Targeted siRNA Therapy for Psoriasis: Translating Preclinical Potential into Clinical Treatments.

Psoriasis is a chronic inflammatory skin disease characterized by the excessive proliferation of keratinocytes and heightened immune activation. Targeting pathogenic genes through small interfering RNA (siRNA) therapy represents a promising strategy for the treatment of psoriasis. This mini-review provides a comprehensive summary of siRNA research targeting the pathogenesis of psoriasis, covering aspects such as keratinocyte function, inflammatory cell roles, preclinical animal studies, and siRNA delivery mechanisms. It details recent advancements in RNA interference that modulate key factors including keratinocyte proliferation (Fibroblast Growth Factor Receptor 2, FGFR2), apoptosis (Interferon Alpha Inducible Protein 6, G1P3), differentiation (Grainyhead Like Transcription Factor 2, GRHL2), and angiogenesis (Vascular Endothelial Growth Factor, VEGF); immune cell infiltration and inflammation (Tumor Necrosis Factor-Alpha, TNF-α; Interleukin-17, IL-17); and signaling pathways (JAK-STAT, Nuclear Factor Kappa B, NF-κB) that govern immunopathology. Despite significant advances in siRNA-targeted treatments for psoriasis, several challenges persist. Continued scientific developments promise the creation of more effective and safer siRNA medications, potentially enhancing the quality of life for psoriasis patients and revolutionizing treatments for other diseases. This article focuses on the most recent research advancements in targeting the pathogenesis of psoriasis with siRNA and explores its future therapeutic prospects.

First Report of Powdery Mildew on Quercus fabri and Q. robur Caused by Erysiphe quercicola in China.

Quercus (Fagaceae) is a genus of ecologically and economically important shrub and tree species (Yin et al. 2018). In April 2022, powdery mildew symptoms were observed on Quercus fabri and Quercus robur leaves on Longwen hill, Guizhou Normal University, Guiyang, China. The incidence was 30% (Q. fabri, n = 50) and 20% (Q. robur, n = 30), respectively. Powdery mildew fungi from these two Quercus species shared similar morphological characteristics. Mycelia occurred on adaxial and abaxial leaf surfaces, forming small to large patches; hyphae were hyaline, 3-7 µm wide; hyphal appressoria were lobed to multilobed, solitary; conidiophores were erect, straight, 36-80 µm long (n = 30); foot cells were followed by 1-2 shorter cells; conidia formed singly, obovoid to ellipsoid, 24-38 × 12-27 µm (n = 50), without fibrosin bodies; no chasmothecia were observed. Based on these characteristics, powdery mildew fungi on both Q. fabri and Q. robur were identified as Erysiphe quercicola (Takamatsu et al. 2007). To confirm the identification, ribosomal DNA internal transcribed spacer (ITS) sequences of two fungal samples from Q. fabri and Q. robur were separately amplified and sequenced using primer pair ITS1/ITS4 (White et al. 1990). The obtained ITS sequences (GenBank accession nos. QR414372 and QR414373, respectively) shared 100% identity, and 99.38-99.84% identity with diverse ITS sequences of E. quercicola (Takamatsu et al. 2015). In a phylogenetic tree based on ITS sequences of Erysiphe species (Takamatsu et al. 2007), QR414372 and QR414373 were grouped in a clade with ITS sequences of E. quercicola. To fulfil Koch's postulates, leaves of three healthy potted Q. fabri plants and three healthy potted Q. robur plants were inoculated by gently pressing diseased Q. fabri and Q. robur leaves onto healthy leaves. Non-inoculated healthy Q. fabri and Q. robur plants served as controls. All plants were incubated in a greenhouse at 25 ± 2°C with 80% relative humidity. Typical powdery mildew symptoms were observed on all inoculated plants 15 days after inoculation, whereas no symptoms were observed on control plants. Fungi separately reisolated from inoculated Q. fabri and Q. robur were morphologically identical to those on their originally diseased plants, and ITS sequences of reisolated fungi shared 100% identity with QR414372 and QR414373. E. quercicola has previously been reported to infect Quercus species, including Q. robur in Australia, Q. crispula, Q. phillyraeoides and Q. serrata in Japan, and Q. phillyraeoides in Korea (Lee et al. 2011). In China, Q. fabri and Q. robur may be infected by E. alphitoides and E. hypophylla, respectively (Zheng et al. 1987). To our knowledge, this is the first report of powdery mildew caused by E. quercicola on Q. fabri and Q. robur in China. This work provides a foundation to protect Quercus plants against this fungal pathogen.

First Report of Powdery Mildew on Sophora flavescens Caused by Erysiphe diffusa in China.

