Multiplex-genome-editing based rapid directional improvement of complex traits in rice.

Although thousands of genes have been identified or cloned in rice (Oryza sativa) in the last two decades, the majority of them have only been separately characterized in specific varieties or single-gene modified backgrounds, thus limiting their practical application. We developed an optimized multiplex genome editing (MGE) toolbox that can efficiently assemble and stably express up to twelve sgRNA targets in a single plant expression vector. In this study, we established the MGE-based Rapid Directional Improvement (MRDI) strategy for directional improvement of complex agronomic traits in one small-scale rice transformation. This approach provides a rapid and practical procedure, encompassing sgRNA assembly, transgene-free screening and the creation of promising germplasm, by combining the precision of gene editing with phenotype-based field breeding. The MRDI strategy was used to generate the full diversity of twelve main agronomic genes in rice cultivar FXZ for the directional improvement of its growth duration and plant architecture. After applying the MRDI to FXZ, ideal plants with the desired traits of early heading date reduced plant height, and more effective panicles were generated without compromising yield, blast resistance and grain quality. Furthermore, the results of whole-genome sequencing (WGS), including the analysis of structural variations (SVs) and single nucleotide variations (SNVs) in the MGE plants, confirmed the high specificity and low frequency of unwanted mutations associated with this strategy. The MRDI breeding strategy would be a robust approach for exploring and applying crucial agronomic genes, as well as for generating novel elite germplasm in the future.

Identification of miR-20b-5p as an inhibitory regulator in cardiac differentiation via TET2 and DNA hydroxymethylation.

BACKGROUND: Congenital heart disease (CHD) is a prevalent congenital cardiac malformation, which lacks effective early biological diagnosis and intervention. MicroRNAs, as epigenetic regulators of cardiac development, provide potential biomarkers for the diagnosis and treatment of CHD. However, the mechanisms underlying miRNAs-mediated regulation of cardiac development and CHD malformation remain to be further elucidated. This study aimed to explore the function of microRNA-20b-5p (miR-20b-5p) in cardiac development and CHD pathogenesis. METHODS AND RESULTS: miRNA expression profiling identified that miR-20b-5p was significantly downregulated during a 12-day cardiac differentiation of human embryonic stem cells (hESCs), whereas it was markedly upregulated in plasma samples of atrial septal defect (ASD) patients. Our results further revealed that miR-20b-5p suppressed hESCs-derived cardiac differentiation by targeting tet methylcytosine dioxygenase 2 (TET2) and 5-hydroxymethylcytosine, leading to a reduction in key cardiac transcription factors including GATA4, NKX2.5, TBX5, MYH6 and cTnT. Additionally, knockdown of TET2 significantly inhibited cardiac differentiation, which could be partially restored by miR-20b-5p inhibition. CONCLUSIONS: Collectively, this study provides compelling evidence that miR-20b-5p functions as an inhibitory regulator in hESCs-derived cardiac differentiation by targeting TET2, highlighting its potential as a biomarker for ASD.

Outer membrane vesicles mediating horizontal transfer of the epidemic blaOXA-232 carbapenemase gene among Enterobacterales.

OXA-232 is one of the most common OXA-48-like carbapenemase derivatives and is widely disseminated in nosocomial settings across countries. The blaOXA-232 gene is located on a 6-kb non-conjugative ColKP3-type plasmid, while the dissemination of blaOXA-232 into different Enterobacterales species and the polyclonal dissemination of OXA-232-producing K. pneumoniae revealed the horizontal transfer of blaOXA-232. However, it's still unclear how this non-conjugative ColKP3 plasmid could facilitate the mobilization of blaOXA-232. Here, we observed the in vivo intraspecies transfer of blaOXA-232 during a nosocomial outbreak of OXA-232-producing K. pneumoniae. We demonstrated the presence of ColKP3 OXA-232 plasmid in the outer membrane vesicles (OMVs) derived from clinical isolates, and OMVs could facilitate the horizontal transfer of blaOXA-232 among Enterobacterales. In contrast, for the most prevalent carbapenemase genes, including blaKPC-2 and blaNDM-1, though the presence of carbapenemase genes and plasmid backbones in the vesicular lumen was observed, OMVs couldn't promote effective transformation, probably due to the low copy number of plasmids in clinical isolates and the low number of plasmids loaded into vesicles. Conjugation assay revealed that the epidemic IncX3 NDM-1 and IncFII(pHN7A8)/IncR KPC-2 plasmids were conjugative and could be horizontally transferred via independent conjugation or with the help of a co-existent conjugative plasmid. For the large-size and low-copy number conjugative plasmids carrying carbapenemase genes, OMVs-mediated gene exchange may only serve as an alternative pathway for horizontal transfer. In conclusion, diverse mobilization strategies were employed by plasmids harboring carbapenemase genes, and plasmids display a proper choice of mobility pathway due to their individual properties.

