High-Performance Hydrogel-Encapsulated Engineered Exosomes for Supporting Endoplasmic Reticulum Homeostasis and Boosting Diabetic Bone Regeneration.

The regeneration of bone defects in diabetic patients still faces challenges, as the intrinsic healing process is impaired by hyperglycemia. Inspired by the discovery that the endoplasmic reticulum (ER) is in a state of excessive stress and dysfunction under hyperglycemia, leading to osteogenic disorder, a novel engineered exosome is proposed to modulate ER homeostasis for restoring the function of mesenchymal stem cells (MSCs). The results indicate that the constructed engineered exosomes efficiently regulate ER homeostasis and dramatically facilitate the function of MSCs in the hyperglycemic niche. Additionally, the underlying therapeutic mechanism of exosomes is elucidated. The results reveal that exosomes can directly provide recipient cells with SHP2 for the activation of mitophagy and elimination of mtROS, which is the immediate cause of ER dysfunction. To maximize the therapeutic effect of engineered exosomes, a high-performance hydrogel with self-healing, bioadhesive, and exosome-conjugating properties is applied to encapsulate the engineered exosomes for in vivo application. In vivo, evaluation in diabetic bone defect repair models demonstrates that the engineered exosomes delivering hydrogel system intensively enhance osteogenesis. These findings provide crucial insight into the design and biological mechanism of ER homeostasis-based tissue-engineering strategies for diabetic bone regeneration.

Shape memory and hemostatic silk-laponite scaffold for alveolar bone regeneration after tooth extraction trauma.

Persistent bleeding and the absence of alveolar bone stress following tooth loss can hinder socket healing, complicating future dental implant procedures, and potentially leading to neighboring tooth instability. Therefore, developing materials that promote alveolar bone regeneration and possess both hemostatic and osteogenic properties is crucial for preserving the extraction sites. This study introduces a silk-based laponite composite scaffold material with proficient hemostatic and osteogenic functions, and excellent shape-memory properties for efficient extraction- site filling. In vitro studies research demonstrated that the scaffold's inherent negative charge of the scaffold significantly enhanced blood coagulation and thrombin generation. Moreover, its porous structure and slightly rough inner surface promoted blood cell adhesion and, improved the hemostatic performance. Furthermore, the scaffold facilitated stem cell osteogenic differentiation by activating the TRPM7 channel through the released of magnesium ions. In vivo tests using rat models confirmed its effectiveness in promoting coagulation and mandibular regeneration. Thus, this study proposes a promising approach for post-extraction alveolar bone regenerative repair. The composite scaffold material, with its hemostatic and osteogenic capabilities and shape-memory features, can potentially enhance dental implant success and overall oral health.

Highly Active Frozen Nanovesicles Microneedles for Senile Wound Healing via Antibacteria, Immunotherapy, and Skin Regeneration.

Senile wound healing risks a variety of health complications and makes both economic and psychological burdens on patients greatly. Poor activity of aged dermal fibroblasts (A-FBs) and local disordered immunoreaction in the deep dermis contribute to delayed wound healing. Therefore, the locally complex microenvironment in deep requires additional processing. Herein, a novel double-layer hyaluronic acid methacrylate (HAMA)/polyvinyl alcohol (PVA) microneedle patch (MNP) coated by young fibroblast-derived exosomes (Y-EXOs) (Y-EXOs@HAMA/PVA MNP) is presented for deep drug delivery, aged wound healing and immunoregulation. A spraying and freeze-drying method is applied for keeping the bioactivity of the nanovesicles. An ideal loading of Y-EXOs and enhanced strength for penetration have realized after circulation for times. The Y-EXOs@HAMA/PVA MNP shows an excellent influence on delayed wound healing of aged skin with active A-FBs, more deposition of collagen and less production of IL-17A compared with application of aged fibroblast-derived exosomes (A-EXOs). Moreover, the content microRNAs in Y-EXOs and A-EXOs are sequenced for further study. This study initiatively demonstrates that Y-EXOs have effective function on both anti-aging and anti-inflammation and Y-EXOs@HAMA/PVA MNP is expected as a novel strategy for deep drug delivery for promoting hard wound healing in aged skin in future clinical application.

