Gut microbiota Parabacteroides distasonis enchances the efficacy of immunotherapy for bladder cancer by activating anti-tumor immune responses.

OBJECTIVE: Bladder cancer(BCa) was a disease that seriously affects patients' quality of life and prognosis. To address this issue, many researches suggested that the gut microbiota modulated tumor response to treatment; however, this had not been well-characterized in bladder cancer. In this study, our objective was to determine whether the diversity and composition of the gut microbiota or the density of specific bacterial genera influence the prognosis of patients with bladder cancer. METHODS: We collected fecal samples from a total of 50 bladder cancer patients and 22 matched non-cancer individuals for 16S rDNA sequencing to investigate the distribution of Parabacteroides in these two groups. Further we conducted follow-up with cancer patients to access the impact of different genera of microorganisms on patients survival. We conducted a Fecal Microbiota Transplantation (FMT) and mono-colonization experiment with Parabacteroides distasonis to explore its potential enhancement of the efficacy of anti-PD-1 immunotherapy in MB49 tumor-bearing mice. Immunohistochemistry, transcriptomics and molecular experiment analyses were employed to uncover the underlying mechanisms. RESULTS: The 16S rDNA showed that abundance of the genus Parabacteroides was elevated in the non-cancer control group compared to bladder cancer group. The results of tumor growth curves showed that a combination therapy of P. distasonis and ICIs treatment significantly delayed tumor growth and increased the intratumoral densities of both CD4+T and CD8+T cells. The results of transcriptome analysis demonstrated that the pathways associated with antitumoral immune response were remarkably upregulated in the P. distasonis gavage group. CONCLUSION: P. distasonis delivery combined with α-PD-1 mAb could be a new strategy to enhance the effect of anti-PD-1 immunotherapy. This effect might be achieved by activating immune and antitumor related pathways.

The dynamic progression of temporomandibular joint osteoarthritis-like lesions elicited by mandibular shift in a rat model.

BACKGROUND: Temporomandibular joint osteoarthritis (TMJ-OA) presents significant challenges due to its complex etiology, often insidious onset, high incidence, and progressive structural deterioration. While research has explored genetic and molecular factors, treatment outcomes remain suboptimal, emphasizing the need for a deeper understanding of disease progression. OBJECTIVE: This study employs a specific mandibular shift rat model to explore the dynamic progression of TMJ-OA-like lesions and evaluate the potential for self-repair at different stages, aiming to inform early diagnosis and preventative strategies. METHODS: Seventy-two female Sprague-Dawley rats were randomized into three groups: a control group (n=24; average weight: 157.23±1.63 g) receiving sham surgery. an experimental group (n=24; average weight: 157.78±1.88 g) subjected to mandibular shift induction, and a removal group (n=24; average weight: 158.11±2.20 g) experiencing mandibular shift for one, two, or four weeks followed by a one-month recovery period (designated as 1w Removal, 2w Removal and 4w Removal, respectively). Histomorphological and molecular analyses were conducted at designated time points. RESULTS: Rats in the 1-week removal group exhibited substantial recovery in condylar morphology, cartilage thickness, extracellular matrix composition, and expression of OA-related genes. Conversely, the 4-week removal group mirrored the experimental group, indicating limited self-repair capacity at later stages. The 2-week removal group presented with variable outcomes, with some animals showing signs of recovery and others resembling the experimental group, indicating a potential transitional phase in the disease process. CONCLUSION: Recovery from early-stage TMJ-OA involves eliminating provoking factors such as occlusal interference or reducing joint loading. However, advanced stages exhibit diminished self-repair capabilities, necessitating additional therapeutic interventions. These findings emphasize the importance of early diagnosis and intervention in TMJ-OA management.

Whole exome sequencing indicating GGCCTG hexanucleotide repeat in patients with spinocerebellar ataxia type 36.

