MdWRKY11 improves copper tolerance by directly promoting the expression of the copper transporter gene MdHMA5

Overuse of fungicides and fertilizers has resulted in copper(Cu)contamination of soils and toxic levels of Cu in apple fruits.To breed Cu-resistant apple(Malus domestica)cultivars,the underlying molecular mechanisms and key genes involved in Cu resistance must be identified.Here,we show that MdWRKY11 increases Cu tolerance by directly promoting the transcription of MdHMA5.MdHMA5 is a Cu transporter that may function in the storage of excess Cu in root cell walls and stems for Cu tolerance in apple.The transcription factor MdWRKY11 is highly induced by excess Cu.MdWRKY11 overexpression in transgenic apple enhanced Cu tolerance and decreased Cu accumulation.Apple calli transformed with an MdWRKY11-RNAi construct exhibited the opposite phenotype.Both an in vivo chromatin immunoprecipitation assay and an in vitro electrophoretic mobility shift assay indicated that MdWRKY11 binds to the promoter of MdHMA5.Furthermore,MdWRKY11 promoted MdHMA5 expression in transgenic apple plants,as revealed by quantitative PCR.Moreover,inhibition of MdWRKY11 expression by RNA interference led to a significant decrease in MdHMA5 transcription.Thus,MdWRKY11 directly regulates MdHMA5 transcription.Our work resulted in the identification of a novel MdWRKY11-MdHMA5 pathway that mediates Cu resistance in apple.

Effects of EMS Treatments on Multiplication and Differentiation of Sugarcane Embryonic Cell Clusters

[ Objective] This study aimed to investigate the effects of EMS （ethyl methane sulfonate） treatments on multiplication and differentiation of sugarcane embryonic cell clusters. [ Method] Sugarcane variety Xintaitang 22 （ROC22） was used as the experimental material. After treated with different concentrations of EMS for different time, sugarcane embryonic cell clusters were collected for subculture, differentiation and rooting, to compare and analyze the correlation of differ- ent EMS treatments with the muhiplicafion and differentiation of sugarcane embryonic cell clusters. [ Result] Treating ROC22 embryonic cell clusters with 0. 10% -0.15% EMS for4-6 h led to the best results, which reached the level of semi-lethal dose. Sugarcane embryonic cell clusters treated with EMS were adopted for subculture; results indicated that browning rate of cell clusters was higher than that in control （CK） but embryonic structure proportion was lower than that in control ; in addition, multiplication multiple of sugarcane embryonic cell clusters was also lower than that in control. After treated with EMS, sugarcane em- bryonic cell clusters exhibited significantly lower bud differentiation rate and higher browning rate compared with control. Furthermore, treating sugarcane embryonic cell clusters with 0.15% EMS for 2 h was conducive to plantlet emergence and rooting of sugarcane embryonic cell clusters. [ Conclusion] This study provided the- oretical basis for effective mutagenesis of sugarcane using EMS.

Study on Major Factors Influencing the Proliferation and Growth of Aseptic Buds of Vietnam Mesona blumes

[Objective]This study aimed to investigate the major factors influencing the proliferation and growth of aseptic buds of Vietnam Mesona blumes,thus providing technical references for establishing rapid propagation system in vitro of Vietnam M.blumes.[Method]The effects of medium components（different basic medium,sucrose concentrations and cytokinins）and explant materials（different explants）on the proliferation of aseptic buds of Vietnam M.blumes were analyzed.[Result]Among MS,Miller and modified White basic medium,MS medium exhibited the best effect on proliferation of Vietnam M.blumes buds with the bud proliferation multiple of 8.53.Among different sucrose concentrations,20.0 g/L sucrose gave the highest bud proliferation multiple of 8.34,while 25.0 g/L sucrose led to the best growth status with the bud proliferation multiple of 7.05.The effect of CPPU on bud proliferation was higher than that of 6-BA and KT,with the bud proliferation multiple of 9.80.Among different explants,top stem exhibited the best effect on bud proliferation with the bud proliferation multiple of 9.35,resulting in robust seedlings.[Conclusion]The most suitable subculture medium for the proliferation and growth of aseptic buds of Vietnam M.blumes is MS＋20.0-25.0 g/L sucrose＋0.5 mg/L CPPU and the most suitable explant is top stem.

