Gasdermin D silencing alleviates airway inflammation and remodeling in an ovalbumin-induced asthmatic mouse model.

Emerging evidence demonstrates that pyroptosis has been implicated in the pathogenesis of asthma. Gasdermin D (GSDMD) is the pyroptosis executioner. The mechanism of GSDMD in asthma remains unclear. The aim of this study was to elucidate the potential role of GSDMD in asthmatic airway inflammation and remodeling. Immunofluorescence staining was conducted on airway epithelial tissues obtained from both asthma patients and healthy controls (HCs) to evaluate the expression level of N-GSDMD. ELISA was used to measure concentrations of cytokines (IL-1ß, IL-18, IL-17A, and IL-10) in serum samples collected from asthma patients and healthy individuals. We demonstrated that N-GSDMD, IL-18, and IL-1ß were significantly increased in samples with mild asthma compared with those from the controls. Then, wild type and Gsdmd-knockout (Gsdmd-/-) mice were used to establish asthma model. We performed histopathological staining, ELISA, and flow cytometry to explore the function of GSDMD in allergic airway inflammation and tissue remodeling in vivo. We observed that the expression of N-GSDMD, IL-18, and IL-1ß was enhanced in OVA-induced asthma mouse model. Gsdmd knockout resulted in attenuated IL-18, and IL-1ß production in both bronchoalveolar lavage fluid (BALF) and lung tissue in asthmatic mice. In addition, Gsdmd-/- mice exhibit a significant reduction in airway inflammation and remodeling, which might be associated with reduced Th17 inflammatory response and M2 polarization of macrophages. Further, we found that GSDMD knockout may improve asthmatic airway inflammation and remodeling through regulating macrophage adhesion, migration, and macrophage M2 polarization by targeting Notch signaling pathway. These findings demonstrate that GSDMD deficiency profoundly alleviates allergic inflammation and tissue remodeling. Therefore, GSDMD may serve as a potential therapeutic target against asthma.

A Randomized, Parallel Design Study to Evaluate the Effects of Different Oral Cleaning Modalities on Gingivitis and Plaque After a 6-Week Period of Home Use.

The study objective was to evaluate the effect of different interdental oral cleaning modalities on gingivitis and plaque following a 6-week period of home use. This was a randomized, parallel, examiner-blinded study. Study subjects were routine manual toothbrush (MTB) users with moderate to severe gingivitis, aged 18 to 65 years. Subjects were required to have a gingival bleeding score of ≥1 on at least 50 gingival sites per the Gingival Bleeding Index (GBI) and to have a minimum average plaque score of ≥0.6 per the Rustogi Modified Navy Plaque Index (RMNPI) following a 3- to 6-hour plaque accumulation period. Subjects were randomly assigned to one of four groups based on the oral care cleaning modality: (1) NON group: MTB alone, (2) FLS group: MTB plus string floss, (3) MPF group: MTB plus a Philips® Sonicare® Power Flosser with the Quad Stream nozzle, or (4) PPF group: Philips Sonicare power toothbrush plus the power flosser. Safety and efficacy measures (Modified Gingival Index [MGI], GBI, and RMNPI) were assessed at baseline, 2 weeks, and 6 weeks. The primary efficacy endpoint was the reduction in gingival inflammation from baseline to week 6 as measured by the MGI. A total of 260 subjects were randomized and 256 subjects completed the study. The adjusted mean percent reduction in gingival inflammation from baseline to week 6 was 14.90% for the NON group, 13.16% for the FLS group, 33.51% for the MPF group, and 49.30% for the PPF group. Pairwise comparisons indicated that both the PPF and MPF groups were statistically significantly different from both the NON and FLS groups. In conclusion, use of either the Philips Sonicare power toothbrush with the Philips Sonicare Power Flosser or an MTB with the Philips Sonicare Power Flosser was statistically superior to an MTB alone and an MTB used with string floss in reducing gingival inflammation following 6 weeks of home use.

Generation of allogeneic CAR-NKT cells from hematopoietic stem and progenitor cells using a clinically guided culture method.

