Liquid-Liquid Phase Separation of DDR1 Counteracts the Hippo Pathway to Orchestrate Arterial Stiffening.

BACKGROUND: The Hippo-YAP (yes-associated protein) signaling pathway is modulated in response to various environmental cues. Activation of YAP in vascular smooth muscle cells conveys the extracellular matrix stiffness-induced changes in vascular smooth muscle cells phenotype and behavior. Recent studies have established a mechanoreceptive role of receptor tyrosine kinase DDR1 (discoidin domain receptor 1) in vascular smooth muscle cells. METHODS: We conduced 5/6 nephrectomy in vascular smooth muscle cells-specific Ddr1-knockout mice, accompanied by pharmacological inhibition of the Hippo pathway kinase LATS1 (large tumor suppressor 1), to investigate DDR1 in YAP activation. We utilized polyacrylamide gels of varying stiffness or the DDR1 ligand, type I collagen, to stimulate the cells. We employed multiple molecular biological techniques to explore the role of DDR1 in controlling the Hippo pathway and to determine the mechanistic basis by which DDR1 exerts this effect. RESULTS: We identified the requirement for DDR1 in stiffness/collagen-induced YAP activation. We uncovered that DDR1 underwent stiffness/collagen binding-stimulated liquid-liquid phase separation and co-condensed with LATS1 to inactivate LATS1. Mutagenesis experiments revealed that the transmembrane domain is responsible for DDR1 droplet formation. Purified DDR1 N-terminal and transmembrane domain was sufficient to drive its reversible condensation. Depletion of the DDR1 C-terminus led to failure in co-condensation with LATS1. Interaction between the DDR1 C-terminus and LATS1 competitively inhibited binding of MOB1 (Mps one binder 1) to LATS1 and thus the subsequent phosphorylation of LATS1. Introduction of the single-point mutants, histidine-745-proline and histidine-902-proline, to DDR1 on the C-terminus abolished the co-condensation. In mouse models, YAP activity was positively correlated with collagen I expression and arterial stiffness. LATS1 inhibition reactivated the YAP signaling in Ddr1-deficient vessels and abrogated the arterial softening effect of Ddr1 deficiency. CONCLUSIONS: These findings identify DDR1 as a mediator of YAP activation by mechanical and chemical stimuli and demonstrate that DDR1 regulates LATS1 phosphorylation in an liquid-liquid phase separation-dependent manner.

Macrophage KLF15 prevents foam cell formation and atherosclerosis via transcriptional suppression of OLR-1.

BACKGROUND: Macrophage-derived foam cells are a hallmark of atherosclerosis. Scavenger receptors, including lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (OLR-1), are the principal receptors responsible for the uptake and modification of LDL, facilitating macrophage lipid load and the uptake of oxidized LDL by arterial wall cells. Krüppel-like factor 15 (KLF15) is a transcription factor that regulates the expression of genes by binding to the promoter during transcription. Therefore, this study aimed to investigate the precise role of macrophage KLF15 in atherogenesis. METHODS: We used two murine models of atherosclerosis: mice injected with an adeno-associated virus (AAV) encoding the Asp374-to-Tyr mutant version of human PCSK9, followed by 12 weeks on a high-fat diet (HFD), and ApoE-/-- mice on a HFD. We subsequently injected mice with AAV-KLF15 and AAV-LacZ to assess the role of KLF15 in the development of atherosclerosis in vivo. Oil Red O, H&E, and Masson's trichome staining were used to evaluate atherosclerotic lesions. Western blots and RT-qPCR were used to assess protein and mRNA levels, respectively. RESULTS: We determined that KLF15 expression was downregulated during atherosclerosis formation, and KLF15 overexpression prevented atherosclerosis progression. KLF15 expression levels did not affect body weight or serum lipid levels in mice. However, KLF15 overexpression in macrophages prevented foam cell formation by reducing OLR-1-meditated lipid uptake. KLF15 directly targeted and transcriptionally downregulated OLR-1 levels. Restoration of OLR-1 reversed the beneficial effects of KLF15 in atherosclerosis. CONCLUSION: Macrophage KLF15 transcriptionally downregulated OLR-1 expression to reduce lipid uptake, thereby preventing foam cell formation and atherosclerosis. Thus, our results suggest that KLF15 is a potential therapeutic target for atherosclerosis.

