The noninvasive nature of photodynamic therapy (PDT) enables the preservation of organ function in cancer patients. However, PDT is impeded by hypoxia in the tumor microenvironment (TME) caused by ...high intracellular oxygen (O
) consumption and distorted tumor blood vessels. Therefore, increasing oxygen generation in the TME would be a promising methodology for enhancing PDT. Herein, we proposed a concept of ferroptosis-promoted PDT based on the biochemical characteristics of cellular ferroptosis, which improved the PDT efficacy significantly by producing reactive oxygen species (ROS) and supplying O
sustainably through the Fenton reaction. In contrast to traditional strategies that increase O
based on decomposition of limited concentration of hydrogen peroxide (H
O
), our methodology could maintain the concentration of H
O
and O
through the Fenton reaction.
: For its association with sensitivity to ferroptosis, solute carrier family 7 member 11 (SLC7A11) expression was characterized by bioinformatics analysis and immunohistochemistry of oral tongue squamous cell carcinoma (OTSCC) specimens. Afterwards, the photosensitizer chlorin e6 (Ce6) and the ferroptosis inducer erastin were self-assembled into a novel supramolecular Ce6-erastin nanodrug through hydrogen bonding and π-π stacking. Then, the obtained Ce6-erastin was extensively characterized and its anti-tumor efficacy towards OTSCC was evaluated both
and
.
: SLC7A11 expression is found to be upregulated in OTSCC, which is a potential target for ferroptosis-mediated OTSCC treatment. Ce6-erastin nanoparticles exhibited low cytotoxicity to normal tissues. More significantly, The over-accumulated intracellular ROS, increased O
concentration and inhibited SLC7A11 expression lead to enhanced toxicity to CAL-27 cells and satisfactory antitumor effects to xenograft tumour mouse model upon irradiation.
: Our ferroptosis promoted PDT approach markedly enhances anticancer actions by relieving hypoxia and promoting ROS production, thereby our work provides a new approach for overcoming hypoxia-associated resistance of PDT in cancer treatment.
High-resolution temperature records spanning the last deglaciation from low latitudes are scarce; however, they are important for understanding the rapid propagation of abrupt climate events ...throughout the Northern Hemisphere and the tropics. Here, we present a branched GDGTs-based temperature reconstruction from the sediments of Maar Lake Huguangyan in tropical China. The record reveals that the mean temperature during the Oldest Dryas was 17.8 °C, which was followed by a two-step increase of 2-3 °C to the Bølling-Allerød, a decrease to 19.8 °C during the Younger Dryas, and a rapid warming at the onset of the Holocene. The Oldest Dryas was about 2 °C warmer than the Younger Dryas. The reconstructed temperature was weighted towards the wintertime since the lake is monomictic and the mixing process in winter supplies nutrients from the lake bottom to the entire water column, greatly promoting biological productivity. In addition, the winter-biased temperature changes observed in the study are more distinctive than the summer-biased temperature records from extra-tropical regions of East Asia. This implies that the temperature decreases during abrupt climatic events were mainly a winter phenomenon. Within the limits of the dating uncertainties, the broadly similar pattern of winter-weighted temperature change observed in both tropical Lake Huguangyan and in Greenland ice cores indicates the occurrence of tightly-coupled interactions between high latitude ice sheets and land areas in the tropics. We suggest that the winter monsoon (especially cold surges) could play an important role in the rapid transmission of the temperature signal from the Arctic to the tropics.
•A branched GDGTs-based temperature reconstruction for the last deglaciation.•Reconstructed temperature is weighted towards wintertime in this monomictic lake.•The Younger Dryas was 3-4 °C cooler than the present day in tropical South China.•Winter monsoon (cold surges) played an important role in temperature changes.
•A dual-mode electronic skin was obtained within the same sensing textile.•The textile can precisely perform temperature detection and pressure perception.•It provides a new conceptual design for the ...next-generation wearable devices.
