Interstitial Fluid Shear Stress Induces the Synthetic Phenotype Switching of VSMCs to Release Pro-calcified Extracellular Vesicles via EGFR-MAPK-KLF5 Pathway.

Phenotypic switching (from contractile to synthetic) of vascular smooth muscle cells (VSMCs) is essential in the progression of atherosclerosis. The damaged endothelium in the atherosclerotic artery exposes VSMCs to increased interstitial fluid shear stress (IFSS). However, the precise mechanisms by which increased IFSS influences VSMCs phenotypic switching are unrevealed. Here, we employed advanced numerical simulations to calculate IFSS values accurately based on parameters acquired from patient samples. We then carefully investigated the phenotypic switching and extracellular vesicles (EVs) secretion of VSMCs under various IFSS conditions. By employing a comprehensive set of approaches, we found that VSMCs exhibited synthetic phenotype upon atherosclerotic IFSS. This synthetic phenotype is the upstream regulator for the enhanced secretion of pro-calcified EVs. Mechanistically, as a mechanotransducer, the epidermal growth factor receptor (EGFR) initiates the flow-based mechanical cues to MAPK signaling pathway, facilitating the nuclear accumulation of the transcription factor krüppel-like factor 5 (KLF5). Furthermore, pharmacological inhibiting either EGFR or MAPK signaling pathway blocks the nuclear accumulation of KLF5 and finally results in the maintenance of contractile VSMCs even under increased IFSS stimulation. Collectively, targeting this signaling pathway holds potential as a novel therapeutic strategy to inhibit VSMCs phenotypic switching and mitigate the progression of atherosclerosis.

Flagellimonas halotolerans sp. nov., a novel bacterium isolated from the South China Sea.

Two Gram-stain-negative strains, designed SYSU M86414T and SYSU M84420, were isolated from marine sediment samples of the South China Sea (Sansha City, Hainan Province, PR China). These strains were aerobic and could grow at pH 6.0-8.0 (optimum, pH 7.0), 4-37 °C (optimum, 28 °C), and in the presence of 0-10 % NaCl (w/v; optimum 3 %). The predominant respiratory menaquinone of strains SYSU M86414T and SYSU M84420 was MK-6. The primary cellular polar lipid was phosphatidylethanolamine. The major cellular fatty acids (>10 %) in both strains were iso-C15 : 0, iso-C15 : 1 G, and iso-C17 : 0 3-OH. The DNA G+C content of strains SYSU M86414T and SYSU M84420 were both 42.10 mol%. Phylogenetic analyses based on 16S rRNA gene sequences and core genes indicated that these novel strains belonged to the genus Flagellimonas and strain SYSU M86414T showed the highest 16S rRNA gene sequence similarity to Flagellimonas marinaquae JCM 11811T (98.83 %), followed by Flagellimonas aurea BC31-1-A7T (98.62 %), while strain SYSU M84420 had highest 16S rRNA gene sequence similarity to F. marinaquae JCM 11811T (98.76 %) and F. aurea BC31-1-A7T (98.55 %). Based on the results of polyphasic analyses, strains SYSU M86414T and SYSU M84420 should be considered to represent a novel species of the genus Flagellimonas, for which the name Flagellimonas halotolerans sp. nov. is proposed. The type strain of the proposed novel isolate is SYSU M86414T (=GDMCC 1.3806T=KCTC 102040T).

Mechanistic exploration and experimental validation of the Xiaochaihu decoction for the treatment of breast cancer by network pharmacology.

