Ultra small gold nanoclusters supported on two-dimensional bismuth selenium nanosheets for synergistic photothermal and photodynamic tumor therapy.

Two-dimensional (2D) bismuth selenium (Bi2Se3) nanosheets have exceptional surface area and superior surface modification capabilities, facilitating the effective loading of nanoprobes, metal particles, and other substances. Additionally, thiolated ultrasmall gold nanoclusters (Au NCs), distinguished by their high photoluminescent activity and modulatable surface charges, enable efficient loading onto the 2D Bi2Se3 surfaces. In this study, we successfully prepared Bi2Se3 nanosheets by sonication-assisted liquid phase exfoliation and loaded Au clusters on their surface through an amide bond reaction. The loading of Au NCs significantly augments the photothermal and photocatalytic capabilities of Bi2Se3 nanosheets and exhibits obvious anti-cancer therapeutic effects through in vitro and in vivo experiments. In summary, the as-prepared AuNC@Bi2Se3 nanocomposites showed combined near-infrared light-initiated photothermal/photodynamic therapy (PTT/PDT) against tumors, demonstrating their potential as novel theranostic agents for biomedical applications.

Application of self-assembly palladium single-atom nanozyme over polyoxometalates in protection against neomycin-induced hearing loss by inhibiting ferroptosis.

Deafness mainly results from irreversible impairment of hair cells (HCs), which may relate to oxidative stress, yet therapeutical solutions is lacked due to limited understanding on the exact molecular mechanism. Herein, mimicking the molecular structure of natural enzymes, a palladium (Pd) single-atom nanozyme (SAN) was fabricated, exhibiting superoxide dismutase and catalase activity, transforming reactive oxygen species (ROS) into O2 and H2O. We examined the involvement of Pd in neomycin-induced HCs loss in vitro and in vivo over zebrafish. Our results revealed that neomycin treatment induced apoptosis in HCs, resulting in substantial of ROS elevation in HEI-OC1 cells, decrease in mitochondrial membrane potential, and increase in lipid peroxidation and iron accumulation, ultimately leading to iron-mediated cell death. Noteworthy, Pd SAN treatment exhibited significant protective effects against HCs damage and impaired HCs function in zebrafish by inhibiting ferroptosis. Furthermore, the application of iron death inducer RSL3 resulted in notable exacerbation of neomycin-induced harm, which was mitigated by Pd administration. Our investigation demonstrates that antioxidants is promising for inhibiting ferroptosis and repairing of mitochondrial function in HCs and the enzyme-mimic SAN provides a good strategy for designing drugs alleviating neomycin-induced ototoxicity.

TMEM52B Isoforms P18 and P20 Differentially Promote the Oncogenesis and Metastasis of Nasopharyngeal Carcinoma.

Transmembrane protein 52B (TMEM52B), a newly identified tumor-related gene, has been reported to regulate various tumors, yet its role in nasopharyngeal carcinoma (NPC) remains unclear. Transcriptomic analysis of NPC cell lines reveals frequent overexpression of TMEM52B, and immunohistochemical results show that TMEM52B is associated with advanced tumor stage, recurrence, and decreased survival time. Depleting TMEM52B inhibits the proliferation, migration, invasion, and oncogenesis of NPC cells in vivo. TMEM52B encodes two isoforms, TMEM52B-P18 and TMEM52B-P20, differing in their N-terminals. While both isoforms exhibit similar pro-oncogenic roles and contribute to drug resistance in NPC, TMEM52B-P20 differentially promotes metastasis. This functional discrepancy may be attributed to their distinct subcellular localization; TMEM52B-P18 is confined to the cytoplasm, while TMEM52B-P20 is found both at the cell membrane and in the cytoplasm. Mechanistically, cytoplasmic TMEM52B enhances AKT phosphorylation by interacting with phosphoglycerate kinase 1 (PGK1), fostering NPC growth and metastasis. Meanwhile, membrane-localized TMEM52B-P20 promotes E-cadherin ubiquitination and degradation by facilitating its interaction with the E3 ubiquitin ligase NEDD4, further driving NPC metastasis. In conclusion, the TMEM52B-P18 and TMEM52B-P20 isoforms promote the metastasis of NPC cells through different mechanisms. Drugs targeting these TMEM52B isoforms may offer therapeutic benefits to cancer patients with varying degrees of metastasis.

