In vivo single-molecule RNA structural profiling.

Cellular RNAs exhibit substantial heterogeneity in structure and function. Recently, Yang et al. developed an in vivo single-molecule RNA structure profiling methodology and revealed that individual isoforms of noncoding transcripts adopt multiple diverse and functionally relevant structural conformations, which change in abundance and structure in response to temperature conditions.

Sex differences in the pleiotropy of hearing difficulty with imaging-derived phenotypes: a brain-wide investigation.

Hearing difficulty (HD) is a major health burden in older adults. While ageing-related changes in the peripheral auditory system play an important role, genetic variation associated with brain structure and function could also be involved in HD predisposition. We analysed a large-scale HD genome-wide association study (GWAS; ntotal = 501 825, 56% females) and GWAS data related to 3935 brain imaging-derived phenotypes (IDPs) assessed in up to 33 224 individuals (52% females) using multiple MRI modalities. To investigate HD pleiotropy with brain structure and function, we conducted genetic correlation, latent causal variable, Mendelian randomization and multivariable generalized linear regression analyses. Additionally, we performed local genetic correlation and multi-trait co-localization analyses to identify genomic regions and loci implicated in the pleiotropic mechanisms shared between HD and brain IDPs. We observed a widespread genetic correlation of HD with 120 IDPs in females, 89 in males and 171 in the sex-combined analysis. The latent causal variable analysis showed that some of these genetic correlations could be due to cause-effect relationships. For seven of them, the causal effects were also confirmed by the Mendelian randomization approach: vessel volume→HD in the sex-combined analysis; hippocampus volume→HD, cerebellum grey matter volume→HD, primary visual cortex volume→HD and HD→fluctuation amplitudes of node 46 in resting-state functional MRI dimensionality 100 in females; global mean thickness→HD and HD→mean orientation dispersion index in superior corona radiata in males. The local genetic correlation analysis identified 13 pleiotropic regions between HD and these seven IDPs. We also observed a co-localization signal for the rs13026575 variant between HD, primary visual cortex volume and SPTBN1 transcriptomic regulation in females. Brain structure and function may have a role in the sex differences in HD predisposition via possible cause-effect relationships and shared regulatory mechanisms.

The flagellar motor protein FliL forms a scaffold of circumferentially positioned rings required for stator activation.

The flagellar motor stator is an ion channel nanomachine that assembles as a ring of the MotA5MotB2 units at the flagellar base. The role of accessory proteins required for stator assembly and activation remains largely enigmatic. Here, we show that one such assembly factor, the conserved protein FliL, forms an integral part of the Helicobacter pylori flagellar motor in a position that colocalizes with the stator. Cryogenic electron tomography reconstructions of the intact motor in whole wild-type cells and cells lacking FliL revealed that the periplasmic domain of FliL (FliL-C) forms 18 circumferentially positioned rings integrated with the 18 MotAB units. FliL-C formed partial rings in the crystal, and the crystal structure-based full ring model was consistent with the shape of the rings observed in situ. Our data suggest that each FliL ring is coaxially sandwiched between the MotA ring and the dimeric periplasmic MotB moiety of the stator unit and that the central hole of the FliL ring has density that is consistent with the plug/linker region of MotB in its extended, active conformation. Significant structural similarities were found between FliL-C and stomatin/prohibitin/flotillin/HflK/C domains of scaffolding proteins, suggesting that FliL acts as a scaffold. The binding energy released upon association of FliL with the stator units could be used to power the release of the plug helices. The finding that isolated FliL-C forms stable partial rings provides an insight into the putative mechanism by which the FliL rings assemble around the stator units.

Interacting myosin head dynamics and their modification by 2'-deoxy-ADP.

