Efficient and Stable Inverted Perovskite Solar Modules Enabled by Solid-Liquid Two-Step Film Formation.

A considerable efficiency gap exists between large-area perovskite solar modules and small-area perovskite solar cells. The control of forming uniform and large-area film and perovskite crystallization is still the main obstacle restricting the efficiency of PSMs. In this work, we adopted a solid-liquid two-step film formation technique, which involved the evaporation of a lead iodide film and blade coating of an organic ammonium halide solution to prepare perovskite films. This method possesses the advantages of integrating vapor deposition and solution methods, which could apply to substrates with different roughness and avoid using toxic solvents to achieve a more uniform, large-area perovskite film. Furthermore, modification of the NiOx/perovskite buried interface and introduction of Urea additives were utilized to reduce interface recombination and regulate perovskite crystallization. As a result, a large-area perovskite film possessing larger grains, fewer pinholes, and reduced defects could be achieved. The inverted PSM with an active area of 61.56 cm2 (10 × 10 cm2 substrate) achieved a champion power conversion efficiency of 20.56% and significantly improved stability. This method suggests an innovative approach to resolving the uniformity issue associated with large-area film fabrication.

Smad2/3/4 complex could undergo liquid liquid phase separation and induce apoptosis through TAT in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) represents one of the most significant causes of mortality due to cancer-related deaths. It has been previously reported that the TGF-ß signaling pathway may be associated with tumor progression. However, the relationship between TGF-ß signaling pathway and HCC remains to be further elucidated. The objective of our research was to investigate the impact of TGF-ß signaling pathway on HCC progression as well as the potential regulatory mechanism involved. METHODS: We conducted a series of bioinformatics analyses to screen and filter the most relevant hub genes associated with HCC. E. coli was utilized to express recombinant protein, and the Ni-NTA column was employed for purification of the target protein. Liquid liquid phase separation (LLPS) of protein in vitro, and fluorescent recovery after photobleaching (FRAP) were utilized to verify whether the target proteins had the ability to drive force LLPS. Western blot and quantitative real-time polymerase chain reaction (qPCR) were utilized to assess gene expression levels. Transcription factor binding sites of DNA were identified by chromatin immunoprecipitation (CHIP) qPCR. Flow cytometry was employed to examine cell apoptosis. Knockdown of target genes was achieved through shRNA. Cell Counting Kit-8 (CCK-8), colony formation assays, and nude mice tumor transplantation were utilized to test cell proliferation ability in vitro and in vivo. RESULTS: We found that Smad2/3/4 complex could regulate tyrosine aminotransferase (TAT) expression, and this regulation could relate to LLPS. CHIP qPCR results showed that the key targeted DNA binding site of Smad2/3/4 complex in TAT promoter region is -1032 to -1182. In addition. CCK-8, colony formation, and nude mice tumor transplantation assays showed that Smad2/3/4 complex could repress cell proliferation through TAT. Flow cytometry assay results showed that Smad2/3/4 complex could increase the apoptosis of hepatoma cells. Western blot results showed that Smad2/3/4 complex would active caspase-9 through TAT, which uncovered the mechanism of Smad2/3/4 complex inducing hepatoma cell apoptosis. CONCLUSION: This study proved that Smad2/3/4 complex could undergo LLPS to active TAT transcription, then active caspase-9 to induce hepatoma cell apoptosis in inhibiting HCC progress. The research further elucidate the relationship between TGF-ß signaling pathway and HCC, which contributes to discover the mechanism of HCC development.

Not One, Not Two, But at Least Three: Activity Origin of Copper Single-Atom Catalysts toward CO2/CO Electroreduction to C2+ Products.

Copper (Cu) single-atom catalysts (SACs) exhibit great potential for generating multicarbon (C2+) products, but the intrinsic activity of single-atom Cu (Cu1) under realistic conditions remains controversial. Herein, we perform extensive calculations with explicit solvation to investigate the underlying mechanism of Cu SACs, disclosing the absence of C2+ activity in Cu1 sites regardless of the different substrates. The original Cu1 sites (first taking Cu1 stably anchored on carbon nitride as an example) cannot facilitate *CO hydrogenation and CO-CO coupling due to the lack of active sites nearby, and they are unstable under operation, causing leaching and aggregation to form small Cu clusters. The derived Cu clusters composed of at least three Cu atoms can efficiently promote CO-CO coupling, as revealed by kinetic analyses. We extend the modeling to other typical Cu SACs and reveal that all of the Cu1 sites are inactive, while the C2+ performance of the derived Cu-cluster catalysts is substrate-dependent. This study offers mechanistic insights into Cu SACs and provides practical guidance for their rational optimization.

