Fibroblast growth factor 3 contributes to neuropathic pain through Akt/mTOR signaling in mouse primary sensory neurons.

Neuropathic pain (NP), a severe chronic pain condition, remains a substantial clinical challenge due to its complex pathophysiology and limited effective treatments. An association between the members of the Fibroblast Growth Factors (FGFs), particularly Fgf3, and the development of NP has become evident. In this study, utilizing a mouse model of NP, we observed a time-dependent increase in Fgf3 expression at both mRNA and protein levels within the dorsal root ganglia (DRG). Functional studies revealed that blocking Fgf3 expression mitigated nerve injury induced nociceptive hypersensitivity, suggesting its pivotal role in pain modulation. Moreover, our findings elucidate that Fgf3 contributes to pain hypersensitivity through the activation of the Akt/mTOR signaling in injured DRG neurons. These results not only shed light on the involvement of Fgf3 in nerve injury-induced NP but also highlight its potential as a promising therapeutic target for pain management. This study thereby advances our understanding of the molecular mechanisms underlying NP and opens new avenues for the development of effective treatment strategies.

Ecological implications and drivers of emerging contaminants in Dongting Lake of Yangtze River Basin, China: A multi-substance risk analysis.

Emerging contaminants (ECs) are increasingly recognized as a global threat to biodiversity and ecosystem health. However, the cumulative risks posed by ECs to aquatic organisms and ecosystems, as well as the influence of anthropogenic activities and natural factors on these risks, remain poorly understood. This study assessed the mixed risks of ECs in Dongting Lake, a Ramsar Convention-classified Typically Changing Wetland, to elucidate the major EC classes, key risk drivers, and magnitude of anthropogenic and natural impacts. Results revealed that ECs pose non-negligible acute (30% probability) and chronic (70% probability) mixed risks to aquatic organisms in the freshwater lake ecosystem, with imidacloprid identified as the primary pollutant stressor. Redundancy analysis (RDA) and structural equation modeling (SEM) indicated that cropland and precipitation were major drivers of EC contamination levels and ecological risk. Cropland was positively associated with EC concentrations, while precipitation exhibited a dilution effect. These findings provide critical insights into the ecological risk status and key risk drivers in a typical freshwater lake ecosystem, offering data-driven support for the control and management of ECs in China.

Metabolic Engineering of Corynebacterium glutamicum for Highly Efficient Production of Ectoine.

Ectoine is a compatible solute that functions as a cell protector from various stresses, protecting cells and stabilizing biomolecules, and is widely used in medicine, cosmetics, and biotechnology. Microbial fermentation has been widely used for the large-scale production of ectoine, and a number of fermentation strategies have been developed to increase the ectoine yield, reduce production costs, and simplify the production process. Here, Corynebacterium glutamicum was engineered for ectoine production by heterologous expression of the ectoine biosynthesis operon ectBAC gene from Halomonas elongata, and a series of genetic modifications were implemented. This included introducing the de3 gene from Escherichia coli BL21 (DE3) to express the T7 promoter, eliminating the lysine transporter protein lysE to limit lysine production, and performing a targeted mutation lysCS301Y on aspartate kinase to alleviate feedback inhibition of lysine. The new engineered strain Ect10 obtained an ectoine titer of 115.87 g/L in an optimized fed-batch fermentation, representing the highest ectoine production level in C. glutamicum and achieving the efficient production of ectoine in a low-salt environment.

MotionDiffuse: Text-Driven Human Motion Generation With Diffusion Model.

Human motion modeling is important for many modern graphics applications, which typically require professional skills. In order to remove the skill barriers for laymen, recent motion generation methods can directly generate human motions conditioned on natural languages. However, it remains challenging to achieve diverse and fine-grained motion generation with various text inputs. To address this problem, we propose MotionDiffuse, one of the first diffusion model-based text-driven motion generation frameworks, which demonstrates several desired properties over existing methods. 1) Probabilistic Mapping. Instead of a deterministic language-motion mapping, MotionDiffuse generates motions through a series of denoising steps in which variations are injected. 2) Realistic Synthesis. MotionDiffuse excels at modeling complicated data distribution and generating vivid motion sequences. 3) Multi-Level Manipulation. MotionDiffuse responds to fine-grained instructions on body parts, and arbitrary-length motion synthesis with time-varied text prompts. Our experiments show MotionDiffuse outperforms existing SoTA methods by convincing margins on text-driven motion generation and action-conditioned motion generation. A qualitative analysis further demonstrates MotionDiffuse's controllability for comprehensive motion generation.

