Simultaneous targeting and suppression of heat shock protein 60 to overcome heat resistance and induce mitochondrial death of tumor cells in photothermal immunotherapy.

As the most aggressive and metastatic subtype of breast cancer, clinical demands of triple negative breast cancer (TNBC) have far not been met. Heat shock protein 60 (HSP60) is over expressed in tumor cells and impair the efficacy of photothermal therapy. In this work, a conjugate composed of self-designed peptide targeting HSP60 and gold nanorods was constructed, referred to as AuNR-P17. Results showed that AuNR-P17 was able to simultaneously down regulate the level of HSP60 and locate in the mitochondria where HSP60 is enriched in the tumor cells of TNBC, which also impeded the interaction between HSP60 and integrin α3, thereby reducing the tumor cells' heat tolerance and metastatic capabilities. At the same time, AuNR-P17 induced remarkable mitochondrial apoptosis when exposed to the laser irradiation of 808 nm. The dual functions of AuNR-P17 led to the decrement of BCL-2 and the activation of p53 and cleaved caspase-3. The danger associated molecular patterns (DAMPs) generated from the mitochondrial apoptosis elicited strong and long-term specific immune responses against TNBC in vivo and ultimately inhibited the tumor metastasis and recurrence with significantly prolonged survival (>100 days) on TNBC mice. In conclusion, this study demonstrated HSP60 a promising potential therapeutic target for triple negative breast cancer and exhibited powerful capacity of AuNR-P17 in photothermal immune therapy.

Effects of earthworm and arbuscular mycorrhizal fungal inoculation on carbon component accumulation and allocation in rocky desertification soils.

Exploring the responses of carbon component accumulation and allocation to arbuscular mycocorrhizal fungi (AM) and earthworm inoculation can provide reference for improving carbon sequestration potential and bioremediation efficiency in rocky desertification soils. In this study, we chose Fraxinus malacophylla as the host plant to inoculate with Funneliformis mosseae (FM), earthworm (E), and E+FM, using no earthworm and mycorrhizae addition as CK to examine the spatiotemporal variations in soil carbon components (i.e., total organic carbon, microbial biomass carbon, easily oxidized organic carbon, and recalcitrant organic carbon) and their allocation (i.e., microbial biomass carbon/total organic carbon, easily oxidized organic carbon/total organic carbon, and recalcitrant organic carbon/total organic carbon). The results showed that 1) The respective and interactive inoculation of E and AM significantly promoted the accumulation of each carbon component. In contrast with the control, the average carbon component levels under three inoculation treatments were ranked as E+FM>E>FM. The three inoculation treatments significantly promoted soil microbial carbon/total organic carbon (30.5%-68.5%) and easily oxidized carbon/total organic carbon (31.2%-39.2%), but decreased recalcitrant organic carbon/total organic carbon (2.9%-16.2%). 2) The spatiotemporal variation in accumulation and allocation of soil carbon components varied between the inoculation treatments. The maximum value of each carbon component occurred in June. The increase in each carbon component was significantly higher in E+FM (33.0%-122.1%) than that in E (31.2%-95.4%) and FM (9.2%-41.3%). The maximum value of microbial biomass carbon/total organic carbon and easily oxidized organic carbon/total organic carbon was observed in June, while that of recalcitrant organic carbon/total organic carbon was recorded in December. In contrast with CK, the amplitude of variation in the proportion of carbon components in total organic carbon under the three inoculation treatments was ranked as E+FM>E>FM. The accumulation and allocation of all carbon components decreased (9.7%-146.2%) along the soil profile. The level of carbon components in the E treatment decreased the smallest. The microbial biomass carbon/total organic carbon and easily oxidized carbon/total organic carbon decreased the least and the recalcitrant organic carbon/total organic carbon decreased the greatest under the E+FM treatment. 3) Changes in soil physicochemical properties under the three inoculation treatments significantly affected the accumulation and allocation of organic carbon components. Soil pH was negatively correlated with carbon component accumulation and allocation, whereas other soil variables were positively correlated with them. 4) The results of principal component analysis showed that soil water content, total nitrogen, and total phosphorus were the main factors driving carbon component accumulation, while soil water content, total phosphorus, and pH were the main factors controlling carbon component allocation. Therefore, we concluded that the earthworms, AM fungi and their interaction affected the accumulation and allocation of carbon components in Yunnan rocky desertification soils, which would primarily depend on the changes of soil water content, acid-base property, as well as nitrogen and phosphorus conditions.

