Diverse Sites Research Articles

Diversity of Bacterial Communities in Sediment in Inland Water Bodies in Relation to Environmental Factors and Human Impacts: A Case Study on Typical Regions in Vietnam

Environmental changes and human impact can alter biodiversity in negative manners that affect mankind’s sustainable development. Particularly, such effects on inland waters are even more concerning, as those ecosystems play essential roles in sustaining human life as well as relevant wildlife. Thus, in this study, we investigated such effects on microbial diversity in inland waters in Vietnam using bacterial communities in sediment as indicators. To do this, we collected sediment samples from various locations in three respective regions (Red river in the north, Ba river in the central area, and Mekong delta flood zone in the south) using standard methods, extracted their total DNA, sequenced their V3-V4 16S rRNA gene fragments using an Illumina Miseq platform and analyzed the sequences to infer the diversity of the bacterial communities in the samples. These communities were compared in terms of richness (alpha diversity) and composition (beta diversity), and the correlations between their diversity levels and environmental factors, as well as human activities, were analyzed by using standard statistical tools. Our results showed that the communities were different from each other solely by region, in richness and critically in composition, although there were some communities distinctively different from all the others. Among environmental factors, only water salinity (and conductivity) had negative correlations with alpha-diversity indices of the bacterial communities, and phosphate concentration and turbidity had positive correlations, while the other factors had almost no correlations, which partially explains the region-specific diversity. These results also suggest that climate change incidences, especially sea intrusion, can have significant effects on microbial diversity in inland waters. The impact of human activities did not appear severe, solely affecting bacterial community richness, but not significantly affecting bacterial community composition. However, apparently reduced bacterial diversity in several sites with intense human impacts and distinct environmental conditions should be noted and deserve further investigation.

Screening of Cross-Reactive Aptamers for the Detection of 24 Quinolones by Using a Liebig's Law-Guided Parallel-Series Strategy.

Quinolones, a widely used class of antibiotics, present significant environmental and health concerns if they excessively remain in the environment and in food. Aptamers specific to quinolones can be applied as bioreceptors for the detection of quinolone residues in the environment and food. The quinolone family contains dozens of different individuals that share the same core structure coupled with various substituents at six different positions. The diversity and complexity of the substitution sites make it a challenge to choose a set of representative molecules that encompass all the desired sites and preserve the core molecular framework for the screening of quinolone-specific aptamers via systematic evolution of ligands by exponential enrichment (SELEX). To address this challenge, we introduce a novel parallel-series strategy guided by Liebig's law for isolating quinolone-specific cross-reactive aptamers by using the library-immobilized SELEX method. Through this approach, we successfully identified 5 aptamers (Apt.AQ01-Apt.AQ05) with high binding affinity and excellent specificity to 24 different quinolone individuals. Among them, Apt.AQ03 showcased optimal performance with affinities ranging from 0.14 to 1.07 μM across the comprehensive set of 24 quinolones, exhibiting excellent specificity against nontarget interferents. The binding performance of Apt.AQ03 was further characterized with microscale thermophoresis, circular dichroism spectra, and an exonuclease digestion assay. By using Apt.AQ03 as a bioreceptor, a fluorescence resonance energy transfer (FRET) aptasensor was developed for the detection of 24 quinolones in milk, achieving a remarkable detection limit of 14.5-21.8 ng/mL. This work not only establishes a robust and effective strategy for selecting cross-reactive aptamers applicable to other small-molecule families but also provides high-quality aptamers for developing various high-throughput and reliable methods for the detection of multiple quinolone residues in food.

Chemical and Chemoenzymatic Synthesis of Peptide and Protein Therapeutics Conjugated with Human N-Glycans.

Glycosylation is one of the most ubiquitous post-translational modifications. It affects the structure and function of peptides/proteins and consequently has a significant impact on various biological events. However, the structural complexity and heterogeneity of glycopeptides/proteins caused by the diversity of glycan structures and glycosylation sites complicates the detailed elucidation of glycan function and hampers their clinical applications. To address these challenges, chemical and/or enzyme-assisted synthesis methods have been developed to realize glycopeptides/proteins with well-defined glycan morphologies. In particular, N-glycans are expected to be useful for improving the solubility, in vivo half-life and aggregation of bioactive peptides/proteins that have had limited clinical applications so far due to their short duration of action in the blood and unsuitable physicochemical properties. Chemical glycosylation performed in a post-synthetic procedure can be used to facilitate the development of glycopeptide/protein analogues or mimetics that are superior to the original molecules in terms of physicochemical and pharmacokinetic properties. N-glycans are used to modify targets because they are highly biodegradable and biocompatible and have structures that already exist in the human body. On the practical side, from a quality control perspective, close attention should be paid to their structural homogeneity when they are to be applied to pharmaceuticals.

