Distinct characteristics of the gut virome in patients with osteoarthritis and gouty arthritis.

BACKGROUND/PURPOSE(S): The gut microbiota and its metabolites play crucial roles in pathogenesis of arthritis, highlighting gut microbiota as a promising avenue for modulating autoimmunity. However, the characterization of the gut virome in arthritis patients, including osteoarthritis (OA) and gouty arthritis (GA), requires further investigation. METHODS: We employed virus-like particle (VLP)-based metagenomic sequencing to analyze gut viral community in 20 OA patients, 26 GA patients, and 31 healthy controls, encompassing a total of 77 fecal samples. RESULTS: Our analysis generated 6819 vOTUs, with a considerable proportion of viral genomes differing from existing catalogs. The gut virome in OA and GA patients differed significantly from healthy controls, showing variations in diversity and viral family abundances. We identified 157 OA-associated and 94 GA-associated vOTUs, achieving high accuracy in patient-control discrimination with random forest models. OA-associated viruses were predicted to infect pro-inflammatory bacteria or bacteria associated with immunoglobulin A production, while GA-associated viruses were linked to Bacteroidaceae or Lachnospiraceae phages. Furthermore, several viral functional orthologs displayed significant differences in frequency between OA-enriched and GA-enriched vOTUs, suggesting potential functional roles of these viruses. Additionally, we trained classification models based on gut viral signatures to effectively discriminate OA or GA patients from healthy controls, yielding AUC values up to 0.97, indicating the clinical utility of the gut virome in diagnosing OA or GA. CONCLUSION: Our study highlights distinctive alterations in viral diversity and taxonomy within gut virome of OA and GA patients, offering insights into arthritis etiology and potential treatment and prevention strategies.

Research Status and Development Trend of Coal Spontaneous Combustion Fire and Prevention Technology in China: A Review.

Coal seam spontaneous combustion fire is not only one of the main forms of the five major mine disasters, but also the main cause of secondary disasters such as mine gas and coal dust explosions. In recent years, with the advancement of mechanization, automation, and intelligent mine construction, spontaneous coal fires in mines have presented a series of new characteristics, and the prevention and control of spontaneous coal fires are also facing new challenges. On the basis of literature research, this paper summarizes and discusses the basic theory of coal spontaneous combustion, monitoring and early warning methods, and prevention and control technology, summarizes the development process of coal spontaneous combustion theory, reviews the research progress of coal spontaneous combustion monitoring and early warning methods and prevention and control technologies, and discusses the future development direction. In terms of the basic theory of spontaneous combustion of coal, from the initial hypothesis of spontaneous combustion of multielement coal to the unified understanding of coal-oxygen composite theory, a complete set of theoretical systems have been established, and a lot of macro and micro studies have been carried out and analyzed from multiple perspectives. In terms of coal spontaneous combustion monitoring and early warning, from the initial single indicator gas early warning to the construction of gas index system, the hierarchical early warning system is studied, and gradually tends to be perfect. With the development of automation and intelligence technology, the monitoring of coal spontaneous combustion disasters has also formed a new monitoring technology with beam tube monitoring as the traditional method, distributed optical fiber, wireless AD hoc network temperature measurement, and a coal spontaneous combustion multiparameter wireless monitoring system. In terms of fire prevention and control, the traditional "prevention" and "treatment" have changed to the "prevention-control-extinction" technical system based on hierarchical early warning, and the focus has gradually shifted to "prevention", and a large number of antifire materials have been developed, including blocking materials and fire-fighting materials. However, the precise inhibition and control of coal spontaneous combustion disasters, the evolution model of coal spontaneous combustion under the conditions of multifactor coupling in the field, the reliability and stability of intelligent monitoring system, the noncontact detection method of fire source, and the collaborative adaptation of multiple prevention and control techniques are not yet clear. In the future development, the mechanism of spontaneous coal combustion and its evolution process and other basic theories should be deeply studied. On the basis of the mechanism optimization early warning method of spontaneous coal combustion process, flame retardant and fire prevention materials should be targeted and developed. On the basis of the spatiotemporal evolution of spontaneous coal combustion, monitoring and monitoring system equipment with high speed, high precision, and high stability should be developed, which should accelerate the realization of accurate dynamic sensing and intelligent early warning of coal spontaneous combustion, and form an active hierarchical collaborative prevention and control system based on the trinity of "prevention-control-extinction" of coal spontaneous combustion. The conclusions and prospects of this paper can be used for reference in the future research direction, and have a certain role in promoting the exchange of research results of coal science and technology workers.

