Brain dysfunctions and neurotoxicity induced by psychostimulants in experimental models and humans:an overview of recent findings

Preclinical and clinical studies indicate that psychostimulants,in addition to having abuse potential,may elicit brain dysfunctions and/or neurotoxic effects.Central toxicity induced by psychostimulants may pose serious health risks since the recreational use of these substances is on the rise among young people and adults.The present review provides an overview of recent research,conducted between 2018 and 2023,focusing on brain dysfunctions and neurotoxic effects elicited in experimental models and humans by amphetamine,cocaine,methamphetamine,3,4-methylenedioxymethamphetamine,methylphenidate,caffeine,and nicotine.Detailed elucidation of factors and mechanisms that underlie psychostimulant-induced brain dysfunction and neurotoxicity is crucial for understanding the acute and enduring noxious brain effects that may occur in individuals who use psychostimulants for recreational and/or therapeutic purposes.

Expanding indications for chronic hepatitis B treatment: Is it really desirable to treat everyone?

Chronic viral hepatitis causes an increased risk of progressive liver disease and hepatocellular carcinoma.On the wave of the World Health Organization’s goal to reduce new cases and deaths from hepatitis B and C by 2030,there is an increasing call to expand the indications for treatment of chronic hepatitis B.Currently,the main goal of treatment is to achieve a functional cure due to the inability of current drugs to completely eradicate the virus.There are still many discrepancies between available guidelines in terms of eligibility for treatment as well as an uncertainty about the appropriate treatment duration.This editorial addresses key questions about the topic and whether indications for treatment should be expanded.

Successful treatment of acute liver failure due to Wilson’s disease: Serendipity or fortuity?

BACKGROUND Acute liver failure(ALF)may be the first and most dramatic presentation of Wilson’s disease(WD).ALF due to WD(WD-ALF)is difficult to distinguish from other causes of liver disease and is a clear indication for liver transplantation.There is no firm recommendation on specific and supportive medical treatment for this condition.AIM To critically evaluate the diagnostic and therapeutic management of WD-ALF patients in order to improve their survival with native liver.METHODS A retrospective analysis of patients with WD-ALF was conducted in two pediatric liver units from 2018 to 2023.RESULTS During the study period,16 children(9 males)received a diagnosis of WD and 2 of them presented with ALF.The first was successfully treated with an unconventional combination of low doses of D-penicillamine and zinc plus steroids,and survived without liver transplant.The second,exclusively treated with supportive therapy,needed a hepatotransplant to overcome ALF.CONCLUSION Successful treatment of 1 WD-ALF patient with low-dose D-penicillamine and zinc plus steroids may provide new perspectives for management of this condition,which is currently only treated with liver transplantation.

What Is the Convenience of Treating a Wetland as an Agricultural Area?

The Gelsari and Lentini marshes, in east-central Sicily, are wetland under heavy anthropogenic pressure. This area is regularly subjected to water withdrawals and agriculture is practiced. Periodic bird census activities had been conducted in this area between 2016 and 2022 with collected data being supplemented with the data from a previous survey conducted between 2010 and 2016. During the censuses, numerous photographs were collected, which were later used for counts. In total, 121 surveys were carried out, with visits occurring approximately 20 times per year, covering all seasons. The data collected, both from bibliography and unpublished observations, were organised in table. 120 species and subspecies have been reported, 41 of which are in Annex I of the Birds Directive. Between 2021 and 2022, a water column measurement was taken in a central area of the Lentini marsh and compared with rainfall data in the area. It was found that water removal, occurring in both marshes in different modes, produced different effects on habitat conservation. Of the two marshes, Lentini is the one in which the existing favorable conditions in its most depressed areas, located below sea level, have allowed for the adequate conservation of the wetland. This environmental improvement having occurred with respect to the previous period has restored to the marsh its historically recognized possibility of not drying up completely during the summer period, allowing permanence of numerous birds. The obtained results suggest total elimination of agriculture and discontinuation of water withdrawals in the Lentini marsh as well as regulation of withdrawals in the Gelsari marsh.