Exploring Binding Pockets in the Conformational States of the SARS-CoV-2 Spike Trimers for the Screening of Allosteric Inhibitors Using Molecular Simulations and Ensemble-Based Ligand Docking.

Understanding mechanisms of allosteric regulation remains elusive for the SARS-CoV-2 spike protein, despite the increasing interest and effort in discovering allosteric inhibitors of the viral activity and interactions with the host receptor ACE2. The challenges of discovering allosteric modulators of the SARS-CoV-2 spike proteins are associated with the diversity of cryptic allosteric sites and complex molecular mechanisms that can be employed by allosteric ligands, including the alteration of the conformational equilibrium of spike protein and preferential stabilization of specific functional states. In the current study, we combine conformational dynamics analysis of distinct forms of the full-length spike protein trimers and machine-learning-based binding pocket detection with the ensemble-based ligand docking and binding free energy analysis to characterize the potential allosteric binding sites and determine structural and energetic determinants of allosteric inhibition for a series of experimentally validated allosteric molecules. The results demonstrate a good agreement between computational and experimental binding affinities, providing support to the predicted binding modes and suggesting key interactions formed by the allosteric ligands to elicit the experimentally observed inhibition. We establish structural and energetic determinants of allosteric binding for the experimentally known allosteric molecules, indicating a potential mechanism of allosteric modulation by targeting the hinges of the inter-protomer movements and blocking conformational changes between the closed and open spike trimer forms. The results of this study demonstrate that combining ensemble-based ligand docking with conformational states of spike protein and rigorous binding energy analysis enables robust characterization of the ligand binding modes, the identification of allosteric binding hotspots, and the prediction of binding affinities for validated allosteric modulators, which is consistent with the experimental data. This study suggested that the conformational adaptability of the protein allosteric sites and the diversity of ligand bound conformations are both in play to enable efficient targeting of allosteric binding sites and interfere with the conformational changes.

Changes in submerged macrophyte diversity, coverage and biomass in a biosphere reserve site after 20 years: A plea for conservation efforts

The conservation of submerged vegetation is crucial in the functioning of aquatic ecosystems. We have assessed, by means of subaquatic quantitative sampling transects, the current status of the hydrophytic flora in 14 lakes in the Lagunas de Ruidera Natural Park, a Biosphere Reserve site in central Spain, surrounded by a semi-arid landscape. The conforming lakes have endured several anthropic pressures for decades (e.g., eutrophication, land-use changes, etc.). By comparing the current with the former status (20 years ago) of hydrophytes in the natural park, substantial negative (species richness loss, decrease in submerged meadow coverage, particularly in the upstream lakes) and positive (natural recovery of meadows after the cut-off of sudden disturbances caused by point pollution sources, improving of trophic state in some lakes, no presence of exotic hydrophytes) changes in the lakes were noticed. We have analyzed that the disappearance of all the hydrophyte (mainly charophytes) stands would represent the loss of ecosystem services. For example, up to 70 t CH4 might be released from the charophyte detritus, an internal pool of phosphorus (as high as 1400 mgP/m2) stored in the charophytes stands could be liberated. Some lakes require special measures, but overall, to preserve this lake complex, and other similar ones, we propose to study, in detail, the causes of submerged vegetation deterioration (focusing on the presence of pesticides –in water and sediments-, and other reasons) to assess the ecological risks, to protect the groundwater resources, preventing the lakes from receiving surficial point and non-point sources of pollution.