Flexible electronic skin is highly desired to realize the real-time tactile sensing and smart health assessment for human beings. Nevertheless, it is still a huge challenge to develop multifunctional electronic skin for human activity monitoring and body temperature detection in a single device without sensory interference. Here, a dual-mode electronic skin was obtained by vertically integrating the pressure sensing layer and temperature sensing layer within the same textile. The textile is composed of piezoelectric polyvinylidene fluoride nanofibrous membrane doped with zinc oxide nanoparticles (PVDF/ZnO NFM) and flexible thermal-resistance carbon nanofibers (CNFs). This all-in-one electronic skin textile can precisely perform pressure perception and temperature detection. For pressure sensing, a high sensitivity of 15.75 mV/kPa and 52.09 mV/kPa can be acquired within the pressure range of 4.9–25 kPa and 25–45 kPa, separately. In addition, it presents a temperature resolution of 0.381% per centigrade with a wide detection range of 25 °C to 100 °C. The electronic skin textile can perform multiple functions of ambient temperature detection, expiratory air temperature monitoring, external pressure perception, human pulse capture, and tactile spatial mapping with excellent sensing capacities. This study provides a new conceptual design for the next-generation wearable electronic skin.
Previous studies have shown that single-frequency microwave radiation can lead to cognitive decline in rats. However, few studies have focused on the combined effects of irradiation with different ...frequencies of microwaves. Our research aimed to investigate the effects of 1.5 GHz and 4.3 GHz microwave radiation, singly and in combination, on cognitive function and hippocampal tissue structure in rats. A total of 140 male Wistar rats were randomly divided into 4 groups: the S group (sham radiation group), L10 group (10 mW/cm
1.5 GHz group), C10 group (10 mW/cm
4.3 GHz band group) and LC10 group (10 mW/cm
1.5 and 4.3 GHz multi-frequency radiation group). For 1-28 days after microwave radiation, we analyzed the average escape latency for the Morris water maze task, electroencephalograms, change in hippocampal tissue structure and ultrastructure, content of the Nissl body in the hippocampus, and activities of lactate dehydrogenase and succinate dehydrogenase. Compared to the S group, all exposure groups showed varying degrees of learning and memory decline and hippocampal structural damage. The results showed that 1.5 GHz and 4.3 GHz microwave radiation was able to induce cognitive impairment and hippocampal tissue damage in rats and combined radiation with both frequencies caused more serious injuries, but none of these damaging effects varied with microwave frequency.
Triboelectric electronic skin has attracted increasing attention in recent years by virtue of the self-powered feature. Complex and harsh technologies are extensively used to create high specific ...surface area to improve the sensitivity of tactile sensing. The fabrication of hierarchical micro or nano structures with efficient and facile strategy remains a tough task. Besides, rarely any progress has been reported to consider the problem of bacterial growth for long time contact of the electronic skin with the human body. Here we report a flexible, transparent, and antibacterial triboelectric electronic skin for sensitive tactile sensing. Inspired by the microstructure of rose petal, a special “replication” method is developed to prepare the sensing layer with uniform and hierarchical nano-in-micro structure, avoiding the diversity and heterogeneity of the rose petal structure. When combined with a fiber-based conductive network and an antibacterial substrate, this highly shape adaptive electronic skin can be attached conformably on any curved surface and allow the functions of distance resolution, multi-tactile sensing, and trajectory recognition in real-time. The work presents a significant advance towards multifunctional electronic skin with excellent practicability.
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A transparent and antibacterial electronic skin is designed for sensitive tactile sensing. This electronic skin can be attached conformably on any curved surface and allow the functions of distance resolution, multi-tactile sensing, and trajectory recognition.
•A transparent and antibacterial electronic skin with good flexibility is designed for sensitive tactile sensing.•Pressure sensitivity approaches 71.52 mV kPa−1 and 10.87 mV kPa−1 in the sensing range of 0–75 kPa and 75–250 kPa, respectively.•This shape adaptive electronic skin can be attached conformably on any curved surface to realize multi-functional applications.
