Evolution of the SPX gene family and its role in the response mechanism to low phosphorus stress in self-rooted apple stock.

BACKGROUND: Phosphorus plays a key role in plant adaptation to adversity and plays a positive role in the yield and quality formation of apples. Genes of the SPX domain-containing family are widely involved in the regulation of phosphorus signalling networks. However, the mechanisms controlling phosphorus deficiency are not completely understood in self-rooted apple stock. RESULTS: In this study, 26 members of the apple SPX gene family were identified by genome-wide analysis, and further divided into four subfamilies (SPX, SPX-MFS, SPX-EXS, and SPX-RING) based on their structural features. The chromosome distribution and gene duplications of MdSPXs were also examined. The promoter regions of MdSPXs were enriched for multiple biotic/abiotic stresses, hormone responses and typical P1BS-related elements. Analysis of the expression levels of 26 MdSPXs showed that some members were remarkably induced when subjected to low phosphate (Pi) stress, and in particular MdSPX2, MdSPX3, and MdPHO1.5 exhibited an intense response to low Pi stress. MdSPX2 and MdSPX3 showed significantly divergent expression levels in low Pi sensitive and insensitive apple species. Protein interaction networks were predicted for 26 MdSPX proteins. The interaction of MdPHR1 with MdSPX2, MdSPX3, MdSPX4, and MdSPX6 was demonstrated by yeast two-hybrid assay, suggesting that these proteins might be involved in the Pi-signaling pathway by interacting with MdPHR1. CONCLUSION: This research improved the understanding of the apple SPX gene family and contribute to future biological studies of MdSPX genes in self-rooted apple stock.

A Functional "Key" Amplified Piezoelectric Effect Modulates ROS Storm with an Open Source for Multimodal Synergistic Cancer Therapy.

Chemodynamic therapy (CDT) is a non-invasive strategy for generating reactive oxygen species (ROS) and is promising for cancer treatment. However, increasing ROS in tumor therapy remains challenging. Therefore, exogenous excitation and inhibition of electron-hole pair recombination are attractive for modulating ROS storms in tumors. Herein, a Ce-doped BiFeO3 (CBFO) piezoelectric sonosensitizer to modulate ROS generation and realize a synergistic mechanism of CDT/sonodynamic therapy and piezodynamic therapy (PzDT) is proposed. The mixed Fe2+ and Ce3+ can implement a circular Fenton/Fenton-like reaction in the tumor microenvironment. Abundant ·OH can be generated by ultrasound (US) stimulation to enhance CDT efficacy. As a typical piezoelectric sonosensitizer, CBFO can produce O2 - owing to the enhanced polarization by the US, resulting in the motion of charge carriers. In addition, CBFO can produce a piezoresponse irradiated upon US, which accelerates the migration rate of electrons/holes in opposite directions and results in energy band bending, further achieving toxic ROS production and realizing PzDT. Density functional theory calculations confirmed that Ce doping shortens the diffusion of electrons and improves the conductivity and catalytic activity of CBFO. This distinct US-enhanced strategy emphasizes the effects of doping engineering and piezoelectric-optimized therapy and shows great potential for the treatment of malignant tumors.

Current perspectives of sudden cardiac death management in hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disorder characterized by left ventricular hypertrophy. Sudden cardiac death (SCD) is a rare but the most catastrophic complication in patients with HCM. Implantable cardioverter-defibrillators (ICDs) are widely recognized as effective preventive measures for SCD. Individualized risk stratification and early intervention in HCM can significantly improve patient prognosis. In this study, we review the latest findings regarding pathogenesis, risk stratification, and prevention of SCD in HCM patients, highlighting the clinic practice of cardiovascular magnetic resonance imaging for SCD management.

Sum and difference frequency generation in a valley-photonic-crystal-like topological system.

