Contrasting Effects Research Articles

Contrasting effects of intracellular and extracellular human PCSK9 on inflammation, lipid alteration and cell death

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is one of the major regulators of low-density lipoprotein receptor (LDLR). Information on role and regulation of PCSK9 in lung is very limited. Our study focuses on understanding the role and regulation of PCSK9 in the lung. PCSK9 levels are higher in Bronchoalveolar lavage fluid (BALF) of smokers with or without chronic obstructive pulmonary diseases (COPD) compared to BALF of nonsmokers. PCSK9-stimulated cells induce proinflammatory cytokines and activation of MAPKp38. PCSK9 transcripts are highly expressed in healthy individuals compared to COPD, pulmonary fibrosis or pulmonary systemic sclerosis. Cigarette smoke extract reduce PCSK9 levels in undifferentiated pulmonary bronchial epithelial cells (PBEC) but induce in differentiated PBEC. PCSK9 inhibition affect biological pathways, induces lipid peroxidation, and higher level of apoptosis in response to staurosporine. Our results suggest that higher levels of PCSK9 in BALF acts as an inflammatory marker. Furthermore, extracellular and intracellular PCSK9 play different roles.

Contrasting luxury effect on urban plant phylogenetic and taxonomic diversity in West African cities

ABSTRACT Urbanization is a driving factor for biodiversity loss and potential climate change by reducing carbon stocks. Understanding how urban development, as mitigated by socio-economic factors alters urban biodiversity is crucial for effective urban planning that maintains or improves environmental resilience. The luxury effect hypothesis predicts that wealthier parts of a city will have higher levels of biodiversity. This effect has been tested widely but we still have limited understanding of how wealth influences urban biodiversity in tropical regions of developing countries where plant species play profound sociocultural roles beyond aesthetics. This study investigates links between household income and the diversity of cultivated plants distribution within neighborhoods of two growing cities in Benin. We conducted a survey of 936 randomly selected households to record their socioeconomic characteristics and survey the cultivated plant species found in household gardens’. This enabled us to estimate household-level diversity metrics including taxonomic diversity and phylogenetic diversity. We found no global support for the luxury effect on phylogenetic diversity but rented properties had lower plant taxonomic diversity along with less phylogenetic diversity than privately owned houses. Taxonomic diversity is higher in the less urbanized areas while phylogenetic diversity is weakened. Household’s cultural connection to plants has a negative effect on both diversity indices. Our results highlight the complex relationships between socioeconomic traits and urban plant diversity distribution in two tropical African cities, which only partly confirmed the luxury effect hypothesis. Disentangling these complex relationships can help city planners and policymakers to take informed decisions to promote sustainable cities.

Reproductive Success of Tree Swallows at Abandoned Mine Drainage Treatment Ponds

Abandoned mine drainage treatment ponds could have contrasting effects on the reproductive success of birds living in the vicinity. The ponds and associated vegetation may, like any other body of freshwater, provide beneficial habitats for the insects that the birds use to feed their young; or instead, the ponds may act as an ecological trap, attracting the birds to a habitat that is poor in quality and negatively impacting their productivity. We monitored nests of an aerial insectivore, the Tree Swallow (Tachycineta bicolor), to determine whether the distance between the ponds and the nests affected various reproductive parameters including clutch size, hatch rate, number of nestlings, nestling size and mass, number of fledglings, fledging rate, and fledge date. Data were collected over two breeding seasons (2022 and 2023) from a swallow population in southwestern Pennsylvania, USA. We found that the nests closest to the treatment ponds had significantly more nestlings and fledglings, earlier fledge dates, and a better fledging rate when compared to nests that were more distant from the ponds. However, all these parameters were well below previously published values, which suggests that the mine drainage ponds provide good nesting habitats relative to what is available in the region but that they do not represent high-quality habitats for this species overall.