IPO创新承诺与企业创新

在推进国家创新驱动发展战略的背景下,资本市场如何影响企业创新是一个值得深究的学术话题。企业创新活动受其创新意愿和创新能力两个方面的影响,既有文献多围绕创新能力进行研究,鲜有文献关注创新意愿这一维度。本文从招股说明书中募集资金是否投向创新入手,考察IPO创新承诺对企业创新的影响。以A股市场2006~2017年IPO成功的企业为样本研究发现,IPO创新承诺能够显著促进企业创新。进一步,我们发现IPO创新承诺提高了企业过会概率,减弱了企业融资面临的不确定性,有利于企业保持创新活动的连贯性,进而推动创新,但这一效应仅在上市后的两年内显著,且无法实现高质量创新的持续。此外,我们还考察了IPO创新承诺的经济后果,研究发现,创新承诺可以降低IPO抑价幅度,并提升企业上市后的业绩。上述结果表明,尽管IPO创新承诺向市场传递出积极信号,但长期来看企业的创新表现并未得到延续,这意味着,IPO核准制在甄别企业创新能力方面缺乏效率。

TBK1:a new target for overcoming cancer immunotherapy resistance

In a recent study published in Nature,Sun et al.(2023)discovered that targeting TANK-binding kinase 1(TBK1)can successfully overcome resistance to immune checkpoint blockade(ICB)treatment and the study revealed its potential mechanism.The authors provided evidence that the disruption of TBK1 signal enhances the blockade of programmed cell death protein-1(PD-1)and promotes anti-tumor immunity in the tumor microenvironment(TME).Tumor cells rely on Janus kinase(JAK)and signal transducer as well as activator of transcription(STAT)signals to elicit an immune response by perceiving tumor necrosis factorα(TNF-α)and interferon-γ(IFN-γ),resulting in receptor-interacting protein kinase(RIPK)-caspase-mediated cell death in tumor cells(Figure 1).

Visual abstraction of dynamic network via improved multi-class blue noise sampling

Massive sequence view (MSV) is a classic timeline-based dynamic network visualization approach. However, it is vulnerable to visual clutter caused by overlapping edges, thereby leading to unexpected misunderstanding of time-varying trends of network communications. This study presents a new edge sampling algorithm called edge-based multi-class blue noise (E-MCBN) to reduce visual clutter in MSV. Our main idea is inspired by the multi-class blue noise (MCBN) sampling algorithm, commonly used in multi-class scatterplot decluttering. First, we take a node pair as an edge class, which can be regarded as an analogy to classes in multi-class scatterplots. Second, we propose two indicators, namely, class overlap and inter-class conflict degrees, to measure the overlapping degree and mutual exclusion, respectively, between edge classes. These indicators help construct the foundation of migrating the MCBN sampling from multi-class scatterplots to dynamic network samplings. Finally, we propose three strategies to accelerate MCBN sampling and a partitioning strategy to preserve local high-density edges in the MSV. The result shows that our approach can effectively reduce visual clutters and improve the readability of MSV. Moreover, our approach can also overcome the disadvantages of the MCBN sampling (i.e., long-running and failure to preserve local high-density communication areas in MSV). This study is the first that introduces MCBN sampling into a dynamic network sampling.

The role of TIA1 and TIAL1 in germinal center B cell function and survival

B cells are essential components of the adaptive immune system and undergo differentiation and maturation during infection or immune stimulation to produce antibodies that can specifically recognize and bind to antigens.Germinal centers(GCs)are microanatomical sites for the clonal expansion and antibody affinity maturation of B cells.In the dark zone(DZ)of the germinal center,B cells rapidly proliferate,and somatic hypermutation(SHM)of B cell antigen receptors(BCRs)occurs.B cells then migrate to the light zone(LZ).

Cryo-EM structure of human κ-opioid receptor-G_(i) complex bound to an endogenous agonist dynorphin A

Dear Editor,The opioid receptor family is divided into four subtypes each paired with their cognate peptide ligand:theμ-opioid receptor(MOR)withβ-endorphin,K-opioid receptor(KOR)with dynorphin A and B,o-opioid receptors(DOR)with enkephalin,and nociceptin opioid receptor(NOR)with nociceptin(Faouzi et al.,2020).These four opioid receptors all primarily couple to heterotrimeric G/G。proteins as well as mediatingβ-arrestin1/2 signaling pathway(Ferre et al.,2019).Activation of these receptors by distinct ligands is linked to a series of physiological responses,such as release of hormones,pain adjustment,drug addiction,stress,and mood regulation(Che et al.,2018).

