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Microtubule assembly takes place at the centrosome and noncentrosomal microtubule-organizing centers (MTOCs). However, the mechanisms controlling the activity of noncentrosomal MTOCs are poorly understood. Here, using the fission yeast Schizosaccharomyces pombe as a model organism, we demonstrate that the kinesin-14 motor Klp2 interacts with the J-domain Hsp70/Ssa1 cochaperone Rsp1, an inhibitory factor of microtubule assembly, and that Klp2 is required for the proper localization of Rsp1 to microtubules. In addition, we demonstrate that Klp2 is not required for the localization of Mto1, a factor promoting microtubule assembly, to microtubules. Moreover, Rsp1-Ssa1 inhibits the interaction of Mto1-Mto2 with the gamma-tubulin small complex. The absence of Klp2 reduces the colocalization of Rsp1 and Mto1 foci on preexisting microtubules, resulting in an increased microtubule-dependent microtubule assembly. Our results suggest that Klp2 regulates the activity of noncentrosomal MTOCs by targeting Rsp1 to the sites of Mto1 activity and reveal a mechanism for the inhibition of noncentrosomal microtubule assembly by a kinesin-14 motor.

The operation of membrane-based reactors is inevitably challenged by fouling. The driving force in these reactors is not only critical for water passage through membranes but also significantly influences fouling, such as biocake formation. This study investigated the differences between biocakes formed under transmembrane pressure (TMP) and forward osmosis (FO) conditions, specifically focusing on their components, spatial structures, and microbial communities. The findings reveal that the MF-biocake, formed under TMP conditions, contained a greater diversity of foulants, microbes, and metabolic products compared to the FO-biocake. Clustering and correlation analyses indicated that MF-biocake formation was predominantly influenced by dead cells, extracellular polymeric substances, and physicochemical parameters, whereas FO-biocake formation was mainly affected by live cells and adhesion forces. Particle image velocimetry tests further highlighted nonselective foulant adsorption in MF-biocake formation versus selective adhesion in FO-biocake formation. These insights enhance our understanding of the distinct characteristics of biocakes formed under TMP- and FO-driven conditions, aiding in the development of more targeted strategies to control biocake formation based on the driving forces., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The last phases of a competitive game are when shoulder injuries most commonly happen, and fatigue is thought to be a major contributing factor, perhaps because of reduced proprioception and motor control. The purpose of this study was to investigate the effect of concentric fatigue on proprioception, motor control, and performance of the upper limb in handball players., Methods: Forty-six right-handed handball players (all males, age 26.1 ± 5.54 years) were included in this test-retest laboratory experiment. Proprioception was assessed using joint reposition sense (JRS), threshold to detection of passive movement (TTDPM), muscle onset latency (MOL), motor control using Y balance test upper quarter (YBT-UQ) and performance using the athletic shoulder test (ASH) before and immediately after fatigue intervention. The fatigue protocol consisted of concentric, maximal effort, isokinetic contractions at 900/sec with sets of 30 repetitions of the shoulder external and internal rotator muscles. Fatigue was determined by a 40% decline in the peak torque over three consecutive contractions despite reinforcing feedback and encouragement., Results: A significant increase in absolute angular error (AAE) was observed in all target angles in both external rotation (ER) and internal rotation (IR) directions (p < 0.01). In addition, there was a significant increase in TTDPM in internal rotation after fatigue intervention (p = 0.020. Variable changes were found in YBT-UQ and ASH tests. Specifically, statistically significant differences were found in anteromedial (AM) (p = 0.041), superolateral (SL) reach directions (p = 0.005), composite score (p = 0.009) in the right hand and inferolateral (IL) reach direction in the left hand (p = 0.020) in the YBT-UQ. In addition, there was a significant reduction in isometric strength (ASH test) in the I position of the right hand (p = 0.010) and all positions of the left hand (p<0.05). Furthermore, there was an increase in MOL scores after fatigue but the increase was not significant (p > 0.05)., Conclusions: Concentric fatigue of the rotator cuff muscles induces notable deficits in joint position awareness, kinesthesia, motor control, and performance of the upper extremity in elite male handball players. Although fatigue reduces reflex reaction time the effect is only marginal., Competing Interests: The authors have declared that no competing interests exist, (Copyright: © 2024 Hadjisavvas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The genome of Buchnera aphidicola National Institute of Advanced Industrial Science and Technology (AIST), an obligate bacterial endosymbiont from a Japanese strain of the pea aphid Acyrthosiphon pisum , was determined. The genome sequence provides valuable information for comparative and evolutionary aspects of the intimate insect-microbe mutualism.

Secretory trafficking in plant cells is facilitated by SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins that drive membrane fusion of cargo-containing vesicles. In Arabidopsis, SYNTAXIN OF PLANTS 132 (SYP132) is an evolutionarily ancient SNARE that functions with syntaxins SYP121 and SYP122 at the plasma membrane. Whereas SYP121 and SYP122 mediate overlapping secretory pathways, albeit with differences in their importance in plant-environment interactions, the SNARE SYP132 is absolutely essential for plant development and survival. SYP132 promotes endocytic traffic of the plasma membrane H+-ATPase AHA1 and aquaporin PIP2;1, and it coordinates plant growth and bacterial pathogen immunity through PATHOGENESIS-RELATED1 (PR1) secretion. Yet, little else is known about SYP132 cargoes. Here, we used advanced quantitative tandem mass tagging (TMT)-MS combined with immunoblot assays to track native secreted cargo proteins in the leaf apoplast. We found that SYP132 supports a basal level of secretion in Arabidopsis leaves, and its overexpression influences salicylic acid and jasmonic acid defense-related cargoes including PR1, PR2, and PR5 proteins. Impairing SYP132 function also suppressed defense-related secretory traffic when challenged with the bacterial pathogen Pseudomonas syringae. Thus, we conclude that, in addition to its role in hormone-related H+-ATPase cycling, SYP132 influences basal plant immunity., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Bioproduction of chemicals by using engineered bacteria is promising for a circular economy but challenged the instability of the introduced plasmid by conventional methods. Here, we developed a two-plasmid INTEGRET system to reliably integrate the targeted gene into the Vibrio natriegens genome, making it a powerful strain for efficient and steady bioproduction without requiring antibiotic addition. The INTEGRET system allows for gene insertion at over 75% inserting efficiency and flexibly controllable gene dosages. Additionally, simultaneous gene insertion at four genomic sites was achieved at 54.3% success rate while maintaining stable inheritance of exogenous sequences across multiple generations. The engineered strain could efficiently synthesize PHB from the fermentation of diverse organic wastes, with an efficiency comparable to those with overexpressed plasmid. When the mixture of seawater and molasses was used as the feedstock, it achieved a high PHB yield of 39.41 wt %. An extended application of the INTEGRET system for imparting the riboflavin production ability to the bacterium was also demonstrated. Our work presents a reliable and efficient genomic editing tool to facilitate the development of sustainable and environmentally benign biological platforms for converting biomass wastes into valuable chemicals.