MicroRNA-2285f regulates milk fat metabolism by targeting MAP2K2 in bovine mammary epithelial cells.

In this study, Holstein dairy cows raised in Ningxia were selected as the research object. Mammary epithelial cells (BMECs) were extracted from the milk of eight Holstein cows with significantly different milk fat expression rates and transcribed for sequencing. Bioinformatics analysis was used to analyse the correlation of fat milk percentage, and the critical miR-2285f regulating milk fat was screened out. The target gene binding sites were predicted, and 293T cells and mammary epithelial cells were used as miRNA and target gene models for functional verification in vitro. The tissue difference of miR-2285f Holstein cows was quantitatively analysed by transfecting miR-2285f mimic and inhibitor. Assay (dual luciferase reporter gene assay) and quantitative real-time PCR (quantitative real-time PCR, qRT-PCR), triglyceride (TAG) detection, oil red O detection of lipid droplets, Western Blot assay, Edu and Flow cytometry, The molecular regulatory effects of miR-2285f and target gene MAP2K2 on milk fat metabolism of Holstein dairy cows were studied. The wild-type vector and mutant vector of map2k2-3'utr were constructed, and double luciferase reporting experiments were conducted to verify that MAP2K2 was one of the target genes of miR-2285f. According to qRT-PCR and Western Blot analysis, miR-2285f mainly regulates the expression of MAP2K2 protein in BMECs at the translation level. Bta-miR-2285f can promote cell proliferation and slow cell apoptosis by regulating MAP2K2. Bta-miR-2285f can promote triglyceride (TAG) and lipid droplet accumulation in mammary epithelial cells by targeting MAP2K2. Bta-miR-2285f can regulate protein levels of fat milk marker gene PPARG by targeting MAP2K2. In conclusion, miR-2285f can target the expression of the MAP2K2 gene, promote the proliferation of dairy mammary epithelial cells, inhibit cell apoptosis and regulate the milk fat metabolism in dairy mammary epithelial cells. The results of this study revealed the function of miR-2285f in regulating the differential expression of fat milk in Holstein dairy cows at the cellular level. They provided a theoretical and experimental basis for analysing the regulation network of milk fat synthesis of Holstein dairy cows and the molecular breeding of dairy cows.

Discovery and mechanistic study of Imperatorin that inhibits HBsAg expression and cccDNA transcription.

Chronic hepatitis B virus (HBV) infection remains a significant global health challenge due to its link to severe conditions like HBV-related cirrhosis and hepatocellular carcinoma (HCC). Although current treatments effectively reduce viral levels, they have limited impact on certain HBV elements, namely hepatitis B surface antigen (HBsAg) and covalently closed circular DNA (cccDNA). This highlights the urgent need for innovative pharmaceutical and biological interventions that can disrupt HBsAg production originating from cccDNA. In this study, we identified a natural furanocoumarin compound, Imperatorin, which markedly inhibited the expression of HBsAg from cccDNA, by screening a library of natural compounds derived from Chinese herbal medicines using ELISA assay and qRT-PCR. The pharmacodynamics study of Imperatorin was explored on HBV infected HepG2-NTCP/PHHs and HBV-infected humanized mouse model. Proteome analysis was performed on HBV infected HepG2-NTCP cells following Imperatorin treatment. Molecular docking and bio-layer interferometry (BLI) were used for finding the target of Imperatorin. Our findings demonstrated Imperatorin remarkably reduced the level of HBsAg, HBV RNAs, HBV DNA and transcriptional activity of cccDNA both in vitro and in vivo. Additionally, Imperatorin effectively restrained the actions of HBV promoters responsible for cccDNA transcription. Mechanistic study revealed that Imperatorin directly binds to ERK and subsequently interfering with the activation of CAMP response element-binding protein (CREB), a crucial transcriptional factor for HBV and has been demonstrated to bind to the PreS2/S and X promoter regions of HBV. Importantly, the absence of ERK could nullify the antiviral impact triggered by Imperatorin. Collectively, the natural compound Imperatorin may be an effective candidate agent for inhibiting HBsAg production and cccDNA transcription by impeding the activities of HBV promoters through ERK-CREB axis.

