Network pharmacology and experimental validation to explore the mechanism of Changji'an formula against irritable bowel syndrome with predominant diarrhea.

Changji'an Formula (CJAF) is a Chinese herbal compound, which is effective against irritable bowel syndrome with predominant diarrhea (IBS-D) in clinic. However, the molecular mechanism has not been well defined. In the current study, the potential targets and signaling pathways of CJAF against IBS-D were predicted using network pharmacology analysis. The pharmacological mechanisms of CJAF against IBS-D and the potential mechanism were validated by using an IBS-D mouse model induced by enema with trinitrobenzene-sulfonic acid (TNBS) plus with restraint stress and further intervened with CJAF. A total of 232 active compounds of CJAF were obtained, a total of 397 potential targets for the active ingredients were retrieved and a total of 219 common targets were obtained as the potential targets of CJAF against IBS-D. GO and KEGG enrichment analyses showed that multiple targets were enriched and could be experimentally validated in a mouse model of IBS-D. The mechanisms were mainly converged on the immune and inflammatory pathways, especially the NF-κB, TNF and IL-17 signaling pathway, which were closely involved in the treatment of CJAF against IBS-D. Animal experiment showed that CJAF alleviated visceral hypersensitivity and diarrhea symptom of IBS-D. CJAF also restored the histological and ultrastructure damage of IBS-D. The result of Western blot showed that CJAF upregulated colonic tight junction proteins of ZO-1, Occludin and Claudin-1. Further results demonstrated that CJAF inhibited the protein expression of NF-κB/NLRP3 inflammasome pathway targets and downregulated proinflammatory mediators of IL-1ß, IL-18, TNF-α. In conclusion, CJAF could effectively reduce inflammatory response and alleviate visceral hypersensitivity as well as diarrhea symptom of IBS-D by inhibiting the NF-κB/NLRP3 signaling pathway. This study not only reveals the mechanism of CJAF against IBS-D, but also provides a novel therapeutic strategy for IBS-D.

Triptolide regulates neutrophil function through the Hippo signaling pathway to alleviate rheumatoid arthritis disease progression.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammatory changes in the joints, the etiology of which is unclear. It is now well established that regulated cell death (RCD) and migration of neutrophils play an important role in the pathogenesis of RA. Tripterygium wilfordii Hook.f (TwHF) is a total saponin extracted from the root of Tripterygium wilfordii Hook.f, a plant of the family Wesleyanaceae, which has strong anti-inflammatory and immunomodulatory effects and has been used as a basic drug in the clinical treatment of RA. Despite the good efficacy of TwHF treatment, the mechanism of action of TwHF remains unclear. Several studies have demonstrated that the drug tripterygium glycosides, in which TwHF is the main ingredient, has achieved excellent efficacy in the clinical treatment of RA. Investigations have also found that TwHF can affect cellular RCD, cell migration, cell proliferation, and the apoptosis-related Hippo signaling pathway. In this study, we first analyzed the RCD and migration differences of neutrophils in patients with RA through network pharmacology and transcriptome analysis. Subsequently, we used electron microscopy, immunofluorescence, and other methods to identify the RCD phenotype of neutrophils. In collagen-induced arthritis (CIA) model, we demonstrated that Triptolide (the main active ingredient in TwHF) could alleviate the progression of arthritis by reducing the bone destruction and the infiltration of neutrophils. Furthermore, in vitro experiments showed that Triptolide induced neutrophil apoptosis, inhibited the formation of neutrophil extracellular traps (NETs), and impeded the neutrophil migration process in a Hippo pathway-dependent manner. Taken together, these findings indicate that Triptolide has potential for treating RA and provide theoretical support for the clinical application of TwHF, as a traditional Chinese medicine, in RA.

Combination of scavenger receptor-A with anti-cyclic citrullinated peptide antibody for the diagnosis of rheumatoid arthritis.

