Metformin Promotes Antitumor Immunity via Endoplasmic-Reticulum-Associated Degradation of PD-L1.

Metformin has been reported to possess antitumor activity and maintain high cytotoxic T lymphocyte (CTL) immune surveillance. However, the functions and detailed mechanisms of metformin's role in cancer immunity are not fully understood. Here, we show that metformin increases CTL activity by reducing the stability and membrane localization of programmed death ligand-1 (PD-L1). Furthermore, we discover that AMP-activated protein kinase (AMPK) activated by metformin directly phosphorylates S195 of PD-L1. S195 phosphorylation induces abnormal PD-L1 glycosylation, resulting in its ER accumulation and ER-associated protein degradation (ERAD). Consistently, tumor tissues from metformin-treated breast cancer patients exhibit reduced PD-L1 levels with AMPK activation. Blocking the inhibitory signal of PD-L1 by metformin enhances CTL activity against cancer cells. Our findings identify a new regulatory mechanism of PD-L1 expression through the ERAD pathway and suggest that the metformin-CTLA4 blockade combination has the potential to increase the efficacy of immunotherapy.

Human lung organoid: Models for respiratory biology and diseases.

The human respiratory system, consisting of the airway and alveoli, is one of the most complex organs directly interfaced with the external environment. The diverse epithelial cells lining the surface are usually the first cell barrier that comes into contact with pathogens that could lead to deadly pulmonary disease. There is an urgent need to understand the mechanisms of self-renewal and protection of these epithelial cells against harmful pathogens, such as SARS-CoV-2. Traditional models, including cell lines and mouse models, have extremely limited native phenotypic features. Therefore, in recent years, to mimic the complexity of the lung, airway and alveoli organoid technology has been developed and widely applied. TGF-ß/BMP/SMAD, FGF and Wnt/ß-catenin signaling have been proven to play a key role in lung organoid expansion and differentiation. Thus, we summarize the current novel lung organoid culture strategies and discuss their application for understanding the lung biological features and pathophysiology of pulmonary diseases, especially COVID-19. Lung organoids provide an excellent in vitro model and research platform.

Intercropping improves faba bean photosynthesis and reduces disease caused by Fusarium commune and cinnamic acid-induced stress.

Modern intensive cropping systems often contribute to the accumulation of phenolic acids in the soil, which promotes the development of soilborne diseases. This can be suppressed by intercropping. This study analyzed the effects of intercropping on Fusarium wilt based on its effect on photosynthesis under stress by the combination of Fusarium commune and cinnamic acid. The control was not inoculated with F. commune, while the faba bean plants (Vicia faba L.) were inoculated with this pathogen in the other treatments. The infected plants were also treated with cinnamic acid. This study examined the development of Fusarium wilt together with its effects on the leaves, absorption of nutrients, chlorophyll fluorescence parameters, contents of photosynthetic pigments, activities of photosynthetic enzymes, gas exchange parameters, and the photosynthetic assimilates of faba bean from monocropping and intercropping systems. Under monocropping conditions, the leaves of the plants inoculated with F. commune grew significantly less, and there was enhanced occurrence of the Fusarium wilt compared with the control. Compared with the plants solely inoculated with F. commune, the exogenous addition of cinnamic acid to the infected plants significantly further reduced the growth of faba bean leaves and increased the occurrence of Fusarium wilt. A comparison of the combination of F. commune and cinnamic acid in intercropped wheat and faba bean compared with monocropping showed that intercropping improved the absorption of nutrients, increased photosynthetic pigments and its contents, electron transport, photosynthetic enzymes, and photosynthetic assimilates. The combination of these factors reduced the occurrence of Fusarium wilt in faba bean and increased the growth of its leaves. These results showed that intercropping improved the photosynthesis, which promoted the growth of faba bean, thus, reducing the development of Fusarium wilt following the stress of infection by F. commune and cinnamic acid. This research should provide more information to enhance sustainable agriculture.

Carbon Micro/Nano Machining toward Miniaturized Device: Structural Engineering, Large-Scale Fabrication, and Performance Optimization.