Sophora flavescens (Fabaceae) is a deciduous subshrub which has been used in Chinese popular medicine for a long history (He et al. 2015). In June 2023, severe powdery mildew symptoms were observed on wild S. flavescens plants on Longwen hill of Guizhou Normal University, Guiyang, China. The incidence was approximately 80% among 100 S. flavescens plants observed. Almost all leaves were infected. Mycelia occurred on both adaxial and abaxial leaf surfaces, petioles, and stems, forming small-to-large patches. Hyphae were hyaline, 5 to 7 µm wide. Hyphal appressoria were solitary. Conidiophores were erect, straight to somewhat flexuous, and 45 to 120 µm long (n = 50). Foot cells were subcylindrical to slightly curved, followed by 2 to 3 shorter cells. Conidia formed singly, were ovoid to cylindrical, 26 to 42 × 12 to18 µm (n = 50). Based on these morphological characteristics, the powdery mildew fungus was tentatively identified as Erysiphe diffusa (Braun and Cook 2012). To confirm the identification, the ribosomal DNA internal transcribed spacer (ITS) and the ribosomal large subunit (LSU) region were amplified and sequenced using primer pairs ITS1/ITS4 (White et al. 1990) and NL1/NL4 (Ziemiecki et al. 1990), respectively. The obtained 647-bp ITS sequence (GenBank accession no. PP130131) displayed 100% identity with the ITS sequences of E. diffusa. The obtained 618-bp LSU sequence (GenBank accession no. PP693303) displayed 100% identity with the ITS sequences of E. diffusa (MT325922 and MT628019) and E. manihoticola (MT106658 and MT106660). Using a phylogenetic tree based on the combined ITS-LSU data, the isolate was grouped in a clade with the E. diffusa strain (GenBank accession no. LC777871). To fulfill Koch's postulates, leaves of three healthy potted S. flavescens plants were inoculated by gently pressing with diseased leaves. Non-inoculated plants were used as controls. All plants were incubated in a greenhouse at 25 ± 2°C, 80% relative humidity. After 15 days, typical powdery mildew symptoms were observed on the inoculated plants, whereas no symptoms were found on the control plants. The reisolated fungus from the inoculated S. flavescens was morphologically identical to that on naturally diseased plants, and the ITS sequence of the reisolated fungus showed 100% identity with PP130131. As the causal fungus of soybean powdery mildew, E. diffusa is known to infect papaya and other legumes, including Lens culinaris and Mimosa caesalpiniifolia (Attanayake et al. 2009; Luz et al. 2019). Particularly, E. diffusa has been previously reported to infect S. flavescens in the United Kingdom (Jones and Baker 2007; Bradshaw et al. 2023), but this is the first report of S. flavescens powdery mildew caused by E. diffusa in China. This work further expands the geographical range of E. diffusa-infected S. flavescens plants.

Single-Photon Emission from Point Defects in Hexagonal Boron Nitride Induced by Plasma Treatment.

Solid-state quantum emitters are gaining significant attention for many quantum information applications. Hexagonal boron nitride (h-BN) is an emerging host material for generating bright, stable, and tunable single-photon emission with narrow line widths at room temperature. In this work, we present a facile and efficient approach to generate high-density single-photon emitters (SPEs) in mechanically exfoliated h-BN through H- or Ar-plasma treatment followed by high-temperature annealing in air. It is notable that the postannealing is essential to suppress the fluorescence background in photoluminescence spectra and enhance emitter stability. These quantum emitters exhibit excellent optical properties, including high purity, brightness, stability, polarization degree, monochromaticity, and saturation intensity. The effects of process parameters on the quality of quantum emitters were systematic investigated. We find that there exists an optimal plasma power and h-BN thickness to achieve a high SPE density. This work offers a practical avenue for generating SPEs in h-BN and holds promise for future research and applications in quantum photonics.

First Report of Powdery Mildew on Berchemia floribunda Caused by Erysiphe berchemiae in China.

