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In an effort to identify novel antibacterial agents, we presented two series of aminoguanidine derivatives that were designed by incorporating 1,2,4-triazol moieties. All compounds exhibited strong in vitro antibacterial activity against a variety of testing strains. Compound 5f was identified as a potent antibacterial agent with a minimum inhibitory concentration (MIC) of 2–8 µg/mL against S. aureus, E. coli, S. epidermidis, B. subtilis, C. albicans, multi-drug resistant Staphylococcus aureus and multi-drug resistant Escherichia coli and low toxicity (Hela > 100 µM). Membrane permeability and transmission electron microscopy (TEM) image studies demonstrated that compound 5f permeabilized bacterial membranes, resulting in irregular cell morphology and the rapid death of bacteria. The results of the present study suggested that aminoguanidine derivatives with 1,2,4-triazol moieties were the intriguing scaffolds for the development of bactericidal agents. [ABSTRACT FROM AUTHOR]

Goji berry (Lycium barbarum L.) is a nutrient‐rich fruit and has received enormous interest for its health benefits. The beneficial effects of goji berry are linked to the absorption of bioactive compounds within the gastrointestinal digestion process and colon fermentation. Nonetheless, how certain bioactive compounds were released, and metabolism changed of the consumption of whole goji berries were still unclear. Therefore, the present study aimed to evaluate the digestion characteristics of key bioactive compounds in whole goji berries with an in vitro digestion model, and the effects of whole goji berries on the structure of gut microbiota were also investigated. Results showed that a significant release of carbohydrates during the digestion process, peaking within the first 15 min of the intestinal phase (421.4 ± 5.82 mg GE/g, dry weight, respectively), was observed, and the phenolic release reached the highest in the first 15 min of the gastric phase. Meanwhile, the bioaccessibilities of phenolic compounds and carbohydrates were determined to be 63.87% and 80.40%, respectively, after intestinal digestion. In addition, the undigested fractions of goji berries could be further fermented to produce short‐chain fatty acids, which decreased the colon pH value (from 7.38 to 6.71) as well as the Firmicutes/Bacteroidetes ratio. Moreover, the goji berries regulated the composition of gut microbiota by promoting beneficial bacteria such as Bacteroides, Parabacteroides, and Paraclostridium, whereas inhibiting the proliferation of harmful bacteria (e.g., Fusobacterium). Our results indicated that the goji berry exhibited significant bioactivity during the digestion and fermentation stage and might provide some new insights into the utilization of goji berries in healthy food processing. [ABSTRACT FROM AUTHOR]

In this paper, the authors study a class of general mean-field BDSDEs whose coefficients satisfy some stochastic conditions. Specifically, the authors prove the existence and uniqueness theorem of solution under stochastic Lipschitz condition and obtain the related comparison theorem. Besides, the authors further relax the conditions and deduce the existence theorem of solutions under stochastic linear growth and continuous conditions, and the authors also prove the associated comparison theorem. Finally, an asset pricing problem is discussed, which demonstrates the application of the general mean-field BDSDEs in finance. [ABSTRACT FROM AUTHOR]

The spatial mapping and prediction of groundwater quality (GWQ) is important for sustainable groundwater management, but several research gaps remain unexplored, including the inaccuracy of spatial interpolation, limited consideration of the geological environment and human activity effects, limitation to specific pollutants, and unsystematic indicator selection. This study utilized the entropy-weighted water quality index (EWQI), the LightGBM model, the pressure-state-response (PSR) framework and SHapley Additive exPlanations (SHAP) analysis to address the above research gaps. The normalized importance (NI) shows that NO3− (0.208), Mg2+ (0.143), SO42− (0.110), Cr6+ (0.109) and Na+ (0.095) should be prioritized as parameters for remediation, and the skewness EWQI distribution indicates that although most sampled locations have acceptable GWQ, a few areas suffer from severely poor GWQ. The PSR framework identifies 13 indicators from geological environments and human activities for the SMP of GWQ. Despite high AUROCs (0.9074, 0.8981, 0.8885, 0.9043) across four random training and testing sets, it was surprising that significant spatial uncertainty was observed, with Pearson correlation coefficients (PCCs) from 0.5365 to 0.8066. We addressed this issue by using the spatial-grid average probabilities of four maps. Additionally, population and nighttime light are key indicators, while net recharge, land use and cover (LULC), and the degree of urbanization have the lowest importance. SHAP analysis highlights both positive and negative impacts of human activities on GWQ, identifying point-source pollution as the main cause of the poor GWQ in the study area. Due to the limited research on this field, future studies should focus on six key aspects: multi-method GWQ assessment, quantitative relationships between indicators and GWQ, comparisons of various spatial mapping and prediction models, the application of the PSR framework for indicator selection, the development of methods to reduce spatial uncertainty, and the use of explainable machine learning techniques in groundwater management. [ABSTRACT FROM AUTHOR]

Key Clinical Message: We report a rare case of thyroid diffuse large B‐cell lymphoma with a BRAFV600E mutation, which mimics poorly differentiated thyroid cancer in fine needle aspiration cytology. [ABSTRACT FROM AUTHOR]

Summary: Large amounts of azurophilic granules are considered to be a morphological feature of acute promyelocytic leukaemia (APL). However, a small percentage of acute myeloid leukaemia (AML) patients also have a large number of azurophilic granules. A large cohort of 3210 AML patients in our hospital was screened to identify AML patients who had a large number of azurophilic granules. The clinical parameters of these patients were collected and compared with typical AML patients (control Group 1) and APL patients (control Group 2). The incidence of AML with a large number of azurophilic granules was 1.26%. The fibrinogen and D‐dimer levels of patients in the study group were more similar to those of patients in control Group 2, as was the incidence of bleeding events. Additionally, patients in the study group had higher FLT3‐ITD and NPM1 mutation rates than patients in control Group 1. Finally, patients in the study group had a higher 30‐day mortality rate than those in control Group 2 (24.2% vs. 9.09%) and showed a higher 30‐day mortality trend than those in control Group 1. Therefore, we should pay more attention to the prevention of coagulation dysfunction and bleeding events for these patients. [ABSTRACT FROM AUTHOR]

Green human resource management (GHRM) has become an indispensable strategy in green management. As the first step of GHRM, green recruitment and selection (GRS) has been emphasised as the important and probably the only practice to help the firm obtain green human capital directly. However, research has shown that not many firms implement GRS in practice, and there is a lack of studies exploring the barriers to GRS. This study fills this gap by examining the barriers to GRS across different industries in China. It adopted a qualitative and inductive approach, which is relatively rare in the GHRM field. Based on interviews with senior managers, a number of barriers were revealed in relation to the two components of GRS: paperless recruitment and green candidates. More specifically, two new factors that have not been reported in the existing literature were identified: the alignment between the job profile, green practices, and profit orientation. These two factors have both theoretical and practical implications. [ABSTRACT FROM AUTHOR]

