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Ethnopharmacological Relevance: Dermatophytes are notorious pathogens capable of infecting various mammals skin, posing serious threats to human health and overall life quality worldwide. Artemisia argyi has been recorded and applied for over a thousand years to treat skin itching. Although it has the potential to be developed as a plant-based antifungal agent, it's antifungal activity and action mechanism of active ingredients are still unclear., Aim of the Study: The aim of this study was to investigate the chemical composition, antifungal activity against skin fungi, and potential mechanisms of Artemisia argyi essential oil (AEO)., Materials and Methods: The chemical composition of AEO was analyzed by gas chromatography-mass spectrometry (GC-MS) firstly. Flat growth restraint and double half dilution tests was performed to evaluate AEO antifungal activity against Microsporum gypseum, Trichophyton mentagrophytes, and Trichophyton rubrum. And then, the physiological mechanism of AEO inhibiting dermatophytes was systematically explored through scanning electron microscopy, relative conductivity, membrane leakage, ROS content, and antioxidant enzyme activity. Finally, the main pathways were screened through transcriptome sequencing, while the related genes expression levels and enzyme activity were validated., Results: Monoterpenes and sesquiterpenoids were the most highly representative class of AEO. AEO had powerful antifungal activity against M. gypseum, T. mentagrophytes, and T. rubrum, with minimum inhibitory concentration (MIC) values of 0.6, 1.2, and 1.2 μL/mL, respectively. Moreover, AEO can also damage the cell membrane integrity of T. mentagrophytes, resulting in cellular extravasation of intracellular substances. Transcriptome analysis revealed that the main target of AEO is to inhibit electron transfer and oxidative phosphorylation during respiration, ultimately leading to obstruction of normal ATP synthesis and energy metabolism in mitochondria. And a large amount of ROS will generate due to the incompletely catalysis of oxygen under mitochondrial complexes. Coupled with the decrease of antioxidant enzyme (SOD, POD) activity, excessive accumulation of ROS will cause serious oxidative damage to cells and eventually exhibiting antifungal activity against dermatophytes., Conclusions: The present study demonstrated that Artemisia argyi was a valuable source of active compounds with antifungal activity. These findings support AEO as a potential agent to inhibit dermatophytes and prevent related dermatophytoses., 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.)

Prostate cancer (PCa) is one of the most common male genitourinary system malignancies. Despite the significant benefits of anti-PD-L1 immune checkpoint inhibitor therapy in other cancers, the reasons for its poor therapeutic efficacy in prostate cancer (PCa) remain unclear.NDR1 plays an important role in innate immunity, but its role in tumor immunity and immunotherapy has not been investigated. The role of NDR1 in the immune microenvironment of PCa and the related mechanisms are unknown. Here, we found a positive correlation between NDR1 and PD-L1 expression in PCa. NDR1 significantly inhibits CD8 + T cell infiltration and function, thereby promoting immune escape in prostate cancer.More importantly, NDR1 inhibition significantly enhanced CD8 + T cell activation, which enhanced the therapeutic effect of anti-PD-L1. Mechanistic studies revealed that NDR1 inhibits ubiquitination-mediated PD-L1 degradation via the deubiquitinase USP10, upregulates PD-L1, and promotes PCa immune escape. Thus, our study suggests a unique PD-L1 regulatory mechanism underlying PCa immunotherapy failure. The significance of NDR1 in PCa immune escape and its mechanism of action were clarified, and combined NDR1/PD-L1 inhibition was suggested as an approach to boost PCa immunotherapy effectiveness., (© 2024. The Author(s).)

Hepatocellular Carcinoma (HCC) remains a leading cause of cancer deaths. Despite the rise of immunotherapies, many HCC patients don't benefit. There's a clear need for biomarkers to guide treatment decisions. This research aims to identify such biomarkers by combining radiological data and machine learning. We analyzed clinical and CT imaging data of 54 HCC patients undergoing immunotherapy. Radiologic features were examined to develop a model predicting short-term immunotherapy effects. We utilized 9 machine learning and 2 ensemble learning techniques using RapidMiner for model construction. We conducted the validation of the above feature combination using 29 HCC patients who received immunotherapy from another hospital, and tested and validated it using XGBoost combined with a genetic algorithm. In 54 HCC patients, radiomics features varied significantly between those with partial response (PR) and stable disease (SD). Key features in Gray Level Run Length Matrix (GLRLM) and in adjacent tissues' Intensity Direct, Neighborhood Gray Tone Difference Matrix (NGTDM), and Shape correlated with short-term immunotherapy efficacy. Selected feature combinations of 15, 19, and 8/15 features yielded better outcomes. Deep learning, random forest, and naive bayes outperformed other methods, with Bagging being more reliable than Adaboost. In the validation set of 29 HCC patients, the mentioned feature combination also demonstrated favorable performance. Furthermore, we achieved improved results when employing XGBoost in conjunction with a genetic algorithm for testing and validation. The machine learning model built with CT image features derived from GLCM, GLRLM, IntensityDirect, NGTDM, and Shape can accurately forecast the short-term efficacy of immunotherapy for HCC., (© 2024. The Author(s).)

Computational synthetic lethality (SL) method has become a promising strategy to identify SL gene pairs for targeted cancer therapy and cancer medicine development. Feature representation for integrating various biological networks is crutial to improve the identification performance. However, previous feature representation, such as matrix factorization and graph neural network, projects gene features onto latent variables by keeping a specific geometric metric. There is a lack of models of gene representational latent space with considerating multiple dimentionalities correlation and preserving latent geometric structures in both sample and feature spaces. Therefore, we propose a novel method to model gene Latent Space using matrix Tri-Factorization (LSTF) to obtain gene representation with embedding variables resulting from the potential interpretation of synthetic lethality. Meanwhile, manifold subspace regularization is applied to the tri-factorization to capture the geometrical manifold structure in the latent space with gene PPI functional and GO semantic embeddings. Then, SL gene pairs are identified by the reconstruction of the associations with gene representations in the latent space. The experimental results illustrate that LSTF is superior to other state-of-the-art methods. Case study demonstrate the effectiveness of the predicted SL associations.

Renal cancer is a highlyheterogeneous malignancy characterized by rising global incidence and mortalityrates. The complex interplay and dysregulation of multiple signaling pathways,including von Hippel-Lindau ( VHL )/hypoxia-inducible factor ( HIF ), phosphoinositide 3-kinase ( PI3K )/protein kinase B ( AKT )/mammalian target of rapamycin ( mTOR ), Hippo-yes-associated protein ( YAP ), Wnt/ß-catenin, cyclic adenosine monophosphate ( cAMP ), and hepatocyte growth factor ( HGF )/ c-Met , contribute to theinitiation and progression of renal cancer. Although surgical resection is thestandard treatment for localized renal cancer, recurrence and metastasiscontinue to pose significant challenges. Advanced renal cancer is associatedwith a poor prognosis, and current therapies, such as targeted agents andimmunotherapies, have limitations. This review presents a comprehensiveoverview of the molecular mechanisms underlying aberrant signaling pathways inrenal cancer, emphasizing their intricate crosstalk and synergisticinteractions. We discuss recent advancements in targeted therapies, includingtyrosine kinase inhibitors, and immunotherapies, such as checkpoint inhibitors.Moreover, we underscore the importance of multiomics approaches and networkanalysis in elucidating the complex regulatory networks governing renal cancerpathogenesis. By integrating cutting-edge research and clinical insights, this review contributesto the development of innovative diagnostic and therapeutic strategies, whichhave the potential to improve risk stratification, precision medicine, andultimately, patient outcomes in renal cancer., Competing Interests: The authors declare no conflict of interests., (© 2024 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.)

Renal cell carcinoma (RCC) is recognized as one of the three primary malignant tumors affecting the urinary system, posing a significant risk to human health and life. Despite advancements in understanding RCC, challenges persist in its diagnosis and treatment, particularly in early detection and diagnosis due to issues of low specificity and sensitivity. Consequently, there is an urgent need for the development of effective strategies to enhance diagnostic accuracy and treatment outcomes for RCC. In recent years, with the extensive research on materials for applications in the biomedical field, some materials have been identified as promising for clinical applications, e.g., in the diagnosis and treatment of many tumors, including RCC. Herein, we summarize the latest materials that are being studied and have been applied in the early diagnosis and treatment of RCC. While focusing on their adjuvant effects, we also discuss their technical principles and safety, thus highlighting the value and potential of their application. In addition, we also discuss the limitations of the application of these materials and possible future directions, providing new insights for improving RCC diagnosis and treatment., 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.)

