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BACKGROUND: Gemmatimonadota bacteria are widely distributed in nature, but their metabolic potential and ecological roles in marine environments are poorly understood. RESULTS: Here, we obtained 495 metagenome-assembled genomes (MAGs), and associated viruses, from coastal to deep-sea sediments around the world. We used this expanded genomic catalog to compare the protein composition and update the phylogeny of these bacteria. The marine Gemmatimonadota are phylogenetically different from those previously reported from terrestrial environments. Functional analyses of these genomes revealed these marine genotypes are capable of degradation of complex organic carbon, denitrification, sulfate reduction, and oxidizing sulfide and sulfite. Interestingly, there is widespread genetic potential for secondary metabolite biosynthesis across Gemmatimonadota, which may represent an unexplored source of novel natural products. Furthermore, viruses associated with Gemmatimonadota have the potential to "hijack" and manipulate host metabolism, including the assembly of the lipopolysaccharide in their hosts. CONCLUSIONS: This expanded genomic diversity advances our understanding of these globally distributed bacteria across a variety of ecosystems and reveals genetic distinctions between those in terrestrial and marine communities. Video Abstract.
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Metagenoma , Filogenia , Genoma Bacteriano , Sedimentos Geológicos/microbiologia , Genômica , Água do Mar/microbiologia , Organismos Aquáticos/genética , Metabolismo Secundário , MetagenômicaRESUMO
Background: Family socioeconomic status (FSES) serves as a significant determinant for subjective well-being. However, extant research has provided conflicting evidence on the correlation between FSES and adolescent students' subjective well-being (SSWB). Methods: Data were collected from 12,058 adolescent students (16 years of age) by the Programme for International Student Assessment (PISA) 2018. Multivariate canonical correlation and Mantel test were utilized to investigate the specific connection between FSES and SSWB. Furthermore, a Gaussian EBICglasso graph-theoretical model was used to capture the topological properties of the FSES-SSWB network and reveal the interplay among multifarious components of FSES and SSWB. Results: FSES was positively correlated with SSWB. In the FSES-SSWB network, parental educational attainment and occupation status demonstrated the highest centrality values, thereby contributing significantly to the relationship between FSES and SSWB. However, family wealth, along with educational and cultural resources, displayed lower centrality values, signifying their weaker roles in this relationship. Conclusion: Our findings suggest that symbolic capital, rather than family affluence, exerts a dominant influence on adolescent SSWB. In other words, SSWB may not be detrimentally influenced by a deficiency in monetary resources. However, it is more susceptible to being unfavorably impacted by inferior parental educational attainment and occupational standing.
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Pregnancy of unknown location (PUL) is a temporary pathologic or physiologic phenomenon of early pregnancy that requires follow up to determine the final pregnancy outcome. Evidence indicated that PUL patients suffer a remarkably higher rate of adverse pregnancy outcomes, represented by ectopic gestation and early pregnancy loss, than the general population. In the past few decades, discussion about PUL has never stopped, and a variety of markers have been widely investigated for the early and accurate evaluation of PUL, including serum biomarkers, ultrasound imaging features, multivariate analysis, and the diagnosis of ectopic pregnancy based on risk stratification. So far, machine learning (ML) methods represented by M4 and M6 logistic regression have gained a level of recognition and are continually improving. Nevertheless, the heterogeneity of PUL markers, mainly caused by the limited sample size, the differences in population and technical maturity, etc., have hampered the management of PUL. With the advancement of multidisciplinary integration and cutting-edge technologies (e.g. artificial intelligence, prediction model development, and telemedicine), novel markers, and strategies for the management of PUL are expected to be developed. In this review, we summarize both conventional and novel markers (represented by artificial intelligence) for PUL assessment and management, investigate their advancements, limitations and challenges, and propose insights on future research direction and clinical application.
