Towards linking lab and field lifetimes of perovskite solar cells.

Metal halide perovskite solar cells (PSCs) represent a promising low-cost thin-film photovoltaic technology, with unprecedented power conversion efficiencies obtained for both single-junction and tandem applications1-8. To push PSCs towards commercialization, it is critical, albeit challenging, to understand device reliability under real-world outdoor conditions where multiple stress factors (for example, light, heat and humidity) coexist, generating complicated degradation behaviours9-13. To quickly guide PSC development, it is necessary to identify accelerated indoor testing protocols that can correlate specific stressors with observed degradation modes in fielded devices. Here we use a state-of-the-art positive-intrinsic-negative (p-i-n) PSC stack (with power conversion efficiencies of up to approximately 25.5%) to show that indoor accelerated stability tests can predict our six-month outdoor ageing tests. Device degradation rates under illumination and at elevated temperatures are most instructive for understanding outdoor device reliability. We also find that the indium tin oxide/self-assembled monolayer-based hole transport layer/perovskite interface most strongly affects our device operation stability. Improving the ion-blocking properties of the self-assembled monolayer hole transport layer increases averaged device operational stability at 50 °C-85 °C by a factor of about 2.8, reaching over 1,000 h at 85 °C and to near 8,200 h at 50 °C, with a projected 20% degradation, which is among the best to date for high-efficiency p-i-n PSCs14-17.

Surface reaction for efficient and stable inverted perovskite solar cells.

Perovskite solar cells (PSCs) with an inverted structure (often referred to as the p-i-n architecture) are attractive for future commercialization owing to their easily scalable fabrication, reliable operation and compatibility with a wide range of perovskite-based tandem device architectures1,2. However, the power conversion efficiency (PCE) of p-i-n PSCs falls behind that of n-i-p (or normal) structure counterparts3-6. This large performance gap could undermine efforts to adopt p-i-n architectures, despite their other advantages. Given the remarkable advances in perovskite bulk materials optimization over the past decade, interface engineering has become the most important strategy to push PSC performance to its limit7,8. Here we report a reactive surface engineering approach based on a simple post-growth treatment of 3-(aminomethyl)pyridine (3-APy) on top of a perovskite thin film. First, the 3-APy molecule selectively reacts with surface formamidinium ions, reducing perovskite surface roughness and surface potential fluctuations associated with surface steps and terraces. Second, the reaction product on the perovskite surface decreases the formation energy of charged iodine vacancies, leading to effective n-type doping with a reduced work function in the surface region. With this reactive surface engineering, the resulting p-i-n PSCs obtained a PCE of over 25 per cent, along with retaining 87 per cent of the initial PCE after over 2,400 hours of 1-sun operation at about 55 degrees Celsius in air.

Climate mismatches with ectomycorrhizal fungi contribute to migration lag in North American tree range shifts.

Climate change will likely shift plant and microbial distributions, creating geographic mismatches between plant hosts and essential microbial symbionts (e.g., ectomycorrhizal fungi, EMF). The loss of historical interactions, or the gain of novel associations, can have important consequences for biodiversity, ecosystem processes, and plant migration potential, yet few analyses exist that measure where mycorrhizal symbioses could be lost or gained across landscapes. Here, we examine climate change impacts on tree-EMF codistributions at the continent scale. We built species distribution models for 400 EMF species and 50 tree species, integrating fungal sequencing data from North American forest ecosystems with tree species occurrence records and long-term forest inventory data. Our results show the following: 1) tree and EMF climate suitability to shift toward higher latitudes; 2) climate shifts increase the size of shared tree-EMF habitat overall, but 35% of tree-EMF pairs are at risk of declining habitat overlap; 3) climate mismatches between trees and EMF are projected to be greater at northern vs. southern boundaries; and 4) tree migration lag is correlated with lower richness of climatically suitable EMF partners. This work represents a concentrated effort to quantify the spatial extent and location of tree-EMF climate envelope mismatches. Our findings also support a biotic mechanism partially explaining the failure of northward tree species migrations with climate change: reduced diversity of co-occurring and climate-compatible EMF symbionts at higher latitudes. We highlight the conservation implications for identifying areas where tree and EMF responses to climate change may be highly divergent.