Characterizations of gut bacteriome, mycobiome, and virome of healthy individuals living in sea-level and high-altitude areas.

BACKGROUND: The contribution of gut microbiota to human high-altitude adaptation remains inadequately understood. METHODS: Here a comparative analysis of gut microbiota was conducted between healthy individuals living at sea level and high altitude using deep whole-metagenome shotgun sequencing, to investigate the adaptive mechanisms of gut microbiota in plateau inhabitants. RESULTS: The results showed the gut bacteriomes in high-altitude individuals exhibited greater within-sample diversity and significant alterations in both bacterial compositional and functional profiles when compared to those of sea-level individuals, indicating the potential selection of unique bacteria associated with high-altitude environments. The strain-level investigation revealed enrichment of Collinsella aerofaciens and Akkermansia muciniphila in high-altitude populations. The characteristics of gut virome and gut mycobiome were also investigated. Compared to sea-level subjects, high-altitude subjects exhibited a greater diversity in their gut virome, with an increased number of viral operational taxonomic units (vOTUs) and unique annotated genes. Finally, correlation analyses revealed 819 significant correlations between 42 bacterial species and 375 vOTUs, while no significant correlations were observed between bacteria and fungi or between fungi and viruses. CONCLUSION: The findings have significantly contributed to an enhanced comprehension of the mechanisms underlying the high-altitude geographic adaptation of the human gut microbiota.

16S rRNA Gene Sequencing of Gut Microbiota in Rheumatoid Arthritis Treated with 99Tc-MDP.

Background: Rheumatoid arthritis (RA) is a common autoimmune disease with the main symptoms being joint swelling and pain. In severe cases, joint deformity or even complete loss of function occurs. Technetium methylene diphosphonate (99Tc-MDP) is widely used for RA treatment in China, but there are no studies on the effects of 99Tc-MDP on intestinal flora. Objective: To explore the effects of 99Tc-MDP treatment on the composition and function of the intestinal flora and to provide new information on the mechanism of 99Tc-MDP in RA treatment. Methods: Stool samples from RA patients before and after 99Tc-MDP treatment were collected to form two groups (Before and After). Total genomic DNA of the samples was extracted for 16S rRNA gene sequencing. The altered composition of the intestinal flora, the key target bacteria regulated by 99Tc-MDP, and the pathways of action of 99 Tc-MDP were analyzed by bioinformatics. Results: A total of 64 fresh stool samples were collected from 32 RA patients. Compared to the Before group, the After group showed increased Bacteroidetes abundance and decreased Firmicutes abundance. At the genus level, Prevotella increased whereas Escherichia decreased. Both α and ß diversity analyses showed that 99Tc-MDP treatment did not affect gut microbial diversity in RA patients. LEfSe analyses and random forest analyses showed Bacteroidetes, Prevotella, Enterococcus, Escherichia and Ruminococcaceae were the main 99Tc-MDP regulating bacteria. Functional enrichment analysis revealed that the functional differences in gut flora of the two groups centered on Metabolism and Genetic Information Processing. Conclusion: This study revealed differences in the composition of the gut microbiota in RA patients before and after 99Tc-MDP treatment. The therapeutic effect of 99Tc MDP is mainly achieved through Bacteroidetes, Prevotella, and Enterococcus. Regulating metabolism and genetic information processing of gut flora may be the mechanism of 99Tc-MDP in treating RA.

Study on Pyrolysis and Oxidation Characteristics of Coal Gangue Based on TGA-DSC.

