Wide-based oblique anastomosis reduces urethral stricture rate following the transverse preputial island flap procedure.

Background: The transverse preputial island flap (TPIF) procedure remains one of the classic single-stage procedures for severe hypospadias repairs. The incidence of postoperative complications remained high. This study aims to describe a modified urethral anastomosis technique during the TPIF procedure for severe hypospadias repairs and report its outcomes. Methods: Data were collected retrospectively from consecutive patients who underwent the TPIF procedure by the same pediatric urologist between January 2018 and June 2023. Collected information included age at surgery, operative details, and outcomes at follow-up. Wide-based oblique anastomosis (WOA) technique was used as a modified urethral anastomosis in all cases. In brief, the dorsal edge of anastomosis was breadthwise anchored to the corpus cavernosum with 4-5 stitches, forming a spade-shaped anastomotic surface. Results: A total of 72 patients were included in the study. The location of the corpus spongiosum division was penile in 27 patients (37.5%) and proximal in 45 patients (62.5%). The median glans width was 13 mm (range, 6-30 mm). The median ventral curvature after degloving was 45° (range, 30-150°). At a median follow-up of 4.1 years, complications occurred in 15 patients (20.8%), including nine cases of fistula, seven cases of urethral diverticulum and two cases of meatal stenosis. No cases of urethral stricture (US), urethral dehiscence, or ventral curvature occurred. Subsequent reoperations for diverticulum repairs showed that the dorsal side of the anastomosis was extensively fixed to the corpus cavernosum, forming a wide-based, spacious lumen. Conclusions: WOA technique is straightforward and effective, especially in the prevention of postoperative US.

High-Order Models for Gas Transport in Multiscale Coal Rock.

The coal reservoirs exhibit great heterogeneity and strong anisotropy in multiscale pore/fracture structures. Developing highly accurate multiscale models for real-time prediction of microgaseous flow in complicated porous media with pronounced contrast in transport coefficients is crucial but not yet available, which is time-consuming, expensive, and even computationally impossible. In this study, a multiscale approximate solution of the gas flow and pressure field is derived in this paper for predicting coalbed methane (CBM) transport in macro-microscopic two-scale porous media of typical coal rocks in Guizhou Province, China, and the detailed finite element algorithm is established. The multiscale approximate solutions are constructed from the first- and second-order auxiliary cell functions and low- or high-order derivatives of the homogenized pressure field, which can accurately approximate the solution of the original problem to a certain extent. The numerical accuracy and validity of the multiscale approximate solutions under various working conditions are analyzed in detail by comparing and verifying the results with the direct numerical simulation results of fine-mesh high-precision finite elements. The results show that the homogenized approximate solution can only roughly capture the characteristics of the macroscopic pressure evolution, the first-order approximate solution can partially reproduce the macro-microscopic pressure oscillation phenomenon, and the second-order approximate solution can accurately predict the pressure profile and its evolution law with time in porous media with macro-micro configuration under various complex conditions. The second- and high-order two-scale approximate solutions constructed in this paper exhibit high numerical accuracy and excellent computational efficiency. We also develop multiscale approximate solutions for predicting microgaseous flow at a low reservoir pressure where the slippage effects are very pronounced. Potential applications of our high-order models to the coal reservoirs with a hierarchical matrix and fractures are discussed. The developed multiscale models exhibit excellent applicability to investigating the crossflow effects and coupling mechanisms between the matrix and cleats or fractures with multiple configurations in the CBM and shale gas reservoirs, which is crucial for the effective implementation of hydraulic fracturing technology. This study provides a fundamental understanding of gas transport in multiscale matrix-fracture networks, which helps to improve the optimization design of hydraulic fracturing in tight reservoirs.

Application and insights of targeted next-generation sequencing in a large cohort of 46,XY disorders of sex development in Chinese.

