PIN1P1 is activated by CREB1 and promotes gastric cancer progression via interacting with YBX1 and upregulating PIN1.

Long noncoding RNAs (lncRNAs) play critical roles in the carcinogenesis and progression of cancers. However, the role and mechanism of the pseudogene lncRNA PIN1P1 in gastric carcinoma remain unclear. The expression and effects of lncRNA PIN1P1 in gastric cancer were investigated. The transcriptional regulation of CREB1 on PIN1P1 was determined by ChIP and luciferase assays. The mechanistic model of PIN1P1 in gastric cancer was further explored by RNA pull-down, RIP and western blot analysis. PIN1P1 was overexpressed in gastric cancer tissues, and upregulated PIN1P1 predicted poor prognosis in patients. CREB1 was directly combined with the promoter region of PIN1P1 to promote the transcription of PIN1P1. CREB1-mediated enhanced proliferation, migration and invasion could be partially reversed by downregulation of PIN1P1. Overexpressed PIN1P1 promoted the proliferation, migration and invasion of gastric cancer cells, whereas decreased PIN1P1 showed the opposite effects. PIN1P1 directly interacted with YBX1 and promoted YBX1 protein expression, leading to upregulation of PIN1, in which E2F1 may be involved. Silencing of YBX1 during PIN1P1 overexpression could partially rescue PIN1 upregulation. PIN1, the parental gene of PIN1P1, was elevated in gastric cancer tissues, and its upregulation was correlated with poor patient outcomes. PIN1 facilitated gastric cancer cell proliferation, migration and invasion. To sum up, CREB1-activated PIN1P1 could promote gastric cancer progression through YBX1 and upregulating PIN1, suggesting that it is a potential target for gastric cancer.

PANoptosis subtypes predict prognosis and immune efficacy in gastric cancer.

PANoptosis is a form of inflammatory programmed cell death that is regulated by the PANoptosome. This PANoptosis possesses key characteristics of pyroptosis, apoptosis, and necroptosis, yet cannot be fully explained by any of these cell death modes. The unique nature of this cell death mechanism has garnered significant interest. However, the specific role of PANoptosis-associated features in gastric cancer (GC) is still uncertain. Patients were categorized into different PAN subtypes based on the expression of genes related to the PANoptosome. We conducted a systematic analysis to investigate the variations in prognosis and tumor microenvironment (TME) among these subtypes. Furthermore, we developed a risk score, called PANoptosis-related risk score (PANS), which is constructed from genes associated with the PANoptosis. We comprehensively analyzed the correlation between PANS and GC prognosis, TME, immunotherapy efficacy and chemotherapeutic drug sensitivity. Additionally, we performed in vitro experiments to validate the impact of Keratin 7 (KRT7) on GC. We identified two PAN subtypes (PANcluster A and B). PANoptosome genes were highly expressed in PANcluster A. PANcluster A has the characteristics of favorable prognosis, abundant infiltration of anti-tumor lymphocytes, and sensitivity to immunotherapy, thus it was categorized as an immune-inflammatory type. Meanwhile, our constructed PANS can effectively predict the prognosis and immune efficacy of GC. Patients with low PANS have a good prognosis, and have the characteristics of high tumor mutation load (TMB), high microsatellite instability (MSI), low tumor purity and sensitivity to immunotherapy. In addition, PANS can also identify suitable populations for different chemotherapy drugs. Finally, we confirmed that KRT7 is highly expressed in GC. Knocking down the expression of KRT7 significantly weakens the proliferation and migration abilities of GC cells. The models based on PANoptosis signature help to identify the TME features of GC and can effectively predict the prognosis and immune efficacy of GC. Furthermore, the experimental verification results of KRT7 provide theoretical support for anti-tumor treatment.

Structure of the CUL1-RBX1-SKP1-FBXO4 SCF ubiquitin ligase complex.

Cullin-RING E3 ubiquitin ligases (CRLs) constitute the largest family of ubiquitin ligase and play important roles in regulation of proteostasis. Here we presented the cryo-EM structure of CRL1FBXO4, a member of Cullin-1 E3 ligase. CRL1FBXO4 adopts a homodimer architecture. Structural analysis revealed that in the CRL1FBXO4 protomer, the substrate recognition subunit FBXO4 interacts both the adaptor protein SKP1, and the scaffold protein CUL1 via hydrophobic and electrostatic interactions. Two FBXO4 forms a domain-swapped dimer in the CRL1FBXO4 structure, which constitutes the basis for the dimerization of CRL1FBXO4. Inspired by the cryo-EM density, we modeled the architecture of whole CRL1FBXO4 as a symmetrical dimer, which provides insights into CRL1FBXO4-medaited turnover of oncogene proteins.

