imipenem, meropenem) exhibited stronger affinity and stability compared with levofloxacin. Moreover, the overexpression of the two-component system genes in carbapenem-resistant A. baumannii enhanced its resistance to carbapenem, providing theoretical and practical insights into carbapenem resistance in respiratory tract infections caused by A. baumannii., (© 2024. The Author(s).)

Human-Object Interaction (HOI), as an important problem in computer vision, requires locating the human-object pair and identifying the interactive relationships between them. The HOI instance has a greater span in spatial, scale, and task than the individual object instance, making its detection more susceptible to noisy backgrounds. To alleviate the disturbance of noisy backgrounds on HOI detection, it is necessary to consider the input image information to generate fine-grained anchors which are then leveraged to guide the detection of HOI instances. However, it has the following challenges. i) how to extract pivotal features from the images with complex background information is still an open question. ii) how to semantically align the extracted features and query embeddings is also a difficult issue. In this paper, a novel end-to-end transformer-based framework (FGAHOI) is proposed to alleviate the above problems. FGAHOI comprises three dedicated components namely, multi-scale sampling (MSS), hierarchical spatial-aware merging (HSAM) and task-aware merging mechanism (TAM). MSS extracts features of humans, objects and interaction areas from noisy backgrounds for HOI instances of various scales. HSAM and TAM semantically align and merge the extracted features and query embeddings in the hierarchical spatial and task perspectives in turn. In the meanwhile, a novel training strategy Stage-wise Training Strategy is designed to reduce the training pressure caused by overly complex tasks done by FGAHOI. In addition, we propose two ways to measure the difficulty of HOI detection and a novel dataset, i.e., HOI-SDC for the two challenges (Uneven Distributed Area in Human-Object Pairs and Long Distance Visual Modeling of Human-Object Pairs) of HOI instances detection. Experiments are conducted on three benchmarks: HICO-DET, HOI-SDC and V-COCO. Our model outperforms the state-of-the-art HOI detection methods, and the extensive ablations reveal the merits of our proposed contribution.

To explore the population structures and dynamics of Rhododendron shrub communities at different stages of succession in northwest Guizhou, China, this study examined the populations of Rhododendron annae and Rhododendron irroratum shrub with two different stages. A space-for-time substitution was employed to establish the diameter class/height structures, static life tables, and survival/mortality rate/disappearance rate curves of both Rhododendron populations with different orders of succession. Their structural and quantitative dynamics were analyzed, and their development trends were predicted. The results showed that, quantitatively, the populations of R. annae and R. irroratum in the two Rhododendron communities with different orders of succession were dominated by age classes one, two, and three as well as height classes i, ii, and iii. The number of Rhododendron plants at the three age classes and the three height classes accounted for 97.61-100% of the total. The quantitative dynamic indices of R. annae and R. irroratum were both greater than 0, with and without considering external interference. In terms of age class and height structures, both Rhododendron populations were expanding populations, presenting "inverted-J-shaped" and irregular pyramid patterns. There was a sufficient number of young individuals, but few or no old individuals. Both survival curves of the populations of R. annae and R. irroratum in the two Rhododendron communities with different orders of succession belonged to the Deevy-II type. In the late stage of succession, the mortality curves and disappearance curves of both Rhododendron populations in these communities presented a trend of increasing first and then decreasing with increasing age class. This result indicates that at each age class, R. annae and R. irroratum showed a trend of gradual increase after two, four, and six years. In brief, the populations of R. annae and R. irroratum have rich reserves of seedlings and saplings, but high mortality and disappearance rates. In this context, it is necessary to reduce human interference and implement targeted conservation measures to promote the natural renewal of Rhododendron populations.

A multifunctional microwave absorber with high thermal conductivity for 5G base station packaging comprising silylated GO/FeSiAl epoxy composites were fabricated by a simple solvent-handling method, and its microwave absorption properties and thermal conductivity were presented. It could act as an applicable microwave absorber for highly integrated 5G base station packaging with 5G antennas within a range of operating frequency of 2.575-2.645 GHz at a small thickness (2 mm), as evident from reflection loss with a maximum of -48.28 dB and an effective range of 3.6 GHz. Such a prominent microwave absorbing performance results from interfacial polarization resonance attributed to a nicely formed GO/FeSiAl interface through silylation. It also exhibits a significant enhanced thermal conductivity of 1.6 W/(mK) by constructing successive thermal channels.

Introduction: Atractylodes lancea is widely distributed in East Asia, ranging from Amur to south-central China. The rhizome of A. lancea is commonly used in traditional Chinese medicine, however, the quality of products varies across different regions with different geochemical characteristics., Method: This study aimed to identify the chemotypes of A. lancea from different areas and screen for chemical markers by quantifying volatile organic compounds (VOCs) using a targeted metabolomics approach based on GC-MS/MS., Results: The A. lancea distributed in Hubei, Anhui, Shaanxi, and a region west of Henan province was classified as the Hubei Chemotype (HBA). HBA is characterized by high content of β-eudesmol and hinesol with lower levels of atractylodin and atractylon. In contrast, the Maoshan Chemotype (MA) from Jiangsu, Shandong, Shanxi, Hebei, Inner Mongolia, and other northern regions, exhibited high levels of atractylodin and atractylon. A total of 15 categories of VOCs metabolites were detected and identified, revealing significant differences in the profiles of terpenoid, heterocyclic compound, ester, and ketone among different areas. Multivariate statistics indicated that 6 compounds and 455 metabolites could serve as candidate markers for differentiating A. lancea obtained from the southern, northern, and Maoshan areas., Discussion: This comprehensive analysis provides a chemical fingerprint of selected A. lancea . Our results highlight the potential of metabolite profiling combined with chemometrics for authenticating the geographical origin of A. lancea ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Wang, Lyu, Wang, Sun, Zhang, Xiang, Guo, Wang, Qin, Wang and Guo.)