PURPOSE: 46,XY disorders of sex development (46,XY DSD) are characterized by incomplete masculinization of genitalia with reduced androgenization. Accurate clinical management remains challenging, especially based solely on physical examination. Targeted next-generation sequencing (NGS) with known pathogenic genes provides a powerful tool for diagnosis efficiency. This study aims to identify the prevalent genetic variants by targeted NGS technology and investigate the diagnostic rate in a large cohort of 46,XY DSD patients, with most of them presenting atypical phenotypes. METHODS: Two different DSD panels were developed for sequencing purposes, targeting a cohort of 402 patients diagnosed with 46,XY DSD, who were recruited from the Department of Urology at Children's Hospital, Zhejiang University School of Medicine (Hangzhou, China). The detailed clinical characteristics were evaluated, and peripheral blood was collected for targeted panels to find the patients' variants. The clinical significance of these variants was annotated according to American College of Medical Genetics and Genomics (ACMG) guidelines. RESULTS: A total of 108 variants across 42 genes were found in 107 patients, including 46 pathogenic or likely pathogenic variants, with 45.7%(21/46) being novel. Among these genes, SRD5A2, AR, FGFR1, LHCGR, NR5A1, CHD7 were the most frequently observed. Besides, we also detected some uncommon causative genes like SOS1, and GNAS. Oligogenic variants were also identified in 9 patients, including several combinations PROKR2/FGFR1/CYP11B1, PROKR2/ATRX, PROKR2/AR, FGFR1/LHCGR/POR, FGFR1/NR5A1, GATA4/NR5A1, WNT4/AR, MAP3K1/FOXL2, WNT4/AR, and SOS1/FOXL2. CONCLUSION: The overall genetic diagnostic rate was 11.2%(45/402), with an additional 15.4% (62/402) having variants of uncertain significance. Additionally, trio/duo patients had a higher genetic diagnostic rate (13.4%) compared to singletons (8.6%), with a higher proportion of singletons (15.1%) presenting variants of uncertain significance. In conclusion, targeted gene panels identified pathogenic variants in a Chinese 46,XY DSD cohort, expanding the genetic understanding and providing evidence for known pathogenic genes' involvement.

46,XY disorders of sex development (46,XY DSD) are conditions where individuals don't fully develop male genitalia due to reduced androgen hormones. Diagnosing these conditions based only on physical exams is difficult. This study used advanced genetic testing called targeted next-generation sequencing (NGS) to identify common genetic variations in a large group of 46,XY DSD patients, many of whom had unusual symptoms. We examined 402 patients with DSD and a 46,XY karyotype, focusing on 142 candidate genes related to sex development. We found genetic variations in 107 patients, including 45 that were likely responsible for their condition. Some of these variations were new discoveries. The most commonly affected genes were SRD5A2, AR, FGFR1, LHCGR, NR5A1, CHD7. We also found that some patients had variations in multiple genes, suggesting complex genetic causes. Overall, we were able to diagnose 11.2% of patients based on our genetic testing, with another15.4% having uncertain results. Patients tested as a trio or duo (with their parents) had a higher diagnosis rate than those tested alone. This study helps expand our understanding of the genetic factors behind 46,XY DSD in the Chinese population.

A review of psoriasis image analysis based on machine learning.

Machine Learning (ML), an Artificial Intelligence (AI) technique that includes both Traditional Machine Learning (TML) and Deep Learning (DL), aims to teach machines to automatically learn tasks by inferring patterns from data. It holds significant promise in aiding medical care and has become increasingly important in improving professional processes, particularly in the diagnosis of psoriasis. This paper presents the findings of a systematic literature review focusing on the research and application of ML in psoriasis analysis over the past decade. We summarized 53 publications by searching the Web of Science, PubMed and IEEE Xplore databases and classified them into three categories: (i) lesion localization and segmentation; (ii) lesion recognition; (iii) lesion severity and area scoring. We have presented the most common models and datasets for psoriasis analysis, discussed the key challenges, and explored future trends in ML within this field. Our aim is to suggest directions for subsequent research.

Fluorescence collection efficiency of atoms in dipole traps.

The fluorescence collection from single atoms and emitters has been extensively utilized in quantum information and quantum optics research. Here, we investigated the collection efficiency of an objective lens by drawing an analogy between the free-space beam (FSB) and a waveguide mode. We explored how efficiency is influenced by their thermal motion within a dipole trap. Furthermore, we introduce an effective energy fraction ratio to quantify potential imperfections in the focusing of the objective lens. Our results provide valuable insights for optimizing the fluorescence collection in single-atom experiments and highlight the importance of considering realistic experimental conditions when estimating achievable efficiencies.

Ureteropelvic Junction Obstruction Caused by Crossing Vessels in Infants and Young Children.