RETINAL MICROVASCULAR CHANGES AND RISK OF CORONARY HEART DISEASE: A Systematic Review and Meta-Analysis.

PURPOSE: To quantify associations between various retinal microvascular changes and the risk of the development of coronary heart disease (CHD). METHODS: PubMed, Embase, Web of Science, and Cochrane Library databases were searched for cohort studies on the association between retinal microvascular changes and incident CHD up to July 31, 2023. The summary risk estimates were estimated using the random-effects model. Subgroup and sensitivity analyses were performed to investigate the potential source of heterogeneity. RESULTS: The authors identified 21 studies that met the inclusion criteria of this meta-analysis through database searching. This study yielded significant associations between retinal microvascular changes, including arteriolar narrowing, venular widening, vessel occlusion, and other retinal vascular signs, and the risk of CHD, with pooled adjusted hazard ratios of 1.20 (95% confidence interval: 1.13-1.27). In sex- and age-stratified analyses, retinal microvascular changes were associated with a greater risk of developing CHD in female patients and younger adults. CONCLUSION: A range of retinal microvascular changes was associated with the risk of CHD, particularly in female patients and younger ages. The results of this study support the concept that retinal microvascular abnormalities may be markers for future CHD. Noninvasive retinal microvascular assessments may be helpful in screening patients with increased CHD risk.

Flexible molecularly imprinted glucose sensor based on graphene sponge and Prussian blue.

To enhance the sensitivity of flexible glucose sensors made with 3-aminophenylboronic acid and pyrrole as functional molecules and a carbon tri-electrode as substrate, graphene sponge (GS) and Prussian blue (PB) were used to enhance the charge transfer between the molecularly imprinted cavities and the electrodes. Electrochemical impedance spectroscopy and cyclic voltammetry showed that modifying the electrode with GS and PB significantly reduced the charge transfer impedance and increased the redox current of the sensor. The sensor has a sensitivity of up to 25.81 µA⋅loge (µM)-1⋅cm-2 for the detection of glucose using differential pulse voltammetry in the range of 7.78 to 600 µM, with a low detection limit of 1.08 µM (S/N = 3). When the pH varies in the range of 5.5 to 7.5, the sensor maintains a certain level of stability for glucose detection. The presence of lactic acid, urea, and ascorbic acid had minimal impact on glucose detection by the sensor. After 20 days of storage at room temperature, the sensor maintains 80 % efficiency. This study supports the development of wearable glucose sensors with high sensitivity, specificity, and stability through molecular imprinting.

The impact of bilateral brachial-ankle pulse wave velocity difference on cardiovascular disease and all-cause mortality.

Background: This study aims to investigate the association between an elevated bilateral pulse wave velocity difference (BPWVD) and cardiovascular diseases (CVDs) and all-cause mortality. Methods: This study included a total of 38,356 participants. A multivariable Cox proportional hazards regression was used to assess the association between high BPWVD and the increased risk of CVDs and all-cause mortality by calculating hazard ratios (HRs) with 95% confidence intervals. Results: A total of 1,213 cases of CVDs were identified over a mean duration of 6.19 years, including 886 cases of cerebral infarction (CI), 105 cases of intracerebral hemorrhage (ICH), and 222 cases of myocardial infarction (MI), along with 1,182 cases of all-cause mortality. The median BPWVD was 42 cm/s (19-80 cm/s). After adjusting for all confounders and baseline brachial-ankle PWV (baPWV), our analysis revealed a significant correlation between a higher risk of CVDs, MI, and all-cause mortality with an increase in BPWVD per standard deviation. HRs (95% confidence interval) were found to be 1.06 (1.01-1.11), 1.11 (1.02-1.21), and 1.07 (1.04-1.10), respectively. Among the participants with higher baPWV on the left side, the HRs (95% confidence interval) were 1.08 (1.02-1.14) for CVDs, 1.27 (1.10-1.46) for incident ICH, 1.16 (1.00-1.24) for incident MI, and 1.10 (1.07-1.15) for all-cause mortality, for per standard deviation increase in BPWVD. Conclusions: Our findings reveal a significant correlation between elevated BPWVD and the risks of developing CVDs and all-cause mortality. This highlights the importance of thoroughly evaluating BPWVD as a means of detecting individuals at risk for CVDs and mortality.