Missense mutation of ISL1 (E283D) is associated with the development of type 2 diabetes.

AIMS/HYPOTHESIS: Mutations in Isl1, encoding the insulin enhancer-binding protein islet-1 (ISL1), may contribute to attenuated insulin secretion in type 2 diabetes mellitus. We made an Isl1E283D mouse model to investigate the disease-causing mechanism of diabetes mellitus. METHODS: The ISL1E283D mutation (c. 849A>T) was identified by whole exome sequencing on an early-onset type 2 diabetes family and then the Isl1E283D knockin (KI) mouse model was created and an IPGTT and IPITT were conducted. Glucose-stimulated insulin secretion (GSIS), expression of Ins2 and other ISL1 target genes and interacting proteins were evaluated in isolated pancreas islets. Transcriptional activity of Isl1E283D was evaluated by cell-based luciferase reporter assay and electrophoretic mobility shift assay, and the expression levels of Ins2 driven by Isl1 wild-type (Isl1WT) and Isl1E283D mutation in rat INS-1 cells were determined by RT-PCR and western blotting. RESULTS: Impaired GSIS and elevated glucose level were observed in Isl1E283D KI mice while expression of Ins2 and other ISL1 target genes Mafa, Pdx1, Slc2a2 and the interacting protein NeuroD1 were downregulated in isolated islets. Transcriptional activity of the Isl1E283D mutation for Ins2 was reduced by 59.3%, and resulted in a marked downregulation of Ins2 expression when it was overexpressed in INS-1 cells, while overexpression of Isl1WT led to an upregulation of Ins2 expression. CONCLUSIONS/INTERPRETATION: Isl1E283D mutation reduces insulin expression and secretion by regulating insulin and other target genes, as well as its interacting proteins such as NeuroD1, leading to the development of glucose intolerance in the KI mice, which recapitulated the human diabetic phenotype. This study identified and highlighted the Isl1E283D mutation as a novel causative factor for type 2 diabetes, and suggested that targeting transcription factor ISL1 could offer an innovative avenue for the precise treatment of human type 2 diabetes.

Prediction of Microvascular Invasion and Recurrence After Curative Resection of LI-RADS Category 5 Hepatocellular Carcinoma on Gd-BOPTA Enhanced MRI.

Objective: This study aims to investigate the predictive value of Gadobenate dimeglumine (Gd-BOPTA) enhanced MRI features on microvascular invasion (MVI) and recurrence in patients with Liver Imaging Reporting and Data System (LI-RADS) category 5 hepatocellular carcinoma (HCC). Methods: A total of 132 patients with LI-RADS category 5 HCC who underwent curative resection and Gd-BOPTA enhanced MRI at our hospital between January 2016 and December 2018 were retrospectively analyzed. Qualitative evaluation based on LI-RADS v2018 imaging features was performed. Logistic regression analyses were conducted to assess the predictive significance of these features for MVI, and the Cox proportional hazards model was used to identify postoperative risk factors of recurrence. The recurrence-free survival (RFS) was analyzed by using the Kaplan-Meier curve and Log rank test. Results: Multivariate logistic regression analysis identified that corona enhancement (odds ratio [OR] = 3.217; p < 0.001), internal arteries (OR = 4.147; p = 0.004), and peritumoral hypointensity on hepatobiliary phase (HBP) (OR = 5.165; p < 0.001) were significantly associated with MVI. Among the 132 patients with LR-5 HCC, 62 patients experienced postoperative recurrence. Multivariate Cox regression analysis showed that mosaic architecture (hazard ratio [HR] = 1.982; p = 0.014), corona enhancement (HR = 1.783; p = 0.039), and peritumoral hypointensity on HBP (HR = 2.130; p = 0.009) were risk factors for poor RFS. Conclusion: MRI features based on Gd-BOPTA can be noninvasively and effectively predict MVI and recurrence of LR-5 HCC patients.

Increased cell-free DNA is associated with oxidative damage in patients with schizophrenia.