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Ensuring drug safety in the early stages of drug development is crucial to avoid costly failures in subsequent phases. However, the economic burden associated with detecting drug off-targets and potential side effects through in vitro safety screening and animal testing is substantial. Drug off-target interactions, along with the adverse drug reactions they induce, are significant factors affecting drug safety. To assess the liability of candidate drugs, we developed an artificial intelligence model for the precise prediction of compound off-target interactions, leveraging multi-task graph neural networks. The outcomes of off-target predictions can serve as representations for compounds, enabling the differentiation of drugs under various ATC codes and the classification of compound toxicity. Furthermore, the predicted off-target profiles are employed in adverse drug reaction (ADR) enrichment analysis, facilitating the inference of potential ADRs for a drug. Using the withdrawn drug Pergolide as an example, we elucidate the mechanisms underlying ADRs at the target level, contributing to the exploration of the potential clinical relevance of newly predicted off-target interactions. Overall, our work facilitates the early assessment of compound safety/toxicity based on off-target identification, deduces potential ADRs of drugs, and ultimately promotes the secure development of drugs.
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BACKGROUND: Radiotherapy (RT) is a widely utilized tumor treatment approach, while a significant obstacle in this treatment modality is the radioresistance exhibited by tumor cells. To enhance the effectiveness of RT, scientists have explored radiosensitization approaches, including the use of radiosensitizers and physical stimuli. Nevertheless, several approaches have exhibited disappointing results including adverse effects and limited efficacy. A safer and more effective method of radiosensitization involves low-intensity ultrasound (LIUS), which selectively targets tumor tissue and enhances the efficacy of radiation therapy. METHODS: This review summarized the tumor radioresistance reasons and explored LIUS potential radiosensitization mechanisms. Moreover, it covered diverse LIUS application strategies in radiosensitization, including the use of LIUS alone, ultrasound-targeted intravascular microbubble destruction, ultrasound-mediated targeted radiosensitizers delivery, and sonodynamic therapy. Lastly, the review presented the limitations and prospects of employing LIUS-RT combined therapy in clinical settings, emphasizing the need to connect research findings with practical applications. RESULTS AND CONCLUSION: LIUS employs cost-effective equipment to foster tumor radiosensitization, curtail radiation exposure, and elevate the quality of life for patients. This efficacy is attributed to LIUS's ability to utilize thermal, cavitation, and mechanical effects to overcome tumor cell resistance to RT. Multiple experimental analyses have underscored the effectiveness of LIUS in inducing tumor radiosensitization using diverse strategies. While initial studies have shown promising results, conducting more comprehensive clinical trials is crucial to confirm its safety and effectiveness in real-world situations.
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Neoplasias , Radiossensibilizantes , Terapia por Ultrassom , Humanos , Neoplasias/radioterapia , Neoplasias/terapia , Radiossensibilizantes/uso terapêutico , Radiossensibilizantes/farmacologia , Terapia por Ultrassom/métodos , Terapia Combinada , Animais , Tolerância a Radiação , Ondas UltrassônicasRESUMO
Radiotherapy causes apoptosis mainly through direct or indirect damage to DNA via ionizing radiation, leading to DNA strand breaks. However, the efficacy of radiotherapy is attenuated in malignant tumor microenvironment (TME), such as hypoxia. Tumor vasculature, due to the imbalance of various angiogenic and anti-angiogenic factors, leads to irregular morphology of tumor neovasculature, disordered arrangement of endothelial cells, and too little peripheral coverage. This ultimately leads to a TME characterized by hypoxia, low pH and high interstitial pressure. This deleterious TME further exacerbates the adverse effects of tumor neovascularization and weakens the efficacy of conventional radiotherapy. Whereas normalization of blood vessels improves TME and thus the efficacy of radiotherapy. In addition to describing the research progress of radiotherapy sensitization and vascular normalization, this review focuses on the strategy and application prospect of modulating vascular normalization to improve the efficacy of radiotherapy sensitization.
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The gas vesicle (GV) is like a hollow nanoparticle consisting of an internal gas and a protein shell, which mainly consists of hydrophobic gas vesicle protein A (GvpA) and GvpC attached to the surface. GVs, first discovered in cyanobacteria, are mainly produced by photosynthetic bacteria (PSB) and halophilic archaea. After being modified and engineered, GVs can be utilized as contrast agents, delivery carriers, and immunological boosters for disease prevention, diagnosis, and treatment with good results due to their tiny size, strong stability and non-toxicity advantages. Many diagnostic and therapeutic approaches based on GV are currently under development. In this review, we discuss the source, function, physical and chemical properties of GV, focus on the current application progress of GV, and put forward the possible application prospect and development direction of GV in the future.
