Comparative Efficacy of Acute Exercise Intervention on Anxiety in Adolescents and Young Adults: A Network Meta-Analysis.

Acute exercise is a promising non-pharmacological therapy for alleviating anxiety. However, the effects of different types of acute exercise on anxiety in adolescents and young adults remain unclear. Therefore, our study aims to conduct a network meta-analysis to compare the effectiveness of various exercise interventions in improving anxiety in adolescents and young adults. We conducted an online literature search in five databases: PubMed, Web of Science, Embase, Cochrane Central Register of Controlled Trials, and PsycINFO. The search was conducted from inception to March 1, 2023, and was limited to English-language publications. Pairwise and network meta-analyses were performed using random-effects models. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework was applied to rate the certainty of evidence. A total of 33 studies involving 1121 participants were included. The network meta-analysis results revealed that mind-body exercise was the most effective intervention for reducing anxiety in adolescents and young adults (SMD = -0.36, 95% CI: -0.70, -0.03, moderate certainty). Additionally, aerobic exercise (SMD = -0.16, 95% CI: -0.28, -0.03, high certainty) showed significant reduction in anxiety, while resistance exercise (SMD = -0.09, 95% CI: -0.33, 0.14, moderate certainty) and multicomponent exercise (SMD = -0.01, 95% CI: -0.59, 0.57, moderate certainty) did not show significant reduction in anxiety. Moderate certainty evidence suggests that acute mind-body exercise may be the most effective type of exercise for reducing anxiety in adolescents and young adults. Future research should focus on conducting more multi-arm randomized controlled trials to provide more direct evidence on the relative effectiveness of different exercise interventions.

In situ formation of biomolecular condensates as intracellular drug reservoirs for augmenting chemotherapy.

Biomolecular condensates, which arise from liquid-liquid phase separation within cells, may provide a means of enriching and prolonging the retention of small-molecule drugs within cells. Here we report a method for the controlled in situ formation of biomolecular condensates as reservoirs for the enrichment and retention of chemotherapeutics in cancer cells, and show that the approach can be leveraged to enhance antitumour efficacies in mice with drug-resistant tumours. The method involves histones as positively charged proteins and doxorubicin-intercalated DNA strands bioorthogonally linked via a click-to-release reaction between trans-cyclooctene and tetrazine groups. The reaction temporarily impaired the phase separation of histones in vitro, favoured the initiation of liquid-liquid phase separation within cells and led to the formation of biomolecular condensates that were sufficiently large to be retained within tumour cells. The controlled formation of biomolecular condensates as drug reservoirs within cells may offer new options for boosting the efficacies of cancer therapies.

Uncovering key mechanisms and intervention therapies in aging skin.

Advancements in understanding skin aging mechanisms, which encompass both external and internal aging processes, have spurred the development of innovative treatments primarily aimed at improving cosmetic appearance. These findings offer the potential for the development of novel therapeutic strategies aimed at achieving long-term, non-therapy-dependent clinical benefits, including the reversal of aging and the mitigation of associated health conditions. Realizing this goal requires further research to establish the safety and efficacy of targeting aging-related skin changes, such as pigmentation, wrinkling, and collagen loss. Systematic investigation is needed to identify the most effective interventions and determine optimal anti-aging treatment strategies. These reviews highlight the features and possible mechanisms of skin aging, as well as the latest progress and future direction of skin aging research, to provide a theoretical basis for new practical anti-skin aging strategies.

Association between prosthesis contour and peri-implantitis in patients compliant with supportive periodontal therapy: A retrospective cohort study.