LC-based lightfield camera prototype for rapidly creating target images optimized by finely adjusting several key coefficients and a LC-guided refocusing-rendering.

A lightfield camera prototype is constructed by directly coupling a liquid-crystal (LC) microlens array with an arrayed photosensitive sensor for performing a LC-guided refocusing-rendering imaging attached by computing disparity map and extracting featured contours of targets. The proposed camera prototype presents a capability of efficiently selecting the imaging clarity value of the electronic targets interested. Two coefficients of the calibration coefficient k and the rendering coefficient C are defined for quantitively adjusting LC-guided refocusing-rendering operations about the images acquired. A parameter Dp is also introduced for exactly expressing the local disparity of the electronic patterns selected. A parallel computing architecture based on common GPU through the OpenCL platform is adopted for improving the real-time performance of the imaging algorithms proposed, which can effectively be used to extract the pixel-leveled disparity and the featured target contours. In the proposed lightfield imaging strategy, the focusing plane can be easily selected and/or further adjusted by loading and/or varying the signal voltage applied over the LC microlenses for realizing a rapid or even intelligent autofocusing. The research lays a solid foundation for continuously developing or upgrading current lightfield imaging approaches.

SULF1 regulates malignant progression of colorectal cancer by modulating ARSH via FAK/PI3K/AKT/mTOR signaling.

BACKGROUND: Colorectal cancer (CRC) has the third highest incidence and second mortality rate of malignant tumors globally, highlighting the urgency to explore the mechanisms underlying CRC progression for refined treatment of this patient population. METHODS: R Studio was used for data sorting and analysis. Cell apoptosis and cell cycle detection were performed by flow cytometry. Quantitative real-time PCR (qRT-PCR) was used to explore mRNA expression levels. Western blotting was used to explore protein expression levels. CCK8, EdU, and colony formation assays were performed to explore the proliferation capacity of CRC cells. Transwell invasion and migration assays, along with the wound healing assay, were used to explore the invasive and migratory abilities of CRC cells. Subcutaneous Xenograft Assay was utilized to evaluate the tumorigenic capacity of CRC cells in vivo. RESULTS: SULF1 was highly expressed in CRC samples and cell lines. The knockdown of SULF1 inhibited the proliferation, invasion, and migration of CRC and increased the rate of cell apoptosis. Meanwhile, we demonstrated that SULF1 could negatively regulate ARSH through the FAK/PI3K/AKT/mTOR pathway. CONCLUSION: We demonstrated that SULF1 could promote CRC progression by regulating ARSH. The SULF1/ARSH/FAK/PI3K/AKT/mTOR signaling pathway represents a promising target for the treatment of this patient population. Colorectal cancer (CRC) has the third highest incidence and second mortality rate of malignant tumors globally. Sulfatase 1 (SULF1) belongs to the sulfatase family, The function of SULF1 in CRC remains elusive. Our study demonstrated that the knockdown of SULF1 could inhibit the proliferation, invasion, and migration of CRC. Meanwhile, our findings indicated that SULF1 could interact with Arylsulfatase Family Member H (ARSH) to regulate the proliferation, invasion, and migration of CRC via the FAK/PI3K/AKT/mTOR signaling pathway. Taken together, our findings suggest that SULF1 might be a new therapeutic target in CRC.

OTU deubiquitinase, ubiquitin aldehyde binding 2 (OTUB2) modulates the stemness feature, chemoresistance, and epithelial-mesenchymal transition of colon cancer via regulating GINS complex subunit 1 (GINS1) expression.

