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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

To evaluate the surgical outcomes in patients with Posner-Schlossman syndrome (PSS) at one year. 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. 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. Penetrating canaloplasty achieves a high success rate in PSS without serious complications. [ABSTRACT FROM AUTHOR]

Predicting the water abundance of coal‐bearing strata is crucial for ensuring mining safety. However, owing to the dispersion and attenuation characteristics caused by pore fluid flow, it is difficult to estimate the water abundance of coal seam roof aquifers using seismic data. To overcome this challenge, we provide the relationship between the frequency‐dependent seismic wave velocity and water saturation based on the Chapman fracture model and the mixing fluid model. We propose a seismic dispersion attribute technique that can use dispersion information as an indicator of water abundance. Numerical experiment results show that the water saturation of the sandstone aquifer is positively correlated with the dispersion attribute. The results of low‐frequency rock physical experiments are roughly consistent with those predicted by the model for the given parameters. Using seismic dispersion attribute inversion and the frequency slice wavelet transform method, we predicted the water abundance of sandstone in the coal seam roof of the Yuwang coal mine in Yunnan Province, China. The predicted sandstone water abundance was compatible with the actual water‐rich scenario observed in well logs and downhole drilling in the study area. Therefore, the method proposed herein has the potential to quantitatively determine the water abundances of sandstone aquifers in coal seam roofs. [ABSTRACT FROM AUTHOR]

This study explores the feasibility of tribological self‐lubricating over a wide temperature range by doping Si and Sn solid solution components on the A‐sites of Ti3AlC2 to adapt to the severe circumstances. The specimens were sintered at 1450°C for 120 min under a pressure of 30 MPa in a vacuum environment, and their dry sliding tribological capabilities against Al2O3 at temperatures ranging from ambient temperature to 800°C were investigated using a rotational ball‐on‐disk tribo‐tester. The findings demonstrated a constantly decreased friction coefficient of Ti3Al0.8Si0.2Sn0.2C2 throughout the temperature range and admirable antifriction at higher temperatures where wear rates were 1–2 orders of magnitude lower than those at room temperature, which was superior to earlier reported Ti3AlC2. The predominant friction surface self‐adaptability mechanisms after solid solution treatment were determined to be tribo‐oxidation wear and tribo‐chemical reactions that played a vital role by examining the microstructural evolutions and tribo‐chemical phase composition on friction surfaces at various temperatures. The tribo‐oxidation‐induced generated lubricant film consisting of TiO2, Al2O3, SnO2 mixture oxide phases, and aluminosilicates was responsible for the decreased friction coefficient and wear rate. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Using appraisal theories of emotions as the theoretical basis, we delineate how perceived overqualification relates to work withdrawal, employee silence, and pro-job unethical behavior through the mediating effects of discrete emotions (i.e., shame and anger). We suggest that perceived overqualification is positively associated with shame and ultimately work withdrawal and employee silence, and it has a positive effect on pro-job unethical behavior through the mediating role of anger as well as the serial mediating effect of shame and anger. Data from a three-wave, time-lagged survey of 225 full-time employees in China, provides support for our theoretical model and hypotheses. Taken together, our results suggest that discrete emotional states can help to interpret how and why overqualified employees exhibit distinct action tendencies. We discuss the theoretical and practical implications of our findings. [ABSTRACT FROM AUTHOR]

Organic acids are a key active component of Pinellia ternata (Thunb.) Breit, and their concentration is closely associated with the quality of P. ternata. Developing an efficient and rapid method for detecting organic acids can offer a valuable technology for real-time assessment of P. ternata quality. In this work, a high-performance liquid chromatography coupled to triple quadrupole mass spectrometry (HPLC-QqQ-MS/MS) approach, combining the optimization of extraction conditions using response surface methodology (RSM), was developed for the simultaneous quantitative analysis of six organic acids in P. ternata. The optimal extraction conditions for organic acids in P. ternata were ultrasonic extraction with a solid–liquid ratio of 1:50, ultrasonic time of 60 min, and extraction temperature of 55 °C. Multiple-reaction monitoring (MRM) scanning was employed for quantification using HPLC-QqQ-MS/MS in negative ionization mode through a single run of 10 min, and the limit of detection (LLOD) and limit of quantification (LLOQ) for organic acids were as low as 0.138 ng/mL and 0.614 ng/mL, respectively. The relative standard deviations (RSDs) of reproducibility, precision, and stability were all lower than 5.0%, and recovery rates were 97.75–107.14%, with RSDs < 5.0%. Finally, this method was successfully applied to determine the investigated organic acids in 12 production regions of P. ternata, revealing significant differences between different production areas. This indicates that the optimized method is suitable for further accurate investigations of organic acids of P. ternata. [ABSTRACT FROM AUTHOR]

