Development and validation of prognostic and diagnostic model for pancreatic ductal adenocarcinoma based on scRNA-seq and bulk-seq datasets.

The 5-year overall survival (OS) of pancreatic ductal adenocarcinoma (PDAC) is only 10%, partly owing to the lack of reliable diagnostic and prognostic biomarkers. The raw gene-cell matrix for single-cell RNA-seq (scRNA-seq) analysis was downloaded from the GSA database. We drew cell atlas for PDAC and normal pancreatic tissues. The inferCNV analysis was used to distinguish tumor cells from normal ductal cells. We identified differential expression genes (DEGs) by comparing tumor cells and normal ductal cells. The common DEGs were used to conduct prognostic and diagnostic model using univariate and multivariate Cox or logistic regression analysis. Four genes, MET, KLK10, PSMB9 and ITGB6, were utilized to create risk score formula to predict OS and to establish diagnostic model for PDAC. Finally, we drew an easy-to-use nomogram to predict 2-year and 3-year OSs. In conclusion, we developed and validated the prognostic and diagnostic model for PDAC based on scRNA-seq and bulk-seq datasets.

PANoptosis: a potential new target for programmed cell death in breast cancer treatment and prognosis.

Breast cancer is a prevalent and severe form of cancer that affects women all over the world. The incidence and mortality of breast cancer continue to rise due to factors such as population growth and the aging of the population. There is a growing area of research focused on a cell death mechanism known as PANoptosis. This mechanism is primarily regulated by the PANoptosome complex and displays important characteristics of cell death, including pyroptosis, apoptosis, and/or necroptosis, without being strictly defined by the cell death pathway. PANoptosis acts as a defensive response to external stimuli and pathogens, contributing to the maintenance of cellular homeostasis and overall stability. Increasing evidence suggests that programmed cell death (PCD) plays an important role in the development of breast cancer, and PANoptosis, as a novel form of PCD, may be a crucial factor in the development of breast cancer, potentially leading to the identification of new therapeutic strategies. Therefore, the concept of PANoptosis not only deepens our understanding of PCD, but also opens up new avenues for treating malignant diseases, including breast cancer. This review aims to provide an overview of the definition of PANoptosis, systematically explore the interplay between PANoptosis and various forms of PCD, and discuss its implications for breast cancer. Additionally, it delves into the current progress and future directions of PANoptosis research in the context of breast cancer, establishing a theoretical foundation for the development of molecular targets within critical signaling pathways related to PANoptosis, as well as multi-target combination therapy approaches, with the goal of inducing PANoptosis as part of breast cancer treatment.

Eu-Based Porphyrin MOF Enables High-Performance Carbon-Based Perovskite Solar Cells.

The low power conversion efficiency (PCE) of hole transport materials (HTM) - free carbon-based perovskite solar cells (C-PSCs) poses a challenge. Here, a novel 2D Eu-TCPP MOF (TCPP; [tetrakis (4-carboxyphenyl) porphyrin]) sandwiched between the perovskite layer and the carbon electrode is used to realize an effective and stable HTM-free C-PSCs. Relying on the synergistic effect of both the metal-free TCPP ligand with a unique absorption spectrum and hydrophobicity and the EuO4(OH)2 chain in the Eu-TCPP MOF, defects are remarkably suppressed and light-harvesting capability is significantly boosted. Energy band alignment is achieved after Eu-TCPP MOF treatment, promoting hole collection. Förster resonance energy transfer results in improved light utilization and protects the perovskite from decomposition. As a result, the HTM-free C-PSCs with Eu-TCPP MOF reach a champion PCE of 18.13%. In addition, the unencapsulated device demonstrates outstanding thermal stability and UV resistance and keeps 80.6% of its initial PCE after 5500 h in a high-humidity environment (65%-85% RH).

Histone variant H2A.Z is required for plant salt response by regulating gene transcription.