Integration between Genomic and Computational Statistical Surveys for the Screening of SNP Genetic Variants in Inflammatory Bowel Disease (IBD) Pediatric Patients*

Inflammatory bowel diseases (IBD) are complex multifactorial disorders that include Crohn’s disease (CD) and ulcerative colitis (UC). Considering that IBD is a genetic and multifactorial disease, we screened for the distribution dynamism of IBD pathogenic genetic variants (single nucleotide polymorphisms;SNPs) and risk factors in four (4) IBD pediatric patients, by integrating both clinical exome sequencing and computational statistical approaches, aiming to categorize IBD patients in CD and UC phenotype. To this end, we first aligned genomic read sequences of these IBD patients to hg19 human genome by using bowtie 2 package. Next, we performed genetic variant calling analysis in terms of single nucleotide polymorphism (SNP) for genes covered by at least 20 read genomic sequences. Finally, we checked for biological and genomic functions of genes exhibiting statistically significant genetic variant (SNPs) by introducing Fitcon genomic parameter. Findings showed Fitcon parameter as normalizing IBD patient’s population variability, as well as inducing a relative good clustering between IBD patients in terms of CD and UC phenotypes. Genomic analysis revealed a random distribution of risk factors and as well pathogenic SNPs genetic variants in the four IBD patient’s genome, claiming to be involved in: i) Metabolic disorders, ii) Autoimmune deficiencies;iii) Crohn’s disease pathways. Integration of genomic and computational statistical analysis supported a relative genetic variability regarding IBD patient population by processing IBD pathogenic SNP genetic variants as opposite to IBD risk factor variants. Interestingly, findings clearly allowed categorizing IBD patients in CD and UC phenotypes by applying Fitcon parameter in selecting IBD pathogenic genetic variants. Considering as a whole, the study suggested the efficiency of integrating clinical exome sequencing and computational statistical tools as a right approach in discriminating IBD phenotypes as well as improving inflammatory bowel disease (IBD) molecular diagnostic process.

Dose-response effect of pre-exercise carbohydrates under muscle glycogen unavailability:Insights from McArdle disease

Background:This study aimed to determine the effect of different carbohydrate(CHO)doses on exercise capacity in patients with McArdle disease—the paradigm of“exercise intolerance”,characterized by complete muscle glycogen unavailability—and to determine whether higher exogenous glucose levels affect metabolic responses at the McArdle muscle cell(in vitro)level.Methods:Patients with McArdle disease(n=8)and healthy controls(n=9)underwent a 12-min submaximal cycling constant-load bout followed by a maximal ramp test 15 min after ingesting a non-caloric placebo.In a randomized,double-blinded,cross-over design,patients repeated the tests after consuming either 75 g or 150 g of CHO(glucose:fructose=2:1).Cardiorespiratory,biochemical,perceptual,and electromyographic(EMG)variables were assessed.Additionally,glucose uptake and lactate appearance were studied in vitro in wild-type and McArdle mouse myotubes cultured with increasing glucose concentrations(0.35,1.00,4.50,and 10.00 g/L).Results:Compared with controls,patients showed the“classical”second-wind phenomenon(after prior disproportionate tachycardia,myalgia,and excess electromyographic activity during submaximal exercise,all p<0.05)and an impaired endurance exercise capacity(-51%ventilatory threshold and55%peak power output,both p<0.001).Regardless of the CHO dose(p<0.05 for both doses compared with the placebo),CHO intake increased blood glucose and lactate levels,decreased fat oxidation rates,and attenuated the second wind in the patients.However,only the higher dose increased ventilatory threshold(+27%,p=0.010)and peak power output(+18%,p=0.007).In vitro analyses revealed no differences in lactate levels across glucose concentrations in wild-type myotubes,whereas a doseresponse effect was observed in McArdle myotubes.Conclusion:CHO intake exerts beneficial effects on exercise capacity in McArdle disease,a condition associated with total muscle glycogen unavailability.Some of these benefits are dose dependent.