BACKGROUND: Colon cancer is one of the most prevalent tumors in the digestive tract, and its stemness feature significantly contribute to chemoresistance, promote the epithelial-mesenchymal transition (EMT) process, and ultimately lead to tumor metastasis. Therefore, it is imperative for researchers to elucidate the molecular mechanisms underlying the enhancement of stemness feature, chemoresistance, and EMT in colon cancer. METHODS: Sphere-formation and western blotting assays were conducted to assess the stemness feature. Edu, flow cytometry, and cell viability assays were employed to evaluate the chemoresistance. Immunofluorescence and western blotting assays were utilized to detect EMT. Immunoprecipitation, ubiquitination, agarose gel electrophoresis, chromatin immunoprecipitation followed by quantitative PCR (chip-qPCR), and dual luciferase reporter gene assays were employed for mechanistic investigations. RESULTS: We demonstrated a markedly higher expression level of OTUB2 in colon cancer tissues compared to adjacent tissues. Furthermore, elevated OTUB2 expression was closely associated with poor prognosis and distant tumor metastasis. Functional experiments revealed that knockdown of OTUB2 attenuated stemness feature of colon cancer, enhanced its sensitivity to oxaliplatin, inhibited its EMT process, ultimately reduced the ability of tumor metastasis. Conversely, overexpression of OTUB2 exerted opposite effects. Mechanistically, we identified OTUB2 as a deubiquitinase for SP1 protein which bound specifically to SP1 protein, thereby inhibiting K48 ubiquitination of SP1 protein. The SP1 protein functioned as a transcription factor for the GINS1, exerting its regulatory effect by binding to the 1822-1830 region of the GINS1 promoter and enhancing its transcriptional activity. Ultimately, alterations in GINS1 expression directly regulated stemness feature, chemosensitivity, and EMT progression in colon cancer. CONCLUSION: Collectively, the OTUB2/SP1/GINS1 axis played a pivotal role in driving stemness feature, chemoresistance, and EMT in colon cancer. These results shed new light on understanding chemoresistance and metastasis mechanisms involved in colon cancer.

Selective SERS Sensing of R6G Molecules Using MoS2 Nanoflowers under Pressure.

Pressure-induced surface-enhanced Raman spectroscopy (PI-SERS) has garnered significant attention as a subfield of SERS detection due to its capacity to regulate the band gap between molecules and substrates through pressure modulation. Currently, SERS detection primarily focuses on single molecules at atmospheric pressure with limited investigations conducted under high pressure conditions. Herein, we employed rose-shaped MoS2 nanoflowers as the SERS substrate and realized selective PI-SERS enhancement of R6G molecules in the binary (MV+R6G) and ternary (MV+R6G+RhB) systems. The MoS2 demonstrated an exceptionally low SERS detection limit of 5 × 10-6 M in binary and ternary systems with equimolar amounts of molecules. High-pressure experimental results indicate that MoS2 displays selective enhancement for R6G molecules, as evidenced by the comparison of the PI-SERS peak intensity ratio between MoS2 and the probe molecules. The proposed enhancement mechanism in binary and ternary SERS systems under high pressure involves pressure-induced changes in both the band structures of the MoS2 substrate and molecules, thereby influencing their charge transfer dynamics. Consequently, this approach holds great promise for practical applications in complex SERS systems operating under extreme conditions.

Conformational Locking as a Strategy to Reverse Ion Recognition Selectivity.

This study delves into the ion recognition capabilities of a novel host molecule, emphasizing the role of conformational locking in dictating ion selectivity. By employing the Buchwald-Hartwig cross-coupling reaction, we have notably shifted the ion receptor's selectivity from K+ to Na+. The findings are supported by computational simulations that reveal differences in binding energies and molecular strain impacting ion recognition. This innovative structural modification broadens the scope for alterations at the calix[4]arene's lower rim, paving the way for new methods and strategies in modulating ion recognition selectivity.

An AIEE-active Triphenylethylene Derivative with Photoresponsive Character for Latent Fingerprints Detection via a Simple Soaking Method.

Latent fingerprints (LFPs) is one of the most important physical evidence in the criminal scene, playing an important role in forensic investigations. Therefore, developing highly sensitive and convenient materials for the visualization of LFPs is of great significance. We designed and synthesized an organic fluorescent molecule TP-PH with aggregation-induced enhanced emission (AIEE) activity. By simply soaking, blue fluorescent images with high contrast and resolution are readily developed on various surfaces including tinfoil, steel, glass and plastic. Remarkably, LFPs can be visualized within 5 min including the first-, second- and tertiary-level details. In addition, TP-PH exhibits interesting photoactivated fluorescence enhancement properties. Under irradiation of 365 nm UV light with a power density of 382 mW/cm2, the fluorescence quantum yield displays approximately 21.5-fold enhancement. Mechanism studies reveals that the photoactivated fluorescence is attributed to the irreversible cyclodehydrogenation reactions under UV irradiation. This work provides a guideline for the design of multifunctional AIEE fluorescent materials.

