In Vitro and In Vivo Anti-Candida albicans Activity of a Scorpion-Derived Peptide.

The increasing infection and drug resistance frequency has encouraged the exploration of new and effective anti-Candida albicans agents. In this study, CT-K3K7, a scorpion antimicrobial peptide derivative, effectively inhibit the growth of C. albicans. CT-K3K7 killed C. albicans cells in a dose-dependent manner, mainly by damaging the plasma membrane. CT-K3K7 could also disrupt the nucleus and interact with nucleic acid. Moreover, CT-K3K7 induced C. albicans cells necrosis via a reactive oxygen species (ROS)-related pathway. Furthermore, CT-K3K7 inhibited the hyphal and biofilm formation of C. albicans. In the mouse skin subcutaneous infection model, CT-K3K7 significantly prevented skin abscess formation and reduced the number of C. albicans cells recovered from the infection area. Taken together, CT-K3K7 has the potential to be a therapeutic for C. albicans skin infections.

Antifungal efficacy of scorpion derived peptide K1K8 against Candida albicans in vitro and in vivo.

As an alternative class of antimicrobial agents, antimicrobial peptides (AMPs) have gained significant attention. In this study, K1K8, a scorpion AMP derivative, showed effective activity against Candida albicans including clinically resistant strains. K1K8 killed C. albicans cells mainly by damaging the cell membrane and inducing necrosis via an ROS-related pathway. K1K8 could also interact with DNA after damaging the nuclear envelope. Moreover, K1K8 inhibited hyphal development and biofilm formation of C. albicans in a dose-dependent manner. In the mouse skin infection model, K1K8 significantly decreased the counts of C. albicans cells in the infection area. Overall, K1K8 is a potential anti-infective agent against skin infections caused by C. albicans.

Focusing on the value of cooperative learning in physical education: a bibliometric analysis.

The shift toward cooperative learning has highlighted the growing advantages of individual learning modes during the transition. Nevertheless, a systematic compilation of the precise classification and developmental dynamics of cooperative learning in PE has been absent. This study aimed to organize the existing progress and significance of collaborative learning. The study entailed a meticulous systematic review process, examining 169 articles in this domain with the aid of visualization software. The results of the study indicate that the overall use of cooperative learning in physical education is on the rise and will reach its highest level in 2021; Second, the keywords, major core scholars, journals, countries, and major research topics; the visual knowledge map reveals the major research topics of intrinsic motivation, cooperative learning, motor skills, self-learning, written expression, and pedagogical models. The research primarily centers on primary and secondary education, followed by teacher training and higher education. At the primary and secondary school levels, there is a specific focus on aspects such as motivation, teacher-student relationships, and the group atmosphere. This research also explores sustainable development and training for PE teachers, model integration, and its influence on students' intrinsic motivation; and finally, the future directions of cooperative learning in PEare summarized. This study provides meaningful and valuable information on how cooperative learning models can be used and developed in various teaching and learning environments, physical education teacher education, and overall student development.

FBANet: Transfer Learning for Depression Recognition Using a Feature-Enhanced Bi-Level Attention Network.

The House-Tree-Person (HTP) sketch test is a psychological analysis technique designed to assess the mental health status of test subjects. Nowadays, there are mature methods for the recognition of depression using the HTP sketch test. However, existing works primarily rely on manual analysis of drawing features, which has the drawbacks of strong subjectivity and low automation. Only a small number of works automatically recognize depression using machine learning and deep learning methods, but their complex data preprocessing pipelines and multi-stage computational processes indicate a relatively low level of automation. To overcome the above issues, we present a novel deep learning-based one-stage approach for depression recognition in HTP sketches, which has a simple data preprocessing pipeline and calculation process with a high accuracy rate. In terms of data, we use a hand-drawn HTP sketch dataset, which contains drawings of normal people and patients with depression. In the model aspect, we design a novel network called Feature-Enhanced Bi-Level Attention Network (FBANet), which contains feature enhancement and bi-level attention modules. Due to the limited size of the collected data, transfer learning is employed, where the model is pre-trained on a large-scale sketch dataset and fine-tuned on the HTP sketch dataset. On the HTP sketch dataset, utilizing cross-validation, FBANet achieves a maximum accuracy of 99.07% on the validation dataset, with an average accuracy of 97.71%, outperforming traditional classification models and previous works. In summary, the proposed FBANet, after pre-training, demonstrates superior performance on the HTP sketch dataset and is expected to be a method for the auxiliary diagnosis of depression.

