Low-valent-tungsten catalysis enables hydroboration of esters and nitriles.

In the research presented herein, low-valent-tungsten-catalyzed hydroboration of esters and nitriles was investigated. Aromatic and aliphatic substrates were smoothly reduced to corresponding alcohol derivatives and N,N-diborylamines in the presence of W(CO)4(NCMe)2. Valuable derivatives were conveniently accessed by introducing a further functionalization process to crude hydroboration mixtures in one pot.

Advances in magnetoelectric composites for promoting bone regeneration: a review.

Repair of large bone defects is one of the clinical problems that have not yet been fully solved. The dynamic balance of bone tissue is regulated by many biological, chemical and physical environmental factors. Simulating the microenvironment of bone tissue in the physiological state through biomimetic materials is an important development direction of tissue engineering in recent years. With the deepening of research, it has been found that when bone tissue is damaged, its surrounding magnetoelectric microenvironment is subsequently destroyed, and providing a magnetoelectric microenvironment in the biomimetic state will be beneficial to promote bone repair. This review describes the piezoelectric effect of natural bone tissue with magnetoelectric stimulation for bone regeneration, provides a detailed account of the historical development of magnetoelectric composites and the current magnetoelectric composites that are most commonly utilized in the field of tissue engineering. Besides, the hypothesized mechanistic pathways through which magnetoelectric composite materials promote bone regeneration are critically examined, including the enhancement of osteogenesis, promotion of cell adhesion and angiogenesis, modulation of bone immunity, and promotion of nerve regeneration.

Effects of variable-temperature drying on the qualities and sweet-substance profile of Zizyphus jujuba Mill. cv. Junzao.

The changes in the qualities and sweet-substance levels of Junzao jujube during variable-temperature drying (VTD) were investigated. The results showed that VTD retains the original color of jujube, reduces its hardness and chewiness, and decreases its wrinkling while shortening the drying time by 13.2% compared with that of constant temperature drying (CTD). "Electronic-tongue" taste analysis showed that the sweetness of VTD jujube is significantly higher than that for CTD. This is shown to be related to the contents of sucrose, fructose, and glucose, as well as the activities of invertase and sucrose synthase enzymes. In addition, the content trends for sweet amino acids are correlated with the temperature gradient used in VTD. Thus, the present study elucidates the factors governing the transformation of sugar substances in jujube during VTD, as well as providing a practical reference for the application of VTD in the jujube industry.

Synergistic nucleation regulation using 4,4',4''-tris(carbazol-9-yl)-triphenylamine and moisture for stably air-processed high-performance perovskite photodetectors.

Perovskite photodetectors (PPDs) offer a promising solution with low cost and high responsivity, addressing the limitations of traditional inorganic photodetectors. However, there is still room for improvement in terms of the dark current and stability of air-processed PPDs. In this study, 4,4',4''-tris(carbazol-9-yl)-triphenylamine (TCTA) was utilized as a nucleation agent to enhance the quality of perovskite films. The synergistic effect of TCTA and moisture promotes rapid nucleation of PbI2-PbCl2, resulting in an increased nucleation rate and the elimination of pinholes in the film. By employing additive engineering, we obtained a PbI2-PbCl2 layer with high coverage, leading to a low density of traps in the corresponding perovskite film. Consequently, the modified PPD exhibits a remarkable reduction in dark current density by over one order of magnitude, reaching 2.4 × 10-10 A cm-2 at -10 mV, along with a large linear dynamic range (LDR) of 183 dB. Furthermore, the resulting PPD demonstrates remarkable stability, retaining 90% of the initial external quantum efficiency (EQE) value even after continuous operation for over 3200 hours. Owing to a fast response time in the nanosecond range, the PPD could convert modulated light signals into electrical signals at a speed of 588 Kbit s-1, highlighting the great potential in the field of optical communication.

Gastroesophageal Reflux Revealed by 18 F-MFBG PET/CT.

ABSTRACT: A 56-year-old woman who had a lung transplant 4 months ago presented frequent vomiting for 1 month. Barium meal and 99m Tc gastroesophageal scintigraphy showed no gastroesophageal reflux. The patient was enrolled in a clinical trial and underwent 18 F-MFBG PET/CT dynamic imaging. At the seventh minute of dynamic imaging, the images revealed reflux from the cardia into the esophagus and reached the oral cavity.