Nonlinear sum frequency generation (SFG) and difference frequency generation (DFG) are fundamental methods to obtain new light sources for various applications. However, most of the on-chip SFG and DFG are based on conventional resonators, lacking robustness against fabrication defects. Here, we demonstrate topologically protected SFG and DFG in a second-order topological photonic system. The mechanism is based on the nonlinear interaction between three high-Q corner modes inside dual topological band gaps. The frequency matching condition for SFG and DFG is precisely satisfied by designing a valley-photonic-crystal-like topological system, which provides more freedoms to tune the corner modes. The topological SFG and DFG are achieved with high conversion efficiency, and the underlying topological physics is revealed. This work opens up avenues toward topologically protected nonlinear frequency conversion, and can find applications in the fields of on-chip single-photon detections and optical quantum memories with robustness against defects.

Angiotensin blockade enhances motivational reward learning via enhancing striatal prediction error signaling and frontostriatal communication.

Adaptive human learning utilizes reward prediction errors (RPEs) that scale the differences between expected and actual outcomes to optimize future choices. Depression has been linked with biased RPE signaling and an exaggerated impact of negative outcomes on learning which may promote amotivation and anhedonia. The present proof-of-concept study combined computational modeling and multivariate decoding with neuroimaging to determine the influence of the selective competitive angiotensin II type 1 receptor antagonist losartan on learning from positive or negative outcomes and the underlying neural mechanisms in healthy humans. In a double-blind, between-subjects, placebo-controlled pharmaco-fMRI experiment, 61 healthy male participants (losartan, n = 30; placebo, n = 31) underwent a probabilistic selection reinforcement learning task incorporating a learning and transfer phase. Losartan improved choice accuracy for the hardest stimulus pair via increasing expected value sensitivity towards the rewarding stimulus relative to the placebo group during learning. Computational modeling revealed that losartan reduced the learning rate for negative outcomes and increased exploitatory choice behaviors while preserving learning for positive outcomes. These behavioral patterns were paralleled on the neural level by increased RPE signaling in orbitofrontal-striatal regions and enhanced positive outcome representations in the ventral striatum (VS) following losartan. In the transfer phase, losartan accelerated response times and enhanced VS functional connectivity with left dorsolateral prefrontal cortex when approaching maximum rewards. These findings elucidate the potential of losartan to reduce the impact of negative outcomes during learning and subsequently facilitate motivational approach towards maximum rewards in the transfer of learning. This may indicate a promising therapeutic mechanism to normalize distorted reward learning and fronto-striatal functioning in depression.

Inhibition of GBP5 activates autophagy to alleviate inflammatory response in LPS-induced lung injury in mice.

BACKGROUND: Pulmonary emphysema is a condition that causes damage to the lung tissue over time. GBP5, as part of the guanylate-binding protein family, is dysregulated in mouse pulmonary emphysema. However, the role of GBP5 in lung inflammation in ARDS remains unveiled. METHODS: To investigate whether GBP5 regulates lung inflammation and autophagy regulation, the study employed a mouse ARDS model and MLE-12 cell culture. Vector transfection was performed for the genetic manipulation of GBP5. Then, RT-qPCR, WB and IHC staining were conducted to assess its transcriptional and expression levels. Histological features of the lung tissue were observed through HE staining. Moreover, ELISA was conducted to evaluate the secretion of inflammatory cytokines, autophagy was assessed by immunofluorescent staining, and MPO activity was determined using a commercial kit. RESULTS: Our study revealed that GBP5 expression was altered in mouse ARDS and LPS-induced MLE-12 cell models. Moreover, the suppression of GBP5 reduced lung inflammation induced by LPS in mice. Conversely, overexpression of GBP5 diminished the inhibitory impact of LPS on ARDS during autophagy, leading to increased inflammation. In the cell line of MLE-12, GBP5 exacerbates LPS-induced inflammation by blocking autophagy. CONCLUSION: The study suggests that GBP5 facilitates lung inflammation and autophagy regulation. Thus, GBP5 could be a potential therapeutic approach for improving ARDS treatment outcomes, but further research is required to validate these findings.

Characterization and functional evidence for Orf2 of Streptomyces sp. 139 as a novel dipeptidase E.

