A cleaved adhesin DNA vaccine targeting dendritic cell against Porphyromonas gingivalis-induced periodontal disease.

BACKGROUND: Arg-gingipain A (RgpA) is the primary virulence factor of Porphyromonas gingivalis and contains hemagglutinin adhesin (HA), which helps bacteria adhere to cells and proteins. Hemagglutinin's functional domains include cleaved adhesin (CA), which acts as a hemagglutination and hemoglobin-binding actor. Here, we confirmed that the HA and CA genes are immunogenic, and using adjuvant chemokine to target dendritic cells (DCs) enhanced protective autoimmunity against P. gingivalis-induced periodontal disease. METHODS: C57 mice were immunized prophylactically with pVAX1-CA, pVAX1-HA, pVAX1, and phosphate-buffered saline (PBS) through intramuscular injection every 2 weeks for a total of three administrations before P. gingivalis-induced periodontitis. The DCs were analyzed using flow cytometry and ribonucleic acid sequencing (RNA-seq) transcriptomic assays following transfection with CA lentivirus. The efficacy of the co-delivered molecular adjuvant CA DNA vaccine was evaluated in vivo using flow cytometry, immunofluorescence techniques, and micro-computed tomography. RESULTS: After the immunization, both the pVAX1-CA and pVAX1-HA groups exhibited significantly elevated P. gingivalis-specific IgG and IgG1, as well as a reduction in bone loss around periodontitis-affected teeth, compared to the pVAX1 and PBS groups (p < 0.05). The expression of CA promoted the secretion of HLA, CD86, CD83, and DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) in DCs. Furthermore, the RNA-seq analysis revealed a significant increase in the chemokine (C-C motif) ligand 19 (p < 0.05). A notable elevation in the quantities of DCs co-labeled with CD11c and major histocompatibility complex class II, along with an increase in interferon-gamma (IFN-γ) cells, was observed in the inguinal lymph nodes of mice subjected to CCL19-CA immunization. This outcome effectively illustrated the preservation of peri-implant bone mass in rats afflicted with P. gingivalis-induced peri-implantitis (p < 0.05). CONCLUSIONS: The co-administration of a CCL19-conjugated CA DNA vaccine holds promise as an innovative and targeted immunization strategy against P. gingivalis-induced periodontitis and peri-implantitis.

The OsMOB1A-OsSTK38 kinase complex phosphorylates CYCLIN C, controlling grain size and weight in rice.

Grain size and weight are crucial yield-related traits in rice (Oryza sativa). Although certain key genes associated with rice grain size and weight have been successfully cloned, the molecular mechanisms underlying grain size and weight regulation remain elusive. Here, we identified a molecular pathway regulating grain size and weight in rice involving the MPS ONE BINDER KINASE ACTIVATOR-LIKE 1A-SERINE/THREONINE-PROTEIN KINASE 38-CYCLIN C (OsMOB1A-OsSTK38-OsCycC) module. OsSTK38 is a nuclear Dbf2-related kinase that positively regulates grain size and weight by coordinating cell proliferation and expansion in the spikelet hull. OsMOB1A interacts with and enhances the autophosphorylation of OsSTK38. Specifically, the critical role of the OsSTK38 S322 site in its kinase activity is highlighted. Furthermore, OsCycC, a component of the Mediator complex, was identified as a substrate of OsSTK38, with enhancement by OsMOB1A. Notably, OsSTK38 phosphorylates the T33 site of OsCycC. The phosphorylation of OsCycC by OsSTK38 influenced its interaction with the transcription factor KNOTTED-LIKE HOMEOBOX OF ARABIDOPSIS THALIANA 7 (OsKNAT7). Genetic analysis confirmed that OsMOB1A, OsSTK38, and OsCycC function in a common pathway to regulate grain size and weight. Taken together, our findings revealed a connection between the Hippo signaling pathway and the cyclin-dependent kinase module in eukaryotes. Moreover, they provide insights into the molecular mechanisms linked to yield-related traits and propose innovative breeding strategies for high-yielding varieties.

