Mussel-inspired antibacterial sponge for highly efficient water purification and sterilization.

With the current expansion of urban areas and industrial development, the increasing discharge of wastewater containing bacteria poses a threat to human health. Although substantial advancements have been made in antibacterial materials, there is still a need for an efficient method that can thoroughly remove bacteria through sterilization and adsorption during wastewater treatment. Here, we report a mussel-inspired antibacterial sponge with outstanding antibacterial efficiency exceeding 95% and a high removal ratio of the bacterial corpses for water purification after contacting for 30 min. The high-efficient antibacterial performance is attributed to the stable releasing property of Ag+ and the charge interaction with quaternary amine salts. Combining the key features, including high-efficient, synergistic mechanism, and corpse capture, the antibacterial sponge shows excellent disinfection effects. This study provides a new method for water purification without bacterial residue.

N,Si co-doped GQDs: Facile green preparation and application in visual identifying dihydroxybenzene isomers and selective quantification of catechol, hydroquinone and antioxidants.

A green economical procedure for preparing N,Si co-doped graphene quantum dots (N,Si-GQDs) using waste toners and ethylene diamine was reported, which not only minimizes waste and promotes recycling but also offers an alternative method for producing N,Si-GQDs. At a pH of 8.5, hydroquinone and catechol underwent oxidation in the presence of air, resulting in the formation of diquinones, specifically p-phenyldiquinone and o-phenyldiquinone. Resorcinol, on the other hand, was converted into monoquinone. The interaction between diquinones and N,Si-GQDs caused a linear fluorescence quenching effect when catechol and hydroquinone were present. However, this effect was minimal in the case of resorcinol. Furthermore, the antioxidants glutathione (GSH) and ascorbic acid (AA) were observed to disrupt the redox equilibrium of catechol and o-phenyldiquinone, leading to the activation of fluorescence. Conversely, hydroquinone and p-phenyldiquinone, due to the highly stable and symmetrical structure of p-phenyldiquinone, did not exhibit this fluorescence activation. Based on the described "Off-On" sensor system, it was possible to visually identify dihydroxybenzene isomers and selectively quantify catechol and hydroquinone in environmental samples, as well as GSH and AA in human serum. The method detection limits were 0.93, 1.35, 2.34, and 1.37 µM for catechol, hydroquinone, GSH, and AA, respectively. In conclusion, the presented procedure offers several advantages, including environmental friendliness, cost-effectiveness, and a means of recycling waste toners. It also demonstrates the successful synthesis of N,Si-GQDs, as well as the potential for their application in the "Off-On" sensor system for the detection and quantification of various analytes.

Self-healing electrical bioadhesive interface for electrophysiology recording.

Electrical bioadhesive interfaces (EBIs) are standing out in various applications, including medical diagnostics, prosthetic devices, rehabilitation, and human-machine interactions. Nonetheless, crafting a reliable and advanced EBI with comprehensive properties spanning electrochemical, electrical, mechanical, and self-healing capabilities remains a formidable challenge. Herein, we develop a self-healing EBI by thoughtfully integrating conducting polymer nanofibers and a typical bioadhesive within a robust hydrogel matrix. The accomplished EBI demonstrates extraordinary adhesion (lap shear strength of 197 kPa), exceptional electrical conductivity (2.18 S m-1), and outstanding self-healing performance. Taking advantage of these attributes, we integrated the EBI into flexible skin electrodes for surface electromyography (sEMG) signal recording from forearm muscles. The engineered skin electrodes exhibit robust adhesion to the skin even when sweating, rapid self-healing from damage, and seamless real-time signal recording with a higher signal-to-noise ratio (39 dB). Our EBI, along with its skin electrodes, offers a promising platform for tissue-device integration, health monitoring, and an array of bioelectronic applications.

Improved mammalian family phylogeny using gap-rare multiple sequence alignment: A timetree of extant placentals and marsupials.