Quantum dots and carbon nanotubes are advanced nanomaterials that show excellent electrical, mechanical, and optical characteristics. This paper proposes perovskite quantum dots (PQDs) grown on the lattice of Multi-Wall Carbon Nanotubes (MWCNTs) as an efficient gas sensor. The developed sensor shows ethanol selectivity when tested with methanol, hexane, benzene, and ethyl acetate at room temperature. It exhibited fast response and recovery times of 15.17 and 2.64 s, respectively, at 10 ppm ethanol with 90% relative humidity. Essential sensor characteristics like sensitivity, stability, repeatability, and scalability are achieved in these sensors. These remarkable sensor characteristics make PQDs/MWCNTs highly attractive for real-world ethanol monitoring applications at ambient temperature. [ABSTRACT FROM AUTHOR]

Mulberry fruits are rich in bioactive components renowned for their antioxidant properties and potential health benefits. This study thoroughly investigated the impact of cultivation modes on the phenological stages, yield, bioactive components, and antioxidant activity of two mulberry cultivars, Yueshen Dashi (YS-DS) and Xinjiang Baisang (XJ-BS). Notably, greenhouse cultivation led to earlier phenology and shorter fruit development maturation durations compared to field cultivation. Despite a decrease in fruit production and firmness, the greenhouse-grown mulberries exhibited higher individual fruit fresh weight. The content of bioactive components, encompassing anthocyanins, polyphenols, flavonoids, and vitamin C, and of antioxidant activity (measured in the FRAP and DPPH radical scavenging assays) was found to be lower in the greenhouse-grown mulberries than in those cultivated in the field. The contents of total polyphenols and flavonoids showed robust positive correlations in the FRAP and DPPH radical scavenging assays, which suggests that the antioxidant activity of mulberry fruit might be primarily attributable to the bioactive components of total polyphenols and flavonoids. Interestingly, the sugar content and hydroxyl radical scavenging activity (HRSA) displayed an inverse relationship between the two cultivars in the greenhouse versus field conditions. The multivariate analysis highlighted distinct patterns for different cultivars under varying cultivation modes. This study underscores the potential to enhance bioactive components and antioxidant activity through effective manipulation of climate conditions, thereby unlocking the full nutritional potential of mulberry fruits on a large scale in greenhouse environments. [ABSTRACT FROM AUTHOR]

The plastic region of piles under seismic loads is a crucial concern in seafloor improvement design. This paper establishes a physical model of the sand compaction pile-immersed tunnel–water pressure system. This research studies pile arrangements that minimize the sand compaction pile plastic region under seismic loads. The experiments were validated through numerical simulations. The results show that "X-shaped" and rectangular pile groups increase the Energy Residual Index (ERI) due to differences in pile spacing and the instability of the quadrilateral prism damping units formed by piles and soil. In this scenario, piles are limited to heavy and mild plastic regions, with boundary depths at L = 2.25 D and L = 2.08 D (L represents the pile length, and D is the pile diameter). Furthermore, increased water pressure amplifies the structural resonance injury, increasing ERI. In conjunction with the soil, hexagonal pile groups create triangular prism damping units that counteract seismic wavefronts. The total kinetic energy and strain energy of the piled foundation are lower than those of the "X-shaped" and rectangular pile groups. The boundaries between the heavy plastic region, the moderate plastic region, and the mild plastic region are located at depths of L = 4 D and L = 8 D, respectively. This study also reveals that a top-heavy mass distribution in the structure leads to maximum deformation in the heavy plastic region. Pile–soil damping units primarily operate within the moderate plastic region. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Featured Application: This paper focuses on the redevelopment of the ABAQUS finite element software using the improved Mohr–Coulomb model, which enables the consideration of soil anisotropy. The findings of this research provide valuable theoretical guidance for on-site construction design, helping to prevent potential hazards arising from incomplete considerations during construction. It is an economical way to use the pile-supported embankment for the construction of the embankment over soft soil. The combined use of piles and reinforcement effectively reduces the differential settlement of the embankment surface. However, the previous analysis of embankment stress and settlement did not take into account the anisotropy in the embankment filler. In this paper, the UMAT subroutine is developed by using the material subroutine interface in ABAQUS 2016 finite element software. The anisotropy of soil cohesion and friction angle has been incorporated into the Mohr–Coulomb yield criterion so that it can consider the anisotropy of soil. The accuracy of the anisotropic yield criterion in this paper is verified by an ABAQUS source program and related engineering examples. It is found that the anisotropy value of soil cohesion is inversely proportional to the stress ratio on the pile–soil interface while being directly proportional to the tensile stress applied to the geogrid. The results show that the anisotropy of the friction angle decreases with the soil arching effect but increases by 23.1% with the tensile stress on the geogrid. The position of the settlement plane remains relatively constant at 2.3 m as the friction angle anisotropy coefficient increases. These research results provide valuable theoretical guidance for on-site construction design. [ABSTRACT FROM AUTHOR]

