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Abstract Defence against pathogens relies on intracellular nucleotide-binding, leucine-rich repeat immune receptors (NLRs) in plants. Hormone signaling including abscisic acid (ABA) pathways are activated by NLRs and play pivotal roles in defence against different pathogens. However, little is known about how hormone signaling pathways are activated by plant immune receptors. Here, we report that a plant NLR Sw-5b mimics the behavior of the ABA receptor and directly employs the ABA central regulator PP2C-SnRK2 complex to activate an ABA-dependent defence against viral pathogens. PP2C4 interacts with and constitutively inhibits SnRK2.3/2.4. Behaving in a similar manner as the ABA receptor, pathogen effector ligand recognition triggers the conformational change of Sw-5b NLR that enables binding to PP2C4 via the NB domain. This receptor-PP2C4 binding interferes with the interaction between PP2C4 and SnRK2.3/2.4, thereby releasing SnRK2.3/2.4 from PP2C4 inhibition to activate an ABA-specific antiviral immunity. These findings provide important insights into the activation of hormone signaling pathways by plant immune receptors.

Abstract The first local mpox outbreak in Guangdong Province, China occurred in June 2023. However, epidemiological data have failed to quickly identify the source and transmission of the outbreak. Here, phylogeny and molecular evolution of 10 monkeypox virus (MPXV) genome sequences from the Guangdong outbreak were characterized, revealing local silent transmissions that may have occurred in Guangdong whose mpox outbreaks suggested a molecular epidemiological correlation with Portugal and several regions of China during the same period. The lineage IIb C.1, which includes all 10 MPXV from Guangdong, shows consistent temporal continuity in both phylogenetic characteristics and unique molecular evolutionary mutation spectrum, reflected in the continuous increase of single nucleotide polymorphisms (SNPs) and shared mutations over time. Compared with the Japan MPXV, the Guangdong MPXV showed higher genomic nucleotide differences and separated 14 shared mutations from the B.1 lineage, comprising 6 non-synonymous mutations in genes linked to host regulation, virus infection, and virus life cycle. The unique mutation spectrum with temporal continuity in IIb C.1, related to apolipoprotein B mRNA-editing catalytic polypeptide-like 3, promotes rapid viral evolution and diversification. The findings contribute to understanding the ongoing mpox outbreak in China and offer insights for developing joint prevention and control strategies.

Abstract Tomato spotted wilt virus (TSWV) is a plant pathogen that causes devastating tomato yield losses worldwide. The Sw-5b gene is one of the most effective resistance genes for TSWV control in tomato plants, and has been widely used in resistance breeding. Molecular markers are specific DNA sequences with known locations on the chromosome; they are indispensable tools in marker-assisted selection, which detects the presence of target genes to expedite breeding. We developed gene-specific molecular markers for Sw-5b to facilitate the accurate distinction of resistance (Sw-5b R ) and susceptibility (Sw-5b S ) alleles of Sw-5b. Using these markers, we successfully detected Sw-5b and determined its genotype (homozygous Sw-5b R , heterozygous Sw-5b R/S , or homozygous Sw-5b S ) in six tomato varieties. Then we successfully applied these markers to 46 commercial tomato cultivars to detect and determine the genotype of Sw-5b. The results revealed a striking absence of the Sw-5b R gene and high TSWV susceptibility among most of the analyzed commercial cultivars. With the assistance of the novel Sw-5b-specific molecular markers, we generated a TSWV-resistant and homozygous Sw-5b R Micro-Tom tomato line, demonstrating the practical application of these markers in plant breeding. In summary, we developed novel gene-specific molecular markers for Sw-5b, and applied them to distinguish Sw-5b alleles for TSWV resistance or susceptibility. This marker set provides a valuable tool for breeding TSWV-resistant tomato varieties.

Osteomyelitis is a debilitating bone disorder characterized by an inflammatory process involving the bone marrow, bone cortex, periosteum, and surrounding soft tissue, which can ultimately result in bone destruction. The etiology of osteomyelitis can be infectious, caused by various microorganisms, or noninfectious, such as chronic nonbacterial osteomyelitis (CNO) and chronic recurrent multifocal osteomyelitis (CRMO). Researchers have turned to animal models to study the pathophysiology of osteomyelitis. However, selecting an appropriate animal model that accurately recapitulates the human pathology of osteomyelitis while controlling for multiple variables that influence different clinical presentations remains a significant challenge. In this review, we present an overview of various animal models used in osteomyelitis research, including rodent, rabbit, avian/chicken, porcine, minipig, canine, sheep, and goat models. We discuss the characteristics of each animal model and the corresponding clinical scenarios that can provide a basic rationale for experimental selection. This review highlights the importance of selecting an appropriate animal model for osteomyelitis research to improve the accuracy of the results and facilitate the development of novel treatment and management strategies.

