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Photodynamic therapy (PDT) has been extensively investigated for decades for tumor treatment because of its non-invasiveness, spatiotemporal selectivity, lower side-effects, and immune activation ability. It can be a promising treatment modality in several medical fields, including oncology, immunology, urology, dermatology, ophthalmology, cardiology, pneumology, and dentistry. Nevertheless, the clinical application of PDT is largely restricted by the drawbacks of traditional photosensitizers, limited tissue penetrability of light, inefficient induction of tumor cell death, tumor resistance to the therapy, and the severe pain induced by the therapy. Recently, various photosensitizer formulations and therapy strategies have been developed to overcome these barriers. Significantly, the introduction of nanomaterials in PDT, as carriers or photosensitizers, may overcome the drawbacks of traditional photosensitizers. Based on this, nanocomposites excited by various light sources are applied in the PDT of deep-seated tumors. Modulation of cell death pathways with co-delivered reagents promotes PDT induced tumor cell death. Relief of tumor resistance to PDT with combined therapy strategies further promotes tumor inhibition. Also, the optimization of photosensitizer formulations and therapy procedures reduces pain in PDT. Here, a systematic summary of recent advances in the fabrication of photosensitizers and the design of therapy strategies to overcome barriers in PDT is presented. Several aspects important for the clinical application of PDT in cancer treatment are also discussed. [ABSTRACT FROM AUTHOR]

During photothermal therapy (PTT), hyperthermia up to 50 °C is required for efficient induction of tumor cell death. Additional increases in temperature can lead to severe damage to adjacent tissues. Conversely, insufficient heating of deep‐seated tumor tissues results in tumor recurrence. Sensitization of tumor cells to PTT may solve this problem. Stress granules (SGs) function in integration of various internal and external stresses to regulate cell viability. However, the role of SGs in PTT is currently unknown. Here, with black phosphorus (BP) nanosheets as photothermal agents, it is found that SGs are induced in tumor by PTT through eukaryotic initiation factor 2α‐dependent pathway and participate in tumor resistance to PTT. To modulate SG formation in tumor, a BP hydrogel is prepared for tumor‐specific delivery and near‐infrared (NIR) light‐controlled release of the SG inhibitor Emetine. Upon NIR‐light irradiation, photothermal conversion of BP nanosheets enables PTT of tumor. Meanwhile, light‐controlled release of Emetine in tumor tissues effectively inhibits PTT‐induced SG formation and sensitizes tumor to PTT, resulting in enhanced tumor inhibition. These results reveal the role of SGs in PTT and present a novel strategy for tumor sensitization to enhance the therapeutic efficacy and reduce the side effects of PTT. [ABSTRACT FROM AUTHOR]

Nanomaterials‐based photothermal therapy (PTT) could efficiently eliminate cancer cells in a noninvasive manner. However, nanoscale photosensitizers still suffer from several drawbacks, limiting them from being an ideal PTT approach against cancer. These include unfavorable biodistribution and poor retention in tumor tissue. In this study, acid‐activatable smart self‐assembly of black phosphorous (BP) and polyoxometalates (POM) is carried out to yield POM@BP with prolonged tumor retention and enhanced efficacy of PTT. The as‐rationally designed POM@BP photosensitizers in acidic tumor microenvironments self‐assemble into nanoparticles with larger sizes, remarkably increasing the light absorption ability of BP nanosheets in PTT of cancer. The as‐obtained POM@BP endows prolonged retention and enhances the photothermal response in tumor tissue by smart self‐assembly of BP into larger nanoparticles. In summary, the proposed potent approach for the rational design and tailor photosensitizer for cancer treatment looks very promising for future scientific breakthroughs in nanomedicine. [ABSTRACT FROM AUTHOR]

The Quaternary sediments in the Yangtze delta are loose and lack precise stratification marks in the lithology. Moreover, due to the limitations of dating methods, it is difficult for Quaternary cores to deliver accurate age constraints. Thus, it is a challenge to establish the Quaternary stratigraphic framework. Gravity core LZK1 was drilled on Hengsha Island, Shanghai, in the Yangtze delta, in 2012. The core was terminated at 403.83 m below the local land surface, the uppermost 291.2 m comprising a thick sequence of Quaternary sediments. This study investigated the stratigraphic subdivision and paleoenvironmental change of the Quaternary sediments. From bottom to top, the Quaternary stratigraphic sequence can be subdivided into the lower Pleistocene Anting Formation, Middle Pleistocene Jiading Formation, Upper Pleistocene Chuansha Formation and Nanhui Formation, Holocene Loutang Formation, Shanghai Formation, and Rudong Formation. According to this study, the Hengsha Island area was dominated by a freshwater lacustrine environment during the early Pleistocene, an alternation of shallow lake and shore lake environment during the Middle Pleistocene, a delta plain to lagoonal environment during the early Upper Pleistocene, a fluvial channel to floodplain environment from the LGM (Last Glacial Maximum) to the end of the Upper Pleistocene, and a delta environment during the Holocene. [ABSTRACT FROM AUTHOR]