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Quantitative analysis of activated neurons in mouse brains by a specific stimulation is usually a primary step to locate the responsive neurons throughout the brain. However, it is challenging to comprehensively and consistently analyze the neuronal activity trace in whole brains of a large cohort of mice from many terabytes of volumetric imaging data. Here, we introduce NEATmap, a deep learning-based high-efficiency, high-precision and user-friendly software for whole-brain neuronal activity trace mapping by automated segmentation and quantitative analysis of immunofluorescence labeled c-Fos+ neurons. We applied NEATmap to study the brain-wide differentiated neuronal activation in response to physical and psychological stressors in cohorts of mice.
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Selenocysteine (Sec) metabolism is crucial for cellular function and ferroptosis prevention and has traditionally been thought to begin with the uptake of the Sec carrier selenoprotein P (SELENOP). Following uptake, Sec released from SELENOP undergoes metabolisation via selenocysteine lyase (SCLY), producing selenide, a substrate used by selenophosphate synthetase 2 (SEPHS2), which provides the essential selenium donor - selenophosphate - for the biosynthesis of the selenocysteine tRNA. Here, we report the discovery of an alternative pathway mediating Sec metabolisation that is independent of SCLY and mediated by peroxiredoxin 6 (PRDX6). Mechanistically, we demonstrate that PRDX6 can readily react with selenide and interact with SEPHS2, potentially acting as a selenium delivery system. Moreover, we demonstrate the presence and functional significance of this alternative route in cancer cells where we reveal a notable association between elevated expression of PRDX6 with a highly aggressive neuroblastoma subtype. Altogether, our study sheds light on a previously unrecognized aspect of Sec metabolism and its implications in ferroptosis, offering new avenues for therapeutic exploitation.
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Modulation of the surface chemistry of air electrodes makes it possible to significantly improve the electrocatalytic performance of solid oxide cells (SOCs). Here, the surface chemistry of BaGd0.8La0.2Co2O6-δ (BGLC) double perovskite is modulated by treatment in an acidic citric acid solution. The treatment leads to corrosion on the surface of BGLC particles, and the effect is dependent on the acidity of the solution. As the acidity of solution is low, Ba cations are selectively dissolved out of the BGLC surface, while as the acidity increases, the corrosion becomes more homogeneous. The Ba surface deficiency remarkably increases the concentration of surface oxygen vacancies and electrocatalytic activity of BGLC. To avoid the loss of Ba-deficient surface during the conventional high temperature sintering process, a sintering-free fabrication route is utilized to directly assemble the Ba-deficient BGLC powder into an air electrode. A single cell with the surface Ba-deficient BGLC electrode shows a peak power density of 1.04 W cm-2 at 750 °C and an electrolysis current density of 1.48 A cm-2 at 1.3 V, much greater than 0.64 W cm-2 and 1.02 A cm-2 of the cell with the pristine BGLC, respectively. This work provides a simple and effective surface chemistry modulation strategy for the development of an efficient air electrode for SOCs.
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Translating artificial intelligence techniques into the realm of cognitive neuroscience holds promise for significant breakthroughs in our ability to probe the intrinsic mechanisms of the brain. The recent unprecedented development of robust AI models is changing how and what we understand about the brain. In this Editorial, we invite contributions for a BMC Neuroscience Collection on "AI and Cognitive Neuroscience".
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Inteligência Artificial , Neurociência Cognitiva , Humanos , Neurociência Cognitiva/métodos , Neurociência Cognitiva/tendências , Encéfalo/fisiologia , Neurociências/métodos , Neurociências/tendênciasRESUMO
CD38 antigen is a glycoprotein that found on the surface of several immune cells, and this property makes its monoclonal antibodies have the effect of targeted elimination of immune cells. Therefore, the CD38 monoclonal antibody (such as daratumumab, Isatuximab) becomes a new treatment option for membranous nephropathy, lupus nephritis, renal transplantation, and other refractory kidney diseases. This review summarizes the application of CD38 monoclonal antibodies in different kidney diseases and highlights future prospects.
