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Liver fibrosis is a major risk factor for hepatocellular carcinoma origin, and its progression not only correlates with oxidative stress and inflammation, but also is encouraged by autophagy hold‐up. Therefore, new solutions to effectively attenuate oxidative stress and inflammation and coincidentally favor autophagy are highly demanded to reverse liver fibrosis, and even hamper its escalation into hepatocellular carcinoma. Herein, the porous manganese‐substituted Prussian blue (PMPB) analogs are harnessed to activate autophagy, scavenge reactive oxygen species (ROS), and suppress inflammation for liver fibrosis therapy. PMPB can effectively inhibit macrophage activation, facilitate macrophage autophagy, eradicate ROS, and blockade cellular cross‐talk, thus impeding further inflammation progression. Moreover, the favorable spontaneous capture of PMPB by Kupffer cells allows more PMPB accumulation in liver to significantly attenuate liver injury and collagen deposition, thereby inhibiting the progression of liver fibrosis. PMPB‐based nanomedicine shows great potentials in promoting autophagy activation, eliminating ROS, inhibiting inflammation, and protecting hepatocytes from oxidative stress‐arised damages, which eventually attenuate the extent of liver fibrosis, holding great promise in clinical translation for treating liver fibrosis. [ABSTRACT FROM AUTHOR]

In recent years, with the increasing energy consumption and carbon emissions, people are paying more and more attention to related measures for energy conservation and emission reduction. As an important conveying component of the HVAC system, the pipe network system plays the function of distributing the fluid medium. However, a large part of the resistance loss is often generated during this transportation process, and the local pressure loss caused by local resistance components (e.g., T-junction) accounts for a large part of the total pressure drop. In this work, the influence of different guide vane positions on the resistance of the T-junction is analyzed. The internal flow field distribution and resistance characteristics of the T-junction are explored by numerical calculation method. The total energy dissipation and resistance reduction rate of the traditional T-junction and the novel T-junction with a guide vane are compared under different flow ratios. The resistance reduction rate of the optimized T-junction with a guide vane is 21.5%. The insertion of guide vanes can reduce the flow resistance and total energy loss of T-junction.

Differentiation between benign and malignant thyroid nodules has been a challenge in clinical practice. Exploring a novel biomarker to determine the malignancy of thyroid nodules has important implications. We semi-quantitatively determined the DNA methylation levels of four CpG sites located at the gene body of HYAL1 in formalin-fixed paraffin-embedded (FFPE) tissue samples from 190 early-stage papillary thyroid cancer (PTC) cases and 190 age- and gender-matched subjects with benign thyroid nodule (BTN). HYAL1 expression was evaluated by immunohistochemical (IHC) staining in another cohort of 55 PTC and 55 matched BTN cases. Covariates-adjusted odds ratios (ORs) for 10% increased methylation were calculated by binary logistic regression. A 165 bp amplicon covering four CpG sites at the second exon of HYAL1 gene was designed. After adjusted for all covariates, higher methylation level of HYAL1_CpG_3,4 in the FFPE tissue was associated with PTC (OR per 10% increased methylation=1.53, p=0.025), even with stage І PTC (OR per 10% increased methylation=1.58, p=0.021). Hypermethylation of HYAL1_CpG_3,4 had a significant association with early-stage PTC in the females (OR per 10% increased methylation=1.60, p=0.028) rather than in the males. Besides, we found the higher expression of HYAL1 protein in PTC than that in BTN patients (IHC score: 2.3 vs. 0.5, p=1.00E-06). Our study suggested altered methylation and expression of HYAL1 could be a novel and potential biomarker in distinguishing malignant and benign thyroid nodules. [ABSTRACT FROM AUTHOR]

To evaluate the association between maternal polymorphisms of NANOS3 rs2016163, HELQ rs4693089, PRIM1 rs2277339, TLK1 rs10183486, ERCC6 rs2228526, EXO1 rs1635501, DMC1 rs5757133, and MSH5 rs2075789 and fetal chromosomal abnormality. This retrospective case-control study included 571 women with fetal chromosome abnormalities (330 pregnant women diagnosed with fetal aneuploidy, 241 with fetal de novo structural chromosome pregnancy) and 811 healthy pregnant women between January 2018 and April 2022. All the above polymorphisms were tested using SNaPshot. All the eight polymorphisms were analyzed for genotypes, alleles, under dominant and recessive genetic models. Significant distribution differences of TLK1 rs10183486 in fetal chromosome structural abnormality were found between the case group and control subjects who were <35 years of age [Genotype: p=0.029; Dominant: OR (95 %CI)=0.46 (0.25–0.82), p=0.01 and allele: OR (95 %CI)=0.47 (0.27–0.82), p=0.01 respectively], while no difference was found in the recessive model [OR (95 %CI)=2.49 (0.31–20.40), p=0.39]. In advanced age subgroups for fetal aneuploidy, significant differences were found in genotypes analysis of PRIM1 rs2277339 (p=0.008), allele analysis of TLK1 rs10183486 [OR (95 %CI)=0.62 (0.42–0.91), p=0.02]. For the fetal chromosome structural abnormality population, HELQ rs4693089 revealed a significant distribution difference (p=0.01) but not in the allele, dominant and recessive genetic models analysis (p>0.05 individually). For older women, maternal PRIM1 rs2277339 and TLK1 rs10183486 polymorphisms may be associated with fetal aneuploidy, while HELQ rs4693089 may be associated with fetal chromosome structural abnormality. Also, carriers of T allele of TLK1 rs10183486 have a lower risk of fetal chromosome structural abnormality in younger women. [ABSTRACT FROM AUTHOR]