Full-Length Transcriptome Profile of Apis cerana Revealed by Nanopore Sequencing.

The Asian honey bee (Apis cerana) plays a crucial role in providing abundant bee products and in maintaining ecological balance. Despite the availability of the genomic sequence of the Asian honey bee, its transcriptomic information remains largely incomplete. To address this issue, here we constructed three pooled RNA samples from the queen, drone, and worker bees of A. cerana and performed full-length RNA sequencing using Nanopore single-molecule sequencing technology. Ultimately, we obtained 160,811 full-length transcript sequences from 19,859 genes, with 141,189 being novel transcripts, of which 130,367 were functionally annotated. We detected 520, 324, and 1823 specifically expressed transcripts in the queen, worker, and drone bees, respectively. Furthermore, we identified 38,799 alternative splicing (AS) events from 5710 genes, 44,243 alternative polyadenylation (APA) sites from 1649 gene loci, 88,187 simple sequence repeats (SSRs), and 17,387 long noncoding RNAs (lncRNAs). Leveraging these transcripts as references, we identified 6672, 7795, and 6804 differentially expressed transcripts (DETs) in comparisons of queen ovaries vs drone testes, worker ovaries vs drone testes, and worker ovaries vs queen ovaries, respectively. Our research results provide a comprehensive set of reference transcript datasets for Apis cerana, offering important sequence information for further exploration of its gene functions.

A novel anti-CTLA-4 nanobody-IL12 fusion protein in combination with a dendritic cell/tumour fusion cell vaccine enhances the antitumour activity of CD8+ T cells in solid tumours.

BACKGROUND: We previously developed a nanobody targeting CTLA-4 and demonstrated that it can boost antitumour T-cell responses in vitro; however, the resulting responses after the injection of T cells into cancer models are usually weak and transient. Here, we explored whether fusing our nanobody to IL-12 would enable it to induce stronger, longer-lasting T-cell immune responses after exposure to immature dendritic cell and tumour cell fusions. RESULTS: The fusion protein enhanced the response of CD8+ T cells to tumour antigens in vitro and led to stronger, more persistent immune responses after the T cells were injected into mice bearing different types of xenografts. CONCLUSION: Our in vitro and in vivo results suggest the anticancer potential of our nanobody-interleukin fusion system and support the clinical application of this fusion approach for various nanobodies.

Thiolated dextrin nanoparticles for curcumin delivery: Stability, in vitro release, and binding mechanism.

To achieve the effective loading and delivery of curcumin, novel disulfide-crosslinked nanoparticles based on modified dextrin were developed for the encapsulation of curcumin. Thiolated dextrin (Dt-SH) was obtained via sodium periodate oxidation and cysteamine grafting. The Dt-SH exhibited a rough, flake-like morphology, was classified as an amorphous material and demonstrated enhanced enzyme resistance. Subsequently, spherical nanoparticles with sizes ranging from 92.52 to 157.12 nm and zeta potentials between +23.59 and + 29.90 mV were self-assembled in an aqueous solution. Thiol modification promoted interconnection and aggregation of the nanoparticles. These nanoparticles exhibited pH-dependent size variations. Taking curcumin as a hydrophobic model, nanoparticles showed intestinal targeted release in vitro. Fluorescence spectroscopy and thermodynamic analysis indicated that curcumin bound to Dt-SH nanoparticles primarily through hydrogen bonding and van der Waals forces, with hydrophobic interactions contributing. These findings supported the potential of thiolated dextrin nanoparticles in the effective delivery of hydrophobic compounds.

Screening of prognostic factors and survival analysis based on histological type for perimenopausal endometrial carcinoma treated with hysterectomy.