BACKGROUND: Xiaochaihu (XCH) decoction is a traditional Chinese prescription that has been recorded in the pharmacopeia of the People's Republic of China. In China, the XCH decoction is used clinically to treat a variety of tumors, including breast cancer. However, its potential mechanism of action is still undefined. METHODS: The chemical compounds in the XCH decoction were identified via Q Exactive Orbitrap LC-MS/MS. Then, we screened the active ingredients and targets in the XCH decoction from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Next, Cytoscape and Metascape were used to construct an active ingredient-target-disease network, which included a protein-protein interaction (PPI) network, GO enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Finally, we used molecular docking and in vitro experiments to verify the results of network pharmacology analysis. RESULTS: More than 70 major compounds were identified by Q Exactive Orbitrap LC-MS/MS analysis from the XCH decoction. A total of 162 active ingredients and 153 targets related to the XCH decoction and breast cancer were identified, and a compound-target-disease network was constructed. GO and KEGG analyses revealed that the XCH decoction regulated the drug response, apoptosis process, cancer pathway, and PI3K/Akt signaling pathway. Molecular docking and experimental validation indicated that the XCH decoction suppressed proliferation and induced apoptosis in breast cancer cells by regulating the expression of apoptosis-related proteins and inhibiting the PI3K/Akt pathway. CONCLUSIONS: This study suggested that the XCH decoction can be used to treat breast cancer by inhibiting cell proliferation, inducing apoptosis and downregulating the PI3K/Akt signaling pathway.

Analysis of nearly 3000 archaeal genomes from terrestrial geothermal springs sheds light on interconnected biogeochemical processes.

Terrestrial geothermal springs are physicochemically diverse and host abundant populations of Archaea. However, the diversity, functionality, and geological influences of these Archaea are not well understood. Here we explore the genomic diversity of Archaea in 152 metagenomes from 48 geothermal springs in Tengchong, China, collected from 2016 to 2021. Our dataset is comprised of 2949 archaeal metagenome-assembled genomes spanning 12 phyla and 392 newly identified species, which increases the known species diversity of Archaea by ~48.6%. The structures and potential functions of the archaeal communities are strongly influenced by temperature and pH, with high-temperature acidic and alkaline springs favoring archaeal abundance over Bacteria. Genome-resolved metagenomics and metatranscriptomics provide insights into the potential ecological niches of these Archaea and their potential roles in carbon, sulfur, nitrogen, and hydrogen metabolism. Furthermore, our findings illustrate the interplay of competition and cooperation among Archaea in biogeochemical cycles, possibly arising from overlapping functional niches and metabolic handoffs. Taken together, our study expands the genomic diversity of Archaea inhabiting geothermal springs and provides a foundation for more incisive study of biogeochemical processes mediated by Archaea in geothermal ecosystems.

Intravital Two-Photon Microscopy of the Transplanted Mouse Lung.

Complications after lung transplantation are largely related to the host immune system responding to the graft. Such immune responses are regulated by crosstalk between donor and recipient cells. A better understanding of these processes relies on the use of preclinical animal models and is aided by an ability to study intra-graft immune cell trafficking in real-time. Intravital two-photon microscopy can be used to image tissues and organs for depths up to several hundred microns with minimal photodamage, which affords a great advantage over single-photon confocal microscopy. Selective use of transgenic mice with promoter-specific fluorescent protein expression and/or adoptive transfer of fluorescent dye-labeled cells during intravital two-photon microscopy allows for the dynamic study of single cells within their physiologic environment. Our group has developed a technique to stabilize mouse lungs, which has enabled us to image cellular dynamics in naïve lungs and orthotopically transplanted pulmonary grafts. This technique allows for detailed assessment of cellular behavior within the vasculature and in the interstitium, as well as for examination of interactions between various cell populations. This procedure can be readily learned and adapted to study immune mechanisms that regulate inflammatory and tolerogenic responses after lung transplantation. It can also be expanded to the study of other pathogenic pulmonary conditions.

Adversarial attacks and adversarial training for burn image segmentation based on deep learning.