Improvement of resistance to rice blast and bacterial leaf streak by CRISPR/Cas9-mediated mutagenesis of Pi21 and OsSULTR3;6 in rice (Oryza sativa L.).

Rice (Oryza sativa L.) is a staple food in many countries around the world, particularly in China. The production of rice is seriously affected by the bacterial leaf streak and rice blast, which can reduce rice yield or even cause it to fail to be harvested. In this study, susceptible material 58B was edited by CRISPR/Cas9, targeting a target of the Pi21 gene and a target of the effector-binding element (EBE) of the OsSULTR3;6 gene, and the mutants 58b were obtained by Agrobacterium-mediated method. The editing efficiency of the two targets in the T0 generation was higher than 90.09%, the homozygous mutants were successfully selected in the T0 generation, and the homozygous mutation rate of each target was higher than 26.67%. The expression of the edited pi21 and EBE of Ossultr3;6 was significantly reduced, and the expression of defense responsive genes was significantly upregulated after infected with rice blast. The lesion areas of rice blast and bacterial leaf streak were significantly reduced in 58b, and the resistance of both was effectively improved. Furthermore, the gene editing events did not affect the agronomic traits of rice. In this study, the resistance of 58b to rice blast and bacterial leaf streak was improved simultaneously. This study provides a reference for using Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 (CRISPR/Cas9) to accelerate the improvement of rice varieties and the development of new materials for rice breeding.

Callous-unemotional traits and externalizing problem behaviors in left-behind preschool children: the role of emotional lability/negativity and positive teacher-child relationship.

BACKGROUND: Callous-unemotional traits and emotional lability/negativity of young children have been regarded as the markers of externalizing problem behaviors. Based on the sensitivity to threat and affiliative reward model and the general aggression model, emotional lability/negativity may act as a mediator in the relationship between callous-unemotional traits and externalizing problem behaviors. Additionally, a positive teacher-child relationship could act as a buffer given the parental absence in left-behind children. However, these links remain unexplored in left-behind preschool children. Therefore, this study explored the link between callous-unemotional traits of left-behind preschool children and externalizing problem behaviors, as well as the mediating role of emotional lability/negativity and the moderating role of a positive teacher-child relationship. METHOD: Data were collected on 525 left-behind children aged 3 to 6 years from rural kindergartens in China. Preschool teachers reported all data through an online survey platform. Moderated mediation analysis was performed to examine whether the mediated relation between callous-unemotional traits and externalizing problem behaviors was moderated by a positive teacher-child relationship. RESULTS: The results showed callous-unemotional traits significantly predicted externalizing problem behaviors and lability/negativity acted as a mediator, while a positive teacher-child relationship acted as a protective factor in moderating the relationship between callous-unemotional traits and emotional lability/negativity. This study identified a moderated mediation effect among the four variables in left-behind preschool children in China. CONCLUSION: The findings provide support for the advancement of theoretical foundations, and provide an avenue for further exploration to support the mental health and overall development of left-behind children during early childhood.

Analysis of 16 mycotoxins in genuine traditional Chinese medicine for five medicinal parts: Classification of analytical method based on PANI@CS extraction-UPLC-MS/MS.

