Individualized prediction of anxiety and depressive symptoms using gray matter volume in a non-clinical population.

Machine learning is an emerging tool in clinical psychology and neuroscience for the individualized prediction of psychiatric symptoms. However, its application in non-clinical populations is still in its infancy. Given the widespread morphological changes observed in psychiatric disorders, our study applies five supervised machine learning regression algorithms-ridge regression, support vector regression, partial least squares regression, least absolute shrinkage and selection operator regression, and Elastic-Net regression-to predict anxiety and depressive symptom scores. We base these predictions on the whole-brain gray matter volume in a large non-clinical sample (n = 425). Our results demonstrate that machine learning algorithms can effectively predict individual variability in anxiety and depressive symptoms, as measured by the Mood and Anxiety Symptoms Questionnaire. The most discriminative features contributing to the prediction models were primarily located in the prefrontal-parietal, temporal, visual, and sub-cortical regions (e.g. amygdala, hippocampus, and putamen). These regions showed distinct patterns for anxious arousal and high positive affect in three of the five models (partial least squares regression, support vector regression, and ridge regression). Importantly, these predictions were consistent across genders and robust to demographic variability (e.g. age, parental education, etc.). Our findings offer critical insights into the distinct brain morphological patterns underlying specific components of anxiety and depressive symptoms, supporting the existing tripartite theory from a neuroimaging perspective.

The role of DGAT1 and DGAT2 in regulating tumor cell growth and their potential clinical implications.

Lipid metabolism is widely reprogrammed in tumor cells. Lipid droplet is a common organelle existing in most mammal cells, and its complex and dynamic functions in maintaining redox and metabolic balance, regulating endoplasmic reticulum stress, modulating chemoresistance, and providing essential biomolecules and ATP have been well established in tumor cells. The balance between lipid droplet formation and catabolism is critical to maintaining energy metabolism in tumor cells, while the process of energy metabolism affects various functions essential for tumor growth. The imbalance of synthesis and catabolism of fatty acids in tumor cells leads to the alteration of lipid droplet content in tumor cells. Diacylglycerol acyltransferase 1 and diacylglycerol acyltransferase 2, the enzymes that catalyze the final step of triglyceride synthesis, participate in the formation of lipid droplets in tumor cells and in the regulation of cell proliferation, migration and invasion, chemoresistance, and prognosis in tumor. Several diacylglycerol acyltransferase 1 and diacylglycerol acyltransferase 2 inhibitors have been developed over the past decade and have shown anti-tumor effects in preclinical tumor models and improvement of metabolism in clinical trials. In this review, we highlight key features of fatty acid metabolism and different paradigms of diacylglycerol acyltransferase 1 and diacylglycerol acyltransferase 2 activities on cell proliferation, migration, chemoresistance, and prognosis in tumor, with the hope that these scientific findings will have potential clinical implications.

High-dose ascorbate exerts anti-tumor activities and improves inhibitory effect of carboplatin through the pro-oxidant function pathway in uterine serous carcinoma cell lines.

OBJECTIVE: Uterine serous carcinoma is a highly aggressive non-endometrioid subtype of endometrial cancer with poor survival rates overall, creating a strong need for new therapeutic strategies to improve outcomes. High-dose ascorbate (vitamin C) has been shown to inhibit cell proliferation and tumor growth in multiple preclinical models and has shown promising anti-tumor activity in combination with chemotherapy, with a favorable safety profile. We aimed to study the anti-tumor effects of ascorbate and its synergistic effect with carboplatin on uterine serous carcinoma cells. METHODS: Cell proliferation was evaluated by MTT and colony formation assays in ARK1, ARK2 and SPEC2 cells. Cellular stress, antioxidant ability, cleaved caspase 3 activity and adhesion were measured by ELISA assays. Cell cycle was detected by Cellometer. Invasion was measured using a wound healing assay. Changes in protein expression were determined by Western immunoblotting. RESULTS: High-dose ascorbate significantly inhibited cell proliferation, caused cell cycle arrest, induced cellular stress, and apoptosis, increased DNA damage, and suppressed cell invasion in ARK1 and SPEC2 cells. Treatment of both cells with 1 mM N-acetylcysteine reversed ascorbate-induced apoptosis and inhibition of cell proliferation. The combination of ascorbate and carboplatin produced significant synergistic effects in inhibiting cell proliferation and invasion, inducing cellular stress, causing DNA damage, and enhancing cleaved caspase 3 levels compared to each compound alone in both cells. CONCLUSIONS: Ascorbate has potent antitumor activity and acts synergistically with carboplatin through its pro-oxidant effects. Clinical trials of ascorbate combined with carboplatin as adjuvant treatment of uterine serous carcinoma are worth exploring.