With the rapid development of micro/nano machining, there is an elevated demand for high-performance microdevices with high reliability and low cost. Due to their outstanding electrochemical, optical, electrical, and mechanical performance, carbon materials are extensively utilized in constructing microdevices for energy storage, sensing, and optoelectronics. Carbon micro/nano machining is fundamental in carbon-based intelligent microelectronics, multifunctional integrated microsystems, high-reliability portable/wearable consumer electronics, and portable medical diagnostic systems. Despite numerous reviews on carbon materials, a comprehensive overview is lacking that systematically encapsulates the development of high-performance microdevices based on carbon micro/nano structures, from structural design to manufacturing strategies and specific applications. This review focuses on the latest progress in carbon micro/nano machining toward miniaturized device, including structural engineering, large-scale fabrication, and performance optimization. Especially, the review targets an in-depth evaluation of carbon-based micro energy storage devices, microsensors, microactuators, miniaturized photoresponsive and electromagnetic interference shielding devices. Moreover, it highlights the challenges and opportunities in the large-scale manufacturing of carbon-based microdevices, aiming to spark further exciting research directions and application prospectives.

Amino acid mutations PB1-V719M and PA-N444D combined with PB2-627K contribute to the pathogenicity of H7N9 in mice.

H7N9 subtype avian influenza viruses (AIVs) cause 1567 human infections and have high mortality, posing a significant threat to public health. Previously, we reported that two avian-derived H7N9 isolates (A/chicken/Eastern China/JTC4/2013 and A/chicken/Eastern China/JTC11/2013) exhibit different pathogenicities in mice. To understand the genetic basis for the differences in virulence, we constructed a series of mutant viruses based on reverse genetics. We found that the PB2-E627K mutation alone was not sufficient to increase the virulence of H7N9 in mice, despite its ability to enhance polymerase activity in mammalian cells. However, combinations with PB1-V719M and/or PA-N444D mutations significantly enhanced H7N9 virulence. Additionally, these combined mutations augmented polymerase activity, thereby intensifying virus replication, inflammatory cytokine expression, and lung injury, ultimately increasing pathogenicity in mice. Overall, this study revealed that virulence in H7N9 is a polygenic trait and identified novel virulence-related residues (PB2-627K combined with PB1-719M and/or PA-444D) in viral ribonucleoprotein (vRNP) complexes. These findings provide new insights into the molecular mechanisms underlying AIV pathogenesis in mammals, with implications for pandemic preparedness and intervention strategies.

The haemagglutinin-neuraminidase protein of velogenic Newcastle disease virus enhances viral infection through NF-κB-mediated programmed cell death.

The haemagglutinin-neuraminidase (HN) protein, a vital membrane glycoprotein, plays a pivotal role in the pathogenesis of Newcastle disease virus (NDV). Previously, we demonstrated that a mutation in the HN protein is essential for the enhanced virulence of JS/7/05/Ch, a velogenic variant NDV strain originating from the mesogenic vaccine strain Mukteswar. Here, we explored the effects of the HN protein during viral infection in vitro using three viruses: JS/7/05/Ch, Mukteswar, and an HN-replacement chimeric NDV, JS/MukHN. Through microscopic observation, CCK-8, and LDH release assays, we demonstrated that compared with Mukteswar and JS/MukHN, JS/7/05/Ch intensified the cellular damage and mortality attributed to the mutant HN protein. Furthermore, JS/7/05/Ch induced greater levels of apoptosis, as evidenced by the activation of caspase-3/8/9. Moreover, JS/7/05/Ch promoted autophagy, leading to increased autophagosome formation and autophagic flux. Subsequent pharmacological experiments revealed that inhibition of apoptosis and autophagy significantly impacted virus replication and cell viability in the JS/7/05/Ch-infected group, whereas less significant effects were observed in the other two infected groups. Notably, the mutant HN protein enhanced JS/7/05/Ch-induced apoptosis and autophagy by suppressing NF-κB activation, while it mitigated the effects of NF-κB on NDV infection. Overall, our study offers novel insights into the mechanisms underlying the increased virulence of NDV and serves as a reference for the development of vaccines.

Salicylic Acid's impact on Sedum alfredii growth and cadmium tolerance: Comparative physiological, transcriptomic, and metabolomic study.