BACKGROUND: To analyze the clinical characteristics of ureteropelvic junction obstruction (UPJO) caused by crossing vessels (CV) in infants and young children. METHODS: A retrospective analysis was performed on children with UPJO who underwent primary surgery. Patients were classified into laparoscopic pyeloplasty (LP) and open pyeloplasty (OP) groups and classified as ≤3 or >3 (years old) groups. Children with CV-caused UPJO were identified. RESULTS: A total of 747 patients were included. Ninety cases of CV were identified. The CV discovery rate was higher in the LP group (78/457, 17.1%) than in the OP group (12/290, 4.1%) (P < 0.001). In the ≤3 group, the CV discovery rate in the LP group (27/144, 18.8%) was higher than that in the OP group (11/274, 4.0%) (P < 0.001). In the LP group, there was no significant difference between ≤3 (27/144, 18.8%) and >3 (51/313, 16.3%) groups in the CV discovery rate. The rate in children with UPJO was not significantly different at any age (P > 0.05). Progressive aggravation of hydronephrosis (21/27, 77.8%) and symptomatic hydronephrosis (44/51, 86.3%) were the main surgical indications in the ≤3 and > 3 groups, respectively. There were no preoperatively confirmed cases of CV in the ≤3 group. In the OP group, five patients underwent reoperation, three of whom were due to failure to detect CV during the initial operation. CONCLUSIONS: The CV distribution is similar in children with UPJO across all ages; CV in infants and young children are not rare. LP should be considered as CV are prone to being missed during OP. LEVELS OF EVIDENCE: III.

Patient self-reported experience and satisfaction with golimumab and etanercept treatments for rheumatic diseases: A cohort study.

Golimumab and etanercept both exhibit good efficacy in treating rheumatic diseases, while the patient self-reported measurement of treatment improvement and injection experience lacks sufficient evidence. Hence, this study aimed to compare the satisfaction with disease improvement and injection experience and the level of injection site reactions (ISRs) between golimumab-treated and etanercept-treated patients with rheumatic diseases. A total of 312 patients with rheumatic diseases were serially enrolled. Among them, 158 patients received golimumab (golimumab group); the other 154 patients were treated with etanercept (etanercept group) according to the actual disease status, physician advice, and patient willingness. Satisfaction with disease improvement was assessed using the 7-point Likert scale; satisfaction with injection experience and level of ISRs were both determined by the 5-point Likert scale. Satisfaction degrees with global injection experience (P = .025), injection device (P = .008), injection frequency (P = .010), and injection convenience (P = .003) were superior in the golimumab group to the etanercept group, while satisfaction degrees with global disease improvement, symptom relief, and speed of action did not vary (all P > .050) between the 2 groups. Discomfort (P = .005), swelling (P < .001), pain (P = .028), and burning (P = .035) levels were lower in the golimumab group than in the etanercept group. In addition, among 56 patients with a history of tumor necrosis factor inhibitor treatment before golimumab, 40 (71.4%) patients preferred golimumab to other tumor necrosis factor inhibitor. After switching to golimumab treatment, the level of ISRs in most patients was reduced or comparable. Golimumab achieves a satisfying injection experience and relieves the level of ISRs over etanercept in patients with rheumatic diseases.

Shape-recovery of implanted shape-memory devices remotely triggered via image-guided ultrasound heating.

Shape-memory materials hold great potential to impart medical devices with functionalities useful during implantation, locomotion, drug delivery, and removal. However, their clinical translation is limited by a lack of non-invasive and precise methods to trigger and control the shape recovery, especially for devices implanted in deep tissues. In this study, the application of image-guided high-intensity focused ultrasound (HIFU) heating is tested. Magnetic resonance-guided HIFU triggered shape-recovery of a device made of polyurethane urea while monitoring its temperature by magnetic resonance thermometry. Deformation of the polyurethane urea in a live canine bladder (5 cm deep) is achieved with 8 seconds of ultrasound-guided HIFU with millimeter resolution energy focus. Tissue sections show no hyperthermic tissue injury. A conceptual application in ureteral stent shape-recovery reduces removal resistance. In conclusion, image-guided HIFU demonstrates deep energy penetration, safety and speed.

Synovial microenvironment-influenced mast cells promote the progression of rheumatoid arthritis.