Neurobiological substrates of the dread of future losses.

When anticipating future losses, people respond by exhibiting 1 of 2 starkly distinct behavioral decision patterns: the dread of future losses (DFL) and the preference of future losses (vs. immediate losses). Yet, how to accurately discriminate between those who exhibit dread vs. preference and uncover the potential neurobiological substrates underlying these 2 groups remain understudied. To address this, we designed a novel experimental task in which the DFL group was defined as selecting immediate-loss options >50% in the trials with approximate subjective value in immediate and delayed options (n = 16), otherwise coding as the preference of future losses (PFL). At the behavioral level, DFL exhibited higher weight for delayed losses than immediate losses via the logistic regression model. At the neural level, DFL manifested hypoactivations on subjective valuations of delayed losses, atypical brain pattern when choosing immediate-loss options, and decreased functional coupling between the valuation and choice-systems when making decisions related to immediate-loss alternatives compared with PFL. Moreover, both these brain activations subserving distinct decision processes and their interactions predicted individual decisions and behavioral preferences. Furthermore, morphological analysis also revealed decreased right precuneus volume in DFL compared with PFL, and brain activations related to valuation and choice process mediated the associations between this region volume and behavioral performances. Taken together, these findings help to clarify potential cognitive and neural mechanisms underlying the DFL and provide a clear discrimination strategy.

Microglia and macrophages in the neuro-glia-vascular unit: From identity to functions.

Although both are myeloid cells located surrounding cerebral vasculature, vessel-associated microglia (VAM) and perivascular macrophages (PVMs) can be distinguished by their distinct morphologies, signatures and microscopic location. As key component of neuro-glia-vascular unit (NGVU), they play prominent roles in neurovasculature development and pathological process of various central nervous system (CNS) diseases, including phagocytosis, angiogenesis, vessel damage/protection and blood flow regulation, therefore serving as potential targets for therapeutics of a broad array of CNS diseases. Herein, we will provide a comprehensive overview of heterogeneity of VAM/PVMs, highlight limitations of current understanding in this field, and discuss possible directions of future investigations.

Distributed attribute representation in the superior parietal lobe during probabilistic decision-making.

Several studies have examined the neural substrates of probabilistic decision-making, but few have systematically investigated the neural representations of the two objective attributes of probabilistic rewards, that is, the reward amount and the probability. Specifically, whether there are common or distinct neural activity patterns to represent the objective attributes and their association with the neural representation of the subjective valuation remains largely underexplored. We conducted two studies (nStudy1 = 34, nStudy2 = 41) to uncover distributed neural representations of the objective attributes and subjective value as well as their association with individual probability discounting rates. The amount and probability were independently manipulated to better capture brain signals sensitive to these two attributes and were presented simultaneously in Study 1 and successively in Study 2. Both univariate and multivariate pattern analyses showed that the brain activities in the superior parietal lobule (SPL), including the postcentral gyrus, were modulated by the amount of rewards and probability in both studies. Further, representational similarity analysis revealed a similar neural representation between these two objective attributes and between the attribute and valuation. Moreover, the SPL tracked the subjective value integrated by the hyperbolic function. Probability-related brain activations in the inferior parietal lobule were associated with the variability in individual discounting rates. These findings provide novel insights into a similar neural representation of the two attributes during probabilistic decision-making and perhaps support the common neural coding of stimulus objective properties and subjective value in the field of probabilistic discounting.

