Sensory discrimination is essential for survival. However, how sensory information is finely controlled in the brain is not well defined. Here, we show that astrocytes control tactile acuity via ...tonic inhibition in the thalamus. Mechanistically, diamine oxidase (DAO) and the subsequent aldehyde dehydrogenase 1a1 (Aldh1a1) convert putrescine into GABA, which is released via Best1. The GABA from astrocytes inhibits synaptically evoked firing at the lemniscal synapses to fine-tune the dynamic range of the stimulation-response relationship, the precision of spike timing, and tactile discrimination. Our findings reveal a novel role of astrocytes in the control of sensory acuity through tonic GABA release.
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•Thalamic astrocytes synthesize GABA via DAO and Aldh1a1 to mediate tonic inhibition•Tonic GABA improves linearity and temporal fidelity of synaptically evoked TC firing•Astrocytic tonic GABA improves tactile discrimination performance
Kwak et al. report that astrocytes synthesize GABA using DAO and Aldh1a1 and release GABA through the Best1 channel to mediate tonic GABA in the thalamus. Astrocytic tonic GABA fine-tunes the dynamic range and precision of stimulation to response of TC firing, thus enhancing the performance of sensory discrimination of mice.
Current treatments for wound healing engage in passive healing processes and rarely participate in stimulating skin cell behaviors for active wound healing. Electric potential difference‐derived ...electrical fields (EFs) are known to modulate skin cell behaviors. Here, a piezoelectric dermal patch is developed that can be applied on skin wound site and EF is generated to promote wound healing. The one‐directionally aligned zinc oxide nanorod‐based piezoelectric patch generates piezoelectric potential upon mechanical deformations induced by animal motion, and induces EF at the wound bed. In vitro and in vivo data demonstrate that the piezoelectric patch promotes the wound healing process through enhanced cellular metabolism, migration, and protein synthesis. This modality may lead to a clinically relevant piezoelectric dermal patch therapy for active wound healing.
A piezoelectric patch that can be applied on skin wounds and generate electric fields (EFs) to promote wound healing is developed. The zinc oxide nanorod‐based patch generates piezoelectric potential upon skin movements, and induces EF at the wound bed. In vitro and in vivo data suggest the patch promotes skin regeneration through enhanced cellular metabolism, migration, and protein synthesis.
We have developed a simple approach for the large-scale synthesis of water-soluble green carbon nanodots (G-dots) from many kinds of large food waste-derived sources. About 120 g of G-dots per 100 kg ...of food waste can be synthesized using our simple and environmentally friendly synthesis approach. The G-dots exhibit a high degree of solubility in water because of the abundant oxygen-containing functional groups around their surface. The narrow band of photoluminescence emission (400–470 nm) confirms that the size of the G-dots (∼4 nm) is small because of a similar quantum effects and emission traps on the surfaces. The G-dots have excellent photostability; their photoluminescence intensity decreases slowly (∼8%) under continuous excitation with a Xe lamp for 10 days. We carried out cell viability assay to assess the effect of cytotoxicity by introducing G-dots in cells such as Chinese hamster ovary cells (CHO-K1), mouse muscle cells (C2C12), and African green monkey kidney cells (COS-7), up to a concentration of 2 mg mL–1 for 24 h. Due to their high photostability and low cytotoxicity, these G-dots are excellent probes for in vitro bioimaging. Moreover, the byproducts (not including G-dots) of G-dot synthesis from large food-waste derived sources promoted the growth and development of seedlings germinated on 3DW-supplemented gauze. Because of the combined advantages of green synthesis, high aqueous stability, high photostability, and low cytotoxicity, the G-dots show considerable promise in various areas, including biomedical imaging, solution state optoelectronics, and plant seed germination and/or growth.
The use of tenofovir (TDF) and entecavir (ETV) in patients with chronic hepatitis B (CHB) has led to a decrease in the incidence of hepatocellular carcinoma (HCC) and liver-related events. However, ...whether there is a difference between the two agents in the extent of improving such outcomes has not been clarified thus far. Therefore, we aimed to compare TDF and ETV on the risk of HCC and mortality.
A total of 7015 consecutive patients with CHB who were treated with TDF or ETV between February 2007 and January 2018 at the liver units of the Catholic University of Korea were screened for study eligibility and 3022 patients were finally analysed. Study end points were HCC and all-cause mortality or liver transplantation (LT) within 5 years after the initiation of antiviral therapy. Propensity score matching (PSM) and inverse probability of treatment weighting methods were used.
