Summary The poor prognosis and rising incidence of esophageal cancer highlight the need for improved detection and prediction methods that are essential prior to treatment. Esophageal cancer is one ...of the most fatal malignancies worldwide, with a dramatic increase in incidence in the Western world occurring over the past few decades. Despite improvements in the management and treatment of esophageal cancer patients, the general outcome remains very poor for overall 5-year survival rates (∼10%) and 5-year postesophagectomy survival rates (∼15–40%). Esophageal cancer is often diagnosed during its advanced stages, the main reason being the lack of early clinical symptoms. In an attempt to improve the outcome of patients after surgery, such patients are often treated with neoadjuvent concurrent chemoradiotherapy (CCRT) in order to decrease tumor size. However, CCRT may enhance toxicity levels and possibly cause a delay in surgery for patients who respond poorly to CCRT. Thus, precise biomarkers that could predict or identify patients who may or may not respond well to CCRT can assist physicians in choosing the appropriate therapy for patients. Identifying susceptible gene and biomarkers can help in predicting the treatment response of patients while improving their survival rates.
Historically, there has been broad consensus that osseointegration represents a homeostasis between a titanium dental implant and the surrounding bone, and that the crestal bone loss characteristic ...of peri‐implantitis is a plaque‐induced inflammatory process. However, this notion has been challenged over the past decade by proponents of a theory that considers osseointegration an inflammatory process characterized by a foreign body reaction and peri‐implant bone loss as an exacerbation of this inflammatory response. A key difference in these two schools of thought is the perception of the relative importance of dental plaque in the pathogenesis of crestal bone loss around implants, with obvious implications for treatment. This review investigates the evidence for a persistent foreign body reaction at osseointegrated dental implants and its possible role in crestal bone loss characteristic of peri‐implantitis. Further, the role of implant‐related material release within the surrounding tissue, particularly titanium particles and corrosion by‐products, in the establishment and progression in peri‐implantitis is explored. While it is acknowledged that these issues require further investigation, the available evidence suggests that osseointegration is a state of homeostasis between the titanium implant and surrounding tissues, with little evidence that a persistent foreign body reaction is responsible for peri‐implant bone loss after osseointegration is established. Further, there is a lack of evidence for a unidirectional causative role of corrosion by‐products and titanium particles as possible non–plaque related factors in the etiology of peri‐implantitis.
Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer featured with high intra-tumoral heterogeneity and poor prognosis. To comprehensively delineate the PDAC ...intra-tumoral heterogeneity and the underlying mechanism for PDAC progression, we employed single-cell RNA-seq (scRNA-seq) to acquire the transcriptomic atlas of 57,530 individual pancreatic cells from primary PDAC tumors and control pancreases, and identified diverse malignant and stromal cell types, including two ductal subtypes with abnormal and malignant gene expression profiles respectively, in PDAC. We found that the heterogenous malignant subtype was composed of several subpopulations with differential proliferative and migratory potentials. Cell trajectory analysis revealed that components of multiple tumor-related pathways and transcription factors (TFs) were differentially expressed along PDAC progression. Furthermore, we found a subset of ductal cells with unique proliferative features were associated with an inactivation state in tumor-infiltrating T cells, providing novel markers for the prediction of antitumor immune response. Together, our findings provide a valuable resource for deciphering the intra-tumoral heterogeneity in PDAC and uncover a connection between tumor intrinsic transcriptional state and T cell activation, suggesting potential biomarkers for anticancer treatment such as targeted therapy and immunotherapy.