Bisdemethoxycurcumin, a curcumin derivative, ameliorates adjuvant-induced arthritis by suppressing inflammatory reactions and macrophage migration.

Rheumatoid arthritis (RA) is a highly prevalent and chronic inflammatory synovial joint disease manifested by hyperplasia and continuous inflammation. Curcumin (Cur) has been studied for alleviating RA. However, poor stability and oral bioavailability restrict its therapeutic value. Bisdemethoxycurcumin (BDMC), a curcumin (Cur) derivative, exerts better stability and oral bioavailability than Cur. However, the efficacy of BDMC on RA has not been fully clarified. The aim of the study was to investigate the therapeutic effects and underlying mechanisms of BDMC on RA. The in-vivo anti-arthritic activity of BDMC was determined via adjuvant-induced arthritis (AIA) rat model. Paw swelling, body weight, arthritic index, and histopathological assessments were performed. RAW264.7 cell was stimulated by lipopolysaccharides (LPS) in vitro. The cell viability were determined by CCK8 assay, while the migration ability was determined using cell wound healing and transwell assays. Furthermore, in-vivo and in-vitro levels of pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6) were assayed by ELISA, and that of IκBα, p-NF-κB, NF-κB, and COX-2 were assessed via Western blot or immunofluorescence. In AIA rat model, it suggested a higher anti-arthritic activity of BDMC than Cur, including amelioration of swelling in hind paws, reduced arthritic index, and alleviated histopathological injury in rats. Furthermore, BDMC also substantially decreased the levels of the aforementioned pro-inflammatory cytokines in both in-vivo and in-vitro, inhibited the IκBα degradation, down-regulated the COX-2 levels and p-NF-κB/NF-κB ratio in AIA rats and LPS-stimulated RAW264.7 cells. Additionally, BDMC showed an inhibitory effect on the migration of LPS-stimulated RAW264.7 cells. BDMC could effectively ameliorate RA by suppressing inflammatory reactions and inhibiting macrophage migration, more potentially than Cur.

Using physiological system networks to elaborate resilience across frailty states.

BACKGROUND: Aging is characterized by loss of resilience, the ability to resist or recover from stressors. Network analysis has shown promise in investigating dynamic relationships underlying resilience. We aimed to use network analysis to measure resilience in a longitudinal cohort of older adults and quantify whole-system vulnerabilities associated with frailty. METHODS: We used data from the Rugao Longitudinal Ageing Study, including 71 biomarkers from participants classified as robust, prefrail, or frail. We quantified biomarker correlations and topological parameters. Additionally, we proposed propagation models to simulate damage and recovery dynamics, investigating network resilience under various conditions. RESULTS: We classified 1754 individuals into robust (n=369), prefrail (n=1103), and frail (n=282) groups with 71 biomarkers. Several biomarkers were linked to frailty, including those related to blood pressure, ECG, kidney function, platelets, white blood cells. Each frailty stage was associated with increased network correlations. The frail network showed increased average degree and connectance, decreased average path length and diameter, and reduced modularity compared to robust and prefrail networks. Hub biomarkers, particularly ß2-microglobulin and platelet count, played a significant role, potentially propagating dysfunction across physiological systems. Simulations revealed that damage to critical hubs led to longer recovery times in the frail network than robust and prefrail networks. CONCLUSION: Network analysis could serve as a valuable tool for quantifying resilience and identifying vulnerabilities in older adults with frailty. Our findings contribute to understanding frailty-related physiological disturbances and offer potential for personalized healthcare interventions targeting resilience in older populations.

OsbHLH92, in the noncanonical brassinosteroid signaling pathway, positively regulates leaf angle and grain weight in rice.