OBJECTIVES: The routine biomarkers for rheumatoid arthritis (RA), including anticyclic citrullinated peptide antibody (anti-CCP), rheumatoid factor (RF), immunoglobulin M (IgM), erythrocyte sedimentation rate (ESR), and C-reaction protein (CRP) have limited sensitivity and specificity. Scavenger receptor-A (SR-A) is a novel RA biomarker identified by our group recently, especially for seronegative RA. Here, we performed a large-scale multicentre study to further assess the diagnostic value of SR-A in combination with other biomarkers for RA. METHODS: The performance of SR-A in combination with other biomarkers for RA diagnosis was first revealed by a pilot study, and was further elucidated by a large-scale multicentre study. A total of 1129 individuals from 3 cohorts were recruited in the study, including RA patients, healthy controls, and patients with other common rheumatic diseases. Diagnostic properties were evaluated by the covariate-adjusted receiver-operating characteristic (AROC) curve, sensitivity, specificity and clinical association, respectively. RESULTS: Large-scale multicentre analysis showed that SR-A and anti-CCP dual combination was the optimal method for RA diagnosis, increasing the sensitivity of anti-CCP by 13% (87% vs 74%) while maintaining a specificity of 90%. In early RA patients, SR-A and anti-CCP dual combination also showed promising diagnostic value, increasing the sensitivity of anti-CCP by 7% (79% vs 72%) while maintaining a specificity of 94%. Moreover, SR-A and anti-CCP dual combination was correlated with ESR, IgM, and autoantibodies of RA patients, further revealing its clinical significance. CONCLUSION: SR-A and anti-CCP dual combination could potentially improve early diagnosis of RA, thus improving the prognosis and reducing mortality.

Macroscale Superlubricity on Nanoscale Graphene Moiré Structure-Assembled Surface via Counterface Hydrogen Modulation.

Interlayer incommensurateness slippage is an excellent pathway to realize superlubricity of van der Waals materials; however, it is instable and heavily depends on twisted angle and super-smooth substrate which pose great challenges for the practical application of superlubricity. Here, macroscale superlubricity (0.001) is reported on countless nanoscale graphene moiré structure (GMS)-assembled surface via counterface hydrogen (H) modulation. The GMS-assembled surface is formed on grinding balls via sphere-triggered strain engineering. By the H modulation of counterface diamond-like carbon (25 at.% H), the wear of GMS-assembled surface is significantly reduced and a steadily superlubric sliding interface between them is achieved, based on assembly face charge depletion and H-induced assembly edge weakening. Furthermore, the superlubricity between GMS-assembled and DLC25 surfaces holds true in wide ranges of normal load (7-11 N), sliding velocity (0.5-27 cm -1s), contact area (0.4×104-3.7×104 µm2), and contact pressure (0.19-1.82 GPa). Atomistic simulations confirm the preferential formation of GMS on a sphere, and demonstrate the superlubricity on GMS-assembled surface via counterface H modulation. The results provide an efficient tribo-pairing strategy to achieve robust superlubricity, which is of significance for the engineering application of superlubricity.

Locking plate versus K-wires and cast fixation in lateral closing-wedge osteotomy for cubitus varus deformity.

Background: The aim of this study was to assess the clinical and radiographic outcomes of cubitus varus treatments based on different fixation methods: Locking plate vs. Kirschner-wires (K-wires) and cast fixation. Methods: This retrospective study of 28 patients was performed in lateral-wedge osteotomy for cubitus varus deformity in our hospital from July 2018 to July 2020. 14 patients in group A were treated by locking plate after lateral closing-wedge osteotomy, whereas other 14 patients were treated by K-wires in group B. We measured the bony union and carrying angle. The clinical and radiographic outcomes were assessed according to the Bellemore criteria. Results: No nonunion, neurovascular injury or myositis ossificans was noted at follow-up. In group A, 1 patient with lateral condylar prominence was found. In group B, 2 patients with pinning site infection were treated successfully with oral antibiotics and 2 patients needed revision surgery for residual varus. According to the Bellemore criteria, statistically significant difference was noted between the two groups (P = 0.0458). In the present study, no statistically significant difference was noted in the length of incision and operation time between the 2 groups (P > 0.05). However, the postoperative carrying angle was significantly different at final follow-up between the 2 groups (P < 0.01). Conclusions: Compared with K-wires and cast fixation, we recommend the wedge osteotomy with lateral locking plate to treat the cubitus varus deformity because locking plate could achieve better functional and cosmetic results and stabilize the distal humerus rigidly.