A novel PANI@CS solid-phase dispersive extractant combined with ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed for the first time, which was used for high-throughput, multi-component, real-time online rapid pretreatment and quantitative classification of 16 mycotoxins from five different medicinal parts of 13 genuine traditional Chinese medicines (TCMs). Ultra performance liquid chromatography combined with triple quadrupole mass spectrometry was used for separation and ESI detection. An internal standard isotope matching calibration was used for quantification purposes to compensate for matrix effects. The limits of detection (LOD) of 16 mycotoxins ranged from 0.1 to 6.0 µg/kg. The linear coefficients (R2) were ≥0.996 in the linear range from 10.0 to 200 µg/L. The recoveries of the 16 mycotoxins ranged from 90.1% to 105.8%, and the relative standard deviations (RSDs) ranged from 1.3% to 4.1%. Thirteen TCMs from five representative medicinal parts were selected and tested under the best sample preparation procedure and chromatographic analysis conditions. The results showed that the method could improve the sensitivity and accuracy of the sample analysis, improve the selectivity and reproducibility of the decolorization and purification of TCMs, which is suitable for the practical application of mycotoxin in trace analysis. This method can also provide a new idea for accurate, efficient, rapid and multi-component online detection of mycotoxins for quality and safety control of TCMs.

Endothelial ACKR1 is induced by neutrophil contact and down-regulated by secretion in extracellular vesicles.

Atypical chemokine receptor-1 (ACKR1), previously known as the Duffy antigen receptor for chemokines, is a widely conserved cell surface protein that is expressed on erythrocytes and the endothelium of post-capillary venules. In addition to being the receptor for the parasite causing malaria, ACKR1 has been postulated to regulate innate immunity by displaying and trafficking chemokines. Intriguingly, a common mutation in its promoter leads to loss of the erythrocyte protein but leaves endothelial expression unaffected. Study of endothelial ACKR1 has been limited by the rapid down-regulation of both transcript and protein when endothelial cells are extracted and cultured from tissue. Thus, to date the study of endothelial ACKR1 has been limited to heterologous over-expression models or the use of transgenic mice. Here we report that exposure to whole blood induces ACKR1 mRNA and protein expression in cultured primary human lung microvascular endothelial cells. We found that contact with neutrophils is required for this effect. We show that NF-κB regulates ACKR1 expression and that upon removal of blood, the protein is rapidly secreted by extracellular vesicles. Finally, we confirm that endogenous ACKR1 does not signal upon stimulation with IL-8 or CXCL1. Our observations define a simple method for inducing endogenous endothelial ACKR1 protein that will facilitate further functional studies.

Differences in organic nitrogen transformation during chicken manure composting with the addition of different disaccharides.

The effect of different carbon sources on nitrogen (N) transformation and N loss through nitrogenous gas volatilization during composting of manure is not clear. Disaccharides had moderate degradation stability compared to monosaccharides and polysaccharides. Therefore, we investigated the effect of adding sucrose (nonreducing sugar) and maltose (reducing sugar) as carbon sources on volatile N loss and hydrolysable organic nitrogen (HON) transformation. HON is composed of bioavailable organic nitrogen (BON) and hydrolysable unknown nitrogen (HUN). Three laboratory-scale experimental groups were conducted with control (CK), 5 % sucrose (SS), and 5 % maltose (MS) addition. Our findings indicated that, while excluding leaching and surface runoff, adding sucrose and maltose decreased the N loss through gas volatilization by 15.78 % and 9.77 %, respectively. The addition of maltose significantly increased the BON content (P < 0.05), which was 6.35 % higher than in CK. The addition of sucrose led to an increase in HUN content (P < 0.05), which was 22.89 % higher than that in CK. In addition, the core microbial communities associated with HON changed after the addition of disaccharides. The transformation of the HON fractions was facilitated by the succession of microbial communities. Ultimately, variation partition analysis (VPA) and structural equation modeling (SEM) verified that the core microbial communities were the major contributors to promoting HON transformation. In summary, adding disaccharides could promote the different transformations of organic nitrogen (ON) and reduce the volatilization of nitrogenous gases by changing the succession of the core microbial communities during composting. This study provided theoretical and technical support for reducing volatile N loss and promoting ON fraction sequestration during composting. Furthermore, the effect of carbon source addition on the nitrogen cycle was also explored.

A sensory neuron-specific long non-coding RNA reduces neuropathic pain by rescuing KCNN1 expression.

