Foreign body reaction (FBR) to implanted biomaterials and medical devices is common and can compromise the function of implants or cause complications. For example, in cell encapsulation, cellular ...overgrowth (CO) and fibrosis around the cellular constructs can reduce the mass transfer of oxygen, nutrients and metabolic wastes, undermining cell function and leading to transplant failure. Therefore, materials that mitigate FBR or CO will have broad applications in biomedicine. Here we report a group of zwitterionic, sulfobetaine (SB) and carboxybetaine (CB) modifications of alginates that reproducibly mitigate the CO of implanted alginate microcapsules in mice, dogs and pigs. Using the modified alginates (SB-alginates), we also demonstrate improved outcome of islet encapsulation in a chemically-induced diabetic mouse model. These zwitterion-modified alginates may contribute to the development of cell encapsulation therapies for type 1 diabetes and other hormone-deficient diseases.
Connexin, a four-pass transmembrane protein, contributes to assembly of gap junctions among neighboring cells and thus facilitates gap junctional intercellular communication (GJIC). Traditionally, ...the roles of connexins were thought to mediate formation of hemichannels and GJIC assembly for transportation of ions and small molecules. Many studies have observed loss of GJIC, due to reduced expression or altered cytoplasmic localization of connexins, in primary tumor cells. Connexins are generally considered tumor-suppressive. However, recent studies of clinical samples suggested a different role of connexins in that expression levels and membrane localization of connexins, including Connexin 43 (Cx43, GJA1) and Connexin 26 (Cx26, GJB2), were found to be enhanced in metastatic lesions of cancer patients. Cx43- and Cx26-mediated GJIC was found to promote cancer cell migration and adhesion to the pulmonary endothelium. Regulatory circuits involved in the induction of connexins and their functional effects have also been reported in various types of cancer. Connexins expressed in stromal cells were correlated with metastasis and were implicated in regulating metastatic behaviors of cancer cells. Recent studies have revealed that connexins can contribute to cellular phenotypes via multiple ways, namely 1) GJIC, 2) C-terminal tail-mediated signaling, and 3) cell-cell adhesion during gap junction formation. Both expression levels and the subcellular localization could participate determining the functional roles of connexins in cancer. Compounds targeting connexins were thus tested as potential therapeutics intervening metastasis or chemoresistance. This review focuses on the recent findings in the correlation between the expression of connexins and patients' prognosis, their roles in metastasis and chemoresistance, as well as the implications and concerns of using connexin-targeting drugs as anti-metastatic therapeutics. Overall, connexins may serve as biomarkers for cancer prognosis and as therapeutic targets for intervening metastasis and chemoresistance.
Ribosomes are essential components of the protein synthesis machinery. The process of ribosome biogenesis is well organized and tightly regulated. Recent studies have shown that ribosomal proteins ...(RPs) have extraribosomal functions that are involved in cell proliferation, differentiation, apoptosis, DNA repair, and other cellular processes. The dysfunction of RPs has been linked to the development and progression of hematological, metabolic, and cardiovascular diseases and cancer. Perturbation of ribosome biogenesis results in ribosomal stress, which triggers activation of the p53 signaling pathway through RPs–MDM2 interactions, resulting in p53‐dependent cell cycle arrest and apoptosis. RPs also regulate cellular functions through p53‐independent mechanisms. We herein review the recent advances in several forefronts of RP research, including the understanding of their biological features and roles in regulating cellular functions, maintaining cell homeostasis, and their involvement in the pathogenesis of human diseases. We also highlight the translational potential of this research for the identification of molecular biomarkers, and in the discovery and development of novel treatments for human diseases.
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.
Abstract
Hydrodynamical interactions between binaries and circumbinary disks (CBDs) play an important role in a variety of astrophysical systems, from young stellar binaries to supermassive black ...hole binaries. Previous simulations of CBDs have mostly employed locally isothermal equations of state. We carry out 2D viscous hydrodynamic simulations of CBDs around equal-mass, circular binaries, treating the gas thermodynamics by thermal relaxation toward equilibrium temperature (the constant-
β
cooling ansatz, where
β
is the cooling time in units of the local Keplerian time). As an initial study, we use the grid-based code
Athena++
on a polar grid, covering an extended disk outside the binary co-orbital region. We find that with a longer cooling time, the accretion variability is gradually suppressed, and the morphology of the CBD becomes more symmetric. The disk also shows evidence of hysteresis behavior depending on the initial conditions. Gas cooling also affects the rate of angular momentum transfer between the binary and the CBD, where given our adopted disk thickness and viscosity (
H
/
r
∼ 0.1 and
α
∼ 0.1), the binary orbit expands while undergoing accretion for most
β
values between 0 and 4.0 except over a narrow range of intermediate
β
values. The validity of using a polar grid excising the central domain is also discussed.