Compartmentalized ocular lymphatic system mediates eye-brain immunity.

The eye, an anatomical extension of the central nervous system (CNS), exhibits many molecular and cellular parallels to the brain. Emerging research demonstrates that changes in the brain are often reflected in the eye, particularly in the retina1. Still, the possibility of an immunological nexus between the posterior eye and the rest of the CNS tissues remains unexplored. Here, studying immune responses to herpes simplex virus in the brain, we observed that intravitreal immunization protects mice against intracranial viral challenge. This protection extended to bacteria and even tumours, allowing therapeutic immune responses against glioblastoma through intravitreal immunization. We further show that the anterior and posterior compartments of the eye have distinct lymphatic drainage systems, with the latter draining to the deep cervical lymph nodes through lymphatic vasculature in the optic nerve sheath. This posterior lymphatic drainage, like that of meningeal lymphatics, could be modulated by the lymphatic stimulator VEGFC. Conversely, we show that inhibition of lymphatic signalling on the optic nerve could overcome a major limitation in gene therapy by diminishing the immune response to adeno-associated virus and ensuring continued efficacy after multiple doses. These results reveal a shared lymphatic circuit able to mount a unified immune response between the posterior eye and the brain, highlighting an understudied immunological feature of the eye and opening up the potential for new therapeutic strategies in ocular and CNS diseases.

Safety and efficacy of peficitinib in Asian patients with rheumatoid arthritis who had an inadequate response or intolerance to methotrexate: results of a multicenter, randomized, double-blind, placebo-controlled phase 3 study.

Background: The efficacy and safety of the oral Janus kinase inhibitor peficitinib were investigated in Asian patients with rheumatoid arthritis (RA). Methods: In this double-blind, phase 3 study, patients from mainland China, Korea, and Taiwan with RA and an inadequate response/intolerance to methotrexate were randomized (1:1:1) to once-daily placebo (N = 128), peficitinib 100 mg (N = 129), or 150 mg (N = 128) in combination with non-biologic DMARDs. At Week 24, patients receiving placebo switched to peficitinib 100 mg or 150 mg. American College of Rheumatology (ACR) 20 response at Week 24/early termination (ET) was the primary endpoint. Adverse events (AEs) were assessed. The study was registered at ClinicalTrials (NCT03660059). Findings: 385 patients were included in the analysis. ACR20 responses were statistically significantly higher in both peficitinib 100 mg (56.6%) and 150 mg (56.3%) groups versus placebo (24.2%); Odds Ratio (95% confidence interval, CI) 4.14 (2.42, 7.08) and 4.07 (2.38, 6.96), respectively (both P < 0.001) at Week 24/ET. The incidence rate of herpes zoster related disease (herpes zoster and varicella) was higher in patients who received peficitinib versus placebo, but no dose dependency was observed (incidence rate/100 patient-years (95% CI): peficitinib 6.7 (4.32, 10.37); placebo 3.7 (0.93, 14.88). Interpretation: In Asian patients with RA and an inadequate response/intolerance to methotrexate, peficitinib 100 mg and 150 mg demonstrated superiority to placebo in the reduction of RA symptoms and was well tolerated. No additional benefit was observed with use of the higher peficitinib dose in this study population of predominantly Chinese patients. Funding: Astellas Pharma.

Sex-specific differences in patients with psoriatic arthritis:a nationwide study from the Chinese Registry of Psoriatic Arthritis (CREPAR IV).