Diversity of bivalve and gastropod species in mangrove restoration areas

Bivalvia and gastropods are two types of mollusks found in mangrove habitats. This group of mollusks performs a vital function in their environment, including serving as a biofilter and decomposing organic waste. The abundance of bivalves and gastropods in their natural environment is presumed to have been impacted by deforestation and restoration processes in mangrove ecosystems. Therefore, this study was conducted to collect information about the composition and variety of bivalves and gastropods in the mangrove restoration area of Bagan Serdang village in North Sumatra. This research was conducted using the plot method with a plot size of 2m x 2m. Observation plots are created along specified paths with alternate placements. According to the findings, up to 19 types of mollusks were discovered at the study site. This investigation discovered 14 snail species and 10 gastropod families. The other five species are Bivalvia from four different families. M. strigata has the greatest density of 0.26 and the highest relative density of 3.90%. At the study site, the bivalve and gastropod diversity index was moderate (2.127), the evenness index was high (0.722), and the dominance index was low (0.211). It is highly recommended to continue to promote vegetation species at the study location in order to improve bivalves and gastropod species and numbers.

Site Diversity Mitigation Technique for Satellite Services for Ku and Ka-band in Tropical Region

The demand for satellite communication has increased which led to spectral congestion. Recently, the satellite services use Ku and Ka-band as additional spectrum for satellite communication services. Ku and Ka-band are categorized as high frequency range which is around 12 to 14 GHz and 20 to 30 GHz respectively. However, the higher frequency will affect the quality of services and lead to signal impairment. This is mainly caused by the atmosphere effect which is oxygen, liquid water, and precipitation. But among the list, rain causes most signal fading due to the scattering and depolarization. The aim of this research is to study the site diversity as mitigation techniques operating at Ku and Ka-band for enhancing the gain of the signal and calculating diversity gain. There are modelling of diversity gain that has been proposed by previous researchers namely Hodge, Panagopolous, ITU-R, X.Yeo and Semire models which were validated in different climate regions respectively. By using all previous modelling of diversity gain, it will also compare with the measured local diversity gain. Suitable modelling that can be used in this tropical region has been proposed by improving the mathematical model that will be suitable in the tropical regions. This is important for encouraging the finding of new theories for the future broadcasting systems to decrease the power loss during the rain fade.

Structure of a metacommunity of urban bees: Species diversity and spatio-temporal modularity

As the globe gets more urbanised, the question about how natural biodiversity is structured in cities becomes increasingly pertinent. To contribute to an answer, we studied species richness and spatio-temporal structure of bees in a North European metropolitan area. A gradient of 13 sites in the city of Aarhus, Denmark, was censused from April to September 2016. Forty species, i.e. 29 solitary species (40 % of all individuals), ten Bombus species (28 %), and Apis mellifera (32 %), were sampled monthly in pan traps. (i) Information about species traits was extracted from the literature, and trait values were correlated and used to characterize the fauna. Most were soil-nesters, pollen generalists, and common. (ii) Habitat diversity within five concentric circles with trap at the centre and radii from 50 m to 1000 m was related to bee α diversity. The relationship was significant only within 1,000 m for all bees and for bumblebees. Solitary bee diversity was uncorrelated with habitat diversity at all spatial levels. (iii) Spatio-temporal structure was analysed as two networks, one for bees linked to sites, and one for bees linked to months. Link patterns were analysed for levels of nestedness, modularity, and spatio-temporal β diversity. The two networks were weakly and non-significantly nested, but strongly modular, being composed of five and four modules of co-occurring bees, respectively. (iv) Finally, we studied total β diversity, βTOTAL, being the sum of species turnover, βTURN, and species loss/gain or nestedness, βNEST. For both site and season, βTURN was higher than βNEST, and site βTOTAL was higher than season βTOTAL. One reason for this metacommunity structure may be a high spatio-temporal habitat patchiness, sustaining a rich biodiversity. Thus, a few large areas may not compensate for the loss of several small patches. Consequently, establishment of many green, even small habitats is recommended.

Optimizing Low-Temperature CO2 methanation with Aluminum-Doped Ni/CeO2 Catalysts: Insights into reaction pathway adjustments and strong Metal-Support interactions