The timing of mammalian diversification in relation to the Cretaceous-Paleogene (KPg) mass extinction continues to be a subject of substantial debate. Previous studies have either focused on limited taxonomic samples with available whole-genome data or relied on short sequence alignments coupled with extensive species samples. In the present study, we improved an existing dataset from the landmark study of Meredith et al. (2011) by filling in missing fragments and further generated another dataset containing 120 taxa and 98 exonic markers. Using these two datasets, we then constructed phylogenies for extant mammalian families, providing improved resolution of many conflicting relationships. Moreover, the timetrees generated, which were calibrated using appropriate molecular clock models and multiple fossil records, indicated that the interordinal diversification of placental mammals initiated before the Late Cretaceous period. Additionally, intraordinal diversification of both extant placental and marsupial lineages accelerated after the KPg boundary, supporting the hypothesis that the availability of numerous vacant ecological niches subsequent to the mass extinction event facilitated rapid diversification. Thus, our results support a scenario of placental radiation characterized by both basal cladogenesis and active interordinal divergences spanning from the Late Cretaceous into the Paleogene.

Ultrahigh pressure field: A friendly pathway for regulating the cellular adhesion and migration capacity of collagen.

Customized control of the biological response between the material matrix and cells is a crucial aspect in the development of the next generation of collagen materials. This study aims to investigate the effects of ultrahigh pressure treatment on the interaction between collagen and cells by subjecting bovine tendon collagen to different intensities of ultrahigh pressure field. The results indicate that ultrahigh pressure treatment alters the spatial folding of collagen, causing distortion of its triple helical conformation and exposing more free amino groups and hydrophobic regions. As a result, collagen's cell adhesion capability and ability to promote cell migration are significantly enhanced. Optimal cell adhesion and migration capabilities are observed in collagen samples treated at 500 MPa for 15 min. However, further increasing the intensity of the ultrahigh pressure treatment leads to severe damage to the triple-helical structure of collagen, along with re-aggregation of free amino groups and hydrophobic moieties, thereby reducing collagen's cell adhesion capability and ability to promote cell migration. Therefore, ultrahigh pressure treatment offers a promising method to effectively regulate collagen-cell adhesion and promote cell migration without the need for external components. This provides a potential means for the customized enhancement of collagen-based material interfaces.

No Incidence of Liver Cancer Was Observed in A Retrospective Study of Patients with Aristolochic Acid Nephropathy.

OBJECTIVE: To assess the risk of aristolochic acid (AA)-associated cancer in patients with AA nephropathy (AAN). METHODS: A retrospective study was conducted on patients diagnosed with AAN at Peking University First Hospital from January 1997 to December 2014. Long-term surveillance and follow-up data were analyzed to investigate the influence of different factors on the prevalence of cancer. The primary endpoint was the incidence of liver cancer, and the secondary endpoint was the incidence of urinary cancer during 1 year after taking AA-containing medication to 2014. RESULTS: A total of 337 patients diagnosed with AAN were included in this study. From the initiation of taking AA to the termination of follow-up, 39 patients were diagnosed with cancer. No cases of liver cancer were observed throughout the entire follow-up period, with urinary cancer being the predominant type (34/39, 87.17%). Logistic regression analysis showed that age, follow-up period, and diabetes were potential risk factors, however, the dosage of the drug was not significantly associated with urinary cancer. CONCLUSIONS: No cases of liver cancer were observed at the end of follow-up. However, a high prevalence of urinary cancer was observed in AAN patients. Establishing a direct causality between AA and HCC is challenging.

Regulation of forkhead box O transcription factor by insulin signaling pathway controls the reproductive diapause of the lady beetle, Coccinella septempunctata.

In biological control programs, knowledge about diapause regulation in natural enemy insects provides important insight for improving long-term storage, transportation, and field adoption of these biological control agents. As a natural predator of agricultural pests, the lady beetle Coccinella septempunctata has been commercially mass-cultured and widely employed in pest management. In some insects, insulin signaling, in conjunction with the downstream transcription factor Forkhead box O (FoxO), are master regulators of multiple physiological processes involved in diapause, but it is unclear whether insulin signaling and FoxO affect the diapause of C. septempunctata. In this study, we use a combination of approaches to demonstrate that insulin signaling and FoxO mediate the diapause response in C. septempunctata. In diapausing beetles, application of exogenous insulin and knocking down expression of CsFoxo with RNA interference (RNAi) both rescued beetles from developmental arrest. In non-diapausing beetles, knocking down expression of the insulin receptor (CsInR) with RNA interference (RNAi) arrested ovarian development and decreased juvenile hormone (JH) content to levels comparable to the diapause state. Taken together, these results suggest that a shutdown of insulin signaling prompts the activation of the downstream FoxO gene, leading to the diapause phenotype.

