Anti-Stress and Anti-ROS Effects of MnOx-Functionalized Thermosensitive Nanohydrogel Protect BMSCs for Intervertebral Disc Degeneration Repair.

Stem cell transplantation has been proven to be a promising strategy for intervertebral disc degeneration (IDD) repair. However, replicative senescence of bone marrow-derived mesenchymal stem cells (BMSCs), shear damage during direct injection, mechanical stress, and the reactive oxygen species (ROS)-rich microenvironment in degenerative intervertebral discs (IVDs) cause significant cellular damage and limit the therapeutic efficacy. Here, an injectable manganese oxide (MnOx)-functionalized thermosensitive nanohydrogel was proposed for BMSC transplantation for IDD therapy. The MnOx-functionalized thermosensitive nanohydrogel not only successfully protected BMSCs from shear force and mechanical stress before and after injection but also repaired the harsh high-ROS environment in degenerative IVDs, thus effectively increasing the viability of BMSCs and resident nucleus pulposus cells (NPCs). The MnOx-functionalized thermosensitive nanohydrogel provides mechanical protection for stem cells and helps to remove endogenous ROS, providing a promising stem cell delivery platform for the treatment of IDD. This article is protected by copyright. All rights reserved.

Piezo1 channel exaggerates ferroptosis of nucleus pulposus cells by mediating mechanical stress-induced iron influx.

To date, several molecules have been found to facilitate iron influx, while the types of iron influx channels remain to be elucidated. Here, Piezo1 channel was identified as a key iron transporter in response to mechanical stress. Piezo1-mediated iron overload disturbed iron metabolism and exaggerated ferroptosis in nucleus pulposus cells (NPCs). Importantly, Piezo1-induced iron influx was independent of the transferrin receptor (TFRC), a well-recognized iron gatekeeper. Furthermore, pharmacological inactivation of Piezo1 profoundly reduced iron accumulation, alleviated mitochondrial ROS, and suppressed ferroptotic alterations in stimulation of mechanical stress. Moreover, conditional knockout of Piezo1 (Col2a1-CreERT Piezo1flox/flox) attenuated the mechanical injury-induced intervertebral disc degeneration (IVDD). Notably, the protective effect of Piezo1 deficiency in IVDD was dampened in Piezo1/Gpx4 conditional double knockout (cDKO) mice (Col2a1-CreERT Piezo1flox/flox/Gpx4flox/flox). These findings suggest that Piezo1 is a potential determinant of iron influx, indicating that the Piezo1-iron-ferroptosis axis might shed light on the treatment of mechanical stress-induced diseases.

The RNA sequencing results revealed the expression of different genes and signaling pathways during chemotherapy resistance in peripheral T-cell lymphoma.

BACKGROUND: Peripheral T-cell lymphoma (PTCL) is a subtype of non-Hodgkin's lymphoma that occurs primarily at extranodal sites and is commonly treated using chemotherapy and radiotherapy. PTCL is more malignant than other lymphoid tumors, resulting in a poor prognosis.The 5-year recurrence rate remains high, and there is a lack of standard treatment for patients with relapse-resistant disease. However, the molecular mechanisms underlying the resistance of peripheral T-cell lymphoma cells to chemotherapeutic drugs, as well as identifying strategies to overcome drug resistance remains unclear. In this study, we aimed to identify pivotal genes and signaling pathways associated with chemotherapy resistance in PTCL. METHODS: In this study, a total of 5 healthy controls and 7 clinical patients were enrolled; 4 patients were classified as chemotherapy sensitive, and 3 patients were classified as chemotherapy resistant. Peripheral blood samples were collected from each participant, and total RNA was extracted from the white blood cells. RNA sequencing was conducted on the Illumina HiSeq platform to obtain comprehensive gene expression profiles. Subsequently, the expression patterns of the DEGs associated with the most enriched signaling pathways, with a special focus on cancer-related genes, were validated using quantitative real-time polymerase chain reaction (qRT-PCR) in peripheral TCL patients. RESULTS: RNA sequencing (RNA-seq) analysis revealed 4063 differentially expressed genes (DEGs) in peripheral T-cell lymphoma specimens from patients with chemotherapy resistance, of which 1128 were upregulated and 2935 were downregulated. Subsequent quantitative gene expression analysis confirmed a differential expression pattern in all the libraries, with 9 downregulated genes and 10 upregulated genes validated through quantitative real-time PCR in 6 clinical specimens from patients with chemotherapy resistance. KEGG pathway analysis revealed significant alterations in several pathways, with 6 downregulated pathways and 9 upregulated pathways enriched in the DEGs. Notably, the TNF signaling pathway, which is extensively regulated, was among the pathways that exhibited significant changes. These findings suggest that DEGs and the TNF signaling pathway may play crucial roles in chemotherapy resistance in peripheral T-cell lymphoma. CONCLUSION: Our study revealed that the expression of specific genes, including TNFRSF1B, TRADD2, and MAP3K7, may play an important role in chemotherapy resistance in peripheral T-cell lymphoma. Moreover, we identified the downregulation of the TNF signaling pathway, a crucial pathway involved in cell survival, death, and differentiation, as a potential contributor to the development of chemotherapy resistance in peripheral T-cell lymphoma. These findings provide valuable insights into the molecular mechanisms underlying chemotherapy resistance and highlight potential targets for overcoming treatment resistance in this challenging disease.

