Comparative proteomics analysis of Shiraia bambusicola revealed a variety of regulatory systems on conidiospore formation.

Shiraia bambusicola is a typical parasitic medicinal fungus of the family Shiraiaceae. The fruiting bodies of S. bambusicola cannot be cultivated artificially, and active substances can be effectively produced via fermentation. The mechanism of conidia production is a research hotspot in the industrial utilization and growth development of S. bambusicola. This study is the first to systematically study the proteomics of conidiospore formation from S. bambusicola. Near-spherical conidia were observed and identified by internal transcribed spacer (ITS) sequence detection. A total of 2,840 proteins were identified and 1,976 proteins were quantified in the mycelia and conidia of S. bambusicola. Compared with mycelia, 445 proteins were differentially expressed in the conidia of S. bambusicola, with 165 proteins being upregulated and 280 proteins being downregulated. The Gene Ontology (GO) annotation results of differential proteomics showed that the biological process of S. bambusicola sporulation is complex. The Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway analysis showed that the differential proteins were mainly involved in starch and sucrose metabolism, biosynthesis of secondary metabolites, microbial metabolism in diverse environments, and other processes. Our in-depth speculative analysis showed that proteins related to carbohydrate metabolism were differentially expressed in conidiospore formation of S. bambusicola, suggesting the involvement of saccharides. Conidiation may increase the synthesis and release of ethanol and polysaccharide proteins such as glycoside hydrolase (GH), suppress host immunity, and facilitate S. bambusicola to infect and colonize of the host. In-depth analysis of differential proteomes will help reveal the molecular mechanism underlying the conidiospore formation of S. bambusicola, which has strong theoretical and practical significance.

A Facile Strategy for Constructing High-Performance Polymer Electrolytes via Anion Modification and Click Chemistry for Rechargeable Magnesium Batteries.

Polymer electrolytes play a crucial role in advancing rechargeable magnesium batteries (RMBs) owing to their exceptional characteristics, including high flexibility, superior interface compatibility, broad electrochemical stability window, and enhanced safety features. Despite these advantages, research in this domain remains nascent, plagued by single preparation approaches and challenges associated with the compatibility between polymer electrolytes and Mg metal anode. In this study, we present a novel synthesis strategy to fabricate a glycerol α,α'-diallyl ether-3,6-dioxa-1,8-octanedithiol-based polymer electrolyte supported by glass fiber substrate (GDT@GF) through anion modification and thiol-ene click chemistry polymerization. The developed route exhibits novelty and high efficiency, leading to the production of GDT@GF membranes featuring exceptional mechanical properties, heightened ionic conductivity, elevated Mg2+ transference number, and commendable compatibility with Mg anode. The assembled modified Mo6S8||GDT@GF||Mg cells exhibit outstanding performance across a wide temperature range and address critical safety concerns, showcasing the potential for applications under extreme conditions. Our innovative preparation strategy offers a promising avenue for the advancement of polymer electrolytes in high-performance rechargeable magnesium batteries, while also opens up possibilities for future large-scale applications and the development of flexible electronic devices.

PDP1 promotes KRAS mutant colorectal cancer progression by serving as a scaffold for BRAF and MEK1.

The oncogenic role of KRAS in colorectal cancer (CRC) progression is well-established. Despite this, identifying effective therapeutic targets for KRAS-mutated CRC remains a significant challenge. This study identifies pyruvate dehydrogenase phosphatase catalytic subunit 1 (PDP1) as a previously unrecognized yet crucial regulator in the progression of KRAS mutant CRC. A substantial upregulation of PDP1 expression is observed in KRAS mutant CRC cells and tissues compared to wild-type KRAS samples, which correlates with poorer prognosis. Functional experiments elucidate that PDP1 accelerates the malignance of KRAS mutant CRC cells, both in vitro and in vivo. Mechanistically, PDP1 acts as a scaffold, enhancing BRAF and MEK1 interaction and activating the MAPK signaling, thereby promoting CRC progression. Additionally, transcription factor KLF5 is identified as the key regulator for PDP1 upregulation in KRAS mutant CRC. Crucially, targeting PDP1 combined with MAPK inhibitors exhibits an obvious inhibitory effect on KRAS mutant CRC. Overall, PDP1 is underscored as a vital oncogenic driver and promising therapeutic target for KRAS mutant CRC.