Cancer immunotherapy with autologous chimeric antigen receptor (CAR) T cells faces challenges in manufacturing and patient selection that could be avoided by using 'off-the-shelf' products, such as allogeneic CAR natural killer T (AlloCAR-NKT) cells. Previously, we reported a system for differentiating human hematopoietic stem and progenitor cells into AlloCAR-NKT cells, but the use of three-dimensional culture and xenogeneic feeders precluded its clinical application. Here we describe a clinically guided method to differentiate and expand IL-15-enhanced AlloCAR-NKT cells with high yield and purity. We generated AlloCAR-NKT cells targeting seven cancers and, in a multiple myeloma model, demonstrated their antitumor efficacy, expansion and persistence. The cells also selectively depleted immunosuppressive cells in the tumor microenviroment and antagonized tumor immune evasion via triple targeting of CAR, TCR and NK receptors. They exhibited a stable hypoimmunogenic phenotype associated with epigenetic and signaling regulation and did not induce detectable graft versus host disease or cytokine release syndrome. These properties of AlloCAR-NKT cells support their potential for clinical translation.

Inhibition of the rapamycin-insensitive mTORC1 /4E-BP1 axis attenuates TGF-ß1-induced fibrotic response in human Tenon's fibroblasts.

Subconjunctival fibrosis is the major cause of failure in both conventional and modern minimally invasive glaucoma surgeries (MIGSs) with subconjunctival filtration. The search for safe and effective anti-fibrotic agents is critical for improving long-term surgical outcomes. In this study, we investigated the effect of inhibiting the rapamycin-insensitive mTORC1/4E-BP1 axis on the transforming growth factor-beta 1(TGF-ß1)-induced fibrotic responses in human Tenon's fibroblasts (HTFs), as well as in a rat model of glaucoma filtration surgery (GFS). Primary cultured HTFs were treated with 3 ng/mL TGF-ß1 for 24 h, followed by treatment with 10 µM CZ415 for additional 24 h. Rapamycin (10 µM) was utilized as a control for mTORC1/4E-BP1 signaling insensitivity. The expression levels of fibrosis-associated molecules were measured using quantitative real-time PCR, Western blotting, and immunofluorescence analysis. Cell migration was assessed through the scratch wound assay. Additionally, a rat model of GFS was employed to evaluate the anti-fibrotic effect of CZ415 in vivo. Our findings indicated that both rapamycin and CZ415 treatment significantly reduced the TGF-ß1-induced cell proliferation, migration, and the expression of pro-fibrotic factors in HTFs. CZ415 also more effectively inhibited TGF-ß1-mediated collagen synthesis in HTFs compared to rapamycin. Activation of mTORC1/4E-BP signaling following TGF-ß1 exposure was highly suppressed by CZ415 but was only modestly inhibited by rapamycin. Furthermore, CZ415 was found to decrease subconjunctival collagen deposition in rats post GFS. Our results suggest that rapamycin-insensitive mTORC1/4E-BP1 signaling plays a critical role in TGF-ß1-driven collagen synthesis in HTFs. This study demonstrated that inhibition of the mTORC1/4E-BP1 axis offers superior anti-fibrotic efficacy compared to rapamycin and represents a promising target for improving the success rate of both traditional and modern GFSs.

Nitroreductase-responsive nanoparticles for in situ fluorescence imaging and synergistic antibacterial therapy of bacterial keratitis.

As bacterial keratitis progresses rapidly, prompt intervention is necessary. Current diagnostic processes are time-consuming and invasive, leading to improper antibiotics for treatment. Therefore, innovative strategies for diagnosing and treating bacterial keratitis are urgently needed. In this study, Cu2-xSe@BSA@NTRP nanoparticles were developed by loading nitroreductase-responsive probes (NTRPs) onto Cu2-xSe@BSA. These nanoparticles exhibited integrated fluorescence imaging and antibacterial capabilities. In vitro and in vivo experiments showed that the nanoparticles produced responsive fluorescence signals in bacteria within 30 min due to an interaction between the released NTRP and bacterial endogenous nitroreductase (NTR). When combined with low-temperature photothermal therapy (PTT), the nanoparticles effectively eliminated E. coli and S. aureus, achieved antibacterial efficacy above 95% and facilitated the re-epithelialization process at the corneal wound site in vivo. Overall, the Cu2-xSe@BSA@NTRP nanoparticles demonstrated potential for rapid, noninvasive in situ diagnosis, treatment, and visualization assessment of therapy effectiveness in bacterial keratitis.

