The 2018 Nobel Prize in Physiology or Medicine was awarded to Tasuku Honjo and James Allison for their discoveries in cancer immunology. Professor Honjo was awarded due to his discovery of the ...programmed death molecule-1 (PD-1) on T cells. Professor Allison discovered another important immunosuppressive molecule: cytotoxic T-lymphocyte antigen-4 (CTLA-4). Suppression of T cell activation by PD-1 and/or CTLA-4 is considered one of the major escape mechanisms of cancer cells. Inhibition of these molecules by immune checkpoint inhibitors can successfully activate the immune system to fight cancer. Checkpoint inhibitors have brought about a major breakthrough in cancer immunotherapy, reviving the hope of curing patients with end-stage cancer, including a wide variety of cancer types. In metastatic malignant melanoma, the previous long-term survival of only 5% can now be extended to 50% with anti-PD-1 plus anti-CTLA-4 combined treatment in the latest report. More checkpoint molecules such as lymphocyte-activation gene 3 and T cell immunoglobulin and mucin domain 3 are under investigation. The achievement of Drs. Honjo and Allison in cancer immunotherapy has encouraged research into other immune-pathological diseases.
This study is a meta-analysis of randomized controlled trials comparing the efficacy of transcutaneous electrical nerve stimulation (TENS) to a control and to other nerve stimulation therapies (NSTs) ...for the treatment of chronic back pain.
Citations were identified in MEDLINE, the Cochrane Library, Google Scholar, and ClinicalTrials.gov through June 2014 using the following keywords: nerve stimulation therapy, transcutaneous electrical nerve stimulation, back pain, chronic pain. Control treatments included sham, placebo, or medication only. Other NSTs included electroacupuncture, percutaneous electrical nerve stimulation, and percutaneous neuromodulation therapy.
Twelve randomized controlled trials including 700 patients were included in the analysis. The efficacy of TENS was similar to that of control treatment for providing pain relief (standardized difference in means SDM = -0.20; 95% confidence interval CI, -0.58 to 0.18; P = 0.293). Other types of NSTs were more effective than TENS in providing pain relief (SDM = 0.86; 95% CI, 0.15-1.57; P = 0.017). Transcutaneous electrical nerve stimulation was more effective than control treatment in improving functional disability only in patients with follow-up of less than 6 weeks (SDM = -1.24; 95% CI, -1.83 to -0.65; P < 0.001). There was no difference in functional disability outcomes between TENS and other NSTs.
These results suggest that TENS does not improve symptoms of lower back pain, but may offer short-term improvement of functional disability.
Nanostructure-based sensors are capable of sensitive and label-free detection for biomedical applications. However, plasmonic sensors capable of highly sensitive detection with high-throughput and ...low-cost fabrication techniques are desirable. We show that capped gold nanoslit arrays made by thermal-embossing nanoimprint method on a polymer film can produce extremely sharp asymmetric resonances for a transverse magnetic-polarized wave. An ultrasmall linewidth is formed due to the enhanced Fano coupling between the cavity resonance mode in nanoslits and surface plasmon resonance mode on periodic metallic surface. With an optimal slit length and width, the full width at half-maximum bandwidth of the Fano mode is only 3.68 nm. The wavelength sensitivity is 926 nm/RIU for 60-nm-width and 1,000-nm-period nanoslits. The figure of merit is up to 252. The obtained value is higher than the theoretically estimated upper limits of the prism-coupling SPR sensors and the previously reported record high figure-of-merit in array sensors. In addition, the structure has an ultrahigh intensity sensitivity up to 48,117%/RIU.
Obesity is a well‐known risk factor for breast cancer formation and is associated with elevated mortality and a poor prognosis. An obesity‐mediated inflammatory microenvironment is conducive to the ...malignant progression of tumors. However, the detailed molecular mechanism is still needed to be clarified. Herein, we identified that breast cancer cells from mice with diet‐induced obesity exhibited increased growth, invasiveness, and stemness capacities. A transcriptome analysis revealed that expressions of interleukin 33 (IL33) signaling pathway‐related genes were elevated in obesity‐associated breast cancer cells. Importantly, IL33 expression was significantly associated with the yes‐associated protein (YAP) signature, and IL33 was transcriptionally regulated by YAP. Suppression of IL33 reduced tumor migration and invasion, while the addition of IL33 activated nuclear factor (NF)‐κB signaling and revived tumor mobility in YAP‐silenced cells. Furthermore, suppression of YAP attenuated IL33 expression which was accompanied by relief of obesity‐mediated immunosuppression. Clinical analyses showed that IL33 expression was markedly associated with macrophage and regulatory T cell infiltration. These findings reveal a crucial role of the YAP/IL33 axis in promoting aggressiveness and immunosuppression of obesity‐associated breast cancer progression.
In light of industrial developments, water pollution by heavy metals as hazardous chemicals has garnered attention. Addressing the urgent need for efficient heavy metal removal from aqueous ...environments, this study delves into using poly-γ-glutamic acid (γ-PGA) for the bioflocculation of heavy metals. Utilizing γ-PGA variants from
with different molecular weights and salt forms (Na-bonded and Ca-bonded), the research evaluates their adsorption capacities for copper (Cu), lead (Pb), and cadmium (Cd) ions. It was found that Na-bonded γ-PGA with a high molecular weight showed the highest heavy metal adsorption (92.2-98.3%), particularly at a 0.5% concentration which exhibited the highest adsorption efficiency. Additionally, the study investigated the interaction of γ-PGA in mixed heavy metal environments, and it was discovered that Na-γ-PGA-HM at a 0.5% concentration showed a superior adsorption efficiency for Pb ions (85.4%), highlighting its selectivity as a potential effective biosorbent for wastewater treatment. This research not only enlightens the understanding of γ-PGA's role in heavy metal remediation but also underscores its potential as a biodegradable and non-toxic alternative for environmental cleanup. The findings pave the way for further exploration into the mechanisms and kinetics of γ-PGA's adsorption properties.