As a well-conserved histone variant, H2A.Z epigenetically regulates plant growth and development as well as the interaction with environmental factors. However, the role of H2A.Z in response to salt stress remains unclear, and whether nucleosomal H2A.Z occupancy work on the gene responsiveness upon salinity is obscure. Here, we elucidate the involvement of H2A.Z in salt response by analysing H2A.Z disorder plants with impaired or overloaded H2A.Z deposition. The salt tolerance is dramatically accompanied by H2A.Z deficiency and reacquired in H2A.Z OE lines. H2A.Z disorder changes the expression profiles of large-scale of salt responsive genes, announcing that H2A.Z is required for plant salt response. Genome-wide H2A.Z mapping shows that H2A.Z level is induced by salt condition across promoter, transcriptional start site (TSS) and transcription ending sites (-1 kb to +1 kb), the peaks preferentially enrich at promoter regions near TSS. We further show that H2A.Z deposition within TSS provides a direct role on transcriptional control, which has both repressive and activating effects, while it is found generally H2A.Z enrichment negatively correlate with gene expression level response to salt stress. This study shed light on the H2A.Z function in salt tolerance, highlighting the complex regulatory mechanisms of H2A.Z on transcriptional activity for yielding appropriate responses to particularly environmental stress.

Elevated liver enzymes in the first trimester are associated with gestational diabetes mellitus: A prospective cohort study.

AIMS: Previous studies have found that a single liver enzyme may predict gestational diabetes mellitus (GDM), but the results have been inconsistent. This study aimed to explore the associations of liver enzymes in early pregnancy with risk of GDM, as well as to independently rank risk factors. METHODS: This prospective cohort study included 1295 women who underwent liver enzyme measurements during early pregnancy and completed GDM assessment in mid-pregnancy. Logistic regression and restricted cubic spline analyses were conducted to assess the relationship between liver enzymes and risk of GDM. Back-propagation artificial neural network was performed to rank independently risk factors of GDM. RESULTS: Women diagnosed with GDM exhibited significantly higher levels of liver enzymes than those without GDM (all p < 0.05). The highest quartile of liver enzymes was associated with higher risk of GDM compared with the lowest quartile, with adjusted odds ratio (ORs) ranging from 2.76 to 8.11 (all p < 0.05). Moreover, the ORs of GDM increased linearly with liver enzymes level (all P for overall association <0.001). Furthermore, Back-propagation artificial neural network identified γ-gamma-glutamyl transferase (GGT) as accounting for the highest proportion in the ranking of GDM risk prediction weights (up to 20.8%). CONCLUSIONS: Single or total elevations of liver enzymes in early pregnancy could predict the GDM occurrence, in which GGT, alkaline Phosphatase, and aspartate aminotransferase were the three most important independent risk factors.

Mid1 promotes synovitis in rheumatoid arthritis via ubiquitin-dependent post-translational modification.

INTRODUCTION: Current anti-rheumatic drugs are primarily modulating immune cell activation, yet their effectiveness remained suboptimal. Therefore, novel therapeutics targeting alternative mechanisms, such as synovial activation, is urgently needed. OBJECTIVES: To explore the role of Midline-1 (Mid1) in synovial activation. METHODS: NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice were used to establish a subcutaneous xenograft model. Wild-type C57BL/6, Mid1-/-, Dpp4-/-, and Mid1-/-Dpp4-/- mice were used to establish a collagen-induced arthritis model. Cell viability, cell cycle, qPCR and western blotting analysis were used to detect MH7A proliferation, dipeptidyl peptidase-4 (DPP4) and Mid1 levels. Co-immunoprecipitation and proteomic analysis identified the candidate protein of Mid1 substrates. Ubiquitination assays were used to determine DPP4 ubiquitination status. RESULTS: An increase in Mid1, an E3 ubiquitin ligase, was observed in human RA synovial tissue by GEO dataset analysis, and this elevation was confirmed in a collagen-induced mouse arthritis model. Notably, deletion of Mid1 in a collagen-induced arthritis model completely protected mice from developing arthritis. Subsequent overexpression and knockdown experiments on MH7A, a human synoviocyte cell line, unveiled a previously unrecognized role of Mid1 in synoviocyte proliferation and migration, the key aspects of synovial activation. Co-immunoprecipitation and proteomic analysis identified DPP4 as the most significant candidate of Mid1 substrates. Mechanistically, Mid1 promoted synoviocyte proliferation and migration by inducing ubiquitin-mediated proteasomal degradation of DPP4. DPP4 deficiency led to increased proliferation, migration, and inflammatory cytokine production in MH7A, while reconstitution of DPP4 significantly abolished Mid1-induced augmentation of cell proliferation and activation. Additionally, double knockout model showed that DPP4 deficiency abolished the protective effect of Mid1 defect on arthritis. CONCLUSION: Overall, our findings suggest that the ubiquitination of DPP4 by Mid1 promotes synovial cell proliferation and invasion, exacerbating synovitis in RA. These results reveal a novel mechanism that controls synovial activation, positioning Mid1 as a promising target for therapeutic intervention in RA.