Horizontal ridge augmentation in the maxillary aesthetic region using the autogenous circular cortical-lamina anchoring technique: A case series study.

AIM: This case series aimed to evaluate the effectiveness of the autologous circular cortical lamina-anchoring (CCA) technique for horizontal bone augmentation in the maxillary aesthetic region. MATERIALS AND METHODS: A total of 25 patients with 28 implants underwent horizontal bone augmentation using CCA followed by implant placement and crown delivery. The primary outcome measures were alveolar ridge width (ARW) and buccal bone thickness (BBT), whereas the secondary outcome measures included marginal bone loss (MBL), mid-facial mucosal margin loss (MML), clinical assessment of peri-implant and aesthetic parameters, patient-reported outcome measures (PROMs), and implant survival rates. RESULTS: All 25 patients with 28 implants completed the treatment, no dropouts occurred. After CCA, the mean ARW at 1, 2, and 4 mm below the alveolar crest significantly increased from 2.38 ± 0.48, 2.85 ± 0.51, and 3.21 ± 0.53 mm to 6.80 ± 0.48, 6.99 ± 0.50, and 8.08 ± 0.52 mm, respectively. At the 3-year follow-up, the mean BBT0 , BBT2 , and BBT4 slightly decreased from 2.51 ± 0.26, 2.63 ± 0.31, and 2.75 ± 0.29 mm to 2.43 ± 0.27, 2.51 ± 0.30, and 2.64 ± 0.28 mm, respectively. Although the overall MBL was <0.15 mm, the results were statistically significant. The mean MML at the 3-year follow-up was 0.02 mm. All implant sites showed acceptable peri-implant and aesthetic outcomes. Incisions healed without complications, and no significant differences in PROMs observed at any time point. The 3-year follow-up showed a 100% implant survival rate. CONCLUSION: The autologous CCA technique is a useful method for increasing ARW and maintaining BBT in the maxillary aesthetic region.

Algorithmic detection of sleep-disordered breathing using respiratory signals: a systematic review.

Background and Objective. Sleep-disordered breathing (SDB) poses health risks linked to hypertension, cardiovascular disease, and diabetes. However, the time-consuming and costly standard diagnostic method, polysomnography (PSG), limits its wide adoption and leads to underdiagnosis. To tackle this, cost-effective algorithms using single-lead signals (like respiratory, blood oxygen, and electrocardiogram) have emerged. Despite respiratory signals being preferred for SDB assessment, a lack of comprehensive reviews addressing their algorithmic scope and performance persists. This paper systematically reviews 2012-2022 literature, covering signal sources, processing, feature extraction, classification, and application, aiming to bridge this gap and provide future research references.Methods. This systematic review followed the registered PROSPERO protocol (CRD42022385130), initially screening 342 papers, with 32 studies meeting data extraction criteria.Results. Respiratory signal sources include nasal airflow (NAF), oronasal airflow (OAF), and respiratory movement-related signals such as thoracic respiratory effort (TRE) and abdominal respiratory effort (ARE). Classification techniques include threshold rule-based methods (8), machine learning models (13), and deep learning models (11). The NAF-based algorithm achieved the highest average accuracy at 94.11%, surpassing 78.19% for other signals. Hypopnea detection sensitivity with single-source respiratory signals remained modest, peaking at 73.34%. The TRE and ARE signals proved to be reliable in identifying different types of SDB because distinct respiratory disorders exhibited different patterns of chest and abdominal motion.Conclusions. Multiple detection algorithms have been widely applied for SDB detection, and their accuracy is closely related to factors such as signal source, signal processing, feature selection, and model selection.

An Automatic Remote Health Risk Assessment system based on LSTM for elderly.

To address the challenges posed by the aging process, we designed and validated an LSTM-based automatic remote health risk assessment system for the elderly. This system consists of a wireless physiological parameter sensing unit, a vital sign prediction unit and a pre-defined risk scoring criteria unit. The vital sign prediction module is composed of five 5-input-1-output neural networks based on the LSTM architecture, which are responsible for predicting the vital signs collected by wireless sensors, including: systolic blood pressure (SBP), pulse rate (PR), respiratory rate (RR), temperature (TEMP), and oxygen saturation (SPO2). The pre-defined health risk scoring criteria is a simplified version of the National Early Warning Score (NEWS), which is responsible for calculating the risk level based on the predicted values. This allows the care team to respond to the medical needs of the elderly in a timely manner. Through experiments, our system can achieve a risk identification accuracy of 74% and MAEs of the predicted values for each parameter are in an acceptable range. Our results suggest that an automated remote health risk assessment system for the elderly using deep learning could be a viable new strategy for home-based monitoring systems.