ASK1-K716R reduces neuroinflammation and white matter injury via preserving blood-brain barrier integrity after traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a significant worldwide public health concern that necessitates attention. Apoptosis signal-regulating kinase 1 (ASK1), a key player in various central nervous system (CNS) diseases, has garnered interest for its potential neuroprotective effects against ischemic stroke and epilepsy when deleted. Nonetheless, the specific impact of ASK1 on TBI and its underlying mechanisms remain elusive. Notably, mutation of ATP-binding sites, such as lysine residues, can lead to catalytic inactivation of ASK1. To address these knowledge gaps, we generated transgenic mice harboring a site-specific mutant ASK1 Map3k5-e (K716R), enabling us to assess its effects and elucidate potential underlying mechanisms following TBI. METHODS: We employed the CRIPR/Cas9 system to generate a transgenic mouse model carrying the ASK1-K716R mutation, aming to investigate the functional implications of this specific mutant. The controlled cortical impact method was utilized to induce TBI. Expression and distribution of ASK1 were detected through Western blotting and immunofluorescence staining, respectively. The ASK1 kinase activity after TBI was detected by a specific ASK1 kinase activity kit. Cerebral microvessels were isolated by gradient centrifugation using dextran. Immunofluorescence staining was performed to evaluate blood-brain barrier (BBB) damage. BBB ultrastructure was visualized using transmission electron microscopy, while the expression levels of endothelial tight junction proteins and ASK1 signaling pathway proteins was detected by Western blotting. To investigate TBI-induced neuroinflammation, we conducted immunofluorescence staining, quantitative real-time polymerase chain reaction (qRT-PCR) and flow cytometry analyses. Additionally, immunofluorescence staining and electrophysiological compound action potentials were conducted to evaluate gray and white matter injury. Finally, sensorimotor function and cognitive function were assessed by a battery of behavioral tests. RESULTS: The activity of ASK1-K716R was significantly decreased following TBI. Western blotting confirmed that ASK1-K716R effectively inhibited the phosphorylation of ASK1, JNKs, and p38 in response to TBI. Additionally, ASK1-K716R demonstrated a protective function in maintaining BBB integrity by suppressing ASK1/JNKs activity in endothelial cells, thereby reducing the degradation of tight junction proteins following TBI. Besides, ASK1-K716R effectively suppressed the infiltration of peripheral immune cells into the brain parenchyma, decreased the number of proinflammatory-like microglia/macrophages, increased the number of anti-inflammatory-like microglia/macrophages, and downregulated expression of several proinflammatory factors. Furthermore, ASK1-K716R attenuated white matter injury and improved the nerve conduction function of both myelinated and unmyelinated fibers after TBI. Finally, our findings demonstrated that ASK1-K716R exhibited favorable long-term functional and histological outcomes in the aftermath of TBI. CONCLUSION: ASK1-K716R preserves BBB integrity by inhibiting ASK1/JNKs pathway in endothelial cells, consequently reducing the degradation of tight junction proteins. Additionally, it alleviates early neuroinflammation by inhibiting the infiltration of peripheral immune cells into the brain parenchyma and modulating the polarization of microglia/macrophages. These beneficial effects of ASK1-K716R subsequently result in a reduction in white matter injury and promote the long-term recovery of neurological function following TBI.

Reactivity of the ventromedial prefrontal cortex, but not the amygdala, to negative emotion faces predicts greed personality trait.

This study explored whether amygdala reactivity predicted the greed personality trait (GPT) using both task-based and resting-state functional connectivity analyses (ntotal = 452). In Cohort 1 (n = 83), task-based functional magnetic resonance imaging (t-fMRI) results from a region-of-interest (ROI) analysis revealed no direct correlation between amygdala reactivity to fearful and angry faces and GPT. Instead, whole-brain analyses revealed GPT to robustly negatively vary with activations in the right ventromedial prefrontal cortex (vmPFC), supramarginal gyrus, and angular gyrus in the contrast of fearful + angry faces > shapes. Moreover, task-based psychophysiological interaction (PPI) analyses showed that the high GPT group showed weaker functional connectivity of the vmPFC seed with a top-down control network and visual pathways when processing fearful or angry faces compared to their lower GPT counterparts. In Cohort 2, resting-state functional connectivity (rs-FC) analyses indicated stronger connectivity between the vmPFC seed and the top-down control network and visual pathways in individuals with higher GPT. Comparing the two cohorts, bilateral amygdala seeds showed weaker associations with the top-down control network in the high group via PPI analyses in Cohort 1. Yet, they exhibited distinct rs-FC patterns in Cohort 2 (e.g., positive associations of GPT with the left amygdala-top-down network FC but negative associations with the right amygdala-visual pathway FC). The study underscores the role of the vmPFC and its functional connectivity in understanding GPT, rather than amygdala reactivity.

Single-Atom Fe-N4 Sites for Catalytic Ozonation to Selectively Induce a Nonradical Pathway toward Wastewater Purification.

