Spinal histamine H4 receptor mediates chronic pruritus via p-ERK in acetone-ether-water (AEW)-induced dry skin mice.

Dry skin is common to many pruritic diseases and is difficult to improve with oral traditional antihistamines. Recently, increasing evidence indicated that histamine H4 receptor (H4R) plays an important role in the occurrence and development of pruritus. Extracellular signal-regulated kinase (ERK) phosphorylation activation in the spinal cord mediates histamine-induced acute and choric itch. However, whether the histamine H4 receptor regulates ERK activation in the dry skin itch remains unclear. In the study, we explore the role of the histamine H4 receptor and p-ERK in the spinal cord in a dry skin mouse model induced by acetone-ether-water (AEW). q-PCR, Western blot, pharmacology and immunofluorescence  were applied in the study. We established a dry skin itch model by repeated application of AEW on the nape of neck in mice. The AEW mice showed typically dry skin histological change and persistent spontaneous scratching behaviour. Histamine H4 receptor, instead of histamine H1 receptor, mediated spontaneous scratching behaviour in AEW mice. Moreover, c-Fos and p-ERK expression in the spinal cord neurons were increased and co-labelled with GRPR-positive neurons in AEW mice. Furthermore, H4R agonist 4-methyhistamine dihydrochloride (4-MH)induced itch. Both 4-MH-induced itch and the spontaneous itch in AEW mice were blocked by p-ERK inhibitor U0126. Finally, intrathecal H4R receptor antagonist JNJ7777120 inhibited spinal p-ERK expression in AEW mice. Our results indicated that spinal H4R mediates itch via ERK activation in the AEW-induced dry skin mice.

Graph Neural Network-Guided Contrastive Learning for Sequential Recommendation.

Sequential recommendation uses contrastive learning to randomly augment user sequences and alleviate the data sparsity problem. However, there is no guarantee that the augmented positive or negative views remain semantically similar. To address this issue, we propose graph neural network-guided contrastive learning for sequential recommendation (GC4SRec). The guided process employs graph neural networks to obtain user embeddings, an encoder to determine the importance score of each item, and various data augmentation methods to construct a contrast view based on the importance score. Experimental validation is conducted on three publicly available datasets, and the experimental results demonstrate that GC4SRec improves the hit rate and normalized discounted cumulative gain metrics by 1.4% and 1.7%, respectively. The model can enhance recommendation performance and mitigate the data sparsity problem.

Speech Recognition of Accented Mandarin Based on Improved Conformer.

The convolution module in Conformer is capable of providing translationally invariant convolution in time and space. This is often used in Mandarin recognition tasks to address the diversity of speech signals by treating the time-frequency maps of speech signals as images. However, convolutional networks are more effective in local feature modeling, while dialect recognition tasks require the extraction of a long sequence of contextual information features; therefore, the SE-Conformer-TCN is proposed in this paper. By embedding the squeeze-excitation block into the Conformer, the interdependence between the features of channels can be explicitly modeled to enhance the model's ability to select interrelated channels, thus increasing the weight of effective speech spectrogram features and decreasing the weight of ineffective or less effective feature maps. The multi-head self-attention and temporal convolutional network is built in parallel, in which the dilated causal convolutions module can cover the input time series by increasing the expansion factor and convolutional kernel to capture the location information implied between the sequences and enhance the model's access to location information. Experiments on four public datasets demonstrate that the proposed model has a higher performance for the recognition of Mandarin with an accent, and the sentence error rate is reduced by 2.1% compared to the Conformer, with only 4.9% character error rate.

[Comparative of functional components, antioxidant and α-glucosidase inhibition activities between Choerospondias axillaris fruit peel vinegar and apple vinegar].

