Uqcr11 alleviates oxidative stress and apoptosis after traumatic brain injury.

Traumatic brain injury (TBI) is a major cause of death and disability that involves brain dysfunction due to external forces. Here, we found lower levels of Ubiquinol-cytochrome c reductase, complex III subunit XI (Uqcr11) expression in the cerebral cortex of TBI mice. A neuronal damage model was constructed using H2O2 or hypoxia reoxygenation (H/R) in vitro. We found that Uqcr11 overexpression attenuated the H2O2-or H/R-induced damage by preventing oxidative stress and neuronal apoptosis in HT22 cells. Moreover, up-regulated Uqcr11 contributed to the restoration of motor, learning, and memory in C57BL/6 mice after TBI, and its underlying mechanism may be associated with promoting neuron survival and inhibited oxidative stress. Collectively, our findings demonstrated that oxidative stress as well as neuronal apoptosis can be ameliorated post-TBI by Uqcr11 overexpression, which provides a potential therapeutic target for TBI.

A Dicyanoisoflurone-based Near-infrared Fluorescence Probe for Highly Sensitive Detection of Hg2.

Due to its high toxicity, long durability, easy absorption by aquatic organisms, and significant bioaccumulation, Hg2+ has caused substantial environmental damage and posed serious threats to human health. Therefore, effective detection of Hg2+ is of utmost importance. In this study, a turn-on fluorescent probe based on dicyanoisoflurone was developed for the detection of Hg2+. The probe exhibited near-infrared fluorescence signal at 660 nm upon excitation by 440 nm UV light in a mixture of CH3CN and HEPES buffer (4:1, v/v, 10 mM, pH = 7.5), with selective binding to Hg2+ in a molar ratio of 1:1. This binding event was accompanied by a visible color change from light yellow to orange. By utilizing the enhanced fluorescence signal change, this probe enables highly sensitive analysis and detection of Hg2+ with excellent selectivity (association constant = 1.63 × 104 M- 1), large Stokes shift (220 nm), high sensitivity (detection limit as low as 5.6 nM), short reaction time (30 s), and a physiological pH range of 7.5-9.5. The probe was successfully employed for detecting of Hg2+ in real water and living cells.

Molecular Engineering to Achieve AIE-active Fluorophore with Near-infrared (NIR) Emission and Temperature-sensitive Property.

Near-infrared organic small molecule luminescent materials have the advantages of easy modification, high quantum efficiency, good biological affinity, and color adjustability; thus, have promising application prospects in the fields of photoelectric devices, sensitive detection, photodynamic therapy, and biomedical imaging. However, traditional organic luminescent molecules have the problems of short emission wavelength, aggregation-causing emission quenching, and low quantum yield. Herein, we successfully synthesized four D-π-A-D light-emitting molecules based on electron-withdrawing malonitrile group and different electron-donating arylamine groups. These compounds showed satisfactory solvatochromism, aggregation-induced emission, red and near-infrared fluorescence, high photoluminescence quantum efficiency and temperature response properties. This successful example of molecular engineering provides a valuable reference for the development of advanced NIR materials with AIE and temperature-sensitive properties.

A dicyanisophorone-based probe for dual sensing Zn2+ and Cd2+ by near-infrared fluorescence.

Zinc ions (Zn2+) and cadmium ions (Cd2+) are widely present in our production and life, which are closely related to human health and environmental protection. Hence, it is essential to detect their concentrations. Herein, we developed a convenient and reliable small-molecule fluorescent probe based on Schiff base of dicyanisophorone and 2-hydrazinopyridine. This probe can be able to selectively detect Zn2+ and Cd2+, showing the advantages of near-infrared emission (the maximum emission wavelength: 668 nm), good selectivity, high sensitivity (the detection limits: 0.21 µM and 0.31 µM, respectively) and rapid response (15 s). It has excellent potential for rapid testing and visual tracking of Zn2+ and Cd2+ in aqueous solution and living cells.