PURPOSE: Poor contour of the implant restoration causes plaque accumulation and increases the risk of peri-implantitis. This study aimed to investigate whether the prosthodontic components of dental implants were associated with the prevalence of peri-implantitis. METHODS: We enrolled 185 patients with 348 implants who underwent at least 1-year follow-up after the delivery of the prosthesis from February 2010 to January 2021. Demographic data of the patients and implants and the follow-up period were recorded. The emergence angle, type of cervical crown contour, and contour angle were analyzed using annual bite-wing radiographs. Peri-implantitis in this study was diagnosed if the peri-implant bone loss was greater than 2 mm between the bite-wing radiographs taken at baseline and the latest. Chi-square test, two-sample t-test, and multivariate logistic regression were used to investigate the differences and odds ratios between the peri-implantitis and non-peri-implantitis groups. RESULTS: The incidence of peri-implantitis was 14.9% during a follow-up period of 1509 days after the delivery of the prosthesis for at least 1-year. Based on the prevalence of non-peri-implantitis and after adjusting for confounding factors, the risk factors identified were bone types for implants (native bone vs. alveolar ridge preservation: adjusted odds ratio = 2.43, P = 0.04). Sex, arch, and guided bone regeneration vs. alveolar ridge preservation have the potential for a statistical difference. CONCLUSIONS: Compared with implants at alveolar ridge preservation sites, implants in the native bone were more prone to peri-implantitis. Further randomized controlled trials are required to determine these associations.

A region-confined PROTAC nanoplatform for spatiotemporally tunable protein degradation and enhanced cancer therapy.

The antitumor performance of PROteolysis-TArgeting Chimeras (PROTACs) is limited by its insufficient tumor specificity and poor pharmacokinetics. These disadvantages are further compounded by tumor heterogeneity, especially the presence of cancer stem-like cells, which drive tumor growth and relapse. Herein, we design a region-confined PROTAC nanoplatform that integrates both reactive oxygen species (ROS)-activatable and hypoxia-responsive PROTAC prodrugs for the precise manipulation of bromodomain and extraterminal protein 4 expression and tumor eradication. These PROTAC nanoparticles selectively accumulate within and penetrate deep into tumors via response to matrix metalloproteinase-2. Photoactivity is then reactivated in response to the acidic intracellular milieu and the PROTAC is discharged due to the ROS generated via photodynamic therapy specifically within the normoxic microenvironment. Moreover, the latent hypoxia-responsive PROTAC prodrug is restored in hypoxic cancer stem-like cells overexpressing nitroreductase. Here, we show the ability of region-confined PROTAC nanoplatform to effectively degrade BRD4 in both normoxic and hypoxic environments, markedly hindering tumor progression in breast and head-neck tumor models.

The complete chloroplast genome of Polyspora axillaris (Theaceae).

Polyspora axillaris (Roxb. ex Ker Gawl.) Sweet 1825, is a shrub or tree that is about 9 meters tall in the Theaceae family, mainly distributed in China and Vietnam, and it is widely used as a green tree species in many regions owing to its rapid growth and good adaptability. It is rich in various beneficial extracts for humans, but there are limited studies on it. In this study, we sequenced and annotated the complete plastome of P. axillaris. The chloroplast genome length of P. axillaris is 156,770 bp, with a total of 132 genes, including 37 tRNA genes, 8 rRNA genes and 87 protein-coding genes. The complete chloroplast genome of P. axillaris contains two Inverted Repeats (IRs) of 26,077 bp, a Large Single-Copy (LSC) region of 86,286 bp and a Small Single-Copy (SSC) region of 18,330 bp. The overall G/C content in the chloroplast is 37.3%. Phylogenetic inference shows that P. axillaris formed a sister relationship with P. hainanensis, along with 10 Theaceae species. The research result of P. axillaris will contribute to the genetic preservation of the species and the phylogenetic study of Polyspora.

Ultrasound Trigger Ce-Based MOF Nanoenzyme For Efficient Thrombolytic Therapy.

