Transcription factor CsMYB36 regulates fruit neck length via mediating cell expansion in cucumber.

The fruit neck is an important agronomic trait of cucumber (Cucumis sativus). However, the underlying genes and regulatory mechanisms involved in fruit neck development are poorly understood. We previously identified a cucumber yellow-green peel (ygp) mutant, whose causal gene is MYB DOMAIN PROTEIN 36 (CsMYB36). This study showed that the ygp mutant exhibited a shortened fruit neck and repressed cell expansion in the fruit neck. Further functional analysis showed that CsMYB36 was also a target gene, and its expression was enriched in the fruit neck. Overexpression of CsMYB36 in the ygp mutant rescued shortened fruit necks. Furthermore, transcriptome analysis and reverse transcription quantitative PCR (RT-qPCR) assays revealed that CsMYB36 positively regulates the expression of an expansin-like A3 (CsEXLA3) in the fruit neck, which is essential for cell expansion. Yeast 1-hybrid and dual-luciferase assays revealed that CsMYB36 regulates fruit neck elongation by directly binding to the promoter of CsEXLA3. Collectively, these findings demonstrate that CsMYB36 is an important gene in the regulation of fruit neck length in cucumber plants.

Lipid Deficiency Contributes to Impaired Alveolar Progenitor Cell Function in Aging and Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is an aging-associated interstitial lung disease resulting from repeated epithelial injury and inadequate epithelial repair. Alveolar type II cells (AEC2) are progenitor cells that maintain epithelial homeostasis and repair the lung after injury. In the current study, we assessed lipid metabolism in AEC2s from human lungs of IPF patients and healthy donors, as well as AEC2s from bleomycin-injured young and old mice. Through single cell RNA sequencing (scRNA-seq), we observed that lipid metabolism-related genes were downregulated in IPF AEC2s and bleomycin-injured mouse AEC2s. Aging aggravated this decrease and hindered recovery of lipid metabolism gene expression in AEC2s after bleomycin injury. Pathway analyses revealed down-regulation of genes related to lipid biosynthesis and fatty acid -oxidation in AEC2s from IPF lungs and bleomycin-injured, aged mouse lungs compared to the respective controls. We confirmed decreased cellular lipid content in AEC2s from IPF lungs and bleomycin-injured, aged mouse lungs using immunofluorescence staining and flow cytometry. We further show that lipid metabolism was associated with AEC2 progenitor function. Lipid supplementation and peroxisome proliferator activated receptor gamma (PPARγ) activation promoted progenitor renewal capacity of both human and mouse AEC2s in 3D organoid cultures. Lipid supplementation also increased AEC2 proliferation and expression of SFTPC in AEC2s. In summary, we identified a lipid metabolism deficiency in AEC2s from lungs of patients with IPF and bleomycin-injured aged mice. Restoration of lipid metabolism homeostasis in AEC2s might promote AEC2 progenitor function and offer new opportunities for therapeutic approaches to IPF. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

CsHLS1-CsSCL28 module regulates compact plant architecture in cucumber.

Increased planting densities boost crop yields. A compact plant architecture facilitates dense planting. However, the mechanisms regulating compact plant architecture in cucurbits remain unclear. In this study, we identified a cucumber (Cucumis sativus) compact plant architecture (cpa1) mutant from an ethyl methane sulfonate (EMS)-mutagenized library that exhibited distinctive phenotypic traits, including reduced leaf petiole angle and leaf size. The candidate mutation causes a premature stop codon in CsaV3_1G036420, which shares similarity to Arabidopsis HOOKLESS 1 (HLS1) encoding putative histone N-acetyltransferase (HAT) protein and was named CsHLS1. Consistent with the mutant phenotype, CsHLS1 was predominantly expressed in leaf petiole bases and leaves. Constitutive overexpressing CsHLS1 in cpa1 restored the wild-type plant architecture. Knockout of CsHLS1 resulted in reduces leaf petiole angle and leaf size and as well as decreased acetylation levels. Furthermore, CsHLS1 directly interacted with CsSCL28 and negatively regulated compact plant architecture in cucumber. Importantly, CsHLS1 knockout increased the photosynthesis rate and leaf nitrogen in cucumbers, thereby maintaining cucumber yield at normal density. Overall, our research provides valuable genetic breeding resource and gene target for creating a compact plant architecture for dense cucumber planting.