Contrasting the pharmacokinetic performance and gut microbiota effects of an amorphous solid dispersion and lipid nanoemulsion for a poorly water-soluble anti-psychotic

Increasing attention is being afforded to understanding the bidirectional relationship that exists between oral drugs and the gut microbiota. Often overlooked, however, is the impact that pharmaceutical excipients exert on the gut microbiota. Subsequently, in this study, we contrasted the pharmacokinetic performance and gut microbiota interactions between two commonly employed formulations for poorly soluble compounds, namely 1) an amorphous solid dispersion (ASD) stabilised by poly(vinyl pyrrolidone) K-30, and 2) a lipid nanoemulsion (LNE) comprised of medium chain glycerides and lecithin. The poorly soluble antipsychotic, lurasidone, was formulated with ASD and LNE due to its rate-limiting dissolution, poor oral bioavailability, and significant food effect. Both the ASD and LNE were shown to facilitate lurasidone supersaturation within in vitro dissolution studies simulating the gastrointestinal environment. This translated into profound improvements in oral pharmacokinetics in rats, with the ASD and LNE exerting comparable ∼ 2.5-fold improvements in lurasidone bioavailability, compared to the pure drug. The oral formulations imparted contrasting effects on the gut microbiota, with the LNE depleting the richness and abundance of the microbial ecosystem, as evidenced through reductions in alpha diversity (Chao1 index) and operational taxonomical units (OTUs). In contrast, the ASD exerted a ‘gut neutral’ effect, whereby a mild enrichment of alpha diversity and OTUs was observed. Importantly, this suggests that ASDs are effective solubility-enhancing formulations that can be used without comprising the integrity of the gut microbiota – an integral consideration in the treatment of mental health disorders, such as schizophrenia, due to the role of the gut microbiota in regulating mood and cognition.

Comparative mathematical modeling reveals the differential effects of high-fat diet and ketogenic diet on the PI3K-Akt signaling pathway in heart

BackgroundObesity is a global health concern associated with increased risk of diseases like cardiovascular conditions including ischemic heart disease, a leading cause of mortality. The ketogenic diet (KD) has potential therapeutic applications in managing obesity and related disorders. However, the intricate effects of KD on diverse physiological conditions remain incompletely understood. The PI3K-Akt signaling pathway is critical for heart health, and its dysregulation implicates numerous cardiac diseases.MethodsWe developed comprehensive mathematical models of the PI3K-Akt signaling pathway under high-fat diet (HFD) and KD conditions to elucidate their differential impacts and quantify apoptosis. Simulations and sensitivity analysis were performed.ResultsSimulations demonstrate that KD can reduce the activation of key molecules like Erk and Trp53 to mitigate apoptosis compared to HFD. Findings align with experimental data, highlighting the potential cardiac benefits of KD. Sensitivity analysis identifies regulators like Trp53 and Bcl2l1 that critically influence apoptosis under HFD.ConclusionsMathematical modeling provides quantitative insights into the contrasting effects of HFD and KD on cardiac PI3K-Akt signaling and apoptosis. Findings have implications for precision nutrition and developing novel therapeutic strategies to address obesity-related cardiovascular diseases.Graphical abstract

Landscape and habitat characteristics jointly drive the urban distribution of a nuisance species

Identifying environmental variables that affect the distribution of pest and/or nuisance species promotes effective management strategies by improving urban planning and the targeted application of direct interventions like population control. Australian white ibis Threskiornis moluccus are considered a nuisance species throughout Australia, having increased significantly in abundance in coastal urban landscapes following declines in their native inland habitats over the past three decades. Few management interventions thus far have successfully reduced conflicts between ibis and humans, necessitating a better understanding of conditions driving ibis distribution and abundance. We surveyed 26 ibis colonies throughout the Moreton Bay region in central eastern Australia and quantified the effects of a range of spatial (e.g. connectivity with waste management facilities, urban land and wetlands) and habitat (e.g. nesting tree species, density and size) variables on ibis and nest abundance. Ibis and their nests were most abundant at sites within 10 km of waste management facilities, and < 60 m from residential or industrial estates. Ibis were also more abundant at sites with tree canopy height < 10 m and lower tree species richness. Nests were most abundant on water bound islands with tree density > 0.5 trees/m2. Urbanisation had contrasting effects, with nest numbers increasing with higher connectivity (i.e. closer proximity) to urban land, while ibis numbers decreased (relative to waste management facilities). Multifaceted approaches are required for controlling ibis populations, including restricting access to anthropogenic food resources, managing the condition of remnant habitats, and considering population control at sites with high connectivity to foraging grounds.