Sugarcane planting areas in China mainly lie on gentle slopes and hilly areas. For easy and smooth operation of track-type sugarcane harvesters in hilly areas, it would be significant to analyse the straight-line driving stability of harvesters in hilly areas. The static overturning angles of a two-track (machine A) and a four-track (machine B) sugarcane harvesters were used as the evaluation index to theoretically analyse the static driving stability of the two harvesters. The results showed that machine A was more stable than machine B when the elevator of machine A was rotated horizontally by + 0°. When machine A with a horizontal rotation angle of 0°–60°, the static driving stability became less stable. The dynamic overturning angle was used as the evaluation indexes to experimentally analyse the dynamic driving stability of the two machines. The results found that machine A was less stable than machine B. The larger the horizontal rotation angle of the elevator of machine A, the less stable in the dynamic driving. The structural stress value was used as the evaluation indexes to make a static analysis of the two machines elevator; the results demonstrated that the strength of the two elevators met all the safety requirements. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

China faces challenges of food security and sustainable agricultural production. However, current studies rarely address the spatial distribution patterns of water consumption and carbon emissions. We studied the irrigation water use efficiency and carbon emission differences of crops in arid areas and their spatial distribution using wheat and maize, two major food crops in the middle reaches of the Heihe River, as examples. Furthermore, we have optimized low-carbon cropping of crops under the multiple objectives of water conservation and economic development. The results show that: (1) The carbon emissions per unit of water consumption for maize are 0.03 × 10−6 t mm−1 and 0.49 × 10−6 t mm−1 for wheat. Irrigation water consumption per unit yield is 515.6 mm t−1 for maize and 426.7 mm t−1 for wheat. (2) The spatial distribution patterns of irrigation water consumption were opposites for maize and wheat. The former has lower irrigation water consumption in the planting area upstream of the Heihe River and higher in the lower reaches. In contrast, the pattern of wheat irrigation is the opposite. (3) After optimizing the cropping mix for both crops, the area planted with wheat should be reduced to 59% of the current size, while maize should be expanded to 104%. The results of the research hold immense importance in guiding the future grain crop planting patterns for water-saving agriculture and low-carbon agriculture development in arid zones worldwide, aligning with the United Nations' Sustainable Development Goals. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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Liner is an important component connecting brake oil pipe and brake in automobile brake system, and the oversize of inner diameter will seriously affect the brake performance of vehicles. Aiming at the problems of low efficiency, poor accuracy and inconsistent detection standards in the manual measurement of liner inner diameter, a method for measuring liner inner diameter based on machine vision was proposed. The inner diameter of liner was preprocessed and located by using bilateral filtering, improved Otsu threshold method and morphological method. An improved Canny edge detection operator was used to extract the inner diameter contour points, and the least square method was used to fit the circle based on Tukey weight function to calculate the inner diameter size. The experimental verification shows that the measurement error value of the detection algorithm is within ± 0.01 mm, the measurement accuracy is 98.9%, the missing rate is 0, and the passing rate is 1.1%, which can meet the actual measurement requirements of enterprises. [ABSTRACT FROM AUTHOR]