Long-term toxicity assessment of antibiotics against Vibrio fischeri: Test method optimization and mixture toxicity prediction.

The current luminescent bacteria test for acute toxicity with short contact time was invalid for antibiotics, and the non-uniformed contact times reported in the literature for long-term toxicity assessment led to incomparable results. Herein, a representative long-term toxicity assessment method was established which unified the contact time of antibiotics and Vibrio fischeri within the bioluminescence increasing period (i.e. 10-100% maximum luminescence) of control samples. The effects of excitation and detoxification of antibiotics such as ß-lactams were discovered. Half maximal inhibitory concentration (IC50) of toxic antibiotics (0.00069-0.061 mmol/L) obtained by this method was 2-3 orders of magnitude lower than acute test, quantifying the underestimated toxicity. As antibiotics exist in natural water as mixtures, an equivalent concentration addition (ECA) model was built to predict mixture toxicity based on physical mechanism rather than mathematical method, which showed great fitting results (R2 = 0.94). Furthermore, interaction among antibiotics was investigated. Antibiotics acting during bacterial breeding period had strong synergistic inhibition (IC50 relative deviation from 0.1 to 0.6) such as macrolides and quinolones. Some antibiotics produced increasing synergistic inhibition during concentration accumulation, such as macrolides. The discharge of antibiotics with severe long-term toxicity and strong synergistic inhibition effect should be seriously restricted.

Expression of PD-1 mitigates phagocytic activities TAM in osteosarcoma.

The high expression of programmed death 1 (PD-1) is a hallmark of T cell exhaustion, consequently inhibiting the anti-tumor immunity, tumor-associated macrophages (TAMs) aggravate Osteosarcoma (OS) progression. However, PD-1 expression on TAMs in OS metastasis remains unclear. Here, we used scRNA-Seq of 15500 individual cells from human OS lung metastatic lesion, identified thirteen major cell clusters. Our data revealed that tumor-infiltrating lymphocytes (TILs) OS lung metastatic accompanied by accumulation of exhausted T cells and regulatory T cells (Tregs). CD3+ T cells from human OS lung metastatic exhibited lower proliferation than in primary tissue. Importantly, TAMs mainly comprise immunosuppressive M2 phenotype in OS metastasis. Mechanistically, we found that PD-1 of TAMs inhibits the phagocytic potency, further promoting the progression of OS metastasis. Therefore, the study provides a strong technical support for OS immunotherapy based on PD-1 inhibitors.

Rapid, Selective, and Chemical-Free Removal of Dissolved Silica from Water via Electrosorption: Feasibility and Mechanisms.