Manganese oxides of various structures (α-, β-, and δ-MnO2 and amorphous) were synthesized by facile methods. The electrocatalytic properties of these materials were systematically investigated for ...catalyzing both oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) in alkaline media. Extensive characterization was correlated with the activity study by investigating the crystal structures (XRD, HRTEM), morphologies (SEM), porosities (BET), surfaces (XPS, O2-TPD/MS), and electrochemical properties (Tafel analysis, Koutechy–Levich plots, and constant-current electrolysis). These combined results show that the electrocatalytic activities are strongly dependent on the crystallographic structures, and follow an order of α-MnO2 > AMO > β-MnO2 > δ-MnO2. Both OER studies and ORR studies reveal similar structure-determined activity trends in alkaline media. In the OER studies, α-MnO2 displays an overpotential of 490 mV compared to 380 mV shown by an Ir/C catalyst in reaching 10 mA cm–2. Meanwhile, α-MnO2 also exhibits stability for 3 h when supplying a constant current density of 5 mA cm–2. This was further improved by adding Ni2+ dopants (ca. 8 h). The superior OER activity was attributed to several factors, including abundant di-μ-oxo bridges existing in α-MnO2 as the protonation sites, analogous to the OEC in PS-II of the natural water oxidation system; the mixed valencies (AOS = 3.7); and the lowest charge transfer resistances (91.8 Ω, η = 430 mV) as revealed from in situ electrochemical impedance spectroscopy (EIS). In the ORR studies, when reaching 3 mA cm–2, α-MnO2 shows 760 mV close to 860 mV for the best ORR catalyst (20% Pt/C). The outstanding ORR activity was due to the strongest O2 adsorption capability of α-MnO2 suggested by temperature-programmed desorption. As a result, this discovery of the structure-related electrocatalytic activities could provide guidance in the further development of easily prepared, scalable, and low-cost catalysts based on metal oxides and their derivatives.
Metal-organic frameworks (MOFs) have recently garnered consideration as an attractive solid substrate because the highly tunable MOF framework can not only serve as an inert host but also enhance the ...selectivity, stability, and/or activity of the enzymes. Herein, we demonstrate the advantages of using a mechanochemical strategy to encapsulate enzymes into robust MOFs. A range of enzymes, namely β-glucosidase, invertase, β-galactosidase, and catalase, are encapsulated in ZIF-8, UiO-66-NH
, or Zn-MOF-74 via a ball milling process. The solid-state mechanochemical strategy is rapid and minimizes the use of organic solvents and strong acids during synthesis, allowing the encapsulation of enzymes into three prototypical robust MOFs while maintaining enzymatic biological activity. The activity of encapsulated enzyme is demonstrated and shows increased resistance to proteases, even under acidic conditions. This work represents a step toward the creation of a suite of biomolecule-in-MOF composites for application in a variety of industrial processes.
Abstract
The relationship between farm size and productivity has long been a topic of debate in development economics. Using farm-level panel data from 2003 to 2013, we investigate the relationship ...between maize yield and farm size in Northern China. After controlling for farm-specific characteristics, we restore a mild U-shaped relationship between maize yield and cropping area from the apparent inverse U-shaped curve. This suggests that an inverse farm size–productivity relationship persists for most small-sized farms. Further analyses demonstrate that farmer input choice between labor and capital is likely to smooth the non-linear farm size–productivity relationship, with capital use being more likely to affect the farm size–productivity relationship at a larger scale. The findings imply that subsidizing farmers to rent land without helping them become better-equipped could result in resource misallocation towards larger farms using less-efficient labor-intensive technologies.
Taiwan experienced two waves of imported infections with Coronavirus Disease 2019 (COVID-19). This study aimed at investigating the genomic variation of severe acute respiratory syndrome coronavirus ...2 (SARS-CoV-2) in Taiwan and compared their evolutionary trajectories with the global strains. We performed culture and full-genome sequencing of SARS-CoV-2 strains followed by phylogenetic analysis. A 382-nucleotides deletion in open reading frame 8 (ORF8) was found in a Taiwanese strain isolated from a patient on February 4, 2020 who had a travel history to Wuhan. Patients in the first wave also included several sporadic, local transmission cases. Genomes of 5 strains sequenced from clustered infections were classified into a new clade with ORF1ab-V378I mutation, in addition to 3 dominant clades ORF8-L84S, ORF3a-G251V and S-D614G. This highlighted clade also included some strains isolated from patients who had a travel history to Turkey and Iran. The second wave mostly resulted from patients who had a travel history to Europe and Americas. All Taiwanese viruses were classified into various clades. Genomic surveillance of SARS-CoV-2 in Taiwan revealed a new ORF8-deletion mutant and a virus clade that may be associated with infections in the Middle East, which contributed to a better understanding of the global SARS-CoV-2 transmission dynamics.