Optimal fertilization is an important measure for managing cultivated grasslands, and a necessary means for maintaining the nutrient balance, yield, and quality of grassland ecosystems. This study aimed to explore the effects of organic fertilizers on the production performance and nutritional quality of cultivated grasslands in karst areas. Two types of monocultured cultivated grasslands (i.e., Medicago sativa and Dactylis glomerata ) were employed as the research objects, and a randomized block design was adopted to investigate the effects of five fertilization gradients on the forage height, coverage, yield, and nutritional quality of the cultivated grasslands. According to the results, the plant height, coverage, and yield of M. sativa first presented an increasing trend, then decreased with increasing fertilization gradient, with a peak at 20-30 t/hm 2 fertilization gradient. The height, coverage, and yield of D. glomerata increased gradually with increase in fertilization gradient, and peaked at 40 t/hm 2 . Meanwhile, the crude protein (CP) and ether extract (EE) contents of both grassland types displayed first presented an increasing trend, then decreased with increasing fertilization gradient, and peaked at 10-30 t/hm 2 fertilization gradient. The neutral detergent fiber (NDF) and acidic detergent fiber (ADF) contents of M. sativa presented "N-shaped" and "M-shaped" change trends with increasing fertilization gradient, while those of D. glomerata showed "V-shaped" and "M-shaped" change trends, reaching minimum values under fertilization gradients of 30 and 20 t/hm 2 , respectively. Year, fertilization, and year × fertilization (Y×F) significantly affected the plant heights, coverages, dry/fresh weight ratios, and yields of M. sativa and D. glomerata . The contribution of coverage to the subordinate function of M. sativa was greatest at a fertilization gradient of 20 t/hm 2 . Meanwhile, the subordinate function values of the height and coverage of D. glomerata increased gradually with increasing fertilization gradient, but the difference in the subordinate function value of height was only 0.09%-0.18% under the fertilization gradient of 20-40 t/hm 2 . Evaluation of forage nutrition revealed 10-30 t/hm 2 and 20-30 t/hm 2 as the optimal organic fertilizer application rates for M. sativa and D. glomerata , respectively., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Tian, Shuai, Jin, Zhang, Wei, Niu, Ma and Zhao.)

Oxidative stress (OS), which impacts lipid metabolic reprogramming, can affect the biological activities of cancer cells. How oxidative stress and phospholipid metabolism (OSPM) influence the prognosis of pancreatic cancer (PC) needs to be elucidated. The metabolic data of 35 pancreatic tumor samples, 34 para-carcinoma samples, and 31 normal pancreatic tissues were obtained from the previously published literature. Pan-cancer samples were obtained from The Cancer Genome Atlas (TCGA). And the Gene Expression Omnibus (GEO), International Cancer Genome Consortium (ICGC), ArrayExpress, and the Genotype-Tissue Expression (GTEx) databases were searched for more PC and normal pancreatic samples. The metabolites in PC were compared with normal and para-carcinoma tissues. The characteristics of the key OSPM genes were summarized in pan-cancer. The random survival forest analysis and multivariate Cox regression analysis were utilized to construct an OSPM-related signature. Based on this signature, PC samples were divided into high- and low-risk subgroups. The dysregulations of the tumor immune microenvironment were further investigated. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was conducted to investigate the expression of genes in the signature in PC and normal tissues. The protein levels of these genes were further demonstrated. In PC, metabolomic studies revealed the alteration of PM, while transcriptomic studies showed different expressions of OSPM-related genes. Then 930 PC samples were divided into three subtypes with different prognoses, and an OSPM-related signature including eight OSPM-related genes (i.e., SLC2A1, MMP14, TOP2A, MBOAT2, ANLN, ECT2, SLC22A3, and FGD6) was developed. High- and low-risk subgroups divided by the signature showed different prognoses, expression levels of immune checkpoint genes, immune cell infiltration, and tumor microenvironment. The risk score was negatively correlated with the proportion of TIL, pDC, Mast cell, and T cell co-stimulation. The expression levels of genes in the signature were verified in PC and normal samples. The protein levels of SLC2A1, MMP14, TOP2A, MBOAT2, ANLN, and SLC22A3 showed up-regulation in PC samples compared with normal tissues. After integrating metabolomics and transcriptomics data, the alterations in OSPM in PC were investigated, and an OSPM-related signature was developed, which was helpful for the prognostic assessment and individualized treatment for PC., (© 2023. Springer Nature Limited.)