Novel insights into the mechanism of dynamic changes in microstructure and physicochemical properties of corn straw pretreated by ball milling and feasibility analysis of anaerobic digestion.

In this study, the effects of Ball milling (BM) pretreatment (0-240 min) on the microstructure, physicochemical properties and subsequent methanogenesis performance of corn straw (CS) were explored, and the feasibility analysis was carried out. The results showed that BM pretreatment destroyed the dense structure of the CS, and the particle size was significantly reduced (D50: 13.85 µm), transforming it into a cell-scale granular form. The number of mesopores increased, the pore volume (PV) (0.032 cm3/g) and specific surface area (SSA) (4.738 m2/g) considerably increased, and the water-absorbent property was improved. The crystalline order of cellulose was disrupted and the crystallinity (CrI) (8.61 %) and crystal size (CrS) (3.37) were remarkably reduced. The cross-links between lignocelluloses were broken, and the relative content and functional groups did not alter obviously. The bulk density (BD), repose angle (RA) and slip angle (SA) dramatically increased. As a result, CS was more readily accessible, attached and utilized by microorganisms and enzymes, causing the hydrolysis and acidification of AD to be greatly facilitated. Compared with the untreated group, the cumulative methane production (CMP) increased by 35.83 %-101.97 %, and the lag phase time (λ) was shortened by 33.04 %-71.17 %. The results of redundancy analysis, Pearson analysis and Mantel test showed that BM pretreatment affects the process of AD by changing the physicochemical factors of CS. The normalization analysis showed that particle size (D90) and BD can be used as direct indicators to evaluate the performance of AD and predict the threshold of biodegradation of CS. Energy analysis and energy conversion assessment showed that BM is a green and efficient AD pretreatment strategy. This result provides a theoretical basis for the industrial application of BM pretreatment towards more energy-efficient and sustainable development.

Integrated mendelian randomization analyses highlight AFF3 as a novel eQTL-mediated susceptibility gene in renal cancer and its potential mechanisms.

BACKGROUNDS: A growing number of expression quantitative trait loci (eQTLs) have been found to be linked with tumorigenesis. In this article, we employed integrated Mendelian randomization (MR) analyses to identify novel susceptibility genes in renal cancer (RC) and reveal their potential mechanisms. METHODS: Two-sample MR analyses were performed to infer causal relationships between eQTLs, metabolites, and RC risks through the "TwoSampleMR" R package. Sensitivity analyses, such as heterogeneity, pleiotropy, and leave-one-out analysis, were used to assess the stability of our outcomes. Summary-data-based MR (SMR) analyses were used to verify the causal relationships among cis-eQTLs and RC risks via the SMR 1.3.1 software. RESULTS: Our results provided the first evidence for AFF3 eQTL elevating RC risks, suggesting its oncogenic roles (IVW method; odds ratio (OR) = 1.0005; 95% confidence interval (CI) = 1.0001-1.0010; P = 0.0285; heterogeneity = 0.9588; pleiotropy = 0.8397). Further SMR analysis validated the causal relationships among AFF3 cis-eQTLs and RC risks (P < 0.05). Moreover, the TCGA-KIRC, the ICGC-RC, and the GSE159115 datasets verified that the AFF3 gene was more highly expressed in RC tumors than normal control via scRNA-sequencing and bulk RNA-sequencing (P < 0.05). Gene set enrichment analysis (GSEA) analysis identified six potential biological pathways of AFF3 involved in RC. As for the potential mechanism of AFF3 in RC, we concluded in this article that AFF3 eQTL could negatively modulate the levels of the X-11,315 metabolite (IVW method; OR = 0.9127; 95% CI = 0.8530-0.9765; P = 0.0081; heterogeneity = 0.4150; pleiotropy = 0.8852), exhibiting preventive effects against RC risks (IVW method; OR = 0.9987; 95% CI = 0.9975-0.9999; P = 0.0380; heterogeneity = 0.5362; pleiotropy = 0.9808). CONCLUSIONS: We concluded that AFF3 could serve as a novel eQTL-mediated susceptibility gene in RC and reveal its potential mechanism of elevating RC risks via negatively regulating the X-11,315 metabolite levels.