Goose astrovirus (GoAstV) has frequently been isolated in China since it was first identified as the etiological agent of visceral gout in goslings in 2017. However, the actual prevalence of GoAstV infection and its economic impact on commercial goose production remain poorly characterized. Here, virus detection and serological testing were conducted to determine the extent of GoAstV infection in commercial goose flocks. We detected GoAstV RNA in 2% (6/300) of dead-in-shell embryos and day-old hatched goslings by RT-PCR, indicating vertical transmission under natural conditions. Using a virus neutralization test, GoAstV antibodies were detected in 41.7%–61.1% of serum samples from four commercial goose flocks, indicating that infections were common. To determine the virus types circulating in the commercial flocks, we isolated 15 GoAstVs from goose tissue samples from farms located in five provinces during 2018–2022. Genomic sequence analysis showed that all sequences were corresponded to GoAstV group 2 (GoAstV-2) but were assigned into three capsid subgroups based on sequence variations in the capsid protein. Representative isolates of capsid subgroups were also antigenically evaluated using cross-neutralization tests in LMH cell cultures. The antigenic relatedness values (R) calculated using the Horsfall formula were between 62% and 86%, indicating that no significant antigenic differences exist between the isolates. Our findings indicate that GoAstV-2 viruses are an important cause of fatal gout in goose flocks, as well as hatchery contamination in China. [ABSTRACT FROM AUTHOR]

Haematopoietic Stem cells (HSCs) have the potential for self-renewal and multilineage differentiation, and their behaviours are finely tuned by the microenvironment. HSC transplantation (HSCT) is widely used in the treatment of haematologic malignancies while limited by the quantity of available HSCs. With the development of tissue engineering, hydrogels have been deployed to mimic the HSC microenvironment in vitro. Engineered hydrogels influence HSC behaviour by regulating mechanical strength, extracellular matrix microstructure, cellular ligands and cytokines, cell–cell interaction, and oxygen concentration, which ultimately facilitate the acquisition of sufficient HSCs. Here, we review recent advances in the application of hydrogel-based microenvironment engineering of HSCs, and provide future perspectives on challenges in basic research and clinical practice. [ABSTRACT FROM AUTHOR]

Metal droplet deposition is of fundamental importance in many industrial and manufacturing processes. An in‐depth understanding of the fundamental issues of metal droplet deposition is particularly crucial for developing droplet deposition‐based engineering manufacturing technologies. This review systematically introduces the evolution of metal droplet deposition stages and characteristic behaviors in terms of metal droplet deposition dynamics. The characteristic morphologies of single‐metal droplets after solidification, that is, gas entrapment, ripples, bulging edges, and splashing, are reviewed. The formation mechanisms and influencing factors of different droplet morphologies are summarized. Moreover, the deposition strategy of multiple metal droplets to promote good interfacial bonding is further concluded. Based on these theoretical foundations, three typical engineering manufacturing techniques based on metal droplet deposition, that is, thermal spraying, soldering, and droplet‐based 3D printing, are presented to elucidate further the advantages and potential of metal droplet deposition applied to engineering manufacturing. Finally, some existing problems and future research perspectives are discussed. [ABSTRACT FROM AUTHOR]

To adapt to the complex and changeable electromagnetic environment of radar detection, improve the jamming effect on frequency‐agile radar and low probability of intercept radar, and solve the problem of poor jamming effect caused by intra‐pulse jamming lagging behind target radar signal, a Convolutional Neural Network—Deep Neural Network jamming waveform generation method, based on prior global information of radar signal, is presented in this study. This proposed method uses two networks to generate the overall interference waveforms. One Convolutional Neural Network—Deep Neural Network derives prior global radar information from local prior radar information, which is used by the other Convolutional Neural Network—Deep Neural Network to generate interference. In the whole scheme, an algorithm to design the intra‐pulse interference waveform based on the prior global information of the radar signal is proposed. The algorithm can generate the interference waveform samples from the number and area of multiple false targets and the relative peak between multiple false targets and the real target area by the relevant parameters. Then, an evaluation system (Matched filter, Constant False Alarm Rate Detector, and Distance resolution etc.) is established to evaluate the global effect of the designed interference waveforms. Finally, the time‐domain Root Mean Squared Errors is used as the loss function to optimise the training of the network and ultimately achieve the requirement of generating intra‐pulse adaptive interference waveforms based on radar signal fragments. The principle of generating interference waveforms is based on various aspects of the evaluation of the interference effect, which enhances the time domain correlation between multiple false target areas, thereby boosting the interference effect on the radar. The experimental results show that the proposed method based on the Convolutional Neural Network—Deep Neural Network can effectively solve the problem of intra‐pulse interference lag and small effective interference area after the pulse pressure of the interference waveform matching filter. This study offers certain reference significance for the adaptive interference waveform design based on radar prior global information. [ABSTRACT FROM AUTHOR]

