Development of an IgG-Fc fusion COVID-19 subunit vaccine,AKS-452

AKS-452 is a biologically-engineered vaccine comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain antigen (Ag) and human IgG1 Fc (SP/RBD-Fc) in clinical development for the induction and augmentation of neutralizing IgG titers against SARS-CoV-2 viral infection to address the COVID-19 pandemic. The Fc moiety is designed to enhance immunogenicity by increasing uptake via Fc-receptors (FcγR) on Ag-presenting cells (APCs) and prolonging exposure due to neonatal Fc receptor (FcRn) recycling. AKS-452 induced approximately 20-fold greater neutralizing IgG titers in mice relative to those induced by SP/RBD without the Fc moiety and induced comparable long-term neutralizing titers with a single dose vs. two doses. To further enhance immunogenicity, AKS-452 was evaluated in formulations containing a panel of adjuvants in which the water-in-oil adjuvant, Montanide™ ISA 720, enhanced neutralizing IgG titers by approximately 7-fold after one and two doses in mice, including the neutralization of live SARS-CoV-2 virus infection of VERO-E6 cells. Furthermore, ISA 720-adjuvanted AKS-452 was immunogenic in rabbits and non-human primates (NHPs) and protected from infection and clinical symptoms with live SARS-CoV-2 virus in NHPs (USA-WA1/2020 viral strain) and the K18 human ACE2-trangenic (K18-huACE2-Tg) mouse (South African B.1.351 viral variant). These preclinical studies support the initiation of Phase I clinical studies with adjuvanted AKS-452 with the expectation that this room-temperature stable, Fc-fusion subunit vaccine can be rapidly and inexpensively manufactured to provide billions of doses per year especially in regions where the cold-chain is difficult to maintain.     

Emerging Aspects of the Body Composition,Bone Marrow Adipose Tissue and Skeletal Phenotypes in Type 1 Diabetes Mellitus

Anthropomorphic measures among type 1 diabetic patients are changing as the obesity epidemic continues. Excess fat mass may impact bone density and ultimately fracture risk. We studied the interaction between bone and adipose tissue in type 1 diabetes subjects submitted to two different clinical managements: (I) conventional insulin therapy or (II) autologous nonmyeloablative hematopoietic stem-cell transplantation (AHST). The study comprised 3 groups matched by age, gender, height and weight: control (C = 24), type 1 diabetes (T1D = 23) and type 1 diabetes treated with AHST (T1D-AHST = 9). Bone mineral density (BMD) and trabecular bone score (TBS) were assessed by dual X-ray absorptiometry (DXA). ¹H Magnetic resonance spectroscopy was used to assess bone marrow adipose tissue (BMAT) in the L3 vertebra, and abdominal magnetic resonance imaging was used to assess intrahepatic lipids (IHL), visceral (VAT) and subcutaneous adipose tissue (SAT). Individuals conventionally treated for T1D were more likely to be overweight (C = 23.8 ± 3.7; T1D = 25.3 ± 3.4; T1D-AHST = 22.5 ± 2.2 Kg/m²; p > 0.05), but there was no excessive lipid accumulation in VAT or liver. Areal BMD of the three groups were similar at all sites; lumbar spine TBS (L3) was lower in type 1 diabetes (p < 0.05). Neither SAT nor VAT had any association with bone parameters. Bone marrow adipose tissue (BMAT) lipid profiles were similar among groups. BMAT saturated lipids were associated with cholesterol, whereas unsaturated lipids had an association with IGF1. Overweight and normal weight subjects with type 1 diabetes have normal areal bone density, but lower trabecular bone scores. Adipose distribution is normal and BMAT volume is similar to controls, irrespective of clinical treatment.     

PTPN6通过抑制SP1/p38 MAPK信号通路促进前列腺癌细胞的化疗敏感性

目的:研究PTPN6对前列腺癌细胞PC3的作用及其作用机制。方法:RT-PCR和Western blot实验检测前列腺癌组织和细胞以及癌旁组织和人前列腺上皮细胞中PTPN6的表达量；CCK-8和EDU染色实验检测PTPN6对前列腺癌细胞PC3增殖的影响；Western blot实验检测耐药相关蛋白P-gp和MRP-1的蛋白表达水平。结果:RT-PCR和Western blot结果显示，PTPN6在前列腺癌组织和细胞中的表达量显著低于癌旁组织和人前列腺上皮细胞中的表达量；过表达PTPN6显著抑制前列腺癌PC3细胞的增殖，并降低PC3细胞的耐药性；进一步的研究结果表明PTPN6可通过抑制SP1，并抑制p38 MAPK通路抑制PC3细胞的增殖和耐药。结论:PTPN6能够抑制前列腺癌细胞PC3的增殖和耐药，提高其化疗敏感性，作用机制是通过调控SP1/p38 MAPK信号通路来实现的，这一结果能够为临床上前列腺癌的诊断和治疗提供分子基础。     

Conservative endodontic management using a calcium silicate bioceramic sealer for delayed root fracture: A case report and review of the literature

