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Straw return has important impacts on black soil protection, food security, and environmental protection. One year of straw return (S1) reduces rice yield and increases greenhouse gas (GHG) emissions. However, the effects of successive years of straw return on rice yield, soil nutrients, and GHG emissions in the northeast rice region are still unclear. Therefore, we conducted four successive years of straw return (S4) in a positional experiment to investigate the effects of different years of straw return on rice yield, soil nutrients, and GHG emissions in the northeast rice region. The experimental treatments included the following: no straw return (S0), a year of straw return (S1), two successive years of straw return (S2), three successive years of straw return (S3), and four successive years of straw return (S4). Compared with S1, the rice yields of S2, S3, and S4 increased by 10.89%, 15.46%, and 16.98%, respectively. But only S4 increased by 4.64% compared to S0, while other treatments were lower than S0. S4 increased panicles per m2 and spikelets per panicle by 9.34% and 8.93%, respectively, compared to S1. Panicles per m2 decreased by 8.06% at S4 compared to S0, while spikelets per panicle increased by 13.23%. Compared with S0, the soil organic carbon, total nitrogen, NH4+-N, NO3--N, available phosphorus, and available potassium of S4 increased by 11.68%, 10.15%, 24.62%, 21.38%, 12.33%, and 13.35%, respectively. Successive years of rice straw return decreased GHG intensity (GHGI). Compared with S1, the GHGI of S4, S3, and S2 decreased by 16.2%, 11.84%, and 9.36%, respectively. Thus, S4 increased rice yield and soil nutrients, reducing GHGI.

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BACKGROUND: The diagnosis of tuberculous pleurisy (TP) presents a significant challenge due to the low bacterial load in pleural effusion (PE) samples. Cell-free Mycobacterium tuberculosis DNA (cf-TB) in PE samples is considered an optimal biomarker for diagnosing TP. This study aimed to evaluate the applicability of cf-TB testing across diverse research sites with a relatively large sample size. METHODS: Patients suspected of TP and presenting with clinical symptoms and radiological evidence of PE were consecutively enrolled by treating physicians from 11 research sites across 6 provinces in China between April 2020 and August 2022. Following centrifugation, sediments obtained from PE were used for Xpert MTB/RIF (Xpert) and mycobacterial culture, while the supernatants were subjected to cf-TB testing. This study employed a composite reference standard to definite TP, which was characterized by any positive result for Mycobacterium tuberculosis (MTB) through either PE culture, PE Xpert, or pleural biopsy. RESULTS: A total of 1412 participants underwent screening, and 1344 (95.2%) were subsequently enrolled in this study. Data from 1241 (92.3%) participants were included, comprising 284 with definite TP, 677 with clinically diagnosed TP, and 280 without TP. The sensitivity of cf-TB testing in definite TP was 73.6% (95% CI 68.2-78.4), significantly higher than both Xpert (40.8%, 95% CI 35.3-46.7, P < 0.001) and mycobacterial culture (54.2%, 95% CI 48.4-59.9, P < 0.001). When clinically diagnosed TP was incorporated into the composite reference standard for sensitivity analysis, cf-TB testing showed a sensitivity of 46.8% (450/961, 95% CI 43.7-50.0), significantly higher than both Xpert (116/961, 12.1%, 95% CI 10.2-14.3, P < 0.001) and mycobacterial culture (154/961, 16.0%, 95% CI 13.8-18.5, P < 0.001). The specificities of cf-TB testing, Xpert, and mycobacterial culture were all 100.0%. CONCLUSIONS: The performance of cf-TB testing is significantly superior to that of Xpert and mycobacterial culture methods, indicating that it can be considered as the primary diagnostic approach for improving TP detection. Trial registration The trial was registered on Chictr.org.cn (ChiCTR2000031680, https://www.chictr.org.cn/showproj.html?proj=49316 ).