Nerve injury to peripheral somatosensory system causes refractory neuropathic pain. Maladaptive changes of gene expression in primary sensory neurons are considered molecular basis of this disorder. Long non-coding RNAs (lncRNAs) are key regulators of gene transcription; however, their significance in neuropathic pain remains largely elusive.Here, we reported a novel lncRNA, named sensory neuron-specific lncRNA (SS-lncRNA), for its expression exclusively in dorsal root ganglion (DRG) and trigeminal ganglion. SS-lncRNA was predominantly expressed in small DRG neurons and significantly downregulated due to a reduction of early B cell transcription factor 1 in injured DRG after nerve injury. Rescuing this downregulation reversed a decrease of the calcium-activated potassium channel subfamily N member 1 (KCNN1) in injured DRG and alleviated nerve injury-induced nociceptive hypersensitivity. Conversely, DRG downregulation of SS-lncRNA reduced the expression of KCNN1, decreased total potassium currents and afterhyperpolarization currents and increased excitability in DRG neurons and produced neuropathic pain symptoms.Mechanistically, downregulated SS-lncRNA resulted in the reductions of its binding to Kcnn1 promoter and heterogeneous nuclear ribonucleoprotein M (hnRNPM), consequent recruitment of less hnRNPM to the Kcnn1 promoter and silence of Kcnn1 gene transcription in injured DRG.These findings indicate that SS-lncRNA may relieve neuropathic pain through hnRNPM-mediated KCNN1 rescue in injured DRG and offer a novel therapeutic strategy specific for this disorder.

Design, synthesis, and antifungal activity of novel dithiin tetracarboximide derivatives as potential succinate dehydrogenase inhibitors.

BACKGROUND: Succinate dehydrogenase inhibitor (SDHI) fungicides are an important class of agricultural fungicides with the advantages of high efficiency and a broad bactericidal spectrum. To pursue novel SDHIs, a series of N-substituted dithiin tetracarboximide derivatives were designed, synthesized, and characterized by 1 H NMR, 13 C NMR, and high resolution mass spectrum (HRMS). RESULTS: These engineered compounds displayed potent fungicidal activity against phytopathogens, including Sclerotinia sclerotiorum, Botrytis cinerea, and Rhizoctonia solani, comparable with that of the commercial SDHI fungicide boscalid. In particular, compound 18 stood out with prominent activity against S. sclerotiorum with a half-maximal effective concentration (EC50 ) value of 1.37 µg ml-1 . Compound 1 exhibited the most potent antifungal activity against B. cinerea with EC50 values of 5.02 µg ml-1 . As for R. solani, 12 and 13 exhibited remarkably inhibitory activity with EC50 values of 4.26 and 5.76 µg ml-1 , respectively. In the succinate dehydrogenase (SDH) inhibition assay, 13 presented significant inhibitory activity with a half-maximal inhibitory concentration (IC50 ) value of 15.3 µm, which was approximately equivalent to that of boscalid (14.2 µm). Furthermore, molecular docking studies revealed that 13 could anchor in the binding site of SDH. CONCLUSION: Taken together, results suggested that the dithiin tetracarboximide scaffold possessed a huge potential to be developed as novel fungicides and SDHIs. © 2023 Society of Chemical Industry.

Ketamine modulates neural stem cell differentiation by regulating TRPC3 expression through the GSK3ß/ß-catenin pathway.

Ketamine, a popular anesthetic, is often abused by people for its hallucinogenic effect. Thus, the safety of ketamine in pediatric populations has been called into question for potential neurotoxic effects. However, ketamine also has neuroprotective effects in many brain injury models. The differentiation of neural stem cells (NSCs) was influenced significantly by ketamine, but the molecular mechanism is still unclear. NSCs were extracted from the hippocampi of postnatal day 1 rats and treated with ketamine to induce NSCs differentiation. Our results found that ketamine promoted neuronal differentiation of NSCs dose-dependently in a small dose range (P < 0.001). The main types of neurons from NSCs were cholinergic (51 ± 4 %; 95 % CI: 41-61 %) and glutamatergic neurons (34 ± 3 %; 95 % CI: 27-42 %). Furthermore, we performed RNA sequencing to promise a more comprehensive understanding of the molecules regulated by ketamine. Finally, we combined bioimaging and multiple molecular biology techniques to clarify that ketamine influences NSC differentiation by regulating transient receptor potential canonical 3 (TRPC3) expressions. Ketamine dramatically repressed TRPC3 expression (MD [95 % CI]=0.67 [0.40-0.95], P < 0.001) with a significant increase of phosphorylated glycogen synthase kinase 3ß (p-GSK3ß; MD [95 % CI]=1.00 [0.74-1.27], P < 0.001) and a decrease of ß-catenin protein expression (MD [95 % CI]=0.60 [0.32-0.89], P = 0.001), thereby promoting the differentiation of NSCs into neurons and inhibiting their differentiation into astrocytes. These results suggest that TRPC3 is necessary for ketamine to modulate NSC differentiation, which occurs partly via regulation of the GSK3ß/ß-catenin pathway.