Imaging transcriptomics offers opportunities to uncover the genetic profiles underlying brain imaging-derived phenotypes (IDPs) but lacks explanation from gene to IDPs. Here, we present a protocol for combining imaging transcriptomics with gene set variation analysis (GSVA) to detect spatio-molecular profiles underlying IDPs in the human cerebellum. We describe the steps for data preparation, model training, model evaluation, key gene identification, and GSVA. Our protocol broadens the way to interpret the biological pathways shaping a wide range of neuroimaging-derived cerebellar properties. For complete details on the use and execution of this protocol, please refer to Wang et al. 1 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Musculoskeletal disease (MSD) is common in ageing cats, resulting in chronic pain and mobility impairment, but diagnosis can be challenging. We hypothesised that there would be differences between cats with and without MSD in paw pressure and spatiotemporal and kinetic gait metrics. A cohort of 53 cats, aged between 7 and 10 years from the North West of the United Kingdom, underwent an orthopaedic examination and walked on a pressure sensitive walkway. Thirty-one of the cats (58%) were determined to be apparently-healthy, based on a normal orthopaedic examination and having no history of MSD, whilst the remaining 22 cats (42%) had findings consistent with MSD; 13/22 cats (59%) had multiple limb involvement, 7/22 (32%) had forelimb involvement and 2/22 (9%) had hindlimb involvement. Bodyweight (P = 0.048) and body condition score (BCS; P = 0.015) were both greater in cats with MSD (mean bodyweight 5.4 ± 1.35 kg; median BCS 6, IQR 6-7.75) compared with apparently-healthy cats (mean bodyweight 4.7 ± 0.94 kg; median BCS 5, IQR 4.5-6.5). There was a relatively large intra-cat variation in spatiotemporal and kinetic gait variables (coefficient of variation >3.0%), whilst a linear mixed-effects model suggested no significant difference in spatiotemporal or kinetic gait variables between apparently-healthy cats and those with MSD. Palmar and plantar pressure asymmetry was assessed by pedobarographic statistical parametric mapping (pSPM) within each individual cat, with no significant difference (P = 0.353) between the apparently heathy cats and those with MSD as to the presence or absence of asymmetry. Given the marked intra-cat variation and the 'multi-limb' nature of MSD in this cohort, it was not possible to differentiate healthy cats from those with MSD based on spatiotemporal and kinetic gait metrics or paw pressure asymmetry. Future work should examine gait in cats with defined musculoskeletal disorders (e.g. hip dysplasia) and also to track longitudinal changes within individual cats to better establish age-related trends., Competing Interests: AJG is an employee of the University of Liverpool, but his post is financially supported by Royal Canin, a division of Mars Petcare. AJG has also received financial remuneration for providing educational material, speaking at conferences, and consultancy work from this company; all such remuneration has been for projects unrelated to the work reported in this manuscript. At the time the study was performed, ND was undertaking a post-graduate studentship funded by Royal Canin. Since October 2020, ND has been employed by International Cat Care, but also holds a part-time post-doctoral research position at the University of Liverpool, funded by Royal Canin. This does not alter our adherence to PLOS ONE policies on sharing data and materials.’, (Copyright: © 2024 Dowgray et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Non-invasive blood pressure monitoring has emerged as a critical frontier in cardiovascular healthcare, with magnetic sensors playing an increasingly pivotal role in wearable health technologies. This comprehensive review critically examines the complex challenges of sensor-skin coupling and its profound impact on the accuracy of blood pressure measurements in patients with hypertension and aortovascular disease. Despite the growing demand for precise, real-time health monitoring, significant limitations persist in current magnetic sensor technologies. Our analysis reveals how intricate interactions between sensor devices and skin characteristics including pigmentation, texture, and elasticity can substantially compromise measurement reliability. We systematically explore innovative approaches to mitigate these challenges, presenting cutting-edge strategies in advanced material development, adaptive calibration techniques, and sophisticated signal processing algorithms. The review synthesizes current research to demonstrate the multidisciplinary approaches necessary for enhancing magnetic sensor performance. By critically analyzing the nuanced interactions between sensor technologies and individual patient physiological profiles, we provide insights into developing more robust, personalized health monitoring systems. Our findings underscore the urgent need for continued innovation in non-invasive blood pressure monitoring, with direct implications for improved clinical assessment and patient outcomes in cardiovascular care., Competing Interests: Declaration of competing interest All Authors declare that they don't have any conflict of interest, (Copyright © 2024. Published by Elsevier Inc.)

Artificial Intelligence (AI) is an emerging tool that could be leveraged to identify the effective conservation solutions demanded by the urgent biodiversity crisis. We present the results of our horizon scan of AI applications likely to significantly benefit biological conservation. An international panel of conservation scientists and AI experts identified 21 key ideas. These included species recognition to uncover 'dark diversity', multimodal models to improve biodiversity loss predictions, monitoring wildlife trade, and addressing human-wildlife conflict. We consider the potential negative impacts of AI adoption, such as AI colonialism and loss of essential conservation skills, and suggest how the conservation field might adapt to harness the benefits of AI while mitigating its risks., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Uranium is the primary fuel for nuclear energy, critical for sustainable, carbon-neutral energy transitions. However, limited terrestrial resources and environmental risks from uranium contamination require innovative immobilization and recovery solutions. In this work, we present a novel uranium recovery method using programmable electroactive living materials (ELMs). Utilizing Shewanella oneidensis , this approach leverages the intrinsic extracellular electron transfer capability of exoelectrogenic species, combining their adaptability and programmability with the robustness of engineered multicellular systems. These exoelectrogenic cells were endowed to selectively capture and enhance U(VI) reduction by expressing uranyl-binding proteins, coupled with a reconfigured transmembrane Mtr electron nanoconduit. By incorporating biofilm-promoting circuits, we improved cell-to-cell interactions and biofilm formation, enabling the stable assembly of ELMs with robust structural integrity. The ELMs demonstrated superior electrogenic activity, achieving a 3.30-fold increase in current density and a 3.15-fold increase in voltage output compared to controls in microbial electrochemical and fuel cells. When applied for uranium recovery, the ELMs exhibited robust U(VI) capture, reduction, and accumulation capabilities, with a maximum capacity of 808.42 μmol/g. This work not only provides a versatile and environmentally friendly solution for uranium recovery, but also highlights the potential of ELMs in sustainable environmental and energy technologies.

Objective: This study aimed to investigate the impact of tumor-associated macrophage (TAM)-derived exosomes on epithelial-mesenchymal transition (EMT) in head and neck squamous cell carcinoma (HNSCC) and the underlying mechanisms involved., Subjects and Methods: Exosomes were isolated and characterized using transmission electron microscopy, nanoparticle size analysis, and western blotting. The effect on EMT in HNSCC cells was assessed using wound healing, transwell invasion, and EMT marker assays. Bioinformatics analysis was conducted to predict key TAM-related long noncoding RNAs and evaluate their relationship with EMT in HNSCC., Results: We observed that treatment with TAM-derived conditioned medium (CM) promoted EMT in HNSCC cells. Within the CM, we observed abundant exosomes that were taken up by HNSCC cells. Furthermore, TAM-derived exosomes promoted EMT in HNSCC cells. Mechanistically, high MIR4435-2HG expression levels were observed in TAM-derived exosomes and in HNSCC cells after treatment with TAM-derived exosomes. Notably, high MIR4435-2HG expression levels may be closely related to molecules that promote EMT in HNSCC., Conclusions: TAM-derived exosomes promote EMT in HNSCC cells by upregulating MIR4435-2HG expression, suggesting that MIR4435-2HG is a candidate target for HNSCC therapy., (© 2024 John Wiley & Sons Ltd.)

