A Dual Encapsulation Strategy for High-Temperature Micro PCM Particles with High Cyclic Durability.

Addressing critical issues such as high-temperature corrosion,  leakage, degradation, and subpar cyclic performance is imperative for phase change materials (PCMs), prompting the development of appropriate encapsulation techniques to surmount these challenges. In this study, a dual encapsulation strategy is proposed for high-temperature micro PCM particles. Al-Si core is microencapsulated via the "solvent evaporation-heating curing" method. Subsequently, TiO2 is employed as the skeleton material for form-stable encapsulation of PCM microcapsules by "cold pressed sintering". Detailed analysis of the crystalline phase transformation mechanism in the sintering synthesis pathway of TiO2 underscore its potential as a robust structural material with exceptional thermal stability. Furthermore, the incorporation of hexagonal boron nitride (hBN) results in a substantial enhancement of the thermal conductivity of the composites, increasing by 121.1-131.3%. The prepared form-stable phase change microcapsules (FSPCMs) are subjected to 5000 thermal cycles in the air atmosphere. There is no observed PCM leakage or composite ruptures in the FSPCM. Moreover, the oxidized mass gain is merely 3.3%, signifying exceptional oxidation resistance. Thermophysical analysis indicates that FSPCM can retain 91.3% of the enthalpy after 2000 cycles, with over 80% preservation after 5000 cycles, underscoring its remarkable cyclic thermal durability.

Functional force stimulation alters motor neuron discharge patterns.

Introduction: Beneficial effects have been observed for mechanical vibration stimulation (MVS), which are mainly attributed to tonic vibration reflex (TVR). TVR is reported to elicit synchronized motor unit activation during locally applied vibration. Similar effects are also observed in a novel vibration system referred to as functional force stimulation (FFS). However, the manifestation of TVR in FFS is doubted due to the use of global electromyography (EMG) features in previous analysis. Our study aims to investigate the effects of FFS on motor unit discharge patterns of the human biceps brachii by analyzing the motor unit spike trains decoded from the high-density surface EMG. Methods: Eighteen healthy subjects volunteered in FFS training with different amplitudes and frequencies. One hundred and twenty-eight channel surface EMG was recorded from the biceps brachii and then decoded after motion-artifact removal. The discharge timings were extracted and the coherence between different motor unit spike trains was calculated to quantify synchronized activation. Results and discussion: Significant synchronization within the vibration cycle and/or its integer multiples is observed for all FFS trials, which increases with increased FFS amplitude. Our results reveal the basic physiological mechanism involved in FFS, providing a theoretical foundation for analyzing and introducing FFS into clinical rehabilitation programs.

The compact Casπ (Cas12l) 'bracelet' provides a unique structural platform for DNA manipulation.

CRISPR-Cas modules serve as the adaptive nucleic acid immune systems for prokaryotes, and provide versatile tools for nucleic acid manipulation in various organisms. Here, we discovered a new miniature type V system, CRISPR-Casπ (Cas12l) (~860 aa), from the environmental metagenome. Complexed with a large guide RNA (~170 nt) comprising the tracrRNA and crRNA, Casπ (Cas12l) recognizes a unique 5' C-rich PAM for DNA cleavage under a broad range of biochemical conditions, and generates gene editing in mammalian cells. Cryo-EM study reveals a 'bracelet' architecture of Casπ effector encircling the DNA target at 3.4 Å resolution, substantially different from the canonical 'two-lobe' architectures of Cas12 and Cas9 nucleases. The large guide RNA serves as a 'two-arm' scaffold for effector assembly. Our study expands the knowledge of DNA targeting mechanisms by CRISPR effectors, and offers an efficient but compact platform for DNA manipulation.

A Capacitive Electrocardiography System With Dedicated Noise-Cancellation Algorithms for Morphological Analysis.