PURPOSE: This study aimed to explore the prognostic factors and survival patterns based on the histological type for the perimenopausal endometrial carcinoma (PIPEC) patients treated with hysterectomy. METHODS: The PIPEC patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Methods of random survival forest (RSF) and Cox regression were used to identify the possible prognostic factors of PIPEC patients. Then overall survival (OS) and cancer-specific survival (CSS) of PIPEC data were analyzed by histological types with regional lymph nodes status and SEER-stage to investigate the survival patterns of the PIPEC patients. RESULTS: A total of 14,178 PIPEC patients were included in the study. We found tumor size, grade, histology, SEER-stage, AJCC-stage, AJCC-T stage, metastasis to distant organs and regional lymph nodes status had a significant survival outcome for PIPEC both for OS and CSS (all p < 0.05). Regardless of regional lymph nodes status and SEER-stage for OS and CSS, the low-grade endometrioid carcinoma had the best prognosis outcome, followed by the mix cell adenocarcinoma and high-grade endometrioid carcinoma, while the carcinosarcoma and undifferentiated carcinoma had relatively poor prognosis outcome. And the survival patterns of different histological types of PIPEC were diverse and changed along with the time. CONCLUSION: We identified the possible prognostic factors of PIPEC patients treated with hysterectomy. And survival analysis based on the regional lymph nodes status and SEER-stage revealed the different histological types of PIPEC had diverse survival patterns, which will be helpful for guiding clinical practice.

A Novel Scale System Based on the Frailty Index and Laboratory Indicators for the Short-Term Prognosis of Patients with Acute Myocardial Infarction: A Retrospective Cohort Study.

Objective: Current scoring systems for short-term prognosis in patients with acute myocardial infarction (AMI) lack coverage of risk factors and have limitations in risk stratification. The aim of this study was to develop a novel assessment system based on laboratory indicators and frailty quantification to better infer short-term prognosis and risk indication in patients with AMI. Methods: A total of 365 patients with MI from January 2022 to June 2023 in Northern Jiangsu Province Hospital were included. The primary endpoint was all-cause mortality and major adverse cardiac events (MACE) during follow-up. A novel scoring model ranging from 0 to 12 was constructed, and the predictive ability of this scoring system was evaluated using the area under the receiver operating characteristic curve (AUC). Results: During follow-up, 68 patients experienced MACE. Five scoring indicators were selected through multivariate logistic regression analysis, resulting in a composite score with an AUC of 0.925, demonstrating good prognostic accuracy. Conclusion: The novel prognostic assessment system, which integrates age, Stress Hyperglycemia Ratio (SHR), Neutrophil to Lymphocyte Ratio (NLR), lactate, and frailty score, exhibits good predictive value for short-term MACE in patients with acute myocardial infarction and may enable more accurate risk classification for future use in MI patient risk management.

Clinical Effectiveness of Automated Coronary CT-derived Fractional Flow Reserve: A Chinese Randomized Controlled Trial.

Background Coronary CT-derived fractional flow reserve (CT-FFR) has been used in patients with suspected coronary artery disease (CAD); however, whether it decreases invasive coronary angiography (ICA) use and affects prognosis remains insufficiently evidenced. Purpose To explore the effectiveness of adding CT-FFR to routine coronary CT angiography (CCTA) on short-term ICA rate and major adverse cardiovascular events (MACE) in a Chinese setting. Materials and Methods A multicenter randomized controlled trial was conducted in 17 Chinese centers, with patient inclusion from May 2021 to September 2021. Eligible individuals with 25%-99% stenosis at CCTA were randomly assigned 1:1 to a strategy of CCTA plus automated CT-FFR or CCTA alone for guiding downstream care. The primary end point was the ICA rate 90 days after enrollment. Secondary end points included 90-day and 1-year MACE rates (comprised of all-cause mortality, nonfatal myocardial infarction, and urgent revascularization) and 1-year cardiac events (comprised of cardiac death, nonfatal myocardial infarction, and urgent revascularization). The Cox proportional hazards model with center effect adjustment was used for survival comparisons. Results A total of 5297 participants (mean age, 63.5 years ± 10.8 [SD]; 3178 male) were included. During the 90-day follow-up, ICA was performed in 263 of 2633 participants (10.0%) in the CCTA plus CT-FFR group and 327 of 2640 participants (12.4%) in the CCTA-alone group (absolute rate difference: -2.40%; 95% CI: -4.10, -0.70; P = .006). The MACE rates at 90 days (0.5% [12 of 2633 participants] vs 0.8% [21 of 2640 participants]; P = .12) and 1 year (2.9% [74 of 2546 participants] vs 2.8% [72 of 2531 participants]; P = .90) were similar for both groups. At 1-year follow-up, fewer cardiac events were observed in the CCTA plus CT-FFR group compared with the CCTA-alone group (0.5% vs 1.1%; adjusted hazard ratio: 0.52; 95% CI: 0.27, 0.99; P = .047). Conclusion CT-FFR added to CCTA led to a lower 90-day ICA rate and similar 1-year MACE rate in a Chinese real-world setting. Further follow-up is warranted to demonstrate the long-term prognostic value of this management approach. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Pundziute-do Prado in this issue.