Dominoes with interlocking consequences triggered by zinc: involvement of microelement-stimulated MSC-derived exosomes in senile osteogenesis and osteoclast dialogue.

As societal aging intensifies, senile osteoporosis has become a global public health concern. Bone microdamage is mainly caused by processes such as enhancing osteoclast activity or reducing bone formation by osteoblast-lineage cells. Compared with young individuals, extracellular vesicles derived from senescent bone marrow mesenchymal stem cells(BMSCs) increase the transient differentiation of bone marrow monocytes (BMMs) to osteoclasts, ultimately leading to osteoporosis and metal implant failure. To address this daunting problem, an exosome-targeted orthopedic implant composed of a nutrient coating was developed. A high-zinc atmosphere used as a local microenvironmental cue not only could inhibit the bone resorption by inhibiting osteoclasts but also could induce the reprogramming of senile osteogenesis and osteoclast dialogue by exosome modification. Bidirectional regulation of intercellular communication via cargoes, including microRNAs carried by exosomes, was detected. Loss- and gain-of-function experiments demonstrated that the key regulator miR-146b-5p regulates the protein kinase B/mammalian target of rapamycin pathway by targeting the catalytic subunit gene of PI3K-PIK3CB. In vivo evaluation using a naturally-aged osteoporotic rat femoral defect model further confirmed that a nutrient coating substantially augments cancellous bone remodeling and osseointegration by regulating local BMMs differentiation. Altogether, this study not only reveals the close link between senescent stem cell communication and age-related osteoporosis but also provides a novel orthopedic implant for elderly patients with exosome modulation capability.

Erucic acid improves the progress of pregnancy complicated with systemic lupus erythematosus by inhibiting the effector function of CD8+ T cells.

Pathogenic CD8+ T cells are pivotal contributors to the onset of systemic lupus erythematosus (SLE). Erucic acid (EA) has been proven to have anti-inflammatory activity. However, the capacity of EA to regulate pathogenic CD8+ T cells in the context of pregnancy complicated with SLE (pSLE) remains unclear. In our investigation, we observed augmented CD8+ T cell effector function juxtaposed with diminished EA levels in pSLE patients relative to healthy pregnant controls. Significantly, plasma EA levels exhibited a negative correlation with the severity of pSLE-associated complications. In blood from patients with pSLE, EA inhibited the effector function of CD8+ T cells, concurrently dampening the maintenance of stem cell-like memory CD8+ T cells. Mechanistically, EA orchestrated the inhibition of CD8+ T cell effector function by impeding signal transducer and activator of transcription 3 phosphorylation and promoting ferroptosis. Moreover, EA supplementation in pregnant MRL/lpr mice manifested as the attenuation of uterine CD8+ T cell effector function, culminating in the mitigation of placental pathological damage. Our findings uncover the immune response modulatory effects of EA upon pathogenic CD8+ cells, thereby unveiling new perspectives for therapeutic strategies targeting pSLE patients.

CGRP-Loaded Porous Microspheres Protect BMSCs for Alveolar Bone Regeneration in the Periodontitis Microenvironment.

Periodontitis is a prevalent dental disease marked by progressive destruction of tooth-supporting tissues, and the recovery of bone defects after periodontitis remains challenging. Although stem cell-based therapy is a promising treatment for periodontal tissue regeneration, the function of mesenchymal stem cells is constantly impaired by the inflammatory microenvironment, leading to compromised treatment outcomes. Herein, calcitonin gene-related peptide (CGRP)-loaded porous microspheres (PMs) are prepared to protect bone marrow mesenchymal stem cells (BMSCs) against inflammatory mediators in periodontitis. The released CGRP can effectively ameliorate the inflammation-induced dysfunction of BMSCs, which may involve suppressing the ROS (reactive oxygen species)/NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3)/Caspase-1 (CASP1) pathway. Moreover, the porous architecture of PMs provides effective cell-carrying capacity and physical protection for BMSCs during transplantation. In vivo experiments demonstrate that CGRP/BMSC-loaded PMs can effectively inhibit inflammation and improve osteogenic activity, resulting in better periodontal bone regeneration. This study focuses on the protection of stem cell function in the inflammatory microenvironment, which is important for stem cell-mediated tissue regeneration and repair under inflammatory conditions.