A single-slope greenhouse (SSG) is the general name of a kind of agricultural greenhouse facility widely used in China. Microclimate studies for SSGs in Weifang, Shandong Province, are relatively scarce. This paper mainly discusses the test data of nine SSGs including temperature, humidity, solar global radiation intensity, CO2 concentration, wind speed, and vapor pressure deficit (VPD) trend. Moreover, the conservation of quality method is used to estimate the ventilation volume and humidity growth after opening the top vent in the greenhouse. Through the analysis in this paper, for local SSGs, the internal environmental change has commonality but its internal environment is still influenced by many factors, such as plant planting density, internal cover, plant growth height, and vent opening time. In addition, the method in this paper can provide a quantitative tool for calculating and controlling humidity for researchers and greenhouse workers and provide a basis for greenhouse ventilation strategies. [ABSTRACT FROM AUTHOR]

Background: The advantages of prophylactic central lymph node dissection (CLND) for clinically node-negative patients remained a great deal of controversies. Our research was aimed to analyze the relationship between cervical central lymph node metastasis (CLNM) and BRAFV600E mutation, ultrasonic and clinicopathologic characterizes in papillary thyroid carcinoma (PTC).Methods and Materials: In current study, a total of 112 consecutive PTC patients who experienced thyroidectomy plus cervical central neck dissection were included in our research. All PTC were pre-operatively analyzed by ultrasonic features, including tumor size, multifocality or not, tumor location, internal components, echogenicity, microcalcification, margins, orientation, taller than wide shape, and internal vascularity. The presence of clinicopathologic factors, including age, sex, T stage, Hashimoto's thyroiditis, and BRAFV600E mutation was then investigated. Univariate and multivariate analysis were conducted to check into the relationship between predictive factors and cervical CLNM in PTC patients, and then a predictive model was also established.Results: Pathologically, 58.0% (65/112) of the PTC patients harbored cervical CLNM. Univariate and multivariate analysis were conducted to identify age < 55 years, tumor size > 10 mm, microcalcification, non-concomitant Hashimoto's thyroiditis and BRAFV600E mutation were predictive factors for cervical CLNM in PTC. The risk score for cervical CLNM in PTC patients was calculated: risk score = 1.284 × (if age < 55 years) + 1.241 × (if tumor size > 10 mm) + 1.143 × (if microcalcification) - 2.097 × (if concomitant Hashimoto's thyroiditis) + 1.628 × (if BRAFV600E mutation).Conclusion: Age < 55 years old, PTC > 10 mm, microcalcification, non-concomitant Hashimoto's thyroiditis and BRAFV600E mutation are predictive factors for cervical CLNM. BRAFV600E mutation by pre-operative US-FNA technology synergized with clinicopathologic and ultrasonic features is expected to guide the appropriate surgical management for PTC patients. [ABSTRACT FROM AUTHOR]

Intratumoral or intestinal microbiota correlates with tumorigenesis and progression, and microbiota regulation for reinforcing various anti‐tumor approaches is of significant importance, which, however, suffers from no precise regulation method and unclear underlying mechanism. Herein, a microbiome metabolism‐engineered phototherapy strategy is established, wherein Nb2C/Au nanocomposite and the corresponding phototherapy are harnessed to realize "chemical" and "physical" bacterial regulations. Flora analysis and mass spectrometry (MS) and metabonomics combined tests demonstrate that the synergistic microbiota regulations can alter the abundance, diversity of intratumoral microbiome, and disrupt metabolic pathways of microbiome and tumor microenvironment, wherein the differential singling pathways and biosynthetic necessities or metabolites that can affect tumor progression are identified. As well, anti‐TNFα is introduced to unite with bacterial regulation to synergistically mitigate bacterial‐induced inflammation, which, along with the metabolism disruptions of intratumoral microbiota and tumor microenvironment, unfreezes tumor resistance and harvests significantly‐intensified phototherapy‐based anti‐tumor outcomes against 4T1 and CT26 tumors. The clear underlying principles of microbiome‐regulated tumorigenesis and the established microbiome metabolism regulation method provide distinctive insights into tumor therapy, and can be also extended to other gut microbiome‐associated lesions interference. [ABSTRACT FROM AUTHOR]