The contraction of striated muscle is driven by cycling myosin motor proteins embedded within the thick filaments of sarcomeres. In addition to cross-bridge cycling with actin, these myosin proteins can enter an inactive, sequestered state in which the globular S1 heads rest along the thick filament surface and are inhibited from performing motor activities. Structurally, this state is called the interacting heads motif (IHM) and is a critical conformational state of myosin that regulates muscle contractility and energy expenditure. Structural perturbation of the sequestered state can pathologically disrupt IHM structure and the mechanical performance of muscle tissue. Thus, the IHM state has become a target for therapeutic intervention. An ATP analogue called 2'-deoxy-ATP (dATP) is a potent myosin activator that destabilizes the IHM. Here, we use molecular dynamics simulations to study the molecular mechanisms by which dATP modifies the structure and dynamics of myosin in a sequestered state. Simulations of the IHM state containing ADP.Pi in both nucleotide binding pockets revealed dynamic motions of the blocked head - free head interface, light chain binding domain, and S2 in this 'inactive' state of myosin. Replacement of ADP.Pi by dADP.Pi triggered a series of structural changes that increased heterogeneity among residue contact pairs at the blocked head - free head interface and a 14% decrease in the interaction energy at the interface. Dynamic changes to this interface were accompanied by dynamics in the light chain binding region. A comparative analysis of these dynamics predicted new structural sites that may affect IHM stability.

Astrocyte coverage of excitatory synapses correlates to measures of synapse structure and function in ferret primary visual cortex.

Most excitatory synapses in the mammalian brain are contacted or ensheathed by astrocyte processes, forming tripartite synapses. Astrocytes are thought to be critical regulators of the structural and functional dynamics of synapses. While the degree of synaptic coverage by astrocytes is known to vary across brain regions and animal species, the reason for and implications of this variability remains unknown. Further, how astrocyte coverage of synapses relates to in vivo functional properties of individual synapses has not been investigated. Here, we characterized astrocyte coverage of synapses of pyramidal neurons in the ferret visual cortex and, using correlative light and electron microscopy, examined their relationship to synaptic strength and sensory-evoked Ca2+ activity. Nearly, all synapses were contacted by astrocytes, and most were contacted along the axon-spine interface. Structurally, we found that the degree of synaptic astrocyte coverage directly scaled with synapse size and postsynaptic density complexity. Functionally, we found that the amount of astrocyte coverage scaled with how selectively a synapse responds to a particular visual stimulus and, at least for the largest synapses, scaled with the reliability of visual stimuli to evoke postsynaptic Ca2+ events. Our study shows astrocyte coverage is highly correlated with structural metrics of synaptic strength of excitatory synapses in the visual cortex and demonstrates a previously unknown relationship between astrocyte coverage and reliable sensory activation.

The fix is not yet in: recommendation for fixation of lungs within physiological/pathophysiological volume range in preclinical pulmonary structure-function studies.

Quantitative characterization of lung structures by morphometrical or stereological analysis of histological sections is a powerful means of elucidating pulmonary structure-function relations. The overwhelming majority of studies, however, fix lungs for histology at pressures outside the physiological/pathophysiological respiratory volume range. Thus, valuable information is being lost. In this perspective article, we argue that investigators performing pulmonary histological studies should consider whether the aims of their studies would benefit from fixation at functional transpulmonary pressures, particularly those of end-inspiration and end-expiration. We survey the pressures at which lungs are typically fixed in preclinical structure-function studies, provide examples of conditions that would benefit from histological evaluation at functional lung volumes, summarize available fixation methods, discuss alternative imaging modalities, and discuss challenges to implementing the suggested approach and means of addressing those challenges. We aim to persuade investigators that modifying or complementing the traditional histological approach by fixing lungs at minimal and maximal functional volumes could enable new understanding of pulmonary structure-function relations.

Mucopolysaccharidosis (MPS IIIA) mice have increased lung compliance and airway resistance, decreased diaphragm strength, and no change in alveolar structure.