Prognosis and risk factors for ASXL1 mutations in patients with newly diagnosed acute myeloid leukemia and myelodysplastic syndrome.

OBJECTIVE: The objective of the study was to determine the prognosis and risk factors for additional sex combs like 1 (ASXL1) mutations in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). POPULATION AND METHODS: This retrospective study enrolled 219 adult patients with newly diagnosed AML and MDS, who were treated in West China Hospital from October 2018 to January 2022. The primary clinical outcome was evaluated by overall survival (OS) followed up to January 2023. Kaplan-Meier analysis and Cox multivariate regression analysis were performed to identify potential prognostic parameters in patients with ASXL1 mutations (mt). RESULTS: A total of 34 (15.53%) ASXL1mt were detected, which occurred more frequently in the elderly and MDS cohorts (p < 0.001). Significantly lower blasts% (p < 0.001) and higher frequencies of mutant RUNX1, SRSF2, STAG2, EZH2, and SETBP1 (p < 0.02) were observed in the ASXL1mt cohort. Patients with ASXL1mt manifested with a worse complete remission rate (p = 0.011), and an inferior OS was shown in subgroups with MDS, co-mutations of RUNX1, SRSF2, or NRAS, as well as mutations in G646W (p < 0.05). Multivariate analysis considering age, diagnosis, co-mutations, and mutation site confirmed an independently adverse prognosis of mutations in G646W (HR = 4.302, 95% CI: 1.150-16.097) or RUNX1 co-mutations (HR = 4.620, 95% CI: 1.385-15.414) in the ASXL1mt cohort. CONCLUSION: Our study indicated that mutations in G646W or RUNX1 co-mutations are closely associated with a dismal clinical outcome in patients with AML and MDS harboring ASXL1mt . Considering the poor prognosis and risk factors in patients with ASXL1mt , more available treatments should be pursued.

Unilateral Bi/Multi-Portal Endoscopy for the Treatment of Complicated Lumbar Degenerative Diseases with Utilization of Uniaxial Spinal Endoscope, Instead of Arthroscope: Technique Note and Clinical Results.

Objective: This article aims to discuss a novel surgical strategy, referred to as unilateral bi/multi-portal endoscopy (UME), which used a uniaxial spinal endoscope instead of an arthroscope in the traditional unilateral biportal endoscopy (UBE) surgical procedure in our study of the treatment of complicated lumbar degenerative diseases. Methods: This retrospective study included 42 patients diagnosed with high-migrated lumbar disc herniation and bilateral spinal stenosis who underwent UME surgery from January 2021 to December 2021. Patients included 20 men and 22 women, with an average age of 55.97±14.92 years. The average follow-up period was 13.19 months. The demographic data, operation time (min), and complications were recorded and analyzed. The visual analogue scale (VAS), Oswestry Disability Index (ODI) scores were used to evaluate the surgical outcomes. Three-dimensional CT scans and MRI were conducted to evaluate the radiographic improvement. Results: A total of 26 patients were diagnosed with lumbar disc herniation and 16 with lumbar spinal stenosis. All 42 patients underwent UME surgery and achieved satisfactory outcomes. The operation time was 154.46±46.09 min. The average follow-up time was 13.19±1.33 months. The preoperative back pain (VAS-Back) and the last follow-up VAS-Back were 3.84±1.00 and 0.70±0.46, respectively (P < 0.05). The preoperative leg pain (VAS-Leg) and the last follow-up VAS-Leg were 6.46±1.08 and 1.03±0.64, respectively (P <0.05). Significant differences existed between preoperative ODI scores (58.70±11.22%) and the last follow-up ODI scores (9.24±3.04%; P<0.05). All patients achieved significant pain relief and functional improvement after the surgery. No severe complications occurred, except for two cases of postoperative dysesthesia and one case suffered from vertebral compression fractures induced by a postoperative accidental injury. Symptoms of numbness disappeared within one week with treatment using dexamethasone and neurotrophic drugs. The vertebral fracture case recovered with percutaneous kyphoplasty treatment. Conclusion: This study suggests that UME is a promising treatment strategy for high-migrated disc herniation and bilateral spinal stenosis.