The genus Berchemia (family Rhamnaceae), a group of climbing plants, is mainly distributed in Asia, Africa, and South America. Berchemia plants are widely used in traditional medicine in some Asian countries (Inoshiri et al. 1987). For example, in Japan, B. racemosa (synonym B. floribunda) is used for the treatment of gallstones, liver diseases, neuralgia, and stomach cramps, and in China, B. floribunda is used for the treatment of rheumatism and lumbago. In August 2022, typical powdery mildew symptoms were observed on wild B. floribunda plants in Huaxi District, Guiyang, Guizhou Province, China. The incidence was approximately 60% among 100 B. floribunda plants observed outdoors. White colonies almost entirely covered on both adaxial and abaxial surfaces of all leaves on symptomatic plants. Infected leaves appeared curled or chlorotic, infection occasionally leading to defoliation. To describe the pathogen morphologically, fungal samples were collected from two individual B. floribunda plants and microscopically characterized. In these samples, hyphae were flexuous to straight, branched, septate, 3-6 µm wide, with lobed hyphal appressoria. Conidiophores were erect, flexuous to straight, and 50-160 µm long (n = 30). Foot cells were subcylindrical to slightly curved-sinuous at the base, 20-40 µm long (n = 30), followed by 2-3 shorter cells. Conidia formed singly, occasionally 2-3 in a chain. Conidia were ellipsoid to ovoid, 20-42 × 12-18 µm (n = 50), without fibrosin bodies. Chasmothecia were not found. For molecular identification, the ribosomal DNA internal transcribed spacers (ITSs) of the two fungal samples were amplified and sequenced using the ITS1/ITS4 primer pair (White et al. 1990). The obtained 649-bp ITS sequences (GenBank accession nos. OR414364 and OR414365, respectively) shared 100% identity, and they showed 99.52% identity with the ITS sequence (GenBank accession no. LC009934) of Erysiphe berchemiae. Phylogenetic analysis grouped OR414364 and OR414365 in a clade with LC009934. Based on morphological and molecular characteristics, the powdery mildew fungus from B. floribunda was identified as E. berchemiae (Braun and Cook 2012). The voucher specimen (accession no. GZNU-BFEE/0820/2022) were deposited at the School of Life Sciences, Guizhou Normal University. Pathogenicity was assessed by gently pressing naturally diseased leaves of B. floribunda onto leaves of three healthy potted 1-year-old B. floribunda plants. Three non-inoculated healthy plants were used as controls. The plants were incubated in a greenhouse at 25 ± 2°C, 80% relative humidity. Similar powdery mildew symptoms were observed on the inoculated plants 9 days after inoculation, whereas the control plants remained symptomless. The reisolated fungus from inoculated leaves was morphologically identical to that observed on the original diseased leaves, and the ITS sequence of the reisolated fungus shared 100% identity with OR414364 and OR414365, fulfilling Koch's postulates. E. berchemiae has previously been described as a powdery mildew pathogen on B. yunnanensis (Chen et al. 1987) and B. kulingensis (Chen 1993) in China and B. racemosa (synonym B. floribunda) in Japan (Braun and Cook 2012; Takamatsu et al. 2015), but this is the first report of E. berchemiae causing disease of B. floribunda in China. This work suggests that E. berchemiae is an important pathogen of Berchemia plants, at least for some species in the genus Berchemia.

Genetically Predicted Apolipoprotein E Levels with the Risk of Panvascular Diseases: A Mendelian Randomization Study.

The aim of this study was to comprehensively assess the causal relationship between the overall genetic effect of circulating ApoE levels and panvascular lesions using newer genome-wide association data and two-sample bidirectional Mendelian randomization (MR) analysis. Two-way MR using single-nucleotide polymorphisms of circulating ApoE as instrumental variables was performed using the highest-priority Genome-wide association study (GWAS) data, with factor-adjusted and data-corrected statistics, to estimate causal associations between circulating ApoE levels and 10 pan-vascular diseases in > 500,000 UK Biobank participants, > 400,000 participants of Finnish ancestry, and numerous participants in a consortium of predominantly European ancestry. Meta-analysis was conducted to assess positive results. After correcting for statistical results, elevated circulating ApoE levels were shown to have a significant protective effect against Cerebral ischemia (CI) [IVW odds ratio (OR) 0.888, 95% Confidence Interval (CI): 0.823-0.958, p = 2.3 × 10-3], Coronary heart disease [IVW OR 0.950,95% CI: 0.924-0.976, p = 2.0 × 10-4] had a significant protective effect and potentially suggestive protective causality against Angina pectoris [IVW odds ratio (OR) 0.961, 95%CI: 0.931-0.991, p = 1.1 × 10-2]. There was a potential causal effect for increased risk of Heart failure (HF) [IVW ratio (OR) 1.040, 95%CI: 1.006-1.060, p = 1.8 × 10-2]. (Bonferroni threshold p < 0.0026, PFDR < 0.05) Reverse MR analysis did not reveal significant evidence of a causal effect of PVD on changes in circulating ApoE levels. Meta-analysis increases reliability of results. Elevated circulating ApoE levels were particularly associated with an increased risk of heart failure. Elevated ApoE levels reduce the risk of cerebral ischemia, coronary heart disease, and angina pectoris, reflecting a protective effect. The possible pathophysiological role of circulating ApoE levels in the development of panvascular disease is emphasized.

Identification of clinical characteristics biomarkers for rheumatoid arthritis through targeted DNA methylation sequencing.