Injecting Excess Na into a P2-Type Layered Oxide Cathode to Achieve Presodiation in a Na-Ion Full Cell.

The initial Na loss limits the theoretical specific capacity of cathodes in Na-ion full cell applications, especially for Na-deficient P2-type cathodes. In this study, we propose a presodiation strategy for cathodes to compensate for the initial Na loss in Na-ion full cells, resulting in a higher specific capacity and a higher energy density. By employing an electrochemical presodiation approach, we inject 0.32 excess active Na into P2-type Na0.67Li0.1Fe0.37Mn0.53O2 (NLFMO), aiming to compensate for the initial Na loss in hard carbon (HC) and the inherent Na deficiency of NLFMO. The structure of the NLFMO cathode converts from P2 to P'2 upon active Na injection, without affecting subsequent cycles. As a result, the HC||NLFMOpreNa full cell exhibits a specific capacity of 125 mAh/g, surpassing the value of 61 mAh/g of the HC||NLFMO full cell without presodiation due to the injected active Na. Moreover, the presodiation effect can be achieved through other engineering approaches (e.g., Na-metal contact), suggesting the scalability of this methodology.

Does international trade reduce global carbon inequality? Evidence from a producer-consumer shared responsibility.

Addressing global carbon inequality constitutes an important task for both international negotiations on climate-change mitigation and the achievement of sustainable development goals. Soaring international trade might become a vigorous modifier for reducing global carbon inequality through production reallocation and economic boosts in different countries. However, this effect remains largely unexplored, not only because of little awareness of the windfall benefits from international trade but also because of debates on quantifying global carbon inequality from both production- and consumption-based perspectives. To avoid incomplete implications from a single perspective, this study first adapted a producer-consumer shared responsibility to evaluate global carbon inequality using the technology-adjusted consumption-based accounting method for 189 countries from 2006 to 2016. A dynamic panel data model was developed to examine the different channels through which international trade affects global carbon inequality in developed and developing countries. The results demonstrate that even with increasing carbon emissions, less global carbon inequality was witnessed from 2006 to 2016. International trade plays an important role in reducing global carbon inequality, mostly by stimulating the economy and increasing household income in developing countries. However, production reallocation via international trade fails in reducing the emission responsibilities of developed countries, rendering this futile in alleviating global carbon inequality. Carbon leakage that transfers carbon-intensive production across borders can lead to this unintended result, and more stringent cross-border regulations such as the carbon border adjustment mechanism can be effective. This study not only highlights the pivotal role of international trade in reducing global carbon inequality but also the future direction of international cooperation on climate change mitigation in a globalized world.

Hsa_circ_0003596 enhances the development of cell renal clear cell carcinoma through the miR-502-5p/IGF1/PI3K/AKT axis.

Accumulating research findings have shown that circular RNAs (circRNAs) play an indispensable role in tumorigenesis and tumor progression. The current study aimed to explore the role and modulatory mechanism of hsa_circ_0003596 in clear cell renal cell carcinoma (ccRCC). Quantitative real-time polymerase chain reaction was adopted to detect the expression of hsa_circ_0003596 in ccRCC tissue and cell lines. 5-Ethynyl-2'-deoxyuridine, cell counting kit 8 and the colony formation assay were utilized to assess the proliferation potential of the ccRCC cells. Transwell along with wound healing assays were adopted to quantify infiltration coupled with the migration potential of the cells. The current research study found that the circRNA hsa_circ_0003596 was overexpressed in ccRCC tissue and cell lines. Further, result showed that hsa_circ_0003596 was associated with distant metastasis of renal cancer. Notably, the knockdown of hsa_circ_0003596 can lower the proliferation, infiltration and migration potential of ccRCC cells. The results of in vivo experiments found that the reduction of hsa_circ_0003596 significantly hampered the growth of tumors in mice. In addition, it was evident that hsa_circ_0003596 acts as a "molecular sponge" for miR-502-5p to upregulate the expression of the microRNA-502-5p (miR-502-5p) target insulin-like growth factor 1 (IGF1R). Furthermore, it was found that the phosphatidylinositol 3-kinase (PI3K)/AKT signaling was the downstream cascade of hsa_circ_0003596/miR-502-5p/IGF1R cascade, which is partly responsible for the cancer-promoting effect. Overall, the results of the present study showed that hsa_circ_0003596 facilitated the proliferation, infiltration and migration of ccRCC through the miR-502-5p/IGF1R/PI3K/AKT axis. Therefore, it was evident that hsa_circ_0003596 can serve as a possible biomarker and therapeutic target against ccRCC.