Mucopolysaccharidosis type IIIA (MPS IIIA) is characterized by neurological and skeletal pathologies caused by reduced activity of the lysosomal hydrolase, sulfamidase, and the subsequent primary accumulation of undegraded heparan sulfate (HS). Respiratory pathology is considered secondary in MPS IIIA and the mechanisms are not well understood. Changes in the amount, metabolism, and function of pulmonary surfactant, the substance that regulates alveolar interfacial surface tension and modulates lung compliance and elastance, have been reported in MPS IIIA mice. Here we investigated changes in lung function in 20-wk-old control and MPS IIIA mice with a closed and open thoracic cage, diaphragm contractile properties, and potential parenchymal remodeling. MPS IIIA mice had increased compliance and airway resistance and reduced tissue damping and elastance compared with control mice. The chest wall impacted lung function as observed by an increase in airway resistance and a decrease in peripheral energy dissipation in the open compared with the closed thoracic cage state in MPS IIIA mice. Diaphragm contractile forces showed a decrease in peak twitch force, maximum specific force, and the force-frequency relationship but no change in muscle fiber cross-sectional area in MPS IIIA mice compared with control mice. Design-based stereology did not reveal any parenchymal remodeling or destruction of alveolar septa in the MPS IIIA mouse lung. In conclusion, the increased storage of HS which leads to biochemical and biophysical changes in pulmonary surfactant also affects lung and diaphragm function, but has no impact on lung or diaphragm structure at this stage of the disease.NEW & NOTEWORTHY Heparan sulfate storage in the lungs of mucopolysaccharidosis type IIIA (MPS IIIA) mice leads to changes in lung function consistent with those of an obstructive lung disease and includes an increase in lung compliance and airway resistance and a decrease in tissue elastance. In addition, diaphragm muscle contractile strength is reduced, potentially further contributing to lung function impairment. However, no changes in parenchymal lung structure were observed in mice at 20 wk of age.

Lack of evidence that Pseudomonas aeruginosa AmpDh3-PA0808 constitute a type VI secretion system effector-immunity pair.

Type VI secretion systems (T6SSs) are cell envelope-spanning protein complexes that Gram-negative bacteria use to inject a diverse arsenal of antibacterial toxins into competitor cells. Recently, Wang et al. reported that the H2-T6SS of Pseudomonas aeruginosa delivers the peptidoglycan recycling amidase, AmpDh3, into the periplasm of recipient cells where it is proposed to act as a peptidoglycan degrading toxin. They further reported that PA0808, the open reading frame downstream of AmpDh3, encodes an immunity protein that localizes to the periplasm where it binds to and inactivates intercellularly delivered AmpDh3, thus protecting against its toxic activity. Given that AmpDh3 has an established role in cell wall homeostasis and that no precedent exists for cytosolic enzymes moonlighting as T6SS effectors, we attempted to replicate these findings. We found that cells lacking PA0808 are not susceptible to bacterial killing by AmpDh3 and that PA0808 and AmpDh3 do not physically interact in vitro or in vivo. Additionally, we found no evidence that AmpDh3 is exported from cells, including by strains with a constitutively active H2-T6SS. Finally, subcellular fractionation experiments and a 1.97 Å crystal structure reveal that PA0808 does not contain a canonical signal peptide or localize to the correct cellular compartment to confer protection against a cell wall targeting toxin. Taken together, these results cast doubt on the assertion that AmpDh3-PA0808 constitutes an H2-T6SS effector-immunity pair.

Scaling up Functional Analyses of the G Protein-Coupled Receptor Rhodopsin.

Eukaryotic cells use G protein-coupled receptors (GPCRs) to convert external stimuli into internal signals to elicit cellular responses. However, how mutations in GPCR-coding genes affect GPCR activation and downstream signaling pathways remain poorly understood. Approaches such as deep mutational scanning show promise in investigations of GPCRs, but a high-throughput method to measure rhodopsin activation has yet to be achieved. Here, we scale up a fluorescent reporter assay in budding yeast that we engineered to study rhodopsin's light-activated signal transduction. Using this approach, we measured the mutational effects of over 1200 individual human rhodopsin mutants, generated by low-frequency random mutagenesis of the GPCR rhodopsin (RHO) gene. Analysis of the data in the context of rhodopsin's three-dimensional structure reveals that transmembrane helices are generally less tolerant to mutations compared to flanking helices that face the lipid bilayer, which suggest that mutational tolerance is contingent on both the local environment surrounding specific residues and the specific position of these residues in the protein structure. Comparison of functional scores from our screen to clinically identified rhodopsin disease variants found many pathogenic mutants to be loss of function. Lastly, functional scores from our assay were consistent with a complex counterion mechanism involved in ligand-binding and rhodopsin activation. Our results demonstrate that deep mutational scanning is possible for rhodopsin activation and can be an effective method for revealing properties of mutational tolerance that may be generalizable to other transmembrane proteins.