Organic electrochemical transistors (OECTs) have been hailed as highly sensitive biomolecular sensors among organic electronic devices due to their superior stability in an aqueous environment and high transconductance. At the same time, plasmon based sensors are known to provide high sensitivity for biosensing due to the highly localized plasmonic field. Here we report a plasmonic OECT (POET) device that synchronizes the advantages of OECTs and plasmonic sensors on a single platform. The platform is fabricated by a simple, cost-effective, and high-throughput nanoimprinting process, which allows plasmonic resonance peak tuning to a given visible wavelength of interest for versatile biosensing. With glucose sensing as proof, a five-times sensitivity enhancement is obtained for POET compared to a regular (non-plasmonic) OECT. Thus, the POET paves the way to a new paradigm of optoelectronic sensors that combines the inherent high sensitivity of OECTs and localized plasmonic field to sense a vast realm of biomolecules. [ABSTRACT FROM AUTHOR]

How to design the ratiometric thermometer with high sensitivity is a monumental challenge. If the sensitivity can be superposed like the stack of toy bricks, the temperature‐sensing performances will be significantly improved. To achieve sensitivity superposition, a method of dual‐wavelength (980 and 379 nm) excitation in consideration of the sensitivity of integral form is designed and the sensitivity is expected to be manipulated. Herein, compared with conventional 980 nm single excitation, the increase in Er3+ luminescence with dual‐wavelength excitation is attributed to its downshifting luminescence. Under multiple exciting methods (980, 379 nm, and dual‐wavelength excitation), temperature‐sensing behaviors based on thermally (TCL) and nonthermally (NTCL) coupled levels are investigated in the range of 213–683 K. The maximum of relative sensitivity is 2.19% K−1 (based on NTCL) with dual‐wavelength excitation, which is higher than that both with 980 nm single excitation and based on conventional TCL. These results reveal that this dual‐wavelength excitation strategy is effective to enhance sensitivity for Tm3+/Er3+‐based thermometer, which provide new insights into the design of ratiometric thermometer with high sensitivity. [ABSTRACT FROM AUTHOR]

Artemisia argyi Levl. et Van (A. argyi) is a traditional medicinal plant, which is widely used in health, food and medicine. Thujone is an important cyclic monoterpene derivative in the volatile oil of A. argyi leaves with multiple efficacy. Although the thujone synthetic pathway has been preliminarily analyzed in very few species, genes related to the thujone content in A. argyi leaves remain largely unknown. In this study, we identify candidate genes involved in the synthesis and regulation of thujone content in A. argyi leaves by the comparative transcriptome analysis of two group materials with high and low thujone content. A total of 89 candidate genes related to thujone content are identified including one gene involved in the mevalonate pathway, three genes involved in the methylerythritol phosphate pathway, 19 genes involved in the metabolic process from geranyl pyrophosphate to thujone (four b-terpene synthase, five cytochrome P450, five dehydrogenase, and five reductase-encoding genes) and 66 transcription factor-encoding genes. Taken together, our results provide valuable gene resources for further analyzing the synthetic and regulatory pathway of thujone in A. argyi. [ABSTRACT FROM AUTHOR]

This paper presents a 132–140 GHz power amplifier (PA) array in 0.13‐µm SiGe BiCMOS technology. The four dielectric‐loaded end‐fire antennas are integrated with the PA array on chip. With the absence of the lossy power combining networks at the output, the presented PA array achieves a measured maximal effective isotropic radiated power of 29.7 dBm. The array size is only 6.14 × 2.49 mm2 and consumes 5.16 W from a single 4 V DC supply. [ABSTRACT FROM AUTHOR]