Objectives: To examine the association of changes in plant-based diet consumption with all-cause mortality among older adults in China. Design: Cohort study. Setting: This cohort study of 11 years used data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), a long-term, nationwide survey covering 23 provinces in China. Participants: A total of 7843 older participants aged ≥60 years were included in this study. Measurements: Changes in plant-based diets consumption (2008–2011) were assessed by 3 graded plant-based diet indices, including an overall plant-based diet index (PDI), a healthful plant-based diet index (hPDI), and an unhealthful plant-based diet index (uPDI). The main outcome was all-cause mortality. Multivariable-adjusted Cox proportional-hazards models were fitted to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) of mortality for changes in PDI, hPDI, and uPDI. Results: A total of 7843 participants (mean [SD] age, 82.2 [10.9] years; 3588 [45.7%] men) were included in this study. During a median (IQR) of 9 (5–10) years of follow-up, 3749 deaths were documented. Compared with older adults whose plant-based diet indices were relatively stable, older adults with the greatest decrease (quintile 1) in PDI, hPDI, and uPDI had respectively 32% (95% CI, 19%–47%) higher, 21% (95% CI, 9%–33%) higher, and 10% (95% CI, 4%–21%) lower risk of death. Compared with older adults whose diet indices were relatively stable, older adults with the greatest increase (quintile 5) in uPDI had a 13% higher risk of death (95% CI, 1%–21%), while no significant associations of the increased PDI and hPDI with all-cause mortality were observed. Conclusion: Maintaining the consumption of overall and healthful plant-based diets, and decreasing the consumption of an unhealthful plant-based diet can be beneficial in preventing or delaying premature death among Chinese older adults.

Styrax, the balsam refined from the trunk of Liquidambar orientalis Mill. has a variety of applications in the perfumery and medical industry, especially for use in traditional Chinese medicine. However, the resources of styrax are in shortage due to being endangered of this plant. Grafting can improve the adaptability of plants to unfavorable environmental conditions. We tried to graft the L. orientalis Mill. on L. formosana Hance which was widely distributed in Jiangsu and Zhejiang provinces of China in an attempt to obtain styrax from grafted L. orientalis Mill. (grafted styrax, SG). Whether SG can become an alternative application of commercially available styrax (SC) need be further investigated. The components of SG were analyzed by GC-MS, and the results showed that the chromatograms of SG, SC, and styrax standard (SS) were consistent. The ration of 12 major chemical components based peak area in SG, SC, and SS were 93.95%, 94.24%, and 95.86% respectively. The assessment of toxicity, antithrombotic activity, and myocardial infarction protection of SG and SC was evaluated by using the zebrafish model, the results showed that SG and SC have the similar toxicological properties as evidenced by acute toxicity test, developmental toxicity and teratogenicity, and long-term toxicity test. Both SG and SC significantly decreased the thrombosis and increased blood flow velocity of zebrafish induced by adrenaline hydrochloride, inhibited myocardial apoptosis, myocardial infarction and myocardial inflammation in zebrafish induced by isoproterenol hydrochloride. Moreover, SG had an obvious improvement effect on cardiac output, while SC has no effect. Collectively, SG is similar to SC in chemical composition, toxicological properties, antithrombotic activity, and myocardial infarction protection effects, and may be used as a substitute for styrax to reduce the collection for wild L. orientalis Mill. and increase the available styrax resources.

Abstract Background Previous studies have investigated the relationships between psychache or meaning in life and suicidal ideation based on sum score of corresponding scale. However, this practice has hampered the fine-grained understanding of their relationships. This network analysis study aimed to conduct a dimension-level analysis of these constructs and the relationships among them in a joint framework, and identify potential intervention targets to address suicidal ideation. Methods Suicidal ideation, psychache, and meaning in life were measured using self-rating scales among 738 adults. A network of suicidal ideation, psychache, and meaning in life was constructed to investigate the connections between dimensions and calculate the expected influence and bridge expected influence of each node. Results “Psychache” was positively linked to “sleep” and “despair”, while “presence of meaning in life” had negative associations with “psychache”, “despair”, and “pessimism”. The most important central nodes were “sleep” and “despair”, and the critical bridge nodes were “presence of meaning in life” and “psychache”. Conclusion These preliminary findings uncover the pathological pathways underlying the relationships between psychache, meaning in life, and suicidal ideation. The central nodes and bridge nodes identified may be potential targets for effectively preventing and intervening against the development and maintenance of suicidal ideation.