Enhanced Adhesion of Copper Films on Fused Silica Glass Substrate by Plasma Pre-Treatment.

A non-thermal atmospheric jet plasma pre-treatment technique was introduced to help the growth of extremely sticky copper films on fused silica glass substrates. A tape test was utilized to assess the bonding quality between copper films and fused silica glass substrates. AFM was used to characterize the sample surface roughness and XPS for chemical bonding characterization. The Owens-Wendt method and a Theta Lite Optical Tensiometer were used to analyze the contact angle and surface energy. The results showed that the surface energy greatly increased from 34.6 ± 0.3 mJ·m-2 to 55.9 ± 0.4 mJ·m-2 after 25 s plasma pre-treatment due to the increasing Si-O and Si-N concentrations, which brought about the electrostatic force increasing at the copper/glass interface. After 25 s plasma pre-treatment, the average surface roughness (Sa) grew from 0.8 ± 0.1 nm to 2.4 ± 0.3 nm. With higher surface roughness, there were more spaces and vacancies for the copper atoms to make contact on the bonded surfaces and increase the mechanical bite force. The electrostatic force and the mechanical bite force on the interface helped to form an atomic diffusion connection layer and improved the interactions between the copper film and the glass substrate. The findings in the SEM supported the conclusions stated above. Therefore, the adhesion between copper films and fused silica glass substrates increased by about 20% by 25 s plasma pre-treatment compared with the untreated glass substrate.

HIF-1α/MMP-9 promotes spinal cord central sensitization in rats with bone cancer pain.

Bone cancer pain (BCP) is one of the most prevalent and serious symptoms of patients with cancer. Currently, the medical interventions used for the treatment of BCP do not act with optimal safety and efficacy. In this study, we appraised whether the hypoxia-inducible factor 1α (HIF-1α)/metalloproteinase-9 (MMP9) axis activates the PI3K/AKT pathway, resulting in elevated spinal cord central sensitization and aggravated BCP. BCP rats were established by tibial injection of Walker 256 cells, followed by different interventions in rats using HIF-1ɑ inhibitor LW6 or antibody treatments. After treatment with LW6 or antibody against HIF-1α, central sensitization in the spinal cord tissues of rats was inhibited, and pain perception in rats was reduced. Moreover, the activation of glial cells in the spinal cord tissues was ameliorated. The expression of MMP9 was remarkably suppressed in spinal cord tissues after inhibition of HIF-1ɑ activity, and the activity of the PI3K/AKT signaling pathway was inhibited. Further activation of MMP9 expression suppressed the alleviating effect of HIF-1ɑ inhibitor LW6 or antibody on pain perception in rats inoculated with tumors. Taken together, our studies suggest a HIF-1α/MMP9-mediated activation of PI3K/AKT in the spinal cord tissues, resulting in increased pain perception in a rat model with BCP.

Potential targeted therapy based on deep insight into the relationship between the pulmonary microbiota and immune regulation in lung fibrosis.

Pulmonary fibrosis is an irreversible disease, and its mechanism is unclear. The lung is a vital organ connecting the respiratory tract and the outside world. The changes in lung microbiota affect the progress of lung fibrosis. The latest research showed that lung microbiota differs in healthy people, including idiopathic pulmonary fibrosis (IPF) and acute exacerbation-idiopathic pulmonary fibrosis (AE-IPF). How to regulate the lung microbiota and whether the potential regulatory mechanism can become a necessary targeted treatment of IPF are unclear. Some studies showed that immune response and lung microbiota balance and maintain lung homeostasis. However, unbalanced lung homeostasis stimulates the immune response. The subsequent biological effects are closely related to lung fibrosis. Core fucosylation (CF), a significant protein functional modification, affects the lung microbiota. CF regulates immune protein modifications by regulating key inflammatory factors and signaling pathways generated after immune response. The treatment of immune regulation, such as antibiotic treatment, vitamin D supplementation, and exosome micro-RNAs, has achieved an initial effect in clearing the inflammatory storm induced by an immune response. Based on the above, the highlight of this review is clarifying the relationship between pulmonary microbiota and immune regulation and identifying the correlation between the two, the impact on pulmonary fibrosis, and potential therapeutic targets.