INTRODUCTION: Spinocerebellar ataxia type 36 (SCA36) is caused by large GGCCTG repeat expansion in the NOP56 gene. The genetic diagnosis based on Southern blot is expensive and time-consuming. This study aimed to evaluate the reliability and effectiveness of whole exome sequencing (WES) for routine genetic diagnosis of suspected SCA36 patients. METHODS: Pathogenic repeat expansions for SCAs including SCA36 were first analyzed based on WES data using ExpansionHunter in five probands from SCA families, then the results were confirmed by triplet repeat primed polymerase chain reaction (TP-PCR) and Southern blot. RESULTS: GGCCTG repeat expansion in NOP56 was indicated in all five probands by WES, then it was found in 11 SCA patients and three asymptomatic individuals by TP-PCR. The sizes of GGCCTG repeat expansions were confirmed to be 1390-1556 by Southern blot. The mean age at onset of the patients was 51.0 ± 9.3 (ranging from 41 to 71), and they presented slowly progressive cerebellar ataxia, atrophy and fasciculation in tongue or limb muscles. CONCLUSION: The patients were clinically and genetically diagnosed as SCA36. This study proposed that WES could be a rapid, reliable, and cost-effective routine test for the preliminarily detection of SCA36 and other ataxia diseases.

Puerariae lobatae Radix ameliorates chronic kidney disease by reshaping gut microbiota and downregulating Wnt/ß­catenin signaling.

Gut microbiota dysfunction is a key factor affecting chronic kidney disease (CKD) susceptibility. Puerariae lobatae Radix (PLR), a traditional Chinese medicine and food homologous herb, is known to promote the gut microbiota homeostasis; however, its role in renoprotection remains unknown. The present study aimed to investigate the efficacy and potential mechanism of PLR to alleviate CKD. An 8­week 2% NaCl­feeding murine model was applied to induce CKD and evaluate the therapeutic effect of PLR supplementary. After gavage for 8 weeks, The medium and high doses of PLR significantly alleviated CKD­associated creatinine, urine protein increasement and nephritic histopathological injury. Moreover, PLR protected kidney from fibrosis by reducing inflammatory response and downregulating the canonical Wnt/ß­catenin pathway. Furthermore, PLR rescued the gut microbiota dysbiosis and protected against high salt­induced gut barrier dysfunction. Enrichment of Akkermansia and Bifidobacterium was found after PLR intervention, the relative abundances of which were in positive correlation with normal maintenance of renal histology and function. Next, fecal microbiota transplantation experiment verified that the positive effect of PLR on CKD was, at least partially, exerted through gut microbiota reestablishment and downregulation of the Wnt/ß­catenin pathway. The present study provided evidence for a new function of PLR on kidney protection and put forward a potential therapeutic strategy target for CKD.

Bifunctional Tb(III)-modified Ce-MOF nanoprobe for colorimetric and fluorescence sensing of α-glucosidase activity.

α-Glucosidase, which directly involves in the metabolism of starch and glycogen and causes an increase in blood sugar level, is the major target enzyme for the precaution and therapy of type II diabetes. Based on the previous work, we adopted a post-synthetic modification method to encapsulate Tb3+ into Ce-MOF nanozyme which owned mixed valence states. Tb@Ce-MOF displayed induced luminescence characteristic and exceptional oxidase-like activity that could oxidize colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue ox-TMB. α-Glucosidase can hydrolyze the substrate l-ascorbic acid-2-O-α-d-glucopyranosyl (AAG) to generate ascorbic acid (AA), which could increase the Ce3+/Ce4+ redox valence mode in Tb@Ce-MOF, leading to the inhibition of the allochroic reaction of TMB and the decreased absorption of ox-TMB at 652 nm. The energy transfer (EnT) process from Ce3+ to Tb3+ will enhance due to the increased Ce3+/Ce4+ mode in Tb@Ce-MOF, which will result in an enhanced fluorescence signal of Tb@Ce-MOF at 550 nm. But the addition of inhibitor acarbose will inhibit the above process. We have constructed a dual-mode detection platform of α-glucosidase and its inhibitor via colorimetric and fluorometric method. The linear range of α-glucosidase were 0.01-0.5 U/mL (colorimetric mode) and 0.8-1.5 U/mL (fluorometric mode), respectively, with a detection limit as low as 0.0018 U/mL. Furthermore, our approach was also successfully employed to the analysis of α-glucosidase in serum samples.

Clinical and genetic characteristics of myotonia congenita in Chinese population.