Nonradical oxidation has been determined to be a promising pathway for the degradation of organic pollutants in heterogeneous catalytic ozonation (HCO). However, the bottlenecks are the rational design of catalysts to selectively induce nonradicals and the interpretation of detailed nonradical generation mechanisms. Herein, we propose a new HCO process based on single-atom iron catalysts, in which Fe-N4 sites anchored on the carbon skeleton exhibited outstanding catalytic ozonation activity and stability for the degradation of oxalic acid (OA) and p-hydroxybenzoic acid (pHBA) as well as the advanced treatment of a landfill leachate secondary effluent. Unlike traditional radical oxidation, nonradical pathways based on surface-adsorbed atomic oxygen (*Oad) and singlet oxygen (1O2) were identified. A substrate-dependent behavior was also observed. OA was adsorbed on the catalyst surface and mainly degraded by *Oad, while pHBA was mostly removed by O3 and 1O2 in the bulk solution. Density functional theory calculations and molecular dynamics simulations revealed that one terminal oxygen atom of ozone preferred bonding with the central iron atom of Fe-N4, subsequently inducing the cleavage of the O-O bond near the catalyst surface to produce *Oad and 1O2. These findings highlight the structural design of an ozone catalyst and an atomic-level understanding of the nonradical HCO process.

Bioinformatics-based analysis of the roles of sex hormone receptors in endometriosis development.

Endometriosis is a hormone-dependent disease in women of reproductive age and seriously affects women's health. To analyze the involvement of sex hormone receptors in endometriosis development, we performed bioinformatics analysis using four datasets derived from the Gene Expression Omnibus (GEO) database, which may help us understand the mechanisms by which the sex hormones act in vivo in endometriosis patients. The enrichment analysis and protein-protein interaction (PPI) analysis of the differentially expressed genes (DEGs) revealed that there are different key genes and pathways involved in eutopic endometrium aberrations of endometriosis patients and endometriotic lesions, and sex hormone receptors, including androgen receptor (AR), progesterone receptor (PGR) and estrogen receptor 1 (ESR1), may play important roles in endometriosis development. Androgen receptor (AR), as the hub gene of endometrial aberrations in endometriotic patients, showed positive expression in the main cell types for endometriosis development, and its decreased expression in the endometrium of endometriotic patients was also confirmed by immunohistochemistry (IHC). The nomogram model established based on it displayed good predictive value.

Probing the Interaction between Isoflucypram Fungicides and Human Serum Albumin: Multiple Spectroscopic and Molecular Modeling Investigations.

To better understand the potential toxicity risks of isoflucypram in humans, The interaction between isoflucypram and HSA (human serum albumin) was studied through molecular docking, molecular dynamics simulations, ultraviolet-visible absorption, fluorescence, synchronous fluorescence, three-dimensional fluorescence, Fourier transform infrared spectroscopies, and circular dichroism spectroscopies. The interaction details were studied using the molecular docking method and molecular dynamics simulation method. The results revealed that the effect of isoflucypram on human serum albumin was mixed (static and dynamic) quenching. Additionally, we were able to obtain important information on the number of binding sites, binding constants, and binding distance. The interaction between isoflucypram and human serum albumin occurred mainly through hydrogen bonds and van der Waals forces. Spectroscopic results showed that isoflucypram caused conformational changes in HSA (human serum albumin), in which the α-helix was transformed into a ß-turn, ß-sheet, and random coil, causing the HSA structure to loosen. By providing new insights into the mechanism of binding between isoflucypram and human serum albumin, our study has important implications for assessing the potential toxicity risks associated with isoflucypram exposure.

Photoacoustic mediated multifunctional tumor antigen trapping nanoparticles inhibit the recurrence and metastasis of ovarian cancer by enhancing tumor immunogenicity.

The hypoimmunogenicity of tumors is one of the main bottlenecks of cancer immunotherapy. Enhancing tumor immunogenicity can improve the efficacy of tumor immunotherapy by increasing antigen exposure and presentation, and establishing an inflammatory microenvironment. Here, a multifunctional antigen trapping nanoparticle with indocyanine green (ICG), aluminum hydroxide (Al(OH)3) and oxaliplatin (OXA) (PPIAO) has been developed for tumor photoacoustic/ultrasound dual-modality imaging and therapy. The combination of photothermal/photodynamic therapy and chemotherapy induced tumor antigen exposure and release through immunogenic death of tumor cells. A timely capture and storage of antigens by aluminum hydroxide enabled dendritic cells to recognize and present those antigens spatiotemporally. In an ovarian tumor model, the photoacoustic-mediated PPIAO NPs combination therapy achieved a transition from "cold tumor" to "hot tumor" that promoted more CD8+ T lymphocytes activation in vivo and intratumoral infiltration, and successfully inhibited the growth of primary and metastatic tumors. An in situ tumor vaccine effect was produced from the treated tumor tissue, assisting mice against the recurrence of tumor cells. This study provided a simple and effective personalized tumor vaccine strategy for better treatment of metastatic and recurrent tumors. The developed multifunctional tumor antigen trapping nanoparticles may be a promising nanoplatform for integrating multimodal imaging monitoring, tumor treatment, and tumor vaccine immunotherapy.

