Several stress‐activated signals are highly responsible for the thermal tolerance and attribute to the poor therapeutic outcome of photothermal therapy (PTT). In this study, the naturally human ...hair‐derived nanoparticles (Hair NPs) with significant photothermal conversion efficacy are explored to combine with stress‐activated signal inhibitors for maximizing the PTT efficiency. During the Hair NPs‐based PTT, two distinct signals are found to be remarkably upregulated. One is the heat‐induced overexpression of HSP90, and the other one is the activation of mitogen‐activated protein kinase (MAPK) signaling pathway. Through the integration of particular inhibitors (17‐allylamino‐17‐demethoxygeldanamycin (17AAG) specifically binding to HSP90 or LY2228820 targeting to p38 MAPK) and the subsequent modification of hyaluronic acid (HA), the resultant Hair NPs‐HA@inhibitor can specifically deliver the inhibitor into tumor cells with minimal side effects on normal tissues, which can specifically block the stressfully activated signals as well as inhibit the expression of their downstream effectors (e.g., MMPs, VEGF) that are closely related with tumor survival and invasion. Without these elements to protect tumor cells or promote tumor progression, the Hair NPs‐induced PTT effect can be much elevated, resulting in a superior antitumor efficacy. These findings represent an effective approach in maximizing PTT effect for fighting against tumor.
Stress‐activated signal inhibition boosted photothermal therapy (PTT): through the integration of specific inhibitors, Hair NPs‐HA@inhibitor can inhibit the typical heat‐activated signals (i.e., HSP90 and p38 MAPK signaling pathway) that are closely related with tumor survival and invasion, leading to the reduced thermoresistance of tumor cells and superior cell killing effect by enhanced PTT.
Neurological complications are common in patients with COVID-19. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal pathogen of COVID-19, has been detected in some ...patient brains, its ability to infect brain cells and impact their function is not well understood. Here, we investigated the susceptibility of human induced pluripotent stem cell (hiPSC)-derived monolayer brain cells and region-specific brain organoids to SARS-CoV-2 infection. We found that neurons and astrocytes were sparsely infected, but choroid plexus epithelial cells underwent robust infection. We optimized a protocol to generate choroid plexus organoids from hiPSCs and showed that productive SARS-CoV-2 infection of these organoids is associated with increased cell death and transcriptional dysregulation indicative of an inflammatory response and cellular function deficits. Together, our findings provide evidence for selective SARS-CoV-2 neurotropism and support the use of hiPSC-derived brain organoids as a platform to investigate SARS-CoV-2 infection susceptibility of brain cells, mechanisms of virus-induced brain dysfunction, and treatment strategies.
Display omitted
•SARS-CoV-2 minimally infects human neurons and astrocytes in 2D and brain organoids•Model developed for hiPSC-derived choroid plexus organoids (CPOs)•SARS-CoV-2 productively infects CPOs and increases cell death•SARS-CoV-2 CPO infection leads to transcriptional upregulation of inflammatory genes
SARS-CoV-2 causes neurological symptoms in a significant portion of patients with COVID-19. Ming and colleagues tested SARS-CoV-2 neurotropism by using monolayer neural cells and brain organoids generated from human pluripotent stem cells and show minimal neuron and astrocyte infection but efficient choroid plexus infection, leading to cell death and functional deficits.
Antibody (Ab)‐based drugs have been widely used in targeted therapies and immunotherapies, leading to significant improvements in tumor therapy. However, the failure of Ab therapy due to the loss of ...target antigens or Ab modifications that affect its function limits its application. In this study, we expanded the application of antibodies (Abs) by constructing a fusion protein as a versatile tool for Ab‐based target cell detection, delivery, and therapy. We first constructed a SpaC Catcher (SpaCC for short) fusion protein that included the C domains of Staphylococcal protein A (SpaC) and the SpyCatcher. SpaCC conjugated with SpyTag‐X (S‐X) to form the SpaCC‐S‐X complex, which binds non‐covalently to an Ab to form the Ab‐SpaCC‐S‐X protein complex. The “X” can be a variety of small molecules such as fluoresceins, cell‐penetrating peptide TAT, Monomethyl auristatin E (MMAE), and DNA. We found that Ab‐SpaCC‐S‐FITC(−TAT) could be used for target cell detection and delivery. Besides, we synthesized the Ab‐SpaCC‐SN3‐MMAE complex by linking Ab with MMAE by SpaCC, which improved the cytotoxicity of small molecule toxins. Moreover, we constructed an Ab‐DNA complex by conjugating SpaCC with the aptamer (Ap) and found that Ab‐SpaCC‐SN3‐Ap boosted the tumor‐killing function of T‐cells by retargeting tumor cells. Thus, we developed a multifunctional tool that could be used for targeted therapies and immunotherapies, providing a cheap and convenient novel drug development strategy.