A major challenge is the development of multifunctional metal–organic frameworks (MOFs), wherein magnetic and electronic functionality can be controlled simultaneously. Herein, we rationally ...construct two 3D MOFs by introducing the redox active ligand tetra(4‐pyridyl)tetrathiafulvalene (TTF(py)4) and spin‐crossover FeII centers. The materials exhibit redox activity, in addition to thermally and photo‐induced spin crossover (SCO). A crystal‐to‐crystal transformation induced by I2 doping has also been observed and the resulting intercalated structure determined. The conductivity could be significantly enhanced (up to 3 orders of magnitude) by modulating the electronic state of the framework via oxidative doping; SCO behavior was also modified and the photo‐magnetic behavior was switched off. This work provides a new strategy to tune the spin state and conductivity of framework materials through guest‐induced redox‐state switching.
A 3D FeII metal–organic framework (MOF) based on the tetrathiafulvalene tetrapyridyl ligand and its I2‐doped analogue were prepared. The TTF moieties provide redox activity, and I2 doping improves the conductive properties. Doping or light irradiation significantly alters the magnetic properties, indicating the material has electronically and photo‐switchable spin‐crossover properties.
SARS‐CoV‐2, the virus that caused the COVID‐19 pandemic, can remain viable and infectious on surfaces for days, posing a potential risk for fomite transmission. Liquid‐based disinfectants, such as ...chlorine‐based ones, have played an indispensable role in decontaminating surfaces but they do not provide prolonged protection from recontamination. Here a safe, inexpensive, and scalable membrane with covalently immobilized chlorine, large surface area, and fast wetting that exhibits long‐lasting, exceptional killing efficacy against a broad spectrum of bacteria and viruses is reported. The membrane achieves a more than 6 log reduction within several minutes against all five bacterial strains tested, including gram‐positive, gram‐negative, and drug‐resistant ones as well as a clinical bacterial cocktail. The membrane also efficiently deactivated nonenveloped and enveloped viruses in minutes. In particular, a 5.17 log reduction is achieved against SARS‐CoV‐2 after only 10 min of contact with the membrane. This membrane may be used on high‐touch surfaces in healthcare and other public facilities or in air filters and personal protective equipment to provide continuous protection and minimize transmission risks.
A safe, inexpensive, and scalable microfibrous polyurethane membrane with chlorine‐immobilizing hydantoin and wettability‐enhancing sulfobetaine functional groups is reported. After chlorination, the membrane exhibits long‐lasting, exceptional killing efficacy against a broad spectrum of bacteria and viruses. In particular, a 5.17 log reduction is observed against SARS‐CoV‐2 after 10 min of contact with the membrane.
Prostate-specific membrane antigen (PSMA) has been found in tumor neovasculature endothelial cells (NECs) of non-prostate cancers and may become the most promising target for anti-tumor therapy. To ...study the value of PSMA as a potential new target for lung cancer treatment, PSMA expression in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) tissues and its relationship with clinicopathology were investigated in the current study.
Immunohistochemistry was used to detect PSMA expression in a total of 150 lung specimens of patients with lung cancer. The data were analyzed using univariate and multivariate statistical analyses.
The percentages of NSCLC patients who had PSMA (+) tumor cells and PSMA (+) NECs were 54.02% and 85.06%, respectively. The percentage of patients younger than 60 years old who had PSMA (+) tumor cells was 69.05%, which was significantly greater than the percentage of patients aged 60 years or older (40.00%, p<0.05). A significant difference was observed in the percentage of NSCLC patients with PMSA (+) NECs and stage I or II cancer (92.98%) and those patients with stage III or IV cancer (76.77%). In the SCLC tissues, NEC PSMA expression (70.00%) did not differ significantly from NSCLC. SCLC tumor cells and normal lung tissues cells were all negative. There was no significant correlation between the presence of PSMA (+) NECs in SCLC patients and the observed clinicopathological parameters.
PSMA is expressed not only in NECs of NSCLC and SCLC but also in tumor cells of most NSCLC patients. The presence of PSMA (+) tumor cells and PSMA (+) NECs in NSCLC was negatively correlated with age and the clinicopathological stage of the patients, respectively.
Rational utilization of the rich light‐bio‐matter interplay taking place in single‐cell analysis represents a new technological direction in the field. The light‐fueled operation is expected to ...achieve advanced photoelectrochemical (PEC) single‐cell analysis with unknown possibilities. Here, a PEC nanoreactor capable of single‐cell sampling and near zero‐background Faradaic detection of intracellular microRNA (miR) is devised by the construction of a small reaction chamber accommodating the target‐triggered hybridization chain reaction for binding the metallointercalator of Ru(bpy)2(dppz)2+ as the signal reporter. Light stimulation of the dsDNA/metallointercalator adduct will induce the generation of photocurrents, underpinning a zero‐biased and near zero‐background PEC method toward Faradaic detection of non‐electrogenic miR at the single‐cell level. Using this nanotool, lower miR concentration in the near‐nucleus region than that in the main cytosol was revealed.
A photoelectrochemical nanoreactor was devised for single‐cell sampling and near zero‐background faradic detection of intracellular microRNA. This platform provided a new perspective for exploring light‐biomatter interplay toward single‐cell studies.
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