Deep learning has been widely applied in the fields of image classification and segmentation, while adversarial attacks can impact the model's results in image segmentation and classification. Especially in medical images, due to constraints from factors like shooting angles, environmental lighting, and diverse photography devices, medical images typically contain various forms of noise. In order to address the impact of these physically meaningful disturbances on existing deep learning models in the application of burn image segmentation, we simulate attack methods inspired by natural phenomena and propose an adversarial training approach specifically designed for burn image segmentation. The method is tested on our burn dataset. Through the defensive training using our approach, the segmentation accuracy of adversarial samples, initially at 54%, is elevated to 82.19%, exhibiting a 1.97% improvement compared to conventional adversarial training methods, while substantially reducing the training time. Ablation experiments validate the effectiveness of individual losses, and we assess and compare training results with different adversarial samples using various metrics.

Organocatalytic Enantioselective 1,12-Addition of Alkynyl Biphenyl Quinone Methides Formed In Situ.

The chemistry of quinone methides formed in situ has been flourishing in recent years. In sharp contrast, the development and utilization of biphenyl quinone methides are rare. Herein, we achieved a remote stereocontrolled 1,12-conjugate addition of biphenyl quinone methides formed in situ for the first time. In the presence of a suitable chiral phosphoric acid, alkynyl biphenyl quinone methides were generated from α-[4-(4-hydroxyphenyl)phenyl]propargyl alcohols, followed by enantioselective 1,12-conjugate addition with indole-2-carboxylates. The strategy enabled the additional alcohols to serve as efficient allenylation reagents, providing a practical access to a broad range of axially chiral allenes bearing (1,1'-biphenyl)-4-ol unit that are previously less accessible. Combined with control experiments, density functional theory calculations shed light on the reaction mechanism, indicating that enantioselectivity originates from the nucleophilic addition of alkynyl biphenyl quinone methides. Notably, not only the presence of biphenyl quinone methides as versatile intermediates was confirmed but also organocatalytic enantioselective 1,12-addition was established for the first time. This work enriched the family of quinone methides and provided a new platform for the remote stereocontrolled transformation of such versatile intermediates.

De Novo Assembly, Characterization, and Comparative Transcriptome Analysis of Mature Male and Female Gonads of Rabbitfish (Siganus oramin) (Bloch & Schneider, 1801).

The rabbitfish, Siganus oramin, is a commercially important table fish in southeastern China. However, there have been few studies on its gonad development and reproduction regulation. Comparative transcriptome analysis was first performed on adult male and female gonads of S. oramin. In total, 47,070 unigenes were successfully assembled and 22,737 unigenes were successfully annotated. Through comparative transcriptome analysis of male and female gonads, a total of 6722 differentially expressed genes were successfully identified, with 3528 upregulated genes and 3154 downregulated genes in the testes. In addition, 39 differentially expressed reproduction-related genes were identified. Finally, quantitative real-time PCR was used to validate the expression levels of several differentially expressed genes. These results provide important data for further studying the function of reproduction-related genes and the molecular mechanism regulating gonad development and reproduction in S. oramin.

3D visualization technology for Learning human anatomy among medical students and residents: a meta- and regression analysis.

