Ardisia gigantifolia ethanolic extract inhibits cell proliferation and targets cancer stem cells in gastric cancer

Objective:To evaluate the effects of ethanol extract from Ardisia gigantifolia leaves on cell proliferation and cancer stem cell(CSC)number in gastric cancer.Methods:The inhibitory effect of Ardisia gigantifolia extract on the proliferation of MKN45 and MKN74 gastric cancer cells was assessed using 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay.Non-adherent culture(3D)model was used to evaluate the effect of the extract on tumorsphere size and number.Moreover,the expression of CD44,ALDH,and p21 was determined by immunofluorescence analysis.Flow cytometric analysis was performed to evaluate cell cycle arrest and the expression of gastric CSC markers CD44 and ALDH.Real-time PCR analysis was also carried out to assess the effect of the extract on the expression of cell cycle-regulated genes.Results:Ardisia gigantifolia extract effectively inhibited cell proliferation with an IC_(50)of 55.7μg/m L in MKN45 cells and 123.6μg/m L in MKN74 cells.The extract also arrested cell cycle in the G_(0)/G_(1)phase as well as significantly reduced the size and number of tumorspheres.The markedly increased expression of p21 was observed at both m RNA and protein levels in the extract-treated adherent cells and tumorspheres.In addition,Ardisia gigantifolia extract significantly reduced the number of CD44-and/or ALDH-expressing gastric CSC.Conclusions:The development of gastric CSC can be inhibited by the ethanol extract of Ardisia gigantifolia.

Recent progress and future directions of the research on nanoplastic-induced neurotoxicity

Many types of plastic products,including polystyrene,have long been used in commercial and industrial applications.Microplastics and nanoplastics,plastic particles derived from these plastic products,are emerging as environmental pollutants that can pose health risks to a wide variety of living organisms,including humans.However,it is not well understood how microplastics and nanoplastics affect cellular functions and induce stress responses.Humans can be exposed to polystyrene-microplastics and polystyrene-nanoplastics through ingestion,inhalation,or skin contact.Most ingested plastics are excreted from the body,but inhaled plastics may accumulate in the lungs and can even reach the brain via the nose-to-brain route.Small-sized polystyrene-nanoplastics can enter cells by endocytosis,accumulate in the cytoplasm,and cause various cellular stresses,such as inflammation with increased pro-inflammatory cytokine production,oxidative stress with generation of reactive oxygen species,and mitochondrial dysfunction.They induce autophagy activation and autophagosome formation,but autophagic flux may be impaired due to lysosomal dysfunction.Unless permanently exposed to polystyrene-nanoplastics,they can be removed from cells by exocytosis and subsequently restore cellular function.However,neurons are very susceptible to this type of stress,thus even acute exposure can lead to neurodegeneration without recovery.This review focuses specifically on recent advances in research on polystyrene-nanoplastic-induced cytotoxicity and neurotoxicity.Furthermore,in this review,based on mechanistic studies of polystyrene-nanoplastics at the cellular level other than neurons,future directions for overcoming the negative effects of polystyrene-nanoplastics on neurons were suggested.

Gut flora in multiple sclerosis:implications for pathogenesis and treatment

Multiple sclerosis is an inflammatory disorder chara cterized by inflammation,demyelination,and neurodegeneration in the central nervous system.Although current first-line therapies can help manage symptoms and slow down disease progression,there is no cure for multiple sclerosis.The gut-brain axis refers to complex communications between the gut flo ra and the immune,nervous,and endocrine systems,which bridges the functions of the gut and the brain.Disruptions in the gut flora,termed dys biosis,can lead to systemic inflammation,leaky gut syndrome,and increased susceptibility to infections.The pathogenesis of multiple sclerosis involves a combination of genetic and environmental factors,and gut flora may play a pivotal role in regulating immune responses related to multiple scle rosis.To develop more effective therapies for multiple scle rosis,we should further uncover the disease processes involved in multiple sclerosis and gain a better understanding of the gut-brain axis.This review provides an overview of the role of the gut flora in multiple scle rosis.