Discrimination of Maturity Stages of Cabernet Sauvignon Wine Grapes Using Visible-Near-Infrared Spectroscopy.

Grape quality and ripeness play a crucial role in producing exceptional wines with high-value characteristics, which requires an effective assessment of grape ripeness. The primary purpose of this research is to explore the possible application of visible-near-infrared spectral (Vis-NIR) technology for classifying the maturity stages of wine grapes based on quality indicators. The reflection spectra of Cabernet Sauvignon grapes were recorded using a spectrometer in the spectral range of 400 nm to 1029 nm. After measuring the soluble solids content (SSC), total acids (TA), total phenols (TP), and tannins (TN), the grape samples were categorized into five maturity stages using a spectral clustering method. A traditional supervised classification method, a support vector machine (SVM), and two deep learning techniques, namely stacked autoencoders (SAE) and one-dimensional convolutional neural networks (1D-CNN), were employed to construct a discriminant model and investigate the association linking grape maturity stages and the spectral responses. The spectral data went through three commonly used preprocessing methods, and feature wavelengths were extracted using a competitive adaptive reweighting algorithm (CARS). The spectral data model preprocessed via multiplicative scattering correction (MSC) outperformed the other two preprocessing methods. After preprocessing, a comparison was made between the discriminant models established with full and effective spectral data. It was observed that the SAE model, utilizing the feature spectrum, demonstrated superior overall performance. The classification accuracies of the calibration and prediction sets were 100% and 94%, respectively. This study showcased the dependability of combining Vis-NIR spectroscopy with deep learning methods for rapidly and accurately distinguishing the ripeness stage of grapes. It has significant implications for future applications in wine production and the development of optoelectronic instruments tailored to the specific needs of the winemaking industry.

SPARC regulates ferroptosis induced by sorafenib in human hepatocellular carcinoma.

BACKGROUND: Secreted protein acidic and rich in cysteine (SPARC) is implicated in cancer progression, but its role and associated molecular mechanism in the sorafenib sensitivity of hepatocellular carcinoma cells (HCC) remains elusive. METHODS: Human HCC cell lines Hep3B and HepG2 were treated with sorafenib alone or combined with activator or inhibitor of ferroptosis. Cell viability assay, reactive oxygen species (ROS) assay, lactate dehydrogenase (LDH) assay and western blot were used to study the regulatory mechanism of SPARC on HCC cells. RESULTS: Overexpression of SPARC enhanced the cytotoxic effect of sorafenib in Hep3B and HepG2 cells compared with parental cells. Depletion of SPARC decreased the cytotoxic effect of sorafenib in Hep3B and HepG2 cells compared with parental cells. Moreover, overexpression of SPARC significantly induced LDH release, whereas depletion of SPARC suppressed the release of LDH in Hep3B and HepG2 cells. Inhibition of ferroptosis exerted a clear inhibitory role against LDH release, whereas activation of ferroptosis promoted the release of LDH in HCC cells, as accompanied with deregulated expression of ferroptosis-related proteins. Furthermore, overexpression of SPARC induced oxidative stress, whereas depletion of SPARC suppressed the production of ROS. Deferoxamine (DFX)-induced inhibition of ferroptosis suppressed the production of ROS, while activation of ferroptosis promoted the contents of ROS in HCC cells exposed to sorafenib. CONCLUSION: Our findings give a better understanding of ferroptosis and its molecular mechanism in HCC cells that is regulated by SPARC in response to sorafenib.

Successful Treatment of Pediatric Refractory Burkitt Lymphoma PTLD after Liver Transplantation using Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy.