Cyclone Global Navigation Satellite System (CYGNSS) launched in recent years, provides a large amount of spaceborne GNSS Reflectometry data with all-weather, global coverage, high space-time resolution, and multiple signal sources, which provides new opportunities for the machine learning (ML) study of sea surface height (SSH) inversion. This article proposes for the first time two different CYGNSS SSH inversion models based on two widely used ML methods, back propagation (BP) neural network and convolutional neural network (CNN). The SSH calculated by using Danmarks Tekniske Universitet (DTU) 18 ocean wide mean SSH (MSSH) model (DTU18) with DTU global ocean tide model is used for verification. According to the strategy of independent analysis of data from different signal sources, the mean absolute error (MAE) of the BP and CNN models’ inversion specular points’ results during 7 days is 1.04 m and 0.63 m, respectively. The CLS 2015 product and Jason-3 data were also used for further validation. In addition, the generalization ability of the model, for 6 days and 13 days training sets, was also evaluated. For 6 days training set, the prediction results’ MAE of the BP model is 11.59 m and 5.90 m for PRN2 and PRN4, and the MAE of the CNN model is 1.37 m and 0.97 m for PRN2 and PRN4, respectively. The results show that BP and CNN inversions are in high agreement with each product, and the CNN model has relatively higher accuracy and better generalization ability.

Sensory attributes strongly influence consumers’ preferences for products. The inoculation of the Klebsiella variicola H8 strain in a reconstituted tobacco leaf concentrate (RTLC) solution increased neutral aroma-enhancing compound (NAEC) production by 45%, decreased the nicotine level by 25%, decreased the water-soluble total sugar content by ~36%, and improved the sensory quality by 5.71%. The production of NAECs such as dihydrokiwi lactone (DHKL: 192.86%), 1,2,3,4-tetrahydro-1,1,6-trimethylnaphthalene (THTMN: 177.77%), 2,4-di-tert-butylphenol (DTBP: 25%), 4-oxoisofolkone (OIFK: 116.66%,) 1,9-heptadecadiene-4,6-diyn-3-ol (HDD: 116.67%), β-damastrone (BDS: 116.67), and megastigmatrienone A (MSTA: 116.67%) was increased. A metagenomics analysis of the microbial community in the fermented RTLC (FRTLC) was performed to elucidate the mechanism by which NAECs were produced. As a result, 24 groups of functional genes were identified, and among them, five families of carbohydrate-active enzymes, (i) glycoside hydrolase (GH), (ii) glycosyltransferase (GT), (iii) polysaccharide lyase (PL), (iv) carbohydrate esterase (CE), and (v) auxiliary active enzyme (AA), were found to be positively correlated with the production of NAECs. However, among the GHs, the GHs annotated from the H8 strain chromosome displayed the highest relative abundance and a positive correlation with the production of NAECs. Specifically, the GH13-14, GH13-20, GH13-38, GH13-25, GH13-10, GH42, and GH28 genes of the H8 strain were relatively more abundant and were key contributors to the production of NAECs. The correlation analyses revealed that the H8 strain plays a leading role among all the microorganisms in FRTLC in the production of NAECs. Our findings support the application of Klebsiella variicola in NAEC production and a reduction in nicotine content in tobacco products.

BackgroundIndoor air pollution has been reported to have adverse effects on the eye; however, the health effects of exposure to cooking with solid fuels on visual impairment remain unclear in China. ObjectiveWe aimed to examine the association between cooking with solid fuels and visual impairment, including distance visual impairment (DVI) and near visual impairment (NVI). MethodsData were obtained from the China Health and Retirement Longitudinal Study, a nationwide survey of adults aged over 45 years who were enrolled in 2011 (Wave 1) and followed up in Wave 2 (2013), Wave 3 (2015), and Wave 4 (2018). We used Cox proportional hazards models to determine the association between solid fuels use and visual impairment. Additionally, the impact of switching cooking fuel types on vision function were examined through wave-specific data analysis (Wave 1 and Wave 4). Interaction and subgroup analyses were performed to explore the potential effect modifiers. Data were collected using the stratified multistage random sampling method and further analyzed using SPSS 27.0 and R 4.2.1 statistical software packages. ResultsA total of 9559 middle-aged and older Chinese adults without visual impairment at baseline were included in the study, with 51.2% (n=4914) of the participants reporting that they cooked with solid fuels. During the follow-up period, 2644 (27.5%) and 3130 (32.6%) participants developed DVI and NVI, respectively. Compared with the clean fuel users, participants who cooked with solid fuels had a higher risk of DVI (hazards ratio [HR] 1.38, 95% CI 1.28-1.50) and NVI (HR 1.18, 95% CI 1.10-1.27). In addition, switching the cooking fuel type from clean to solid fuels was associated with an elevated risk of DVI (HR 1.51, 95% CI 1.15-1.98) and NVI (HR 1.39, 95% CI 1.06-1.82) compared to persistently using clean fuels during the follow-up period, although no protective effect of switching from solid to clean fuels on NVI was found (P=.52). In subgroup analysis, we found that cooking with solid fuels increased the risk of DVI in participants younger than 65 years (HR 1.41, 95% CI 1.28-1.55), men (HR 1.45, 95% CI 1.28-1.65), urban residents (HR 1.41, 95% CI 1.08-1.75), and smokers (HR 1.43, 95% CI 1.25-1.64). By contrast, negative effects of cooking with solid fuels on NVI were found in nonsmokers (HR 1.21, 95% CI 1.11-1.33) and urban residents (HR 1.20, 95% CI 1.10-1.37). ConclusionsCooking with solid fuels was associated with an increased risk of visual impairment among middle-aged and older Chinese adults. These findings indicate that promoting the utilization of clean fuels is conducive to reducing the burden of visual impairment for the public.