Expression and immobilization of novel N-glycan-binding protein for highly efficient purification and enrichment of N-glycans, N-glycopeptides, and N-glycoproteins.

Comprehensive and selective enrichment of N-glycans, N-glycopeptides, and N-glycoproteins prior to analysis is of great significance in N-glycomics research, reducing sample complexity, removing impurity interference, increasing sample abundance and enhancing signal intensity. However, only an Fbs1 (F-box protein that recognizes sugar chain 1) GYR variant (Fg) can enrich these N-glycomolecules solely due to its substantial binding affinity for the core pentasaccharide motif of N-glycans. Stationary phase separation is commonly used to enrich N-glycomolecules efficiently. Herein, DNA encoding the Fg was cloned into pGEX-4T-1, and the protein was expressed with a GST tag, which facilitates the convenient and efficient immobilization of recombinant GST-tagged Fg to GSH agarose resin. The yield of the GST-tagged Fg reached to 0.05 g/L after optimization of the induction condition, and the purified protein exhibited good identification ability and excellent stability for months. In particular, the immobilized GST-tagged Fg can enrich N-glycans released by PNGase F and capture derivatized N-glycans possessing an intact terminal N-acetyl glucosamine (GlcNAc). Validation of immobilized GST-tagged Fg with standard N-glycopeptides and N-glycoproteins revealed its high loading capacity, sensitivity, and selectivity. The novel immobilized GST-tagged Fg is a convenient and efficient enrichment material specific for N-glycans, N-glycopeptides, and N-glycoproteins, suggesting excellent performance and prospects for industrial application.

The Association of Preoperative Diabetes With Postoperative Delirium in Older Patients Undergoing Major Orthopedic Surgery: A Prospective Matched Cohort Study.

BACKGROUND: Postoperative delirium (POD) is a common form of postoperative brain dysfunction, especially in the elderly. However, its risk factors remain largely to be determined. This study aimed to investigate whether (1) preoperative diabetes is associated with POD after elective orthopedic surgery and (2) intraoperative frontal alpha power is a mediator of the association between preoperative diabetes and POD. METHODS: This was a prospective matched cohort study of patients aged 60 years or more, with a preoperative diabetes who underwent elective orthopedic surgery. Nondiabetic patients were matched 1:1 to diabetic patients in terms of age, sex, and type of surgery. Primary outcome was occurrence of POD, assessed using the 3-minute Diagnostic Confusion Assessment Method (3D-CAM) once daily from 6 pm to 8 pm during the postoperative days 1-7 or until discharge. Secondary outcome was the severity of POD which was assessed for all participants using the short form of the CAM-Severity. Frontal electroencephalogram (EEG) was recorded starting before induction of anesthesia and lasting until discharge from the operating room. Intraoperative alpha power was calculated using multitaper spectral analyses. Mediation analysis was used to estimate the proportion of the association between preoperative diabetes and POD that could be explained by intraoperative alpha power. RESULTS: A total of 138 pairs of eligible patients successfully matched 1:1. After enrollment, 6 patients in the diabetes group and 4 patients in the nondiabetes group were excluded due to unavailability of raw EEG data. The final analysis included 132 participants with preoperative diabetes and 134 participants without preoperative diabetes, with a median age of 68 years and 72.6% of patients were female. The incidence of POD was 16.7% (22/132) in patients with preoperative diabetes vs 6.0% (8/134) in patients without preoperative diabetes. Preoperative diabetes was associated with increased odds of POD after adjustment of age, sex, body mass index, education level, hypertension, arrhythmia, coronary heart disease, and history of stroke (odds ratio, 3.2; 95% confidence interval [CI], 1.4-8.0; P = .009). The intraoperative alpha power accounted for an estimated 20% (95% CI, 2.6-60%; P = .021) of the association between diabetes and POD. CONCLUSIONS: This study suggests that preoperative diabetes is associated with an increased risk of POD in older patients undergoing major orthopedic surgery, and that low intraoperative alpha power partially mediates such association.

Patient-derived Immunocompetent Tumor Organoids: A Platform for Chemotherapy Evaluation in the Context of T-cell Recognition.