The unavoidable and detrimental formation of silica scale in engineered processes necessitates the urgent development of effective, economic, and sustainable strategies for dissolved silica removal from water. Herein, we demonstrate a rapid, chemical-free, and selective silica removal method using electrosorption. Specifically, we confirm the feasibility of exploiting local pH dynamics at the electrodes in flow-through electrosorption, achieved through a counterintuitive cell configuration design, to induce ionization and concomitant electrosorption of dissolved silica. In addition, to improve the feasibility of silica electrosorption under high-salinity solutions, we developed a silica-selective anode by functionalizing porous activated carbon cloths with aluminum hydroxide nanoparticles (Al(OH)3-p-ACC). The modification markedly enhances silica sorption capacity (2.8 vs 1.1 mgsilica ganode-1) and reduces the specific energy consumption (13.3 vs 19.8 kWh kgsilica-1). Notably, the modified electrode retains remarkable silica sorption capacity even in the presence of high concentrations of co-occurring ions (up to 100 mM NaCl). The mechanisms underlying the superior silica removal stability and selectivity with the Al(OH)3-p-ACC electrode are also elucidated, revealing a synergistic interaction involving outer-sphere and inner-sphere complexation between dissolved silica and Al(OH)3 nanoparticles on the electrodes. Moreover, we find that effective regeneration of the electrodes may be achieved by applying a reverse potential during discharge, although complete regeneration of the modified electrodes may necessitate alternative materials or process optimization. We recommend the adoption of feedwater-specific designs for the development of future silica-selective electrodes in electrosorption capable of meeting silica removal demands across a wide range of engineered systems.

The New Role of HNF1A-NAS1/miR-214/INHBA Signaling Axis in Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer and one of the leading causes of death worldwide. Seriously threatens human life and health. Previous studies have identified that inhibin ßA (INHBA) could induce tumorgenesis and progression of CRC through the regulation of the TGF-ß/Smad signal axis. The abnormal expression of INHBA is related to the poor prognosis of patients. The aim of this study was to identify the molecular mechanism of HNF1A-AS1 and miR-214 regulating INHBA and carcinogenesis through bioinformatics combined with experiments. METHODS: The expression of HNF1A-AS1, miRNA-214-5p, INHBA in pan-cancer and CRC were investigated in the Cancer Genome Atlas (TCGA). The correlation between HNF1A-AS1 and immune-related genes or miRNAs was explored via the Gene Expression Profiling Interactive Analysis (GEPIA) and volcano plots, respectively. The association between HNF1A-AS1 and differentially expressed miRNAs was constructed by TargetScan. The miRDB, miRWalk, and TargetScan databases were utilized to predict the target genes of hsa-miR-214. The expression of INHBA in tissues and cell lines of CRC was examined by RT-qPCR and western blot assay. RESULTS: The INHBA and HNF1A-AS1 expressions were increased in Colon adenocarcinoma (COAD) and Rectum adenocarcinoma (READ) of the TCGA database. Hsa-miR-214 was relatively less expressed in CRC tissues compared with para-cancer tissues. The expression of HNF1A-AS1 was negatively correlated with hsa-miR-214. INHBA was one of the target genes of hsa-miR-214 based on miRDB, miRWalk, and TargetScan databases. The specific binding sites of INHBA-3'UTR and miR-214-5p were identified by starBase. The expression level of INHBA was positively correlated with the T stage of tumor and negatively correlated with overall survival (OS) and disease-free survival (DFS) in CRC patients. The results of RT-qPCR and western blot indicated that the expression of INHBA in tissues and cell lines in CRC was higher than those in para-carcinoma tissues and normal colon cell lines, respectively. CONCLUSIONS: These findings suggested that HNF1A-AS1 and miRNA-214-5p were key upstream non-coding RNAs of INHBA. The HNF1A-AS1/miR-214/INHBA signal axis plays a significant role in the tumorgenesis and progression of CRC. By interfering with HNF1A-AS1 and INHBA genes on HT29 and SW480 cells, it was found that HNF1A-AS1 and INHBA genes may be important target genes in CRC.

En Bloc Resection for Spinal Cord Hemangioblastomas: Surgical Technique and Clinical Outcomes.