A drone delivery system, characterized by its low energy consumption, high efficiency, and extensive coverage capability, has been adopted as an effective solution to overcome the limitations of traditional ground transportation. However, due to strong interactions between urban structures and wind, the wind environment in the low-altitude airspace of urban areas poses significant safety risks for drone operations, a challenge that remains unresolved. To mitigate these risks, this study presents a methodology for precisely defining the no-fly zones (NFZs) for drone operations using computational fluid dynamics (CFD) simulations. Three hazardous indices—safe, deviation, and unsafe—are proposed to indicate the drone operation status. High-resolution CFD models of urban wind environments in a real city area are coupled with meteorological wind data to provide statistical results for the three indices. The Reynolds-averaged Navier–Stokes turbulence model is employed to simulate two wind environments, standard wind and strong wind, under 36 incoming flow directions. Considering eight flight orientations of drone operating in horizontal planes at various heights, a set of maps for the occurrence probability of the three hazardous indices is provided. These maps can be utilized to determine safe areas, identify no-fly zones corresponding to high occurrence probabilities of deviation and unsafe indices, and establish efficient flight paths for drone operations. [ABSTRACT FROM AUTHOR]

In response to the increasing number of agents and changing task scenarios in multi-agent collaborative systems, existing collaborative strategies struggle to effectively adapt to new task scenarios. To address this challenge, this paper proposes a knowledge distillation method combined with a domain separation network (DSN-KD). This method leverages the well-performing policy network from a source task as the teacher model, utilizes a domain-separated neural network structure to correct the teacher model's outputs as supervision, and guides the learning of agents in new tasks. The proposed method does not require the pre-design or training of complex state-action mappings, thereby reducing the cost of transfer. Experimental results in scenarios such as UAV surveillance and UAV cooperative target occupation, robot cooperative box pushing, UAV cooperative target strike, and multi-agent cooperative resource recovery in a particle simulation environment demonstrate that the DSN-KD transfer method effectively enhances the learning speed of new task policies and improves the proximity of the policy model to the theoretically optimal policy in practical tasks. [ABSTRACT FROM AUTHOR]

Investigating the intricate pathways through which FH06 fermentation broth exerts lipid-lowering and weight-loss effects is pivotal for advancing our comprehension of metabolic regulation and therapeutic interventions. Ultrahigh-performance liquid chromatography quadrupole electrostatic field orbit trap mass spectrometry (UHPLC-QE-MS) detection and the ChEMBL database were used to determine the effective compounds in the FH06 fermentation broth and predict their targets. The TTD database and DisGeNET database were used to query obesity-related targets. The STRING database was used to construct protein interaction information. The Gene Ontology (GO) database and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database were used to perform biological function annotation (GO) and KEGG pathway enrichment analyses of the targets. Results: A total of 85 effective compounds were screened from the fermentation broth of FH06; these compounds may act on TP53, PPARG, TNF, and other targets through 10 signaling pathways, such as the chemical carcinogenesis-receptor activation and lipid and atherosclerosis pathways, and exert pharmacological effects, such as hypoglycemic effects and weight loss. They also have anti-inflammatory, antioxidant, antitumor, and immunoregulatory effects. These findings reveal the active ingredients of FH06 fermentation broth and its multi-target and multi-channel characteristics in lipid lowering and weight loss. This study has positive implications for the clinical treatment of obesity using FH06, providing a theoretical and scientific basis for further developing of FH06-assisted lipid-lowering products. [ABSTRACT FROM AUTHOR]

The land use change (LUC) and urbanization caused by human activities have markedly increased the occurrence of landslides, presenting significant challenges in accurately predicting landslide susceptibility despite decades of model advancements. This study, focusing on the Li River Valley (LRV) within the Yongding District, China, employs two common models, namely an analytic hierarchy process–comprehensive index (AHP-CI) model and a logistic regression (LR) model to assess landslide susceptibility (LS). The AHP-CI model is empirically based, with the advantage of being constructible and applicable at various scales without a dataset, though it remains highly subjective. The LR model is a statistical model that requires a training set. The two models represent heuristic and statistical approaches, respectively, to assessing LS. Meanwhile, the basic geological and environmental conditions are considered in the AHP-CI model, while the LR model accounts for the conditions of LUC and urbanization. The results of the multicollinearity diagnostics reflect the rationality of the predisposing factor selection (1.131 < VIF < 4.441). The findings reveal that the AHP-CI model underperforms in LUC and urbanization conditions (AUROC = 0.645, 0.628, and 0.667 for different validation datasets). However, when all the time-varying human activity predisposing factors are considered, the LR model (AUROC = 0.852) performs significantly better under the conditions of solely considering 2010 (AUROC = 0.744) and 2020 (AUROC = 0.810). The CA–Markov model was employed to project the future land use for the short-term (2025), mid-term (2030), and long-term (2040) planning periods. Based on these projections, maps of future LS were created. Importantly, this paper discussed the relationships between landslide management and regional sustainable development under the framework of the UN SDGs, which are relevant to Goal 1, Goal 11, Goal 13, and Goal 15. Finally, this study highlights the importance of integrating strategic land planning, reforestation efforts, and a thorough assessment of human impact predisposing factors with SDG-aligned LS predictions, advocating for a comprehensive, multi-stakeholder strategy to promote sustainable landslide mitigation. [ABSTRACT FROM AUTHOR]

Microplastics (MPs) have been considered an emerging environmental pollutant which, when combined with toxic metals, enter the circulatory system of mammals and eventually cause damage. Therefore, it is important to study the toxicity of the mixture of MPs and heavy metals for evaluating risk assessment of mammals. In the present study, the toxicological effects of different concentrations of polystyrene (PS)-MPs alone or in combination with cadmium chloride (CdCl2) during chronic exposure (8 weeks) were evaluated using intragastric administration in mice. Using comparative analysis, it was revealed that PS-MPs alone or in combination with Cd could destroy the normal structural morphology of liver tissue and increase the levels of two biochemical indicators of liver damage, thereby inducing changes in antioxidant and hyperoxide capacities. In addition, PS-MPs and/or Cd activated the antioxidant signaling pathway Nrf2-Keap1 and affected the endogenous apoptosis signaling pathway p53-Bcl-2/Bax, thus promoting apoptosis. These findings suggested that exposure to MPs alone or in combination with Cd led to adverse effects on the liver. Furthermore, it was revealed that co-exposure to MPs and Cd reduced Cd toxicity, thereby highlighting the possibility MPs may act as carriers of other toxic substances and coordinate with them. Therefore, evaluating the synergistic or anti-agonistic effects of MPs on the toxicity and bioavailability of xenobiotics is in the future critical in environmental toxicological studies. [ABSTRACT FROM AUTHOR]

As constituents of one of the vital agricultural ecosystems, paddy fields exert significant influence on the global carbon cycle. Therefore, conducting observations and simulations of CO2 flux in rice paddy is of significant importance for gaining deeper insights into the functionality of agricultural ecosystems. This study utilized an eddy covariance system to observe and analyze the CO2 flux in a rice paddy field in Eastern China and also introduced and parameterized the Jarvis multiplicative model to predict the CO2 flux. Results indicate that throughout the observation period, the range of CO2 flux in the paddy field was −0.1 to −38.4 μmol/(m2·s), with a mean of −12.9 μmol/(m2·s). The highest CO2 flux occurred during the rice flowering period with peak photosynthetic activity and maximum CO2 absorption. Diurnal variation in CO2 flux exhibited a "U"-shaped curve, with flux reaching its peak absorption at 11:30. The CO2 flux was notably higher in the morning than in the afternoon. The nocturnal CO2 flux remained relatively stable, primarily originating from respiratory CO2 emissions. The rice canopy CO2 flux model was revised using boundary line analysis, elucidating that photosynthetically active radiation, temperature, vapor pressure deficit, phenological stage, time, and concentration are pivotal factors influencing CO2 flux. The simulation of CO2 flux using the parameterized model, compared with measured values, reveals the efficacy of the established parameter model in simulating rice CO2 flux. This study holds significant importance in comprehending the carbon cycling process within paddy ecosystems, furnishing scientific grounds for future climate change and environmental management endeavors. [ABSTRACT FROM AUTHOR]