Accurate analysis of living circulating tumor cells (CTCs) plays a crucial role in cancer diagnosis and prognosis evaluation. However, it is still challenging to develop a facile method for accurate, sensitive, and broad-spectrum isolation of living CTCs. Herein, inspired by the filopodia-extending behavior and clustered surface-biomarker of living CTCs, we present a unique bait-trap chip to achieve accurate and ultrasensitive capture of living CTCs from peripheral blood. The bait-trap chip is designed with the integration of nanocage (NCage) structure and branched aptamers. The NCage structure could "trap" the extended filopodia of living CTCs and resist the adhesion of filopodia-inhibited apoptotic cells, thus realizing the accurate capture (∼95% accuracy) of living CTCs independent of complex instruments. Using an in-situ rolling circle amplification (RCA) method, branched aptamers were easily modified onto the NCage structure, and served as "baits" to enhance the multi-interactions between CTC biomarker and chips, leading to ultrasensitive (99%) and reversible cell capture performance. The bait-trap chip successfully detects living CTCs in broad-spectrum cancer patients and achieves high diagnostic sensitivity (100%) and specificity (86%) of early prostate cancer. Therefore, our bait-trap chip provides a facile, accurate, and ultrasensitive strategy for living CTC isolation in clinical. STATEMENT OF SIGNIFICANCE: A unique bait-trap chip integrated with precise nanocage structure and branched aptamers was developed for the accurate and ultrasensitive capture of living CTCs. Compared with the current CTC isolation methods that are unable to distinguish CTC viability, the nanocage structure could not only "trap" the extended-filopodia of living CTCs, but also resist the adhesion of filopodia-inhibited apoptotic cells, thus realizing the accurate capture of living CTCs. Additionally, benefiting from the "bait-trap" synergistic effects generated by aptamer modification and nanocage structure, our chip achieved ultrasensitive, reversible capture of living CTCs. Moreover, this work provided a facile strategy for living CTC isolation from the blood of patients with early-stage and advanced cancer, exhibiting high consistency with the pathological diagnosis., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Introduction: Cancer remains a substantial burden on society. Our objective was to update projections on the number of new cancer diagnoses in the United States by age, race, ethnicity, and sex through 2040., Materials and Methods: Population-based cancer incidence data were obtained using Surveillance, Epidemiology, and End Results (SEER) data. Population estimates were made using the 2010 US Census data population projections to calculate future cancer incidence. Trends in age-adjusted incidence rates for 23 cancer types along with total cancers were calculated and incorporated into a second projection model., Results: If cancer incidence remains stable, annual cancer diagnoses are projected to increase by 29.5% from 1.86 million to 2.4 million between 2020 and 2040. This increase outpaces the projected US population growth of 12.3% over the same period. The population of older adults is projected to represent an increasing proportion of total cancer diagnoses with patients ≥65 years old comprising 69% of all new cancer diagnoses and patients ≥85 years old representing 13% of new diagnoses by 2040. Cancer diagnoses are projected to increase in racial minority groups, with a projected 44% increase in Black Americans (from 222,000 to 320,000 annually), and 86% in Hispanic Americans (from 175,000 to 326,000 annually)., Discussion: The landscape of cancer care will continue to change over the next several decades. The burden of disease will remain substantial, and the growing proportion of older and minority patients with cancer remains of particular interest. These projections should help guide future health policy and research priorities., Competing Interests: Declaration of Competing Interest There are no conflicts of interest related to this study. Disclosures include: Benjamin D. Smith is supported by a grant from the Cancer Prevention and Research Institute of Texas (RP160674) and the NIHR01 CA207216-01 and is an Andrew Sabin Family Fellow. He has an equity interest in Oncora Medical and received prior research funding from Varian Medical Systems, both unrelated to the current submission. Grant R. Williams received honorium from Carevive Systems unrelated to the current submission. Yuefeng Wang is a consultant for MASEP and on the advisory board for Novocure unrelated to this submission. Matthew T. Ballo is a consultant for Novocure unrelated to this submission. Noam A. VanderWalde is a consultant and advisory board member for Concerto Health AI unrelated to this submission., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Atractylodes lancea rhizome (AR) has high medicinal and economic value. A previous study has reported that the accumulation of sesquiterpenoids in AR has obvious advantages under bamboo canopy. A concrete shade value to promote the cultivation of high-quality AR has not been established. In this study, 80% shading was screened at six different light intensities (100%, 80%, 60%, 40%, 20%, 7%), and the mechanism was explored in terms of photosynthetic efficiency and phytohormones levels. The results indicated that the total sesquiterpenoid content of 80% mild shading increased by 58%, 52%, and 35%, respectively, compared to 100% strong light in seedling, expansion, and harvest stages and increased by 144%, 178%, and 94%, respectively, compared with 7% low light. The sesquiterpenoids hinesol and β-eudesmol contributed approximately 70% to the differential contribution ratio between mild shading and strong light (100%) or between mild shading and low light (7%). Furthermore, HMGR, DXR, and FPPS genes, which regulate sesquiterpenoid synthesis, were significantly upregulated in 80% mild shading. Transpiration rate; the intercellular CO 2 concentration; net photosynthetic rate; and levels of jasmonic acid, abscisic acid, and gibberellin were strongly correlated (r > 0.85) with sesquiterpenoid accumulation. Cis-acting elements responding to light and phytohormones were present within the promoter regions of HMGR, DXR, and FPPS. Therefore, 80% shading promotes the synthesis and accumulation of sesquiterpenoids in AR by regulating photosynthetic efficiency and phytohormone production, thereby promoting transcriptional expression., (© 2022. The Author(s).)

Atractylodes lancea is an important medicinal plant in traditional Chinese medicine, its rhizome is rich of volatile secondary metabolites with medicinal values and is largely demanded in modern markets. Currently, supply of high-yield, high-quality A. lancea is mainly achieved via cultivation. Certain soil microbes can benefit plant growth, secondary metabolism and induce resistance to environmental stresses. Hence, studies on the effects of soil microbe communities and isolates microorganisms on A. lancea is extremely meaningful for future application of microbes on cultivation. Here we investigated the effects of the inoculation with an entire soil microbial community on the growth, resistance to drought, and accumulation of major medicinal compounds (hinesol, β-eudesmol, atractylon and atractylodin) of A. lancea . We analyzed the interaction between A. lancea and the soil microbes at the phylum and genus levels under drought stress of different severities (inflicted by 0%, 10% and 25% PEG6000 treatments). Our results showed that inoculation with soil microbes promoted the growth, root biomass yield, medicinal compound accumulation, and rendered drought-resistant traits of A. lancea , including relatively high root:shoot ratio and high root water content under drought. Moreover, our results suggested drought stress was more powerful than the selectivity of A. lancea in shaping the root-associated microbial communities; also, the fungal communities had a stronger role than the bacterial communities in protecting A. lancea from drought. Specific microbial clades that might have a role in protecting A. lancea from drought stress were identified: at the genus level, the rhizospheric bacteria Bacillus , Dylla and Actinomadura , and rhizospheric fungi Chaetomium , Acrophialophora , Trichoderma and Thielava , the root endophytic bacteria Burkholderia-Caballeronia-Paraburkholderia , Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium , Dylla and Actinomadura , and the root endophytic fungus Fusarium were closely associated with A. lancea under drought stress. Additionally, we acquired several endophytic Paenibacillus , Paraburkholderia and Fusarium strains and verified they had differential promoting effects on the medicinal compound accumulation in A. lancea root. This study reports the interaction between A. lancea and soil microbe communities under drought stress, and provides insights for improving the outcomes in A. lancea farming via applying microbe inoculation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Wang, Kang, Wang, Zhang, Yang, Zhou, Xiang, Huang, Liu and Guo.)