No difference was observed between TDF and ETV in the incidence rates of HCC in the entire cohort (HR 1.030; 95% CI 0.703 to 1.509, PSM model, p=0.880) and subgroups of patients with chronic hepatitis and cirrhosis. Also, no difference was observed between TDF and ETV in the incidence rates of all-cause mortality or LT in the entire cohort (HR 1.090; 95% CI 0.622 to 1.911, PSM model, p=0.763), and patients with chronic hepatitis and cirrhosis.
This study has demonstrated the clinical outcomes in patients with CHB who received TDF or ETV treatment. There was no difference in the intermediate-term risk of HCC and mortality or LT between the two drugs.
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•The flexible antibacterial ZnO nanopiilar arrays were sucessfully fabricated by assistance of sonochemical reaction.•The ZnO formation mechanism is also proposed and investigated ...using FT-IR and XRD.•Antibacterial efficiency was depthly investigated using realistic pathogetnic bacteria model of E. coli O157:H7 and S. aureus.•ZnO nanopiilar arrays have improved antibacterial behavior because of nanotopological effects and electrostatic interaction.
Antibacterial activity is essential and highly demanded in worldwide to prevent potential bacterial infection. Here in this work, we report a new approch for the fabrication of flexible zinc oxide nanopillar arrays (ZG-NPA) film with an efficient antibacterial activity. A flexible NPA film served as a substrate for the rapid formation of ZnO by using ultrasound-assisted method. The enhancement of antibacterial activity were induced by cellular damages because of nano topological effects and electrostatic interaction between bacteria and ZG-NPA. Owing to the benefits of combination with flexibility, high surface areas from nano-features and excellent antibacterial efficiency (>80%) of ZG-NPA, the film can show great potential for use as novel biomaterials for preventing bacterial infections.
Treating hepatocellular carcinoma with transarterial chemoembolization (TACE) induces both local inflammation in the tumor microenvironment as well as systemic inflammation. We analyzed serum ...cytokine response to TACE to evaluate this. Serum samples obtained from 203 HCC patients treated with TACE were analyzed for inflammatory cytokines including interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12, IL-13, IL-17, IL-22, TNF-α, IFN-γ, and C-reactive protein (CRP) levels. Cytokine concentrations were measured at day 0 (D0, baseline, n = 203), day3 (D3, n = 156), day7 (D7, n = 147), and day 60 (D60, n = 115) after TACE. Network analysis of the cytokines was performed to understand their interactive relationship. After TACE, IL-1β, -6,-9, -12, and -22 increased by D60. IL-2, -5, -10, -17A and INF-γ decreased by D60, and IL-4, -13 and TNF-α revealed stable concentration. D0 network revealed that IL-2, -4, -5, and -10 formed a module. D3 network had the highest clustering coefficient and average degree that revealed similar pattern as CRP. D7 network revealed that IL-6, -9 and CRP were isolated from the network. D60 network had the lower network heterogeneity and lower clustering coefficient, network diameter, shortest path and characteristic path length. Degree correlation revealed that assortative network turned to disassortative network by D60 indicating that the network gained scale free feature. D60 cytokine network retained inflammatory function and these parameters indicated that the systemic inflammation induced by TACE appeared to be attenuated by D60. IL-9 at D3 and D7 seemed to be related to anti-tumor effect and IL-6 at D7 and D60, and IL-22 at D60 was related to regenerative but not pro- or anti- inflammatory function. Median survival month of patient group with high and low values of cytokine with P-values were as follows: D0 CRP, 9.5 and 54.2 months (P<0.0001); D0 IL-2, 39.9 and 56.1 months (P = 0.0084); D3 CRP, 31.3 and 55.1 months (P = 0.0056); D7 CRP, 28.7 and 50.7 months (P = 0.0065), respectively. TACE is associated with systemic inflammation which appears to peak at Day 3 and resolve by D60. Among the tested cytokines, IL-6 and IL-22 appear to play a regenerative role.
In spite of the recent successes in transistors and solar cells utilizing poly(3-hexylthiophene) (P3HT) nanofibrils, systematic analysis on the growth kinetics has not been reported due to the lack ...of analytical tools. This study proposed a simple spectroscopic method to obtain the crystallinity of P3HT in solutions. On the basis of the analytical approach, we found that the crystallinity hysteresis upon temperature is a simple function of the solubility parameter difference (Δδ) between the P3HT and the solvents. When Δδ ≥ 0.7, a cooling (−20 °C)-and-heating (25 °C) process allowed the preparation of solutions including 1D crystal seeds dispersed in the solution. Simple coating of the seeded solutions completed the growth of the seeds into long nanofibrils at the early stage of the coating and thereby achieved almost 100% crystallinity in the resulting films without any postannealing process. The existence of PCBM for bulk-heterojunction (BHJ) solar cells did not affect the nucleation and growth of the nanofibrils during the cooling-and-heating process. The solar cells prepared from the solutions with Δδ ≥ 0.7 had solar conversion efficiencies higher than the conventional thermally annealed cells.