This study aims to examine the individual and combined effects of soil moisture (SM) and vapor pressure deficit (VPD) on ecosystem productivity in Southwest China. Utilizing the community land model (CLM) to simulate the regional soil moisture and vapor pressure deficit, we analyzed their impacts on ecosystem productivity through a data binning approach and employed sun-induced chlorophyll fluorescence yield (SIFyield) as a productivity indicator. Our findings highlight a significant coupling effect between SM and VPD, which diminishes with finer temporal data resolution. The data binning analysis indicates that VPD has a predominant influence on SIFyield across 70% of the study area, whereas SM is more influential in the remaining 30%. Notably, the correlation between SIFyield and SM, modulated by VPD, is stronger in forest and shrubland ecosystems, whereas in grasslands, the influence pattern is reversed, with VPD having a more significant impact. The study concludes that in Southwest China, ecosystem productivity is more significantly affected by VPD than by SM. [ABSTRACT FROM AUTHOR]

In this paper, we consider the general mean-field backward doubly stochastic differential equations (mean-field BDSDEs) whose generator f can be discontinuous in y. We prove the existence theorem of solutions under stochastic linear growth conditions and also obtain the related comparison theorem. Naturally, we present those results under the linear growth condition, which is a special case of the stochastic condition. Finally, a financial claim sale problem is discussed, which demonstrates the application of the general mean-field BDSDEs in finance. [ABSTRACT FROM AUTHOR]

The rapid advancement of remote sensing technology has given rise to numerous global- and regional-scale medium- to high-resolution land cover (LC) datasets, making significant contributions to the exploration of worldwide environmental shifts and the sustainable governance of natural resources. Nonetheless, owing to the inherent uncertainties embedded within remote sensing imagery, LC datasets inevitably exhibit inaccuracies. In this study, a local accuracy assessment of LC datasets in Southwest China was conducted. The datasets utilized in our analysis include ESA WorldCover, CLCD, Esri Land Cover, CRLC, FROM-GLC10, GLC_FCS30, GlobeLand30, and SinoLC-1. This study employed a sampling approach that combines proportional allocation and stratified random sampling (SRS) to gather sample points and compute confusion matrices to validate eight LC products. The local accuracy of the eight LC maps differs significantly from the overall accuracy provided by the original authors in Southwest China. ESA WorldCover and CLCD demonstrate higher local accuracy than other products in Southwest China, with their overall accuracy (OA) values being 87.1% and 85.48%, respectively. Simultaneously, we computed the area for each LC map based on categories, quantifying uncertainty through the reporting of confidence intervals for both accuracy and area parameters. This study aims to validate and compare eight LC datasets and assess precision and area of diverse spatial resolution datasets for mapping and monitoring across Southwest China. [ABSTRACT FROM AUTHOR]

A novel method, known as the vector potential random flow generation (VPRFG) method, is introduced for synthesizing divergence-free homogeneous isotropic turbulence with arbitrary spectra. First, the proposed approach employs the random-flow-generation-based method to create a vector potential field. Subsequent application of the curl operation to this field produces a turbulent flow that inherently satisfies the divergence-free condition. In the formulas of the proposed method, we explicitly impose arbitrary homogeneous isotropic three-dimensional spatial cross-spectral density (CSD) and Taylor's frozen hypothesis. This ensures that the generated turbulence conforms to prescribed statistical characteristics, including energy spectra, one-dimensional spatial power spectral density (PSD), temporal PSD, spatial coherence function, turbulent kinetic energy, and Reynolds stress. Additionally, the theoretical accuracy of the proposed method is validated through numerical examples, employing the von Kármán energy spectrum as the target value. Finally, large eddy simulations of homogeneous isotropic temporal-decaying box turbulence generated by the VPRFG method demonstrate a close alignment with the experimental results. [ABSTRACT FROM AUTHOR]

Previous evidence has confirmed that branched-chain aminotransferase-1 (BCAT1), a key enzyme governing branched-chain amino acid (BCAA) metabolism, has a role in cancer aggression partly by restricting αKG levels and inhibiting the activities of the αKG-dependent enzyme family. The oncogenic role of BCAT1, however, was not fully elucidated in acute myeloid leukemia (AML). In this study, we investigated the clinical significance and biological insight of BCAT1 in AML. Using q-PCR, we analyzed BCAT1 mRNAs in bone marrow samples from 332 patients with newly diagnosed AML. High BCAT1 expression independently predicts poor prognosis in patients with AML. We also established BCAT1 knockout (KO)/over-expressing (OE) AML cell lines to explore the underlying mechanisms. We found that BCAT1 affects cell proliferation and modulates cell cycle, cell apoptosis, and DNA damage/repair process. Additionally, we demonstrated that BCAT1 regulates histone methylation by reducing intracellular αKG levels in AML cells. Moreover, high expression of BCAT1 enhances the sensitivity of AML cells to the Poly (ADP-ribose) polymerase (PARP) inhibitor both in vivo and in vitro. Our study has demonstrated that BCAT1 expression can serve as a reliable predictor for AML patients, and PARP inhibitor BMN673 can be used as an effective treatment strategy for patients with high BCAT1 expression. Key messages: High expression of BCAT1 is an independent risk factor for poor prognosis in patients with CN-AML. High BCAT1 expression in AML limits intracellular αKG levels, impairs αKG-dependent histone demethylase activity, and upregulates H3K9me3 levels. H3K9me3 inhibits ATM expression and blocks cellular DNA damage repair process. Increased sensitivity of BCAT1 high expression AML to PARP inhibitors may be used as an effective treatment strategy in AML patients. [ABSTRACT FROM AUTHOR]

Background: Aquilegia is a model system for studying the evolution of adaptive radiation. However, very few studies have been conducted on the Aquilegia mitochondrial genome. Since mitochondria play a key role in plant adaptation to abiotic stress, analyzing the mitochondrial genome may provide a new perspective for understanding adaptive evolution. Results: The Aquilegia amurensis mitochondrial genome was characterized by a circular chromosome and two linear chromosomes, with a total length of 538,736 bp; the genes included 33 protein-coding genes, 24 transfer RNA (tRNA) genes and 3 ribosomal RNA (rRNA) genes. We subsequently conducted a phylogenetic analysis based on single nucleotide polymorphisms (SNPs) in the mitochondrial genomes of 18 Aquilegia species, which were roughly divided into two clades: the European-Asian clade and the North American clade. Moreover, the genes mttB and rpl5 were shown to be positively selected in European-Asian species, and they may help European and Asian species adapt to environmental changes. Conclusions: In this study, we assembled and annotated the first mitochondrial genome of the adaptive evolution model plant Aquilegia. The subsequent analysis provided us with a basis for further molecular studies on Aquilegia mitochondrial genomes and valuable information on adaptive evolution in Aquilegia. [ABSTRACT FROM AUTHOR]