From Li to Na: Exploratory Analysis of Fe-Based Phosphates Polyanion-Type Cathode Materials by Mn Substitution.

Both LiFePO4 (LFP) and NaFePO4 (NFP) are phosphate polyanion-type cathode materials, which have received much attention due to their low cost and high theoretical capacity. Substitution of manganese (Mn) elements for LFP/NFP materials can improve the electrochemical properties, but the connection between local structural changes and electrochemical behaviors after Mn substitution is still not clear. This study not only achieves improvements in energy density of LFP and cyclic stability of NFP through Mn substitution, but also provides an in-depth analysis of the structural evolutions induced by the substitution. Among them, the substitution of Mn enables LiFe0.5 Mn0.5 PO4 to achieve a high energy density of 535.3 Wh kg-1 , while NaFe0.7 Mn0.3 PO4 exhibits outstanding cyclability with 89.6% capacity retention after 250 cycles. Specifically, Mn substitution broadens the ion-transport channels, improving the ion diffusion coefficient. Moreover, LiFe0.5 Mn0.5 PO4 maintains a more stable single-phase transition during the charge/discharge process. The transition of NaFe0.7 Mn0.3 PO4 to the amorphous phase is avoided, which can maintain structural stability and achieve better electrochemical performance. With systematic analysis, this research provides valuable guidance for the subsequent design of high-performance polyanion-type cathodes.

Virulence and community dynamics of fungal species with vertical and horizontal transmission on a plant with multiple infections.

The virulence evolution of multiple infections of parasites from the same species has been modeled widely in evolution theory. However, experimental studies on this topic remain scarce, particularly regarding multiple infections by different parasite species. Here, we characterized the virulence and community dynamics of fungal pathogens on the invasive plant Ageratina adenophora to verify the predictions made by the model. We observed that A. adenophora was highly susceptible to diverse foliar pathogens with mixed vertical and horizontal transmission within leaf spots. The transmission mode mainly determined the pathogen community structure at the leaf spot level. Over time, the pathogen community within a leaf spot showed decreased Shannon diversity; moreover, the vertically transmitted pathogens exhibited decreased virulence to the host A. adenophora, but the horizontally transmitted pathogens exhibited increased virulence to the host. Our results demonstrate that the predictions of classical models for the virulence evolution of multiple infections are still valid in a complex realistic environment and highlight the impact of transmission mode on disease epidemics of foliar fungal pathogens. We also propose that seedborne fungi play an important role in structuring the foliar pathogen community from multiple infections within a leaf spot.

Native plants change the endophyte assembly and growth of an invasive plant in response to climatic factors.

Climate change, microbial endophytes, and local plants can affect the establishment and expansion of invasive species, yet no study has been performed to assess these interactions. Using a growth chamber, we integrated the belowground (rhizosphere soils) and aboveground (mixture of mature leaf and leaf litter) microbiota into an experimental framework to evaluate the impacts of four native plants acting as microbial inoculation sources on endophyte assembly and growth of the invasive plant Ageratina adenophora in response to drought stress and temperature change. We found that fungal and bacterial enrichment in the leaves and roots of A. adenophora exhibited distinct patterns in response to climatic factors. Many fungi were enriched in roots in response to high temperature and drought stress; in contrast, many bacteria were enriched in leaves in response to low temperature and drought stress. Inoculation of microbiota from phylogenetically close native plant species (i.e., Asteraceae Artemisia atrovirens) causes the recipient plant A. adenophora (Asteraceae) to enrich dominant microbial species from inoculation sources, which commonly results in a lower dissimilar endophytic microbiota and thus produces more negative growth effects when compared to non-Asteraceae inoculations. Drought, microbial inoculation source, and temperature directly impacted the growth of A. adenophora. Both drought and inoculation also indirectly impacted the growth of A. adenophora by changing the root endophytic fungal assembly. Our data indicate that native plant identity can greatly impact the endophyte assembly and host growth of invasive plants, which is regulated by drought and temperature.IMPORTANCEThere has been increasing interest in the interactions between global changes and plant invasions; however, it remains to quantify the role of microbial endophytes in plant invasion with a consideration of their variation in the root vs leaf of hosts, as well as the linkages between microbial inoculations, such as native plant species, and climatic factors, such as temperature and drought. Our study found that local plants acting as microbial inoculants can impact fungal and bacterial enrichment in the leaves and roots of the invasive plant Ageratina adenophora and thus produce distinct growth effects in response to climatic factors; endophyte-mediated invasion of A. adenophora is expected to operate more effectively under favorable moisture. Our study is important for understanding the interactions between climate change, microbial endophytes, and local plant identity in the establishment and expansion of invasive species.