Teacher-Assessed Linguistic and Social Abilities in Chinese Children's Reading Acquisition: A Longitudinal Study.

The study explored the relationship between teacher assessments of students' general language-cognitive and social-emotional abilities and Chinese children's reading development over an academic year. A series of reading measures (including reading vocabulary, reading comprehension, and lexical inferencing ability) were administered to Chinese-speaking second graders (N = 123) across time. Meanwhile, their six head teachers and assistant head teachers were asked to complete assessments of their language-cognitive and social-emotional abilities prior to the first data collection. By utilizing multivariate analyses, the results demonstrated that teacher-assessed linguistic and social abilities contributed to children's reading abilities within and across time after autoregressive effects were controlled for. More specifically, language and cognitive abilities made a more salient contribution to reading performance over time. The study suggests that teacher assessments could have diagnostic and preventive functions for enhancing sustainable reading development among Chinese elementary-age students.

The mechanism of the Shuang Bai Su Qing recipe in treating periodontitis based on network pharmacology and molecular docking technology.

AIM: To explore the material basis of action of the Shuang Bai Su Qing recipe in the treatment of periodontitis using network pharmacology. METHODS: Using TCMSP, we screened the chemical components of 5 drugs. The components were input into the UniProt and PubChem databases to obtain target proteins; Genecards, Online Mendelian Inheritance in Man (OMIM), and CEO databases were used to screen target proteins for periodontal disease. The targets were imported into the Cytoscape software to obtain intersecting targets, and conduct visual analysis to build the PPI network. The intersecting targets were then input into the Matescape database and subjected to biological process (BP) analysis, molecular function (MF) analysis, cell component (CC) analysis, and KEGG enrichment analysis. RESULTS: Twenty-seven TCM chemical components were obtained, with 198 target proteins associated with drugs and 2587 target proteins for periodontitis. Ten core targets were identified. Gene Ontology (GO) functional enrichment analysis yielded results for 20 BP, 11 MF, and 10 CC. KEGG analysis revealed that the main mechanisms of action were related to MAPK signaling pathway. Molecular docking results showed that luteolin strongly bind to TNF, IL6, and IL1B target proteins. CONCLUSION: The mechanism underlying the treatment of periodontitis with the recipe formula may be closely related to multiple targets in the MAPK signaling pathway.

Transforming Hetera-Buckybowls into Chiral Conjugated Polycycles Incorporating Epoxycyclooctadiene: a Two-Step Approach.

Chiral π-conjugated polycycles have garnered increasing attention due to versatile applications in optoelectronic materials and biological sciences. In this study, we report the synthesis of chiral π-conjugated polycycles incorporating a chiral epoxycyclooctadiene moiety. Our synthetic strategy capitalizes on the novel reactions of hetera-buckybowl triselenasumanene (TSS) and is achieved in two-step manner. Firstly, the TSS is regio-selectively transformed into its ortho-quinone form. Subsequently, the nucleophilic addition reactions of TSS ortho-quinone by phenylethynides are metal ion-dependent. When utilizing (phenylethynyl)magnesium bromide as the nucleophile, two phenylethynyls are furnished onto the edged benzene ring of TSS. When the nucleophile is (phenylethynyl)lithium, a cascade of nucleophilic addition, intermolecular electron-transfer, ring-opening, and tetradehydro-Diels-Alder (TDDA) reactions occur sequentially in one-pot, ultimately affording chiral π-conjugated polycycles featuring the epoxycyclooctadiene moiety as an integral part of their backbones. This work represents a step forward in the synthesis of chiral π-conjugated polycycles using TSS as synthon.

Colonization of extended-spectrum ß-lactamase-producing Enterobacteriaceae does not affect subsequent infection and liver transplant outcomes: a retrospective observational cohort study.