Coal gangue spontaneous combustion has caused serious environmental and ecological problems. To investigate the reaction kinetic parameters of the gangue and the exothermic characteristics of the spontaneous combustion of the influence of the law, this study employs the thermogravimetric method to explore the characteristic parameters of the pyrolysis and oxidative combustion process of the gangue from the perspective of thermodynamics, and, at the same time, using the differential scanning calorimetry (DSC) on the exothermic effect of the gangue to explore the gangue to obtain the gangue and the original coal TG/DTG/DSC curves to be compared and from the perspective of thermodynamics. The change rule and potential parameters in the pyrolysis and oxidative combustion process of coal gangue (CG) were analyzed, the oxidation kinetic properties of CG were studied, and the reaction mechanism of oxidative spontaneous combustion of CG was further explained. The results show that the TG/DTG/DSC curves of CG in different gas atmospheres will have significant differences in all stages, and in the process of pyrolysis and oxidative combustion, the thermogravimetric curves of CG and those of the original coal show a consistent trend, except for the large difference in peak amplitude in different stages; in different gas atmospheres, as the rate of warming increases, the TG/DTG/DSC curves of the gangue are tilted toward the high-temperature region, they are inclined to the high-temperature region with the increase of the heating rate, and the phenomenon of "hysteresis" of characteristic temperature occurs. The research results provide a theoretical basis for the construction of a spontaneous combustion early warning system based on the fine division of gangue pyrolysis and oxidation combustion stages.

Associations of the circulating levels of cytokines with risk of systemic sclerosis: a bidirectional Mendelian randomized study.

Objective: Systemic sclerosis(SSc) remains unclear, studies suggest that inflammation may be linked to its pathogenesis. Hence, we conducted a bidirectional Mendelian randomization (MR) analysis to evaluate the association between cytokine and growth factor cycling levels and the risk of SSc onset. Methods: In our study, the instrumental variables(IVs) for circulating cytokines were sourced from the genome-wide association study (GWAS) dataset of 8293 Finnish individuals. The SSc data comprised 302 cases and 213145 controls, and was included in the GWAS dataset. We employed four methods for the MR analysis: MR Egger, Inverse variance weighted (IVW), Weighted medium, and Weighted Mode, with IVW being the primary analytical method. Sensitivity analyses were performed using heterogeneity testing, horizontal pleiotropy testing, and the Leave One Out (LOO) method. We also conducted a reverse MR analysis to determine any reverse causal relationship between SSc and circulating cytokines. Results: After Bonferroni correction, MR analysis revealed that the Interleukin-5 (IL-5) cycle level was associated with a reduced risk of SSc [odds ratio (OR)=0.48,95% confidence interval (CI): 0.27-0.84, P=0.01]. It also indicated that the Stem cell growth factor beta (SCGF-ß) cycling level might elevate the risk of SSc (OR = 1.36, 95% CI: 1.01-1.83, P = 0.04). However, the reverse MR analysis did not establish a causal relationship between SSc and circulating cytokine levels. Additionally, sensitivity analysis outcomes affirm the reliability of our results. Conclusion: Our MR study suggests potential causal relationships between IL-5, SCGF-ß, and the risk of SSc. Further research is essential to determine how IL-5 and SCGF-ß influence the development of SSc.

Pleiotropic effects of different exonic nucleotide changes at the same position contribute to hemophilia B phenotypic variation.

BACKGROUND: The disease-causing effects of genetic variations often depend on their location within a gene. Exonic changes generally lead to alterations in protein production, secretion, activity, or clearance. However, owing to the overlap between proteins and splicing codes, missense variants can also affect messenger RNA splicing, thus adding a layer of complexity and influencing disease phenotypes. OBJECTIVES: To extensively characterize a panel of 13 exonic variants in the F9 gene occurring at 6 different factor IX positions and associated with varying severities of hemophilia B (HB). METHODS: Computational predictions, splicing analysis, and recombinant factor IX assays were exploited to characterize F9 variants. RESULTS: We demonstrated that 5 (38%) of 13 selected F9 exonic variants have pleiotropic effects. Although bioinformatic approaches accurately classified effects, extensive experimental assays were required to elucidate and deepen the molecular mechanisms underlying the pleiotropic effects. Importantly, their characterization was instrumental in developing tailored RNA therapeutics based on engineered U7 small nuclear RNA to mask cryptic splice sites and compensatory U1 small nuclear RNA to enhance exon definition. CONCLUSION: Overall, albeit a multitool bioinformatic approach suggested the molecular effects of multiple HB variants, the deep investigation of molecular mechanisms revealed insights into the HB phenotype-genotype relationship, enabling accurate classification of HB variants. Importantly, knowledge of molecular mechanisms allowed the development of tailored RNA therapeutics, which can also be translated to other genetic diseases.

Efficacy of adalimumab combined with Tripterygium wilfordii Hook F in the treatment of patient with rheumatoid arthritis: A multicenter, open-label, randomized-controlled trial.