Contrasting effect of different crowding agents on pseudoknot RNA stability

Contrasting effect of different crowding agents on pseudoknot RNA stability

Being a big fish in a little pond: student group composition, perceived academic standing, and young people’s academic self-concept

Upper secondary school students with a strong academic self-concept are more likely to complete their studies and thus increase their well-being in the future. Previous research on the big-fish-little-pond-effect (BFLPE) has thoroughly established the negative contrast effect of average group academic achievement on students’ academic self-concept. Many of these studies have been criticised for assuming the underlying social comparison without testing it. Here, survey and registered data from 1,047 Icelandic adolescents are used to explore the role of social comparison in the BFLPE. Models of hierarchical regression showed that students’ ideas about their relative position within their group of students mediated the effect of group average achievement on academic self-concept. This strengthens the assumption of social comparison being the underlying factor of the BFLPE. No assimilation effect between the type of school and academic self-concept was found. Implications for educators, school authorities, and policymakers are discussed.

The frequency and chemical phenotype of neighboring plants determine the effects of intraspecific plant diversity.

Associational effects, whereby plants influence the biotic interactions of their neighbors, are an important component of plant-insect interactions. Plant chemistry has been hypothesized to mediate these interactions. The role of chemistry in associational effects, however, has been unclear in part because the diversity of plant chemistry makes it difficult to tease apart the importance and roles of particular classes of compounds. We examined the chemical ecology of associational effects using backcross-bred plants of the Solanum pennellii introgression lines. We used eight genotypes from the introgression line system to establish 14 unique neighborhood treatments that maximized differences in acyl sugars, proteinase inhibitor, and terpene chemical diversity. We found that the chemical traits of the neighboring plant, rather than simply the number of introgression lines within a neighborhood, influenced insect abundance on focal plants. Furthermore, within-chemical class diversity had contrasting effects on herbivore and predator abundances, and depended on the frequency of neighboring plant chemotypes. Notably, we found insect mobility-flying versus crawling-played a key role in insect response to phytochemistry. We highlight that the frequency and chemical phenotype of plant neighbors underlie associational effects and suggest this may be an important mechanism in maintaining intraspecific phytochemical variation within plant populations.

Tree species richness and mycorrhizal types drive soil nitrogen cycling by regulating soil microbial community composition and diversity in tropical forests

A growing body of evidence indicates that tree mycorrhizal association and species richness pronouncedly affect soil nitrogen (N) cycling. However, most studies have been conducted in temperate forests, and the roles of soil microbial communities have been largely overlooked. Here, based on 11 long-term dynamic monitoring sites in tropical forests, we investigated the effects of the dominance of trees associated with arbuscular mycorrhizal (AM) (by basal area) and tree species richness on soil N cycling, and explored the role of soil bacteria, archaea and fungi. Our results showed contrasting effects of AM tree dominance and tree species richness, with AM tree dominance-induced increases in soil ammonium N, nitrate N and the rate of net N nitrification, and tree species richness-caused decreases in ammonium N, nitrate N, the rate of net N mineralization and ammonification. Moreover, we found that the “plant-soil-microbe” interactions mainly triggered the changes in net N mineralization, ammonification and nitrification. It was mainly bacterial composition that directly affected soil N mineralization and ammonification, while fungal diversity only changed soil N ammonification. For soil N nitrification, the abundance of ammonia-oxidizing archaea (AOA) was the main drivers. These findings reveal the discrepancy in effects of the AM tree dominance and tree species richness on soil N cycling, highlighting microbe-mediated mechanisms in regulating soil N mineralization, ammonification and nitrification.

Abstract Tu020: Contrasting effect of Ox-PAPC and PC-KLH in atherosclerotic plaques or peripheral blood T cell, macropahges and dendritic cell activation