Aspartyl dipeptidase (dipeptidase E) can hydrolyze Asp-X dipeptides (where X is any amino acid), and the enzyme plays a key role in the degradation of peptides as nutrient sources. Dipeptidase E remains uncharacterized in Streptomyces. Orf2 from Streptomyces sp. 139 is located in the exopolysaccharide biosynthesis gene cluster, which may be a novel dipeptidase E with "S134-H170-D198" catalytic triad by sequence and structure comparison. Herein, recombinant Orf2 was expressed in E. coli and characterized dipeptidase E activity using the Asp-ρNA substrate. The optimal pH and temperature for Orf2 are 7.5 and 40 ℃; Vmax and Km of Orf2 are 0.0787 mM·min-1 and 1.709 mM, respectively. Orf2 exhibits significant degradation activities to Asp-Gly-Gly, Asp-Leu, Asp-His, and isoAsp-Leu and minimal activities to Asp-Pro and Asp-Ala. Orf2 contains a Ser-His-Asp catalytic triad characterized by point mutation. In addition, the Asp147 residue of Orf2 is also proven to be critical for the enzyme's activity through molecular docking and point mutation. Transcriptome analysis reveals the upregulation of genes associated with ribosomes, amino acid biosynthesis, and aminoacyl-tRNA biosynthesis in the orf2 mutant strain. Compared with the orf2 mutant strain and WT, the yield of crude polysaccharide does not change significantly. However, crude polysaccharides from the orf2 mutant strain exhibit a wider range of molecular weight distribution. The results indicate that the Orf2 links nutrient stress to secondary metabolism as a novel dipeptidase E. KEY POINTS: • A novel dipeptidase E with a Ser-His-Asp catalytic triad was characterized from Streptomyces sp. 139. • Orf2 was involved in peptide metabolism both in vitro and in vivo. • Orf2 linked nutrient stress to mycelia formation and secondary metabolism in Streptomyces.

Clinical features of Mycoplasma pneumoniae pneumonia in children without fever.

BACKGROUND: Mycoplasma pneumoniae (MP) is one of the most common causes of community-acquired pneumonia in children. Most children have fever. In 2021, we found that the proportion of children without fever increased. The aim of this study is to summarize the differences in the clinical characteristics of children with MP pneumonia who are febrile or not, and to raise awareness of children who are not febrile. METHOD: Demographic information of the children was collected on admission. Clinical manifestations during the course of the disease and the first laboratory, imaging, and pulmonary function tests before discharge were recorded and compared. RESULTS: From August to December, a total of 542 people were included in the study. We found that older children were more likely to have fever. Inflammatory indicators including procalcitonin (P = 0.030), C-reaction protein (P < 0.001), erythrocyte sedimentation rate (P < 0.001), ferritin (P = 0.040) and the rate of atelectasis (P = 0.049) of febrile children were higher in febrile children. However, the elevated lactate dehydrogenase and pulmonary function impairment (P all > 0.05), especially the small airway function impairment, are no lower in afebrile children than in febrile children. CONCLUSION: The fever rate is lower in younger children, but wheezing is more common. In afebrile children, the impairment of organ and lung function was no less than in febrile children. Therefore, attention should also be paid to children who are not febrile.

An Advanced Tool Wear Forecasting Technique with Uncertainty Quantification Using Bayesian Inference and Support Vector Regression.

Tool wear prediction is of great significance in industrial production. Current tool wear prediction methods mainly rely on the indirect estimation of machine learning, which focuses more on estimating the current tool wear state and lacks effective quantification of random uncertainty factors. To overcome these shortcomings, this paper proposes a novel method for predicting cutting tool wear. In the offline phase, the multiple degradation features were modeled using the Brownian motion stochastic process and a SVR model was trained for mapping the features and the tool wear values. In the online phase, the Bayesian inference was used to update the random parameters of the feature degradation model, and the future trend of the features was estimated using simulation samples. The estimation results were input into the SVR model to achieve in-advance prediction of the cutting tool wear in the form of distribution densities. An experimental tool wear dataset was used to verify the effectiveness of the proposed method. The results demonstrate that the method shows superiority in prediction accuracy and stability.