The COVID-19 outbreak caused by SARS-CoV-2 in late 2019 has spread rapidly across the world to form a global epidemic of respiratory infectious diseases. Increased investigations on diagnostic tools are currently implemented to assist rapid identification of the virus because mass and rapid diagnosis might be the best way to prevent the outbreak of the virus. This critical review discusses the detection principles, fabrication techniques, and applications on the rapid detection of SARS-CoV-2 with three categories: rapid nuclear acid augmentation test, rapid immunoassay test and biosensors. Special efforts were put on enhancement of nanomaterials on biosensors for rapid, sensitive, and low-cost diagnostics of SARS-CoV-2 virus. Future developments are suggested regarding potential candidates in hospitals, clinics and laboratories for control and prevention of large-scale epidemic. [ABSTRACT FROM AUTHOR]

This letter, published in the Annals of Hematology, reports on a case of a patient with myeloid/lymphoid neoplasm with eosinophilia (MLN-eo) who presented with an osteolytic lesion. The patient experienced progressive osteodynia and was found to have multiple punched-out osteolytic lesions. The patient underwent chemotherapy and achieved bone marrow complete remission, but unfortunately, the osteolytic lesion persisted and the patient eventually died. The study also conducted RNA sequencing and found that osteoclast-related pathways were enriched in the patient's transcriptional profiles. This case highlights the rare occurrence of osteolytic lesions in MLN-eo patients and suggests a potential role of FIP1L1-PDGFRA rearrangement and RUNX1 mutation in causing the osteolytic lesion. [Extracted from the article]

KMT2A-rearranged acute myeloid leukemia (KMT2Ar-AML) is an aggressive subtype of AML with poor response and prognosis. KMT2Ar-AML has been demonstrated to be sensitive to BCL2 inhibitor venetoclax (VEN), but these patients are unable to benefit from current VEN-based regimen (VEN plus azacitidine or low dose-cytarabine), so a novel and KMT2A rearrangement-specific targeting partner is required, and MENIN inhibitor (MEN1i) is a promising one. Herein, we investigated the effect and mechanism of VEN plus MEN1i in KMT2Ar-AML. Our results showed that VEN and MEN1i exhibited a striking synergistic effect in KMT2Ar-AML cell lines (in vitro), primary KMT2Ar-AML cells (ex vivo), and MOLM13 xenotransplantation model (in vivo). Furthermore, we found that VEN plus MEN1i significantly enhanced apoptotic induction in KMT2Ar-AML cell lines. VEN or MEN1i monotherapy disrupted balance of BCL-2/BCL-XL or down-regulated HOXA9/MEIS1, respectively, but these mechanisms were not further strengthened by their combination. RNA-Sequencing identified that HDAC9 was specifically repressed by VEN plus MEN1i rather than monotherapy. We demonstrated that HDAC9 was indispensable for KMT2Ar-AML proliferation and its repression contributed to proliferation inhibition of VEN plus MEN1i. Moreover, we found that hypoxia induced HDAC9 expression in KMT2Ar-AML, and VEN plus MEN1i inhibited hypoxia pathway, especially HIF-1A, and its target HDAC9. As our results indicated, VEN plus MEN1i-mediated HDAC9 down-regulation was partially dependent on HIF-1A repression in KMT2Ar-AML. Hypoxia induction sensitized KMT2Ar-AML to VEN plus MI-503-mediated proliferation inhibition and apoptosis induction. Therefore, repressing HIF-1A-induced HDAC9 contributed to the synergistic effect of VEN and MEN1i in KMT2Ar-AML. [ABSTRACT FROM AUTHOR]

This article, published in the Chemistry of Natural Compounds journal, discusses the identification of potent inhibitors targeting Protein Tyrosine Phosphatase 1B (PTP1B). PTP1B is an enzyme that plays a role in insulin and leptin signaling pathways and is considered a promising therapeutic target for the management of Type 2 Diabetes. The researchers synthesized and tested a series of derivatives of Ursolic acid (UA) for their PTP1B inhibitory activity. Compound 1f exhibited the most pronounced activity, with an inhibition rate of 56.22%, providing significantly improved activity compared to UA. Molecular modeling studies also supported the binding ability of compound 1f with PTP1B. The study suggests that further structural optimization could lead to the development of new potential therapeutic agents for the treatment of Type 2 Diabetes. [Extracted from the article]

Deubiquitinases (DUBs) play important roles in various human cancers and targeting DUBs is considered as a novel anticancer therapeutic strategy. Overexpression of ubiquitin specific protease 7 and 22 (USP7 and USP22) are associated with malignancy, therapy resistance, and poor prognosis in many cancers. Although both DUBs are involved in the regulation of similar genes and signaling pathways, such as histone H2B monoubiquitination (H2Bub1), c-Myc, FOXP3, and p53, the interdependence of USP22 and USP7 expression has never been described. In the study, we found that targeting USP7 via either siRNA-mediated knockdown or pharmaceutical inhibitors dramatically upregulates USP22 in cancer cells. Mechanistically, the elevated USP22 occurs through a transcriptional pathway, possibly due to desuppression of the transcriptional activity of SP1 via promoting its degradation upon USP7 inhibition. Importantly, increased USP22 expression leads to significant activation of downstream signal pathways including H2Bub1 and c-Myc, which may potentially enhance cancer malignancy and counteract the anticancer efficacy of USP7 inhibition. Importantly, targeting USP7 further suppresses the in vitro proliferation of USP22-knockout (USP22-Ko) A549 and H1299 lung cancer cells and induces a stronger activation of p53 tumor suppressor signaling pathway. In addition, USP22-Ko cancer cells are more sensitive to a combination of cisplatin and USP7 inhibitor. USP7 inhibitor treatment further suppresses in vivo angiogenesis and tumor growth and induced more apoptosis in USP22-Ko cancer xenografts. Taken together, our findings demonstrate that USP7 inhibition can dramatically upregulate USP22 in cancer cells; and targeting USP7 and USP22 may represent a more effective approach for targeted cancer therapy, which warrants further study. 51f9aZhqcv_kcNHk2RbtxA Video Abstract [ABSTRACT FROM AUTHOR]