With the acceleration of industrialization, Cd pollution has emerged as a major threat to soil ecosystem health and food safety. Hyperaccumulating plants like Sedum alfredii Hance are considered to be used as part of an effective strategy for the ecological remediation of Cd polluted soils. This study delved deeply into the physiological, transcriptomic, and metabolomic responses of S. alfredii under cadmium (Cd) stress when treated with exogenous salicylic acid (SA). We found that SA notably enhanced the growth of S. alfredii and thereby increased absorption and accumulation of Cd, effectively alleviating the oxidative stress caused by Cd through upregulation of the antioxidant system. Transcriptomic and metabolomic data further unveiled the influence of SA on photosynthesis, antioxidant defensive mechanisms, and metal absorption enrichment pathways. Notably, the interactions between SA and other plant hormones, especially IAA and JA, played a central role in these processes. These findings offer us a comprehensive perspective on understanding how to enhance the growth and heavy metal absorption capabilities of hyperaccumulator plants by regulating plant hormones, providing invaluable strategies for future environmental remediation efforts.

The combination of high uric acid and high C-reactive protein increased the risk of cardiovascular disease: A 15-year prospective cohort study.

BACKGROUND AND AIMS: Uric acid (UA) and C-reactive protein (CRP) may interact synergistically to accelerate the initiation and progression of cardiovascular disease (CVD). This study investigated the effects of a combination of high UA and high CRP on the risks of CVD. METHODS AND RESULTS: A total of 90,270 participants recruited from the Kailuan study were included, who were divided into four groups according to the presence/absence of hyperuricemia and inflammation. Cox regression was applied to evaluate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of CVD. C-statistics, net classification index (NRI), and integrated discrimination improvement (IDI) were used to compare the incremental predictive of UA, CRP, and their combined effects on CVD. Mediation analysis was to explore the impact of CRP on the association between UA and CVD. Over a median follow-up of 14.95 years, we identified 11398 incident CVD cases. Compared to the low UA/low CRP group, the high UA/low CRP, low UA/high CRP and high UA/high CRP groups showed progressively higher risks of CVD, HR (95% CI): 1.18(1.10-1.27), 1.27(1.21-1.33) and 1.50 (1.33-1.69), respectively. The incorporation of UA and CRP into the traditional China-PAR model led to improvement in the C-statistic, NRI, and IDI, and was better than incorporation of either UA or CRP alone. Mediation analysis showed that CRP mediated the association between UA and CVD, accounting for 11.57% of the total effects. CONCLUSIONS: High UA/high CRP is associated with increased risks of CVD. Incorporation of both UA and CRP provided additional value for risk stratification.

Rabies Virus Infection Causes Pyroptosis of Neuronal Cells.

Rabies virus (RABV) is a neurotropic virus that causes fatal neurological disease, raising serious public health issues and attracting extensive attention in society. To elucidate the molecular mechanism of RABV-induced neuronal damage, we used hematoxylin-eosin staining, transmission electron microscopy, transcriptomics analysis, and immune response factor testing to investigate RABV-infected neurons. We successfully isolated the neurons from murine brains. The specificity of the isolated neurons was identified by a monoclonal antibody, and the viability of the neurons was 83.53-95.0%. We confirmed that RABV infection induced serious damage to the neurons according to histochemistry and transmission electron microscope (TEM) scanning. In addition, the transcriptomics analysis suggested that multiple genes related to the pyroptosis pathway were significantly upregulated, including gasdermin D (Gsdmd), Nlrp3, caspase-1, and IL-1ß, as well as the chemokine genes Ccl2, Ccl3, Ccl4, Ccl5, Ccl7, Ccl12, and Cxcl10. We next verified this finding in the brains of mice infected with the rRC-HL, GX074, and challenge virus standard strain-24 (CVS-24) strains of RABV. Importantly, we found that the expression level of the Gsdmd protein was significantly upregulated in the neurons infected with different RABV strains and ranged from 691.1 to 5764.96 pg/mL, while the basal level of mock-infected neurons was less than 100 pg/mL. Taken together, our findings suggest that Gsdmd-induced pyroptosis is involved in the neuron damage caused by RABV infection.

Identification of spontaneous age-related cataract in Microtus fortis. / ä¸œæ–¹ç”°é¼ è‡ªå‘æ€§å¹´é¾„ç›¸å ³æ€§ç™½å† éšœçš„é‰´å®š.

