Objective
To determine whether a combination of B cell depletion and BAFF blockade is more effective than monotherapy in treating models of spontaneous or accelerated systemic lupus erythematosus ...(SLE) in (NZB × NZW)F1 mice.
Methods
Clinical parameters such as disease progression–free survival, proteinuria, and renal injury were assessed in models of spontaneous, interferon‐α (IFNα)–accelerated, or pristane‐accelerated lupus in (NZB × NZW)F1 mice. Treatment arms included anti‐CD20 (B cell depletion), B lymphocyte stimulator receptor 3 fusion protein (BR‐3‐Fc) (BAFF blockade), the combination of anti‐CD20 and BR‐3‐Fc, isotype control, or cyclophosphamide. In models of spontaneous, IFNα‐accelerated, or pristane‐accelerated lupus, mice were treated for 24 weeks, 8 weeks, or 12 weeks, respectively. Peripheral and resident B cell subsets and various autoantibodies were examined.
Results
Compared to B cell depletion or BAFF blockade alone, combined therapy significantly improved disease manifestations in all 3 lupus models. In addition, marginal zone B cells, plasmablasts, and circulating and tissue plasma cells were decreased more effectively. Dual B cell immunotherapy also reduced multiple classes of pathogenic autoantibodies, consistent with its observed effectiveness in reducing immune complex–mediated renal injury.
Conclusion
Dual immunotherapy via B cell depletion and BAFF blockade is more efficacious than single agent immunotherapy in murine SLE models, and this combination treatment is predicted to be an effective strategy for immunotherapy in human SLE.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Influenza B virus (IBV) causes annual influenza epidemics around the world. Here we use an in vivo plasmablast enrichment technique to isolate a human monoclonal antibody, 46B8 that neutralizes all ...IBVs tested in vitro and protects mice against lethal challenge of all IBVs tested when administered 72 h post infection. 46B8 demonstrates a superior therapeutic benefit over Tamiflu and has an additive antiviral effect in combination with Tamiflu. 46B8 binds to a conserved epitope in the vestigial esterase domain of hemagglutinin (HA) and blocks HA-mediated membrane fusion. After passage of the B/Brisbane/60/2008 virus in the presence of 46B8, we isolated three resistant clones, all harbouring the same mutation (Ser301Phe) in HA that abolishes 46B8 binding to HA at low pH. Interestingly, 46B8 is still able to protect mice against lethal challenge of the mutant viruses, possibly owing to its ability to mediate antibody-dependent cellular cytotoxicity (ADCC).
By contrast with the rich, wurztite-related, one-dimensional nanostructure of ZnO and its wide variety of applications, there only exists a few methods for the controlled and designed synthesis of ...one-dimensional CdSe nanostructures. Here, we describe a low-temperature and directed preparation of CdSe nanowires in a simple one-step, template-free electrochemical deposition. The preparation takes advantage of both the wurtzite structure characteristics and current-induced preferential orientation. High-resolution transmission electron microscopy (TEM) images and selected area electron diffraction (SAED) patterns clearly verify that the prepared CdSe nanowires have a single-crystal wurtzite structure and grow along the 0001 (c-axis). With the discovery of other one-dimensional CdSe nanostructures and CdS nanowires, it is anticipated that this electrochemical synthesis method can be extended to other nanostructures of CdSe and to other II−VI semiconductors and can also be developed into a systematic synthesis for nanostructured semiconductors. The average diameter of the thus prepared CdSe nanowires is larger than those synthesized by chemical vapor deposition (CVD) and solution−liquid−solid (SLS) methods. This may be an advantage in some applications, for example, as the light-harvesting material in photovoltaic cells. Organic/inorganic hybrid photovoltaic cells fabricated with CdSe nanowires and PEDOT:PSS give a good photovoltaic performance, demonstrating the attractive potential of CdSe nanowire applications in photovoltaics.