Sea surface height (SSH) retrieval based on spaceborne Global Navigation Satellite System Reflectometry (GNSS-R) usually uses the GNSS-R geometric principle and delay-Doppler map (DDM). The traditional method condenses the DDM information into a single scalar measure and requires error model correction. In this article, the idea of using machine learning methods to retrieve SSH is proposed. Specifically, two widely-used methods, principal component analysis combined with support vector regression (PCA-SVR) and convolution neural network (CNN), are used for verification and comparative analysis based on the observation data provided by Techdemosat-1 (TDS-1). According to the DDM inversion method, ten features from TDS-1 Level 1 data are selected as inputs; The SSH verification model based on the Danmarks Tekniske Universitet (DTU) 15 ocean wide mean SSH model and the DTU global ocean tide model is used as output verification of SSH. For the hyperparameters in the machine learning model, a grid search strategy is used to find the optimal values. By analyzing the TDS-1 data from 31 GPS satellites, the mean absolute error (MAE), root-mean-square error (RMSE) and coefficient of determination (R2) of the PCA-SVR inversion model are 0.61 m, 1.72 m, and 99.56%, respectively; and the MAE, RMSE, and R2 of the CNN inversion model is 0.71 m, 1.27 m, and 99.76%, respectively. In addition, the time required to train the PCA-SVR and CNN inversion models is also analyzed. Overall, the technique proposed in this article can be confidently applied to SSH inversion based on TDS-1 data.

Abstract Background Copper was used for many years in aquaculture operations as an effective algaecide or a parasite treatment of fish. It is an essential nutrient with numerous functions in organisms, but is toxic at high concentrations. However, the toxicity of copper to fish remains unclear. In this study, we used the piebald naked carp, Gymnocypris eckloni, as a model. RNA-seq data from different tissues, including gills, kidney, and liver, were used to investigate the underlying mechanism of copper toxicology in G. eckloni. Results We compared the transcriptomes from different tissues with different time durations of copper ion treatment. After 72 h copper ion treatment, the number of genes with different expression in gills and liver changed dramatically, but not in kidneys. In KEGG functional enrichment, the pattern of differentially expressed genes (DEGs) was also similar in the gills and liver. The most enriched pathway of DEGs was “Ribosome” in both tissues. Furthermore, we analyzed the expression levels of genes involved in oxidative stress response and protein synthesis using qPCR and RNA-seq data. Our results showed that several genes involved in oxidative stress response were up-regulated both in gills and liver. Up-regulation of these genes indicated that copper treatment caused oxidative stress, which is likely to result in ribosome damage. In addition, our results showed that the expression of Eef1b2, a transcription elongation factor, was decreased in the liver under oxidative stress, and the expression of translation initiation factors Eif4ebp1 and eIF2α, and elongation factor eEF2 was up-regulated. These results supported the idea that oxidative stress inhibits protein synthesis in cells. Conclusions Our results indicate that copper exposure caused different responses in different tissues, since the gene expression patterns changed substantially either in the gills or liver, while the effect on the kidney was relatively weak. Furthermore, our results indicated that the expression pattern of the genes involved in the ribosome, which is a complex molecular machine orchestrating protein synthesis in the cell, together with translation initiation factor and elongation factors, were affected by copper exposure both in the gills and liver of piebald naked carp. This result leads us to speculate that the downregulation of global protein synthesis is an acute response strategy of fish to metal-induced oxidative stress. Moreover, we speculate that this strategy not only exists in the selective translation of proteins but also exists in the specific translation of functional proteins in tissues and cells.