Cell-free DNA (cfDNA) has been found to be elevated in patients with schizophrenia (SZ), potentially derived from activated apoptosis, but the underlying mechanisms remain unknown. Moreover, whether the concentrations of cfDNA are altered with disease stage has not been investigated, which limits its clinical application as an auxiliary diagnostic marker for SZ. Using an improved fluorescence correlation spectroscopy (FCS) method that does not require DNA extraction, we measured the molar concentrations of cfDNA in plasma samples of 191 patients with SZ, 78 patients with mood disorders (MD) and 65 healthy controls (HC). We also analyzed the cfDNA composition from either the nucleus or mitochondria, oxidation markers and biochemical indexes to explore the potential mechanistic associations of the increased cfDNA levels. We found that in SZ patients, the cfDNA levels were significantly increased (P = 0.003) regardless of the different disease stages or antipsychotic medication use. Furthermore, qPCR revealed that cell-free nuclear DNA (cf-nDNA) (P = 0.041) but not cell-free mitochondrial DNA (cf-mtDNA) was elevated in SZ patients. Moreover, decreased SOD activity in SZ patients (P = 0.005) was negatively correlated with cfDNA levels (P = 0.047), and fasting blood glucose was positively correlated with cfDNA levels in SZ patients (P = 0.013). Our study provides evidence to support that the elevated cfDNA may be a convenient, effective and stable trait indicator of SZ. Further analysis showed that it mainly came from nucleus, suggesting increased apoptosis, and potentially related to oxidative stress and high blood glucose levels in patients.

Research progress in the development of 3D skin models and their application to in vitro skin irritation testing.

Toxicological assessment of chemicals is crucial for safeguarding human health and the environment. However, traditional animal experiments are associated with ethical, technical, and predictive limitations in assessing the toxicity of chemicals to the skin. With the recent development of bioengineering and tissue engineering, three-dimensional (3D) skin models have been commonly used as an alternative for toxicological studies. The skin consists of the subcutaneous, dermis, and epidermis. All these layers have crucial functions such as physical and biological protection and thermoregulation. The epidermis is the shallowest layer protecting against external substances and media. Because the skin is the first contact point for many substances, this organ is very significant for assessing local toxicity following skin exposure. According to the classification of the United Nations Global Harmonized System, skin irritation is a major potentially hazardous characteristic of chemicals, and this characteristic must be accurately assessed and classified for enhancing chemical safety management and preventing and reducing chemical accidents. This review discusses the research progress of 3D skin models and introduces their application in assessing chemical skin irritation.

Detection of Cadmium in Human Biospecimens by a Cadmium-Selective Whole-Cell Biosensor Based on Deoxyviolacein.

Cadmium poses a severe health risk, impacting various bodily systems. Monitoring human exposure is vital. Urine and blood cadmium serve as critical biomarkers. However, current urine and blood cadmium detection methods are expensive and complex. Being cost-effective, user-friendly, and efficient, visual biosensing offers a promising complement to existing techniques. Therefore, we constructed a cadmium whole-cell biosensor using CadR10 and deoxyviolacein pigment in this study. We assessed the sensor for time-dose response, specific response to cadmium, sensitivity response to cadmium, and stability response to cadmium. The results showed that (1) the sensor had a preferred signal-to-noise ratio when the incubation time was 4 h; (2) the sensor showed excellent specificity for cadmium compared to the group 12 metals and lead; (3) the sensor was responsive to cadmium down to 1.53 nM under experimental conditions and had good linearity over a wide range from 1.53 nM to 100 µM with good linearity (R2 = 0.979); and (4) the sensor had good stability. Based on the excellent results of the performance tests, we developed a cost-effective, high-throughput method for detecting urinary and blood cadmium. Specifically, this was realized by adding the blood or urine samples into the culture system in a particular proportion. Then, the whole-cell biosensor was subjected to culture, n-butanol extraction, and microplate reading. The results showed that (1) at 20% urine addition ratio, the sensor had an excellent curvilinear relationship (R2 = 0.986) in the range of 3.05 nM to 100 µM, and the detection limit could reach 3.05 nM. (2) At a 10% blood addition ratio, the sensor had an excellent nonlinear relationship (R2 = 0.978) in the range of 0.097-50 µM, and the detection limit reached 0.195 µM. Overall, we developed a sensitive and wide-range method based on a whole-cell biosensor for the detection of cadmium in blood and urine, which has the advantages of being cost-effective, ease of operation, fast response, and low dependence on instrumentation and has the potential to be applied in the monitoring of cadmium exposure in humans as a complementary to the mainstream detection techniques.

