Construction and validation of classification models for predicting the response to concurrent chemo-radiotherapy of patients with esophageal squamous cell carcinoma based on multi-omics data.

BACKGROUND: Concurrent chemo-radiotherapy (CCRT) is the preferred non-surgical treatment for patients with locally advanced esophageal squamous cell carcinoma (ESCC). Unfortunately, some patients respond poorly, which leads to inappropriate or excessive treatment and affects patient survival. To accurately predict the response of ESCC patients to CCRT, we developed classification models based on the clinical, serum proteomic and radiomic data. METHODS: A total of 138 ESCC patients receiving CCRT were enrolled in this study and randomly split into a training cohort (n = 92) and a test cohort (n = 46). All patients were classified into either complete response (CR) or incomplete response (non-CR) groups according to RECIST1.1. Radiomic features were extracted by 3Dslicer. Serum proteomic data was obtained by Olink proximity extension assay. The logistic regression model with elastic-net penalty and the R-package "rms" v6.2-0 were applied to construct classification and nomogram models, respectively. The area under the receiver operating characteristic curves (AUC) was used to evaluate the predictive performance of the models. RESULTS: Seven classification models based on multi-omics data were constructed, of which Model-COR, which integrates five clinical, five serum proteomic, and seven radiomic features, achieved the best predictive performance on the test cohort (AUC = 0.8357, 95 % CI: 0.7158-0.9556). Meanwhile, patients predicted to be CR by Model-COR showed significantly longer overall survival than those predicted to be non-CR in both cohorts (Log-rank P = 0.0014 and 0.027, respectively). Furthermore, two nomogram models based on multi-omics data also performed well in predicting response to CCRT (AUC = 0.8398 and 0.8483, respectively). CONCLUSION: We developed and validated a multi-omics based classification model and two nomogram models for predicting the response of ESCC patients to CCRT, which achieved the best prediction performance by integrating clinical, serum Olink proteomic, and radiomic data. These models could be useful for personalized treatment decisions and more precise clinical radiotherapy and chemotherapy for ESCC patients.

Five previously undescribed citrinin derivatives from the endophytic fungus Penicillium citrinum GZWMJZ-836.

Penicillium citrinum GZWMJZ-836 is an endophytic fungus from Drynaria roosii Nakaike. Five previously undescribed citrinin derivatives (1-5) and six intermediates related to their biosynthesis (6-11) were obtained from the extract of this strain's solid fermentation using multiple column chromatography separations, including high-performance liquid chromatography. The structures of these compounds were determined through comprehensive spectroscopic analyses, primarily using NMR and HRESIMS data. The stereochemistry was mainly confirmed by ECD calculations, and the configurations of C-7' in compounds 4 and 5 were determined using 13C NMR calculations. Compounds 4-5 and 8 showed antibacterial activity against five strains, with minimum inhibitory concentration values ranging from 7.8 to 125 µM. Compounds 4 and 7 exhibited inhibitions against three plant pathogenic fungi, with IC50 values ranging from 66.6 to 152.1 µM. Additionally, a putative biosynthetic pathway for compounds 1-5 derived from citrinin was proposed.

Identifying the distinct roles of dual dopants in stabilizing the platinum-nickel nanowire catalyst for durable fuel cell.

Stabilizing active PtNi alloy catalyst toward oxygen reduction reaction is essential for fuel cell. Doping of specific metals is an empirical strategy, however, the atomistic insight into how dopant boosts the stability of PtNi catalyst still remains elusive. Here, with typical examples of Mo and Au dopants, we identify the distinct roles of Mo and Au in stabilizing PtNi nanowires catalysts. Specifically, due to the stronger interaction between atomic orbital for Ni-Mo and Pt-Au, the Mo dopant mainly suppresses the outward diffusion of Ni atoms while the Au dopant contributes to the stabilization of surface Pt overlayer. Inspired by this atomistic understanding, we rationally construct the PtNiMoAu nanowires by integrating the different functions of Mo and Au into one entity. Such catalyst assembled in fuel cell cathode thus presents both remarkable activity and durability, even surpassing the United States Department of Energy technical targets for 2025.

Covalently Functionalized MoS2 Initiated Gelation of Hydrogels for Flexible Strain Sensing.