SETD3-mediated histidine methylation of MCM7 regulates DNA replication by facilitating chromatin loading of MCM.

The minichromosome maintenance complex (MCM) DNA helicase is an important replicative factor during DNA replication. The proper chromatin loading of MCM is a key step to ensure replication initiation during S phase. Because replication initiation is regulated by multiple biological cues, additional changes to MCM may provide better understanding towards this event. Here, we report that histidine methyltransferase SETD3 promotes DNA replication in a manner dependent on enzymatic activity. Nascent-strand sequencing (NS-seq) shows that SETD3 regulates replication initiation, as depletion of SETD3 attenuates early replication origins firing. Biochemical studies reveal that SETD3 binds MCM mainly during S phase, which is required for the CDT1-mediated chromatin loading of MCM. This MCM loading relies on histidine-459 methylation (H459me) on MCM7 which is catalyzed by SETD3. Impairment of H459 methylation attenuates DNA synthesis and chromatin loading of MCM. Furthermore, we show that CDK2 phosphorylates SETD3 at Serine-21 during the G1/S phase, which is required for DNA replication and cell cycle progression. These findings demonstrate a novel mechanism by which SETD3 methylates MCM to regulate replication initiation.

NLRP1 inflammasome in neurodegenerative disorders: From pathology to therapies.

Neuroinflammation is a critical component in neurodegenerative disorders. The inflammasome, facilitates the cleavage of caspase-1, leading to the maturation and subsequent secretion of inflammatory factors interleukin (IL)-1ß and IL-18. Consequently, pyroptosis mediated by gasdermin D, exacerbates neuroinflammation. Among the inflammasomes, NLRP1/3 are predominant in the central nervous system (CNS), Although NLRP1 was the earliest discovered inflammasome, the specific involvement of NLRP1 in neurodegenerative diseases remains to be fully elucidated. Recently, the discovery of an endogenous inhibitor of NLRP1, dipeptidyl peptidase 9, suggests the feasibility of producing of small-molecule drugs targeting NLRP1. This review describes the latest findings on the role of the NLRP1 inflammasome in the pathology of neurodegenerative disorders, including Alzheimer's disease, and summarises the regulatory mechanisms of NLRP1 inflammasome activation in the CNS. Furthermore, we highlight the recent progress in developing small-molecule and biological inhibitors that modulate the NLRP1 infammasome for the treatment of neurodegenerative disorders, some of which are advancing to preclinical testing. SIGNIFICANCE STATEMENT: The objective of this review is to synthesise the research on the structure, activation, and regulatory mechanisms of the NLRP1 inflammasome, along with its potential impact on both acute and chronic neurodegenerative conditions. The discovery of endogenous inhibitors, such as dipeptidyl peptidase 9 and thioredoxin, and their interaction with NLRP1 suggest the possibility of developing NLRP1-targeted small-molecule drugs for the treatment of neurodegenerative disorders. This review also discusses the use of both direct and indirect NLRP1 inhibitors as prospective therapeutic strategies for these conditions.

Comparative and phylogenetic analysis of the chloroplast genomes of four commonly used medicinal cultivars of Chrysanthemums morifolium.