Single-cell and microarray chip analysis revealed the underlying pathogenesis of ulcerative colitis and validated model genes in diagnosis and drug response.

The morbidity rate of ulcerative colitis (UC) in the world is increasing year by year, recurrent episodes of diarrhea, mucopurulent and bloody stools, and abdominal pain are the main symptoms, reducing the quality of life of the patient and affecting the productivity of the society. In this study, we sought to develop robust diagnostic biomarkers for UC, to uncover potential targets for anti-TNF-ɑ drugs, and to investigate their associated pathway mechanisms. We collected single-cell expression profile data from 9 UC or healthy samples and performed cell annotation and cell communication analysis. Revealing the possible pathogenesis of ulcerative colitis by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) analysis. Based on the disease-related modules obtained from weighted correlation network analysis (WGCNA) analysis, we used Lasso regression analysis and random forest algorithm to identify the genes with the greatest impact on disease (EPB41L3, HSD17B3, NDRG1, PDIA5, TRPV3) and further validated the diagnostic value of the model genes by various means. To further explore the relationship and mechanism between model genes and drug sensitivity, we collected gene expression profiles of 185 UC patients before receiving anti-tumor necrosis factor drugs, and we performed functional analysis based on the results of differential analysis between NR tissues and R tissues, and used single-sample GSEA (ssGSEA) and CIBERSORT algorithms to explore the important role of immune microenvironment on drug sensitivity. The results suggest that our model is not only helpful in aiding diagnosis, but also has implications for predicting drug efficacy; in addition, model genes may influence drug sensitivity by affecting immune cells. We suggest that this study has developed a diagnostic model with higher specificity and sensitivity, and also provides suggestions for clinical administration and drug efficacy prediction.

Clinical evaluations of alveolar ridge preservation in compromised extraction sockets with cortical-lamina anchoring technique: Case series study.

OBJECTIVE: The objective of this study is to retrospectively evaluate the clinical outcomes of alveolar ridge preservation (ARP) in the compromised extraction sockets using autogenous cortical-lamina anchoring technique (CAT). MATERIAL AND METHODS: Twenty patients were treated with ARP in the compromised extraction sockets by applying CAT. Then implant placement and crown delivery was performed. A planned follow-up was performed by analyzing various outcome measures to evaluate the clinical outcomes, including primary outcome measures [radiographic assessment of residual alveolar ridge height (RARH) and residual alveolar ridge width (RARW)] and secondary outcome measures [clinical assessment of the healing of the soft and hard tissue, survival rates of implants, marginal bone loss (MBL) evaluation of implants, buccal bone thickness (BBT), and esthetic treatment outcomes]. RESULTS: Among the 20 patients, 17 were consecutively treated and 3 dropped out after implant crown delivery because of loss to follow-up. After the ARP, the initial RARH (12.37 mm) significantly increased to 19.29 mm (P < .05). No significant difference was detected in the RARW before (7.92 ± 1.18 mm) and after (7.92 ± 1.18 mm) the ARP, but reduce to 6.99 ± 1.18 mm at the implant placement and 6.64 ± 0.77 mm at the 3-year follow-up (P < .05). The MBL at the implant crown delivery (0.13 ± 0.12 mm) significantly increased to 0.31 ± 0.14 mm at 1-year follow-up and 0.56 ± 0.23 mm at 3-year follow-up, respectively. The bone loss was limited (<1 mm) but statistically significant (P < .05). The BBT at the implant placement (2.53 ± 0.56 mm) significantly reduced to 2.23 ± 0.44 mm at implant crown delivery and 2.14 ± 0.40 mm at 3-year follow-up, respectively. The bone loss was also limited (<0.5 mm) but statistically significant (P < .05). Each implant site showed acceptable aesthetic outcome and the average score was 16.4. The incisions healed uneventful in all patients and the implant survival rate was 100% during the 3-year follow-up. CONCLUSION: Autogenous CAT was successfully applied to preserve the height and width of alveolar ridge in the compromised extraction sockets.

Circ_0000069 contributes to the growth, metastasis and glutamine metabolism in renal cell carcinoma (RCC) via regulating miR-125a-5p-dependent SLC1A5 expression.