Engineering allorejection-resistant CAR-NKT cells from hematopoietic stem cells for off-the-shelf cancer immunotherapy.

The clinical potential of current FDA-approved chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapy is encumbered by its autologous nature, which presents notable challenges related to manufacturing complexities, heightened costs, and limitations in patient selection. Therefore, there is a growing demand for off-the-shelf universal cell therapies. In this study, we have generated universal CAR-engineered NKT (UCAR-NKT) cells by integrating iNKT TCR engineering and HLA gene editing on hematopoietic stem cells (HSCs), along with an ex vivo, feeder-free HSC differentiation culture. The UCAR-NKT cells are produced with high yield, purity, and robustness, and they display a stable HLA-ablated phenotype that enables resistance to host cell-mediated allorejection. These UCAR-NKT cells exhibit potent antitumor efficacy to blood cancers and solid tumors, both in vitro and in vivo, employing a multifaceted array of tumor-targeting mechanisms. These cells are further capable of altering the tumor microenvironment by selectively depleting immunosuppressive tumor-associated macrophages and myeloid-derived suppressor cells. In addition, UCAR-NKT cells demonstrate a favorable safety profile with low risks of graft-versus-host disease and cytokine release syndrome. Collectively, these preclinical studies underscore the feasibility and significant therapeutic potential of UCAR-NKT cell products and lay a foundation for their translational and clinical development.

Efficient word segmentation is preserved in older adult readers: Evidence from eye movements during Chinese reading.

College-aged readers use efficient strategies to segment and recognize words in naturally unspaced Chinese text. Whether this capability changes across the adult lifespan is unknown, although segmenting words in unspaced text may be challenging for older readers due to visual and cognitive declines in older age, including poorer parafoveal processing of upcoming characters. Accordingly, we conducted two eye movement experiments to test for age differences in word segmentation, each with 48 young (18-30 years) and 36 older (65+ years) native Chinese readers. Following Zhou and Li (2021), we focused on the processing of "incremental" three-character words, like (meaning "kindergartens"), which contain an embedded two-character word (e.g., , meaning "children"). In Experiment 1, either the three-character word or its embedded word was presented as the target word in sentence contexts where the three-character word always was plausible, and the embedded word was either plausible or implausible. Both age groups produced similar plausibility effects, suggesting age constancy in accessing the embedded word early during ambiguity processing before ultimately assigning an incremental word analysis. Experiment 2 provided further evidence that both younger and older readers access the embedded word early during ambiguity processing, but rapidly select the appropriate (incremental) word. Crucially, the findings suggest that word segmentation strategies do not differ with age. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Trabectedin Enhances Oncolytic Virotherapy by Reducing Barriers to Virus Spread and Cytotoxic Immunity in Preclinical Pediatric Bone Sarcoma.

We previously reported that the DNA alkylator and transcriptional-blocking chemotherapeutic agent trabectedin enhances oncolytic herpes simplex viroimmunotherapy in human sarcoma xenograft models, though the mechanism remained to be elucidated. Here we report trabectedin disrupts the intrinsic cellular anti-viral response which increases viral transcript spread throughout the human tumor cells. We also extended our synergy findings to syngeneic murine sarcoma models, which are poorly susceptible to virus infection. In the absence of robust virus replication, we found trabectedin enhanced viroimmunotherapy efficacy by reducing immunosuppressive macrophages and stimulating granzyme expression in infiltrating T and NK cells to cause immune-mediated tumor regressions. Thus, trabectedin enhances both the direct virus-mediated killing of tumor cells and the viral-induced activation of cytotoxic effector lymphocytes to cause tumor regressions across models. Our data provide a strong rationale for clinical translation as both mechanisms should be simultaneously active in human patients.