Smart Nanoplatforms Responding to the Tumor Microenvironment for Precise Drug Delivery in Cancer Therapy.

The tumor microenvironment (TME) is a complex and dynamic entity, comprising stromal cells, immune cells, blood vessels and extracellular matrix, which is intimately associated with the occurrence and development of cancers, as well as their therapy. Utilizing the shared characteristics of tumors, such as an acidic environment, enzymes and hypoxia, researchers have developed a promising cancer therapy strategy known as responsive release of nano-loaded drugs, specifically targeted at tumor tissues or cells. In this comprehensive review, we provide an in-depth overview of the current fundamentals and state-of-the-art intelligent strategies of TME-responsive nanoplatforms, which include acidic pH, high GSH levels, high-level adenosine triphosphate, overexpressed enzymes, hypoxia and reductive environment. Additionally, we showcase the latest advancements in TME-responsive nanoparticles. In conclusion, we thoroughly examine the immediate challenges and prospects of TME-responsive nanopharmaceuticals, with the expectation that the progress of these targeted nanoformulations will enable the exploitation, overcoming or modulation of the TME, ultimately leading to significantly more effective cancer therapy.

NIR-II Light-Driven Genetically Engineered Exosome Nanocatalysts for Efficient Phototherapy against Glioblastoma.

Glioblastoma (GBM) poses a significant therapeutic challenge due to its invasive nature and limited drug penetration through the blood-brain barrier (BBB). In response, here we present an innovative biomimetic approach involving the development of genetically engineered exosome nanocatalysts (Mn@Bi2Se3@RGE-Exos) for efficient GBM therapy via improving the BBB penetration and enzyme-like catalytic activities. Interestingly, a photothermally activatable multiple enzyme-like reactivity is observed in such a nanosystem. Upon NIR-II light irradiation, Mn@Bi2Se3@RGE-Exos are capable of converting hydrogen peroxide into hydroxyl radicals, oxygen, and superoxide radicals, providing a peroxidase (POD), oxidase (OXD), and catalase (CAT)-like nanocatalytic cascade. This consequently leads to strong oxidative stresses to damage GBM cells. In vitro, in vivo, and proteomic analysis further reveal the potential of Mn@Bi2Se3@RGE-Exos for the disruption of cellular homeostasis, enhancement of immunological response, and the induction of cancer cell ferroptosis, showcasing a great promise in anticancer efficacy against GBM with a favorable biosafety profile. Overall, the success of this study provides a feasible strategy for future design and clinical study of stimuli-responsive nanocatalytic medicine, especially in the context of challenging brain cancers like GBM.

Evaluation of activities of daily living using an electronic version of the Longshi Scale in patients with stroke: reliability, consistency, and preference.