The inflammatory damage caused by thrombus formation and dissolution can increase the risk of thrombotic complications on top of cell death and organ dysfunction caused by thrombus itself. Therefore, a rapid and precise thrombolytic therapy strategy is in urgent need to effectively dissolve thrombus and resist oxidation simultaneously. In this study, Ce-UiO-66, a cerium-based metal-organic framework (Ce-MOF) with reactive oxygen species (ROS) scavenging properties, encapsulated by low-immunogenic mesenchymal stem cell membrane with inflammation-targeting properties, is used to construct a targeted nanomedicine Ce-UiO-CM. Ce-UiO-CM is applied in combination with external ultrasound stimulation for thrombolytic therapy in rat femoral artery. Ce-UiO-66 has abundant Ce (III)/Ce (IV) coupling sites that react with hydrogen peroxide (H2O2) to produce oxygen, exhibiting catalase (CAT) activity. The multi-cavity structure of Ce-UiO-66 can generate electron holes, and its pore channels can act as micro-reactors to further enhance its ROS scavenging capacity. Additionally, the porous structure of Ce-UiO-66 and the oxygen produced by its reaction with H2O2 may enhance the cavitation effects of ultrasound, thereby improving thrombolysis efficacy.

Use of customized 3-dimensional printed mandibular prostheses with a dental implant pressure-reducing device in mandibular body defect: A finite element study performing multiresponse surface methodology.

Background/purpose: Segmental body defects of the mandible result in the complete loss of the affected region. In our previous study, we investigated the clinical applicability of a customized mandible prosthesis (CMP) with a pressure-reducing device (PRD) in an animal study. In this study, we further incorporated dental implants into the CMP and explored the use of dental implant PRD (iPRD) designs. Materials and methods: By employing a finite element analysis approach, we created 4 types of CMP: CMP, CMP with iPRD, CMP-PRD, and CMP-PRD with iPRD. We developed 2 parameters for the iPRD: cone length (CL) in the upper part and spring pitch (SP) in the lower part. Using the response surface methodology (RSM), we determined the most suitable structural assignment for the iPRD. Results: Our results indicate that CMP-PRD had the highest von Mises stress value for the entire assembly (1076.26 MPa). For retentive screws and abutments, CMP with iPRD had the highest von Mises stress value (319.97 and 452.78 MPa, respectively). CMP-PRD had the highest principal stress (131.66 MPa) in the anterior mandible. The iPRD reduced principal stress in both the anterior and posterior mandible. Using the RSM, we generated 25 groups for comparison to achieve the most favorable results for the iPRD and we might suggest the CL to 12 mm and the SP to 0.4 mm in the further clinical trials. Conclusion: Use of the PRD and iPRD in CMP may resolve the challenges associated with CMP, thereby promoting its usage in clinical practice.

Integrating artificial intelligence in osteosarcoma prognosis: the prognostic significance of SERPINE2 and CPT1B biomarkers.

The principal aim of this investigation is to identify pivotal biomarkers linked to the prognosis of osteosarcoma (OS) through the application of artificial intelligence (AI), with an ultimate goal to enhance prognostic prediction. Expression profiles from 88 OS cases and 396 normal samples were procured from accessible public databases. Prognostic models were established using univariate COX regression analysis and an array of AI methodologies including the XGB method, RF method, GLM method, SVM method, and LASSO regression analysis. Multivariate COX regression analysis was also employed. Immune cell variations in OS were examined using the CIBERSORT software, and a differential analysis was conducted. Routine blood data from 20,679 normal samples and 437 OS cases were analyzed to validate lymphocyte disparity. Histological assessments of the study's postulates were performed through immunohistochemistry and hematoxylin and eosin (HE) staining. AI facilitated the identification of differentially expressed genes, which were utilized to construct a prognostic model. This model discerned that the survival rate in the high-risk category was significantly inferior compared to the low-risk cohort (p < 0.05). SERPINE2 was found to be positively associated with memory B cells, while CPT1B correlated positively with CD8 T cells. Immunohistochemical assessments indicated that SERPINE2 was more prominently expressed in OS tissues relative to adjacent non-tumorous tissues. Conversely, CPT1B expression was elevated in the adjacent non-tumorous tissues compared to OS tissues. Lymphocyte counts from routine blood evaluations exhibited marked differences between normal and OS groups (p < 0.001). The study highlights SERPINE2 and CPT1B as crucial biomarkers for OS prognosis and suggests that dysregulation of lymphocytes plays a significant role in OS pathogenesis. Both SERPINE2 and CPT1B have potential utility as prognostic biomarkers for OS.