'Boju' and 'Huaiju' are cultivars of the Chrysanthemum (Chrysanthemum morifolium Ramat.) in the family Asteraceae, valued for their medicinal, tea, and ornamental properties, and valued by individuals. However, the yield and quality of medicinal chrysanthemums are limited by the characteristics of the germplasm resources, including the identification at the varieties and cultivation levels. Currently, research characterizing the chloroplast genomes of medicinal Chrysanthemum flowers is relatively limited. This study conducted chloroplast whole-genome sequencing on two cultivars of Chrysanthemum, 'Boju' and 'Huaiju', and compared them with the previously published chloroplast genomes of 'Hangbaiju' and 'Gongju'. The study analyzed the chloroplast genome structures of these four medicinal Chrysanthemums, identifying mutation hotspots and clarifying their phylogenetic relationships. The chloroplast genome sizes of four medicinal Chrysanthemum cultivation products ranged from 151,057 to 151,109 bp, with GC content ranging from 37.45% to 37.76%. A total of 134 genes were identified, including 89 protein-coding genes, 37 ribosomal RNA genes, and 8 transfer RNA genes. Comparative genomic analysis revealed 159 large repeat sequences, 276 simple sequence repeats, 1 gene, and 8 intergenic regions identified as highly variable regions. Nucleotide diversity (Pi) values were high (≥ 0.004) for the petN-psbM, trnR-UCU-trnT-GGU, trnT-GGU-psbD, ndhC-trnV-UCA, ycf1, ndhI-ndhG, trnL-UGA-rpl32, rpl32-ndhF, and ndhF-ycf1 fragments, aiding in variety identification. Phylogenetic analysis revealed consistent results between maximum likelihood and Bayesian inference trees, showing that the four medicinal Chrysanthemum cultivars, along with their wild counterparts and related species, evolved as a monophyletic group, forming a sister clade to Artemisia and Ajania. Among the six Chrysanthemum species, the wild Chrysanthemum diverged first (Posterior probability = 1, bootstrap = 1,000), followed by Ajania, while C. indicum and C. morifolium clustered together (Bootstrap = 100), indicating their closest genetic relationship. The chloroplast whole-genome data and characteristic information provided in this study can be used for variety identification, genetic conservation, and phylogenetic analysis within the family Asteraceae.

Modulation of p-Block Electron Orbits in Metal-Organic Frameworks for CO2 Capture and Electrochemical Reduction.

Developing catalysts with excellent CO2 capture capability and electrochemical CO2 reduction reaction (CO2RR) at a wide potential range simultaneously is significant but remains a formidable challenge. Here, two novel InMg defective trinuclear cluster-based MOFs (SNNU-41 and SNNU-42) with abundant p-block unsaturated coordinated sites were reported and exhibited good CO2 capture and CO2RR performance simultaneously. Due to the suitable micropores, SNNU-41 showed higher CO2 capture ability at different adsorption pressure conditions. On account of the rigid framework and the closer p band center to Fermi level, SNNU-42 accelerated the conversion of CO2 molecule to C1 efficiency. Notably, via adjusting the ratio of p-block metal (In) in the SNNU-42 framework, the performance of the CO2RR was promoted drastically. SNNU-42 with the InMg (1:1.8) mixed cluster delivered an excellent Faradaic efficiency of 91.3% for C1 products and high selectivity of 72.0% for HCOOH at -2.5 V (vs Ag/Ag+) with a total current density of 77.2 mA cm-2. This work provides a possibility for efficient CO2 capture and CO2RR electrocatalysts through the modulation of electronic structures and composition in MOFs.

Identification of biological significance of different stages of varicose vein development based on mRNA sequencing.