New challenges in hepatocellular carcinoma:A role for PIWIinteracting RNAs?

Hepatocellular carcinoma(HCC)is the most common and deadliest subtype of liver cancer worldwide and,therefore,poses an enormous threat to global health.Understanding the molecular mechanisms underlying the development and progression of HCC is central to improving our clinical approaches.PIWIinteracting RNAs(piRNAs)are a class of small non-coding RNAs that bind to PIWI family proteins to regulate gene expression at transcriptional and posttranscriptional levels.A growing body of work shows that the dysregulation of piRNAs plays a crucial role in the progression of various human cancers.In this editorial,we report on the current knowledge of HCC-associated piRNAs and their potential clinical utility.Based on the editorial by Papadopoulos and Trifylli,on the role and clinical evaluation of exosomal circular RNAs in HCC,we highlight this other emerging class of non-coding RNAs.

Tau's function and dysfunction in the brain:when small changes have big consequences

With the increase of life expectancy and population growth,neurodegenerative diseases have risen too and are projected to be a major health public concern by 2050.Neurodegenerative diseases are characterized by the progressive decline of cognitive function leading to the subsequent loss of autonomy.Although the underlying causes of neurodegeneration are not well understood,aging is the main risk factor.

Tuning beneficial calcineurin phosphatase activation to counterα-synuclein toxicity in a yeast model of Parkinson’s disease

Calcineurin(CN)is a calcium-and calmodulindependent serine/threonine that has been studied in many model organisms including yeast,filamentous fungi,plants,and mammals.Its biological functions range from ion homeostasis and virulence in lower eukaryotes to T-cell activation in humans by human nuclear factors of activated T-cells.CN is a heterodimeric protein consisting of a catalytic subunit,calcineurin A(Cna1p),which contains an active site with a dinuclear metal center,and a regulatory Ca^(2+) binding subunit called calcineurin B(Cnb1p)required to activate Cna1p.The calcineurin B subunit has been highly conserved through evolution:For example,the mammalian calcineurin B shows 54%identity with calcineurin B from Saccharomyces cerevisiae.

秸秆-磷石膏联用对赤泥的腐殖质组分和微生物群落的影响

腐殖化过程是赤泥土壤化及堆场生态修复的重要环节。本研究采用腐殖质分级和高通量测序技术,探究了秸秆和磷石膏联用对赤泥腐殖质组分和微生物群落的影响。结果表明,秸秆-磷石膏联用显著增加赤泥胡敏酸和富里酸含量,提高微生物群落多样性和丰富度,促进赤泥腐殖化过程。施用秸秆后,赤泥中葡萄糖苷酶、纤维素水解酶、多酚氧化酶和过氧化物酶分别升高7.15~8.76倍、5.64~7.12倍、2.69~4.57倍和2.59~4.24倍,显著增加Devosiaceae、Rhizobiaceae、Flavobacteriaceae、Caulobacteraceae和Cellvibrionaceae等具有纤维素降解和固氮功能微生物类群相对丰度,提高微生物群落稳定性。研究结果为外源生物质促进腐殖质累积、驱动赤泥成土进程提供科学依据。

Recent progress on Sn_(3)O_(4)nanomaterials for photocatalytic applications

Tin(IV)oxide(Sn_(3)O_(4))is layered tin and exhibits mixed valence states.It has emerged as a highly promising visible-light pho-tocatalyst,attracting considerable attention.This comprehensive review is aimed at providing a detailed overview of the latest advance-ments in research,applications,advantages,and challenges associated with Sn_(3)O_(4)photocatalytic nanomaterials.The fundamental con-cepts and principles of Sn_(3)O_(4)are introduced.Sn_(3)O_(4)possesses a unique crystal structure and optoelectronic properties that allow it to ab-sorb visible light efficiently and generate photoexcited charge carriers that drive photocatalytic reactions.Subsequently,strategies for the control and improved performance of Sn_(3)O_(4)photocatalytic nanomaterials are discussed.Morphology control,ion doping,and hetero-structure construction are widely employed in the optimization of the photocatalytic performance of Sn_(3)O_(4)materials.The effective imple-mentation of these strategies improves the photocatalytic activity and stability of Sn_(3)O_(4)nanomaterials.Furthermore,the review explores the diverse applications of Sn_(3)O_(4)photocatalytic nanomaterials in various fields,such as photocatalytic degradation,photocatalytic hydro-gen production,photocatalytic reduction of carbon dioxide,solar cells,photocatalytic sterilization,and optoelectronic sensors.The discus-sion focuses on the potential of Sn_(3)O_(4)-based nanomaterials in these applications,highlighting their unique attributes and functionalities.Finally,the review provides an outlook on the future development directions in the field and offers guidance for the exploration and de-velopment of novel and efficient Sn_(3)O_(4)-based nanomaterials.Through the identification of emerging research areas and potential avenues for improvement,this review aims to stimulate further advancements in Sn_(3)O_(4)-based photocatalysis and facilitate the translation of this promising technology into practical applications.