BACKGROUND: 3D visualization technology applies computers and other devices to create a realistic virtual world for individuals with various sensory experiences such as 3D vision, touch, and smell to gain a more effective understanding of the relationships between real spatial structures and organizations. The purpose of this study was to comprehensively evaluate the effectiveness of 3D visualization technology in human anatomy teaching/training and explore the potential factors that affect the training effects to better guide the teaching of classroom/laboratory anatomy. METHODS: We conducted a meta-analysis of randomized controlled studies on teaching human anatomy using 3D visualization technology. We extensively searched three authoritative databases, PubMed, Web of Science, and Embase; the main outcomes were the participants' test scores and satisfaction, while the secondary outcomes were time consumption and enjoyment. Heterogeneity by I² was statistically determined because I²> 50%; therefore, a random-effects model was employed, using data processing software such as RevMan, Stata, and VOSviewer to process data, apply standardized mean difference and 95% confidence interval, and subgroup analysis to evaluate test results, and then conduct research through sensitivity analysis and meta-regression analysis. RESULTS: Thirty-nine randomized controlled trials (2,959 participants) were screened and included in this study. The system analysis of the main results showed that compared with other methods, including data from all regions 3D visualization technology moderately improved test scores as well as satisfaction and enjoyment; however, the time that students took to complete the test was not significantly reduced. Meta-regression analysis also showed that regional factorsaffected test scores, whereas other factors had no significant impact. When the literature from China was excluded, the satisfaction and happiness of the 3D virtual-reality group were statistically significant compared to those of the traditional group; however, the test results and time consumption were not statistically significant. CONCLUSION: 3D visualization technology is an effective way to improve learners' satisfaction with and enjoyment of human anatomical learning, but it cannot reduce the time required for testers to complete the test. 3D visualization technology may struggle to improve the testers' scores. The literature test results from China are more prone to positive results and affected by regional bias.

A 2-order additive fuzzy measure identification method based on hesitant fuzzy linguistic interaction degree and its application in credit assessment.

To reflect both fuzziness and hesitation in the evaluation of interactivity between attributes in the identification process of 2-order additive fuzzy measure, this work uses the hesitant fuzzy linguistic term set (HFLTS) to describe and depict the interactivity between attributes. Firstly, the interactivity between attributes is defined by the supermodular game theory. According to this definition, a linguistic term set is established to characterize the interactivity between attributes. Under the linguistic term set, the experts employ linguistic expressions generated by context-free grammar to qualitatively describe the interactivity between attributes. Secondly, through the conversion function, the linguistic expressions are transformed into the hesitant fuzzy linguistic term sets (HFLTSs). The individual evaluation results of all experts were further aggregated with the defined hesitant fuzzy linguistic weighted power average operator (HFLWPA). Thirdly, based on the standard Euclidean distance formula of the hesitant fuzzy linguistic elements (HFLEs), the hesitant fuzzy linguistic interaction degree (HFLID) between attributes is defined and calculated by constructing a piecewise function. As a result, a 2-order additive fuzzy measure identification method based on HFLID is proposed. Based on the proposed method, using the Choquet fuzzy integral as nonlinear integration operator, a multi-attribute decision making (MADM) process is then presented. Taking the credit assessment of the big data listed companies in China as an application example, the analysis results of application example prove the feasibility and effectiveness of the proposed method. This work successfully reflects both the fuzziness and hesitation in evaluating the interactivity between attributes in the identification process of 2-order additive fuzzy measure, enriches the theoretical framework of 2-order additive fuzzy measure, and expands the applicability and methodology of 2-order additive fuzzy measure in multi-attribute decision making.

Chelativorans salis sp. nov., a slightly halophilic bacterium isolated from an enrichment system with saline lake sediment.

A Gram-stain-negative, non-motile, and slightly halophilic alphaproteobacterium, designated strain EGI FJ00035T, was isolated from enrichment sediment samples of a saline lake in Xinjiang Uygur Autonomous Region, PR China. The taxonomic position of the isolate was determined using the polyphasic taxonomic and phylogenomic analyses. Phylogenetic analysis based on the 16S rRNA gene sequences indicated that strain EGI FJ00035T formed a distinct clade with 'Chelativorans alearense' UJN715 and 'Chelativorans xinjiangense' lm93 with sequence similarities of 98.44 and 98.22 %, respectively, while sharing less than 96.7 % with other valid type strains. The novel isolate could be distinguished from other species of the genus Chelativorans by its distinct phenotypic, physiological, and genotypic characteristics. Optimal growth of strain EGI FJ00035T occurred on marine agar 2216 at pH 7.0 and 30 °C. The major respiratory quinone was Q-10, while the major fatty acids (>5 %) were C19 : 0 cyclo ω8c, summed feature 8 (C17 : 1 ω6c and/or C17 : 1 ω7c), C16 : 0, C18 : 0, and iso-C17 : 0. The detected polar lipids included diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, unidentified aminophospholipids, unidentified glycolipids, and an unidentified lipid. Based on its genome sequence, the G+C content of strain EGI FJ00035T was 63.2 mol%. The average nucleotide identity, average amino acid identity, and digital DNA-DNA hybridization values of strain EGI FJ00035T against related members of the genus Chelativorans were below the thresholds for delineation of a novel species. According our polyphasic taxonomic data, strain EGI FJ00035T represents a new species of the genus Chelativorans, for which the name Chelativorans salis sp. nov. is proposed. The type strain of the proposed novel isolate is EGI FJ00035T (=KCTC 92251T=CGMCC 1.19480T).