OBJECTIVES: Rheumatoid arthritis (RA) is a complex disease with a challenging diagnosis, especially in seronegative patients. The aim of this study is to investigate whether the methylation sites associated with the overall immune response in RA can assist in clinical diagnosis, using targeted methylation sequencing technology on peripheral venous blood samples. METHODS: The study enrolled 241 RA patients, 30 osteoarthritis patients (OA), and 30 healthy volunteers control (HC). Fifty significant cytosine guanine (CG) sites between undifferentiated arthritis and RA were selected and analyzed using targeted DNA methylation sequencing. Logistic regression models were used to establish diagnostic models for different clinical features of RA, and six machine learning methods (logit model, random forest, support vector machine, adaboost, naive bayes, and learning vector quantization) were used to construct clinical diagnostic models for different subtypes of RA. Least absolute shrinkage and selection operator regression and detrended correspondence analysis were utilized to screen for important CGs. Spearman correlation was used to calculate the correlation coefficient. RESULTS: The study identified 16 important CG sites, including tumor necrosis factort receptor associated factor 5 (TRAF5) (chr1:211500151), mothers against decapentaplegic homolog 3 (SMAD3) (chr15:67357339), tumor endothelial marker 1 (CD248) (chr11:66083766), lysosomal trafficking regulator (LYST) (chr1:235998714), PR domain zinc finger protein 16 (PRDM16) (chr1:3307069), A-kinase anchoring protein 10 (AKAP10) (chr17:19850460), G protein subunit gamma 7 (GNG7) (chr19:2546620), yes1 associated transcriptional regulator (YAP1) (chr11:101980632), PRDM16 (chr1:3163969), histone deacetylase complex subunit sin3a (SIN3A) (chr15:75747445), prenylated rab acceptor protein 2 (ARL6IP5) (chr3:69134502), mitogen-activated protein kinase kinase kinase 4 (MAP3K4) (chr6:161412392), wnt family member 7A (WNT7A) (chr3:13895991), inhibin subunit beta B (INHBB) (chr2:121107018), deoxyribonucleic acid replication helicase/nuclease 2 (DNA2) (chr10:70231628) and chromosome 14 open reading frame 180 (C14orf180) (chr14:105055171). Seven CG sites showed abnormal changes between the three groups (P < 0.05), and 16 CG sites were significantly correlated with common clinical indicators (P < 0.05). Diagnostic models constructed using different CG sites had an area under the receiver operating characteristic curve (AUC) range of 0.64-0.78 for high-level clinical indicators of high clinical value, with specificity ranging from 0.42 to 0.77 and sensitivity ranging from 0.57 to 0.88. The AUC range for low-level clinical indicators of high clinical value was 0.63-0.72, with specificity ranging from 0.48 to 0.74 and sensitivity ranging from 0.72 to 0.88. Diagnostic models constructed using different CG sites showed good overall diagnostic accuracy for the four subtypes of RA, with an accuracy range of 0.61-0.96, a balanced accuracy range of 0.46-0.94, and an AUC range of 0.46-0.94. CONCLUSIONS: This study identified potential clinical diagnostic biomarkers for RA and provided novel insights into the diagnosis and subtyping of RA. The use of targeted deoxyribonucleic acid (DNA) methylation sequencing and machine learning methods for establishing diagnostic models for different clinical features and subtypes of RA is innovative and can improve the accuracy and efficiency of RA diagnosis.

First Report of Rust Disease on Alcea rosea caused by Puccinia modiolae in China.