Phytophthora RxLR effector PcSnel4B promotes degradation of resistance protein AtRPS2.

Phytophthora capsici deploys effector proteins to manipulate host immunity and facilitate its colonization. However, the underlying mechanisms remain largely unclear. In this study, we demonstrated that a Sne-like (Snel) RxLR effector gene PcSnel4 is highly expressed at the early stages of P. capsici infection in Nicotiana benthamiana. Knocking out both alleles of PcSnel4 attenuated the virulence of P. capsici, while expression of PcSnel4 promoted its colonization in N. benthamiana. PcSnel4B could suppress the hypersensitive reaction (HR) induced by Avr3a-R3a and RESISTANCE TO PSEUDOMONAS SYRINGAE 2 (AtRPS2), but it did not suppress cell death elicited by Phytophthora infestin 1 (INF1) and Crinkler 4 (CRN4). COP9 signalosome 5 (CSN5) in N. benthamiana was identified as a host target of PcSnel4. Silencing NbCSN5 compromised the cell death induced by AtRPS2. PcSnel4B impaired the interaction and colocalization of Cullin1 (CUL1) and CSN5 in vivo. Expression of AtCUL1 promoted the degradation of AtRPS2 and disrupted HR, while AtCSN5a stabilized AtRPS2 and promoted HR, regardless of the expression of AtCUL1. PcSnel4 counteracted the effect of AtCSN5 and enhanced the degradation of AtRPS2, resulting in HR suppression. This study deciphered the underlying mechanism of PcSnel4-mediated suppression of HR induced by AtRPS2.

Green Tea Polyphenols Alleviate Kidney Injury Induced by Di(2-Ethylhexyl) Phthalate in Mice.

INTRODUCTION: Di(2-ethylhexyl) phthalate (DEHP) is a common plasticizer. Studies have revealed that DEHP exposure can cause kidney damage. Green tea is among the most popular beverages in China. Green tea polyphenols (GTPs) have been proven to have therapeutic effects on organ damage induced by heavy metal exposure. However, few studies have reported on GTP-relieving DEHP-induced kidney damage. METHODS: C57BL/6J male mice aged 6-8 weeks were treated with distilled water (control group), 1,500 mg/kg/d DEHP + corn oil (model group), 1,500 mg/kg/d DEHP + corn oil + 70 mg/kg GTP (treatment group), corn oil (oil group), and 70 mg/kg GTP (GTP group) by gavage for 8 weeks, respectively. The renal function of mice and renal tissue histopathology of each group were evaluated. The renal tissues of mice in the model, treatment, and control groups were analyzed using high-throughput sequencing. We calculated the differentially expressed microRNAs (miRNAs) and messenger RNAs (mRNAs) using the limma R package, the CIBERSORT algorithm was used to predict immune infiltration, the starBase database was used to screen the miRNA-mRNA regulatory axis, and immunohistochemical analyses were performed to verify protein expression. RESULTS: GTP alleviated the deterioration of renal function, renal inflammation and fibrosis, and mitochondrial and endoplasmic reticulum lesions induced by DEHP in mice. Differential immune infiltrations of plasma, dendritic, T, and B cells were noted between the model and treatment groups. We found that three differentially expressed miRNAs (mmu-miR-383-5p, mmu-miR-152-3p, and mmu-miR-144-3p), three differentially expressed mRNAs (Ddit4, Dusp1, and Snx18), and three differentially expressed proteins (Ddit4, Dusp1, and Snx18) played crucial roles in the miRNA-mRNA-protein regulatory axes when GTPs mitigate DEHP-induced kidney damage in mice. CONCLUSION: GTP can alleviate DEHP-induced kidney damage and regulate immune cell infiltration. We screened four important miRNA-mRNA-protein regulatory axes of GTP, mitigating DEHP-induced kidney damage in mice.

Magnetic Resonance Elastography of Anterior Mediastinal Tumors.