OBJECTIVES: To elucidate the sex-specific differences in demographic features, clinical characteristics, and quality of life in Chinese patients with psoriatic arthritis (PsA). METHODS: A total of 1,074 patients with PsA registered between December 2018 and June 2021 from the Chinese REgistry of Psoriatic ARthritis (CREPAR) cohort were selected. The baseline data on demographics, clinical characteristics, commonly used laboratory tests, comorbidities, and quality of life assessments were collected for this cross-sectional analysis. RESULTS: A total of 1,074 patients were included in this study, 585 (54.47%) of them were male and 489 (45.53%) were female. The age at PsA onset in male patients was earlier than that in female patients (38.10 ± 12.79 vs 40.37 ± 13.41, p = 0.005). For clinical characteristics, male patients presented with higher rates of axial involvement (43.89% vs 37.74%, p = 0.044) and nail involvement (66.15% vs 58.08%, p = 0.006), while female patients presented with higher rates of peripheral arthritis (89.57% vs 83.93%, p = 0.007). For laboratory tests, men presented with a higher percentage of HLA-B27 positivity than women (24.65% vs 16.70%, p = 0.002) and had higher levels of CRP (median 9.70 vs 5.65, p < 0.001). Regarding disease assessment indices, male patients scored higher in PASI and BASFI (median 5.00 vs 3.00, p = 0.007 and 1.80 vs 1.40, p = 0.012, respectively). No sex difference was found in rates of achieving remission. Factors associated with disease remission were also analyzed in both sexes. CONCLUSION: Demographic and clinical characteristics tend to vary between male and female patients with PsA. Male patients reported more functional limitations in daily life. Key Points • The demographic and clinical features vary greatly between male and female patients with PsA. • Male patients reported more functional burden in daily life as measured by BASFI.

LncRNA HCG18 promotes inflammation and apoptosis in intervertebral disc degeneration via the miR-495-3p/FSTL1 axis.

Intervertebral disc degeneration (IDD) causes pain in the back and neck. This study investigated the role of long non-coding RNA HLA complex group 18 (HCG18) in a cell model of IDD. An IDD model was established by stimulating nucleus pulposus (NP) cells with interleukin (IL)-1ß. MTT assay was performed to evaluate NP cell viability. The apoptosis was detected by flow cytometry. The expressions of HCG18, microRNA (miR)-495-3p, and follistatin-like protein-1 (FSTL1) were measured by RT-qPCR. The interactions of miR-495-3p with HCG18 and FSTL1 were analyzed by luciferase reporter assay. IL-1ß stimulation upregulated HCG18 and FSTL1, but downregulated miR-495-3p in NP cells. Silencing of HCG18 or FSTL1, as well as miR-495-3p overexpression in NP cells alleviated IL-1ß-induced apoptosis and inflammation of NP cells. Both HCG18 and FSTL1 had binding sites for miR-495-3p. Overexpression of FSTL1 abolished the effects of HCG18 silencing on IL-1ß-induced apoptosis and inflammation. The HCG18/miR-495-3p/FSTL1 axis is essential for IDD development. Therapeutic strategies targeting this axis may be used for IDD treatment.

New cyclophilin D inhibitor rescues mitochondrial and cognitive function in Alzheimer's disease.