Linc01588 deletion inhibits the malignant biological characteristics of hydroquinone-induced leukemic cells via miR-9-5p/SIRT1.

Leukemia caused by environmental chemical pollutants has attracted great attention, the malignant leukemic transformation model of TK6 cells induced by hydroquinone (HQ) has been previously found in our team. However, the type of leukemia corresponding to this malignant transformed cell line model needs further study and interpretation. Furthermore, the molecular mechanism of malignant proliferation of leukemic cells induced by HQ remains unclear. This study is the first to reveal the expression of aberrant genes in leukemic cells of HQ-induced malignant transformation, which may correspond to chronic lymphocytic leukemia (CLL). The expression of Linc01588, a long non-coding RNA (lncRNA), was significantly up-regulated in CLL patients and leukemic cell line model which previously described. After gain-of-function assays and loss-of-function assays, feeble cell viability, severe apoptotic phenotype and the increased secretion of TNF-α were easily observed in malignant leukemic TK6 cells with Linc01588 deletion after HQ intervention. The tumors derived from malignant TK6 cells with Linc01588 deletion inoculated subcutaneously in nude mice were smaller than controls. In CLL and its cell line model, the expression of Linc01588 and miR-9-5p, miR-9-5p and SIRT1 were negative correlation respectively in CLL and cell line model, while the expression of Linc01588 and SIRT1 were positive correlation. The dual-luciferase reporter assay showed that Linc01588 & miR-9-5p, miR-9-5p & SIRT1 could bind directly, respectively. Furthermore, knockdown of miR-9-5p successfully rescued the severe apoptotic phenotype and the increased secretion of TNF-α caused by the Linc01588 deletion, the deletion of Linc01588 in human CLL cell line MEC-2 could also inhibit malignant biological characteristics, and the phenotype caused by the deletion of Linc01588 could also be rescued after overexpression of SIRT1. Moreover, the regulation of SIRT1 expression in HQ19 cells by Linc01588 and miR-9-5 P may be related to the Akt/NF-κB pathway. In brief, Linc01588 deletion inhibits the malignant biological characteristics of HQ-induced leukemic cells via miR-9-5p/SIRT1, and it is a novel and hopeful clue for the clinical targeted therapy of CLL.

Development of a Highly Sensitive, Visual Platform for the Detection of Cadmium in Actual Wastewater Based on Evolved Whole-Cell Biosensors.

A whole-cell biosensor (WCB) is a convenient and cost-effective method for detecting contaminants. However, the practical application of the cadmium WCBs has been hampered by performance deficiencies, such as low sensitivity, specificity, and responsive strength. In this study, to improve the performance of cadmium WCBs, the cadmium transcription factor (CadC) and its DNA binding site (CadO), the key sensing module of the biosensor, were successively and separately subjected to a two-step directed evolution: 6-round random mutagenesis for CadC and 2-round saturation mutagenesis for CadO. For practical application, the GFP reporter gene was replaced with the lacZ gene and a facile and rapid smartphone detection platform for actual water samples was established by optimizing the reaction systems with detergents. The results showed that the evolved cadmium fluorescent biosensor CadO66 exhibited a higher specificity and a detection limit of 0.034 µg/L, representing a 19-fold reduction compared to the wild-type cadmium biosensor. The detergent sodium dodecylbenzenesulfonate effectively enhanced the visualization of WCB B0033-lacZ. Using the fluorescent WCB CadO66 and the visual WCB B0033-lacZ to analyze the cadmium contents of the actual water samples, the results were also consistent with a graphite furnace atomic absorption spectrometer. Taken together, this study indicates that the two-step directed evolution of CadC and CadO can efficiently improve the performance of cadmium WCBs, further promoting the utilization of WCB in actual sample detection and presenting a promising and feasible method for rapid sample detection.