An End-to-End Inclination State Monitoring Method for Collaborative Robotic Drilling Based on Resnet Neural Network.

The collaborative robot can complete various drilling tasks in complex processing environments thanks to the high flexibility, small size and high load ratio. However, the inherent weaknesses of low rigidity and variable rigidity in robots bring detrimental effects to surface quality and drilling efficiency. Effective online monitoring of the drilling quality is critical to achieve high performance robotic drilling. To this end, an end-to-end drilling-state monitoring framework is developed in this paper, where the drilling quality can be monitored through online-measured vibration signals. To evaluate the drilling effect, a Canny operator-based edge detection method is used to quantify the inclination state of robotic drilling, which provides the data labeling information. Then, a robotic drilling inclination state monitoring model is constructed based on the Resnet network to classify the drilling inclination states. With the aid of the training dataset labeled by different inclination states and the end-to-end training process, the relationship between the inclination states and vibration signals can be established. Finally, the proposed method is verified by collaborative robotic drilling experiments with different workpiece materials. The results show that the proposed method can effectively recognize the drilling inclination state with high accuracy for different workpiece materials, which demonstrates the effectiveness and applicability of this method.

The use of customized 3D-printed mandibular prostheses with pressure-reducing device: A clinical trial.

BACKGROUND: Segmental bone defects of the mandible result in the complete loss of the affected region. We had incorporated the pressure-reducing device (PRD) designs into the customized mandible prostheses (CMP) and conducted a clinical trial to evaluate this approach. METHODS: Seven patients were enrolled in this study. We examined the association among the history of radiotherapy, the number of CMP regions, the number of chin regions involved, and CMP exposure. RESULTS: We included five men and two women with an average age of 55 years. We excised tumors with an average weight of 147.8 g and the average weight of the CMP was 68.5 g. No significant difference between the two weights was noted (p = 0.3882). Three patients received temporary dentures and the CMP remained stable in all patients. CONCLUSION: The use of PRD in CMP may address the previous challenges associated with CMP, but further research is necessary.

A DNA/Upconversion Nanoparticle Complex Enables Controlled Co-Delivery of CRISPR-Cas9 and Photodynamic Agents for Synergistic Cancer Therapy.

Photodynamic therapy (PDT) depends on the light-irradiated exciting of photosensitizer (PS) to generate reactive oxygen species (ROS), which faces challenges and limitations in hypoxia and antioxidant response of cancer cells, and limited tissue-penetration of light. Herein, a multifunctional DNA/upconversion nanoparticles (UCNPs) complex is developed which enables controlled co-delivery of CRISPR-Cas9, hemin, and protoporphyrin (PP) for synergistic PDT. An ultralong single-stranded DNA (ssDNA) is prepared via rolling circle amplification (RCA), which contains recognition sequences of single guide RNA (sgRNA) for loading Cas9 ribonucleoprotein (RNP), G-quadruplex sequences for loading hemin and PP, and linker sequences for combining UCNP. Cas9 RNP cleaves the antioxidant regulator nuclear factor E2-related factor 2 (Nrf2), improving the sensitivity of cancer cells to ROS, and enhancing the synergistic PDT effect. The G-quadruplex/hemin DNAzyme mimicks horseradish peroxidase (HRP) to catalyze the endogenous H2O2 to O2, overcoming hypoxia condition in tumors. The introduced UCNP converts NIR irradiation with deep tissue penetration to light with shorter wavelength, exciting PP to transform the abundant O2 to 1O2. The integration of gene editing and PDT allows substantial accumulation of 1O2 in cancer cells for enhanced cell apoptosis, and this synergistic PDT has shown remarkable therapeutic efficacy in a breast cancer mouse model.

Solution-Processed 1D Wurtzite ZnS Nanostructures with Controlled Crystallographic Orientation and Tunable Band-Edge Emission.