Climate change determines the sign of productivity trends in US forests.

Forests are integral to the global land carbon sink, which has sequestered ~30% of anthropogenic carbon emissions over recent decades. The persistence of this sink depends on the balance of positive drivers that increase ecosystem carbon storage-e.g., CO2 fertilization-and negative drivers that decrease it-e.g., intensifying disturbances. The net response of forest productivity to these drivers is uncertain due to the challenge of separating their effects from background disturbance-regrowth dynamics. We fit non-linear models to US forest inventory data (113,806 plot remeasurements in non-plantation forests from ~1999 to 2020) to quantify productivity trends while accounting for stand age, tree mortality, and harvest. Productivity trends were generally positive in the eastern United States, where climate change has been mild, and negative in the western United States, where climate change has been more severe. Productivity declines in the western United States cannot be explained by increased mortality or harvest; these declines likely reflect adverse climate-change impacts on tree growth. In the eastern United States, where data were available to partition biomass change into age-dependent and age-independent components, forest maturation and increasing productivity (likely due, at least in part, to CO2 fertilization) contributed roughly equally to biomass carbon sinks. Thus, adverse effects of climate change appear to overwhelm any positive drivers in the water-limited forests of the western United States, whereas forest maturation and positive responses to age-independent drivers contribute to eastern US carbon sinks. The future land carbon balance of forests will likely depend on the geographic extent of drought and heat stress.

On-device lead sequestration for perovskite solar cells.

Perovskite solar cells, as an emerging high-efficiency and low-cost photovoltaic technology1-6, face obstacles on their way towards commercialization. Substantial improvements have been made to device stability7-10, but potential issues with lead toxicity and leaching from devices remain relatively unexplored11-16. The potential for lead leakage could be perceived as an environmental and public health risk when using perovskite solar cells in building-integrated photovoltaics17-23. Here we present a chemical approach for on-device sequestration of more than 96 per cent of lead leakage caused by severe device damage. A coating of lead-absorbing material is applied to the front and back sides of the device stack. On the glass side of the front transparent conducting electrode, we use a transparent lead-absorbing molecular film containing phosphonic acid groups that bind strongly to lead. On the back (metal) electrode side, we place a polymer film blended with lead-chelating agents between the metal electrode and a standard photovoltaic packing film. The lead-absorbing films on both sides swell to absorb the lead, rather than dissolve, when subjected to water soaking, thus retaining structural integrity for easy collection of lead after damage.

Single-cell tumor heterogeneity landscape of hepatocellular carcinoma: unraveling the pro-metastatic subtype and its interaction loop with fibroblasts.

BACKGROUND: Tumor heterogeneity presents a formidable challenge in understanding the mechanisms driving tumor progression and metastasis. The heterogeneity of hepatocellular carcinoma (HCC) in cellular level is not clear. METHODS: Integration analysis of single-cell RNA sequencing data and spatial transcriptomics data was performed. Multiple methods were applied to investigate the subtype of HCC tumor cells. The functional characteristics, translation factors, clinical implications and microenvironment associations of different subtypes of tumor cells were analyzed. The interaction of subtype and fibroblasts were analyzed. RESULTS: We established a heterogeneity landscape of HCC malignant cells by integrated 52 single-cell RNA sequencing data and 5 spatial transcriptomics data. We identified three subtypes in tumor cells, including ARG1+ metabolism subtype (Metab-subtype), TOP2A+ proliferation phenotype (Prol-phenotype), and S100A6+ pro-metastatic subtype (EMT-subtype). Enrichment analysis found that the three subtypes harbored different features, that is metabolism, proliferating, and epithelial-mesenchymal transition. Trajectory analysis revealed that both Metab-subtype and EMT-subtype originated from the Prol-phenotype. Translation factor analysis found that EMT-subtype showed exclusive activation of SMAD3 and TGF-ß signaling pathway. HCC dominated by EMT-subtype cells harbored an unfavorable prognosis and a deserted microenvironment. We uncovered a positive loop between tumor cells and fibroblasts mediated by SPP1-CD44 and CCN2/TGF-ß-TGFBR1 interaction pairs. Inhibiting CCN2 disrupted the loop, mitigated the transformation to EMT-subtype, and suppressed metastasis. CONCLUSION: By establishing a heterogeneity landscape of malignant cells, we identified a three-subtype classification in HCC. Among them, S100A6+ tumor cells play a crucial role in metastasis. Targeting the feedback loop between tumor cells and fibroblasts is a promising anti-metastatic strategy.