The authors present an Ag‐GeTe‐based conductive bridge memory that allows radio frequency (RF) input and transmission. The RF input modifies the resistance switching characteristics and the memory device can switch the order of harmonics of the transmitted RF wave. The transmittance for the RF input above 500 MHz was higher than 0.5 for both the low‐resistance state (LRS) and the high‐resistance state (HRS). Below 500 MHz the transmittance decreased with decreasing frequency and depended on the resistance state (LRS or HRS). At 20 MHz, the transmission for the HRS was 0.02, while that for the LRS was 0.2. An RF input of 20 MHz at 10 dBm modified the SET voltage from 0.19 to 0.05 V, and the RESET voltage from −0.17 to −0.05 V. The RF wave transmitted through the LRS consisted almost entirely of fundamental waves, while that in the HRS provided harmonics or frequency multiplication up to the fifth order at 150 MHz at 10 dBm. Heat cycle measurements with RF input revealed the difference between the non‐linear resistance producing the frequency multiplication and the DC resistance. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is the fourth most lethal cancer. Effective treatments are lacking, and our knowledge of the pathogenic mechanisms in play is poor. Oridonin from the Chinese herb Rabdosia rubescens exerts various anticancer activities. However, the dose-dependent effects of oridonin on human GC remain unclear. Here, we found that oridonin inhibited GC cell growth in a time- and dose-dependent manner. Low-dose oridonin induced GC cell cycle arrest at G0/G1 and cell senescence by suppressing the c-Myc-AP4 pathway and enhancing p53-p21 signaling. AP4 overexpression partly abrogated the oridonin-induced senescence of GC cells. High-dose oridonin induced apoptosis and autophagy, with the autophagy inhibitor BafA1 attenuating oridonin-induced apoptosis. Together, the findings indicate that oridonin at different doses modulates GC cell senescence and apoptosis; oridonin may thus usefully treat GC. [ABSTRACT FROM AUTHOR]

Abstract Background Natural antisense transcripts (NATs) are endogenous RNA molecules that exhibit partial or complete complementarity to other RNAs, and that may contribute to the regulation of molecular functions at various levels. In recent years, large-scale NAT screens in several model organisms have produced much data, but there is no database to assemble all these data. AntiCODE intends to function as an integrated NAT database for this purpose. Results This release of antiCODE contains more than 30,000 non-redundant natural sense-antisense transcript pairs from 12 eukaryotic model organisms. In order to provide an integrated NAT research platform, efficient browser, search and Blast functions have been included to enable users to easily access information through parameters such as species, accession number, overlapping patterns, coding potential etc. In addition to the collected information, antiCODE also introduces a simple classification system to facilitate the study of natural antisense transcripts. Conclusion Though a few similar databases also dealing with NATs have appeared lately, antiCODE is the most comprehensive among these, comprising almost all currently detected NAT pairs.

Esophageal cancer micro environment factor WNT2 was critical in cancer metastasis. However, very little is known about WNT2 receptors and their role in the malignant progression of ESCC. The clinical significance and underlying molecular mechanisms of FZD2, one of the receptors of WNT2, was further investigated in ESCC. We found that FZD2 expression was positively correlated with WNT2 levels in clinical ESCC specimens through database analysis. Upregulated FZD2 expression was detected in 69% (69/100) of the primary ESCC cases examined, and increased FZD2 expression was significantly correlated with poor prognosis (P < 0.05). Mechanistically, FZD2 induced the migration and invasion of ESCC cells by regulating the FZD2/STAT3 signaling. In vivo xenograft experiments further revealed the metastasis-promoting role of FZD2 in ESCC. Moreover, we found that the WNT2 ligand could stabilize and phosphorylate the FZD2 receptor by attenuating FZD2 ubiquitination, leading to the activation of STAT3 signaling and the initiation of ESCC cell metastasis. Collectively, our data revealed that a novel non-canonical WNT2/FZD2/STAT3 signaling axis is critical for ESCC progression. Strategies targeting this specific signaling axis might be developed to treat patients with ESCC. [ABSTRACT FROM AUTHOR]