Optimized Pore Nanospace through the Construction of a Cagelike Metal-Organic Framework for CO2/N2 Separation.

The development of metal-organic framework (MOF) adsorbents with a potential molecule sieving effect for CO2 capture and separation from flue gas is of critical importance for reducing the CO2 emissions to the atmosphere yet challenging. Herein, a cagelike MOF with a suitable cage window size falling between CO2 and N2 and the cavity has been constructed to evaluate its CO2/N2 separation performance. It is noteworthy that the introduction of coordinated dimethylamine (DMA) and N,N'-dimethylformamide (DMF) molecules not only significantly reduces the cage window size but also enhances the framework-CO2 interaction via C-H···O hydrogen bonds, as proven by molecular modeling, thus leading to an improved CO2 separation performance. Moreover, transient breakthrough experiments corroborate the efficient CO2/N2 separation, revealing that the introduction of DMA and DMF molecules plays a vital role in the separation of a CO2/N2 gas mixture.

Molecular cloning and functional characterization of peroxiredoxin 4 (prx 4) in freshwater crayfish, Procambarus clarkii.

Peroxiredoxin (Prx), which is a newly discovered member of the antioxidant protein family, performs important biological functions in intracellular signal transduction. In the present study, a peroxiredoxin 4 gene was cloned from crayfish for the first time and named Pc-prx 4. According to the amino acid sequence signature, Pc-Prx 4 was identified as the typical 2-Cys Prx molecule, which possessed two conserved cysteines (Cys98 and Cys219). Time-course expression patterns post V. harveyi infection revealed that Pc-prx 4 was likely related to crayfish innate immune defense responses. In particular, the highest fold upregulation of the Pc-prx 4 mRNA transcript reached approximately 170 post V. harveyi infection in the crayfish hepatopancreas. The results of the mixed functional oxidase assay showed that rPc-Prx 4△ could resist the damaging effect of reactive oxygen species generated from the thiol/Fe3+/O2- reaction system to some extent. In addition, the results of the RNAi assay revealed that the crayfish survival rate was obviously increased post injection of V. harveyi when Pc-prx 4 was knocked down. Further study revealed that both hemolymph melanization and PO activity were strengthened to different degrees in the RNAi assay. Therefore, we speculated that the increase in the crayfish survival rate was likely due to the increase in hemolymph melanization. The obviously reinforced hemolymph melanization was directly caused by the upregulation of hemolymph PO activity, which was induced by the knockdown of Pc-prx 4. However, further studies are still indispensable for illuminating the molecular mechanism of Pc-prx 4 in the crayfish innate immune defense system.

Control of lupus activity during pregnancy via the engagement of IgG sialylation: novel crosstalk between IgG sialylation and pDC functions.

Immunoglobulin (IgG) glycosylation affects the effector functions of IgG in a myriad of biological processes and has been closely associated with numerous autoimmune diseases, including systemic lupus erythematosus (SLE), thus underlining the pathogenic role of glycosylation aberration in autoimmunity. This study aims to explore the relationship between IgG sialylation patterns and lupus pregnancy. Relative to that in serum samples from the control cohort, IgG sialylation level was aberrantly downregulated in serum samples from the SLE cohort at four stages (from preconception to the third trimester of pregnancy) and was significantly associated with lupus activity and fetal loss during lupus pregnancy. The type I interferon signature of pregnant patients with SLE was negatively correlated with the level of IgG sialylation. The lack of sialylation dampened the ability of IgG to suppress the functions of plasmacytoid dendritic cells (pDCs). RNA-seq analysis further revealed that the expression of genes associated with the spleen tyrosine kinase (SYK) signaling pathway significantly differed between IgG- and deSia-IgG-treated pDCs. This finding was confirmed by the attenuation of the ability to phosphorylate SYK and BLNK in deSia-IgG. Finally, the coculture of pDCs isolated from pregnant patients with SLE with IgG/deSia-IgG demonstrated the sialylation-dependent anti-inflammatory function of IgG. Our findings suggested that IgG influences lupus activity through regulating pDCs function via the modulation of the SYK pathway in a sialic acid-dependent manner.