Most of the anticancer compounds synthesized by chemists are primarily evaluated for their direct cytotoxic effects at the cellular level, often overlooking the critical role of the immune system. In this study, we developed a patient-derived, T-cell-retaining tumor organoid model that allows us to evaluate the anticancer efficacy of chemical drugs under the synergistic paradigm of antigen-specific T-cell-dependent killing, which may reveal the missed drug hits in the simple cytotoxic assay. We evaluated clinically approved platinum (Pt) drugs and a custom library of twenty-eight PtIV compounds. We observed low direct cytotoxicity of Pt drugs, but variable synergistic effects in combination with immune checkpoint inhibitors (ICIs). In contrast, the majority of PtIV compounds exhibited potent tumor-killing capabilities. Interestingly, several PtIV compounds went beyond direct tumor killing and showed significant immunosynergistic effects with ICIs, outstanding at sub-micromolar concentrations. Among these, Pt-19, PtIV compounds with cinnamate axial ligands, emerged as the most therapeutically potent, demonstrating pronounced immunosynergistic effects by promoting the release of cytotoxic cytokines, activating immune-related pathways and enhancing T cell receptor (TCR) clonal expansion. Overall, this initiative marks the first use of patient-derived immunocompetent tumor organoids to explore and study chemotherapy, advancing their path toward more effective small molecule drug discovery.

Characterization of N-glycome profile in mouse brain tissue regions by MALDI-TOF/MS.

Glycosylation is one of the most common types of post-translational modifications in mammals. It is well known that N-glycans play a key role in cell adhesion, differentiation, synapsis, and myelination during the development of the mammalian central nervous system (CNS). Neuropathological symptoms (such as epilepsy and Alzheimer's disease) are usually accompanied by N-glycosylation changes. In this study, we extracted N-glycan chains from eight regions of the mouse brain, and combined high-throughput, high-resolution matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) with the Fmoc N-hydroxysuccinimide ester (Fmoc-OSU) derivatization method to improve the sensitivity of glycan detection to characterize the total N-glycans in the mouse brain. A total of 96 N-glycan moieties were detected. An exhaustive examination of the relative abundance of N-glycans, coupled with a comparative analysis of differences, has uncovered discernible variations of statistical significance, including high mannose, fucosylated, sialylated, and galactosylated N-glycans. According to our investigations, a thorough and regionally specific cartography of glycans within the brain can facilitate the investigation of glycan-mediated mechanisms related to both the developmental trajectory and functional output of the brain. Additionally, this approach may serve as a basis for identifying potential biomarkers that are relevant to various brain-associated pathologies.

Photonic generation of dual-band dual-chirp waveforms with anti-dispersion transmission.

A photonic approach for generating dual-band dual-chirp waveforms with the capability of anti-dispersion transmission is proposed. In this approach, an integrated dual-drive dual-parallel Mach-Zehnder modulator (DD-DPMZM) is adopted to realize single-sideband modulation of a RF input and double-sideband modulation of baseband signal-chirped RF signals. By properly presetting the central frequencies of the RF input and the bias voltages of DD-DPMZM, dual-band dual-chirp waveforms with anti-dispersion transmission can be achieved after photoelectronic conversion. A complete theoretical analysis of the operation principle is presented. Full experimental verification of the generation and anti-dispersion transmission of dual-chirp waveforms centered at 2.5 and 7.5 GHz as well as 2 and 6 GHz over two dispersion compensating modules with dispersion values equivalent to 120 km or 100 km standard single-mode fiber is successfully carried out. The proposed system features a simple architecture, excellent reconfigurability, and immunity to dispersion-induced power fading, which are highly desired in distributed multi-band radar networks with optical-fiber-based transmission.

A Multi-Task Road Feature Extraction Network with Grouped Convolution and Attention Mechanisms.

To cope with the challenges of autonomous driving in complex road environments, the need for collaborative multi-tasking has been proposed. This research direction explores new solutions at the application level and has become a hot topic of great interest. In the field of natural language processing and recommendation algorithms, the use of multi-task learning networks has been proven to reduce time, computing power, and storage usage in various task coupling cases. Due to the characteristics of the multi-task learning network, it has also been applied to visual road feature extraction in recent years. This article proposes a multi-task road feature extraction network that combines group convolution with transformer and squeeze excitation attention mechanisms. The network can simultaneously perform drivable area segmentation, lane line segmentation, and traffic object detection tasks. The experimental results of the BDD-100K dataset show that the proposed method performs well for different tasks and has a higher accuracy than similar algorithms. The proposed method provides new ideas and methods for the autonomous road perception of vehicles and the generation of highly accurate maps in visual-based autonomous driving processes.