In the immunocompromised setting, recipients of solid-organ or hematopoietic stem-cell transplants carry an increased risk of post-transplant lymphoproliferative disorder (PTLD). Burkitt lymphoma (BL) PTLD is a rare form of monomorphic B-cell PTLD, which lacks a standard best treatment. Here, we report the successful treatment of refractory BL-PTLD with autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy. A male patient was diagnosed with BL-PTLD, with an increasing Epstein-Barr virus (EBV) viral load, at 21 months after undergoing living liver transplantation from his mother due to neonatal biliary atresia. After 10 cycles rituximab +/- intensive chemotherapy and surgical tumor resection, the tumors significantly advanced. Next-generation sequencing (NGS) was performed on formalin-fixed paraffin-embedded tumor tissue, revealing one mutation in exon 5, TP53: p.A159 V, which may be associated with chemo-resistance. Thus, treatment was started with autologous anti-CD19 CAR T-cell therapy. We administered 9.0 × 106/kg autologous anti-CD19 CAR T-cells, after conditioning with cyclophosphamide and fludarabine. Unexpectedly, the patient experienced only mild (Grade II) cytokine release syndrome (CRS) without neurotoxicity. Finally, he went into complete remission (CR), and has achieved 16-month event-free survival to date. In addition, liver function has remained stably within the normal range without any immunosuppressive therapy. The literature includes only five previously reported BL cases treated with CAR T-cell therapy. In conclusion, the present case suggests that autologous anti-CD19 CAR T-cell therapy may represent a new therapeutic option for some cases of refractory BL-PTLD.Clinical trial number: ChiCTR2000032211.

Relationship between chest CT manifestations and immune response in COVID-19 patients.

OBJECTIVES: To study the correlations of lymphocytes and cytokines between changes of lung lesion volumes in patients with COVID-19, and to predict these correlations. METHODS: 93 patients with COVID-19 were divided into mild and severe groups. The data of lymphocyte subgroups and cytokines were collected, the imaging characteristics were measured, and correlation analysis was performed to analyze the differences. RESULTS: 60 mild and 33 severe patients were included. Lymphocyte subsets decreased in both groups. The reduction percentages of the absolute lymphocytes value in mild and severe groups were 32% and 64%, respectively. The lung CT lesion volume of all patients was 241.45 ± 282.92 cm3, among which the mild group was 151.29 ± 226.04 cm3, and the severe group was 405.38 ± 304.90 cm3, respectively. In critically ill patients, the decrease of the absolute value of CD4+ T cells and the increase of IL-6 levels are significantly correlated with the volume of lung lesions. CONCLUSIONS: The absolute values of CD3+, CD4+, and CD8+ T cells are lower in patients with COVID-19, while the levels of IL-6 and IL-10 are increased. The severity of lung lesions predicts poor clinical outcomes and may be a predictor of the transition from mild to severe.

Characteristic findings by phototrichogram in southern Chinese women with Female pattern hair loss.

OBJECTIVES: To investigate the characteristics of hairs in Female pattern hair loss (FPHL) patients and healthy females in Southern China. MATERIALS AND METHODS: Three fundamental hair parameters in different scalp areas of 90 Southern Chinese FPHL patients and 83 healthy controls were analyzed by phototrichogram. RESULTS: Female pattern hair loss patients showed reduced hair density, hair diameter, and terminal/vellus hair ratio. The reduction correlated with the severity of Ludwig staging. Midscalp was the most affected area in FPHL, but occipital and temporal sites were also involved. In normal women, the highest hair density was observed in midscalp, followed by occipital and temporal areas. Peak hair density at midscalp sites was reached at 20s group, then declined with age. Maximum hair diameter at midscalp and occipital sites occurred in 40s group. Terminal/vellus hair ratio tended to increase with age and peak on 50-60s group. CONCLUSION: Reduced hair density and hair diameter, and miniaturization of hair follicles are the characteristics of FPHL in Southern Chinese women. Occipital and temporal sites are also affected in FPHL. Age-associated changes might have an influence on the hair condition. The values of hair parameters obtained in this study will help to establish reference data for better evaluation of hair disorders.

MCP-1 produced by keratinocytes is associated with leucocyte recruitment during elicitation of nickel-induced occupational allergic contact dermatitis.