A novel algorithm for multi‐subband signal fusion achieves performance superior to traditional all‐pole model, matrix pencil algorithm and deep‐neural‐network (Deep neural network (DNN)). The method uses a deep‐learning autoencoder more fully described as a multi‐subband fusion autoencoder (MSFAE). This autoencoder comprises two parts: a multi‐subband encoder and a full‐band decoder. Full‐band echo distance envelopes are used as training data for the full‐band autoencoder, to obtain the full‐band coding and the full‐band decoder. Then, the multi‐subband echo distance envelopes are used as training data, and the full‐band coding is used as labels, to train the multi‐subband encoder. Finally, the multi‐subband encoder and the full‐band decoder are combined to obtain the MSFAE. The multi‐subband distance envelopes are input to the MSFAE to obtain the full‐band distance envelopes, improving the radar distance resolution and obtaining high‐resolution range profiles. In contrast with the traditional all‐pole model and matrix pencil algorithm, the authors' MSFAE directly processes the information in the frequency domain, avoiding the error of pole estimation in the echo domain. In contrast with DNN, the authors' MSFAE needs only multi‐subband distance envelopes as input, avoiding noise subband redundancy. The experimental results show that the fusion accuracy of MSFAE is higher than the traditional all‐pole model, matrix pencil algorithm and DNN. The MSFAE has superior performance using the fusion method, even at low signal‐to‐noise ratio. [ABSTRACT FROM AUTHOR]

Mulberry (Morus L.; Moraceae; Rosales) is an economically important tree with a long history in China and valued for its rich nutrient, flavor content, medicinal value and useful ecological functions. Morus species are widely distributed in Asia, Europe, North and South America and Africa and exhibit obvious differences in morphological characteristics and phenological stages due to being distributed in diverse climate zones. The morphological description of the phenological stages of black mulberry (Morus nigra L.) has been established in Mediterranean climates and this study extended the BBCH scale for application in different Morus species, especially for mulberry trees grown in subtropical monsoon climates. In this study, we used the BBCH (Biologische Bundesanstalt, Bundessortenamt and CHemische Industrie) scale to describe in detail the phenological growth stages for Morus species in Wuhan, China (a subtropical monsoon climate). Based on this general scale, eight principal stages, i.e., bud, leaf and shoot development stage, inflorescence emergence stage, flowering stage, fruit development stage, fruit maturation stage, senescence and beginning of dormancy stage, were described. We provide photographic images of some primary and secondary developmental stages to better define and standardize morphological characteristics and phenological descriptions of these mulberries (Morus spp.). In addition, because the color of mulberry fruit varies from white, purple, black, or pink to red at maturity, with mostly monosexual flowers, we have also presented detailed descriptions of morphological traits of flower sexuality and fruit color among these four species. In addition, two late phenological germplasms (late bud sprouting associated with late blooming and late fruit ripening) were screened out according to the BBCH scale. Overall, this study will contribute to advance the field of mulberry breeding and implementation of agronomic practices and facilitate convenient communication between mulberry cultivators and researchers in different areas. [ABSTRACT FROM AUTHOR]

Although STK38 (serine-threonine kinase 38) has been proven to play an important role in cancer initiation and progression based on a series of cell and animal experiments, no systemic assessment of STK38 across human cancers is available. We firstly performed a pan-cancer analysis of STK38 in this study. The expression level of STK38 was significantly different between tumor and normal tissues in 15 types of cancers. Meanwhile, a prognosis analysis showed that a distinct relationship existed between STK38 expression and the clinical prognosis of cancer patients. Furthermore, the expression of STK38 was related to the infiltration of immune cells, such as NK cells, memory CD4+ T cells, mast cells and cancer-associated fibroblasts in a few cancers. There were three immune-associated signaling pathways involved in KEGG analysis of STK38. In general, STK38 shows a significant prognostic value in different cancers and is closely associated with cancer immunity. [ABSTRACT FROM AUTHOR]

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secretory serine protease synthesized primarily by the liver. It mainly promotes the degradation of low-density lipoprotein receptor (LDL-R) by binding LDL-R, reducing low-density lipoprotein cholesterol (LDL-C) clearance. In addition to regulating LDL-R, PCSK9 inhibitors can also bind Toll-like receptors (TLRs), scavenger receptor B (SR-B/CD36), low-density lipoprotein receptor-related protein 1 (LRP1), apolipoprotein E receptor-2 (ApoER2) and very-low-density lipoprotein receptor (VLDL-R) reducing the lipoprotein concentration and slowing thrombosis. In addition to cardiovascular diseases, PCSK9 is also used in pancreatic cancer, sepsis, and Parkinson's disease. Currently marketed PCSK9 inhibitors include alirocumab, evolocumab, and inclisiran, as well as small molecules, nucleic acid drugs, and vaccines under development. This review systematically summarized the application, preclinical studies, safety, mechanism of action, and latest research progress of PCSK9 inhibitors, aiming to provide ideas for the drug research and development and the clinical application of PCSK9 in cardiovascular diseases and expand its application in other diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: Androgen receptor splice variant 7 (AR-V7) has always been considered a key driver for triggering enzalutamide resistance of castration-resistant prostate cancer (CRPC). In recent years, both the homeostasis of AR-V7 protein and AR-V7's relationship with LncRNAs have gained great attention with in-depth studies. Starting from protein stability and LncRNA, the paper discusses and summarizes the mechanisms and drugs that affect the CRPC patients' sensitivity to enzalutamide by regulating the protein or transcriptional stability of AR-V7, hoping to provide therapeutic ideas for subsequent research to break through the CRPC therapeutic bottleneck. 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. [ABSTRACT FROM AUTHOR]