The fungal mycobiome:a new hallmark of cancer revealed by pan-cancer analyses

In a recent study published in Cell,1 a group led by Ravid Straussman and Rob Knight characterized fungi across multiple types of cancer and revealed their distribution,relationships with immune cells,and possible prognostic value.Meanwhile,another study led by Anders B.Dohlman and Iliyan D.Iliev2 reported a similar pan-cancer mycobiome analysis of diverse body sites and identified tumor-associated fungi.

The loss of epigenetic information:not only consequences but a cause of mammalian aging

In a recent study published in Cell,Yang et al.revealed that changes in epigenetic landscapes caused by faithful DNA repair are key drivers accelerating aging of mammalian organs or tissues.1 Impressively,changes in H3K27ac landscape during aging process influence cell identity maintenance,and this aging process can be reversed by the inducible expression of pioneer transcription factors,Oct4,Sox2,and Klf4(OSK)in the living mammals.In mammals,global and local changes of DNA methylation occur in the genome during aging.Additionally,general loss of histones and global chromatin remodeling have been observed in all aging models,while in reverse reprograming of cell fate can lead to global changes in the epigenetic and rejuvenated epigenome,suggesting the potential of reprogramming for the reversal of aging.2 However,as no systematic studies revealed the characteristics of epigenomic changes during aging,it remains unclear whether the changes in epigenetic landscape are the consequences(marks)or direct cause of aging.

FXR inhibition: an innovative prophylactic strategy against SARS-CoV-2 infection

A recent study by Brevini et al.was published in Nature and proposed a critical role of farnesoid X receptor(FXR)signaling in controlling ACE2 expression.Inhibitors of FXR signaling,ursodeoxycholic acid(UDCA)and z-guggulsterone(ZGG),have been proven to reduce ACE2 expression and susceptibility to SARS-CoV-2 infection in human tissues,providing an innovative strategy for SARS-CoV-2 treatment and prevention.

Deciphering dynamic changes of the aging transcriptome with COVID-19 progression and convalescence in the human blood

Dear Editor,Overwhelming evidence suggests that age itself is a prominent risk factor for COVID-19 morbidity and mortality.^(1,2)However,the molecular basis of aging’s effect on SARS-CoV-2 susceptibility and COVID-19 severity in adults is still not fully understood.Thus,we hypothesized that aging-related cellular landscape alterations influence clinical manifestations,which is critical for determining likely intervention targets to slow the transmission of COVID-19 and reduce severe symptoms.

Motile cilia and microvillar:accomplices of SARS-CoV-2 in penetratingg mucuss barrier and infecting airway epithelium

Recently in Cell,Chien et al.published their new findings on severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)penetrating through the'mucosal,barrier of,respiratory by hijacking the cilia and microvilli of nasal epithelial cells,and elucidated the specific mechanism in detail using electron microscopy as well as phosphoproteomics.This study fully explained the way of SARS-CoV-2 breaking through the mucus barrier to infect nasal epithelial cells,and provided a novel direction for the blocking treatment of respiratory tract infections.The culprit of coronavirus disease 2019(COviD-19)pandemic,SARS-CoV-2.

;he regulation of TGF-β/SMAD signaling by protein deubiquitination

Transforming growth factor-β （TGF-β） members are key cytokines that control embryogenesis and tissue homeostasis via transmembrane TGF-β type II （TβR II） and type I （TβRI） and serine/threonine kinases receptors. Aberrant activation of TGF-β signaling leads to diseases, including cancer. In advanced cancer, the TGF-β/SMAD pathway can act as an oncogenic factor driving tumor cell invasion and metastasis, and thus is considered to be a therapeutic target. The activity of TGF-β/SMAD pathway is known to be regulated by ubiquitination at multiple levels. As ubiquitination is reversible, emerging studies have uncovered key roles for ubiquitin-removals on TGF-β signaling components by deubiquitinating enzymes （DUBs）. In this paper, we summarize the latest findings on the DUBs that control the activity of the TGF-β signaling pathway. The regula- tory roles of these DUBs as a driving force for cancer progression as well as their underlying working mech- anisms are also discussed.

Role of pyroptosis in inflammation and cancer

Pyroptosis is a form of programmed cell death mediated by gasdermin and is a product of continuous cell expansion until the cytomembrane ruptures,resulting in the release of cellular contents that can activate strong inflammatory and immune responses.Pyroptosis,an innate immune response,can be triggered by the activation of inflammasomes by various influencing factors.Activation of these inflammasomes can induce the maturation of caspase-1 or caspase-4/5/11,both of which cleave gasdermin D to release its N-terminal domain,which can bind membrane lipids and perforate the cell membrane.Here,we review the latest advancements in research on the mechanisms of pyroptosis,newly discovered influencing factors,antitumoral properties,and applications in various diseases.Moreover,this review also provides updates on potential targeted therapies for inflammation and cancers,methods for clinical prevention,and finally challenges and future directions in the field.