Mutations in the FOXO3 Gene and Their Effects on Meat Traits in Gannan Yaks.

The FOXO3 gene, a prominent member of the FOXO family, has been identified as a potential quantitative trait locus for muscle atrophy and lipid metabolism in livestock. It is also considered a promising candidate gene for meat quality traits such as Warner-Bratzler shear force (WBSF) and water holding capacity (WHC). The aim of this study was to identify sequence mutations in the FOXO3 gene of yaks and to analyze the association of genotypes and haplotypes with meat traits such as WBSF and WHC. Quantitative reverse-transcriptase PCR (RT-qPCR) was applied to determine the expression levels of FOXO3 in yak tissues, with the results revealing a high expression in the yak longissimus dorsi muscle. Exons of the FOXO3 gene were then sequenced in 572 yaks using hybrid pool sequencing. Five single nucleotide polymorphisms were identified. Additionally, four effective haplotypes and four combined haplotypes were constructed. Two mutations of the FOXO3 gene, namely C>G at exon g.636 and A>G at exon g.1296, were associated with cooked meat percentage (CMP) (p < 0.05) and WBSF (p < 0.05), respectively. Furthermore, the WBSF of the H2H3 haplotype combination was significantly lower than that of other combinations (p < 0.05). The findings of this study suggest that genetic variations in FOXO3 could be a promising biomarker for improving yak meat traits.

Atorvastatin Calcium Ameliorates Cognitive Deficits Through the AMPK/Mtor Pathway in Rats with Vascular Dementia.

AIM: In this study, the protective effects of atorvastatin calcium (AC) on nerve cells and cognitive improvement in vivo and in vitro were investigated by establishing cell models and vascular dementia (VD) rat models. BACKGROUND: VD is a neurodegenerative disease characterized by cognitive deficits caused by chronic cerebral hypoperfusion. AC has been studied for its potential to cure VD but its efficacy and underlying mechanism are still unclear. OBJECTIVE: The mechanism of action of AC on cognitive deficits in the early stages of VD is unclear. Here, the 2-vessel occlusion (2-VO) model in vivo and the hypoxia/reoxygenation (H/R) cell model in vitro was established to investigate the function of AC in VD. METHODS: The spatial learning and memory abilities of rats were detected by the Morris method. The IL-6, tumour necrosis factor-α (TNF-α), malondialdehyde (MDA) and superoxide dismutase (SOD) in cell supernatant was tested by ELISA kits. After behavioural experiments, rats were anaesthetized and sacrificed, and their brains were extracted. One part was immediately fixed in 4% paraformaldehyde for H&E, Nissl, and immunohistochemical analyses, and the other was stored in liquid nitrogen. All data were shown as mean ± SD. Statistical comparison between the two groups was performed by Student's t-test. A two-way ANOVA test using GraphPad Prism 7 was applied for escape latency analysis and the swimming speed test. The difference was considered statistically significant at p < 0.05. RESULTS: AC decreased apoptosis, increased autophagy, and alleviated oxidative stress in primary hippocampal neurons. AC regulated autophagy-related proteins in vitro by western blotting. VD mice improved cognitively in the Morris water maze. Spatial probing tests showed that VD animals administered AC had considerably longer swimming times to the platform than VD rats. H&E and Nissl staining showed that AC reduces neuronal damage in VD rats. Western blot and qRT-PCR indicated that AC in VD rats inhibited Bax and promoted LC3-II, Beclin-1, and Bcl-2 in the hippocampus region. AC also improves cognition via the AMPK/mTOR pathway. CONCLUSION: This study found that AC may relieve learning and memory deficits as well as neuronal damage in VD rats by changing the expression of apoptosis/autophagy-related genes and activating the AMPK/mTOR signalling pathway in neurons.