Effects of microplastics and lead exposure on gut oxidative stress and intestinal inflammation in common carp (Cyprinus carpio L.).

Microplastics (MPs) are increasingly being detected in freshwater environments, which have the potential to cause combined toxicity with other contaminants on aquatic organisms. To reveal the ecological risks, the combined effects of lead (Pb) and polyvinyl chloride microplastics (MPs) were explored in the gut of common carp (Cyprinus carpio L.). The results confirmed that exposure of Pb alone accelerated Pb accumulation, increased oxidative stress, and activated the inflammation response of the gut. However, the aforementioned effects all decreased under the co-exposure of Pb and MPs. In addition, MPs altered intestinal microbial community of common carp, especially the abundance of immune system-related species. All measured variables were organized for partial least square path modeling, which revealed the combined effects of Pb and MPs on inflammation response. The results implied that MPs reduced inflammation response in two ways, including the reduction of intestinal Pb accumulation and the alteration of the intestinal microbial community. Overall, this study provides a novel aspect of ecological effects on aquatic animals from Pb and MPs exposure. The interesting results remind us that when exploring the ecological risks of MPs, combined effects from other toxic substances must be considered simultaneously.

Regulating macrophage-MSC interaction to optimize BMP-2-induced osteogenesis in the local microenvironment.

Bone morphogenetic protein (BMP-2) has been approved by the FDA to promote bone regeneration, but uncertain osteogenic effect and dose-dependent side effects may occur. Osteoimmunomodulation plays an important role in growth factor-based osteogenesis. Here, we explored how proinflammatory signals affect the dose-dependent osteogenic potential of BMP-2. We observed that the expression level of local IL-1ß did not increase with the dose of BMP-2 in the mouse osteogenesis model. A low dose of BMP-2 could not promote new bone formation, but trigger the release of IL-1ß from M1 macrophages. As the dose of BMP-2 increased, the IL-1ß expression and M1 infiltration in local microenvironment were inhibited by IL-1Ra from MSCs under osteogenic differentiation induced by BMP-2, and new bone tissues formed, even excessively. Anti-inflammatory drugs (Dexamethasone, Dex) promoted osteogenesis via inhibiting M1 polarization and enhancing BMP-2-induced MSC osteo-differentiation. Thus, we suggest that the osteogenic effect of BMP-2 involves macrophage-MSC interaction that is dependent on BMP-2 dose and based on IL-1R1 ligands, including IL-1ß and IL-1Ra. The dose of BMP-2 could be reduced by introducing immunoregulatory strategies.

Knowledge and data-driven prediction of organ failure in critical care patients.

Purpose: The early detection of organ failure mitigates the risk of post-intensive care syndrome and long-term functional impairment. The aim of this study is to predict organ failure in real-time for critical care patients based on a data-driven and knowledge-driven machine learning method (DKM) and provide explanations for the prediction by incorporating a medical knowledge graph. Methods: The cohort of this study was a subset of the 4,386 adult Intensive Care Unit (ICU) patients from the MIMIC-III dataset collected between 2001 and 2012, and the primary outcome was the Delta Sequential Organ Failure Assessment (SOFA) score. A real-time Delta SOFA score prediction model was developed with two key components: an improved deep learning temporal convolutional network (S-TCN) and a graph-embedding feature extraction method based on a medical knowledge graph. Entities and relations related to organ failure were extracted from the Unified Medical Language System to build the medical knowledge graph, and patient data were mapped onto the graph to extract the embeddings. We measured the performance of our DKM approach with cross-validation to avoid the formation of biased assessments. Results: An area under the receiver operating characteristic curve (AUC) of 0.973, a precision of 0.923, a NPV of 0.989, and an F1 score of 0.927 were achieved using the DKM approach, which significantly outperformed the baseline methods. Additionally, the performance remained stable following external validation on the eICU dataset, which consists of 2,816 admissions (AUC = 0.981, precision = 0.860, NPV = 0.984). Visualization of feature importance for the Delta SOFA score and their relationships on the basic clinical medical (BCM) knowledge graph provided a model explanation. Conclusion: The use of an improved TCN model and a medical knowledge graph led to substantial improvement in prediction accuracy, providing generalizability and an independent explanation for organ failure prediction in critical care patients. These findings show the potential of incorporating prior domain knowledge into machine learning models to inform care and service planning. Supplementary Information: The online version of this article contains supplementary material available 10.1007/s13755-023-00210-5.