BACKGROUND: Circular RNAs (circRNAs) have emerged as critical mediators in various cancers, including renal cell carcinoma (RCC). In the present research, the functions of circ_0000069 in RCC were explored. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) assay, western blot assay and immunohistochemistry (IHC) assay were performed for the expression of circ_0000069, microRNA-125a-5p (miR-125a-5p) and solute carrier family 1 member 5 (SLC1A5). Cell Counting Kit-8 (CCK-8) assay and 5'-ethynyl-2'-deoxyuridine (EdU) assay were performed for cell proliferation. Flow cytometry assay was manipulated for cell apoptosis. Transwell assay and wound-healing assay were utilized for cell invasion and migration. Glutamine metabolism level was evaluated by examining glutamine consumption, α-ketoglutarate production and glutamate production. Dual-luciferase reporter assay was used to analyze the relationships of circ_0000069, miR-125a-5p and SLC1A5. Murine xenograft model assay was conducted to analyze the function of circ_0000069 in vivo. RESULTS: Circ_0000069 level was abnormally upregulated in RCC tissues and cells. Knockdown of circ_0000069 inhibited the proliferation, invasion, migration and glutamine metabolism and promoted the apoptosis in RCC cells in vitro and restrained tumor growth in vivo. Circ_0000069 served as the sponge for miR-125a-5p. MiR-125a-5p inhibition ameliorated the effects of circ_0000069 knockdown on RCC cell malignant behaviors. SLC1A5 was identified as the target gene of miR-125a-5p. Moreover, miR-125a-5p overexpression repressed the progression of RCC cells, while SLC1A5 elevation abrogated the effect. CONCLUSION: Circ_0000069 knockdown inhibited the carcinogenesis of RCC by regulating miR-125a-5p/SLC1A5 axis.

Analysis of m6A modulator-mediated methylation modification patterns and the tumor microenvironment in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer. In the development and progression of LUAD, epigenetic aberration plays a crucial role. However, the function of RNA N6-methyladenosine (m6A) modifications in the LUAD progression is unknown. The m6A regulator modification patterns in 955 LUAD samples were analyzed comprehensively. Patterns were systematically correlated with the tumor microenvironment (TME) cell-infiltration characteristics. Using principal component analysis algorithms, the m6Ascore was generated to quantify m6A modification patterns in individual tumors. Then, their values for predicting prognoses and therapeutic response in LUAD patients were assessed. Three distinct m6A modification patterns in LUAD were identified. Among them, the prognosis of m6Acluster C was the best, while the prognosis of m6Acluster A was the worst. Interestingly, the characterization of TME cell infiltration and biological behavior differed among the three patterns. To evaluate m6A modification patterns within individual tumors, an m6Ascore signature was constructed. The results showed that the high m6Ascore group was associated with a better prognosis; tumor somatic mutations and tumor microenvironment differed significantly between the high- and low- m6Ascore groups. Furthermore, in the cohort with anti-CTLA-4 treatment alone, patients with a high m6Ascore had higher ICI scores, which indicated significant therapeutic advantage and clinical benefits.

Safety and Viral Shedding of Live Attenuated Influenza Vaccine (LAIV) in Chinese Healthy Juveniles and Adults: A Phase â Randomized, Double-Blind, Placebo-Controlled Study.

This study was a randomized, double-blind, placebo-controlled study to evaluate the safety and viral shedding of live attenuated influenza vaccine (LAIV) in Chinese healthy juveniles and adults. A total of 80 Eligible volunteers were divided into two age groups (≥18 and 3-17 years old). Volunteers were randomly and equally assigned to the experimental group and placebo-controlled group by ratio of 3:1 in each age group. Vaccination was carried out in steps. Totally, 34 (56.67%) adverse events and 24 (40.00%) adverse reactions of the LAIV group were reported. Most adverse reactions were grade 1 and grade 2, and the incidence of adverse reactions that grade 3 was 5%. The most common local reaction was runny nose/nasal congestion (n = 4, 6.67%). And the most common general reaction was fever (n = 10, 16.67%). There were no statistically significant differences in the incidence of total adverse reactions, different grades of adverse reactions, and symptoms between the experimental group and placebo-controlled group. No severe adverse events were reported. Three subjects (5.00%) had been detected vaccine strains on the 3rd day after LAIV vaccination; one was type B and the other two were H3N2. Four subjects (6.67%) had been detected with vaccine strains on the 7th day after LAIV vaccination, all were H3N2. There were no subjects detected carrying the influenza virus on the 15th day after vaccination. There were no statistically significant differences in the positive rate of vaccine strains of influenza virus between the experimental group and placebo-controlled group. The vaccine was well tolerated and not associated with increased rates in adverse reactions or the occurrence of severe adverse events. Pathogenicity of shed vaccine virus to surrounding people was not observed. Thus, Phase Ⅱ study can be carried out as scheduled.