Surviving winter on the Qinghai-Xizang Plateau:Extensive reversible protein phosphorylation plays a dominant role in regulating hypometabolism in hibernating Nanorana parkeri

Changes in protein abundance and reversible protein phosphorylation(RPP)play important roles in regulating hypometabolism but have never been documented in overwintering frogs at high altitudes.To test the hypothesis that protein abundance and phosphorylation change in response to winter hibernation,we conducted a comprehensive and quantitative proteomic and phosphoproteomic analysis of the liver of the Xizang plateau frog,Nanorana parkeri,living on the Qinghai-Xizang Plateau.In total,5170 proteins and 5695 phosphorylation sites in 1938 proteins were quantified.Based on proteomic analysis,674 differentially expressed proteins(438 up-regulated,236 down-regulated)were screened in hibernating N.parkeri versus summer individuals.Functional enrichment analysis revealed that higher expressed proteins in winter were significantly enriched in immune-related signaling pathways,whereas lower expressed proteins were mainly involved in metabolic processes.A total of 4251 modified sites(4147 up-regulated,104 down-regulated)belonging to 1638 phosphoproteins(1555 up-regulated,83 down-regulated)were significantly changed in the liver.During hibernation,RPP regulated a diverse array of proteins involved in multiple functions,including metabolic enzymatic activity,ion transport,protein turnover,signal transduction,and alternative splicing.These changes contribute to enhancing protection,suppressing energy-consuming processes,and inducing metabolic depression.Moreover,the activities of phosphofructokinase,glutamate dehydrogenase,and ATPase were all significantly lower in winter compared to summer.In conclusion,our results support the hypothesis and demonstrate the importance of RPP as a regulatory mechanism when animals transition into a hypometabolic state.

Vaccinia-related kinase 2 variants differentially affect breast cancer growth by regulating kinase activity

Genetic information is transcribed from genomic DNA to mRNA,which is then translated into threedimensional proteins.mRNAs can undergo various post-transcriptional modifications,including RNA editing that alters mRNA sequences,ultimately affecting protein function.In this study,RNA editing was identified at the 499th base(c.499)of human vaccinia-related kinase 2(VRK2).This RNA editing changes the amino acid in the catalytic domain of VRK2 from isoleucine(with adenine base)to valine(with guanine base).Isoleucine-containing VRK2 has higher kinase activity than the valine-containing VRK2,which leads to an increase in tumor cell proliferation.Earlier we reported that VRK2 directly interacts with dystrobrevin-binding protein(dysbindin)and results in reducing its stability.Herein,we demonstrate that isoleucine-containing VRK2 decreases the level of dysbindin than valinecontaining VRK2.Dysbindin interacts with cyclin D and thereby regulates its expression and function.The reduction in the level of dysbindin by isoleucine-containing VRK2 further enhances the cyclin D expression,resulting in increased tumor growth and reduction in survival rates.It has also been observed that in patient samples,VRK2 level was elevated in breast cancer tissue compared to normal breast tissue.Additionally,the isoleucine form of VRK2 exhibited a greater increase in breast cancer tissue.Therefore,it is concluded that VRK2,especially dependent on the 167th variant amino acid,can be one of the indexes of tumor progression and proliferation.