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. DNA methyltransferase 3A, a mutated gene associated with hematologic malignancies in age-related clonal haematopoiesis lacks targeted therapies. Here, the authors screen carbon nanomaterials and find graphdiyne oxide binds to mutant cells and disrupts cellular processes with a therapeutic effect in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Underwater images have low quality, and underwater targets have different sizes. The mainstream target detection networks cannot achieve good results in detecting objects from underwater images. In this study, a lightweight underwater multiscale target detection model with an attention mechanism is designed to solve the above problems. In this model, MobileNetv3 is used as the backbone network for preliminary feature extraction. The lightweight feature extraction module (LFEM) pays attention to the feature map at the channel and space levels. The features with large weights are promoted, while the features with small weights are suppressed. Meanwhile, cross-group information exchange enriches the semantic information and location information of the objects. The context aggregation module (CIAM) pools the extracted feature maps to obtain feature pyramids, and it uses the upsampling-feature refinement-cascade addition (URC) method to effectively fuse global context information and enhance the feature representation. The scale normalization for feature pyramids (SNFP) performs adaptive multiscale perception and multianchor detection on feature maps to cover objects of different sizes and realize multiscale object detection in underwater images. The proposed network can realize lightweight feature extraction, effectively handle the global relationship between the underwater scene and the object while expanding the receptive field, traverse the objects of different scales, and achieve adaptive multianchor detection of multiscale objects in underwater images. The experimental results indicate that our method achieves an average accuracy of 81.94% and a detection speed of 44.3 FPS on a composite dataset. Also, our method is better than the mainstream object detection networks in terms of detection accuracy, lightweight design, and real-time performance. [ABSTRACT FROM AUTHOR]

We herein report on the synthesis of a pentacyclic triterpene functionalized through derivation of betulinic acid with hydroxybenzotriazole. The compound was fully characterized by proton (1H-NMR), carbon-13 (13C-NMR), heteronuclear single quantum coherence (HSQC) and distortionless enhancement by polarization transfer (DEPT-135 and DEPT-90) nuclear magnetic resonance. Ultraviolet (UV), and Fourier-transform infrared (FTIR) spectroscopies as well as and high-resolution mass spectrometry (HRMS) were also adopted. Computational studies were conducted to foresee the interactions between compound 3 and phosphodiesterase 9, a relevant target in the field of neurodegenerative diseases. Additionally, preliminary calculation of physico-chemical descriptors was performed to evaluate the drug-likeness of compound 3. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Hypsizygus marmoreus is a representative edible mushroom with low-temperature fruiting after a long postripening (LFLP). Clarifying the mechanism of LFLP and applying a rigorous low-temperature-limited process will optimize the mushroom cultivation process. This study performed an integrative multi-omics analysis of the molecular mechanism of LFLP in combination with genetic, physiological, and cultivation confirmation. The results showed that the amino acid content was increased during LFLP, mainly arginine. pH analysis showed acidification in the postripening stage and alkalization in the substrates of the reproductive growth stage. An enzyme activity test confirmed the increased enzyme activity of arginase and citrate synthase in the postripening stage. Weighted gene coexpression network analysis of the transcriptome and metabolomics indicated that pH variation is correlated mainly with changes in citrate and arginine. Multi-omics reveals a straightforward way of providing enriched materials for amino acid biosynthesis, namely, synergistically elevating citric acid and arginine through enhanced activity of the arginine synthesis branch pathway in the citrate cycle. Our study confirmed that GCN2 mediated metabolic adaptation by enhancing protein translation, highlighting its regulatory role during LFLP. Exogenously added citric acid and arginine shortened the postripening period by 10 days and increased the fruiting body yield by 10.2~15.5%. This research sheds light on the molecular mechanism of LFLP in H. marmoreus and highlights the promising application of nutrient accumulation in high-efficiency cultivation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