Based on the idea of plant metabolomics, ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) was used to compare the chemical composition between 6 batches of fruit vinegar brewed from Choerospondias axillaris fruit peel and 6 batches of apple vinegar purchased from 3 companies. Antioxidant and α-glucosidase inhibition activities were also tested in vitro. A total of 43 compounds were identified by reference substance, liquid chromatography-mass spectrometry(LC-MS/MS) fragmentation information or literature data. A total of 40 compounds were identified in the C. axillaris fruit peel vinegar. A total of 16 compounds were identified in apple vinegar. There were 13 common ingredients including organic acids and esters such as citric acid, 2-isopropyl malic acid, and triethyl citrate. The results of partial leastsquares-discriminant analysis(PLS-DA) indicated that they had 33 significantly different compounds such as proanthocyanidin oligomer, quercetin-3-O-rhamnoside and heptadecanoic acid. The proanthocyanidins and flavonoid glycosides in C. axillaris peel vinegar were more abundant than apple vinegar, so it had better health function than ordinary fruit vinegar. The results showed that C. axillaris fruit peel vinegar had stronger antioxidant and α-glucosidase inhibition activities in vitro. The vinegar brewed from waste C. axillaris fruit peel had more chemical ingredients than the apple vinegar. C. axillaris fruit peel vinegar had better biological activity and health function, so it had good development prospect. This study provided the scientific evidence for exploiting the C. axillaris fruit peel into high value-added products. It also provided ideas for the comprehensive development and utilization of similar Chinese medicine waste.

[Analysis of standard decoction of salt-processed Psoraleae Fructus].

The traditional Chinese medicine standard decoction is prepared on the basis of the theory of traditional Chinese medicine and clinical application. With reference to the modern extraction method,the single decoction of traditional Chinese medicine is prepared by the standardized process,and the establishment of its quality standards is conducive to standardizing clinical medication. This research is to set an evaluation standard for the quality of salt-processed Psoraleae Fructus standard decoction. Twelve batches of salt-processed Psoraleae Fructus standard decoctions were prepared. The contents of psoralen and isopsoralen were determined,the transfer and extract rates were calculated,and the pH value was measured; HPLC fingerprint method was established for analysis. The results of the 12 batches of samples revealed that the transfer rates of psoralen and isopsoralen were 17. 10%-26. 40%,14. 70%-22. 70%,respectively; the extract rate was between 14. 7%-27. 0%,and the pH value was between 5. 4-6. 9. Moreover,7 common chromatographic peaks were determined based on fingerprint by using similarity evaluation system for chromatographic fingerprint of traditional Chinese medicine( 2012 A).The similarities of the 12 batches of samples were analyzed and compared,and the results showed that the similarities were all higher than0. 9. In this study,the preparation method for salt-processed Psoraleae Fructus decoction was standard,with high similarities in fingerprint. This study build a convenient and reliable method of comprehensive quality evaluation,with a high precision,stability and repeatability,which can provide a reference for the quality control of salt-processed Psoraleae Fructus dispensing granules.

[Establishment of "quantitative analysis of multi-components by single marker" method for phenolic acids in compound Danshen Tablets and its application in mass transfer law].

To construct a quality management model for the whole industry chain of compound Danshen Tablets,and quality control system for all key links in the production of compound Danshen Tablets. In this paper,with salvianolic acid B as internal reference substance,three batches of mix standards were prepared,and three sets of relative correlation factors between salvianolic acid B and other phenolic acids were calculated in parallel. Finally,the correlation factors are obtained on average. The quality transfer process was studied by optimizing the concentration of Salvia miltiorrhiza extract. The results showed that RSD among three sets of relative correlation factors ranged between 1. 7%-4. 1%,with no significant difference between the quantitative result of two methods. In addition,the quality transfer study showed that with the rise of the concentration temperature,the content of phenolic acid components changed,which had a significant effect on the salvianolic acid B at more than 80 ℃. It was suggested to rationally control the concentration temperature during the industrial production. The results of this study provide a methodology for the establishment of the quality control system for the whole industry chain of compound Danshen Tablets,and quality control methods for the improvement of the quality of medicinal materials and finished medicine products.

[Effects of"Grain for Green "on the Spatial Distribution of Soil Carbon and Nitrogen in Purple Hilly Area of China].