Selection and validation of optimal reference genes for RT-qPCR analyses in Aphidoletes aphidimyza Rondani (Diptera: Cecidomyiidae).

Aphidoletes aphidimyza is a predator that is an important biological agent used to control agricultural and forestry aphids. Although many studies have investigated its biological and ecological characteristics, few molecular studies have been reported. The current study was performed to identify suitable reference genes to facilitate future gene expression and function analyses via quantitative reverse transcription PCR. Eight reference genes glyceraldehyde-3-phosphate dehydrogenase (GAPDH), RPS13, RPL8, RPS3, α-Tub, ß-actin, RPL32, and elongation factor 1 alpha (EF1-α) were selected. Their expression levels were determined under four different experimental conditions (developmental stages, adult tissues, sugar treatment, and starvation treatment) using qRT-PCR technology. The stability was evaluated with five methods (Ct value, geNorm, NormFinder, BestKeeper, and RefFinder). The results showed that GAPDH, RPL32, and EF1-α were ranked as the best reference gene combinations for measuring gene expression levels among different developing stages and in various starvation treatments. RPL8 and RPS3 were recommended to normalize the gene expression levels among different adult tissues. RPL32, ß-actin, and EF1-α were recommended sugar-feeding conditions. To validate the utility of the selected reference pair, RPL8, and RPS3, we estimated the tissue-biased expression level of a chemosensory protein gene (AaphCSP1). As expected, AaphCSP1 is highly expressed in the antennae and lowly expressed in the abdomen. These findings will lay the foundation for future research on the molecular physiology and biochemistry of A. aphidimyza.

Energy Band Engineering Guided Design of Bidirectional Catalyst for Reversible Li-CO2 Batteries.

Li-CO2 batteries arouse great interest in the context of carbon neutralization, but their practicability is severely hindered by the sluggish CO2 redox reaction kinetics at the cathode, which brings about formidable challenges such as high overpotential and low Coulombic efficiency. For the complex multi-electron transfer process, the design of catalysts at the molecular or atomic level and the understanding of the relationship between electron state and performance are essential for the CO2 redox. However, little attention is paid to it. In this work, using Co3 S4 as a model system, density functional theory (DFT) calculations reveal that the adjusted d-band and p-band centers of Co3 S4 with the introduction of Cu and sulfur vacancies are hybridized between CO2 and Li species, respectively, which is conducive to the adsorption of reactants and the decomposition of Li2 CO3 , and the experimental results further verify the effectiveness of energy band engineering. As a result, a highly efficient bidirectional catalyst is produced and shows an ultra-small voltage gap of 0.73 V and marvelous Coulombic efficiency of 92.6%, surpassing those of previous catalysts under similar conditions. This work presents an effective catalyst design and affords new insight into the high-performance cathode catalyst materials for Li-CO2 batteries.

Distribution and association of antimicrobial resistance and virulence characteristics in Enterococcus spp. isolates from captive Asian elephants in China.