Revealing the logical relationship between the structure, reaction mechanism and performance of the catalyst is a key step in the design of low-temperature CO2 methanation catalyst. The elemental Al was introduced into Ni/CeO2 using a co-precipitation method to form a composite support CeO2-Al2O3 loaded nickel-based catalyst. It was found that the incorporation of Al significantly improved the catalytic performance of low-temperature CO2 methanation. Notably, at a molar ratio of Al/Ce equal to 0.1, the catalyst exhibited optimal CO2 conversion of 88.83% and CH4 selectivity of 99.96% at 240 ℃. The addition of appropriate amounts of Al not only increases the specific surface area of the catalyst but also maintains a moderate strong interaction between metal Ni-support, thereby promoting the formation of active metal Ni species. Furthermore, the presence of Al leads to an increase in oxygen vacancy concentration, which facilitates the generation of numerous hydroxyl groups. Consequently, this alters the distribution of basic sites on the catalyst surface, resulting in a shift from the CO* pathway to a dual pathway involving both CO* and formate pathways. Remarkably, these divergent reaction pathways correspond to distinct active sites, thereby maximizing the utilization of each region within the catalyst. The diversity of reaction pathways and active sites represents pivotal factors for enhancing the catalytic performance of low-temperature CO2 methanation catalysts.

Diversity and Distribution of Culicidian Fauna in Urban and Rural Areas of Setif Region (North-East Algeria).

Objective: The study explored larval mosquito breeding sites in urban and rural areas from March 2021 to February 2022 in the North-East region of Algeria to provide information on larval biology and ecology of different mosquito species. Methodology: It focused on the effect of the physicochemical characteristics of the breeding sites (pH and water temperature), area, and months on the larval mosquito abundance. Diversity index and equitability were calculated for the registered mosquito species in both areas. Results: Months significantly affected the larval mosquito abundances, with a clear abundance increase from March to August 2021, and then, a clear decrease to February 2022. The interactions between rural and urban areas, water pH, and water temperature as well affected the mosquito abundance. Twelve species of Culicidae were identified and distributed in three genera: Culex, Culiseta, and Aedes. Culex pipiens was the most dominant species in rural and urban sites, with a rate of 69% and 48%, respectively. In rural site, Aedes caspius and Aedes vexans occupied the second position with value of 7-8% each. In urban sites, the second position was occupied by Culiseta longiareolata (36%) and then by Culex theileri (10%). In terms of site diversity, only one site was highly diversified in rural sites, El Hchichia (H' = 1.12 bits). In urban sites, Setif Center, Guellel an Ain Trick, had almost similar diversity with values between 1.03 and 1.04 bits. Equitability values were 0.48 in rural sites and 0.55 in urban sites. Therefore, the Culicidae species presented in these study sites are moderately balanced. Conclusion: The present study provides key tools for planning a better vector control through the information on the effect of some factors on the proliferation of mosquitoes in the urban and rural sites of the Setif region and on the Culicidae diversity and abundance.

Littoral phytoplankton and zooplankton communities in a tropical reservoir: Pantabangan Reservoir, the Philippines

Abstract Littoral phytoplankton and zooplankton diversity are influenced by the water quality parameters and their trophic interactions. In the largest reservoir of the Philippines, this study examined the water quality and plankton community composition in the littoral zone across three sampling sites and four depths. Of the three sites, one is located near active fish cages, one near the mouth of a tributary and one near an outlet of an upstream dam. A total of 36 phytoplankton and 34 zooplankton taxa were identified, with most taxa belonging to Chlorophyta and Cyclopoida. The most abundant phytoplankton and zooplankton taxa were Aulacoseira and Microcyclops, respectively. The three most abundant phytoplankton (Aulacoseira, Oscillatoria, Volvox) were most positively correlated with the nutrient levels [total nitrogen (TN), total phosphorus (TP) and TN:TP ratio]. A significant interaction of sampling site and depth was recorded for the phytoplankton’s Shannon diversity index and community composition. The decreased zooplankton diversity amidst decreased phytoplankton diversity in the aquaculture site aligns with the effect of lowered resource heterogeneity on zooplankton. The increased phytoplankton diversity and decreased zooplankton density and taxon richness at shallower depths were probably linked with the light availability.

Implementing a pharmacist-integrated collaborative model of medication treatment for opioid use disorder in primary care: study design and methodological considerations