In order to remedy the lack of research on the effect of "Grain for Green" on soil carbon （C） and nitrogen （N） distribution on slope soil in purple hilly areas of Sichuan Basin, China, a study was conducted on a long-term observation site established in the Wanan small watershed of Yanting Agro-ecological Experimental Station of Purple Soil, Chinese Academy of Sciences. The morphology, content, and storage of C and N in soil at different slope positions of farmland and the artificial forests in rehabilitated land with a history of approximately 30 years were compared. Our results showed that "Grain for Green" significantly increased soil organic carbon （SOC） content and SOC stock in all soil layers. The SOC stock of the surface layer （0-20 cm） increased by 25.86 t·hm-2, and the annual SOC stocks ratio was 0.89 t·hm-2. Soil total nitrogen （TN） content increased slightly but only in the 0-20 cm soil layer. Compared with those in sloping farmland, the differences in available C and N nutrients such as soil nitrate N （NO3--N）, ammonia N （NH4+-N）, and dissolved organic C （DOC） in the whole soil profile （0-70 cm） were basically not significant （P > 0.05）. In addition, our research also found that slope position had significant effects on the contents of TN, SOC, NO3--N, NH4+-N, and DOC in farmland soil （P< 0.05）. The variation trend of soil NO3--N, NH4+-N, and DOC contents along the slope was as follows： upper slope < middle slope < lower slope, whereas the soil TN and SOC contents were highest in the lower slope, followed by the upper slope and middle slope. The position of the slope had a significant impact only on DOC content in forest soil, which increased along the slope. This research indicated that when evaluating the impact of land use changes on soil C and N stocks in the purple soil hilly region, the influence of topographic factors cannot be ignored.

[Impact of Land Use Change on Carbon Storage in Urban Agglomerations in the Guanzhong Plain].

It is important to study the impact of land use change on terrestrial ecosystem carbon stocks in urban agglomerations for the optimization of land use structure and sustainable development in urban agglomerations. Based on the patch-generating land use simulation (PLUS) model and integrated valuation of ecosystem services and trade-offs (InVEST) model, a simulation was developed that predicted the land use change and carbon stock of the Guanzhong Plain urban agglomeration in 2040 under different scenarios and further analyzed the impact of land use change on carbon stock. The results showed that:① The land use types of the Guanzhong Plain urban agglomeration were mainly cultivated land, forest land, and grassland, which accounted for more than 90 % of the total study area. ② From 2000 to 2020, the carbon stock in the Guanzhong Plain showed a continuous downward trend, with cropland, woodland, and grassland being the main sources of carbon stock in the Guanzhong Plain, and the overall carbon stock declined by 15.12×106 t, with the spatial distribution presenting the distribution characteristics of "high in the north and south and low in the middle." ③ By 2040, the carbon stock would decrease the most under the urban development scenario, with a total reduction of 27.08×106 t, and the least under the ecological development scenario, with a total reduction of 4.14×106t. The research results can provide data support for the high-quality development and rational land use planning of the Guanzhong Plain urban agglomeration.

[Spatial Distribution Characteristics of Soil Carbon and Nitrogen in Citrus Orchards on the Slope of Purple Soil Hilly Area].

Since the 1990s, a large area of sloping farmland in a purple soil hilly region of southwest China was converted into an orchard to prevent soil erosion, increase soil fertility, and elevate economic benefits for farmers. In order to explore the spatial distribution of soil carbon (C) and nitrogen (N) fractions on the slope of returning arable lands to citrus orchards in purple soil hilly areas, a soil sampling event was carried out in a citrus orchard at the Yanting Agro-ecological Experimental Station of Purple Soil, Chinese Academy of Sciences, to examine the differences in soil C and N fractions and their influencing factors. The results showed that the slope position had significant effects on the contents of soil total nitrogen (TN), nitrate nitrogen (NO3--N), and dissolved organic carbon (DOC) (P < 0.05), but the effects were not obvious regarding the total organic carbon (SOC) and ammonia nitrogen (NH4+-N) of the soil (P > 0.05). For topsoil (0-30 cm), the variation trend of soil NO3--N content along the slope was upper slope < middle slope < lower slope, whereas the TN and DOC contents along the slope exhibited the trend of upper slope > middle slope > lower slope. The contents of soil C and N in each slope position generally showed a downward trend with increasing soil depth (0-30 cm). The contents of soil TN, SOC, NO3--N, and DOC were significantly affected by soil depth (P < 0.05). The TN storage (0-30 cm) significantly decreased from the top to the bottom within the soil slope, with a value of 2.37, 1.89, and 1.62 t·hm-2 (reported as N) for the upper slope, middle slope, and lower slope, respectively. There was no significant difference in SOC reserves along the slope, with a range from 56.12 to 58.48 t·hm-2 (reported as C). Our results provide scientific basis for understanding the spatial distribution of soil nutrients of the restored farmland in purple soil hilly areas. Our research suggests that the spatial distribution of soil carbon and nitrogen storage should not be ignored when predicting the response of soil nutrients to land use change.