OBJECTIVE: Capacitive electrocardiography (cECG) has been proposed for ambulatory cardiac health monitoring. However, due to the high sensitivity of capacitive electrodes to various noise sources, particularly the power-line interference (PLI) and motion artifacts (MA), the existing capacitive systems are only verified in terms of RR interval. The aim of the present study is to explore the feasibility of using cECG for morphological analysis, and thus to extract clinical meaningful parameters. METHODS: A capacitive electrode with active guarding is realized. A phase-locked-loop (PLL) based adaptive canceller is employed to remove PLI from the cECG. Wavelet analysis is adopted to cancel other noises. The developed capacitive system and algorithms are evaluated by real ECG measurements on 7 volunteers using 3-lead configuration. The correlation coefficient (CC) between the processed cECG and the wet ECG is calculated in two different conditions: with and without the QRS complex. Several frequently used diagnostic parameters, i.e., RR interval, QRS interval, P segment, T segment, ST segment, are extracted and compared with that obtained from the wet ECG. RESULTS: High CCs are observed between the cECG and the wet ECG in both conditions, i.e., 0.97±0.03 with the QRS complex and 0.92±0.07 without the QRS complex. Besides, RR interval extracted from the two different ECG signals are identical for each subject. Other diagnostic parameters are quite similar. SIGNIFICANCE: Our results suggest cECG to be reliable for ambulatory heart rate monitoring. The results also indicate the feasibility of using cECG for clinical diagnosis.

A new Neoleptophlebia Kluge, 1997 species from eastern China (Ephemeroptera: Leptophlebiidae).

The genus Neoleptophlebia Kluge, 1997 includes five Asian species. Three of them were reported from northeastern Asia and two were found from Chinese Taiwan Island, leaving a huge geographic gap on the Chinese mainland. Here we find a new one, which is named N. uncinata Zhou sp. nov., from Nanjing municipality, eastern China. Via field collecting and indoor rearing, all life stages were obtained, and its nymphs are found living in small creeks (with a width less than 1 m) and shallow waters (with a depth less than 30 cm). Diagnostically, the imago of this new species has larger lateral penial appendages than its congeners, and its nymph has subequal broadened segments II and III of maxillary and labial palpi. Biogeographically, this species bridges two northern and southern groups of the genus.

3D Ti3C2Tx MXene-Matrigel with Electroacoustic Stimulation to Promote the Growth of Spiral Ganglion Neurons.

Cochlear implantation has become the most effective treatment method for patients with profound and total hearing loss. However, its therapeutic efficacy is dependent on the number and normal physiological function of cochlear implant-targeted spiral ganglion neurons (SGNs). Electrical stimulation can be used as an effective cue to regulate the morphology and function of excitatory cells. Therefore, it is important to develop an efficient cochlear implant electroacoustic stimulation (EAS) system to study the behavior of SGNs. In this work, we present an electrical stimulation system constructed by combining a cochlear implant and a conductive Ti3C2Tx MXene-matrigel hydrogel. SGNs were cultured in the Ti3C2Tx MXene-matrigel hydrogel and exposed to electrical stimulation transduced by the cochlear implant. It was demonstrated that low-frequency stimulation promoted the growth cone development and neurite outgrowth of SGNs as well as signal transmission between cells. This work may have potential value for the clinical application of the Ti3C2Tx MXene hydrogel to optimize the postoperative listening effect of cochlear implantation and benefit people with sensorineural hearing loss.

Prediction of Water Distributions and Displacement at Protein-Ligand Interfaces.

The retention and displacement of water molecules during formation of ligand-protein interfaces play a major role in determining ligand binding. Understanding these effects requires a method for positioning of water molecules in the bound and unbound proteins and for defining water displacement upon ligand binding. We describe an algorithm for water placement and a calculation of ligand-driven water displacement in >9000 protein-ligand complexes. The algorithm predicts approximately 38% of experimental water positions within 1.0 Å and about 83% within 1.5 Å. We further show that the predicted water molecules can complete water networks not detected in crystallographic structures of the protein-ligand complexes. The algorithm was also applied to solvation of the corresponding unbound proteins, and this allowed calculation of water displacement upon ligand binding based on differences in the water network between the bound and unbound structures. We illustrate use of this approach through comparison of water displacement by structurally related ligands at the same binding site. This method for evaluation of water displacement upon ligand binding may be of value for prediction of the effects of ligand modification in drug design.

Influence of Electrode Configuration on Muscle-Fiber-Conduction-Velocity Estimation Using Surface Electromyography.