BACKGROUND: Preoperative differentiation of the types of mediastinal tumors is essential. Magnetic resonance (MR) elastography potentially provides a noninvasive method to assess the classification of mediastinal tumor subtypes. PURPOSE: To evaluate the use of MR elastography in anterior mediastinal masses and to characterize the mechanical properties of tumors of different subtypes. STUDY TYPE: Prospective. SUBJECTS: 189 patients with anterior mediastinal tumors (AMTs) confirmed by histopathology (62 thymomas, 53 thymic carcinomas, 57 lymphomas, and 17 germ cell tumors). FIELD STRENGTH/SEQUENCE: A gradient echo-based 2D MR elastography sequence and a diffusion-weighted imaging (DWI) sequence at 3.0 T. ASSESSMENT: Stiffness and apparent diffusion coefficients (ADC) were measured in AMTs using MR elastography-derived elastograms and DWI-derived ADC maps, respectively. The aim of this study is to identify whether MR elastography can differentiate between the histological subtypes of ATMs. STATISTICAL TESTS: One-way analysis of variance (ANOVA), two-way ANOVA, Pearson's linear correlation coefficient (r), receiver operating characteristic (ROC) curve analysis; P < 0.05 was considered significant. RESULTS: Lymphomas had significantly lower stiffness than other AMTs (4.0 ± 0.63 kPa vs. 4.8 ± 1.39 kPa). The mean stiffness of thymic carcinomas was significantly higher than that of other AMTs (5.6 ± 1.41 kPa vs. 4.2 ± 0.94 kPa). Using a cutoff value of 5.0 kPa, ROC analysis showed that lymphomas could be differentiated from other AMTs with an accuracy of 59%, sensitivity of 97%, and specificity of 38%. Using a cutoff value of 5.1 kPa, thymic carcinomas could be differentiated from other AMTs with an accuracy of 84%, sensitivity of 67%, and specificity of 90%. However, there was an overlap in the stiffness values of individual thymomas (4.2 ± 0.71; 3.9-4.5), thymic carcinomas (5.6 ± 1.41; 5.0-6.1), lymphomas (4.0 ± 0.63; 3.8-4.2), and germ cell tumors (4.5 ± 1.79; 3.3-5.6). DATA CONCLUSION: MR elastography-derived stiffness may be used to evaluate AMTs of various histologies. TECHNICAL EFFICACY: Stage 2.

Performance and characterization of snail adhesive mucus as a bioflocculant against toxic Microcystis.

Toxic Microcystis blooms are widespread in aquatic bodies, posing major threats to aquatic and human life. Recently, bioflocculants have attracted considerable attention as a promising biomaterial for Microcystis management. In search of a novel organism that can produce an efficient bioflocculant for controlling harmful algae sustainably, the native gastropod Cipangopaludina chinensis was co-cultured continuously with toxic Microcystis under different initial algal cell densities. The bioflocculation effect of snail mucus on toxic Microcystis, microcystin removal, and toxin accumulation in snails was investigated. In addition, the properties of the adhesive mucus were characterized using microscopic, X-ray diffraction, infrared spectroscopy, and polysaccharide and proteome analyses. Microcystis cells were captured and flocculated by the snail mucus; removal efficiencies of up to 89.9% and 84.8% were achieved for microalgae and microcystin-leucine arginine (MC-LR), respectively, when co-cultured with C. chinensis for only one day. After nine-day exposure, less than 5.49 µg/kg DW microcystins accumulated in the snails, indicating safety for human consumption. The snail mucus contained 104.3 µg/mg protein and 72.7 µg/mg carbohydrate, which provide several functional groups beneficial for Microcystis bioflocculation. The main monosaccharide subunits of polysaccharides are galactose, galactosamine, glucosamine, fucose, glucose, and mannose. Most of them are key components of polysaccharides in many bioflocculants. Gene Ontology analysis indicated the protein enrichment in binding processes and catalytic activity, which may account for Microcystis bioflocculation via protein binding or enzymatic reactions. The findings indicate that native C. chinensis secretes adhesive mucus that can act as bioflocculant for toxic Microcystis from ambient water and can be an effective and eco-friendly tool for Microcystis suppression.

Resistance risk assessment of mefentrifluconazole in Corynespora cassiicola and the control of cucumber target spot by a two-way mixture of mefentrifluconazole and prochloraz.