BACKGROUND: The Longshi Scale is a pictorial assessment tool for evaluating activities of daily living (ADL) in patients with stroke. The paper-based version presents challenges; thus, the WeChat version was created to enhance accessibility. Herein, we aimed to validate the inter-rater and test-retest reliabilities of the WeChat version of the Longshi Scale and explore its potential clinical applications. METHODS: We recruited 115 patients with stroke in the study. The ADL results of each patient were assessed using both the WeChat and paper-based version of the Longshi Scale; each evaluation was conducted by 28 health professionals and 115 caregivers separately. To explore the test-retest reliability of the WeChat version, 22 patients were randomly selected and re-evaluated by health professionals using the WeChat version. All evaluation criteria were recorded, and all evaluators were surveyed to indicate their preference between the two versions. RESULTS: Consistency between WeChat and the paper-based Longshi Scale was high for ADL scores by health professionals (ICC2,1 = 0.803-0.988) and caregivers (ICC2,1 = 0.845-0.983), as well as for degrees of disability (κw = 0.870 by professionals; κw = 0.800 by caregivers). Bland-Altman analysis showed no significant discrepancies. The WeChat version exhibited good test-retest reliability (κw = 0.880). The WeChat version showed similar inter-rater reliability in terms of the ADL score evaluated using the paper-based version (ICC2,1 = 0.781-0.941). The time to complete assessments did not differ significantly, although the WeChat version had a shorter information entry time (P < 0.001, 95% confidence interval: -43.463 to -15.488). Health professionals favored the WeChat version (53.6%), whereas caregivers had no significant preference. CONCLUSIONS: The WeChat version of the Longshi Scale is reliable and serves as a suitable alternative for health professionals and caregivers to assess ADL levels in patients with stroke. The WeChat version of the Longshi Scale is considered user-friendly by health professionals, although it is not preferred by caregivers. TRIAL REGISTRATION: This study was approved by the Ethics Committee of the Second People's Hospital of Shenzhen (approval number: 20210812003-FS01) and registered on the Clinical Trial Register Center website: clinicaltrials.gov on January 31, 2022 (registration no.: NCT05214638).

Organic dye-loaded reduced titanium dioxide as a broadband saturable absorber for ultrafast fiber lasers.

As a rising star among metal oxide nanomaterials, titanium dioxide (TiO2) has been widely investigated and employed in optical applications because of its excellent optical properties. In this work, we demonstrate the efficient and broadband nonlinear photonic properties of methylene blue (MB)-loaded reduced TiO2 (TiO2-x-MB) and explore the performance of a TiO2-x-MB-microfiber photonic device in broadband ultrafast photonics. Within an erbium-doped fiber laser (EDFL) system, utilizing the TiO2-x-MB-microfiber photonic device as a saturable absorber (SA), steady mode-locked pulses together with chaotic pulses were successfully achieved at the wavelength of 1.55 µm. Furthermore, by incorporating the TiO2-x-MB SA into a thulium-doped fiber laser (TDFL) system, an ultrashort single pulse and multiple pulses were obtained at 2.0 µm. These results indicate that TiO2-x-MB is an excellent nanomaterial for use in mode-locked lasers, being an alternative candidate for ultrafast fiber lasers via exploiting the chemical and physical properties of oxide nanomaterials.

Helical Nanographenes Bearing Pentagon-Heptagon Pairs by Stepwise Dehydrocyclization.

The incorporation of pentagon-heptagon pairs into helical nanographenes lacks a facile synthetic route, and the impact of these pairs on chiroptical properties remains unclear. In this study, a method for the stepwise construction of pentagon-heptagon pairs in helical nanographenes by the dehydrogenation of [6]helicene units was developed. Three helical nanographenes containing pentagon-heptagon pairs were synthesized and characterized using this approach. A wide variation in the molecular geometries and photophysical properties of these helical nanographenes was observed, with changes in the helical length of these structures and the introduction of the pentagon-heptagon pairs. The embedded pentagon-heptagon pairs reduced the oxidation potential of the synthesized helical nanographenes. The high isomerization energy barriers enabled the chiral resolution of the helicene enantiomers. Chiroptical investigations revealed remarkably enhanced circularly polarized luminescence and luminescence dissymmetry factors with an increasing number of the pentagon-heptagon pairs.

Employing Noble Metal-Porphyrins to Engineer Robust and Highly Active Single-Atom Nanozymes for Targeted Catalytic Therapy in Nasopharyngeal Carcinoma.