Epithelial cells play a crucial role in asthma, contributing to chronic inflammation and airway hyperresponsiveness. m6A modification, which involves key proteins such as the demethylase fat mass and obesity‐associated protein (FTO), is crucial in the regulation of various diseases, including asthma. However, the role of FTO in epithelial cells and the development of asthma remains unclear. In this study, we investigated the demethylase activity of FTO using a small‐molecule inhibitor FB23 in epithelial cells and allergic inflammation in vivo and in vitro. We examined the FTO‐regulated transcriptome‐wide m6A profiling by methylated RNA immunoprecipitation sequencing (MeRIP‐seq) and RNA‐seq under FB23 treatment and allergic inflammation conditions. Immunofluorescence staining was performed to assess the tissue‐specific expression of FTO in asthmatic bronchial mucosa. We demonstrated that FB23 alleviated allergic inflammation in IL‐4/IL‐13‐treated epithelial cells and house dust mite (HDM)‐induced allergic airway inflammation mouse model. The demethylase activity of FTO contributed to the regulation of TNF‐α signaling via NF‐κB and epithelial–mesenchymal transition‐related pathways under allergic inflammation conditions in epithelial cells. FTO was expressed in epithelial, submucosal gland, and smooth muscle cells in human bronchial mucosa. In conclusion, FB23‐induced inhibition of FTO alleviates allergic inflammation in epithelial cells and HDM‐induced mice, potentially through diverse cellular processes and epithelial–mesenchymal transition signaling pathways, suggesting that FTO is a potential therapeutic target in asthma management. [ABSTRACT FROM AUTHOR]

Temperature change affects human health and asthma.[[1]] Serum IgE concentrations were shown to be significantly lower in experimental asthmatic mice treated at thermoneutral (30°C) than those treated at standard housing temperature (20°C).[3] A recent study found that the exosomes of mast cells (MC) can compete with MC to bind serum IgE and reduce asthma symptoms.[4] This study aimed to investigate whether temperature directly affects MC-derived exosomes in mediating the high-affinity receptor for IgE (Fc RI)-dependent MC activation and ovalbumin-induced asthma. In summary, this study provides evidence of the temperature-dependent regulation of MC-derived exosomes through regulation of Rab3a expression, which protected against Fc RI-dependent MC activation in vitro and experimental asthma in vivo. Temperature regulates Rab3a and mast cell-derived exosomal Fc RI to inhibit mast cell activation. [Extracted from the article]

Background: Blood cell properties effectively reflect immune status. Basophil and CD8+ CD27+ T cell levels are correlated with narcolepsy, but their causal association is unclear. This study aims to evaluate the causality between blood cell count and narcolepsy risk at the genetic level. Methods: Two-sample Mendelian randomization (MR) analyses were performed on 35 published blood cell properties, using genome-wide association study (GWAS) datasets and one published GWAS dataset of narcolepsy, to explore causality between blood cell count and narcolepsy risk. Inverse variance weighted, MR-Egger, and weighted median approaches were employed for the MR analysis, odds ratio (OR) calculations, and heterogeneity tests of single nucleotide polymorphisms were conducted with the TwoSampleMR package in R. Multivariable Mendelian randomization (MVMR) was used to adjust the analysis further and eliminate the mediation effect between exposures. Results: Basophil counts, total basophil neutrophil counts, total neutrophil eosinophil counts, granulocyte counts, and myeloid white cell counts showed inverse associations with narcolepsy risk based on the two-sample MR analysis. MVMR confirmed that only basophil counts were significantly associated with narcolepsy risk for the blood cell properties tested (OR = 0.23, 95% confidence interval 0.08–0.62; p = 0.004, power = 99.99%). Each standard deviation increase in basophil count (0.03 per nL), compared to the median level (0.04 per nL), decreased narcolepsy risk by 77%. Conclusion: Higher white blood cell counts, especially basophil counts, are protective factors for narcolepsy. Basophil counts has great potential to be used as a new biomarker to shorten diagnostic delay and to monitor the therapeutic effects of treatments for narcolepsy. [ABSTRACT FROM AUTHOR]