Recent advances in lipid nanovesicles for targeted treatment of spinal cord injury.

The effective regeneration and functional restoration of damaged spinal cord tissue have been a long-standing concern in regenerative medicine. Treatment of spinal cord injury (SCI) is challenging due to the obstruction of the blood-spinal cord barrier (BSCB), the lack of targeting of drugs, and the complex pathophysiology of injury sites. Lipid nanovesicles, including cell-derived nanovesicles and synthetic lipid nanovesicles, are highly biocompatible and can penetrate BSCB, and are therefore effective delivery systems for targeted treatment of SCI. We summarize the progress of lipid nanovesicles for the targeted treatment of SCI, discuss their advantages and challenges, and provide a perspective on the application of lipid nanovesicles for SCI treatment. Although most of the lipid nanovesicle-based therapy of SCI is still in preclinical studies, this low immunogenicity, low toxicity, and highly engineerable nanovesicles will hold great promise for future spinal cord injury treatments.

HSPA8 acts as an amyloidase to suppress necroptosis by inhibiting and reversing functional amyloid formation.

Ultra-stable fibrous structure is a hallmark of amyloids. In contrast to canonical disease-related amyloids, emerging research indicates that a significant number of cellular amyloids, termed 'functional amyloids', contribute to signal transduction as temporal signaling hubs in humans. However, it is unclear how these functional amyloids are effectively disassembled to terminate signal transduction. RHIM motif-containing amyloids, the largest functional amyloid family discovered thus far, play an important role in mediating necroptosis signal transduction in mammalian cells. Here, we identify heat shock protein family A member 8 (HSPA8) as a new type of enzyme - which we name as 'amyloidase' - that directly disassembles RHIM-amyloids to inhibit necroptosis signaling in cells and mice. Different from its role in chaperone-mediated autophagy where it selects substrates containing a KFERQ-like motif, HSPA8 specifically recognizes RHIM-containing proteins through a hydrophobic hexapeptide motif N(X1)φ(X3). The SBD domain of HSPA8 interacts with RHIM-containing proteins, preventing proximate RHIM monomers from stacking into functional fibrils; furthermore, with the NBD domain supplying energy via ATP hydrolysis, HSPA8 breaks down pre-formed RHIM-amyloids into non-functional monomers. Notably, HSPA8's amyloidase activity in disassembling functional RHIM-amyloids does not require its co-chaperone system. Using this amyloidase activity, HSPA8 reverses the initiator RHIM-amyloids (formed by RIP1, ZBP1, and TRIF) to prevent necroptosis initiation, and reverses RIP3-amyloid to prevent necroptosis execution, thus eliminating multi-level RHIM-amyloids to effectively prevent spontaneous necroptosis activation. The discovery that HSPA8 acts as an amyloidase dismantling functional amyloids provides a fundamental understanding of the reversibility nature of functional amyloids, a property distinguishing them from disease-related amyloids that are unbreakable in vivo.

Nanostructures and Nanotechnologies for the Detection of Extracellular Vesicle.

Liquid biopsy has been taken as a minimally invasive examination and a promising surrogate to the clinically applied tissue-based test for the diagnosis and molecular analysis of cancer. Extracellular vesicles (EVs) carry complex molecular information from the tumor, allowing for the multicomponent analysis of cancer and would be beneficial to personalized medicine. In this review, the advanced nanomaterials and nanotechniques for the detection and molecular profiling of EVs, highlight the advantages of nanotechnology in the high-purity isolation and the high-sensitive and high-specific identification of EVs, are summarized. An outlook on the clinical application of nanotechnology-based liquid biopsy in the diagnosis, prognostication, and surveillance of cancer is also provided. It provides information for developing liquid biopsy based on EVs by discussing the advantages and challenges of functionalized nanomaterials and various nanotechnologies.

m6 A Reader YTHDF1-Targeting Engineered Small Extracellular Vesicles for Gastric Cancer Therapy via Epigenetic and Immune Regulation.