Background and Objective: With the aging of the global population becoming severe, Alzheimer's disease (AD) has become one of the world's most common senile diseases. Many studies have suggested that the brain's left-right asymmetry is one of the possible diagnostic landmarks for AD. However, most published approaches to classification problems may not adequately explore the asymmetry between the left and right hemispheres. At the same time, the relationship between asymmetry traits and other classifier features remains understudied., Methods: In this paper, we proposed an asymmetry enhanced attention network (ASEAN) for AD diagnosis that effectively combines the anatomical asymmetry characteristics of the brain to enhance the accuracy and stability of classification tasks. First, we proposed a multi-scale asymmetry feature extraction module (MSAF) that can extract the asymmetry features of the brain from various scales. Second, we proposed an asymmetry refinement module (ARM) that considers the dependency between feature maps to suppress the irrelevant regions of the asymmetric feature maps. In addition, a parameter-free attention module was introduced to infer 4D attention weights and improve the network's representation capability., Results: The proposed method achieved performance improvements on two databases: Alzheimer's Disease Neuroimaging Initiative (ADNI) and Australian Imaging, Biomarkers and Lifestyle (AIBL). For the classification tasks on ADNI, the proposed method achieves 92.1% accuracy, 96.2% sensitivity, and 91.3% specificity on the AD vs. CN (Cognitively Normal) task. Compared with state-of-the-art methods, the proposed method could achieve comparable results., Conclusion: The proposed model can extract long-range left-right brain similarity as complementary information and improve the model's diagnostic performance. A large number of experiments also support the model's validity. At the same time, this work provides a valuable reference for other neurological diseases, particularly those that exhibit left-right brain asymmetry during development., 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 Elsevier Ltd. All rights reserved.)

Automatic brain structure segmentation in Magnetic Resonance Image (MRI) plays an important role in the diagnosis of various neuropsychiatric diseases. However, most existing methods yield unsatisfactory results due to blurred boundaries and complex structures. Improving the segmentation ability requires the model to be explicit about the spatial localization and shape appearance of targets, which correspond to the low-frequency content features and the high-frequency edge features, respectively. Therefore, in this paper, to extract rich edge and content feature representations, we focus on the composition of the feature and utilize a frequency decoupling (FD) block to separate the low-frequency and high-frequency parts of the feature. Further, a novel edge-aware network (EA-Net) is proposed for jointly learning to segment brain structures and detect object edges. First, an encoder-decoder sub-network is utilized to obtain multi-level information from the input MRI, which is then sent to the FD block to complete the frequency separation. Further, we use different mechanisms to optimize both the low-frequency and high-frequency features. Finally, these two parts are fused to generate the final prediction. In particular, we extract the content mask and the edge mask from the optimization feature with different supervisions, which forces the network to learn the boundary features of the object. Extensive experiments are performed on two public brain MRI T1 scan datasets (the IBSR dataset and the MALC dataset) to evaluate the effectiveness of the proposed algorithm. The experiments show that the EA-Net achieves the best performance compared with the state-of-the-art methods, and improves the segmentation DSC score by 1.31% at most compared with the U-Net model and its variants. Moreover, we evaluate the EA-Net under different noise disturbances, and the results demonstrate the robustness and superiority of our method under low-quality noisy MRI. Code is available at https://github.com/huqian999/EA-Net., 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 Elsevier Ltd. All rights reserved.)

Purpose: Currently, the most commonly applied method for the determination of breast cancer subtypes is to test estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67 by immunohistochemistry (IHC). However, the IHC method has substantial intraobserver and interobserver variability. ESR1, PGR, ERBB2, and MKi67 mRNA tests by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay may improve the diagnostic objectivity and efficiency. Here, we compared the concordance between RT-qPCR and IHC for assessment of the same biomarkers and evaluated the subtypes., Methods: A total of 265 eligible cases were divided into a training cohort and a validation cohort, and the expressions of ER/ESR1, PR/PGR, HER2/ERBB2, and Ki67/MKI67 were tested by IHC and RT-qPCR. Then, the appropriate cutoff of RT-qPCR was calculated in the training cohort. The concordance between RT-qPCR and IHC was calculated for individual marker. In addition, we investigated the subtypes based on the RT-qPCR results., Results: The Spearman correlation coefficients between ER/ESR1, PR/PGR, HER2/ERBB2, and Ki67/MKI67 by IHC and RT-qPCR were 0.768, 0.699, 0.762, and 0.387, respectively. The cutoff values for the RT-qPCR assay of ESR1 (1%), PGR (1%), ERBB2, and MKi67 (14%) were 35.539, 32.139, 36.398, and 29.176, respectively. The overall percent agreement (OPA) between ER/ESR1, PR/PGR, HER2/ERBB2, and Ki67/MKI67 by IHC and RT-qPCR was 92.48%, 73.68%, 92.80%, and 74.44%, respectively. A total of 224 (84.53%) specimens were concordant for the breast cancer subtypes (IHC-based type) by RT-qPCR., Conclusion: Evaluation of breast cancer biomarker status by RT-qPCR was highly concordant with IHC. RT-qPCR can be used as a supplementary method to detect molecular markers of breast cancer., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Given environmental or hydrological functions influenced by changing river networks in the development of rapid urbanization, a clear understanding of the relationships between comprehensive urbanization (CUB) and river network characteristics (RNC), storage capacity (RSC), and regulation capacity (RRC) is urgently needed. In the rapidly urbanized Tai Lake Plain (TLP), China, various methods and multisource data were integrated to estimate the dynamics of RNC, RSC, and RRC as well as their interactions with urbanization. The bivariate Moran's I methods were applied to detect and visualize the spatial dependency of RNC, RSC, or RRC on urbanization. Geographically weighted regression (GWR) model was set up to characterize spatial heterogeneity of urbanization influences on RNC, RSC and RRC. Our results indicated that RNC, RSC and RRC variables each showed an overall decreasing trend across space from 1960s to 2010s, particularly in those of tributary rivers. RNC, RSC, or RRC had globally negative correlations with CUB, respectively, but looking at local scale the spatial correlations between each pair were categorized as four types: high-high, high-low, low-low, and low-high. GWR was identified to accurately predict the response of most RNC, RSC, or RRC variables to CUB (R 2 : 0.6-0.8). The predictive ability of GWR was spatially non-stationary. The obtained relationships presented different directions and strength in space. All variables except for the water surface ratio (Wp) were more positively affected by CUB in the middle eastern parts of TLP. Drainage density, RSC and RRC variables were more negatively influenced by CUB in the northeast compared to other parts. The quantitative results of spatial relationships between urbanization and RNC, RSC or RRC can provide location-specific guidance for river environment protection and regional flood risk 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 © 2022 Elsevier B.V. All rights reserved.)