1D compound semiconductor nanomaterials possess unique physicochemical properties that strongly depend on their size, composition, and structures. ZnS has been widely investigated as one of the most important semiconductors, and the control of crystallographic orientation of 1D ZnS nanostructures is still challenging and crucial to exploring their anisotropic properties. Herein, a solution-processed strategy is developed to synthesize 1D wurtzite (w-)ZnS nanostructures with the specific <002> and <210> orientations by co-decomposing the copper dibutyldithiocarbamate {[(C4 H9 )2 NCS2 ]2 Cu, i.e., R2 Cu} and zinc dibutyldithiocarbamate (R2 Zn) precursors in the mixed solvents of oleylamine and 1-dodecanethoil. A solution-solid-solid (SSS)-Oriented growth mechanism is proposed, which includes oriented nucleation dominated and SSS growth dominated stages. The crystallographic orientation mainly depends on the interfacial energy and ligand effect. The 1D w-ZnS nanostructures with controlled crystallographic orientation display unique morphologies, i.e., <002>-oriented w-ZnS nanorod enclosed with {110} facets while <210>-oriented w-ZnS nanobelt enclosed with wide (002) and narrow (110) facets. The bandgap of 1D w-ZnS nanostructures can be tuned from 3.94 to 3.82 eV with the crystallographic growth direction varied from <002> to <210>, thus leading to the tunable band-edge emission from ≈338 to ≈345 nm.

Comparative clinical significance and biological roles of PFKFB family members in oral squamous cell carcinoma.

BACKGROUND: Cancer cells promote glycolysis, which supports rapid cell growth and proliferation. Phosphofructokinase-fructose bisphosphatases (PFKFBs), a family of bidirectional glycolytic enzymes, play key roles in the regulation of glycolysis in many types of cancer. However, their roles in oral squamous cell carcinoma (OSCC), the most common type of oral cancer, are still unknown. METHODS: We compared the gene expression levels of PFKFB family members and analyzed their clinical significance in oral cancer patients, whose clinical data were obtained the Cancer Genome Atlas database. Moreover, real-time quantitative polymerase chain reaction, western blotting, assays for cell viability, cell cycle, cell migration and viability of cell spheroid were performed in scramble and PFKFB-silenced cells. RESULTS: We discovered that PFKFB3 expression in tumor tissues was slightly higher than that in tumor adjacent normal tissues but that PFKFB4 expression was significantly higher in the tumor tissues of oral cancer patients. High PFKFB3 and PFKFB4 expression had different effects on the prognosis of oral cancer patients with different clinicopathological outcomes. Our data showed that PFKFB3 and PFKFB4 play different roles; PFKFB3 is involved in cell viability, G2/M cell cycle progression, invasion, and migration, whereas PFKFB4 is involved in the drug resistance and cancer stemness of OSCC cells. Furthermore, oral cancer patients with co-expressions of PFKFB3/cell cycle or EMT markers and PFKFB4/stemness markers had poor prognosis. CONCLUSIONS: PFKFB3 and PFKFB4 play different biological roles in OSCC cells, which implying that they might be potential prognostic biomarkers for OSCC patients with certain clinicopathological outcomes.

Reliability and validity of the Chinese version of the achievement emotions questionnaire for physical education in university students.