Quantum phase synchronization via exciton-vibrational energy dissipation sustains long-lived coherence in photosynthetic antennas.

The lifetime of electronic coherences found in photosynthetic antennas is known to be too short to match the energy transfer time, rendering the coherent energy transfer mechanism inactive. Exciton-vibrational coherence time in excitonic dimers which consist of two chromophores coupled by excitation transfer interaction, can however be much longer. Uncovering the mechanism for sustained coherences in a noisy biological environment is challenging, requiring the use of simpler model systems as proxies. Here, via two-dimensional electronic spectroscopy experiments, we present compelling evidence for longer exciton-vibrational coherence time in the allophycocyanin trimer, containing excitonic dimers, compared to isolated pigments. This is attributed to the quantum phase synchronization of the resonant vibrational collective modes of the dimer, where the anti-symmetric modes, coupled to excitonic states with fast dephasing, are dissipated. The decoupled symmetric counterparts are subject to slower energy dissipation. The resonant modes have a predicted nearly 50% reduction in the vibrational amplitudes, and almost zero amplitude in the corresponding dynamical Stokes shift spectrum compared to the isolated pigments. Our findings provide insights into the mechanisms for protecting coherences against the noisy environment.

Universal organophosphate pesticides detection by peptide based fluorescent probes.

In practical applications, the rapid and efficient detection of universal organophosphorus pesticides (OPs) can assist inspectors in quickly identifying the presence of OPs in samples. However, this presents a challenge for most well-established methods, typically designed to detect only a specific type of organophosphorus molecule at a time. In this proof-of-concept study, we draw inspiration from the structural similarities among OPs to develop innovative peptide-based fluorescence probes for the first time, which could efficiently detect a broad range of OPs within a mere 3 min. Analysis of fluorescence curve fitting reveals a clear linear correlation between the fluorescent intensity of the peptide probes and the concentration of OPs. Additionally, the selectivity analysis indicates that these peptide fluorescent probes exhibit an excellent response to various OPs while maintaining sufficient selectivity for detecting other pesticide types. Accurate sample analysis has also highlighted the potential of these peptide probes as practical tools for the rapid detection of OPs in actual vegetable samples. In summary, this proof-of-concept study presents an innovative approach to designing and developing ultrafast, universally peptide-based OP probes. These custom-designed peptide probes may facilitate rapid sample screening and offer initial quantification for OPs, potentially saving valuable time and effort in practical OP detection.

Evaluating the impact of automatic positive airway pressure therapy on cardiovascular risk index and vascular behavior in patients with obstructive sleep apnea: a study on heterogeneity in the therapeutic response.