Glutamine maintains the stability of alveolar structure and function after lung transplantation by inhibiting autophagy.

Excessive autophagy may lead to degradation and damage of alveolar epithelial cells after lung transplantation, eventually leading to alveolar epithelial cell loss, affecting the structural integrity and function of alveoli. Glutamine (Gln), a nutritional supplement, regulates autophagy through multiple signaling pathways. In this study, we explored the protective role of Gln on alveolar epithelial cells by inhibiting autophagy. In vivo, a rat orthotopic lung transplant model was carried out to evaluate the therapeutic effect of glutamine. Ischemia/reperfusion (I/R) induced alveolar collapse, edema, epithelial cell apoptosis, and inflammation, which led to a reduction of alveolar physiological function, such as an increase in peak airway pressure, and a decrease in lung compliance and oxygenation index. In comparison, Gln preserved alveolar structure and function by reducing alveolar apoptosis, inflammation, and edema. In vitro, a hypoxia/reoxygenation (H/R) cell model was performed to simulate IR injury on mouse lung epithelial (MLE) cells and human lung bronchus epithelial (Beas-2B) cells. H/R impaired the proliferation of epithelial cells and triggered cell apoptosis. In contrast, Gln normalized cell proliferation and suppressed I/R-induced cell apoptosis. The activation of mTOR and the downregulation of autophagy-related proteins (LC3, Atg5, Beclin1) were observed in Gln-treated lung tissues and alveolar epithelial cells. Both in vivo and in vitro, rapamycin, a classical mTOR inhibitor, reversed the beneficial effects of Gln on alveolar structure and function. Taken together, Glnpreserved alveolar structure and function after lung transplantation by inhibiting autophagy.

Recent advances in the multifaceted functions of Cys2/His2-type zinc finger proteins in plant growth, development, and stress responses.

Recent research has highlighted the importance of Cys2/His2-type zinc finger proteins (C2H2-ZFPs) in plant growth and in responses to various stressors, and the complex structures of C2H2-ZFP networks and the molecular mechanisms underlying their responses to stress have received considerable attention. Here, we review the structural characteristics and classification of C2H2-ZFPs, and consider recent research advances in their functions. We systematically introduce the roles of these proteins across diverse aspects of plant biology, encompassing growth and development, and responses to biotic and abiotic stresses, and in doing so hope to lay the foundations for further functional studies of C2H2-ZFPs in the future.

Progress in the Use of Echocardiography in Patients with Tumors.

Advances in cancer treatment have increased patient survival rates, shifting clinical focus towards minimizing treatment-related morbidity, including cardiovascular issues. Since echocardiography allows for a comprehensive non-invasive assessment at all cancer stages, it is well suited to monitor cardiovascular disease secondary to oncology treatment. This has earned it significant attention in the study of cardiac tumors and treatment-induced cardiac alterations. Ultrasound methods-ranging from transthoracic and transesophageal echocardiography to ultrasound diagnostic techniques including myocardial strain imaging, myocardial work indices, three-dimensional cardiac imaging-offer a holistic view of both the tumor and its treatment impact cardiac function. Stress echocardiography, myocardial contrast echocardiography, and myocardial acoustic angiography further augment this capability. Together, these echocardiographic techniques provide clinicians with early detection opportunities for cardiac damage, enabling timely interventions. As such, echocardiography continues to be instrumental in monitoring and managing the cardiovascular health of oncology patients, complementing efforts to optimize their overall treatment and survival outcomes.