Leukemia is a kind of hematological malignancy originating from bone marrow, which provides essential signals for initiation, progression, and recurrence of leukemia. However, how to specifically deliver drugs to the bone marrow remains elusive. Here, we develop biomimetic vesicles by infusing hematopoietic stem and progenitor cell (HSPC) membrane with liposomes (HSPC liposomes), which migrate to the bone marrow of leukemic mice via hyaluronic acid-CD44 axis. Moreover, the biomimetic vesicles exhibit superior binding affinity to leukemia cells through intercellular cell adhesion molecule-1 (ICAM-1)/integrin β2 (ITGB2) interaction. Further experiments validate that the vesicles carrying chemotherapy drug cytarabine (Ara-C@HSPC-Lipo) markedly inhibit proliferation, induce apoptosis and differentiation of leukemia cells, and decrease number of leukemia stem cells. Mechanically, RNA-seq reveals that Ara-C@HSPC-Lipo treatment induces apoptosis and differentiation and inhibits the oncogenic pathways. Finally, we verify that HSPC liposomes are safe in mice. This study provides a method for targeting bone marrow and treating leukemia., (© 2024. The Author(s).)

Purpose: To evaluate the surgical outcomes in patients with Posner-Schlossman syndrome (PSS) at one year., Methods: A prospective interventional study in PSS patients with penetrating canaloplasty. Main outcome measure was success rate (6 mmHg≤ intraocular pressure (IOP) ≤ 21 mmHg) with or without medications., Results: Thirteen eyes in 13 patients with PSS underwent complete catheterization. The mean IOP and medications (Meds) were reduced to 16.1 ± 4.8 mmHg on 0.5 ± 1.0 Meds at 12 months. Complete and qualified success rates were 61.5% and 84.6% at 12 months. The postoperative recurrent rate of PSS was 69.2%, the mean peak IOP during attacks and episodes were decreased to 26.7 ± 8.3 mmHg and 1.7 ± 2.0 times respectively. Transient IOP spike (61.5%) and hyphema (38.5%) were the two most common postoperative complications., Conclusion: Penetrating canaloplasty achieves a high success rate in PSS without serious complications.

Pinellia ternata (Thunb.) Breit is a traditional Chinese medicine with important pharmacological effects. However, its cultivation is challenged by soil degradation following excessive use of chemical fertilizer. We conducted an experiment exploring the effects of replacing chemical fertilizers with organic fertilizers (OF) on the growth and yield of P. ternata, as well as on the soil physicochemical properties and microbial community composition using containerized plants. Six fertilization treatments were evaluated, including control (CK), chemical fertilizer (CF), different proportions of replacing chemical fertilizer with organic fertilizer (OM 1-4 ). Containerized P. ternata plants in each OF treatment had greater growth and yield than the CK and CF treatments while maintaining alkaloid content. The OM 3 treatment had the greatest yield among all treatments, with an increase of 42.35% and 44.93% compared to the CK and CF treatments, respectively. OF treatments improved soil quality and fertility by enhancing the activities of soil urease (S-UE) and sucrase (S-SC) enzymes while increasing soil organic matter and trace mineral elements. OF treatments increased bacterial abundance and changed soil community structure. In comparison to the CK microbial groups enriched in OM 3 were OLB13, Vicinamibacteraceae, and Blrii41. There were also changes in the abundance of gene transcripts among treatments. The abundance of genes involved in the nitrogen cycle in the OM 3 has increased, specifically promoting the transformation of N-NO 3 - into N-NH 4 + , a type of nitrogen more easily absorbed by P. ternata. Also, genes involved in "starch and sucrose metabolism" and "plant hormone signal transduction" pathways were positively correlated to P. ternata yield and were upregulated in the OM 3 treatment. Overall, OF in P. ternata cultivation is a feasible practice in advancing sustainable agriculture and is potentially profitable in commercial production., (© 2024. The Author(s).)

Introduction: Chrysanthemum morifolium Ramat. is a perennial herb in the Compositae family, often employed in traditional Chinese medicine due to its medicinal value. The planting of C. morifolium faces the challenges of continuous cropping, and intercropping is able to somewhat overcome the obstacles of continuous cropping., Methods: In our study, we designed two different C. morifolium -maize intercropping patterns, including C. morifolium -maize narrow-wide row planting (IS) and C. morifolium -maize middle row planting (IM). Compared with monoculture, the agronomic traits, yield, active ingredients, soil physicochemical properties, soil enzyme activities, and rhizosphere soil microbial communities of C. morifolium and maize were measured under the two C. morifolium -maize intercropping patterns., Results: The findings indicated that (1) Intercropping elevated the agronomic traits, yield, and active ingredients of C. morifolium , especially in C. morifolium -maize narrow-wide row planting pattern, which indicating that interspecific distance played an important role in intercropping system; (2) Intercropping enhanced soil physicochemical properties and enzyme activities of C. morifolium and maize; (3) Intercropping altered rhizosphere soil microbial communities of C. morifolium and maize, making microbial interrelationships more complex. (4) Intercropping could recruit a large number of beneficial microorganisms enrich in the soil, including Bacillus , Sphingomonas , Burkholderia-Caballeronia-Paraburkholderia , Chaetomium , and Ceratorhiza , which may increase the content of AN, NN, AvK, ExCa, AvCu, AvZn and other nutrients in soil and promoted the growth and quality of C. morifolium., Discussion: In summary, intercropping with maize could promote the accumulation of beneficial microorganisms in the soil, thus improving the overall growing environment, and finally realizing the growth and improvement of C. morifolium ., 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 Liao, Chen, Li, Wei, Wu, Wang, Liu, Miao and Liu.)

Epigenetic modification shapes differentiation trajectory and regulates the exhaustion state of chimeric antigen receptor T (CAR-T) cells. Limited efficacy induced by terminal exhaustion closely ties with intrinsic transcriptional regulation. However, the comprehensive regulatory mechanisms remain largely elusive. Here, we identify class I histone deacetylase inhibitors (HDACi) as boosters of CAR-T cell function by high-throughput screening of chromatin-modifying drugs, in which M344 and chidamide enhance memory maintenance and resistance to exhaustion of CAR-T cells that induce sustained antitumor efficacy both in vitro and in vivo. Mechanistically, HDACi decrease HDAC1 expression and enhance H3K27ac activity. Multi-omics analyses from RNA-seq, ATAC-seq, and H3K27ac CUT&Tag-seq show that HDACi upregulate expression of TCF4, LEF1, and CTNNB1, which subsequently activate the canonical Wnt/β-catenin pathway. Collectively, our findings elucidate the functional roles of class I HDACi in enhancing CAR-T cell function, which provides the basis and therapeutic targets for synergic combination of CAR-T cell therapy and HDACi treatment., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Microplastics (MPs) are contaminants ubiquitously found in the global biosphere that enter the body through inhalation or ingestion, posing significant risks to human health. Recent studies emerge that MPs are present in the bone marrow and damage the hematopoietic system. However, it remains largely elusive about the specific mechanisms by which MPs affect hematopoietic stem cells (HSCs) and their clinical relevance in HSC transplantation (HSCT). Here, we established a long-term MPs intake mouse model and found that MPs caused severe damage to the hematopoietic system. Oral gavage administration of MPs or fecal transplantation of microbiota from MPs-treated mice markedly undermined the self-renewal and reconstitution capacities of HSCs. Mechanistically, MPs did not directly kill HSCs but disrupted gut structure and permeability, which eventually ameliorated the abundance of Rikenellaceae and hypoxanthine in the intestine and inactivated the HPRT-Wnt signaling in bone marrow HSCs. Furthermore, administration of Rikenellaceae or hypoxanthine in mice as well as treatment of WNT10A in the culture system substantially rescued the MPs-induced HSC defects. Finally, we validated in a cohort of human patients receiving allogenic HSCT from healthy donors, and revealed that the survival time of patients was negatively correlated with levels of MPs, while positively with the abundance of Rikenellaceae, and hypoxanthine in the HSC donors' feces and blood. Overall, our study unleashes the detrimental roles and mechanisms of MPs in HSCs, which provides potential strategies to prevent hematopoietic damage from MPs and serves as a fundamental critique for selecting suitable donors for HSCT in clinical practice., (© 2024. The Author(s).)