Circ_0004771 Promotes Hypoxia/Reoxygenation Induced Cardiomyocyte Injury via Activation of Mitogen-Activated Protein Kinase Signaling Pathway.

This study aimed to observe the mechanism and effect of circ_0004771 on cardiomyocyte injury in acute myocardial infarction (AMI). The differences in circ_0004771 expression in the blood of AMI patients and healthy volunteers were observed by Real-Time Quantitative Reverse Transcription-Polymerase Chain Reaction. AMI cell models were constructed by hypoxia/reoxygenation (H/R)-induced injury in human cardiomyocytes (AC16 cells). The changes of circ_0004771 expression in AMI cells were observed. After transfection with the knockdown or overexpression of circ_0004771 vector in AMI cells, Cell Counting Kit-8 (CCK-8) assay and propidium iodide/FITC-Annexin V staining were performed to detect cell proliferation and apoptosis levels, extracellular lactate dehydrogenase (LDH) activity, malondialdehyde (MDA) concentration, and superoxide dismutase (SOD) activity. Expression levels of Mitogen-activated protein kinase (MAPK) signaling pathway-related proteins (p-MEK1/2, MEK1/2, p-ERK1/2, ERK1/2), and endoplasmic reticulum (ER) stress proteins (GRP78 and CHOP-1) were observed in each group of cells by western blot method. The expression level of circ_0004771 was significantly reduced in both clinical samples and cells of AMI. When circ_0004771 was knocked down in AMI cells, it resulted in a decrease in cell proliferation level and significant increase in apoptosis level. The inhibition of circ_0004771 expression caused leakage of LDH in AMI cells, accumulation of intracellular MDA, and inhibition of SOD activity. In addition, the knockdown of circ_0004771 significantly increased the levels of p-MEK1/2, p-ERK1/2, GRP78, and CHOP-1 in H/R-induced AC16 cells. However, the overexpression of circ_0004771 resulted in the opposite result as when circ_0004771 was knocked down. A low level of circ_0004771 in AMI activates the MAPK signaling pathway in cardiomyocytes as well as encourages intracellular oxidative stress and ER stress, thereby inhibiting cell proliferation and promoting apoptosis.

Melatonin, an endogenous hormone, modulates Th17 cells via the reactive-oxygen species/TXNIP/HIF-1α axis to alleviate autoimmune uveitis.

BACKGROUND: Melatonin, an indoleamine produced by the pineal gland, plays a pivotal role in maintaining circadian rhythm homeostasis. Recently, the strong antioxidant and anti-inflammatory properties of melatonin have attracted attention of researchers. We evaluated the therapeutic efficacy of melatonin in experimental autoimmune uveitis (EAU), which is a representative animal model of human autoimmune uveitis. METHODS: EAU was induced in mice via immunization with the peptide interphotoreceptor retinoid binding protein 1-20 (IRBP1-20). Melatonin was then administered via intraperitoneal injection to induce protection against EAU. With EAU induction for 14 days, clinical and histopathological scores were graded to evaluate the disease progression. T lymphocytes accumulation and the expression of inflammatory cytokines in the retinas were assessed via flow cytometry and RT-PCR, respectively. T helper 1 (Th1), T helper 17 (Th17), and regulatory T (Treg) cells were detected via flow cytometry for both in vivo and in vitro experiments. Reactive-oxygen species (ROS) from CD4 + T cells was tested via flow cytometry. The expression of thioredoxin-interacting protein (TXNIP) and hypoxia-inducible factor 1 alpha (HIF-1α) proteins were quantified via western blot. RESULTS: Melatonin treatment resulted in notable attenuation of ocular inflammation in EAU mice, evidenced by decreasing optic disc edema, few signs of retinal vasculitis, and minimal retinal and choroidal infiltrates. Mechanistic studies revealed that melatonin restricted the proliferation of peripheral Th1 and Th17 cells by suppressing their transcription factors and potentiated Treg cells. In vitro studies corroborated that melatonin restrained the polarization of retina-specific T cells towards Th17 and Th1 cells in addition to enhancing the proportion of Treg cells. Pretreatment of retina-specific T cells with melatonin failed to induce EAU in naïve recipients. Furthermore, the ROS/ TXNIP/ HIF-1α pathway was shown to mediate the therapeutic effect of melatonin in EAU. CONCLUSIONS: Melatonin regulates autoimmune T cells by restraining effector T cells and facilitating Treg generation, indicating that melatonin could be a hopeful treatment alternative for autoimmune uveitis.