Mitochondrial dysfunction is an early pathological feature of Alzheimer disease and plays a crucial role in the development and progression of Alzheimer's disease. Strategies to rescue mitochondrial function and cognition remain to be explored. Cyclophilin D (CypD), the peptidylprolyl isomerase F (PPIase), is a key component in opening the mitochondrial membrane permeability transition pore, leading to mitochondrial dysfunction and cell death. Blocking membrane permeability transition pore opening by inhibiting CypD activity is a promising therapeutic approach for Alzheimer's disease. However, there is currently no effective CypD inhibitor for Alzheimer's disease, with previous candidates demonstrating high toxicity, poor ability to cross the blood-brain barrier, compromised biocompatibility and low selectivity. Here, we report a new class of non-toxic and biocompatible CypD inhibitor, ebselen, using a conventional PPIase assay to screen a library of ∼2000 FDA-approved drugs with crystallographic analysis of the CypD-ebselen crystal structure (PDB code: 8EJX). More importantly, we assessed the effects of genetic and pharmacological blockade of CypD on Alzheimer's disease mitochondrial and glycolytic bioenergetics in Alzheimer's disease-derived mitochondrial cybrid cells, an ex vivo human sporadic Alzheimer's disease mitochondrial model, and on synaptic function, inflammatory response and learning and memory in Alzheimer's disease mouse models. Inhibition of CypD by ebselen protects against sporadic Alzheimer's disease- and amyloid-ß-induced mitochondrial and glycolytic perturbation, synaptic and cognitive dysfunction, together with suppressing neuroinflammation in the brain of Alzheimer's disease mouse models, which is linked to CypD-related membrane permeability transition pore formation. Thus, CypD inhibitors have the potential to slow the progression of neurodegenerative diseases, including Alzheimer's disease, by boosting mitochondrial bioenergetics and improving synaptic and cognitive function.

Adipose-derived mesenchymal stem cell exosomes ameliorate spinal cord injury in rats by activating the Nrf2/HO-1 pathway and regulating microglial polarization.

As of now, there are no satisfactory treatments for spinal cord injury (SCI), so new therapeutic approaches are necessary to be explored. Adipose-derived mesenchymal stem cell exosomes (ADMSC-Exo), delightfully, show remarkable therapeutic effects. Therefore, we try to investigate the effects and mechanisms of ADMSC-Exo on SCI, as well as to provide novel approaches for the treatment of SCI. Adipose-derived mesenchymal stem cells (ADMSC) were isolated from rats and then exosomes (Exo) were extracted from the cells. The extracted Exo were identified by flow cytometry, transmission electron microscopy and nanoparticle tracking analysis (NTA). Then, the SCI rat model was established by the spinal cord impactor and injected with 200 µl PBS or Exo into their tail veins at 30 min, 24 h, and 48 h after surgery. The rats in the Control group and Exo group only exposed the spine. Motor function recovery was assessed on days 0, 7, 14, 21, and 28; histopathological changes and apoptosis levels in spinal cord tissues were observed by HE staining and TUNEL staining; the levels of inflammatory cytokines TNF-a, IL-6, and MCP-1 in spinal cord tissues were measured by ELISA; the expression levels of iNOS, IL-12, Arg1, and Mrc1 in spinal cord tissues were detected by qRT-PCR; and Nrf2, HO-1, and NQO1 protein expression in spinal cord tissues were detected by Western blot. ADMSC-Exo were successfully isolated and identified. ADMSC-Exo significantly relieved SCI and promoted motor function recovery in SCI rats. Moreover, ADMSC-Exo inhibited the expression of both inflammatory factors in the spinal cord tissues and M1 microglia, promoted the expression of M2 microglia, and activated the Nrf2/HO-1 pathway. Altogether, ADMSC-Exo can not only ameliorate SCI, but also promote the motor function recovery of rats. And the mechanism of ADMSC-Exo improving SCI may be achieved by activating Nrf2/HO-1 pathway and microglial polarization.

Identification and Localization of Cell Types in the Mouse Olfactory Bulb Using Slide-SeqV2.

Spatial transcriptomics maps RNA molecules to the location in a tissue where they are expressed. Here we document the use of Slide-SeqV2 to visualize gene expression in the mouse olfactory bulb (OB). This approach relies on spatially identified beads to locate and quantify individual transcripts. The expression profiles associated with the beads are used to identify and localize individual cell types in an unbiased manner. We demonstrate the various cell types and subtypes with distinct spatial locations in the olfactory bulb that are identified using Slide-SeqV2.