MiR-29a-3p mediates phosphatase and tensin homolog and inhibits osteoarthritis progression.

Despite substantial progress in clinical trials of osteoarthritis (OA) gene therapy, the prevalence of OA is still on the rise. MiRNAs have a potential biomarker and therapeutic target for OA. OA cartilage and chondrosarcoma cells were studied to determine the role of miR-29a-3p and PTEN. OA cartilage and human chondrosarcoma cells (SW1353) were obtained. miR-29a-3p and PTEN signature expression was determined by RT-qPCR. The binding relationship between miR-29a-3p and PTEN was investigated by dual-luciferase reporter gene and western blot assay. TUNEL, immunohistochemistry, CCK-8, and flow cytometry were utilized to determine the proliferation and apoptosis of SW1353 cells. This study indicated downregulation of miR-29a-3p expression and upregulation of PTEN expression in human OA primary chondrocytes or OA tissue samples, compared with the normal cartilage cells or tissues. PTEN expression was negatively correlated with miR-29a-3p expression, and miR-29a-3p targeted PTEN mechanistically. miR-29a-3p reduced SW1353 cell activity and proliferation and promoted cell apoptosis. However, the aforementioned effects could be reversed by downregulating PTEN. miR-29a-3p can stimulate chondrocyte proliferation and inhibit apoptosis by inhibiting PTEN expression.

Single-cell RNA sequencing and immune repertoire analysis revealed dynamic immune characteristics associated with peripheral blood during sepsis.

Sepsis is a potentially fatal condition arising from an abnormal immune response to an infection, which can result in organ failure and even death. To explore the mechanism underlying the dysregulated immune response during sepsis and identify potential therapeutic targets, single-cell RNA sequencing (scRNA-seq) and immune repertoire analysis were conducted to depict the cellular landscape of peripheral blood cells in septic mice. We observed significant alterations in the number and proportion of peripheral blood cell populations driven by sepsis. By combining single-cell gene expression profiles and B cell receptor (BCR) repertoire analysis, we discerned that infection inflicted serious damage on the antigen presentation ability of B cells and the diversity of BCR in a short time. In addition, we found that the cecal ligation and puncture procedure in mice inhibited the communication signals of CD4+ and CD8+ T cells and decreased the interactions between B cells and other cells. Our study provides detailed insights into the dynamic changes in the biological characteristics of peripheral blood cells driven by sepsis and provides important advances in our understanding of immune disorders during sepsis.

Chemically Powered Nanomotors with Magnetically Responsive Function for Targeted Delivery of Exosomes.

Janus structure plays a crucial role in achieving chemically driven nanomotors with exceptional motion performance. However, Janus-structured chemically driven nanomotors with magnetic responsiveness are commonly fabricated by sputtering metal films. In the study, a self-assembly technique is employed to asymmetrically modify the surfaces of magnetic silica (SiO2@Fe3O4) nanoparticles with platinum nanoparticles, resulting in the formation of this kind nanomotors. Compared to platinum film, platinum nanoparticles exhibit a larger surface area and a higher catalytic activity. Hence, the nanomotors demonstrate improved diffusion capabilities at a significantly lower concentration (0.05%) of hydrogen peroxide (H2O2). Meanwhile, exosomes have gained attention as a potential tool for the efficient delivery of biological therapeutic drugs due to their biocompatibility. However, the clinical applications of exosomes are limited by their restricted tropism. The previously obtained nanomotors are utilized to deliver exosomes, greatly enhancing its targetability. The drug doxorubicin (DOX) is subsequently encapsulated within exosomes, acting as a representative drug model. Under the conditions of H2O2 concentration at the tumor site, the exosomes exhibited a significantly enhanced rate of entry into the breast cancer cells. The utilization of the nanomotors for exosomes presents a novel approach in the development of hybrid chemically and magnetically responsive nanomotors.