Background: Atherosclerosis is a chronic inflammation characterized by accumulation of immune cells, oxidized low density lipoprotein (OxLDL) and dead cells in the lesions, both of the latter have the hapten phosphorylcholine (PC) as an important antigen. PC is also exposed on microorganisms and other compounds and needs a carrier to be antigenic. Antibodies against PC (anti-PC) ameliorates deleterious effects of both OxLDL and dead cells. Oxidized-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphatidylcholine (Ox-PAPC) is a major compound in the lipid moiety of OxLDL exposing PC. Methods: We studied effect of Ox-PAPC and PC with keyhole limpet cyanid (KLH) on T cells, dendritic cells (DC) and macrophages (MQ). We examined the influence of Ox-PAPC and PC conjugated to KLH (PC-KLH) on T cells, DC, and MQ from peripheral blood or atherosclerotic plaques. We investigated phospholipid and glutathione (GSH) levels in the blood plasma of healthy controls (n=30) and patients (n=30). Results: Ox-PAPC, in contrast to PAPC and PC-KLH, independently of DC, induced proinflammatory T cell activation, which was inhibited by mito tempo, inhibitor of reactive oxygen species (ROS). Ox-PAPC triggered inflammatory activities while reducing metabolic activities in T cells. PC-KLH, on the other hand, reduced CD86 and CD11C, proinflammatory cytokines, and induced anti-inflammatory IL-10 in DC. Ox-PAPC induced ROS, GSH, and proinflammatory MQ activation, inhibited by Mito tempo or GSH inhibitor. Additionally, Ox-PAPC, in the presence of PCSK9, elevated CD86 expression and lipid peroxidation. Patients exhibited higher GSH levels comapre to control groups, associated with phospholipid levels. Conclusions: The study reveals the differential effects of Ox-PAPC on various immune cell types, showcasing T cell activation independent of DC and heightened macrophage activation in the presence of PCSK9. Ox-PAPC-induced redox imbalance regulates T cell activation, apoptosis, and MQ activation, potentially rendering plaques more vulnerable and contributing to lesion formation and thus plaque rupture. In contrast, PC-KLH had anti-inflammatory effects, inducing anti-inflammatory cytokines from T cells, DC and MQ. PC-effects thus vary from proinflammatory to anti-inflammatory depending on presentation. Inhibition of OxPAPC effects by agents such as anti-PC could thus be anti-atherogenic, while on the other hand PC presented on a protein as KLH could be anti-atherogenic and anti-inflammatory itself.

The interacting effects of talker, contrast, and listener variability in cross-language speech perception.

Building on previous observations of variability in speech research, we examine variability in speech perception study materials associated with the specific talker and contrast under examination. English-speaking listeners completed a web-based auditory AXB task involving Hindi dental-retroflex stop contrasts produced by four talkers. Main effects of talker and contrast, as well as the interaction of the two, were observed. Further, there was a great deal of individual listener variation. These findings complicate our ability to characterize the difficulty that Hindi dental-retroflex contrasts pose for English speakers, and lead to critical questions concerning the generalizability of speech perception study findings.

The impact of chemical pollution across major life transitions: a meta-analysis on oxidative stress in amphibians.

Among human actions threatening biodiversity, the release of anthropogenic chemical pollutants which have become ubiquitous in the environment, is a major concern. Chemical pollution can induce damage to macromolecules by causing the overproduction of reactive oxygen species, affecting the redox balance of animals. In species undergoing metamorphosis (i.e. the vast majority of the extant animal species), antioxidant responses to chemical pollution may differ between pre- and post-metamorphic stages. Here, we meta-analysed (N = 104 studies, k = 2283 estimates) the impact of chemical pollution on redox balance across the three major amphibian life stages (embryo, tadpole, adult). Before metamorphosis, embryos did not experience any redox change while tadpoles activate their antioxidant pathways and do not show increased oxidative damage from pollutants. Tadpoles may have evolved stronger defences against pollutants to reach post-metamorphic life stages. In contrast, post-metamorphic individuals show only weak antioxidant responses and marked oxidative damage in lipids. The type of pollutant (i.e. organic versus inorganic) has contrasting effects across amphibian life stages. Our findings show a divergent evolution of the redox balance in response to pollutants across life transitions of metamorphosing amphibians, most probably a consequence of differences in the ecological and developmental processes of each life stage.

Comparative analysis of heavy rainfall area between landfalling typhoon LUPIT (2109) and typhoon LISA (9610)