ASA-BiSeNet: improved real-time approach for road lane semantic segmentation of low-light autonomous driving road scenes.

The solution to the problem of road environmental perception is one of the essential prerequisites to realizing the autonomous driving of intelligent vehicles, and road lane detection plays a crucial role in road environmental perception. However, road lane detection in complex road scenes is challenging due to poor illumination conditions, the occlusion of other objects, and the influence of unrelated road markings. It also hinders the commercial application of autonomous driving technology in various road scenes. In order to minimize the impact of illumination factors on road lane detection tasks, researchers use deep learning (DL) technology to enhance low-light images. In this study, road lane detection is regarded as an image segmentation problem, and road lane detection is studied based on the DL approach to meet the challenge of rapid environmental changes during driving. First, the Zero-DCE++ approach is used to enhance the video frame of the road scene under low-light conditions. Then, based on the bilateral segmentation network (BiSeNet) approach, the approach of associate self-attention with BiSeNet (ASA-BiSeNet) integrating two attention mechanisms is designed to improve the road lane detection ability. Finally, the ASA-BiSeNet approach is trained based on the self-made road lane dataset for the road lane detection task. At the same time, the approach based on the BiSeNet approach is compared with the ASA-BiSeNet approach. The experimental results show that the frames per second (FPS) of the ASA-BiSeNet approach is about 152.5 FPS, and its mean intersection over union is 71.39%, which can meet the requirements of real-time autonomous driving.

Chinese Registry of Psoriatic Arthritis (CREPAR): I. Clinical characteristics of Chinese patients with psoriatic arthritis.

AIM: To describe the clinical characteristics of Chinese patients with psoriatic arthritis (PsA) using the data recorded in the Chinese Registry of Psoriatic Arthritis (CREPAR). METHODS: This is a cross-sectional study based on the CREPAR registry, which is a prospective registry founded in December 2018. Data regarding clinical characteristics and treatment of patients were collected during every visit. Data recorded at enrollment were extracted, analyzed, and compared with data in other registries or cohorts. RESULTS: A total of 1074 patients were registered from December 2018 to June 2021. Of these, 929 (86.5%) patients had a history of peripheral arthritis, and 844 patients (78.6%) had peripheral arthritis at enrollment, of which polyarthritis is the most common subtype. Axial involvement was present in 39.9% of patients, and 50 (4.7%) patients had axial involvement only. More than half of the patients (55.4%) had at least two musculoskeletal presentations at enrollment. The prevalence of low disease activity and remission according to DAPSA were 26.4% and 6.8%, respectively. Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biological DMARDs were used in 64.9% and 29.1% of patients, respectively. Among patients with different musculoskeletal presentations, patients with dactylitis had the highest proportion of nonsteroidal anti-inflammatory and csDMARD use. The proportion of patients receiving bDMARDs was highest in axial PsA. CONCLUSION: The CREPAR registry has provided information on Chinese patients with PsA. Compared with data in other registries or cohorts, the disease activity of patients in CREPAR was higher, and the proportion of bDMARD use was lower.

MicroRNA-29b-3p promotes intestinal permeability in IBS-D via targeting TRAF3 to regulate the NF-κB-MLCK signaling pathway.