BackgroundPharmacists remain an underutilized resource in the treatment of opioid use disorder (OUD). Although studies have engaged pharmacists in dispensing medications for OUD (MOUD), few studies have evaluated collaborative care models in which pharmacists are an active, integrated part of a primary care team offering OUD care.MethodsThis study seeks to implement a pharmacist integrated MOUD clinical model (called PrIMO) and evaluate its feasibility, acceptability, and impact across four diverse primary care sites. The Consolidated Framework for Implementation Research is used as an organizing framework for study development and interpretation of findings. Implementation Facilitation is used to support PrIMO adoption. We assess the primary outcome, the feasibility of implementing PrIMO, using the Stages of Implementation Completion (SIC). We evaluate the acceptability and impact of the PrIMO model at the sites using mixed-methods and combine survey and interview data from providers, pharmacists, pharmacy technicians, administrators, and patients receiving MOUD at the primary care sites with patient electronic health record data. We hypothesize that it is feasible to launch delivery of the PrIMO model (reach SIC Stage 6), and that it is acceptable, will positively impact patient outcomes 1 year post model launch (e.g., increased MOUD treatment retention, medication regimen adherence, service utilization for co-morbid conditions, and decreased substance use), and will increase each site’s capacity to care for patients with MOUD (e.g., increased number of patients, number of prescribers, and rate of patients per prescriber).DiscussionThis study will provide data on a pharmacist-integrated collaborative model of care for the treatment of OUD that may be feasible, acceptable to both site staff and patients and may favorably impact patients’ access to MOUD and treatment outcomes.Trial registration: The study was registered on Clinicaltrials.gov (NCT05310786) on April 5, 2022, https://www.clinicaltrials.gov/study/NCT05310786?id=NCT05310786&rank=1

Probes for the heterogeneity of muscimol binding sites in rat brain.

Introduction: The plant-based alkaloid muscimol is a potent agonist of inhibitory GABAA-neurotransmitter receptors. GABAA receptors are a heterogeneous family of pentameric complexes, with 5 out of 19 subunits assembling around the central anion pore. Muscimol is considered to bind to all receptor subtypes at the orthosteric drug binding site at the β+/α- interface. Recently, we observed that the antipsychotic drugs clozapine (CLZ), loxapine (LOX) and chlorpromazine (CPZ) although exerting functional inhibition on multiple GABAA receptor subtypes showed diverging results in displacing 3H-muscimol. While a complete displacement could be observed in hippocampal membranes by bicuculline (BIC), and no displacement with CPZ, the compounds CLZ and LOX competed partially. Non-sigmoidal, complex dose response curves were indicative of multiple sites. In the current study we now aimed to investigate more extensively this heterogeneity of bicuculline sensitive muscimol sites in rat brain. Methods: We tested membranes from four different brain regions (hippocampus, cerebellum, thalamus and striatum) and selected recombinantly expressed subunit combinations with displacement assays. 3H-muscimol displacement was tested with BIC, LOX, CLZ and CPZ. In silico ligand structural analysis and computational docking was performed. Results: We observed a unique pharmacology of each tested compound in the studied brain regions. Combining two of the tested ligands suggests that in striatum all CLZ sites are contained in the pool of LOX sites, while the CPZ sites may in part be non-overlapping with LOX sites. Experiments on recombinantly expressed receptors indicate, that BIC can displace 3H-muscimol from all tested receptors, while LOX and CLZ display different and variable competition indicative of multiple sites. Molecular docking produced structural correlates of the observed diversity of muscimol sites on the basis of bicuculline bound experimental structures. Discussion: These findings indicate that 3H-muscimol binding sites in rat brain are heterogeneous, with different populations of receptors, which are CPZ, LOX or CLZ sensitive or insensitive. These binding sites show a varying distribution in different rat brain regions. Molecular docking suggests that the so-called loop F region of α subunits drives the observed differences.

Empire, diversity & development: evidence from Afghan provinces

ABSTRACT In this paper, we explore the effects of historical and contemporary ethnolinguistic diversity on socio-economic development in Afghanistan. Using a dataset of Afghan provinces, we find that historical ethnolinguistic borders are strongly associated with income, provision of public goods, and political preferences in Afghanistan. Pashtun areas exhibit higher levels of income and public goods provision as well as political support for the incumbent. There has been a persistent rule of Pashtun leaders in Afghanistan during the last three centuries. Furthermore, we instrument measures of contemporary ethnolinguistic diversity by the diversity of archaeological sites that belong to different ancient and medieval empires. We argue that higher levels of contemporary diversity are likely to induce lower levels of conflict, higher levels of income and trust, and lower levels of individualism.

Growth of infants delivered by mothers with HIV in Guangxi, China: An 18-month longitudinal follow-up study, 2015-2021.