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This study aims to elucidate the therapeutic effect and mechanism of Jingfang Granules on acute lung injury, and to investigate the regulatory effect of Jingfang Granules on the metabolic disorders of endogenous metabolites in feces and the homeostasis of intestinal microbiota in acute lung injury, mice were randomly divided into a sham group, a model group, and a Jingfang Granules group. After modeling, the mice were continuously administered for 6 days. Using ultra-high performance liquid chromatography quadrupole/electrostatic field orbital trap high-resolution mass spectrometry(UHPLC-HESI-QE-Orbitrap-MS/MS) metabolomics technology and 16S rRNA high-throughput sequencing technology, changes in endogenous small molecule substances and gut microbiota in mouse intestines were determined, and potential biomarkers were identified. The results showed that Jingfang Granules can regulate 11 biomarkers, including L-glutamic acid, succinic acid, arachidonic acid, linoleic acid, linolenic acid, phenylalanine, sphingosine, 2-hydroxy-2-methyl butyric acid, pyruvate, tryptophan, and palmitic acid. Metabolic pathway analysis was conducted on these 11 biomarkers using the online software MetaboAnalyst, identifying potential major metabolic pathways. Among them, a total of 10 metabolic pathways are closely related to the treatment of acute lung injury with Jingfang Granules, including alanine, aspartate and glutamate metabolism, aminoacyl-tRNA biosynthesis, citrate cycle(TCA cycle), alyoxylate and dicarboxylate metabolism, arginine and proline metabolism, linoleic acid metabolism and linolenic acid metabolism, nitrogen metabolism, D-glutamine and D-gluta-matemetabolism, phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism. The results of gut microbiota showed significant differences in bacteria, mainly including Bacteroides, Akkermansia, Lachnospiraceae＿NK4A136＿group, Lachnochlostridium, and Klebsiella. Spearman analysis confirms that Akkermansia and Lachnospiraceae＿NK4A136＿group is a significant positive correlation between the abundance of succinic acid, arachidonic acid, linolenic acid, linoleic acid, butyric acid, and pyruvate in the group; Bacteroides, Klebsiella, Lachnochlostrium are significantly positively correlated with the abundance of L-glutamic acid, phenylalanine, and sphingosine. The above results indicate that the therapeutic effect of Jingfang Granules on acute lung injury is achieved by improving the imbalance of gut microbiota in mice with acute lung injury, balancing the metabolism of alanine, biosynthesis of aminoacyl tRNA, aspartic acid, glutamate, tricarboxylic acid cycle, biosynthesis of phenylalanine, tyrosine, tryptophan, and metabolism of linoleic acid.

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Neurodevelopment and neuronal function are modulated by multiple factors including environment,genetics and epigenetics.As a post-translational modification,N-glycosylation is catalyzed by glycosyltransferase and involves in diverse biological processes.N-glycosylation is abundant in neuronal system,regulates the development and maturation of synapse,and inflammatory response of glial cells.The dysregulation of N-glycosylation induces neurological disorders including Alzheimer's disease,congenital disorders of glycosylation,schizophrenia and epilepsy.In the present review,we have summarized the progresses of N-glycosylation in regulating neuronal and astrocytic function,and its roles in neurological disorders and related mechanisms.

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Objective To evaluate the testing capabilities of laboratories,analyze existing issues,and improve testing quality,through carrying out the external quality assessment(EQA)of clinical laboratories for human papillomavirus(HPV)type 6 and 11 nucleic acid detection.Methods EQA plan was carried out twice a year.Each panel contains 4 positive samples,including one strong positive sample and one weak positive sample of HPV6 and HPV11,made from cervical secretions from patients with clinical manifestations of condyloma acuminata(CA)and positive for HPV6 or HPV11(from Shanghai First Maternity and Infant Hospital).One negative sample was cultured from the C-33A cell line(from Chinese Academy of Sciences).Samples were sent to participating laboratories by cold chain,and laboratories were required to detect test samples and upload their results within the specified time.Shanghai Center for Clinical Laboratory(SCCL)calculated the scores of each laboratory based on the return results.Results A total of 163 sample panels were sent out in the 6 rounds of EQA plan and 140 valid reports were received.The laboratory qualification rate was 96.43%(135/140)and the sample compliance rate was 97.86%(685/700).There were 13 false negative results and 2 false positive results,with weakly positive samples accounting for 76.92%(10/13)of the false negative results.Conclusion The detection accuracy of HPV6/11 nucleic acid in each laboratory was relatively high,and the detection ability of weak positive samples in individual laboratories may need to be improved.The laboratory could discover problems and improve its quality management by participating in EQA.