Cystic ovary disease (COD) alters structure and function of the bovine oviduct.

Cystic ovary disease (COD) is a common cause of subfertility in dairy cattle. Therefore, the aim of this study was to provide novel concepts for cyst classification and to investigate the effects of COD on tubal microarchitecture, oviductal metabolic function, and the formation of the sperm reservoir. Bovine Fallopian tubes affected by follicular cysts, follicular cysts with luteinization and luteal cysts were investigated by a variety of microscopic and histological techniques and compared to control cows in metestrus and diestrus. We defined three types of cysts involved in COD, each of which had a characteristic wall thickness, inner wall appearance and cellular pattern within the cyst aspirate. Regarding the Fallopian tube, each cyst type was associated with a characteristic morphology, specifically the microarchitecture of the folds in ampulla, epithelial cell ratios, and ciliated/secretory cell size and form. Furthermore, each cyst type showed different patterns of tubal glycoprotein and acidic mucopolysaccharide synthesis, which was highly variable as compared to the controls. Our studies are the first to characterize the effects of COD on the Fallopian tube, which promotes the establishment of novel, cyst-specific therapeutic concepts in cattle and helps gain a holistic view of the causes of subfertility in cows with COD.

The Reduced Gray Matter Volume and Functional Connectivity of the Cerebellum in Type 2 Diabetes Mellitus with High Insulin Resistance.

INTRODUCTION: Insulin resistance is widely thought to be a critical feature in type 2 diabetes mellitus (T2DM), and there is significant evidence indicating a higher abundance of insulin receptors in the human cerebellum than cerebrum. However, the specific structural or functional changes in the cerebellum related to T2DM remain unclear, and the association between cerebellar alterations, insulin resistance, cognition, and emotion is yet to be determined. METHODS: We investigated neuropsychological performance, and structural and functional changes in specific cerebellar subregions in 43 T2DM patients with high insulin resistance (T2DM-highIR), 72 T2DM patients with low insulin resistance (T2DM-lowIR), and 50 controls. Furthermore, the correlation and stepwise multiple linear regression analysis were performed. RESULTS: Compared to the controls, T2DM exhibited lower cognitive scores and higher depressive/anxious scores. Furthermore, T2DM-highIR patients showed reduced gray matter volume (GMV) in the right cerebellar lobules VIIb, Crus I/II, and T2DM showed reduced GMV in left lobules I-IV compared to controls. Additionally, functional connectivity decrease was observed between the right lobules I-V and orbital part of the superior frontal gyrus in T2DM-highIR compared to both T2DM-lowIR and controls. Notably, there were negative correlations between the GMV of the lobules VIIb, Crus I/II, and updated homeostatic model assessment of insulin resistance, and positive correlation with executive/visuospatial performance in T2DM patients. CONCLUSIONS: These results suggest that the cerebellar lobules VIIb, Crus I/II, represent vulnerable brain regions in the context of insulin resistance. Overall, this study offers new insights into the neuropathophysiological mechanisms of brain impairment in patients with T2DM.

Structure and function analyses of the SRC gene in Pacific white shrimp Litopenaeus vannamei.

SRC gene encodes scavenger receptor class C, a member of the scavenger receptor family, and has only been identified and investigated in invertebrates. Our previous studies have revealed that SRC is a novel candidate gene associated with body weight in Pacific white shrimp (Litopenaeus vannamei). In order to comprehend the underlying mechanism by which LvSRC affects shrimp growth, we analyzed the structure, phylogeny, expression profiles and RNA interference (RNAi) of this gene in L. vannamei. We found that LvSRC contains two CCP domains and one MAM domain, with the highest expression level in the heart and relatively low expression level in other tissues. Notably, LvSRC exhibited significantly higher expression levels in the fast-growing group among groups with different growth rates, suggesting its potential involvement as a gene contributing to the growth of L. vannamei. RNAi of LvSRC inhibited body length and body weight gain compared to the control groups. Moreover, through RNA-seq analysis, we identified 598 differentially expressed genes (DEGs), including genes associated with growth, immunity, protein processing and modification, signal transduction, lipid synthesis and metabolism. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed significant changes in the signaling pathways related to growth, lipid metabolism and immune response, suggesting that LvSRC exhibits the potential to participate in diverse physiological processes and immune regulation. These findings deepen our understanding of the structure and function of the SRC in shrimp and lay the foundation for further research into the regulatory mechanism of LvSRC. Additionally, they provide potential applications in shrimp genetics and breeding.