Betalains protect various body organs through antioxidant and anti-inflammatory pathways

Betalains are natural coloring pigments with betalamic acid as the core structure of all subclasses.Besides their coloring properties,betalains exhibit various biological activities,including antioxidant and anti-inflammatory properties,which are highly imperative.Further in-vivo studies reported that betalains protect various body organs,leading to health enhancement.Body organs,including the heart,liver,kidney,lung,etc.,are important for a healthy life.However,these organs can be affected or damaged by various stress factors,toxicants,and harmful substances.Recent studies have claimed that betalains could protect all vital organs of the body through antioxidant and anti-inflammatory mechanisms.This review article described the in-vivo antioxidant and anti-inflammatory activities of betalains in various cell-line or animal models.A comprehensive discussion has been provided on the mechanism of action of betalains in protecting various body organs,including cardio-protective effect,hepato-protective ability,renal protection capacity,repro-protective ability,neuro-protective effect,lung protection,and gut protection ability.Finally,future research directions and conclusions have been outlined.

When Fleeing Matters:Differences in Escape Behaviours of Three Northeast Asian Anurans

Prey species may have their own optimal escape strategy to balance predation risks and the energetic cost of fleeing.Some species have an advantage when maintaining a short fleeing distance,while others may favour an earlier escape based on microhabitat,size,or body condition.Here,we examined the escape behaviour of the three syntopic Northeast Asian anuran species:Mongolian toads(Strauchbufo raddei),Amur brown frogs(Rana amurensis),and Japanese treefrogs(Dryophytes japonicus)in Mongolia,Russia,China and DPR Korea.We examined flight initiation distance(FID;the distance from a potential predator to the point when the individual starts to flee)and distance fled(DF;distance between flight initiation and flight termination points)of each species and the effects of microhabitat,sex,and body size.Strauchbufo raddei and R.amurensis had a longer FID than D.japonicus,and S.raddei also had a longer DF than D.japonicus.These trends remained similar when dividing FID and DF by a size proxy(snout-vent length)for all individuals.This suggests that the treefrog D.japonicus used a strategy to stay immobile even when they were detected,and the toad S.raddei reacted quicker and more sensitively to predators despite the presence of toxin.Female S.raddei had a significantly longer FID than males suggesting that females are more sensitive to predation risk in this species,but body size was not significant for any of the three species.Our results indicate that the three sympatric species have different escaping strategies,likely related to differences in physiology and crypticity.

Recent updates on nano-phyto-formulations based therapeutic intervention for cancer treatment

Cancer is a leading cause of death globally,with limited treatment options and several limitations.Chemotherapeutic agents often result in toxicity which long-term conventional treatment.Phytochemicals are natural constituents that are more effective in treating various diseases with less toxicity than the chemotherapeutic agents providing alternative therapeutic approaches to minimize the resistance.These phytoconstituents act in several ways and deliver optimum effectiveness against cancer.Nevertheless,the effectiveness of phyto-formulations in the management of cancers may be constrained due to challenges related to inadequate solubility,bioavailability,and stability.Nanotechnology presents a promising avenue for transforming current cancer treatment methods through the incorporation of phytochemicals into nanosystems,which possess a range of advantageous characteristics such as biocompatibility,targeted and sustained release capabilities,and enhanced protective effects.This holds significant potential for future advancements in cancer management.Herein,this review aims to provide intensive literature on diverse nanocarriers,highlighting their applications as cargos for phytocompounds in cancer.Moreover,it offers an overview of the current advancements in the respective field,emphasizing the characteristics that contribute to favourable outcomes in both in vitro and in vivo settings.Lastly,clinical development and regulatory concerns are also discussed to check on the transformation of the concept as a promising strategy for combination therapy of phytochemicals and chemotherapeutics that could lead to cancer management in the future.