Occurrence of root rot caused by Fusarium fujikuroi and Fusarium proliferatum on peanut in China.

Root rot of peanut, caused by Fusarium spp., is a devastating disease in most peanut cultivation regions. In this reported outbreak, Fusarium root rot of peanut has been observed in Henan province, China in July 2021. About 20% of peanuts in a field (0.66 ha) were affected. Early symptoms comprised the wilt of the lower leaves, and the darkening of the vascular tissue of roots, which turned brown. Progressively, the whole plant wilted, the roots rotted, and the plant ultimately died. Pathogenic species were isolated from plants showing symptoms of root rot in the field. A total of 206 Fusarium isolates were generated, and 16 isolates were preliminarily identified as Fusarium fujikuroi based on morphological characteristics. Isolates were obtained and grown on PDA plates. Isolates developed floccose white aerial mycelia with reddish-pink coloration in the medium in 2 weeks on the benchtop. Macroconidia were 3-5 septate, measuring 27.5 to 48.8 × 2.6 to 3.8 µm (avg. 36.7 × 3.6 µm, n=50). Microconidia were abundant in chains, mainly asepatate, oval to kidney-shaped, 4.0 to 11.6 × 2.5 to 4.1 µm (avg. 5.8 ×3.1 µm, n=50). DNA was extracted from mycelium and the following genes were amplified and sequenced: the internal transcribed spacer (ITS) region using ITS1/ITS4 primers (White et al.1990) (Genbank assessions MZ831304 to MZ831308), the partial calmodulin gene (CAM, primer CL1/CL2A, O'Donnell.)(Genbank assession MZ856333 to MZ856337) and the partial translation elongation factor (EF-1α) using primer EF1/EF2 (Geiser et al.)(Genbank assession MZ856338 to MZ8564342). FUSARIUM-ID analysis showed 98.18% to 100% similarity with sequences of the F. fujikuroi species complex. The phylogenetic analysis was conducted using a neighbor-joining algorithm based on the ITS, CAM, and EF-1α gene sequences. The isolates were clustered with F. fujikuroi clade (Supplementary Fig.1). Koch's postulates were conducted using a sand-cornmeal-inoculum-layer method (Bilgi et al.). Briefly, 400 ml plastic boxes were filled with 15g of sterilized premium-grade coarse vermiculite, followed by a 15 g of inoculum prepared as sand-cornmeal mixture inoculum. The inoculum for each F. fujikuroi isolates was prepared by infesting a pre-sterilized sand-cornmeal mixture with three 5 mm plugs of cultures. Three F. fujikuroi isolates and PDA plugs were inoculated to serve as positive control and non-inoculated control treatments, respectively. The completed colonization of the sand-cornmeal mixture was finished by incubating at 25 ℃ for 7-10 days. Eight pre-germinated seeds of cv. Luhua No.1 was then covered with another 8 g of vermiculite. Peanuts were grown at 25 °C with 85% relative humidity under a light/dark cycle of 14h/10h. After 14 days of incubation, the inoculated plants showed typical symptoms of root rot similar to those in the field: pre-emergence damping-off, reddish-brown lesions on the tap, and lateral roots. F. fujikuroi was successfully re-isolated from inoculated plants but not from the controls and identified as described above. F. fujikuroi was reported to cause bakanae disease of rice (Amatulli et. al.), and root rot of soybeans (Zhao et. al.). To the best of our knowledge, this is the first record of F. fujikuroi causing root rot of peanut in China.

First Report of Anthracnose Caused by Colletotrichum kahawae and Colletotrichum horri on Tea-oil Tree in China.