Myotonia congenita (MC) is a rare hereditary muscle disease caused by variants in the CLCN1 gene. Currently, the correlation of phenotype-genotype is still uncertain between dominant-type Thomsen (TMC) and recessive-type Becker (BMC). The clinical data and auxiliary examinations of MC patients in our clinic were retrospectively collected. Electromyography was performed in 11 patients and available family members. Whole exome sequencing was conducted in all patients. The clinical and laboratory data of Chinese MC patients reported from June 2004 to December 2022 were reviewed. A total of 11 MC patients were included in the study, with a mean onset age of 12.64 ± 2.73 years. The main symptom was muscle stiffness of limbs. Warm-up phenomenon and percussion myotonia were found in all patients. Electromyogram revealed significant myotonic charges in all patients and two asymptomatic carriers, while muscle MRI and biopsy showed normal or nonspecific changes. Fourteen genetic variants including 6 novel variants were found in CLCN1. Ninety-eight Chinese patients were re-analyzed and re-summarized in this study. There were no significant differences in the demographic data, clinical characteristics, and laboratory findings between 52 TMC and 46 BMC patients. Among the 145 variants in CLCN1, some variants, including the most common variant c.892 G>A, could cause TMC in some families and BMC in others. This study expanded the clinical and genetic spectrum of Chinese patients with MC. It was difficult to distinguish between TMC and BMC only based on the clinical, laboratory, and genetic characteristics.

UiO-66-NH2 initiated cascade reaction: Constructing a ratiometric fluorescence sensor for ultrasensitive detection of nerve agent simulant.

BACKGROUND: Highly toxic organophosphorus nerve agents often exist in the form of gas in the environment and can damage human neuroregulatory system by inhibiting the activity of acetylcholinesterase (AChE). However, fluorescent probes based on small organic molecules bring a secondary burden to environment, and their sensitivity and specificity for sarin simulant diethyl chlorophosphate (DCP) detection are unsatisfactory. Nanozyme cascade systems with signal amplification can be used for highly sensitive identification of analytes, but are rarely used in ratiometric analysis of DCP. Combination of enzyme cascades and ratiometric fluorescence ensures the accuracy and sensitivity of the output signal. RESULTS: We prepared a self-assembled nanohybrid (Ag-AuNCs@UiO-66-NH2) by metal-organic framework material and gold nanoclusters. On the one hand, UiO-66-NH2 with enzyme-like activity was used to hydrolyze DCP into diethyl phosphate (DEP) and chloridion (Cl-). Cl- hindered aggregation-induced enhanced emission (AIEE) of AuNCs by binding with Ag+ and decreased the fluorescence of AuNCs. On the other hand, ligand metal charge transfer effect (LMCT) of UiO-66-NH2 was blocked by DCP to enhance the fluorescence of UiO-66-NH2. Combining ratiometric analysis and nanozyme cascade reaction, an ultra-sensitive fluorescence sensor for detecting DCP was constructed, and ensured the accuracy of experimental results. In addition, Ag-AuNCs@UiO-66-NH2 was embedded into the agarose hydrogel substrate, the resulting agarose hydrogel film allowed quantitative assessment of DCP vapor and high sensitivity was demonstrated (detection limit as low as 1.02 ppb). SIGNIFICANCE: A strategy combining enzyme cascade with ratiometric fluorescence was proposed, which improved the accuracy and sensitivity of the analysis results. The soft-solid platform based on agarose hydrogel film was constructed to realize the quantitative monitoring of sarin simulant gas. The LOD value obtained in this work is much lower than the immediately life-threatening or health threatening concentration of sarin.

Venetoclax plus a hypomethylating agent versus cytarabine, aclarubicin, and granulocyte colony-stimulating factor chemotherapy as a first-line therapy for newly diagnosed acute myeloid leukemia: A propensity score-matched analysis.

BACKGROUND: Both venetoclax plus a hypomethylating agent (VEN/HMA) and cytarabine, aclarubicin, and granulocyte colony-stimulating factor (CAG) are low-intensity regimens for older patients with acute myeloid leukemia (AML) that show good efficacy and safety. It is unknown how VEN/HMA compares with the CAG regimen for the treatment of newly diagnosed AML. METHODS: The outcomes of patients with newly diagnosed AML treated with VEN/HMA were compared with those of patients treated with a CAG-based regimen. Propensity score matching between these two cohorts at a 1:1 ratio was performed according to age at diagnosis, sex, Eastern Cooperative Oncology Group performance status, state of fitness, and European LeukemiaNet (ELN) 2022 risk stratification to minimize bias. RESULTS: A total of 84 of 96 patients in the VEN/HMA cohort were matched with 84 of 147 patients in the CAG cohort. VEN/HMA resulted in a better response than the CAG-based regimens, as indicated by a higher composite complete remission (CRc) rate (82.1% vs. 60.7%; p = .002) and minimal residual disease negativity rate (88.2% vs. 68.2%; p = .009). In patients with an ELN adverse risk, VEN/HMA was associated with a higher CRc rate compared to CAG (80.5% vs. 58.3%; p = .006). VEN/HMA was associated with longer event-free survival (EFS) (median EFS, not reached vs. 4.5 months; p = .0004), whereas overall survival (OS) was comparable between the two cohorts (median OS, not reached vs. 18 months; p = .078). CONCLUSIONS: The VEN/HMA regimen may result in a better response than CAG-based treatment in older patients with newly diagnosed AML.