BACKGROUND: Spinal cord hemangioblastomas are rare benign and highly vascular tumors that develop either sporadically or as part of von Hippel-Lindau (VHL) disease. Generally, complete resection without significant neurologic deficit remains considerably challenging due to the risk of massive bleeding. The current study therefore aimed to describe en bloc resection of spinal cord hemangioblastomas according to the typical anatomical structures of peripheral lesions and evaluate the neurofunctional prognosis of this technique. METHODS: A total of 39 spinal cord hemangioblastomas from a series of 19 patients who underwent en bloc resection were retrospectively analyzed. In all cases, clinical and radiologic characteristics, as well as surgical tenets, were retrospectively determined and analyzed. Short- and long-term outcomes were analyzed using the McCormick grade and Odom's criteria. Factors significantly associated with poor neurologic function after en bloc resection were also determined. RESULTS: All 39 spinal cord hemangioblastomas, including 28 intramedullary, 2 intramedullary-extramedullary, and 9 extramedullary lesions, were located dorsally or dorsolaterally (100.0%). The most common lesion location was the thoracic segment (53.8%), with most of the lesions being accompanied by syringomyelia (94.7%). Long-term follow-up (mean: 103 ± 50.4 months) for prognosis determination revealed that 88.2% (15/17) of all cases had stable or improved neurofunctional outcomes according to the McCormick grade and Odom's criteria. Only one case with VHL disease developed recurrence 4 years after surgery. Additionally, statistical analysis showed that VHL disease was an independent prognostic factor associated with deteriorating neurologic function (p = 0.015). CONCLUSIONS: En bloc resection facilitated satisfactory long-term functional outcomes in patients with spinal cord hemangioblastomas. Given that VHL disease was identified as a predictor of poor long-term outcomes, regular long-term follow-up of patients with VHL-associated spinal cord hemangioblastoma seems necessary.

Recent advances and prospects of metal-organic frameworks in cancer therapies.

Metal-organic frameworks (MOFs) have been broadly applied in biomedical and other fields. MOFs have high porosity, a large comparative area, and good biostability and have attracted significant attention, especially in cancer therapies. This paper presents the latest applications of MOFs in chemodynamic therapy (CDT), sonodynamic therapy (SDT), photodynamic therapy (PDT), photothermal therapy (PTT), immunotherapy (IT), and combination therapy for breast cancer. A combination therapy is the combination of two different treatment modalities, such as CDT and PDT combination therapy, and is considered more effective than separate therapies. Herein, we have also discussed the advantages and disadvantages of combination therapy in the treatment of breast cancer. This paper aims to illustrate the potential of MOFs in new cancer therapeutic approaches, discuss their potential advantages, and provide some reflections on the latest research results.

A New Cd(II)-Based Coordination Polymer for Efficient Photocatalytic Removal of Organic Dyes.

Coordination polymers (CPs) are a diverse class of multi-dimensional compounds that show promise as photocatalysts for degrading dyes in polluted water. Herein, a new 1D Cd(II)-based coordination polymer with the formula [Cd(bpyp)(nba)2] (1) (bpyp = 2,5-bis(pyrid-4-yl)pyridine and Hnba = 4-nitrobenzoic acid) is synthesized and characterized. In 1, the two carboxyl groups of two different nba- ligands show µ2-η1:η1 and µ1-η1:η1 coordination modes to connect the CdII centers and sit on either side of the chain along the b direction. The produced CP 1 was utilized as the photocatalyst in the process of the photodegradation of methyl blue (MB), methyl orange (MO), rhodamine B (RhB), and methyl violet (MV) dyes when exposed to UV light. The photocatalytic degradation activities of CP 1 were analyzed, and the results suggest that it exhibits an extraordinary efficiency in the degradation of MB, MV, MO, and RhB. RhB has a 95.52% efficiency of degradation, whereas MV has a 58.92% efficiency, MO has 35.44%, and MB has 29.24%. The photodecomposition of dyes is catalyzed mostly by •O2- and •OH-, as shown by research involving the trapping of radicals.

New 5,5-(1,4-Phenylenebis(methyleneoxy)diisophthalic Acid Appended Zn(II) and Cd(II) MOFs as Potent Photocatalysts for Nitrophenols.