Transition metal dichalcogenides (TMDs), with superior mechanical and electrical conductivity, are one of the most promising two-dimensional materials for creating a generation of intelligent and flexible electronic devices. However, due to the high van der Waals and electrostatic attraction, TMD nanomaterials tend to aggregate in dispersants to achieve a stable state, thus severely limiting their further applications. Surface chemical modification is a common strategy for improving the dispersity of TMD nanomaterials; however, there are still constraints such as limited functionalization methods, low grafting rate, and difficult practice application. Thus, it is challenging to develop innovative surface modification systems. Herein, we covalently modify an olefin molecule on surface-inert MoS2, and the modified MoS2 can be used as not only a catalyst for hydrogel polymerization, but also a cross-linker in the hydrogel network. Specifically, allyl is covalently grafted onto chemically exfoliated MoS2, and this modified MoS2 can be uniformly dispersed in polar solvents (such as acetone, N,N-dimethylformamide, and ethanol), remaining stable for more than 2 weeks. The allyl-modified MoS2 can catalyze the polymerization of polyacrylamide hydrogel and then integrate in the network, which increases the tensile strength of the composite hydrogel. The flexible sensor based on the composite hydrogel exhibits an ideal operating range of 600% and a quick response time of 150 ms. At the same time, the flexible device can also track the massive axial stretching movements of human joints, making it a reliable option for the next wave of wearable sensing technology.

A universal synthesis of ultrathin Pd-based nanorings for efficient ethanol electrooxidation.

Metallic nanorings (NRs) with open hollow structures are of particular interest in energy-related catalysis due to their unique features, which include the high utilization of active sites and facile accessibility for reactants. However, there is still a lack of general methods for synthesizing Pd-based multimetallic NRs with a high catalytic performance. Herein, we develop a template-directed strategy for the synthesis of ultrathin PdM (M = Bi, Sb, Pb, BiPb) NRs with a tunable size. Specifically, ultrathin Pd nanosheets (NSs) are used as a template to steer the deposition of M atoms and the interatomic diffusion between Pd and M, subsequently resulting in the hollow structured NRs. Taking the ethanol oxidation reaction (EOR) as a proof-of-concept application, the PdBi NRs deliver a substantially improved activity relative to the Pd NSs and commercial Pd/C catalysts, simultaneously showing outstanding stability and CO tolerance. Mechanistically, density functional theory (DFT) calculations disclose that the incorporation of Bi reduces the energy barrier of the rate-determining step in the EOR C2-path, which, together with the high ratio of exposed active sites, endows the PdBi NRs with an excellent EOR activity. We believe that our work can illuminate the general synthesis of multimetallic NRs and the rational design of advanced electrocatalysts.

Toxic metals in the regulation of epithelial-mesenchymal plasticity: demons or angels?

Epithelial cells can trans-differentiate into motile mesenchymal cells through a dynamic process known as epithelial-mesenchymal transition (EMT). EMT is crucial in embryonic development and wound healing but also contributes to human diseases such as organ fibrosis and cancer progression. Heavy metals are environmental pollutants that can affect human health in various ways, including causing cancers. The cytotoxicity and carcinogenicity of heavy metals are complex, and studies have demonstrated that some of these metals can affect the progress of EMT. Here, we focus on reviewing the roles of six environmentally common toxic metals concerning EMT: arsenic (AS), cadmium (Cd), cobalt (Co), chromium (Cr), nickel (Ni), and copper (Cu). Noteworthily, the effects of these elements on EMT may vary according to the form, dose, and exposure time; the dual role of heavy metals (e.g., AS, Cd, and Cu) on EMT is also observed, in which, sometimes they can promote while sometimes inhibit the EMT process. Given the vast number of toxicologically relevant metals that exist in nature, we believe a comprehensive understanding of their effects on EMT is required to dictate in what circumstances these metals act more likely as demons or angels.

Diagnostic efficacy of FibroScan for liver inflammation in patients with chronic hepatitis B: a single-center study with 1185 liver biopsies as controls.

BACKGROUND: Noninvasive diagnostic technologies that can dynamically monitor changes in liver inflammation are highly important for the management of chronic hepatitis B (CHB) patients and thus warrant further exploration. This study assessed the diagnostic efficacy of FibroScan for liver inflammation in CHB patients. METHODS: A total of 1185 patients were selected, and ultrasound-guided liver biopsy was performed within 1 month after the FibroScan test. The liver stiffness measurement (LSM), the reliability criteria (IQR/M) of LSM, the quality of liver biopsy (complete portal area, PA), and the liver inflammation grades were the main observation items of this study. With liver biopsy as the control, the diagnostic efficacy of FibroScan for liver inflammation in CHB patients was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: The grade of liver inflammation was positively correlated with the stage of fibrosis (rho = 0.829, P < 0.001). Different grades of inflammation will have significant rise in LSM values within the same fibrosis stage, and LSM values were positively correlated with liver inflammation grade and fibrosis stage, and the rho is 0.579 and 0.593 respectively (P < 0.001). Significant differences in the LSM of FibroScan were observed among different grades of liver inflammation (P < 0.0001). Liver biopsy (PA > 10) served as the control, and the cutoff point and the area under ROC curves (AUCs) of the LSMs for different inflammation grades were as follows: G2, 8.6 kPa, 0.775; G3 9.8 kPa, 0.818; and G4, 11.0 kPa; 0.832. With LSM cutoff values of 8.6 kPa, 9.8 kPa and 11.0 kPa, FibroScan showed certain diagnostic value for CHB patients with G2, G3 and G4 liver inflammation, especially those with G4 inflammation. CONCLUSIONS: The grade of liver inflammation was positively correlated with the stage of fibrosis, different grades of inflammation will have significant rise in LSM values within the same fibrosis stage. In addition to liver fibrosis, FibroScan could evaluate liver inflammation in CHB patients in a noninvasive manner.