Yolk-Shell MnSe/ZnSe Heterostructures with Selenium Vacancies Encapsulated in Carbontubes for High-Efficiency Sodium/Potassium Storage.

The pursuit of high-performance batteries has propelled the investigation into advanced materials and design methodologies. Herein, the yolk-shell MnSe/ZnSe heterojunction encapsulated in hollow carbontubes (MnSe/ZnSe@HCTs) is prepared as a prospective electrode material for sodium/potassium batteries. The band structure in the heterojunction is methodically adjusted and regulated by intentionally utilizing Mn with unpaired electrons in the 3d orbital. The ZnSe shell confer effectively mitigates volumetric expansion challenges inherent in ions insertion/extraction processes and 1D carbontubular conductive substrate avert the aggregation of MnSe/ZnSe nanoparticles. Concurrently, the heterojunctions implantation induces sublattice distortion and charge redistribution, enriching active sites and regulating band structure. The selenium vacancies within these heterojunctions contribute to the provision of abundant active sites, thereby promoting efficient ions insertion/extraction. In sodium-ion batteries (SIBs), MnSe/ZnSe@HCTs present a superior capacity of 475 mA hg-1 at 0.1 A g-1 and sustains a capacity of 408.5 mAh g-1 even after 1000 cycles. In potassium-ion batteries (KIBs), MnSe/ZnSe@HCTs deliver a higher specific capacity of 422 mAh g-1 at a current density of 0.1 A g-1 and maintain a high coulombic efficiency of 99% after 1000 cycles. The yolk-shell structured MnSe/ZnSe heterojunction demonstrates excellent electrode properties for high-performance sodium/potassium batteries, holding significant promise for future energy storage applications.

Electrodeposition of Ni/Cu Bimetallic Conductive Metal-Organic Frameworks Electrocatalysts with Boosted Oxygen Reduction Activity for Zinc-Air Batteries.

Zinc-air batteries employing non-Pt cathodes hold significant promise for advancing cathodic oxygen reduction reaction (ORR). However, poor intrinsic electrical conductivity and aggregation tendency hinder the application of metal-organic frameworks (MOFs) as active ORR cathodes. Conductive MOFs possess various atomically dispersed metal centers and well-aligned inherent topologies, eliminating the additional carbonization processes for achieving high conductivity. Here, a novel room-temperature electrochemical cathodic electrodeposition method is introduced for fabricating uniform and continuous layered 2D bimetallic conductive MOF films cathodes without polymeric binders, employing the organic ligand 2,3,6,7,10,11-hexaiminotriphenylene (HITP) and varying the Ni/Cu ratio. The influence of metal centers on modulating the ORR performance is investigated by density functional theory (DFT), demonstrating the performance of bimetallic conductive MOFs can be effectively tuned by the unpaired 3d electrons and the Jahn-Teller effect in the doped Cu. The resulting bimetallic Ni2.1Cu0.9(HITP)2 exhibits superior ORR performance, boasting a high onset potential of 0.93 V. Moreover, the assembled aqueous zinc-air battery demonstrates high specific capacity of 706.2 mA h g-1, and exceptional long-term charge/discharge stability exceeding 1250 cycles.

Nuclear Magnetic Resonance-Based Metabolomics and Risk of CKD.