Irritable bowel syndrome with predominant diarrhea (IBS-D) is characterized by increased intestinal permeability. Previous studies have shown that the microRNA-29 gene is involved in the regulation of intestinal permeability in patients with IBS-D. NF-κB was proved to play a key role in inflammatory response of intestine and resultant disruption of tight junction integrity, whose activity could be inhibited by TNF Receptor-Associated Factor 3 (TRAF3). However, the exact mechanism that induces increased intestinal permeability in IBS-D patients has not been clarified. In this study, we found that microRNA-29b­3p (miR-29b-3p) was significantly upregulated, while TRAF3 was decreased and the NF-κB-MLCK pathway was activated within the colonic tissue of IBS-D patients. Subsequently, we confirmed the targeting relationship between miR-29b-3p and TRAF3 through a double-luciferase reporter assay. Lentivirus transfection of NCM460 cells with miR-29b-3p-overexpressing and -silencing vectors demonstrated that the expression of TRAF3 was negatively correlated with the level of miR-29b-3p. The NF-κB/MLCK pathway was activated in the miR-29b-3p-overexpressing group and inhibited to some extent in the miR-29b-3p-silencing group. Results in WT and miR-29 knockout mice showed that miR-29b-3p levels were increased, TRAF3 levels were decreased, and the NF-κB/MLCK signaling was activated in the WT IBS-D group as compared with the WT control group. The protein levels of TRAF3 and TJs in the miR-29b-/- IBS-D group were partially recovered and NF-κB/MLCK pathway indicators were, to a certain extent, decreased as compared with the WT IBS-D group. These results suggested that miR-29b-3p deletion enhances the TRAF3 level in IBS-D mice and alleviates the high intestinal permeability. In brief, through the analysis of intestinal tissue samples from IBS-D patients and miR-29b-/- IBS-D mice, we showed that miR-29b-3p is involved in the pathogenesis of intestinal hyperpermeability in IBS-D via targeting TRAF3 to regulate the NF-κB-MLCK signaling pathway.

Tunable, Wide-Temperature, and Macroscale Superlubricity Enabled by Nanoscale Van Der Waals Heterojunction-to-Homojunction Transformation.

Achieving macroscale superlubricity of van der Waals (vdW) nanopowders is particularly challenging, due to the difficulty in forming ordered junctions before friction and the friction-induced complex contact restructuration among multiple nanometer-sized junctions. Here, a facile way is reported to achieve vdW nanopowder-to-heterojunction conversion by graphene edge-oxygen (GEO) incorporation. The GEO effectively weakens the out-of-plane edge-edge and in-plane plane-edge states of the vdW nanopowder, leading to a coexistent structure of nanoscale homojunctions and heterojunctions on the grinding balls. When sliding on diamond-like carbon surfaces, the ball-supported structure governs macroscale superlubricity by heterojunction-to-homojunction transformation among the countless nanoscale junctions. Furthermore, the transformation guides the tunable design of superlubricity, achieving superlubricity (µ ≈ 0.005) at wide ranges of load, velocity, and temperature (-200 to 300 °C). Atomistic simulations reveal the GEO-enhanced conversion of vdW nanopowder to heterojunctions and demonstrate the heterojunction-to-homojunction transformation superlubricity mechanism. The findings are of significance for the macroscopic scale-up and engineering application of structural superlubricity.

Development and validation of KASP markers for resistance to Phytophthora capsici in Capsicum annuum L.

Resistance of Capsicum annuum to Phytophthora blight is dependent on the genetic background of the resistance source and the Phytophthora capsici isolate, which poses challenges for development of generally applicable molecular markers for marker-assisted selection. In this study, the resistance to P. capsici of C. annuum was genetically mapped to chromosome 5 within a 1.68-Mb interval by genome-wide association study analysis of 237 accessions. In this candidate region, 30 KASP markers were developed using genome resequencing data for a P. capsici-resistant line (0601 M) and a susceptible line (77,013). Seven of these KASP markers, located in the coding region of a probable leucine-rich repeats receptor-like serine/threonine-protein kinase gene (Capana05g000704), were validated in the 237 accessions, which showed an average accuracy of 82.7%. The genotyping of the seven KASP markers strongly corresponded with the phenotype of 42 individual plants in a pedigree family (PC83-163) developed from the P. capsici-resistant line CM334. This research provides a set of efficient and high-throughput KASP markers for marker-assisted selection of resistance to P. capsici in C. annuum. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01367-3.

Risk factors for avascular necrosis in patients with systemic lupus erythematosus: a multi-center cohort study of Chinese SLE Treatment and Research Group (CSTAR) Registry XXII.