Objective: Pituitary adenylate-cyclase activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are two neuropeptides that exhibit anti-inflammatory and neuroprotective properties, modulating the production of cytokines and chemokines, and the behavior of immune cells. However, the relationship between PACAP and VIP levels and Parkinson’s disease (PD) are not clear. The aim of the current study was to evaluate serum PACAP and VIP levels in PD patients and to analysis the correlation between neuropeptide levels and non-motor symptoms.Methods: In this cross-sectional study, we enrolled 72 patients with idiopathic PD and 71 healthy volunteers. Serum PACAP and VIP levels were measured using an enzyme-linked immunosorbent assay (ELISA) kit. Non-motor symptoms were assessed with the Non-Motor Symptoms Scale (NMSS) for PD, including total and single-item scores.Results: The serum PACAP levels of PD patients were significantly lower than those of healthy controls [(76.02 ± 43.78) pg/ml vs. (154.96 ± 76.54) pg/ml, P < 0.001]; and the serum VIP levels of PD patients were also significantly lower than those of healthy controls [(109.56 ± 15.39) pg/ml vs. (136.46 ± 24.16) pg/ml, P < 0.001]. PACAP levels were inversely correlated only with the score on NMSS item five, assessing Attention/memory (r = −0.276, P < 0.05) and lower serum PACAP levels were detected in the cognitive dysfunction subgroup than in the cognitively intact subgroup [(61.87 ± 32.66) pg/ml vs. (84.51 ± 47.59) pg/ml, P < 0.05]; meanwhile, VIP levels were inversely correlated with the NMSS total score (r = −0.285, P < 0.05) and the single-item scores for item one, assessing Cardiovascular (r = −0.257, P < 0.05) and item three, assessing Mood/cognition (r = −0.373, P < 0.05), and lower serum VIP levels were detected in the anxiety subgroup and depression subgroup than in the non-anxiety subgroup and non-depression subgroup, respectively [(107.45 ± 15.40) pg/ml vs. (116.41 ± 13.67) pg/ml, P < 0.05]; [(104.45 ± 15.26) pg/ml vs. (113.43 ± 14.52) pg/ml, P < 0.05].Conclusion: The serum PACAP and VIP levels of PD patients were significantly lower than those of healthy controls. The non-motor symptoms significantly negatively correlated with serum PACAP level was cognitive dysfunction, while mood disorder was significantly correlated with serum VIP level.

Natural coumarins contribute to the aroma of licorice, and they are often used as a flavoring and stabilizing agents. However, coumarins usage in food has been banned by various countries due to its toxic effect. In this study, a strain of HSM-C2 that can biodegrade coumarin with high efficiency was isolated from soil and identified as Pseudomonas putida through performing 16S rDNA sequence analysis. The HSM-C2 catalyzed the biodegradation up to 99.83% of 1 mg/mL coumarin within 24 h under optimal culture conditions, such as 30 °C and pH 7, which highlights the strong coumarin biodegrading potential of this strain. The product, such as dihydrocoumarin, generated after the biodegradation of coumarin was identified by performing GC-MS analysis. The present study provides a theoretical basis and microbial resource for further research on coumarin biodegradation.

Introduction: Heme oxygenase-1 (HO-1) is a 32 kDa stress-response protein implicated in the pathogenesis of Parkinson’s disease (PD). Biliverdin is derived from heme through a reaction mediated by HO-1 and protects cells from oxidative stress. However, iron and carbon monoxide produced by the catabolism of HO-1 exert detrimental effects on patients with PD. The purpose of this study was to determine whether plasma HO-1 levels represent a biomarker of PD and to further explore the underlying mechanism of increased HO-1 levels by applying voxel-based morphometry (VBM).Methods: We measured plasma HO-1 levels using an enzyme-linked immunosorbent assay (ELISA) in 156 subjects, including 81 patients with early- and advanced-stage PD and 75 subjects without PD. The analyses were adjusted to control for confounders such as age, sex, and medication. We analyzed T1-weighted magnetic resonance imaging (MRI) data from 74 patients with PD using VBM to elucidate the association between altered brain volumes and HO-1 levels. Then, we compared performance on MMSE sub-items between PD patients with low and high levels of HO-1 using Mann-Whitney U tests.Results: Plasma HO-1 levels were significantly elevated in PD patients, predominantly those with early-stage PD, compared with controls (p < 0.05). The optimal cutoff value for patients with early PD was 2.245 ng/ml HO-1 [area under the curve (AUC) = 0.654]. Plasma HO-1 levels were unaffected by sex, age, and medications (p > 0.05). The right hippocampal volume was decreased in the subset of PD patients with high HO-1 levels (p < 0.05). A weak correlation was observed between right hippocampal volume and plasma HO-1 levels (r = −0.273, p = 0.018). There was no difference in total MMSE scores between the low- and high-HO-1 groups (p > 0.05), but the high-HO-1 group had higher language scores than the low-HO-1 group (p < 0.05).Conclusions: Plasma HO-1 levels may be a promising biomarker of early PD. Moreover, a high plasma concentration of the HO-1 protein is associated with a reduction in right hippocampal volume.