The cucumber target spot, caused by Corynespora cassiicola, is a major cucumber disease in China. Mefentrifluconazole, a new triazole fungicide, exhibits remarkable efficacy in controlling cucumber target spot. However, the resistance risk and mechanism remain unclear. In this study, the inhibitory activity of mefentrifluconazole against 101 C. cassiicola isolates was determined, and the results indicated that the EC50 values ranged between 0.15 and 12.85 µg/mL, with a mean of 4.76 µg/mL. Fourteen mefentrifluconazole-resistant mutants of C. cassiicola were generated from six parental isolates in the laboratory through fungicide adaptation or UV irradiation. The resistance was relatively stable after ten consecutive transfers on a fungicide-free medium. No cross-resistance was observed between mefentrifluconazole and pyraclostrobin, fluopyram, prochloraz, mancozeb, or difenoconazole. Investigations into the biological characteristics of the resistant mutants revealed that six resistant mutants exhibited an enhanced compound fitness index (CFI) compared to the parental isolates, while others displayed a reduced or comparable CFI. The overexpression of CcCYP51A and CcCYP51B was detected in the resistant mutants, regardless of the presence or absence of mefentrifluconazole. Additionally, a two-way mixture of mefentrifluconazole and prochloraz at a concentration of 7:3 demonstrated superior control efficacy against the cucumber target spot, achieving a protection rate of 80%. In conclusion, this study suggests that the risk of C. cassiicola developing resistance to mefentrifluconazole is medium, and the overexpression of CcCYP51A and CcCYP51B might be associated with mefentrifluconazole resistance in C. cassiicola. The mefentrifluconazole and prochloraz two-way mixture presented promising control efficacy against the cucumber target spot.

High resistance risk of Phytophthora colocasiae to azoxystrobin in southeastern of China.

Quinone outside inhibitor (QoI) has been applied to manage taro leaf blight caused by Phytophthora colocasiae in southeastern of China for many years. The risk of P. colocasiae to QoI and the potential resistant mechanism remain unknown. In this study, the 74 P. colocasiae strains were sampled from southeastern of China. Sequence analysis of the QoI target Cytb showed one nucleotide variant in the fragment of this gene in this population, producing two haplotypes. The nucleotide variant leads to codon change at 142 (GGT to GCT) producing A142 (alanine) and G142 (glycine) in Hap_1 and Hap_2 strains, respectively. The sensitivity differentiation to azoxystrobin of two haplotypes were observed in vitro. The Hap_1 and Hap_2 strains were confirmed resistant and sensitive by control efficacy of label rate fungicide application, which was 3.0% and 88.8% treated with 500 µg/mL azoxystrobin, respectively. In addition, 10.0 µg/mL azoxystrobin plus 50 µg/mL salicylhydroxamic acid (SHAM) supplemented in PDA medium was identified as a discriminatory dose for differentiation of these two phenotype strains. The azoxystrobin resistant frequency reached 86.5%, indicating prevalence of QoI resistance in the field. Further fitness related features showed that no significant difference in temperature sensitivity, mycelial growth rate, sporangia production, zoospore release and aggressiveness between azoxystrobin-resistant and sensitive strains indicating no potential fitness cost for azoxystrobin resistance. Taken together, azoxystrobin resistance need to be taken into consideration to manage taro leaf blight in southeastern of China.

Sensitivity analysis and point mutations in BcSDHB confer cyclobutrifluram resistance in Botrytis cinerea from China.

Botrytis cinerea is one of the most destructive pathogens worldwide. It can damage over 200 crops, resulting in significant yield and quality losses. Cyclobutrifluram, a new generation of succinate dehydrogenase inhibitors, exhibits excellent inhibitory activity against B. cinerea. However, the baseline sensitivity and resistance of B. cinerea to cyclobutrifluram remains poorly understood. This study was designed to monitor the sensitivity frequency distribution, assess the resistance risk, and clarify the resistance mechanism of B. cinerea to cyclobutrifluram. The baseline sensitivity of B. cinerea isolates to cyclobutrifluram was 0.89 µg/mL. Cyclobutrifluram-resistant B. cinerea populations are present in the field. Six resistant B. cinerea isolates investigated in this study possessed enhanced compound fitness index compared to the sensitive isolates according to mycelial growth, mycelial dry weight, conidiation, conidial germination rate, and pathogenicity. Cyclobutrifluram exhibited no cross-resistance with tebuconazole, fludioxonil, cyprodinil, or iprodione. Sequence alignment revealed that BcSDHB from cyclobutrifluram-resistant B. cinerea isolates had three single substitutions (P225F, N230I, or H272R). Molecular docking verified that these mutations in BcSDHB conferred cyclobutrifluram resistance in B. cinerea. In conclusion, the resistance risk of B. cinerea to cyclobutrifluram is high, and the point mutations in BcSDHB (P225F, N230I, or H272R) confer cyclobutrifluram resistance in B. cinerea. This study provided important insights into cyclobutrifluram resistance in B. cinerea and offered valuable information for monitoring and managing cyclobutrifluram resistance in the future.