Generation of human induced pluripotent stem cell line (XWHNi004-A) from a male with APOE gene mutation.

Genetic polymorphism of apolipoprotein E (APOE) confers differential susceptibility to Alzheimer's disease (AD), and APOE ɛ4 variants is the most powerful risk factor for this disease. Here, we report the generation of a human induced pluripotent stem cell (iPSC) line carrying the APOE ɛ4/ɛ4 genotype from peripheral blood mononuclear cells (PBMCs) isolated from a male with a family history of AD utilizing non-integrative Sendai virus vector. The iPSC maintains their original genotype, highly express endogenous pluripotency markers, displays a normal karyotype, and retains the ability to differentiate into cells representative of the three germ layers.

Rendering of 3D scenes in analytical polygon-based computer holography with texture mapping.

A computer-generated hologram (CGH) is a technique that generates an object light field by superimposing elementary holograms. Unlike traditional holography, this technique does not require the generation of an additional reference light to interfere with the calculated object light field. Texture mapping is a method that enhances the realism of 3D scenes. A fast method is presented that allows users to render holograms of 3D scenes consisting of triangular meshes with texture mapping. All calculations are performed with analytical expressions to ensure that the holograms generated by this method are fast and can reconstruct three-dimensional scenes with high quality. Using this method, a hologram of a three-dimensional scene consisting of thousands of triangles is generated. Our algorithm generates the same reconstruction results as those of Kim et al. [Appl. Opt.47, D117 (2008)APOPAI0003-693510.1364/AO.47.00D117], but significantly reduces the computation time (the computation time of our algorithm is only one-third of that of Kim et al.'s algorithm). The results show that the proposed method is computationally efficient as compared to a previous work. The proposed method is verified by simulations and optical experiments.

Peptide-Functionalized Inorganic Oxide Nanomaterials for Solid Cancer Imaging and Therapy.

The diagnosis and treatment of solid tumors have undergone significant advancements marked by a trend toward increased specificity and integration of imaging and therapeutic functions. The multifaceted nature of inorganic oxide nanomaterials (IONs), which boast optical, magnetic, ultrasonic, and biochemical modulatory properties, makes them ideal building blocks for developing multifunctional nanoplatforms. A promising class of materials that have emerged in this context are peptide-functionalized inorganic oxide nanomaterials (PFIONs), which have demonstrated excellent performance in multifunctional imaging and therapy, making them potential candidates for advancing solid tumor diagnosis and treatment. Owing to the functionalities of peptides in tumor targeting, penetration, responsiveness, and therapy, well-designed PFIONs can specifically accumulate and release therapeutic or imaging agents at the solid tumor sites, enabling precise imaging and effective treatment. This review provides an overview of the recent advances in the use of PFIONs for the imaging and treatment of solid tumors, highlighting the superiority of imaging and therapeutic integration as well as synergistic treatment. Moreover, the review discusses the challenges and prospects of PFIONs in depth, aiming to promote the intersection of the interdisciplinary to facilitate their clinical translation and the development of personalized diagnostic and therapeutic systems by optimizing the material systems.

Troxerutin improves cognitive function and forkhead box F2 expression in the hippocampus via modulating the microbial composition and the intestinal barrier function in diabetes mellitus mice.

Recent studies have found that gut microbes may affect blood-brain barrier (BBB) integrity. This study was to investigate the relationship between gut microbes and forkhead box F2 (FOXF2) and the mechanism of troxerutin improving diabetic cognitive dysfunction (DCD). Diabetic mice were used in this study for the prophylactic application of troxerutin (60 mg/kg/d) for 8 weeks. The cognitive function was assessed using the Morris water maze (MWM) and novel object recognition (NOR) tasks, and the changes of intestinal microbial composition were observed through 16S rRNA gene sequencing. The content of short-chain fatty acids (SCFAs) in feces was determined by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and the intestinal barrier function was assessed by enzyme-linked immunosorbent assay (ELISA) and western blotting. Troxerutin up-regulated FOXF2 expression in the hippocampus of mice, improving DCD. Meanwhile, it reversed the intestinal microbial composition (increased the abundance of the phylum Bacteroidota, as well as fecal propionic acid and butyric acid levels) and improved the intestinal barrier (increased the level of claudin-1 and significantly reduced the circulating lipopolysaccharide binding protein (LBP) levels). When intestinal microorganisms were removed with an antibiotic cocktail, the improvement of hippocampal FOXF2 expression and DCD by troxerutin attenuated accordingly, suggesting that troxerutin improved DCD by up-regulating the expression of hippocampal FOXF2 through the regulation of intestinal microbial composition and the intestinal barrier. In summary, troxerutin improved DCD by up-regulating the expression of hippocampal FOXF2 through the regulation of intestinal microbial composition and the intestinal barrier.