Enterococcus spp., as an opportunistic pathogen, are widely distributed in the environment and the gastrointestinal tracts of both humans and animals. Captive Asian elephants, popular animals at tourist attractions, have frequent contact with humans. However, there is limited information on whether captive Asian elephants can serve as a reservoir of antimicrobial resistance (AMR). The aim of this study was to characterize AMR, antibiotic resistance genes (ARGs), virulence-associated genes (VAGs), gelatinase activity, hemolysis activity, and biofilm formation of Enterococcus spp. isolated from captive Asian elephants, and to analyze the potential correlations among these factors. A total of 62 Enterococcus spp. strains were isolated from fecal samples of captive Asian elephants, comprising 17 Enterococcus hirae (27.4%), 12 Enterococcus faecalis (19.4%), 8 Enterococcus faecium (12.9%), 7 Enterococcus avium (11.3%), 7 Enterococcus mundtii (11.3%), and 11 other Enterococcus spp. (17.7%). Isolates exhibited high resistance to rifampin (51.6%) and streptomycin (37.1%). 50% of Enterococcus spp. isolates exhibited multidrug resistance (MDR), with all E. faecium strains demonstrating MDR. Additionally, nine ARGs were identified, with tet(M) (51.6%), erm(B) (24.2%), and cfr (21.0%) showing relatively higher detection rates. Biofilm formation, gelatinase activity, and α-hemolysin activity were observed in 79.0, 24.2, and 14.5% of the isolates, respectively. A total of 18 VAGs were detected, with gelE being the most prevalent (69.4%). Correlation analysis revealed 229 significant positive correlations and 12 significant negative correlations. The strongest intra-group correlations were observed among VAGs. Notably, we found that vancomycin resistance showed a significant positive correlation with ciprofloxacin resistance, cfr, and gelatinase activity, respectively. In conclusion, captive Asian elephants could serve as significant reservoirs for the dissemination of AMR to humans.

MdNup62 involved in salt and osmotic stress tolerance in apple.

Abiotic stress of plants has serious consequences on the development of the apple industry. Nuclear pore complexes (NPCs) control nucleoplasmic transport and play an important role in the regulation of plant abiotic stress response. However, the effects of NPCs on apple salt and osmotic stress responses have not been reported yet. In this study, we analyzed the expression and function of NUCLEOPORIN 62 (MdNup62), a component of apple NPC. MdNup62 expression was significantly increased by salt and mannitol (simulated osmotic stress) treatment. The MdNup62-overexpressing (OE) Arabidopsis and tomato lines exhibited significantly reduced salt stress tolerance, and MdNup62-OE Arabidopsis lines exhibited reduced osmotic stress tolerance. We further studied the function of HEAT SHOCK FACTOR A1d (MdHSFA1d), the interacting protein of MdNup62, in salt and osmotic stress tolerance. In contrast to MdNup62, MdHSFA1d-OE Arabidopsis lines showed significantly enhanced tolerance to salt and osmotic stress. Our findings suggest a possible interaction of MdNup62 with MdHSFA1d in the mediation of nuclear and cytoplasmic transport and the regulation of apple salt and osmotic stress tolerance. These results contribute to the understanding of the salt and osmotic stress response mechanism in apple.

N-Trifluoromethylselenophthalimide, an Electrophilic Trifluoromethylselenolation Reagent and Its Application for the Synthesis of 4-Trifluoromethylselenolated Isoxazoles.

A new electrophilic trifluoromethylselenolation reagent, N-trifluoromethylselenophthalimide (Phth-SeCF3), was developed. A strategy for the synthesis of 4-trifluoromethylselenolated isoxazoles through electrophilic trifluoromethylselenolation cyclization has been established by using Phth-SeCF3 as an electrophilic reagent. Moreover, this protocol has the features of broad substrate scope, good functional group tolerance, and high yields.

Vacuum ultraviolet irradiation for reduction of the toxicity of wastewater towards mammalian cells: Removal mechanism, changes in organic compounds, and toxicity alternatives.

Vacuum ultraviolet (VUV, 185 + 254 nm) irradiation performs well for oxidation of model pollutants. However, oxidation of pollutants does not necessarily lead to a reduction in toxicity. Currently, a comprehensive understanding of the effect of VUV irradiation on the toxicity of real wastewater is still lacking. In this study, the influence of VUV irradiation on the toxicity of secondary effluents to Chinese hamster ovary (CHO) cells was investigated. The induction units of endogenous reactive oxygen species (ROS) and 8-hydroxyguanosine (8-OHdG) in cells continuously decreased with prolonged irradiation time. After 36 min of irradiation, the cytotoxicity and the genotoxicity of the secondary effluents were reduced by 57%-63% and 56%-61%, respectively. The UV (254 nm), •OH, and other substances generated during the VUV irradiation directly drive toxicity changes of wastewater. The contribution of •OH generated during VUV irradiation to the reductions in cytotoxicity and genotoxicity of the secondary effluents reached 72%-78% and 77%-84%, respectively. Hydroxyl radicals generated during VUV irradiation played an important role in the detoxification. The relative signal intensity of dissolved organic carbon (DOC) > 500 Da was partially removed, whereas that of DOC < 500 Da was small changed. Since the content of DOC > 500 Da in the samples was much lower than that of DOC < 500 Da, the removal of total DOC was only 15.8%-20.0% after 36 min of irradiation. The UV254 values and the fluorescence intensity values for different molecular weights (MWs) were all reduced effectively by VUV irradiation. Electron-rich organic compounds of all MWs were all sensitive to VUV irradiation. There were mono-linear relationships between changes in chemical indexes and changes in cytotoxicity or genotoxicity. The total fluorescence intensity (Ex: 220-420 nm, Em: 280-560 nm) was identified as the best indicator of the reduction in toxicity.

