Cell metabolism pathways involved in the pathophysiological changes of diabetic peripheral neuropathy

Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diabetic peripheral neuropathy expose the urgent need for cell metabolism research.Given the lack of comprehensive understanding of energy metabolism changes and related signaling pathways in diabetic peripheral neuropathy,it is essential to explore energy changes and metabolic changes in diabetic peripheral neuropathy to develop suitable treatment methods.This review summarizes the pathophysiological mechanism of diabetic peripheral neuropathy from the perspective of cellular metabolism and the specific interventions for different metabolic pathways to develop effective treatment methods.Various metabolic mechanisms(e.g.,polyol,hexosamine,protein kinase C pathway)are associated with diabetic peripheral neuropathy,and researchers are looking for more effective treatments through these pathways.

Mitophagy in intracerebral hemorrhage:a new target for therapeutic intervention

Intracerebral hemorrhage is a life-threatening condition with a high fatality rate and severe sequelae.However,there is currently no treatment available for intracerebral hemorrhage,unlike for other stroke subtypes.Recent studies have indicated that mitochondrial dysfunction and mitophagy likely relate to the pathophysiology of intracerebral hemorrhage.Mitophagy,or selective autophagy of mitochondria,is an essential pathway to preserve mitochondrial homeostasis by clearing up damaged mitochondria.Mitophagy markedly contributes to the reduction of secondary brain injury caused by mitochondrial dysfunction after intracerebral hemorrhage.This review provides an overview of the mitochondrial dysfunction that occurs after intracerebral hemorrhage and the underlying mechanisms regarding how mitophagy regulates it,and discusses the new direction of therapeutic strategies targeting mitophagy for intracerebral hemorrhage,aiming to determine the close connection between mitophagy and intracerebral hemorrhage and identify new therapies to modulate mitophagy after intracerebral hemorrhage.In conclusion,although only a small number of drugs modulating mitophagy in intracerebral hemorrhage have been found thus far,most of which are in the preclinical stage and require further investigation,mitophagy is still a very valid and promising therapeutic target for intracerebral hemorrhage in the long run.

A novel mechanism of PHB2-mediated mitophagy participating in the development of Parkinson's disease

Endoplasmic reticulum stress and mitochondrial dysfunction play important roles in Parkinson s disease,but the regulato ry mechanism remains elusive.Prohibitin-2(PHB2)is a newly discove red autophagy receptor in the mitochondrial inner membrane,and its role in Parkinson’s disease remains unclear.Protein kinase R(PKR)-like endoplasmic reticulum kinase(PERK)is a factor that regulates cell fate during endoplasmic reticulum stress.Parkin is regulated by PERK and is a target of the unfolded protein response.It is unclear whether PERK regulates PHB2-mediated mitophagy thro ugh Parkin.In this study,we established a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced mouse model of Parkinson’s disease.We used adeno-associated virus to knockdown PHB2 expression.Our res ults showed that loss of dopaminergic neurons and motor deficits were aggravated in the MPTP-induced mouse model of Parkinson’s disease.Ove rexpression of PHB2 inhibited these abnormalities.We also established a 1-methyl-4-phenylpyridine(MPP+)-induced SH-SY5Y cell model of Parkinson’s disease.We found that ove rexpression of Parkin increased co-localization of PHB2 and microtubule-associated protein 1 light chain 3,and promoted mitophagy.In addition,MPP+regulated Parkin involvement in PHB2-mediated mitophagy through phosphorylation of PERK.These findings suggest that PHB2 participates in the development of Parkinson’s disease by intera cting with endoplasmic reticulum stress and Parkin.

Resilience and response:Unveiling the impacts of extreme droughts on forests through integrated dendrochronological and remote sensing analyses