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•MC-LR entered HT-22 cells in a concentration-dependent pattern.•MC-LR exposure induced oxidative stress in HT-22 cells.•MC-LR exposure induced mitochondrial fragmentation in HT-22 ...cells.•MC-LR exposure could induce apoptotic way of HT-22 cells death.•MC-LR exposure induced mitochondrial fragmentation in hippocampus of mice and neurodegeneration.
Microcystin–leucine–arginine (MC-LR) can cross the blood–brain barrier (BBB) and demonstrate potent acute hippocampal neurotoxicity. Chronic exposure to MC-LR has been confirmed to cause learning and memory deficits in mice, but the potential molecular mechanism of MC-LR-caused neurotoxicity is still unclear. In this research, we observed that MC-LR induced oxidative stress, mitochondrial fission and apoptosis in HT-22 hippocampal neurons. Moreover, further studies identified that MC-LR induced mitochondrial fragmentation via activating Dynamin-related protein 1 (Drp1) and Mitochondrial fission factor (Mff), contributing to apoptosis of hippocampal neuronal cells. The observed effects were associated with increased intracellular Ca2+ and reduced activity of protein phosphatases 2A (PP2A) as results of MC-LR exposure in hippocampal neuron cells. Ca2+ activates CaMK II and Akt to enhance phosphorylation of Drp1 at Ser616 residue. Inhibition of PP2A activity increased AMPK activity to mediate phosphorylation of Mff. Our data proved that MC-LR can cause mitochondrial fragmentation in hippocampal neurons, which provides novel perception to explore the underlying molecular mechanism associated with MC-LR-induced neurotoxicity and Alzheimer’s disease-like changes.
Hepatitis B virus (HBV) reactivation is a serious complication for patients with lymphoma treated with rituximab-containing chemotherapies, despite lamivudine prophylaxis treatment. An optimal ...prophylactic antiviral protocol has not been determined.
To compare the efficacy of entecavir and lamivudine in preventing HBV reactivation in patients seropositive for the hepatitis B surface antigen with untreated diffuse large B-cell lymphoma receiving chemotherapy treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).
Randomized, open-label, phase 3 study conducted from February 2008 through December 2012 at 10 medical centers in China. This study was a substudy of a parent study designed to compare a 3-week with a 2-week R-CHOP chemotherapy regimen for untreated diffuse large B-cell lymphoma. Patients enrolled in the parent study who were seropositive for the hepatitis B surface antigen and had normal liver function, serum HBV DNA levels of less than 103 copies/mL, and no prior antiviral therapy were randomized to entecavir (n = 61) or lamivudine (n = 60).
Daily entecavir (0.5 mg) or lamivudine (100 mg) beginning 1 week before the initiation of R-CHOP treatment to 6 months after completion of chemotherapy.
The primary efficacy end point was the incidence of HBV-related hepatitis. The secondary end points included rates of HBV reactivation, chemotherapy disruption due to hepatitis, and treatment-related adverse events.
There were 121 patients randomly assigned to receive entecavir (n = 61) or lamivudine (n = 60). The date of last patient follow-up was May 25, 2013. The rates were significantly lower for the entecavir group vs the lamivudine group for HBV-related hepatitis (0% vs 13.3%, respectively; difference between groups, 13.3% 95% CI, 4.7% to 21.9%; P = .003), HBV reactivation (6.6% vs 30%; difference, 23.4% 95% CI, 10.2% to 36.6%; P = .001), and chemotherapy disruption (1.6% vs 18.3%; difference, 16.7% 95% CI, 6.4% to 27.0%; P = .002). Of the 61 patients in the entecavir group, 15 (24.6%) experienced treatment-related adverse events. Of 60 patients in the lamivudine group, 18 (30%) experienced treatment-related adverse events (difference between entecavir and lamivudine groups, 5.4% 95% CI, -10.5% to 21.3%; P = .50).