We compared the post-treatment overall survival (OS) and recurrence-free survival (RFS) between patients with Child-Turcotte-Pugh (CTP) class-A and single small (≤3 cm) hepatocellular carcinoma (HCC) ...treated by surgical resection (SR) and radiofrequency ablation (RFA).
We retrospectively analyzed 391 HCC patients with CTP class-A who underwent SR (n=232) or RFA (n=159) as first-line therapy for single small (≤3 cm) HCC. Survival was compared according to the tumor size (≤2 cm/2-3 cm) and the presence of cirrhosis. Inverse probability of treatment weighting (IPW) method was used to estimate the average causal effect of treatment.
The median follow-up period was 64.8 months (interquartile range, 0.1-162.6). After IPW, the estimated OS was similar in the SR and RFA groups (P=0.215), and even in patients with HCC of ≤2 cm (P=0.816) and without cirrhosis (P=0.195). The estimated RFS was better in the SR group than in the RFA groups (P=0.005), also in patients without cirrhosis (P<0.001), but not in those with HCC of ≤2 cm (P=0.234). The weighted Cox proportional hazards model with IPW provided adjusted hazard ratios (95% confidence interval) for OS, and the RFS after RFA versus SR were 0.698 (0.396-1.232) (P=0.215) and 1.698 (1.777-2.448) (P=0.005), respectively.
SR was similar for OS compared to RFA, but was better for RFS in patients with CTP class-A and single small (≤3 cm) HCC. The RFS was determined by the presence or absence of cirrhosis. Hence, SR rather than RFA should be considered in patients without cirrhosis to prolong the RFS, although there is no OS difference.
Tumor-associated immune response plays a critical role in cancer pathogenesis. This study evaluated clinical implications of T cell cytokines and regulatory T cells (Tregs) in HCC patients treated ...with TACE. Whole blood was obtained for analysis of T cell cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12p70, IL-13, IL-17A, IL-22, IFN-γ, and TNF-α) and Tregs from 142 HCC patients. Patients with CTP class A had a significantly lower proportion of detectable IL-4 or IL-6, but a higher proportion of detectable IL-22 than patients with CTP class B/C. IL-6 level was well correlated with tumor stage and undetectable IL-17A was associated with extrahepatic metastasis. The overall survival rate was significantly higher in patients who had undetectable IL-6 or detectable IL-22 than patients who did not. IL-6 among cytokines remained independently predictive factor for survival. Increased IFN-γ/IL-10 ratio and no increase in IL-6 level following TACE were associated with prolonged survival, and baseline Tregs could affect Th1/Th2 balance. T cell cytokines are associated with a variety of clinical aspects of HCC, and IL-6 is the most significant predictor of survival. A shift toward increased Th1 response and no increase in IL-6 level exert favorable immunologic effects on HCC prognosis.
The comparative efficacy and safety between lenvatinib and hepatic artery infusion chemotherapy (HAIC) in patients with unresectable hepatocellular carcinoma (HCC) is still unclear. This multicenter ...historical cohort study enrolled 244 patients who were treated with HAIC (n = 173) or lenvatinib (n = 71) between 2012 and 2020. Propensity score matching (PSM) was performed, and 52 patients were selected per group. Clinical outcomes and safety were compared. Objective response rate (ORR) was not different between the two groups (26.0% vs. 23.1%, p = 0.736). Before PSM, the HAIC group had a higher proportion of Child-Pugh B and portal vein tumor, whereas the lenvatinib group had more patients with extrahepatic metastases, which was adjusted after PSM. There were no differences in progression-free survival (PFS) and overall survival (OS) after PSM (HAIC vs. lenvatinib, median PFS, 3.6 vs. 4.0 months, p = 0.706; median OS 10.8 vs. 7.9 months, p = 0.106). Multivariate Cox-regression showed that alpha-fetoprotein ≤1000 ng/mL was only an associated factor for OS after PSM in all patients (hazard ratio = 0.421, p = 0.011). Subgroup analysis for patients with a high tumor burden beyond the REFLECT eligibility criteria revealed that the HAIC group (n = 29) had a significantly longer OS than did the lenvatinib group (n = 30) (10.0 vs. 5.4 months, p = 0.004). More patients in the HAIC group achieved better liver function than those in the lenvatinib group at the time of best responses. There was no difference in the incidence of grade 3 and 4 adverse events between the two groups. Therefore, lenvatinib is comparable to HAIC in terms of ORR and OS in unresectable HCC meeting REFLECT eligibility criteria.
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