Large common bile duct stones in high-risk elderly patients: Immediate endoscopic stone removal or elective stone removal? A single-center retrospective study.

BACKGROUND AND OBJECTIVE: For high-risk elderly patients with chronic diseases, endoscopic stone removal for large common bile duct stones is associated with a high risk of adverse events and incomplete stone removal. The aim of this study was to investigate whether the treatment strategy of short-term biliary plastic stent placement followed by elective endoscopic stone removal is more effective and safer than immediate endoscopic stone removal. METHODS: The data of 262 high-risk elderly patients who received endoscopic retrograde cholangiopancreatography (ERCP) for large common bile duct (CBD) stones from 2017 to 2022 were retrospectively analyzed. The patients were divided into group A (immediate stone removal) and group B (stent drainage + elective stone removal). The baseline data of the 2 groups were matched 1:1 by propensity score matching. The stone clearance rate, ERCP procedure time, total hospital stay, and procedure-related adverse events were compared between the matched groups. In group B, stone size before and after stent placement, hospital stay, procedure time and adverse events of two ERCPs were compared. RESULTS: A total of 57 pairs of patients were successfully matched between the 2 groups. The stone clearance rate in group B was higher than that in group A (89.5% vs. 75.3, P = 0.049). The total hospital stay in group B was longer than that in group A (11.86 ± 3.912 d vs. 19.14 ± 3.176 d, P<0.001). The total adverse event rate in group A was higher than that in group B (29.8% vs. 12.3%, P = 0.005). The incidence of cholangitis/cholecystitis after ERCP was significantly higher in group A than in group B (7.0% vs. 0.9% P = 0.029). There was no significant difference in the incidence of post-ERCP pancreatitis, bleeding, pneumonia, and cardio-cerebrovascular events between the 2 groups. There were no perforation cases in either group. After plastic biliary stent placement in group B, the stone size was significantly smaller than before stent placement (1.59 ± 0.544 cm vs. 1.95 ± 0.543 cm, P < 0.001), and there was no significant difference in the total adverse event incidence between the two ERCP procedures (18.8% vs. 10.9%, P = 0.214). CONCLUSION: For high-risk elderly patients with large CBD stones, the treatment strategy involving temporary placement of plastic stent and elective endoscopic stone removal is safer and more effective than immediate stone removal.

Risk Factors for Mortality in Severe Fever with Thrombocytopenia Syndrome Patients with Central Nervous System Complications.

BACKGROUND Severe fever with thrombocytopenia syndrome (SFTS) is a zoonotic viral hemorrhagic fever caused by the SFTS virus (SFTSV), which is a newly identified tick-borne bunyavirus, recently named Dabie bandavirus. In rural China, SFTSV or Dabie bandavirus is commonly transmitted by Haemaphysalis longicornis, the Asian longhorned tick. In recent years, SFTS has been of great concern due to its high morbidity and mortality. The present study investigated the risk factors for mortality in patients with SFTS complicated by central nervous system involvement. MATERIAL AND METHODS We studied 69 SFTS patients hospitalized between 2013 and 2020. We analyzed the laboratory test results and clinical data through univariate and multivariate regression. RESULTS Neurological complications occurred in 59 patients in the survival group and 10 in the mortality group. No significant gender difference was found between the 2 groups. No significant difference was found in age, hospitalization duration, or occurrence of encephalitis between the 2 groups. The mean duration of hospitalization and course of the disease in the mortality group were significantly shorter than those in the survival group (P<0.01). The mean values of platelet count, potassium, and sodium in the mortality group were significantly lower, while the mean values of aspartate aminotransferase, lactic dehydrogenase, creatine kinase-MB (CK-MB) and procalcitonin were higher than those in the survival group. Low platelet count and high CK-MB were independent risk factors for mortality in patients. For each unit increase in platelet count, the risk of mortality decreased by 24.2%, and for each unit increase in CK-MB, the probability of mortality increased by 118.6%. CONCLUSIONS Decreased platelets and increased CK-MB were independent risk factors for mortality in encephalitis patients. SFTS patients with encephalitis should be monitored for changes in these 2 indicators.