Extreme droughts are anticipated to have detrimental impacts on forest ecosystems,especially in water-limited regions,due to the influence of climate change.However,considerable uncertainty remains regarding the patterns in species-specific responses to extreme droughts.Here,we conducted a study integrating dendrochronology and remote sensing methods to investigate the mosaic-distributed maple-oak(native)natural forests and poplar plantations(introduced)in the Horqin Sandy Land,Northeast China.We assessed the impacts of extreme droughts on tree performances by measuring interannual variations in radial growth and vegetation index.The results showed that precipitation and self-calibrated palmer drought severity index(scPDSI)are the major factors influencing tree-ring width index(RWI)and normalized difference vegetation index(NDVI).The severe droughts between 2000 and 2004 resulted in reduced RWI in the three studied tree species as well as led to NDVI reductions in both the maple-oak natural forests and the poplar plantations.The RWI reached the nadir during the2000-2004 severe droughts and remained at low levels two years after the severe drought,creating a legacy effect.In contrast to the lack of significant correlation between RWI and scPDSI,NDVI exhibited a significant positive correlation with scPDSI indicating the greater sensitivity of canopy performance to droughts than radial growth.Furthermore,interspecific differences in RWI and NDVI responses were observed,with the fast-growing poplar species experiencing a more significant RWI decrease and more negative NDVI anomaly during severe droughts than native species,highlighting the species-specific trade-offs between drought resilience and growth rate.This study emphasizes the importance of combining tree-level radial growth with landscape-scale canopy remote sensing to understand forest resilience and response.Our study improves our understanding of forest responses to extreme drought and highlights species differences in climate responses,offering crucial insights for optimizing species selection in sustainable afforestation and forest management in water-limited regions under the influence of climate change.

Impact of microplastics and nanoplastics on liver health:Current understanding and future research directions

With continuous population and economic growth in the 21st century,plastic pollution is a major global issue.However,the health concern of microplastics/nanoplastics(MPs/NPs)decomposed from plastic wastes has drawn public attention only in the recent decade.This article summarizes recent works dedicated to understanding the impact of MPs/NPs on the liver-the largest digestive organ,which is one of the primary routes that MPs/NPs enter human bodies.The interrelated mechanisms including oxidative stress,hepatocyte energy re-distribution,cell death and autophagy,as well as immune responses and inflammation,were also featured.In addition,the disturbance of microbiome and gut-liver axis,and the association with clinical diseases such as metabolic dysfunction-associated fatty liver disease,steatohepatitis,liver fibrosis,and cirrhosis were briefly discussed.Finally,we discussed potential directions in regard to this trending topic,highlighted current challenges in research,and proposed possible solutions.

Polypore funga and species diversity in tropical forest ecosystems of Africa,America and Asia,and a comparison with temperate and boreal regions of the Northern Hemisphere

Polypores play a cru cial role in energy recycling and forest regeneration in forest ecosystems.The majority of them are wood degraders;some are forest pathogens and others are ectomycorrhizal symbionts.The basidiocarps provide food and shelter for many organisms,mostly invertebrates,but also some vertebrates,as well as food and medicine for humans.Despite extensive research on the species diversity and phylogenetic relationships of polypores in recent years,there remains a lack of comprehensive understanding of their distribution patterns and species composition at the large scale.Checklists of polypores from the tropical zone,including tropical Africa,tropical America,and tropical Asia,were analyzed for species diversity,distribution patterns,major taxa,and nutritional modes.A total of 1,902 polypore species was found in the three regions,representing 8 orders,46families,and 250 genera of Agaricomycetes.The orders Polyporales(especially the family Polyporaceae)and Hymenochaetales(especially the family Hymenochaetaceae)had the most prolific taxa,with their species accounting for 93.4%of the total polypores listed.Each of 1,565(or 82.3%)of the total 1,902 species were found in only one of the three regions studied,and we treat them temporarily as"regional endemic species".Only 141species were shared among all three regions,accounting for a mere 7.4%.Tropical Africa and tropical America had the greatest number of shared species and the highest S?rensen similarity index(SC)value.Tropical forests had a higher species richness compared with temperate to boreal forests of the Northern Hemisphere,and in addition,also a higher proportion of white rot polypores compared to brown rot and ectomycorrhizal species.This study outlines the distribution patterns and species diversity of polypores in the world,shedding light on their ecological significance in diverse ecosystems.