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ADP-Ribosil Ciclase 1 , Anticorpos Monoclonais , Nefropatias , Humanos , ADP-Ribosil Ciclase 1/imunologia , ADP-Ribosil Ciclase 1/antagonistas & inibidores , ADP-Ribosil Ciclase 1/metabolismo , Anticorpos Monoclonais/uso terapêutico , Nefropatias/imunologia , Animais , Glicoproteínas de Membrana/imunologia , Glicoproteínas de Membrana/antagonistas & inibidores , Transplante de Rim , Anticorpos Monoclonais Humanizados/uso terapêuticoRESUMO
BACKGROUND: Sonodynamic therapy (SDT) has shown promise as a non-invasive cancer treatment due to its local effects and excellent tissue penetration. However, the limited accumulation of sonosensitizers at the tumor site hinders its therapeutic efficacy. Although nanosonosensitizers have improved local tumor accumulation through passive targeting via the enhanced permeability and retention effect (EPR), achieving sufficient accumulation and penetration into tumors remains challenging due to tumor heterogeneity and inaccurate targeting. Bacteria have become a promising biological carrier due to their unique characteristic of active targeting and deeper penetration into the tumor. METHODS: In this study, we developed nanosonosensitizers consisting of sonosensitizer, hematoporphyrin monomethyl ether (HMME), and perfluoro-n-pentane (PFP) loaded poly (lactic-co-glycolic) acid (PLGA) nanodroplets (HPNDs). These HPNDs were covalently conjugated onto the surface of Escherichia coli Nissle 1917 (EcN) using carbodiimine chemistry. EcN acted as an active targeting micromotor for efficient transportation of the nanosonosensitizers to the tumor site in triple-negative breast cancer (TNBC) treatment. Under ultrasound cavitation, the HPNDs were disrupted, releasing HMME and facilitating its uptakes by cancer cells. This process induced reactive oxygen species (ROS)-mediated cell apoptosis and immunogenic cell death (ICD) in vitro and in vivo. RESULTS: Our bacteria-driven nanosonosensitizer delivery system (HPNDs@EcN) achieved superior tumor localization of HMME in vivo compared to the group treated with only nanosonosensitizers. This enhanced local accumulation further improved the therapeutic effect of SDT induced-ICD therapeutic effect and inhibited tumor metastasis under ultrasound stimulation. CONCLUSIONS: Our research demonstrates the potential of this ultrasound-responsive bacteria-driven nanosonosensitizer delivery system for SDT in TNBC. The combination of targeted delivery using bacteria and nanosonosensitizer-based therapy holds promise for achieving improved treatment outcomes by enhancing local tumor accumulation and stimulating ICD.
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Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Morte Celular Imunogênica , Apoptose , Bactérias , GlicóisRESUMO
Our previous work developed acoustic response bacteria, which enable the precise tuning of transgene expression through ultrasound. However, it is still difficult to visualize these bacteria in order to guide the sound wave to precisely irradiate them. Here, we develop ultrasound-visible engineered bacteria and chemically modify them with doxorubicin (DOX) on their surfaces. These engineered bacteria (Ec@DIG-GVs) can produce gas vesicles (GVs), providing a real-time imaging guide for remote hyperthermia high-intensity focused ultrasound (hHIFU) to induce the expression of the interferon (IFN)-γ gene. The production of IFN-γ can kill tumor cells, induce macrophage polarization from the M2 to the M1 phenotype, and promote the maturation of dendritic cells. DOX can be released in the acidic tumor microenvironment, resulting in immunogenic cell death of tumor cells. The concurrent effects of IFN-γ and DOX activate a tumor-specific T cell response, producing the synergistic anti-tumor efficacy. Our study provides a promising strategy for bacteria-mediated tumor chemo-immunotherapy.