RATIONALE & OBJECTIVE: Chronic kidney disease (CKD) leads to lipid and metabolic abnormalities, but a comprehensive investigation of lipids, lipoprotein particles, and circulating metabolites associated with the risk of CKD has been lacking. We examined the associations of nuclear magnetic resonance (NMR)-based metabolomics data with CKD risk in the UK Biobank study. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: A total of 91,532 participants in the UK Biobank Study without CKD and not receiving lipid-lowering therapy. EXPOSURE: Levels of metabolites including lipid concentration and composition within 14 lipoprotein subclasses, as well as other metabolic biomarkers were quantified via NMR spectroscopy. OUTCOME: Incident CKD identified using ICD codes in any primary care data, hospital admission records, or death register records. ANALYTICAL APPROACH: Cox proportional hazards regression models were used to estimate hazard ratios and 95% confidence intervals. RESULTS: We identified 2,269 CKD cases over a median follow-up period of 13.1 years via linkage with the electronic health records. After adjusting for covariates and correcting for multiple testing, 90 of 142 biomarkers were significantly associated with incident CKD. In general, higher concentrations of very-low-density lipoprotein (VLDL) particles were associated with a higher risk of CKD whereas higher concentrations of high-density lipoprotein (HDL) particles were associated with a lower risk of CKD. Higher concentrations of cholesterol, phospholipids, and total lipids within VLDL were associated with a higher risk of CKD, whereas within HDL they were associated with a lower risk of CKD. Further, higher triglyceride levels within all lipoprotein subclasses, including all HDL particles, were associated with greater risk of CKD. We also identified that several amino acids, fatty acids, and inflammatory biomarkers were associated with risk of CKD. LIMITATIONS: Potential underreporting of CKD cases because of case identification via electronic health records. CONCLUSIONS: Our findings highlight multiple known and novel pathways linking circulating metabolites to the risk of CKD. PLAIN-LANGUAGE SUMMARY: The relationship between individual lipoprotein particle subclasses and lipid-related traits and risk of chronic kidney disease (CKD) in general population is unclear. Using data from 91,532 participants in the UK Biobank, we evaluated the associations of metabolites measured using nuclear magnetic resonance testing with the risk of CKD. We identified that 90 out of 142 lipid biomarkers were significantly associated with incident CKD. We found that very-low-density lipoproteins, high-density lipoproteins, the lipid concentration and composition within these lipoproteins, triglycerides within all the lipoprotein subclasses, fatty acids, amino acids, and inflammation biomarkers were associated with CKD risk. These findings advance our knowledge about mechanistic pathways that may contribute to the development of CKD.

Preclinical monitoring of radiation-induced brain injury via GluCEST MRI and resting-state fMRI at 7 T: an exploratory study on MRI-guided OAR avoidance.

PURPOSE: To assess the value of glutamate chemical exchange saturation transfer (GluCEST) after whole-brain radiotherapy (WBRT) as an imaging marker of radiation-induced brain injury (RBI) and to preliminarily show the feasibility of multiparametric MRI-guided organ at risk (OAR) avoidance. METHODS: Rats were divided into two groups: the control (CTRL) group (n = 9) and the RBI group (n = 9). The rats in the RBI group were irradiated with an X­ray radiator and then subjected to a water maze experiment 4 weeks later. In combination with high-performance liquid chromatography (HPLC), we evaluated the value of GluCEST applied to glutamate changes for RBI and investigated the effect of such changes on glutamatergic neuronal function. RESULTS: The average GluCEST values were markedly lower in the hippocampus and cerebral cortex. Positive correlations were observed between GluCEST values and regional homogeneity (ReHo) values in both the hippocampus and the cerebral cortex. HPLC showed a positive correlation with GluCEST values in the hippocampus. GluCEST values were positively correlated with spatial memory. CONCLUSION: GluCEST MRI provides a visual assessment of glutamate changes in RBI rats for monitoring OAR cognitive toxicity reactions and may be used as a biomarker of OAR avoidance as well as metabolism to facilitate monitoring and intervention in radiation damage that occurs after radiotherapy.

A Transformer-Based microvascular invasion classifier enhances prognostic stratification in HCC following radiofrequency ablation.

BACKGROUND & AIMS: We aimed to develop a Transformer-based deep learning (DL) network for prognostic stratification in hepatocellular carcinoma (HCC) patients undergoing RFA. METHODS: A Swin Transformer DL network was trained to establish associations between magnetic resonance imaging (MRI) datasets and the ground truth of microvascular invasion (MVI) based on 696 surgical resection (SR) patients with solitary HCC ≤3 cm, and was validated in an external cohort (n = 180). The multiphase MRI-based DL risk outputs using an optimal threshold of .5 was employed as a MVI classifier for prognosis stratification in the RFA cohort (n = 180). RESULTS: Over 90% of all enrolled patients exhibited hepatitis B virus infection. Liver cirrhosis was significantly more prevalent in the RFA cohort compared to the SR cohort (72.2% vs. 44.1%, p < .001). The MVI risk outputs exhibited good performance (area under the curve values = .938 and .883) for predicting MVI in the training and validation cohort, respectively. The RFA patients at high risk of MVI classified by the MVI classifier demonstrated significantly lower recurrence-free survival (RFS) and overall survival rates at 1, 3 and 5 years compared to those classified as low risk (p < .001). Multivariate cox regression modelling of a-fetoprotein > 20 ng/mL [hazard ratio (HR) = 1.53; 95% confidence interval (95% CI): 1.02-2.33, p = .047], high risk of MVI (HR = 3.76; 95% CI: 2.40-5.88, p < .001) and unfavourable tumour location (HR = 2.15; 95% CI: 1.40-3.29, p = .001) yielded a c-index of .731 (bootstrapped 95% CI: .667-.778) for evaluating RFS after RFA. Among the three risk factors, MVI was the most powerful predictor for intrahepatic distance recurrence. CONCLUSIONS: The proposed MVI classifier can serve as a valuable imaging biomarker for prognostic stratification in early-stage HCC patients undergoing RFA.