[Spatial Distribution of Nitrogen and Phosphorus Nutrients in the Main Stream and Typical Tributaries of Tuojiang River and Fujiang River].

The Tuojiang River and Fujiang River, two important tributaries of the upper reaches of the Yangtze River, have serious water pollution problems, among which nitrogen (N) and phosphorus (P) are the most important pollutants. Therefore, the aim of this study was to identify the influencing factors of water quality in different spaces and provide a scientific basis for the prevention and control of surface water pollution in the upper reaches of the Yangtze River and its tributaries. Water samples of trunk and tributaries in the Tuojiang River and Fujiang River were collected, and the spatial distribution characteristics of water N and P were analyzed. The results showed that the Tuojiang River and Fujiang River showed serious pollution of total nitrogen (TN), with a water quality worse Ⅴ-section proportion as high as 94% and 50%, respectively. Both rivers showed that TN and TP concentrations in the tributaries were higher than those in the main stream. For both rivers, total phosphorus (TP), with moderate pollution, was mainly concentrated in Ⅱ, Ⅲ, and Ⅳ class water quality, whereas the P pollution was more serious for the Fujiang River compared to that of the Fujiang River. For the Tuojiang River, nitrate nitrogen (NN) concentration from upstream to downstream showed a trend of decreasing after the first increase, with the maximum concentration of ammonium nitrogen (AN) exhibiting at the upstream site. In particular, TP concentration increased significantly after rivers flowed through a city. For the Fujiang River trunk stream, TN and NN concentration exhibited a gradually increasing trend from the middle to lower reaches. Generally, our study revealed that TN, TP, and NN in the rivers were affected by water pH and water temperature (T). Therefore, the control of N and P pollution in rivers should pay attention to the influence of water environmental factors.

Serum uric acid: A risk factor for right ventricular dysfunction and prognosis in heart failure with preserved ejection fraction.

Background: Hyperuricemia and right ventricular dysfunction (RVD) are both widespread in heart failure with preserved ejection fraction (HFpEF) patients. RVD is associated with a poor prognosis in HFpEF. The correlation between serum uric acid (UA) levels and right ventricular function is unclear. The prognostic performance of UA in patients with HFpEF needs further validation. Methods and results: A total of 210 patients with HFpEF were included in the study and divided into two groups according to UA level: the normal UA group (≤7 mg/dl) and the high UA group (>7 mg/dl). The variables examined included clinical characteristics, echocardiography, and serum biochemical parameters. Right ventricular function was assessed by tricuspid annular plane systolic excursion (TAPSE) and tricuspid annular peak systolic velocity (TAPSV). Baseline characteristics were compared between the two groups, and the correlation between baseline UA and RVD was assessed using multifactorial binary logistic regression. Kaplan-Meier curves were used to describe all-cause mortality and heart failure readmission. Results showed that right ventricular function parameters were worse in the high UA group. After adjusting for UA, left ventricular posterior wall thickness (LVPWT), N-terminal B-type natriuretic peptide (NT-proBNP), atrial fibrillation (AF), and low-density lipoprotein cholesterol (LDL-C), UA (odds ratio = 2.028; p < 0.001) was independently associated with RVD, and UA >7 mg/dl (HR = 2.98; p < 0.001) was associated with heart failure readmission in patients with HFpEF. Conclusion: Elevated serum UA is closely associated with RVD and significantly associated with the heart failure readmission rate in patients with HFpEF.