Single-atom nanozymes (SANzymes) emerge as promising alternatives to conventional enzymes. However, chemical instability limits their application. Here, a systematic synthesis of highly active and stable SANzymes is presented by leveraging noble metal-porphyrins. Four noble metal-porphyrins are successfully synthesized to mimic the active site of natural peroxidases through atomic metal-N coordination anchored to the porphyrin center. These noble metal-porphyrins are integrated into a stable and biocompatible Zr-based metal-organic framework (MxP, x denoting Ir, Ru, Pt, and Pd). Among these, MIrP demonstrates superior peroxidase-like activity (685.61 U mg-1 ), catalytic efficiency, and selectivity compared to horseradish peroxidase (267.71 U mg-1 ). Mechanistic investigations unveil heightened catalytic activity of MIrP arises from its robust H2 O2 adsorption capacity, unique rate-determining step, and low energy threshold. Crucially, MIrP exhibits remarkable chemical stability under both room temperature and high H2 O2 concentrations. Further, through modification with (-)-Epigallocatechin-3-Gallate, a natural ligand for Epstein-Barr virus (EBV)-encoded latent membrane protein 1, targeted SANzyme (MIrPHE) tailored for EBV-associated nasopharyngeal carcinoma is engineered. This study not only presents an innovative strategy for augmenting the catalytic activity and chemical stability of SANzymes but also highlights the substantial potential of MIrP as a potent nanomedicine for targeted catalytic tumor therapy.

Inhibition of histone methyltransferase PRMT5 attenuates cisplatin-induced hearing loss through the PI3K/Akt-mediated mitochondrial apoptotic pathway.

This study aimed to evaluate the therapeutic potential of inhibiting protein arginine methyltransferase 5 (PRMT5) in cisplatin-induced hearing loss. The effects of PRMT5 inhibition on cisplatin-induced auditory injury were determined using immunohistochemistry, apoptosis assays, and auditory brainstem response. The mechanism of PRMT5 inhibition on hair cell survival was assessed using RNA-seq and Cleavage Under Targets and Tagment-quantitative polymerase chain reaction (CUT&Tag-qPCR) analyses in the HEI-OC1 cell line. Pharmacological inhibition of PRMT5 significantly alleviated cisplatin-induced damage to hair cells and spiral ganglion neurons in the cochlea and decreased apoptosis by protecting mitochondrial function and preventing the accumulation of reactive oxygen species. CUT&Tag-qPCR analysis demonstrated that inhibition of PRMT5 in HEI-OC1 cells reduced the accumulation of H4R3me2s/H3R8me2s marks at the promoter region of the Pik3ca gene, thus activating the expression of Pik3ca. These findings suggest that PRMT5 inhibitors have strong potential as agents against cisplatin-induced ototoxicity and can lay the foundation for further research on treatment strategies of hearing loss.

Diagnosis of nasopharyngeal carcinoma using an ultrasensitive immunoassay method based on nanoparticles.

The detection of the antibody of Epstein-Barr virus (EBV) is critical for the diagnosis of nasopharyngeal carcinoma (NPC). An accurate and scalable point-of-care detection method would support the screening, diagnosis, and monitoring of NPC patients. In this study, firstly, we made an antibody enrichment element, antigen-MNPs, which can screen out specific antibodies in a complex sample. Secondly, signal-amplifying elements were synthesized by labelling inorganic quantum dots (QDs) and anti-antibodies on the surface of flop-ferritin. A sandwich structure is formed among antigen-MNPs, target-antibodies, and anti-antibodies-flop-ferritin@QDs. The antibodies are quantified by fluorescence intensity with a limit of detection (LOD) as low as 10-11 g mL-1. Moreover, the method can detect different types of antibodies and was employed to examine 10 sera from NPC patients and 10 sera from healthy individuals. The result indicates that the simultaneous detection of anti-EBNA-IgG and anti-EBNA-IgA provides an efficient route for early diagnosis of NPC.