Tea-oil tree (Camellia oleifera Abel) is an important economic woody plant in southern China. The buds, fruits, and leaves of tea oil tree are all susceptible to the disease, causing the wilt or even fall of the plant. Every year, the disease incidence of anthracnose reached 20%-40% in diseased fields. In 2020, leaves with anthracnose were collected from the main producing areas of tea-oil tree in Yunnan Province and Guizhou Province, China. To isolate the pathogen, several fragments of diseased tissues (5×5mm) were disinfected in 75% alcohol for 40 s, and rinsed 3 times in sterilized water. Then, tissues were placed on PDA medium and incubated at 26℃ for 5 days. Fungal isolates with morphology characteristics similar to Colletotrichum spp. were consistently recovered from diseased tissues. Eighteen fungal isolates were obtained. Among them, 3 representative single-spore isolates (C2, gy15, Ch) were picked for further analysis. The isolates C2 and gy15 on the PDA were gray-white in the initial stage, and later became olive green and spread to the edge. Abundant orange-red conidial masses were present in the colony surface. Conidia were cylindrical and with blunt circles at both ends, with a size of 9.9 µm ~ 21.8 µm × 4.0 µm ~ 6.8 µm (n=50). The hyphae of isolate Ch on PDA were thin, cotton-like, gray to gray-black; the center of the back of the colony was brown, and the color of the colony became darker, and concentric rings could be produced. The conidia were cylindrical , with blunt circles at both ends, with a size of 6.3 µm ~15.0 µm × 3.2 µm ~ 7.0µm (n=50). In order to further identify the pathogens, the internal transcribed spacer (ITS) region of ribosomal DNA, actin (ACT), chitin synthase (CHS), ß-tubulin (TUB2), calmodulin (CAL) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were amplified (Weir et al. 2012; Yang et al. 2009). The resulting sequences were deposited under the GenBank accession numbers OK148894, OM397909, OM249943, OL422149, OM184266 and OM718003 for C2,OK148975, OM397910, OM249944, OL422150, OM184267, OM718004 for gy15, OK148976, OM397911, OM249945, OL422151, OM184268 and OM718005 for Ch. A BLAST search showed that the sequences of isolates C2 and gy15 had 99.57% to 100% similarity to the type strain of Colletotrichum kahawae ICMP12952. The sequences of isolate Ch had 99.03% to 100% similarity to the type strain of Colletotrichum horri ICMP 17968. Further, a phylogenetic tree based on the combined ITS, ACT, CHS, TUB, CAL, and GAPDH sequence using the neighbor-joining algorithm revealed that the isolates were C. kahawae and C. horri (Fig. 1). Pathogenicity assays were conducted on healthy leaves collected from 1-year-old tea-oil tree. The experiments were repeated twice. The leaves were surface-sterilized with 75% ethanol. After drying, they were placed in a plastic box pre-laid with sterilized absorbent paper. The leaf surface was slightly pierced with a sterile needle, and each stab wound was inoculated with 10 µL of conidial suspension (1×106 conidia/ml). All inoculated leaves were placed in a moist chamber at 25℃ with 80% relative humidity. After 10 days, inoculated leaves showed similar symptoms as observed in the field, whereas controls remained symptomless. C. kahawae and C. horri were re-isolated from the diseased leaves, and identifed by sequencing. C. kahawae is widespread on coffee in Africa (Waller et al. 1993). C. horri has been associated with fruit and stem diseases of Diospyros kaki from China, Japan, and New Zealand (Weir et al. 2010). To our knowledge, this is the first report of C. kahawa and C. horri causing anthracnose of tea-oil tree.

Factors Underlying the Prevalence of Pythium Infection of Corn Seeds Following Seed Treatment Application of Tebuconazole.

Microbial communities are essential for soil health, but fungicide application may have significant effects on their structure. It is difficult to predict whether nontarget pathogens of applied fungicides in the soil will cause crop damage. Tebuconazole is a triazole fungicide that can be used as a seed treatment and, thereby, introduced to the soil. However, seed-applied tebuconazole has a potential risk of causing poor emergence of corn (Zea mays) seedlings. Using soil with a history of poor corn seedling emergence, we demonstrate through TA cloning and isolation that the poor emergence of corn seedlings from tebuconazole-coated corn seeds was primarily because of infection by surviving soil pathogens, specifically Pythium species that are not targeted by tebuconazole, rather than the phytotoxic effects of tebuconazole. Bioassay tests on tebuconazole-amended media showed that tebuconazole can suppress soil fungi while allowing Pythium to grow. Pythium species primarily contributing to the corn seed rot were more pathogenic at cooler temperatures. Furthermore, the nontarget biocontrol agent of Trichoderma spp. was strongly inhibited by tebuconazole. Taken together, the nontarget effects of tebuconazole are likely not significant under favorable plant growing conditions but are considerable because of low-temperature stress.

Primary Mode of Action of the Novel Sulfonamide Fungicide against Botrytis cinerea and Field Control Effect on Tomato Gray Mold.