Life forms affect beta-diversity patterns of larch forests in China

Beta-diversity reflects the spatial changes in community species composition which helps to understand how communities are assembled and biodiversity is formed and maintained. Larch(Larix) forests, which are coniferous forests widely distributed in the mountainous and plateau areas in North and Southwest China, are critical for maintaining the environmental conditions and species diversity. Few studies of larch forests have examined the beta-diversity and its constituent components(species turnover and nestedness-resultant components). Here, we used 483 larch forest plots to determine the total betadiversity and its components in different life forms(i.e., tree, shrub, and herb) of larch forests in China and to evaluate the main drivers that underlie this beta-diversity. We found that total betadiversity of larch forests was mainly dependent on the species turnover component. In all life forms,total beta-diversity and the species turnover component increased with increasing geographic, elevational, current climatic, and paleoclimatic distances. In contrast, the nestedness-resultant component decreased across these same distances. Geographic and environmental factors explained 20%-25% of total beta-diversity, 18%-27% of species turnover component, and 4%-16% of nestedness-resultant component. Larch forest types significantly affected total beta-diversity and species turnover component. Taken together, our results indicate that life forms affect beta-diversity patterns of larch forests in China, and that beta-diversity is driven by both niche differentiation and dispersal limitation. Our findings help to greatly understand the mechanisms of community assemblies of larch forests in China.

Polyoxidovanadates a new therapeutic alternative for neurodegenerative and aging diseases

Aging is a natural phenomenon characterized by a progressive decline in physiological integrity,leading to a deterioration of cognitive function and increasing the risk of suffering from chronic-degenerative diseases,including cardiovascular diseases,osteoporosis,cancer,diabetes,and neurodegeneration.Aging is considered the major risk factor for Parkinson’s and Alzheimer’s disease develops.Likewise,diabetes and insulin resistance constitute additional risk factors for developing neurodegenerative disorders.Currently,no treatment can effectively reverse these neurodegenerative pathologies.However,some antidiabetic drugs have opened the possibility of being used against neurodegenerative processes.In the previous framework,Vanadium species have demonstrated a notable antidiabetic effect.Our research group evaluated polyoxidovanadates such as decavanadate and metforminium-decavanadate with preventive and corrective activity on neurodegeneration in brain-specific areas from rats with metabolic syndrome.The results suggest that these polyoxidovanadates induce neuronal and cognitive restoration mechanisms.This review aims to describe the therapeutic potential of polyoxidovanadates as insulin-enhancer agents in the brain,constituting a therapeutic alternative for aging and neurodegenerative diseases.

Making wheat salt tolerant:What is missing?

The growing global population presents a significant challenge to ensuring food security,further compounded by the increasing threat of salinity to agricultural productivity.Wheat,a major staple food providing 20%of the total caloric intake for humans,is susceptible to salinity stress.Developing new salttolerant wheat cultivars using wheat breeding techniques and genetic modifications is crucial to addressing this issue while ensuring the sustainability and efficiency of wheat production systems within the prevailing climate trend.This review overviews the current landscape in this field and explores key mechanisms and associated genetic traits that warrant attention within breeding programs.We contend that traditional approaches to breeding wheat for Na^(+)exclusion have limited applicability across varying soil salinity levels,rendering them inefficient.Moreover,we question current phenotyping approaches,advocating for a shift from whole-plant assessments to cell-based phenotyping platforms.Finally,we propose a broader use of wild wheat relatives and various breeding strategies to tap into their germplasm pool for inclusion in wheat breeding programs.

Genome-wide identification of the pectate lyase(PEL)gene family members in Malvaceae,and their contribution to cotton fiber quality

Pectin is a major constituent of the plant cell wall.Pectate lyase(PEL,EC 4.2.2.2)uses anti-β-elimination chemistry to cleave theα-1,4 glycosidic linkage in the homogalacturonan region of pectin.However,limited information is available on the comprehensive and evolutionary analysis of PELs in the Malvaceae.In this study,we identified 597PEL genes from 10 Malvaceae species.Phylogenetic and motif analyses revealed that these PELs are classified into six subfamilies:Clades I,II,III,IV,Va,and Vb.The two largest subfamilies,Clades I and II,contained 237 and222 PEL members,respectively.The members of Clades Va and Vb only contained four or five motifs,far fewer than the other subfamilies.Gene duplication analysis showed that segmental duplication played a crucial role in the expansion of the PEL gene family in Gossypium species.The PELs from Clades I,IV,Va,and Vb were expressed during the fiber elongation stage,but nearly all PEL genes from Clades II and III showed no expression in any of the investigated fiber developmental stages.We further performed single-gene haplotype association analysis in 2,001G.hirsutum accessions and 229 G.barbadense accessions.Interestingly,14 PELs were significantly associated with fiber length and strength traits in G.barbadense with superior fiber quality,while only eight GhPEL genes were found to be significantly associated with fiber quality traits in G.hirsutum.Our findings provide important information for further evolutionary and functional research on the PEL gene family members and their potential use for fiber quality improvement in cotton.