N6 -methyladenosine (m6 A) modulators decide the fate of m6 A-modified transcripts and drive cancer development. RNA interference targeting m6 A modulators promise to be an emerging cancer therapy but is challenging due to its poor tumor targeting and high systematic toxicity. Here engineered small extracellular vesicles (sEVs) with high CD47 expression and cyclic arginine-glycine-aspartic (c(RGDyC)) modification are developed for effective delivery of short interfering RNA against m6 A reader YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) to treat gastric cancer via epigenetic and immune regulation. This nanosystem efficiently depletes YTHDF1 expression and suppresses gastric cancer progression and metastasis through hampering frizzled7 translation and inactivating Wnt/ß-catenin pathway in an m6 A dependent manner. Loss of YTHDF1 mediates overexpression of interferon (IFN)-γ receptor 1 and enhances IFN-γ response, promoting expression of major histocompatibility complex class I on tumor cells to achieve self-presentation of the immunogenic tumor cells to stimulate strong cytotoxic T lymphocytes responses. CD47 expression on the engineered sEVs can competitively bind with signal regulatory protein α to enhance phagocytosis of the tumor cells by tumor-associated macrophages. This versatile nanoplatform provides an efficient and low toxic strategy to inhibit epigenetic regulators and holds great potential in promoting immunotherapy.

Enhanced photodynamic therapy through multienzyme-like MOF for cancer treatment.

Overcoming resistance to apoptosis is a major challenge in cancer therapy. Recent research has shown that manipulating mitochondria, the organelles critical for energy metabolism in tumor cells, can increase the effectiveness of photodynamic therapy and trigger apoptosis in tumor cells. However, there is currently insufficient research and effective methods to exploit mitochondrial damage to induce apoptosis in tumor cells and improve the effectiveness of photodynamic therapy. In this study, we present a novel nanomedicine delivery and therapeutic system called PyroFPSH, which utilizes a nanozymes-modified metal-organic framework as a carrier. PyroFPSH exhibits remarkable multienzyme-like activities, including glutathione peroxidase (GPx) and catalase (CAT) mimicry, allowing it to overcome apoptosis resistance, reduce endogenous glutathione levels, and continuously generate reactive oxygen species (ROS). In addition, PyroFPSH can serve as a carrier for the targeted delivery of sulfasalazine, a drug that can induce mitochondrial depolarization in tumor cells, thereby reducing oxygen consumption and energy supply in the mitochondria of tumor cells and weakening resistance to other synergistic treatment approaches. Our experimental results highlight the potential of PyroFPSH as a versatile nanoplatform in cancer treatment. This study expands the biomedical applications of nanomaterials as platforms and enables the integration of various novel therapeutic strategies to synergistically improve tumor therapy. It deepens our understanding of multienzyme-mimicking active nanocarriers and mitochondrial damage through photodynamic therapy. Future research can further explore the potential of PyroFPSH in clinical cancer treatment and improve its drug loading capacity, biocompatibility and targeting specificity. In summary, PyroFPSH represents a promising therapeutic approach that can provide new insights and possibilities for cancer treatment.

Early Education Application Software Based on Artificial Intelligence VR Technology.

In order to solve the problems of restricted classroom and lack of repeated training in good curriculum, the design and development of a school life adaptation curriculum based on VR is proposed. This study identified six life adaptation themes for design and development (recognizing facial expressions, crossing the road, how to get lost, shopping, taking public transport, and job interview) and set the objectives, design principles, specific content, teaching evaluation, and other aspects of virtual reality life adaptation course. Combined with the characteristics of virtual reality, the implementation suggestions and matters needing attention are put forward. The results showed that, in the recognition of human facial expressions, 51 experts thought it was appropriate, 3 experts thought it needed to be modified, and no expert thought it was inappropriate. On the topic of crossing the road, 46 experts thought it was appropriate, eight thought it needed to be modified, and no expert thought it was inappropriate. On the theme of taking public transportation, 48 experts thought it was appropriate, 6 experts thought it needed to be modified, and no expert thought it was inappropriate. For the three major topics of how to get lost, shopping, and job interview, 2-3 experts put forward different opinions and think that the topic is not appropriate mainly because the grade arrangement is not appropriate. Conclusion. The VR-based curriculum for school life adaptation has been reviewed by experts and revised by researchers. It is scientific, interesting, and operable, solves the teaching problems of life adaptation teachers, and provides a safe, reliable, and effective practice channel for students.