OBJECTIVE: Muscle fiber conduction velocity (MFCV) is an important myoelectric parameter and can be estimated by analysing surface electromyography (EMG). Among many factors, electrode configuration plays a key role on MFCV estimation. Most studies adopt bipolar configuration (BC) for CV estimation. However, a thorough understanding of the underlying mechanism is lacking, confusing the design of the most appropriate EMG measurement setup for CV estimation. The aim of this study is therefore to systematically investigate the influence of electrode configuration on MFCV estimation. METHODS: Four possible configurations are considered, including BC, monopolar configuration (MC), common average reference (CAR), and a special monopolar configuration (SMC) using a fixed channel on the active muscle as reference. For each configuration, mathematical models computing the time delay between adjacent channels are derived and evaluated by dedicated simulation as well as real EMG measurements. MFCV was calculated using the maximum likelihood algorithm with and without channel normalization. RESULTS: The simulation results are in line with the mathematical models. The CVs estimated from the real EMG with and without normalization are 4.3 ±0.7 and 7.2 ±3.7 m/s, 5.7 ±1.3 and 20.4 ±4.7 m/s, 9.0 ±3.4 and 20.6 ±9.8 m/s, and 5.5 ±2.5 and 5.5 ±2.4 m/s for BC, MC, SMC, and CAR, respectively. CONCLUSION: Our results show normalized BC to produce the most accurate CV estimation, in line with the mathematical models and the simulation results. SIGNIFICANCE: These findings enable a better understanding of the influence of electrode configuration on MFCV estimation, providing useful information for EMG measurement setup design aiming at MFCV studies.

Eculizumab in Asian patients with anti-aquaporin-IgG-positive neuromyelitis optica spectrum disorder: A subgroup analysis from the randomized phase 3 PREVENT trial and its open-label extension.

Background Eculizumab, a terminal complement inhibitor, significantly reduced the risk of relapse compared with placebo in patients with anti-aquaporin-4 immunoglobulin G-positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD) in the PREVENT trial. We report efficacy and safety analyses in Asian patients in PREVENT and its open-label extension (OLE). Methods PREVENT was a double-blind, randomized, phase 3 trial. Patients with AQP4+ NMOSD were randomly assigned (2:1) to receive intravenous eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo. Patients who completed PREVENT could receive eculizumab in an OLE. Analyses were performed in a prespecified subgroup of Asian patients. Results Of 143 patients enrolled, 52 (36.4%) were included in the Asian subgroup (eculizumab, n = 37; placebo, n = 15); 45 Asian patients received eculizumab in the OLE. Most Asian patients (86.5%) received concomitant immunosuppressive therapy. During PREVENT, one adjudicated relapse occurred in patients receiving eculizumab and six occurred in patients receiving placebo in the Asian subgroup (hazard ratio, 0.05; 95% confidence interval: 0.01-0.35; p = 0.0002). An estimated 95.2% of Asian patients remained relapse-free after 144 weeks of eculizumab treatment. Upper respiratory tract infections, headache, and nasopharyngitis were the most common adverse events with eculizumab in the Asian subgroup. Conclusion Eculizumab reduces the risk of relapse in Asian patients with AQP4+ NMOSD, with a benefit-risk profile similar to the overall PREVENT population. The benefits of eculizumab were maintained during long-term therapy. Clinical trial registration ClinicalTrials.gov identifiers: NCT01892345 (PREVENT); NCT02003144 (open-label extension).

Long-Term Safety and Efficacy of Eculizumab in Aquaporin-4 IgG-Positive NMOSD.

OBJECTIVE: During PREVENT (NCT01892345), eculizumab significantly reduced relapse risk versus placebo in patients with aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-IgG+ NMOSD). We report an interim analysis of PREVENT's ongoing open-label extension (OLE; NCT02003144) evaluating eculizumab's long-term safety and efficacy. METHODS: Patients who completed PREVENT could enroll in the OLE to receive eculizumab (maintenance dose = 1,200 mg/2 weeks, after a blinded induction phase). Safety and efficacy data from PREVENT and its OLE (interim data cut, July 31, 2019) were combined for this analysis. RESULTS: Across PREVENT and the OLE, 137 patients received eculizumab and were monitored for a median (range) of 133.3 weeks (5.1-276.9 weeks), for a combined total of 362.3 patient-years (PY). Treatment-related adverse event (AE) and serious adverse event (SAE) rates were 183.5 in 100 PY and 8.6 in 100 PY, respectively. Serious infection rates were 10.2 in 100 PY in eculizumab-treated patients versus 15.1 in 100 PY in the PREVENT placebo group. No patient developed a meningococcal infection. At 192 weeks (3.7 years), 94.4% (95% confidence interval [CI], 88.6-97.3) of patients remained adjudicated relapse-free. The adjudicated annualized relapse rate was 0.025 (95% CI = 0.013-0.048) in all eculizumab-treated patients versus 0.350 (95% CI = 0.199-0.616) in the PREVENT placebo group. During the OLE, 37% of patients (44 of 119 patients) stopped or decreased background immunosuppressive therapy use. INTERPRETATION: This analysis demonstrates that eculizumab's long-term safety profile in NMOSD is consistent with its established profile across other indications. This analysis also demonstrated the sustained ability of long-term eculizumab treatment to reduce relapse risk in patients with AQP4-IgG+ NMOSD. ANN NEUROL 2021;89:1088-1098.