What makes helpful online mental health information? Empirical evidence on the effects of information quality and responders' effort.

Although online health communities are popular in supporting mental health, factors leading to the helpfulness of mental health information are still under-investigated. Based on the elaboration likelihood model and motivation theory, we incorporate two types of health information-related constructs, i.e., information quality (central route) and responders' effort (peripheral route), and adopt reputation as an extrinsic motivation to build our model. We crawl data from a Chinese online mental health community and extract 11 key variables, and then analyze the model with negative binomial regression. The empirical results indicate that the effect of the length of health information on its helpfulness votes is positively significant, while the effect of readability of health information on its helpfulness votes is relatively negative. In terms of responders' effort, both the timelines of the response and interactive feedback have a significant positive impact on helpfulness of health information votes, while these effects are negatively moderated by the online reputation of responders. This study contributes to the literature on information evaluation mechanisms in online health communities.

Loss of GNE Predicts Lymph Node Metastasis in Early Gastric Cancer.

Endoscopic surgery is increasingly utilized for the treatment of early gastric cancer (EGC) worldwide, whereas lymph node metastasis (LNM) remains a critical risk factor for the relapse of EGC after endoscopic surgery. Therefore, identifying potential predictive factors and understanding the molecular mechanisms are urgently needed for improving the outcome of EGC patients with LNM. UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) is the key enzyme in the process of biosynthesis of CMP-Neu5Ac from UDP-N-acetylglucosamine (UDP-GlcNAc), which acts as a substrate for several reactions in glycan metabolism. In this study, we found that GNE was down-regulated in EGC patients with LNM. GNE expression as well as localization, tumor size, intravascular tumor thrombi and Lauren's classification were further identified as independent predictive factors for LNM. Combining GNE expression with traditional risk factors, including tumor size and differentiation degrees, could generate a better model for predicting LNM in EGC patients. Overall, our study implies that low GNE expression is a potential predictor of LNM in EGC.

Pollution, Exposure and Risk of Biogenic Amines in Canned Sea Fish: Classification of Analytical Methods Based on Carbon Spheres QuEChERS Extraction Combined with HPLC.

This study investigated the pollution characteristics, exposure levels and health risk assessments of seven kinds of biogenic amines (BAs) in eight varieties of canned sea fish products (n = 131) on the Chinese market. Carbon spheres QuEChERS mixed dispersion solid phase extraction combined with HPLC was used for the classification and analysis of batch samples. The average recovery of single BAs obtained by this method is 92.3~97.7%, and the relative standard deviation is 1.9~4.8%. Different varieties of samples have different degrees of pollution, the mass concentration of single BAs range 0.45~27.74 mg/kg, and the total concentration of ΣBAs range 18.77~368.50 mg/kg, of which the concentration of Σ4BAs range 11.53~368.50 mg/kg. The composition of four BAs is mainly putrescine, cadaverine, histamine and tyramine, which always play an important role in the exposure level and risk assessment of samples. The exposure level of BAs in the human body ranges 67.03~209.52 µg∙kg−1∙d−1. The health risk assessment shows that the gender trend of exposure risk level of BAs is male > female (young age), female > male (middle and old age), the age trend is young age > old age > middle age, and the regional trend is city > countryside. The food safety index of BAs in samples is 0.0062~0.0195, which is far less than 1, so the risk is within the controllable range.