The role of artificial intelligence in the development of anticancer therapeutics from natural polyphenols: Current advances and future prospects.

Natural polyphenols, abundant in the human diet, are derived from a wide variety of sources. Numerous preclinical studies have demonstrated their significant anticancer properties against various malignancies, making them valuable resources for drug development. However, traditional experimental methods for developing anticancer therapies from natural polyphenols are time-consuming and labor-intensive. Recently, artificial intelligence has shown promising advancements in drug discovery. Integrating AI technologies into the development process for natural polyphenols can substantially reduce development time and enhance efficiency. In this study, we review the crucial roles of natural polyphenols in anticancer treatment and explore the potential of AI technologies to aid in drug development. Specifically, we discuss the application of AI in key stages such as drug structure prediction, virtual drug screening, prediction of biological activity, and drug-target protein interaction, highlighting the potential to revolutionize the development of natural polyphenol-based anticancer therapies.

Thiocyanate promoted difunctionalization and cyclization of unsaturated C-C bonds to construct 1-sulfur-2-nitrogen-functionalized alkenes and 2-thiocyanate indolines.

An unprecedented one-pot route to achieve highly regioselective 1-sulfur-functionalized 2-nitrogen-functionalized alkenes and 2-thiocyanate indolines from unsymmetrical ynamides (readily and generally available amides) using the commercially available inexpensive iodobenzene diacetate (PIDA) as the oxidant and potassium thiocyanate (KSCN) as the thiocyanate (SCN) source has been developed. The interconversion of thiocyanate (SCN) and isothiocyanate (NCS) groups simultaneously forms C-N and C-S bonds in this metal-free approach, while introducing important functional groups into homemade alkynes. A radical-chain mechanism, involving competing kinetically controlled chain transfer at the S atom and sterically-controlled chain transfer at the N atom of the thiocyanogen molecule in this mild approach, is proposed.

TP53 to mediate immune escape in tumor microenvironment: an overview of the research progress.

Increasing evidence suggests that key cancer-causing driver genes continue to exert a sustained influence on the tumor microenvironment (TME), highlighting the importance of immunotherapeutic targeting of gene mutations in governing tumor progression. TP53 is a prominent tumor suppressor that encodes the p53 protein, which controls the initiation and progression of different tumor types. Wild-type p53 maintains cell homeostasis and genomic instability through complex pathways, and mutant p53 (Mut p53) promotes tumor occurrence and development by regulating the TME. To date, it has been wildly considered that TP53 is able to mediate tumor immune escape. Herein, we summarized the relationship between TP53 gene and tumors, discussed the mechanism of Mut p53 mediated tumor immune escape, and summarized the progress of applying p53 protein in immunotherapy. This study will provide a basic basis for further exploration of therapeutic strategies targeting p53 protein.

The classical D1 dopamine receptor antagonist SCH23390 is a functional sigma-1 receptor allosteric modulator.