Benefits of eculizumab in AQP4+ neuromyelitis optica spectrum disorder: Subgroup analyses of the randomized controlled phase 3 PREVENT trial.

BACKGROUND: Antibodies to the aquaporin-4 (AQP4) water channel in neuromyelitis optica spectrum disorder (NMOSD) are reported to trigger the complement cascade, which is implicated in astrocyte damage and subsequent neuronal injury. The PREVENT study demonstrated that the terminal complement inhibitor eculizumab reduces adjudicated relapse risk in patients with anti-AQP4 immunoglobulin G-positive (AQP4+) NMOSD. The objective of this analysis was to evaluate the efficacy of eculizumab in reducing relapse risk and its safety in AQP4+ NMOSD across clinically relevant subgroups in PREVENT. METHODS: In the randomized, double-blind, time-to-event, phase 3 PREVENT trial, 143 adults received eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo (2:1), with stable-dose concomitant immunosuppressive therapy (IST) permitted (except rituximab and mitoxantrone). Post hoc analyses of relapses and adverse events were performed for prespecified and post hoc subgroups based on concomitant IST and prior rituximab use, demographic and disease characteristics, and autoimmune comorbidity. RESULTS: The significant reduction in relapse risk observed for eculizumab versus placebo in the overall PREVENT population was consistently maintained across subgroups based on concomitant IST and previous rituximab use, age, sex, region, race, time since clinical onset of NMOSD, historical annualized relapse rate, baseline Expanded Disability Status Scale score, and history of another autoimmune disorder. The serious infection rate was lower with eculizumab than placebo regardless of rituximab use in the previous year, concomitant IST use, or history of another autoimmune disorder. CONCLUSION: Across a wide range of clinically relevant AQP4+ NMOSD patient subgroups in PREVENT, eculizumab therapy was consistently effective versus placebo in reducing relapse risk, with no apparent increase in serious infection rate. TRIAL REGISTRATION: NCT01892345 (ClinicalTrials.gov).

A rapid molecular diagnostic method for spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a common autosomal recessive disorder which has been considered as the second common cause of infant death, with an estimated prevalence of 1 in 10,000 live births. The disorder is caused by survival motor neuron 1 gene (SMN1) deficiency leading to limb weakness, difficult swallowing and abnormal breathing. Here, a fast and accurate method for SMA detection has been developed. Genomic DNA sample collected from whole blood, amniotic fluid, or dried blood spots can be analysed by using the Clarity™ Digital PCR (dPCR) System for determining the copy numbers of SMN1 and SMN2 genes. Two hundred and fourteen clinical samples determined by qPCR-based method were enrolled and used to establish the cut-off ranges for unaffected individual, SMA carrier and SMA patient categories. After setting the cut-off range for each group, 12 samples were analyzed by both dPCR-based method and MLPA (multiplex ligation-dependent probe amplification), the current testing golden standard for SMA, and 100% concordant results between the two testing methods were performed. CSB SMA Detection Kit combined with dPCR platform provides a robust and precise approach to distinguish unaffected individuals, SMA carrier and SMA patients. This rapid molecular diagnostic method can be adapted to pre-pregnancy eugenics inspection, prenatal testing as well as newborns screening and help physicians or genetic counselors to improve population SMA incidence.

Long non­coding RNA BCYRN1 promotes prostate cancer progression via elevation of HDAC11.