Exosome modification to better alleviates endoplasmic reticulum stress induced chondrocyte apoptosis and osteoarthritis.

Osteoarthritis (OA) is characterized by cartilage matrix degeneration and chondrocyte apoptosis. Prolonged endoplasmic reticulum (ER) stress participates in chondrocyte apoptosis and cartilage degeneration in OA progression. miR-486-5p could suppress the apoptosis of nucleus pulposus cells and cardiomyocyte, yet whether miR-486-5p modified exosomes could modulate ER stress and apoptosis of chondrocytes remain unknown. We validated the increased inflammation and ER stress in OA synovium and cartilage, and the inhibition of ER stress could attenuate the IL-1ß induced chondrocyte apoptosis. Administration of exogenous miR-486-5p could inhibit the ER stress, alleviate chondrocytes apoptosis and promote matrix regeneration. In comparison with direct administration of miR-486-5p and miR-486-5p overexpressing ADSCs, miR-486-5p modified exosomes indicated a better effect in modulating chondrocyte homeostasis. MiR-486-5p containing exosomes could also regulate macrophage polarization. Our IVIS imaging data validated that intraarticular injection of miR-486-5p containing exosomes could sustain for at least 7 days. MiR-486-5p containing exosomes showed a better effect on alleviating rats OA compared with direct administration of miR-486-5p and miR-486-5p overexpressing ADSCs. Our data demonstrated that miR-486-5p modified exosomes have a better effect on alleviating chondrocyte apoptosis and osteoarthritis. This study provides evidence of this efficient strategy of exosomal miRNA delivery and the miRNA-based therapy for OA.

Identification of a HOXD13 variant in a Mongolian family with incomplete penetrance syndactyly by exon sequencing.

BACKGROUND: Syndactyly (SD) refers to a deformity caused by the fusion and limb differentiation disorder of soft tissues and/or skeletons to varying extents between adjacent fingers (toes). The main features of this disease are phenotypic heterogeneity and genetic heterogeneity. In this study, we examined four generations of a Chinese Mongolian with different phenotypes of syndactylia and analysed and identified the pathogenic genetic variants of SD by exon sequencing. METHODS: The clinical phenotypes of patients were analysed, and the hands and feet were examined by X-ray. The pedigree was drawn, and the family data were analysed. Peripheral blood was collected from the family members, and genomic DNA was extracted. The candidate genes of SD were identified by exon sequencing, and the mutation sites of the captured candidate genes were amplified by PCR and verified by Sanger sequencing. RESULTS: The family has congenital syndactyly, which is an autosomal dominant disease. At present, this condition has been passed down for 4 generations and was identified in 9 patients, including 4 males and 5 females. Five patients, I2, II4, III5, III,7 and III10, had unilateral syndactyly, and four patients, III16, IV3, IV6 and IV7, had bilateral finger syndactyly. All of their toes were unaffected. The proband and the other patients in this family had a c.917G > A (p.R306Q) mutation, which is located at position 917 of the second exon of the HOXD13 gene. This mutation results in a change in the amino acid at position 306, in which arginine is changed to glutamine. This mutation cosegregates in unaffected individuals and affected patients in this family. Moreover, 201 Mongolian genome databases and a thousand human genome databases were referenced to further confirm that the pathogenic genetic variant that causes syndactyly in this family is found in HOXD13. CONCLUSION: This study found that the mutation site of the pathogenic gene in this family was HOXD13, c.917G > A (p.R306Q). The phenotype of the family member III12 was normal, but this member was also a carrier of the pathogenic genetic variant. This indicates that the disease of this family has incomplete penetrance characteristics. Our results further enrich the expression profile of the HOXD13 gene.