Pathogenicity analysis and comparative genomics reveal the different infection strategies between the generalist Metarhizium anisopliae and the specialist Metarhizium acridum.

BACKGROUND: The fungal genera Metarhizium contain many important multiple species that are used as biocontrol agents and as model organisms for exploring insect-fungal interactions. Metarhizium spp. exhibit different traits of pathogenicity, suggesting that the pathogenesis can be quite distinctive. However, the underlying differences in their pathogenesis remain poorly understood. RESULTS: Pathogenicity analysis showed that Metarhizium anisopliae (strain CQMa421) displayed higher virulence against oriental migratory locusts, Locusta migratoria manilensis (Meyen), than the acridid-specific specie Metarhizium acridum (strain CQMa102). Relative to M. acridum, M. anisopliae possessed a higher conidial hydrophobicity, increased ability to penetrate the host, accelerated growth under hypoxia and enhanced ability for the utilization of different carbon sources. Different distributions of carbohydrate epitopes at cell wall surface of M. anisopliae might also contribute to successful evasion of host immune defenses. Comparative genomics showed that M. anisopliae has 98 more virulence-related secreted proteins (133) than M. acridum (35), which can be functionally classified as hydrolases, virulence effectors, cell wall degradation and stress tolerance-related proteins, and helpful to the cuticle penetration and host internal environment adaption. In addition, differences in genomic clusters specifically related to secondary metabolites, including the clusters of Indole-NRPS hybrid, T1PKS-NRPS like hybrid, Betalactone, Fungal-Ripp and NRPS-Terpene hybrid, may lead to differences in core virulence-related secondary metabolite genes in M. acridum (18) and M. anisopliae (36). CONCLUSION: The comparative study provided new insights into the different infection strategies between M. anisopliae and M. acridum, and further facilitate the identification of virulence-related genes for the improvement of mycoinsecticides. © 2023 Society of Chemical Industry.

Engineering the Ultrasensitive Visual Whole-Cell Biosensors by Evolved MerR and 5' UTR for Detection of Ultratrace Mercury.

The existing mercury whole-cell biosensors (WCBs, parts per billion range) are not able to meet the real-world requirements due to their lack of sensitivity for the detection of ultratrace mercury in the environment. Ultratrace mercury is a potential threat to human health via the food chain. Here, we developed an ultrasensitive mercury WCB by directed evolution of the mercury-responsive transcriptional activator (MerR) sensing module to detect ultratrace mercury. Subsequently, the mutant WCB (m4-1) responding to mercury in the parts per trillion range after 1 h of induction was obtained. Its detection limit (LOD) was 0.313 ng/L, comparable to those of some analytical instruments. Surprisingly, the m4-1 WCB also responded to methylmercury (LOD = 98 ng/L), which is far more toxic than inorganic mercury. For more convenient detection, we have increased another green fluorescent protein reporter module with an optimized 5' untranslated region (5' UTR) sequence. This yields two visual WCBs with an enhanced fluorescence output. At a concentration of 2.5 ng/L, the fluorescence signals can be directly observed by the naked eye. With the combination of mobile phone imaging and image processing software, the 2GC WCB provided simple, rapid, and reliable quantitative and qualitative analysis of real samples (LOD = 0.307 ng/L). Taken together, these results indicate that the ultrasensitive visual whole-cell biosensors for ultratrace mercury detection are successfully designed using a combination of directed evolution and synthetic biotechnology.

Variation in Acetyl-CoA Carboxylase Beta Gene and Its Effect on Carcass and Meat Traits in Gannan Yaks.