UDP-glucose dehydrogenase (UGD; EC1.1.1.22) is a NAD+-dependent enzyme that catalyzes the two-fold oxidation of UDP-glucose (UDP-Glc) to produce UDP-glucuronic acid and plays an important role in plant cell wall synthesis. A total of 42 UGD genes from four Gossypium genomes including G. hirsutum, G. arboretum, G. barbadense, and G. raimondii were identified and found that the UGD gene family has conservative evolution patterns in gene structure and protein domain. The growth of fibers can be effectively promoted after adding the UDP-Glc to the medium, and the GhUGD gene expression enhanced. In addition, the transgenic Arabidopsis lines over-expressing GH_D12G1806 had longer root lengths and higher gene expression level than the wild-type plants of Columbia-0. These results indicated that UGD may play important roles in cotton fiber development and has a guiding significance for dissecting fiber development mechanism.

ObjectiveMelatonin is the major hormone produced and secreted at night by the pineal gland into the cerebrospinal fluid (CSF) and circulation. The relationship between plasma melatonin levels and Parkinson’s disease is not clear. The aim of the current study was to assess plasma melatonin levels in Parkinson’s disease (PD) patients and to analysis the relationship between plasma melatonin levels and non-motor symptoms.Participants and MethodsIn this cross-sectional study, we evaluated 61 patients with idiopathic PD [males n = 30 (49.2%), average age 62.4 years (range: 46–73 years)] and a total of 58 healthy volunteers [males n = 30 (51.7%), average age 64.3 years (range: 45–70 years)] who participated in the study. Plasma melatonin levels were measured using an enzyme-linked immunosorbent assay. The severity of disease in PD patients was scored by the Unified Parkinson’s Disease Rating Scale and the Hoehn and Yahr Staging scale. The quality of life in PD patients was assessed by the 39-item Parkinson’s Disease Questionnaire. The non-motor symptoms were assessed by the 14-item Hamilton Anxiety Rating Scale, the 24-item Hamilton Depression Rating Scale, the Parkinson Disease Sleep Scale, the Epworth Sleepiness Scale and the Non-Motor Symptoms Scale for PD.ResultsCompared with the healthy controls, the plasma melatonin levels were significantly higher in PD patients (12.82 ± 4.85 vs. 19.40 ± 4.23, P < 0.001). Plasma melatonin levels were significantly associated with the levodopa equivalent daily dose (r = −0.262, P < 0.05, n = 61). Higher plasma melatonin concentrations were detected in the negative cardiovascular symptom group than in the cardiovascular symptom group (20.13 ± 3.74 vs. 16.93 ± 3.74, P < 0.05). Higher plasma melatonin concentrations were detected in the non-sleep-disorders group than in the sleep disorders group (22.12 ± 5.93 vs. 18.86 ± 3.66, P < 0.05). In addition, the plasma melatonin concentration was higher in the group without gastrointestinal dysfunction than in the gastrointestinal dysfunction group (21.71 ± 4.44 vs. 18.35 ± 3.74, P < 0.05).ConclusionThis study revealed that the plasma melatonin levels in PD patients were significantly higher than those in healthy controls. Non-motor symptoms that were significantly negatively correlated with plasma melatonin levels were cardiovascular symptoms, sleep disorders, and gastrointestinal dysfunction. Plasma melatonin levels have the closest relationship with sleep disorders. There was a correlation between plasma melatonin levels and sleep quality in patients with PD. The remaining non-motor symptoms were not related to plasma melatonin levels.

The correction of wavefront aberration plays a vital role in active optics. The traditional correction algorithms based on the deformation of the mirror cannot effectively deal with disturbances in the real system. In this study, a new algorithm called deep learning correction algorithm (DLCA) is proposed to compensate for wavefront aberrations and improve the correction capability. The DLCA consists of an actor network and a strategy unit. The actor network is utilized to establish the mapping of active optics systems with disturbances and provide a search basis for the strategy unit, which can increase the search speed; The strategy unit is used to optimize the correction force, which can improve the accuracy of the DLCA. Notably, a heuristic search algorithm is applied to reduce the search time in the strategy unit. The simulation results show that the DLCA can effectively improve correction capability and has good adaptability. Compared with the least square algorithm (LSA), the algorithm we proposed has better performance, indicating that the DLCA is more accurate and can be used in active optics. Moreover, the proposed approach can provide a new idea for further research of active optics.