APP and APLP1 are degraded through autophagy in response to proteasome inhibition in neuronal cells

Amyloid beta(Aβ)precursor protein(APP)is a key protein in the pathogenesis of Alzheimer’s disease(AD).Both APP and its paralogue APLP1(amyloid beta precursor-like protein 1)have multiple functions in cell adhesion and proliferation.Previously it was thought that autophagy is a novel beta-amyloid peptide(Aβ)-generating pathway activated in AD.However,the protein proteolysis of APLP1 is still largely unknown.The present study shows that APLP1 is rapidly degraded in neuronal cells in response to stresses,such as proteasome inhibition.Activation of the endoplasmic reticulum(ER)stress by proteasome inhibitors induces autophagy,causing reduction of mature APLP1/APP.Blocking autophagy or JNK stress kinase rescues the protein expression for both APP and APLP1.Therefore,our results suggest that APP/APLP1 is degraded through autophagy and the APLP1 proteolysis is mainly mediated by autophagy-lysosome pathway.

The function and clinical application of extracellular vesicles in innate immune regulation

The innate immune system plays a crucial role in the host defense against viral and microbial infection.Exosomes constitute a subset of extracellular vesicles(EVs)that can be released by almost all cell types.Owing to their capacity to shield the payload from degradation and to evade recognition and subsequent removal by the immune system,exosomes efficiently transport functional components to recipient cells.Accumulating evidence has recently shown that exosomes derived from tumor cells,host cells and even bacteria and parasites mediate the communication between the invader and innate immune cells and thus play an irreplaceable function in the dissemination of pathogens and donor cell-derived molecules,modulating the innate immune responses of the host.In this review,we describe the current understanding of EVs(mainly focusing on exosomes)and summarize and discuss their crucial roles in determining innate immune responses.Additionally,we discuss the potential of using exosomes as biomarkers and cancer vaccines in diagnostic and therapeutic applications.

SARS-CoV-2 Omicron variant:recent progress and future perspectives

Since the outbreak of the coronavirus disease 2019(COVID-19)pandemic,there have been a few variants of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),one of which is the Omicron variant(B.1.1.529).The Omicron variant is the most mutated SARS-CoV-2 variant,and its high transmissibility and immune evasion ability have raised global concerns.Owing to its enhanced transmissibility,Omicron has rapidly replaced Delta as the dominant variant in several regions.However,recent studies have shown that the Omicron variant exhibits reduced pathogenicity due to altered cell tropism.In addition.

Cuproptosis:a new v form of programmed cell death

A recent study by Tsvetkov et al.was published in Science and proposed a novel form of copper-induced cell death.Tsvetkov et al.revealed that excess intracellular copper induces the aggregation of lipoylated dihydrolipoamide S-acetyltransferase(DLAT),which is associated with the mitochondrial tricarboxylic acid(TCA)cycle,resulting in proteotoxic stress and leading to a novel form of cell death termed cuproptosis[1].

Ferroptosis in cancer and cancer immunotherapy

The hallmark of tumorigenesis is the successful circumvention of cell death regulation for achieving unlimited replication and immortality.Ferroptosis is a newly identified type of cell death dependent on lipid peroxidation which differs from classical programmed cell death in terms of morphology,physiology and biochemistry.The broad spectrum of injury and tumor tolerance are the main reasons for radiotherapy and chemotherapy failure.The effective rate of tumor immunotherapy as a new treatment method is less than 30%.Ferroptosis can be seen in radiotherapy,chemotherapy,and tumor immunotherapy;therefore,fer-roptosis activation may be a potential strategy to overcome the drug resistance mechanism of traditional cancer treatments.In this review,the characteristics and causes of cell death by lipid peroxidation in ferroptosis are briefly described.In addition,the three metabolic regulations of ferroptosis and its crosstalk with classical signaling pathways are summarized.Collectively,these findings sug-gest the vital role of ferroptosis in immunotherapy based on the interaction of ferroptosis with tumor immunotherapy,chemotherapy and radiotherapy,thus,indicating the remarkable potential of ferroptosis in cancer treatment.