Reverse transcription quantitative polymerase chain reaction (RT-qPCR) is an accurate method for quantifying gene expression levels. Choosing appropriate reference genes to normalize the data is essential for reducing errors. Gelsemium elegans is a highly poisonous but important medicinal plant used for analgesic and anti-swelling purposes. Gelsenicine is one of the vital active ingredients, and its biosynthesis pathway remains to be determined. In this study, G. elegans leaf tissue with and without the application of one of four hormones (SA, MeJA, ETH, and ABA) known to affect gelsenicine synthesis, was analyzed using ten candidate reference genes. The gene stability was evaluated using GeNorm, NormFinder, BestKeeper, ∆CT, and RefFinder. The results showed that the optimal stable reference genes varied among the different treatments and that at least two reference genes were required for accurate quantification. The expression patterns of 15 genes related to the gelsenicine upstream biosynthesis pathway was determined by RT-qPCR using the relevant reference genes identified. Three genes 8-HGO, LAMT, and STR, were found to have a strong correlation with the amount of gelsenicine measured in the different samples. This research is the first study to examine the reference genes of G. elegans under different hormone treatments and will be useful for future molecular analyses of this medically important plant species. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal nematodes (GINs) have seriously affected the production and earnings of animal husbandry in various countries, while some species of GINs infect humans. At present, little is known about the species and prevalence of GINs in Qinghai‐Tibetan Plateau (QTP). Methods: In this study, 528 fresh faecal samples were collected from typical areas in different altitudes with seven species of livestock in Qinghai, Tibet, Gansu and Yunnan Provinces. ITS‐2 rRNA gene of nematodes was employed to detect by PCR and sequencing analysis. Phylogenetic analysis of related sequences was performed using MEGA 6.0 software. Results: The overall prevalence of GINs was 80.3% with 20 species of GINs detected, while Teladorsagia circumcincta was the dominant one, and four of which were zoonotic species such as Trichostrongylus colubriformis, Trichostrongylus axei, Trichostrongylus vitrinus and Oesophagostomum stephanostomum. Conclusion: The study provided panoptic information on the prevalence and species diversity of GINs in QTP area, which is useful and valuable for reference of measure formulation in livestock husbandry and public health concerns. The parasites of T. circumcincta, Cylicocyclus nassatus, Strongylus edentatus, Cylicostephanus longibursatus, Telephlebia brevicauda, Cyathostomum catinatum, Mecistocirrus digitatus, Cooperia punctata, Cylicodontophorus bicoronatus, Nematodirus oiratianus and Oesophagostomum asperum were firstly reported the presence in QTP area. The study also showed that horse could be infected by T. circumcincta, goat could be infected by C. nassatus, cattle could be infected by S. edentatus and C. bicoronatus,and O. stephanostomum could infect yak, cattle and Mongolian sheep in worldwide. Nevertheless, more investigations are needed, such as microscopic examination, to accurately determine the species in the region. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is a highly heterogeneous cancer with major challenges in both prevention and therapy. Metformin, adenosine monophosphate‐activated protein kinase (AMPK) activator, has been suggested to reduce the incidence of HCC when used for patients with diabetes in preclinical and clinical studies. However, the possible effects of metformin and their mechanisms of action in non‐diabetic HCC have not been adequately investigated. Methods: Fah−/− mice were used to construct a liver‐injury‐induced non‐diabetic HCC model for exploring hepatocarcinogenesis and therapeutic potential of metformin. Changes in relevant tumour and biochemical indicators were measured. Bulk and single‐cell RNA‐sequencing analyses were performed to validate the crucial role of proinflammatory/pro‐tumour CD8+ T cells. In vitro and in vivo experiments were performed to confirm Cyp26a1‐related antitumour mechanisms of metformin. Results: RNA‐sequencing analysis showed that chronic liver injury led to significant changes in AMPK‐, glucose‐ and retinol metabolism‐related pathways in Fah−/− mice. Metformin prevented the formation of non‐diabetic HCC in Fah−/− mice with chronic liver injury. Cyp26a1 ddexpression in hepatocytes was significantly suppressed after metformin treatment. Moreover, downregulation of Cyp26a1 occurred in conjunction with increased levels of all‐trans‐retinoic acid (atRA), which is involved in the activation of metformin‐suppressed hepatocarcinogenesis in Fah−/− mice. In contrast, both CD8+ T‐cell infiltration and proinflammatory/pro‐tumour cytokines in the liver were significantly upregulated in Fah−/− mice during chronic liver injury, which was notably reversed by either metformin or atRA treatment. Regarding mechanisms, metformin regulated the decrease in Cyp26a1 enzyme expression and increased atRA expression via the AMPK/STAT3/Gadd45β/JNK/c‐Jun pathway. Conclusions: Metformin inhibits non‐diabetic HCC by upregulating atRA levels and downregulating CD8+ T cells. This is the first reporting that the traditional drug metformin regulates the metabolite atRA via the Cyp26a1‐involved pathway. The present study provides a potential application of metformin and atRA in non‐diabetic HCC. [ABSTRACT FROM AUTHOR]

Summary: Glutamine metabolic reprogramming in acute myeloid leukaemia (AML) cells contributes to the decreased sensitivity to antileukemic drugs. Leukaemic cells, but not their myeloid counterparts, largely depend on glutamine. Glutamate dehydrogenase 1 (GDH1) is a regulation enzyme in glutaminolysis. However, its role in AML remains unknown. Here, we reported that GDH1 was highly expressed in AML: high GDH1 was one of the independent negative prognostic factors in AML cohort. The dependence of leukaemic cells on GDH1 was proved both in vitro and in vivo. High GDH1 promoted cell proliferation and reduced survival time of leukaemic mice. Targeting GDH1 eliminated the blast cells and delayed AML progression. Mechanistically, GDH1 knockdown inhibited glutamine uptake by downregulating SLC1A5. Moreover, GDH1 invalidation also inhibited SLC3A2 and abrogated the cystine‐glutamate antiporter system Xc−. The reduced cystine and glutamine disrupted the synthesis of glutathione (GSH) and led to the dysfunction of glutathione peroxidase‐4 (GPX4), which maintains the lipid peroxidation homeostasis by using GSH as a co‐factor. Collectively, triggering ferroptosis in AML cells in a GSH depletion manner, GDH1 inhibition was synthetically lethal with the chemotherapy drug cytarabine. Ferroptosis induced by inhibiting GDH1 provides an actionable therapeutic opportunity and a unique target for synthetic lethality to facilitate the elimination of malignant AML cells. [ABSTRACT FROM AUTHOR]

Acyl-CoA synthetase long chain family member 5 (ACSL5), is a member of the acyl-CoA synthetases (ACSs) family that activates long chain fatty acids by catalyzing the synthesis of fatty acyl-CoAs. The dysregulation of ACSL5 has been reported in some cancers, such as glioma and colon cancers. However, little is known about the role of ACSL5 in acute myeloid leukemia (AML). We found that the expression of ACSL5 was higher in bone marrow cells from AML patients compared with that from healthy donors. ACSL5 level could serve as an independent prognostic predictor of the overall survival of AML patients. In AML cells, the ACSL5 knockdown inhibited cell growth both in vitro and in vivo. Mechanistically, the knockdown of ACSL5 suppressed the activation of the Wnt/β-catenin pathway by suppressing the palmitoylation modification of Wnt3a. Additionally, triacsin c, a pan-ACS family inhibitor, inhibited cell growth and robustly induced cell apoptosis when combined with ABT-199, the FDA approved BCL-2 inhibitor for AML therapy. Our results indicate that ACSL5 is a potential prognosis marker for AML and a promising pharmacological target for the treatment of molecularly stratified AML. [ABSTRACT FROM AUTHOR]