The Impact of ZIP8 Disease-Associated Variants G38R, C113S, G204C, and S335T on Selenium and Cadmium Accumulations: The First Characterization.

The metal cation symporter ZIP8 (SLC39A8) is a transmembrane protein that imports the essential micronutrients iron, manganese, and zinc, as well as heavy toxic metal cadmium (Cd). It has been recently suggested that selenium (Se), another essential micronutrient that has long been known for its role in human health and cancer risk, may also be transported by the ZIP8 protein. Several mutations in the ZIP8 gene are associated with the aberrant ion homeostasis of cells and can lead to human diseases. However, the intricate relationships between ZIP8 mutations, cellular Se homeostasis, and human diseases (including cancers and illnesses associated with Cd exposure) have not been explored. To further verify if ZIP8 is involved in cellular Se transportation, we first knockout (KO) the endogenous expression of ZIP8 in the HeLa cells using the CRISPR/Cas9 system. The elimination of ZIP8 expression was examined by PCR, DNA sequencing, immunoblot, and immunofluorescence analyses. Inductively coupled plasma mass spectrometry indicated that reduced uptake of Se, along with other micronutrients and Cd, was observed in the ZIP8-KO cells. In contrast, when ZIP8 was overexpressed, increased Se uptake could be detected in the ZIP8-overexpressing cells. Additionally, we found that ZIP8 with disease-associated single-point mutations G38R, G204C, and S335T, but not C113S, showed reduced Se transport ability. We then evaluated the potential of Se on Cd cytotoxicity prevention and therapy of cancers. Results indicated that Se could suppress Cd-induced cytotoxicity via decreasing the intracellular Cd transported by ZIP8, and Se exhibited excellent anticancer activity against not all but only selected cancer cell lines, under restricted experimental conditions. Moreover, clinical-based bioinformatic analyses revealed that up-regulated ZIP8 gene expression was common across multiple cancer types, and selenoproteins that were significantly co-expressed with ZIP8 in these cancers had been identified. Taken together, this study concludes that ZIP8 is an important protein in modulating cellular Se levels and provides insights into the roles of ZIP8 and Se in disease prevention and therapy.

Epimutational effects of electronic cigarettes.

Electronic cigarettes (e-cigarettes), since they do not require tobacco combustion, have traditionally been considered less harmful than conventional cigarettes (c-cigarettes). In recent years, however, researchers have found many toxic compounds in the aerosols of e-cigarettes, and numerous studies have shown that e-cigarettes can adversely affect the human epigenome. In this review, we provide an update on recent findings regarding epigenetic outcomes of e-cigarette aerosols. Moreover, we discussed the effects of several typical e-cigarette ingredients (nicotine, tobacco-specific nitrosamines, volatile organic compounds, carbonyl compounds, and toxic metals) on DNA methylation, histone modifications, and noncoding RNA expression. These epigenetic effects could explain some of the diseases caused by e-cigarettes. It also reminds the public that like c-cigarettes, inhaling e-cigarette aerosols could also be accompanied with potential epigenotoxicity on the human body.

Ubiquitin carboxyl-terminal hydrolase isozyme L1/UCHL1 suppresses epithelial-mesenchymal transition and is under-expressed in cadmium-transformed human bronchial epithelial cells.

Cadmium (Cd), a highly toxic heavy metal, is widespreadly distributed in the environment. Chronic exposure to Cd is associated with the development of several diseases including cancers. Over the decade, many researches have been carried on various models to examine the acute effects of Cd; yet, limited knowledge is known about the long-term Cd exposure, especially in the human lung cells. Previously, we showed that chronic Cd-exposed human bronchial epithelial BEAS-2B cells exhibited transformed cell properties, such as anchorage-independent growth, augmented cell migration, and epithelial-mesenchymal transition (EMT). To study these Cd-transformed cells more comprehensively, here, we further characterized their subproteomes. Overall, a total of 63 differentially expressed proteins between Cd-transformed and passage-matched control cells among the five subcellular fractions (cytoplasmic, membrane, nuclear-soluble, chromatin-bound, and cytoskeletal) were identified by mass spectrometric analysis and database searching. Interestingly, we found that the thiol protease ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1) is one of the severely downregulated proteins in the Cd-transformed cells. Notably, the EMT phenotype of Cd-transformed cells can be suppressed by forced ectopic expression of UCHL1, suggesting UCHL1 as a crucial modulator in the maintenance of the proper differentiation status in lung epithelial cells. Since EMT is considered as a critical step during malignant cell transformation, finding novel cellular targets that can antagonize this transition may lead to more efficient strategies to inhibit cancer development. Our data report for the first time that UCHL1 may play a function in the suppression of EMT in Cd-transformed human lung epithelial cells, indicating that UCHL1 might be a new therapeutic target for chronic Cd-induced carcinogenesis. Graphical abstract.