α-Synuclein oligomers and fibrils:partners in crime in synucleinopathies

The misfolding and aggregation of a-synuclein is the general hallmark of a group of devastating neurodegenerative pathologies referred to as synucleinopathies,such as Parkinson’s disease,dementia with Lewy bodies,and multiple system atrophy.In such conditions,a range of different misfolded aggregates,including oligomers,protofibrils,and fibrils,are present both in neurons and glial cells.Growing expe rimental evidence supports the proposition that solu ble oligomeric assemblies,formed during the early phases of the aggregation process,are the major culprits of neuronal toxicity;at the same time,fibrillar confo rmers appear to be the most efficient at propagating among interconnected neurons,thus contributing to the spreading ofα-synuclein pathology.Moreover,α-synuclein fibrils have been recently repo rted to release soluble and highly toxic oligomeric species,responsible for an immediate dysfunction in the recipient neurons.In this review,we discuss the current knowledge about the plethora of mechanisms of cellular dysfunction caused byα-synuclein oligome rs and fibrils,both contributing to neurodegeneration in synucleinopathies.

Effect of the orientation of non-spherical metal nanoparticle with respect to light polarization on its transient optical response

Nanoparticles with non-spherical shapes are now being widely used for various photonic applications.We observe experimentally that the magnitude as well as the time dependence of the transient absorption of a colloid of silver nanoplatelets depends on the relative polarization of the pump and probe pulses.There have been a few reports about the dependence of the transient signal magnitude on polarization,but little information is available on its temporal dependence.Using a theoretical model,we show that this observed behavior arises from the fact that the energy absorption by a non-spherical nanoparticle depends on,among other factors,the nanoparticle orientation with respect to the pump and probe polarization directions.It is essential to consider this when estimating nanoparticle characteristics such as carrier thermalization time,carrier–phonon scattering time,and complex polarizability from transient absorption measurements.

Prenatal and postnatal drug exposure:focus on persistent central effects

Clinical studies indicate significant use of prescription,nonprescription and social/recreational drugs by women during pregnancy;however,limited knowledge exists about the detrimental effects that this practice may have on the developing central nervous system of the fetus.Importantly,few experimental and clinical data are available on how gestational exposure could exacerbate the effects of the same or a different drug consumed by the offspring later in life.The present review summarizes recent findings on the central toxicity elicited by several classes of drugs,administered prenatally and postnatally in experimental animals and humans,focusing on prescription and nonprescription analgesics,anti-inflammatory agents,alcohol and nicotine.

Production of palmitoleic acid by oleaginous yeast Scheffersomyces segobiensis DSM 27193 using systematic dissolved oxygen regulation strategy

Palmitoleic acid(POA)can be naturally found only in few oil seeds and has significant applications in pharmaceutical industry.Recently,the isolated oleaginous yeast Scheffersomyces segobiensis DSM 27193 was identified with high content of POA in its intracellular lipid(13.80%).In this study,process optimization focused on dissolved oxygen regulation to improve POA production was conducted.Dynamic agitation was found to do significant enhancement on POA-rich lipid production than aeration regulation.Under the best condition of 1000 r·min^(-1)of agitation and 1 vvm(airvolume/culture volume/min)of aeration,no ethanol was detected during the whole fermentation process,while a dry biomass concentration of 44.80 g·L^(-1)with 13.43 g·L^(-1)of lipid and 2.93 g·L^(-1)of POA was achieved.Transcription analysis revealed that the ethanol synthetic pathway was downregulated under the condition of high agitation,while the expression of the key enzymes responsible for lipid and POA accumulation were enhanced.

Chiral Dirac Fermion in a Collinear Antiferromagnet

In a Dirac semimetal, the massless Dirac fermion has zero chirality, leading to surface states connected adiabatically to a topologically trivial surface state as well as vanishing anomalous Hall effect. Recently, it is predicted that in the nonrelativistic limit of certain collinear antiferromagnets, there exists a type of chiral“Dirac-like” fermion, whose dispersion manifests four-fold degenerate crossing points formed by spin-degenerate linear bands, with topologically protected Fermi arcs. Such an unconventional chiral fermion, protected by a hidden SU(2) symmetry in the hierarchy of an enhanced crystallographic group, namely spin space group, is not experimentally verified yet. Here, by angle-resolved photoemission spectroscopy measurements, we reveal the surface origin of the electron pocket at the Fermi surface in collinear antiferromagnet CoNb3S6. Combining with neutron diffraction and first-principles calculations, we suggest a multidomain collinear antiferromagnetic configuration, rendering the the existence of the Fermi-arc surface states induced by chiral Dirac-like fermions.Our work provides spectral evidence of the chiral Dirac-like fermion caused by particular spin symmetry in CoNb_(3)S_(6), paving an avenue for exploring new emergent phenomena in antiferromagnets with unconventional quasiparticle excitations.