Microstructure and Perfusion Alterations of Globus Pallidus in Neonates with Hyperbilirubinemia.

BACKGROUND: Previous studies have indicated the abnormality of the globus pallidus in neonates with hyperbilirubinemia. OBJECTIVE: This study aims to explore the microstructure and cerebral perfusion of globus pallidus in neonatal hyperbilirubinemia by using Diffusion Tensor Imaging (DTI) and Arterial Spin Labeling (ASL) approaches. METHODS: Thirty-seven neonates were enrolled in this study, which were classified into Bilirubin-Induced Neurologic Dysfunction (BIND) group (hyperbilirubinemia with BIND, n=12), non-BIND group (hyperbilirubinemia without BIND, n=15), and healthy controls (HC) group (n=10). The quantitative values of globus pallidus were calculated from DTI, including the Apparent Diffusion Coefficient (ADC), the Fractional Anisotropy (FA), and Volume Ratio (VR) values. Additionally, the relative Cerebral Blood Flow (rCBF) values were obtained from ASL. RESULTS: It was observed that the mean DTI signal of globus pallidus was significantly different among the three groups (p < 0.05). However, there were no significant differences in the rCBF of globus pallidus among the three groups (p > 0.05). A positive correlation was also observed between the fractional anisotropy (FA) value and serum bilirubin level (r = 0.561, p = 0.002), while the VR value showed a negative correlation with serum bilirubin level (r=-0.484, p=0.011). The area under the curve (AUC) of FA, VR, and FA and VR combined was 0.897, 0.858, and 0.933, respectively. CONCLUSION: The alterations of microstructure in globus pallidus, especially FA and VR value, may be valuable and sensitive at the early stage of hyperbilirubinemia encephalopathy, suggesting that early hyperbilirubinemia may lead to cytotoxic edema and decreased permeability of the cell membrane.

Ideal cardiovascular health index and high-normal blood pressure in elderly people: evidence based on real-world data.

Limited information is available on the cardiovascular health (CVH) index and risk of high-normal blood pressure (HNBP) in elderly people. Randomized cluster sampling, multivariate logistic regression, and mediating effects analysis were used in this study analyze the relationship between CVH index and HNBP in the elderly. 1089 non-hypertensive residents aged 65 years or older completed the study. The positive rate of HNBP was 75.85% (male vs. female: 76.13% vs. 75.64%, P = 0.852); The ideal rate of CVH (ideal CVH index ≥ 5 items) was 14.51% (male vs. female: 15.91% vs. 13.46%, P = 0.256). Compared with people with 0-2 ideal CVH index, the risk of HNBP in people with 4 ideal indexes and ≥ 5 ideal indexes decreased by 50% and 63%, respectively, and their OR (95% CI) were 0.50 (0.31, 0.81) and 0.37 (0.21, 0.66), respectively. The results of the trend test showed that the risk of HNBP decreased by 32% for every increase in the ideal CVH index (trend P < 0.001) and TyG index does not play a mediating role in this relationship. That is, increasing the number of ideal CVH index may effectively reduce the risk of HNBP in elderly by one-third.

Transcriptome analysis reveals the role of Long noncoding RNAs (lncRNA) in specific deposition of inosine monphosphate in Jingyuan chickens.