Mast cells are phenotypically and functionally heterogeneous, and their state is possibly controlled by local microenvironment. Therefore, specific analyses are needed to understand whether mast cells function as powerful participants or dispensable bystanders in specific diseases. Here, we show that degranulation of mast cells in inflammatory synovial tissues of patients with rheumatoid arthritis (RA) is induced via MAS-related G protein-coupled receptor X2 (MRGPRX2), and the expression of MHC class II and costimulatory molecules on mast cells are upregulated. Collagen-induced arthritis mice treated with a combination of anti-IL-17A and cromolyn sodium, a mast cell membrane stabilizer, show significantly reduced clinical severity and decreased bone erosion. The findings of the present study suggest that synovial microenvironment-influenced mast cells contribute to disease progression and may provide a further mast cell-targeting therapy for RA.

Magnetic-free polarization rotation in an atomic vapor cell.

Magnetic-free nonreciprocal optical devices have attracted great attention in recent years. Here, we investigated the magnetic-free polarization rotation of light in an atom vapor cell. Two mechanisms of magnetic-free nonreciprocity have been realized in ensembles of hot atoms, including electromagnetically induced transparency and optically-induced magnetization. For a linearly polarized input probe light, a rotation angle up to 86.4° has been realized with external control and pump laser powers of 10 mW and is mainly attributed to the optically-induced magnetization effect. Our demonstration offers a new approach to realize nonreciprocal devices, which can be applied to solid-state atom ensembles and may be useful in photonic integrated circuits.

Endoscopic combined intrarenal surgery composed of micro-perc and retrograde intrarenal surgery in the treatment of complex kidney stones in children.

OBJECTIVE: This research aims to explore the efficiency and safety of endoscopic combined intrarenal surgery (Micro-ECIRS) composed of micro-percutaneous nephrolithotomy (Micro-perc) and retrograde intrarenal surgery (RIRS) in the Galdakao-modified supine Valdivia (GMSV) position for a single session for the treatment of complex nephrolithiasis in children. MATERIALS AND METHODS: This study retrospectively reviewed patients aged < 18 years who underwent Micro-ECIRS in the GMSV position for renal stones larger than 2 cm under ultrasound guidance between August 2020 to May 2022 at our institution. RESULTS: A total of 13 patients (8 males and 5 females) received Micro-ECIRS for renal stones under ultrasound guidancewhile adopting the GMSV position. The average stone size was 2.7 cm (range: 2.1-3.7 cm). Among them, 6 patients had left kidney stones, 5 patients had right kidney stones, and 2 patients had bilateral kidney stones. The mean operative time was 70.5 min (range: 54-93 min). The mean hospital stay was 6.4 days (range: 4-9 days). The mean hemoglobin decrease was 8.2 g/L (range: 5.1-12.4 g/L). The total number of kidneys that had complete stone clearance was 8 kidneys at 48 h postoperatively, 11 kidneys at 2 weeks postoperatively, and 14 kidneys at 1 month postoperatively. CONCLUSION: Our results demonstrate that Micro-ECIRS while patients are in the GMSV position is a safe and effective method for the treatment of complex children nephrolithiasis. However, all children made three hospital visits and received anesthesia three times. Further research is needed to confirm these findings.

PRL2 regulates neutrophil extracellular trap formation which contributes to severe malaria and acute lung injury.

Excessive host immune responses contribute to severe malaria with high mortality. Here, we show that PRL2 in innate immune cells is highly related to experimental malaria disease progression, especially the development of murine severe malaria. In the absence of PRL2 in myeloid cells, Plasmodium berghei infection results in augmented lung injury, leading to significantly increased mortality. Intravital imaging revealed greater neutrophilic inflammation and NET formation in the lungs of PRL2 myeloid conditional knockout mice. Depletion of neutrophils prior to the onset of severe disease protected mice from NETs associated lung injury, and eliminated the difference between WT and PRL2 CKO mice. PRL2 regulates neutrophil activation and NET accumulation via the Rac-ROS pathway, thus contributing to NETs associated ALI. Hydroxychloroquine, an inhibitor of PRL2 degradation alleviates NETs associated tissue damage in vivo. Our findings suggest that PRL2 serves as an indicator of progression to severe malaria and ALI. In addition, our study indicated the importance of PRL2 in NET formation and tissue injury. It might open a promising path for adjunctive treatment of NET-associated disease.

New Potentiality of Bioactive Substances: Regulating the NLRP3 Inflammasome in Autoimmune Diseases.