The genomic and epigenetic footprint of local adaptation to variable climates in kiwifruit

A full understanding of adaptive genetic variation at the genomic level will help address questions of how organisms adapt to diverse climates.Actinidia eriantha is a shade-tolerant species,widely distributed in the southern tropical region of China,occurring in spatially heterogeneous environments.In the present study we combined population genomic,epigenomic,and environmental association analyses to infer population genetic structure and positive selection across a climatic gradient,and to assess genomic offset to climatic change for A.eriantha.The population structure is strongly shaped by geography and influenced by restricted gene f low resulting from isolation by distance due to habitat fragmentation.In total,we identified 102 outlier loci and annotated 455 candidate genes associated with the genomic basis of climate adaptation,which were enriched in functional categories related to development processes and stress response;both temperature and precipitation are important factors driving adaptive variation.In addition to single-nucleotide polymorphisms(SNPs),a total of 27 single-methylation variants(SMVs)had significant correlation with at least one of four climatic variables and 16 SMVswere located in or adjacent to genes,several of whichwere predicted to be involved in plant response to abiotic or biotic stress.Gradient forest analysis indicated that the central/east populations were predicted to be at higher risk of future population maladaptation under climate change.Our results demonstrate that local climate factors impose strong selection pressures and lead to local adaptation.Such information adds to our understanding of adaptive mechanisms to variable climates revealed by both population genome and epigenome analysis.

Mangrove forests as a nature-based solution for coastal flood protection:Biophysical and ecological considerations

Nature-based coastal protection is increasingly recognised as a potentially sustainable and cost-effective solution to reduce coastal flood risk.It uses coastal ecosystems such as mangrove forests to create resilient designs for coastal flood protection.However,to use mangroves effectively as a nature-based measure for flood risk reduction,we must understand the biophysical processes that govern risk reduction capacity through mangrove ecosystem size and structure.In this perspective,we evaluate the current state of knowledge on local physical drivers and ecological processes that determine mangrove functioning as part of a nature-based flood defence.We show that the forest properties that comprise coastal flood protection are well-known,but models cannot yet pinpoint how spatial heterogeneity of the forest structure affects the capacity for wave or surge attenuation.Overall,there is relatively good understanding of the ecological processes that drive forest structure and size,but there is a lack of knowledge on how daily bed-level dynamics link to long-term biogeomorphic forest dynamics,and on the role of combined stressors influencing forest retreat.Integrating simulation models of forest structure under changing physical(e.g.due to sea-level change)and ecological drivers with hydrodynamic attenuation models will allow for better projections of long-term natural coastal protection.

Genome assembly of the snow lotus species Saussurea involucrata provides insights into acacetin and rutin biosynthesis and tolerance to an alpine environment

Dear Editor,Understanding the evolution and survival mechanisms of endangered wild medicinal herbs is crucial for their cultivation,utilization,and conservation.The snow lotus species Saussurea involucrata(Kar.&Kir.)Sch.Bip.(2n=32)(i.e.the well-known Tianshan snow lotus)which belongs to the eudicot family Asteraceae,is a famous traditional Chinese medicinal herb having anti-inflammatory.