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IJS, KILJ, NUK, PNG, UL, UM
B cell immunotherapy has emerged as a mainstay in the treatment of lymphomas and autoimmune diseases. Although the microenvironment has recently been demonstrated to play critical roles in B cell ...homeostasis, its contribution to immunotherapy is unknown. To analyze the in vivo factors that regulate mechanisms involved in B cell immunotherapy, we used a murine model for human CD20 (hCD20) expression in which treatment of hCD20(+) mice with anti-hCD20 mAbs mimics B cell depletion observed in humans. We demonstrate in this study that factors derived from the microenvironment, including signals from the B cell-activating factor belonging to the TNF family/BLyS survival factor, integrin-regulated homeostasis, and circulatory dynamics of B cells define distinct in vivo mechanism(s) and sensitivities of cells in anti-hCD20 mAb-directed therapies. These findings provide new insights into the mechanisms of immunotherapy and define new opportunities in the treatment of cancers and autoimmune diseases.
Abstract
Background
Postoperative acute pain is a common issue following thoracic surgery. Acupotomy is a common and safe intervention method for pain treatment in clinical practice. In previous ...preliminary experiments, we found that acupotomy has a good clinical effect and good safety in the treatment of pain after thoracoscopic surgery. However, due to a lack of a rigorous design and an adequate sample size, its efficacy still requires further confirmation. The purpose of this study will be to explore the efficacy and safety of acupotomy combined with patient-controlled analgesia (PCA) for the treatment of pain after video-assisted thoracic surgery (VATS).
Methods
The study will be a single-centre, parallel group, randomized controlled trial.
Seventy patients with significant pain after thoracoscopic surgery with a visual analogue scale (VAS) score ≥ 7 will be included and randomly distributed into two groups: G1, the acupotomy combined with PCA group; and G2, the conventional PCA group. The primary outcome measure is pain scores at rest and coughing evaluated with the VAS by a blinded observer in the postanaesthesia care unit (PACU) and postoperatively at 1, 2, 4, 8, 12, 24, 48, and 72 h. The secondary outcome measures are postoperative requirements for rescue analgesia, the cumulative amount of self-administered analgesics, the level of sedation (LOS), the Bruggemann comfort scale (BCS), and the functional activity score (FAS) concerning adverse effects and patient satisfaction.
Discussion
This trial has the potential to identify an innovative and effective analgesic method for postoperative pain management for VATS. The findings may advocate for the inclusion of the treatment of comorbid pain after thoracoscopy in current pain management practice guidelines.
Trial registration
Chinese Clinical Trial Registry
ChiCTR1900027191
. Registered on 4 November 2019
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Ocean waves are a promising source of renewable energy, but harvesting this irregular low-frequency energy is challenging due to technological limitations. In this paper, a pendulum plate-based ...triboelectric nanogenerator (PP-TENG) is proposed. The PP-TENG absorbs wave energy through the pendulum plate installed at the bottom of the device, which generates a swing effect. This drives the motion of the upper TENG power generation unit and generates a charge transfer on the surface of a film of polymer PTFE and nylon, materials which are very sensitive to the low-frequency wave environment. The PP-TENG was tested after building a semi-physical simulation test platform. When the polymer materials were PTFE with a thickness of 0.01 mm and nylon with a thickness of 0.02 mm, 33 commercial LED lamps could be lit simultaneously. Moreover, under short-circuit conditions, the current reached 2.45 μA, and under open-circuit conditions, the voltage reached 212 V. When the PP-TENG was connected in series with a resistor with a resistance of 3 × 10
Ω, its maximum peak power density reached 6.74 mW/m
. It can be concluded that the PP-TENG is characterised by low fabrication costs and excellent energy conversion efficiency. The combination of a pendulum wave energy converter with a TENG shows great output performance. This research lays a solid foundation for practical applications of the proposed structure in the future.
Abstract
Background
Epilepsy is a severe chronic neurologic disease with a prevalence of 0.7% worldwide; anti-seizure medications (ASMs) are the mainstay of epilepsy treatment. The effects of ...sociodemographic factors on the characteristics of initial treatment in patients with newly diagnosed focal epilepsy in Western China are unknown. This study was conducted to explore sociodemographic factors associated with initial treatment characteristics.
Methods
Patients with focal epilepsy on continuous ASM treatment who visited to our epilepsy center at Sichuan Provincial People’s Hospital between January 2018 and December 2019 were recruited. Data on initial treatment status and sociodemographic variables were obtained from the patients with a questionnaire designed by our researchers. We examined whether sociodemographic factors were associated with epileptic patients’ access to neurologists and prescriptions of individual ASMs
.