BACKGROUNDThe success rate of conservative endodontic management for root fracture varies greatly based on different methods used. It has been rarely reported that calcium silicate-based materials are applied in root fracture treatment. CASE SUMMARYA 38-year-old male patient presented with spontaneous pain from the upper left anterior teeth for 1 wk. The spontaneous pain was subsequently relieved, but pain on mastication persisted for 3 d. The patient had a dental trauma from a boxing match 15 years ago. Cone beam computed tomography showed that the maxillary left central incisor had oblique fracture lines and a radiolucent lesion around the fracture line. The tooth was diagnosed with an oblique root fracture with no healing and symptomatic apical periodontitis. In the following conservative endodontic management, the coronal and apical fragments of the canal both were chemo-mechanically prepared and obturated using a single cone gutta-percha with iRoot SP (Innovative BioCreamix Inc, Vancouver, Canada), a new calcium silicate-based bioceramic root canal sealer. At follow-ups at 1, 6, 12, and 24 mo, the patient was asymptomatic and the radiolucency around the fracture line was healing radiographically. CONCLUSIONConservative root canal treatment is an alternative treatment in some cases of oblique root fracture with no healing. The application of bioceramic sealers and single core obturation techniques may also be essential to obtain an excellent outcome.     

Analgesic effects and hemodynamic mechanisms of perpendicular and transverse needling at Sanyinjiao (SP 6) in patients with primary dysmenorrhea: A randomized controlled trial

ObjectiveTo explore the analgesic effects and uterine hemodynamics of perpendicular needling (PN) and transverse needling (TN) at SP 6 in patients with primary dysmenorrhea (PD).MethodsIn this randomized controlled trial, patients with PD diagnosed with cold-dampness congealing pattern were randomly assigned in a ratio of 1:1 to receive PN or TN at bilateral SP 6 for 10 min. Acupuncture was performed when the menstrual pain score was over 40 mm on the first day of menstruation, as measured using the visual analog scale for pain (VAS-P). The primary outcome was average menstrual pain (VAS-P). Secondary outcomes included the pulsatility index (PI), resistance index (RI), and systolic-diastolic peaks ratio (S/D) in uterine arteries as measured using color Doppler ultrasonography; anxiety as assessed using the Hamilton Anxiety Rating Scale (HAMA), blood pressure (BP), and heart rate (HR).ResultsForty-eight patients completed the study. The TN group exhibited a significant reduction in VAS-P scores (–5.71 mm, 95% confidence interval (CI): –8.78, –2.63, P = .001), RI values (–0.05, 95% CI: –0.09, –0.01, P = .015), and HAMA values (–2.50, 95% CI: –4.78, –0.22, P = .032) when compared with the PN group. No significant differences in PI, S/D, BP, or HR values were observed between the two groups (P > .05).ConclusionTN at SP 6 was superior to PN in alleviating menstrual pain and anxiety in patients with PD. This analgesic effect of TN may be due to its better ability to improve uterine arterial blood flow via decreases in RI values.     

Unilateral ligature-induced periodontitis influences the expression of neuropeptides in the ipsilateral and contralateral trigeminal ganglion in rats

OBJECTIVES: Expression of neuronal neuropeptides in inflammatory conditions is altered. The changes in expression of substance P (SP) and calcitonin gene-related peptide (CGRP) in ipsilateral and contralateral trigeminal ganglion (TG) neurons were investigated by immunohistochemistry one week after unilateral ligature-induced periodontitis in rats. DESIGN: A retrograde nerve tracer Fluorogold (FG) was applied into the gingival sulcus of the second maxillary molar to identify the neurons in TG that specifically innervate the inflamed gingivomucosa. In addition, neurons from the corresponding maxillary and the adjacent mandibular-ophthalmic regions in TG were analysed. RESULTS: Statistically significantly higher frequencies of CGRP-positive neurons, regardless of their size, were found in TG ipsilateral to the periodontitis (83% and 73% in FG-labelled and maxillary regions, respectively) than in the control group without periodontitis (52% and 42% in FG-labelled and maxillary regions, respectively). The frequency of small FG-labelled SP-positive neurons in the ipsilateral TG (60%) was significantly higher than in the control TG (25%). In the contralateral TG the frequency of CGRP-positive neurons in maxillary region (66%) was significantly higher than in the control group. Surprisingly, the number of SP-positive neurons in all regions of contralateral TG decreased when compared to control and ipsilateral TGs. CONCLUSIONS: Taken together, these results implicate a role of neurogenic component in the pathogenesis of periodontitis. The contralateral response in the TG could be mediated through the transmedian neurological pathways crossing in the trigeminal nuclear complex or through the systemic inflammatory reaction and the activation of the so called "neuro-immune axis".     

熔附条件对牙科复合树脂中SP1 SiO_2表面结构及形态的影响

目的:研究熔附温度和熔附时间对多微孔纳米二氧化硅粒子(SP1 SiO2)表面结构及形态的影响。方法:将SP1SiO2以250℃/h的升温速度分别升至500、650、800、950、1100℃,并分别保持10、30min和3h制作试样,进行表面结构及形态测试。结果:随烧结温度的增高和时间的延长,SP1 SiO2颗粒表面的Si-OH键特征峰值逐渐减弱,条件为950℃、10min和30min,650℃、3h时完全消失;随着熔附温度的升高和熔附时间的延长颗粒增大、粒度分布变窄。结论:熔附温度和熔附时间影响SP1 SiO2颗粒表面的Si-OH含量和颗粒大小、粒度分布。     

In vivo biocompatibility of an interim denture resilient liner containing antifungal drugs

Statement of problem

Antifungal agents incorporated into interim denture resilient liners have been suggested as an adjunct treatment for denture stomatitis (DS). However, before applying this protocol to humans, biocompatibility analysis of such drugs in animal models is required.