Remediation effect of walnut shell biochar on Cu and Pb co-contaminated soils in different utilization types.

Biochar, with its dual roles of soil remediation and carbon sequestration, is gradually demonstrating great potential for sustainability in agricultural and ecological aspects. In this study, a porous biochar derived from walnut shell wastes was prepared via a facile pyrolysis coupling with in-situ alkali etching method. An incubation study was conducted to investigate its performance in stabilizing copper (Cu) and lead (Pb) co-contaminated soils under different utilization types. The biochar effectively decreased the bioavailable Cu (8.5-91.68%) and Pb (5.03-88.54%), while increasing the pH, CEC, and SOM contents in both soils. Additionally, the results of sequential extraction confirmed that biochar promoted the transformation of the labile fraction of Cu and Pb to stable fractions. The mechanisms of Cu and Pb stabilization were found to be greatly dependent on the soil types. For tea plantation yellow soil, the main approach for stabilization was the complexation of heavy metals with abundant organic functional groups and deprotonation structure. Surface electrostatic adsorption and cation exchange contributed to the immobilization of Cu and Pb in vegetable-cultivated purple soil. This research provides valuable information for the stabilization of Cu and Pb co-contaminated soils for different utilization types using environmentally-friendly biochar.

Transient nuclear deformation primes epigenetic state and promotes cell reprogramming.

Cell reprogramming has wide applications in tissue regeneration, disease modelling and personalized medicine. In addition to biochemical cues, mechanical forces also contribute to the modulation of the epigenetic state and a variety of cell functions through distinct mechanisms that are not fully understood. Here we show that millisecond deformation of the cell nucleus caused by confinement into microfluidic channels results in wrinkling and transient disassembly of the nuclear lamina, local detachment of lamina-associated domains in chromatin and a decrease of histone methylation (histone H3 lysine 9 trimethylation) and DNA methylation. These global changes in chromatin at the early stage of cell reprogramming boost the conversion of fibroblasts into neurons and can be partially reproduced by inhibition of histone H3 lysine 9 and DNA methylation. This mechanopriming approach also triggers macrophage reprogramming into neurons and fibroblast conversion into induced pluripotent stem cells, being thus a promising mechanically based epigenetic state modulation method for cell engineering.

High power single-frequency 1112†nm laser by an insertable Nd:YAG/YAG bonded monolithic planar ring oscillator.

A high power single-frequency operation at 1112 nm with novel insertable monolithic planar ring oscillator based on a Nd:YAG/YAG bonded crystal is proposed. In a proof-of-principle experiment, a finely designed coating on the output surface is carried out to ensure single-wavelength oscillation at 1112 nm, together with a half-wave plate and a Tb3Ga5O12 crystal inserted in the open space of the bonded block to realize the unidirectional operation with power scalability. Consequently, the single-frequency laser delivers an output power of 3.9 W at 1112.3 nm with a slope efficiency of 58.6% and an optical-to-optical efficiency of 17.7%. The power fluctuation is measured to be within ± 0.26% over 20 min, and the laser linewidth is estimated to be 4.15 MHz (Δλ = 0.017 pm).

Sub-pm linewidth, high pulse energy, high beam quality microsecond-pulse Ti:sapphire laser at 766.699†nm.

In this letter, a sub-pm linewidth, high pulse energy and high beam quality microsecond-pulse 766.699 nm Ti:sapphire laser pumped by a frequency-doubled Nd:YAG laser is demonstrated. At an incident pump energy of 824 mJ, the maximum output energy of 132.5 mJ at 766.699 nm with linewidth of 0.66 pm and a pulse width of 100 µs is achieved at a repetition rate of 5 Hz. To the best of our knowledge, this is the highest pulse energy at 766.699 nm with pulse width of hundred micro-seconds for a Ti:sapphire laser. The beam quality factor M2 is measured to be 1.21. It could be precisely tuned from 766.623 to 766.755 nm with a tuning resolution of 0.8 pm. The wavelength stability is measured to be less than ±0.7 pm over 30 min. The sub-pm linewidth, high pulse energy and high beam quality Ti:sapphire laser at 766.699 nm can be used to create a polychromatic laser guide star together with a home-made 589 nm laser in the mesospheric sodium and potassium layer for the tip-tilt correction resulting in the near-diffraction limited imagery on a large telescope.