[Spatiotemporal Distribution Characteristics of Air Pollution and Health Risks in Key Cities of China].

Based on the monitoring data of five pollutants in 168 key cities under air pollution prevention and control in China from 2015 to 2020, using the MAKESENS model and the aggregate risk index(ARI), this study quantitatively analyzed the spatial and temporal distribution characteristics of air pollution and health risks in China and the six urban agglomerations. The results showed that:① PM2.5 pollution was the most serious pollution in Chinese key cities. Only 15% of the cities' six-year average concentrations of PM2.5 reached the National Secondary Standard, followed by that of NO2; 77% of the cities' six-year average concentrations of NO2 reached the National Secondary Standard. The urban agglomerations of Beijing-Tianjin-Hebei and Fenwei plain had the most serious air pollution, and the six-year average concentrations of PM2.5, SO2, CO, and NO2 were higher than those of other urban agglomerations. ② The concentrations of PM2.5, SO2, CO, and NO2 in key cities of China showed a decreasing trend, whereas the concentration of O3 in other urban agglomerations showed an increasing trend, except in the Chengdu-Chongqing urban agglomeration. The concentration of SO2 in the urban agglomerations of Beijing-Tianjin-Hebei and Fenwei plain changed the most significantly. ③ The health risk of air pollution in the key cities of China generally showed a decreasing trend, with a sharp decline from 2017 to 2018, and the population exposed to extremely high risks dropped from 160 million to 32.54 million. The urban agglomeration in the middle reaches of the Yangtze River had the most significant decline in health risks, whereas the key cities in China faced higher health risks in spring and winter seasons. ④ The Beijing-Tianjin-Hebei and Fenwei plain urban agglomerations had the highest health risks, and the urban agglomeration in the middle reaches of the Yangtze River had the lowest; O3 gradually replaced PM2.5 as the main pollutant affecting the health risk. These results can provide a reference for evaluating the effectiveness of urban air pollution control in China during the 13th Five-Year Plan period.

Effects of Bacillus licheniformis on growth performance, immune and antioxidant functions, and intestinal microbiota of broilers.

Bacillus licheniformis (BL) has been widely regarded as an important growth promoter in recent years. However, its usage in animal industry still needs more foundations. The aim of our study was to study the effects of BL on the growth performance, immunity, oxidative function and intestinal flora of broilers. A total of 760 one-day-old yellow-feathered broilers were randomly divided into 4 groups with 10 replicates per group and 19 broilers per replicate. The broilers in the control group (CON) were fed with basal diet. The treatment groups were supplemented with 250 mg/kg (BL250), 500 mg/kg (BL500) and 750 mg/kg (BL750) BL in the basal diet for 70 d. Results showed that BL groups significantly increased the body weight (BW) and average daily gain (ADG), decreased average daily feed intake (ADFI) and feed conversion ratio (FCR). In addition, the spleen and bursa indexes were higher in the BL groups than that in the CON group at d 70. BL supplementation also markedly increased the levels of immunoglobulins Y (IgY), IgA and anti-inflammatory interleukin 10 (IL-10), reduced the levels of proinflammatory IL-1ß, tumor necrosis factor α (TNF-α) and IL-2 in the serum at 70 d in a concentration-dependent manner. Besides, BL addition significantly increased the levels of series antioxidant enzymes including total antioxidant capacity (T-AOC), glutathione peroxidase (GPX), superoxide dismutase (SOD), and catalase (CAT), and decreased the level of malondialdehyde (MDA) in the serum. Moreover, BL groups showed an obvious increase of isobutyric acid markedly and BL500 group significantly promoted the level of isovaleric acid in cecal contents of broilers. Finally, microbial analysis showed that BL supplementation presented visual separations of microbial composition and increased the relative abundance of p_Proteobacteria, g_Elusimicrobium, and g_Parasutterella comparing with the CON group. Together, this study inferred that dietary BL supplementation improved the growth performance, immune and antioxidant functions, changed the intestinal microflora structure and metabolites of yellow-feathered broilers, which laid a good basis for the application of probiotics in the future.