Traditional engineering education of innovative thinking mainly focused on knowledge imparting, thinking and learning, but it weakens the cultivation of students' practical ability. In this paper, a new pattern of innovative thinking engineering education is proposed, which combines abstract design innovation with specific robot maker practice. By offering general course for all professional students, it teaches the theory, methods and tools of systematic innovative thinking, and cultivates students' system design methods and innovative thinking. Taking the design and production process of robots as the object and content of practical teaching, the traditional teaching pattern centered on teachers, classrooms and textbooks is changed, teachers' reflection on teaching is promoted, so that it can be truly changedfrom a lecturer to an inspirator of learning, at the same time, teaching flexibility is increased, and students' highlevel thinking and practical abilities are improved. Classroom statistics show that 92.14% of the students think that their innovative thinking ability has been improved, and 90.71% of the students consider that their practical ability has been enhanced. It shows that the engineering education innovation pattern with design ideas and robot maker practice can inspire students' innovative thinking, while improving students' robotic practical ability.

A 1521 bp gene encoding for a novel fructosyltransferase from Aspergillus oryzae ZZ-01 (AoFT) has been amplified by RACE and TAIL PCR, and functionally overexpressed in Escherichia coli BL 21-CodonPlus (DE3)-RIL. The recombinant A. oryzae ZZ-01 fructosyltransferases (r-AoFT) was purified to homogeneity after Ni-NTA affinity and Superdex-200 gel filtration chromatography. SDS-PAGE analysis of the purified r-AoFT revealed a single protein band with an apparent molecular mass of 60.0 kDa. The r-AoFT enzyme exhibited its optimal activity at 55 °C and pH 5.5, and maintained about 63% of its activity even after 60 min of treatment at 60 °C. The addition of Mg2+ led to an increase in the activity of r-AoFT, whereas Zn2+, Cu2+ and Ni2+ led to a reduction in its activity. Six site-directed mutants of r-AoFT (D39A, D164A, E216A, N38L, S99A and Y282A) were constructed and characterized biochemically. The N38L, S99A and Y282A mutants had lower Km and higher Vmax values than the wild-type enzyme, highlighting their higher binding affinity for the substrates. These results therefore suggest that r-AoFT could be used for the enzymatic synthesis of Suc6A from sucrose and glucose 6-acetate.

Objective: This retrospective cohort study aimed to investigate the composition and diversity of lung microbiota in patients with severe pneumonia and explore its association with short-term prognosis. Methods: A total of 301 patients diagnosed with severe pneumonia underwent bronchoalveolar lavage fluid metagenomic next-generation sequencing (mNGS) testing from February 2022 to January 2024. After applying exclusion criteria, 236 patients were included in the study. Baseline demographic and clinical characteristics were compared between survival and non-survival groups. Microbial composition and diversity were analyzed using alpha and beta diversity metrics. Additionally, LEfSe analysis and machine learning methods were employed to identify key pathogenic microorganism associated with short-term mortality. Microbial interaction modes were assessed through network co-occurrence analysis. Results: The overall 28-day mortality rate was 37.7% in severe pneumonia. Nonsurvival patients had a higher prevalence of hypertension and exhibited higher APACHE II and SOFA scores, higher procalcitonin (PCT), and shorter hospitalization duration. Microbial α and β diversity analysis showed no significant differences between the two groups. However, distinct species diversity patterns were observed, with the non-survival group showing a higher abundance of Acinetobacter baumannii, Klebsiella pneumoniae, and Enterococcus faecium, while the survival group had a higher prevalence of Corynebacterium striatum and Enterobacter. LEfSe analysis identified 29 distinct terms, with 10 potential markers in the non-survival group, including Pseudomonas sp. and Enterococcus durans. Machine learning models selected 16 key pathogenic bacteria, such as Klebsiella pneumoniae, significantly contributing to predicting short-term mortality. Network co-occurrence analysis revealed greater complexity in the non-survival group compared to the survival group, with differences in central genera. Conclusion: Our study highlights the potential significance of lung microbiota composition in predicting short-term prognosis in severe pneumonia patients. Differences in microbial diversity and composition, along with distinct microbial interaction modes, may contribute to variations in short-term outcomes. Further research is warranted to elucidate the clinical implications and underlying mechanisms of these findings. [ABSTRACT FROM AUTHOR]

During the production period of shale gas, proppant particles and rock debris are produced together, which will seriously erode the elbows of gathering pipelines. In response to this problem, this paper takes the elbow of the gathering pipeline in the Changning Shale Gas Field as an example to test the erosion rate and material removal mechanism of the test piece at different angles of the elbow through experiments and compares the four erosion models with the experimental results. Through analysis, it is found that the best prediction model for quartz sand-carbon steel erosion is the Oka model. Based on the Oka model, FLUENT software was used to simulate and analyze the law of erosion of the elbow of the gas gathering pipeline under different gas flow velocities, gas gathering pressure, particle size, length of L1, and bending directions of the elbow. And a spiral pipeline structure is proposed to reduce the erosion rate of the elbow under the same working conditions. The results show that this structure can reduce erosion by 34%. [ABSTRACT FROM AUTHOR]