Consortin (CNST) is a protein located on the trans-Golgi network that can target transmembrane proteins to the plasma membrane. Although CNST was discovered more than 10 years ago, there are still not enough studies on its function. During our search for possible new acute myeloid leukemia (AML) markers, we found that CNST was overexpressed in almost all patients with AML. By analyzing profiling data from public databases, we found that CNST expression inversely correlated with overall survival among AML patients. There was a great variation in CNST expression among different subtypes of AML, and the expression was the highest in the t(8,21) subtype, which was probably due to the direct regulation of CNST transcription by RUNX1-RUNX1T1. In addition, we analyzed the expression of CNST in different cells of the hematopoietic system. We found that CNST was associated with the low differentiation degrees of hematopoietic cells and had the highest expression level in leukemia stem cells (LSCs). Finally, we analyzed the CNST-related gene network and found that the genes negatively correlated with CNST are involved in various immune-related pathways, which indicates that CNST is likely related to immune evasion, LSC niche retention, and assembly of stress granules. In conclusion, our study suggests that CNST has the potential to be a diagnostic and prognostic biomarker for AML., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Zhang, Zhao, Zhu, Li, Yang, Zhao, Zhang, Wang, Zhu, Ding and Li.)

Glucocorticoids are essential participants in the regulation of lipid metabolism. On a tissue-specific level, glucocorticoid signal is controlled by 11β-Hydroxysteroid dehydrogenase 1 (11β-HSD1). Up-regulation of 11β-HSD1 expression during non-alcoholic fatty liver disease (NAFLD) has been previously shown, while 11β-HSD1 inhibition has been shown to reduce hepatic lipids in NAFLD, but the underlying mechanisms remain unclear. Here, in this study, we created in vitro cell culture and in vivo transgenic hepatocyte-specific 11β-HSD1 mouse models of NAFLD to determine the regulatory mechanisms of 11β-HSD1 during lipid metabolism dysfunction. We found that 11β-HSD1 overexpression activated glucocorticoid receptors and promoted their nuclear translocation, and then stimulating gp78. The induction of gp78 sharply reduced expression of Insig2, but not Insig1, which led to up-regulation of lipogenesis regulatory proteins including SREBP1, FAS, SCD1, and ACC1. Our results suggested that overexpression of 11β-HSD1 induced lipid accumulation, at least partially through the GR/gp78/Insig2/SREBP1 pathway, which may serve as a potential diagnostic and therapeutic target for treatment of NAFLD., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Clinically, accurate pathological diagnosis is often challenged by insufficient tissue amounts and the unaffordability of additional immunohistochemical or genetic tests; thus, there is an urgent need for a universal approach to improve the subtyping of lung cancer without the above limitations. Here we aimed to develop a deep learning system to predict the immunohistochemistry (IHC) phenotype directly from whole-slide images (WSIs) to improve the subtyping of lung cancer from surgical resection and biopsy specimens., Methods: A total of 1914 patients with lung cancer from three independent hospitals in China were enrolled for WSI-based immunohistochemical feature prediction system (WIFPS) development and validation., Results: The WIFPS could directly predict the IHC status of nine subtype-specific biomarkers, including CK7, TTF-1, Napsin A, CK5/6, P63, P40, CD56, Synaptophysin, and Chromogranin A, achieving average areas under the curve (AUCs) of 0.912, 0.906, and 0.888 and overall diagnostic accuracies of 0.925, 0.941, and 0.887 in the validation datasets of total, external surgical resection specimens and biopsy specimens, respectively. The histological subtyping performance of the WIFPS remained comparable with that of general pathologists (GPs), with Cohen's kappa values ranging from 0.7646 to 0.8282. Furthermore, the WIFPS could be trained to not only predict the IHC status of anaplastic lymphoma kinase (ALK), programmed death-1 (PD-1), and programmed death ligand 1 (PD-L1), but also predict EGFR and KRAS mutation status, with AUCs from 0.525 to 0.917, as detected in separate populations., Conclusions: In this study, the WIFPS showed its proficiency as a useful complement to traditional histologic subtyping for integrated immunohistochemical spectrum prediction as well as potential in the detection of gene mutations., (Copyright © 2022 Elsevier B.V. All rights reserved.)

In the present paper, the designed thermomechanical process was applied to prepare ferrite/bainite multiphase microstructures in Si-rich low-alloy steel with a carbon content of 0.33 wt.% (0.33C) and 0.21 wt.% (0.21C). The microstructures were analyzed by scanning electron microscope, transmission electron microscope, and electron backscatter diffraction, and the mechanical properties (tensile and impact properties) were tested. The results showed that, on the premise of obtaining 15 vol.% ferrite in both steels, the ferrite grains in the 0.33C steel were polygonal with an average grain size of 2.2 μm, recrystallized more completely. However, the ferrite grains in the 0.21C steel were mainly long strip-shaped with a width of 2-4 μm, and the recrystallization degree was poor. In addition, upon increasing the austempering temperature, bainite ferrite laths were formed in the 0.33C steel, and the thickness was in the range of 81-123 nm. The morphology of bainite ferrite in the 0.21C steel gradually changed from lath to granular. Upon increasing the austempering temperature, the tensile strength and yield strength of both steels increased and the elongation decreased slightly. The impact energy of the two steels showed different trends upon increasing the austempering temperature, in which the impact energy of the 0.33C steel increased, while that of the 0.21C steel decreased. This is due to the difference size of the martensite-austenite constituents in the two steels.

Osteosarcoma (OS) is the most common primary malignant bone tumor. Prospero homeobox 1 (PROX1) is a key transcription factor involved in some cancers, but the role of PROX1 in OS is unclear. This study aimed to explore the clinical and biology significance of PROX1 in OS. Fifty-four OS tissues and matched nontumor tissues were collected to explore the relationship between PROX1 expression and clinical characteristics and prognosis. qRT-PCR and immunohistochemistry were used to investigate the expression patterns of PROX1 in OS tissues and cells. CCK-8, wound healing, and transwell assays were used to detect the effects of PROX1 on the proliferation, migration, and invasion of OS cells. Transcriptome sequencing, bioinformatics analysis and qRT-PCR were used to explore the regulatory network of PROX1. PROX1 was significantly higher in OS tissues and cells compared to normal tissues and cell lines. In OS patients, high expression of PROX1 was associated with Enneking stage (P < 0.001) and M classification (P < 0.001). High PROX1 expression predicted a poorer overall survival (P = 0.0047). Compared with untreated cells, OS cells overexpressing PROX1 showed higher proliferation, migration, and invasion abilities, while knockdown of PROX1 suppressed these abilities. The results of Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that the down regulated genes were mainly enriched in TNF signaling pathway, MAPK signaling pathway, and neuroactive ligand-receptor interaction. High PROX1 expression was significantly associated with poor overall survival in OS patients. PROX1 may be a promising prognostic marker and therapeutic target for OS patients.