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This paper proposes a two-dimensional precision level for real-time measurement using a zoom fast Fourier transform (zoom FFT)-based decoupling algorithm that was developed and integrated in an FPGA. This algorithm solves the contradiction between obtaining high resolution and obtaining high measurement speed, and achieves both high angle-resolution measurement and real-time measurement. The proposed level adopts a silicone-oil surface as the angle-sensitive interface and combines the principle of homodyne interference. By analyzing the frequency of the interference fringes, the angle variation can be determined. The zoom-FFT-based decoupling algorithm improves the system's frequency resolution of the interference fringes, thereby significantly enhancing the angle resolution. Furthermore, this algorithm improves the efficiency of angle decoupling, while the angle decoupling process can also be transplanted to the board to realize real-time measurement of the level. Finally, a prototype based on the level principle was tested to validate the effectiveness of the proposed method. The principle analysis and test results showed that the angle resolution of the prototype improved from 9 arcsec to about 0.1 arcsec using this angle-solution method. At the same time, the measurement repeatability of the prototype was approximately ±0.2 arcsec. In comparison with a commercial autocollimator, the angle measurement accuracy reached ±0.6 arcsec.

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Fructus Psoraleae (FP), one of the important traditional Chinese medicines, is widely used in clinic and has been reported to be hepatotoxic. However, there is no report on the mechanism of FP-induced hepatotoxicity based on the theory of You Gu Wu Yun. In this study, plasma samples of rats with different kidney deficiency syndromes were investigated using a lipidomics approach based on UPLC/Q-TOF-MS technique. Firstly, multivariate statistical analysis, VIP value test, statistical test and other methods were used to find the lipid metabolites in the two syndrome model groups that were different from the normal group. The screening of differential lipid metabolites revealed that there were 12 biomarkers between the blank group and the kidney-yang deficiency model group as well as 16 differential metabolites between the kidney-yin deficiency model group, and finally a total of 17 relevant endogenous metabolites were identified, which could be used as differential lipid metabolites to distinguish between kidney-yin deficiency and kidney-yang deficiency evidence. Secondly, the relative content changes of metabolites in rats after administration of FP decoction were further compared to find the substances associated with toxicity after administration, and the diagnostic ability of the identified biomarkers was evaluated using a receiver operating characteristic curve (ROC). Results a total of 14 potential differential lipid metabolites, including LysoPC(20:0/0:0) and LysoPC(16:0/0:0), which may be related to hepatotoxicity in rats with kidney-yin deficiency syndrome were further screened, namely, the potential active lipid metabolites related to hepatotoxicity in rats induced by FP. Finally, cluster analysis, MetPA analysis and KEGG database were used to analyze metabolic pathways. It was discovered that the metabolism of glycerophospholipid and sphingolipid may be strongly related to the mechanism of hepatotoxicity brought on by FP. Overall, we described the lipidomics changes in rats treated with FP decoction and screened out 14 lipid metabolites related to hepatotoxicity in rats with kidney-yin deficiency, which served as a foundation for the theory of "syndrome differentiation and treatment" in traditional Chinese medicine and a guide for further investigation into the subsequent mechanism.

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BACKGROUND: Chromosomal Xq28 region duplication encompassing methyl-CpG-binding protein 2 (MECP2) results in an identifiable phenotype and global developmental delay known as MECP2 duplication syndrome (MDS). This syndrome has a wide range of clinical manifestations, including abnormalities in appearance, neurodevelopment, and gastrointestinal motility; recurrent infections; and spasticity. Here, we report a case of confirmed MDS at our institution. CASE SUMMARY: A 12-year-old Chinese boy presented with intellectual disability (poor intellectual [reasoning, judgment, abstract thinking, and learning] and adaptive [lack of communication and absent social skills, apraxia, and ataxia] functioning) and dysmorphism. He had no history of recurrent infections, seizures, or bowel dysfunction, which is different from that in reported cases. Microarray comparative genomic hybridization confirmed MECP2 duplication in the patient and his mother who is a carrier. The duplication size was the same in the patient and his mother. No prophylactic antibiotic or anti-seizure therapy was offered to the patient or his mother before or after the consultation. CONCLUSION: MDS is rare and has various clinical presentations. Clinical suspicion is critical in patients presenting with developmental delays.

