Microbiota is just beginning to be recognized as an important player in carcinogenesis and the interplay among microbes is greater than expected. Pancreatic ductal adenocarcinoma (PDAC) is a highly ...lethal disease for which mortality closely parallels incidence. Early detection would provide the best opportunity to increase survival rates. Specific well-studied oral, gastrointestinal, and intrapancreatic microbes and some kinds of hepatotropic viruses and bactibilia may have potential etiological roles in pancreatic carcinogenesis, or modulating individual responses to oncotherapy. Concrete mechanisms mainly involve perpetuating inflammation, regulating the immune system-microbe-tumor axis, affecting metabolism, and altering the tumor microenvironment. The revolutionary technology of omics has generated insight into cancer microbiomes. A better understanding of the microbiota in PDAC might lead to the establishment of screening or early-stage diagnosis methods, implementation of cancer bacteriotherapy, adjustment of therapeutic efficacy even alleviating the adverse effects, creating new opportunities and fostering hope for desperate PDAC patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Soft electronics that seamlessly interface with skin are of great interest in health monitoring and human–machine interfaces. However, achieving mechanical softness, skin adhesiveness, and high ...conductivity concurrently has always been a major challenge due to the difficulty in bonding dissimilar materials while retaining their respective properties. Herein, the mechanically interlocked hydrogel–elastomer hybrid is reported as a viable solution to this problem. Hydrogels with low moduli and high adhesiveness are employed as the substrate, while porous elastomer webs are used as matrices to load conductive films and lock the hydrogels through a mechanically interlocked structure. The bonding strength between the hydrogel and elastomer in the interlocking hybrid structure is 14.3 times of that obtained via the physical stacking method. As a proof of concept, interlocking hybrids are used as on‐skin electrodes for electrophysiological signal recording including electromyography and electrocardiography. The robust hybrid electrodes are able to detect signals after multiple cycles. The proposed strategy not only is an effective approach to achieve interlocking structures, but also provides a new perspective for soft and stretchable electronics.
A novel hydrogel–elastomer hybrid is developed by mechanical interlocking. Porous elastomer webs are used as matrices to load conductive materials and lock hydrogels through an interlocking structure to achieve mechanically soft and skin‐adhesive electrodes. The interlocking hybrid is used as an on‐skin electrode for recording electrophysiological signals.
Fiber‐shaped stretchable strain sensors with small testing areas can be directly woven into textiles. This paves the way for the design of integrated wearable devices capable of obtaining real‐time ...mechanical feedback for various applications. However, for a simple fiber that undergoes uniform strain distribution during deformation, it is still a big challenge to obtain high sensitivity. Herein, a new strategy, surface strain redistribution, is reported to significantly enhance the sensitivity of fiber‐shaped stretchable strain sensors. A new method of transient thermal curing is used to achieve the large‐scale fabrication of modified elastic microfibers with intrinsic microbeads. The proposed strategy is independent of the active materials utilized and can be universally applied for various active materials. The strategy used here will shift the vision of the sensitivity enhancement method from the active materials design to the mechanical design of the elastic substrate, and the proposed strategy can also be applied to nonfiber‐shaped stretchable strain sensors.
Surface strain redistribution in substrates significantly enhances sensitivity of fiber‐shaped stretchable strain sensors fabricated by thermal‐transient‐curing and Plateau–Rayleigh instability. Poly(dimethylsiloxane) (PDMS) microfibers with beads are produced in large scale. The beads regulate strain distribution. Novel sensors are well adhered to textiles for monitoring sports activities. This study opens up a new perspective of fiber‐shaped sensors and a method to enhance sensitivity.
Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive type of GI tumour, and it possesses deregulated cellular energetics. Although recent advances in PDAC biology have led to the discovery ...of recurrent genetic mutations in
,
and
, which are related to this disease, clinical application of the molecular phenotype of PDAC remains challenging.
We combined molecular imaging technology (positron emission tomography/CT) and immunohistochemistry to evaluate the correlation between the maximum standardised uptake value and SMAD4 expression and examined the effect of SMAD4 on glycolysis through in vitro and in vivo experiments. Furthermore, we identified the effect of SMAD4 on metabolic reprogramming by metabolomics and glucose metabolism gene expression analyses. Dual luciferase reporter assays and chromatin immunoprecipitation were performed to identify whether SMAD4 functioned as a transcription factor for phosphoglycerate kinase 1 (PGK1) in PDAC cells. Proliferative and metastatic assays were performed to examine the effect of PGK1 on the malignant behaviour of PDAC.