Nanocavities inscribed in a gold thin film are optimized and designed to form a metasurface. We demonstrate both numerically and experimentally the creation of surface plasmon (SP) vortex carrying ...orbital angular momentum in the metasurface under linearly polarized optical excitation that carries no optical angular momentum. Moreover, depending on the orientation of the exciting linearly polarized light, we show that the metasurface is capable of providing dynamic switching between SP vortex formation or SP subwavelength focusing. The resulting SP intensities are experimentally measured using a near-field scanning optical microscope and are found in excellent quantitative agreements as compared to the numerical results.
Aims
To use experimental periodontitis models in rats to investigate the correlation between local expression of the complement components C3b and C4b in periodontal tissues and disease severity, and ...to assess the therapeutic effects of targeting C3b/C4b on inflammatory bone loss.
Materials and Methods
The gingival expression of C3, C3b, and C4b in animal experimental periodontitis models were analysed immunohistochemically. The therapeutic effects of the C3b/C4b inhibitor (SB002) on ligation‐induced experimental periodontitis was examined using biochemical, histological, and immunohistochemical analyses.
Results
The gingival expression levels of C3, C3b, and C4b were positively correlated with the severity of periodontitis. Moreover, both single and multiple injections of the C3b/C4b inhibitor had preventive and therapeutic effects on alveolar bone loss in ligation‐induced experimental periodontitis with no associated adverse consequences.
Conclusions
The association between C3b/C4b and periodontitis may provide a basis for the development of novel therapeutic strategies for periodontitis and other inflammatory diseases.
Improper acetabulum component position is a significant risk factor for postoperative dislocation after total hip arthroplasty. Several radiographic two‐dimensional methods exist for measuring ...acetabulum component anteversion, but they cannot distinguish between anteversion and retroversion. “Liaw's version,” initially proposed as a simple mathematical standardized two‐dimensional method, was modified to the computerized ellipse method, proving superior accuracy to traditional two‐dimensional methods. In this article, we demonstrated its application in detecting and measuring retroverted acetabulum component. We obtained anteroposterior pelvis radiographs from a patient undergoing total hip arthroplasty on the day of surgery and 2 weeks postoperatively. The computerized ellipse method was used to measure the acetabulum component orientation. Upon comparison, the difference between θ assigned to be retroverted (9.52–8.56 = 0.96) is much smaller than the difference between θ assigned to be anteverted (23.81–18.86 = 4.95), leading us to determine retroversion. This was further confirmed by computed tomography at the 6‐week follow‐up. We propose that using the computerized ellipse method to measure Liaw's version can be a valuable tool in identifying acetabulum component retroversion on anteroposterior radiographs during routine postoperative follow‐up and retrospective assessments of total hip arthroplasty patients.
The computerized ellipse method, as far as we know, is the first two‐dimensional radiographic method capable of distinguishing retroverted acetabular components in plain radiographs. The Elliversion software facilitates a quick and easy measurement process. Although further cases are necessary to determine the reliability of this method, it can be suggested as a tool for detecting acetabular component retroversion on anteroposterior radiographs during routine postoperative follow‐up and retrospective reviews of patients who have undergone THA.
Nanostructure-based sensors are capable of sensitive and label-free detection for biomedical applications. However, high-throughput and low-cost fabrication techniques are the main issues which ...should be addressed. In this study, chip-based nanostructures for intensity-sensitive detection were fabricated and tested using a thermal-annealing-assisted template-stripping method. Large-area uniform nanoslit arrays with a 500 nm period and various slit widths, from 30 to 165 nm, were made on plastic films. A transverse magnetic-polarized wave in these gold nanostructures generated sharp and asymmetric Fano resonances in transmission spectra. The full width at half-maximum bandwidth decreased with the decrease of the slit width. The narrowest bandwidth was smaller than 10 nm. Compared to nanoslit arrays on glass substrates using electron-beam lithography, the proposed chip has a higher intensity sensitivity up to 10367%/RIU (refractive index unit) and reaches a figure of merit up to 55. The higher intensity sensitivity for the template-stripped nanostructure is attributed to a smoother gold surface and larger grain sizes on the plastic film, which reduces the surface plasmon propagation loss.
Open Data Processing Services (ODPS) offers vast storage capacity and excellent efficiency, which collects and stores a lot of data. As an essential component of ODPS, location-based services (LBS) ...are widely used in many aspects. However, LBS generates tens of thousands trajectories, which have a significant likelihood of revealing personal information. In order to address this kind of privacy concerns, a novel model, namely Privacy-Aware Trajectory Generation Model with Differential Privacy (DP-TrajGAN), is proposed in this paper. Firstly, the long short-term memory network (LSTM) is improved and introduced into in the generative adversarial network (GAN) to learn the original distribution. Subsequently, the privacy-preserving of GAN is further enhanced using differential privacy (DP) while retaining the original features of the trajectories, which is called DP-TrajGAN. Furthermore, the privacy budget allocation in the DP is modeled using the Partially Observable Markov Decision Process (POMDP), which takes into account the trade-off between privacy and utility. The experimental findings demonstrate that, when compared to other models, DP-TrajGAN can provide higher quality trajectories with retained statistical features and effective privacy preservation.
•LSTM is applied in DP-TrajGAN to learn the distribution of trajectories.•Differential privacy is exploited to resist background knowledge attacks.•POMDP is applied in DP-TrajGAN to balance the utility and privacy.•The performance is analyzed under different datasets with other models.
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