A new model of Notch signalling: Control of Notch receptor cis-inhibition via Notch ligand dimers.

All tissue development and replenishment relies upon the breaking of symmetries leading to the morphological and operational differentiation of progenitor cells into more specialized cells. One of the main engines driving this process is the Notch signal transduction pathway, a ubiquitous signalling system found in the vast majority of metazoan cell types characterized to date. Broadly speaking, Notch receptor activity is governed by a balance between two processes: 1) intercellular Notch transactivation triggered via interactions between receptors and ligands expressed in neighbouring cells; 2) intracellular cis inhibition caused by ligands binding to receptors within the same cell. Additionally, recent reports have also unveiled evidence of cis activation. Whilst context-dependent Notch receptor clustering has been hypothesized, to date, Notch signalling has been assumed to involve an interplay between receptor and ligand monomers. In this study, we demonstrate biochemically, through a mutational analysis of DLL4, both in vitro and in tissue culture cells, that Notch ligands can efficiently self-associate. We found that the membrane proximal EGF-like repeat of DLL4 was necessary and sufficient to promote oligomerization/dimerization. Mechanistically, our experimental evidence supports the view that DLL4 ligand dimerization is specifically required for cis-inhibition of Notch receptor activity. To further substantiate these findings, we have adapted and extended existing ordinary differential equation-based models of Notch signalling to take account of the ligand dimerization-dependent cis-inhibition reported here. Our new model faithfully recapitulates our experimental data and improves predictions based upon published data. Collectively, our work favours a model in which net output following Notch receptor/ligand binding results from ligand monomer-driven Notch receptor transactivation (and cis activation) counterposed by ligand dimer-mediated cis-inhibition.

The first report and biological characterization of Avian Orthoavulavirus 16 in wild migratory waterfowl and domestic poultry in China reveal a potential threat to birds.

AbstractThe Avulavirus within the family Paramyxoviridae includes at least 22 different species, and is known to cause different types of infections and even be fatal in multiple avian species. There is limited knowledge of the genetic and biological information of Avulavirus species -2 to 22 in domestic and wild birds and the disease significance of these viruses in birds is not fully determined, although as many as 10 new distinct species have been identified from wild birds and domestic poultry around the world in the last decade. This study aimed to use PCR, virus isolation, and sequencing to genetically and biologically characterize Avian Orthoavulavirus 16 (AOAV-16) in wild birds and domestic poultry collected from different locations in China between 2014 and 2022. Of five isolated AOAV-16 strains (Y1 to Y5), only the Y4 strain had a hemagglutination (HA)-negative result. All of these isolates were low virulent viruses for chickens, except Y3 which was detected simultaneously with avian influenza virus (AIV) of H9N2 subtype. Furthermore, at least four different types of intergenic sequences (IGS) between the HN and L genes junction, and the recombination event as well as interspecific transmission by wild migratory birds, existed within the species AOAV-16. These findings and results of other reported AOAV-16 strains recommend strict control measures to limit contact between wild migratory birds and domestic poultry and imply potential threats to commercial poultry and even public health challenges worldwide.

Acid-triggered controlled release and fluorescence-switchable phthalocyanine nanoassemblies combined with O2-economizer for tumor imaging and collaborative photodynamic antitumor therapy.