Inosine monphosphate (IMP) is one of the important indicators for evaluating meat flavor, and long noncoding RNAs (lncRNAs) play an important role in its transcription and post-transcriptional regulation. Currently, there is little information about how lncRNA regulates the specific deposition of IMP in chicken muscle. In this study, we used transcriptome sequencing to analyze the lncRNAs of the breast and leg muscles of the Jingyuan chicken and identified a total of 357 differentially expressed lncRNAs (DELs), of which 158 were up-regulated and 199 were down-regulated. There were 2,203 and 7,377 cis- and trans-regulated target genes of lncRNAs, respectively, and we identified the lncRNA target genes that are involved in NEGF signaling pathway, glycolysis/ glucoseogenesis and biosynthesis of amino acids pathways. Meanwhile, 621 pairs of lncRNA-miRNA-mRNA interaction networks were constructed with target genes involved in purine metabolism, fatty acid metabolism, and biosynthesis of amino acids. Next, three interacting meso-networks gga-miR-1603-LNC_000324-PGM1, gga-miR-1768-LNC_000324-PGM1 and gga-miR-21-LNC_011339- AMPD1 were identified as closely associated with IMP-specific deposition. Both differentially expressed genes (DEGs) PGM1 and AMPD1 were significantly enriched in IMP synthesis and metabolism-related pathways, and participated in the anabolic process of IMP in the form of organic matter synthesis and energy metabolism. This study obtained lncRNAs and target genes affecting IMP-specific deposition in Jingyuan chickens based on transcriptome analysis, which deepened our insight into the role for lncRNAs in chicken meat quality.

ESM1 enhances fatty acid synthesis and vascular mimicry in ovarian cancer by utilizing the PKM2-dependent warburg effect within the hypoxic tumor microenvironment.

BACKGROUND: The hypoxic tumor microenvironment is a key factor that promotes metabolic reprogramming and vascular mimicry (VM) in ovarian cancer (OC) patients. ESM1, a secreted protein, plays an important role in promoting proliferation and angiogenesis in OC. However, the role of ESM1 in metabolic reprogramming and VM in the hypoxic microenvironment in OC patients has not been determined. METHODS: Liquid chromatography coupled with tandem MS was used to analyze CAOV3 and OV90 cells. Interactions between ESM1, PKM2, UBA2, and SUMO1 were detected by GST pull-down, Co-IP, and molecular docking. The effects of the ESM1-PKM2 axis on cell glucose metabolism were analyzed based on an ECAR experiment. The biological effects of the signaling axis on OC cells were detected by tubule formation, transwell assay, RT‒PCR, Western blot, immunofluorescence, and in vivo xenograft tumor experiments. RESULTS: Our findings demonstrated that hypoxia induces the upregulation of ESM1 expression through the transcription of HIF-1α. ESM1 serves as a crucial mediator of the interaction between PKM2 and UBA2, facilitating the SUMOylation of PKM2 and the subsequent formation of PKM2 dimers. This process promotes the Warburg effect and facilitates the nuclear translocation of PKM2, ultimately leading to the phosphorylation of STAT3. These molecular events contribute to the promotion of ovarian cancer glycolysis and vasculogenic mimicry. Furthermore, our study revealed that Shikonin effectively inhibits the molecular interaction between ESM1 and PKM2, consequently preventing the formation of PKM2 dimers and thereby inhibiting ovarian cancer glycolysis, fatty acid synthesis and vasculogenic mimicry. CONCLUSION: Our findings demonstrated that hypoxia increases ESM1 expression through the transcriptional regulation of HIF-1α to induce dimerization via PKM2 SUMOylation, which promotes the OC Warburg effect and VM.

Investigation of ENO2 as a promising novel marker for the progression of colorectal cancer with microsatellite instability-high.

BACKGROUND: Microsatellite instability-high (MSI-H) has emerged as a significant biological characteristic of colorectal cancer (CRC). Studies reported that MSI-H CRC generally had a better prognosis than microsatellite stable (MSS)/microsatellite instability-low (MSI-L) CRC, but some MSI-H CRC patients exhibited distinctive molecular characteristics and experienced a less favorable prognosis. In this study, our objective was to explore the metabolic transcript-related subtypes of MSI-H CRC and identify a biomarker for predicting survival outcomes. METHODS: Single-cell RNA sequencing (scRNA-seq) data of MSI-H CRC patients were obtained from the Gene Expression Omnibus (GEO) database. By utilizing the copy number variation (CNV) score, a malignant cell subpopulation was identified at the single-cell level. The metabolic landscape of various cell types was examined using metabolic pathway gene sets. Subsequently, functional experiments were conducted to investigate the biological significance of the hub gene in MSI-H CRC. Finally, the predictive potential of the hub gene was assessed using a nomogram. RESULTS: This study revealed a malignant tumor cell subpopulation from the single-cell RNA sequencing (scRNA-seq) data. MSI-H CRC was clustered into two subtypes based on the expression profiles of metabolism-related genes, and ENO2 was identified as a hub gene. Functional experiments with ENO2 knockdown and overexpression demonstrated its role in promoting CRC cell migration, invasion, glycolysis, and epithelial-mesenchymal transition (EMT) in vitro. High expression of ENO2 in MSI-H CRC patients was associated with worse clinical outcomes, including increased tumor invasion depth (p = 0.007) and greater likelihood of perineural invasion (p = 0.015). Furthermore, the nomogram and calibration curves based on ENO2 showed potential prognosis predictive performance. CONCLUSION: Our findings suggest that ENO2 serves as a novel prognostic biomarker and is associated with the progression of MSI-H CRC.