OBJECTIVES: Age-related cataract is the most common type of adult cataract and a leading cause of blindness. Currently, there are few reports on the establishment of animal models for age-related cataract. During the experimental breeding of Microtus fortis (M. fortis), we first observed that M. fortis aged 12 to 15 months could naturally develop cataracts. This study aims to explore the possibility of developing them as an animal model for age-related cataract via identifing and analyzing spontaneous cataract in M. fortis. METHODS: The 12-month-old healthy M. fortis were served as a control group and 12-month-old cataractous M. fortis were served as an experimental group. The lens transparency was observed using the slit-lamp biomicroscope. Hematoxylin and eosin staining was used to detect pathological changes in the lens. Biochemical detection methods were applied to detect blood routine, blood glucose levels, the serum activities of superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in both groups. Finally, real-time RT-PCR was used to detect the transcription levels of cataract-related genes in the lens of 2 groups. RESULTS: Compared with the control group, the lens of cataract M. fortis showed severely visible opacity, the structure of lens was destroyed seriously, and some pathological damage, such as swelling, degeneration/necrosis, calcification, hyperplasia, and fiber liquefaction were found in lens epithelial cells (LECs). The fibrous structure was disorganized and irregularly distributed with morgagnian globules (MGs) aggregated in the degenerated lens fibers. There was no statistically significant difference in blood glucose levels between the experimental and control groups (P>0.05). However, white blood cell (WBC) count (P<0.05), lymphocyte count (P<0.01), and lymphocyte ratio (P<0.05) were significantly decreased, while neutrophil percentage (P<0.05) and monocyte ratio (P<0.01) were significantly increased. The serum activities of SOD and GSH-Px (both P<0.05) were both reduced. The mRNAs of cataract-related genes, including CRYAA, CRYBA1, CRYBB3, Bsfp1, GJA3, CRYBA2, MIP, HspB1, DNase2B, and GJA8, were significantly downregultaed in the lenses of the experimental group (all P<0.05). CONCLUSIONS: There are significant differences in lens pathological changes, peroxidase levels, and cataract-related gene expression between cataract and healthy M. fortis. The developed cataract spontaneously in M. fortis is closely related to age, the cataract M. fortis might be an ideal animal model for the research of age-related cataract.

Ephrin receptor A10 monoclonal antibodies and the derived chimeric antigen receptor T cells exert an antitumor response in mouse models of triple-negative breast cancer.

Expression of the receptor tyrosine kinase ephrin receptor A10 (EphA10), which is undetectable in most normal tissues except for the male testis, has been shown to correlate with tumor progression and poor prognosis in several malignancies, including triple-negative breast cancer (TNBC). Therefore, EphA10 could be a potential therapeutic target, likely with minimal adverse effects. However, no effective clinical drugs against EphA10 are currently available. Here, we report high expression levels of EphA10 in tumor regions of breast, lung, and ovarian cancers as well as in immunosuppressive myeloid cells in the tumor microenvironment. Furthermore, we developed anti-EphA10 monoclonal antibodies (mAbs) that specifically recognize cell surface EphA10, but not other EphA family isoforms, and target tumor regions precisely in vivo with no apparent accumulation in other organs. In syngeneic TNBC mouse models, we found that anti-EphA10 mAb clone #4 enhanced tumor regression, therapeutic response rate, and T cell-mediated antitumor immunity. Notably, the chimeric antigen receptor T cells derived from clone #4 significantly inhibited TNBC cell viability in vitro and tumor growth in vivo. Together, our findings suggest that targeting EphA10 via EphA10 mAbs and EphA10-specific chimeric antigen receptor-T cell therapy may represent a promising strategy for patients with EphA10-positive tumors.

Tafenoquine and its derivatives as inhibitors for the severe acute respiratory syndrome coronavirus 2.

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has severely affected human lives around the world as well as the global economy. Therefore, effective treatments against COVID-19 are urgently needed. Here, we screened a library containing Food and Drug Administration (FDA)-approved compounds to identify drugs that could target the SARS-CoV-2 main protease (Mpro), which is indispensable for viral protein maturation and regard as an important therapeutic target. We identified antimalarial drug tafenoquine (TFQ), which is approved for radical cure of Plasmodium vivax and malaria prophylaxis, as a top candidate to inhibit Mpro protease activity. The crystal structure of SARS-CoV-2 Mpro in complex with TFQ revealed that TFQ noncovalently bound to and reshaped the substrate-binding pocket of Mpro by altering the loop region (residues 139-144) near the catalytic Cys145, which could block the catalysis of its peptide substrates. We also found that TFQ inhibited human transmembrane protease serine 2 (TMPRSS2). Furthermore, one TFQ derivative, compound 7, showed a better therapeutic index than TFQ on TMPRSS2 and may therefore inhibit the infectibility of SARS-CoV-2, including that of several mutant variants. These results suggest new potential strategies to block infection of SARS-CoV-2 and rising variants.