The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is an essential component of the human innate immune system, and is closely associated with adaptive immunity. In most cases, the activation of the NLRP3 inflammasome requires priming and activating, which are influenced by various ion flux signals and regulated by various enzymes. Aberrant functions of intracellular NLRP3 inflammasomes promote the occurrence and development of autoimmune diseases, with the majority of studies currently focused on rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis. In recent years, a number of bioactive substances have shown new potentiality for regulating the NLRP3 inflammasome in autoimmune diseases. This review provides a concise overview of the composition, functions, and regulation of the NLRP3 inflammasome. Additionally, we focus on the newly discovered bioactive substances for regulating the NLRP3 inflammasome in autoimmune diseases in the past three years.

Clonorchis sinensis calcium-binding protein Cs16 causes acute hepatic injury possibly by reprogramming the metabolic pathway of bone marrow-derived monocytes.

Introduction: Clonorchis sinensis infection results in various complications in the liver and biliary systems and is a neglected tropical disease in Eastern Asia. In this study, we report that C. sinensis calcium-binding protein Cs16 activates host immune cells and induces immunopathology in liver. Methods: Immunohistochemistry was used to detect the localization of Cs16 in C. sinensis adult worms. ELISA was used to detect the serum levels of anti-Cs16 IgG antibody in infected humans and mice. Bile duct injection model was used to figure out the role of Cs16 in vivo. RT-qPCR and ELISA were used to detect the cytokine production from Cs16-treated BMMs in vitro. Seahorse assay was used to detect the metabolic pathway of Cs16-treated BMMs in vitro. Result: Cs16 localizes in the tegument and gut of C. sinensis. Humans and mice with C. sinensis infection exhibited increased levels of anti-Cs16-specific antibody. Using the bile duct injection technique, we found that Cs16 induced obvious inflammation and hepatic necrosis in vivo. Cs16 treatment caused the upregulation of inflammatory cytokines in innate immune cells. Moreover, Cs16-treated monocytes relied more on the glycolytic metabolic pathway. Discussion: Our findings suggest that Cs16 is a potential pathogenic factor derived from C. sinensis adult worm. By reprogramming the metabolic pathway of innate immune cells, Cs16 triggers pro-inflammatory responses in the liver, and therefore, Cs16 is a potential target for the prevention and treatment of clonorchiasis.

Flectobacillus longus sp. nov. and Flectobacillus rivi sp. nov., isolated from streams in China and reclassification of Flectobacillus rhizosphaerae as a synonym of Flectobacillus roseus.

Three Gram-stain-negative, aerobic, rod-shaped, non-motile strains (LYT7WT, DC10W and LFS242WT) were isolated from streams in PR China. Comparisons based on the 16S rRNA gene sequences showed that these three strains showed high 16S rRNA gene sequence similarity to Flectobacillus roseus GFA-11T (99.2, 98.8 and 99.8 %, respectively) and Flectobacillus rhizosphaerae JC289T (98.8, 98.6 and 99.4 %, respectively), and less than 96.6 % to other species of the genus Flectobacillus. The phylogenetic tree reconstructed based on the 16S rRNA gene sequences showed that strains LYT7WT, DC10W, LFS242WT, F. roseus GFA-11T and F. rhizosphaerae JC289T formed a tight cluster. The phylogenomic tree also supported the above robust phylogenetic relationships. The calculated OrthoANIu and digital DNA-DNA hybridization values between strains LYT7WT and DC10W were 95.2 % and 61.9 %, respectively. Although these values are located in the transition region for species demarcation, the similar physiological and genotypic characteristics supported that strains LYT7WT and DC10W should belong to the same species. The pairwise OrthoANIu and digital DNA-DNA hybridization values between strain LFS242WT and its related strains were less than 91.8 and 45.3 %, respectively, indicating that strain LFS242WT should represent an independent novel species of the genus Flectobacillus. It should be noticed that the pairwise OrthoANIu and digital DNA-DNA hybridization values between strains F. roseus LMG 24501T and F. rhizosphaerae KCTC 42575T were 96.9 and 73.1 %, respectively. The similar physiological and genotypic characteristics also supported that F. rhizosphaerae Ramaprasad et al. 2015 should be a synonym of F. roseus Sheu et al. 2009. Combining the above descriptions, strains LYT7WT, DC10W and LFS242WT should represent two novel species of the genus Flectobacillus, for which the names Flectobacillus longus sp. nov. (type strain LYT7WT=GDMCC 1.3222T=KCTC 92561T) and Flectobacillus rivi sp. nov. (type strain LFS242WT=GDMCC 1.3223T=KCTC 92562T) are proposed.