A novel score to predict progression in anterior circulation single subcortical infarction patients.

OBJECTIVE: Progressive infarction (PI) has a negative effect on functional prognosis. Our study aimed to develop and validate a risk score for predicting PI in patients with anterior circulation single subcortical infarction (ACSSI). METHODS: Between January 2020 and October 2022, we retrospectively enrolled 638 eligible patients with ACSSI. Two-thirds of the eligible patients were randomly allocated to the training cohort (n = 425). Another resampling sample was formed through the bootstrap method and was used as the validation group (n = 425). Multivariate logistic regression analysis was used to identify the independent factors associated with PI. Each factor was then point assigned based on ß-coefficient and a risk scoring system was developed. This scoring system was internally validated through 1000-bootstrap resamplings. The C-statistic and Hosmer-Lemeshow test were used to assess model discrimination and calibration. RESULTS: PI occurred in 121 patients, accounting for 19.0% of the total patients. A 7-point NTS score system based on the initial NIHSS score, triglyceride-glucose index, and the number of infarct slices on axial diffusion-weighted imaging was developed. The NTS score showed good discrimination and calibration in the training cohort (C-statistic = 0.686; p value of Hosmer-Lemeshow test = 0.797) and validation cohort (C-statistic = 0.681; p value of Hosmer-Lemeshow test = 0.451). The three risk levels for predicting PI in the training and validation cohorts based on NTS score were as follows: low (0-2, 9.6% vs. 9.3%), intermediate (3-5, 28.2% vs. 26.7%), and high risk (6-7, 60.2% vs. 57.4%). INTERPRETATION: The NTS score is a valid and convenient risk score for predicting PI in ACSSI patients.

TG/HDL-c ratio as a predictor of progressive infarction in patients with anterior circulation single subcortical infarction.

BACKGROUND: The contributors predicting progressive infarction (PI) in patients with anterior circulation single subcortical infarction (ACSSI) and pontine single infarction (PSI) may be unidentical. The role of triglyceride to high-density lipoprotein cholesterol (TG/HDL-c) ratio on PI is unclear. The purpose of our study is to evaluate the correlation between TG/HDL-c ratio and PI in patients with ACSSI or PSI. METHODS: Between January 2020 and October 2022, we retrospectively enrolled 738 patients including 638 ACSSI patients and 100 PSI patients to analyze. Demographic characteristics, clinical information, and laboratory data were collected within 24 h of admission. RESULTS: PI occurred in 143 (19.4%) patients. In univariate analysis, patients with PI had higher initial National Institutes of Health Stroke Scale (NIHSS) scores, higher discharge NIHSS scores, higher levels of fasting glucose, total cholesterol, TG, low-density lipoprotein cholesterol, and TG/HDL-c ratio, but lower levels of creatinine compared to patients with non-PI (p < .05). Furthermore, the results of the subgroup analyses revealed the independent association between TG/HDL-c ratio and PI in ACSSI patients (OR 1.079, 95% CI 1.009-1.153, p = .026) rather than in PSI patients. Additionally, a receiver operating characteristic curve indicated that the optimal predictive cutoff value of the TG/HDL-c ratio was 3.985, and a TG/HDL-c ratio ≥3.985 was more likely to experience PI in ACSSI patients. CONCLUSION: In conclusion, the TG/HDL-c ratio was independently associated with PI in patients with ACSSI.

Has the Integrated Medical Insurance System promoted return-to-hometown entrepreneurship among migrant workers? Evidence from China.