A Fiber Supercapacitor with High Energy Density Based on Hollow Graphene/Conducting Polymer Fiber Electrode.

A hollow graphene/conducting polymer composite fiber is created with high mechanical and electronic properties and used to fabricate novel fiber-shaped supercapacitors that display high energy densities and long life stability. The fiber supercapacitors can be woven into flexible powering textiles that are particularly promising for portable and wearable electronic devices.

Superelastic supercapacitors with high performances during stretching.

A fiber-shaped supercapacitor that can be stretched over 400% is developed by using two aligned carbon nanotube/polyaniline composite sheets as electrodes. A high specific capacitance of approximately 79.4 F g(-1) is well maintained after stretching at a strain of 300% for 5000 cycles or 100.8 F g(-1) after bending for 5000 cycles at a current density of 1 A g(-1). In particular, the high specific capacitance is maintained by 95.8% at a stretching speed as high as 30 mm s(-1).

Electrochromic fiber-shaped supercapacitors.

An electrochromic fiber-shaped super-capacitor is developed by winding aligned carbon nanotube/polyaniline composite sheets on an elastic fiber. The fiber-shaped supercapacitors demonstrate rapid and reversible chromatic transitions under different working states, which can be directly observed by the naked eye. They are also stretchable and flexible, and are woven into textiles to display designed signals in addition to storing energy.

Elastic and wearable wire-shaped lithium-ion battery with high electrochemical performance.

A stretchable wire-shaped lithium-ion battery is produced from two aligned multi-walled carbon nanotube/lithium oxide composite yarns as the anode and cathode without extra current collectors and binders. The two composite yarns can be well paired to obtain a safe battery with superior electrochemical properties, such as energy densities of 27 Wh kg(-1) or 17.7 mWh cm(-3) and power densities of 880 W kg(-1) or 0.56 W cm(-3), which are an order of magnitude higher than the densities reported for lithium thin-film batteries. These wire-shaped batteries are flexible and light, and 97 % of their capacity was maintained after 1000 bending cycles. They are also very elastic as they are based on a modified spring structure, and 84 % of the capacity was maintained after stretching for 200 cycles at a strain of 100 %. Furthermore, these novel wire-shaped batteries have been woven into lightweight, flexible, and stretchable battery textiles, which reveals possible large-scale applications.

Smart, stretchable supercapacitors.

Smart supercapacitors are developed by depositing conducting polymers onto aligned carbon-nanotube sheets. These supercapacitors rapidly and reversibly demonstrate color changes in response to a variation in the level of stored energy and the chromatic transitions can be directly observed by the naked eye.

A twisted wire-shaped dual-function energy device for photoelectric conversion and electrochemical storage.

A wire-shaped energy device that can perform photoelectric conversion and electrochemical storage was developed through a simple but effective twisting process. The energy wire exhibited a high energy conversion efficiency of 6.58 % and specific capacitance of 85.03 µF cm(-1) or 2.13 mF cm(-2), and the two functions were alternately realized without sacrificing either performance.

Novel graphene/carbon nanotube composite fibers for efficient wire-shaped miniature energy devices.

Novel nanostructured composite fibers based on graphene and carbon nanotubes are developed with high tensile strength, electrical conductivity, and electrocatalytic activity. As two application demonstrations, these composite fibers are used to fabricate flexible, wire-shaped dye-sensitized solar cells and electrochemical supercapacitors, both with high performances, for example, a maximal energy conversion efficiency of 8.50% and a specific capacitance of ca. 31.50 F g(-1). These miniature wire-shaped devices are further shown to be promising for flexible and portable electronic facilities.

Twisted aligned carbon nanotube/silicon composite fiber anode for flexible wire-shaped lithium-ion battery.

Twisted, aligned carbon nanotube/silicon composite fibers with remarkable mechanical and electronic properties are designed to develop novel flexible lithium-ion batteries with a high cyclic stability. The core-sheath architecture and the aligned structure of the composite nanotube offer excellent combined properties.

Integrated polymer solar cell and electrochemical supercapacitor in a flexible and stable fiber format.

An all-solid-state, coaxial and self-powered "energy fiber" is demonstrated that simultaneously converts solar energy to electric energy and further stores it. The "energy fiber" is flexible and can be scaled up for the practical application by the well-developed textile technology, and may open a new avenue to future photoelectronics and electronics.