Spatio-temporal variation and environmental drivers of chlorophyll a concentration and diatom community in four small urban lakes of Kunming, China.

Chlorophyll a (Chla) and diatom community structure are two indicators of lake water quality. In this study, we investigated the environmental parameters, chlorophyll a, and diatom community of four small urban lakes in Kunming (Beitan, Beihu, Nanhu and Longtan lakes in the campus of Yunnan Normal University) between March 2017 and December 2019. The results showed that the concentrations of total nitrogen (TN), total phosphorus (TP), and Chla in the four lakes showed significant seasonal fluctuation. The Chla concentration in Nanhu Lake, which had the highest nutrient level among the four lakes, was significantly higher than that in the other three lakes and largely affected by TN. In comparison, water temperature significantly contributed to the increases in Chla concentration in the other three lakes. Water temperature and TN were significantly correlated with Chla across the four lakes. Diatom assemblages in Beitan, Nanhu, and Longtan lakes were dominated by planktonic diatoms, and benthic diatoms were dominant in the shallowest lake Beihu, suggesting that water depth significantly affected the proportion of planktonic diatoms and dominant taxa. Water depth, TN, TP, transparency, and water temperature affected the spatio-temporal changes of diatom community structure, with water temperature as the major factor in causing the seasonal variation in diatom community, and TN and TP as the major drivers for community variation among lakes within the same season.

Comparison and subsets analysis of peripheral CD4+T cells in patients with psoriasis and psoriatic arthritis.

Psoriatic arthritis (PsA) is a disease that transformed from psoriasis (PsO), and its underlying mechanisms are still not fully understood. Overactivation of the immune system is a key factor driving inflammatory diseases. Our goal is to define the unbalanced subsets of peripheral blood CD4 +T cells between PsO and PsA patients. Blood samples from 43 patients (23 PsA and 20 PsO) and 36 healthy donors (HD) were studied. Peripheral blood mononuclear cells (PBMC) were separated from blood and underwent fluorescent staining to assess CD4+T cell subsets by flow cytometry. We found that frequencies of various CD4+T cells including Th1, Th2, Th17, and Tfh were higher in the patients with PsO or PsA than those of healthy donors, indicating the general expansion of CD4+T cells in inflammatory conditions. More importantly, we observed the significant imbalance of Th1/Th2 between patients with PsO and PsA. Pearson correlation analysis showed that Th1/Th2 ratio was positively correlated with disease activity in psoriatic arthritis (DAPSA), Tfh/Tfr ratio was positively correlated with DAPSA score and visual analogue scale (VAS) score in PsA patients. Together, our results highlight the CD4+T cell changes in the transition from PsO to PsA, may contribute to early assessment and intervention.

Vogesella aquatica sp. nov. and Vogesella margarita sp. nov., isolated from rivers in Southwest China.

Eight Gram-stain-negative, aerobic, short rod-shaped and motile strains (DC21WT, LYT5WT, LYT10W, LYT16W, LYT22W, LYT23W, LYT24W and SH7W) were isolated from rivers in Southwest China. Comparisons based on the 16S rRNA gene sequences showed that strain DC21WT shared the highest 16S rRNA gene sequence similarity (99.6 %) with Vogesella mureinivorans 389T, strain LYT5WT shared 99.2 % with Vogesella fluminis Npb-07T, and the other isolated strains took Vogesella indigofera DSM 3303T as their most similar strain, respectively. The phylogenetic trees reconstructed based on the 16S rRNA gene sequences also supported that strains V. mureinivorans 389T, V. fluminis Npb-07T and V. indigofera DSM 3303T were the closest neighbours of the isolated strains. The phylogenomic tree showed similar phylogenetic relationships among these strains. The calculated OrthoANIu and digital DNA-DNA hybridization values among strains DC21WT, LYT5WT and other related strains were less than 93.7 and 53.7 %, respectively. The calculated OrthoANIu and digital DNA-DNA hybridization values among strains LYT10W, LYT16W, LYT22W, LYT23W, LYT24W, SH7W and V. indigofera DSM 3303T ranged from 94.8 to 97.2 % and from 59.8 to 74.9 %, respectively. Although these values were located in the transition region of species demarcation, their similar phenotypic, biochemical and genotypic characteristics supported that these six strains should be assigned to the species V. indigofera. Comparative genomic analyses showed that only V. indigofera DSM 3303T harboured 19 genes encoding the Type VI secretion system. Combining above descriptions, strains DC21WT and LYT5WT should represent two independent novel species of the genus Vogesella, for which the names Vogesella aquatica sp. nov. (type strain DC21WT=GDMCC 1.3220T=KCTC 92556T) and Vogesella margarita sp. nov. (type strains LYT5WT=GDMCC 1.3213T=KCTC 92549T) are proposed, respectively.