Clinical effect of day case arthroscopic surgery in tibial-eminence fracture in adults using button plates.

Background: The tibial-eminence fracture (TEF) is an anterior cruciate-ligament avulsion fracture with a low incidence. Many surgical techniques have been described, but none of them allow early functional exercise, and there are many postoperative complications. Purposes: This study aimed to evaluate the early clinical efficacy and complications of day case arthroscopic-surgery treatment of adult TEF with button plates. Methods: We retrospectively analyzed patients with TEF treated with arthroscopic surgery. Clinical subjective evaluation included International Knee Documentation Committee (IKDC) subjective score, Lysholm Knee Score, and Visual Analog Scale (VAS) score. Knee joint scores were evaluated by Lysholm score. Clinical objective assessment included the Lachman test, anterior-drawer test (ADT), IKDC, and range of motion. We assessed patient quality of life using a life summary table. Assessment of fracture healing and internal fixation was based on lateral x-rays of the knee joint. We measured and evaluated patient satisfaction at the last follow-up in accordance with Marsh criteria. Results: At final follow-up (average follow-up time, 28.23 ± 3.14 months), we evaluated results from 22 patients (22 knees). Average patient age during surgery was 33.64 ± 6.96 years. Average time from injury to surgery was 6.59 ± 1.47 h. Postoperative function was better than pre-operative function in all patients. IKDC subjective score, Lysholm score, and VAS score were better at final follow-up than before surgery. Differences in Lachman test and ADT scores before and after surgery were statistically significant. According to Intra-articular button position classification, 6 patients (6 knees) showed ideal position (A), 16 patients (16 knees) showed nearly ideal position (B), and none of the patients had nonideal position (C). The fractures of 22 patients healed completely; 2 patients had a 5°-10° knee joint dysfunction, and 1 had an abnormal knee sound. According to intra-articular button position classification, the rate of ideal position was 100%. Patient satisfaction rate was 81.8%. Conclusion: Day surgery using double-button plates to treat TEF could achieve anatomical reduction, power and stability, as well as good clinical efficacy.

Image-free multi-character recognition.

The recently developed image-free sensing technique decouples semantic information directly from compressed measurements without image reconstruction, which maintains the advantages of both the light hardware and software. However, the existing attempts have failed to classify multi-semantic information with multiple targets in the practical fieldof-view. In this Letter, we report a novel image-free sensing technique to tackle the multi-target recognition challenge for the first time, to the best of our knowledge. Different from the convolutional layer stack of image-free single-pixel networks, the reported convolutional recurrent neural network (CRNN) uses the bidirectional LSTM architecture to predict the distribution of multiple characters simultaneously. The framework enables capture of the long-range dependencies, providing a high recognition accuracy of multiple characters. We demonstrate the technique's effectiveness in license plate detection, which achieves a recognition accuracy of 87.60% at a sampling rate of 5% with a refresh rate higher than 100 FPS.

Machine Learning-Assisted Dual-Marker Detection in Serum Small Extracellular Vesicles for the Diagnosis and Prognosis Prediction of Non-Small Cell Lung Cancer.