An important way to reduce urban-rural disparity lies in encouraging migrant workers to return to their hometowns for entrepreneurship. This paper examines the effect of the Integrated Medical Insurance System on the return-to-hometown entrepreneurship among migrant workers. Using microdata from the China Household Finance Survey (CHFS) spanning from 2013 to 2019, we find that the Integrated Medical Insurance System (IMIS) significantly increases the likelihood of migrant workers returning to their hometowns for entrepreneurship by 0.44%. This result remains stable after a series of robustness checks. Heterogeneity results indicate that this "pullback effect" is more pronounced for those who are male and with lower educational levels, higher income, larger social networks, and lower risk preferences. Finally, the interaction between the Mass Entrepreneurship and Innovation policy (MEI) and IMIS can create a more significant combined effect in promoting the return of migrant workers to their hometowns for entrepreneurial activities.

Pyrolytic Modification of Heavy Coal Tar by Multi-Polymer Blending: Preparation of Ordered Carbonaceous Mesophase.

In order to achieve the high-value utilization of heavy tar for the production of enhanced-performance graphite foam carbon, the carbon mesophase was ready from the heavy component of low-temperature coal tar, and the coal tar was modified by styrene-butadiene-styrene (SBS), polyethylene (PE) and ethylene-vinyl-acetate (EVA) copolymers. The order degree of the carbonite mesophase was analyzed using a polarizing microscope test, Fourier transform infrared spectroscopy and X-ray diffraction to screen out the most suitable copolymer type and addition amount. Furthermore, the mechanism of modification by this copolymer was analyzed. The results showed that adding SBS, PE and EVA to coal tar would affect the order of carbonaceous mesophase; however, at an addition rate of 10.0 wt.%, the linear-structure SBS copolymer with a styrene/butadiene ratio (S/B) of 30/70 exhibited the optimal degree of ordering in the carbonaceous mesophase. Its foam carbon prepared by polymer modification is the only one that forms a graphitized structure, with d002 of 0.3430 nm, and the maximum values of Lc and La are 3.54 nm and 2.22 nm, respectively. This is because, under elevated pressure and high-temperature conditions, SBS underwent chain scission, releasing a more significant number of methyl and other free radicals that interacted with the coal tar constituents. As a result, it reduced the affinity density of heavy coal tar molecules, enhanced fluidity, promoted the stacking of condensed aromatic hydrocarbons and increased the content of soluble carbonaceous mesophase, ultimately leading to a more favorable alignment of the carbonaceous mesophase.

Salivary miR-150-5p as an indicator of periodontitis severity and regulator of human periodontal ligament fibroblast behavior by targeting AIFM2.

OBJECTIVE: This study aimed to evaluate the role of miR-150-5p in the onset and progression of periodontitis, and reveal the potential molecular mechanism underlying its function and to explore a novel biomarker for periodontitis. BACKGROUND: Periodontitis is the leading cause of tooth loss in adults, emphasizing the need for a biomarker to improve its early detection and prevention. The association of miR-150-5p with diseases related to Fuscobacterium nucleatum implies its potential involvement in periodontitis. METHODS: The expression of miR-150-5p in the saliva of patients with periodontitis (n = 77) and healthy individuals (n = 43) was assessed by PCR. Human gingival fibroblasts (HGFs) were induced with an osteogenic culture medium. The regulatory effect of miR-150-5p on the proliferation and migration of HGFs was assessed by CCK8 and transwell assays. Osteogenic differentiation was estimated based on the expression of corresponding factors through western blotting, and the inflammatory response was evaluated by measuring the levels of pro-inflammatory cytokines using ELISA. RESULTS: Significant upregulation of miR-150-5p was observed in patients with periodontitis, which sensitively distinguished them and was closely associated with the severity and periodontal index of the condition. In HGFs, osteogenic induction (OI) resulted in increased miR-150-5p levels, which negatively regulated the expression of AIFM2. Silencing miR-150-5p significantly attenuated OI-induced suppression of proliferation and migration of HGFs. The silencing also alleviated inflammation and osteogenic differentiation, which was reversed upon AIFM2 knockdown. CONCLUSION: Upregulated miR-150-5p in periodontitis served as a diagnostic biomarker, indicating the occurrence and aggravation of disease condition. Silencing miR-150-5p inhibited the osteogenic differentiation and inflammation of HGFs by negatively modulating AIFM2.

Potentiation of the lateral habenula-ventral tegmental area pathway underlines the susceptibility to depression in mice with chronic pain.