Reliability of pictorial Longshi Scale for informal caregivers to evaluate the functional independence and disability.

AIM: The pictorial Longshi Scale was designed to assess patients' functional ability in the Chinese context, which is gradually used by some informal caregivers. However, its reliability compared with healthcare professionals has not been examined. DESIGN: A multi-centre cross-sectional study conducted in 24 Chinese hospitals. METHODS: We recruited patients undergoing rehabilitation treatment and informal caregiver dyads. Informal caregivers and healthcare professionals evaluated patients' functional ability using the Longshi Scale according to three levels (bedridden, domestic and community). The Kappa coefficient and McNemar-Bowker test were used to examine the consistency and accuracy between the two parallel assessments. RESULTS: This study involved 947 patients (mean age: 46.07 ± 11.72 years) and informal caregiver dyads (64.86 ± 12.94 years). Most patients were males (66.3%), while most caregivers were females (60.7%). Over 70% of patients and caregiver dyads had a secondary-school education and lower. Around 90% of caregivers were relatives (spouse, 42.8%; offspring, 20.7%; siblings: 13.3%; parent, 12.0%) of patients. The agreement in sub-levels of the Longshi Scale between caregivers and healthcare professionals ranges from 73%-89%, and the corresponding Kappa coefficients range from 0.504-0.786. Caregivers were more likely to assign fewer patients to the bedridden group and more to the domestic group than healthcare professionals. The subgroup analysis by education level indicated that the difference in assigning patients into three degrees of functional disability was only significant in those with primary-school education, while non-significant in those with secondary-school education and higher. CONCLUSION: The evaluation outcomes of functional ability using the Longshi Scale are similar between informal caregivers and healthcare professionals. However, informal caregivers' education level is a dominant factor in affecting the assessment accuracy compared with healthcare professionals. Informal caregivers with a secondary-school education and higher are supported to evaluate patients' functional ability independently.

Metastatic Patterns and Prognosis of Patients with Sinonasal Carcinoma: A Population-Based Study.

INTRODUCTION: The aim of this study was to summarize the incidence, risk factors, and prognostic factors of distant metastasis of sinonasal carcinoma. METHODS: We collected data for patients diagnosed with sinonasal carcinoma from 2010 to 2015 from the SEER database and analyzed the risk factors for distant metastasis via univariate and multivariate logistic regression analysis. In addition, univariate and multivariate Cox regression analysis models were used to describe the factors related to the overall survival of patients with distant metastasis. RESULTS: A total of 2,255 patients were included in the study, including 86 in the distant metastasis group and 2,169 in the nondistant metastasis group. In the univariate and multivariate logistic regression analyses, we found that the risk factors affecting distant metastasis were poorly differentiated tumor grade (HR = 1.932, 95% CI: 1.082-3.452, p = 0.026), advanced T stage (T3-T4) (HR = 4.302, 95% CI: 2.047-9.039, p < 0.001), and advanced N stage (HR = 3.093, 95% CI: 1.911-5.005, p < 0.001). Moreover, elderly patients had a poorer prognosis than young patients (HR = 1.792, 95% CI: 1.096-2.931, p = 0.02) and that surgical treatment improved the survival rate of tumor patients with distant metastasis (HR = 0.450, 95% CI: 0.247-0.821, p = 0.009). CONCLUSION: Tumor grade, T stage, and N stage are risk factors for distant metastasis in sinonasal carcinoma, while an age of less than 65 years and surgery were positive prognostic factors for sinonasal carcinoma patients with distant metastasis.

[Effects of orofacial myofunctional therapy on postoperative outcomes of upper airway surgery for adults with severe obstructive sleep apnea].