Microplastics can enter the human body through the food chain and can cause cardiovascular or cerebrovascular diseases; thus, it is essential to detect microplastics sensitively and accurately. Traditional methods have some drawbacks, such as a low sensitivity and complicated experimental procedures, so it is difficult to detect microplastics less than 1 μm. While surface enhanced Raman scattering technology can compensate for these shortcomings, there are fewer reports on the quantitative detection of microplastics using SERS technology. In this study, SERS and an internal standard method were utilized to detect microplastics qualitatively and quantitatively. The electric field enhancement effect of common gold, silver, and copper substrates were simulated by the finite element method, and the influence rule of structural parameters on the enhancement factor was obtained to optimize structural parameters. Subsequently, a gold nanopyramid array substrate was prepared using the colloidal sphere template method. Finally, the prepared substrate was applied to detect polystyrene microplastics with a diameter of 500 nm, and the detection of limit is 1.8 × 10 -4 mg mL -1 in the quantitative range of 2-2 × 10 -4 mg mL -1 , and the correlation coefficient of the linear regression equation is 0.9918. The experimental results showed that this proposal has a lower detection limit and a wider quantitative range and expands ideas for the qualitative and quantitative detection of microplastics in seawater.

Methylglyoxal (MGO) scavenging capacity of fiber-bound polyphenols from highland barley during colonic fermentation and its potential role in modulating MGO-induced detrimental effects on gut microbiota were studied. Results showed that only 25.3 % of polyphenols were released after 24 h of colonic fermentation. More than 45.5 % of MGO was scavenged by the residual fiber-bound polyphenols in the model system, showing a vital role in scavenging MGO in the colonic lumen compared to the released polyphenols. Moreover, MGO promoted the increase of gut pathogens (Escherichia-Shigella and Klebsiella) and inhibited the proliferation of Megasphaera, Bifidobacterium and Megamonas, as well as reduced short-chain fatty acids (SCFAs) concentration. The addition of fiber-bound polyphenols of highland barley could effectively counteract MGO-induced detrimental consequences on gut microbiota and SCFAs production. These results demonstrate that fiber-bound polyphenols from highland barley can exert beneficial role through scavenging MGO and promises to be a functional ingredient to maintain colon heath., 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.)

Zinc-ion batteries (ZIBs) have attracted an increasing attention as a potential low-cost, environmentally friendliness, and high-safety energy storage system. Among them, transition metal vanadates with high oxidation state vanadium have great potential in ZIBs cathode research due to their high theoretical capacity. However, many vanadate particles still inevitably suffer from low ion mobility, low electrical conductivity and stability. Cation doping or compositing is an effective pathway capable of enhancing electrical conductivity. In this work, layered Cu-Fe 2 VO 4 porous nanorods are obtained by introducing Cu 2+ into MIL-88A(Fe) (a metal-organic framework; MIL stands for materials from Institute Lavoisier) and further ion-exchanged with NH 4 VO 3 , exhibiting excellent zinc storage properties as an cathode. The existence of oxygen vacancies and the change of electronic structure caused by Cu 2+ substituting part of Fe 2+ enhanced the conductivity and electron transfer rate. It delivers a reversible discharge capacity of 237 mAh/g at 0.3 A/g and a satisfactory high rate capacity of 126 mAh/g after 30 cycles at 5 A/g, and stable cycling performance (198 mAh/g after 1000 cycles at 1 A/g). Furthermore, the energy density can reached to 230.97 Wh kg -1 at 208.6 W kg -1 . The assembled quasi-solid-state ZIBs maintain a high capacitance retention of 75% after 8000 cycles at 1 A/g., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Whole grain insoluble dietary fiber (IDF) is a good source of bound-form polyphenols. In the present study, insoluble dietary fiber rich in bound polyphenols (BP-IDF) from quinoa, rye and wheat was prepared. The carbonyl scavenging capacities of these three BP-IDFs and the effects of in vitro gastrointestinal (GI) digestion and colonic fermentation on their scavenging activities were studied. The results indicated that the fiber-bound polyphenols from quinoa showed the highest carbonyl scavenging capacity compared to those from rye and wheat. After colonic fermentation, more than 73% of the bound polyphenols were still retained in the fermented residues of the quinoa BP-IDF. The fiber-bound polyphenols in the GI-digested residues of quinoa retained considerable carbonyl scavenging activities. During the fermentation process, the residual fiber-bound polyphenols in the fermented residues still scavenged 35.8% to 45.2% of methylglyoxal, 19.3% to 25.4% of glyoxal, 50.7% to 60.5% of acrolein and 5.2% to 9.7% of malondialdehyde, showing a critical role in the scavenging of carbonyl compounds compared to the released and metabolized polyphenols. These findings confirm the capacity of fiber-bound polyphenols from three whole grains to scavenge carbonyls during in vitro digestion and fermentation processes, suggesting that they could be used as functional ingredients to maintain continuous defenses against carbonyls along the digestive tract.

Branched-chain keto-acid dehydrogenase kinase (BCKDK) is the rate-limiting enzyme of branched-chain amino acid (BCAA) metabolism. In the last six years, BCKDK has been used as a kinase to promote tumor proliferation and metastasis. Renal cell carcinoma (RCC) is a highly vascularized tumor. A high degree of vascularization promotes tumor metastasis. Our objective is to explore the relationship between BCKDK and RCC metastasis and its specific mechanism. In our study, BCKDK is highly expressed in renal clear cell carcinoma and promotes the migration of clear cell renal cell carcinoma (ccRCC). Exosomes from ccRCC cells can promote vascular permeability and angiogenesis, especially when BCKDK is overexpressed in ccRCC cells. BCKDK can also augment the miR-125a-5p expression in ccRCC cells and derived exosomes, thereby decreasing the downstream target protein VE-cadherin level, weakening adhesion junction expression, increasing vascular permeability, and promoting angiogenesis in HUVECs. The novel BCKDK/Exosome-miR-125a-5p/VE-cadherin axis regulates intercellular communication between ccRCC cells and HUVECs. BCKDK plays a critical role in renal cancer metastasis, may be used as a molecular marker of metastatic ccRCC, and even may become a potential target of clinical anti-vascular therapy for ccRCC., (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Boron neutron capture therapy (BNCT) is one of the most promising treatments among neutron capture therapies due to its long-term clinical application and unequivocally obtained success during clinical trials. Boron drug and neutron play an equivalent crucial role in BNCT. Nevertheless, current clinically used l-boronophenylalanine (BPA) and sodium borocaptate (BSH) suffer from large uptake dose and low blood to tumor selectivity, and that initiated overwhelm screening of next generation of BNCT agents. Various boron agents, such as small molecules and macro/nano-vehicles, have been explored with better success. In this featured article, different types of agents are rationally analyzed and compared, and the feasible targets are shared to present a perspective view for the future of BNCT in cancer treatment. This review aims at summarizing the current knowledge of a variety of boron compounds, reported recently, for the application of BCNT., (© 2023 Wiley Periodicals LLC.)

Synthetic lethality (SL) is a potential cancer therapeutic strategy and drug discovery. Computational approaches to identify synthetic lethality genes have become an effective complement to wet experiments which are time consuming and costly. Graph convolutional networks (GCN) has been utilized to such prediction task as be good at capturing the neighborhood dependency in a graph. However, it is still a lack of the mechanism of aggregating the complementary neighboring information from various heterogeneous graphs. Here, we propose the Multiple Attention Graph Convolution Networks for predicting synthetic lethality (MAGCN). First, we obtain the functional similarity features and topological structure features of genes from different data sources respectively, such as Gene Ontology data and Protein-Protein Interaction. Then, graph convolutional network is utilized to accumulate the knowledge from neighbor nodes according to synthetic lethal associations. Meanwhile, we propose a multiple graphs attention model and construct a multiple graphs attention network to learn the contribution factors of different graphs to generate embedded representation by aggregating these graphs. Finally, the generated feature matrix is decoded to predict potential synthetic lethal interaction. Experimental results show that MAGCN is superior to other baseline methods. Case study demonstrates the ability of MAGCN to predict human SL gene pairs.