Photodynamic therapy (PDT) has emerged as a highly efficacious therapeutic modality for malignant tumors owing to its non-invasive property and minimal adverse effects. However, the pervasive hypoxic microenvironment within tumors significantly compromises the efficacy of oxygen-dependent PDT, posing a formidable challenge to the advancement of high-efficiency PDT. Here, we developed a nanostructured photosensitizer (PS) assembled by cationic and anionic zinc phthalocyanines to load oxygen-throttling drug atovaquone (ATO), which was subsequently coated with polydopamine to obtain the final product ATO/ZnPc-CA@DA. ATO/ZnPc-CA@DA exhibited excellent stability, particularly in the blood milieu. Interestingly, the acidic microenvironment can trigger drug release from ATO/ZnPc-CA@DA, leading to a significant enhancement in fluorescence and an augmented generation of reactive oxygen species (ROS). ATO/ZnPc-CA@DA can induce synergistic cytotoxicity of PS and ATO, and significantly enhance the killing ability against tumor cells under hypoxic conditions. The mechanism underlying cytotoxicity of ATO/ZnPc-CA@DA was demonstrated to be associated with augmented cell apoptosis, disruption of mitochondrial membrane potential, diminished ATP production, heightened intracellular ROS generation, and reduced intracellular oxygen consumption. The animal experiments indicated that ATO/ZnPc-CA@DA possessed enhanced tumor targeting capability, along with a reduction in PS distribution within normal organs. Furthermore, ATO/ZnPc-CA@DA exhibited enhanced inhibitory effect on tumor growth and caused aggravated damage to tumor tissue. The construction strategy of nanostructured PS and the synergistic antitumor principle of combined oxygen-throttling drugs can be applied to other PSs, thereby advancing the development of photodynamic antitumor therapy and promoting the clinical translation.

Oral administration of probiotic spore ghosts for efficient attenuation of radiation-induced intestinal injury.

Radiation-induced intestinal injury is the most common side effect during radiotherapy of abdominal or pelvic solid tumors, significantly impacting patients' quality of life and even resulting in poor prognosis. Until now, oral application of conventional formulations for intestinal radioprotection remains challenging with no preferred method available to mitigate radiation toxicity in small intestine. Our previous study revealed that nanomaterials derived from spore coat of probiotics exhibit superior anti-inflammatory effect and even prevent the progression of cancer. The aim of this work is to determine the radioprotective effect of spore coat (denoted as spore ghosts, SGs) from three clinically approved probiotics (B.coagulans, B.subtilis and B.licheniformis). All the three SGs exhibit outstanding reactive oxygen species (ROS) scavenging ability and excellent anti-inflammatory effect. Moreover, these SGs can reverse the balance of intestinal flora by inhibiting harmful bacteria and increasing the abundance of Lactobacillus. Consequently, administration of SGs significantly reduce radiation-induced intestinal injury by alleviating diarrhea, preventing X-ray induced apoptosis of small intestinal epithelial cells and promoting restoration of barrier integrity in a prophylactic study. Notably, SGs markedly improve weight gain and survival of mice received total abdominal X-ray radiation. This work may provide promising radioprotectants for efficiently attenuating radiation-induced gastrointestinal syndrome and promote the development of new intestinal predilection.

Phylogeny and Fungal Community Structures of Helotiales Associated with Sclerotial Disease of Mulberry Fruits in China.

Mulberry fruit sclerotiniose is a prevalent disease caused by the fungal species Ciboria shiraiana, C. carunculoides, and Scleromitrula shiraiana of the order Helotiales, and severely affects the production of mulberry. However, these species have only been identified using morphological and rDNA-ITS sequence analyses, and their genetic variation is unclear. To address this, morphological and two-locus (ITS and RPB2) phylogenetic analyses were conducted using culture-dependent and independent methods for 49 samples from 31 orchards across four provinces in China. Illumina MiSeq sequencing was used to assess the fungal communities obtained from fruits varying in disease severity and color from an orchard in Wuhan. Conidial suspensions of C. shiraiana and C. carunculoides isolated from diseased fruits, diseased fruits affected with hypertrophy and pellet sorosis sclerotiniose, and mycelia of Sclerotinia sclerotiorum were determined to be pathogenic to the mulberry cultivar YSD10. However, fruits inoculated with S. sclerotiorum mycelia exhibited nontypical disease symptoms, and mycelia and conidia obtained from C. carunculoides and S. shiraiana strains were not pathogenic. Maximum parsimony and Bayesian analyses using the sequences of the assessed loci indicated species variability with no evidence of geographic specialization. Metagenomic analysis revealed that the diversity of fungal communities was reduced with disease progression. Furthermore, within a single fruit, the presence of two Ciboria spp. was detected. These results provide novel insights into Ciboria spp., revealing the secondary infections caused by conidia in diseased fruits, genetic variations of the pathogens, and the occurrence of coinfection. This improved understanding of fungal pathogens will aid in developing effective disease control strategies.