With widespread application of voltage source converter (VSC) as a key energy-conversion power electronic device by using the phase-locked loop (PLL) technique for synchronization, the system dynamics has become much complicated. In this paper, the nonlinear dynamics and transient stability of the PLL-based VSC system are investigated, within a unified framework of the (normalized) generalized swing equation. It is found that there are three different types of bifurcation, including the generalized saddle-node, Hopf, and homoclinic bifurcations. Within the coexistence parameter region, the basin boundary of the stable equilibrium point shows either a closed-loop or a fish-like pattern. With the help of the equal area criterion (EAC), the transient stabilities under different transient disturbances including short circuit, voltage dip, and power rise are analyzed. Because the equivalent damping of the VSC is state-dependent, the theoretical results based on the EAC are examined. Furthermore, based on the analytical results from the generalized swing equation, the principle for all major transient stability enhancement methods is uncovered. All these findings are well verified by extensive electromagnetic transient simulations. Therefore, the generalized swing equation provides a deeper physical insight and plays a crucial role in transient stability problems in power-electronic-dominated power systems, similar to the swing equation in traditional power systems. [ABSTRACT FROM AUTHOR]

The electromagnetic (EM) coupling effects of microstrip antennas have become increasingly prominent in complicated electric systems. In this article, a hybrid method is proposed based on the combination of cavity eigenmode theory and BLT equation. First, the internal electric field generated by the transmission lines inside the resonant cavity is obtained via cavity eigenmode theory. Then, the coupling mechanism between the electric field and microstrip antenna is established through radiation coupling interference. On this basis, the BLT equation and numerical integration method are applied to determine the induced voltage at the target microstrip antenna. Eventually, the proposed approach is validated by a full-wave simulation method and the impact of the microstrip antenna parameters on the coupling interference is discussed. This article provides an analytical method for calculating the coupling of a microstrip antenna. Compared with numerical simulation, this method has certain potential advantages in solving closed electrically large objects. Furthermore, duplicate modeling can be avoided in the same type of scenario. [ABSTRACT FROM AUTHOR]

In order to explore the relationship between the filling surface angle and the dynamic characteristics of the filling body under impact load, this paper uses the Hopkinson pressure bar (SHPB) test system to study the influence of different filling surface angles, different cement–sand ratios and different strain rates on the dynamic peak strength, dynamic strength growth factor and failure mode of the filling body. The results show that with the increase in the average strain rate, the dynamic peak strength and dynamic strength growth factor of the layered filling body increase gradually. With the increase in the filling surface angle, the static and dynamic peak strength of the layered filling body decreases gradually, but there is no obvious change law linking the dynamic strength growth factor and filling surface angle. According to the failure mode analysis and the LS-DYNA numerical simulation results for the layered filling body, with the increase in the filling surface angle, the failure mode of the layered filling body changes from splitting failure under tension to shear failure. The research results in this paper can provide theoretical support for the stability of underground layered filling bodies. [ABSTRACT FROM AUTHOR]

A novel wideband and compact water antenna with optically transparent characteristic is presented in this communication. This antenna mainly consists of a fan-shaped cylindrical radiator, a top disk, a cylindrical base, and a water reflector. Based on two resonant modes, this antenna can achieve wideband characteristic. Meanwhile, when combined with fan-shaped radiator and top disk loading, the overall dimensions can be greatly reduced without compromising impedance matching. The ground made of distilled water is used for full transparency. The proposed antenna covers frequency range from 1.16 to 2.79 GHz for $S_{11} < -10$ dB. As far as we know, the proposed antenna shows the widest relative bandwidth (82.5%) in the field of transparent antennas, without sacrificing size and radiation performance. [ABSTRACT FROM AUTHOR]

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. [Display omitted] • Screening of chromatin-modifying drugs identifies class I HDACi as boosters of CAR-T cells • Class I HDACi enhance persistence and in vivo antitumor efficacy of CAR-T cells • Class I HDACi decrease HDAC1 expression and enhance H3K27ac activity • Multi-omics reveal class I HDACi activating the Wnt pathway in CAR-T cells In this study, Zhu et al. show that class I HDAC inhibitors, particularly M344 and chidamide, markedly improve persistence and antitumor efficacy of CAR-T cells by regulation of the HDAC1-H3K27ac axis and activation of the canonical Wnt/β-catenin signaling pathway. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]