Waveguide-Integrated Light-Emitting Metal-Insulator-Graphene Tunnel Junctions.

Ultrafast interfacing of electrical and optical signals at the nanoscale is highly desired for on-chip applications including optical interconnects and data processing devices. Here, we report electrically driven nanoscale optical sources based on metal-insulator-graphene tunnel junctions (MIG-TJs), featuring waveguided output with broadband spectral characteristics. Electrically driven inelastic tunneling in a MIG-TJ, realized by integrating a silver nanowire with graphene, provides broadband excitation of plasmonic modes in the junction with propagation lengths of several micrometers (∼10 times larger than that for metal-insulator-metal junctions), which therefore propagate toward the junction edge with low loss and couple to the nanowire waveguide with an efficiency of ∼70% (∼1000 times higher than that for metal-insulator-metal junctions). Alternatively, lateral coupling of the MIG-TJ to a semiconductor nanowire provides a platform for efficient outcoupling of electrically driven plasmonic signals to low-loss photonic waveguides, showing potential for applications at various integration levels.

Advances in Therapeutics to Alleviate Cognitive Decline and Neuropsychiatric Symptoms of Alzheimer's Disease.

Dementia exists as a 'progressive clinical syndrome of deteriorating mental function significant enough to interfere with activities of daily living', with the most prevalent type of dementia being Alzheimer's disease (AD), accounting for about 80% of diagnosed cases. AD is associated with an increased risk of comorbidity with other clinical conditions such as hypertension, diabetes, and neuropsychiatric symptoms (NPS) including, agitation, anxiety, and depression as well as increased mortality in late life. For example, up to 70% of patients diagnosed with AD are affected by anxiety. As aging is the major risk factor for AD, this represents a huge global burden in ageing populations. Over the last 10 years, significant efforts have been made to recognize the complexity of AD and understand the aetiology and pathophysiology of the disease as well as biomarkers for early detection. Yet, earlier treatment options, including acetylcholinesterase inhibitors and glutamate receptor regulators, have been limited as they work by targeting the symptoms, with only the more recent FDA-approved drugs being designed to target amyloid-ß protein with the aim of slowing down the progression of the disease. However, these drugs may only help temporarily, cannot stop or reverse the disease, and do not act by reducing NPS associated with AD. The first-line treatment options for the management of NPS are selective serotonin reuptake inhibitors/selective noradrenaline reuptake inhibitors (SSRIs/SNRIs) targeting the monoaminergic system; however, they are not rational drug choices for the management of anxiety disorders since the GABAergic system has a prominent role in their development. Considering the overall treatment failures and side effects of currently available medication, there is an unmet clinical need for rationally designed therapies for anxiety disorders associated with AD. In this review, we summarize the current status of the therapy of AD and aim to highlight novel angles for future drug therapy in our ongoing efforts to alleviate the cognitive deficits and NPS associated with this devastating disease.

Penifuranone A: A Novel Alkaloid from the Mangrove Endophytic Fungus Penicillium crustosum SCNU-F0006.

One previously undescribed alkaloid, named penifuranone A (1), and three known compounds (2-4) were isolated from the mangrove endophytic fungus Penicillium crustosum SCNU-F0006. The structure of the new alkaloid (1) was elucidated based on extensive spectroscopic data analysis and single-crystal X-ray diffraction analysis. Four natural isolates and one new synthetic derivative of penifuranone A, compound 1a, were screened for their antimicrobial, antioxidant, and anti-inflammatory activities. Bioassays revealed that penifuranone A (1) exhibited strong anti-inflammatory activity in vitro by inhibiting nitric oxide (NO) production in lipopolysaccharide-activated RAW264.7 cells with an IC50 value of 42.2 µM. The docking study revealed that compound 1 exhibited an ideal fit within the active site of the murine inducible nitric oxide synthase (iNOS), establishing characteristic hydrogen bonds.

Professional values education for undergraduate nursing students: developing a framework based on the professional values growth theory.