Based on the ERA5 reanalysis data and the surface observations from automatic weather stations, a comparative analysis has been conducted to investigate the differences in heavy rainfall distributions caused by two landfalling tropical cyclones (TCs): LUPIT (2109) and LISA (9610). The two TCs have similar tracks, intensity and landing points, but show different asymmetric features in their rainstorm location relative to their tracks. The results indicate that the TC rainfall differences are mainly caused by different rainstorm formation mechanisms. The wind shear contributes most to the rainstorm of LISA, while land-sea contrast and topographical effect are the main factors of LUPIT rainstorm. Under the influence of strong environmental vertical wind shear and the weak cold air invasion from the west, the circulation center of LISA tilts westward with height, which cooperates with the low-level water vapor convergence and vertical ascending movement on the western side of the TC center to jointly cause the heavy rainstorm to the west of LISA center. In contrast, LUPIT has weak environmental vertical wind shear and no obvious structure tilting with height. Topographic effect plays a crucial role in causing the heavy rainstorm on the north of TC center. The southeasterly jet is blocked by the Taimu Mountain in the northeastern Fujian Province, and the strong ascending motion caused by the terrain-induced convergence appears to the north of LUPIT center. In addition, the moisture convergence is more pronounced in the north and weaker in the south. The intrusion of weak cold air from the east to the coastal areas of central-northern Fujian, and the moisture-convergence distribution, jointly cause the heavy rainstorm to the north of LUPIT.

Canopy structural heterogeneity drives α and β species–genetic diversity correlations in a Chinese subtropical forest

Patterns and drivers of species–genetic diversity correlations (SGDCs) have been broadly examined across taxa and ecosystems and greatly deepen our understanding of how biodiversity is maintained. However, few studies have examined the role of canopy structural heterogeneity, which is a defining feature of forests, in shaping SGDCs. Here, we determine what factors contribute to α- and β-species–genetic diversity correlations (i.e., α- and β-SGDCs) in a Chinese subtropical forest. For this purpose, we used neutral molecular markers to assess genetic variation in almost all adult individuals of the dominant tree species, Lithocarpus xylocarpus, across plots in the Ailaoshan National Natural Reserve. We also quantified microhabitat variation by quantifying canopy structure heterogeneity with airborne laser scanning on 20 1-ha subtropical forest plots. We found that species α-diversity was negatively correlated with genetic α-diversity. Canopy structural heterogeneity was positively correlated with species α-diversity but negatively correlated with genetic α-diversity. These contrasting effects contributed to the formation of a negative α-SGDC. Further, we found that canopy structural heterogeneity increases species α-diversity and decreases genetic α-diversity by reducing the population size of target species. Species β-diversity, in contrast, was positively correlated with genetic β-diversity. Differences in canopy structural heterogeneity between plots had non-linear parallel effects on the two levels of β-diversity, while geographic distance had a relatively weak effect on β-SGDC. Our study indicates that canopy structural heterogeneity simultaneously affects plot-level community species diversity and population genetic diversity, and species and genetic turnover across plots, thus driving α- and β-SGDCs.

Novel method for assessing sinusoidal obstruction syndrome using four-dimensional computed tomography.

Todiagnose sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD), transabdominal ultrasonography is usually used to detect hemodynamic changes, but we tried to detect the changes using four-dimensional computed tomography (4D-CT). A 42-year-old Japanese woman was diagnosedwith late-onsetSOS/VOD with transabdominal ultrasonography and was also assessed using 4D-CT. Method We analyzed the portal vein (PV) contrast effect every 1.5seconds and plotted the values of the contrast effect. With this graph, we analyzedthreehemodynamic parameters. We found that these parameterscorrelatedwiththe patient's status and indicated stasis due to sinusoid constriction. 4D-CT may become a helpful tool to diagnose and follow up with SOS/VOD.