We provide compelling evidence that the glycolytic enzyme PGK1 is repressed by transforming growth factor-β/SMAD4. Loss of SMAD4 induces PGK1 upregulation in PDAC, which enhances glycolysis and aggressive tumour behaviour. Notably, in SMAD4-negative PDAC, nuclear PGK1 preferentially drives cell metastasis via mitochondrial oxidative phosphorylation induction, whereas cytoplasmic PGK1 preferentially supports proliferation by functioning as a glycolytic enzyme. The PDAC progression pattern and distinct PGK1 localisation combine to predict overall survival and disease-free survival.
PGK1 is a decisive oncogene in patients with SMAD4-negative PDAC and can be a target for the development of a therapeutic strategy for SMAD4-negative PDAC.
Flexible electronic devices are necessary for applications involving unconventional interfaces, such as soft and curved biological systems, in which traditional silicon‐based electronics would ...confront a mechanical mismatch. Biological polymers offer new opportunities for flexible electronic devices by virtue of their biocompatibility, environmental benignity, and sustainability, as well as low cost. As an intriguing and abundant biomaterial, silk offers exquisite mechanical, optical, and electrical properties that are advantageous toward the development of next‐generation biocompatible electronic devices. The utilization of silk fibroin is emphasized as both passive and active components in flexible electronic devices. The employment of biocompatible and biosustainable silk materials revolutionizes state‐of‐the‐art electronic devices and systems that currently rely on conventional semiconductor technologies. Advances in silk‐based electronic devices would open new avenues for employing biomaterials in the design and integration of high‐performance biointegrated electronics for future applications in consumer electronics, computing technologies, and biomedical diagnosis, as well as human–machine interfaces.
Silk fibroin is an ancient biomaterial with exquisite mechanical, optical, and electrical properties. Its intriguing properties and environmental benignity render silk fibroin compelling for the advancement of next‐generation biocompatible and biodegradable flexible electronic devices.
Flexible electronics have witnessed exciting progress in academia over the past decade, but most of the research outcomes have yet to be translated into products or gain much market share. For mass ...production and commercialization, industrial adoption of newly developed functional materials and fabrication techniques is a prerequisite. However, due to the disparate features of academic laboratories and industrial plants, translating materials and manufacturing technologies from labs to fabs is notoriously difficult. Therefore, herein, key challenges in the materials manufacturing of flexible electronics are identified and discussed for its lab‐to‐fab translation, along the four stages in product manufacturing: design, materials supply, processing, and integration. Perspectives on industry‐oriented strategies to overcome some of these obstacles are also proposed. Priorities for action are outlined, including standardization, iteration between basic and applied research, and adoption of smart manufacturing. With concerted efforts from academia and industry, flexible electronics will bring a bigger impact to society as promised.
Flexible electronics have witnessed tremendous progress in academia over the past decade, but their industrial adoption lags behind. To stimulate faster lab‐to‐fab translation, the current status of flexible electronics is reviewed, critical challenges in materials manufacturing during lab‐to‐fab translation are identified, and perspectives on research and development that can expedite the translation process are proposed.
Stretchable conductors are the basic units of advanced flexible electronic devices, such as skin‐like sensors, stretchable batteries and soft actuators. Current fabrication strategies are mainly ...focused on the stretchability of the conductor with less emphasis on the huge mismatch of the conductive material and polymeric substrate, which results in stability issues during long‐term use. Thermal‐radiation‐assisted metal encapsulation is reported to construct an interlocking layer between polydimethylsiloxane (PDMS) and gold by employing a semipolymerized PDMS substrate to encapsulate the gold clusters/atoms during thermal deposition. The stability of the stretchable conductor is significantly enhanced based on the interlocking effect of metal and polymer, with high interfacial adhesion (>2 MPa) and cyclic stability (>10 000 cycles). Also, the conductor exhibits superior properties such as high stretchability (>130%) and large active surface area (>5:1 effective surface area/geometrical area). It is noted that this method can be easily used to fabricate such a stretchable conductor in a wafer‐scale format through a one‐step process. As a proof of concept, both long‐term implantation in an animal model to monitor intramuscular electric signals and on human skin for detection of biosignals are demonstrated. This design approach brings about a new perspective on the exploration of stretchable conductors for biomedical applications.
Thermal‐radiation‐assisted metal encapsulation is used to prepare large‐scale high‐performance stretchable conductors that possess high stretchability, stability and adhesion and large surface area. They are used to simultaneously monitor electromyography and skin deformation and implanted to detect intramuscular signals. This study offers a new path for highly stable stretchable conductors and related biointerface applications.