To investigate the expression profile of monocyte chemoattractant peptide-1 (MCP-1) by keratinocytes after nickel exposure and to identify its role for leucocyte migration during nickel-induced occupational allergic contact dermatitis (OACD), 26 workers diagnosed with nickel-induced OACD were enrolled. Skin biopsies from the positive nickel-challenged sites at different time points were assessed by immunohistochemistry (IHC) for MCP-1, CD68, CD45RO, and in situ hybridization (ISH) for MCP-1, using chronic periumbilical dermititis as controls. The expressions of MCP-1 in HaCaT cell culture after nickel treatment were quantified by enzyme-linked immunosorbent assay. The results showed that at positive nickel-challenged sites, strong expressions of MCP-1, both messenger RNA (mRNA) and protein, were detected in the basal keratinocytes during the early phase (24-48 h after nickel application), paralleled by the recruitment of CD68+ and CD45RO+ cells to the skin compartments. The expressions of MCP-1 declined gradually in the late phase (72-96 h after nickel application). Treatment with nickel sulfate at noncytotoxic concentrations (0.01-100 µM) induced a concentration-related elevation of MCP-1 expression by HaCaT cells compared to the untreated cells. The data indicated that a temporal expression pattern of MCP-1 produced by keratinocytes after nickel exposure was involved in the complex process of mononuclear cell infiltration during elicitation of nickel-induced OACD. Targeting MCP-1 might be a potential therapeutic strategy for OACD.

Elevation of Circulating Th17/Th22 Cells Exposed to Low-Level Formaldehyde and Its Relevance to Formaldehyde-Induced Occupational Allergic Contact Dermatitis.

OBJECTIVES: The aim of this study was to investigate the effects of formaldehyde exposure on Th17 and Th22 cells and its relevance to human occupational allergic contact dermatitis (OACD). METHODS: Circulating IL17-/IL22-secreting cells and serum IL17/IL22 levels in formaldehyde-exposed workers at Occupational Exposure Limit and nonexposed controls were assessed. RESULTS: The IL17 and IL22 cell population were detected in both CD3CD8 and CD3CD8 cells. The percentages of circulating IL17 and IL22 T cells in the workers with and without ACD history were all elevated, which were more remarkable in the ones with ACD history. Serum levels of IL17 and IL22 between the workers and controls were not significantly different. CONCLUSIONS: Low-level formaldehyde exposure may increase circulating IL17-/IL22-producing T cells (CD8 and CD8), possibly involved in the development of human OACD. But it may not alter serum levels of IL17/IL22 before the appearance of OACD symptoms.

Temporal effect of local hyperthermia on murine contact hypersensitivity.

BACKGROUND: The sensitization and elicitation phases are involved in the immunopathogenesis of contact hypersensitivity (CHS). Langerhans cells (LCs) are believed to play pivotal roles in the sensitization stage of CHS. Local hyperthermia on skin induces the migration as well as maturation of epidermal LCs. Although fever-range whole body hyperthermia and local hyperthermia at 43°C prior to sensitization were reported to suppress CHS, the effects of different temperatures and the timing sequence of local hyperthermia on CHS have not been tackled. METHODS: Local hyperthermia was applied to murine dorsal skin 3 days prior to, concurrent with, or 2 days post sensitization with fluorescein isothiocyanate (FITC) in BALB/c mice. Local hyperthermia temperatures at 37°C, 39°C, 41°C and 43°C were applied to mouse dorsal skin and the severity of CHS was calculated by measuring the swelling response of the challenged ears. RESULTS: Local hyperthermia at 39°C, 41°C and 43°C prior to sensitization reduced the severity of CHS, as compared with that at 37°C. The suppression of CHS was temperature dependent in that higher temperature had a stronger effect. On the contrary, the hyperthermia treatments, either concurrent with or post-sensitization, resulted in an enhanced temperature-dependent ear swelling response. CONCLUSIONS: The severity of murine CHS could be influenced by local hyperthermia at the sensitization stage in a temperature dependent manner. The temporal effect of local hyperthermia suggested a novel factor in interpreting the severity of allergic contact dermatitis.