Essential procedures of single-cell RNA sequencing in multiple myeloma and its translational value.

Multiple myeloma (MM) is a malignant neoplasm characterized by clonal proliferation of abnormal plasma cells. In many countries, it ranks as the second most prevalent malignant neoplasm of the hematopoietic system. Although treatment methods for MM have been continuously improved and the survival of patients has been dramatically prolonged, MM remains an incurable disease with a high probability of recurrence. As such, there are still many challenges to be addressed. One promising approach is single-cell RNA sequencing (scRNA-seq), which can elucidate the transcriptome heterogeneity of individual cells and reveal previously unknown cell types or states in complex tissues. In this review, we outlined the experimental workflow of scRNA-seq in MM, listed some commonly used scRNA-seq platforms and analytical tools. In addition, with the advent of scRNA-seq, many studies have made new progress in the key molecular mechanisms during MM clonal evolution, cell interactions and molecular regulation in the microenvironment, and drug resistance mechanisms in target therapy. We summarized the main findings and sequencing platforms for applying scRNA-seq to MM research and proposed broad directions for targeted therapies based on these findings.

Sorafenib Resistance Contributed by IL7 and MAL2 in Hepatocellular Carcinoma Can Be Overcome by Autophagy-Inducing Stapled Peptides.

Drug resistance poses a great challenge in systemic therapy for hepatocellular carcinoma (HCC). However, the underlying molecular mechanisms associated with resistance to anti-cancer drugs, such as Sorafenib, remain unclear. In this study, we use transposon insertional mutagenesis to generate Sorafenib-resistant HCC cell lines in order to identify potential drug resistant causative genes. Interleukin 7 (IL7) and mal, T cell differentiation protein 2 (MAL2) were identified as candidate genes that promote survival by activating JAK/STAT and PI3K/AKT signaling pathways. Sorafenib-resistant cells exhibited higher clonogenic survival and lower drug sensitivity due to IL7 and MAL2 upregulation. Higher anti-apoptotic effect, clonogenic survival and increased PI3K/AKT/STAT3 activities were observed in IL7 and MAL2 co-overexpressing cells compared with controls or cells overexpressing IL7 or MAL2 individually. Given the critical role of MAL2 in endocytosis, we propose that MAL2 might facilitate the endocytic trafficking of IL7 and its cognate receptors to the plasma membrane, which leads to upregulated JAK/STAT and PI3K/AKT signaling pathways and Sorafenib resistance. Additionally, our previous studies showed that an autophagy-inducing stapled peptide promoted the endolysosomal degradation of c-MET oncogene and overcame adaptive Sorafenib resistance in c-MET+ HCC cells. In this study, we demonstrate that these stapled peptides readily induced autophagy and inhibited the proliferation of both wild-type and Sorafenib-resistant HCC cells co-overexpressing both IL7 and MAL2. Furthermore, these peptides showed synergistic cytotoxicity with Sorafenib in drug-resistant HCC cells co-overexpressing both IL7 and MAL2. Our studies suggest that targeting autophagy may be a novel strategy to overcome IL7/MAL2-mediated Sorafenib resistance in HCC.

Single-Cell Analysis Reveals Malignant Cells Reshape the Cellular Landscape and Foster an Immunosuppressive Microenvironment of Extranodal NK/T-Cell Lymphoma.