Indian monsoon drove the dispersal of the thoracica group of Scytodes spitting spiders

We examined the global biogeography of the Scytodes thoracica group of spitting spiders based on 23 years of sampling at the species level(61 species in the thoracica group and 84 species of Scytodes)using DNA data from six loci.Our results indicated that the thoracica group initially dispersed from Southeast Asia to East Africa between 46.5 and 33.0 million years ago,and dispersal events intensified between Southeast/South Asia and East/South Africa from the early to late Miocene.The timing of these events indicates that Asian-African faunal exchange of the thoracica group was driven by the Indian monsoon,and the pattern of dispersal suggests that colonialization took root when the Indian monsoon shifted from a North-South direction to an East-West direction from the middle Eocene.

How to fill the biodiversity data gap:Is it better to invest in fieldwork or curation?

Data gaps and biases are two important issues that affect the quality of biodiversity information and downstream results.Understanding how best to fill existing gaps and account for biases is necessary to improve our current information most effectively.Two current main approaches for obtaining and improving data include(1)curation of biological collections,and(2)fieldwork.However,the comparative effectiveness of these approaches in improving biodiversity data remains little explored.We used the Flora de Bogota project to study the magnitude of change in species richness,spatial coverage,and sample coverage of plant records based on curation versus fieldwork.The process of curation resulted in a decrease in species richness(synonym and error removal),but it significantly increased the number of records per species.Fieldwork contributed to a slight increase in species richness,via accumulation of new records.Additionally,curation led to increases in spatial coverage,species observed by locality,the number of plant records by species,and localities by species compared to fieldwork.Overall,curationwas more efficient in producing new information compared to fieldwork,mainly because of the large number of records available in herbaria.We recommend intensive curatorial work as the first step in increasing biodiversity data quality and quantity,to identify bias and gaps at the regional scale that can then be targeted with fieldwork.The stepwise strategy would enable fieldwork to be planned more costeffectively given the limited resources for biodiversity exploration and characterization.

Modifications in aroma characteristics of'Merlot'dry red wines aged in American,French and Slovakian oak barrels with different toasting degrees

Aging in oak barrels is widely used in enology which could bring flavor changes and aromatic complexity to wines.In the present study,the aroma compounds were analyzed from the‘Merlot’dry red wines,which were fermented in two types of fermenters(stainless steel tank and rotated oak barrel)and aged in six types of oak barrels(three geographic origins×two toasting degrees)for different time(0,3,6 and 9 months,respectively).Results showed that 30 volatiles were associated with barrels and increased during oak aging.The fermenters could influence the intensities of the toast,leathery,smoky,fruity,floral and caramel aromas.The concentration of whisky lactone,eugenol,cis-isoeugenol,and the intensities of the toast and spicy aromas were highest in the wines aged in American oak and were lowest in the wines aged in French oak barrels.The concentrations of guaiacol,syringol,trans-isoeugenol,furfural alcohol,vanilla,cis-whisky lactone enabled the medium toasting barrels to be distinguished from the light toasting ones.The compounds originating from the barrels could be used to distinguish the types of different barrels,but the other general grape-derived and fermentation-derived volatiles could not.The fermenters,oak species and toasting degrees of the barrels all had significant effects on the aroma profiles of the aged‘Merlot’dry red wines,but the influence of the geographic origin was not obvious.

Historical biogeography and evolutionary diversification of Lilium(Liliaceae): New insights from plastome phylogenomics

Here, we infer the historical biogeography and evolutionary diversification of the genus Lilium. For this purpose, we used the complete plastomes of 64 currently accepted species in the genus Lilium(14plastomes were newly sequenced) to recover the phylogenetic backbone of the genus and a timecalibrated phylogenetic framework to estimate biogeographical history scenarios and evolutionary diversification rates of Lilium. Our results suggest that ancient climatic changes and geological tectonic activities jointly shaped the distribution range and drove evolutionary radiation of Lilium, including the Middle Miocene Climate Optimum(MMCO), the late Miocene global cooling, as well as the successive uplift of the Qinghai-Tibet Plateau(QTP) and the strengthening of the monsoon climate in East Asia during the late Miocene and the Pliocene. This case study suggests that the unique geological and climatic events in the Neogene of East Asia, in particular the uplift of QTP and the enhancement of monsoonal climate, may have played an essential role in formation of uneven distribution of plant diversity in the Northern Hemisphere.