BACKGROUND: Achievement emotions have a significant impact on both the learning process and outcomes. However, there is currently no brief and effective questionnaire available to evaluate Chinese university students' achievement emotions in physical education courses. This study aimed to examine the reliability and validity of the Achievement Emotions for Physical Education Questionnaire (AEQ-PE) in a sample of Chinese university students, while also investigating its measurement invariance across gender and grade levels. METHODS: A cluster randomization sampling method was used to select 694 first- and second-year university students in Shanghai, China for the survey. Descriptive statistics, item analysis, reliability testing, and measurement invariance testing were conducted on the full sample (n = 694). Subsequently, the full sample was randomly divided into two groups, with Sample 1 (n = 347) undergoing exploratory factor analysis (EFA), and Sample 2 (n = 347) undergoing confirmatory factor analysis (CFA) to test the structural validity, convergent validity, and discriminant validity of the Chinese version of the Achievement Emotions Questionnaire for Physical Education (AEQ-PE-C). Finally, Sample 3 (n = 45), which was retested one month later, was used to evaluate test-retest reliability. RESULTS: The Chinese version of the Achievement Emotions Questionnaire for Physical Education consists of 6 dimensions and 24 items, with good item discrimination. The EFA supported a 6-factor structure model, while the CFA demonstrated good model fit indices (χ2/df = 3.086, CFI = 0.928, TLI = 0.916, RMSEA = 0.078) and good convergent and discriminant validity. The questionnaire exhibits high internal consistency reliability (0.794) and excellent test-retest reliability (0.792). Furthermore, the multi-group analysis confirms that the AEQ-PE-C questionnaire has measurement invariance across gender and grade levels. CONCLUSION: The Chinese version of the Achievement Emotions Questionnaire for Physical Education has good reliability and validity, as well as measurement invariance across gender and grade levels, making it an effective tool for measuring achievement emotions in physical education among Chinese university students.

A Smart DNA-Based Nanosystem Containing Ribosome-Regulating siRNA for Enhanced mRNA Transfection.

Messenger RNA (mRNA) transfection is the prerequisite for the application of mRNA-based therapeutics. In hard-to-transfect cells, such as macrophages, the effective transfection of mRNA remains a long-standing challenge. Herein, a smart DNA-based nanosystem is reported containing ribosome biogenesis-promoting siRNA, realizing efficient mRNA transfection in macrophages. Four monomers are copolymerized to form a nanoframework (NF), including N-isopropylacrylamide (NIPAM) as the skeleton and acrydite-DNA as the initiator to trigger the cascade assembly of DNA hairpins (H1-polyT and H2-siRNA). By virtue of the phase transition characteristic of polymeric NIPAM, below the lower critical solution temperature (LCST, ≈34 °C), the NF swells to expose polyT sequences to hybridize with the polyA tail of mRNA. Above the LCST, the NF deswells to encapsulate mRNA. The disulfide bond in the NF responds to glutathione, triggering the disassembly of the nanosystem; the siRNA and mRNA are released in response to triphosadenine and RNase H. The siRNA down-regulates the expression of heat shock protein 27, which up-regulates the expression of phosphorylated ribosomal protein S6. The nanosystem shows satisfactory mRNA transfection and translation efficiency in a mouse model. It is envisioned that the DNA-based nanosystem will provide a promising carrier to deliver mRNA in hard-to-transfect cells and promote the development of mRNA-based therapeutics.

Prevalence of peri-implantitis after alveolar ridge preservation at periodontitis and nonperiodontitis extraction sites: A retrospective cohort study.

INTRODUCTION: Periodontitis is the main indication for dental extraction and often leads to peri-implantitis (PI). Alveolar ridge preservation (ARP) is an effective means of preserving ridge dimensions after extraction. However, whether PI prevalence is lower after ARP for extraction after periodontitis remains unclear. This study investigated PI after ARP in patients with periodontitis. MATERIALS AND METHODS: This study explored the 138 dental implants of 113 patients. The reasons for extraction were categorized as periodontitis or nonperiodontitis. All implants were placed at sites treated using ARP. PI was diagnosed on the basis of radiographic bone loss of ≥3 mm, as determined through comparison of standardized bitewing radiographs obtained immediately after insertion with those obtained after at least 6 months. Chi-square and two-sample t testing and generalized estimating equations (GEE) logistic regression model were employed to identify risk factors for PI. Statistical significance was indicated by p < 0.05. RESULTS: The overall PI prevalence was 24.6% (n = 34). The GEE univariate logistic regression demonstrated that implant sites and implant types were significantly associated with PI (premolar vs. molar: crude odds ratios [OR] = 5.27, 95% confidence intervals [CI] = 2.15-12.87, p = 0.0003; bone level vs. tissue level: crude OR = 5.08, 95% CI = 2.10-12.24; p = 0.003, respectively). After adjustment for confounding factors, the risks of PI were significantly associated with implant sites (premolar vs. molar: adjusted OR [AOR] = 4.62, 95% CI = 1.74-12.24; p = 0.002) and implant types (bone level vs. tissue level: AOR = 6.46, 95% CI = 1.67-25.02; p = 0.007). The reason for dental extraction-that is, periodontitis or nonperiodontitis-was not significantly associated with PI. CONCLUSION: ARP reduces the incidence of periodontitis-related PI at extraction sites. To address the limitations of our study, consistent and prospective randomized controlled trials are warranted.