Chaohu Lake is the fifth largest freshwater lake in China that meets the needs of surrounding industries for water, tourism, and flood storage, making it important for the socio-economic development and modernization of Anhui Province. As an important ecological wetland in the lower reaches of the Yangtze River, many rare bird habitats are present along the coast of Chaohu Lake. Therefore, it is eco-economically important to study antibiotic pollution in Chaohu Lake. To unveil antibiotic contamination in Chaohu Lake, surface water and sediment samples were collected from the main basin of Chaohu Lake by steamship in June 2022. Solid phase extraction and ultra-performance liquid chromatography-mass spectrometry （SPE-UPLC-MS） was used to determine the occurrence of 31 target antibiotics, including tetracyclines, sulfonamides, macrolides, and quinolones. The study focused on the spatial distribution, source analysis, and risk assessment of various antibiotics in the surface water and sediments of the main basin of Chaohu Lake. The occurrences of 20 different antibiotics were successively identified in the surface water and sediments of Chaohu Lake. These antibiotics included sulfonamides, quinolones, macrolides, tetracyclines, and others. Significant spatial differences in antibiotics were found between surface water and sediments. The horizontal spatial distribution results indicated differences in species and concentration of antibiotics in surface water and sediments. The vertical spatial distribution results showed that many types of antibiotics had consistent vertical distribution characteristics in surface water and sediments at the same point. The principal component analysis results indicated that the source of antibiotics in surface water was similar to that in sediment and considered with the actual distribution of existing industries around Chaohu Lake； the main sources were livestock and poultry breeding sewage, aquaculture sewage, and household sewage. The ecological risk quotient （RQ） results indicated that norfloxacin in the surface water of Chaohu Lake posed a high risk to algae （RQ &gt; 1）, while sulfamethoxazole and doxycycline posed a medium risk to algae （0.1 ≤ RQ &lt; 1）. The health risk quotient （HRQ） showed that the risk of exposure to antibiotics through drinking water was very low （HRQ &lt; 0.01）. Our findings provide scientific support for decision makers to control antibiotic pollution and reduce the management costs of antibiotic watershed pollution.

Bats possess a range of distinctive characteristics, including flight, echolocation, impressive longevity, and the ability to harbor various zoonotic pathogens. Additionally, they account for the second-highest species diversity among mammalian orders, yet their phylogenetic relationships and demographic history remain underexplored. Here, we generated de novo assembled genomes for 17 bat species and 2 of their mammalian relatives (the Amur hedgehog and Chinese mole shrew), with 12 genomes reaching chromosome-level assembly. Comparative genomics and ChIP-seq assays identified newly gained genomic regions in bats potentially linked to the regulation of gene activity and expression. Notably, some antiviral infection-related gene under positive selection exhibited the activity of suppressing cancer, evidencing the linkage between virus tolerance and cancer resistance in bats. By integrating published bat genome assemblies, phylogenetic reconstruction established the proximity of noctilionoid bats to vesper bats. Interestingly, we found 2 distinct patterns of ancient population dynamics in bats and population changes since the last glacial maximum does not reflect species phylogenetic relationships. These findings enriched our understanding of adaptive mechanisms and demographic history of bats., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Entomopathogenic ascomycetes are important natural regulators of insect pest populations and an increasingly adopted microbial control option. Fungal virulence in entomopathogenic ascomycetes can be modified by mycoviruses, viruses that infect fungi, whereas the possible role of these viruses on the physical and biochemical properties of the virus-containing fungal strains and on their ecological fitness has remained largely unexplored. Here, utilizing a Beauveria bassiana strain naturally infected with two mycoviruses, Beauveria bassiana partitivirus 2 (BbPV-2) and Beauveria bassiana polymycovirus 1 (BbPmV-1), we found that the mycovirus-containing strain is hypervirulent towards the experimental insect Galleria mellonella and shows major physical and biochemical changes in spore size, isoelectric point, and Pr1 activity, but even more impactful, the mycoviral infection confers a significant environmental- abiotic and biotic stress tolerance to the fungus. Hence, mycovirus infection expanded the temperature range for fungal growth and germination, and improved tolerance to osmotic stress, water stress, and UV-B radiation. Similarly, the antagonistic activity of the mycovirus-containing strain against Trichoderma harzianum was increased as compared to the mycovirus-free one. Taken together, these data suggest for the first time a mycovirus related adaptation of key traits indicators of environmental competence of a beneficial fungus, rendering these mycoviruses as potent tools for entomopathogenic fungal strain selection and development as mycoinsecticides., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Histone H2B ubiquitination (H2Bub) is positively linked to transcriptional activation, but the genetic programs affected by H2Bub to enhance drought tolerance remain largely unknown. Here, we show that OsbZIP27 interacts directly with OsHUB1/2 to regulate drought tolerance in rice by binding to the promoters of OsHAK1 and OsGLN1 to achieve H2Bub and transcriptional activation. Consistently, mutations in OsbZIP27 reduce transcription of OsHAK1 and OsGLN1, resulting in increased sensitivity to drought stress. Moreover, loss of OsHUB1 and OsHUB2 function causes hypersensitivity to drought stress, whereas OsHUB2 overexpression enhances drought tolerance. Together, our results indicate that OsbZIP27 coordinates with OsHUB1/2 to enhance rice drought tolerance by increasing H2Bub and expression of OsHAK1 and OsGLN1., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2024 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.)

The purpose of this study was to compare the internal and external load in continuous and intermittent small-sided games (SSG) formats. Eight semi-professional soccer players participated in the study, and they completed three protocols: (a) I-intermittent SSG protocol (Int-I, 4 sets of 4 min with a 3 min recovery); (b) Continuous SSG protocol (Con, 2 sets of 8 min with a 3 min recovery); (c) II-SSG protocol (Int-II, 4 sets of 4 min, where each set includes 1 min of exercise with varying recovery periods (10, 20, 30 s), with a 3 min recovery period between sets). A one-way analysis of variance (ANOVA) was used to analyze the dependent variables, with significance determined at p < 0.05. The three protocols differed in total distance covered and in distance covered at speeds >19 km/h, with the Int-II protocol resulting in the greatest distance covered ( p < 0.05). Additionally, players in the Con protocol exercised at a higher percentage of their maximum heart rate (%HRmax) ( p < 0.05), while the highest RPE value was observed in the Int-I interval protocol ( p < 0.05). The external load experienced by players in intermittent SSG protocols is higher, while internal load (%HRmax) remains relatively low. This effect is especially notable in the new intermittent exercise model proposed in this study, which incorporates progressively increasing recovery times within each exercise set. Coaches can use this model to increase players' external load without causing a heightened perception of fatigue.