Objective: To investigate the colonization rate of extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E), subsequent infections by ESBL-E and ESBL-producing gram-negative bacilli (ESBL-GNB), and the effect of ESBL-E colonization on clinical outcomes in liver transplantation (LT) recipients. Methods: This is a retrospective cohort study that included patients who underwent LT at Shanghai Renji Hospital between July 2016 and December 2017. Rectal swabs from LT patients at the postoperative ICU enrollment were screened anonymously for ESBL-E carriage. Demographics data, laboratory indexes, operative complications, and clinical course information were also obtained. The extent of ESBL-E colonization, the subsequent infection rates of ESBL-E and ESBL-GNB, and the clinical outcomes were compared between ESBL-E colonized and non-colonized patients. Results: In total, 496 liver transplant recipients (387 males) were included in this study. ESBL-E colonization was detected in 240 patients (48.4%). There was no significant difference between the rates of ESBL-E infection (5.8 vs. 3.1%, p = 0.143), Ischemia-reperfusion ≥ 3 (27.9 vs. 24.6%, p = 0.403), acute kidney injury (39.6 vs. 38.7%, p = 0.835), acute rejection (2.1 vs. 1.6%, p = 0.664), graft versus host reaction (1.3 vs. 1.2%, p = 0.937), duration of hospitalization (22 vs. 23 days, p = 0.568), 90-day mortality (7.1 vs. 4.7%, p = 0.262) and 1-year mortality (12.9 vs. 9.3%, p = 0.265) in patients with and without ESBL-E colonization. Though the ESBL-GNB infection rate was higher in ESBL-E colonized patients (12.1 vs. 6.6%, p = 0.037), multivariate analysis showed that ESBL-E colonization did not increase the risk of ESBL-GNB infection (Model 1: aOR 1.755, 95% CI: 0.911-3.380, p = 0.093; Model 2: aOR 1.556, 95% CI: 0.761-3.181, p = 0.226). The ESBL-producing bacteria spectrum of colonization was significantly different from that of infections occurring after LT, with only three colonization events leading to infection by the same pathogen identified. Conclusion: ESBL-E colonization in liver transplant patients is not associated with ESBL-E infection, nor is it a risk factor for post-transplant ESBL-GNB infection. Additionally, ESBL-E colonization does not lead to worse prognoses when compared with non-colonized patients. Clinical trial registration: Chinese Clinical Trial Registry, Identifier [ChiCTR2100043034].

Xiaoyin Jiedu Granules may alleviate psoriasis-like skin diseases in mice by regulating sphingosine 1-phosphate receptor expression and reducing Th17 cells.

Sphingosine-1-phosphate (S1P) is associated with the onset and severity of psoriasis, a chronic inflammatory skin disease linked to innate and adaptive immune responses. This study explores the therapeutic effect of Xiaoyin Jiedu Granules, a combination of traditional Chinese medicines, on psoriasis-like skin lesions in mice and the underlying mechanism. We used imiquimod (IMQ) to induce psoriasis-like dermatitis in mice; the effects of Xiaoyin Jiedu Granules on S1P receptors (S1PRs) were investigated using histology and immunohistochemistry. The effects of Xiaoyin Jiedu Granules on the proliferation, differentiation, and activation of the NF-κB pathway in keratinocytes were verified using quantitative polymerase chain reaction (qPCR) and western blotting analyses. CD4+Th17 cells were screened using flow cytometry; the effects of Xiaoyin Jiedu Granules on the differentiation of Th17 cells and the content of related inflammatory factors were also verified. S1PR1-5 was highly expressed in psoriatic lesions. Xiaoyin Jiedu Granules significantly inhibited the secretion of proliferation-related proteins (K6, K16, K17, and IL-36γ) and proinflammatory cytokines (IL-17 and IL-22), transformation of Th17 cells, and activation of the NF-κB pathway and effectively alleviated IMQ-induced psoriasis-like dermatitis. Overall, our findings indicate that Xiaoyin Jiedu Granules have anti-inflammatory activity against S1PR expression, keratinocytes, and immune cells and can therefore mitigate psoriasis. Inhibiting the expression of S1PRs may be an effective treatment strategy against psoriasis.

Examining the dimensionality of morphological knowledge and morphological awareness and their effects on second language vocabulary knowledge.