Translocation of telomerase reverse transcriptase coincided with ATP release in postnatal cochlear supporting cells

The spontaneous bursts of electrical activity in the developing auditory system are derived from the periodic release of adenosine triphosphate(ATP)by supporting cells in the Kölliker’s organ.However,the mechanisms responsible for initiating spontaneous ATP release have not been determined.Our previous study revealed that telomerase reverse transcriptase(TERT)is expressed in the basilar membrane during the first postnatal week.Its role in cochlear development remains unclear.In this study,we investigated the expression and role of TERT in postnatal cochlea supporting cells.Our results revealed that in postnatal cochlear Kölliker’s organ supporting cells,TERT shifts from the nucleus into the cytoplasm over time.We found that the TERT translocation tendency in postnatal cochlear supporting cells in vitro coincided with that observed in vivo.Further analysis showed that TERT in the cytoplasm was mainly located in mitochondria in the absence of oxidative stress or apoptosis,suggesting that TERT in mitochondria plays roles other than antioxidant or anti-apoptotic functions.We observed increased ATP synthesis,release and activation of purine signaling systems in supporting cells during the first 10 postnatal days.The phenomenon that TERT translocation coincided with changes in ATP synthesis,release and activation of the purine signaling system in postnatal cochlear supporting cells suggested that TERT may be involved in regulating ATP release and activation of the purine signaling system.Our study provides a new research direction for exploring the spontaneous electrical activity of the cochlea during the early postnatal period.

ROS Balance Autoregulating Core-Shell CeO_(2)@ZIF-8/Au Nanoplatform for Wound Repair

Reactive oxygen species(ROS)plays important roles in living organisms.While ROS is a double-edged sword,which can eliminate drug-resistant bacteria,but excessive levels can cause oxidative damage to cells.A core–shell nanozyme,Ce O_(2)@ZIF-8/Au,has been crafted,spontaneously activating both ROS generating and scavenging functions,achieving the multifaceted functions of eliminating bacteria,reducing inflammation,and promoting wound healing.The Au Nanoparticles(NPs)on the shell exhibit high-efficiency peroxidase-like activity,producing ROS to kill bacteria.Meanwhile,the encapsulation of Ce O_(2) core within ZIF-8 provides a seal for temporarily limiting the superoxide dismutase and catalase-like activities of Ce O_(2) nanoparticles.Subsequently,as the ZIF-8 structure decomposes in the acidic microenvironment,the Ce O_(2) core is gradually released,exerting its ROS scavenging activity to eliminate excess ROS produced by the Au NPs.These two functions automatically and continuously regulate the balance of ROS levels,ultimately achieving the function of killing bacteria,reducing inflammation,and promoting wound healing.Such innovative ROS spontaneous regulators hold immense potential for revolutionizing the field of antibacterial agents and therapies.

Community structure and species diversity dynamics of a subtropical evergreen broad-leaved forest in China:2005 to 2020

Here,we characterize the temporal and spatial dynamics of forest community structure and species diversity in a subtropical evergreen broad-leaved forest in China.We found that community structure in this forest changed over a 15-year period.Specifically,renewal and death of common species was large,with the renewal of individuals mainly concentrated within a few populations,especially those of Aidia canthioides and Cryptocarya concinna.The numbers of individual deaths for common species were concentrated in the small and mid-diameter level.The spatial distribution of community species diversity fluctuated in each monitoring period,showing a more dispersed diversity after the 15-year study period,and the coefficient of variation on quadrats increased.In 2010,the death and renewal of the community and the spatial variation of species diversity were different compared to other survey years.Extreme weather may have affected species regeneration and community stability in our subtropical monsoon evergreen broad-leaved forests.Our findings suggest that strengthening the monitoring and management of the forest community will help better understand the long-and short-term causes of dynamic fluctuations of community structure and species diversity,and reveal the factors that drive changes in community structure.