BACKGROUND: Education has been recognised as necessary in forming and internalising professional values. The system and instructors' content in existing educational institutions focus on developing students' knowledge, skills and practices. Still, the development of values has yet to achieve significant effects, leading to a crisis in students' professional identity. AIMS: To construct a professional values growth theory for undergraduate nursing students and develop a corresponding education framework. METHODS: Through the review, some databases(PubMed、CINAHL、Web of Science、Wiley and Google Scholars)were searched using a systematic search strategy to collect relevant literature on professional values education. Based on the nursing professional values growth theory (Li and Li, Nursing Ethics In press, 2022), a theory of professional values growth of nursing undergraduates was developed using the method of theory derivation. Two rounds of expert meetings were conducted to review and revise an education framework of professional values of nursing undergraduates derived from that theory. FINDINGS: A total of 10 studies were included. The contents of two themes were analysed: theories and models and the current status of the professional values development of nursing students. The resulting professional values growth theory for undergraduate nursing students consists of five parts: key aspects, decisive opportunities, drivers, embodiment (humanistic sentiments, moral emotions), and outcomes. A total of five experts in the relevant fields were invited to this study. After two rounds of expert meetings, an education framework for undergraduate nursing students was finally developed, which consists of four parts: education objectives, education process and content, environment and conditions, and evaluation. CONCLUSION: The education framework developed in this study has practical implications for the development of professional values of undergraduate nursing students, providing educational strategies and methods for the growth and internalisation of professional values of undergraduate nursing students.

Effect of the L74I Polymorphism on Fitness of Cabotegravir-Resistant Variants of Human Immunodeficiency Virus 1 Subtype A6.

The presence of human immunodeficiency virus (HIV) 1 subtype A6, characterized by the L74I integrase (IN) polymorphism, is associated with confirmed virologic failure in clinical trials of long-acting cabotegravir and rilpivirine. We investigated the effect of L74I on replication capacity (RC) of recombinant viruses carrying this polymorphism in combination with various IN stand-transfer inhibitor resistance mutations. The presence of L74I conferred greater RC to recombinant viruses expressing HIV-1 A6 IN when present together with G118R, G140R, Q148H, and R263K; no significant difference in RC was observed for the Q148K or R mutants. These findings may explain, in part, the association of HIV-1 subtype A6 with virologic failure.

Complete chloroplast genomes provide insights into evolution and phylogeny of Zingiber (Zingiberaceae).

BACKGROUND: The genus Zingiber of the Zingiberaceae is distributed in tropical, subtropical, and in Far East Asia. This genus contains about 100-150 species, with many species valued as important agricultural, medicinal and horticultural resources. However, genomic resources and suitable molecular markers for species identification are currently sparse. RESULTS: We conducted comparative genomics and phylogenetic analyses on Zingiber species. The Zingiber chloroplast genome (size range 162,507-163,711 bp) possess typical quadripartite structures that consist of a large single copy (LSC, 86,986-88,200 bp), a small single copy (SSC, 15,498-15,891 bp) and a pair of inverted repeats (IRs, 29,765-29,934 bp). The genomes contain 113 unique genes, including 79 protein coding genes, 30 tRNA and 4 rRNA genes. The genome structures, gene contents, amino acid frequencies, codon usage patterns, RNA editing sites, simple sequence repeats and long repeats are conservative in the genomes of Zingiber. The analysis of sequence divergence indicates that the following genes undergo positive selection (ccsA, ndhA, ndhB, petD, psbA, psbB, psbC, rbcL, rpl12, rpl20, rpl23, rpl33, rpoC2, rps7, rps12 and ycf3). Eight highly variable regions are identified including seven intergenic regions (petA-pabJ, rbcL-accD, rpl32-trnL-UAG, rps16-trnQ-UUG, trnC-GCA-psbM, psbC-trnS-UGA and ndhF-rpl32) and one genic regions (ycf1). The phylogenetic analysis revealed that the sect. Zingiber was sister to sect. Cryptanthium rather than sect. Pleuranthesis. CONCLUSIONS: This study reports 14 complete chloroplast genomes of Zingiber species. Overall, this study provided a solid backbone phylogeny of Zingiber. The polymorphisms we have uncovered in the sequencing of the genome offer a rare possibility (for Zingiber) of the generation of DNA markers. These results provide a foundation for future studies that seek to understand the molecular evolutionary dynamics or individual population variation in the genus Zingiber.