Morphological knowledge and morphological awareness are multidimensional and both have been confirmed to make important contributions to vocabulary knowledge. However, the extant literature has not made a clear demarcation between morphological knowledge and morphological awareness. The current study examined the underlying components of morphological knowledge and morphological awareness as well as their effects on vocabulary knowledge. The performance of 226 tenth- and eleventh-graders on five tasks was investigated using confirmatory factor analysis and structural equation modeling. Results demonstrated that morphological knowledge and morphological awareness were two distinct constructs. In regard to the direct and indirect effects between morphological knowledge and vocabulary, it was indicated that morphological knowledge made a significant indirect effect on vocabulary knowledge through morphological awareness. However, the direct effect of morphological knowledge on vocabulary knowledge was not significant. Findings from the current study have important implications to adolescent EFL students' vocabulary instruction and research.

How phonological and orthographic decoding complicates the simple view of reading in Chinese: examining mediation through listening comprehension.

Advocates of the science of reading have invoked the simple view of reading (SVR) to justify an approach that foregrounds decoding in early reading instruction. SVR describes reading comprehension as the product of decoding and listening comprehension. The current study examined the complexity of the SVR, focusing on the phonological and orthographic decoding in third-grade readers of Chinese. One hundred and forty-three students participated in this study. The measures included phonological decoding (pinyin invented spelling), orthographic decoding, listening comprehension and reading comprehension. Drawing upon regression analyses and multivariate path models, the study found that phonological decoding at both segmental and suprasegmental processing significantly predicted Chinese reading comprehension, yet a more significant effect of orthographic decoding surfaced. And the best-fitting model suggested listening comprehension was better characterized as a mediator rather than a covariance with decoding component in the decoding-reading relation when orthographic decoding was incorporated into decoding component to evaluate the validity of the SVR in Chinese. The results imply that orthographic decoding is a legitimate decoding component and that the two decoding constructs alone are insufficient for higher-level reading ability (reading comprehension) since the contribution appears to be mediated through the path route of oral language capacity (indexed by listening comprehension). This enriches the current understanding of the SVR in non-alphabetic languages and indicates that decoding training on both phonological and orthographic dimension should be highlighted in early Chinese reading instruction.

Performance of Two Matrix-Assisted Laser Desorption Ionization-Time-of-Flight Mass Spectrometry (MALDI-TOF MS) Systems for Identification of the Viridans Group Streptococci.

Background: Due to similar colony morphology among viridans group streptococci (VGS), the differentiation of VGS species remains difficult in routine clinical microbiology. Recently, matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) has been described as a fast method for identifying various bacteria at species level, and also for the VGS strains. Methods: A total of 277 VGS isolates were identified with the two MALDI-TOF MS systems (VITEK MS and Bruker Biotyper). The tuf and rpoB gene sequencing was used as the reference identification method for comparison. Results: Based on tuf and rpoB gene sequencing, 84 isolates were S. pneumoniae and 193 strains were other VGS isolates including S. anginosus group (n=91, 47.2%), S. mitis group (n=80, 41.5%), S. bovis group (n=11, 5.7%), S. salivarius group (n=10, 5.2%), and S. mutans group (n=1, 0.5%). VITEK MS and Bruker Biotyper accurately identified 94.6% and 89.9% of all VGS isolates, respectively. VITEK MS showed better identification results than Bruker Biotyper for S. mitis group including S. pneumoniae and S. bovis group, but for other VGS isolates, two MALDI-TOF MS systems showed comparable identification performance. However, VITEK MS was able to identify S. gallolyticus to the subspecies level with high-confidence (S. gallolyticus ssp. pasteurianus), while the Bruker Biotyper system could not. While Bruker Biotyper system could be able to correctly differentiate the subspecies of S. salivarius from S. vestibularis, VITEK MS poorly identify. Conclusion: This study demonstrated that two MALDI-TOF MS systems allowed discrimination for most VGS isolates with different identification performance, but Bruker Biotyper could produce more misidentifications and VITEK MS system. It is crucial to be familiar with the performance of MALDI-TOF MS systems used in clinical microbiology.

IPA1 improves drought tolerance by activating SNAC1 in rice.