Cancer is a multifaceted disease that results from co-mutations of multi biological molecules. A promising strategy for cancer therapy involves in exploiting the phenomenon of Synthetic Lethality (SL) by targeting the SL partner of cancer gene. Since traditional methods for SL prediction suffer from high-cost, time-consuming and off-targets effects, computational approaches have been efficient complementary to these methods. Most of existing approaches treat SL associations as independent of other biological interaction networks, and fail to consider other information from various biological networks. Despite some approaches have integrated different networks to capture multi-modal features of genes for SL prediction, these methods implicitly assume that all sources and levels of information contribute equally to the SL associations. As such, a comprehensive and flexible framework for learning gene cross-network representations for SL prediction is still lacking. In this work, we present a novel Triple-Attention cross-network Representation learning for SL prediction (TARSL) by capturing molecular features from heterogeneous sources. We employ three-level attention modules to consider the different contribution of multi-level information. In particular, feature-level attention can capture the correlations between molecular feature and network link, node-level attention can differentiate the importance of various neighbors, and network-level attention can concentrate on important network and reduce the effects of irrelated networks. We perform comprehensive experiments on human SL datasets and these results have proven that our model is consistently superior to baseline methods and predicted SL associations could aid in designing anti-cancer drugs.

Background: The gastrointestinal (GI) tract is a major site of lipid oxidation, and the lipid oxidation products are related to an increased risk of various chronic diseases. In this study, the inhibition capacity of bound-polyphenol rich insoluble dietary fiber (BP-IDF) from highland barley (HB) to lipid oxidation was evaluated during simulated GI digestion., Results: We found that the level of lipid hydroperoxides (LOOH) and aldehydes were significantly inhibited when highland barley bound-polyphenol rich insoluble dietary fiber (HBBP-IDF) co-digestion with cooked pork. The lipid oxidation products were more effectively scavenged during simulated gastric digestion, with inhibition of 77.4% for LOOH, 52.3% for malondialdehyde, 46.5% for 4-hydroxy-2-hexenal and 48.7% for 4-hydroxy-2-nonenel, respectively. The fiber-bound polyphenols are the principal scavengers of lipid oxidation products., Conclusion: These findings suggest that HBBP-IDF could be used as a functional ingredient able to scavenge lipid oxidation products across the GI tract. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Breast cancer is the most common malignant cancer in women worldwide. Cancer metastasis is the major cause of cancer-related deaths. BCKDK is associated with various diseases, including proliferation, migration, and invasion in multiple types of human cancers. However, the relevance of BCKDK to the development and progression of breast cancers and its function is unclear. This study found that BCKDK was overexpressed in breast cancer, associated with poor prognosis, and implicated in tumor metastasis. The downregulation of BCKDK expression inhibited the migration of human breast cancer cells in vitro and diminished lung metastasis in vivo. BCKDK perturbed the cadherin-catenin complex at the adherens junctions (AJs) and assembled focal adhesions (FAs) onto the extracellular matrix, thereby promoting the directed migration of breast cancer cells. We observed that BCKDK acted as a conserved regulator of the ubiquitination of cytoskeletal protein talin1 and the activation of the FAK/MAPK pathway. Further studies revealed that BCKDK inhibited the binding of talin1 to E3 ubiquitin ligase-TRIM21, leading to the decreased ubiquitination/degradation of talin1. In conclusion, identifying BCKDK as a biomarker for breast cancer metastasis facilitated further research on diagnostic biomarkers. Elucidating the mechanism by which BCKDK exerted its biological effect could provide a new theoretical basis for developing new markers for breast cancer metastasis and contribute to developing new therapies for the clinical treatment of breast cancer patients., (© 2023. The Author(s).)

Introduction: Duck circovirus (DuCV) infection is currently recognized as an important immunosuppressive disease in commercial duck flocks in China. Specific antibodies against DuCV viral proteins are required to improve diagnostic assays and understand the pathogenesis of DuCV infection., Methods and Results: To generate DuCV-specific monoclonal antibodies (mAbs), a recombinant DuCV capsid protein without the first 36 N-terminal amino acids was produced in Escherichia coli . Using the recombinant protein as an immunogen, a mAb was developed that reacted specifically with the DuCV capsid protein, expressed in E. coli and baculovirus systems. Using homology modeling and recombinant truncated capsid proteins, the antibody-binding epitope was mapped within the region of 144 IDKDGQIV 151 , which is exposed to solvent in the virion capsid model structure. To assess the applicability of the mAb to probe the native virus antigen, the murine macrophage cell line RAW267.4 was tested for DuCV replicative permissiveness. Immunofluorescence and Western blot analysis revealed that the mAb recognized the virus in infected cells and the viral antigen in tissue samples collected from clinically infected ducks., Discussion: This mAb, combined with the in vitro culturing method, would have widespread applications in diagnosing and investigating DuCV pathogenesis., 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 Li, Liu, Ren, Fu, Shi, Zhao, Huang and Su.)

Hematologic malignancies (HMs) pose a serious threat to patients' health and life, and the five-year overall survival of HMs remains low. The lack of understanding of the pathogenesis and the complex clinical symptoms brings immense challenges to the diagnosis and treatment of HMs. Traditional therapeutic strategies for HMs include radiotherapy, chemotherapy, targeted therapy and hematopoietic stem cell transplantation. Although immunotherapy and cell therapy have made considerable progress in the last decade, nearly half of patients still relapse or suffer from drug resistance. Recently, studies have emerged that nanomaterials, nanotechnology and nanomedicine show great promise in cancer therapy by enhancing drug targeting, reducing toxicity and side effects and boosting the immune response to promote durable immunological memory. In this review, we summarized the strategies of recently developed nanomaterials, nanotechnology and nanomedicines against HMs and then proposed emerging strategies for the future designment of nanomedicines to treat HMs based on urgent clinical needs and technological progress., (© 2023. The Author(s).)

Although anti-PD-L1 therapy has been used in the clinical treatment of renal cell carcinoma (RCC), a proportion of patients are not sensitive to it, which may be attributed to the heterogeneity of PD-L1 expression. Here, we demonstrated that high TOPK (T-LAK cell-originated Protein Kinase) expression in RCC promoted PD-L1 expression by activating ERK2 and TGF-β/Smad pathways. TOPK was positively correlated with PD-L1 expression levels in RCC. Meanwhile, TOPK significantly inhibited the infiltration and function of CD8 + T cells and promoted the immune escape of RCC. Moreover, inhibition of TOPK significantly enhanced CD8 + T cell infiltration, promoted CD8 + T cell activation, enhanced anti-PD-L1 therapeutic efficacy, and synergistically enhanced anti-RCC immune response. In conclusion, this study proposes a new PD-L1 regulatory mechanism that is expected to improve the effectiveness of immunotherapy for RCC., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

Recently, a novel poplar mosaic disease caused by bean common mosaic virus (BCMV) was investigated in Populus alba var. pyramidalis in China. Symptom characteristics, physiological performance of the host, histopathology, genome sequences and vectors, and gene regulation at the transcriptional and posttranscriptional levels were analyzed and RT-qPCR (quantitative reverse transcription PCR) validation of expression was performed in our experiments. In this work, the mechanisms by which the BCMV pathogen impacts physiological performance and the molecular mechanisms of the poplar response to viral infection were reported. The results showed that BCMV infection decreased the chlorophyll content, inhibited the net photosynthesis rate (Pn) and stomatal conductance (Gs), and significantly changed chlorophyll fluorescence parameters in diseased leaves. Transcriptome analysis revealed that the expression of the majority of DEGs (differentially expressed genes) involved in the flavonoid biosynthesis pathway was promoted, but the expression of all or almost all DEGs associated with photosynthesis-antenna proteins and the photosynthesis pathway was inhibited in poplar leaves, suggesting that BCMV infection increased the accumulation of flavonoids but decreased photosynthesis in hosts. Gene set enrichment analysis (GSEA) illustrated that viral infection promoted the expression of genes involved in the defense response or plant-pathogen interaction. MicroRNA-seq analysis illustrated that 10 miRNA families were upregulated while 6 families were downregulated in diseased poplar leaves; moreover, miR156, the largest family with the most miRNA members and target genes, was only differentially upregulated in long-period disease (LD) poplar leaves. Integrated transcriptome and miRNA-seq analyses revealed 29 and 145 candidate miRNA-target gene pairs; however, only 17 and 76 pairs, accounting for 2.2% and 3.2% of all DEGs, were authentically negatively regulated in short-period disease (SD) and LD leaves, respectively. Interestingly, 4 miR156/SPL (squamosa promoter-binding-like protein) miRNA-target gene pairs were identified in LD leaves: the miR156 molecules were upregulated, but SPL genes were downregulated. In conclusion, BCMV infection significantly changed transcriptional and posttranscriptional gene expression in poplar leaves, inhibited photosynthesis, increased the accumulation of flavonoids, induced systematic mosaic symptoms, and decreased physiological performance in diseased poplar leaves. This study elucidated the fine-tuned regulation of poplar gene expression by BCMV; moreover, the results also suggested that miR156/SPL modules played important roles in the virus response and development of viral systematic symptoms in plant virus disease., 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, Zhang, Shen, Li, Fu, Li, Li, Liu, Su, Zhang and Zhao.)