Botrytis cinerea is considered an important plant pathogen and is responsible for significant crop yield losses. With the frequent application of commercial fungicides, B. cinerea has developed resistance to many frequently used fungicides. Therefore, it is necessary to develop new kinds of fungicides with high activity and new modes of action to solve the increasingly serious problem of resistance. During our screening of fungicide candidates, one novel sulfonamide compound, N-(2-trifluoromethyl-4-chlorphenyl)-2-oxocyclohexyl sulfonamide (L13), has been found to exhibit good fungicidal activity against B. cinerea. In this work, the mode of action of L13 against B. cinerea and the field control effect on tomato gray mold was studied. L13 had good control against B. cinerea resistant to carbendazim, diethofencarb, and iprodione commercial fungicides in the pot culture experiments. SEM and TEM observations revealed that L13 could cause obvious morphological and cytological changes to B. cinerea, including excessive branching, irregular ramification or abnormal configuration, and the decomposition of cell wall and vacuole. L13 induced more significant electrolyte leakage from hyphae than procymidone as a positive control. L13 had only a minor effect on the oxygen consumption of intact mycelia, with 2.15% inhibition at 50 µg/mL. In two locations over 2 years, the field control effect of L13 against tomato gray mold reached 83% at a rate of 450 g ai ha-1, better than the commercial fungicide of iprodione. Moreover, toxicological tests demonstrated the low toxicological effect of L13. This research seeks to provide technical support and theoretical guidance for L13 to become a real commercial fungicide.

Stochastic Order and Generalized Weighted Mean Invariance.

In this paper, we present order invariance theoretical results for weighted quasi-arithmetic means of a monotonic series of numbers. The quasi-arithmetic mean, or Kolmogorov-Nagumo mean, generalizes the classical mean and appears in many disciplines, from information theory to physics, from economics to traffic flow. Stochastic orders are defined on weights (or equivalently, discrete probability distributions). They were introduced to study risk in economics and decision theory, and recently have found utility in Monte Carlo techniques and in image processing. We show in this paper that, if two distributions of weights are ordered under first stochastic order, then for any monotonic series of numbers their weighted quasi-arithmetic means share the same order. This means for instance that arithmetic and harmonic mean for two different distributions of weights always have to be aligned if the weights are stochastically ordered, this is, either both means increase or both decrease. We explore the invariance properties when convex (concave) functions define both the quasi-arithmetic mean and the series of numbers, we show its relationship with increasing concave order and increasing convex order, and we observe the important role played by a new defined mirror property of stochastic orders. We also give some applications to entropy and cross-entropy and present an example of multiple importance sampling Monte Carlo technique that illustrates the usefulness and transversality of our approach. Invariance theorems are useful when a system is represented by a set of quasi-arithmetic means and we want to change the distribution of weights so that all means evolve in the same direction.

Cobalt Nanoparticles and Atomic Sites in Nitrogen-Doped Carbon Frameworks for Highly Sensitive Sensing of Hydrogen Peroxide.

In situ monitoring of hydrogen peroxide (H2 O2 ) during its production process is needed. Here, an electrochemical H2 O2 sensor with a wide linear current response range (concentration: 5 × 10-8 to 5 × 10-2 m), a low detection limit (32.4 × 10-9 m), and a high sensitivity (568.47 µA mm-1 cm-2 ) is developed. The electrocatalyst of the sensor consists of cobalt nanoparticles and atomic Co-Nx moieties anchored on nitrogen doped carbon nanotube arrays (Co-N/CNT), which is obtained through the pyrolysis of the sandwich-like urea@ZIF-67 complex. More cobalt nanoparticles and atomic Co-Nx as active sites are exposed during pyrolysis, contributing to higher electrocatalytic activity. Moreover, a portable screen-printed electrode sensor is constructed and demonstrated for rapidly detecting (cost ≈40 s) H2 O2 produced in microbial fuel cells with only 50 µL solution. Both the synthesis strategy and sensor design can be applied to other energy and environmental fields.

Paralogous CYP51 Genes of Colletotrichum spp. Mediate Differential Sensitivity to Sterol Demethylation Inhibitors.

Colletotrichum spp. isolates contain two paralogous CYP51 genes that encode sterol 14-demethylase enzymes; however, their role in sensitivity to demethylation inhibitor (DMI) fungicides is yet to be determined. In this study, each of the two genes from Colletotrichum fioriniae and C. nymphaeae was able to rescue the function of CYP51 in the yeast Saccharomyces cerevisiae, demonstrating their independent function. Deletion of CYP51A led to increased sensitivity to propiconazole, diniconazole, prothioconazole, cyproconazole, epoxiconazole, flutriafol, prochloraz, and difenoconazole in C. fioriniae, and to the same fungicides and tebuconazole in C. nymphaeae, with the exception of prochloraz. Deletion of CYP51B in C. fioriniae and CYP51B in C. nymphaeae made mutants increasingly sensitive to five of nine DMI fungicides tested. The results suggest species-specific, differential binding of DMI fungicides onto the two CYP51 enzymes. Pairing DMIs with different effects on CYP51A and -B deletion mutants resulted in synergistic effects, as determined in mycelial growth inhibition experiments. Deletion mutants showed no fitness penalty in terms of mycelial growth, sporulation, and virulence. Our study elucidates the effect of CYP51A and CYP51B of Colletotrichum spp. on DMI sensitivity, suggesting that using a mixture of DMIs may improve the efficacy for anthracnose management.