Contributions of climate change and urbanization to urban flood hazard changes in China's 293 major cities since 1980.

The growing incidence of urban flood disasters poses a major challenge to urban sustainability in China. Previous studies have reported that climate change and urbanization exacerbate urban flood risk in some major cities of China. However, few assessments have quantified the contributions of these two factors to urban flood changes in recent decades at the nationwide scale. Here, surface runoff caused by precipitation extremes was used as the urban flood hazard to evaluate the impacts of climate change and urbanization in China's 293 major cities. This study assessed the contributions of these drivers to urban flood hazard changes and identified the hotspot cities with increased trends under both factors during the past four decades (1980-2019). The results showed that approximately 70% of the cities analyzed have seen an increase of urban flood hazard in the latest decade. Urbanization made a positive contribution to increased urban flood hazards in more than 90% of the cities. The contribution direction of climate change showed significant variations across China. Overall, the absolute contribution rate of climate change far outweighed that of urbanization. In half of the cities (mainly distributed in eastern China), both climate change and urbanization led to increased urban flood hazard over the past decade. Among them, 33 cities have suffered a consecutive increase in urban flood hazard driven by both factors.

Comparing glycemic traits in defining diabetes among rural Chinese older adults.

BACKGROUND: We sought to identify the optimal cut-off of glycated hemoglobin (HbA1c) for defining diabetes and to assess the agreements of fasting plasma glucose (FPG), fasting serum glucose (FSG), and HbA1c in defining diabetes among rural older adults in China. METHODS: This population-based cross-sectional study included 3547 participants (age ≥61 years, 57.8% women) from the Multidomain Interventions to Delay Dementia and Disability in Rural China from 2018-2019; of these, 3122 had no previously diagnosed diabetes. We identified the optimal cut-off of HbA1c against FPG ≥7.0 mmol/L for defining diabetes by using receiver operating characteristic curve and Youden index. The agreements of FPG, FSG, and HbA1c in defining diabetes were assessed using kappa statistics. RESULTS: Among participants without previously diagnosed diabetes (n = 3122), the optimal HbA1c cut-off for defining diabetes was 6.5% (48 mmol/mol), with the sensitivity of 88.9%, specificity of 93.7%, and Youden index of 0.825. The correlation coefficients were 0.845 between FPG and FSG, 0.574 between FPG and HbA1c, and 0.529 between FSG and HbA1c in the total sample (n = 3547). The kappa statistic for defining diabetes was 0.962 between FSG and FPG, and 0.812 between HbA1c and FPG. CONCLUSIONS: The optimal cut-off of HbA1c for diagnosing diabetes against FPG >7.0 mmol/L is ≥6.5% in Chinese rural-dwelling older adults. The agreement in defining diabetes using FPG, FSG, and HbA1c is nearly perfect. These results have relevant implications for diabetes research and clinical practice among older adults in China. CLINICAL TRIAL REGISTRATION: The protocol of MIND-China was registered in the Chinese Clinical Trial Registry (ChiCTR, www.chictr.org.cn; registration no.: ChiCTR1800017758).

Effect of the staging comprehensive treatment with acupuncture-moxibustion on Bell's facial palsy in the acute stage. / 针灸分期综合治疗急性期贝尔面瘫疗效观察.