Eupatorium adenophorum is a noxious invasive weed that is distributed throughout subtropical areas worldwide. Enemy release may be at least one of the reasons underlying its success as an invader. In this study, we observed damage to the epidermis, cortex, phloem, cambium, and xylem tissues of roots and stems around the root collar of E. adenophorum growing in an experimental field in Yunnan Province, southwest China. The damage was caused by Dorylus orientalis, a polyphagous ant feeding on the weed and resulted in the death of the plants by interrupting nutrient exchange between shoots and roots. This ant showed selectivity for the invader to some extent. The finding of D. orientalis and other native enemies indicate that E. adenophorum may gradually naturalize in introduced landscapes. In addition, this ant may have potential for use as a biocontrol agent against the invader. [ABSTRACT FROM AUTHOR]

Abstract The Yangtze (Changjiang) mega-delta, China, has a high risk of coastal erosion owing to the recent high rate of relative sea-level rise and reduced sediment supply. The study of the Holocene evolution of the delta can provide information about its response to rapid sea-level rise and changes in sediment supply caused by climate or human activity, although this has yet to be fully explored because of the lack of integrated studies using age-constrained sedimentary records. Here we document stratigraphic architecture and morphological changes over the last 11,700 years and estimate the amount of sediment trapped in the delta region on a millennial scale using a dataset of 344 sediment cores, 658 radiocarbon and 28 optically stimulated luminescence (OSL) ages (of which we obtained 64 cores, 345 radiocarbon and 28 OSL ages, and the others we sourced from the literature). Using this dataset we present the temporal and spatial morphodynamic evolution of the entire Yangtze River mouth from its early Holocene transgressive estuary to a mid- to late-Holocene regressive delta, making it possible to produce a quantitative and sequential analysis of sediment deposition. A destructive phase of the river mouth region was identified at 10 to 8 cal. kyr BP, including significant coastal erosion of tidal flats and troughs within the estuary and of tidal ridge-and-trough topography offshore; these resulted from the reshaping of the river mouth morphology caused by rapid sea-level rise at that time. As a result, the rate of sediment trapping at the river mouth declined from an average of 224 Mt yr−1 at 11.7–10 cal. kyr BP to 137 Mt yr−1 between 10 and 8 cal. kyr BP. Since delta initiation 8000 years ago, a retreat of the subaqueous delta occurred and the sediment trapping rate declined from 151 Mt yr−1 at 8–6 cal. kyr BP to 99–113 Mt yr−1 between 6 and 2 cal. kyr BP, caused by the reduction in sediment supply linked to summer monsoon weakening ~6000 years ago. In the last 2000 years the sediment trapping rate has increased to 162 Mt yr−1 due to intensified human activity. The present-day level of sedimentation in delta (49 Mt yr−1 in 2003–2011), after the completion of the Three Gorges Dam, is far lower than the 'natural' range in the Holocene. We thus infer a potential for system regime shift in terms of coastal erosion and a transition to a new equilibrium in delta morphology in the near future. [ABSTRACT FROM AUTHOR]

Water mass variations in the early Yangtze estuary during the postglacial transgression have not been thoroughly studied. This research gap has hampered the understanding of riverine sediment ‘source to sink’ processes in this region. This study presents the results of integrated analyses of grain size, pollen-spore-dinocyst assemblages, benthic foraminifera and ostracods from a borehole, H5, located at the northern Yangtze mouth, to investigate the complete sedimentary history and associated variations in coastal currents since 19 ka. At the core site, a fluvial floodplain developed from ca. 19–11.3 ka, whereas an estuary to shelf to subaqueous delta prevailed during most of the Holocene. Based on changes in the dominant microfauna species, which mainly consist of Chinese coastal water species, two main current patterns were distinguished: one dominated by the Yellow Sea coastal current (YSCC) before ca. 7.9 ka and one dominated by the Yangtze dilute water (YDW). Marked increases in open-sea saline species, including Bolivina robusta , and stratified water dinocyst species Spiniferites ramous and Spiniferites spp. were interpreted as the encroachment of the Taiwan warm current (TWWC) and the intensification of the YDW, respectively. The YDW and TWWC penetrated the area dominated by the YSCC before 7.9 ka, which was likely related to intensity variations in the Kuroshio Current (KC) and Asian summer monsoon (ASM). Under maximal ASM and KC conditions, upwelling resulted from the intensified intrusion of the TWWC, as indicated by the blooming of Bolivina robusta from 7.9–6.3 ka. After ca. 6 ka, the YDW clearly weakened due to the decline of the ASM, yet the Yangtze plume prevailed due to the rapid seaward migration of the Yangtze mouth. Considering the dominance of the YSCC in the early Holocene, Yellow River-derived sediment likely represented a large proportion of the material delivered to the early Yangtze estuary. [ABSTRACT FROM AUTHOR]