Acetyl-CoA carboxylase beta (ACACB) is a functional candidate gene that impacts fat deposition. In the present study, we sequenced exon 37-intron 37, exon 46-intron 46, and intron 47 of yak ACACB using hybrid pool sequencing to search for variants and genotyped the gene in 593 Gannan yaks via Kompetitive allele-specific polymerase chain (KASP) reaction to determine the effect of ACACB variants on carcass and meat quality traits. Seven single nucleotide polymorphisms were detected in three regions. Eight effective haplotypes and ten diplotypes were constructed. Among them, a missense variation g.50421 A > G was identified in exon 37 of ACACB, resulting in an amino acid shift from serine to glycine. Correlation analysis revealed that this variation was associated with the cooking loss rate and yak carcass weight (p = 0.024 and 0.012, respectively). The presence of haplotypes H5 and H6 decreased Warner-Bratzler shear force (p = 0.049 and 0.006, respectively), whereas that of haplotypes H3 and H4 increased cooking loss rate and eye muscle area (p = 0.004 and 0.034, respectively). Moreover, the presence of haplotype H8 decreased the drip loss rate (p = 0.019). The presence of one and two copies of haplotypes H1 and H8 decreased the drip loss rate (p = 0.028 and 0.004, respectively). However, haplotype H1 did not decrease hot carcass weight (p = 0.011), whereas H3 increased the cooking loss rate (p = 0.007). The presence of one and two copies of haplotype H6 decreased Warner-Bratzler shear force (p = 0.014). The findings of the present study suggest that genetic variations in ACACB can be a preferable biomarker for improving yak meat quality.

Directed evolution of TetR for constructing sensitive and broad-spectrum tetracycline antibiotics whole-cell biosensor.

Antibiotic abuse is the main reason for the drug resistance of pathogenic bacteria, posing a potential health risk. Antibiotic surveillance is critical for preventing antibiotic contamination. This study aimed to develop a sensitive and broad-spectrum whole-cell biosensor for tetracycline antibiotics (TCs) detection. Wild-type TCs-responsive biosensor was constructed by introducing a tetracycline operon into a sfGFP reporter plasmid. Using error-prone PCR, mutation libraries containing approximately 107 variants of the tetracycline repressor (TetR) gene were generated. The tigecycline-senstive mutants were isolated using high-throughput flow cytometric sorting. After 2 rounds of directed evolution, a mutant epS2-22 of TerR was isolated and assembled as a TCs biosensor. The epS2-22 biosensor was more sensitive and broad-spectrum than the wild-type biosensors. The detection limits of the epS2-22 biosensor for seven TCs were 4- to 62-fold lower than the wild-type biosensor (no response to tigecycline). Meanwhile, the epS2-22 biosensor had a shorter detection time and a stronger signal output than the wild type. In addition, the evolved epS2-22 biosensor showed excellent performance in detecting low traces of TCs in environmental water. These results suggest that directed evolution is a powerful tool for developing high-performance whole-cell biosensors, and the evolved epS2-22 biosensors have the potential for wider applications in real-world TCs detection.

Development of a mammalian cell-based ZZ display system for IgG quantification.

BACKGROUND: Biological laboratories and companies involved in antibody development need convenient and versatile methods to detect highly active antibodies. METHODS: To develop a mammalian cell-based ZZ display system for antibody quantification, the eukaryotic ZZ-displayed plasmid was constructed and transfected into CHO cells. After screening by flow cytometric sorting, the stable ZZ display cells were incubated with reference IgG and samples with unknown IgG content for 40 min at 4℃, the relative fluorescence intensity of cells was analyzed and the concentration of IgG was calculated. RESULTS: By investigating the effects of different display-associated genetic elements, a eukaryotic ZZ-displaying plasmid with the highest display efficiency were constructed. After transfection and screening, almost 100% of the cells were able to display the ZZ peptide (designated CHO-ZZ cells). These stable CHO-ZZ cells were able to capture a variety of IgG, including human, rabbit, donkey and even mouse and goat. CHO-ZZ cells could be used to quantify human IgG in the range of approximately 12.5-1000 ng/mL, and to identify high-yielding engineered monoclonal cell lines. CONCLUSIONS: We have established a highly efficient CHO-ZZ display system in this study, which enables the quantification of IgG from various species under physiological conditions. This system offers the advantage of eliminating the need for antibody purification and will contribute to antibody development.