贡嘎山东坡的鸟类多样性和区系

经过7年5次野外系统调查并综合有关文献,贡嘎山东坡分布有鸟类336种,其中,留鸟204种(60.7%),夏候鸟89种(26.5%),冬候鸟18种(5.4%),旅鸟25种(7.4%);东洋界物种205种(61.0%),古北界物种105种(31.3%),广布种26种(7.7%);雀形目Passeriformes鸟类245种(72.9%);繁殖鸟类293种(87.2%)。本地区有国家Ⅰ级重点保护鸟类3种,国家Ⅱ级重点保护鸟类29种;横断山-喜马拉雅地区特有鸟类53种;CITES附录Ⅰ鸟类3种,附录Ⅱ鸟类25种;世界自然保护联盟濒危物种红色名录濒危鸟类1种,易危鸟类2种。研究发现,东洋界物种的海拔分布下限平均、上限平均、中点平均和海拔跨度平均都低于古北界物种,但仅海拔分布中点平均和上限平均差异有统计学意义(P<0.05),体现了东洋界和古北界物种对高海拔环境适应能力的不同可能与其不同的生物地理演化历史有关;东洋界占优势的特有种(51/53)海拔分布下限平均、中点平均和上限平均显著高于非特有物种,体现出东洋界特有种对高山环境的适应也许与其特有化过程有关。贡嘎山东坡鸟类丰富度在中海拔1 800~2 800 m的落叶阔叶混交林和针阔叶混交林中最高,在高海拔和低海拔物种丰富度较低,物种丰富度呈中峰模式,鸟类生态群落随植物群落结构变化而呈现一定的垂直生态替代规律。

聚缩醛树脂义齿修复KennedyⅡ类牙列缺损的生物力学研究

目的利用光弹模型研究聚缩醛树脂义齿(隐形义齿)修复KennedyⅡ类牙列缺损的生物力学。方法建立下颌KennedyⅡ类牙列缺损((?)缺失)光弹模型,分别设计和制作聚缩醛树脂全隐形义齿、混合型隐形义齿和传统的金属支架可摘局部义齿。模拟双侧及单侧后牙加载,观察加载时三种义齿设计基牙和缺牙区牙槽嵴的载荷光弹图像,分别记录应力分布情况并加以分析和比较。结果三种义齿设计光弹模型应力分布分析显示,在单侧和双侧加载时,全隐形义齿基牙和缺牙区牙槽嵴承受压力最大,传统的金属支架可摘局部义齿(金属支架设计)承受压力沿基牙牙体长轴传导,基牙和剩余牙槽嵴承受压力最小且分布最均匀。结论对于KennedyⅡ类牙列缺损,全隐形义齿修复对基牙和剩余牙槽嵴损伤较大;而传统的金属支架可摘局部义齿使支持组织受力均匀、合理,应作为设计的首选。

This work was supported by the European Research Council Advanced Grant(ETAP-742985 to H.T.and J.F.)and by the Ministry of Science and Technology(grant 110-2636-B-005-001 to K.-J.L.).

Plant root-nodule symbiosis(RNS)with mutualistic nitrogen-fixing bacteria is restricted to a single clade of angiosperms,the Nitrogen-Fixing Nodulation Clade(NFNC),and is best understood in the legume family.Nodulating species share many commonalities,explained either by divergence from a common ancestor over 100 million years ago or by convergence following independent origins over that same time period.Regardless,comparative analyses of diverse nodulation syndromes can provide insights into constraints on nodulation—what must be acquired or cannot be lost for a functional symbiosis—and the latitude for Plant Communications Genomic landscape of nodulation variation in the symbiosis.However,much remains to be learned about nodulation,especially outside of legumes.Here,we employed a large-scale phylogenomic analysis across 88 species,complemented by 151 RNA-seq libraries,to elucidate the evolution of RNS.Our phylogenomic analyses further emphasize the uniqueness of the transcription factor NIN as a master regulator of nodulation and identify key muta-tions that affect its function across the NFNC.Comparative transcriptomic assessment revealed nodule-specific upregulated genes across diverse nodulating plants,while also identifying nodule-specific and nitrogen-response genes.Approximately 70%of symbiosis-related genes are highly conserved in the four representative species,whereas defense-related and host-range restriction genes tend to be lineage specific.Our study also identified over 900000 conserved non-coding elements(CNEs),over 300000 of which are unique to sampled NFNC species.NFNC-specific CNEs are enriched with the active H3K9ac mark and are correlated with accessible chromatin regions,thus representing a pool of candidate regula-tory elements for genes involved in RNS.Collectively,our results provide novel insights into the evolution of nodulation and lay a foundation for engineering of RNS traits in agriculturally important crops.