Normal veins could develop to varicose vein (VV) by some risk factors, and might further progress to shallow vein thrombosis (SVT). However, the molecular mechanism of key genes associated with the progression and regression of VV are still not thorough enough. In this study, the healthy control (HC), VV, and SVT vascular samples were collected for transcriptome sequencing. The differentially expressed genes (DEGs) were screened by "DESeq2", including DEGs1 (HC vs. VV), DEGs2 (HC vs. SVT) and DEGs3 (VV vs. SVT). And their functional enrichment analyses were conducted by "ClusterProfiler". The receiver operating characteristic (ROC) curve was used to obtain the key genes (KGs) of the pathogenesis of VV and SVT. The qRT-PCR assay was performed to validate the expressions of KGs. Immune cell infiltration analyses were conducted based on ssGSEA method. The competitive endogenous RNAs (ceRNAs) regulatory network was constructed. The target drugs of KGs were predicted using DrugBank database. The biofunctions of DACT3 were further investigated through a series of experiments in vitro. All of these DEGs were associated with inflammation and immunity related functions. Immune cell infiltration was significantly different between VV and SVT. Six key genes including PLP2, DACT3, LRRC25, PILRA, MSX1 and APOD that were associated with the progression and regression of VV were screened. The expression of LRRC25 and PILRA was significantly negatively associated with central memory T cell, and significantly positively associated with B cell. Besides, XIST was the critical regulator of multiple KGs. Cimetidine was potential drug for VV and SVT therapy. Overexpression of DACT3 significantly inhibited the proliferation and migration of vascular smooth muscle cells (VSMCs), and affected their cell cycle and phenotypic transition. This study identified six key genes associated with the progression and regression of VV. Among them, DACT3 was proved to hinder VV progression. These findings may help to deepen understanding its underlying mechanisms.

Exosomal miR-552-3p isolated from BALF of patients with silicosis induces fibroblast activation.

BACKGROUND: Silica particles can cause silicosis, a disease characterized by diffuse fibrosis of the lungs. Various signaling pathways composed of different types of cells and cytokines are involved in the development of silicosis. Exosomes have become a research hotspot recently. However, the role of exosomal microRNA (miRNA) in silicosis remains unclear. METHODS: In this study, we generated exosomal miRNA sequences from exosomes isolated from bronchoalveolar lavage fluid (BALF) of silicosis patients and the control group by high-throughput sequencing. Functional annotation and analysis of miRNA identified key target miRNAs. Levels of target miRNAs were analyzed in patient and animal samples and cells. Effects of increased miRNA were assessed through protein levels in target signaling pathways in cells treated with silica, miRNA mimics, and inhibitors. RESULTS: Our study identified 40 up-regulated and 70 down-regulated miRNAs, with miR-552-3p and its putative target gene Caveolin 1 (CAV1) as targets for further research. We found that the levels of exosomal miR-552-3p increased in silicosis patients' BALF samples, silicosis model mice, and A549 cells exposed to silica. Inhibition of miR-552-3p suppressed the expression of fibrosis markers. The increased miR-552-3p leads to the up-regulation of fibronectin and α-smooth muscle actin (α-SMA) and the suppression of caveolin 1 in fibroblast cells. Mitogen-activated protein kinase (MAPK) signaling pathways are activated in cells treated with silica and miR-552-3p mimics. CONCLUSIONS: These results help to understand exosomal miRNA-mediated intercellular communication and its key role in fibroblast activation and silicosis.

Oncolytic herpes simplex virus propagates tertiary lymphoid structure formation via CXCL10/CXCR3 to boost antitumor immunity.

Inducing tertiary lymphoid structure (TLS) formation can fuel antitumor immunity. It is necessary to create mouse models containing TLS to explore strategies of TLS formation. Oncolytic herpes simplex virus-1 (oHSV) exhibited intense effects in preclinical and clinical trials. However, the role of oHSV in TLS formation remains to be elucidated. Here, we observed the presence of TLS in 4MOSC1 and MC38 subcutaneous tumour models. Interestingly, oHSV evoked TLS formation, and increased infiltration of B cells and stem-like TCF1+CD8+ T cells proliferation. Mechanistically, oHSV increased the expression of TLS-related chemokines, along with upregulated CXCL10/CXCR3 to facilitate TLS formation. Notably, CXCL10 and CXCR3 were favourable prognostic factors for cancer patients, and closely related with immune cells infiltration. Inhibiting CXCL10/CXCR3 reduced TCF1+CD8+ T cells and granzyme B expression, and impaired oHSV-mediated TLS formation. Furthermore, oHSV-mediated TLS formation revealed superior response and survival rate when combined with αPD-1 treatment. Collectively, these findings indicate that oHSV recruits stem-like TCF1+CD8+ T cells through CXCL10/CXCR3 pathway to propagate TLS formation, and warrants future antitumor immunity development.

[Effects of ant nesting on seasonal dynamics of soil CH4 emissions in a tropical rubber-plantation forest]. / 蚂蚁筑巢对热带橡胶人工林土壤甲烷排放季节动态的影响.