Multifunctional nanoaggregates are widely used in cancer phototheranostics. However, it is challenging to construct their multifunctionality with a single component, and deliver them rapidly and efficiently without complex modifications. Herein, a NIR‐absorbing small molecule named TBT‐2(TP‐DPA) is designed and certify its theranostic potentials. Then, their nanoaggregates, which are simply encapsulated by DSPE‐PEG, demonstrate a photothermal efficiency of 51% while keeping a high photoluminescence quantum yield in the NIR region. Moreover, the nanoaggregates can be excited and delivered by an 808 nm pulse laser to solid tumors within only 40 min. The delivery efficiency and theranostic efficacy are better than that of the traditional enhanced permeability and retention (EPR) effect (generally longer than 24 hours). This platform is first termed as the photoinduced thermoacoustic (PTA) process, and confirm its application requires both NIR‐responsive materials and pulse laser irradiation. This study not only inspires the design of multifunctional nanoaggregates, but also offers a feasible approach to their fast delivery. The platform reported here provides a promising prospect to boost the development of multifunctional theranostic drugs and maximize the efficacy of used medicines for their clinical applications. [ABSTRACT FROM AUTHOR]

In this article, a class of fractional coupled nonlinear Schrödinger equations (FCNLS) is suggested to describe the traveling waves in a fractal medium arising in ocean engineering, plasma physics and nonlinear optics. First, the modified Kudryashov method is adopted to solve exactly for solitary wave solutions. Second, an efficient and promising method is proposed for the FCNLS by coupling the Laplace transform and the Adomian polynomials with the homotopy perturbation method, and the convergence is proved. Finally, the Laplace-HPM technique is proved to be effective and reliable. Some 3D plots, 2D plots and contour plots of these exact and approximate solutions are simulated to uncover the critically important mechanism of the fractal solitary traveling waves, which shows that the efficient methods are much powerful for seeking explicit solutions of the nonlinear partial differential models arising in mathematical physics. [ABSTRACT FROM AUTHOR]

Interspecific competition occurs fiercely between invasive and native species which occupy similar niche. Here, we report the competitive mechanism underlying the displacement of Bursaphelenchus mucronatus by Bursaphelenchus xylophilus. In the early stage of the competition, population of both species increase significantly, but their abundance rates were differentiated, B. xylophilus increased, whereas B. mucronatus decreased. Unexpectedly, sex ratio of female to male of both species increased sharply and peaked at 4.87 and 3.88, respectively, which were outclassed that of noncompetitive conditions (2.77 and 2.21). Thereafter, the sex ratio of B. xylophilus declined and stabilized at 2.81, but the sex ratio of B. mucronatus declined till no B. mucronatus was left, indicating the interspecific competition could be dominated by female. The mating behaviors showed that for both species, the mating success rate of one couple dropped slightly when one male or female of other species was added, but dropped significantly when two males or females were added. Surprisingly, almost no successful mating was observed when three males or females of other species were added. We therefore hypothesize that the mating opportunity of one couple could be deprived by the other species once three or more male or female were added. Further, threshold value of competitive displacement experiments and model analysis were completely consistent with the above experiments. Our results elucidate the crucial role of sex ratio in interspecific competition for the first time, as well as their mating disruption, directing a wonderful story of female-dominated war between two xylophilus group nematode species. [ABSTRACT FROM AUTHOR]

Introduction: Chronic subjective tinnitus has become an increasingly serious hazard that affects the health-related quality of life for millions of people. Due to the lack of curative treatment strategies, this study aims to introduce a novel acoustic therapy named the modified tinnitus relieving sound (MTRS) for tinnitus and to evaluate the efficacy of MTRS in comparison with unmodified music (UM) which served as a control. Methods and analysis: A randomized, double-blinded, controlled, clinical trial will be carried out. Sixty-eight patients with subjective tinnitus will be recruited and randomly allocated into two groups in 1:1 ratio. The primary outcome is Tinnitus Handicapped Inventory (THI); the secondary outcomes are the Hospital Anxiety and Distress Scale (HADS; HADS subscales for Anxiety (HADS-A) and Depression (HADS-D)), Athens Insomnia Scale (AIS), the visual analog scale (VAS) for tinnitus, and tinnitus loudness matched by sensation level (SL). Assessment will be performed at baseline and at 1, 3, 9, and 12 months post-randomization. The sound stimulus will be persistent until 9 months after randomization, and be interdictory in the last three months. Data collected during the intervention process will be analyzed and compared to baseline. Ethics and dissemination: This trial received ethical approval from the Institutional Review Board (IRB) of Eye & ENT Hospital of Fudan University (No. 2017048). The study results will be disseminated via academic journals and conferences. Funding: This study is supported by the Shanghai Shenkang Development Program (SHDC12019119), the Excellent Doctors-Excellent Clinical Researchers Program (SYB202008), the Shanghai Rising-Star Program (23QC1401200), the Shanghai Rising Stars of Medical Talent Youth Development Program (2021–99), the National Natural Science Foundation of China (81800912), and the National Natural Science Foundation of Shanghai (21ZR1411800). Trial registration: ClinicalTrials.gov NCT04026932. Registered on 18 July 2019. [ABSTRACT FROM AUTHOR]

Drought is a meteorological phenomenon that negatively impacts agricultural production. In recent years, southwest China has frequently experienced agricultural droughts; these have significantly impacted the economy and the ecological environment. Although several studies have been conducted on agricultural droughts, few have examined the factors driving agricultural droughts from the perspective of water and energy balance. This study aimed to address this gap by utilizing the Standardized Soil Moisture Index (SSMI) and the Budyko model to investigate agricultural drought in southwest China. The study identified four areas in Southwest China with a high incidence of agricultural drought from 2000 to 2020. Yunnan and the Sichuan-Chongqing border regions experienced drought in 10% of the months during the study period, while Guangxi and Guizhou had around 8% of months with drought. The droughts in these regions exhibited distinct seasonal characteristics, with Yunnan experiencing significantly higher drought frequency than other periods from January to June, while Guizhou and other areas were prone to severe droughts in summer and autumn. The Budyko model is widely used as the mainstream international framework for studying regional water and energy balance. In this research, the Budyko model was applied to analyze the water and energy balance characteristics in several arid regions of southwest China using drought monitoring data. Results indicate that the water and energy balances in Yunnan and Sichuan-Chongqing are more moisture-constrained, whereas those in Guizhou and Guangxi are relatively stable, suggesting lower susceptibility to extreme droughts. Furthermore, during severe drought periods, evapotranspiration becomes a dominant component of the water cycle, while available water resources such as soil moisture decrease. After comparing the causes of drought and non-drought years, it was found that the average rainfall in southwest China is approximately 30% below normal during drought years, and the temperature is 1–2% higher than normal. These phenomena are most noticeable during the spring and winter months. Additionally, vegetation transpiration is about 10% greater than normal during dry years in Southwest China, and soil evaporation increases by about 5% during the summer and autumn months compared to normal conditions. [ABSTRACT FROM AUTHOR]

After one course of VAA regimen, 10 patients (83.3%) achieved CR, 1 patient (8.3%) achieved CRi and 1 patient (8.3%) achieved partial remission (PR). The VEN-sensitive AML cells MV4-11 (IC SB 50 sb = 4.506 nM) and VEN-resistant AML cells THP-1 (IC50 = 738.4 nM; Figure S1A) were used to evaluate whether the combination treatment of LDAC plus VA regimen performed robust synergistic killing in AML cells. [Extracted from the article]