BACKGROUND: Avascular necrosis is a common organ damage in SLE patients, which can influence patients' life quality. Conflicting results exist in risk factors of AVN in SLE patients. The aim of this study was to illustrate risk factors predicting the occurrence of avascular necrosis (AVN), also known as osteonecrosis, in systemic lupus erythematosus (SLE) patients in Chinese SLE Treatment and Research Group (CSTAR), a multi-center cohort of Chinese SLE patients. METHODS: SLE patients in CSTAR without existing AVN at registration were included. At least two follow-ups and an observation period of no less than 2 years for AVN event were required. Univariate and multivariate Cox regression analyses were used to evaluate risk factors for AVN in SLE patients. Coefficient B was transformed to risk score for the development of a risk stratification model. RESULTS: One hundred six (2.59%) of 4091 SLE patients were diagnosed AVN during follow-ups of no less than 2 years. Multi-variate Cox regression analysis suggested that SLE onset age ≤ 30 (HR 1.616, p 0.023), arthritis (HR 1.642, p 0.018), existing organ damage (SDI ≥ 1) at registration (HR 2.610, p < 0.001), positive anti-RNP (HR 1.709, p 0.006), and high glucocorticoid maximum daily dose at registration (HR 1.747, p 0.02) were independent risk factors. A risk stratification system was developed according to the risk factors, and patients were divided into high risk (3-6) and low risk (0-2). The AUC of 0.692 indicated moderate discrimination. The calibration curve in internal validation was drawn. CONCLUSION: Patients with SLE onset age ≤ 30, arthritis, existing organ damage (SDI ≥ 1) at registration, positive anti-RNP, and high glucocorticoid maximum daily dose at registration are at high risk for AVN and require attention.

Management of Rheumatoid Arthritis With a Digital Health Application: A Multicenter, Pragmatic Randomized Clinical Trial.

IMPORTANCE: Digital health applications have been shown to be effective in the management of chronic diseases with simple treatment targets. The potential clinical value of digital health applications in rheumatoid arthritis (RA) has not been well studied. OBJECTIVE: To investigate whether assessing patient-reported outcomes using digital health applications could result in disease control for patients with RA. DESIGN, SETTING, AND PARTICIPANTS: This is a multicenter, open-label randomized clinical trial in 22 tertiary hospitals across China. Eligible participants were adult patients with RA. Participants were enrolled from November 1, 2018, to May 28, 2019, with a 12-month follow-up. The statisticians and rheumatologists who assessed disease activity were blinded. Investigators and participants were not blind to group assignment. Analysis was conducted from October 2020 to May 2022. INTERVENTIONS: Participants were randomly assigned at a 1:1 ratio (block size of 4) to a smart system of disease management group (SSDM) or a conventional care control group. Upon the completion of the 6-month parallel comparison, patients in the conventional care control group were instructed to use the SSDM application for an extension of 6 months. MAIN OUTCOMES AND MEASURES: The primary outcome was the rate of patients with disease activity score in 28 joints using the C-reactive protein (DAS28-CRP) of 3.2 or less at month 6. RESULTS: Of 3374 participants screened, 2204 were randomized, and 2197 patients with RA (mean [SD] age, 50.5 [12.4] years; 1812 [82.5%] female) were enrolled. The study included 1099 participants in the SSDM group and 1098 participants in the control group. At month 6, the rate of patients with DAS28-CRP of 3.2 or less was 71.0% (780 of 1099 patients) in the SSDM group vs 64.5% (708 of 1098 patients) in the control group (difference between groups, 6.6%; 95% CI, 2.7% to 10.4%; P = .001). At month 12, the rate of patients with DAS28-CRP of 3.2 or less in the control group increased to a level (77.7%) that was comparable with that (78,2%) in the SSDM group (difference between groups, -0.2%; 95% CI, -3.9% to 3.4%; P = .90). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of RA, the use of a digital health application with patient-reported outcomes was associated with an increase in disease control rate. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03715595.