Results
A total of 569 patients completed this study. We found that patients with a higher education level, aged < 16 years, and with a higher household disposable income were more likely to receive treatment from a neurologist than their counterparts. Patients with a lower personal income level and who were treated at a junior hospital were more likely to receive prescriptions for carbamazepine, and those who were younger than 16 years were less likely to receive prescriptions for carbamazepine and oxcarbazepine. Patients with a higher education level, with a higher household disposable income level, who were younger than 16 years, and who were treated at a senior hospital were more likely to receive prescriptions for levetiracetam than their counterparts. Adult, female patients with focal epilepsy treated at a senior hospital were more likely to receive prescriptions for lamotrigine.
Conclusions
This observation suggests that sociodemographic characteristics are associated with access to neurologists and prescriptions of individual antiepileptic drugs. These data may help public health officials establish guidelines for doctors and distribute resources according to the needs of different patient groups.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Polyaniline/Au nanocomposite modified nanoelectrodes based dopamine nanosensors have been developed. The polyaniline/Au nanocomposite film was deposited at the exposed end of the nanoelectrode tip by ...a surface-graft polymerization method to fabricate a desired modified nanoelectrode. With this modified method, the nanocomposites firmly adhered on the electrode surface and the modified nanoelectrode still had a sharp tip, which was proved by the scanning electron microscope. The electrochemical measurement shows the polyaniline/Au nanocomposite modified film has a good and stable redox activity in neutral solution. The modified nanoelectrode exhibits the excellent electrocatalytic activity towards the oxidations of ascorbic acid and dopamine in phosphate buffer solution. The separation of anodic peak potential of dopamine and ascorbic acid reaches 250
mV. Differential pulse voltammograms results illustrate that dopamine can be selectively determined in the presence of thousands times higher concentration of ascorbic acid with a wide linear range from 200 to 0.3
μM and the detection limit is 0.1
μM. This study provides a simple method for the construction of dopamine nanosensors that have a good sensitivity, wide linear range and stable response. The nanosensors are hopeful to be applied to the detection of dopamine in vivo.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Monoclonal antibodies (mAbs) have enabled numerous basic research discoveries and therapeutic approaches for many protein classes. However, there still exist a number of target classes, such as ...multi-pass membrane proteins, for which antibody discovery is difficult, due in part to lack of high quality, recombinant protein. Here we describe the impact of several parameters on antigen expression and the development of mAbs against human claudin 4 (CLDN4), a potential multi-indication cancer target. Using gene gun-based DNA delivery and bioluminescence imaging, we optimize promoter type by comparing expression profiles of four robust in vivo promoters. In addition, we observe that most vectors rapidly lose expression, ultimately reaching almost background levels by three days post-delivery. Recognizing this limitation, we next explored skin pretreatment strategies as an orthogonal method to further boost the efficiency of mAb generation. We show that SDS pretreatment can boost antigen expression, but fails to significantly increase mAb discovery efficiency. In contrast, we find that sandpaper pretreatment yields 5-fold more FACS+ anti-CLDN4 hybridomas, without impacting antigen expression. Our findings coupled with other strategies to improve DNA immunizations should improve the success of mAb discovery against other challenging targets and enable the generation of critical research tools and therapeutic candidates.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
n-ZnO nanorods/p-CuSCN heterojunction light-emitting diodes (LEDs) have been fabricated using low-temperature electrochemical method. The
I–
V characteristics of the heterojunction LEDs show obvious ...rectifying behavior. The typical room-temperature electroluminescence spectra obtained from this heterostructure device under forward bias exhibit a strong visible emission across the spectral region from 350 to 600
nm centered at 530
nm. The intensity of the visible emission rises more quickly than that of the ultraviolet emission with the increasing bias. Photocurrent and Raman spectra reveal that the growth process of CuSCN can induce more surface states and defects in the ZnO nanorods, which confirms the enhancement of visible emission from the ZnO nanorods/p-CuSCN heterostructure. Compared with the ZnO-only LEDs, a p-type CuSCN layer used as a hole-transporting material can balance the electrons and holes injection rates in the heterojunction LEDs. The processing procedure in this work is a low-cost, low-temperature and convenient way to fabricate ZnO-based heterojunction light-emitting diodes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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