Interplay between lncRNA RP11-367G18.1 variant 2 and YY1 plays a vital role in hypoxia-mediated gene expression and tumorigenesis.

BACKGROUND: The hypoxia-responsive long non-coding RNA, RP11-367G18.1, has recently been reported to induce histone 4 lysine 16 acetylation (H4K16Ac) through its variant 2; however, the underlying molecular mechanism remains poorly understood. METHODS: RNA pull-down assay and liquid chromatography-tandem mass spectrometry were performed to identify RP11-367G18.1 variant 2-binding partner. The molecular events were examined utilizing western blot analysis, real-time PCR, luciferase reporter assay, chromatin immunoprecipitation, and chromatin isolation by RNA purification assays. The migration, invasion, soft agar colony formation, and in vivo xenograft experiments were conducted to evaluate the impact of RP11-367G18.1 variant 2-YY1 complex on tumor progression. RESULTS: In this study, RNA sequencing data revealed that hypoxia and RP11-367G18.1 variant 2 co-regulated genes were enriched in tumor-related pathways. YY1 was identified as an RP11-367G18.1 variant 2-binding partner that activates the H4K16Ac mark. YY1 was upregulated under hypoxic conditions and served as a target gene for hypoxia-inducible factor-1α. RP11-367G18.1 variant 2 colocalized with YY1 and H4K16Ac in the nucleus under hypoxic conditions. Head and neck cancer tissues had higher levels of RP11-367G18.1 and YY1 which were associated with poor patient outcomes. RP11-367G18.1 variant 2-YY1 complex contributes to hypoxia-induced epithelial-mesenchymal transition, cell migration, invasion, and tumorigenicity. YY1 regulated hypoxia-induced genes dependent on RP11-367G18.1 variant 2. CONCLUSIONS: RP11-367G18.1 variant 2-YY1 complex mediates the tumor-promoting effects of hypoxia, suggesting that this complex can be targeted as a novel therapeutic strategy for cancer treatment.

Liquid-Free, Self-Repairable, Recyclable, and Highly Stretchable Colorless Solid Ionic Conductive Elastomers for Strain/Temperature Sensors.

Solid-state ionic conductive elastomers (ICEs) can fundamentally overcome the disadvantages of hydrogels and ionogels (their liquid components tend to leak or evaporate), and are considered to be ideal materials for flexible ionic sensors. In this study, a liquid-free ionic polyurethane (PU) type conductive elastomer (ICE-2) was synthesized and studied. The PU type matrix with microphase separation endowed ICE-2 with excellent mechanical versatility. The disulfide bond exchange reaction in the hard phase and intermolecular hydrogen bonds contributed to damage repairing ability. ICE-2 exhibited good ionic conductivity (2.86×10-6  S/cm), high transparency (average transmittance >89 %, 400~800 nm), excellent mechanical properties (tensile strength of 3.06 MPa, elongation at break of 1760 %, and fracture energy of 14.98 kJ/m2 ), appreciable self-healing ability (healing efficiency >90 %), satisfactory environmental stability, and outstanding recyclability. The sensor constructed by ICE-2 could not only realize the perception of temperature changes, but also accurately and sensitively detect various human activities, including joint movements and micro-expression changes. This study provides a simple and effective strategy for the development of flexible and soft ionic conductors for sensors and human-machine interfaces.

Waterproof, Light Responsive, and Highly Sensitive Fabric Strain Sensor for Flexible Electronics.

Corrosion resistant, durable, and lightweight flexible strain sensor with multiple functionalities is an urgent demand for modern flexible wearable devices. However, currently developed wearable devices are still limited by poor environmental adaptability and functional singleness. In this work, a conductive fabric with multifunctionality in addition to sensing was successfully prepared by assembling zero dimensional silver nanoparticles (AgNPs) and one-dimensional carbon nanotubes (CNTs) layer by layer on the surface of the elastic polypropylene nonwoven fabric (named PACS fabric). Polystyrene-block-poly(ethylene-co-butylene)-block-polystyrene (SEBS) added as binder materials favored strong interaction between conductive fillers and the fabric. Benefiting from the synergistic interaction among the conductive fillers with different dimensions and the fabric, the strain sensor based on the conductive fabric showed high sensitivity (GF up to 8064), wide detection range (0-200%), and excellent stability and durability (more than 10000 stretch-release cycles). Besides, the prepared conductive fabric showed superhydrophobicity (water contact angle = 154°) with excellent durability. This ensured the performance stability of the fabric sensor in harsh environments. At the same time, the fabric also showed excellent photothermal conversion performance (90 °C at a power density of 0.2 W/cm2 within 20 s). The PACS fabric strain sensor proved excellent performance and environmental adaptability, revealing great potential to be applied in human motion monitoring, self-cleaning, biomedicine, and other fields.