Does Fintech Affect Bank Profitability? Empirical Insights from Malaysia

Objectives: This study investigates the influence of Fintech on the profitability of Malaysian banks. It aims to assess both accounting measures, such as Return on Assets (ROA) and Net Interest Margin (NIM), and market performance measures, including Tobin's Q. The research utilizes bank-level metrics like the intangible asset ratio and the ATM-to-branch ratio, along with a country-level Fintech index that combines data on ATM, smartphone usage, and internet penetration. The study seeks to understand the complex dynamics between Fintech investments and bank profitability, providing insights for various stakeholders, including policymakers, banks, investors, and consumers. Methods: The research employs a panel regression analysis to explore the relationship between Fintech developments and bank profitability. The analysis covers publicly listed banks in Malaysia from 2010 to 2022. Key variables include the intangible asset ratio as a proxy for IT investment in Fintech, the ATM-to-branch ratio, and a comprehensive Fintech index at the country level. The study also considers market risk exposure, using Value at Risk (VaR) as an indicator. The approach is grounded in the resource-based view theory, suggesting that Fintech can provide competitive advantages through data analytics, mobile technology, and enhanced cybersecurity. Results: The findings reveal that Fintech investments at the bank level, indicated by the intangible asset ratio, have a positive impact on NIM. This supports the notion that technology-driven innovations can enhance profitability. However, the study also uncovers a contrasting effect at the country level, where broader Fintech development appears to negatively impact bank profitability. This suggests a more complex interplay between technological advancement and market dynamics, including increased competition from digital payment systems and peer-to-peer lending platforms. Additionally, the research highlights that banks with higher exposure to market risk, as indicated by VaR, tend to achieve better profitability metrics, such as ROA, NIM, and Tobin's Q. Conclusion: The study concludes that while Fintech investments at the bank level can enhance profitability, broader Fintech development in the country may pose challenges to traditional banking profitability due to increased competition and market disruption. The results underscore the importance of strategic agility, advanced risk management, and innovation in banking practices to navigate the evolving financial landscape. The findings offer valuable insights for stakeholders, emphasizing the need for tailored regulatory approaches, strategic investments in technology, and innovations that focus on consumer needs. This nuanced understanding of the Fintech-bank profit nexus can help guide more informed decision-making in the industry.

Neolignans and Diarylnonanoid Derivatives with Anti-inflammatory Activity from Myristica fragrans Houtt. Seeds.

Myristica fragrans Houtt. is rich in lignans, neolignans, and diarylnonanoids, with well-documented anti-inflammatory properties. However, there is limited research on the conjugated forms of diarylnonanoids, neolignans, monoterpenes, and others and their anti-inflammatory effects. Our study isolated 33 new compounds (2-7, 9-22, and 41-52), including two neolignans, alongside various neolignan-diarylnonanoid, propenylbenzene-diarylnonanoid, 2,3-dimethylbutane-type lignan-diarylnonanoid, and monoterpene-diarylnonanoid conjugates, along with previously reported compounds (1, 8, and 23-40). Their chemical structures were determined via spectroscopic analyses. Compounds 2, 4, 9, 11, 12, 14, 17, and 18 exhibited potent inhibition of NF-κB/AP1 and IRF signaling induced by TLR agonists. Notably, stereoisomers showed distinct behavior, while 10R,11R-isomers induced cytotoxicity, and 10S,11R-isomers produced contrasting effects, especially within group-I compounds.

Elevated testosterone levels during moult have contrasting effects on structural and carotenoid‐based plumage colours in Eurasian Blue Tits

Elevated testosterone levels during moult have contrasting effects on structural and carotenoid‐based plumage colours in Eurasian Blue Tits

The atypical antipsychotics lurasidone and olanzapine exert contrasting effects on the gut microbiome and metabolic function of rats.

Antipsychotics such as olanzapine are associated with significant metabolic dysfunction, attributed to gut microbiome dysbiosis. A recent notion that most psychotropics are detrimental to the gut microbiome has arisen from consistent findings of metabolic adverse effects. However, unlike olanzapine, the metabolic effects of lurasidone are conflicting. Thus, this study investigates the contrasting effects of olanzapine and lurasidone on the gut microbiome to explore the hypothesis of 'gut neutrality' for lurasidone exposure. Using Sprague-Dawley rats, the effects of olanzapine and lurasidone on the gut microbiome were explored. Faecal and blood samples were collected weekly over a 21-day period to analyse changes to the gut microbiome and related metabolic markers. Lurasidone triggered no significant weight gain or metabolic alterations, instead positively modulating the gut microbiome through increases in mean operational taxonomical units (OTUs) and alpha diversity. This novel finding suggests an underlying mechanism for lurasidone's metabolic inertia. In contrast, olanzapine triggered a statistically significant decrease in mean OTUs, substantial compositional variation and a depletion in short-chain fatty acid abundance. Microbiome depletion correlated with metabolic dysfunction, producing a 30% increase in weight gain, increased pro-inflammatory cytokine expression, and increased blood glycaemic and triglyceride levels. Our results challenge the notion that all antipsychotics disrupt the gut microbiome similarly and highlights the potential benefits of gut-neutral antipsychotics, such as lurasidone, in managing metabolic side effects. Further research is warranted to validate these findings in humans to guide personalised pharmacological treatment regimens for schizophrenia.