Prostate cancer is a serious threat to men's health worldwide. While previous studies have demonstrated that long non­coding RNAs (lncRNAs) are closely associated with the initiation and development of several types of cancer, the role of lncRNAs in the progression of prostate cancer remains incompletely understood. In the present study, the lncRNA brain cytoplasmic RNA 1 (BCYRN1) was found to be overexpressed in prostate tumors compared with healthy tissues. Furthermore, the expression of BCYRN1 was found to be associated with Gleason score and lymph node metastasis. It was demonstrated that BCYRN1 silencing using small interfering RNA (siRNA) inhibited the proliferation of prostate cancer cells. The results of the present study indicated the presence of a reciprocal regulatory association between BCYRN1 and microRNA (miR)­939­3p. In addition, it was observed that BCYRN1 directly sponged miR­939­3p to upregulate histone deacetylase 11 (HDAC11) expression in prostate cancer cells. Moreover, transfection of recombinant HDAC11 reversed the inhibition of cell proliferation that was induced by BCYRN1 siRNA. A positive correlation between BCYRN1 and HDAC11 mRNA expression levels was also identified in prostate tumor and healthy tissues. Therefore, the findings of the present study may provide novel insight into the effects of lncRNAs on prostate cancer, and may enable the development of new therapeutic methods for patients with prostate cancer.

Long non-coding RNA FER1L4 inhibits prostate cancer progression via sponging miR-92a-3p and upregulation of FBXW7.

BACKGROUND: Dysregulation of long non-coding RNAs (lncRNAs) is involved in development of prostate cancer. However, the molecular mechanisms of many lncRNAs in prostate cancer have not been studied yet. METHODS: The lncRNA Fer-1-like protein 4 (FER1L4) expression was explored in prostate tumors and normal prostate tissues by RT-qPCR and bioinformatic analysis. Overexpression of FER1L4 was performed to evaluate its role in prostate cancer cell proliferation and survival. The molecular mechanism of FER1L4 was investigated by dual luciferase reporter assay, RNA pull down assay, western blotting and RT-qPCR. RESULTS: It was found that FER1L4 was lower in prostate cancer tissues than normal tissues. Higher expression of FER1L4 was associated with prostate cancer tissues of early stage (AJCC stage I/II). Overexpression of FER1L4 inhibited cell proliferation and promoted cell apoptosis in prostate cancer cells. Bioinformatic analysis, RT-qPCR, RNA pull down assay and dual luciferase assay showed that FER1L4 upregulated F-box/WD repeat-containing protein 7 (FBXW7) tumor suppressor via sponging miR-92a-3p. Silencing of FBXW7 reversed the cell phenotypes caused by FER1L4 overexpression in prostate cancer cells. CONCLUSION: The data demonstrated that FER1L4, a downregulated lncRNA in prostate cancer, was pivotal for cell proliferation and survival of prostate cancer. The study provided new sights into understanding of the signaling network in prostate cancer and implied that FER1L4 might be a biomarker for patients with prostate cancer.

Matrine Restrains Cell Growth and Metastasis by Up-Regulating LINC00472 in Bladder Carcinoma.

PURPOSE: Bladder Carcinoma (BC) is a malignant carcinoma with a high incidence in masculinity. We preliminarily researched the efficacy and mechanism of matrine (MAT) in T24 and 5637 cells. PATIENTS AND METHODS: CCK-8, flow cytometry, migration and invasion means were adopted to detect cell viability, apoptosis, migratory and invasive potentials. Moreover, LINC00472 expression was changed via transfection assays and was tested by RT-qPCR. Western blot was used for investigating the levels of CyclinD1, p53, Bcl-2, Bax, pro-Caspase-3, Cleaved-Caspase-3, ß-actin, programmed cell death protein 4 (PDCD4) and relate-proteins of cell pathways. Tumor volume and weight were tested via animal experiments. RESULTS: MAT could not affect the growth of SV-HUC-1 cell but MAT promoted tumor cell apoptosis but restrained viability, invasion and migration. Furthermore, LINC00472 was prominently low expressed in BC tissues. MAT positively regulated LINC00472 and transfection with si-00472 could partly reverse the efficacies of MAT. Moreover, MAT enhanced PDCD4 expression by up-regulating LINC00472. Besides, we discovered MAT elevated PTEN but restrained PI3K/AKT proteins. Finally, tumor volume and weight were declined by MAT in vivo via up-regulating LINC00472. CONCLUSION: MAT restrained cell growth and metastasis but promoted PDCD4 expression by up-regulating LINC00472 via restraining PTEN/PI3K/AKT pathway in BC.