In this paper, a general class of time-symmetric mean-field stochastic systems, namely the so-called mean-field forward-backward doubly stochastic differential equations (mean-field FBDSDEs, in short) are studied, where coefficients depend not only on the solution processes but also on their law. We first verify the existence and uniqueness of solutions for the forward equation of general mean-field FBDSDEs under Lipschitz conditions, and we obtain the associated comparison theorem; similarly, we also verify those results about the backward equation. As the above two comparison theorems' application, we prove the existence of the maximal solution for general mean-field FBDSDEs under some much weaker monotone continuity conditions. Furthermore, under appropriate assumptions we prove the uniqueness of the solution for the equations. Finally, we also obtain a comparison theorem for coupled general mean-field FBDSDEs. [ABSTRACT FROM AUTHOR]

Background: Identifying therapeutic targets and prognostic biomarkers significantly contributes to individualized treatment of acute myeloid leukemia (AML). Dihydropyrimidinase‐like 2 (DPYSL2) expression was decreased in homoharringtonine (HHT)‐resistant AML cells, which were established by our group. DPYSL2 plays an important role in axon growth and has oncogene effect in glioblastoma. However, little research has been conducted to investigate the function of DPYSL2 in AML pathogenesis. Methods: Auto‐docking was used to reveal the targeting relationship between HHT and DPYSL2. Overall survival (OS), event‐free survival (EFS), and relapse‐free survival (RFS) were used to evaluate the prognostic impact of DPYSL2 for AML. ShRNA was used to knockdown the expression of SPATS2L. Apoptosis was assessed by flow cytometry. In vivo growth and survival were assessed using a xenotransplantation mice model. RNA sequencing was performed to elucidate the molecular mechanisms underlying the role of SPATS2L in AML and were confirmed by Western blot. Results: We found DPYSL2 was the target of HHT. Next, we found AML cell lines and patients had higher DPYSL2 expression levels than the normal samples. Further multivariate analysis demonstrated that high DPYSL2 expression was an independent poor prognostic factor for OS, EFS, and RFS in AML. Inhibition of DPYSL2 expression suppressed cell growth, induced apoptosis in AML cell lines, and prolonged the survival of AML xenograft NCG mice. Through RNA‐seq analysis from TCGA and our data, the JAK2/STAT3/STAT5‐PI3K P85/AKT/GSK3b axis was thought to be the critical pathway in regulating DPYSL2 in AML development. Conclusions: We first time confirmed that DPYSL2 was a target of HHT and played an oncogene role in AML by regulating JAK/STAT signaling pathway. Therefore, DPYSL2 could serve as a novel prognostic marker and therapeutic target for AML treatment. [ABSTRACT FROM AUTHOR]

Hexagonal boron nitride (h-BN) is an excellent support material for nanocatalysts due to its two-dimensional (2D) architectural morphology and physicochemical stability. In this study, a chemically stable, recoverable, eco-friendly, and magnetic h-BN/Pd/Fe2O3 catalyst was prepared by a one-step calcination process, in which Pd and Fe2O3 nanoparticles (NPs) were uniformly decorated on the surface of h-BN via a typical adsorption–reduction procedure. In detail, nanosized magnetic (Pd/Fe2O3) NPs were derived from a Prussian blue analogue prototype, a well-known porous metal–organic framework, and then further surface-engineered to produce magnetic BN nanoplate-supported Pd nanocatalysts. The structural and morphological features of h-BN/Pd/Fe2O3 were investigated by spectroscopic and microscopic characterization techniques. Moreover, the h-BN nanosheets endow it with stability and appropriate chemical anchoring sites which solve the problems of inefficient reaction rate and high consumption caused by the inevitable agglomeration of precious metal NPs. Under mild reaction conditions, the developed nanostructured h-BN/Pd/Fe2O3 as the catalyst shows high yield and efficient reusability in reducing nitroarenes into the corresponding anilines using sodium borohydride (NaBH4) as a reductant. [ABSTRACT FROM AUTHOR]

The classification of White blood cells (WBCs) plays an important role. However, the traditional method of blood smear analysis is laborious. This paper presented a classification method of WBCs based on hyperspectral images and Deep learning (DL). The U-net network was proposed to extract spectral features of WBCs region of interest (ROI) under the pseudo-color images with specific hyperspectral images (420.8, 557.2 and 667.4 nm). For spectral features and the pseudo-colour images of hyperspectral data, attention-aided one and two-dimensional convolutional neural networks were applied to establish WBCs classification models, respectively. The overall average accuracy can reach 94.20% and 92.60%, respectively. A fusion network was constructed to make full use of the spectral and image spatial features, and its classification accuracy reached 96.20%. In terms of overall average accuracy, the fusion network model was the optimal, but for individual types of WBCs, each network had its own unique advantages. [ABSTRACT FROM AUTHOR]

In this work, a cost-effective, environmentally friendly, and convenient method for synthesizing a novel heterogeneous catalyst via modification of polystyrene using tetrazole-copper magnetic complex [Ps@Tet-Cu(II)@Fe3O4] has been successfully developed. The synthesized complex was analyzed using TEM (transmission electron microscopy), HRTEM (high resolution-transmission electron microscopy), STEM (scanning transmission electron microscopy), FFT (Fast Fourier transform), XRD (X-ray diffraction), FT-IR (Fourier transform-infrared spectroscopy), TG/DTG (Thermogravimetry and differential thermogravimetry), ICP-OES (Inductively coupled plasma-optical emission spectrometry), Vibrating sample magnetometer (VSM), EDS (energy dispersive X-ray spectroscopy), and elemental mapping. N-Sulfonyl-N-aryl tetrazoles were synthesized in high yields from N-sulfonyl-N-aryl cyanamides and sodium azide using Ps@Tet-Cu(II)@Fe3O4 nanocatalyst. The Ps@Tet-Cu(II)@Fe3O4 complex can be recycled and reused easily multiple times using an external magnet without significant loss of catalytic activity. [ABSTRACT FROM AUTHOR]

BACKGROUND: Fatty acid oxidation has been considered as an important energy source for tumorigenesis and development. Several studies have investigated the role of CPT1A, a kind of fatty acid oxidation rate-limiting enzyme, in AML. However, prognostic value and regulatory network of another subtype, CPT1B in AML remains elusive. This study aims to clarify the independent prognostic role of CPT1B in CN-AML based on clinical data and molecular level data (mRNA, miRNA and lncRNA). OBJECTIVE: The aim of this study is to investigate the prognostic value of CPT1B in AML patients. METHODS: First, we analyzed the CPT1B expression in AML cohort via the online database "GEPIA". Subsequently, miRNA-mRNA and ceRNA networks were constructed to help predict the role of CPT1B in AML. Several molecules which showed the prognostic value and metabolic function of CPT1B were identified. Finally, the expression of CPT1B in our own cohort of 324 CN-AML patients was analyzed to clarify the results. RESULTS: It was found that CPT1B was markedly higher in AML patients compared to normal people and this upregulation was associated with the poor clinical outcome. Several molecules revealed the possible regulatory mechanism of CPT1B in AML. CONCLUSION: CPT1B is a potential prognostic factor and a therapeutic target for AML treatment. [ABSTRACT FROM AUTHOR]