OBJECTIVES: To evaluate the efficacy and safety of adalimumab (ADA) combined with Tripterygium wilfordii Hook F (TwHF) in the treatment of methotrexate (MTX)-inadequate response patients with rheumatoid arthritis (RA). METHODS: In this multicenter, open-label, randomized controlled clinical trial, 64 RA patients with inadequate response to MTX were 1:1 randomly assigned into treatment or control groups. The treatment group was treated with ADA in combination with TwHF, and the control group was treated with ADA in combination with MTX for 24 weeks. The primary endpoint was the percentage of patients having low disease activity (2.6 ≤ DAS28-ESR < 3.2) and remission rates (DAS28-ESR < 2.6) at week 24. RESULTS: In total, 53 of the 64 patients (82.8%) completed this 24-week clinical trial. By intent-to-treat (ITT) analysis, a comparable outcome was observed between the two groups. The percentage of patients achieving low disease activity in the treatment group and control group were 43.8% and 46.9% (95% CI, 21.28 to 27.48, p = .802). Percentage of patients achieving low disease activity rates were respectively 28.1% and 31.3% in the treatment group and control group (95% CI, 19.18 to 25.58, p = .784). In per-protocol (PP) analysis, the results were consistent with the ITT model. The incidence of adverse events was comparable between the two groups. CONCLUSIONS: There were no significant differences in efficacy and safety between ADA combined with TwHF versus ADA combined with MTX in the treatment of RA. TwHF might be an alternative treatment for RA patients who are intolerant to MTX.

A putative E3 ubiquitin ligase substrate receptor degrades transcription factor SmNAC to enhance bacterial wilt resistance in eggplant.

Bacterial wilt caused by Ralstonia solanacearum is a severe soil-borne disease globally, limiting the production in Solanaceae plants. SmNAC negatively regulated eggplant resistance to Bacterial wilt (BW) though restraining salicylic acid (SA) biosynthesis. However, other mechanisms through which SmNAC regulates BW resistance remain unknown. Here, we identified an interaction factor, SmDDA1b, encoding a substrate receptor for E3 ubiquitin ligase, from the eggplant cDNA library using SmNAC as bait. SmDDA1b expression was promoted by R. solanacearum inoculation and exogenous SA treatment. The virus-induced gene silencing of the SmDDA1b suppressed the BW resistance of eggplants; SmDDA1b overexpression enhanced the BW resistance of tomato plants. SmDDA1b positively regulates BW resistance by inhibiting the spread of R. solanacearum within plants. The SA content and the SA biosynthesis gene ICS1 and signaling pathway genes decreased in the SmDDA1b-silenced plants but increased in SmDDA1b-overexpression plants. Moreover, SmDDB1 protein showed interaction with SmCUL4 and SmDDA1b and protein degradation experiments indicated that SmDDA1b reduced SmNAC protein levels through proteasome degradation. Furthermore, SmNAC could directly bind the SmDDA1b promoter and repress its transcription. Thus, SmDDA1b is a novel regulator functioning in BW resistance of solanaceous crops via the SmNAC-mediated SA pathway. Those results also revealed a negative feedback loop between SmDDA1b and SmNAC controlling BW resistance.

Multimodal spatiotemporal monitoring of basal stem cell-derived organoids reveals progression of olfactory dysfunction in Alzheimer's disease.

Olfactory dysfunction (OD) is a highly prevalent symptom and an early sign of neurodegenerative diseases in humans. However, the roles of peripheral olfactory system in disease progression and the mechanisms behind neurodegeneration remain to be studied. Olfactory epithelium (OE) organoid is an ideal model to study pathophysiology in vitro, yet the reliance on 3D culture condition limits continual in situ monitoring of organoid development. Here, we combined impedance biosensors and live imaging for real-time spatiotemporal analysis of OE organoids morphological and physiological features during Alzheimer's disease (AD) progression. The impedance measurements showed that organoids generated from basal stem cells of APP/PS1 transgenic mice had lower proliferation rate than that from wild-type mice. In concert with the biosensor measurements, live imaging enabled to visualize the spatial and temporal dynamics of organoid morphology. Abnormal protein aggregation and accumulation, including amyloid plaques and neurofibrillary tangles, was found in AD organoids and increased as disease progressed. This multimodal in situ bioelectrical measurement and imaging provide a new platform for investigating onset mechanisms of OD, which would shed new light on early diagnosis and treatment of neurodegenerative disease.