Alcea rosea, belonging to the Alcea genus in the Malvaceae family, originated from China, but it is now grown worldwide. A. rosea has been widely used in traditional Chinese medicine to alleviate constipation, pain, swelling, and sores. In February 2023, typical symptoms of fungal infection were observed on A. rosea at Guizhou Normal University in Guiyang, Guizhou Province, China. The disease incidence was over 90% (n = 100) for the surveyed A. rosea plants, and the disease severity range from 30% to 90%. The initial symptoms of A. rosea rust were the appearance of chlorotic spots on the leaves. Subsequently, numerous reddish to dark-brown erumpent pustules (telia) were observed. Gradually, the entire plant was covered by rust and the center of each lesion turned brown, necrotic, and ruptured over times, eventually causing defoliation. Voucher specimens of infected A. rosea leaves as representative samples have been deposited at Guizhou Normal University (GNU2023LS008). Telia are round in shape, mostly aggregated in mass, with a diameter of 0.28-0.78 mm (0.46 mm, n = 20). They range in color from reddish-brown to dark brown, and are mainly hypophyllous but occasionally formed on the adaxial leaf surface. The teliospores are fusoid with dimensions of 31.3-93.8 × 10.9-21.3 µm (57.5 × 15.1 µm average, n = 50), hyaline or yellowish to light-brown in color, mostly two-celled, with a smooth wall (1.5-3.0 µm) and a thickened apex (3.0-9.0 µm). However, teliospores which are one-, three-, or four-celled with a notch at the apex, are rarely observed. The morphological characteristics of host symptoms and teliospores were similar to those of Puccinia modiolae (Aime and Abbasi 2018; Albu et al. 2019). For phylogenetic analysis, genomic DNA was extracted from the teliospores of infected leaves. To confirm the species-level identification, PCR was performed on the extracted DNA to amplify the ribosomal DNA internal transcribed spacer (ITS) and large subunit (LSU) regions using primer pairs ITS1/ITS4 (Schoch et al. 2012) and NL1/NL4 (Ziemiecki et al. 1990), respectively. The resulting ITS DNA sequence (GenBank accession no. OR607960) showed 100% identity with P. modiolae sequences (OP369291.1), when the query coverage was 100%. The LSU DNA sequence obtained (OR607961.2) shared 99.85% similarity with P. modiolae (MK458702.1). A phylogenetic tree was constructed using MEGA7.0 and the maximum likelihood method based on the ITS and LSU sequences. The fungal isolates collected in this study and several reference sequences of P. modiolae were grouped within a clade that included the isolates reported on A. rosea in Korea (Ryu et al. 2023), with 100% bootstrap support. Pathogenicity testing was conducted by gently pressing spore powder of naturally diseased leaves onto young leaves of three healthy A. rosea plants, with three noninoculated healthy plants serving as controls. The inoculated and noninoculated plants were kept in a growth chamber at the 26°C with a 12 hour light/dark cycle and 80% humidity. After 2 weeks, all inoculated A. rosea plants showed characteristic disease symptoms of rust infection and telia of P. modiolae, while control plants remained symptomless. The pathogen was identical to that observed on the original diseased leaves. The study results indicate that the causal fungus responsible for the disease is P. modiolae, which has been previously reported on Malvaceae plants (Farr and Rossman 2022). To the best of our knowledge, this is the first report of P. modiolae on A. rosea in China. This study will contribute to an increased understanding of the host range of Puccinia modiolae.

CRISPR/Cas9-mediated enhancement of semi-dwarf glutinous traits in elite Xiangdaowan rice (Oryza sativa L.): targeting SD1 and Wx genes for yield and quality improvement.

In rice cultivation, the traits of semi-dwarfism and glutinous texture are pivotal for optimizing yield potential and grain quality, respectively. Xiangdaowan (XDW) rice, renowned for its exceptional aromatic properties, has faced challenges due to its tall stature and high amylose content, resulting in poor lodging resistance and suboptimal culinary attributes. To address these issues, we employed CRISPR/Cas9 technology to precisely edit the SD1 and Wx genes in XDW rice, leading to the development of stable genetically homozygous lines with desired semi-dwarf and glutinous characteristics. The sd1-wx mutant lines exhibited reduced gibberellin content, plant height, and amylose content, while maintaining hardly changed germination rate and other key agronomic traits. Importantly, our study demonstrated that exogenous GA3 application effectively promoted growth by compensating for the deficiency of endogenous gibberellin. Based on this, a semi-dwarf glutinous elite rice (Oryza sativa L.) Lines was developed without too much effect on most agronomic traits. Furthermore, a comparative transcriptome analysis unveiled that differentially expressed genes (DEGs) were primarily associated with the anchored component of the membrane, hydrogen peroxide catabolic process, peroxidase activity, terpene synthase activity, and apoplast. Additionally, terpene synthase genes involved in catalyzing the biosynthesis of diterpenoids to gibberellins were enriched and significantly down-regulated. This comprehensive study provides an efficient method for simultaneously enhancing rice plant height and quality, paving the way for the development of lodging-resistant and high-quality rice varieties.

Does the openness of the Boundary Shell system influence the sustainable development of the high-tech industry?

High-technology industries have gained substantial recognition as pivotal drivers of economic growth and technological advancement in modern society. The imperative of sustainable development in high-tech industries cannot be overemphasized, as it plays a crucial role in enabling long-term growth, fostering innovation, and assuming environmental responsibility. This article presents a study on sustainable development in high-tech industries using Boundary Shell theory. The study investigates the role of the stable and sustainable entropy criterion for the Boundary Shell system of high-tech industries from an entropy balance perspective. It analyzes the upper and lower limits of the Boundary Shell support force. Additionally, it improves the traditional boundary system ratio model to comprehensively and objectively evaluate the sustainable development of high-tech industries. The results illustrate that the Boundary Shell of industrial innovation is stronger than that of external dependency, with a reversed ranking of internal evaluation factor strengths compared to the traditional model. This research integrates reaction-diffusion equations theory with entropy balance equations theory to address sustainability issues in the high-tech industry. We further analyze the sustainable development of the high-tech industry through a Boundary Shell theory perspective to advance sustainability in high-tech industries. Moreover, it provides useful insights into the sustainable development of high-tech industries.