The prevention of mother-to-child transmission of HIV has been a global success. But little is known about the growth parameters of infants delivered by mothers with HIV or the drug resistance of infants with HIV in China. The study aimed to assess growth parameters and drug resistance in Chinese infants exposed to HIV. We conducted an 18-month longitudinal follow-up study of 3283 infants (3222 without HIV; 61 with HIV) born to mothers with HIV in the Guangxi Zhuang Autonomous Region between January 2015 and December 2021. The weight and length of all participants was recorded. In addition, genetic subtypes and drug resistance analysis were performed for infants with HIV. Compared with infants without HIV, those with HIV had significantly lower weight/length Z-scores, except at 18 months of age. The length/age Z-scores of infants with HIV was significantly reduced, except at 1 month of age. The weight/age Z-scores of infants with HIV were significantly lower at all follow-up time points. The weight/length Z-scores of male infants without HIV were significantly lower than for female infants without HIV at all follow-up time points. Male infants without HIV had lower length/age and weight/age Z-scores than female infants at the remaining follow-up points, except at 1 month of age. Of a total of 61 infants with HIV, subtype and drug-resistance data were obtained from 37 (60.66%) samples. Infants with HIV were dominated by the CRF01_AE genotype and showed a diversity of mutation sites dominated by non-nucleoside reverse transcriptase inhibitor resistance. Our study demonstrates the growth of infants exposed to HIV in southwest China and provides detailed information on subtype distribution and drug resistance of those with HIV. Nutritional support and drug-resistance surveillance for infants exposed to HIV need to be strengthened.

Glutathione Induced In situ Synthesis of Cu Single‐Atom Nanozymes with Anaerobic Glycolysis Metabolism Interference for Boosting Cuproptosis

AbstractSingle‐atom nanozyme (SAzyme) has sparked increasing interest for catalytic antitumor treatment due to their more tunable and diverse active sites than natural metalloenzymes in complex physiological conditions. However, it is usually a hard task to precisely conduct catalysis at tumor sites after intravenous injection of those SAzyme with high reactivity. Moreover, the explorations of SAzymes in the anticancer application are still in its infancy and need to be developed. Herein, an in situ synthesis strategy for Cu SAzyme was constructed to convert adsorbed copper ions into isolated atoms anchored by oxygen atoms (Cu−O2/Cu−O4) via GSH‐responsive deformability of supports. Our results suggest that the in situ activation process could further facilitate the dissociation of copper ions and the consumption of glutathione, thereby leading to copper deposition in cytoplasm and triggering cuproptosis. Moreover, the in situ synthesis of Cu SAzyme with peroxidase‐like activity enabled the intracellular reactive oxygen species production, resulting in specifically disturbance of copper metabolism pathway. Meanwhile, the in situ exposed glucose transporter (GLUT) inhibitor phloretin (Ph) can block the glycose uptake to boost cuproptosis efficacy. Overall, this in situ activation strategy effectively diminished the off‐target effects of SACs‐induced catalytic therapies and introduced a promising treatment paradigm for advancing cuproptosis‐associated therapies.

Glutathione Induced In situ Synthesis of Cu Single-Atom Nanozymes with Anaerobic Glycolysis Metabolism Interference for Boosting Cuproptosis.

Single-atom nanozyme (SAzyme) has sparked increasing interest for catalytic antitumor treatment due to their more tunable and diverse active sites than natural metalloenzymes in complex physiological conditions. However, it is usually a hard task to precisely conduct catalysis at tumor sites after intravenous injection of those SAzyme with high reactivity. Moreover, the explorations of SAzymes in the anticancer application are still in its infancy and need to be developed. Herein, an in situ synthesis strategy for Cu SAzyme was constructed to convert adsorbed copper ions into isolated atoms anchored by oxygen atoms (Cu-O2/Cu-O4) via GSH-responsive deformability of supports. Our results suggest that the in situ activation process could further facilitate the dissociation of copper ions and the consumption of glutathione, thereby leading to copper deposition in cytoplasm and triggering cuproptosis. Moreover, the in situ synthesis of Cu SAzyme with peroxidase-like activity enabled the intracellular reactive oxygen species production, resulting in specifically disturbance of copper metabolism pathway. Meanwhile, the in situ exposed glucose transporter (GLUT) inhibitor phloretin (Ph) can block the glycose uptake to boost cuproptosis efficacy. Overall, this in situ activation strategy effectively diminished the off-target effects of SACs-induced catalytic therapies and introduced a promising treatment paradigm for advancing cuproptosis-associated therapies.