Plant-based yogurt has several advantages over traditional yogurt, such as being lactose and cholesterol-free, making it more suitable for individuals with cardiovascular and gastrointestinal diseases. The formation mechanism of the gel in plant-based yogurt needs more attention because it is associated with the gel properties of yogurt. Most plant proteins, except for soybean protein, have poor functional abilities, such as solubility and gelling properties, which limits their application in most food items. This often results in undesirable mechanical quality of plant-based products, particularly plant-based yogurt gels, including grainy texture, high syneresis, and poor consistency. In this review, we summarize the common formation mechanism of plant-based yogurt gel. The main ingredients, including protein and non-protein components, as well as their interactions involved in the gel are discussed to understand their effects on gel formation and properties. The main interventions and their effects on gel properties are highlighted, which have been shown to improve the properties of plant-based yogurt gels effectively. Each type of intervention method may exhibit desirable advantages in different processes. This review provides new opportunities and theoretical guidance for efficiently improving the gel properties of plant-based yogurt for future consumption.

During recent years, microrobots have drawn extensive attention owing to their good controllability and great potential in biomedicine. Powered by external physical fields or chemical reactions, these untethered microdevices are promising candidates for in vivo complex tasks, such as targeted delivery, imaging and sensing, tissue engineering, hyperthermia, and assisted fertilization, among others. However, in clinical use, the biodegradability of microrobots is significant for avoiding toxic residue in the human body. The selection of biodegradable materials and the corresponding in vivo environment needed for degradation are increasingly receiving attention in this regard. This review aims at analyzing different types of biodegradable microrobots by critically discussing their advantages and limitations. The chemical degradation mechanisms behind biodegradable microrobots and their typical applications are also thoroughly investigated. Furthermore, we examine their feasibility and deal with the in vivo suitability of different biodegradable microrobots in terms of their degradation mechanisms; pathological environments; and corresponding biomedical applications, especially targeted delivery. Ultimately, we highlight the prevailing obstacles and perspective solutions, ranging from their manufacturing methods, control of movement, and degradation rate to insufficient and limited in vivo tests, that could be of benefit to forthcoming clinical applications.

Glaucoma is one of the most common optic neuropathies, featuring progressive retinal ganglion cell damage and visual field loss (Tham et al., 2014; Xu et al., 2020). Currently, the only effective treatment for this condition is the reduction of intraocular pressure (IOP) (Palmberg, 2001; Heijl et al., 2002). Canaloplasty is a proven bleb-independent surgery with good efficacy and safety profiles in primary open-angle glaucoma (POAG) (Gołaszewska et al., 2021). However, early transient postoperative IOP elevation has been reported in up to 30% of cases (Riva et al., 2019), similar to that commonly observed in other internal drainage glaucoma surgeries such as implantation using iStent (0%-21.0%), CyPass (10.8%), and Hydrus (4.8%-6.5%) (Lavia et al., 2017). This complication may be a predictor of poor reserve in the outflow system and is potentially associated with surgical failure. Nonetheless, the exact pathophysiology of glaucoma remains unknown, and studies clarifying the risk factors for postoperative IOP elevation have been scarce.

Equity in the inheritance culture of family property is an important component of humanistic health in modern living environments. The inheritance of property under Chinese traditional family culture is the material basis for the continuation of family and clan. This study demonstrates the equity component embedded in traditional family inheritance culture and further studies of the healthy human settlements environment. Based on the theory of "equal share for all sons" in ancient China and the "equity" and "justice" that are of modern significance, this paper analyzes the family division culture of individual traditional housing and the corresponding impact indices of family division equity. Taking Renhe Village, a typical local residential building of the middle and late Qing Dynasty as the research object, this study built a spatial syntax data model and 3D simulation technology for the simulation analysis of space and climate. The results show that Renhe Village meets the requirements of the equity evaluation system of housing property rights distribution in terms of the natural unit indicator (quantity, lighting, ventilation) and the overall spatial indicator (privacy, centrality, convenience). In other words, equity does not mean an absolute average share, but an equity culture formed after six evaluation indices under the subdivision of two indicators are balanced. Based on the above, an equity system model of housing property rights distribution was established, and the weight of the ancients' attention to the housing distribution standard was explored. It is further found that the ancients attached more importance to light among the natural unit indicators, and attached the most importance to centrality in the overall spatial indicators. These findings provide new ideas for understanding the equity of property inheritance under Chinese traditional family culture. They also provide quantifiable criteria for the distribution of modern rural housing and social security housing, and ultimately provide a reference for the humanistic public health of the modern living environment., 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 Shu, Li, Wu, Chen and Ding.)

Cobalt mediated perovskite oxides (Ca-Fe-Co-x) were prepared for heterogeneous Fenton-like, which exhibited excellent tetracycline (TC) degradation efficiency and wider pH suitability (3-11). Experimental results showed that Ca-Fe-Co-1.0 sample displayed the highest degradation rate could reach 80.5% under neutral conditions, and maintain at around 80% after four cycles. The analysis of degradation mechanism showed that the redox of Fe 2+ /Fe 3+ and Co 2+ /Co 3+ significant enhanced the activation of H 2 O 2 to superoxide radical (∙O 2 - ). Meanwhile, the hydroxyl radical (∙OH) was also detected by ESR analysis. In addition, the possible degradation pathway and mechanism of TC were deduced via UPLC-QTOF/MS analysis and density functional theory (DFT) calculations. The toxicity of TC and its intermediates were also evaluated by the ECOSAR software. The Ca-Fe-Co-1.0/nanocellulose aerogel (NCA) displayed highly removal efficiency of TC wastewater in the long-term operation conduction. This study provided a feasible method to design and synthesis heterogeneous Fenton-like catalysts for antibiotic degradation., 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.)

Coal pyrolysis wastewater (CPW) contained all kinds of toxic and harmful components, which would seriously threaten the natural environment and human health. However, the traditional advanced oxidation processes frequently failed to remove phenolic substances. An A 2 BO 4 -type perovskite (La 2 CuO 4 ) was successfully synthesized through sol-gel process and first applied in the treatment of CPW. More than 90% of 3, 5-dimethylphenol (DMP) was removed within 200 min at neutral conditions. Moreover, La 2 CuO 4 also displayed excellent catalytic activity and stability in the actual CPW treatment process. Results demonstrated that DMP was removed through the attack of ∙OH, ∙O 2 - and 1 O 2 in La 2 CuO 4 /H 2 O 2 system. The La 2 CuO 4 were more favorable for H 2 O 2 activation and have a lower adsorption energy than LaFeO 3 . XPS of fresh and spent La 2 CuO 4 illustrated that the decomposition of hydrogen peroxide (H 2 O 2 ) was mainly due to the redox cycle between surface copper and oxygen species. Moreover, the possible degradation pathway of DMP was deduced by identifying degradation products and analyzing density functional theory (DFT) calculations. This research provided a novel strategy for the development of perovskite-based catalytic materials on the treatment of practical CPW., 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 Inc. All rights reserved.)

