Cancer immunotherapies, including adoptive T cell transfer and immune checkpoint blockades, have recently shown considerable success in cancer treatment. Nevertheless, transferred T cells often ...become exhausted because of the immunosuppressive tumor microenvironment. Immune checkpoint blockades, in contrast, can reinvigorate the exhausted T cells; however, the therapeutic efficacy is modest in 70–80% of patients. To address some of the challenges faced by the current cancer treatments, here T‐cell‐membrane‐coated nanoparticles (TCMNPs) are developed for cancer immunotherapy. Similar to cytotoxic T cells, TCMNPs can be targeted at tumors via T‐cell‐membrane‐originated proteins and kill cancer cells by releasing anticancer molecules and inducing Fas‐ligand‐mediated apoptosis. Unlike cytotoxic T cells, TCMNPs are resistant to immunosuppressive molecules (e.g., transforming growth factor‐β1 (TGF‐β1)) and programmed death‐ligand 1 (PD‐L1) of cancer cells by scavenging TGF‐β1 and PD‐L1. Indeed, TCMNPs exhibit higher therapeutic efficacy than an immune checkpoint blockade in melanoma treatment. Furthermore, the anti‐tumoral actions of TCMNPs are also demonstrated in the treatment of lung cancer in an antigen‐nonspecific manner. Taken together, TCMNPs have a potential to improve the current cancer immunotherapy.
T‐cell‐membrane‐coated nanoparticles (TCMNPs) are developed for cancer immunotherapy. The TCMNPs can be targeted at tumors and kill cancer cells while being resistant to the pro‐tumoral factors in the tumor microenvironment. Indeed, the TCMNPs exhibit a higher therapeutic efficacy than current cancer treatments based on immune checkpoint blockade, and they are effective for the treatment of various tumors.
Polyunsaturated fatty acids (PUFAs) are considered to be critical nutrients to regulate human health and development, and numerous fatty acid desaturases play key roles in synthesizing PUFAs. Given ...the lack of delta-12 and -15 desaturases and the low levels of conversion to PUFAs, humans must consume some omega-3 and omega-6 fatty acids in their diet. Many studies on fatty acid desaturases as well as PUFAs have shown that fatty acid desaturase genes are closely related to different human physiological conditions. Since the first front-end desaturases from cyanobacteria were cloned, numerous desaturase genes have been identified and animals and plants have been genetically engineered to produce PUFAs such as eicosapentaenoic acid and docosahexaenoic acid. Recently, a biotechnological approach has been used to develop clinical treatments for human physiological conditions, including cancers and neurogenetic disorders. Thus, understanding the functions and regulation of PUFAs associated with human health and development by using biotechnology may facilitate the engineering of more advanced PUFA production and provide new insights into the complexity of fatty acid metabolism.
A 1.2 V 20 nm 307 GB/s high-bandwidth memory (HBM) DRAM is presented to satisfy a high-bandwidth requirement of high-performance computing application. The HBM is composed of buffer die and multiple ...core dies, and each core die has 8 Gb DRAM cell array with additional 1 Gb ECC array. At-speed wafer level, a u-bump IO test scheme and an adaptive refresh scheme considering temperature distribution are proposed to guarantee test coverage and stable operation in a power-efficient manner.
The smartphone has many attractive attributes and characteristics that could make it highly addictive, particularly in adolescents. The purpose of this study was to examine the prevalence of young ...adolescents in risk of smartphone addiction and the psychological factors associated with smartphone addiction. Four hundred ninety middle school students completed a self-questionnaire measuring levels of smartphone addiction, behavioral and emotional problems, self-esteem, anxiety, and adolescent-parent communication. One hundred twenty-eight (26.61%) adolescents were in high risk of smartphone addiction. This latter group showed significantly more severe levels of behavioral and emotional problems, lower self-esteem, and poorer quality of communication with their parents. Multiple regression analysis revealed that the severity of smartphone addiction is significantly associated with aggressive behavior (β = .593, t = 3.825) and self-esteem (β = −.305, t = −2.258). Further exploratory and confirmatory studies should consider different sites, demographics, technological mobile devices, platforms, and applications.
Purpose
To evaluate the arthroscopic findings of subtalar joints, including interosseous talocalcaneal ligament (ITCL) tear, in patients with chronic lateral ankle instability (CLAI) and sinus tarsi ...pain.