SCH23390 is a widely used D1 dopamine receptor (D1R) antagonist that also elicits some D1R-independent effects. We previously found that the benzazepine, SKF83959, an analog of SCH23390, produces positive allosteric modulation of the Sigma-1 receptor (Sig1R). SCH23390 does not bind to the orthodoxic site of Sig1R but enhances the binding of 3H (+)-pentazocine to Sig1R. In this study, we investigated whether SCH23390 functions as an allosteric modulator of Sig1R. We detected increased Sig1R dissociation from binding immunoglobulin protein (BiP) and translocation of Sig1R to the plasma membrane in response to SCH23390 in transfected HEK293T and SH-SY5Y cells, respectively. Activation of Sig1R by SCH23390 was further confirmed by inhibition of GSK3ß activity in a time- and dose-dependent manner; this effect was blocked by pretreatment with the Sig1R antagonist, BD1047, and by knockdown of Sig1R. SCH23390 also inhibited GSK3ß in wild-type mice but not in Sig1R knockout mice. Finally, we showed that SCH23390 allosterically modulated the effect of the Sig1R agonist SKF10047 on inhibition of GSK3ß. This positive allosteric effect of SCH23390 was further confirmed via promotion of neuronal protection afforded by SKF10047 in primary cortical neurons challenged with MPP+. These results provide the first evidence that SCH23390 elicits functional allosteric modulation of Sig1R. Our findings not only reveal novel pharmacological effects of SCH23390 but also indicate a potential mechanism for SCH23390-mediated D1R-independent effects. Therefore, attention should be paid to these Sig1R-mediated effects when explaining pharmacological responses to SCH23390.

Zonation of bulk and rhizosphere soil bacterial communities and their covariation patterns along the elevation gradient in riparian zones of three Gorges reservoir, China.

Zonation is a typical pattern of soil distribution and species assembly across riparian habitats. Microorganisms are essential members of riparian ecosystems and whether soil microbial communities demonstrate similar zonation patterns and how bulk and rhizosphere soil microorganisms interact along the elevation (submergence stress) gradient remain largely unknown. In this study, bulk and rhizosphere (dominant plant) soil samples were collected and investigated across riparian zones where the submergence stress intensity increased as the elevation decreased. Results showed that the richness of bacterial communities in bulk and rhizosphere soil samples was significantly different and presented a zonation pattern along with the submergence stress gradient. Bulk soil at medium elevation that underwent moderate submergence stress had the most abundant bacterial communities, while the species richness of rhizobacteria at low elevation that experienced serious submergence stress was the highest. Additionally, principal coordinate analysis (PCoA) and significance tests showed that bulk and rhizosphere soil samples were distinguished according to the structure of bacterial communities, and so were bulk or rhizosphere soil samples from different elevations. Redundancy analysis (RDA) and Mantel test suggested that bacterial communities of bulk soil mainly relied on the contents of soil organic matter, total carbon (TC), total nitrogen (TN), sodium (Na), calcium (Ca) and magnesium (Mg). Contrastingly, the contents of Na and Mg were the main factors explaining the variation in rhizobacterial community composition. Correlation and microbial source tracking analyses showed thatthe relationship of bulk and rhizosphere soil bacteria became much stronger, and the rhizosphere soil may get more bacterial communities from bulk soil with the increase in submergence severity. Our results suggest that the abiotic and biotic components of the riparian ecosystem are closely covariant along the submergence stress gradient and imply that the bacterial community may be a key node linking soil physiochemical properties and vegetation communities.

Nanomaterial-related hemoglobin-based oxygen carriers, with emphasis on liposome and nano-capsules, for biomedical applications: current status and future perspectives.

Oxygen is necessary for life and plays a key pivotal in maintaining normal physiological functions and treat of diseases. Hemoglobin-based oxygen carriers (HBOCs) have been studied and developed as a replacement for red blood cells (RBCs) in oxygen transport due to their similar oxygen-carrying capacities. However, applications of HBOCs are hindered by vasoactivity, oxidative toxicity, and a relatively short circulatory half-life. With advancements in nanotechnology, Hb encapsulation, absorption, bioconjugation, entrapment, and attachment to nanomaterials have been used to prepare nanomaterial-related HBOCs to address these challenges and pend their application in several biomedical and therapeutic contexts. This review focuses on the progress of this class of nanomaterial-related HBOCs in the fields of hemorrhagic shock, ischemic stroke, cancer, and wound healing, and speculates on future research directions. The advancements in nanomaterial-related HBOCs are expected to lead significant breakthroughs in blood substitutes, enabling their widespread use in the treatment of clinical diseases.