Genetic analyses of ancient tea trees provide insights into the breeding history and dissemination of Chinese Assam tea(Camellia sinensis var.assamica)

Chinese Assam tea(Camellia sinensis var.assamica)is an important tea crop with a long history of cultivation in Yunnan,China.Despite its potential value as a genetic resource,its genetic diversity and domestication/breeding history remain unclear.To address this issue,we genotyped 469 ancient tea plant trees representing 26 C.sinensis var.assamica populations,plus two of its wild relatives(six and three populations of C.taliensis and C.crassicolumna,respectively)using 16 nuclear microsatellite loci.Results showed that Chinese Assam tea has a relatively high,but comparatively lower gene diversity(H_(S)=0.638)than the wild relative C.crassicolumna(H_S=0.658).Clustering in STRUCTURE indicated that Chinese Assam tea and its two wild relatives formed distinct genetic groups,with considerable interspecific introgression.The Chinese Assam tea accessions clustered into three gene pools,corresponding well with their geographic distribution.However,New Hybrids analysis indicated that 68.48%of ancient Chinese Assam tea plants from Xishuangbanna were genetic intermediates between the Puer and Lincang gene pools.In addition,10%of the ancient Chinese Assam tea individuals were found to be hybrids between Chinese Assam tea and C.taliensis.Our results suggest that Chinese Assam tea was domesticated separately in three gene pools(Puer,Lincang and Xishuangbanna)in the Mekong River valley and that the hybrids were subsequently selected during the domestication process.Although the domestication history of Chinese Assam tea in southwestern Yunnan remains complex,our results will help to identify valuable genetic resources that may be useful in future tea breeding programs.

Emergence of taurine as a therapeutic agent for neurological disorders

Taurine is a sulfur-containing,semi-essential amino acid that occurs naturally in the body.It alternates between inflammation and oxidative stress-mediated injury in various disease models.As part of its limiting functions,taurine also modulates endoplasmic reticulum stress,Ca^(2+)homeostasis,and neuronal activity at the molecular level.Taurine effectively protects against a number of neurological disorders,including stro ke,epilepsy,cerebral ischemia,memory dysfunction,and spinal cord injury.Although various therapies are available,effective management of these disorders remains a global challenge.Approximately 30 million people are affected worldwide.The design of taurine fo rmation co uld lead to potential drugs/supplements for the health maintenance and treatment of central nervous system disorders.The general neuroprotective effects of taurine and the various possible underlying mechanisms are discussed in this review.This article is a good resource for understanding the general effects of taurine on various diseases.Given the strong evidence for the neuropharmacological efficacy of taurine in various experimental paradigms,it is concluded that this molecule should be considered and further investigated as a potential candidate for neurotherapeutics,with emphasis on mechanism and clinical studies to determine efficacy.

Biomimetic natural biomaterials for tissue engineering and regenerative medicine:new biosynthesis methods,recent advances,and emerging applications

Biomimetic materials have emerged as attractive and competitive alternatives for tissue engineering(TE)and regenerative medicine.In contrast to conventional biomaterials or synthetic materials,biomimetic scaffolds based on natural biomaterial can offer cells a broad spectrum of biochemical and biophysical cues that mimic the in vivo extracellular matrix(ECM).Additionally,such materials have mechanical adaptability,micro-structure interconnectivity,and inherent bioactivity,making them ideal for the design of living implants for specific applications in TE and regenerative medicine.This paper provides an overview for recent progress of biomimetic natural biomaterials(BNBMs),including advances in their preparation,functionality,potential applications and future challenges.We highlight recent advances in the fabrication of BNBMs and outline general strategies for functionalizing and tailoring the BNBMs with various biological and physicochemical characteristics of native ECM.Moreover,we offer an overview of recent key advances in the functionalization and applications of versatile BNBMs for TE applications.Finally,we conclude by offering our perspective on open challenges and future developments in this rapidly-evolving field.