Dopamine receptor (DAR) and dopa decarboxylase (DDC) mediate hepatopancreas antibacterial innate immune reactions in Procambarus clarkii.

Dopa is decarboxylated by dopa decarboxylase (DDC) to form dopamine, which is a significant signaling molecule in the neuroendocrine system. The dopamine receptor (DAR) is an important transmembrane receptor responsible for receiving extracellular signals in the DAR-mediated signaling pathway. In the present study, the expression patterns of Pc-dar were investigated after bacterial challenge. The obviously changed expression patterns showed Pc-dar was related to the antibacterial innate immunity. Endogenous Pc-DDC enzymatic activities were obviously downregulated after Pc-ddc dsRNA injection. The expression level of Pc-dar mRNA was obviously upregulated after bacterial injection when the expression level of Pc-ddc was knocked down. In addition, the upregulation trend of endogenous Pc-DDC enzymatic activities was obviously restrained after bacterial stimulation when Pc-ddc was knocked down. Finally, melanization was downregulated in crayfish hemolymph compared with the dsGFP injection group. In the RNAi assay, the results of qRT-PCR showed that Toll (TLRs) signaling pathway-related genes were activated in the early stages of bacterial stimulation when Pc-ddc was knocked down. Four tested ROS-related antioxidant enzyme genes were significantly upregulated after bacterial challenge compared with the dsGFP injection group. The above results indicated that Pc-DDC and Pc-DAR play important mediating roles in the neuroendocrine immune (NEI) system of crayfish.

Orchestration of energy metabolism and osteogenesis by Mg2+ facilitates low-dose BMP-2-driven regeneration.

The clinical application of bone morphogenetic protein-2 (BMP-2) is limited by several factors, including ineffectiveness at low doses and severe adverse effects at high doses. To address these efficacy and safety limitations, we explored whether orchestration of energy metabolism and osteogenesis by magnesium ion (Mg2+) could reduce the dose and thereby improve the safety of BMP-2. Our results demonstrated that rapid metabolic activation triggered by BMP-2 was indispensable for subsequent osteogenesis. Moreover, inadequate metabolic stimulation was shown to be responsible for the ineffectiveness of low-dose BMP-2. Next, we identified that Mg2+, as an ''energy propellant", substantially increased cellular bioenergetic levels to support the osteogenesis via the Akt-glycolysis-Mrs2-mitochondrial axis, and consequently enhanced the osteoinductivity of BMP-2. Based on the mechanistic discovery, microgel composite hydrogels were fabricated as low-dose BMP-2/Mg2+ codelivery system through microfluidic and 3D printing technologies. An in vivo study further confirmed that rapid and robust bone regeneration was induced by the codelivery system. Collectively, these results suggest that this bioenergetic-driven, cost-effective, low-dose BMP-2-based strategy has substantial potential for bone repair.

Hollow Cobalt Oxide/Carbon Hybrids Aid Metabolic Encoding for Active Systemic Lupus Erythematosus during Pregnancy.

A noninvasive, easy operation, and accurate diagnostic protocol is highly demanded to assess systemic lupus erythematosus (SLE) activity during pregnancy, promising real-time activity monitoring during the whole gestational period to reduce adverse pregnancy outcomes. Here, machine learning of serum metabolic fingerprints (SMFs) is developed to assess the SLE activity for pregnant women. The SMFs are directly extracted through a hollow-cobalt oxide/carbon (Co3 O4 /C)-composite-assisted laser desorption/ionization mass spectrometer (LDI MS) platform. The Co3 O4 /C composite owns enhanced light absorption, size-selective trapping, and better charge-hole separation, enabling improved ionization efficiency and selectivity for LDI MS detection toward small molecules. Metabolic fingerprints are collected from ≈0.1 µL serum within 1 s without enrichment and encoded by the optimized elastic net algorithm. The averaged area under the curve (AUC) value in the differentiation of active SLE from inactive SLE and healthy controls reaches 0.985 and 0.990, respectively. Further, a simplified panel based on four identified metabolites is built to distinguish SLE flares in pregnant women with the highest AUC value of 0.875 for the blind test. This work sets an accurate and practical protocol for SLE activity assessment during pregnancy, promoting precision diagnosis of disease status transitions in clinics.