Programmable optical switching integrated chip for 4-bit binary true/inverse/complement code conversions based on fluorinated photopolymers.

In this work, programmable optical switching integrated chips for 4-bit binary true/inverse/complement optical code conversions (OCCs) are proposed based on fluorinated photopolymers. Fluorinated bis-phenol-A novolac resin (FAR) with low absorption loss and fluorinated polyacrylate (FPA) with high thermal stability are self-synthesized as core and cladding layer, respectively. The basic architecture of operating unit for the photonic chip designed is composed of directional coupler Mach-Zehnder interferometer (DC-MZI) thermo-optic (TO) switching, X-junction, and Y-bunching waveguide structures. The waveguide module by cascading 16 operating units could realize OCCs function through optical transmission matrix. The response time of the 4-bit binary OCCs is measured as about 300 µs. The insertion loss and extinction ratio of the actual chip are obtained as about 10.5 dB and 15.2 dB, respectively. The electric driving power consumption for OCCs is less than 6 mW. The true/inverse/complement OCCs are achieved by the programmable modulation circuit. The proposed technique is suitable for achieving optical digital computing system with high-speed signal processing and low power consumption.

Characterizations of the multi-kingdom gut microbiota in Chinese patients with gouty arthritis.

OBJECTIVE: The gut microbial composition has been linked to metabolic and autoimmune diseases, including arthritis. However, there is a dearth of knowledge on the gut bacteriome, mycobiome, and virome in patients with gouty arthritis (GA). METHODS: We conducted a comprehensive analysis of the multi-kingdom gut microbiome of 26 GA patients and 28 healthy controls, using whole-metagenome shotgun sequencing of their stool samples. RESULTS: Profound alterations were observed in the gut bacteriome, mycobiome, and virome of GA patients. We identified 1,117 differentially abundant bacterial species, 23 fungal species, and 4,115 viral operational taxonomic units (vOTUs). GA-enriched bacteria included Escherichia coli_D GENOME144544, Bifidobacterium infantis GENOME095938, Blautia_A wexlerae GENOME096067, and Klebsiella pneumoniae GENOME147598, while control-enriched bacteria comprised Faecalibacterium prausnitzii_G GENOME147678, Agathobacter rectalis GENOME143712, and Bacteroides_A plebeius_A GENOME239725. GA-enriched fungi included opportunistic pathogens like Cryptococcus neoformans GCA_011057565, Candida parapsilosis GCA_000182765, and Malassezia spp., while control-enriched fungi featured several Hortaea werneckii subclades and Aspergillus fumigatus GCA_000002655. GA-enriched vOTUs mainly attributed to Siphoviridae, Myoviridae, Podoviridae, and Microviridae, whereas control-enriched vOTUs spanned 13 families, including Siphoviridae, Myoviridae, Podoviridae, Quimbyviridae, Phycodnaviridae, and crAss-like. A co-abundance network revealed intricate interactions among these multi-kingdom signatures, signifying their collective influence on the disease. Furthermore, these microbial signatures demonstrated the potential to effectively discriminate between patients and controls, highlighting their diagnostic utility. CONCLUSIONS: This study yields crucial insights into the characteristics of the GA microbiota that may inform future mechanistic and therapeutic investigations.

Acute generalized exanthematous pustulosis caused by hydroxychloroquine in a patient with rheumatoid arthritis and CARD14 mutation: Case report.

RATIONALE: Acute generalized exanthematous pustulosis (AGEP) is a serious adverse skin reaction characterized by the rapid appearance of densely distributed, small, sterile pustules with erythema. However, its pathogenesis is not fully understood. Hydroxychloroquine is widely used for the treatment of autoimmune diseases. Some patients presenting with AGEP have IL36RN and CARD14 gene mutations. Our report describes a patient with rheumatoid arthritis and AGEP associated with hydroxychloroquine and a newly discovered CARD14 gene mutation. PATIENT CONCERNS: A 28-year-old woman with rheumatoid arthritis, treated with leflunomide therapy without marked relief of joint pain, developed multiple rashes with pruritis covering the body 5 days after switching to hydroxychloroquine treatment. DIAGNOSES: Based on the patient's history, symptoms, and histopathological findings, AGEP was diagnosed. INTERVENTIONS: Whole-exome sequencing and Sanger validation revealed no mutations in the IL36RN gene; however, a CARD14 gene mutation was present. The patient was treated using ketotifen fumarate tablets, dexamethasone sodium phosphate, calcium gluconate injection, methylprednisolone injection, vitamins C and B12, hydrocortisone butyrate cream, Reed acne cream, potassium chloride tablets, and pantoprazole enteric-coated capsules. OUTCOMES: The rash improved after 15 days. LESSONS SUBSECTIONS: There has been little basic research on AGEP-related genetics, and the CARD14 mutation may underlie several pustular rashes, including AGEP and generalized pustular psoriasis. Follow-up studies and further accumulation of patient data are required.