Cynanchum stauntonii is a perennial herb plant of the Asclepiadaceae family. The dried roots and rhizomes have been used as medicine in China for 1500 years and are considered a remedy for cough and phlegm. In recent years, the wild C. stauntonii resources have not been sufficient for market demand, therefore, a large artificial cultivation area was established in Xinzhou, Tuanfeng and Macheng in Hubei province. In March and April 2022, serious outbreaks of seedling blight were observed in C. stauntonii in Xinzhou county (N30°48'12″, E114°49'24″), and the disease occurred on 10 to 15% of plants in five C. stauntonii nursery beds. Early symptoms included withered tips, chlorosis, stunting, yellow leaves and leaf drop, and later, seedlings die in patches. To determine the causal agent of disease, pieces (5 mm × 5 mm) of diseased tissue at the junction of disease and healthy tissue were surface disinfected by soaking in 75% ethanol for 3 min, rinsed three times with sterilized water, and pieces were placed on PDA at 25°C. Fungal isolates obtained were yellow-brown at the center and pink to white toward the periphery, and dark red pigments were observed in the agar. Isolates were cultured in synthetic low nutrient agar (SNA) and carnation leaf agar to observe the spore morphology. The macroconidia were sickle-shaped with 3-4 septate, with sizes of 30.26±2.36×3.77±0.53 μm on SNA and 33.52±2.20×3.81±0.48 μm on carnation leaf agar (n=30). Morphological characteristics of the isolates were consistent with those of Fusarium sp in the Fusarium Laboratory Manual (Leslie et al. 2006). Furthermore, the genomic DNA from a representative isolate BQ-2 was extracted, the ITS, TEF-1α, RPB1 and RPB2 genes were amplified with primers ITS1/ITS4, EF1/EF2, Fa/G2R and 5F2/7cr, respectively (Zhang et al. 2022). BLAST analysis showed that the ITS (ON935780.1), TEF-1α (OP985126.1), RPB1 (OP985125.1) and RPB2 (OP985124.1) amplicon sequence were 99.44%, 98.94%, 99.88% and 100% identical to the sequences of F. tricinctum strain (KU350724.1, AB674264.1, LC701712.1, MW474678.1), respectively. A phylogenetic tree constructed based on a concatenated sequence (ITS, TEF-1α, RPB1, RPB2) using the neighbor-joining and maximum likelihood method in MEGA7 revealed that BQ-2 grouped with concatenated sequences from four representative F. tricinctum isolates in GenBank. Based on the morphological characteristics and molecular identification, the strain BQ-2 was identified as F. tricinctum. For pathogenicity tests, 5 mm pieces of a BQ-2 colony on PDA were placed on excised leaves of healthy C. stauntonii wounded with a needle (n=5) and kept at 25±2℃. Leaves treated PDA were used as a control (Li et al.2020). After three days inoculation, the mycelia proliferated and began to infect leaf tissues. Ten days later, large parts of the detached leaves were extensively infested with the pathogen and brown. For live plant inoculation, stem bases of five healthy seedlings were punctured with sterile needle and then inoculated with BQ-2 mycelia from PDA. Controls were treated with only PDA. The seedlings began wilting after three days and at five days showed typical disease symptoms, similar to those observed in the field. The controls were asymptomatic. The pathogen was reisolated from the diseased tissues, and the colonies and microscopic characteristics were similar to those of BQ-2. To the best of our knowledge, this is the first report of F. tricinctum causing seedling blight on C. stauntonii in China. This report will provide resources and reference for controlling the increased incidence and economic losses of seedling blight on C. stauntonii.

Psoriasis is an immune-mediated, persistent inflammatory disease with a genetic predisposition, and the involvement of multiple organs in psoriasis remains indicative of systemic disease. Atherosclerosis (AS) is a common complication of patients with severe or prolonged psoriasis. The specific pathogenesis of psoriasis is still unclear. Current studies suggest that psoriasis is a polygenic genetic disease with the interaction of multiple factors such as heredity and environment. Keratinocytes are proliferated through immune-mediated inflammatory pathway, which leads to cell activation, infiltration of dermis cells and release of inflammatory factors. Activation of inflammatory cells and pro-inflammatory factors play an important role in the progression of psoriasis and atherosclerosis. Studies have found that there is a close relationship between psoriasis and atherosclerosis, and systemic inflammation may be the common feature of psoriasis and AS. This paper attempts to explore the possibility of the relationship between psoriasis and atherosclerotic comorbidities from the aspects of potential epidemiology and immune mechanism, in order to provide some reference for the subsequent scientific research., 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, Chen, Liu, Huang, Yu, Du, Long, Chen, Chen, Guo, Li, Jiang, Wang and Lu.)

Prunella vulgaris L. is a perennial herb plant of the Lamiaceae family, and its dried spicas have been widely used as medicine, health-promoting food or tea around the world. P. vulgaris is distributed all over the world, such as Europe, Asia, northwestern Africa and North America, as well as the Huaihe River Basin and the middle and lower Yangtze River Basin in China. In February 2022, a serious disease like gray mold occurred in planting fields of P. vulgaris in Wuhan, Hubei (N30°27'07″, E114°15'49″), causing approximately 20% of plants were diseased in the field. Early symptoms were characterized by small, round gray-brown lesions on the leaves of P. vulgaris. Later, a large number of stems and leaves are wilted or necrotic, associated with wet rot and waterlogged spots and covered with light gray or grayish white flocculent mildew layer. To determine the causal agent of disease, 10 plants with the typical symptoms were collected from fields. The stems and leaves of diseased plants were cut into pieces (2 to 3 mm×5 mm), disinfected with 75% ethanol for 3 minutes, rinsed 3 times with sterile water. Each lesion sample was isolated and purified using separate PDA petri dishes at 25°C, and ultimately all samples yielded morphologically consistent pure strain colonies. From the 10 isolates obtained, XKC-1 was chosen as a representative isolate for further study. XKC-1 colonies showed gray aerial mycelia, which were fast-growing and grew over the whole plate (9 cm) after 4 days. In addition, some black and hard sclerotia (1.88±0.94 mm, n=50) with round or irregular shape developed on the colonies after approximately 10 days of incubation at 25°C (Fig. 2A, B). XKC-1 showed branched conidiophores with enlarged apical cells and numerous conidia (Fig. 2C). Unicellular conidia were colorless or gray, ellipsoid or ovoid, smooth and 7.91-12.38 μm × 10.08-13.82 μm (n=30) in size (Fig. 2D). Based on morphological characteristics, the isolate was initially identified as Botrytis sp. (Ellis 1971). To further identify the species, the genomic DNA of XKC-1 was extracted, and the ITS, LSU and G3PDH genes were amplified with the primers ITS1/ITS4, LROR/LR5 (Zhou et al. 2022) and G3PDH-F/G3PDH-R (Jin et al. 2022), respectively. The results indicated that the ITS (ON090404), LSU (ON090417), and G3PDH (ON169893) sequences were 99.80%, 100% and 99.46% identical to the sequences of Botrytis cinerea Pers. strain (MK370693.1, MN148533.1, MN630267.1), respectively. A phylogenetic tree constructed based on a concatenated sequence (ITS, LSU, G3PDH) using the neighbor-joining method in MEGA7 (Tamura et al. 2013) revealed that XKC-1 grouped with concatenated sequences from three representative B. cinerea isolates in GenBank. Based on the morphological characteristics and molecular identification, the strain XKC-1 was identified as Botrytis cinerea. For pathogenicity tests on detached leaves, 5 mm PDA cakes prepared from XKC-1 were placed on the leaves obtained from healthy P. vulgaris after wounding with a needle (n=10), while PDA medium without mycelia were used as control (25 ± 2°C) (Li et al.2020). Mycelia began to germinate and infect plant tissues at 1 dpi. A large part of the leaves showed water soaked spots covered with mycelia on the surface at 4 dpi. For whole plant inoculations, stem bases of five P. vulgaris seedlings were pierced with sterile needle, and then inoculated with three XKC-1 mycelium PDA cakes. Five plants were inoculated with three PDA cakes without mycelia as a control. After 2-4 days, lesions appeared on the leaves and covered with a gray-white mycelial layer, similar to those observed in the field. However, controls remained symptom free. The pathogen was reisolated from the diseased tissues, the colonies, microscopic characteristics and molecular identification were consistent with those of XKC-1. To our knowledge, this is a first report of B. cinerea causing gray mold on P. vulgaris in Hubei, China. This report would provide resources and reference for controlling of the increased incidence and economic losses of gray mold on P. vulgaris.