Myeloid-Specific SIRT6 Deletion Protects Against Particulate Matter (PM2.5)-Induced Airway Inflammation.

Purpose: Particulate matter (PM2.5) is a common risk factor for airway inflammation. Alveolar macrophages play a critical role in airway inflammation. Sirtuin 6 (SIRT6) is a class Ill histone deacetylase that exerts an anti-inflammatory effect in airway diseases. However, the role of SIRT6 on PM2.5-induced airway inflammation in macrophages remains unclear. We aimed to determine whether SIRT6 protects against PM2.5-induced airway inflammation in macrophages. Methods: The effect of SIRT6 on PM2.5-induced airway inflammation was assessed by using THP1 cells or bone marrow-derived macrophages (BMDMs) exposed to PM2.5 in vitro and myeloid cell-specific SIRT6 conditional knockout mice (Sirt6fl/fl-LysMCre) in vivo. Results: PM2.5 increased SIRT6 expression in THP1 cells, but SIRT6 gene silencing decreased PM2.5 induced inflammatory cytokines in THP1 cells. Moreover, the expression of SIRT6 and inflammatory cytokines was also decreased in BMDMs with myeloid-specific deletion of SIRT6 after stimulation of PM2.5. In vivo, Sirt6fl/fl-LysMCre mice substantially decreased airway inflammation in response to PM2.5 exposure. Conclusion: Our results revealed that SIRT6 promotes the PM2.5-induced airway inflammation in macrophages and indicated that inhibition of SIRT6 in macrophages may represent therapeutic strategy for airway disorders induced by airborne particulate pollution.

Large Spontaneous Polarization Ferroelectric Property, Switchable Second-Harmonic Generation Responses, and Magnetism in an Fe-Based Compound.

Since the switchable spontaneous polarization of ferroelectric materials endows it with many useful properties such as a large pyroelectric coefficient, switchable spontaneous polarization, and semiconductor, it has a wide range of application prospects, and the research of high-performance molecular ferroelectric materials has become a hot spot. We obtained a 0D organic-inorganic hybrid ferroelectric [(CH3)3NCH2CH2CH3]2FeCl4 (1) with well-defined ferroelectric domains and excellent domain inversion and exhibited a relatively large spontaneous polarization (Ps = 9 µC/m-2) and a Curie temperature (Tc) of 394 K. Furthermore, compound 1 belongs to the non-centrosymmetrical space group Cmc21 and has a strong second-harmonic generation signal. Interestingly, we also performed magnetic tests on 1, which confirmed that it is a magnetic material. This work provides clues for exploring the application of high-performance molecular ferroelectric materials in future multifunctional smart devices.

Investigating the Effects and Mechanism of Rhodiola Rosea Injection on Cardiac Function in Rats with Chronic Heart Failure.