Role of BraRGL1 in regulation of Brassica rapa bolting and flowering.

Gibberellin (GA) plays a major role in controlling Brassica rapa stalk development. As an essential negative regulator of GA signal transduction, DELLA proteins may exert significant effects on stalk development. However, the regulatory mechanisms underlying this regulation remain unclear. In this study, we report highly efficient and inheritable mutagenesis using the CRISPR/Cas9 gene editing system in BraPDS (phytoene desaturase) and BraRGL1 (key DELLA protein) genes. We observed a loss-of-function mutation in BraRGL1 due to two amino acids in GRAS domain. The flower bud differentiation and bolting time of BraRGL1 mutants were significantly advanced. The expression of GA-regulatory protein (BraGASA6), flowering related genes (BraSOC1, BraLFY), expansion protein (BraEXPA11) and xyloglucan endotransferase (BraXTH3) genes was also significantly upregulated in these mutants. BraRGL1-overexpressing plants displayed the contrasting phenotypes. BraRGL1 mutants were more sensitive to GA signaling. BraRGL1 interacted with BraSOC1, and the interaction intensity decreased after GA3 treatment. In addition, BraRGL1 inhibited the transcription-activation ability of BraSOC1 for BraXTH3 and BraLFY genes, but the presence of GA3 enhanced the activation ability of BraSOC1, suggesting that the BraRGL1-BraSOC1 module regulates bolting and flowering of B. rapa through GA signal transduction. Thus, we hypothesized that BraRGL1 is degraded, and BraSOC1 is released in the presence of GA3, which promotes the expression of BraXTH3 and BraLFY, thereby inducing stalk development in B. rapa. Further, the BraRGL1-M mutant promoted the flower bud differentiation without affecting the stalk quality. Thus, BraRGL1 can serve as a valuable target for the molecular breeding of early maturing varieties.

Dual-layer optical encryption fluorescent polymer waveguide chip based on optical pulse-code modulation technique.

Information encryption technique has broad applications in individual privacy, military confidentiality, and national security, but traditional electronic encryption approaches are increasingly unable to satisfy the demands of strong safety and large bandwidth of high-speed data transmission over network. Optical encryption technology could be more flexible and effective in parallel programming and multiple degree-of-freedom data transmitting application. Here, we show a dual-layer optical encryption fluorescent polymer waveguide chip based on optical pulse-code modulation technique. Fluorescent oligomers were doped into epoxy cross-linking SU-8 polymer as a gain medium. Through modifying both the external pumping wavelength and operating frequency of the pulse-code modulation, the sender could ensure the transmission of vital information is secure. If the plaintext transmission is eavesdropped, the external pumping light will be switched, and the receiver will get warning commands of ciphertext information in the standby network. This technique is suitable for high-integration and high-scalability optical information encryption communications.

A High-Continuity Genome Assembly of Chinese Flowering Cabbage (Brassica rapa var. parachinensis) Provides New Insights into Brassica Genome Structure Evolution.