Construction of Water-Stable Rare-Earth Organic Frameworks with Ambient High Proton Conductivity Based on Zirconium Sandwiched Heteropolytungstate.

Water-stable proton-conducting materials owning excellent performances at ambient temperatures are currently one of the crucial challenges. Herein, four water-stable three-dimensional polyoxometalate-based rare-earth organic frameworks have been successfully synthesized and formulated as H{Ln4(L)2(H2O)21[Zr3(OH)3(PW9O34)2]}·15H2O (1-3) (Ln = La (1), Ce (2), Pr (3); L = 3,5-pyridine dicarboxylic acid), which are the first examples of MOFs constructed by a zirconium sandwiched polyoxoanion. There are abundant coordinated water molecules functionalizing the PrIII centers, and simultaneously, plenty of lattice water molecules are fitted into the channel of the framework. A continuous H-bonding network is found between the architectures and plays an important role in stabilizing the structure. Benefiting from the consecutive H-bonding networks, compounds 1-3 showed high proton conductivities at ambient temperature (up to 1.05 × 10-3 S·cm-1 under 98% RH) by a synergistic effect of the combined components.

Effects of Clostridium butyricum Capsules Combined with Rosuvastatin on Intestinal Flora, Lipid Metabolism, Liver Function and Inflammation in NAFLD Patients.

The objective of this study was to investigate the effects of Clostridium butyricum capsules combined with rosuvastatin on the intestinal flora, lipid metabolism, liver function and inflammation in patients with nonalcoholic fatty liver disease (NAFLD). For this purpose, a total of 96 patients with NAFLD were selected as research subjects and randomly divided into a control group (n=48) and an observation group (n=48). The Control group was treated with rosuvastatin, based on which observation group received Clostridium butyricum capsule treatment. The efficacy in the two groups of patients was compared, and the intestinal flora, lipid metabolism, liver function and inflammation were observed. Results showed that the efficacy in the observation group was significantly better than that in the control group (p<0.05). After treatment, the content of Eubacterium rectale in the observation group was lower than that in the control group, while the content of Bacteroides thetaiotaomicron and Bifidobacteria was notably higher than that in the control group (p<0.05). Moreover, the observation group had remarkably lower levels of total cholesterol (TC), triglyceride (TG), free fatty acids (FFA), total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), procollagen III peptide (PIIIP), collagen-IV (C-IV), hyaluronicacid (HA) and laminin (LN) as well as lower levels of tumor necrosis factor-alpha (TNF-α), catabolite activator protein (CAP) and interleukin-6 (IL-6) in serum than the control group (p<0.05). It was concluded that Clostridium butyricum capsules combined with rosuvastatin can effectively improve intestinal flora imbalance, reduce blood lipid levels, and alleviate liver fibrosis and liver function damage in the treatment of NAFLD, so it is of therapeutic value.

Cu,Zn Dopants Boost Electron Transfer of Carbon Dots for Antioxidation.

Enzyme-mimicking nanomaterials for antioxidative therapy is a promising star to treat more than 200 diseases or control their progressions through scavenging excessive reactive oxygen species (ROS), such as O2•- and H2 O2 . However, they can inversely produce stronger ROS (e.g., •OH) under many disease conditions (e.g., low pH for myocardial ischemia). Herein, a biocompatible -Cu-O-Zn- bimetallic covalent doped carbon dots (CuZn-CDs) processing both catalase (CAT) and superoxide dismutase activities are reported, mainly because of their abundant electrons and the excellent electron transfer abilities. In addition, Cu dopant helps to balance the positive charge at Zn dopant resulting from low pH, enabling CuZn-CDs to still process CAT ability rather than peroxidase ability. Benefiting from it, CuZn-CDs exhibit sufficient in vitro ROS scavenging ability and cardiomyocyte protective effect against ROS-induced damage. In vivo results further demonstrate that CuZn-CDs can protect the heart from ischemia-reperfusion injury. In addition to antioxidative therapy, the rapid renal clearance and low toxicity properties of CuZn-CDs in animal model reveal high biocompatibility which will facilitate clinical use.