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PURPOSE: Emergence agitation is a common postoperative complication during recovery in children. The purpose of this study is to explore whether the use of ice popsicle could prevent emergence agitation in children undergoing oral surgery with sevoflurane anaesthesia. DESIGN AND METHODS: In this prospective randomized controlled study, 100 children undergoing oral surgery were randomly assigned to Group 1 which received ice popsicle after emergence (intervention, n = 50) or Group 2 which received verbal encouragement from their parents (control, n = 50). The primary outcome was the 2-hour postoperative incidence of EA. RESULTS: Group 1 had a significant lower incidence of emergence agitation (22% vs 58%, P < 0.001) compared with Group 2. The mean agitation score was significantly lower in Group 1 vs Group 2 at 10  minutes (1.64 vs 2.12, P = 0.024) and 20 min (1.60 vs 2.14, P = 0.004) after emergence. The peak agitation and pain scores were significantly lower in Group 1 than in Group 2 (P < 0.001). CONCLUSIONS: Findings from this study suggest that ice popsicle is an effective, cheap, pleasurable, and easily administered method for alleviating emergence agitation in paediatric patients after oral surgery under general anaesthesia. These results are worthy of confirmation in other surgeries. PRACTICE IMPLICATIONS: This approach is highly accepted by both children and their parents, and our findings support the effectiveness of ice popsicle in relieving emergence agitation and pain after oral surgery in children. CLINICAL TRIALS REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800015634.

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To add value to ordinary kitchen waste, heterogeneous acid-base catalytic methanolysis was conducted to produce high-value liquid biofuels, methyl levulinate (ML) and fatty acid methyl esters (FAMEs). Yields of 53.3 % ML and 98.5 % FAME were achieved by methanolysis of kitchen waste under the co-catalysis of carbon-silica composite (C/Si-SO3H) and zirconium modified ultrastable Y zeolite (Zr/USY). These target products can be easily recovered from the methanolic phase and can be purified at the end of the reaction. The collaborative combination of C/Si-SO3H and Zr/USY exhibited higher activity than their commercial counterpart. This strategy can be applied to differently composed kitchen waste and kitchen waste with different water content. Product yields were predicted using an artificial neural network method, and the relative importance of the influencing factors was investigated by the random forest method. The systematic insight gained from this work supports the value-added utilization of kitchen waste.

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Objective: To establish and optimize a TaqMan-probe quantitative real-time PCR (qPCR) assay for the detection of 7 important Rickettsiales pathogens and simultaneous identification of the infection types. Methods: Based on the ompB gene of Rickettsia prowazekii, Rickettsia mooseri and spotted fever group rickettsiae, the groEL gene of Orientia tsutsugamushi, the 16S rRNA of Ehrlichia chaffeensis, the gltA gene of Anaplasma phagocytophilum and the com1 gene of Coxiella burnetii, we synthesized primers and TaqMan-probes and optimized the reaction system and reaction process to same solution. The sensitivity, specificity and reproducibility of this assay were evaluated and the assay was used for the detection of simulated and actual samples. Results: The Ct value of the standard curves of the 7 pathogens showed a good linear relationship with the number of DNA copies (all R2 >0.990 0), the minimum detection limit was 10 copies/μl, showing good specificity. In the 96 tick nucleic acid extracts, Coxiella burnetii was detected in 1 sampleand spotted fever group Rickettsiae was detected in 3 samples. In the 80 blood samples from patients with undefined febrile illness, Orientia tsutsugamushi was detected in 1 sample and spotted fever group rickettsiae was detected in 2 samples. Conclusions: In this study, based on the established TaqMan-probe qPCR assay, the reaction system and reaction condition of the 7 important pathogens of Rickettsiales were optimized to the same solution. This method overcomes the shortcomings of using different reaction systems and reaction conditions for different pathogens, which can precisely identify the species of 7 important pathogens of Rickettsiales in clinical sample detections and is important for the infection type identification and laboratory detection time reduction to facilitate precise treatment of the patients.