Identification of immunological characterization and Anoikis-related molecular clusters in rheumatoid arthritis.

Objective: To investigate the potential association between Anoikis-related genes, which are responsible for preventing abnormal cellular proliferation, and rheumatoid arthritis (RA). Methods: Datasets GSE89408, GSE198520, and GSE97165 were obtained from the GEO with 282 RA patients and 28 healthy controls. We performed differential analysis of all genes and HLA genes. We performed a protein-protein interaction network analysis and identified hub genes based on STRING and cytoscape. Consistent clustering was performed with subgrouping of the disease. SsGSEA were used to calculate immune cell infiltration. Spearman's correlation analysis was employed to identify correlations. Enrichment scores of the GO and KEGG were calculated with the ssGSEA algorithm. The WGCNA and the DGIdb database were used to mine hub genes' interactions with drugs. Results: There were 26 differentially expressed Anoikis-related genes (FDR = 0.05, log2FC = 1) and HLA genes exhibited differential expression (P < 0.05) between the disease and control groups. Protein-protein interaction was observed among differentially expressed genes, and the correlation between PIM2 and RAC2 was found to be the highest; There were significant differences in the degree of immune cell infiltration between most of the immune cell types in the disease group and normal controls (P < 0.05). Anoikis-related genes were highly correlated with HLA genes. Based on the expression of Anoikis-related genes, RA patients were divided into two disease subtypes (cluster1 and cluster2). There were 59 differentially expressed Anoikis-related genes found, which exhibited significant differences in functional enrichment, immune cell infiltration degree, and HLA gene expression (P < 0.05). Cluster2 had significantly higher levels in all aspects than cluster1 did. The co-expression network analysis showed that cluster1 had 51 hub differentially expressed genes and cluster2 had 72 hub differentially expressed genes. Among them, three hub genes of cluster1 were interconnected with 187 drugs, and five hub genes of cluster2 were interconnected with 57 drugs. Conclusion: Our study identified a link between Anoikis-related genes and RA, and two distinct subtypes of RA were determined based on Anoikis-related gene expression. Notably, cluster2 may represent a more severe state of RA.

Genome mining reveals novel biosynthetic gene clusters in entomopathogenic bacteria.

The discovery of novel bioactive compounds produced by microorganisms holds significant potential for the development of therapeutics and agrochemicals. In this study, we conducted genome mining to explore the biosynthetic potential of entomopathogenic bacteria belonging to the genera Xenorhabdus and Photorhabdus. By utilizing next-generation sequencing and bioinformatics tools, we identified novel biosynthetic gene clusters (BGCs) in the genomes of the bacteria, specifically plu00736 and plu00747. These clusters were identified as unidentified non-ribosomal peptide synthetase (NRPS) and unidentified type I polyketide synthase (T1PKS) clusters. These BGCs exhibited unique genetic architecture and encoded several putative enzymes and regulatory elements, suggesting its involvement in the synthesis of bioactive secondary metabolites. Furthermore, comparative genome analysis revealed that these BGCs were distinct from previously characterized gene clusters, indicating the potential for the production of novel compounds. Our findings highlighted the importance of genome mining as a powerful approach for the discovery of biosynthetic gene clusters and the identification of novel bioactive compounds. Further investigations involving expression studies and functional characterization of the identified BGCs will provide valuable insights into the biosynthesis and potential applications of these bioactive compounds.

A comprehensive review of Tripterygium wilfordii hook. f. in the treatment of rheumatic and autoimmune diseases: Bioactive compounds, mechanisms of action, and future directions.

Rheumatic and autoimmune diseases are a group of immune system-related disorders wherein the immune system mistakenly attacks and damages the body's tissues and organs. This excessive immune response leads to inflammation, tissue damage, and functional impairment. Therapeutic approaches typically involve medications that regulate immune responses, reduce inflammation, alleviate symptoms, and target specific damaged organs. Tripterygium wilfordii Hook. f., a traditional Chinese medicinal plant, has been widely studied in recent years for its application in the treatment of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis. Numerous studies have shown that preparations of Tripterygium wilfordii have anti-inflammatory, immunomodulatory, and immunosuppressive effects, which effectively improve the symptoms and quality of life of patients with autoimmune diseases, whereas the active metabolites of T. wilfordii have been demonstrated to inhibit immune cell activation, regulate the production of inflammatory factors, and modulate the immune system. However, although these effects contribute to reductions in inflammatory responses and the suppression of autoimmune reactions, as well as minimize tissue and organ damage, the underlying mechanisms of action require further investigation. Moreover, despite the efficacy of T. wilfordii in the treatment of autoimmune diseases, its toxicity and side effects, including its potential hepatotoxicity and nephrotoxicity, warrant a thorough assessment. Furthermore, to maximize the therapeutic benefits of this plant in the treatment of autoimmune diseases and enable more patients to utilize these benefits, efforts should be made to strengthen the regulation and standardized use of T. wilfordii.

