For decades, hydrogen (H2) gas has been recognized as an excellent antioxidant molecule that holds promise in treating many diseases like Alzheimer's, stroke, cancer, and so on. For the first time, active hydrogen is demonstrated to be highly efficient in antibacterial, antibiofilm, and wound‐healing applications, in particular when used in combination with the photothermal effect. As a proof of concept, a biocompatible hydrogen‐releasing PdH nanohydride, displaying on‐demand controlled active hydrogen release property under near‐infrared laser irradiation, is fabricated by incorporating H2 into Pd nanocubes. The obtained PdH nanohydride combines both merits of bioactive hydrogen and photothermal effect of Pd, exhibiting excellent in vitro and in vivo antibacterial activities due to its synergistic hydrogen‐photothermal therapeutic effect. Interestingly, combinational hydrogen‐photothermal treatment is also proved to be an excellent therapeutic methodology in healing rats' wound with serious bacterial infection. Moreover, an in‐depth antibacterial mechanism study reveals that two potential pathways are involved in the synergistic hydrogen‐photothermal antibacterial effect. One is to upregulate bacterial metabolism relevant genes like dmpI, narJ, and nark, which subsequently encode more expression of oxidative metabolic enzymes to generate substantial reactive oxygen species to induce DNA damage and another is to cause severe bacterial membrane damage to release intracellular compounds like DNA.
Significant bone remodeling with disordered osteoclastogenesis has been implicated in the pathogenesis of psoriatic arthritis (PsA). And there is a high prevalence of the metabolic syndrome (MS) in PsA patients. Adipokines, especially leptin and adiponectin, have recently been reported to be involved in the development and regulation of some autoimmune diseases. In this study, we examined the alternation of circulating osteoclastogenesis related cytokines [tumor necrosis factor-α (TNF-α), osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL)] and adipokines (leptin, adiponectin, resistin, chemerin, omentin) in PsA patients, and analysed the correlations between these factors and osteoclast precursors numbers, radiographic damage scores, and disease activity index. 41 PsA patients, 20 psoriasis patients, and 24 healthy controls were recruited. Blood samples were obtained for detecting the levels of TNF-α, OPG, RANKL and the adipokines. The numbers of osteoclast precursors (OCs) in peripheral blood were assessed. Radiographs of affected joints in PsA patients were scored for erosion, joint-space narrowing, osteolysis, and new bone formation. Compared with healthy controls, patients with PsA had higher TNF-α, RANKL, OCs, leptin and omentin but lower adiponectin and chemerin. Increased serum levels of TNF-α, RANKL, leptin, and omentin were positively correlated with OCs numbers. In contrast, serum adiponectin levels were decreased in PsA patients and negatively correlated with OCs numbers. TNF-α, RANKL and leptin were positively correlated with Psoriatic Arthritis Joint Activity Index (PsAJAI). Only TNF-α was positively correlated with radiographic damage scores. Our data demonstrated that systemic expression of soluble mediators of osteoclastogenesis and adipokines were disordered in PsA. Certain adipokines were elevated in the circulation of patients with PsA and might contribute to pathogenesis of arthritis. Prospective studies will be of interest to determine the pluripotent effects of adipokines on osteoclastogenesis in chronic inflammatory rheumatic diseases. Future studies may lead to novel therapeutic strategies.
As sessile organisms, plants have evolved a wide range of defence pathways to cope with environmental stress such as heat shock. However, the molecular mechanism of these defence pathways remains unclear in rice. In this study, we found that OsHSFA2d, a heat shock transcriptional factor, encodes two main splice variant proteins, OsHSFA2dI and OsHSFA2dII in rice. Under normal conditions, OsHSFA2dII is the dominant but transcriptionally inactive spliced form. However, when the plant suffers heat stress, OsHSFA2d is alternatively spliced into a transcriptionally active form, OsHSFA2dI, which participates in the heat stress response (HSR). Further study found that this alternative splicing was induced by heat shock rather than photoperiod. We found that OsHSFA2dI is localised to the nucleus, whereas OsHSFA2dII is localised to the nucleus and cytoplasm. Moreover, expression of the unfolded protein response (UNFOLDED PROTEIN RESPONSE) sensors, OsIRE1, OsbZIP39/OsbZIP60 and the UNFOLDED PROTEIN RESPONSE marker OsBiP1, was up-regulated. Interestingly, OsbZIP50 was also alternatively spliced under heat stress, indicating that UNFOLDED PROTEIN RESPONSE signalling pathways were activated by heat stress to re-establish cellular protein homeostasis. We further demonstrated that OsHSFA2dI participated in the unfolded protein response by regulating expression of OsBiP1.