Predicting the associations of miRNAs and diseases may uncover the causation of various diseases. Many methods are emerging to tackle the sparse and unbalanced disease related miRNA prediction. Here, we propose a Probabilistic matrix decomposition combined with neighbor learning to identify MiRNA-Disease Associations utilizing heterogeneous data(PMDA). First, we build similarity networks for diseases and miRNAs, respectively, by integrating semantic information and functional interactions. Second, we construct a neighbor learning model in which the neighbor information of individual miRNA or disease is utilized to enhance the association relationship to tackle the spare problem. Third, we predict the potential association between miRNAs and diseases via probability matrix decomposition. The experimental results show that PMDA is superior to other five methods in sparse and unbalanced data. The case study shows that the new miRNA-disease interactions predicted by the PMDA are effective and the performance of the PMDA is superior to other methods.

Prostate cancer (PCa) has the second highest incidence of malignancies occurring in men worldwide. The first-line therapy of PCa is androgen deprivation therapy (ADT). Nonetheless, most patients progress to castration-resistant prostate cancer (CRPC) after being treated by ADT. As a second-generation androgen receptor (AR) antagonist, enzalutamide (ENZ) is the current mainstay of new endocrine therapies for CRPC in clinical use. However, almost all patients develop resistance during AR antagonist therapy due to various mechanisms. At present, ENZ resistance (ENZR) has become challenging in the clinical treatment of CRPC. AR splice variant 7 (AR-V7) refers to a ligand-independent and constitutively active variant of the AR and is considered a key driver of ENZR in CRPC. In this review, we summarize the mechanisms and biological behaviors of AR-V7 in ENZR of CRPC to contribute novel insights for CRPC therapy.

Suppose that the opposite changes of two emissions with temperature variation may result in a high sensitivity for a ratiometric thermometer; therefore, we design such a thermometer based on thermal quenching and negative thermal quenching materials. Herein, the Sc 2 Mo 3 O 12 :Yb 3+ /Er 3+ and Bi 2 MoO 6 :Yb 3+ /Tm 3+ crystals are synthesized via the solid-state reaction, respectively, which have the properties of negative thermal expansion (NTE) and positive thermal expansion (PTE). The composite is obtained through simple mechanical mixing between NTE and PTE crystals, in which the Er 3+ and Tm 3+ luminescence exhibit enhancement and quenching with increasing temperature, respectively. Based on the fluorescence intensity ratio (FIR) technique, the maximum relative sensitivity of the thermometer is 3.80% K -1 in the temperature range of 305-425 K. More importantly, the δT ≈ 0.24 K is relatively small meaning excellent accuracy. These findings indicate that the lanthanide-doped NTE and PTE composites may be good candidates for high sensitivity and accuracy thermometry.

DNA methyltransferase 3 A (DNMT3A) is the most frequently mutated gene in acute myeloid leukemia (AML). Although chemotherapy agents have improved outcomes for DNMT3A-mutant AML patients, there is still no targeted therapy highlighting the need for further study of how DNMT3A mutations affect AML phenotype. Here, we demonstrate that cell adhesion-related genes are predominantly enriched in DNMT3A-mutant AML cells and identify that graphdiyne oxide (GDYO) display an anti-leukemia effect specifically against these mutated cells. Mechanistically, GDYO directly interacts with integrin β2 (ITGB2) and c-type mannose receptor (MRC2), which facilitate the attachment and cellular uptake of GDYO. Furthermore, GDYO binds to actin and prevents actin polymerization, thus disrupting the actin cytoskeleton and eventually leading to cell apoptosis. Finally, we validate the in vivo safety and therapeutic potential of GDYO against DNMT3A-mutant AML cells. Collectively, these findings demonstrate that GDYO is an efficient and specific drug candidate against DNMT3A-mutant AML., (© 2022. The Author(s).)

Fungal pathogens can induce canker lesions, wilting, and even dieback in many species. Trees can suffer serious physiological effects from stem cankers. In this study, we investigated the effects of Botryosphaeria dothidea ( B . dothidea ) on Populus bolleana ( P. bolleana ) leaves photosynthesis and stomatal responses, when stems were inoculated with the pathogen. To provide experimental and theoretical basis for preventing poplar canker early. One-year-old poplar stems were inoculated with B . dothidea using an epidermal scraping method. In the early stage of B . dothidea inoculation (2-14 days post inoculation, dpi), the gas exchange, stomatal dynamics, hormone content, photosynthetic pigments content, chlorophyll fluorescence parameters, and non-structural carbohydrate (NSC) were evaluated to elucidate the pathophysiological mechanism of B . dothidea inhibiting photosynthesis. Compared with the control groups, B . dothidea noteworthily inhibited the net photosynthetic rate ( P n ), stomatal conductance ( G s ), intercellular CO 2 concentration ( C i ), transpiration rate ( T r ), and other photosynthetic parameters of poplar leaves, but stomatal limit value ( L s ) increased. Consistent with the above results, B . dothidea also reduced stomatal aperture and stomatal opening rate. In addition, B . dothidea not only remarkably reduced the content of photosynthetic pigments, but also decreased the maximum photochemical efficiency ( F v / F m ), actual photochemical efficiency ( Φ PSII ), electron transfer efficiency (ETR), and photochemical quenching coefficient ( q P ). Furthermore, both chlorophyll and Φ PSII were positively correlated with P n . In summary, the main reason for the abated P n under stem canker pathogen was that B . dothidea not merely inhibited the stomatal opening, but hindered the conversion of light energy, electron transfer and light energy utilization of poplar leaves. In general, the lessened CO 2 and P n would reduce the synthesis of photosynthetic products. Whereas, sucrose and starch accumulated in poplar leaves, which may be due to the local damage caused by B . dothidea inoculation in phloem, hindering downward transport of these products., 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 Xing, Li, Li, Shen, Li, Zhao and Zhang.)

Background: Allelopathy is expressed through the release of plant chemicals and is considered a natural alternative for sustainable weed management. Artemisia argyi (A. argyi) is widely distributed throughout Asia, and often dominates fields due to its strong allelopathy. However, the mechanism of A. argyi allelopathy is largely unknown and need to be elucidated at the physiological and molecular levels., Results: In this study, we used electron microscopy, ionomics analysis, phytohormone profiling, and transcriptome analysis to investigate the physiological and molecular mechanisms of A. argyi allelopathy using the model plant rice (Oryza sativa) as receptor plants. A. argyi water extract (AAWE)-treated rice plants grow poorly and display root morphological anomalies and leaf yellowing. We found that AAWE significantly inhibits rice growth by destroying the root and leaf system in multiple ways, including the integrity of ultrastructure, reactive oxygen species (ROS) homeostasis, and the accumulation of soluble sugar and chlorophyll synthesis. Further detection of the hormone contents suggests that AAWE leads to indole-3-acetic acid (IAA) accumulation in roots. Moreover, ionomics analysis shows that AAWE inhibits the absorption and transportation of photosynthesis-essential mineral elements, especially Mg, Fe, and Mn. In addition, the results of transcriptome analysis revealed that AAWE affects a series of crucial primary metabolic processes comprising photosynthesis in rice plants., Conclusions: This study indicates that A. argyi realizes its strongly allelopathy through comprehensive effects on recipient plants including large-scale IAA synthesis and accumulation, ROS explosion, damaging the membrane system and organelles, and obstructing ion absorption and transport, photosynthesis and other pivotal primary metabolic processes of plants. Therefore, AAWE could potentially be developed as an environmentally friendly botanical herbicide due to its strong allelopathic effects., (© 2022. The Author(s).)