Effect of vacancy defects on anisotropic electronic transport behaviors of CoN4C2based 2D devices: a first-principles study.

The strong anisotropic electronic transport properties of the single-atom-thick material CoN4C2monolayer hold immense importance for the advancement of the electronics industry. Using density functional theory combined with non-equilibrium Green's function systematically studied the electronic structural properties and anisotropic electronic transport properties of the CoN4C2monolayer. The results show that Co, N, and C single-atom vacancy defects do not change the electronic properties of the CoN4C2monolayer, which remains metallic. The pristine device and the devices composed of Co, N single-atom vacancy defects exhibit stronger electronic transport along the armchair direction than the zigzag direction, which exhibit strong anisotropy, and a negative differential resistance (NDR) effect can be observed. In contrast to the results mentioned above, the device with C single-atom vacancy defects only exhibits the NDR effect. Among them, the device with the N single-atom vacancy defect regime exhibits the strongest anisotropy, with anIZ/IAof up to 7.95. Moreover, based on the strongest anisotropy exhibited by N single-atom vacancy defects, we further studied the influence of different sites of the N-atom vacancy on the electronic transport properties of the devices. The results indicate that N-1, N-2, N-3, N-12, N-23, N-123, N-1234, and N-12345 model devices did not change the high anisotropy and NDR effect of the device, and among them the N-1234 exhibits the strongest anisotropy, theIZ/IAreaches 6.12. A significant NDR effect is also observed for the electronic transport along the armchair direction in these devices. However, the current gradually decreases as an increase of the number of N defects. These findings showcase the considerable potential for integration of the CoN4C2monolayer in switching devices and NDR-based multifunctional nanodevices.

Gene Expression Profiling Reveals Potential Players of Sex Determination and Asymmetrical Development in Chicken Embryo Gonads.

Despite the notable progress made in recent years, the understanding of the genetic control of gonadal sex differentiation and asymmetrical ovariogenesis in chicken during embryonic development remains incomplete. This study aimed to identify potential key genes and speculate about the mechanisms associated with ovary and testis development via an analysis of the results of PacBio and Illumina transcriptome sequencing of embryonic chicken gonads at the initiation of sexual differentiation (E4.5, E5.5, and E6.5). PacBio sequencing detected 328 and 233 significantly up-regulated transcript isoforms in females and males at E4.5, respectively. Illumina sequencing detected 95, 296 and 445 DEGs at E4.5, E5.5, and E6.5, respectively. Moreover, both sexes showed asymmetrical expression in gonads, and more DEGs were detected on the left side. There were 12 DEGs involved in cell proliferation shared between males and females in the left gonads. GO analysis suggested that coagulation pathways may be involved in the degradation of the right gonad in females and that blood oxygen transport pathways may be involved in preventing the degradation of the right gonad in males. These results provide a comprehensive expression profile of chicken embryo gonads at the initiation of sexual differentiation, which can serve as a theoretical basis for further understanding the mechanism of bird sex determination and its evolutionary process.

Novel quantitative structure activity relationship models for predicting hexadecane/air partition coefficients of organic compounds.

Predicting the logarithm of hexadecane/air partition coefficient (L) for organic compounds is crucial for understanding the environmental behavior and fate of organic compounds and developing prediction models with polyparameter linear free energy relationships. Herein, two quantitative structure activity relationship (QSAR) models were developed with 1272 L values for the organic compounds by using multiple linear regression (MLR) and support vector machine (SVM) algorithms. On the basis of the OECD principles, the goodness of fit, robustness and predictive ability for the developed models were evaluated. The SVM model was first developed, and the predictive capability for the SVM model is slightly better than that for the MLR model. The applicability domain (AD) of these two models has been extended to include more kinds of emerging pollutants, i.e., oraganosilicon compounds. The developed QSAR models can be used for predicting L values of various organic compounds. The van der Waals interactions between the organic compound and the hexadecane have a significant effect on the L value of the compound. These in silico models developed in current study can provide an alternative to experimental method for high-throughput obtaining L values of organic compounds.