Metal-organic frameworks (MOFs) are peculiar multimodal materials that find photocatalytic applications for the decomposition of lethal molecules present in the wastewater. In this investigation, two new d10-configuration-based MOFs, [Zn2(L)(H2O)(bbi)] (1) and [Cd2(L)(bbi)] (2) (5,5-(1,4-phenylenebis(methyleneoxy)diisophthalic acid (H2L) and 1,1'-(1,4-butanediyl)bis(imidazole) (bbi)), have been synthesized and characterized. The MOF 1 displayed a (4,6)-connected (3.43.52)(32.44.52.66.7) network topology, while 2 had a (3,10)-connected network with a Schläfli symbol of (410.511.622.72)(43)2. These MOFs have been employed as photocatalysts to photodegrade nitrophenolic compounds, especially p-nitrophenol (PNP). The photocatalysis studies reveal that 1 displayed relatively better photocatalytic performance than 2. Further, the photocatalytic efficacy of 1 has been assessed by altering the initial PNP concentration and photocatalyst dosage, which suggest that at 80 ppm PNP concentration and at its 50 mg concentration the MOF 1 can photo-decompose around 90.01% of PNP in 50 min. Further, radical scavenging experiments reveal that holes present over 1 and ·OH radicals collectively catalyze the photodecomposition of PNP. In addition, utilizing density of states (DOS) calculations and Hirshfeld surface analyses, a plausible photocatalysis mechanism for nitrophenol degradation has been postulated.

Survival analysis of patients with advanced non-small cell lung cancer receiving EGFR-TKI treatment of Yunnan in southwestern China: a real-world study.

Importance: Patients with EGFR mutations who have advanced-stage non-small cell lung cancer (NSCLC) already receive tyrosine kinase inhibitors (TKIs) as the standard first-line therapy. Notably, Yunnan is a regional high incidence area of lung cancer in the highlands with a high rate of rare EGFR mutations. Overall, lung cancer patients in Xuanwei may present a distinct subgroup globally. Recent studies suggested that the NSCLC cohort in Xuanwei harbored a significantly higher uncommon mutation rate. However, little was known about the clinicopathological features and treatment efficacy of EGFR-TKI in Yunnan NSCLC patients. Objective: This study aimed to investigate the clinical impact of histologic type on the survival outcomes of patients with stage IIIB and IV NSCLC receiving EGFR-TKI treatment of Yunnan in southwestern China. Methods: In this retrospective study, we enrolled advanced NSCLC patients (IIIB-IV) with EGFR mutations who were first diagnosed and treated at Yunnan Cancer hospital from January 2016 to December 2019. Sociodemographics, lifestyle, survival, and clinicopathological characteristics of the patients were collected. The Kaplan-Meier method was used to assess the OS and PFS of patients. An analysis of prognostic factors was conducted using Cox regression. Results: A total of 468 eligible patients were included. The median progression-free survival (PFS) and overall survival(OS) were 11.30(95% CI, 10.12-12.48) months and 30.30(95% CI, 26.24-34.36) months. Based on survival analysis among all the patients,females(HR=0.815;95% CI:0.671-0.989; P=0.017), Xuanwei origin (HR=0.776; 95% CI: 0.609-0.989; P=0.040), sample types(HR=0.780; 95% CI: 0.642-0.947; P=0.012) had a longer PFS. Multivariable analysis showed that only the sample type was an independent factor on median PFS with EGFR-TKI therapy. Patients less than 60 years old (HR=1.433; 95% CI:1.134-1.812, P=0.003)had better OS, but objectives with BMI≥24kg/m2(HR=0.653; 95% CI: 0.500-0.864; P=0.002), females(HR=0.776; 95% CI:0.613-0.982; P=0.035)and patients with tissue sample type (HR=0.760; 95% CI:0.600-.0961; P=0.022) had better OS. Notably, subgroup analysis of our study also found that PFS was significantly better in patients with G719X, L861Q, S768I, G719X+L861Q, and G719X+S768I in Xuanwei than classical mutation ones, including 19-Del and L858R (median 22.7 vs. 12.0 months, HR=0.523, P=0.010), while PFS was inferior in patients with rare mutations of EGFR in non-Xuanwei than the classical mutation ones (median 5.10 vs. 11.10 months, HR=1.760, P=0.015). Conclusion: NSCLC patients in Yunnan displayed a unique EGFR mutation profile, especially a higher prevalence of EGFR uncommon and compound mutations subtype. This study indicates prognostic factors of NSCLC treated with EGFR-TKI in Yunan and Xuanwei. This study will provide new clinical evidence for EGFR-TKI-targeted therapy in patients with rare EGFR mutations in China and worldwide. More researchs were needed for NSCLC EGFR-TKI therapy and medical insurance policy-making in Yunnan, Xuanwei area and uncommon especially.