Objective:To investigate the effect of orofacial myofunctional therapy on the clinical efficacy of upper airway surgery for adults with severe obstructive sleep apnea（OSA）. Methods:A total of 48 patients with OSA who underwent upper airway surgery in the Shenzhen Second People's Hospital from June 2020 to September 2021 were included in this study. These patients were randomly divided into the combination group（21 cases） and the surgery group（27 cases）. The effective rate, AHI, minimum blood oxygen saturation, snoring events and Epworth sleepiness scale scores at 6 months after operation were compared and analyzed between the two groups. Results:The proportions of AHI, LSaO2, snoring events, and total snoring time in the combined group at 6 months after operation were（14.77±9.15） times/h, （81.19±6.52）%, （172.43±73.67） times, and（13.16±6.02）%. The proportion of AHI, LSaO2, snoring events, and total snoring time in surgical group at 6 months after operation was（23.87±10.6） times/h, （80.78±4.88）%, （235.81±83.23） times, （17.58±5.94）%. Compared with preoperative 6 months after operation, the proportion of AHI, snoring events, and total snoring time was significantly decreased, and LSaO2was significantly increased, and the differences were statistically significant（P<0.05）. The time of snoring and the proportion of snoring to time were significantly improved compared with those in the simple operation group, and the differences were statistically significant（P<0.05）. Conclusion:This study verified that orofacial myofunctional therapy can improve the clinical efficacy after upper airway surgery for adults with severe obstructive sleep apnea.

A Questionnaire-Based Ensemble Learning Model to Predict the Diagnosis of Vertigo: Model Development and Validation Study.

BACKGROUND: Questionnaires have been used in the past 2 decades to predict the diagnosis of vertigo and assist clinical decision-making. A questionnaire-based machine learning model is expected to improve the efficiency of diagnosis of vestibular disorders. OBJECTIVE: This study aims to develop and validate a questionnaire-based machine learning model that predicts the diagnosis of vertigo. METHODS: In this multicenter prospective study, patients presenting with vertigo entered a consecutive cohort at their first visit to the ENT and vertigo clinics of 7 tertiary referral centers from August 2019 to March 2021, with a follow-up period of 2 months. All participants completed a diagnostic questionnaire after eligibility screening. Patients who received only 1 final diagnosis by their treating specialists for their primary complaint were included in model development and validation. The data of patients enrolled before February 1, 2021 were used for modeling and cross-validation, while patients enrolled afterward entered external validation. RESULTS: A total of 1693 patients were enrolled, with a response rate of 96.2% (1693/1760). The median age was 51 (IQR 38-61) years, with 991 (58.5%) females; 1041 (61.5%) patients received the final diagnosis during the study period. Among them, 928 (54.8%) patients were included in model development and validation, and 113 (6.7%) patients who enrolled later were used as a test set for external validation. They were classified into 5 diagnostic categories. We compared 9 candidate machine learning methods, and the recalibrated model of light gradient boosting machine achieved the best performance, with an area under the curve of 0.937 (95% CI 0.917-0.962) in cross-validation and 0.954 (95% CI 0.944-0.967) in external validation. CONCLUSIONS: The questionnaire-based light gradient boosting machine was able to predict common vestibular disorders and assist decision-making in ENT and vertigo clinics. Further studies with a larger sample size and the participation of neurologists will help assess the generalization and robustness of this machine learning method.

Inhibiting DNA methylation alleviates cisplatin-induced hearing loss by decreasing oxidative stress-induced mitochondria-dependent apoptosis via the LRP1-PI3K/AKT pathway.