Purpose
To report the clinical outcomes and evaluate the efficacy of a novel bubble ultra‐wide field viewing system for vitreoretinal surgery.
Design
Prospective, noncomparative, interventional case ...series.
Participants
One hundred and fifty‐one eyes of 146 consecutive patients with proliferative diabetic retinopathy (PDR), vitreous haemorrhage originating from retinal vein occlusion (VH‐RVO), epiretinal membrane (EM), macular hole (MH) or retinal detachment (RD) who underwent vitreoretinal surgery using the bubble ultra‐wide field viewing system were included.
Methods
A standard phacoemulsification was performed on each patient. Core humour and mid‐peripheral vitreous humour were removed using a planoconcave lens. A suitably sized bubble was infused to attach to the posterior capsule or the anterior chamber depending on the integrity of the posterior capsule. The planoconcave lens and the air bubble formed the wide‐angle viewing system, through which peripheral vitrectomy was performed.
Main Outcome Measures
Range of applications, field of view, model validation and complications were recorded.
Results
The new ultra‐wide field viewing system was successfully applied in all eyes, including 34 with PDR, 28 VH‐RVO, 28 EM, 25 MH and 36 RD. Peripheral vitrectomy, local or panretinal laser photocoagulation, and removal of the peripheral proliferative membrane were successfully performed while viewing through this system. Maximum peripheral retinal area observable during the procedure was positively correlated with pupil diameter. Model analysis results showed that when the pupil diameter was 6 mm, the maximum field of view was approximately 128.1‐ 148.0 degrees with this system. Of 142 eyes, the main intraoperative complication was iatrogenic retinal breaks (IRBs) in 8 eyes (5.3%) and posterior capsule injury by vitreous cutter during bubble removal in 6 eyes (4.2%). The postsurgery mean best‐corrected visual acuity (BCVA) (0.48 ± 0.39 logMAR) was significantly improved compared with the preoperative mean BCVA (1.60 ± 1.08 logMAR, p < 0.001). No incidents of postoperative choroidal detachment, secondary glaucoma or endophthalmitis were recorded.
Conclusions
For patients with lens excision or absence, vitreoretinal surgery can be successfully performed using the novel viewing system described here. The system is a safe, convenient and economical ultra‐wide field viewing system with a wide range of applications.
Bacteria can act as a promising anti‐tumor platform due to their specific targeting capacity to the tumor microenvironment. In this study, it is discovered that intravenous administration of ...Escherichia coli TOP10 induces rapid and intense blood coagulation in tumor tissues instead of normal tissues. It is demonstrated that E. coli TOP10 can act as an activator of a coagulation cascade to trigger abnormal hemorrhage, blood coagulation, and inflammation with abundant macrophages recruitment in tumors. In addition, the recruited macrophages are principally polarized by lipopolysaccharide in the bacterial wall to the anti‐tumor M1‐like phenotype. Based on the above finding, coagulation‐tropism blood platelets decorated with CD47 antibodies (Anti‐CD47), which possess tropism for bacteria‐treated tumors are further prepared. As a result, Anti‐CD47 blocks the “don't eat me” signal from tumor cells, consequently promoting the phagocytosis of polarized M1‐like phenotype macrophages for tumor cells. This manipulation of local blood coagulation in tumors may find great potential for accurately delivering immune checkpoint inhibitors and facilitating tumor immunotherapy.
Living Escherichia coli TOP10 is demonstrated to induce rapid and intense blood coagulation specifically in tumors, along with macrophages recruitment and polarization. The coagulation‐tropism blood platelets decorated with CD47 antibodies (Anti‐CD47) are prepared for promoting the phagocytosis of polarized macrophages for tumor cells.
Abstract
Recently, monolayer molybdenum disulphide (MoS
2
) has emerged as a promising and non–precious electrocatalyst for hydrogen evolution reaction. However, its performance is largely limited by ...the low density and poor reactivity of active sites within its basal plane. Here, we report that domain boundaries in the basal plane of monolayer MoS
2
can greatly enhance its hydrogen evolution reaction performance by serving as active sites. Two types of effective domain boundaries, the 2H-2H domain boundaries and the 2H-1T phase boundaries, were investigated. Superior hydrogen evolution reaction catalytic activity, long-term stability and universality in both acidic and alkaline conditions were achieved based on a multi-hierarchy design of these two types of domain boundaries. We further demonstrate that such superior catalysts are feasible at a large scale by applying this multi-hierarchy design of domain boundaries to wafer-scale monolayer MoS
2
films.