β-Catenin, the core element of the Wnt/β-catenin pathway, is a multifunctional and evolutionarily conserved protein which performs essential roles in a variety of developmental and homeostatic processes. Despite its crucial roles, the mechanisms that control its context-specific functions in time and space remain largely unknown. The Wnt/β-catenin pathway has been extensively studied in planarians, flatworms with the ability to regenerate and remodel the whole body, providing a ‘whole animal’ developmental framework to approach this question. Here we identify a C-terminally truncated β-catenin (β-catenin4), generated by gene duplication, that is required for planarian photoreceptor cell specification. Our results indicate that the role of β-catenin4 is to modulate the activity of β-catenin1, the planarian β-catenin involved in Wnt signal transduction in the nucleus, mediated by the transcription factor TCF-2. This inhibitory form of β-catenin, expressed in specific cell types, would provide a novel mechanism to modulate nuclear β-catenin signaling levels. Genomic searches and in vitro analysis suggest that the existence of a C-terminally truncated form of β-catenin could be an evolutionarily conserved mechanism to achieve a fine-tuned regulation of Wnt/β-catenin signaling in specific cellular contexts. [ABSTRACT FROM AUTHOR]

Although much evidence points to a Late Mesozoic large silicic igneous province in SE South China (SESC), diverse Andean-type and non-Andean-type models have been proposed to explain its origins. New age, isotope, and trace element data on zircon from wells in East China Sea (ECS) and offshore-onshore tectonomagmatic comparisons allow reassessment of the geodynamic interactions (ca. 200–86 Ma) between the Cathaysia-based arc and intraplate activity from a large mantle wedge framework. In region, remnants of the West ECS arc, Ryukyu-Taiwan mélange, and SESC intraplate define a trench–arc–intraplate architecture. Changes in arc magmatic states (flare-ups and lulls; high U/Yb, low T , variable εHf (t)) permit identification of a cycle of arc initiation, thickening, decline, arc-root removal, and arc migration, highly correlating with changes of Izanagi subduction beneath East Asia. Voluminous intraplate silicic magmatism operated in response to the slab stagnation dynamics: slab dehydration, lithospheric delamination, fluid-fluxed crustal anataxis, and crustal–mantle melt hybridization in crustal hot zones. Such geodynamic scenarios, unlike an Andean-type continental margin, instead result in the construction of a Late Mesozoic Cathaysian-type active continental margin. • A model of non-Andean-type Cathaysian continental margin is proposed based on offshore-onshore tectonomagmatic correlations. • The model reveals a link between the arc, intraplate, and slab subduction systems from the large mantle wedge perspective. • Drilled data confirm the western East China Sea and Cathaysia domains sharing a unified Paleoproterozoic Cathaysian basement. [ABSTRACT FROM AUTHOR]

[Display omitted] • Providing brief description of the pathogenesis of Alzheimer's disease and limitation of traditional treatments. • Presenting the representative photochemical principles of ROS generation and mechanisms of photodynamic AD therapy. • Summarizing the state-of-the-art advances in this field, ranging from molecular catalysis to photo-nanomedicine. • Discussing challenges and outlooking the future direction of photodynamic therapy for Alzheimer's disease. Alzheimer's disease (AD) is a major form of dementia, closely associated with the filamentous assembly of amyloid-β (Aβ) and Tau protein in the brain, which can cause memory and learning deficits. Over the world, developing available AD drugs has been considered as one of the major goals in AD research not only for pharmacology but also for chemistry and biomedicine. However, current strategies to treat AD disease are mainly based on chemotherapy, while very limited AD drugs have been approved by FDA. As an alternative, recently great efforts have been dedicated to employing the photodynamic therapy (PDT) approach to intervene the AD-related protein (e.g., amyloid-β and Tau) aggregations via photon-triggered reactive oxygen species generation. Although photodynamic AD therapy remains in its infancy and many concerns need to be dissolved, it is still believed to serve as a promising alternative to reverse the dilemma of Alzheimer's treatment. With this hope in mind, here we aim to draw a blueprint for this emerging area. In this review, we not only summarize the photochemical principles of AD therapy and the states-of-the-art photodynamic molecules/photo-nanomedicine that are capable of regulating the AD pathological proteins, but also, also the most important, overview the pros and cons of photodynamic AD therapy and give some suggestions for overcoming the challenges in this field. It is our hope that the progress made to date, as summarized in this paper, can inspire future efforts to seek out more promising photochemical approaches, better fitting the clinical requirements of AD therapy. [ABSTRACT FROM AUTHOR]