CELLO2GO (http://cello.life.nctu.edu.tw/cello2go/) is a publicly available, web-based system for screening various properties of a targeted protein and its subcellular localization. Herein, we ...describe how this platform is used to obtain a brief or detailed gene ontology (GO)-type categories, including subcellular localization(s), for the queried proteins by combining the CELLO localization-predicting and BLAST homology-searching approaches. Given a query protein sequence, CELLO2GO uses BLAST to search for homologous sequences that are GO annotated in an in-house database derived from the UniProt KnowledgeBase database. At the same time, CELLO attempts predict at least one subcellular localization on the basis of the species in which the protein is found. When homologs for the query sequence have been identified, the number of terms found for each of their GO categories, i.e., cellular compartment, molecular function, and biological process, are summed and presented as pie charts representing possible functional annotations for the queried protein. Although the experimental subcellular localization of a protein may not be known, and thus not annotated, CELLO can confidentially suggest a subcellular localization. CELLO2GO should be a useful tool for research involving complex subcellular systems because it combines CELLO and BLAST into one platform and its output is easily manipulated such that the user-specific questions may be readily addressed.
Although 5-methylcytosine (m
C) is a widespread modification in RNAs, its regulation and biological role in pathological conditions (such as cancer) remain unknown. Here, we provide the ...single-nucleotide resolution landscape of messenger RNA m
C modifications in human urothelial carcinoma of the bladder (UCB). We identify numerous oncogene RNAs with hypermethylated m
C sites causally linked to their upregulation in UCBs and further demonstrate YBX1 as an m
C 'reader' recognizing m
C-modified mRNAs through the indole ring of W65 in its cold-shock domain. YBX1 maintains the stability of its target mRNA by recruiting ELAVL1. Moreover, NSUN2 and YBX1 are demonstrated to drive UCB pathogenesis by targeting the m
C methylation site in the HDGF 3' untranslated region. Clinically, a high coexpression of NUSN2, YBX1 and HDGF predicts the poorest survival. Our findings reveal an unprecedented mechanism of RNA m
C-regulated oncogene activation, providing a potential therapeutic strategy for UCB.
Inspired by nature's flexible and adaptable organisms, soft robotics are motorless robots made from highly compliant materials to work in confined environments and manipulate delicate objects. ...However, soft robots often suffer from early failure because of unexpected damage. At the same time, it is challenging to manufacture the geometrically complex structures of soft robots. This study introduces resins based on deep eutectic solvents (DES) to fabricate a pneumatically driven soft gripper using digital light processing (DLP). The resins consist of choline chloride (ChCl) as a hydrogen bond acceptor, glycerol (Gly), and acrylamide (AAm) as hydrogen bond donors. By utilizing the intense hydrogen bonding within DES, the resin can be rapidly cured by photopolymerization to form tough ionogels without chemical crosslinkers. The DES ionogels exhibit remarkable toughness and self‐healing performance compared to common hydrogels. Furthermore, the ionogels show not only efficient energy‐dissipating behavior but also achieve rapid self‐recovery. Finally, the DLP‐printed soft gripper from the DES‐based resin performs successful actuation and healing of macroscopic damages. This work presents a simple strategy to 3D print a soft robotic gripper with high toughness and self‐healing capability.
This work demonstrates a simple strategy for the additive manufacturing of tough and self‐healable soft robotic gripper. The resin based on deep eutectic solvents can be rapidly cured to form tough ionogels without chemical crosslinkers by harnessing its intense hydrogen bonding interactions. Furthermore, the ionogels show not only efficient energy‐dissipating behavior, but also rapid self‐recovery.
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