Coxsackieviruses A10 (CV-A10) and A6 (CV-A6) have been associated with increasingly occurred sporadic hand-foot-mouth disease (HFMD) cases and outbreak events globally. However, our understanding of ...epidemiological and genetic characteristics of these new agents remains far from complete. This study was to explore the circulation of CV-A10 and CV-A6 in HFMD and their genetic characteristics in China. A hospital based surveillance was performed in three heavily inflicted regions with HFMD from March 2009 to August 2011. Feces samples were collected from children with clinical diagnosis of HFMD. The detection and genotyping of enteroviruses was performed by real-time PCR and sequencing of 5'UTR/VP1 regions. Phylogenetic analysis and selection pressure were performed based on the VP1 sequences. Logistic regression model was used to identify the effect of predominant enterovirus serotypes in causing severe HFMD. The results showed 92.0% of 1748 feces samples were detected positive for enterovirus, with the most frequently presented serotypes as EV-71 (944, 54.0%) and CV-A16 (451, 25.8%). CV-A10 and CV-A6 were detected as a sole pathogen in 82 (4.7%) and 44 (2.5%) cases, respectively. Infection with CV-A10 and EV-71 were independently associated with high risk of severe HFMD (OR = 2.66, 95% CI: 1.40-5.06; OR = 4.81, 95% CI: 3.07-7.53), when adjusted for age and sex. Phylogenetic analysis revealed that distinct geographic and temporal origins correlated with the gene clusters based on VP1 sequences. An overall ω value of the VP1 was 0.046 for CV-A10 and 0.047 for CV-A6, and no positively selected site was detected in VP1 of both CV-A10 and CV-A6, indicating that purifying selection shaped the evolution of CV-A10 and CV-A6. Our study demonstrates variety of enterovirus genotypes as viral pathogens in causing HFMD in China. CV-A10 and CV-A6 were co-circulating together with EV-71 and CV-A16 in recent years. CV-A10 infection might also be independently associated with severe HFMD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Recent evidence indicates that the abnormal differentiation of bone marrow‐derived mesenchymal stem cells (BMSCs) plays a pivotal role in the pathogenesis of osteoporosis. LncRNA SNHG1 has been found ...to be associated with the differentiation ability of BMSCs. In this study, we aimed to elucidate the role of lncRNA SNHG1 and its associated pathway on the differentiation of BMSCs in osteoporosis. Mice that underwent bilateral ovariectomy (OVX) were used as models of osteoporosis. Induced osteogenic or adipogenic differentiation was performed in mouse BMSCs. Compared to sham animals, lncRNA SNHG1 expression was upregulated in OVX mice. Also, the in vitro expression of SNHG1 was increased in adipogenic BMSCs but decreased in osteogenic BMSCs. Moreover, overexpression of SNHG1 enhanced the adipogenic capacity of BMSCs but inhibited their osteogenic capacity as determined by oil red O, alizarin red, and alkaline phosphatase staining, while silencing of SNHG1 led to the opposite results. LncRNA SNHG1 interacting with the RNA‐binding polypyrimidine tract‐binding protein 1 (PTBP1) promoted osteoprotegerin (Opg) methylation and suppressed Opg expression via mediating DNA methyltransferase (DNMT) 1. Furthermore, Opg was showed to regulate BMSC differentiation. Knockdown of SNHG1 decreased the expressions of adipogenic related genes but increased that of osteogenic related genes. However, the knockdown of Opg partially reversed those effects. In summary, lncRNA SNHG1 upregulated the expression of DNMT1 via interacting with PTBP1, resulting in Opg hypermethylation and decreased Opg expression, which in turn enhanced BMSC adipogenic differentiation and contributed to osteoporosis.
Although some progress has been made on stretchable supercapacitors, traditional stretchable supercapacitors fabricated by predesigning structured electrodes for device assembling still lack the ...device‐level editability and programmability. To adapt to wearable electronics with arbitrary configurations, it is highly desirable to develop editable supercapacitors that can be directly transferred into desirable shapes and stretchability. In this work, editable supercapacitors for customizable shapes and stretchability using electrodes based on mechanically strengthened ultralong MnO2 nanowire composites are developed. A supercapacitor edited with honeycomb‐like structure shows a specific capacitance of 227.2 mF cm−2 and can be stretched up to 500% without degradation of electrochemical performance, which is superior to most of the state‐of‐the‐art stretchable supercapacitors. In addition, it maintains nearly 98% of the initial capacitance after 10 000 stretch‐and‐release cycles under 400% tensile strain. As a representative of concept for system integration, the editable supercapacitors are integrated with a strain sensor, and the system exhibits a stable sensing performance even under arm swing. Being highly stretchable, easily programmable, as well as connectable in series and parallel, an editable supercapacitor with customizable stretchability is promising to produce stylish energy storage devices to power various portable, stretchable, and wearable devices.
Editable supercapacitors with customizable stretchability, which can be directly transformed into various customizable shapes and stretchable structures, are developed. In particular, the supercapacitor with a honeycomb‐like structure can maintain nearly 98% initial capacitance even after 10 000 stretch‐and‐release cycles under reversible 400% tensile strain.
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