Modifications of plant architecture can increase planting density, regulate photosynthesis, and improve crop yields. Many basic helix-loop-helix (bHLH) transcription factors participate in the brassinosteroid (BR) signaling pathway and are critical for plant architecture morphogenesis in rice. However, the number of identified bHLH genes suitable for improving production value is still limited. In this study, we cloned Lam1, encoding the typical bHLH transcription factor OsbHLH92. OsbHLH92 knockout (KO) lines exhibit erect leaves. Decreases in the number and size of parenchyma cell layers on the adaxial side of the lamina joint in KO lines were the main reason for the decreased leaf angle. Genetic experiments verify that OsBU1 and its homologs are downstream of OsbHLH92, which is involved in the noncanonical RGA1-mediated BR signaling pathway. OsbHLH91, an OsbHLH92 homolog, plays both conserved and differentiated roles relative to OsbHLH92. Notably, OsbHLH92-KO lines show erect leaves without the acquisition of adverse agronomic traits. Moreover, by driving a specific panicle promoter, OsbHLH92 can greatly increase productivity by at least 10%. This study identifies new components of the BR signaling pathway, demonstrates the importance of OsbHLH92 in improving planting density and crop productivity, and broadens our knowledge of typical and atypical bHLH family members in rice.

The diagnostic value of shear-wave elastography in the salivary glands of patients with primary Sjögren syndrome.

OBJECTIVE: We aimed to quantify the extent of salivary gland fibrosis using shear-wave elastography (SWE) to assess its diagnostic value for primary Sjögren syndrome (pSS). METHODS: A total of 58 pSS patients and 44 controls underwent SWE ultrasound evaluation of the parotid and submandibular glands. We measured the degree of salivary gland fibrosis in all participants and investigated the diagnostic accuracy of SWE for pSS and its relationship to disease progression. RESULTS: The diagnostic sensitivity, specificity, and accuracy of pSS were highest when the critical Young's modulus values of the parotid and submandibular glands were 18.4 and 15.9 kPa, respectively, effectively improving the diagnostic value of pSS. The area under the SWE curve of the submandibular gland was higher than that of the parotid gland (z = 2.292, P = 0.02), suggesting that the submandibular gland was damaged earlier. The mean parotid gland thickness of pSS patients was thicker than in healthy controls (mean ± standard deviation 2.5 ± 0.3 vs 2.4 ± 0.2, P = 0.013]. SWE had a 70.3% sensitivity for diagnosing pSS patients with a disease duration of 5 years, but this did not differ significantly from pSS patients with a longer disease duration. CONCLUSIONS: SWE is a valid diagnostic method for pSS. The degree of salivary gland fibrosis related to secretory function and pathological progression, and quantitative measurements of tissue elasticity provide objective criteria for predicting damage in pSS.

SHORT ROOT and INDETERMINATE DOMAIN family members govern PIN-FORMED expression to regulate minor vein differentiation in rice.

C3 and C4 grasses directly and indirectly provide the vast majority of calories to the human diet, yet our understanding of the molecular mechanisms driving photosynthetic productivity in grasses is largely unexplored. Ground meristem cells divide to form mesophyll or vascular initial cells early in leaf development in C3 and C4 grasses. Here we define a genetic circuit composed of SHORT ROOT (SHR), INDETERMINATE DOMAIN (IDD), and PIN-FORMED (PIN) family members that specifies vascular identify and ground cell proliferation in leaves of both C3 and C4 grasses. Ectopic expression and loss-of-function mutant studies of SHR paralogs in the C3 plant Oryza sativa (rice) and the C4 plant Setaria viridis (green millet) revealed the roles of these genes in both minor vein formation and ground cell differentiation. Genetic and in vitro studies further suggested that SHR regulates this process through its interactions with IDD12 and 13. We also revealed direct interactions of these IDD proteins with a putative regulatory element within the auxin transporter gene PIN5c. Collectively, these findings indicate that a SHR-IDD regulatory circuit mediates auxin transport by negatively regulating PIN expression to modulate minor vein patterning in the grasses.

Molecularly Imprinted Polymer Nanospheres with Hydrophilic Shells for Efficient Molecular Recognition of Heterocyclic Aromatic Amines in Aqueous Solution.