LINC00536 Promotes Breast Cancer Progression by Regulating ROCK1 via Sponging of miR-214-5p.

Accumulating evidence has shown that long noncoding RNAs (lncRNAs) play a significant role in regulating gene expression and participating in the progression of various malignancies. In our study, by analyzing data from The Cancer Genome Atlas (TCGA), LINC00536 was found to be highly expressed in breast cancer (BC) tissues, but its function and clinical significance in BC are still unknown. Therefore, we aimed to explore the role and molecular mechanism of LINC00536 in BC. We collected human BC tissue specimens and validated that LINC00536 was overexpressed in BC tissues. Increased LINC00536 expression was associated with advanced TNM stage, larger tumor diameter, lymph node metastasis and poor prognosis in patients with BC. Univariate and multivariate Cox regression analyses showed that high LINC00536 expression was an independent prognostic risk factor for overall survival in BC patients. Furthermore, quantitative reverse transcription PCR (qRT-PCR) showed that LINC00536 was upregulated in BC cell lines. Then, we confirmed that LINC00536 silencing-inhibited BC cell proliferation, migration, and invasion and led to cell cycle arrest in vitro. Animal experiments showed that knockdown of LINC00536 expression suppressed tumorigenesis in vivo. Mechanistically, LINC00536 serves as a ceRNA for miR-214-5p, increasing the expression of ROCK1, which acts as a tumor promoter in BC. Rescue assays revealed that miR-214-5p inhibition or ROCK1 overexpression could neutralize the suppressive effects of LINC00536 knockdown on cell proliferation, migration and invasion. Our data indicated that LINC00536 accelerates BC progression by regulating the miR-214-5p/ROCK1 pathway, which might provide a new perspective to investigate the development process of BC.

Exploring the impact of emissions trading schemes on income inequality between urban and rural areas.

While the Paris Agreement and 2030 Agenda for Sustainable Development are the two most important global governance agendas, in practice they have been implemented in isolation. This calls for the need to focus on the potential policy synergies between emission reduction policies and Sustainable Development Goals (SDGs). This paper therefore aims to explore whether the emissions trading scheme (ETS) policy-one of the most effective ways to fulfill the target determined by the Paris Agreement, would facilitate reducing income inequality (SDG10). By combining a difference-in-difference estimation and propensity score matching technique based on a balanced panel dataset for 31 Chinese provinces from 2010 to 2018, we quantify the impact of ETS policy on income inequality between urban and rural areas in China. The results demonstrate that compared with the regions without ETS, the Theil index between rural and urban areas with ETS decreased by 0.018 on average in China. In addition, the ETS would perform better in regions with low urbanization level and high coal dependence. Hence it is vital to speed up the establishment of a unified ETS market in China. This is particularly true for inner underdeveloped regions in China. These findings proven to be robust according to a series of tests challenge the view that SDG 10 has the least relevance to climate action and suggest rethinking the effectiveness and applicability of ETS. Therefore, our research can not only serve as a reference for the development of ETS in China and elsewhere, but also inform decision makers who are seeking for policy synergies between the Paris Agreement and SDGs.

Dearomatization-Rearomatization Reaction of Metal-Polarized Aza-ortho-Quinone Methides.

Metal-polarized aza-ortho-quinone methides (aza-o-QMs) are a unique and efficient handle for azaheterocycle synthesis. Despite great achievements, the potential of these reactive intermediates has not yet been fully exploited, especially the new reaction modes. Herein, we disclosed an unprecedented dearomatization process of metal-polarized aza-o-QMs, affording transient dearomatized spiroaziridine intermediates. Based on this serendipity, we accomplished three sequential dearomatization-rearomatization reactions of benzimidazolines with aza-sulfur ylides, enabling the divergent synthesis of bis-nitrogen heterocycles with high efficiency and flexibility. Moreover, experimental and theoretical studies were performed to explain the proposed mechanisms and observed selectivity. Further cellular evaluation of the dibenzodiazepine products identified a hit compound for new antitumor drugs.