Drought is a major abiotic stress to rice (Oryza sativa) during growth. Ideal Plant Architecture (IPA1), the first cloned gene controlling the ideal plant type in rice, has been reported to function in both ideal rice plant architecture and biotic resistance. Here, we report that the IPA1/OsSPL14, encoding a transcriptional factor, positively regulates drought tolerance in rice. The IPA1 is constitutively expressed and regulated by H2O2, abscisic acid, NaCl and polyethylene glycol 6000 treatments in rice. Furthermore, the IPA1-knockout plants showed much greater accumulation of H2O2 as measured by 3,3'-diaminobenzidine staining in leaves compared with WT plants. Yeast one-hybrid, dual-luciferase and electrophoretic mobility shift assays indicated that the IPA1 directly activates the promoter of SNAC1. Expression of SNAC1 is significantly down-regulated in IPA1 knockout plants. Further investigation indicated that the IPA1 plays a positive role in drought-stress tolerance by inducing reactive oxygen species scavenging in rice. Together, these findings indicated that the IPA1 played important roles in drought tolerance by regulating SNAC1, thus activating the antioxidant system in rice.

Non-selective language activation in L2 lexical inference and text comprehension: Comparing skilled and less-skilled readers.

Non-selective language activation refers to the automatic co-activation of L1 and L2 information. In L2 reading, the activated L1 information can be utilized to different degrees to facilitate lexical inference and text comprehension. The current study examined the contributions of L1-L2 translation and lexical inference to text comprehension. Hierarchical regression models showed that in general, lexical inference contributed to text comprehension over L1-L2 translation. The results indicated that L2 learners did not use activated L1 information mechanically. That is because successful lexical inference incorporates learners' ability to strategically utilize contextual information and integrate word meanings to update the context. The study further classified the participants into two groups using k-means cluster. Among the less skilled group of participants, L1-L2 translation was related to both lexical inference and text comprehension. However, lexical inference was not significantly related to text comprehension. Among the more skilled group of participants, lexical inference predicted text comprehension only after school, grade to start English learning, and L1-L2 translation were controlled for. The results of the two groups demonstrated that while L1 information was utilized in both groups, strategic and effective usage of information in two languages differentiated skilled L2 readers from less skilled L2 readers.

Cross-linguistic influence of phonological awareness and phonological recoding skills in Chinese reading acquisition among early adolescent students.

This study investigated crosslinguistic phonological awareness and phonological recoding skills in Chinese reading acquisition among early Chinese adolescent students. 76 Chinese children participated in this study and finished a series of reading measurements over 1 year (from Grade 5 to Grade 6). In Grade 5, they were assessed by Chinese phonological awareness (syllable, onset, rhyme, phoneme, and tone awareness), English phonological awareness (syllable, onset, and rime, phoneme awareness) as well as English and Chinese phonological recoding skills. In Grade 6, the students completed the measurement of Chinese lexical inferencing ability. Subsequent hierarchical regression analyses showed that Time 1 (Grade 5) Chinese phonological awareness and recoding skills made a joint intra-lingual contribution to later Chinese lexical inferencing ability. Moreover, English phonological recoding skills had a unique inter-lingual contribution to later Chinese lexical inferencing ability after age, nonverbal intelligence, and English phonological awareness were controlled for. Results expanded the self-teaching hypothesis to account for variations within and across languages over time and underscored the uniqueness of inter-lingual phonological recoding in later orthographic and semantic learning.

Concurrent and longitudinal contributions of phonological awareness to early adolescent Chinese reading acquisition.

This study investigated universal and language-specific phonological awareness in reading development among Chinese early adolescent students. Seventy-six children participated in this study and completed a series of reading tasks at two data collection points across Grades 5 and 6. In Grade 5, universal phonological awareness (syllable, onset, rhyme, and phoneme awareness), language-specific phonological awareness (tone awareness) as well as character recognition and production measurements were administered to the participants. Lexical inferencing ability was measured in Grade 6. Character recognition and lexical inference were coded as the outcome variables. Subsequent multiple regression analyses showed that Time 1 (Grade 5) language-universal onset and phoneme awareness predicted character recognition and production at Time 1. More strikingly, the study demonstrated that language-specific tone awareness exerted a longitudinal effect on later lexical inferencing ability after controlling for age and nonverbal intelligence. Results underscored both the universality and language specificity of phonological awareness and provided empirical evidence to substantiate the facilitative role of early language-specific psycholinguistic grain size in later reading performance.

Prosodic Transfer in English Literacy Skills among Chinese Elementary-Age Students: Controlling for Non-Verbal Intelligence.