CO2浓度升高与硝化抑制剂对冬小麦田间N2O排放量的影响

以冬小麦中麦175为供试品种,利用农田开放式CO_2浓度增高(FACE)系统,研究未来大气高CO_2浓度对冬小麦田间N_2O排放的影响,以及施用硝化抑制剂(2-氯-6-三氯甲基吡啶)是否可以起到抑制冬小麦田间N_2O的排放量升高的潜能。试验结果表明:CO_2浓度升高显著提高冬小麦田间N2O的排放增幅达到67.6%,追肥灌溉后小麦田N_2O排放量较大,随着冬小麦生育进程的推进N_2O的排放量逐渐减少,硝化抑制剂对中麦175田间N_2O排放量的影响并不明显。因此,在未来高CO_2浓度环境条件下,可以通过采取相应的耕作制度和栽培技术措施等来降低冬小麦田N_2O的排放量。试验结果对冬小麦田间是否选择施用2-氯-6-三氯甲基吡啶来控制N_2O的排放起到一定的参考作用。

Non-polypoid colorectal neoplasms:Classification,therapy and follow-up

In the last years,an increasing interest has been raised on non-polypoid colorectal tumors(NPT) and in particular on large flat neoplastic lesions beyond 10 mm tending to grow laterally,called laterally spreading tumors(LST).LSTs and large sessile polyps have a greater frequency of high-grade dysplasia and local invasiveness as compared to pedunculated lesions of the same size and usually represent a technical challenge for the endoscopist in terms of either diagnosis and resection.According to the Paris classification,NPTs are distinguished in slightly elevated(0-Ⅱa,less than 2.5 mm),flat(0-Ⅱb) or slightly depressed(0-Ⅱc).NPTs are usually flat or slightly elevated and tend to spread laterally while in case of depressed lesions,cell proliferation growth progresses in depth in the colonic wall,thus leading to an increased risk of submucosal invasion(SMI) even for smaller neoplasms.NPTs may be frequently missed by inexperienced endoscopists,thus a careful training and precise assessment of all suspected mucosal areas should be performed.Chromoendoscopy or,if possible,narrow-band imaging technique should be considered for the estimation of SMI risk of NPTs,and the characterization of pit pattern and vascular pattern may be useful to predict the risk of SMI and,therefore,to guide the therapeutic decision.Lesions suitable to endoscopic resection are those confined to the mucosa(or superficial layer of submucosa in selected cases) whereas deeper invasion makes endoscopic therapy infeasible.Endoscopic mucosal resection(EMR,piecemeal for LSTs > 20 mm,en bloc for smaller neoplasms) remains the first-line therapy for NPTs,whereas endoscopic submucosal dissection in high-volume centers or surgery should be considered for large LSTs for which en bloc resection is mandatory and cannot be achieved by means of EMR.After piecemeal EMR,follow-up colonoscopy should be performed at 3 mo to assess resection completeness.In case of en bloc resection,surveillance colonoscopy should be scheduled at 3 years for adenomatous lesions ≥ 1 cm,or in presence of villous features or high-grade dysplasia patients(regardless of the size),while less intensive surveillance(colonoscopy at 5-10 years) is needed in case of single(or two) NPT < 1 cm presenting tubular features or low-grade dysplasia at histology.

Biodegradability of soil water soluble organic carbon extracted from seven different soils

Water soluble organic carbon （WSOC） is considered the most mobile and reactive soil carbon source and its characterization is an important issue for soil ecology study. A biodegradability test was set up to study WSOC extracted from 7 soils differently managed. WSOC was extracted from soil with water （soil/water ratio of 1：2, W/V） for 30 min, and then tested for biodegradability by a liquid state respirometric test. Result obtained confirmed the finding that WSOC biodegradability depended on the both land use and management practice. These results suggested the biodegradability test as suitable method to characterize WSOC, and provided useful information to soil fertility.