Chronic pain often develops severe mood changes such as depression. However, how chronic pain leads to depression remains elusive and the mechanisms determining individuals' responses to depression are largely unexplored. Here we found that depression-like behaviors could only be observed in 67.9% of mice with chronic neuropathic pain, leaving 32.1% of mice with depression resilience. We determined that the spike discharges of the ventral tegmental area (VTA)-projecting lateral habenula (LHb) glutamatergic (Glu) neurons were sequentially increased in sham, resilient and susceptible mice, which consequently inhibited VTA dopaminergic (DA) neurons through a LHbGlu-VTAGABA-VTADA circuit. Furthermore, the LHbGlu-VTADA excitatory inputs were dampened via GABAB receptors in a pre-synaptic manner. Regulation of LHb-VTA pathway largely affected the development of depressive symptoms caused by chronic pain. Our study thus identifies a pivotal role of the LHb-VTA pathway in coupling chronic pain with depression and highlights the activity-dependent contribution of LHbGlu-to-VTADA inhibition in depressive behavioral regulation.

Effects of the preoperative use of artificial tears combined with recombinant bovine basic fibroblast growth factor on cataract patients complicated with dry eyes / Efeitos do uso pré-operatório de lágrimas artificiais combinadas com fator de crescimento de fibroblastos básicos bovinos recombinantes em pacientes com catarata complicada com olhos secos

ABSTRACT Purpose: To assess the effects of the preoperative application of artificial tears combined with recombinant bovine basic fibroblast growth factor on the ocular surface function and inflammatory factor levels after operation in cataract patients complicated with dry eyes. Methods: A total of 118 cataract patients (118 eyes) complicated with dry eyes treated from February 2019 to February2020 were assigned to control and observation groups (n=59 eyes/group) using a random number table. One week before the operation, the control group was administered 0.1% sodium hyaluronate eye drops (artificial tears), based on which the observation group received Beifushu eye drops (recombinant bovine basic fibroblast growth factor), both 6 times daily for 1 week. A comparison was made between the scores of clinical symptoms and the indices of ocular surface function, inflammatory factors in tears, and oxidative stress indices before and after the operation. The ocular surface function was evaluated by an ocular surface disease index questionnaire, tear film breakup-time assay, Schirmer's I test, and corneal fluorescein stain test. The inflammatory factors in tears were measured. Results: No significant differences were noted in the general data and clinical symptom score, ocular surface disease index, tear film breakup-time, Schirmer's I test score, fluorescein stain score, interleukin-6, tumor necrosis factor-alpha, malondialdehyde, superoxide dismutase, lipid peroxide, and total antioxidant capacity before treatment between the 2 groups (p>0.05). After treatment, the clinical symptom score, ocular surface disease index, fluorescein stain score, tumor necrosis factor-alpha, interleukin-6, malondial-dehyde and lipid peroxide declined significantly, and tear film breakup-time, Schirmer's I test score, superoxide dismutase, and total antioxidant capacity increased in both the groups. The improvements in the clinical symptom score as well as in the indices of ocular surface function, inflammatory factors, and oxidative stress were more prominent in the observation group than in the control group (p<0.05). Conclusions: Artificial tears combined with recombinant bovine basic fibroblast growth factor before operation. significantly improved the ocular surface function, reduced inflammatory factors in tears, and alleviated dry eye symptoms after operation in cataract patients.