RHD variants in D¯ Chinese pregnant women arose difficulties in management during pregnancy. Therefore, this study aims to precisely manage D¯ pregnant women by evaluating the spectrum of RHD mutations in D¯ pregnant women and getting insight into the possible rare alleles of RHD. A total of 76 D¯ pregnant women were analyzed by performing polymerase chain reactions with sequence-specific primers (PCR-SSP), the 10 RHD exons Sanger sequencing, RHD zygosity detection, and mRNA sequencing (mRNA-seq). About 40% of alleles are variations of RHD, including RHD 1227A homozygous, RHD-CE(2-9)-D, et al. Therefore, we developed a molecular diagnostic strategy for Chinese women, and most D¯ pregnant women can be diagnosed with this simple decision tree. After RHD genotyping for D¯ pregnancy women, we eliminated at least 15% unnecessary ante- and postpartum injections of Rh immunoglobulin (RhIG). As the first pedigree study and the first functional analysis under physiological conditions, mRNA-seq revealed that c.336-1G>A mutation mainly led to the inclusion of the intron 2, which indirectly explained the D¯ phenotype in this family. We also developed a robust protocol for determining fetal RhD status from maternal plasma. All 31 fetuses were predicted as RhD positive and confirmed the RhD status after birth., Competing Interests: Authors XP, ZZ, LA, and YZ were employed by the company Tianjin Super Biotechnology Developing Co., Ltd. Authors JP and MW were employed by the company Zhejiang Biosan Biotechnology Co., Ltd. Author JZ was employed by the company BGI-Shenzhen. 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 © 2021 Zhang, Zeng, Wang, Fan, Chen, Yang, Shi, Xu, Fu, Sheng, Xuan, Pan, Zhang, Ai, Zhang, Pan, Zhao and Wang.)

Backgrounds: To determine the potential survival benefit associated with robotic-assisted laparoscopic prostatectomy (RALP) compared to open radical prostatectomy (ORP) for prostate cancer., Summary of Background Data: RALP has become the dominant surgical approach for localized disease in the absence of randomized clinical evidence and despite of the factor that RALP is more expensive than ORP., Methods: We performed a cohort study involving patients who underwent RALP and ORP for localized prostate cancer at the Commission on Cancer- accredited hospitals in the United States. Overall survival was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards models, and propensity score-matched analyses. An interrupted time-series analysis using the surveillance, epidemiology, and end results program database was also performed., Results: From 2010 to 2011, 37,645 patients received RALP and 12,655 patients received ORP. At a median follow-up of 60.7 months, RALP was associated with improved overall survival by both univariate [hazard ratio (HR), 0.69; P < 0.001] and multivariate analysis (HR, 0.76; P < 0.001) compared with ORP. Propensity score-matched analysis demonstrated improved 5-year all-cause mortality (3.9% vs 5.5%, HR, 0.73; P < 0.001) for RALP. The interrupted time-series analysis demonstrated the adoption of robotic surgery coincided with a systematic improvement in the 5-year cancer-specific survival rate of 0.17% (95% confidence interval, 0.06-0.25) per year after 2003 (P = 0.004 for change of trend), as compared to the time before adoption of RALP (1998-2003, annual percentage change, 0.01%; 95% confidence interval, -0.06 to 0.08). Sensitivity analysis suggested that the results from the interrupted time-series analysis were consistent with the improvement in the all-cause mortality demonstrated in the survival analysis (P = 0.87)., Conclusions: In this epidemiologic analysis, RALP was associated with a small but statistically significant improvement in 5-year all-cause mortality compared to ORP for localized prostate cancer. This is the first time in the literature to report a survival benefit with RALP. Our findings have significant quality and cost implications, and provide assurance regarding a dominant adoption of more expensive technology in the absence of randomized controlled trials., Competing Interests: The authors report no conflicts of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Camrelizumab (a PD-1 inhibitor) has been used as a potential therapy in unresectable advanced esophageal squamous cell carcinoma (ESCC) along with adjuvant treatment in locally advanced ESCC, exhibiting an acceptable efficacy and safety profile. This pilot study was designed to further investigate the clinical value and tolerance of neoadjuvant camrelizumab plus chemotherapy in locally advanced ESCC., Methods: A total of 16 patients with locally advanced ESCC were recruited. Patients received 2 cycles of neoadjuvant therapy including 2 doses of camrelizumab concurrent with 2 cycles of paclitaxel plus carboplatin followed by surgery 4 weeks afterward. Then, the treatment response after neoadjuvant therapy, R0 resection rate, tumor regression grade (TRG), and pathological complete remission (pCR) rate were measured. Besides, adverse events were documented. At last, progression-free survival (PFS) and overall survival (OS) were assessed., Results: Generally, objective remission rate (ORR) was 81.3% whereas disease control rate (DCR) was 100% after neoadjuvant therapy. Concerning TRG grade, 31.3, 37.5, 18.8, and 12.5% patients reached TRG0, TRG1, TRG2, and TRG3, respectively. Then, pCR rate and R0 resection rate were 31.3 and 93.8%, respectively. Besides, mean PFS and OS were 18.3 months (95%CI: (16.2-20.5) months) and 19.2 months (95%CI: (17.7-20.7) months), respectively, with a 1-year PFS of 83% and OS of 90.9%. Adverse events included white blood cell decrease (37.5%), neutrophil decrease (31.3%), reactive cutaneous capillary endothelial proliferation (37.5%), and nausea or vomiting (25.0%), which were relatively mild and manageable., Conclusion: Neoadjuvant camrelizumab plus chemotherapy exhibits good efficacy and acceptable tolerance in patients with locally advanced ESCC., (© 2021. The Author(s).)