Role of signaling lymphocytic activation molecule family of receptors in the pathogenesis of rheumatoid arthritis: insights and application.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and joint damage. The signaling lymphocytic activation molecule (SLAMF) family of receptors are expressed on various hematopoietic and non-hematopoietic cells and can regulate both immune cell activation and cytokine production. Altered expression of certain SLAMF receptors contributes to aberrant immune responses in RA. In RA, SLAMF1 is upregulated on T cells and may promote inflammation by participating in immune cell-mediated responses. SLAMF2 and SLAMF4 are involved in regulating monocyte tumor necrosis factor production and promoting inflammation. SLAMF7 activates multiple inflammatory pathways in macrophages to drive inflammatory gene expression. SLAMF8 inhibition can reduce inflammation in RA by blocking ERK/MMPs signaling. Of note, there are differences in SLAMF receptor (SFR) expression between normal and arthritic joint tissues, suggesting a role as potential diagnostic biomarkers. This review summarizes recent advances on the roles of SLAMF receptors 1, 2, 4, 7, and 8 in RA pathogenesis. However, further research is needed to elucidate the mechanisms of SLAMF regulation of immune cells in RA. Understanding interactions between SLAMF receptors and immune cells will help identify selective strategies for targeting SLAMF signaling without compromising normal immunity. Overall, the SLAMF gene family holds promise as a target for precision medicine in RA, but additional investigation of the underlying immunological mechanisms is needed. Targeting SLAMF receptors presents opportunities for new diagnostic and therapeutic approaches to dampen damaging immune-mediated inflammation in RA.

Discovery of Unusual Sesterterpenoids from Colquhounia coccinea var. mollis and Their Metabolic Implications.

Three unusual sesterterpenoids featuring unprecedented rearranged colquhounane (C25) and tetranorcolquhounane (C21) frameworks, colquhounoids E (1) and F (3) and norcolquhounoid F (2), were isolated from a Lamiaceae medicinal plant Colquhounia coccinea var. mollis. Their structures were elucidated by spectroscopic analysis and quantum chemical calculations. A biomimetic inspired regioselective cyclopropane cleavage was achieved under acidic conditions. The immunosuppressive activities of these new sesterterpenoids were also evaluated.

A flexible quasi-likelihood model for microbiome abundance count data.

In this article, we present a flexible model for microbiome count data. We consider a quasi-likelihood framework, in which we do not make any assumptions on the distribution of the microbiome count except that its variance is an unknown but smooth function of the mean. By comparing our model to the negative binomial generalized linear model (GLM) and Poisson GLM in simulation studies, we show that our flexible quasi-likelihood method yields valid inferential results. Using a real microbiome study, we demonstrate the utility of our method by examining the relationship between adenomas and microbiota. We also provide an R package "fql" for the application of our method.

Comparison of Outcomes Between Early and Late Tracheostomy.

BACKGROUND: The timing of tracheostomy in ventilated patients remains controversial. This study aimed to compare the effect of early tracheostomy (≤7 d) with late tracheostomy (>7 d) on the prognosis of patients requiring prolonged mechanical ventilation. METHODS: This was a retrospective observational cohort study. The data of 175 patients who received tracheostomy at the ICU between January 1, 2015-July 31, 2022, were collected. Patients were excluded from the study if medical records were incomplete or they underwent tracheostomy as part of a planned operation procedure. One-to-one propensity score matching was used to correct the baseline characteristics between the early and late tracheostomy groups. The treatment process and outcomes were compared between the two groups. The primary outcome was the incidence of ventilator-associated pneumonia (VAP) between groups. RESULTS: After propensity score matching, 88 subjects were included in the analysis. Compared with the late tracheostomy group, the incidence of VAP, hospital length of stay, sedation-free days, ventilator-free days, and ICU-free days were longer in the early tracheostomy group. There were no significant differences in the 90-d mortality between the two groups. CONCLUSIONS;: Early tracheostomy can reduce the occurrence of complications for ICU patients.

Curcumin Increases Radiosensitivity of Radioresistant Nasopharyngeal Cancer.