Artemisia argyi Levl. et Van is an important Asteraceae species with a high medicinal value. There are abundant A. argyi germplasm resources in Asia, especially in China, but the evolutionary relationships of these varieties and the systematic localization of A. argyi in the family Asteraceae are still unclear. In this study, the chloroplast (cp) genomes of 72 A. argyi varieties were systematically analyzed. The 72 varieties originated from 47 regions in China at different longitudes, latitudes and altitudes, and included both wild and cultivated varieties. The A. argyi cp genome was found to be ∼151 kb in size and to contain 114 genes, including 82 protein-coding, 28 tRNA, and 4 rRNA genes. The number of short sequence repeats (SSRs) in A. argyi cp genomes ranged from 35 to 42, and most of them were mononucleotide A/T repeats. A total of 196 polymorphic sites were detected in the cp genomes of the 72 varieties. Phylogenetic analysis demonstrated that the genetic relationship between A. argyi varieties had a weak relationship with their geographical distribution. Furthermore, inverted repeat (IR) boundaries of 10 Artemisia species were found to be significantly different. A sequence divergence analysis of Asteraceae cp genomes showed that the variable regions were mostly located in single-copy (SC) regions and that the coding regions were more conserved than the non-coding regions. A phylogenetic tree was constructed using 43 protein-coding genes common to 67 Asteraceae species. The resulting tree was consistent with the traditional classification system; Artemisia species were clustered into one group, and A. argyi was shown to be closely related to Artemisia lactiflora and Artemisia montana . In summary, this study systematically analyzed the cp genome characteristics of A. argyi and compared cp genomes of Asteraceae species. The results provide valuable information for the definitive identification of A. argyi varieties and for the understanding of the evolutionary relationships between Asteraceae species., 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 Chen, Miao, Luo, Li, Wang, Luo, Zhao and Liu.)

TOPK/PBK (T-LAK Cell-Originated Protein Kinase) is a serine/threonine kinase that is highly expressed in a variety of human tumors and is associated with poor prognosis in many types of human malignancies. Its activation mechanism is not yet fully understood. A bidirectional signal transduced between TOPK and ERK2 (extracellular signal-regulated kinase 2) has been reported, with ERK2 able to phosphorylate TOPK at the Thr9 residue. However, mutated TOPK at Thr9 cannot repress cellular transformation. In the present study, Ser32 was revealed to be a novel phosphorylated site on TOPK that could be activated by ERK2. Phospho-TOPK (S32) was found to be involved in the resistance of renal cell carcinoma (RCC) to sorafenib. Herein, combined a TOPK inhibitor with sorafenib could promoted the apoptosis of sorafenib-resistant RCC. High expression of HGF/c-met contributes to activation of p-TOPK (S32) during the development of sorafenib resistance in RCC. The current research presents a possible mechanism of sorafenib resistance in RCC and identifies a potential diagnostic marker for predicting sorafenib resistance in RCC, providing a valuable supplement for the clinically targeted treatment of advanced RCC., (© 2022. The Author(s).)

After spinal cord injury (SCI), a large number of blood-derived macrophages infiltrate the lesion site and phagocytose myelin debris to become foamy macrophages, which leads to chronic inflammation. The drug D-4F, an apolipoprotein A-I peptidomimetic made of D-amino acids, has been reported to promote the lipid metabolism of foamy macrophages in atherosclerosis. However, the role and mechanism of D-4F in SCI are still unclear. In this study, we found that D-4F can promote the removal of myelin debris, reduce the formation of foamy macrophages in the lesion core and promote neuroprotection and recovery of motor function after SCI. These beneficial functions of D-4F may be related to its ability to upregulate the expression of ATP-binding cassette transporter A1 (ABCA1), the main transporter that mediates lipid efflux in foamy macrophages because inhibiting the activity of ABCA1 can reverse the effect of D-4F in vitro . In conclusion, D-4F may be a promising candidate for treating SCI by promoting the clearance of myelin debris by foamy macrophages via the ABCA1 pathway.

Allelopathy is considered an environmentally friendly and resource-conserving approach to weed control because allelochemicals degrade easily and cause less pollution than traditional chemical herbicides. In this study, the allelopathic active constituents of Artemisia argyi were elucidated by activity-guided isolation and ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). First, a crude extract prepared in water was fractionated using macroporous resin D101 to obtain three fractions (Fr.A-C). Combined with the allelopathic activity assay on Setaria viridis and Portulaca oleracea , Fr.C was determined to be the most active fraction. We identified 14 compounds in the active fraction (Fr.C) using UPLC-QTOF-MS, including 13 phenolic compounds. Accordingly, phenolic components have been suggested as the main allelochemicals in A. argyi . Thereafter, Fr.C was further isolated by octadecylsilyl (ODS) chromatography to obtain eight subfractions (Fr.C-1-Fr.C-8). Finally, isochlorogenic acid A (ICGAA) was purified from Fr.C-3 by semipreparative liquid chromatography, which was detected in the growth environment of A. argyi . Furthermore, we evaluated the allelopathic effects of ICGAA on six weeds from different families and genera for the first time. The results showed that ICGAA is a novel allelochemical with broad herbicidal activity. In addition, we analyzed the inhibitory effect and molecular mechanism of ICGAA on the growth of S. viridis seedlings. Optical microscopy and transmission electron microscopy (TEM) revealed the degradation of membrane structures and organelles after ICGAA treatment. Transcriptome and real-time polymerase chain reaction (RT-qPCR) analysis showed that ICGAA inhibited the growth of weeds mainly by inhibiting the diterpenoid biosynthesis pathway (especially gibberellins, GAs). The decrease of gibberellin (GA) contents after ICGAA treatment also confirmed these results. In brief, this study provides new material sources and theoretical support for developing biological herbicides for agroecosystems.

Aims: This study investigated the antifungal activity and mechanisms of ethyl acetate extract of Artemisia argyi (EAAA) against Verticillium dahliae., Methods and Results: Optical and scanning electron microscopy observation showed that 2.0 mg ml -1 EAAA treatment reduced spore germination rate to 4.56%. Histochemical staining showed that 2.0 mg ml -1 EAAA treatment increased reactive oxygen species (ROS) by more than two times. Physiological test showed that EAAA treatment decreased the contents of soluble proteins and sugars, and reduced the activities of malate dehydrogenase and succinate dehydrogenase by nearly half. Transcriptome analysis showed that EAAA treatment down-regulated the expression of genes involved in primary metabolic pathways of V. dahliae., Conclusions: Our results revealed that EAAA inhibited the growth and development of V. dahliae from multiple levels and multiple targets, including inhibiting the germination and development of V. dahliae spores, destroying the structure of cell membranes, inducing ROS burst, reducing the activities of respiratory-related enzymes and down-regulating the expression of genes in primary metabolic pathways., Significance and Impact of the Study: The mechanism of the multitarget effects of EAAA against V. dahliae may limit the potential of fungus developing resistance and provide the efficient methods to control verticillium wilt disease in the future., (© 2021 The Society for Applied Microbiology.)

Artemisia argyi is widely distributed in Asia, and it often becomes the dominant population in the field because of its strong ecological niche competitiveness. Allelochemicals secreted by plants are generally considered an important reason for their dominance in ecological competition. In this study, the allelochemicals in A. argyi were screened by a series of experiments and their mechanisms were explored via transcriptomics. First, the inhibitory effects of A. argyi on Echinochloa crusgalli , Setaria viridis , Portulaca oleracea and Amaranthus retroflexus were evaluated. Then, we carried out a qualitative and quantitative analysis of the chemical composition of the aqueous extract of A. argyi to screen for potential allelochemicals that can inhibit weed growth. Four potential allelochemicals were quantified: neochlorogenic acid (5-CQA), chlorogenic acid (3-CQA), cryptochlorogenic acid (4-CQA), and caffeic acid (CA). Coincidentally, their allelopathic effects on weeds seemed to be identical to their content, in the order CA>4-CQA>5-CQA>3-CQA. These findings suggested that CA might be the main allelopathic compound in the aqueous extract of A. argyi . Subsequently, the allelopathic effect and molecular mechanism of CA on S. viridis leaves were investigated. The physiological results showed that CA significantly induced reactive oxygen species (ROS) production, led to malondialdehyde (MDA) accumulation, and disrupted enzyme activities (POD, SOD, CAT) in S. viridis leaves. Moreover, transcriptome results revealed that CA inhibited S. viridis growth by downregulating multiple genes involved in gibberellin (GA) and phytoalexin biosynthesis and Mitogen-activated protein kinase (MAPK) signaling pathways. In addition, differentially expressed genes (DEGs) related to the biosynthesis and signaling pathways of phytohormones were verified by Quantitative Real-Time PCR (RT-qPCR). Taken together, this study may be the first to identify allelochemicals and explore their molecular mechanism about A. argyi . Importantly, the ecological advantages of A. argyi could be applied to ecological regulation and the development of botanical herbicides., 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 Chen, Li, Zhu, Guo, Ji, Miao, Guo, Du and Liu.)