De Novo Construction of Chiral Aminoindolines by Cu-Catalyzed Asymmetric Cyclization and Subsequent Discovery of an Unexpected Sulfonyl Migration.

Searching for efficient strategies to access structurally novel aminoindolines is of great significance for drug discovery. However, catalytic asymmetric de novo construction of aminoindoline scaffolds with functionality primed for diversification still remains elusive. Here, we report a Cu-catalyzed asymmetric cyclization of ethynyl benzoxazinones with amines, producing chiral 3-aminoindolines in good yield and with high enantioselectivity (up to 97% yield and 98:2 er). Moreover, a radical-mediated sulfonyl migration of these products was unexpectedly found, further affording new chiral 3-aminoindolines bearing alkenyl sulfonyl groups with retained enantiopurity (up to 84% yield and 98:2 er). Bioactivity evaluations indicate that these 3-aminoindolines show notable antitumor activities and chirality is proven to have a significant impact on their antitumor activity.

Glycoproteomics revealed novel N-glycosylation biomarkers for early diagnosis of lung adenocarcinoma cancers.

Circulating biomarkers play important roles in diagnosis of malignant tumors. N-glycosylation is an important post-translation patter and obviously affect biological behaviors of malignant tumor cells. However, the role of N-glycosylation sites in early diagnosis of tumors still remains further investigation. In this study, plasma from 20 lung adenocarcinoma (LUAD), which were all classified as stage I, as well as 20 normal controls (NL) were labeled and screened by mass spectrometry (MS). Total 39 differential N-glycosylation sites were detected in LUAD, 17 were up-regulated and 22 were down-regulated. In all differential sites, ITGB3-680 showed highest potential in LUAD which showed 99.2% AUC, 95.0% SP and 95.0% SN. Besides, APOB-1523 (AUC: 89.0%, SP: 95.0%, SN: 70.0%), APOB-2982 (AUC: 86.8%, SP: 95.0%, SN: 45.0%) and LPAL2-101 (AUC: 81.1%, SP: 95.0%, SN: 47.4%) also acted as candidate biomarkers in LUAD. Combination analysis was then performed by random forest model, all samples were divided into training group (16 cases) and testing group (4 cases) and conducted by feature selection, machine learning, integrated model of classifier and model evaluation. And the results indicated that combination of differential sites could reach 100% AUC in both training and testing group. Taken together, our study revealed multiple N-glycosylation sites which could be applied as candidate biomarkers for early diagnosis diagnosis of LUAD.

Linearization of nonlinear frequency modulated continuous wave generation using model-based reinforcement learning.

The prevalence of machine learning (ML) opens up new directions for plenty of scientific fields. The development of optics technologies also benefits from it. However, due to the complex properties of nonlinear and dynamic optical systems, optical system control with ML is still in its infancy. In this manuscript, to demonstrate the feasibility of optical system control using reinforcement learning (RL), i.e., a branch of ML, we solve the linearization problem in the frequency modulated continuous wave (FMCW) generation with the model-based RL method. The experiment results indicate an excellent improvement in the linearity of the generated FMCW, showing a sharp peak in the frequency spectrum. We confirm that the RL method learns the implicit physical characteristics very well and accomplishes the goal of the linear FMCW generation effectively, indicating that the marriage of ML and optics systems could have the potential to open a new era for the development of optical system control.

Depth-dependent drivers of soil microbial necromass carbon across Tibetan alpine grasslands.