Among patients seropositive for the hepatitis B surface antigen with diffuse large B-cell lymphoma undergoing R-CHOP chemotherapy, the addition of entecavir compared with lamivudine resulted in a lower incidence of HBV-related hepatitis and HBV reactivation. If replicated, these findings support the use of entecavir in these patients.
clinicaltrials.gov Identifier: NCT01793844; Chinese Clinical Trial Registry Identifier: CTR-TRC-11001687.
Ferroptosis is a new type of programmed cell death that is different from apoptosis, cell necrosis, and autophagy, which might be involved in development of sepsis. However, the potential role of ...ferroptosis-related genes (FRGs) in sepsis remained unclear. We identified 41 ferroptosis-related differential expression genes by weighted correlation network and differential expression analysis. The hub module of 41 ferroptosis-related differential expression genes in the protein-protein interaction network was identified. Next, we estimated diagnostic values of genes in hub modules. TLR4, WIPI1, and GABARAPL2 with high diagnostic value were selected for construction of risk prognostic model. The high risk-scored patients had significantly higher mortality than the patients with low risk scores in discovery dataset. Furthermore, the risk scores of nonsurvivor were higher than those of survivor in validation dataset. It suggested that risk score was significantly correlated to prognosis in sepsis. Then, we constructed a nomogram for improving the clinical applicability of risk signature. Moreover, the risk score was significantly associated with immune infiltration in sepsis. Our comprehensive analysis of FRGs in sepsis demonstrated the potential roles in diagnosis, prognosis, and immune infiltration. This work may benefit in understanding FRGs in sepsis and pave a new path for diagnosis and assessment of prognosis.
Perovskite solar cells have emerged as one of the most promising thin-film photovoltaic (PV) technologies and have made a strong debut in the PV field. However, they still face difficulties with ...up-scaling to module-level devices and long-term stability issue. Here, we report the use of a room-temperature nonvolatile Lewis base additive, diphenyl sulfoxide(DPSO), in formamidinium-cesium (FACs) perovskite precursor solution to enhance the nucleation barrier and stabilize the wet precursor film for the scalable fabrication of uniform, large-area FACs perovskite films. With a parallel-interconnected module design, the resultant solar module realized a certified quasi-stabilized efficiency of 16.63% with an active area of 20.77 cm
The encapsulated modules maintained 97 and 95% of their initial efficiencies after 10,000 and 1187 hours under day/night cycling and 1-sun equivalent white-light light-emitting diode array illumination with maximum power point tracking at 50°C, respectively.
Crohn’s disease (CD), a subtype of inflammatory bowel disease (IBD), causes chronic gastrointestinal tract inflammation. Thirty percent of patients do not respond to anti-tumor necrosis factor (TNF) ...therapy. Sialylation is involved in the pathogenesis of IBD. We aimed to identify potential biomarkers for diagnosing CD and predicting anti-TNF medication outcomes in CD. Three potential biomarkers (SERPINB2, TFPI2, and SLC9B2) were screened using bioinformatics analysis and machine learning based on sialylation-related genes. Moreover, the combined model of SERPINB2, TFPI2, and SLC9B2 showed excellent diagnostic value in both the training and validation cohorts. Importantly, a Sial-score was constructed based on the expression of SERPINB2, TFPI2, and SLC9B2. The Sial-low group showed a lower level of immune infiltration than the Sial-high group. Anti-TNF therapy was effective for 94.4% of patients in the Sial-low group but only 15.8% in the Sial-high group. The Sial-score had an outstanding ability to predict and distinguish between responders and non-responders. Our comprehensive analysis indicates that SERPINB2, TFPI2, and SLC9B2 play essential roles in pathogenesis and anti-TNF therapy resistance in CD. Furthermore, it may provide novel concepts for customizing treatment for individual patients with CD.
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