TMT proteomics analysis of a pseudocereal crop, quinoa (Chenopodium quinoa Willd.), during seed maturation.

Quinoa (Chenopodium quinoa Willd.), an Andean native crop, is increasingly popular around the world due to its high nutritional content and stress tolerance. The production and the popularity of this strategic global food are greatly restricted by many limiting factors, such as seed pre-harvest sprouting, bitter saponin, etc. To solve these problems, the underlying mechanism of seed maturation in quinoa needs to be investigated. In this study, based on the investigation of morphological characteristics, a quantitative analysis of its global proteome was conducted using the combinational proteomics of tandem mass tag (TMT) labeling and parallel reaction monitoring (PRM). The proteome changes related to quinoa seed maturation conversion were monitored to aid its genetic improvement. Typical changes of morphological characteristics were discovered during seed maturation, including mean grain diameter, mean grain thickness, mean hundred-grain weight, palea, episperm color, etc. With TMT proteomics analysis, 581 differentially accumulated proteins (DAPs) were identified. Functional classification analysis and Gene Ontology enrichment analysis showed that most DAPs involved in photosynthesis were downregulated, indicating low levels of photosynthesis. DAPs that participated in glycolysis, such as glyceraldehyde-3-phosphate dehydrogenase, pyruvate decarboxylase, and alcohol dehydrogenase, were upregulated to fulfill the increasing requirement of energy consumption during maturation conversion. The storage proteins, such as globulins, legumins, vicilins, and oleosin, were also increased significantly during maturation conversion. Protein-protein interaction analysis and function annotation revealed that the upregulation of oleosin, oil body-associated proteins, and acyl-coenzyme A oxidase 2 resulted in the accumulation of oil in quinoa seeds. The downregulation of ß-amyrin 28-oxidase was observed, indicating the decreasing saponin content, during maturation, which makes the quinoa "sweet". By the PRM and qRT-PCR analysis, the expression patterns of most selected DAPs were consistent with the result of TMT proteomics. Our study enhanced the understanding of the maturation conversion in quinoa. This might be the first and most important step toward the genetic improvement of quinoa.

Tribenzotriquinacenes bearing six-fold benzofuran extensions: electron-rich C3v-symmetrical hosts for C60.

New tribenzotriquinacene (TBTQ) hosts bearing six-fold peripheral benzofuran functionalization have been synthesized. The three polycondensed arene wings were shown to operate optically independently and to generate deeply bowl-shaped C(3v)-symmetrical frameworks that act as relatively weak hosts toward C(60), as revealed by (1)H NMR spectroscopy.

Myosin 1b promotes migration, invasion and glycolysis in cervical cancer via ERK/HIF-1α pathway.

BACKGROUND: Increasing evidence indicated that metabolic reprograming is essential and has been regarded as a hallmark of cancer. Although the biological functions of Myosin 1b (Myo1b) have been reported in several malignancies, the correlation between Myo1b and cancer metabolism, and its underlying mechanisms remain elusive, particularly in cervical cancer (CC). METHODS: Myo1b and other glycolytic enzymes expression levels were examined in CC cells and tumor tissues from xenograft models by quantitative real-time PCR, Western blot and immunohistochemistry. The biological impacts and regulatory mechanisms of Myo1b on cell migration, invasion and glycolysis were explored. Also, the effects of Myo1b on carcinogenesis and metastasis in nude mice were investigated. RESULTS: Upregulation of Myo1b was found in CC tissues and associated with poor prognosis. Overexpressed Myo1b not only significantly elevated CC cell glycolysis, migration and invasion in vitro, but also promoted tumorigenesis and metastasis in vivo. Conversely, Myo1b knockdown had opposite consequences. Moreover, our study suggested that Myo1b stimulated ERK/HIF-1α pathway and its downstream glycolysis associated genes to modulate the glycolysis, migration and invasion of CC. CONCLUSION: These findings provide evidence that Myo1b regulates migration, invasion and glycolysis in CC through ERK/HIF-1α pathway, suggesting a promising remedial target in treatment of CC.