Type 2 diabetes mellitus (T2DM) is characterised by endothelial dysfunction, leading to increased risk of cardiovascular disease. Emerging evidence suggest that HWI may favourably improve vascular function but data are limited in individual with T2DM. The aim was to investigate whether repeated hot water immersion (HWI) improved macrovascular, microvascular and central haemodynamic function in individuals with T2DM. Fourteen individuals completed a pre-post experimental study where participants were assessed pre- and post-8-10 × 1 h HWI sessions (40 °C water) undertaken within a 14-day period. During HWIs, body position was adjusted to clamp rectal temperature at 38.5-39.0 °C for the duration of the immersion. Stroke volume index (SVi), cardiac index (Q˙ i), resting heart rate (HR), systolic blood pressure (SBP), diastolic BP (DBP), brachial flow-mediated dilation (FMD) and cutaneous microvascular endothelial function (via transdermal iontophoresis) and plasma [nitrate] and [nitrite] (NOX; via ozone chemiluminescence) were assessed pre- and post HWI. Neither brachial FMD measures of macrovascular endothelial function (p = 0.43) or forearm microvascular function (ACh max, p = 0.63; ACh area under curve (AUC), p = 0.63; insulin max, p = 0.51; insulin AUC, p = 0.86) or NOX (p = 0.38) were changed. Q˙ i (p < 0.01), SVi (p < 0.02) and resting HR (p < 0.01) were all significantly reduced following the 10-days HWI intervention. SBP was reduced (p = 0.03), whereas DBP was unchanged (p = 0.56). HWI may represent an appropriate intervention to improve Q˙ I, SVi and BP in individuals with T2DM, but not macrovascular endothelial or cutaneous microvascular function., Competing Interests: Declaration of competing interest All authors report no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Pollen has an extraordinary ability to convert from a dry state to an extremely rapidly growing state. During pollination, pollen receives water and Ca 2+ from the contacting pistil, which will be a directional cue for pollen tube germination. The subsequent rapid activation of directional vesicular transport must support the pollen tube growth, but the molecular mechanism leading to this process is largely unknown. We established a luciferase-based pollination assay to screen genetic mutants defective in the early stage after pollination. We identified a plant-specific VPS13, Arabidopsis thaliana VPS13a as important for pollen germination, and studied its molecular function. AtVPS13a mutation severely affected pollen germination and lipid droplet discharge from the rough endoplasmic reticulum. Cellular accumulation patterns of AtVPS13a and a secretory vesicle marker were synchronized at the polarized site, with a slight delay to the local Ca 2+ elevation. We found a brief Ca 2+ spike after initiation of pollen hydration, which may be related to the directional cues for pollen tube emergence. Although this Ca 2+ dynamics after pollination was unaffected by the absence of AtVPS13a, the mutant suffered reduced cell wall deposition during pollen germination. AtVPS13a mediates pollen polarization, by regulating proper directional vesicular transport following Ca 2+ signaling for directional tube outgrowth., (© 2024 The Author(s). New Phytologist © 2024 New Phytologist Foundation.)

Corynebacterium diphtheriae is a multi-drug resistant bacteria responsible for the life-threatening respiratory illness, diphtheria which can lead to severe Nervous system disorders, mainly infecting the lungs, heart, and kidneys if left untreated. In the current study, Corynebacterium diphtheriae MtrA response regulator protein was targeted, which regulates a two-component system of bacterial pathogenesis, and initiates DNA replication and cell division. In the current study a computational approach have been described for drug development against C. diphtheriae infections by inhibiting MtrA protein by small molecules acting as potential inhibitors against it. Molecular docking analysis of the equilibrated MtrA protein revealed compound-0.2970, compound-0.3029, and compound-0.3016 from Asinex Library as the promising inhibitors based on their lowest binding energies (-9.8 kJ/mol, -9.2 kJ/mol, and -8.9 kJ/mol), highest gold scores (40.53, 47.41, and 48.41), drug-likeness and pharmacokinetic properties. The MD simulation studies of the identified top-ranked inhibitors at 100 ns elucidated the system stability and fluctuations in the binding pocket of MtrA protein. Molecular Dynamics Simulations of the top three docked complexes further revealed that the standard binding pocket was retained ensuring the system stability. The rearrangements of H-bonds, van der Waals, pi-pi, and solid hydrophobic interactions were also observed. The binding free energy calculations (MM/PBSA and MM/GBSA) suggested a fundamental binding capability of the ligand to the target receptor MtrA. Therefore, the current study has provided excellent candidates acting as potent inhibitors for developing therapeutic drugs against C. diphtheriae infections. However, in vivo and in vitro animal experiments and accurate clinical trials are needed to validate the potential inhibitory effect of these compounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Abiotic D-proteins that selectively bind to natural L-proteins have gained significant biotechnological interest. However, the underlying structural principles governing such heterochiral protein-protein interactions remain largely unknown. In this study, we present the de novo design of D-proteins consisting of 50-65 residues, aiming to target specific surface regions of L-proteins or L-peptides. Our designer D-protein binders exhibit nanomolar affinity toward an artificial L-peptide, as well as two naturally occurring proteins of therapeutic significance: the D5 domain of human tropomyosin receptor kinase A (TrkA) and human interleukin-6 (IL-6). Notably, these D-protein binders demonstrate high enantiomeric specificity and target specificity. In cell-based experiments, designer D-protein binders effectively inhibited the downstream signaling of TrkA and IL-6 with high potency. Moreover, these binders exhibited remarkable thermal stability and resistance to protease degradation. Crystal structure of the designed heterochiral D-protein-L-peptide complex, obtained at a resolution of 2.0 Å, closely resembled the design model, indicating that the computational method employed is highly accurate. Furthermore, the crystal structure provides valuable information regarding the interactions between helical L-peptides and D-proteins, particularly elucidating a novel mode of heterochiral helix-helix interactions. Leveraging the design of D-proteins specifically targeting L-peptides or L-proteins opens up avenues for systematic exploration of the mirror-image protein universe, paving the way for a diverse range of applications., Competing Interests: Competing interests: K.S., S.L., Y.Z., B.Z., T.W., L.L. and P.L. are inventors on a provisional patent application submitted by the Westlake University for the function of the d-proteins in this study., (© 2024. The Author(s).)