AIM: To study the effect of Rhodiola Rosea injection on cardiac function and the reninangiotensin- aldosterone system (RASS) in rats with chronic heart failure. BACKGROUND: Rhodiola Rosea injection, a traditional Chinese medication for relieving blood stasis and improving blood circulation, is an excellent therapeutic for treating coronary heart disease-angina pectoris. Rhodiola Rosea injection's major component, salidroside, protects the cardiovascular system. But there isn't much first-hand evidence about how injectable Rhodiola Rosea affects heart failure. OBJECTIVES: In this study, a rat model of heart failure was established, and the effect of Rhodiola rosea injection on myocardial cell morphology, cardiac function, and ventricular remodelling in rats with heart failure was investigated. METHODS: 66 SD male rats were selected; 10 were randomly selected as a blank control group, and 56 were treated intraperitoneally with doxorubicin (4 g/g). After 6 weeks, all animals had LVEF 60%. Established a heart failure model. Each group had 14 rats: model control, low-dose, mediumdose, and high-dose Rhodiola Rosea injection. The 2 mL/kg of Rhodiola Rosea injection was injected into the tail vein once a day for 2 weeks. Both the blank and control groups received normal daily saline. After 2 weeks, the echocardiographic index, RASS-related index, and serum BNP level were assessed in all rats, and myocardial tissue morphology was observed. MiRNA423-5p, miRNA499-5p, and miRNA210-3p were extracted from peripheral blood. Rhodiola rosea injection on its expression was compared to healthy control rats. RESULTS: 6 mL/kg Rhodiola Rosea injection lowered LVEDV and LVESV while increasing LVEF and LVFS. Injections of 6 mL/kg Rhodiola Rosea reduce plasma levels of miR-210-3p, miR-423- 5p, miRNA-499, and BNP in heart failure model rats. The 6 mL/kg Rhodiola Rosea injection can restore the RASS indexes of heart failure rats to the level of the normal group. CONCLUSION: The present study offers preliminary evidence supporting the use of Rhodiola Rosea injection in the treatment of heart failure and offers a solid foundation for clinical off-label medication use.

Directly Evolved AlkS-Based Biosensor Platform for Monitoring and High-Throughput Screening of Alkane Production.

Biosynthetic alkane using acyl-ACP aldehyde reductase (AAR) and aldehyde-deformylating oxygenase (ADO) from cyanobacteria is considered a promising alternative for the production of biofuels and chemical feedstocks. However, the lack of suitable screening methods to improve the catalytic efficiency of AAR and ADO has hindered further improvements in alkane production. Herein, a novel alkane biosensor was developed based on transcriptional factor AlkS by directed evolution, which shows sensitive dynamic response curves for exogenous long-chain alkanes as well as in situ monitoring of endogenously produced alkanes. The evolved biosensor enables high-throughput screening of alkane-producing strains from the AAR and ADO mutant library, which led to a 13-fold increase in the production of long-chain alkanes, including a 22-fold increase of C15. This study is the first to improve the alkane production through biosensors, which provides a good reference for the establishment of microbial cell factories for alkane production.

Microcystin-LR-induced nuclear translocation of cGAS promotes mutagenesis in human hepatocytes by impeding homologous recombination repair.

Microcystin-LR (MC-LR) has been recognized as a typical hepatotoxic cyclic peptides produced by cyanobacteria. Nowadays, due to the frequent occurrence of cyanobacterial blooms, the underlying hepatotoxic mechanism of MC-LR has become the focus of attention. In our present work, the mutagenic effect of MC-LR on human normal hepatic (HL-7702) cells regulated by cGAS was mainly studied. Here, we showed that exposure to MC-LR for 1-4 days could activate the cGAS-STING signaling pathway and then trigger immune response in HL-7702 cells. Notably, relative to the treatment with 1 µM MC-LR for 1-3 days, it was observed that when HL-7702 cells were exposed to 1 µM MC-LR for 4 days, the mutation frequency at the Hprt locus was remarkably increased. In addition, cGAS in HL-7702 cells was also found to complete the nuclear translocation after 4-day exposure. Moreover, co-immunoprecipitation and homologous recombination (HR)-directed DSB repair assay were applied to show that homologous recombination repair was inhibited after 4-day exposure. However, the intervention of the nuclear translocation of cGAS by transfecting BLK overexpression plasmid restored homologous recombination repair and reduced the mutation frequency at the Hprt locus in HL-7702 cells exposed to MC-LR. Our study unveiled the distinct roles of cGAS in the cytoplasm and nucleus of human hepatocytes as well as potential mutagenic mechanism under the early and late stage of exposure to MC-LR, and provided a novel insight into the prevention and control measures about the hazards of cGAS-targeted MC-LR.