Cisplatin-related ototoxicity is a critical side effect of chemotherapy and can lead to irreversible hearing loss. This study aimed to assess the potential effect of the DNA methyltransferase (DNMT) inhibitor RG108 on cisplatin-induced ototoxicity. Immunohistochemistry, apoptosis assay, and auditory brainstem response (ABR) were employed to determine the impacts of RG108 on cisplatin-induced injury in murine hair cells (HCs) and spiral ganglion neurons (SGNs). Rhodamine 123 and TMRM were utilized for mitochondrial membrane potential (MMP) assessment. Reactive oxygen species (ROS) amounts were evaluated by Cellrox green and Mitosox-red probes. Mitochondrial respiratory function evaluation was performed by determining oxygen consumption rates (OCRs). The results showed that RG108 can markedly reduce cisplatin induced damage in HCs and SGNs, and alleviate apoptotic rate by protecting mitochondrial function through preventing ROS accumulation. Furthermore, RG108 upregulated BCL-2 and downregulated APAF1, BAX, and BAD in HEI-OC1 cells, and triggered the PI3K/AKT pathway. Decreased expression of low-density lipoprotein receptor-related protein 1 (LRP1) and high methylation of the LRP1 promoter were observed after cisplatin treatment. RG108 treatment can increase LRP1 expression and decrease LRP1 promoter methylation. In conclusion, RG108 might represent a new potential agent for preventing hearing loss induced by cisplatin via activating the LRP1-PI3K/AKT pathway.

FGF-2 signaling in nasopharyngeal carcinoma modulates pericyte-macrophage crosstalk and metastasis.

Molecular signaling in the tumor microenvironment (TME) is complex, and crosstalk among various cell compartments in supporting metastasis remains poorly understood. In particular, the role of vascular pericytes, a critical cellular component in the TME, in cancer invasion and metastasis warrants further investigation. Here, we report that an elevation of FGF-2 signaling in samples from patients with nasopharyngeal carcinoma (NPC) and xenograft mouse models promoted NPC metastasis. Mechanistically, tumor cell-derived FGF-2 strongly promoted pericyte proliferation and pericyte-specific expression of an orphan chemokine (C-X-C motif) ligand 14 (CXCL14) via FGFR1/AHR signaling. Gain- and loss-of-function experiments validated that pericyte-derived CXCL14 promoted macrophage recruitment and polarization toward an M2-like phenotype. Genetic knockdown of FGF2 or genetic depletion of tumoral pericytes blocked CXCL14 expression and tumor-associated macrophage (TAM) infiltration. Pharmacological inhibition of TAMs by clodronate liposome treatment resulted in a reduction of FGF-2-induced pulmonary metastasis. Together, these findings shed light on the inflammatory role of tumoral pericytes in promoting TAM-mediated metastasis. We provide mechanistic insight into an FGF-2/FGFR1/pericyte/CXCL14/TAM stromal communication axis in NPC and propose an effective antimetastasis therapy concept by targeting a pericyte-derived inflammation for NPC or FGF-2hi tumors.

Prognostic Nomograms for Predicting Overall Survival and Cancer-Specific Survival in Patients with Head and Neck Mucosal Melanoma.

Background: Accurate forecasting of the risk of death is crucial for people living with head and neck mucosal melanoma (HNMM). We aimed to establish and validate an effective prognostic nomogram for HNMM. Methods: Patients with HNMM who underwent surgery between 2010 and 2015 were selected from the Surveillance, Epidemiology, and End Results (SEER) database for model construction. After eliminating invalid and missing clinical information, 288 patients were ultimately identified and randomly divided into a training cohort (199 cases) and a validation cohort (54 cases). Univariate and multivariate Cox proportional hazards regression analyses were performed in the training cohort to identify prognostic variables. Independent influencing factors were used to build the model. Through internal verification (training cohort) and external verification (validation cohort), the concordance indexes (C-indexes) and calibration curves were used to evaluate the predictive value of the nomogram. Results: For the training cohort, five independent risk predictors, namely age, location, T stage, N stage, and surgery, were selected, and nomograms with estimated 1- and 3-year overall survival (OS) and cancer-specific survival (CSS) were established. The C-index showed that the predictive performance of the nomogram was better than that of the TNM staging system and was internally verified (through the training queue: OS: 0.764 vs 0.683, CSS: 0.783 vs 0.705) and externally verified (through the verification queue: OS: 0.808 vs 0.644, CSS: 0.823 vs 0.648). The calibration curves also showed good agreement between the prediction based on the nomogram and the observed survival rate. Conclusion: The nomogram prediction model can more accurately predict the prognosis of HNMM patients than the traditional TNM staging system and may be beneficial for guiding clinical treatment.