Cross-species scRNA-seq reveals the cellular landscape of retina and early alterations in type 2 diabetes mice.

Single-cell RNA sequencing (scRNA-seq) analysis have provided an unprecedented resolution for the studies on diabetic retinopathy (DR). However, the early changes in the retina in diabetes remain unclear. A total of 8 human and mouse scRNA-seq datasets, containing 276,402 cells were analyzed individually to comprehensively delineate the retinal cell atlas. The neural retinas were isolated from the type 2 diabetes (T2D) and control mice, and scRNA-seq analysis was conducted to evaluate the early effects of diabetes on the retina. Bipolar cell (BC) heterogeneity were identified. We found some stable BCs across multiple datasets, and explored their biological functions. A new RBC subtype (Car8_RBC) in the mouse retina was validated using the multi-color immunohistochemistry. AC149090.1 was significantly upregulated in the rod cells, ON cone BCs (CBCs), OFF CBCs, and RBCs in T2D mice. Additionally, the interneurons, especially BCs, were the most vulnerable cells to diabetes by integrating scRNA-seq and genome-wide association studies (GWAS) analyses. In conclusion, this study delineated a cross-species retinal cell atlas and uncovered the early pathological alterations in the retina of T2D mice.

Sharp needle reconstructs peripheral outflow for patients with malfunctional arteriovenous fistula.

OBJECTIVE: To investigate the feasibility and efficacy of combining ultrasound-guided sharp needle technique with percutaneous transluminal angioplasty (PTA) for treating outflow stenosis or dysfunction in arteriovenous fistula (AVF) among hemodialysis patients. METHODS: From October 2021 to March 2023, patients with occluded or malfunctional fistula veins not amenable to regularly angioplasty were retrospectively enrolled in the study. They underwent ultrasound-guided sharp needle intervention followed by PTA. Data on the location and length between the two veins, technical success, clinical outcomes, and complications were collected. Patency rates post-angioplasty were calculated through Kaplan-Meier analysis. RESULTS: A total of 23 patients were included. The mean length of the reconstructed extraluminal segment was 3.18 cm. The sharp needle opening was performed on the basilic vein (60.9%), brachial vein (26.1%), or upper arm cephalic vein (13%) to create outflow channels. Postoperatively, all cases presented with mild subcutaneous hematomas around the tunneling site and minor diffuse bleeding. The immediate patency rate for the internal fistulas was 100%, with 3-month, 6-month, and 12-month patency rates at 91.3%, 78.3%, and 43.5%, respectively. CONCLUSION: Sharp needle technology merged with PTA presents an effective and secure minimally invasive method for reconstructing the outflow tract, offering a new solution for recanalizing high-pressure or occluded fistulas.

Synergistic effects of Co-pyrolysis on the immobilization and transformation of lead (Pb), chromium (Cr), nickel (Ni), and fluorine (F) in phosphogypsum-biomass mixtures.