Methods
A total of 118 ankles (109 patients) having CLAI with sinus tarsi pain who had undergone subtalar arthroscopy and lateral ankle ligament surgery were evaluated. The medical records, radiologic images, and the arthroscopic images and videos were reviewed. ITCL tears were classified into 4 grades: grade 0 (no tear), grade 1 (mild), grade 2 (moderate), and grade 3 (severe). The efficacy of magnetic resonance imaging (MRI) in diagnosing ITCL tears was also evaluated by comparing preoperative official readings of MRI to arthroscopic findings. The pre- and postoperative functional scores were also assessed.
Results
The overall tear rate of ITCL was 107/118 (90.7%). There were 29 ankles (23.6%) with grade 1, 42 ankles (35.6%) with grade 2, and 36 ankles (30.5%) with grade 3 tears. Isolated lateral ankle instability (LAI) was diagnosed in 43 ankles (36.4%), subtalar instability (STI) in 30 ankles (25.4%), and LAI with STI in 45 ankles (38.1%). There was a statistically significant relationship between the ITCL tear grade and the final diagnosis. ITCL tear was confirmed or suspected in 81 ankles (68.6%) on preoperative MRI. Pain Visual Analog Score and functional outcome scores including the American Orthopaedic Foot & Ankle Society and Karlsson–Peterson scores showed significant improvement after the surgery.
Conclusion
A high rate (90.7%) of ITCL tears was noted in CLAI patients with sinus tarsi pain. ITCL damage may play an important role in subtalar instability in patients with CLAI and sinus tarsi pain. Subtalar arthroscopic evaluation for ITCL tear is important for correct diagnosis for CLAI with sinus tarsi pain.
Level of evidence
IV.
Background:
This study examines the correction of lesser toe valgus deviation following proximal chevron metatarsal osteotomy (PCMO) and Akin osteotomy in moderate to severe hallux valgus patients, ...while identifying influencing factors.
Method:
Among 89 patients (116 feet), those with moderate to severe hallux valgus underwent PCMO and Akin osteotomy. Radiologic assessments included preoperative metatarsus adductus angle (MAA), hallux valgus angle (HVA), intermetatarsal angle (IMA), valgus angles of the second to fourth metatarsophalangeal joints, and hallux valgus recurrence. Assessments included visual analog scale (VAS) pain scores, American Orthopaedic Foot & Ankle Society (AOFAS) scores, and patient satisfaction over an average follow-up of 30.6 ± 21.2 (range, 12-99) months.
Results:
The mean preoperative HVA of 34.4 degrees decreased to 8.7 degrees at final follow-up. The valgus angles of the second, third, and fourth toes improved by 37.1%, 27%, and 44.5%, respectively. In metatarsus adductus patients, lesser toe valgus angles were significantly higher both preoperatively and at final follow-up. Hallux valgus recurrence patients had higher preoperative and final follow-up IMA and valgus angles in the second and third toes. Nonrecurrence patients showed greater decreases in these angles. A larger HVA correction corresponded to a greater decrease in lesser toe valgus deviation. VAS and AOFAS scores improved significantly at the last follow-up.
Conclusion:
The study found a significant reduction in the valgus angle of the second, third, and fourth toes after PCMO and Akin osteotomy in moderate to severe hallux valgus cases, without additional surgeries on lesser toes. The lesser toe angular reductions were less pronounced in patients with metatarsus adductus or with hallux valgus recurrence.
Level of Evidence:
Level IV, case series.
Purpose
There are controversies about combining distal tibia medial opening-wedge osteotomy (DTMO) with fibular valgization osteotomy (FVO) when performing supramalleolar osteotomy (SMO) for medial ...ankle osteoarthritis. This study aimed to assess the effect of FVO on the coronal translation of the mechanical axis by comparing the improvement of radiological indices after DTMO with and without FVO.
Methods
Forty-three ankles (mean follow-up: 42.0 months) were reviewed after SMO. Among them, 35/43 (81.4%) underwent DTMO with FVO, while 8/43 (18.6%) underwent DTMO only. To evaluate the effect of FVO radiologically, the medial gutter space (MGS) and talus centre migration (TCM) were measured.
Results
Post-operatively, MGS and TCM were not significantly different after DTMO only and DTMO with FVO. However, the improvement of MGS was significantly higher in the combined FVO group (0.8 mm (standard deviation SD 0.8 mm) vs. 1.5 mm (SD 0.8 mm);
p
= 0.015). More lateral translation of the talus was achieved in the FVO group (5.1 mm (SD 2.3 mm) vs. 7.5 mm (SD 3.0 mm);
p
= 0.033). However, the changes in the MGS and TCM were not significantly correlated with the clinical outcomes (
p
> 0.05).