Carbonized Polymer Dots Assemble in Proton-Conducting Channels to Enhance the Conductivity and Selectivity Simultaneously for High-Performance Fuel Cells.

Fabricating polymer electrolyte membranes (PEMs) simultaneously with high ion conductivity and selectivity has always been an ultimate goal in many membrane-integrated systems for energy conversion and storage. Constructing broader ion-conducting channels usually enables high-efficient ion conductivity while often bringing increased crossover of other ions or molecules simultaneously, resulting in decreased selectivity. Here, the ultra-small carbon dots (CDs) with the selective barriers are self-assembled within proton-conducting channels of PEMs through electrostatic interaction to enhance the proton conductivity and selectivity simultaneously. The functional CDs regulate the nanophase separation of PEMs and optimize the hydration proton network enabling higher-efficient proton transport. Meanwhile, the CDs within proton-conducting channels prevent fuel from permeating selectively due to their repelling and spatial hindrance against fuel molecules, resulting in highly enhanced selectivity. Benefiting from the improved conductivity and selectivity, the open-circuit voltage and maximum power density of the direct methanol fuel cell (DMFC) equipped with the hybrid membranes raised by 23% and 93%, respectively. This work brings new insight to optimize polymer membranes for efficient and selective transport of ions or small molecules, solving the trade-off of conductivity and selectivity.

MPK6-mediated HY5 phosphorylation regulates light-induced anthocyanin accumulation in apple fruit.

Light is known to regulate anthocyanin pigment biosynthesis in plants on several levels, but the significance of protein phosphorylation in light-induced anthocyanin accumulation needs further investigation. In this study, we investigated the dynamics of the apple fruit phosphoproteome in response to light, using high-performance liquid chromatography-tandem mass spectrometry analysis. Among the differentially phosphorylated proteins, the bZIP (basic leucine zipper) transcription factor, HY5, which has been identified as an anthocyanin regulator, was rapidly activated by light treatment of the fruit. We hypothesized that phosphorylated MdHY5 may play a role in light-induced anthocyanin accumulation of apple fruit. Protein interaction and phosphorylation assays showed that mitogen-activated protein kinase MdMPK6 directly interacted with, and activated, MdHY5 via phosphorylation under light conditions, thereby increasing its stability. Consistent with this finding, the suppression of the mitogen-activated protein kinase genes MdMPK6 or MdHY5 resulted in an inhibition of anthocyanin accumulation, and further showed that light-induced anthocyanin accumulation is dependent on MdMPK6 kinase activity, and is required for maximum MdHY5 activity. Under light conditions, active MdMPK6 phosphorylated MdHY5 leading to accumulation of phospho-MdHY5, which enhanced the binding of MdHY5 to its target anthocyanin related genes in fruit. Our findings reveal an MdMPK6-MdHY5 phosphorylation pathway in light-induced anthocyanin accumulation, providing new insights into the regulation of light-induced anthocyanin biosynthesis in apple fruit at both the transcriptional and post-translational levels.

Prognostic significance of preoperative serum tumor markers in hepatoid adenocarcinoma of stomach (HAS).