Asticcacaulis aquaticus sp. nov., Asticcacaulis currens sp. nov. and Asticcacaulis machinosus sp. nov., isolated from streams in PR China.

Three Gram-stain-negative, aerobic, rod-shaped, stalked and motile strains with a polar flagellum (BYS171WT, DXS10WT and LKC15WT) were isolated from streams in PR China. Comparisons based on 16S rRNA gene sequences showed that strains BYS171WT and DXS10WT had the highest 16S rRNA gene sequence similarities (98.1 and 98.6 %, respectively) to Asticcacaulis excentricus CB 48T, and strain LKC15WT showed 99.6 % similarity to Asticcacaulis endophyticus ZFGT-14T. These three strains showed 16S rRNA gene sequence similarities of less than 96.9 % to other species of the genus Asticcacaulis. A phylogenetic tree reconstructed based on 16S rRNA gene sequences also showed that strains BYS171WT and DXS10WT took A. excentricus CB 48T as their closest neighbour, and strain LKC15WT formed a tight cluster with A. endophyticus ZFGT-14T. The phylogenomic tree also showed that these three strains belong to the genus Asticcacaulis and form a distinct clade with the species of the genus Asticcacaulis. The major cellular fatty acids of these three strains were summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c), summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c), C16 : 0 and 11-methyl C18 : 1 ω7c. Their polar lipids mainly consisted of phosphatidylglycerol, unidentified glycolipids and nitrogen-containing phosphoglycolipids. The calculated OrthoANIu and digital DNA-DNA hybridization values among strains BYS171WT, DXS10WT, LKC15WT and other related strains were less than 87.2 % and 34.0 %, respectively, indicating that these three strains should represent three independent novel species of the genus Asticcacaulis, for which the names Asticcacaulis aquaticus sp. nov. (type strain BYS171WT=GDMCC 1.3226T=KCTC 92612T), Asticcacaulis currens sp. nov. (type strain DXS10WT=GDMCC 1.3224T=KCTC 92543T) and Asticcacaulis machinosus sp. nov. (type strain LKC15WT=GDMCC 1.3225T=KCTC 92544T) are proposed.

CX-4945 inhibits fibroblast-like synoviocytes functions through the CK2-p53 axis to reduce rheumatoid arthritis disease severity.

Fibroblast-like synoviocytes (FLS) mediate many pathological processes in rheumatoid arthritis (RA), including pannus formation, bone erosion, and inflammation. RA FLS have unique aggressive phenotypes and exhibit several tumor cell-like characteristics, including hyperproliferation, excessive migration and invasion. Casein kinase 2 (CK2) is reportedly overexpressed in numerous tumor types, and targeted inhibition of CK2 has therapeutic benefits for tumors. However, the expression level of CK2 and its functions in RA FLS remain unclear. Herein, we aimed to elucidate whether CK2 is responsible for the aggressive phenotypes of RA FLS and whether targeted therapy can alleviate the severity of RA. We found that CK2 subunits were elevated in RA FLS compared with osteoarthritis FLS, and the activity of CK2 also markedly increased in RA FLS. Targeted inhibition of CK2 using CX-4945 suppressed RA FLS proliferation through cell cycle arrest. Cell migration and invasion were also inhibited by CX-4945 treatment. Moreover, CX-4945 reduced Interleukin-6 (IL-6), CC motif chemokine ligand 2 (CCL2) and Matrix metalloproteinase-3 (MMP-3) secretion in RA FLS. Further proteomic investigation revealed that p53 signaling pathway significantly changes after CX-4945 treatment in RA FLS. The siRNA-mediated p53 knockdown partly abolished the anti-proliferation and reduced IL-6, MMP-3 secretion effects of CX-4945. Furthermore, CX-4945 administration alleviates arthritis severity in CIA mice. Collectively, our results demonstrated the abnormal elevation of CK2 and its positive association with abnormal phenotypes in RA FLS. Our novel findings suggest the possible therapeutic potential of CX-4945 for RA.