Interleukin enhancer binding factor 2 (IEBF 2) was involved in the regulation of the antibacterial immune reactions in fresh water crayfish, Procambarus clarkii.

Although interleukin and interleukin analogues which play important immunomodulatory roles in mammals have not yet been reported in invertebrates, interleukin enhancer binding factor (IEBF) which acts as a transcription factor has been recently studied in several crustaceans and it may be involved in innate immune defence against pathogens. In this study, an IEBF 2 homologue was identified in the fresh water crayfish, Procambarus clarkii. The significantly changed expression levels of Pc-iebf 2 after bacterial challenge revealed the possibility of its participation in defence against bacterial infection. The results of an RNAi assay showed that the crayfish survival rate was obviously decreased after dsIEBF 2 injection, compared with the control groups. And S. aureus proliferation was obviously enhanced at 24 and 48 h post bacterial injection, when Pc-iebf 2 was knocked down. The possible molecular mechanisms for the innate immune regulation functions of Pc-IEBF 2 were also investigated. We speculated that Pc-IEBF 2 plays an important role in defending against bacterial infection in crayfish. It could regulate some innate immune responses by affecting the Toll signalling pathway, melanisation, and cell apoptosis.

Ubiquitin-associated protein 2 like (UBAP2L) enhances growth and metastasis of gastric cancer cells.

Ubiquitin-proteasome pathway has emerged as therapeutic targets for cancer. GEPIA database analysis showed that the expression of ubiquitin-associated protein 2 like (UBAP2L) in gastric cancer specimens was significantly higher than that in non-tumor tissue, and its high expression is associated with poor survival of gastric cancer patients. This study aims to investigate the role of UBAP2L in gastric cancer. Real-time PCR and western blot results showed that UBAP2L expression was upregulated in gastric cancer cell lines. Loss- and gain-of-function experiments demonstrated that silencing of UBAP2L inhibited proliferation, migration and invasion, and induced apoptosis of gastric cancer cells, and overexpression of UBAP2L played opposite roles. Nude mice inoculated with UBAP2L-silenced gastric cancer cells generated smaller xenografted tumors in vivo. Furthermore, UBAP2L activated Wnt/ß-catenin signaling - the accumulation of nuclear ß-catenin and the expression of its downstream targets (cyclin D1, AXIN-2 and c-MYC) was facilitated, whereas knockdown of UBAP2L deactivated this signaling. The tumor-suppressing effect of UBAP2L silencing was abolished by forced activation of ß-cateninS33A. UBAP2L has been confirmed as a novel and direct target of miR-148b-3p. The anti-tumor effect of miR-148b-3p was partly reversed by UBAP2L overexpression. The expression of miR-148b-3p was negatively correlated with that of UBAP2L in gastric cancer samples. Overall, our study indicates that UBAP2L is required to maintain malignant behavior of gastric cancer cells, which involves the activation of Wnt/ß-catenin signaling pathway. We propose UBAP2L as a potential therapeutic target against gastric cancer.

High-risk factors for adverse pregnancy outcomes in systemic lupus erythaematosus: a retrospective study of a Chinese population.