Heterocyclic aromatic amine molecularly imprinted polymer nanospheres with surface-bound dithioester groups (haa-MIP) were firstly synthesized via reversible addition-fragmentation chain transfer (RAFT) precipitation polymerization. Then, a series of core-shell structural heterocyclic aromatic amine molecularly imprinted polymer nanospheres with hydrophilic shells (MIP-HSs) were subsequently prepared by grafting the hydrophilic shells on the surface of haa-MIP via on-particle RAFT polymerization of 2-hydroxyethyl methacrylate (HEMA), itaconic acid (IA), and diethylaminoethyl methacrylate (DEAEMA). The haa-MIP nanospheres showed high affinity and specific recognition toward harmine and its structural analogs in organic solution of acetonitrile, but lost the specific binding ability in aqueous solution. However, after the grafting of the hydrophilic shells on the haa-MIP particles, the surface hydrophilicity and water dispersion stability of the polymer particles of MIP-HSs greatly improved. The binding of harmine by MIP-HSs with hydrophilic shells in aqueous solutions is about two times higher than that of NIP-HSs, showing an efficient molecular recognition of heterocyclic aromatic amines in aqueous solution. The effect of hydrophilic shell structure on the molecular recognition property of MIP-HSs was further compared. MIP-PIA with carboxyl groups containing hydrophilic shells showed the highest selective molecular recognition ability to heterocyclic aromatic amines in aqueous solution.

Preparation of Functionalized Zr-Based MOFs and MOFs/GO for Efficient Removal of 1,3-Butadiene from Cigarette Smoke.

Removal of 1,3-butadiene from cigarette smoke plays an important role in human health and environmental protection. Herein, a series of UiO-66 X% containing different ratios of the -NH2 group was synthesized via the solvothermal method by using terephthalic acid (H2BDC) and 2-aminoterephthalic acid (NH2-BDC) as ligands. Using GO as support, a series of UiO-66-NH2/GO Y% were prepared by controlling the ratio of UiO-66-NH2 and GO. The effects of -NH2 and GO contents on the structure and composition of MOFs were investigated. Finally, the different -NH2 contents of UiO-66 X% and the different GO contents of UiO-66-NH2/GO Y% were applied in 1,3-butadiene removal from cigarette smoke. The results showed that UiO-66 X% with the higher contents of -NH2 showed a higher rate of 1,3-butadiene removal, and UiO-66-NH2/GO Y% with the GO contents of 5% showed the highest removal rate of about 33.85%, which was 25.54% higher than that of activated carbon. In addition, the saturation capacity of the adsorbent materials for 1,3-butadiene was as high as 210.01-239.54 mg/g, showing great potential in reducing harmful components in cigarette smoke and environmental protection.

Case report: Refractory intestinal Behçet's syndrome successfully treated with tofacitinib: A report of four cases.

Behçet's syndrome (BS) is a chronic form of relapsing multisystem vasculitis, characterized by recurrent oral and genital ulcers. Intestinal BS is a special type of BS. Volcano-shaped ulcers in the ileocecum are a typical finding of intestinal BS, and punched-out ulcers can be observed in the intestine or esophagus. At present, there is no recognized radical treatment for intestinal BS. Glucocorticoids and immunosuppressants are currently the main drugs used to improve the condition. Although it has been reported that monoclonal anti-TNF antibodies may be effective for some refractory intestinal BS, further randomized, prospective trials are necessary to confirm these findings. Some patients are restricted from using biological agents because of serious allergic reactions of drugs, inconvenient drug injections or the impact of the novel coronavirus epidemic. If endoscopic remission (endoscopic healing) is not achieved for a prolonged period of time, serious complications, such as perforation, fistula formation, and gastrointestinal bleeding can be induced. Therefore, it is necessary to develop new treatment methods for controlling disease progression. We reviewed the relevant literature, combined with the analysis of the correlation between the pathogenesis of BS and the mechanism of Janus kinase (JAK) inhibition, and considered that tofacitinib (TOF) may be effective for managing refractory intestinal BS. We report for the first time that four patients with severe refractory intestinal BS were successfully treated with TOF. We hope to provide valuable information on JAK inhibitors as potential therapeutic targets for the treatment of severe refractory intestinal BS.