A Cell-Permeable Photosensitizer for Selective Proximity Labeling and Crosslinking of Aggregated Proteome.

Intracellular proteome aggregation is a ubiquitous disease hallmark with its composition associated with pathogenicity. Herein, this work reports on a cell-permeable photosensitizer (P8, Rose Bengal derivative) for selective photo induced proximity labeling and crosslinking of cellular aggregated proteome. Rose Bengal is identified out of common photosensitizer scaffolds for its unique intrinsic binding affinity to various protein aggregates driven by the hydrophobic effect. Further acetylation permeabilizes Rose Bengal to selectively image, label, and crosslink aggregated proteome in live stressed cells. A combination of photo-chemical, tandem mass spectrometry, and protein biochemistry characterizations reveals the complexity in photosensitizing pathways (both Type I & II), modification sites and labeling mechanisms. The diverse labeling sites and reaction types result in highly effective enrichment and identification of aggregated proteome. Finally, aggregated proteomics and interaction analyses thereby reveal extensive entangling of proteostasis network components mediated by HSP70 chaperone (HSPA1B) and active participation of autophagy pathway in combating proteasome inhibition. Overall, this work exemplifies the first photo induced proximity labeling and crosslinking method (namely AggID) to profile intracellular aggregated proteome and analyze its interactions.

Re-framing the importance of Group B Streptococcus as a gut-resident pathobiont.

Streptococcus agalactiae (Group B Streptococcus, GBS) is a Gram-positive bacterial species that causes disease in humans across the lifespan. While antibiotics are used to mitigate GBS infections, it is evident that antibiotics disrupt human microbiomes (which can predispose people to other diseases later in life), and antibiotic resistance in GBS is on the rise. Taken together, these unintended negative impacts of antibiotics highlight the need for precision approaches for minimizing GBS disease. One possible approach involves selectively depleting GBS in its commensal niches before it can cause disease at other body sites or be transmitted to at-risk individuals. One understudied commensal niche of GBS is the adult gastrointestinal (GI) tract, which may predispose colonization at other body sites in individuals at risk for GBS disease. However, a better understanding of the host-, microbiome-, and GBS-determined variables that dictate GBS GI carriage is needed before precise GI decolonization approaches can be developed. In this review, we synthesize current knowledge of the diverse body sites occupied by GBS as a pathogen and as a commensal. We summarize key molecular factors GBS utilizes to colonize different host-associated niches to inform future efforts to study GBS in the GI tract. We also discuss other GI commensals that are pathogenic in other body sites to emphasize the broader utility of precise de-colonization approaches for mitigating infections by GBS and other bacterial pathogens. Finally, we highlight how GBS treatments could be improved with a more holistic understanding of GBS enabled by continued GI-focused study.

Substantial urbanization-driven declines of larval and adult moths in a subtropical environment.

Recent work has shown the decline of insect abundance, diversity and biomass, with potential implications for ecosystem services. These declines are especially pronounced in regions with high human activity, and urbanization is emerging as a significant contributing factor. However, the scale of these declines and the traits that determine variation in species-specific responses remain less well understood, especially in subtropical and tropical regions, where insect diversity is high and urban footprints are rapidly expanding. Here, we surveyed moths across an entire year in protected forested sites across an urbanization gradient to test how caterpillar and adult life stages of subtropical moths (Lepidoptera) are impacted by urbanization. Specifically, we assess how urban development affects the total biomass of caterpillars, abundance of adult moths and quantify how richness and phylogenetic diversity of macro-moths are impacted by urban development. Additionally, we explore how life-history traits condition species' responses to urban development. At the community level, we find that urban development decreases caterpillar biomass and adult moth abundance. We also find sharp declines of adult macro-moths in response to urban development across the phylogeny, leading to a decrease in species richness and phylogenetic diversity in more urban sites. Finally, our study found that smaller macro-moths are less impacted by urban development than larger macro-moths in subtropical environments, perhaps highlighting the tradeoffs of metabolic costs of urban heat favoring smaller moths over the relative benefits of dispersal for larger moths. In summary, our research underscores the far-reaching consequences of urbanization on moths and provides compelling evidence that urban forests alone may not be sufficient to safeguard biodiversity in cities.