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Doxorrubicina , Imunoterapia , Interferon gama , Imunoterapia/métodos , Animais , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Interferon gama/metabolismo , Camundongos , Humanos , Linhagem Celular Tumoral , Neoplasias/terapia , Neoplasias/imunologia , Neoplasias/patologia , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Camundongos Endogâmicos C57BL , Macrófagos/metabolismo , Macrófagos/imunologia , Feminino , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Bactérias/genética , Ondas UltrassônicasRESUMO
Background: Over the years, there has been extensive exploration of the association between testosterone and lipid profiles, yet the precise mechanisms underlying their interaction remain incompletely elucidated. Similarly, there is a dearth of research on the correlation between serum apolipoprotein B (apoB) and serum total testosterone (TT), particularly within specific populations. Methods: We conducted a cross-sectional study to assess the relationship between serum TT concentration and serum apoB concentration. Using the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2016, we employed weighted generalized linear models, weighted univariate, weighted multivariate analysis, and smooth curve fitting to assist in exploring the relationship between serum TT and apoB. Serum apoB concentration served as the independent variable, and serum TT concentration as the dependent variable. ApoB was divided into four quartiles-Q1 (<0.7g/L, N=691), Q2 (≥0.7g/L to <0.9g/L, N=710), Q3 (≥0.9g/L to <1.1g/L, N=696), and Q4 (≥1.1g/L, N=708)-thereby further solidifying the stable association between the two. Additionally, the application of smooth curve fitting will contribute to a more detailed elucidation of the specific relationship between serum TT concentration and serum apoB concentration under different factors (Drinking, Smoke, Diabetes, Hypertension, and High cholesterol level.). Results: The results indicate a negative correlation between serum TT concentration and apoB concentration (ß=-113.4; 95% CI: -146.6, -80.2; P<0.001). After adjusting for confounding variables, the negative correlation between apoB concentration and TT concentration remains significant (ß=-61.0; 95% CI: -116.7, -5.2; P=0.040). When apoB concentration was converted from a continuous variable to a categorical variable (quartiles: Q1<0.7g/L; Q2:≥0.7g/L to<0.9g/L; Q3:≥0.9g/L to <1.1g/L; Q4: ≥1.1g/L), TT level of participants in the highest quartile (≥1.1g/L) was -47.2 pg/mL (95% CI: -91.2, -3.3; P=0.045) lower than that in the lowest quartile (<0.7g/L). The smooth curve fitting diagram revealed differences in the relationship between TT concentration and apoB among individuals with different cardiovascular disease (CVD) risk factors. Conclusions: This study elucidates a robust inverse correlation between serum TT concentration and apoB concentration, maintaining statistical significance even upon adjustment for confounding factors. These findings present a promising avenue for addressing the prevention and treatment of low testosterone and CVD.
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Doenças Cardiovasculares , Neoplasias , Adulto , Masculino , Humanos , Testosterona , Inquéritos Nutricionais , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Estudos Transversais , Apolipoproteínas B , Apolipoproteínas , Fatores de Risco de Doenças CardíacasRESUMO
Massive increases in the risks of depressive disorders and the ensuing suicide have become the overarching menace for children/adolescents. Despite global consensus to instigate psychological healthcare policy for these children/adolescents, their effects remain largely unclear neither from a small amount of official data nor from small-scale scientific studies. More importantly, in underprivileged children/adolescents in lower-middle-economic-status countries/areas, the data collection may not be as equally accessible as in developed countries/areas, thus resulting in underrepresented observations. To address these challenges, we released a large-scale and multi-center cohort dataset (n = 249,772) showing the effects of primary psychological healthcare on decreasing depression and suicidal ideation in these children/adolescents who were underrepresented in previous studies or current healthcare systems, including unattended children/adolescents, orphans, children/adolescents in especially difficult circumstances, and "left-behind" and "single-parenting" children/adolescents. We provided all individual data recording the depressive symptoms and suicide ideation that had been collected at baseline (Oct 2022) and half-year follow-up (May 2023) from practicing this psychological healthcare system.
