Hydrogel-based strain sensors have been widely investigated owing to their intrinsic flexible and extensible properties. However, integrating good mechanical properties and excellent strain ...sensitivity into one hydrogel remains a challenge. In this work, a dual physical cross-linked carboxymethyl cellulose-Fe
3+
/polyacrylamide (CMC-Fe
3+
/PAAm) double network hydrogel was developed by facile two-step method. In this hydrogel, the Fe
3+
cross-linked CMC acts as the first network for dissipating energy and hydrophobic association PAAm acts as the second network to maintain the integrity of hydrogel. Owing to these physical interactions, the as-prepared hydrogel shows good mechanical properties (e.g., tensile strength, 1.82 MPa; toughness, 6.52 MJ/m
3
). Furthermore, these mechanical behaviors can be modulated by adjusting the solid content, CMC/PAAm ratio, Fe
3+
concentration and soaking time in Fe
3+
solution. Moreover, the obtained hydrogel shows excellent self-recovery and anti-fatigue property due to the reversibility of dual physical cross-linked interactions. Additionally, the CMC-Fe
3+
/PAAm hydrogel shows good conductivity (1.82 S/m), strain sensitivity (gauge factor = 4.02 at 50–600% strain), and fast response time (260 ms). Based on the high strain sensitivity, the CMC-Fe
3+
/PAAm hydrogel can fabricate a flexible strain sensor for precisely monitoring various human motions. This study suggests that the CMC-Fe
3+
/PAAm hydrogel exhibits potential application in the flexible and stretchable strain sensors.
Graphic abstract
Abnormal proline-rich protein 11 (PRR11) expression is associated with various tumors. However, there are few reports concerning PRR11 with prognostic risk, immune infiltration, or immunotherapy of ...bladder urothelial carcinoma (BLCA). This study is based on online databases, such as Oncomine, GEPIA, HPA, LinkedOmics, TIMER, ESTIMATE and TISIDB, and BLCA data downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus, we employed an array of bioinformatics methods to explore the potential oncogenic roles of PRR11, including analyzing the relationship between PRR11 and prognosis, tumor mutational burden (TMB), microsatellite instability, and immune cell infiltration in BLCA. The results depict that PRR11 is highly expressed in BLCA, and BLCA patients with higher PRR11 expression have worse outcomes. In addition, there was a significant correlation between PRR11 expression and TMB and tumor immune infiltration. These findings suggest that PRR11 can be used as a potential marker for BLCA patient assessment and risk stratification to improve clinical prognosis, and its potential regulatory mechanism in the BLCA tumor microenvironment and targeted therapy is worthy of further investigation.
Oleandrin is a highly lipid-soluble cardiac glycoside isolated from the plant
(Apocynaceae) and is used as a traditional herbal medicine due to its excellent pharmacological properties. It is widely ...applied for various disease treatments, such as congestive heart failure. Recently, oleandrin has attracted widespread attention due to its extensive anti-cancer and novel anti-viral effects. However, oleandrin has a narrow therapeutic window and exhibits various toxicities, especially typical cardiotoxicity, which is often fatal. This severe toxicity and low polarity have significantly hindered its application in the clinic. This review describes natural sources, structural properties, and detection methods of oleandrin. Based on reported poisoning cases and sporadic animal experiments, the pharmacokinetic characteristics of oleandrin are summarized, so as to infer some possible phenomena, such as enterohepatic circulation. Moreover, the relevant factors affecting the pharmacokinetics of oleandrin are analyzed, and some research approaches that may ameliorate the pharmacokinetic behavior of oleandrin are proposed. With the toxicology of oleandrin being thoroughly reviewed, the development of safe clinical applications of oleandrin may be possible given potential research strategies to decrease toxicity.