Building upon the prosodic transfer hypothesis, the current study aims to examine the intermediary effect of English stress on the relation between Chinese lexical tone awareness and English word-level literacy (reading and spelling) as well as the moderating effect of English oral vocabulary proficiency on the cross-linguistic association. Grade 4 Chinese learners of English (N = 224) participated in this study and were assessed for their tone and stress sensitivity, English oral vocabulary, English word reading, and English word spelling. Mediated multivariate analyses with moderation were used to explore: (1) whether the influence of lexical tone perception on L2 word reading and spelling was mediated by English stress as posited in the prosodic transfer hypothesis; (2) whether the effects of tone on English word reading and spelling performance varied as a function of oral vocabulary levels. The findings revealed a direct positive relationship between Chinese tone and English word reading and spelling, and the relationship was mediated by English stress awareness. Furthermore, the direct pathway from tone to English word-level literacy skills were moderated by oral vocabulary and the relationship between tone and English word-level skills became stronger as oral vocabulary levels increased; however, such strength reached a plateau among children without adequate oral vocabulary skills. These findings suggest the necessity to incorporate word spelling as an outcome in the cross-suprasegmental phonological transfer models of early literacy development. Additionally, the current study endorses the complexity of cross-language prosodic transfer. It points to a precise threshold for sufficient L2 oral vocabulary skills to enable tone transfer in English word-level literacy attainment.

The dimensionality of morphological awareness in reading comprehension among Chinese early adolescent readers.

Recent research has included multiple measures of morphological awareness to address the dimensionality of morphological construct in the context of modeling skilled reading. However, a majority of studies have an Anglocentric focus. The current study aims to extend the previous studies to logographic learners by evaluating the dimensionality of morphological awareness in higher-order reading comprehension among Chinese adolescent readers. A total of 686 early adolescent students (339 fifth-grade students and 347 sixth-grade students) participated in the study. They completed a series of morphological awareness measurements (morpheme recognition, morpheme discrimination, and compound structure awareness), vocabulary knowledge, lexical inference and reading comprehension. By testing three alternative path models, the study showed that morphological awareness and vocabulary knowledge were best represented as parallel covariates in predicting Chinese reading comprehension. More important, the study highlighted the mediator of lexical inference in associating morphological awareness, vocabulary knowledge and reading comprehension among Chinese readers. Empirical findings suggest that morphological awareness and vocabulary knowledge seem to be under a unitary construct in logographic reading acquisition and that word-meaning inference ability connects the path between morphological awareness and reading comprehension. These findings contribute to the complexity in the conceptualization of Chinese morphological awareness and reading instruction by examining the ways in which the morphological construct supports higher-order reading development.

Molecular mechanisms of Biyu decoction as treatment for psoriasis: A network pharmacology and molecular docking study.

BACKGROUND: The therapeutic effects of a combination of Chinese medicines called Biyu decoction have been clinically verified, although its molecular targets in psoriasis remain unknown. AIM: To explore the molecular mechanisms of Biyu decoction for psoriasis treatment. METHODS: In this network pharmacology and molecular docking study, the Traditional Chinese Medicine Systems Pharmacology database was searched for Biyu decoction active ingredients. GeneCards, Online Mendelian Inheritance in Man, PharmGkb, Therapeutic Target Database, and DrugBank databases were searched for psoriasis-related genes. The genes targeted by the decoction's active ingredient and disease genes were intersected to obtain predictive targets of the drug during psoriasis treatment. Cytoscape 3.8.0 was used to construct a drug component/ target disease network. The The functional protein association networks database and Cytoscape were used to construct a protein-protein interaction network and streamline the core network. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used for pathway enrichment analysis. Molecular docking technology was used to verify the drug component/target disease network. RESULTS: We screened 117 major active ingredients, including quercetin, kaempferol, naringenin, and acetyl-shikonin, and identified 213 gene targets, such as MAPK3, JUN, FOS, MYC, MAPK8, STAT3, and NFKBIA. Using a molecular docking analysis, the main active ingredients demonstrated good binding to the core targets. The Gene Ontology analysis showed that these ingredients were significantly associated with biological activities, such as transcription factor DNA binding, RNA polymerase II-specific DNA binding of transcription factors, and cytokine receptor binding; responses to lipopolysaccharides, molecules of bacterial origin, and oxidative stress; and were mainly distributed in membrane rafts, microdomains, and regions. The Kyoto Encyclopedia of Genes and Genomes analysis showed that decoction ingredients act on Th17 cell differentiation, tumor necrosis factor and mitogen-activated protein signaling pathways, the interleukin-17 signaling pathway, and the PI3K-Akt signaling pathway. CONCLUSION: Biyu decoction may be effective against psoriasis through multi-component, multi-target, and multi-channel synergy.