Cloning and characterization of proliferating cell nuclear antigen gene of Alexandrium catenella (Dinoflagellate) with respect to cell growth

Harmful algal blooms （HABs） have been affecting negatively the shellfish and aquaculture industries around the world. Though a lot of efforts have been made to disclose the changes of environmental factors involved and their effects on the HABs events, the molecular mechanism of this process remains unclear. To address this problem, proliferating cell nuclear antigen gene （pcna） was isolated and characterized from Alexandrium catenella. It showed high homology to those of other dinoflagellates （89% and 91% homology to Pfiesteria piscicid and Pyrocystis lunula, respectively）, and also 42%–43% homology to those of plant and animals. The expression level of pcna revealed by quantitative real time PCR was the lowest at the late lagging cell growth phase, increased to the highest at the late exponential phase, and then decreased at the stationary phase. Though the cell growth rate was also changing, no positive correlation between pcna expression level and cell growth rate was displayed throughout the whole cell growth stages （r 2 =0.024 6）. However, the pcna expression level had the similar trend with the change of cell growth rate throughout the whole growing process, e.g., from increasing at the earlier cell growth stage to decreasing at the following stages, though slightly lagging to the latter.

Early life stress-induced neuroinflammation and neurological disorders: a novel perspective for research

Childhood maltreatment(CM)has been consistently linked with numerous detrimental outcomes concerning physical and psychological health.However,few studies have explored vulnerability to neurological disorders after CM.Early life adversity,in the form of poverty,stress and abuse,has been associated with decline in cognitive function and dementia later in life(Short and Baram,2019).Robust preclinical data suggest that early life stress(ELS)may increase the risk and worsen the course of neurological disorders such as Alzheimer’s(AD)and Parkinson’s(PD)diseases,and traumatic brain injury(TBI)(Lesuis et al.,2018;Short and Baram,2019;He et al.,2020;Catale et al.,2021;Sanchez et al.,2021).

Genetic and biochemical aspects of quorum sensing in the bacterial lifestyle and pathogenesis

Quorum sensing is the biochemical communication system within bacterial cells which may instigate their virulence factors,and hence,is imperative for pathogenesis.Such a system optimizes metabolic and behavioral activities played by the densely populated bacterial community as well as the production of the concomitant response against diffusible or secreted signals.Thus,the multi-layered signal transduction networks of quorum sensing help bacteria acclimatize to the disadvantages by increasing their confrontation ability aided by biofilm formation.Previous studies unraveled the impact of quorum sensing in the microbial interactions both within a single species and between several species.The development of the synthetic ecological models has added advantages in the studies of microbial sociability in natural habitats as well as aided in drug designing.Current review highlighted the up-to-date knowledge on the basic mechanisms of quorum sensing and its influence to accelerate the bacterial resistance against different environmental stimuli or synthetic drugs along with the factors affecting the quorum sensing system,and the harmful role of quorum sensing in food spoilage.The information gathered in this review would be beneficial to understand the metabolic cross talk as well as the virulence traits of the pathogenic microorganisms in course of their pathogenesis augmented by quorum sensing.

Can glial cells save neurons in epilepsy?

Epilepsy is a neurological disorder caused by the pathological hyper-synchronization of neuronal discharges.The fundamental research of epilepsy mechanisms and the targets of drug design options for its treatment have focused on neurons.However,approximately 30%of patients suffering from epilepsy show resistance to standard anti-epileptic chemotherapeutic agents while the symptoms of the remaining 70%of patients can be alleviated but not completely removed by the current medications.Thus,new strategies for the treatment of epilepsy are in urgent demand.Over the past decades,with the increase in knowledge on the role of glia in the genesis and development of epilepsy,glial cells are receiving renewed attention.In a normal brain,glial cells maintain neuronal health and in partnership with neurons regulate virtually every aspect of brain function.In epilepsy,however,the supportive roles of glial cells are compromised,and their interaction with neurons is altered,which disrupts brain function.In this review,we will focus on the role of glia-related processes in epileptogenesis and their contribution to abnormal neuronal activity,with the major focus on the dysfunction of astroglial potassium channels,water channels,gap junctions,glutamate transporters,purinergic signaling,synaptogenesis,on the roles of microglial inflammatory cytokines,microglia-astrocyte interactions in epilepsy,and on the oligodendroglial potassium channels and myelin abnormalities in the epileptic brain.These recent findings suggest that glia should be considered as the promising next-generation targets for designing anti-epileptic drugs that may improve epilepsy and drug-resistant epilepsy.