First Report of Pythium torulosum Causing Corn Root Rot in Northeastern China.

In October 2017, we collected five soil samples from each of several fields with a history of severe corn (Zea mays) seedling disease in Heilongjiang province of China. Affected seedlings were wilted with severe root rot, and a high incidence of seedling death was observed in the fields. Corn seeds were seeded in the collected soil samples and grown in a growth chamber for 21 days set at the following incubation temperatures: 21℃/7℃ for 6 days, 10℃/3℃ for 4 days, 16℃/7℃ for 5 days, 20℃/20℃ for 6 days (16 h/8 h, light/dark) (Tang et al. 2019). The corn seedlings in the growth chamber showed the same symptoms observed in the field as mentioned above. Corn root rot samples were collected from several symptomatic plants in the growth chamber to isolate the possible pathogen. Symptomatic roots were washed in 0.5% NaOCl for 2 min, rinsed in sterile water and cut into 1-2 mm segments and then plated on corn meal agar amended with pimaricin (5 µg/ml), ampicillin (250 µg/ml), rifampicin (10 µg/ml), pentachloronitrobenzene (50 µg/ml), and benomyl (10 µg/ml) (PARP+B), which is selective for oomycetes (Jeffers and Martin 1986). After 3 days of incubation in the dark at 25℃, colonies were transferred to 10% V8 juice agar and incubated at 25℃ for 2 weeks. Six isolates were identified as Pythium torulosum based on the morphology of sexual and asexual structures following van der Plaats-Niterink's key (van der Plaats-Niterink 1981). On 10% V8 juice agar, the hypha were aseptate and colonies had filamentous sporangia with a dendroid or globose structure. The oogonia were globose or subglobose, laevis, terminal, rarely intercalary, ranging from 12-19 (average 16) µm. Antheridia were mostly sessile or brachypodous, and each oogonium was supplied by 1-2 antheridia cells. Oospores were globose, plerotic, ranging from 9-16 (average 13) µm. For the molecular identification, two molecular targets, the internal transcribed spacer (ITS) region of ribosomal DNA and cytochrome c oxidase subunit II (CoII), were amplified and sequenced using universal primer sets DC6/ITS4 (Cooke et al. 2000) and FM58/FM66 (Villa et al. 2006), respectively for one isolate, "copt". BLAST analyses of a 971 bp ITS segment amplified from copt (GenBank Accession No. MT830918) showed 99.79% identity with a P. torulosum isolate (GenBank Accession No. AY598624.2). For the COⅡ gene of copt, BLAST analyses of a 553 bp segment (GenBank Accession MT843570) showed 98.37% identity with P. torulosum isolate (GenBank Accession No. AB095065.1). Thus, the isolate, copt, was identified as P. torulosum based on morphological characteristics and molecular analysis. To confirm pathogenicity and Koch's postulates, a pathogenicity test was conducted as described by Zhang et al. (2000). Briefly, a 5 mm culture plug from the P. torulosum isolate, copt, was transferred to a 9-cm petri dish containing 20mL 10% V8 juice agar and incubated in the dark at 25℃ for 7 days. The culture was cut into small pieces and mixed with a sterilized soil mix (40% organic peat substrate, 40% perlite, and 20% soil) at a ratio of one petri dish per 100 g soil mix. Ten corn seeds were planted at a depth of 2 cm in a 500-mL pot containing the inoculated soil mix. The control pots were mock inoculated with plain 10% V8 juice agar. Pots were incubated in a greenhouse at temperatures ranging from 21 to 23℃. There were four replications. After 14 days, corn roots brown and rotted were observed, which was similar to those observed in the field and growth chamber. Control plants remained symptomless and healthy. P. torulosum copt was consistently re-isolated from the symptomatic roots. To our knowledge, this is the first report of P. torulosum causing root rot of corn in Northeastern China. Corn is an important crop in Heilongjiang and the occurrence of root rot caused by this pathogen may be a new threat to corn plants. There is a need to develop management measures to control the disease.