A defining feature of successful vaccination is the ability to induce long-lived antigen-specific memory cells. T follicular helper (Tfh) cells specialize in providing help to B cells in mounting ...protective humoral immunity in infection and after vaccination. Memory Tfh cells that retain the CXCR5 expression can confer protection through enhancing humoral response upon antigen re-exposure but how they are maintained is poorly understood. CXCR5
memory Tfh cells in human blood are divided into Tfh1, Tfh2, and Tfh17 cells by the expression of chemokine receptors CXCR3 and CCR6 associated with Th1 and Th17, respectively. Here, we developed a new method to induce Tfh1, Tfh2, and Tfh17-like (iTfh1, iTfh2, and iTfh17) mouse cells in vitro. Although all three iTfh subsets efficiently support antibody responses in recipient mice with immediate immunization, iTfh17 cells are superior to iTfh1 and iTfh2 cells in supporting antibody response to a later immunization after extended resting in vivo to mimic memory maintenance. Notably, the counterpart human Tfh17 cells are selectively enriched in CCR7
central memory Tfh cells with survival and proliferative advantages. Furthermore, the analysis of multiple human cohorts that received different vaccines for HBV, influenza virus, tetanus toxin or measles revealed that vaccine-specific Tfh17 cells outcompete Tfh1 or Tfh2 cells for the persistence in memory phase. Therefore, the complementary mouse and human results showing the advantage of Tfh17 cells in maintenance and memory function supports the notion that Tfh17-induced immunization might be preferable in vaccine development to confer long-term protection.
Zwitterions have aroused much interest to endow implantable medical devices with anti-fouling and anti-thrombosis performance, due to their ability to form a hydrated layer that can provide a good ...barrier against protein and cell adhesion. Herein, tyramine modified sulfobetaine-derived sodium hyaluronan (HST) hydrogel coating was fabricated, in which hyaluronan (HA) was used as polysaccharide skeleton to graft zwitterionic sulfobetaine, and tyramine was introduced as crosslinker to construct both the network of hydrogel and a strong covalent bond between coating and substrate. Hydrogel coating was prepared by spin coating or painting HST prepolymer solution under ultraviolet light irradiation. The obtained HST hydrogel coating shows good stability. Moreover, in addition to its outstanding anti-fouling performance and good biocompatibility, it can effectively prevent thrombosis in blood circulation
ex vivo
. This work offers a universal strategy to prepare a high-performance anti-fouling and anti-thrombosis coating, which is expected to promote the development of functional coatings for biomedical materials.
Currently, it is a challenge to develop hemostatic materials with high water absorption capacity and anti-fatigue properties for quickly preventing massive hemorrhage from arteries and visceral ...organs. A series of polyacrylic acid/chitosan (PAA/CS) cryogels were prepared by a cryostructurization technique to improve mechanical performance and hemostatic efficiency of chitosan (CS). In this system, the chemically cross-linked PAA network was used as a framework to improve water absorption behaviors and mechanical strength. The CS network was co-blended by hydrogen bonding and electrostatic interactions, both of which synergistically promoted hemostasis. These cryogels had high porosity (>94%), rapid water absorption rate (<3 s), high blood absorption capacity (>2000%), outstanding mechanical strength, and fatigue resistance. Moreover, the results of cytotoxicity and hemolysis demonstrated that the cryogels had good biocompatibility. Notably, the PAA/CS cryogels exhibited superior whole blood coagulation ability and red blood cell and platelet adhesion ability compared to those of commercial hemostatic dressing (gauze, gelatin sponges, and CS sponges). Based on these results, mouse femoral artery hemorrhage models and liver hemorrhage models were prepared to investigate the hemostatic ability of the prepared PAA/CS cryogels. Results suggested that the hemostatic ability of PAA
5
/CS cryogels was superior to that of commercial hemostatic materials. Therefore, the PAA/CS cryogels showed potential application in preventing massive hemorrhage from arteries and visceral organs.
Epidermolysis bullosa acquisita (EBA) is an autoimmune blistering disorder characterized and caused by autoantibodies against type VII collagen (COL7). Although it has been noticed that EBA in both ...patients and mice is associated with an increased scratching, it is not clear whether and how the scratching contributes to disease manifestation. Hence, we here aimed to validate this clinical observation and also to investigate the potential contribution of increased scratching in EBA pathogenesis in mice. Longitudinal assessment of scratching behavior revealed an increased frequency of scratching as early as 12 hours after injection of anti-COL7 IgG into the skin of mice. Subsequently, scratching events became even more frequent in mice. In contrast, mice injected with a control antibody showed an unaltered scratching behavior throughout the observation period. Based on these observations, we hypothesized that mechanical irritation may promote the induction of inflammation in experimental EBA. To challenge this assumption, the local anesthetic dyclonine hydrochloride was topically applied before injection of anti-COL7 IgG. Dyclonine hydrochloride reduced the scratching events and impaired clinical disease manifestation. In therapeutic experimental settings, i.e. administration of the local anesthetic 24 hours after injection of anti-COL7 IgG, dyclonine hydrochloride only inhibited the scratching behavior, but had no significant effect on clinical disease development. In addition, eosinophils were detected in the skin before the injection of anti-COL7 IgG and significantly increased 48 hours after the antibody injection. Collectively, our results suggest that scratching behavior contributes to the initiation phase of disease manifestation in experimental EBA.