Lung cancer is the leading cause of cancer death globally, with non-small cell lung cancer accounting for the majority (85%) of cases. Standard treatments including chemotherapy and radiotherapy present multiple adverse effects. Medicinal plants, used for centuries, are traditionally processed by methods such as boiling and oral ingestion, However, water solubility, absorption, and hepatic metabolism reduce phytoceutical bioavailability. More recently, isolated molecular compounds from these plants can be extracted with these phytoceuticals administered either individually or as an adjunct with standard therapy. Phytoceuticals have been shown to alleviate symptoms, may reduce dosage of chemotherapy and, in some cases, enhance pharmaceutical mechanisms. Research has identified many phytoceuticals' actions on cancer-associated pathways, such as oncogenesis, the tumour microenvironment, tumour cell proliferation, metastasis, and apoptosis. The development of novel nanoparticle delivery systems such as solid lipid nanoparticles, liquid crystalline nanoparticles, and liposomes has enhanced the bioavailability and targeted delivery of pharmaceuticals and phytoceuticals. This review explores the biological pathways associated with non-small cell lung cancer, a diverse range of phytoceuticals, the cancer pathways they act upon, and the pros and cons of several nanoparticle delivery systems., (© 2024 The Author(s). Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

An increase in scholarly publishing has been accompanied by a proliferation of potentially illegitimate publishers (PIP), commonly known as "predatory publishers". These PIP often engage in fraudulent practices and publish articles that are not subject to the same scrutiny as those published in journals from legitimate publishers (LP). This places academics at risk, in particular students who utilize journal articles for learning and assignments. This analysis sought to characterise PIP in physiology, as this has yet to be determined, and identify overlaps in lists of PIP and LP used to provide guidance on legitimacy of journals. Searching seven databases (2 of PIP, 5 of LP), this analysis identified 67 potentially illegitimate journals (PIJ) that explicitly include "physiology" in their titles, with 8801 articles being published in them. Of these articles, 39% claimed to be indexed in GoogleScholar, and 9% were available on PubMed. This resulted in 17 publications 'infiltrating' PubMed and attracting >100 citations in the process. Overlap between lists of PIP and LP was present, with eight PIJ occurring in both LP and PIP lists. Two of these journals appeared to be 'phishing' journals, and six were genuine infiltrations into established databases; indicating that LP lists cannot be solely relied upon as proof a journal is legitimate. This analysis indicates that physiology is not immune to the threat of PIP, and that future work is required by educators to ensure students do not fall prey to their use.

Redox cycling of iron plays a pivotal role in both nutrient acquisition by living organisms and the geochemical cycling of elements in aquatic environments. In nature, iron cycling is mediated by microbial Fe(II)-oxidizers and Fe(III)-reducers or through the interplay of biotic and abiotic iron transformation processes. Here, we unveil a specific iron cycling process driven by one single phototrophic species, Rhodobacter ferrooxidans SW2. It exhibits the capability to reduce Fe(III) during bacterial cultivation. A c -type cytochrome is identified with Fe(III)-reducing activity, implying the linkage of Fe(III) reduction with the electron transport system. R. ferrooxidans SW2 can mediate iron redox transformation, depending on the availability of light and/or organic substrates. Iron cycling driven by anoxygenic photoferrotrophs is proposed to exist worldwide in modern and ancient environments. Our work not only enriches the theoretical basis of iron cycling in nature but also implies multiple roles of anoxygenic photoferrotrophs in iron transformation processes., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Kai-Li Wang et al.)

NK cells and macrophages constitute the predominant immune cell subsets in the decidua during the first trimester of pregnancy, with macrophages typically adopting an anti-inflammatory phenotype. Conversely, in the third trimester, macrophages undergo a shift towards a pro-inflammatory phenotype concurrent with a reduction in NK cell numbers. The direct regulatory impact of NK cells on macrophage phenotype remains poorly explored. In our investigation, we observed that ICAM1 + macrophages stimulate the expression of intracellular C3 in LFA1 + decidual NK cells. Notably, Cathepsin W within NK cells exhibit the potential to generate active C3b fragments, effectively inhibit the proinflammatory phenotype of macrophages by binding to VSIG4. Our study unveils a direct regulatory mechanism orchestrated by decidual NK cells over macrophages, providing a potential pathogenic explanation for recurrent spontaneous abortion., Competing Interests: Declarations Ethics approval and consent to participate All human samples used in the present study were obtained under the approval of the Ethics Committee of the University of Science and Technology of China (2022KY-015; Hefei, China). Competing interests The authors declare no potential conflicts of interest., (© 2024. The Author(s).)

This Technical Resource describes genome sequencing data for 61 isolates of the bacterial pathogen Xanthomonas campestris pv. campestris collected from Brassica and Raphanus crops between 2010 and 2021 in Serbia. We present the raw sequencing reads and annotated contig-level genome assemblies and determine the races of ten isolates. The data can be used to test hypotheses and phylogeographic analyses and inform the design of informative molecular markers for population genetics studies. When combined with phenotypic data, they could be used to dissect relationships between genotypes and phenotypes such as host range and virulence. Finally, these genome sequences expand our inventory of plasmids known to reside in this pathogen., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2024 The Authors.)

Captagon is a synthetic stimulant combining amphetamine and theophylline. Initially introduced in 1961 as a treatment for hyperactivity, depression, and narcolepsy, Captagon was later classified as a Schedule 1 controlled substance due to its addictive and hallucinogenic properties. Despite its global prohibition in 1986, the trade of counterfeit products is widespread, especially in south-east Europe and far-east Asia, with its production being on the rise in Middle Eastern regions. This paper presents a quantitative data-driven bibliometric analysis of the existing literature on Captagon up to July 2024. It aims to delineate the structure and development of knowledge surrounding the substance, including key contributing countries, authors, prominent sources, and recurring thematic keywords. The quantitative and data-driven results were then used to guide the narrative discussion on Captagon. Findings indicate that current research predominantly focuses on Captagon's use and impact in conflict zones, often exploring its interaction with other substances used by civilians and militias. Results also show a growing trend in Captagon research, with Saudi Arabia, Jordan, and Iraq emerging as main contributors to the literature. Despite the attention in specific regions, a considerable gap remains in understanding the mechanisms of action of Captagon (particularly regarding its metabolism, toxicology, mortality risk), and in developing protocols for its discontinuation. Additionally, the drug's inconsistent composition requires further analyses to better predict risks and establish effective management strategies. Addressing these gaps will be crucial for the development of novel interventions and policies to mitigate the adverse effects of Captagon and improve public health systems worldwide., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

There is increasing evidence that thirdhand exposure to e-cigarette vapor (e-vapor) can have detrimental effects on the lungs. However, whether maternal exposure during pregnancy results in harmful changes to the offspring is unknown. Using two different e-cigarette settings (low vs. high power), BALB/c mice were subjected to thirdhand e-vapor (e-vapor deposited onto towels, towels changed daily) in the absence or presence of nicotine, before, during, and after pregnancy. Male adult offspring were then infected with mouse-adapted influenza A virus (A/PR/8/34 H1N1; Flu) and lung and bone marrow immune cell responses were assessed 7 days postinfection. Maternal thirdhand exposure to low-power ( M LP) or high-power ( M HP) e-vapor with nicotine ( M LP + NIC and M HP + NIC, respectively) increased the percentage of lung immune cells and neutrophils in the bone marrow. Interestingly, Flu-infected offspring from M LP + NIC and M HP + NIC groups had lower percentages of lung alveolar macrophages and more pronounced increases in neutrophils in the bone marrow, when compared with offspring from M Sham Flu controls. Flu infection also decreased the percentage of lung CD4+ T cells and increased the percentage of lung CD8+ T cells, irrespective of maternal exposure ( M LP -/+ NIC and M HP -/+ NIC). Significantly, both M LP + NIC and M HP + NIC resulted in blunted activation of lung CD4+ T cells, but only M LP + NIC caused blunted activation of lung CD8+ T cells. Together, we show for the first time that maternal thirdhand exposure to e-vapor results in significant, long-lived effects on lung and bone marrow immune cell responses in offspring at baseline and response to Flu infection. NEW & NOTEWORTHY Maternal exposure to environmental residues of e-cigarette use has significant effects on immune cell responses in the lungs and bone marrow of offspring at both baseline and in response to influenza A virus (Flu) infection.