SIRT1 restores mitochondrial structure and function in rats by activating SIRT3 after cerebral ischemia/reperfusion injury.

Mitochondrial dysfunction contributes to cerebral ischemia-reperfusion (CI/R) injury, which can be ameliorated by Sirtuin-3 (SIRT3). Under stress conditions, the SIRT3-promoted mitochondrial functional recovery depends on both its activity and expression. However, the approach to enhance SIRT3 activity after CI/R injury remains unelucidated. In this study, Sprague-Dawley (SD) rats were intracranially injected with either adeno-associated viral Sirtuin-1 (AAV-SIRT1) or AAV-sh_SIRT1 before undergoing transient middle cerebral artery occlusion (tMCAO). Primary cortical neurons were cultured and transfected with lentiviral SIRT1 (LV-SIRT1) and LV-sh_SIRT1 respectively before oxygen-glucose deprivation/reoxygenation (OGD/R). Afterwards, rats and neurons were respectively treated with a selective SIRT3 inhibitor, 3-(1H-1,2,3-triazol-4-yl) pyridine (3-TYP). The expression, function, and related mechanism of SIRT1 were investigated by Western Blot, flow cytometry, immunofluorescence staining, etc. After CI/R injury, SIRT1 expression decreased in vivo and in vitro. The simulation and immune-analyses reported strong interaction between SIRT1 and SIRT3 in the cerebral mitochondria before and after CI/R. SIRT1 overexpression enhanced SIRT3 activity by increasing the deacetylation of SIRT3, which ameliorated CI/R-induced cerebral infarction, neuronal apoptosis, oxidative stress, neurological and motor dysfunction, and mitochondrial respiratory chain dysfunction, promoted mitochondrial biogenesis, and retained mitochondrial integrity and mitochondrial morphology. Meanwhile, SIRT1 overexpression alleviated OGD/R-induced neuronal death and mitochondrial bioenergetic deficits. These effects were reversed by AAV-sh_SIRT1 and the neuroprotective effects of SIRT1 were partially offset by 3-TYP. These results suggest that SIRT1 restores the structure and function of mitochondria by activating SIRT3, offering neuroprotection against CI/R injury, which signifies a potential approach for the clinical management of cerebral ischemia.

Let's get biophysical - How to get your favorite protein's digits.

In these days of information overload and high-throughput analysis, it is easy to lose focus on the study of individual proteins. It is our conjecture that such investigations are still crucially important and offer uniquely penetrative insights. We thus present a discussion of biophysical methods to allow readers to get to know their protein of interest better. Although this perspective is not written with the expert in mind, we hope that for interdisciplinary scientists, or researchers who do not routinely perform biophysical analyses, the content will be helpful and inspiring.

Functional brain activity is highly associated with cortical myelination in neonates.

Functional organization of the human cerebral cortex is highly constrained by underlying brain structures, but how functional activity is associated with different brain structures during development is not clear, especially at the neonatal stage. Since long-range functional connectivity is far from mature in the dynamically developing neonatal brain, it is of great scientific significance to investigate the relationship between different structural and functional features at the local level. To this end, for the first time, correlation and regression analyses were performed to examine the relationship between cortical morphology, cortical myelination, age, and local brain functional activity, as well as functional connectivity strength using high-resolution structural and resting-state functional MRI data of 177 neonates (29-44 postmenopausal weeks, 98 male and 79 female) from both static and dynamic perspectives. We found that cortical myelination was most strongly associated with local brain functional activity across the cerebral cortex than other cortical structural features while controlling the age effect. These findings suggest the crucial role of cortical myelination in local brain functional development at birth, providing valuable insights into the fundamental biological basis of functional activity at this early developmental stage.