Suppression of TGFß-Induced Interleukin-6 Secretion by Sinulariolide from Soft Corals through Attenuation of the p38-NF-kB Pathway in Carcinoma Cells.

Sinulariolide (SC-1) is a natural product extracted from the cultured-type soft coral Sinularia flexibilis and possesses anti-inflammation, anti-proliferative, and anti-migratory in several types of cancer cells. However, the molecular pathway behind its effects on inflammation remains poorly understood. Since inflammatory cytokines such as TGFß, TNFα, IL-1, IL-6, and IL-8 activate transcription factors such as Smads, NF-κB, STAT3, Snail, Twist, and Zeb that drive the epithelial-to-mesenchymal transition (EMT), in this study, we focus on the investigation in effects of SC-1 on TGFß-induced interleukin-6 (IL-6) releases in an in vitro cell culture model. We showed that both intracellular IL-6 expression and secretion were stimulated by TGFß and associated with strong upregulation of IL-6 mRNA and increased transcription in A549 cells. SC-1 blocked TGFß-induced secretion of IL-6 while showing no effect on the induction of fibronectin and plasminogen activator inhibitor-1 genes, indicating that SC-1 interferes with only a subset of TGFß activities. In addition, SC-1 inhibits TGFß-induced IL-6 by suppressing p38 MAPK signaling and subsequently inhibits NF-κB and its nuclear translocation without affecting the canonical Smad pathway and receptor turnover. Overall, these data suggest that p38 may involve in the inhibition of SC-1 in IL-6 release, thus illustrating an inhibitory effect for SC-1 in the suppression of inflammation, EMT phenotype, and tumorigenesis.

Framework-Hotspot Enhanced Trans Cleavage of CRISPR-Cas12a for Clinical Samples Detection.

The trans-cleavage property of CRISPR-Cas12a system makes it an excellent tool for disease diagnosis. Nevertheless, most methods based on CRISPR-Cas system still require pre-amplification of the target to achieve the desired detection sensitivity. Here we generate Framework-Hotspot reporters (FHRs) with different local densities to investigate their effect on trans-cleavage activity of Cas12a. We find that the cleavage efficiency increases and the cleavage rate accelerates with increasing reporter density. We further construct a modular sensing platform with CRISPR-Cas12a-based target recognition and FHR-based signal transduction. Encouragingly, this modular platform enables sensitive (100 fM) and rapid (<15 min) detection of pathogen nucleic acids without pre-amplification, as well as detection of tumor protein markers in clinical samples. The design provides a facile strategy for enhanced trans cleavage of Cas12a, which accelerates and broadens its applications in biosensing.

CRISPR/Cas systems for the detection of nucleic acid and non-nucleic acid targets.

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems are becoming powerful tools for disease biomarkers detection. Due to the specific recognition, cis-cleavage and nonspecific trans-cleavage capabilities, CRISPR/Cas systems have implemented the detection of nucleic acid targets (DNA and RNA) as well as non-nucleic acid targets (e.g., proteins, exosomes, cells, and small molecules). In this review, we first summarize the principles and characteristics of various CRISPR/Cas systems, including CRISPR/Cas9, Cas12, Cas13 and Cas14 systems. Then, various types of applications of CRISPR/Cas systems used in detecting nucleic and non-nucleic acid targets are introduced emphatically. Finally, the prospects and challenges of their applications in biosensing are discussed.