STUDY OBJECTIVES: This study investigated the impact of APAP therapy on vascular behavior and its potential to lower cardiovascular risk in patients with OSA, as well as differentiating APAP therapy heterogeneity. METHODS: All participants were diagnosed with OSA by portable monitoring, and pulse wave parameters and cardiac risk composite parameter index (CRI) were obtained by photoplethysmography before and after APAP. Clustering analysis of pulse wave parameters before APAP in the high-risk population was performed using k-means clustering. Linear regression was used to assess the associations of changes in CRI and pulse wave parameters with clinical characteristics. RESULTS: Eighty-two patients with OSA underwent APAP therapy. The CRI after APAP was significantly lower than before APAP (0.38± 0.33 and 0.58 ± 0.31, respectively; p < 0.001). All pulse wave parameters (except irregular pulse) were significantly different (p < 0.001) in patients with OSA and in the high-risk responders group after versus before APAP. The differences in pulse wave parameters after versus before APAP were not significant in the high-risk non-responders group, except for RCRD and pulse rate variability. Four clusters were obtained from the clustering analysis of pulse wave parameters before APAP in the high-risk responders group. CONCLUSIONS: APAP reduces the CRI in patients with OSA by altering vascular behavior. Overnight photoplethysmography monitoring of pulse wave parameters can be used to assess whether patients with OSA will benefit from APAP.

Improvement of Pre-check and Triage Efficiency and Guarantee of Maternal and Infant Safety in Pandemic Situation.

Objective: The objective of this study was to enhance the efficiency of pre-check and triage procedures in gynecology and obstetrics, while ensuring the safety of maternal and infant patients during the COVID-19 pandemic. Methods: Between March 2020 and July 2022, the workflow in gynecology and obstetrics was optimized, and the management of medical staff working in outpatient, ward, and obstetric ward settings was strengthened. Special protocols were developed and implemented for pregnant women, parturients, and neonates. Detailed procedures and routes were established for patient movement from outpatient areas to wards, with strict adherence to pandemic prevention and control measures. Information-based methods were employed to track and monitor the health status of high-risk pregnant women, parturients, and their families, facilitating accurate and efficient pre-check and triage processes. Results: The implementation of these measures yielded favorable outcomes. No cases of COVID-19 infection were reported among pregnant women and parturients admitted to Liangzhou Hospital. The source of infection was effectively controlled, ensuring the safety of the patients. Conclusion: This study demonstrates the significance of improving pre-check and triage efficiency, strengthening the management of medical staff, and implementing specialized measures for pregnant women, parturients, and neonates to ensure their safety during the COVID-19 pandemic. The established protocols and procedures can serve as a valuable reference for other healthcare facilities seeking to enhance their pandemic prevention and control strategies in gynecology and obstetrics settings.

Concurrent Administration of COVID-19 and Influenza Vaccines Enhances Spike-Specific Antibody Responses.

Background: The bivalent COVID-19 mRNA boosters became available in fall 2022 and were recommended alongside the seasonal influenza vaccine. However, the immunogenicity of concurrent vs separate administration of these vaccines remains unclear. Methods: Here, we analyzed antibody responses in health care workers who received the bivalent COVID-19 booster and the influenza vaccine on the same day or on different days through systems serology. Antibody-binding and functional responses were characterized at peak responses and after 6 months following vaccination. Results: IgG1 and neutralization responses to SARS-CoV-2 XBB.1.5 were higher at peak and after 6 months following concurrent administration as compared with separate administration of the COVID-19 and influenza vaccines. While similar results were not observed for influenza responses, no interference was noted with concurrent administration. Conclusions: These data suggest that concurrent administration of these vaccines may yield higher and more durable SARS-CoV-2 neutralizing antibody responses while maintaining responses against influenza.

Construction of a novel Eu-MOF material based on different detection mechanisms and its application in sensing pollutants aniline, F- and Hg2.

Aniline is an organic pollutant with carcinogenicity and teratogenicity, while F- and Hg2+ are toxic ions that are easily soluble in water. When they are released to the environment, they will pose a threat to human health. Designing a material that can simultaneously detect three types of pollutants is of great significance. In this paper, a novel rare earth metal organic framework material (Eu-MOF) with three-dimensional structure based on 1-methylimidazole-4,5-dicarboxylic acid was synthesized for the first time through solvent thermal method. It has excellent luminescent performance and can be used as a multifunctional fluorescent probe to detect aniline, F-, and Hg2+ based on photoinduced electron transfer, energy competitive absorption, and ion exchange mechanisms, with detection limits of 1.79 × 10-8, 8.13 × 10-8, and 8.83 × 10-7 M, respectively. It is worth noting that Eu-MOF can detect F- and Hg2+ in real water samples, such as lake water and green tea water, with favorable recovery rates.