Localized tumor photothermal cancer ablation is a minimally invasive therapeutic modality for combating cancer, but it often suffers from low therapeutic efficacy and poor precision due to the poor accumulation and non-uniform distribution of used photothermal-conversion agents in tumor tissue via the typical intravenous administration. To address this, an injectable and phase-changeable composite bio-injection consisting of biocompatible two-dimensional (2D) niobium carbide (Nb2C) MXene and the plant-originating protein, zein, has been engineered for near infrared (NIR)-II-triggered tumor photothermal ablation. Zein can respond to aqueous microenvironments and also external photo-triggers from the NIR-II bio-window (1064 nm), and transforms into a solid bio-implant after solvent exchange between ethanol and water. Which, thus, traps Nb2C MXene and heat, improving ablation efficiency and enabling the precise and complete eradication of 4T1 breast tumor cells without additional safety concerns. More significantly, shear wave elastography (SWE) as a deep-penetration imaging mode that can reflect the ablated outcomes via monitoring tissue density variation, has been employed to guide the photo-thermal ablation process to further improve the ablation precision. Thus, this compatible and phase-changeable bio-injection capable of improving photo-thermal ablation efficiency holds great potential in clinical applications. [ABSTRACT FROM AUTHOR]

Intellectual disability (ID), one of the most common human developmental disorders, can be caused by genetic mutations in Cullin 4B (Cul4B) and cereblon (CRBN). CRBN is a substrate receptor for the Cul4A/B-DDB1 ubiquitin ligase (CRL4) and can target voltage- and calcium-activated BK channel for ER retention. Here we report that ID-associated CRL4CRBN mutations abolish the interaction of the BK channel with CRL4, and redirect the BK channel to the SCFFbxo7 ubiquitin ligase for proteasomal degradation. Glioma cell lines harbouring CRBN mutations record density-dependent decrease of BK currents, which can be restored by blocking Cullin ubiquitin ligase activity. Importantly, mice with neuron-specific deletion of DDB1 or CRBN express reduced BK protein levels in the brain, and exhibit similar impairment in learning and memory, a deficit that can be partially rescued by activating the BK channel. Our results reveal a competitive targeting of the BK channel by two ubiquitin ligases to achieve exquisite control of its stability, and support changes in neuronal excitability as a common pathogenic mechanism underlying CRL4CRBN–associated ID. [ABSTRACT FROM AUTHOR]

A dimeric Keggin-type phosphotungstate (ODA)10[(PW11FeO39)2O]·9H2O (abbreviated as ODA10[(PW11Fe)2], ODA = octadecyltrimethylammonium bromide) was synthesized and investigated comprehensively its antitumor activity on MCF-7 and A549 cells. The dimeric structure and amorphous morphology were characterized by FT-IR, UV-vis-DRS, SEM and XRD. The in vitro MTT assay of ODA10[(PW11Fe)2] showed anticancer activity on MCF-7 and A549 cells in a dose- and time-dependent manner, and the IC50 values for MCF-7 and A549 cells at 48 h were 5.83 μg/ml and 3.23 μg/ml, respectively. The images of the ODA10[(PW11Fe)2]-treated cells observed by inverted biological microscope exhibited the characteristic morphology of apoptosis. Flow cytometric analysis showed cell apoptosis and cycle arrested at S phase induced by ODA10[(PW11Fe)2]. The above results illuminated the main mechanism of the antitumor action of ODA10[(PW11Fe)2] on MCF-7 and A549 cells, indicating that this dimeric phosphotungstate is a promising anticancer drug. [ABSTRACT FROM AUTHOR]

This review provides a comprehensive analysis of available peer-reviewed literature in which graphene and/or its derivatives are incorporated into a polymer matrix in order to enhance the final properties and functionalities of the three dimensional (3D) printed structure. Research in which graphene derivatives have been incorporated into plastic 3D printing technologies such as Fused deposition modeling (FDM), Stereolithography (SLA), Selective laser sintering, Inkjet 3D printing, Extrusion-based printing and Binder-jet printing is presented. For certain design requirements and applicability of the material, great care needs to be taken to select the appropriate printing method. Factors which play a key role in final performance of the printed parts are identified, including dispersion of graphene or its derivatives in matrix, interfacial interaction between graphene or its derivatives and matrix, printing orientation, nanofiller's aspect ratio, reduction of graphene oxide and ink viscosity. In fact, the multifunctional applications of the 3D printed structures based on graphene or graphitic filler composites open up the countless possibilities of current research. Although great progress has been made in exploring the mechanical, electrical, optical and thermal, characteristics of these materials, significant research and development need to be done to fully fetch their inherent potential. This article serves the purpose to researchers to improve latest research outcomes and explore new graphene–based nanocomposites for different applications. [ABSTRACT FROM AUTHOR]