Co-pyrolysis of biomass with phosphogypsum (PG) presents an effective strategy for facilitating the recycling of PG resources. However, it is crucial to note the environmental threats arising from the presence of Pb, Cr, Ni, and F in PG. This study investigated the effect of immobilization and transformation of four elements during co-pyrolysis with biomass and its components. The co-pyrolysis experiments were carried out in a tube furnace with a mixture of PG and corn stover (CS), cellulose (C), lignin (L), glucose (G). Co-pyrolysis occurred at varying temperatures (600 °C, 700 °C, 800 °C, and 900 °C) and different addition ratios (10%, 15%, and 20%). The results indicated that an increase in co-pyrolysis temperature was more conducive to the immobilization and transformation of harmful elements in PG, demonstrating significant efficacy in controlling F. Additionally, the addition of biomass components exerts a significant impact on inhibiting product toxicity, with small molecules such as glucose playing a prominent role in this process. The mechanism underlying the control of harmful elements during co-pyrolysis of PG and biomass was characterized by three main aspects. Firstly, biomass components have the potential to melt-encapsulate the harmful elements in PG, leading to precipitation. Secondly, the pyrolysis gas produced during the co-pyrolysis process contributes to the formation of a rich pore structure in the product. Finally, this process aids in transforming hazardous substances into less harmful forms and stabilizing these elements. The findings of this study are instrumental in optimizing the biomass and PG blend to mitigate the environmental impact of their co-pyrolysis products.

Global air pollution exposure and congenital anomalies: an updated systematic review and meta-analysis of epidemiological studies.

A systematic review and meta-analysis was conducted to evaluate recent epidemiological evidence on the association of air pollution with congenital anomalies (CAs). Of 11,014 records, 49 were finally included in this meta-analysis. Per 10 µg/m3 increase in air pollutant, PM10 exposure during the 1st month of pregnancy and at the first trimester (T1) was associated with increased overall CAs. Further, exposure to PM10 was associated with congenital heart disease (OR = 1.055, 95% CI: 1.035, 1.074) and patent ductus arteriosus (OR = 1.094, 95% CI: 1.020, 1.168) at T1, with chromosomal anomalies during the entire pregnancy and with nervous system anomalies when exposure occurred 3 months prior to pregnancy, during the 1st, 2nd months of pregnancy and at T1. Besides, a significant association with overall CAs was observed for a combined exposure of PM10 and SO2 during the 1st month of gestation (OR: 1.101, 95% CI: 1.023, 1.180). A combined exposure of PM10 and CO was also associated with tetralogy of Fallot during 3-8 weeks of gestation (OR: 1.016, 95% CI: 1.005, 1.027). No significant associations were observed between PM2.5, NO2, and O3 exposure and CAs.

The effect of China's birth policy changes on birth defects-A large hospital-based cross-sectional study.

A retrospective analysis of birth data hospital-based obtained from 14 monitoring areas in the Huaihe River Basin from 2009 to 2019 was conducted. Trend in the total prevalence of birth defects (BDs) and subgroups were analyzed using the Joinpoint Regression model. The incidence of BDs increased gradually from 118.87 per 10,000 in 2009 to 241.18 per 10,000 in 2019 (AAPC = 5.91, P < 0.001). Congenital heart diseases were the most common subtype of BDs. The proportion of maternal age younger than 25 decreased but the age 25-40 years increased significantly (AAPC<20=-5.58; AAPC20-24=-6.38; AAPC25-29 = 5.15; AAPC30-35 = 7.07; AAPC35-40 = 8.27; All P < 0.05). Compared with the one-child policy period, the risk of BDs was greater for groups among maternal age younger than 40 years during the partial and universal two-child policy period (P < 0.001). The incidence of BDs and the proportion of women with advanced maternal age in Huaihe River Basin is increasing. There was an interaction between changes in birth policy and the mother's age on the risk of BDs.

The association between retinol-binding protein 4 and risk of type 2 diabetes: A systematic review and meta-analysis.

Retinol-binding protein 4 (RBP4) was controversially associated with type 2 diabetes mellitus (T2DM). This meta-analysis aimed at evaluating the association between RBP4 level and T2DM risk. MEDLINE and EMBASE were searched to identify relevant studies up to 3 December 2022. Random effects model was used to pool multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Publication bias was estimated by Funnel plot and Egger's test, it was considered to be significant when P < 0.05. Eight studies including 8087 participants were finally included. Compared to those with the lowest level, subjects with the highest level of RBP4 have a higher risk of T2DM (OR = 1.47, 95% CI: 1.16-1.78, P < 0.001, I2 = 86.9%). No publication bias among the included studies was found (t = 0.94, P = 0.377). This meta-analysis indicated that high RBP4 level was associated with increasing risk of T2DM.