With the successful implementation of the Surviving Sepsis Campaign guidelines, post-sepsis in-hospital mortality to sepsis continues to decrease. Those who acutely survive surgical sepsis will ...either rapidly recover or develop a chronic critical illness (CCI). CCI is associated with adverse long-term outcomes and 1-year mortality. Although the pathobiology of CCI remains undefined, emerging evidence suggests a post-sepsis state of pathologic myeloid activation, inducing suboptimal lymphopoiesis and erythropoiesis, as well as downstream leukocyte dysfunction. Our goal was to use single-cell RNA sequencing (scRNA-seq) to perform a detailed transcriptomic analysis of lymphoid-derived leukocytes to better understand the pathology of late sepsis.
A mixture of whole blood myeloid-enriched and Ficoll-enriched peripheral blood mononuclear cells from four late septic patients (post-sepsis day 14-21) and five healthy subjects underwent Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq).
We identified unique transcriptomic patterns for multiple circulating immune cell subtypes, including B- and CD4
, CD8
, activated CD4
and activated CD8
T-lymphocytes, as well as natural killer (NK), NKT, and plasmacytoid dendritic cells in late sepsis patients. Analysis demonstrated that the circulating lymphoid cells maintained a transcriptome reflecting immunosuppression and low-grade inflammation. We also identified transcriptomic differences between patients with bacterial
fungal sepsis, such as greater expression of cytotoxic genes among CD8
T-lymphocytes in late bacterial sepsis.
Circulating non-myeloid cells display a unique transcriptomic pattern late after sepsis. Non-myeloid leukocytes in particular reveal a host endotype of inflammation, immunosuppression, and dysfunction, suggesting a role for precision medicine-guided immunomodulatory therapy.
Analysis of Single-Cell RNA-seq Data Dong, Xiaoru; Bacher, Rhonda
Methods in molecular biology (Clifton, N.J.),
2023, Letnik:
2629
Journal Article
As single-cell RNA sequencing experiments continue to advance scientific discoveries across biological disciplines, an increasing number of analysis tools and workflows for analyzing the data have ...been developed. In this chapter, we describe a standard workflow and elaborate on relevant data analysis tools for analyzing single-cell RNA sequencing data. We provide recommendations for the appropriate use of commonly used methods, with code examples and analysis interpretations.
Introduction
High altitude (HA) exposure leads to cognitive impairment while the underlying mechanism is still unclear. Brain functional network is crucial for advanced functions, and its alteration ...is implicated in cognitive decline in multiple diseases. The aim of current study was to investigate the topological changes in HA‐exposed brain functional network.
Methods
Based on Shaanxi‐Tibet immigrant cohort, neuropsychological tests and resting‐state functional MRI were applied to evaluate the participants' cognitive function and functional connection (FC) changes, respectively. GRETNA toolbox was used to construct the brain functional network. The gray matter was parcellated into 116 anatomically defined regions according to Automated Anatomical Labeling atlas. Subsequently, the mean time series for each of the 116 regions were extracted and computed for Pearson's correlation coefficients. The relation matrix was further processed and seen as brain functional network. Correlation between functional network changes and neuropsychological results was also examined.
Results
The cognitive performance was impaired by HA exposure as indicated by neuropsychological test. HA exposure led to alterations of degree centrality and nodal efficiency in multiple brain regions. Moreover, two subnetworks were extracted in which the FCs significantly decreased after exposure. In addition, the alterations in FCs within above two subnetworks were significantly correlated with changes of memory and reaction time.
Conclusions
Our results suggest that HA exposure modulates the topological property of functional network and FCs of some important regions, which may impair the attention, perception, memory, motion ignition, and modulation processes, finally decreasing cognitive performance in neuropsychological tests.
High altitude (HA) exposure modulates the topological property of functional network and functional connections (FCs) of some important regions, which may impair the attention, perception, memory, motion ignition, and modulation processes, finally decreasing cognitive performance in neuropsychological tests.
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