RESUMO Objetivo: Avaliar os efeitos da aplicação pré-operatória de lágrimas artificiais combinadas com o fator de crescimento de fibroblastos básicos bovinos recombinantes na função da superfície ocular e níveis de fator inflamatório após cirurgia em pacientes com catarata complicada com olhos secos. Métodos: Um total de 118 pacientes com catarata complicada com olhos secos (118 olhos), tratados entre fevereiro de 2019 e fevereiro de 2020, foram divididos em grupos de controle e de observação (n=59, 59 olhos) usando uma tabela de números aleatórios. Uma semana antes da cirurgia, o grupo controle recebeu colírio de hialuronato de sódio a 0,1% (lágrimas artificiais), enquanto o grupo de observação recebeu colírio Beifushu (fator de crescimento de fibroblastos básicos bovinos recombinantes), ambos, seis vezes ao dia, por uma semana. Antes do tratamento e um mês após a cirurgia, os escores de sintomas clínicos, índices de função da superfície ocular, níveis de fatores inflamatórios nas lágrimas e índices de estresse oxidativo foram comparados. A função da superfície ocular foi avaliada pelo questionário do índice de doença da superfície ocular, ensaio de tempo de ruptura do filme lacrimal, teste I de Schirmer e teste de coloração por fluoresceína da córnea. Os níveis de fatores inflamatórios nas lágrimas foram medidos. Resultados: Não houve diferenças significativas nos dados gerais e no escore de sintomas clínicos, índice de doença da superfície ocular, tempo de ruptura do filme lacrimal, escore do teste I de Schirmer, pontuação do teste de coloração por fluoresceína da córnea, interleucina-6, fator de necrose tumoral alfa, malondialdeído, superóxido dismutase, peróxido lipídico e capacidade antioxidante total antes do tratamento entre os dois grupos (p>0,05). Após o tratamento, o escore de sintomas clínicos, índice de doença da superfície ocular, escore do teste de coloração por fluoresceína da córnea, fator de necrose tumoral alfa, interleucina-6, malondialdeído e peróxido lipídico diminuíram significativamente, e o tempo de ruptura do filme lacrimal, escore do teste I de Schirmer, superóxido dismutase e a capacidade antioxidante total aumentou em ambos os grupos. As melhorias no escore de sintomas clínicos, bem como os índices de função da superfície ocular, fatores inflamatórios e estresse oxidativo foram mais proeminentes no grupo de observação do que no grupo controle (p<0,05). Conclusões: Lágrimas artificiais combinadas com fator de crescimento de fibroblastos básicos recombinantes antes da cirurgia melhoram notavelmente a função da superfície ocular, diminuem os níveis de fatores inflamatórios nas lágrimas e aliviam os sintomas de olho seco após a cirurgia em pacientes com catarata complicada com olhos secos.

Zirconium-based metal-organic framework loaded agarose hydrogels for fluorescence turn-on detection of nerve agent simulant vapor.

Developing reliable sensors that accurately detect deadly chemical gases is critical to global security. Nerve agents are one of the most dangerous chemicals in the world and are often found in gaseous forms in the environment, which remain a challenge to detect because of their low levels. In this paper, a fluorescent probe based on a Zr-based metal-organic framework UiO-66-NH2 was proposed. The specific binding between the Zr-O site of UiO-66-NH2 and diethyl chlorophosphate (DCP) blocked the ligand-to-metal charge transfer (LMCT) process in UiO-66-NH2, thereby enabling the fluorescence turn-on detection of DCP. More importantly, a simple and portable hydrogel soft-solid platform (UiO-66-NH2@Aga) was constructed by incorporating UiO-66-NH2 into the formation process of agarose (Aga) hydrogel for fast and sensitive detection of gaseous DCP. When the hydrogel was exposed to a low concentration of DCP vapor, its fluorescence changed from colorless to bright blue, allowing visualization of the DCP gas for analysis. The UiO-66-NH2@Aga integrated solid-state platform showed an excellent response to DCP vapor in the detection range of 1.98 to 9.90 ppm and with a detection limit of 1.16 ppm. This work opened up a unique way to design a convenient, low cost and practical gas physical examination platform.

Colorimetric and photothermal immunosensor for sensitive detection of cancer biomarkers based on enzyme-mediated growth of gold nanostars on polydopamine.

BACKGROUND: Detecting cancer biomarker levels in body fluids is essential for medical diagnosis. Enzyme-linked immunosorbent assay (ELISA) has been broadly used to detect cancer biomarkers. However, colorimetric ELISA based solely on nanoparticles (NPs) are susceptible to environmental influences, which often results in the detection inaccuracy, being limited in clinical applications. In this regard, the dual-mode approach would add signal diversity to the detection, making the results more reliable. RESULTS: We present colorimetric and photothermal immunosensor that enables direct reading of the color and temperature of the solution. A core-satellite nanoprobe constructed by polydopamine (PDA) as the core and gold seeds as satellites is rationally designed as the signal reporter. When ascorbic acid is present in the solution, PDA can cooperate with ascorbic acid to reduce chloroauric acid and mediate the growth of gold seeds on the PDA surface, inducing a redshift of the localized surface plasmon resonance peak of the nanosensor and the change in photothermal conversion efficiency. The method is further combined with the sandwiched immunoassay to construct an alkaline phosphatase based colorimetric and photothermal ELISA for the highly sensitive and accurate evaluation and detection of prostate-specific antigen (PSA). The linear range was from 0.05 to 100 ng mL-1 with a detection limit of 6.71 pg mL-1 for the colorimetric detection, while the linear range was from 0.5 to 90 ng mL-1 with a detection limit of 0.13 ng mL-1 in the photothermal analysis. The accurate detection of PSA levels in serum samples was well demonstrated with the dual-mode approach. SIGNIFICANCE: The presented immunoassay allows straightforward, sensitive, and selective readout by color and temperature without advanced instrumentation. Particularly, the LOD was much lower than the threshold in clinical trials for PSA. Therefore, this method has a great prospect in the early diagnosis of cancer biomarkers based on a dual-mode multifunctional platform.