OBJECTIVES: To compare the clinical effect on Bell's facial palsy in the acute stage between the staging comprehensive treatment with acupuncture-moxibustion and western medication. METHODS: Sixty patients with Bell's facial palsy in the acute stage were randomly divided into an observation group and a control group, with 30 cases in each one. The patients in the control group were administered orally with prednisone acetate tablets and methylcobalamin tablets until the 28th day of illness. In the observation group, the staging comprehensive treatment with acupuncture-moxibustion was adopted. On the affected side, Qianzheng (EX-HN 16), Yifeng (TE 17), Sibai (ST 2), Yangbai (GB 14), Jiache (ST 6), Dicang (ST 4) and Touwei (ST 8), etc. were stimulated. In the acute stage (Day 1 to 7 of illness), the routine acupuncture and the point-toward-point needle insertion were delivered, no any manipulation was exerted at acupoints, and the needles were retained for 30 min. In the subacute stage (Day 8 to 14 of illness), on the base of the treatment as the acute stage, the depth of needle insertion was adjusted at a part of acupoints and the even needling technique was operated by twisting needle. Besides, electroacupuncture (EA) was attached to Qianzheng (EX-HN 16) and Dicang (ST 4), with continuous wave of low intensity and high frequency, 100 Hz, for 20 min. In the recovery stage (Day 15 to 28 of illness), on the base of the treatment as the subacute stage, the heavy stimulation of acupuncture was given, in which, the sticking and lifting needle techniques were delivered after the needles were inserted from Sibai (ST 2) toward Dicang (ST 4), and from Dicang (ST 4) toward Jiache (ST 6), separately; warm needling was operated at Yifeng (TE 17), and EA changed to stimulate the acupoints with the intermittent wave of high intensity and low frequency, 2 Hz, for 30 min. Acupuncture-moxibustion was given once every other day until the end of the 28th day of illness. The level of House-Brackmann facial nerve function rating scale (H-B grade),the score of Sunnybrook facial nerve grading system (Sunnybrook), the score of facial disability index (FDI), the temperature difference in the infrared thermal imaging facial area and electromyogram (EMG) situation of the affected muscle group were observed before and after treatment in the two groups. Using musculoskeletal ultrasound,the facial nerve diameter was detected and the clinical effect was compared between the two groups. RESULTS: After treatment, the level of H-B grade, Sunnybrook score, the scores of physical function and social life function in FDI were improved when compared with those before treatment in the patients of either group (P<0.01, P<0.05), and the results of these evaluations in the observation group were better than those of the control group (P<0.05). After treatment, the temperature difference of the frontal area, the eye area, the zygomatic area and the mouth corner was declined in comparison with that before treatment in the two groups (P<0.05), and the temperature difference in each area in the observation group was lower than that of the control group (P<0.05).The root mean square (RMS) of the frontal muscle group, the zygomatic muscle group and the orbicularis muscle group on the affected side increased in comparison with that before treatment in the two groups (P<0.01), and RMS of the observation group was higher than that of the control group (P<0.05) after treatment. Before treatment, the diameter of the facial nerve on the affected side was larger than that on the healthy side (P<0.01), and after treatment, the diameter on the affected side was reduced when compared with that before treatment in the two groups (P<0.01); the diameter of the facial nerve on the affected side in the observation group was smaller than that of the control group (P<0.05), while, the diameter on the affected side was larger when compared with the healthy side in the control group (P<0.05). The total effective rate of the observation group was 93.3% (28/30), higher than that of the control group (83.3% [25/30], P<0.05). CONCLUSIONS: The staging comprehensive treatment with acupuncture-moxibustion is clearly effective on Bell's facial palsy in the acute stage, which affirms the effectiveness of acupuncture-moxibustion for the acute stage of Bell's facial palsy in comparison with conventional western medication.

Clinical significance of abdominal computed tomography and colonoscopy in the evaluation of phlebosclerotic colitis.