Abstract: Planarians can regenerate their head within days. This process depends on the direction of adult stem cells to wound sites and the orchestration of their progenitors to commit to appropriate lineages and to arrange into patterned tissues. We identified a zinc finger transcription factor, Smed-ZicA, as a downstream target of Smed-FoxD, a Forkhead transcription factor required for head regeneration. Smed-zicA and Smed-FoxD are co-expressed with the Wnt inhibitor notum and the Activin inhibitor follistatin in a cluster of cells at the anterior-most tip of the regenerating head – the anterior regeneration pole – and in surrounding stem cell progeny. Depletion of Smed-zicA and Smed-FoxD by RNAi abolishes notum and follistatin expression at the pole and inhibits head formation downstream of initial polarity decisions. We suggest a model in which ZicA and FoxD transcription factors synergize to control the formation of Notum- and Follistatin-producing anterior pole cells. Pole formation might constitute an early step in regeneration, resulting in a signaling center that orchestrates cellular events in the growing tissue. [Copyright &y& Elsevier]

To examine the applicability of C/N and organic carbon stable isotope (δ13C) in studies of the Holocene sea level and freshwater discharge in the large river mouth of Yangtze, we observed the distribution of carbon, nitrogen and δ13C in a late-Quaternary core (ZK9) collected from the present subaqueous delta. We also collected published data of the two proxies for the suspended particulate matter (SPM) and surficial sediments from the lower Yangtze River to the adjacent East China Sea. The results show that the estuarine front is an important boundary for terrestrial and marine contribution of the organic component in the modern sedimentary environment. In the core ZK9, sediments deposited during c. 13–9 cal. ka BP are characterized by high values of TOC (0.54–1.16%), CaCO3 (0.35% on average), and C/N (>12), which reflect an inner tidal estuarine environment dominated by C3 terrestrial organic carbon input. During c. 9–0.7 cal. ka BP, both TOC content (0.57% on average) and C/N ratio (<10) decrease remarkably while TN increases, indicating a lower estuarine or shallow marine environment. An abrupt sea level rise from c. 9 cal. ka BP resulted in a deeper water environment and reduced terrestrial input at the core location. The low δ13C values (−24.23‰ on average) before c. 6 cal. ka BP reflect a dominantly terrestrial source of organic matter associated with increased freshwater discharge into the estuary during that time. The sediments since c. 6 cal. ka BP are characterized by increasing δ13C up to −24.1 to −23.39‰, reflecting more contribution from marine algae as freshwater discharge fell. We suggest that in the Yangtze River mouth the C/N ratio indicates an abrupt sea level rise at c. 9 cal. ka BP, while δ13C is more useful in reflecting freshwater discharge. [ABSTRACT FROM AUTHOR]

Abstract: AMS 14C ages of post-glacial core sediments from the subaqueous Yangtze delta, along with sedimentary structures and distributions of grain size, pollen spores, and dinoflagellate cysts, show an estuarine depositional system from 13 to 8.4 cal ka BP and a deltaic system from 5.9 cal ka BP to the present. The estuarine system consists of intertidal to subtidal flat, estuarine, and estuarine-front facies, characterized by sand–mud couplets and a high sedimentation rate. The deltaic system includes nearshore shelf and prodelta mud featured by lower sedimentation rate, markedly fewer coastal wetland herbaceous pollens, and more dinoflagellate cysts. We explain the extremely high sedimentation rate during 9.2–8.4 cal ka BP at the study site as a result of rapid sea-level rise, high sediment load due to the unstable monsoonal climate, and subaqueous decrease of elevation from inner to outer estuary. A depositional hiatus occurred during 8.2–5.9 cal ka BP, the transition from estuarine to deltaic system, caused possibly by a shortage of sediment supply resulting from delta initiation in paleo-incised Yangtze valley and strong tidal or storm-related reworking in offshore areas. The subsequent development of deltaic system at the study site indicates accelerated progradation of Yangtze delta post-5.9 cal ka BP. [Copyright &y& Elsevier]