1.9†µJ external-cavity dumped ultra-broad-area semiconductor nanosecond laser.

An external-cavity dumped nanosecond (ns) ultra-broad-area laser diode (UBALD) at around 966 nm with high pulse energy is demonstrated. A 1 mm UBALD is used to produce high output power and high pulse energy. A Pockels cell (PC) combines with two polarization beam splitters (PBSs) and is employed to cavity-dump a UBALD operating at 10 kHz repetition rate. At a pump current of 23 A, 11.4 ns pulses with a maximum pulse energy of ≈1.9 µJ and a maximum peak power of ≈166 W are achieved. The beam quality factor is measured to be M x 2=19.5 in the slow axis direction and M y 2=2.17 in the fast axis direction. Moreover, maximum average output power stability is confirmed, with a power fluctuation of less than 0.8% rms over 60 min. To the best of our knowledge, this is the first high-energy external-cavity dumped demonstration from an UBALD.

Multilevel synergically controlling wavefront correction of a high-power slab laser system.

We present a multilevel synergically controlling wavefront correction method that can apply in a slab laser system. To fully utilize the response frequency and the stroke of actuators of the single deformable mirror (DM), we design a set of multilevel wavefront correction devices to reduce the root-mean square of wavefront aberration before the DM. As the wavefront of slab geometry solid-state lasers mainly consists of fourth and longitudinally distributed aberration, such as 5th, 9th, and 14th orders of Legendre polynomials. We design a precompensating level of the aberration with a slow-drift mirror, fast-steer mirror, one-dimensional adjustable slab-aberration compensator, and beam-shaping system to reduce these orders of wavefront aberration with low spatial resolution and large stroke. As the controlling bandwidth of different devices is diverse, the coupling oscillation between the precompensating level and adaptive optics (AO) level occurs, then we develop the multilevel synergically control to address the coupling. With the precompensating level, the experimental result shows the residual wavefront aberration of the slab laser is compensated well by the AO level effectively within the compensating capability. We clean up a 9.8 kW slab laser system with the beam quality ß of far-field focus spots improved from 17.71 to 2.24 times the diffraction limit.

Agricultural nonpoint source pollutant loads into water bodies in a typical basin in the middle reach of the Yangtze River.

Phosphorus and nitrogen pollution from agricultural nonpoint sources heavily burden the water environment, and a scientific calculating system is needed to calculate the pollutant loads under the water pollution treatment. This study established a system to calculate the coefficients of agricultural nonpoint source pollutants into water bodies in the subregion in Poyang Lake basin in the middle reach of the Yangtze River combining with multiple driving factors. Validation results showed that the errors of the typical unit were 30.58% for total phosphorus (TP), 13.43% for total nitrogen (TN) and 33.93% for ammonia nitrogen (NH3-N), respectively. The errors of the subregion were 26.92% for TP, 31.83% for TN and 29.15% for NH3-N, respectively. Besides, there were higher TP and TN loads in the east area of subregion in both units and county scales, which indicated the heavy phosphorus and nitrogen burden on water environment. In contrast, higher NH3-N loads occurred in the north area of subregion. The establishment of coefficient system for agricultural pollutants into water bodies and the pollutant loads calculation would provide enlightenment for water pollution treatment and agricultural nonpoint source pollution controlling.

Three point mutations in AaCYP51 combined with induced overexpression of AaCYP51 conferred low-level resistance to mefentrifluconazole in Alternaria alternata.