Ant nests can affect the process and seasonal dynamics of forest soil methane emissions through mediating methane oxidation/reduction microorganisms and physicochemical environments. To explore the process and mechanism by which ant nests affect soil methane emissions from Hevea brasiliensis plantation in Xishuangbanna, we measured the seasonal dynamics of methane emissions from ant nest and non-nest soils by using static chamber-gas chromatography method, and analyzed the effect of ant nesting on the changes in functional microbial diversity, microhabitats, and soil nutrients in the plantations. The results showed that: 1) Ant nests significantly affected the mean annual soil methane emissions in tropical plantation. Methane emissions in ant nest were decreased by 59.9% than the non-nest soil. In the dry season, ant nest soil was a methane sink (-1.770 µg·m-2·h-1), which decreased by 87.2% compared with the non-nest soil, while it was a methane source (0.703 µg·m-2·h-1) that increased by 152.7% in the wet season. 2) Ant nesting affected methane emissions via changing soil temperature, humidity, carbon and nitrogen concentrations. In contrast to the control, the mean annual temperature, humidity, and carbon and nitrogen content increased by 4.9%-138.5% in ant nest soils, which explained 90.1%, 97.3%, 27.3%-90.0% of the variation in methane emissions, respectively. 3) Ant nesting affected the emission dynamics through changing the diversity and community structure of methane functional microbe. Compared with the control, the average annual methanogen diversity (Ace, Chao1, Shannon, and Simpson indices) in the ant nest ranged from -9.9% to 61.2%, which were higher than those (-8.7%-31.2%) of the methane-oxidising bacterial communities. The relative abundance fluctuations of methanogens and methanotrophic bacteria were 46.76% and -6.33%, respectively. The explaining rate of methanogen diversity to methane emissions (78.4%) was higher than that of oxidizing bacterial diversity (54.5%), the relative abundance explained by the dominant genus of methanogens was 68.9%. 4) The structural equation model showed that methanogen diversity, methanotroph diversity, and soil moisture were the main factors controlling methane emissions, contributing 95.6%, 95.0%, and 91.2% to the variations of emissions, respectively. The contribution (73.1%-87.7%) of soil temperature and carbon and nitrogen components to the emission dynamics was ranked the second. Our results suggest that ant nesting mediates the seasonal dynamics of soil methane emissions, primarily through changing the diversity of methane-function microorganisms and soil water conditions. The research results deepen the understanding of the mechanism of biological regulation of methane emission in tropical forest soil.

Anemia, blood cell indices, genetic correlations, and brain structures: A comprehensive analysis of roles in Parkinson's disease risk.

INTRODUCTION: Anemia may contribute significantly to the onset of Parkinson's disease (PD). Current research on the association between anemia and PD risk is inconclusive, and the relationships between anemia-related blood cell indices and PD incidence require further clarification. This study aims to investigate the relationships between anemia, blood cell indicators, and PD risk using a thorough prospective cohort study. METHODS: We used data from the UK Biobank, a prospective cohort study of 502,649 participants, and ultimately, 365,982 participants were included in the analysis. Cox proportional hazards models were utilized to adjust for confounding factors, aiming to thoroughly explore the associations between anemia and blood cell indices with the risk of incident PD. The interaction between anemia and Polygenic Risk Score (PRS) for PD was also examined. Linear regression and mediation analyses assessed potential mechanisms driven by brain structures, including grey matter volume. RESULTS: During a median follow-up of 14.24 years, 2513 participants were diagnosed with PD. Anemia considerably increased PD risk (hazard ratio [HR] 1.98, 95 % confidence interval [CI]: 1.81-2.18, P < 0.001) after adjustments. Those with high PRS for anemia had an 83 % higher PD incidence compared to low PRS participants. Sensitivity analyses confirmed result robustness. Linear regression showed that anemia correlated with grey matter volumes and most white matter tracts. Furthermore, mediation analyses identified that the volume of grey matter in Thalamus mediates the relationship between anemia and PD risk. CONCLUSION: In summary, we consider there to be a substantial correlation between anemia and increased PD risk.

GmBSK1-GmGSK1-GmBES1.5 regulatory module controls heat tolerance in soybean.