NADPH oxidase 4(NOX4)as a biomarker and therapeutic target in neurodegenerative diseases

Diseases like Alzheimer’s and Parkinson’s diseases are defined by inflammation and the damage neurons undergo due to oxidative stress. A primary reactive oxygen species contributor in the central nervous system, NADPH oxidase 4, is viewed as a potential therapeutic touchstone and indicative marker for these ailments. This in-depth review brings to light distinct features of NADPH oxidase 4, responsible for generating superoxide and hydrogen peroxide, emphasizing its pivotal role in activating glial cells, inciting inflammation, and disturbing neuronal functions. Significantly, malfunctioning astrocytes, forming the majority in the central nervous system, play a part in advancing neurodegenerative diseases, due to their reactive oxygen species and inflammatory factor secretion. Our study reveals that aiming at NADPH oxidase 4 within astrocytes could be a viable treatment pathway to reduce oxidative damage and halt neurodegenerative processes. Adjusting NADPH oxidase 4 activity might influence the neuroinflammatory cytokine levels, including myeloperoxidase and osteopontin, offering better prospects for conditions like Alzheimer’s disease and Parkinson’s disease. This review sheds light on the role of NADPH oxidase 4 in neural degeneration, emphasizing its drug target potential, and paving the path for novel treatment approaches to combat these severe conditions.

Tanshinone ⅡA improves Alzheimer’s disease via RNA nuclearenriched abundant transcript 1/microRNA-291a-3p/member RAS oncogene family Rab22a axis

BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has shown potential neuroprotective effects;however,the mechanisms underlying such a function remain unclear.AIM To investigate potential Tan-ⅡA neuroprotective effects in AD and to elucidate their underlying mechanisms.METHODS Hematoxylin and eosin staining was utilized to analyze structural brain tissue morphology.To assess changes in oxidative stress and neuroinflammation,we performed enzyme-linked immunosorbent assay and western blotting.Additionally,the effect of Tan-ⅡA on AD cell models was evaluated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Genetic changes related to the long non-coding RNA(lncRNA)nuclear-enriched abundant transcript 1(NEAT1)/microRNA(miRNA,miR)-291a-3p/member RAS oncogene family Rab22a axis were assessed through reverse transcription quantitative polymerase chain reaction.RESULTS In vivo,Tan-ⅡA treatment improved neuronal morphology and attenuated oxidative stress and neuroinflammation in the brain tissue of AD mice.In vitro experiments showed that Tan-ⅡA dose-dependently ameliorated the amyloid-beta 1-42-induced reduction of neural stem cell viability,apoptosis,oxidative stress,and neuroinflammation.In this process,the lncRNA NEAT1-a potential therapeutic target-is highly expressed in AD mice and downregulated via Tan-ⅡA treatment.Mechanistically,NEAT1 promotes the transcription and translation of Rab22a via miR-291a-3p,which activates nuclear factor kappa-B(NF-κB)signaling,leading to activation of the pro-apoptotic B-cell lymphoma 2-associated X protein and inhibition of the anti-apoptotic B-cell lymphoma 2 protein,which exacerbates AD.Tan-ⅡA intervention effectively blocked this process by inhibiting the NEAT1/miR-291a-3p/Rab22a axis and NF-κB signaling.CONCLUSION This study demonstrates that Tan-ⅡA exerts neuroprotective effects in AD by modulating the NEAT1/miR-291a-3p/Rab22a/NF-κB signaling pathway,serving as a foundation for the development of innovative approaches for AD therapy.

Biodiversity responses to insular fragmentation in Amazonia: Two decades of research in the Balbina Hydroelectric Reservoir

As hydropower development expands across lowland tropical forests,flooding and concomitant insular fragmentation have become important threats to biodiversity.Newly created insular landscapes serve as natural laboratories to investigate biodiversity responses to fragmentation.One of these most iconic landscapes is the Balbina Hydroelectric Reservoir in Brazilian Amazonia,occupying>400000 ha and comprising>3500 forest islands.Here,we synthesise the current knowledge on responses of a wide range of biological groups to insular fragmentation at Balbina.Sampling has largely concentrated on a set of 22 islands and three mainland sites.In total,39 studies were conducted over nearly two decades,covering 17 vertebrate,invertebrate,and plant taxa.Although species responses varied according to taxonomic group,island area was consistently included and played a pivotal role in 66.7%of all studies examining patterns of species diversity.Species persistence was further affected by species traits,mostly related to species capacity to use/traverse the aquatic matrix or tolerate habitat degradation,as noted for species of vertebrates and orchid bees.Further research is needed to improve our understanding of such effects on wider ecosystem functioning.Environmental Impact Assessments must account for changes in both the remaining habitat amount and configuration,and subsequent long-term species losses.