The oxidative pentose phosphate (OPP) pathway provides metabolic intermediates for the shikimate pathway and directs carbon flow to the biosynthesis of aromatic amino acids (AAAs), which serve as basic protein building blocks and precursors of numerous metabolites essential for plant growth. However, genetic evidence linking the two pathways is largely unclear. In this study, we identified 6-phosphogluconate dehydrogenase 2 (PGD2), the rate-limiting enzyme of the cytosolic OPP pathway, through suppressor screening of arogenate dehydrogenase 2 (adh2) in Arabidopsis. Our data indicated that a single amino acid substitution at position 63 (glutamic acid to lysine) of PGD2 enhanced its enzyme activity by facilitating the dissociation of products from the active site of PGD2, thus increasing the accumulation of AAAs and partially restoring the defective phenotype of adh2. Phylogenetic analysis indicated that the point mutation occurred in a well-conserved amino acid residue. Plants with different amino acids at this conserved site of PGDs confer diverse catalytic activities, thus exhibiting distinct AAAs producing capability. These findings uncover the genetic link between the OPP pathway and AAAs biosynthesis through PGD2. The gain-of-function point mutation of PGD2 identified here could be considered as a potential engineering target to alter the metabolic flux for the production of AAAs and downstream compounds., (© 2024. Science China Press.)

α-Melanocyte stimulating hormone (α-MSH) is a peptide hormone released from the intermediate lobe of the pituitary which regulates body pigmentation. In addition to the pituitary, α-MSH is also produced in the midbrain, and exerts both anorexigenic and an anxiogenic actions. Acyl ghrelin and cholecystokinin are peripheral hormones derived from the digestive tract which affect the brain to control food intake and feeding behavior in vertebrates. In the present study, hypothesizing that plasma α-MSH may also stimulate the brain and exert central effects, we examined whether peripherally administered α-MSH affects food intake and psychomotor activity using a goldfish model. Intraperitoneal (IP) administration of α-MSH at 100 pmol g -1 body weight (BW) reduced food consumption and enhanced thigmotaxis. These α-MSH-induced actions were blocked by intracerebroventricular administration of HS024, an antagonist of the melanocortin 4 receptor (MC4R), at 50 pmol g -1 BW, whereas these actions were not attenuated by pretreatment with an IP-injected excess amount of capsaicin, a neurotoxin that destroys primary sensory (vagal and splanchnic) afferents, at 160 nmol g -1 BW. Transcripts for the MC4R showed higher expression in the diencephalon in other regions of the brain. These results suggest that, in goldfish, IP administered α-MSH is taken up by the brain, and also acts as anorexigenic and anxiogenic factor via the MC4R signaling pathway., (© 2024 British Society for Neuroendocrinology.)

Pandemics originating from zoonotic viruses have posed significant threats to human health and agriculture. Recent discoveries have revealed that wild-rice plants also harbour viral pathogens capable of severely impacting rice production, a cornerstone food crop. In this study, we conducted virome analysis on ~1000 wild-rice individual colonies and discovered a novel single-strand positive-sense RNA virus prevalent in these plants. Through comprehensive genomic characterization and comparative sequence analysis, this virus was classified as a new species in the genus Polerovirus, designated Rice less tiller virus (RLTV). Our investigations elucidated that RLTV could be transmitted from wild rice to cultivated rice via a specific insect vector, the aphid Rhopalosiphum padi, causing less tiller disease symptoms in rice plants. We generated an infectious cDNA clone for RLTV and demonstrated systemic infection of rice cultivars and induction of severe disease symptoms following mechanical inoculation or stable genetic transformation. We further illustrated transmission of RLTV from stable transgenic lines to healthy rice plants by the aphid vector, leading to the development of disease symptoms. Notably, our database searches showed that RLTV and another polerovirus isolated from a wild plant species are widely circulating not only in wild rice but also cultivated rice around the world. Our findings provide strong evidence for a wild plant origin for rice viruses and underscore the imminent threat posed by aphid-transmitted rice Polerovirus to rice cultivar., (© 2024 John Wiley & Sons Ltd.)

Dysfunction of the ribosome manifests during cellular senescence and contributes to tissue aging, functional decline, and development of aging-related disorders in ways that have remained enigmatic. Here, we conducted a comprehensive CRISPR-based loss-of-function (LOF) screen of ribosome-associated genes (RAGs) in human mesenchymal progenitor cells (hMPCs). Through this approach, we identified ribosomal protein L22 (RPL22) as the foremost RAG whose deficiency mitigates the effects of cellular senescence. Consequently, absence of RPL22 delays hMPCs from becoming senescent, while an excess of RPL22 accelerates the senescence process. Mechanistically, we found in senescent hMPCs, RPL22 accumulates within the nucleolus. This accumulation triggers a cascade of events, including heterochromatin decompaction with concomitant degradation of key heterochromatin proteins, specifically heterochromatin protein 1γ (HP1γ) and heterochromatin protein KRAB-associated protein 1 (KAP1). Subsequently, RPL22-dependent breakdown of heterochromatin stimulates the transcription of ribosomal RNAs (rRNAs), triggering cellular senescence. In summary, our findings unveil a novel role for nucleolar RPL22 as a destabilizer of heterochromatin and a driver of cellular senescence, shedding new light on the intricate mechanisms underlying the aging process., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Exploiting electrogenic microorganisms as unconventional chassis hosts offers potential solutions to global energy and environmental challenges. However, their limited electrogenic efficiency and metabolic versatility, due to genetic and metabolic constraints, hinder broader applications. Herein, we developed a multifaceted approach to fabricate an enhanced electrogenic chassis, starting with streamlining the genome by removing extrachromosomal genetic material. This reduction led to faster lactate consumption, higher intracellular NADH/NAD + and ATP/ADP levels, and increased growth and biomass accumulation, as well as promoted electrogenic activity. Transcriptome profiling showed an overall activation of cellular metabolism. We further established a molecular toolkit with a vector vehicle incorporating native replication block and refined promoter components for precise gene expression control. This enabled engineered primary metabolism for greater environmental robustness and fine-tuned extracellular electron transfer (EET) for improved efficiency. The enhanced chassis demonstrated substantially improved pollutant biodegradation and radionuclide removal, establishing a new paradigm for utilizing electrogenic organisms as novel biotechnology chassis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Epidemiological research has failed to confirm laterality of lesion site as a neurobiological source of post-stroke psychopathology. However, acquired communication disorders have proved to be a key risk factor for depression, apart from established parameters such as pre-stroke psychopathology and physical immobility., Objectives: The present work examines a new predictor of post-stroke psychopathology: psychological flexibility. This concept describes an accepting attitude toward irreversible loss following stroke while using remaining agency., Design: Overall, 70 individuals engaged in a cross-sectional study conducted in the subacute stage after an ischemic or hemorrhagic event, a period with elevated prevalence of mental-health problems (2 weeks to 6 months after stroke)., Methods: Outcomes included standardized self-report and clinician-rated measures of depression, anxiety disorders, and general psychopathology (Beck Depression Inventory; Hospital Anxiety and Depression Scale; ICD-10 Symptom Rating; Hamilton Depression Rating Scale) alongside lack of psychological flexibility (Acceptance and Action Questionnaire II). The study design controlled for pre-stroke psychopathology and physical immobility (Barthel Index)., Results: Partial correlation analyses revealed a significant medium-to-large association between the entire set of clinical outcomes and lack of psychological flexibility ( r  ⩽ 0.62, p  < 0.001). In moderator analyses, the magnitude of this association did not vary significantly with diagnosis of acquired communication disorders (i.e., aphasia, apraxia of speech or dysarthria; separately or combined)., Conclusion: The current results demonstrate a substantial link between post-stroke psychopathology and psychological flexibility. This finding opens new avenues for research on depression and other mental-health problems in stroke survivors with and without acquired communication disorders., Registration: www.drks.de; identifier: DRKS00031204., (© The Author(s), 2024.)