Extranodal natural killer/T-cell lymphoma (NKTCL) is an aggressive type of lymphoma associated with Epstein-Barr virus (EBV) and characterized by heterogeneous tumor behaviors. To better understand the origins of the heterogeneity, this study utilizes single-cell RNA sequencing (scRNA-seq) analysis to profile the tumor microenvironment (TME) of NKTCL at the single-cell level. Together with in vitro and in vivo models, the study identifies a subset of LMP1+ malignant NK cells contributing to the tumorigenesis and development of heterogeneous malignant cells in NKTCL. Furthermore, malignant NK cells interact with various immunocytes via chemokines and their receptors, secrete substantial DPP4 that impairs the chemotaxis of immunocytes and regulates their infiltration. They also exhibit an immunosuppressive effect on T cells, which is further boosted by LMP1. Moreover, high transcription of EBV-encoded genes and low infiltration of tumor-associated macrophages (TAMs) are favorable prognostic indicators for NKTCL in multiple patient cohorts. This study for the first time deciphers the heterogeneous composition of NKTCL TME at single-cell resolution, highlighting the crucial role of malignant NK cells with EBV-encoded LMP1 in reshaping the cellular landscape and fostering an immunosuppressive microenvironment. These findings provide insights into understanding the pathogenic mechanisms of NKTCL and developing novel therapeutic strategies against NKTCL.

Nuclear Factor Erythroid 2-Related Factor 2 is Essential for Low-Normobaric Oxygen Treatment-Mediated Blood-Brain Barrier Protection Following Ischemic Stroke.

Cerebral ischemia/reperfusion (I/R) injury increases blood-brain barrier (BBB) permeability, leading to hemorrhagic transformation and brain edema. Normobaric oxygen (NBO) is a routine clinical treatment strategy for this condition. However, its neuroprotective effects remain controversial. This study investigated the effect of different NBO concentrations on I/R injury and explores the involvement of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in the underlying mechanism. A mouse middle cerebral artery occlusion (MCAO) model, and an oxygen and glucose deprivation (OGD) model featuring mouse brain microvascular endothelial cells (ECs) called bEnd.3, were used to investigate the effect of NBO on I/R injury. A reactive oxygen species (ROS) inducer and Nrf2-knockdown by RNA were used to explore whether the Nrf2 pathway mediates the effect of NBO on cerebrovascular ECs. In the early stage of MCAO, 40% O2 NBO exposure significantly improved blood perfusion in the ischemic area and effectively relieved BBB permeability, cerebral edema, cerebral injury, and neurological function after MCAO. In the OGD model, 40% O2 NBO exposure significantly reduced apoptosis, inhibited ROS generation, reduced ER stress, upregulated the expression of tight junction proteins, and stabilized the permeability of ECs. Blocking the Nrf2 pathway nullified the protective effect of 40% O2 NBO on ECs after OGD. Finally, our study confirmed that low concentrations of NBO have a neuroprotective effect on I/R by activating the Nrf2 pathway in ECs.

A novel capsid-XL32-derived adeno-associated virus serotype prompts retinal tropism and ameliorates choroidal neovascularization.

Gene therapy has been adapted, from the laboratory to the clinic, to treat retinopathies. In contrast to subretinal route, intravitreal delivery of AAV vectors displays the advantage of bypassing surgical injuries, but the viral particles are more prone to be nullified by the host neutralizing factors. To minimize such suppression of therapeutic effect, especially in terms of AAV2 and its derivatives, we introduced three serine-to-glycine mutations, based on the phosphorylation sites identified by mass spectrum analysis, to the XL32 capsid to generate a novel serotype named AAVYC5. Via intravitreal administration, AAVYC5 was transduced more effectively into multiple retinal layers compared with AAV2 and XL32. AAVYC5 also enabled successful delivery of anti-angiogenic molecules to rescue laser-induced choroidal neovascularization and astrogliosis in mice and non-human primates. Furthermore, we detected fewer neutralizing antibodies and binding IgG in human sera against AAVYC5 than those specific for AAV2 and XL32. Our results thus implicate this capsid-optimized AAVYC5 as a promising vector suitable for a wide population, particularly those with undesirable AAV2 seroreactivity.