Soil pH: a key edaphic factor regulating distribution and functions of bacterial community along vertical soil profiles in red soil of pomelo orchard.

BACKGROUND: Soil microbes exist throughout the soil profile and those inhabiting topsoil (0-20 cm) are believed to play a key role in nutrients cycling. However, the majority of the soil microbiology studies have exclusively focused on the distribution of soil microbial communities in the topsoil, and it remains poorly understood through the subsurface soil profile (i.e., 20-40 and 40-60 cm). Here, we examined how the bacterial community composition and functional diversity changes under intensive fertilization across vertical soil profiles [(0-20 cm (RS1), 20-40 cm (RS2), and 40-60 cm (RS3)] in the red soil of pomelo orchard, Pinghe County, Fujian, China. RESULTS: Bacterial community composition was determined by 16S rRNA gene sequencing and interlinked with edaphic factors, including soil pH, available phosphorous (AP), available nitrogen (AN), and available potassium (AK) to investigate the key edaphic factors that shape the soil bacterial community along with different soil profiles. The most dominant bacterial taxa were Proteobacteria, Acidobacteria, Actinobacteria, Chloroflexi, Crenarchaeota, and Bacteriodetes. Bacterial richness and diversity was highest in RS1 and declined with increasing soil depth. The distinct distribution patterns of the bacterial community were found across the different soil profiles. Besides, soil pH exhibited a strong influence (pH ˃AP ˃AN) on the bacterial communities under all soil depths. The relative abundance of Proteobacteria, Actinobacteria, Crenarchaeota, and Firmicutes was negatively correlated with soil pH, while Acidobacteria, Chloroflexi, Bacteriodetes, Planctomycetes, and Gemmatimonadetes were positively correlated with soil pH. Co-occurrence network analysis revealed that network topological features were weakened with increasing soil depth, indicating a more stable bacterial community in the RS1. Bacterial functions were estimated using FAPROTAX and the relative abundance of functional bacterial community related to metabolic processes, including C-cycle, N-cycle, and energy production was significantly higher in RS1 compared to RS2 and RS3, and soil pH had a significant effect on these functional microbes. CONCLUSIONS: This study provided the valuable findings regarding the structure and functions of bacterial communities in red soil of pomelo orchards, and highlighted the importance of soil depth and pH in shaping the soil bacterial population, their spatial distribution and ecological functioning. These results suggest the alleviation of soil acidification by adopting integrated management practices to preserve the soil microbial communities for better ecological functioning.

Intercropping alleviated the phytotoxic effects of cinnamic acid on the root cell wall structural resistance of faba bean and reduced the occurrence of Fusarium wilt.

Soilborne Fusarium wilt is a key factor restricting the cultivation of faba bean. Intercropping faba bean and wheat effectively alleviate faba bean Fusarium wilt. This study analyzed the mechanism by which cinnamic acid promotes Fusarium wilt and the mechanism that enables intercropping alleviated Fusarium wilt. Faba beans were inoculated with Fusarium oxysporum f. sp. fabae (FOF), while the controls were not inoculated. Different concentrations of cinnamic acid were added to the inoculated plants to study the occurrence of Fusarium wilt, seedling growth, the activities of cell wall degradation enzyme (CWDESs) produced by FOF in the root, defense enzymes, total phenolics and lignin, levels of expression of the pathogenesis-related genes (PRs) PR1, PR2, and PR10, and changes in the submicroscopic cell wall structure of the roots under monocropping and intercropping systems. Cinnamic acid increased the activities of CWDEs produced by FOF in the roots, increased the activities of phenylalanine ammonia lyase and polyphenol oxidase and the contents of total phenolics and lignin, and upregulated the levels of expression of PRs in the root, but it decreased the activity of peroxidase. Transmission electron microscopy (TEM) observations identified severe damage and disruption of the root cell walls, and numerous FOF mycelia entered the cytoplasm from the cell wall. The combination of these factors increased the occurrence of Fusarium wilt. The activities of CWDEs produced by FOF in the roots decreased by intercropping wheat with faba bean, which increased the resistance of the root cell walls to infection and decreased the Fusarium wilt.