Small extracellular vesicles (sEVs) carry molecular information from their source cells and are desired biomarkers for cancer diagnosis. We establish a machine learning-assisted dual-marker detection method to analyze the expression of epidermal growth factor receptor (EGFR) and C-X-C chemokine receptor 4 (CXCR4) in serum sEVs for the diagnosis and prognosis prediction of non-small cell lung cancer (NSCLC). We find that the serum sEV EGFR and CXCR4 are significantly higher in advanced stage NSCLC (A/NSCLC) patients compared to early stage NSCLC (E/NSCLC) patients and the healthy donors (HDs). A receiver operating characteristic curve (ROC) analysis demonstrates that the combination of EGFR and CXCR4 in serum sEVs as an efficient diagnostic index and malignant degree indicator for NSCLC. Machine learning further shows a diagnostic accuracy of 97.4% for the training cohort and 91.7% for the validation cohort based on the combinational marker. Moreover, this machine leaning-assisted serum sEV analysis successfully predicts the possibility of tumor relapse in three NSCLC patients by comparing their serum sEVs before and three days after surgery. This study provides an intelligent serum sEV-based assay for the diagnosis and prognosis prediction of NSCLC, and will benefit the precision management of NSCLC.

Photophysical properties of a boron analogue of coumarin.

In this report, we present a study into the structure and electronic properties of difluoroboronsalicylaldoxime (DFBS), a boron-based structural analog of coumarin. The modification of the heterocyclic ring of coumarin with boron results in a compound with similar structural parameters and molecular orbitals to coumarin. DFT and TDDFT calculations reveal a significant stabilization of the LUMO in DFBS; this is supported by a ∼40 nm red shift of the lowest electronic transition in the absorption spectrum. Interestingly, DFBS is emissive, while unmodified coumarin is effectively non-radiative. Comparisons between DFBS, emissive coumarin variants, and unmodified coumarin suggest that the charge transfer character of the transition contributes to the fluorescence.

Quantitative Nanomechanical Analysis of Small Extracellular Vesicles for Tumor Malignancy Indication.

The nanomechanical properties of tumor-derived small extracellular vesicles (sEVs) are essential to cancer progression. Here, nanoindentation is utilized on atomic force microscopy (AFM) to quantitatively investigate the nanomechanical properties of human breast cancer cell-derived sEVs at single vesicle level and explore their relationship with tumor malignancy and vesicle size. It is demonstrated that the stiffness of the sEVs results from the combined contribution of the bending modulus and osmotic pressure of the sEVs. The stiffness and osmotic pressure increase with increasing malignancy of the sEVs and decrease with increasing size of the sEVs. The bending modulus decreases with increasing malignancy of the sEVs and is lower in smaller sEVs. This study builds relationship between the nanomechanical signature of the sEV and tumor malignancy, adding information for better understanding cancer mechanobiology.

The MLKL kinase-like domain dimerization is an indispensable step of mammalian MLKL activation in necroptosis signaling.

MLKL phosphorylation by RIP3 is the commitment step of necroptosis execution, which could induce MLKL activation featured as MLKL monomer-oligomer transition. Here, we reported that the dimerization of the MLKL kinase-like domain was the direct consequence of RIP3 triggered MLKL-phosphorylation. Two inter-dimer interfaces were found in the crystal structure of human MLKL. Mutations destroying both interfaces could prevent RIP3-induced MLKL oligomerization and necroptosis efficiently. Moreover, we confirmed MLKL self-assembly by the internal coiled-coil region is necessary for MLKL oligomerization and function. The mutations disrupting coiled-coil self-assembly repressed necroptosis, but it did not prevent RIP3-induced dimerization of the MLKL kinase-like domain. So that, MLKL activation is a sequential process, which begins with kinase-like domain dimerization, and followed by internal coiled-coil region self-assembly to form a proper MLKL oligomer. Besides human MLKL, structural and functional analysis showed the kinase-like domain dimerization was conserved among mammalian species, suggesting it is a general step of the RIP3-induced MLKL activation process.

Proton therapy for craniopharyngioma in adults: a protocol for systematic review and meta-analysis.