Synthesis and optical resolution of inherently chiral difunctionalized tribenzotriquinacenes.

The synthesis of several inherently chiral tribenzotriquinacenes (TBTQs) bearing one single mono- or difunctionalized aromatic nucleus and the optical resolution of one of these derivatives, a TBTQ-based salicylic acid (11), are described for the first time. Efficient access to enantiopure, inherently chiral tribenzotriquinacenes may lay a foundation for studies of novel container compounds, supramolecular aggregation, chiral recognition, and asymmetric catalysis.

[Spatial-temporal Variations and the Regulators of Nitrate Status in Shallow Groundwater of the Typical Mountainous Agricultural Watershed in the Upper Reaches of the Yangtze River].

Shallow groundwater is the main drinking water supply for the mountainous area in the upper reaches of the Yangtze River, while its quality is often degraded by nitrate (NO3--N) pollution due to intensive agricultural production activities. In the present study, we selected a mountainous agricultural watershed in the upper reaches of the Yangtze River to investigate the land use, management, and hydrogeological conditions, aiming to clarify the spatial-temporal variations in NO3--N concentration of shallow groundwater, thereby exploring the key regulators. The results showed that the NO3--N concentrations of the groundwater ranged from 0.40 to 12.51 mg ·L-1in the study area, and the exceeding ratio was nearly 30%. On an average, NO3--N concentrations for the wet season were higher than that for the dry season, indicating great variations in NO3--N concentration across different seasons. In addition, the spatial variations of NO3--N concentration in groundwater were also significant among different sub-catchment, which was mainly due to variations in the groundwater table depth and land uses. Furthermore, the significant correlations between the NO3--N concentrations and concentrations of Cl-, NH4+-N, DOC, and SO42- in the shallow groundwater were also explored in this study, suggesting that the NO3--N concentrations were likely to depend on the chemical factors of the shallow groundwater in the study area. Overall, our current study highlights that the characterization of spatial-temporal variations of NO3--N status in shallow groundwater and illustration of key regulators are essential to mitigate NO3--N pollution and prevent quality degradation of shallow groundwater in mountainous rural areas of the upper Yangtze River watershed.

Isolation and characterization of Bacillus subtilis strain 1-L-29, an endophytic bacteria from Camellia oleifera with antimicrobial activity and efficient plant-root colonization.

Endophytic bacteria, which are common in plant tissues, may help to control plant pathogens and enhance plant growth. Camellia oleifera, an oil-producing plant, is widely grown in warm, subtropical, hilly regions in China. However, C. oleifera is strongly negatively affected by C. oleifera anthracnose, which is caused by Colletetrichum fructicola. To find a suitable biocontrol agent for C. oleifera anthracnose, 41 endophytes were isolated from the stems, leaves, and roots of C. oleifera. Bacterial cultures were identified based on analyses of 16S rDNA sequences; most strains belonged to the genus Bacillus. The antagonistic effects of these strains on C. fructicola were tested in vitro. In total, 16 strains inhibited C. fructicola growth, with B. subtilis strain 1-L-29 being the most efficient. Strain 1-L-29 demonstrated antagonistic activity against C. siamense, C. asianum, Fusarium proliferatum, Agaricodochium camellia, and Pseudomonas syringae. In addition, this strain produced indole acetic acid, solubilized phosphate, grew on N-free media, and produced siderophores. To facilitate further microecological studies of this strain, a rifampicin-resistant, green fluorescent protein (GFP)-labeled strain, 1-L-29gfpr, was created using protoplast transformation. This plasmid had good segregational stability. Strain 1-L-29gfpr was re-introduced into C. oleifera and successfully colonized root, stem, and leaf tissues. This strain remained at a stable concentration in the root more than 20 d after inoculation. Fluorescence microscopic analysis showed that strain 1-L-29gfpr thoroughly colonized the root surfaces of C. fructicola as well as the root vascular tissues of Arabidopsis thaliana.