Frequency-Dependent Microstate Characteristics for Mild Cognitive Impairment in Parkinson's Disease.

Cognitive impairment is typically reflected in the time and frequency variations of electroencephalography (EEG). Integrating time-domain and frequency-domain analysis methods is essential to better understand and assess cognitive ability. Timely identification of cognitive levels in early Parkinson's disease (ePD) patients can help mitigate the risk of future dementia. For the investigation of the brain activity and states related to cognitive levels, this study recruited forty ePD patients for EEG microstate analysis, including 13 with mild cognitive impairment (MCI) and 27 without MCI (control group). To determine the specific frequency band on which the microstate analysis relies, a deep learning framework was employed to discern the frequency dependence of the cognitive level in ePD patients. The input to the convolutional neural network consisted of the power spectral density of multi-channel multi-point EEG signals. The visualization technique of gradient-weighted class activation mapping was utilized to extract the optimal frequency band for identifying MCI samples. Within this frequency band, microstate analysis was conducted and correlated with the Montreal Cognitive Assessment (MoCA) Scale. The deep neural network revealed significant differences in the 1-11.5Hz spectrum of the ePD-MCI group compared to the control group. In this characteristic frequency band, ePD-MCI patients exhibited a pattern of global microstate disorder. The coverage rate and occurrence frequency of microstate A and D increased significantly and were both negatively correlated with the MoCA scale. Meanwhile, the coverage, frequency and duration of microstate C decreased significantly and were positively correlated with the MoCA scale. Our work unveils abnormal microstate characteristics in ePD-MCI based on time-frequency fusion, enhancing our understanding of cognitively related brain dynamics and providing electrophysiological markers for ePD-MCI recognition.

Knockout of Rnf213 Ameliorates Cerebral Ischemic-reperfusion Injury by Inhibiting Neuronal Apoptosis Through the Akt/GSK-3ß/ß-catenin/Bcl-2 Pathway.

Previous studies by us and others have shown that RING finger protein 213 (RNF213) is associated with cerebrovascular disease and systemic vasculopathy. Indeed, Rnf213 mRNA expression is increased in cerebral ischemia reperfusion injury (CIRI). The purpose of the present study was to investigate the role of Rnf213 in CIRI. Using the middle cerebral artery occlusion (MCAO) model, we confirmed that the expression of RNF213 protein was significantly upregulated in neurons in the ischemic penumbra. Rnf213 knockout mice were successfully generated using CRISPR/Cas9 technology. According to TTC staining and Bederson neurological scale, removal of Rnf213 decreased brain infarct volume and improved neurological deficit score, although the restoration of cerebral blood flow after MCAO was similar in WT and Rnf213-/- mice. In addition, the levels of p-Akt, p-GSK-3ß, ß-catenin and Bcl-2 were significantly increased 24 h after MCAO in the ischemic penumbra of the Rnf213-/- mice compared to WT mice, indicating that Rnf213 removal may ameliorate neuronal apoptosis by regulating the Akt/GSK-3ß/ß-catenin/Bcl-2 signaling pathway. Taken together, our study reveals that Rnf213 regulates neuronal apoptosis in CIRI, therefore impacting on brain infarct volume in brain ischemia.

Distinct dual enzyme-like activities of Fe-N-C single-atom nanozymes enable discriminative detection of cellular glutathione.

Fe-N-C single-atom nanozymes readily achieved discriminative detection of glutathione (GSH) over other biothiols with similar structure due to the difference between POD-like and OXD-like activities regarding the kind of reactive oxygen species. This colorimetric sensor demonstrated the heterogeneity of GSH levels in different cells and accurately monitored cellular GSH fluctuation.