Simultaneous Mapping of Amino Neurotransmitters and Nucleoside Neuromodulators on Brain Tissue Sections by On-Tissue Chemoselective Derivatization and MALDI-MSI.

Neurotransmitters (NTs) and neuromodulators (NMs) are two of the most important neurochemicals in the brain, and their imbalances in specific brain regions are thought to underlie certain neurological disorders. We present an on-tissue chemoselective derivatization mass spectrometry imaging (OTCD-MSI) method for the simultaneous mapping of NTs and NMs. Our derivatization system consists of a pyridiniumyl-benzylboronic acid based derivatization reagent and pyrylium salt, which facilitate covalent charge labeling of molecules containing cis-diol and primary amino, respectively. These derivatization systems improved the detection sensitivity of matrix-assisted laser desorption/ionization (MALDI)-MSI and simplified the identification of amino NTs and nucleoside NMs by the innate chemoselectivity of derivatization reagents and the unique isotopic pattern of boron-derivative reagents. We demonstrated the ability of the developed method on brain sections from a hypoxia mouse model and control. The simultaneous imaging of NTs and NMs provided a method for exploring how hypoxic stress and drugs affect specific brain regions through neurotransmitter modulation.

Core-shell structured hollow copper sulfide@metal-organic framework for magnetic resonance imaging guided photothermal therapy in second near-infrared biological window.

Multifunctional core-shell hybrids formed by integration of metal-organic framework (MOF) and functional materials have attracted extensive attention as promising theranostic nanoplatforms due to their combined novel properties and enhanced therapeutic efficacy. Recently, the second near-infrared (NIR-II, 1000-1700 nm) laser-induced photothermal therapy (PTT) as compared to the NIR-I(700-950 nm) laser-induced PTT has displayed improved therapeutic effects owing to its merits that include deeper tissue penetration and increased maximum permissible exposure. Herein, a novel core-shell hollow copper sulfide@metal-organic framework (HCuS@MIL-100) has been successfully fabricated by a layer-by-layer technique for the first time and their collective theranostic effects are investigated in vitro and in vivo. In this platform, the inner HCuS was applied as the NIR-II photothermal agent with excellent NIR-II absorption feature, leading to impressive photothermal effects under irradiation by 1064 nm light. With MIL-100 as the shell, HCuS@MIL-100 not only displayed optimal biocompatibility but also presented superior T2 magnetic resonance imaging (MRI) ability. In the current study multifunctional hollow core-shell HCuS@MIL-100 are fabricated for the MRI-guided PTT. This study also offers a facile and effective strategy for the development of novel theranostic platforms with high efficiency through the integration of MOFs and functional materials.

Arabidopsis nucleoporin NUP96 mediates plant salt tolerance by modulating the transcription of salt-responsive genes.

MAIN CONCLUSION: Physiological and molecular tests show that NUP96 plays an important role in the plant response to salt stress, resulting from the reprogramming of transcriptomic profiles, which are likely to be mediated by the influence on the nuclear/cytosol shuttling of the key regulators of salt tolerance. As a key component of the nuclear pore complex (NPC), nucleoporin 96 (NUP96) is critical for modulating plant development and interactions with environmental factors, but whether NUP96 is involved in the salt response is still unknown. Here, we analyzed the role of Arabidopsis NUP96 under salt stress. The loss-of-function mutant nup96 exhibited salt sensitivity in terms of rosette growth and root elongation, and showed attenuated capacity in maintaining ion and ROS homeostasis, which could be compensated for by the overexpression of NUP96. RNA sequencing revealed that many salt-responsive genes were misregulated after NUP96 mutation, and especially NUP96 is required for the expression of a large portion of salt-induced genes. This is likely correlated with the activity in facilitating nuclear/cytosol transport of the underlying regulators in salt tolerance such as the transcription factor ATAP2, targeted by eight downregulated genes in nup96 under salt stress. Our results illustrate that NUP96 plays an important role in the salt response, probably by regulating the nucleocytoplasmic shuttling of key mRNAs or proteins associated with plant salt responsiveness.