Reconstruction of Scalp and Skull Defects by a Free Anterolateral Thigh Flap Combined With Fascia Lata and Vastus Lateralis Muscle.

BACKGROUND: Reconstruction of composite scalp and skull defects is a great challenge for plastic surgeons, and this study aimed to report the therapeutic regimen of using free ALT flaps with fascia lata and vastus lateralis muscle to cover scalp and cranial defects. METHODS: A retrospective analysis was performed including 10 patients with composite scalp and skull defects who were treated with a free ALT flap with fascia lata and vastus lateralis muscle from January 2012 to June 2020. All patients underwent a 1-stage operation and were followed up for 1 year with clinical data including sex, age, etiology, skull defect area, scalp defect area, flap area, dura mater involvement, recipient vessel, donor site repair, lumbar cistern drainage, and complications. RESULTS: All flaps survived well, 2 patients developed complications, one had cerebrospinal fluid leakage, and another experienced partial skin graft necrosis; All patients were satisfied with both the appearance and functional outcomes of the procedure. CONCLUSION: Free tissue transplantation is an effective method for large defects of the scalp and skull. The combination of a free ALT flap with fascia lata and vastus lateralis muscle, which has a long pedicle, convenient flap designs, less donor-site morbidity, and effective prevention of cerebrospinal fluid leakage, is an ideal choice to repair the composite scalp and cranial defects in stage 1.

A multifunctional antibody fusion protein 57103 targeting CD24, IL-4R, and αvß3 for treating cancer and regulating the tumor microenvironment.

Cancer is one of the top 10 fatal diseases worldwide, among which advanced metastatic carcinoma has the highest mortality rate. Sunitinib and immune checkpoint blockers are commonly used to treat metastatic renal carcinoma with limited efficacy. Therefore, there is an urgent need to develop novel targeted therapies for metastatic renal cancer. In this study, we designed an antibody fusion protein, 57103, that simultaneously targeted the cluster of differentiation 24 (CD24), interleukin 4 receptor (IL-4R), and integrin receptors αvß3 and α5ß1. In vitro assays showed that 57103 significantly suppressed the proliferation, migration, invasion, colony formation, and adhesion abilities of renal cancer cells, resulting in a comprehensive and significant antitumor effect. Furthermore, 57103 inhibited angiogenesis, promoted THP1-derived M0-type macrophage phagocytosis, and enhanced the antibody-dependent cellular cytotoxicity of peripheral blood mononuclear and NK92MI-CD16a cells. In vivo experiments revealed significant inhibition of tumor growth in ACHN cell xenograft nude mice and an MC38-hCD24 tumor-bearing mouse model. Immunohistochemical analysis showed that 57103 decreased the proliferation and induced the apoptosis of renal cancer cells, while inhibiting angiogenesis. The MC38-hPDL1 and MC38-hCD24-hPDL1 tumor-bearing mouse models further offer the possibility of combining 57103 with the PDL1 antagonist atezolizumab. In conclusion, 57103 is a potential candidate drug for the treatment of metastatic renal carcinoma or PDL1-overexpressing cancer.

Polyacrylamide/sodium alginate/sodium chloride photochromic hydrogel with high conductivity, anti-freezing property and fast response for information storage and electronic skin.