Anthropogenic As pollution mediated by submarine groundwater discharge in a marine ranch.

Arsenic (As) pollution, is a global problem, threatening human health and ecological security, especially in the bay environment with dense population and human activities. Among potential pathways of As into the bay, submarine groundwater discharge (SGD) has not received adequate attention due to its invisibility. We determined As and 222Rn activity concentrations in different water mass. Spatial variation of dissolved As concentration in the groundwater was large and attributed to the adjacent local industries. By combining 222Rn mass balance modeling with As concentrations measured, the SGD-derived As fluxes was conservatively estimated to be 1310 kg As d-1 and 5880 kg As d-1 in the dry and wet seasons, respectively. The migration of arsenic may be enhanced by rainfall and dissolved carbon. The amount of SGD derived As input to the bay was greater than the total combined As input from river discharge, atmosphere, sewage drainage, and diffusion from sediment.

Prognostic nomogram for predicting lower extremity deep venous thrombosis in ruptured intracranial aneurysm patients who underwent endovascular treatment.

Background: Lower extremity deep vein thrombosis (DVT) is one of the major postoperative complications in patients with ruptured intracranial aneurysms (RIA) who underwent endovascular treatment (EVT). However, patient-specific predictive models are still lacking. This study aimed to construct and validate a nomogram model for estimating the risk of lower extremity DVT for RIA patients who underwent EVT. Methods: This cohort study enrolled 471 RIA patients who received EVT in our institution between 1 January 2020 to 4 February 2022. Perioperative information on participants is collected to develop and validate a nomogram for predicting lower extremity DVT in RIA patients after EVT. Predictive accuracy, discriminatory capability, and clinical effectiveness were evaluated by concordance index (C-index), calibration curves, and decision curve analysis. Result: Multivariate logistic regression analysis showed that age, albumin, D-dimer, GCS score, middle cerebral artery aneurysm, and delayed cerebral ischemia were independent predictors for lower extremity DVT. The nomogram for assessing individual risk of lower extremity DVT indicated good predictive accuracy in the primary cohort (c-index, 0.92) and the validation cohort (c-index, 0.85), with a wide threshold probability range (4-82%) and superior net benefit. Conclusion: The present study provided a reliable and convenient nomogram model developed with six optimal predictors to assess postoperative lower extremity DVT in RIA patients, which may benefit to strengthen the awareness of lower extremity DVT control and supply appropriate resources to forecast patients at high risk of RIA-related lower extremity DVT.

Prediction nomogram based on 18F-FDG PET/CT and clinical parameters for patients with diffuse large B-cell lymphoma.