Microbial necromass carbon (C) has been considered an important contributor to persistent soil C pool. However, there still lacks large-scale systematic observations on microbial necromass C in different soil layers, particularly for alpine ecosystems. Besides, it is still unclear whether the relative importance of biotic and abiotic variables such as plant C input and mineral properties in regulating microbial necromass C would change with soil depth. Based on the combination of large-scale sampling along a ~2200 km transect across Tibetan alpine grasslands and biomarker analysis, together with a global data synthesis across grassland ecosystems, we observed a relatively low proportion of microbial-derived C in Tibetan alpine grasslands compared to global grasslands (topsoil: 45.4% vs. 58.1%; subsoil: 41.7% vs. 53.7%). We also found that major determinants of microbial necromass C depended on soil depth. In topsoil, both plant C input and mineral protection exerted dominant effects on microbial necromass C. However, in subsoil, the physico-chemical protection provided by soil clay particles, iron-aluminum oxides, and exchangeable calcium dominantly facilitated the preservation of microbial necromass C. The differential drivers over microbial necromass C between soil depths should be considered in Earth system models for accurately forecasting soil C dynamics and its potential feedback to global warming.

Exosome-derived lnc-HOXB8-1:2 induces tumor-associated macrophage infiltration to promote neuroendocrine differentiated colorectal cancer progression by sponging hsa-miR-6825-5p.

INTRODUCTION: Neuroendocrine differentiation (NED) in colorectal cancer (CRC) cells has been known for decades, and our previous meta-analysis indicated that CRC patients with neuroendocrine differentiation have a lower 5-year survival rate. In recent years, an increasing number of studies have found that exosome-derived long non-coding RNAs (lncRNAs) play important roles in cancer progression and metastasis. However, the functions and mechanism of exosome-derived lncRNAs in CRC with neuroendocrine differentiation are not yet fully clear. MATERIALS AND METHODS: The clinical significance of NED was assessed in a retrospective study of 105 patients. Next-generation sequencing and bioinformatics analysis were conducted to select lnc-HOXB8-1:2 for further study. Using immunohistochemistry, qRT-PCR, western blot, transwell assay, immunofluorescence assay, fluorescence in situ hybridization assay and dual-luciferase reporter assay, the oncogenic role of exosome-derived lnc-HOXB8-1:2 was determined in CRC with NED. The mechanism underlying the lnc-HOXB8-1:2/hsa-miR-6825-5p/CXCR3 axis was also explored. RESULTS: NED was a risk factor for the progression and mortality of CRC. lnc-HOXB8-1:2, derived from exosomes secreted by neuroendocrine differentiated colon cancer cells, was identified in our study. The proportion of M2 macrophages and the migration and invasion capacities of tumor-associated macrophages (TAMs) markedly increased after the addition of neuroendocrine differentiated CRC cell-derived exosomes. More excitingly, the expression of lnc-HOXB8-1:2 and the protein level of CXCR3 were also upregulated in TAMs. The lnc-HOXB8-1:2/hsa-miR-6825-5p/CXCR3 axis was predicted via miRanda software and confirmed by the dual-luciferase reporter assay. Furthermore, the increased expression of lnc-HOXB8-1:2 was accompanied by downregulation of hsa-miR-6825-5p expression and upregulation of CXCR3 protein levels. Overexpression of hsa-miR-6825-5p also reduced CXCR3 expression. CONCLUSION: lnc-HOXB8-1:2 in exosomes derived from neuroendocrine differentiated CRC cells acted as a ceRNA competitively binding hsa-miR-6825-5p to upregulate CXCR3 expression and leading to TAM infiltration and M2 polarization, which promotes neuroendocrine differentiated CRC progression.

Human cerebral organoids establish subcortical projections in the mouse brain after transplantation.

Numerous studies have used human pluripotent stem cell-derived cerebral organoids to elucidate the mystery of human brain development and model neurological diseases in vitro, but the potential for grafted organoid-based therapy in vivo remains unknown. Here, we optimized a culturing protocol capable of efficiently generating small human cerebral organoids. After transplantation into the mouse medial prefrontal cortex, the grafted human cerebral organoids survived and extended projections over 4.5 mm in length to basal brain regions within 1 month. The transplanted cerebral organoids generated human glutamatergic neurons that acquired electrophysiological maturity in the mouse brain. Importantly, the grafted human cerebral organoids functionally integrated into pre-existing neural circuits by forming bidirectional synaptic connections with the mouse host neurons. Furthermore, compared to control mice, the mice transplanted with cerebral organoids showed an increase in freezing time in response to auditory conditioned stimuli, suggesting the potentiation of the startle fear response. Our study showed that subcortical projections can be established by microtransplantation and may provide crucial insights into the therapeutic potential of human cerebral organoids for neurological diseases.