Eculizumab in Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing, autoimmune, inflammatory disorder that typically affects the optic nerves and spinal cord. At least two thirds of cases are associated with aquaporin-4 antibodies (AQP4-IgG) and complement-mediated damage to the central nervous system. In a previous small, open-label study involving patients with AQP4-IgG-positive disease, eculizumab, a terminal complement inhibitor, was shown to reduce the frequency of relapse. METHODS: In this randomized, double-blind, time-to-event trial, 143 adults were randomly assigned in a 2:1 ratio to receive either intravenous eculizumab (at a dose of 900 mg weekly for the first four doses starting on day 1, followed by 1200 mg every 2 weeks starting at week 4) or matched placebo. The continued use of stable-dose immunosuppressive therapy was permitted. The primary end point was the first adjudicated relapse. Secondary outcomes included the adjudicated annualized relapse rate, quality-of-life measures, and the score on the Expanded Disability Status Scale (EDSS), which ranges from 0 (no disability) to 10 (death). RESULTS: The trial was stopped after 23 of the 24 prespecified adjudicated relapses, given the uncertainty in estimating when the final event would occur. The mean (±SD) annualized relapse rate in the 24 months before enrollment was 1.99±0.94; 76% of the patients continued to receive their previous immunosuppressive therapy during the trial. Adjudicated relapses occurred in 3 of 96 patients (3%) in the eculizumab group and 20 of 47 (43%) in the placebo group (hazard ratio, 0.06; 95% confidence interval [CI], 0.02 to 0.20; P<0.001). The adjudicated annualized relapse rate was 0.02 in the eculizumab group and 0.35 in the placebo group (rate ratio, 0.04; 95% CI, 0.01 to 0.15; P<0.001). The mean change in the EDSS score was -0.18 in the eculizumab group and 0.12 in the placebo group (least-squares mean difference, -0.29; 95% CI, -0.59 to 0.01). Upper respiratory tract infections and headaches were more common in the eculizumab group. There was one death from pulmonary empyema in the eculizumab group. CONCLUSIONS: Among patients with AQP4-IgG-positive NMOSD, those who received eculizumab had a significantly lower risk of relapse than those who received placebo. There was no significant between-group difference in measures of disability progression. (Funded by Alexion Pharmaceuticals; PREVENT ClinicalTrials.gov number, NCT01892345; EudraCT number, 2013-001150-10.).

Repetitive intrathecal injection of human NMO-IgG with complement exacerbates disease severity with NMO pathology in experimental allergic encephalomyelitis mice.

Neuromyelitis optica (NMO) is recognized as a different CNS autoimmune disease from multiple sclerosis (MS). Whether NMO-IgG contributes directly to the pathogenesis of NMO or is just a serologic marker of autoimmune responses of the disease needs to be clarified. We created MOG-induced experimental autoimmune encephalomyelitis (EAE) mice by passively transferring NMO-IgG to model the pathogenic findings in NMO patients. The mice were divided into three groups and administered intrathecal PBS, human complement with IgG from normal subjects, or IgG from AQP4(+) patients on days 8 and 11 after immunization. The EAE scores of EAE mice with intrathecal NMO-IgG injection were significantly elevated 14 days post-immunization. All of the mice were sacrificed for brain and spinal cord pathology analysis on day 21 post-immunization. Compared to mice given normal human IgG, EAE mice injected with NMO-IgG had markedly decreased AQP4 and glial fibrillary acidic protein (GFAP) expression and fluorescent intensity in the brain and spinal cord but more scattered deposition of complement (C9neo). Thus, our studies not only support the pathogenic role of NMO-IgG with complement in NMO disease but also provide a platform for the development of future therapeutics.

Immunopathogenic Mechanisms and Novel Immune-Modulated Therapies in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease of unknown etiology. It is characterized by the presence of rheumatoid factor and anticitrullinated peptide antibodies. The orchestra of the inflammatory process among various immune cells, cytokines, chemokines, proteases, matrix metalloproteinases (MMPs), and reactive oxidative stress play critical immunopathologic roles in the inflammatory cascade of the joint environment, leading to clinical impairment and RA. With the growing understanding of the immunopathogenic mechanisms, increasingly novel marked and potential biologic agents have merged for the treatment of RA in recent years. In this review, we focus on the current understanding of pathogenic mechanisms, highlight novel biologic disease-modifying antirheumatic drugs (DMRADs), targeted synthetic DMRADs, and immune-modulating agents, and identify the applicable immune-mediated therapeutic strategies of the near future. In conclusion, new therapeutic approaches are emerging through a better understanding of the immunopathophysiology of RA, which is improving disease outcomes better than ever.