Microecological characteristics of water bodies/sediments and microbial remediation strategies after 50 years of pollution exposure in ammunition destruction sites in China.

The effects of long-term ammunition pollution on microecological characteristics were analyzed to formulate microbial remediation strategies. Specifically, the response of enzyme systems, N/O stable isotopes, ion networks, and microbial community structure/function levels were analyzed in long-term (50 years) ammunition-contaminated water/sediments from a contamination site, and a compound bacterial agent capable of efficiently degrading trinitrotoluene (TNT) while tolerating many heavy metals was selected to remediate the ammunition-contaminated soil. The basic physical and chemical properties of the water/sediment (pH (up: 0.57-0.64), nitrate (up: 1.31-4.28 times), nitrite (up: 1.51-5.03 times), and ammonium (up: 7.06-70.93 times)) were changed significantly, and the significant differences in stable isotope ratios of N and O (nitrate nitrogen) confirmed the degradability of TNT by indigenous microorganisms exposed to long-term pollution. Heavy metals, such as Pb, Zn, Cu, Cd, Cs, and Sb, have synergistic toxic effects in ammunition-contaminated sites, and significantly decreased the microbial diversity and richness in the core pollution area. However, long-term exposure in the edge pollution area induced microorganisms to use TNT as a carbon and nitrogen sources for life activities and growth and development. The Bacteroidales microbial group was significantly inhibited by ammunition contamination, whereas microorganisms such as Proteobacteria, Acidobacteriota, and Comamonadaceae gradually adapted to this environmental stress by regulating their development and stress responses. Ammunition pollution significantly affected DNA replication and gene regulation in the microecological genetic networks and increased the risk to human health. Mg and K were significantly involved in the internal mechanism of microbial transport, enrichment, and metabolism of TNT. Nine strains of TNT-utilizing microbes were screened for efficient TNT degradation and tolerance to typical heavy metals (copper, zinc and lead) found in contaminated sites, and a compound bacterial agent prepared for effective repair of ammunition-contaminated soil significantly improved the soil ecological environment.

Causal association between serum 25-hydroxyvitamin D levels and right ventricular structure and function: A Mendelian randomization study.

BACKGROUND AND AIM: Deficient concentrations of vitamin D have been linked to several cardiovascular conditions, but the causal relationship between serum 25-hydroxyvitamin D (25(OH)D) levels and right ventricular structure and function remains unclear. Mendelian randomization (MR) was employed to inspect this association. METHODS AND RESULTS: Genetic instrumental variables associated with 25(OH)D levels were acquired from genome-wide association studies (GWAS) analyses. Summary statistics for right ventricular structure and function, including right ventricular end diastolic volume, right ventricular end systolic volume, right ventricular stroke volume, and right ventricular ejection fraction, were acquired from publicly available GWAS datasets. For the primary analysis, the inverse variance weighted (IVW) method was utilized in performing the MR analysis. Additionally, secondly analyses were conducted to estimate the robustness and consistency of the attained conclusions. The MR analysis did not reveal a considerable causal association between serum 25(OH)D levels and right ventricular end diastolic volume (ß: 0.112, 95% confident interval [CI]: -0.006 to 0.230, p = 0.063), right ventricular end systolic volume (ß: 0.102, 95% CI: -0.021 to 0.226, p = 0.105), right ventricular stroke volume (ß: 0.095, 95% CI: -0.018 to 0.207, p = 0.099), or right ventricular ejection fraction (ß: -0.005, 95% CI: -0.123 to 0.112, p = 0.928). CONCLUSIONS: Our findings did not reveal any substantial evidence supporting a causal relationship between serum 25(OH)D levels and the structure and function of the right ventricle. These findings suggest that serum 25(OH)D levels may not directly influence right ventricular parameters assessed.