Chinese flowering cabbage (Brassica rapa var. parachinensis) is a popular and widely cultivated leaf vegetable crop in Asia. Here, we performed a high quality de novo assembly of the 384 Mb genome of 10 chromosomes of a typical cultivar of Chinese flowering cabbage with an integrated approach using PacBio, Illumina, and Hi-C technology. We modeled 47,598 protein-coding genes in this analysis and annotated 52% (205.9/384) of its genome as repetitive sequences including 17% in DNA transposons and 22% in long terminal retrotransposons (LTRs). Phylogenetic analysis reveals the genome of the Chinese flowering cabbage has a closer evolutionary relationship with the AA diploid progenitor of the allotetraploid species, Brassica juncea. Comparative genomic analysis of Brassica species with different subgenome types (A, B and C) reveals that the pericentromeric regions on chromosome 5 and 6 of the AA genome have been significantly expanded compared to the orthologous genomic regions in the BB and CC genomes, largely driven by LTR-retrotransposon amplification. Furthermore, we identified a large number of structural variations (SVs) within the B. rapa lines that could impact coding genes, suggesting the functional significance of SVs on Brassica genome evolution. Overall, our high-quality genome assembly of the Chinese flowering cabbage provides a valuable genetic resource for deciphering the genome evolution of Brassica species and it can potentially serve as the reference genome guiding the molecular breeding practice of B. rapa crops.

Activation of Platelet mTORC2/Akt Pathway by Anti-ß2GP1 Antibody Promotes Thrombosis in Antiphospholipid Syndrome.

BACKGROUND: Anti-ß2GP1 (ß2-glycoprotein 1) antibodies are the primary pathogenic antibody to promote thrombosis in antiphospholipid syndrome (APS), yet the underlying mechanism remains obscure. We aimed to explore the intracellular pathway that mediated platelet activation. METHODS: Platelets were isolated from patients with APS and subjected to RNA sequencing. Platelet aggregation, the release of platelet granules, platelet spreading, and clot retraction were detected to evaluate platelet activation. We purified anti-ß2GP1 antibodies from patients with APS and the total IgG from healthy donors to stimulate platelets with/without FcγRIIA (Fcγ receptor IIA) blocking antibody or Akt (protein kinase B) inhibitor. Platelet-specific Sin1 (stress-activated protein kinase-interacting protein) deficiency mice were established. The thrombus model of inferior vena cava flow restriction, ferric chloride-induced carotid injury model, and laser-induced vessel wall injury in cremaster arterioles model were constructed after administration of anti-ß2GP1 antibodies. RESULTS: Combined RNA sequencing and bioinformatics analysis suggested that APS platelets exhibited increased levels of mRNA associated with platelet activation, which was in line with the hyperactivation of APS platelets in response to stimuli. Platelet activation in APS platelets was accompanied by upregulation of the mTORC2 (mammalian target of the rapamycin complex 2)/Akt pathway and increased levels of SIN1 phosphorylation at threonine 86. Anti-ß2GP1 antibody derived from patients with APS enhanced platelet activation and upregulated the mTORC2/Akt pathway. Moreover, the Akt inhibitor weakened the potentiating effect of the anti-ß2GP1 antibody on platelet activation. Notably, Sin1 deficiency suppresses anti-ß2GP1 antibody-enhanced platelet activation in vitro and thrombosis in all 3 models. CONCLUSIONS: This study elucidated the novel mechanism involving the mTORC2/Akt pathway, which mediates the promotion of platelet activation and induction of thrombosis by the anti-ß2GP1 antibody. The findings suggest that SIN1 may be a promising therapeutic target for the treatment of APS.

Triple-layered optical interconnecting integrated waveguide chip based on epoxy cross-linking fluorinated polymer photonic platform.

In this study, a triple-layered optical interconnecting integrated waveguide chip was designed and fabricated using an epoxy cross-linking polymer photonic platform. Fluorinated photopolymers FSU-8 and AF-Z-PC EP were self-synthesized as waveguide cores and cladding materials, respectively. The triple-layered optical interconnecting waveguide device comprised 4 × 4 arrayed waveguide grating (AWG) -based wavelength-selective switching (WSS) arrays, 4 × 4 multi-mode interference (MMI) -cascaded channel-selective switching (CSS) arrays, and 3 × 3 direct-coupling (DC) interlayered switching arrays. The overall optical polymer waveguide module was fabricated by direct UV writing. For the multilayered WSS arrays, the wavelength-shifting sensitivity was ∼0.48 nm/°C. For the multilayered CSS arrays, the average switching time was ∼280 µs, and the maximum power consumption was <30 mW. For interlayered switching arrays, the extinction ratio approximated 15.2 dB. The transmission loss for the triple-layered optical waveguide chip was measured as 10.0-12.1 dB. The flexible multilayered photonic integrated circuits (PIC) can be used in high-density integrated optical interconnecting systems with a large-volume optical information transmission capacity.