Pathological MVI diagnosis could help to determine the prognosis and need for adjuvant therapy in hepatocellular carcinoma (HCC). However, narrative reporting (NR) would miss relevant clinical information and non-standardized sampling would underestimate MVI detection. Our objective was to explore the impact of innovative synoptic reporting (SR) and seven-point sampling (SPRING) protocol on microvascular invasion (MVI) rate and patient outcomes. In retrospective cohort, we extracted MVI status from NR in three centers and re-reviewed specimen sections by SR recommended by the College of American Pathologists (CAP) in our center. In prospective cohort, our center implemented the SPRING protocol, and external centers remained traditional pathological examination. MVI rate was compared between our center and external centers in both cohorts. Recurrence-free survival (RFS) before and after implementation was calculated by Kaplan-Meier method and compared by the log-rank test. In retrospective study, we found there was no significant difference in MVI rate between our center and external centers [10.3% (115/1112) vs. 12.4% (35/282), P=0.316]. In our center, SR recommended by CAP improved the MVI detection rate from 10.3 to 38.6% (P<0.001). In prospective study, the MVI rate in our center under SPRING was significantly higher than external centers (53.2 vs. 17%, P<0.001). RFS of MVI (-) patients improved after SPRING in our center (P=0.010), but it remained unchanged in MVI (+) patients (P=0.200). We conclude that the SR recommended by CAP could help to improve MVI detection rate. Our SPRING protocol could help to further improve the MVI rate and optimize prognostic stratification for HCC patients., 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 Liao, Liu, Wei, Wang, Chen, Cao, Zhou, Xiao, Chen, Peng, Li and Kuang.)

Objective: To explore the molecular mechanism of a case where RhD genotyping did not match serological results., Methods: The serological results of 8 members from two generations of this family were analyzed. And according to Mendelian law of inheritance, RhD genotyping, zygotic type determination and gene sequencing were performed for the family members., Results: The proband and one of her cousins have the same RhD alleles, both of them have a 336-1G>A intron variant RhD allele and a complete RhD deletion allele. The variant alleles are inherited from two of their parents with blood relationship, while the complete-deleted alleles come from the other. 336-1G>A means that the last base G of the second intron of the RhD gene is mutated to A, which leads to a negative RhD serology and a positive genotype in the proband., Conclusion: There was a rare 336-1G> A intron variant gene (RhD * 01N.25) in this family, which was a recessive gene relative to the RhD gene and resulted in RhD phenotype negative.

Background: Targeted therapy and immunotherapy put forward higher demands for accurate lung cancer classification, as well as benign versus malignant disease discrimination. Digital whole slide images (WSIs) witnessed the transition from traditional histopathology to computational approaches, arousing a hype of deep learning methods for histopathological analysis. We aimed at exploring the potential of deep learning models in the identification of lung cancer subtypes and cancer mimics from WSIs., Methods: We initially obtained 741 WSIs from the First Affiliated Hospital of Sun Yat-sen University (SYSUFH) for the deep learning model development, optimization, and verification. Additional 318 WSIs from SYSUFH, 212 from Shenzhen People's Hospital, and 422 from The Cancer Genome Atlas were further collected for multi-centre verification. EfficientNet-B5- and ResNet-50-based deep learning methods were developed and compared using the metrics of recall, precision, F1-score, and areas under the curve (AUCs). A threshold-based tumour-first aggregation approach was proposed and implemented for the label inferencing of WSIs with complex tissue components. Four pathologists of different levels from SYSUFH reviewed all the testing slides blindly, and the diagnosing results were used for quantitative comparisons with the best performing deep learning model., Results: We developed the first deep learning-based six-type classifier for histopathological WSI classification of lung adenocarcinoma, lung squamous cell carcinoma, small cell lung carcinoma, pulmonary tuberculosis, organizing pneumonia, and normal lung. The EfficientNet-B5-based model outperformed ResNet-50 and was selected as the backbone in the classifier. Tested on 1067 slides from four cohorts of different medical centres, AUCs of 0.970, 0.918, 0.963, and 0.978 were achieved, respectively. The classifier achieved high consistence to the ground truth and attending pathologists with high intraclass correlation coefficients over 0.873., Conclusions: Multi-cohort testing demonstrated our six-type classifier achieved consistent and comparable performance to experienced pathologists and gained advantages over other existing computational methods. The visualization of prediction heatmap improved the model interpretability intuitively. The classifier with the threshold-based tumour-first label inferencing method exhibited excellent accuracy and feasibility in classifying lung cancers and confused nonneoplastic tissues, indicating that deep learning can resolve complex multi-class tissue classification that conforms to real-world histopathological scenarios.

Pyrogenic char (biochar) with a high sorption capacity (B-HSC) can sequester hazardous chemicals (e.g., phenanthrene). However, when sorption inhibits bioavailability of some functional chemicals (e.g., the herbicidal efficacy of diuron in soil), biochar with a low sorption capacity (B-LSC) is required to prevent sorption effects. The pyrolytic B-HSC generation has been reported, but information on B-LSC formation is scarce. How fast B-HSC and B-LSC could be generated is unknown until now. Here, biochars were rapidly prepared (the shortest heating time reached 5 min and the cooling time reached < 30 min) by a direct-pyrolysis method by directly exposing packaged rice straw and pine wood to 350 °C, 500 °C and 700 °C and out-of-furnace cooling at room temperature. The sorption of diuron, phenanthrene, and twelve other chemicals was investigated. B-HSCs were obtained within 30 min of rice straw pyrolysis, and the biochar K d values quickly increased to 7-730-fold that of the raw biomass as -OH and C-O-C in (hemi)cellulose of rice straw rapidly degraded, increasing hydrophobic interactions between the char and chemicals (solubility ≤ 82.8 g/L). In contrast, B-LSCs were generated within 30 min of PW pyrolysis, and the K d values of the biochars were 0.2-3.0-fold that of the raw biomass, as the surface area development and hydrophobicity-driven sorption were probably delayed by the late degradation of lignin aromatic C-O and phenolic -OH. Biochar amendment revealed an enhancement effect of B-HSC but not of B-LSC on soil sorption. The fast formation of B-LSC and B-HSC provides a guide to develop time- and cost-effective technique in pyrolytically producing weakly or strongly sorbing biochars for organic chemical 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 © 2021 Elsevier Ltd. All rights reserved.)