With the increasing demand for blue dyes, it is of vital importance to develop a green and efficient biocatalyst to produce indigo. This study constructed a hydrogen peroxide-dependent catalytic system for the direct conversion of indole to indigo using P450BM3 with the assistance of dual-functional small molecules (DFSM). The arrangements of amino acids at 78, 87, and 268 positions influenced the catalytic activity. F87G/T268V mutant gave the highest catalytic activity with kcat of 1402 min−1 and with a yield of 73%. F87A/T268V mutant was found to produce the indigo product with chemoselectivity as high as 80%. Moreover, F87G/T268A mutant was found to efficiently catalyze indole oxidation with higher activity (kcat/Km = 1388 mM−1 min−1) than other enzymes, such as the NADPH-dependent P450BM3 (2.4-fold), the Ngb (32-fold) and the Mb (117-fold). Computer simulation results indicate that the arrangements of amino acid residues in the active site can significantly affect the catalytic activity of the protein. The DFSM-facilitated P450BM3 peroxygenase system provides an alternative, simple approach for a key step in the bioproduction of indigo. [ABSTRACT FROM AUTHOR]

Exuberant large T‐cell proliferations in Kikuchi disease can potentially be misdiagnosed as lymphoma. In this study, we explore their clinicopathological features and summarize key points that can be used to distinguish them from T‐cell lymphoma. The cohort consisted of 25 cases of Kikuchi disease with an exuberant large T‐cell proliferation, which, in part, mimicked lymphoma. The median age was 25 years with a female:male ratio of 4:1. By B‐scan ultrasonography, patients presented with either isolated lymphadenopathy (68%) involving the cervical and axillary regions or generalized lymphadenopathy (32%). Histologically, lymph nodes showed paracortical and interfollicular expansion by sheets of large cells associated with karyorrhectic debris. Histiocytes and plasmacytoid dendritic cells were present in the background. No case showed complete effacement of lymph node architecture. The large cells were CD8‐positive cytotoxic T‐cells with a high proliferation rate. These T‐cells showed decreased BCL‐2 in 17 (68%) cases. CD5 expression was decreased in 10 (40%) cases. Histiocytes in the background were positive for myeloperoxidase. Clonal TRG and/or TRB rearrangements were detected in 2 of 10 (20%) cases. In conclusion, large T‐cell proliferations in Kikuchi disease can be alarming at the morphologic and immunophenotypic levels and need to be distinguished from T‐cell lymphoma. Clinical features helpful in the differential diagnosis include young patients and lymphadenopathy involving the cervical and axillary regions. Major pathologic features helpful in this differential diagnosis include partial involvement of the lymph node and the presence of karyorrhectic debris, crescent‐shaped histiocytes, and/or loose aggregates of plasmacytoid dendritic cells. [ABSTRACT FROM AUTHOR]

In this article, the generalized Jacobi elliptic function expansion method with four new Jacobi elliptic functions was used to the generalized fractional (3 + 1)-dimensional Kadomtsev–Petviashvili (GFKP) equation with the Atangana-Baleanu-Riemann fractional derivative, and abundant new types of analytical solutions to the GFKP were obtained. It is well known that there is a tight connection between symmetry and travelling wave solutions. Most of the existing techniques to handle the PDEs for finding the exact solitary wave solutions are, in essence, a case of symmetry reduction, including nonclassical symmetry and Lie symmetries etc. Some 3D plots, 2D plots, and contour plots of these solutions were simulated to reveal the inner structure of the equation, which showed that the efficient method is sufficient to seek exact solutions of the nonlinear partial differential models arising in mathematical physics. [ABSTRACT FROM AUTHOR]

Single-phase α-cordierite glass-ceramics for a low-temperature co-fired ceramic (LTCC) substrate were fabricated from tuff as the main raw material, using the non-stoichiometric formula of α-cordierite with excess MgO without adding any sintering additives. The sintering/crystallization behavior and the various performances of dielectric properties, thermal expansion, and flexural strength of the glass-ceramics were detected. The results indicated that only single-phase α-cordierite crystal was precipitated from the basic glass sintered at the range 875–950 °C, and μ-cordierite crystal was not observed during the whole sintering-crystallization process. The properties of glass-ceramics were first improved and then deteriorated with the increase in tuff content and sintering temperature. Fortunately, the glass-ceramics sintered at 900 °C with 45 wt.% tuff content possessed excellent properties: high densify (2.62 g∙cm−3), applicable flexural strength (136 MPa), low dielectric loss (0.010, at 10 MHz), low dielectric constant (5.12, at 10 MHz, close to α-cordierite), and suitable coefficients of thermal expansion (CTE, 3.89 × 10−6 K−1). [ABSTRACT FROM AUTHOR]

Recently, platelet to white blood cell ratio (PWR) was reported as an independent prognostic predictor in acute promyelocytic leukemia. Acute myeloid leukemia (AML) often presents with abnormal platelet counts and white blood cell counts (WBC) at disease diagnosis. However, the clinical impact of PWR on cytogenetically normal AML (CN-AML) is still unclear. Therefore, we evaluate its prognostic impact on CN-AML patients. We recorded the clinical information at the time of disease diagnosis, and calculated the ratio of platelet counts to WBC in 338 patients with CN-AML. To assess the prognostic value of PWR, we divided patients into low, intermediate and high group based on the values of PWR. The independent prognostic value of PWR was investigated in the context of the well-established predictors including white blood cell counts, age, and genes of NPM1, FLT3-ITD, CEBPA, and DNMT3A mutations. Receiver operating characteristic (ROC) curve was used to assess the performance of its prognostic prediction. Higher PWR have the higher levels of platelet counts, but lower levels of white blood cell counts, percentage of bone marrow blasts, FLT3-ITD and NPM1 mutations. The performance of survival prediction was comparable between PWR alone and combined molecular biomarkers. Moreover, PWR had the additional prognostic information to the molecular biomarkers. Finally, PWR was associated with favorable overall survival and event free survival in CN-AML patients independent of genetic subtypes and clinical parameters. We found PWR was an independent prognostic predictor in CN-AML. [ABSTRACT FROM AUTHOR]

Chemodynamic therapy (CDT) offers a promising alternative to conventional cancer treatment. However, the limited acidity and H2O2 concentration in tumor microenvironment (TME) severely impair the anticancer effects of CDT. In this study, we report a microemulsion-assisted coassembly method to prepare iron(III) tetraphenylporphyrin (FeTPP) and magnetic (Fe3O4) nanocomposite material (FeTPP@Fe3O4), using photoactive FeTPP and Fe3O4 nanocrystals as building blocks. The self-assembling nature of FeTPP results in disordered aggregation and fluorescence quenching, leading to a high light-to-heat conversion efficiency. Continuously, the photo-thermal effect enhances the catalytic decomposition of hydrogen peroxide (H2O2) in the Fenton reaction on Fe3O4 nanocrystals to generate highly toxic hydroxyl radicals (·OH) to destroy cancer cells. This cascade reaction produces a synergistic therapeutic effect between CDT and photothermal therapy (PTT), which significantly amplifies the therapeutic effect and enhances the treatment outcome of cancer patients. The highly efficient tumor catalytic therapy in vivo results confirmed that this nanomedicine treatment is an excellent biocompatible catalytic nanomedicine therapy achieved through a photo-enhanced Fenton reaction activity approach. [ABSTRACT FROM AUTHOR]