INTRODUCTION: Heat stress poses a severe threat to the growth and production of soybean (Glycine max). Brassinosteroids (BRs) actively participate in plant responses to abiotic stresses, however, the role of BR signaling pathway genes in response to heat stress in soybean remains poorly understood. OBJECTIVES: In this study, we investigate the regulatory mechanisms of GmBSK1 and GmBES1.5 in response to heat stress and the physiological characteristics and yield performance under heat stress conditions. METHODS: Transgenic technology and CRISPR/Cas9 technology were used to generated GmBSK1-OE, GmBES1.5-OE and gmbsk1 transgenic soybean plants, and transcriptome analysis, LUC activity assay and EMSA assay were carried out to elucidate the potential molecular mechanism underlying GmBSK1-GmBES1.5-mediated heat stress tolerance in soybean. RESULTS: CRISPR/Cas9-generated gmbsk1 knockout mutants exhibited increased sensitivity to heat stress due to a reduction in their ability to scavenge reactive oxygen species (ROS). The expression of GmBES1.5 was up-regulated in GmBSK1-OE plants under heat stress conditions, and it directly binds to the E-box motif present in the promoters of abiotic stress-related genes, thereby enhancing heat stress tolerance in soybean plants. Furthermore, we identified an interaction between GmGSK1 and GmBES1.5, while GmGSK1 inhibits the transcriptional activity of GmBES1.5. Interestingly, the interaction between GmBSK1 and GmGSK1 promotes the localization of GmGSK1 to the plasma membrane and releases the transcriptional activity of GmBES1.5. CONCLUSION: Our findings suggest that both GmBSK1 and GmBES1.5 play crucial roles in conferring heat stress tolerance, highlighting a potential strategy for breeding heat-tolerant soybean crops involving the regulatory module consisting of GmBSK1-GmGSK1-GmBES1.5.

3D Bioprinting of Engineered Living Materials with Extracellular Electron Transfer Capability for Water Purification.

Attention is widely drawn to the extracellular electron transfer (EET) process of electroactive bacteria (EAB) for water purification, but its efficacy is often hindered in complex environmental matrices. In this study, the engineered living materials with EET capability (e-ELMs) were for the first time created with customized geometric configurations for pollutant removal using three-dimensional (3D) bioprinting platform. By combining EAB and tailored viscoelastic matrix, a biocompatible and tunable electroactive bioink for 3D bioprinting was initially developed with tuned rheological properties, enabling meticulous manipulation of microbial spatial arrangement and density. e-ELMs with different spatial microstructures were then designed and constructed by adjusting the filament diameter and orientation during the 3D printing process. Simulations of diffusion and fluid dynamics collectively showcase internal mass transfer rates and EET efficiency of e-ELMs with different spatial microstructures, contributing to the outstanding decontamination performances. Our research propels 3D bioprinting technology into the environmental realm, enabling the creation of intricately designed e-ELMs and providing promising routes to address the emerging water pollution concerns.

Iron promotes both ferroptosis and necroptosis in the early stage of reperfusion in ischemic stroke.

Programmed cell death contributes to neurological damage in ischemic stroke, especially during the reperfusion stage. Several cell death pathways have been tested preclinically and clinically, including ferroptosis, necroptosis, and apoptosis. However, the sequence and complex interplay between cell death pathways during ischemia/reperfusion remains under investigation. Here, we unbiasedly investigated cell death pathways during ischemia/reperfusion by utilizing RNA sequencing analysis and immunoblot assays and revealed that ferroptosis and necroptosis occurred early post-reperfusion, followed by apoptosis. Ferroptosis inhibitor Liproxstatin-1 effectively inhibited necroptosis during reperfusion, while the necroptosis inhibitor Necrostatin-1 suppressed protein expression consistent with ferroptosis activation. Protein-protein interaction analysis and iron chelation therapy by deferoxamine mesylate indicate that iron is capable of promoting both ferroptosis and necroptosis in middle cerebral artery occlusion/repression modeled mice. Treatment of cells with iron led to a disruption in redox balance with activated necroptosis and increased susceptibility to ferroptosis. Collectively, these data uncovered a complex interplay between ferroptosis and necroptosis during ischemic stroke and indicated that multiple programmed cell death pathways may be targeted co-currently.