INTRODUCTION: Craniopharyngioma is the most challenging to treat brain tumour with high recurrence rates, which can be effectively reduced by adjuvant radiotherapy. In recent years, proton therapy (PT), with its physical properties of heavy ion beam, that is, Prague peak phenomenon, has been more frequently used in patients with craniopharyngioma. Compared with conventional X-ray beam radiotherapy, PT can reduce the damage to normal tissues and enlarge the damage to tumours. Some studies have shown that PT has advantages in the treatment of craniopharyngioma in adults. However, the optimal management of craniopharyngioma remains controversial. The purpose of this study was to evaluate the efficacy and safety of PT for craniopharyngioma in adults. METHODS AND ANALYSIS: We will search six databases (MEDLINE, EMBASE, Web of Science, the Cochrane Library, Amed, Scopus), clinical research registration websites and grey literature, aiming to identify randomised controlled trials (RCTs) on PT for craniopharyngioma in adults between 1 January 1954 and 28 September 2021. In the RCTs, PT will be used as the intervention group, and conventional X-ray beam radiotherapy will be used as the comparator group. Tumour recurrence and survival will be the primary outcome, and treatment-related toxicity will be the secondary outcome. The study selection, data extraction, bias risk and quality evaluation will be operated by two to four researchers independently. We will use Review Manager V.5.2 (RevMan V.5.2) for data analysis. If there is significant heterogeneity, we will identify the source of heterogeneity by subgroup analysis. ETHICS AND DISSEMINATION: Our study is based on existing RCTs and does not require ethical approval. The results of the study will be published in a peer-reviewed journal or at a related conference. PROSPERO REGISTRATION NUMBER: CRD42020200909.

Medium-Term Clinical Results of High-Flexion Knee Prostheses in Patients with Rheumatoid Arthritis.

OBJECTIVE: This study was performed to evaluate the function and satisfaction outcome of patients with rheumatoid arthritis (RA) who underwent total knee arthroplasty (TKA) with high-flexion prostheses. MATERIALS AND METHODS: Twenty-two patients (35 knees) using high-flexion prostheses (Zimmer, Warsaw, IN) were followed up for a period of 7-11 years from February 2007 to December 2009. Clinical and radiographic follow-up was performed using Hospital for Special Surgery (HSS), Short-Form 36 scores (SF-36), American Knee Society score (KSS), and Knee Society Total Knee Arthroplasty Roentgenographic Evaluation and Scoring System. Patient satisfaction assessments took place at the final follow-up sessions using the Marsh Satisfaction Questionnaire. RESULTS: The average ROM improved from preoperative 68.43° ± 33.78° to 95.54° ± 7.03° at the final follow-up. The HSS score and KSS score for pain improved from (46.49 ± 12.73) points to (85.46 ± 3.90) points and from 20.57 ± 5.91 points to 47.43 ± 3.51 points at the follow-up evaluation, respectively. Physical Component Summary(PCS) and Physical Component Summary (MCS) scores were 45.38 and 52.56, respectively by the end of follow-up. Deep venous thrombosis developed in one patient and one patient required surgical revision due to infection. There were no instances of prosthetic loosening. The satisfaction rate of patients was 95.5%. CONCLUSION: Although this particular model of TKA did not yield high-flexion angles (ie, 140°) required for kneeling, squatting, or rising from the floor, significant clinical and radiographic gains were evident in these patients with RA.

The structure of a minimum amyloid fibril core formed by necroptosis-mediating RHIM of human RIPK3.

Receptor-interacting protein kinases 3 (RIPK3), a central node in necroptosis, polymerizes in response to the upstream signals and then activates its downstream mediator to induce cell death. The active polymeric form of RIPK3 has been indicated as the form of amyloid fibrils assembled via its RIP homotypic interaction motif (RHIM). In this study, we combine cryogenic electron microscopy and solid-state NMR to determine the amyloid fibril structure of RIPK3 RHIM-containing C-terminal domain (CTD). The structure reveals a single protofilament composed of the RHIM domain. RHIM forms three ß-strands (referred to as strands 1 through 3) folding into an S shape, a distinct fold from that in complex with RIPK1. The consensus tetrapeptide VQVG of RHIM forms strand 2, which zips up strands 1 and 3 via heterozipper-like interfaces. Notably, the RIPK3-CTD fibril, as a physiological fibril, exhibits distinctive assembly compared with pathological fibrils. It has an exceptionally small fibril core and twists in both handedness with the smallest pitch known so far. These traits may contribute to a favorable spatial arrangement of RIPK3 kinase domain for efficient phosphorylation.