BACKGROUND: The role of preoperative serum tumor markers in HAS patients was vague, we designed the study to explore the effect of preoperative serum tumor markers on predicting the prognosis of HAS patients. METHODS: A total of 139 patients were included according to the different tumor makers. X-tile tool was employed to identify the optimal cut-off values of respective tumor makers. Multivariate analyses were conducted to determine independent risk factors. RESULTS: The optimal cut-off value of alpha-fetoprotein (AFP) for 3-years overall survival (OS) and recurrence-free survival (RFS) was 516 ng/mL. Patients with high-level AFP values assumed significantly worse OS and RFS than those with low-level AFP values (P = 0.028 and P = 0.011, respectively). The optimal cut-off value of Carbohydrate antigen (CA)19-9 for OS and RFS was 51.3 U/mL. And the survival results were similar with AFP in the aspects of OS and RFS (P = 0.009 and P < 0.001, respectively). Multivariate analyses showed that high serum AFP was an independent risk factor for OS and RFS of HAS patients (HR7.264; 95% CI 1.328-39.738; P = 0.022 and HR 2.688; 95% CI 0.922-7.836; P = 0.070, respectively). CA19-9 could perform as a fair substitute to predict the HAS patients' OS and RFS when the preoperative serum AFP was unavailable (HR 7.816; 95% CI 2.084-29.308; P = 0.002 and HR 4.386; 95% CI 1.824-10.547; P = 0.001, respectively). Other tumor markers didn't present significant influences. CONCLUSIONS: Applying preoperative serum AFP level to predict the HAS patients' prognosis is feasible and preoperative serum high-AFP is an independent risk factor for OS and RFS of HAS patients. Preoperative serum CA19-9 could be an alternative choice when AFP was absent.

Staphylococcus warneri strain XSB102 exacerbates psoriasis and promotes keratinocyte proliferation in imiquimod-induced psoriasis-like dermatitis mice.

Psoriasis is one of the common chronic inflammatory skin diseases worldwide. The skin microbiota plays a role in psoriasis through regulating skin homeostasis. However, the studies on the interactions between symbiotic microbial strains and psoriasis are limited. In this study, Staphylococcus strain XSB102 was isolated from the skin of human, which was identified as Staphylococcus warneri using VITEK2 Compact. To reveal the roles of Staphylococcus warneri on psoriasis, XSB102 were applied on the back of imiquimod-induced psoriasis-like dermatitis mice. The results indicated that it exacerbated the psoriasis and significantly increased the thickening of the epidermis. Furthermore, in vitro experiments confirmed that inactivated strain XSB102 could promote the proliferation of human epidermal keratinocytes (HaCaT) cell. However, real-time quantitative PCR and immunofluorescence results suggested that the expression of inflammatory factors such as IL-17a, IL-6, and so on were not significantly increased, while extracellular matrix related factors such as Col6a3 and TGIF2 were significantly increased after XSB102 administration. This study indicates that Staphylococcus warneri XSB102 can exacerbate psoriasis and promote keratinocyte proliferation independently of inflammatory factors, which paves the way for further exploration of the relationship between skin microbiota and psoriasis.

Computational study of novel natural inhibitors targeting Kirsten rat sarcoma viral oncogene homolog G12C.

Lung adenocarcinoma is one of the most aggressive and rapidly fatal types of malignant lung tumor. Molecular docking and virtual screening were effectively and systematically used to identify specific targets in malignant tumors and screen potential drugs. Here, we screen perfect leading compounds from a medicate library (ZINC15 database) and analyze their properties (conveyance, absorption, metabolism, excretion, and harmless forecasts) with potential inhibition of Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) G12C. Further results demonstrated that ZINC000013817014 and ZINC000004098458 were screened out from the ZINC15 database and were identified to have a much better binding affinity and more favorable interaction vitality binding with KRAS G12C and less rat carcinogenicity, Ames mutagenicity, way better dissolvability in water and noninhibition with cytochrome P-450 2D6. Molecular dynamics simulation analysis indicated that the binding capacity of these two compounds and KRAS G12C, ZINC000013817014-KRAS G12C, and ZINC000004098458-KRAS G12C is stable in the natural environment. Our findings reveal that ZINC000013817014 and ZINC000004098458 were perfect leading compounds to be inhibitors binding with KRAS G12C, which were selected as safe drug candidates and a cornerstone for KRAS G12C-related medicine plan and improvement. What is more, we have conducted a Cell Counting Kit-8 to verify the exactly inhibitory effects of the two selected drugs on Lung adenocarcinoma. This study establishes a solid framework for systematic anticancer medication research and development.