Only rarely have polyoxometalates been found to form core–shell nanoclusters. Here, we succeeded in isolating a series of rare giant and all‐inorganic core–shell cobalt polyoxoniobates (Co−PONbs) ...with diverse shapes, nuclearities and original topologies, including 50‐nuclearity {Co12Nb38O132}, 54‐nuclearity {Co20Nb34O128}, 62‐nuclearity {Co26Nb36O140} and 87‐nuclearity {Co33Nb54O188}. They are the largest Co−PONbs and also the polyoxometalates containing the greatest number of Co ions and the largest cobalt clusters known thus far. These molecular Co−PONbs have intriguing and atomically precise core–shell architectures comprising unique cobalt oxide cores and niobate oxide shells. In particular, the encapsulated cobalt oxide cores with different nuclearities have identical compositions, structures and mixed‐valence Co3+/Co2+ states as the different sized Co−O moieties of the bulk cubic‐spinel Co3O4, suggesting that they can serve as various molecular models of the cubic‐spinel Co3O4. The successful construction of the series of the Co−PONbs reveals a feasible and versatile synthetic method for making rare core–shell heterometallic PONbs. Further, these new‐type core–shell bimetal species are promising cluster molecular catalysts for visible‐light‐driven CO2 reduction.
A series of rare Co−Nb‐based core–shell polyoxometalates containing 50, 54, 62 and 87 metal polyhedra is prepared. The cobalt oxide cores correspond to increasingly large molecular analogues of infinite cubic‐spinel Co3O4. They are the largest cobalt polyoxoniobates and the polyoxometalates with the greatest number of Co ions and the highest‐nuclearity cobalt clusters known thus far. They are shown to be efficient photocatalysts for CO2 reduction.
Lanthanide-doped upconversion nanoparticles (UCNPs) have attracted considerable interest due to their superior physicochemical features, such as large anti-Stokes shifts, low autofluorescence ...background, low toxicity and high penetration depth, which make them extremely suitable for use as alternatives to conventional downshifting luminescence bioprobes like organic dyes and quantum dots for various biological applications. A fundamental understanding of the photophysics of lanthanide-doped UCNPs is of vital importance for discovering novel optical properties and exploring their new applications. In this review, we focus on the most recent advances in the development of lanthanide-doped UCNPs as potential luminescent nano-bioprobes by means of our customized lanthanide photophysics measurement platforms specially designed for upconversion luminescence, which covers from their fundamental photophysics to bioapplications, including electronic structures (energy levels and local site symmetry of emitters), excited-state dynamics, optical property designing, and their promising applications for
in vitro
biodetection of tumor markers. Some future prospects and efforts towards this rapidly growing field are also envisioned.
The latest advances in lanthanide-doped upconversion nanoparticles were comprehensively reviewed, which covers from their fundamental photophysics to biodetection.
BRI1-EMS suppressor (BES)/brassinazole-resistant (BZR) family transcription factors are involved in a variety of physiological processes, but the biological functions of some BES/BZR transcription ...factors remain unknown; moreover, it is not clear if any of these proteins function in the regulation of plant stress responses. Here, wheat (
) brassinazole-resistant 2 (
)-overexpressing plants exhibited drought tolerant phenotypes, whereas downregulation of
in wheat by RNA interference resulted in elevated drought sensitivity. electrophoretic mobility shift assay and luciferase reporter analysis illustrate that TaBZR2 directly interacts with the gene promoter to activate the expression of
glutathione s-transferase-1 (
), which functions positively in scavenging drought-induced superoxide anions (O
). Moreover, TaBZR2 acts as a positive regulator in brassinosteroid (BR) signaling. Exogenous BR treatment enhanced TaBZR2-mediated O
scavenging and antioxidant enzyme gene expression. Taken together, we demonstrate that a BES/BZR family transcription factor, TaBZR2, functions positively in drought responses by activating
and mediates the crosstalk between BR and drought signaling pathways. Our results thus provide new insights into the mechanisms underlying how BES/BZR family transcription factors contribute to drought tolerance in wheat.
The microbiota in the human gut is strongly correlated with the progression of colorectal cancer (CRC) and with therapeutic responses to CRC. Here, by leveraging the higher concentration of the ...pro-tumoural Fusobacterium nucleatum and the absence of antineoplastic butyrate-producing bacteria in the faecal microbiota of patients with CRC, we show that-in mice with orthotopic colorectal tumours or with spontaneously formed colorectal tumours-oral or intravenous administration of irinotecan-loaded dextran nanoparticles covalently linked to azide-modified phages that inhibit the growth of F. nucleatum significantly augments the efficiency of first-line chemotherapy treatments of CRC. We also show that oral administration of the phage-guided irinotecan-loaded nanoparticles in piglets led to negligible changes in haemocyte counts, immunoglobulin and histamine levels, and liver and renal functions. Phage-guided nanotechnology for the modulation of the gut microbiota might inspire new approaches for the treatment of CRC.
PDF