Background: Radiation therapy has attracted much attention in the treatment of patients with hepatocellular carcinoma (HCC). However, the association between radiotherapy-related fatigue and HCC has been examined in only a few studies. Purpose: This study was designed to explore the change over time in fatigue in patients with HCC treated with radiotherapy and related factors. Methods: One hundred patients were enrolled in this prospective longitudinal study using convenience sampling at a medical center in northern Taiwan. The Functional Assessment of Chronic Illness Therapy-Fatigue scale, the Brief Pain InventoryShort Form, and the psychological subscale of Memorial Symptom Assessment Scale-Short Form were used to assess the symptoms at five time points: before radiotherapy (T0), during treatment (T1), and at 1 month (T2), 3 months (T3), and 6 months (T4) after radiotherapy. The generalized estimating equations method was used to determine the changes in fatigue and the influencing factors. Results: Fatigue levels at T1, T2, T3, and T4 were significantly higher than that at T0. Higher fatigue was significantly associated with lower income and poorer functional status. Having worse pain levels and psychological symptoms were both associated with higher fatigue. Conclusions/Implications for Practice: The results indicate fatigue does not recover to the baseline (pretherapy) level by 6 months after radiotherapy. Thus, fatigue in patients with HCC receiving radiotherapy should be regularly and effectively assessed, and patients experiencing pain and psychological symptoms should be given greater attention from clinicians. [ABSTRACT FROM AUTHOR]

More than 50 years of efforts to identify the major cytokine responsible for red blood cell (RBC) production (erythropoiesis) led to the identification of erythropoietin (EPO) in 1977 and its receptor (EPOR) in 1989, followed by three decades of rich scientific discovery. We now know that an elaborate oxygen-sensing mechanism regulates the production of EPO, which in turn promotes the maturation and survival of erythroid progenitors. Engagement of the EPOR by EPO activates three interconnected signaling pathways that drive RBC production via diverse downstream effectors and simultaneously trigger negative feedback loops to suppress signaling activity. Together, the finely tuned mechanisms that drive endogenous EPO production and facilitate its downstream activities have evolved to maintain RBC levels in a narrow physiological range and to respond rapidly to erythropoietic stresses such as hypoxia or blood loss. Examination of these pathways has elucidated the genetics of numerous inherited and acquired disorders associated with deficient or excessive RBC production and generated valuable drugs to treat anemia, including recombinant human EPO and more recently the prolyl hydroxylase inhibitors, which act partly by stimulating endogenous EPO synthesis. Ongoing structure–function studies of the EPOR and its essential partner, tyrosine kinase JAK2, suggest that it may be possible to generate new “designer” drugs that control selected subsets of cytokine receptor activities for therapeutic manipulation of hematopoiesis and treatment of blood cancers.

In the population of patients with prostate cancer, survivorship has come to the forefront of continuity-of-care. In addition to urinary control, erectile function is a significant issue after radical pelvic surgery. Penile prosthesis surgery remains an excellent option for restoring erectile function to those for whom more conservative measures have failed. This review article outlines the anatomical, surgical and post-operative consideration involved in the placement of a penile prosthesis in this special patient population.

Plant intracellular nucleotide- binding domain, leucine-rich repeat- containing recep- tors (NLRs) activate a robust immune response upon detection of pathogen effectors. How NLRs induce downstream immune defense genes remains poorly understood. The Mediator complex plays a central role in transducing signals from gene-specific transcription factors to the transcription machinery for gene transcription/activation. In this study, we demonstrate that MED10b and MED7 of the Mediator complex mediate jasmonate-dependent transcription repression, and coiled-coil NLRs (CNLs) in Solanaceae modulate MED10b/MED7 to activate immunity. Using the tomato CNL Sw-5b, which confers resistance to tospovirus, as a model, we found that the CC domain of Sw-5b directly interacts with MED10b. Knockout/down of MED10b and other subunits including MED7 of the middle module of Mediator activates plant defense against tospovirus. MED10b was found to directly interact with MED7, and MED7 directly interacts with JAZ proteins, which function as transcriptional repressors of jasmonic acid (JA) signaling. MED10b–MED7–JAZ together can strongly repress the expression of JA-responsive genes. The activated Sw-5b CC interferes with the interac- tion between MED10b and MED7, leading to the activation of JA-dependent defense signaling against tospovirus. Furthermore, we found that CC domains of various other CNLs including helper NLR NRCs from Solanaceae modulate MED10b/MED7 to activate defense against different pathogens. Together, our findings reveal that MED10b/ MED7 serve as a previously unknown repressor of jasmonate-dependent transcription repression and are modulated by diverse CNLs in Solanaceae to activate the JA-specific defense pathways. [ABSTRACT FROM AUTHOR]