It remains unknown whether the Chinese tree shrew, regarded as the closest sister of primate, has evolved a dorsolateral prefrontal cortex (dlPFC) comparable with primates that is characterized by a fourth layer (L4) enriched with granular cells and reciprocal connections with the mediodorsal nucleus (MD). Here, we reported that following AAV-hSyn-EGFP expression in the MD neurons, the fluorescence micro-optical sectioning tomography revealed their projection trajectories and targeted brain areas, such as the hippocampus, the corpus striatum, and the dlPFC. Cre-dependent transsynaptic viral tracing identified the MD projection terminals that targeted the L4 of the dlPFC, in which the presence of granular cells was confirmed via cytoarchitectural studies by using the Nissl, Golgi, and vGlut2 stainings. Additionally, the L5/6 of the dlPFC projected back to the MD. These results suggest that the tree shrew has evolved a primate-like dlPFC which can serve as an alternative for studying cognition-related functions of the dlPFC., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Nie et al.)

Background: First-episode schizophrenia (FES) is a complex and progressive psychiatric disorder. The etiology of FES involves genetic, environmental, and neurobiological factors. This study investigates the association between alterations in structural-functional (SC-FC) coupling and transcriptional expression in FES., Methods: This study encompassed a cohort of 214 participants, comprising 111 FES patients and 103 healthy controls (HC). Furthermore, we examined the abnormalities within SC-FC coupling in FES and their correlations with meta-analytic cognitive terms, neurotransmitters, and transcriptional patterns through partial least squares regression (PLS), involving similarity with other psychiatric disorders or psychiatric-related diseases, functional enrichments, special cell types, peripheral inflammation, and cortical layers., Results: FES patients exhibited lower SC-FC coupling in the visual, sensorimotor, and ventral attention networks compared to controls. Furthermore, case-control t-maps revealed a negative correlation with neurotransmitters such as serotonin and dopamine, while showing a positive correlation with opioids. Positive t-maps were associated with cognitive functions, including reasoning, judgment, and action, whereas negative t-maps correlated with cognitive functions such as learning, stress, and mood. Moreover, there was a significant overlap between genes linked to abnormalities in SC-FC coupling and those dysregulated in inflammatory bowel diseases. PLS2- genes linked to SC-FC coupling demonstrated significant enrichment in pathways related to immunity and inflammation, as well as in cortical layers I and V. Conversely, PLS2 + genes were primarily enriched in synaptic signaling processes, specific excitatory neurons, and layers II and IV. Additionally, changes in SC-FC coupling were negatively associated with gene expression related to antipsychotics and lymphocytes., Conclusions: These findings offer a new perspective on the complex interplay between SC-FC coupling abnormalities and transcriptional expression in the initial phases of schizophrenia., (© 2024. The Author(s).)

Many insects are obligatorily associated with and dependent on specific microbial species as essential mutualistic partners. In the host insects, such microbial mutualists are usually maintained in specialized cells or organs, called bacteriocytes or symbiotic organs. Hence, potentially exponential microbial growth cannot be realized but must be strongly constrained by spatial and resource limitations within the host cells or tissues. How such endosymbiotic bacteria grow, divide, and proliferate is important for understanding the interactions and dynamics underpinning intimate host-microbe symbiotic associations. Here we report that Blattabacterium , the ancient and essential endosymbiont of cockroaches, exhibits unexpectedly high rates of cell division (20%-58%) and, in addition, the cell division is asymmetric (average asymmetry index >1.5) when isolated from the German cockroach Blattella germanica . The asymmetric division of endosymbiont cells at high frequencies was observed irrespective of host tissues (fat bodies vs ovaries) or developmental stages (adults vs nymphs vs embryos) of B. germanica , and also observed in several different cockroach species. By contrast, such asymmetric and frequent cell division was observed neither in Buchnera , the obligatory bacterial endosymbiont of aphids, nor in Pantoea , the obligatory bacterial gut symbiont of stinkbugs. Comparative genomics of cell division-related genes uncovered that the Blattabacterium genome lacks the Min system genes that determine the cell division plane, which may be relevant to asymmetric cell division. These observations combined with comparative symbiont genomics provide insight into what processes and regulations may underpin the growth, division, and proliferation of such bacterial mutualists continuously constrained under within-host conditions.IMPORTANCEDiverse insects are dependent on specific bacterial mutualists for their survival and reproduction. Due to the long-lasting coevolutionary history, such symbiotic bacteria tend to exhibit degenerative genomes and suffer uncultivability. Because of their microbiological fastidiousness, the cell division patterns of such uncultivable symbiotic bacteria have been poorly described. Here, using fine microscopic and quantitative morphometric approaches, we report that, although bacterial cell division usually proceeds through symmetric binary fission, Blattabacterium , the ancient and essential endosymbiont of cockroaches, exhibits frequent and asymmetric cell division. Such peculiar cell division patterns were not observed with other uncultivable essential symbiotic bacteria of aphids and stinkbugs. Gene repertoire analysis revealed that the molecular machinery for regulating the bacterial cell division plane are lost in the Blattabacterium genome, suggesting the possibility that the general trend toward the reductive genome evolution of symbiotic bacteria may underpin their bizarre cytological/morphological traits., Competing Interests: The authors declare no conflict of interest.