The early detection and accurate histopathological diagnosis of gastric cancer increase the chances of successful treatment. The worldwide shortage of pathologists offers a unique opportunity for the use of artificial intelligence assistance systems to alleviate the workload and increase diagnostic accuracy. Here, we report a clinically applicable system developed at the Chinese PLA General Hospital, China, using a deep convolutional neural network trained with 2,123 pixel-level annotated H&E-stained whole slide images. The model achieves a sensitivity near 100% and an average specificity of 80.6% on a real-world test dataset with 3,212 whole slide images digitalized by three scanners. We show that the system could aid pathologists in improving diagnostic accuracy and preventing misdiagnoses. Moreover, we demonstrate that our system performs robustly with 1,582 whole slide images from two other medical centres. Our study suggests the feasibility and benefits of using histopathological artificial intelligence assistance systems in routine practice scenarios.

Water level (a vital indicator for flood warnings and water management in floodplains) has been changed notably due to climatic and anthropogenic forces; however, very little is known about the relative effects of these agents. In this study, we take the Taihu Plain as an example to investigate potential factors driving changes in water level components through quantiles from 1954 to 2014. To quantify the extent of water level component changes attributable to climate variability and human activity, several non-stationary models considering rainfall, tide, evaporation, and hydraulic regulation as covariates are established based on generalized additive models for location, scale, and shape. The results indicate that most water level components increased over time and changed abruptly around the mid-1980s. As for climatic factors, the variability of rainfall, tide and evaporation significantly affected water level variation based on most quantiles from 1954 to 2014. Among several kinds of human activities, hydraulic regulation was a key factor influencing water level based on a high correlation coefficient. Positive effects were identified from hydraulic regulation regarding the association between rainfall and water level components; these effects depend on water level quantiles and the amount of rainfall occurrence. Our study has broad implications, providing a better understanding of water level variation and regional flood management.

Tumor-treating fields (TTFields) are a noninvasive antimitotic cancer treatment consisting of low-intensity alternating electric fields delivered to the tumor or tumor bed via externally applied transducer arrays. In multiple in vitro and in vivo cancer cell lines, TTFields therapy inhibits cell proliferation, disrupts cell division, interferes with cell migration and invasion, and reduces DNA repair. Human trials in patients with primary glioblastoma showed an improvement in overall survival, and trials in patients with unresectable malignant pleural mesothelioma showed favorable outcomes compared with historical control. This led to U.S. Food and Drug Administration approval in both clinical situations, paving the way for development of trials investigating TTFields in other malignancies. Although these trials are ongoing, the existing evidence suggests that TTFields have activity outside of neuro-oncology, and further study into the mechanism of action and clinical activity is required. In addition, because TTFields are a previously unrecognized antimitotic therapy with a unique mode of delivery, the oncological community must address obstacles to widespread patient and provider acceptance. TTFields will likely join surgery, systemic therapy, and radiation therapy as a component of multimodality management of patients with solid malignancies. IMPLICATIONS FOR PRACTICE: Tumor-treating fields (TTFields) exhibit a broad range of antitumor activities. Clinically, they improve overall survival for patients with newly diagnosed glioblastoma. The emergence of TTFields has changed the treatment regimen for glioblastoma. Clinicians need to understand the practical issues surrounding its use in the multidisciplinary management of patients with glioblastoma. With ongoing clinical trials, TTFields likely will become another treatment modality for solid malignancies., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© 2019 The Authors. The Oncologist published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

Firm immobilization of catalysts on the predesigned position over substrates is an essential process for producing flexible circuits by the electroless deposition (ELD) process. In this work, a compatible Ag + complex was developed and directly printed on the poly(ethylene terephtalate) (PET) film through a micro inkjet printing instrument to trigger the deposition of ultrafine copper patterns with approximately 20 μm in width. Morphological and elementary characterization verified that the nanosized silver catalyst was uniformly distributed in the bridge layer, which could enhance the adhesion between the PET film and deposited copper patterns. Moreover, after 30 min of ELD, the copper patterns exhibited a low resistivity of 2.68 × 10 -6 Ω·cm and maintained considerable conductivity even after 2000 times of cyclical bending. These interesting conductive and mechanical features demonstrate the tremendous potential of this Ag + complex-assisted copper deposition in the interconnection of high-density integrated flexible electronics.

We aimed to investigate the absorption-enhancing effect (AEE) of caproyl-modified G2 PAMAM dendrimer (G2-AC) on peptide and protein drugs via the pulmonary route. In this study, G2 PAMAM dendrimer conjugates modified with caproic acid was synthesized, the pulmonary absorption of insulin as models with or without G2-AC were evaluated. The results indicated that G2-AC6 exhibited a greatest AEE for insulin in various caproylation levels of G2-AC. G2-AC6 could significantly enhance the absorption of insulin, and the AEE of G2-AC6 was concentration-dependent. In toxicity tests, G2-AC6 displayed no measurable cytotoxicity to the pulmonary membranes over a concentration range from 0.1% (w/v) to 1.0% (w/v). Measurements of the TEER and permeability showed that G2-AC6 significantly reduced the TEER value of CF and increased its P app value. The results suggested that G2-AC6 could cross epithelial cells by means of a combination of paracellular and transcellular pathways. These findings suggested G2-AC6 at lower concentrations (below 1.0%, w/v) might be promising absorption enhancers for increasing the pulmonary absorption of peptide and protein drugs.

The graphene/Si heterojunction is attractive for high gain and broadband photodetection through photogating effect. However, the photoresponsivity in these devices are still limited to under 1 A W -1 if no narrowband absorption-enhanced nanostructures were used. In this paper, the effects of barriers on photoresponse are systematically studied at 1550 nm wavelength. Different barrier heights are obtained through selection of substrates, graphene doping and electrical tuning. Lower barrier height for graphene side and higher barrier height for silicon side are found to be beneficial for better infrared photoresponse. Through Polyetherimide doping of graphene and back-gated electrical modulation, the responsivity finally reached 5.71 A W -1 , which to our knowledge is among the best results for graphene-based infrared photodetectors with graphene adopted as a light-absorption material. It is found that the thermionic emission efficiency of indirect transition in graphene is related to the difference in emissioin barrier height, and the lifetime of photoinduced carriers in the channel can be enhanced by built-in potential. These results lay the foundation for the photodetection applicatioins of graphene/Si heterojunction in the longer-wavelength infrared region.