OBJECTIVE: To clarify high-risk factors for adverse pregnancy outcomes (APOs) in systemic lupus erythaematosus (SLE). DESIGN: A retrospective chart review study. SETTING: Data were collected in a tertiary medical centre, Shanghai, China, from November 2010 to December 2018. PARTICIPANTS: A total of 513 pregnancies with SLE were retrospectively analysed. Twenty-seven patients who underwent artificial abortions due to personal reasons were excluded. PRIMARY OUTCOME MEASURES: APOs were primary outcomes, including foetal loss, premature birth, small for gestational age (SGA), asphyxia neonatorum, composite foetal APOs and hypertensive disorders of pregnancy (HDP). Multivariable logistic regression and Spearman correlation analysis were performed to determine the risk factors for APOs in SLE. RESULTS: Risk factors for foetal loss included prepregnancy hypertension, hypocomplementaemia-C3, anticardiolipin antibodies-IgM positivity and disease flares during pregnancy. Risk factors for premature birth included disease flares, use of immunosuppressive agents and HDP. Moreover, twin pregnancy, disease flares and HDP were risk factors for SGA, and prepregnancy hypertension was an independent risk factor for asphyxia neonatorum. Independent risk factors for composite foetal APOs included twin pregnancy, prepregnancy hypertension, disease flares during pregnancy, HDP, hypocomplementaemia-C3 and the use of immunosuppressive agents. Risk factors for SLE complicated with HDP included prepregnancy hypertension, renal disorders and thrombocytopaenia. Conversely, the use of aspirin was a protective factor against foetal loss and premature birth. The ds-DNA value had a low diagnostic value for APOs, whereas the extent of complement reduction may predict the incidence of composite foetal APOs and foetal loss. Proteinuria occurring in the first 20 gestational weeks may lead to APOs. CONCLUSION: Established risk factors for each APO were identified in this study. Indicators with more predictive significance have been screened out from conventional indicators, which may help clinicians predict the pregnancy outcome of patients with SLE more accurately and minimise the incidence of APOs.

Promoting Oral Mucosal Wound Healing with a Hydrogel Adhesive Based on a Phototriggered S-Nitrosylation Coupling Reaction.

The wet and highly dynamic environment of the mouth makes local treatment of oral mucosal diseases challenging. To overcome this, a photo-crosslinking hydrogel adhesive is developed inspired by the success of light-curing techniques in dentistry. The adhesive operates on a fast (within 5 s) phototriggered S-nitrosylation coupling reaction and employs imine anchoring to connect to host tissues. Unlike other often-used clinical agents that adhere weakly and for short durations, this thin, elastic, adhesive, and degradable cyclic o-nitrobenzyl-modified hyaluronic acid gel protects mucosal wounds from disturbance by liquid rinsing, oral movement, and friction for more than 24 h. The results from both rat and pig oral mucosa repair models demonstrate that this new gel adhesive creates a favorable microenvironment for tissue repair and can shorten tissue healing time. This study thus illustrates a therapeutic strategy with the potential to advance the treatment of oral mucosal defects in the clinic.

Knockdown of miR­205­5p alleviates the inflammatory response in allergic rhinitis by targeting B­cell lymphoma 6.

Allergic rhinitis (AR) is an IgE­mediated upper airway disease with a high worldwide prevalence. MicroRNA (miR)­205­5p upregulation has been observed in AR; however, its role is poorly understood. The aim of the present study was to investigate the effect of miR­205­5p on AR­associated inflammation. To establish an AR model, BALB/c mice were sensitized using an intraperitoneal injection of ovalbumin (OVA) on days 0, 7 and 14, followed by intranasal challenge with OVA on days 21­27. A lentiviral sponge for miR­205­5p was used to downregulate miR­205­5p in vivo via intranasal administration on days 20­26. Reverse transcription­quantitative PCR revealed that miR­205­5p was upregulated in AR mice. Notably, miR­205­5p knockdown reduced the frequency of nose­rubbing and sneezing, and attenuated pathological alterations in the nasal mucosa. The levels of total and OVA­specific IgE, cytokines IL­4, IL­5 and IL­13, and inflammatory cells, were decreased by miR­205­5p knockdown in AR mice. In addition, miR­205­5p knockdown inhibited nucleotide­binding oligomerization domain­like receptor family pyrin domain­containing 3 (NLRP3) inflammasome activation by reducing the expression levels of NLRP3, apoptosis-associated speck-like protein containing a CARD, cleaved caspase­1 and IL­1ß by western blot analysis. B­cell lymphoma 6 (BCL6) was confirmed as a target of miR­205­5p by luciferase reporter assay. In conclusion, the present findings suggested that miR­205­5p knockdown may attenuate the inflammatory response in AR by targeting BCL6, which may be a potential therapeutic target for AR.