Tomato early blight is a significant disease that causes substantial losses to tomato yield and quality. Mefentrifluconazole, an isopropanol-azole subgroup of triazole fungicides, has been registered in China for controlling various plant diseases, including tomato early blight, grape anthracnose, and apple brown spot. However, limited information is available on the mefentrifluconazole resistance risk and mechanism in plant pathogens. The sensitivity to mefentrifluconazole of 122 isolates of Alternaria alternata, one of the causal agents of tomato early blight, collected from different provinces in China, was evaluated. The results showed a unimodal curve for the sensitivity frequency, with an average EC50 of 0.306 µg/mL. Through fungicide adaption, six resistant mutants (N4, N5, T4, T5, NG1, and NG10) were obtained from three parental isolates, with a mutation frequency of 3.28 × 10-4 and resistance factors ranging between 19 and 147. The survival fitness of the resistant mutants, except for NG1, was significantly lower than that of their parental isolates. Positive cross-resistance was observed between mefentrifluconazole and difenoconazole or fenbuconazole, whereas no cross-resistance was found with three non-DMI fungicides. Furthermore, three distinct point mutations were detected in the AaCYP51 protein of the resistant mutants: I300S in T4 and T5; A303T in N4, NG1, and NG10; and A303V in N5. Compared to the parental isolates, the AaCYP51 gene was overexpressed in all six resistant mutants when treated with mefentrifluconazole. In summary, the resistance risk of A. alternata to mefentrifluconazole was low, and point mutations and overexpression of the AaCYP51 gene were identified as contributing factors to mefentrifluconazole resistance in A. alternata.

Energy-Saving Adaptive Routing for High-Speed Railway Monitoring Network Based on Improved Q Learning.

In high-speed railway operational monitoring network systems targeting railway infrastructure as its monitoring objective, there is a wide variety of sensor types with diverse operational requirements. These systems have varying demands on data transmission latency and network lifespan. Most of the previous research focuses only on prolonging network lifetime or reducing data transmission delays when designing or optimizing routing protocols, without co-designing the two. In addition, due to the harsh operating environment of high-speed railways, when the network changes dynamically, the traditional routing algorithm generates unnecessary redesigns and leads to high overhead. Based on the actual needs of high-speed railway operation environment monitoring, this paper proposes a novel Double Q-values adaptive model combined with the existing reinforcement learning method, which considers the energy balance of the network and real-time data transmission, and constructs energy saving and delay. The two-dimensional reward avoids the extra overhead of maintaining a global routing table while capturing network dynamics. In addition, the adaptive weight coefficient is used to ensure the adaptability of the model to each business of the high-speed railway operation environment monitoring system. Finally, simulations and performance evaluations are carried out and compared with previous studies. The results show that the proposed routing algorithm extends the network lifecycle by 33% compared to the comparison algorithm and achieves good real-time data performance. It also saves energy and has fewer delays than the other three routing protocols in different situations.

[Clinical and neuroelectrophysiological features of botulism in children: an analysis of eight sporadic cases]. / 8例散发儿童肉毒中毒的临床特点及神经电生理分析.

OBJECTIVES: To study the clinical and neuroelectrophysiological features of botulism in children. METHODS: A retrospective analysis was conducted on the clinical data of eight children who were diagnosed with botulism in the Department of Neurology, Hunan Children's Hospital, from August 2015 to October 2022. RESULTS: All eight children were found to have symmetrical cranial nerve palsy and flaccid paralysis of the extremities, with a descending pattern. Seven children presented with respiratory muscle paralysis. Electrophysiological examinations revealed decreased compound muscle action potential (CMAP) amplitudes in 5 children, increased CMAP amplitudes exceeding 40.0% in 6 children during high-frequency repetitive nerve stimulation, and short duration, low amplitude, and polyphasic motor unit action potentials in 4 children. CONCLUSIONS: The main clinical features of botulism in children include symmetric, descending flaccid paralysis starting from cranial nerves, with the possibility of respiratory muscle paralysis. Electrophysiological abnormalities associated with it include decreased CMAP amplitudes, increased CMAP amplitudes during high-frequency repetitive nerve stimulation, and short duration, low amplitude, and polyphasic motor unit action potentials.

Primary aberration optimization for double-plane symmetric beam shaping systems using a pair of curved reference surfaces.

The geometric aberration of centered refracting double-plane symmetric optical systems (DPSOS) is investigated. For DPSOS with different defocus values in the tangential plane and the sagittal plane (astigmatic wavefront), a pair of curved reference surfaces which vanishes the quadratic terms of the optical path difference (OPD) between a general ray and a reference ray are deduced. With the curved reference surfaces, the primary (fourth-order) wave aberration function for DPSOS is calculated and analyzed, which can be used for beam shaping designs with astigmatic input wavefront, such as slab lasers and semiconductor lasers. Further, the proposed curved reference surfaces can be applied to analyze the aberrations of general DPSOS.