2C is a highly conserved picornaviral non-structural protein with ATPase activity and plays a multifunctional role in the viral life cycle as a promising target for anti-picornavirus drug development. While the structure-function of enteroviral 2Cs have been well studied, cardioviral 2Cs remain largely uncharacterized. Here, an endogenous ATP molecule was identified in the crystal structure of 2C from encephalomyocarditis virus (EMCV, Cardiovirus A). The ATP is bound into the ATPase active site with a unique compact conformation. Notably, the γ-phosphate of ATP directly interacts with Arg311 (conserved in cardioviral 2Cs), and its mutation significantly inhibits the ATPase activity. Unexpectedly, this mutation remarkably promotes 2C self-oligomerization and viral replication efficiency. Molecular dynamic simulations showed that the Arg311 side chain is highly dynamic, indicating it may function as a switch between the activation state and the inhibition state of ATPase activity. A hexameric ring model of EMCV 2C full length indicated that the C-terminal helix may get close to the N-terminal amphipathic helices to form a continuous positive region for RNA binding. The RNA-binding studies of EMCV 2C revealed that the RNA length is closely associated with the RNA-binding affinities and indicated that the substrate may wrap around the outer surface of the hexamer. Our studies provide a biochemical framework to guide the characterization of EMCV 2C and the essential role of arginine in cardioviral 2C functions., Importance: Encephalomyocarditis virus (Cardiovirus A) is the causative agent of the homonymous disease, which may induce myocarditis, encephalitis, and reproductive disorders in various mammals. 2C protein is functionally indispensable and a promising target for drug development involving broad-spectrum picornaviral inhibitors. Here, an endogenous ATP molecule with a unique conformation was discovered by a combination of protein crystallography and high-performance liquid chromatography in the encephalomyocarditis virus (EMCV) 2C structure. Biochemical and structural characterization analysis of EMCV 2C revealed the critical role of conserved Arg311 in ATPase activity and self-oligomerization of EMCV 2C. The viral replication kinetics and infectivity study suggested that the residue negatively regulated the infectivity titer and virus encapsulation efficiency of EMCV and is, therefore, crucial for 2C protein to promote viral replication. Our systemic structure-function analysis provides unique insights into the function and regulation mechanism of cardioviral 2C protein., Competing Interests: The authors declare no conflict of interest.

Drought poses a significant challenge to global crop productivity, necessitating innovative approaches to bolster plant resilience. Leveraging transgenic technology to bolster drought tolerance in crops emerges as a promising strategy for addressing the demands of a rapidly growing global populace. AtZAT10/STZ1, a C2H2-type zinc finger protein transcription factor has shown to significantly improve Arabidopsis' tolerance to various abiotic stresses. In this study, we reports that AtSTZ1 confers notable drought resistance in upland cotton ( Gossypium hirsutum ), amplifying cotton fiber yield under varying conditions, including irrigated and water-limited environments, in field trials. Notably, AtSTZ1 -overexpressing transgenic cotton showcases enhanced drought resilience across critical growth stages, including seed germination, seedling establishment, and reproductive phases. Morphological analysis reveals an expanded root system characterized by an elongated taproot system, increased lateral roots, augmented root biomass, and enlarged cell dimensions from transgenic cotton plants. Additionally, higher contents of proline, chlorophyll, soluble sugars, and enhanced ROS-scavenging enzyme activities are observed in leaves of transgenic plants subjected to drought, underscoring improved physiological adaptations. Furthermore, transgenic lines exhibit heightened photosynthetic rate, increased water use efficiency, and larger stomatal and epidermal cell sizes, coupled with a decline in leaf stomatal conductance and density, as well as diminished transpiration rates compared to the wild type counterparts. Transcriptome profiling unveils 106 differentially expressed genes in transgenic cotton leaves post-drought treatment, including protein kinases, transcription factors, aquaporins, and heat shock proteins, indicative of an orchestrated stress response. Collectively, these findings underscore the capacity of AtSTZ1 to augment the expression of abiotic stress-related genes in cotton following drought conditions, thus presenting a compelling candidate for genetic manipulation aimed at enhancing crop resilience., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Qin, He, Yang, Zhang, Li, Zhu, Xu, Jiao, Xiang, Wang and Wu.)

Background: Understanding the interaction between environmental conditions, crop yields, and soil health is crucial for sustainable agriculture in a changing climate. Management practices to limit disease are a balancing act. For example, in potato production, dry conditions favour common scab (Streptomyces spp.) and wet conditions favour blackleg disease (Pectobacterium spp.). The exact mechanisms involved and how these link to changes in the soil microbiome are unclear. Our objectives were to test how irrigation management and bacterial pathogen load in potato seed stocks impact: (i) crop yields; (ii) disease development (blackleg or common scab); and (iii) soil microbial community dynamics., Methods: We used stocks of seed potatoes with varying natural levels of Pectobacterium (Jelly [high load], Jelly [low load] and Estima [Zero - no Pectobacterium]). Stocks were grown under four irrigation regimes that differed in the timing and level of watering. The soil microbial communities were profiled using amplicon sequencing at 50% plant emergence and at harvest. Generalised linear latent variable models and an annotation-free mathematical framework approach (ensemble quotient analysis) were then used to show the interacting microbes with irrigation regime and Pectobacterium pathogen levels., Results: Irrigation increased blackleg symptoms in the plots planted with stocks with low and high levels of Pectobacterium (22-34%) but not in the zero stock (2-6%). However, withholding irrigation increased common scab symptoms (2-5%) and reduced crop yields. Irrigation did not impact the composition of the soil microbiome, but planting stock with a high Pectobacterium burden resulted in an increased abundance of Planctomycetota, Anaerolinea and Acidobacteria species within the microbiome. Ensemble quotient analysis highlighted the Anaerolinea taxa were highly associated with high levels of Pectobacterium in the seed stock and blackleg symptoms in the field., Conclusions: We conclude that planting seed stocks with a high Pectobacterium burden alters the abundance of specific microbial species within the soil microbiome and suggest that managing pathogen load in seed stocks could substantially affect soil communities, affecting crop health and productivity. Video Abstract., (© 2024. The Author(s).)

The amyloid fibrils of α-synuclein (α-syn) are crucial in the pathology of Parkinson's disease (PD), with the intrinsically disordered region (IDR) of its C-terminal playing a key role in interacting with receptors like LAG3 and RAGE, facilitating pathological neuronal spread and inflammation. In this study, we identified Givinostat (GS) as an effective inhibitor that disrupts the interaction of α-syn fibrils with receptors such as LAG3 and RAGE through high-throughput screening. By exploring the structure-activity relationship and optimizing GS, we developed several lead compounds, including GSD-16-24. Utilizing solution-state and solid-state NMR, along with cryo-EM techniques, we demonstrated that GSD-16-24 binds directly to the C-terminal IDR of α-syn monomer and fibril, preventing the fibril from binding to the receptors. Furthermore, GSD-16-24 significantly inhibits the association of α-syn fibrils with membrane receptors, thereby reducing neuronal propagation and pro-inflammatory effects of α-syn fibrils. Our findings introduce a novel approach to mitigate the pathological effects of α-syn fibrils by targeting their IDR with small molecules, offering potential leads for the development of clinical drugs to treat PD.