The objective of this study was to develop a nomogram including parameters assessed by 18F-FDG PET/CT and clinical parameters for patients with diffuse large B-cell lymphoma (DLBCL) to predict progression-free survival (PFS). A total of 181 patients with pathologically diagnosed DLBCL at Sichuan Cancer Hospital and Institute from March 2015 to December 2020 were enrolled in this retrospective study. The area under the receiver operating characteristic (ROC) curve (AUC) was used to calculate the optimal cutoff values of the semiquantitative parameters (SUVmax, TLG, MTV, and Dmax) for PFS. A nomogram was constructed according to multivariate Cox proportional hazards regression. The predictive and discriminatory capacities of the nomogram were then measured using the concordance index (C-index), calibration plots, and Kaplan-Meier curves. The predictive and discriminatory capacities of the nomogram and the International Prognostic Index of the National Comprehensive Cancer Network (NCCN-IPI) were compared via the C-index and AUC. Multivariate analysis demonstrated that male gender and pretreatment Ann Arbor stage III-IV, non-GCB, elevated lactate dehydrogenase (LDH), number of extranodal organ involvement (Neo)>1, MTV≥152.8 cm3, and Dmax ≥53.9 cm were associated with unfavorable PFS (all p<0.05). The nomogram, including gender, Ann Arbor stage, pathology type, Neo, LDH levels, MTV, and Dmax, showed good prediction accuracy, with a C-index of 0.760 (95% CI: 0.727-0.793), which was higher than that of NCCN-IPI (0.710; 95% CI: 0.669-751). The calibration plots for 2-year demonstrated good consistency between the predicted and observed probabilities for survival time. We established a nomogram including MTV, Dmax, and several clinical parameters to predict the PFS of patients with DLBCL, and the nomogram showed better predictability and higher accuracy than NCCN-IPI.

Discovery of therapeutic targets for spinal cord injury based on molecular mechanisms of axon regeneration after conditioning lesion.

BACKGROUND: Preinjury of peripheral nerves triggers dorsal root ganglia (DRG) axon regeneration, a biological change that is more pronounced in young mice than in old mice, but the complex mechanism has not been clearly explained. Here, we aim to gain insight into the mechanisms of axon regeneration after conditioning lesion in different age groups of mice, thereby providing effective therapeutic targets for central nervous system (CNS) injury. METHODS: The microarray GSE58982 and GSE96051 were downloaded and analyzed to identify differentially expressed genes (DEGs). The protein-protein interaction (PPI) network, the miRNA-TF-target gene network, and the drug-hub gene network of conditioning lesion were constructed. The L4 and L5 DRGs, which were previously axotomized by the sciatic nerve conditioning lesions, were harvested for qRT-PCR. Furthermore, histological and behavioral tests were performed to assess the therapeutic effects of the candidate drug telmisartan in spinal cord injury (SCI). RESULTS: A total of 693 and 885 DEGs were screened in the old and young mice, respectively. Functional enrichment indicates that shared DEGs are involved in the inflammatory response, innate immune response, and ion transport. QRT-PCR results showed that in DRGs with preinjury of peripheral nerve, Timp1, P2ry6, Nckap1l, Csf1, Ccl9, Anxa1, and C3 were upregulated, while Agtr1a was downregulated. Based on the bioinformatics analysis of DRG after conditioning lesion, Agtr1a was selected as a potential therapeutic target for the SCI treatment. In vivo experiments showed that telmisartan promoted axonal regeneration after SCI by downregulating AGTR1 expression. CONCLUSION: This study provides a comprehensive map of transcriptional changes that discriminate between young and old DRGs in response to injury. The hub genes and their related drugs that may affect the axonal regeneration program after conditioning lesion were identified. These findings revealed the speculative pathogenic mechanism involved in conditioning-dependent regenerative growth and may have translational significance for the development of CNS injury treatment in the future.

An up-conversion Ba3In(PO4)3:Er3+/Yb3+ phosphor that enables multi-mode temperature measurements and wide-gamut 'temperature mapping'.

At present, most fluorescent materials that can be used for optical temperature measurement exhibit poor thermochromic performance, which limits their applications. In this study, the phosphor Ba3In(PO4)3:Er/Yb was synthesized with a high doping concentration of Yb3+, and it emitted composition- and temperature-induced wide color gamut up-conversion luminescence from red to green. Four modes of fluorescence thermometry can be realized in the temperature range of 303-603 K, which is based on the ratio of fluorescence intensity between thermally coupled energy levels and non-thermally coupled energy levels, color coordinate shift, and fluorescence decay lifetime, respectively. The highest Sr value obtained was 0.977% K-1. Taking advantage of the fact that temperature can significantly change the luminous color of the phosphor Ba3In(PO4)3:0.02Er3+/0.05Yb3+, we demonstrated 'temperature mapping' on a smooth metal surface with multiple optical encryptions. These results indicate that the Ba3In(PO4)3:Er/Yb phosphor is an excellent fluorescent material for thermal imaging and has great application potential in temperature visualization measurement and optical encryption.