A Highly Sensitive CRISPR-Empowered Surface Plasmon Resonance Sensor for Diagnosis of Inherited Diseases with Femtomolar-Level Real-Time Quantification.

The clustered regularly interspaced short palindromic repeats (CRISPR) molecular system has emerged as a promising technology for the detection of nucleic acids. Herein, the development of a surface plasmon resonance (SPR) sensor that is functionalized with a layer of locally grown graphdiyne film, achieving excellent sensing performance when coupled with catalytically deactivated CRISPR-associated protein 9 (dCas9), is reported. dCas9 protein is immobilized on the sensor surface and complexed with a specific single-guide RNA, enabling the amplification-free detection of target sequences within genomic DNA. The sensor, termed CRISPR-SPR-Chip, is used to successfully analyze recombinant plasmids with only three-base mutations with a limit of detection as low as 1.3 fM. Real-time monitoring CRISPR-SPR-Chip is used to analyze clinical samples of patients with Duchenne muscular dystrophy with two exon deletions, which are detected without any pre-amplification step, yielding significantly positive results within 5 min. The ability of this novel CRISPR-empowered SPR (CRISPR-eSPR) sensing platform to rapidly, precisely, sensitively, and specifically detect a target gene sequence provides a new on-chip optic approach for clinical gene analysis.

Functional Independence and Disability Evaluation in Stroke Patients: Optimal Cutoff Scores for a Pictorial-Based Longshi Scale, Barthel Index, and Modified Rankin Scale.

INTRODUCTION: The modified Rankin Scale (mRS) and Barthel Index (BI) are widely used to measure functional outcomes worldwide. The Longshi Scale (LS), a novel pictorial-based instrument, was designed to improve the simplicity and convenience of measuring functional outcomes in the Chinese context. However, the disagreements in functional outcomes assessed by the mRS, BI, and LS are misleading, particularly in stroke patients. This study aimed to identify the optimal cutoff scores of LS and BI according to the mRS in Chinese stroke patients with different levels of functional disability. METHODS: The mRS, BI, and LS were applied to evaluate functional independence and disability in 7364 stroke patients in a multi-center cross-sectional study. Stroke patients were categorized into bedridden, domestic, and community groups in advance using the LS, indicating severe, moderate, and mild functional disability, respectively. The optimal cut-off scores of the LS and BI according to the mRS were identified via sensitivity, specificity, and Youden's index and stratified by different levels of functional disability determined by LS. We also plotted the receiver operator characteristic (ROC) curves of sensitivity and specificity and determined the area under the curve (AUC). RESULTS: In the bedridden group, LS and BI cutoff scores with the highest Youden's index were 5 and 10 for mRS 4, and the AUCs for the ROC curve were 0.848 and 0.863 for mRS 4. In the domestic group, LS and BI cutoff scores with the highest Youden's index were 5 and 65 for mRS 3, and the AUCs for the ROC curve were 0.796 and 0.826 for mRS 3. In the community group, LS cutoff scores with the highest sum of sensitivity and specificity were 9, 9, and 8 for mRS grades 0, 1, and 2, respectively, while the BI cutoff scores with the highest sum of sensitivity and specificity were 100, 100, and 95, respectively, while the AUCs for the ROC curve were 0.697 and 0.735 for mRS 2, 0.694 and 0.716 for mRS 1, and 0.628, and 0.660 for mRS 0. CONCLUSIONS: The mRS is more precise to determine mild functional disability, whereas BI can provide more specific information on moderate and severe levels in stroke patients. Although LS was a less precise was to determine moderate and severe levels than BI, it is much simpler and more convenient to be applied to a large-scale population.