Phenol-soluble modulin contributes to the dispersal of Staphylococcus epidermidis isolates from catheters.

Staphylococcus epidermidis (S. epidermidis), a human commensal, has been implicated in invasive infection in humans due to their ability to form biofilm. It is assumed that when a biofilm is dispersed it will subsequently cause a more severe infection. The clinical significance of S. epidermidis isolated from sterile body fluid (BF) remains unclear, and might be related to dispersal from catheter-associated biofilm infection. To evaluate this relationship, we evaluated S. epidermidis isolates from catheters (CA) or BF in hospitalized patients. Sequence type 2 (ST2) is the most prevalent type isolated from infection sites. Although the specific STs were also observed in isolates from different sites, we observed that the main sequence type was ST2, followed by ST59, among all the 114 isolates from different infection sites. Interestingly, ST2 strains isolated from BF exhibited significantly thicker biofilm than those from CA. The thicker biofilm was due to the higher expression of accumulation-associated protein (aap) but not intercellular adhesion (ica) operon. Moreover, the transcription of PSMδ and PSMε were significantly increased in ST2 strains isolated from BF. Although the bacterial loads on catheters were similar infected by CA- or BF-originated strains in mouse biofilm-associated infection model, we observed a higher CFU in peri-catheter tissues infected by ST2 clones isolated from BF, suggesting that S. epidermidis with thicker biofilm formation might be able to disperse. Taken together, our data suggested that S. epidermidis originated from diverse infection sites exhibited different biofilm forming capacity. The major ST2 clone isolated from BF exhibited thicker biofilm by increasing the expression of Aap. The higher expression of PSM of these strains may contribute to bacteria dispersal from biofilm and the following bacterial spread.

[Screening of Differential Expression Autophagy Genes Related to the Prognosis of Diffuse Large B-Cell Lymphoma and Establishment of an Autophagy Model].

OBJECTIVE: To screen the differential expression of diffuse large B-cell lymphoma (DLBCL) autophagy-related gene (ARG), explore the mechanism of differential expression of autophagy gene (DEARG) in the occurrence and development of DLBCL and establish a prognostic model. METHODS: Using the NCICCR database containing clinical information and gene expression profile data of 481 patients with DLBCL and the HADb database containing 232 ARGs, the differential expression of ARG in DLBCL was determined by R language, the relationship between ARG and the occurrence and development of DLBCL was analyzed by GO and KEGG, the polygene prognostic model was established by Cox regression algorithm, the survival curve was drawn by Kaplan-Meier method, and the reliability of the prognostic model was evaluated by ROC curve. RESULTS: A total of 122 DEARGs were extracted from lymph node samples of 481 patients with DLBCL and 5 normal lymph nodes, including 4 up-regulated genes and 118 down-regulated genes. GO enrichment mainly focused on ontological annotations such as mitochondrial autophagy, autophagy regulation, and cell response to external stimuli. KEGG enrichment was mainly concentrated in cell senescence, NOD-like receptor signal pathway, PI3K-Akt signal pathway, and PD-1/PD-L1 signal pathway. Survival analysis was performed on 230 samples with complete clinical information. Univariate Cox analysis showed that 20 ARGs were significantly correlated with overall survival of DLBCL patients. Nine prognostic ARGs (HIF1A, CAPN1, ITPR1, PRKCQ, TRAIL, HDAC1, TSC2, NRG3, and MAPK3) were screened by multivariate Cox regression to establish DLBCL ARG prognostic model. Kaplan-Meier survival curve analysis showed that there was significant difference in survival rate between high risk group and low risk group (P<0.001). Multivariate Cox regression analysis showed that international prognostic index and risk value were independent prognostic indicators of DLBCL patients (P<0.05), the area under ROC curve was 0.762 and 0.747, respectively. CONCLUSION: DLBCL ARG prognostic model can be used to predict the prognosis of patients, but it still needs to be confirmed by a large sample of clinical studies.