Conclusion
Our radiological evaluation confirmed a significant medial gutter space widening and lateral talar translation after the addition of FVO. The SMO with fibular osteotomy allows greater shifting of the talus and, therefore, the weight-bearing axis.
Recently, combinations of 2D van der Waals (2D vdW) materials and organic materials have attracted attention because they facilitate the formation of various heterojunctions with excellent interface ...quality owing to the absence of dangling bonds on their surface. In this work, a double negative differential resistance (D‐NDR) characteristic of a hybrid 2D vdW/organic tunneling device consisting of a hafnium disulfide/pentacene heterojunction and a 3D pentacene resistor is reported. This D‐NDR phenomenon is achieved by precisely controlling an NDR peak voltage with the pentacene resistor and then integrating two distinct NDR devices in parallel. Then, the operation of a controllable‐gain amplifier configured with the D‐NDR device and an n‐channel transistor is demonstrated using the Cadence Spectre simulation platform. The proposed D‐NDR device technology based on a hybrid 2D vdW/organic heterostructure provides a scientific foundation for various circuit applications that require the NDR phenomenon.
In this work, a double negative differential resistance (D‐NDR) characteristic of a hybrid 2D van der Waals (2D vdW)/organic tunneling device consisting of a hafnium disulfide/pentacene heterojunction and a 3D pentacene resistor is reported. Then the operation of a controllable‐gain amplifier configured with the D‐NDR device and an n‐channel transistor is demonstrated using the Cadence Spectre simulation platform.
The supramalleolar osteotomy is a joint-preserving surgical procedure. It is a very good treatment option for the asymmetric varus ankle and medial compartment osteoarthritis. The primary objective ...of the procedure is to shift medial concentration of stress toward the lateral intact articular cartilage to redistribute the joint loads during ambulation. Several studies have shown that deformities of the ankle result in uneven load distribution in the ankle joint, which eventually leads to articular cartilage degeneration. Since the lateral articular cartilage is intact, joint-sacrificing procedures such as total ankle replacement or ankle arthrodesis are not the most appropriate treatment choices for medial compartment arthritis. Results of supramalleolar osteotomies are very promising in terms of functional outcome and pain relief. In younger patients with medial compartment varus ankle osteoarthritis or even with a normal tibial anterior surface angle, supramalleolar osteotomies can be performed to realign the ankle to promote regeneration of the asymmetrically damaged cartilage. In this review article, we will discuss the indications, complications, surgical techniques, and outcomes of the supramalleolar osteotomy reported in the current literature.
Background Atopic dermatitis (AD) and psoriasis are the 2 most common chronic inflammatory skin diseases. There is an unmet medical need to overcome limitations for transcutaneous drug development ...posed by the skin barrier. Objective We aimed to identify a novel transdermal delivery peptide and to develop a transcutaneously applicable immunomodulatory protein for treating AD and psoriasis. Methods We identified and generated reporter proteins conjugated to astrotactin 1–derived peptide (AP), a novel transdermal delivery peptide of human origin, and analyzed the intracellular delivery efficiency of these proteins in mouse and human skin cells and tissues using multiphoton confocal microscopy. We also generated a recombinant therapeutic protein, AP–recombinant protein tyrosine phosphatase (rPTP), consisting of the phosphatase domain of the T-cell protein tyrosine phosphatase conjugated to AP. The immunomodulatory function of AP-rPTP was confirmed in splenocytes on cytokine stimulation and T-cell receptor stimulation. Finally, we confirmed the in vivo efficacy of AP-rPTP transdermal delivery in patients with oxazolone-induced contact hypersensitivity, ovalbumin-induced AD-like, and imiquimod-induced psoriasis-like skin inflammation models. Results AP-conjugated reporter proteins exhibited significant intracellular transduction efficacy in keratinocytes, fibroblasts, and immune cells. In addition, transcutaneous administration of AP-dTomato resulted in significant localization into the dermis and epidermis in both mouse and human skin. AP-rPTP inhibited phosphorylated signal transducer and activator of transcription (STAT) 1, STAT3, and STAT6 in splenocytes and also regulated T-cell activation and proliferation. Transcutaneous administration of AP-rPTP through the paper-patch technique significantly ameliorated skin tissue thickening, inflammation, and cytokine expression in both AD-like and psoriasis-like dermatitis models. Conclusion We identified a 9-amino-acid novel transdermal delivery peptide, AP, and demonstrated its feasibility for transcutaneous biologic drug development. Moreover, AP-rPTP is a novel immunomodulatory drug candidate for human dermatitis.
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