Photochromic hydrogels have promising prospects in areas such as wearable device, information encryption technology, optoelectronic display technology, and electronic skin. However, there are strict requirements for the properties of photochromic hydrogels in practical engineering applications, especially in some extreme application environments. The preparation of photochromic hydrogels with high transparency, high toughness, fast response, colour reversibility, excellent electrical conductivity, and anti-freezing property remains a challenge. In this study, a novel photochromic hydrogel (PAAm/SA/NaCl-Mo7) was prepared by loading ammonium molybdate (Mo7) and sodium chloride (NaCl) into a dual-network hydrogel of polyacrylamide (PAAm) and sodium alginate (SA) using a simple one-pot method. PAAm/SA/NaCl-Mo7 hydrogel has excellent conductivity (175.9 S/cm), water retention capacity and anti-freezing properties, which can work normally at a low temperature of -28.4 °C. In addition, the prepared PAAm/SA/NaCl-Mo7 hydrogel exhibits fast response (<15 s), high transparency (>70 %), good toughness (maximum elongation up to 1500 %), good cyclic compression properties at high compressive strains (60 %), good biocompatibility (78.5 %), stable reversible discolouration and excellent sensing properties, which can be used for photoelectric display, information storage and motion monitoring. This work provides a new inspiration for the development of flexible electronic skin devices.

Fluorescence visualization of CO2-responsive phase transfer materials targeting at the heterogeneous interfacial reactions in advanced oxidation of naphthenic acid in wastewater.

Treatment of naphthenic acids (NAs) in wastewater is necessary due to its high toxicity and difficult degradation. In the heterogeneous Fenton-like advanced oxidation of organic pollutant system, the insufficient accessibility of oxidizing agent and NAs greatly hamper the reaction efficiency. CO2-responsive phase transfer materials derived from polyethylene glycol (PEG)-based deep eutectic solvents were specific targeted at the immiscible-binary phase system. The NAs oxidative degradation process was optimized including the kinds of catalyst (Molecular weight of PEG, constitute of DESs, and dosage.), temperature, flow rate of CO2, et al. With the help of fluorescence properties of catalyst, the hydrophilic-hydrophobic interaction was visual-monitored and further studied. The amphipathic property of PEG-200/Sodium persulfate/Polyether amine 230 (PEA230) greatly reduced the aqueous/organic phase transfer barrier between sodium persulfate and NAs (up to 84 %), thus accreting oxidation rate. The surface tension decreased from 35.364 mN/m to 28.595 mN/m. To control the reaction rate, the CO2 respond structure of amido played an important role. In addition, the interfacial transfer intermediates and oxidation pathways were also explored by nuclear magnetic resonance, flourier transform infrared spectroscopy, surface tension, and radical inhibition experiments. The mechanism of advanced oxidation of NAs catalyzed by CO2-responsive phase transfer catalyst was proposed, which would made up for the deficiency of the system theory of heterogeneous chemical oxidation of organic pollutants.

Serum Uric Acid Combined with Homocysteine as a Predictive Biomarker of Lupus Nephritis.

Serum uric acid (UA) and homocysteine (Hcy) are potential biomarkers of systemic lupus erythematosus (SLE). In this study, the expressions of UA and Hcy in SLE patients and the predictive value of these two parameters for lupus nephritis (LN) were studied. A total of 476 SLE patients were recruited to this case-control study, of which 176 SLE patients diagnosed with LN and 300 without LN. Serum UA and Hcy levels were analyzed. Multivariate logistic regression analysis was used to evaluate the relationship between serum UA and Hcy and LN. The receiver operating characteristic (ROC) curves were used to predict the role of combination of serum UA and Hcy in LN. We found that serum UA and Hcy levels in SLE patients with LN were significantly higher than those in controls (p<0.05). Multivariate logistic regressions showed that serum UA (OR+=+1.003, 95+% CI: 1.001-1.006, p+=+0.003), apolipoprotein B (Apo B) (OR+=+21.361, 95+% CI: 2.312-195.373, p+=+0.007) and Hcy (OR+=+1.042, 95+% CI: 1.011-1.080, p+=+0.014) were independent markers of LN. Combined serum UA and Hcy revealed a better result (AUC+=+0.718, 95+% CI: 0.670-0.676, p<0.001) in prediction of LN compared to that of the serum UA (AUC+=+0.710) and Hcy (AUC+=+0.657) independently. In conclusion, serum UA and Hcy could be predictive biomarkers of LN, and joint detection of serum UA and Hcy might be useful in the clinical setting.