Multi-omics analyses reveal interactions between the skin microbiota and skin metabolites in atopic dermatitis.

Introduction: Atopic dermatitis (AD) is one of the most common inflammatory skin diseases. Skin microecological imbalance is an important factor in the pathogenesis of AD, but the underlying mechanism of its interaction with humans remains unclear. Methods: 16S rRNA gene sequencing was conducted to reveal the skin microbiota dynamics. Changes in skin metabolites were tracked by LC-MS metabolomics. We then explored the potential mechanism of interaction by analyzing the correlation between skin bacterial communities and metabolites in corresponding skin-associated samples. Results: Samples from 18 AD patients and 18 healthy volunteers (HVs) were subjected to 16S rRNA gene sequencing and LC-MS metabolomics. AD patients had dysbiosis of the skin bacterial community with decreased species richness and evenness. The relative abundance of the genus Staphylococcus increased significantly in AD, while the abundances of the genera Propionibacterium and Brevundimonas decreased significantly. The relative abundance of the genera Staphylococcus in healthy females was significantly higher than those in healthy males, while it showed no difference in AD patients with or without lesions. The effects of AD status, sex and the presence or absence of rashes on the number of differentially abundant metabolites per capita were successively reduced. Multiple metabolites involved in purine metabolism and phenylalanine metabolism pathways (such as xanthosine/xanthine and L-phenylalanine/trans-cinnamate) were increased in AD patients. These trends were much more obvious between female AD patients and female HVs. Spearman correlation analysis revealed that the genus Staphylococcus was positively correlated with various compounds involved in phenylalanine metabolism and purine metabolic pathways. The genera Brevundimonas and Lactobacillus were negatively correlated with various compounds involved in purine metabolism, phenylalanine metabolism and sphingolipid signaling pathways. Discussion: We suggest that purine metabolism and phenylalanine metabolism pathway disorders may play a certain role in the pathogenic mechanism of Staphylococcus aureus in AD. We also found that females are more likely to be colonized by the genus Staphylococcus than males. Differentially abundant metabolites involved in purine metabolism and phenylalanine metabolism pathways were more obvious in female. However, we should notice that the metabolites we detected do not necessarily derived from microbes, they may also origin from the host.

Identification of an anaplastic subtype of prostate cancer amenable to therapies targeting SP1 or translation elongation.

Histopathological heterogeneity is a hallmark of prostate cancer (PCa). Using spatial and parallel single-nucleus transcriptomics, we report an androgen receptor (AR)-positive but neuroendocrine-null primary PCa subtype with morphologic and molecular characteristics of small cell carcinoma. Such small cell-like PCa (SCLPC) is clinically aggressive with low AR, but high stemness and proliferation, activity. Molecular characterization prioritizes protein translation, represented by up-regulation of many ribosomal protein genes, and SP1, a transcriptional factor that drives SCLPC phenotype and overexpresses in castration-resistant PCa (CRPC), as two potential therapeutic targets in AR-indifferent CRPC. An SP1-specific inhibitor, plicamycin, effectively suppresses CRPC growth in vivo. Homoharringtonine, a Food And Drug Administration-approved translation elongation inhibitor, impedes CRPC progression in preclinical models and patients with CRPC. We construct an SCLPC-specific signature capable of stratifying patients for drug selectivity. Our studies reveal the existence of SCLPC in admixed PCa pathology, which may mediate tumor relapse, and establish SP1 and translation elongation as actionable therapeutic targets for CRPC.