Gut microbiota combined with fecal metabolomics reveals the effects of FuFang Runzaoling on the microbial and metabolic profiles in NOD mouse model of Sjögren's syndrome.

OBJECTIVE: Sjögren's syndrome (SS) is an inflammatory autoimmune disease characterized by high levels of chronic lymphocyte infiltration. Differences and dysfunction in the gut microbiota and metabolites may be closely related to the pathogenesis of SS. The purpose of this study was to reveal the relationship between the gut microbiota and metabolome in NOD mice as a model of SS and the role of FuFang Runzaoling (FRZ), which is a clinically effective in treating SS. METHODS: NOD mice were gavaged with FRZ for 10 weeks. The ingested volume of drinking water, submandibular gland index, pathologic changes of the submandibular glands, and serum cytokines interleukin (IL)-6, IL-10, IL-17 A, and tumor necrosis factor-alpha (TNF-α) were determined. The roles of FRZ on gut microbiota and fecal metabolites were explored by 16 S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MC), respectively. The correlation between them was determined by Pearson correlation analysis. RESULTS: Compared with the model group, the drinking water volume of NOD mice treated with FRZ increased and the submandibular gland index decreased. FRZ effectively ameliorated lymphocyte infiltration in the small submandibular glands in mice. Serum levels of IL-6, TNF-α, and IL-17 A decreased, and IL-10 increased. The Firmicutes/Bacteroidetes ratio in the FRZ treatment group was higher. FRZ significantly downregulated the relative abundance of the family Bacteroidaceae and genus Bacteroides, and significantly upregulated the relative abundance of genus Lachnospiraceae_UCG-001. Orthogonal projections to latent structures discriminant analysis (OPLS-DA) revealed the significant change in fecal metabolites after FRZ treatment. Based on criteria of OPLS-DA variable influence on projection > 1, P < 0.05, and fragmentation score > 50, a total of 109 metabolites in the FRZ-H group were differentially regulated (47 downregulated and 62 upregulated) compared to their expressions in the model group. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed enriched metabolic of sphingolipid metabolism, retrograde endocannabinoid signaling, GABAergic synapse, necroptosis, arginine biosynthesis, and metabolism of histidine, alanine, aspartate, and glutamate. Correlation analysis between gut microbiota and fecal metabolites suggested that the enriched bacteria were related to many key metabolites. CONCLUSIONS: Taken together, we found FRZ could reduce the inflammatory responses in NOD mice by regulating the gut microbiota, fecal metabolites, and their correlation to emerge a therapeutic effect on mice with SS. This will lay the foundation for the further studies and applications of FRZ, and the use of gut microbiotas as drug targets to treat SS.

Identification and characterization analysis of candidate genes controlling mushroom leaf development in Chinese kale by BSA-seq.

Mushroom leaves (MLs) are malformed leaves that develop from the leaf veins in some of Chinese kale genotypes. To study the genetic model and molecular mechanism of ML development in Chinese kale, the F2 segregation population was constructed by two inbred lines, genotype Boc52 with ML and genotype Boc55 with normal leaves (NL). In the present study, we have identified for the first time that the development of mushroom leaves may be affected by the change of adaxial-abaxial polarity of leaves. Examination of the phenotypes of F1 and F2 segregation populations suggested that ML development is controlled by two dominant major genes inherited independently. BSA-seq analysis showed that a major quantitative trait locus (QTL) qML4.1 that controls ML development is located within 7.4 Mb on chromosome kC4. The candidate region was further narrowed to 255 kb by linkage analysis combined with insertion/deletion (InDel) markers, and 37 genes were predicted in this region. According to the expression and annotation analysis, a B3 domain-containing transcription factor NGA1-like gene, BocNGA1, was identified as a key candidate gene for controlling ML development in Chinese kale. Fifteen single nucleotide polymorphisms (SNPs) were found in coding sequences and 21 SNPs and 3 InDels found in the promoter sequences of BocNGA1 from the genotype Boc52 with ML. The expression levels of BocNGA1 in ML genotypes are significantly lower than in the NL genotypes, which suggests that BocNGA1 may act as a negative regulator for ML genesis in Chinese kale. This study provides a new foundation for Chinese kale breeding and for the study of the molecular mechanism of plant leaf differentiation. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01364-6.