OBJECTIVES: To study the effects of curcumin on the proliferation, invasion, apoptosis, and radiosensitivity of the radioresistant nasopharyngeal carcinoma (NPC) C6661-IR strain as well as the potential radiosensitization mechanism. METHODS: NPC cells were continuously irradiated with different intensities of radiation to induce radiation-resistant cell lines. A plate clone formation assay was used to evaluate the effect of curcumin on the radiosensitivity of NPC cells. 3-(4,5-Dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide thiazolyl blue (MTT) assay was conducted to detect changes in cell viability. Flow cytometry was employed to analyze apoptosis percentage as well as Transwell® assay and immunofluorescence assay to observe cell invasion. Western blotting was applied to detect the expression levels of Bax, Bcl-2, and pro/cleaved-caspase 3. MiR-205-5p mimics and si-TP53INP1 were synthesized and transfected into C6661-IR cells, and the cells were then incubated with 10 µm/L curcumin. Real-time quantitative reverse transcription PCR (RT-qPCR) was used to measure miR-205-5p levels and western blotting was conducted to detect the expression of TP53INP1. RESULTS: The optimal radiation dose of X-ray was 6 Gy, and this dose was used in all subsequent experiments. Curcumin treatment significantly inhibited the proliferation and invasion of C6661-IR cells, promoted apoptosis and enhanced radiosensitivity. Compared to the 0 Gy+Cur group and the 6 Gy+Cur group, the miR-205-5p levels were higher in the C6661-IR cells of the 0 Gy and 6 Gy groups. Moreover, miR-204-5p was found to directly target TP53INP1. Curcumin downregulated miR-205-5p levels and upregulated TP53INP1 expression (p < 0.05). Thus, modulation of miR-205-5p or TP53INP1 expression attenuates the biological effects of curcumin on C6661-IR cells. CONCLUSIONS: Curcumin inhibited the proliferation and invasion of C6661-IR, promoted apoptosis, and enhanced its radiosensitivity to X-rays by mediating miR-205-5p/TP53INP1 expression.

Circulating DNA methylation level of CXCR5 correlates with inflammation in patients with rheumatoid arthritis.

OBJECTIVES: To assess the differences in circulating DNA methylation levels of CXCR5 between rheumatoid arthritis (RA) and osteoarthritis (OA) and healthy controls (HC), and the correlation of methylation changes with clinical characteristics of RA patients. METHODS: Peripheral blood samples were collected from 239 RA patients, 30 patients with OA, and 29 HC. Target region methylation sequencing to the promoter region of CXCR5 was achieved using MethylTarget. The methylation level of cg04537602 and methylation haplotype were compared among the three groups, and the correlation between methylation levels and clinical characteristics of RA patients was performed by Spearman's rank correlation analysis. RESULTS: The methylation level of cg04537602 was significantly higher in the peripheral blood of RA patients compared with OA patients (p = 1.3 × 10-3 ) and in the HC group (p = 5.5 × 10- 4 ). The sensitivity was enhanced when CXCR5 methylation level combined with rheumatoid factor and anti-cyclic citrullinated peptide with area under curve (AUC) of 0.982 (95% confidence interval 0.970-0.995). The methylation level of cg04537602 in RA was positively correlated with C-reactive protein (CRP) (r = .16, p = .01), and in RA patients aged 60 years and above, cg04537602 methylation levels were positively correlated with CRP (r = .31, p = 4.7 × 10- 4 ), tender joint count (r = .21, p = .02), visual analog scales score (r = .21, p = .02), Disease Activity Score in 28 joints (DAS28) using the CRP level DAS28-CRP (r = .27, p = 2.1 × 10- 3 ), and DAS28-ESR (r = .22, p = .01). We also observed significant differences of DNA methylation haplotypes in RA patients compared with OA patients and HC, which was consistent with single-loci-based CpG methylation measurement. CONCLUSION: The methylation level of CXCR5 was significantly higher in RA patients than in OA and HC, and correlated with the level of inflammation in RA patients, our study establishes a link between CXCR5 DNA methylation and clinical features that may help in the diagnosis and disease management of RA patients.

Transport Layer Engineering by Hydrochloric Acid for Efficient Perovskite Solar Cells with a High Open-Circuit Voltage.

A large number of defect states that exist at the interface between a perovskite film and an electron transport layer (ETL) are detrimental to the efficiency and the stability of perovskite solar cells (PSCs). It is still a challenge to simultaneously passivate the defects on both sides by a stable and low-cost ion compound. Herein, we demonstrate a simple and effective versatile strategy by introducing hydrochloric acid into SnO2 precursor solution to passivate the defects in both SnO2 and perovskite layers and simultaneously reduce the interface energy barrier, ultimately achieving a high-performance and hysteresis-free PSCs. Hydrogen ions can neutralize -OH groups on the SnO2 surface, whereas the Cl- can not only combine with Sn4+ in ETL but also suppress the Pb-I antisite defects formed at the buried interface. The reduced nonradiative recombination and the favorable energy level alignment result in a significantly increased efficiency from 20.71 to 22.06% of PSCs due to the enhancement of open-circuit voltage. In addition, the stability of the device can also be improved. This work presents a facile and promising approach for the development of highly efficient PSCs.