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Depressão , Ideação Suicida , Adolescente , Criança , Humanos , Depressão/psicologia , Depressão/terapia , Fatores Socioeconômicos , Estudos Multicêntricos como AssuntoRESUMO
Procrastination has adverse consequences across cultural contexts. Behavioral research found a positive correlation between punishment sensitivity and procrastination. However, little is known about the neural substrates underlying the association between them. We employed voxel-based morphometry (VBM) and resting-state functional connectivity (RSFC) methods to address this issue with two independent samples. In Sample 1, behavioral results found that punishment sensitivity was positively related to procrastination. The VBM analysis showed that punishment sensitivity was negatively correlated with gray matter volume in left putamen. Subsequently, the RSFC results revealed that left putamen - left middle temporal gyrus (MTG) connectivity was positively associated with punishment sensitivity. More crucially, mediation analysis indicated that left putamen - left MTG connectivity mediated the relationship between punishment sensitivity and procrastination. The aforementioned results were validated in Sample 2. Altogether, left putamen - left MTG connectivity might be the neural signature of the association between punishment sensitivity and procrastination.
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Mapeamento Encefálico , Procrastinação , Mapeamento Encefálico/métodos , Putamen/diagnóstico por imagem , Punição , Imageamento por Ressonância Magnética/métodos , Substância Cinzenta , Lobo Temporal/diagnóstico por imagemRESUMO
AIMS: This study aimed to illuminate the neuropathological landscape of attention deficit hyperactivity disorder (ADHD) by a multiscale macro-micro-molecular perspective from in vivo neuroimaging data. METHODS: The "ADHD-200 initiative" repository provided multi-site high-quality resting-state functional connectivity (rsfc-) neuroimaging for ADHD children and matched typically developing (TD) cohort. Diffusion mapping embedding model to derive the functional connectome gradient detecting biologically plausible neural pattern was built, and the multivariate partial least square method to uncover the enrichment of neurotransmitomic, cellular and chromosomal gradient-transcriptional signatures of AHBA enrichment and meta-analytic decoding. RESULTS: Compared to TD, ADHD children presented connectopic cortical gradient perturbations in almost all the cognition-involved brain macroscale networks (all pBH <0.001), but not in the brain global topology. As an intermediate phenotypic variant, such gradient perturbation was spatially enriched into distributions of GABAA/BZ and 5-HT2A receptors (all pBH <0.01) and co-varied with genetic transcriptional expressions (e.g. DYDC2, ATOH7, all pBH <0.01), associated with phenotypic variants in episodic memory and emotional regulations. Enrichment models demonstrated such gradient-transcriptional variants indicated the risk of both cell-specific and chromosome- dysfunctions, especially in enriched expression of oligodendrocyte precursors and endothelial cells (all pperm <0.05) as well enrichment into chromosome 18, 19 and X (pperm <0.05). CONCLUSIONS: Our findings bridged brain macroscale neuropathological patterns to microscale/cellular biological architectures for ADHD children, demonstrating the neurobiologically pathological mechanism of ADHD into the genetic and molecular variants in GABA and 5-HT systems as well brain-derived enrichment of specific cellular/chromosomal expressions.
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Transtorno do Deficit de Atenção com Hiperatividade , Conectoma , Transcriptoma , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Transtorno do Deficit de Atenção com Hiperatividade/patologia , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Criança , Masculino , Feminino , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/metabolismo , Córtex Cerebral/fisiopatologia , Córtex Cerebral/patologia , Adolescente , Neurotransmissores/metabolismoRESUMO
The endometrium microvessel system, responsible for supplying oxygen and nutrients to the embryo, holds significant importance in evaluating endometrial receptivity (ER). Visualizing this system directly can significantly enhance ER evaluation. Currently, clinical methods like Narrow-band hysteroscopy and Color Doppler ultrasound are commonly used for uterine blood vessel examination, but they have limitations in depth or resolution. Endoscopic Photoacoustic Imaging (PAE) has proven effective in visualizing microvessels in the digestive tract, while its adaptation to uterine imaging faces challenges due to the uterus's unique physiological characteristics. This paper for the first time that uses high-resolution PAE in vivo to capture a comprehensive network of endometrial microvessels non-invasively. Followed by continuous observation and quantitative analysis in the endometrial injury model, we further corroborated that PAE detection of endometrial microvessels stands as a valuable indicator for evaluating ER. The PAE system showcases its promising potential for integration into reproductive health assessments.