Background: Neoadjuvant chemotherapy (NAC) is commonly utilized in preoperative treatment for local breast cancer, and it gives high clinical response rates and can result in pathologic complete response (pCR) in 6-25% of patients. In recent years, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has been increasingly used to assess the pathological response of breast cancer to NAC. In present analysis, we assess the diagnostic performance of DCE-MRI in evaluating the pathological response of breast cancer to NAC. Materials and Methods:A systematic search in PubMed, the Cochrane Library, and Web of Science for original studies was performed. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess the methodological quality of the included studies. Patient, study, and imaging characteristics were extracted, and sufficient data to reconstruct 2 × 2 tables were obtained. Data pooling, heterogeneity testing, forest plot construction, meta-regression analysis and sensitivity analysis were performed using Stata version 12.0 (StataCorp LP, College Station, TX).Results: Eighteen studies (969 patients with breast cancer) were included in the present meta-analysis. The pooled sensitivity and specificity of DCE-MRI were 0.80 (95% confidence interval [CI]: 0.70, 0.88) and 0.84 (95% [CI]: 0.79, 0.88), respectively. Meta-regression analysis found no significant factors affecting heterogeneity. Sensitivity analysis showed that studies that set pathological complete response (pCR) (n = 14) as a responder showed a tendency for higher sensitivity compared with those that set pCR and near pCR together (n = 5) as a responder (0.83 vs. 0.72), and studies (n = 14) that used DCE-MRI to early predict the pathological response of breast cancer had a higher sensitivity (0.83 vs. 0.71) and equivalent specificity (0.80 vs. 0.86) compared to studies (n = 5) that assessed the response after NAC completion. Conclusion:Our results indicated that DCE-MRI could be considered an important auxiliary method for evaluating the pathological response of breast cancer to NAC and Cheng et al.Breast Cancer Response in DCE-MRI used as an effective method for dynamically monitoring the efficacy during NAC. DCE-MRI also performed well in predicting the pCR of breast cancer to NAC. However, due to the heterogeneity of the included studies, caution should be exercised in applying our results.
Plasmonic nanoparticles with an intrinsic chiral structure have emerged as a promising chiral platform for applications in biosensing, medicine, catalysis, separation, and photonics. Quantitative understanding of the correlation between nanoparticle structure and optical chirality becomes increasingly important but still represents a significantly challenging task. Here we demonstrate that tunable signal reversal of circular dichroism in the seed-mediated chiral growth of plasmonic nanoparticles can be achieved through the hybridization of bichiral centers without inverting the geometric chirality. Both experimental and theoretical results demonstrated the opposite sign of circular dichroism of two different bichiral geometries. Chiral molecules were found to not only contribute to the chirality transfer from molecules to nanoparticles but also manipulate the structural evolution of nanoparticles that synergistically drive the formation of two different chiral centers. By deliberately adjusting the concentration of chiral molecules and other synthetic parameters, such as the reducing agent concentration, the capping surfactant concentration, and the amount of Au precursor, we have been able to fine-tune the circular dichroism reversal of bichiral Au nanoparticles. We further demonstrate that the structure of chiral molecules and the crystal structure of Au seeds play crucial roles in the formation of Au nanoparticles with bichiral centers. The insights gained from this work not only shed light on the underlying mechanisms dictating the intriguing geometric and chirality evolution of bichiral plasmonic nanoparticles but also provide an important knowledge framework that guides the rational design of bichiral plasmonic nanostructures toward chiroptical applications.
O2‐delivering nanosystems have been used to antagonize hypoxia‐induced tumor therapeutic resistance. However, short‐time oxygen storage is still a bottleneck for these O2‐delivering nanosystems, which results in a decrease in blood circulation time and accumulation of oxygen in tumors, thus reducing the tumor therapeutic efficacy. Herein, a long‐term oxygen storage nanosystem (O2‐PIr@Si@PDA) is designed to overcome hypoxia for the treatment of nasopharyngeal carcinoma. This nanosystem is constructed by using perfluorooctyl bromide (PFOB) core as the oxygen carrier, functionalized with an oxygen sensitive probe (Ir(III) complex) and subsequently enclosed with an ultrathin‐walled silica shell. Due to the silica shell, this nanosystem can store oxygen for longer than 7 days. The oxygen in the O2‐PIr@Si@PDA nanosystem can be released quickly with the temperature‐responsive rupture of the silicon shell under near‐infrared (NIR) irradiation. The oxygen storage and release can be self‐monitored using the Ir(III) complex with its luminescence effect. As expected, this multifunctional nanosystem in combination with NIR irradiation not only inhibits tumor growth by alleviating hypoxia, but also enhances the effect of oxygen‐sensitized radiotherapy against nasopharyngeal carcinoma. Taken together, this study offers a novel strategy for designing long‐term oxygen storing nanosystem to relieve tumor hypoxia, thus improving the precise cancer therapeutic efficacy.
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