Triboelectric Nanogenerators-Based Therapeutic Electrical Stimulation on Skin: from Fundamentals to Advanced Applications.

Discovery of the amazing and vital therapeutic roles of electrical stimulation (ES) on skin has sparked tremendous efforts to investigate ES suppliers. Among them, triboelectric nanogenerators (TENGs), as a self-sustainable bioelectronic system, can generate self-powered and biocompatible ES for achieving superior therapeutic effects on skin applications. Here, a brief review of the application of TENGs-based ES on skin is presented, with specific discussions of the fundamentals of TENGs-based ES and its feasibility to be applied for adjusting physiological and pathological processes of skin. Then, a comprehensive and in-depth depiction of emerging representative skin applications of TENGs-based ES is categorized and reviewed, with particular descriptions about its therapeutic effects on achieving antibacterial therapy, promoting wound healing, and facilitating transdermal drug delivery. Finally, the challenges and perspectives for further advancing TENGs-based ES toward a more powerful and versatile therapeutic strategy are discussed, particularly regarding opportunities in fundamental multidisciplinary research and biomedical applications.

Free-standing membrane incorporating single-atom catalysts for ultrafast electroreduction of low-concentration nitrate.

The release of wastewaters containing relatively low levels of nitrate (NO3-) results in sufficient contamination to induce harmful algal blooms and to elevate drinking water NO3- concentrations to potentially hazardous levels. In particular, the facile triggering of algal blooms by ultra-low concentrations of NO3- necessitates the development of efficient methods for NO3- destruction. However, promising electrochemical methods suffer from weak mass transport under low reactant concentrations, resulting in long treatment times (on the order of hours) for complete NO3- destruction. In this study, we present flow-through electrofiltration via an electrified membrane incorporating nonprecious metal single-atom catalysts for NO3- reduction activity enhancement and selectivity modification, achieving near-complete removal of ultra-low concentration NO3- (10 mg-N L-1) with a residence time of only a few seconds (10 s). By anchoring Cu single atoms supported on N-doped carbon in a carbon nanotube interwoven framework, we fabricate a free-standing carbonaceous membrane featuring high conductivity, permeability, and flexibility. The membrane achieves over 97% NO3- removal with high N2 selectivity of 86% in a single-pass electrofiltration, which is a significant improvement over flow-by operation (30% NO3- removal with 7% N2 selectivity). This high NO3- reduction performance is attributed to the greater adsorption and transport of nitric oxide under high molecular collision frequency coupled with a balanced supply of atomic hydrogen through H2 dissociation during electrofiltration. Overall, our findings provide a paradigm of applying a flow-through electrified membrane incorporating single-atom catalysts to improve the rate and selectivity of NO3- reduction for efficient water purification.

Promising Mass-Productive 4-Inch Commercial SERS Sensor with Particle in Micro-Nano Porous Ag/Si/Ag Structure Using in Auxiliary Diagnosis of Early Lung Cancer.

The construction of commercial surface enhanced Raman scattering (SERS) sensors suitable for clinical applications is a pending problem, which is heavily limited by the low production of high-performance SERS bases, because they usually require fine or complicated micro/nano structures. To solve this issue, herein, a promising mass-productive 4-inch ultrasensitive SERS substrate available for early lung cancer diagnosis is proposed, which is designed with a special architecture of particle in micro-nano porous structure. Benefitting from the effective cascaded electric field coupling inside the particle-in-cavity structure and efficient Knudsen diffusion of molecules within the nanohole, the substrate exhibits remarkable SERS performance for gaseous malignancy biomarker, with the limit of detection is 0.1 ppb and the average relative standard deviation value at different scales (from cm2 to µm2 ) is ≈16.5%. In practical application, this large-sized sensor can be further divided into small ones (1 × 1 cm2 ), and more than 65 chips will be obtained from just one 4-inch wafer, greatly increasing the output of commercial SERS sensor. Further, a medical breath bag composed of this small chip is designed and studied in detail here, which suggested high-specificity recognition for lung cancer biomarker in mixed mimetic exhalation tests.