Clinical manifestations of phlebosclerotic colitis (PC) exhibit significant variability, necessitating diverse treatment strategies depending on disease severity. However, there is limited research exploring the relationship between imaging findings and disease severity. Hence, this retrospective study aimed to analyze the correlation between computed tomography (CT) findings, colonoscopic features, and disease severity. This study compared the abdominal CT characteristics, colonoscopy findings, and treatment modalities of 45 PC patients. CT images were assessed for the severity of mesenteric venous calcification, maximum colonic wall thickness, number of involved colonic segments, and presence of pericolic inflammation. Colonoscopic images were assessed for dark purple discoloration mucosa, erosive and ulcerative lesions, mucosal edema, luminal narrowing, and the number of involved colonic segments. In addition, patients were categorized into three groups: the observation (n = 15), medical treatment (n = 19), and operation (n = 11) groups. In CT images, a significant difference in pericolic inflammation (p = 0.039) was observed among groups. Further, significant differences in dark purple discoloration mucosa (p = 0.033), erosive or ulcerative lesions (p < 0.001), mucosal edema (p < 0.001), luminal narrowing (p = 0.012), and the number of involved colonic segments (p = 0.001) were observed in colonoscopy. Moreover, we found positive correlations between CT and colonoscopy features. In conclusion, CT manifestations and colonoscopy findings exhibited correlation with disease severity in PC. When limited to one diagnostic tool, observations from that tool can infer potential manifestations of the alternative tool.

Intra-subject enveloped multilayer fuzzy sample compression for speech diagnosis of Parkinson's disease.

Machine learning-based Parkinson's disease (PD) speech diagnosis is a current research hotspot. However, existing methods use each corpus sample as the base unit for modeling. Since different corpus samples within the same subject have different sensitive speech features, it is difficult to obtain unified and stable sensitive speech features (diagnostic markers) that reflect the pathology of the whole subject. Therefore, this study aims at compressing the corpus samples within the subject to facilitate the search for diagnostic markers with high diagnostic accuracy. A two-step sample compression module (TSCM) can solve the problem above. It includes two major parts: sample pruning module (SPM) and sample fuzzy clustering mechanism (SFCMD). Based on stacking multiple TSCMs, a multilayer sample compression module (MSCM) is formed to obtain multilayer compression samples. After that, simultaneous sample/feature selection mechanism (SS/FSM) is designed for feature selection. Based on the multilayer compression samples processed by MSCM and SS/FSM, a novel ensemble learning algorithm (EMSFE) is designed with sparse fusion ensemble learning mechanism (SFELM). The proposed EMSFE is validated by visualization of extracted features and performance comparison with related algorithms. The experimental results show that the proposed algorithm can effectively extract the stable diagnostic markers by compressing the corpus samples within the subject. Furthermore, based on LOSO cross validation, the proposed algorithm with extreme learning machine (ELM) classifier can achieve the accuracy of 92.5%, 93.75% and 91.67% on three datasets, respectively. The proposed EMSFE can extract unified and stable sensitive features that accurately reflect the overall pathology of the subject, which can better meet the requirements of clinical applications.The code and datasets can be found in: https://github.com/wywwwww/EMSFE-supplementary-material.git.

A D-Y Shaped Neuropeptide Y Mimetic Peptide-Dye Self-Assembly with Maximal Emission Beyond 1300 nm and Glioma Mitochondrial Activity Modulation.

Neuropeptide Y (NPY), as one of the most abundant neuropeptides known, is widely distributed in the central and peripheral nervous system. However, most of the reported NPY-mimetic peptides are hard to cross the blood-brain barrier, target glioma mitochondria, and achieve self-assembly nanostructure in situ. Here, based on the α-helix structure of the novel chiral NPY-mimetic peptides D/LNPY(14), a Y-shaped peptide is designed with the sequences that can be recognized by enterokinase and achieved nanofibers conversion in glioma cell mitochondria. Coupling the Y-shaped NPY-mimetic peptide with the NIR-II fluorophore IR1048, a red-shifting of the fluorescence spectrum beyond 1300 nm is achieved through self-assembly. After the self-assembly in glioma mitochondria, the formed nanofibers can promote intracellular mitochondrial ROS production and extend the NIR-II fluorescence imaging time to at least 7 days in vivo. This work for the first time endows the self-assembly of α-helical-based chiral NPY-mimetic peptides, providing a novel strategy for glioma subcellular regulation enhanced antitumor treatment guided by NIR-II fluorescence imaging.