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In recent years, artificial intelligence (AI) and oncology are rapidly integrated and developed, gradually moving towards clinical application. In China, the incidence and mortality of gastric cancer rank first among various tumors. The development of AI technologies such as convolutional neural network, narrow-band imaging magnifying endoscope, full-field digital section and survival circulation network has the potential to be applied to early screening, auxiliary diagnosis, pathological diagnosis, prognosis analysis, as well as individualized diagnosis and treatment process of gastric cancer. However, AI medical treatment still has many problems such as insufficient data sample size and difficulty in integration. Reasonable design and application of AI technology is expected to provide more scientific and accurate diagnosis and treatment for patients with gastric cancer, improve the overall survival rate and quality of life of patients with gastric cancer, and achieve more breakthroughs in the medical field.

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Abstract@#Myopia has become a major global public health problem. Exposure to outdoor light may explain the protective effect of outdoor activities on myopia. Currently, a growing number of studies focus on the effects of the spectrum on eye health. Recent studies have found that violet light may have a protective effect on myopia, but the mechanism of action between violet light and myopia is not yet fully understood. The paper reviews the association between violet light and myopia prevention and control, and the possible mechanisms of violet light and myopia to provide a reference value for further exploration of the role of violet light on myo pia .

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Cavity-enhanced electro-optic comb generators (CEEOCGs) can provide optical frequency combs with excellent stability and configurability. The existing methods for CEEOCGs spectrum characterization, however, are based on approximations and have suffered from either iterative calculations or limited applicable conditions. In this paper, we show a spectrum characterization method by accumulating the optical electrical field with respect to the count of the round-trip propagation inside of CEEOCGs. The identity transformation and complete analysis of the intracavity phase delay were conducted to eliminate approximations and be applicable to arbitrary conditions, respectively. The calculation efficiency was improved by the noniterative matrix operations. Setting the maximum propagation count as 1000, the spectrum of the center ±300 comb modes can be characterized with merely the truncation error of floating-point numbers within 1.2 s. More importantly, the effects of all CEEOCG parameters were comprehensively characterized for the first time. Accordingly, not only the exact working condition of CEEOCG can be identified for further optimization, but also the power of each comb mode can be predicted accurately and efficiently for applications in optical communications and waveform synthesis.

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High content imaging(HCI) technique that combines automatic high throughput with high-resolution cell imaging, is characterized by abundant data information, high imaging sensitivity, easy visualization and standardization, and is commonly used in the cellular(or subcellular) phenotypic analysis. Abundant phenotypic information can be obtained by using HCI in one experiment, including cellular morphology, cellular structure, and signal transduction pathways of related functions, on the basis of the maintenance of the integrity of cellular structures and functions. Multiple studies have shown that a series of dynamic spatio-temporal interactive change processes were induced by the disturbance of cells by specific factors, making cell phenotypes change accordingly, especially for the slight perturbation response of cells. Generally, the detection of one or several endpoint effect indicators is often difficult to accurately and comprehensively reflect the overall efficacy information of traditional Chinese medicine(TCM) because of its unique characteristics of multi-components and multi-targets. The application of HCI is thus helpful to discover the effective components and their action modes in the complex system of TCM. This paper reviewed the application progress in the HCI technique in the screening of active components and their regulation mechanism to provide references for further research.

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Selective catalytic conversion of carbohydrates to 5-ethoxymethylfurfural (EMF) is a critical approach to the biorefinery. In this work, solid acid catalysts of γ-AlOOH and CeO2@B2O3 were used to convert carbohydrates to EMF in a one-pot process, performed in an ethanol/DMSO solvent system. The synergistic effect of γ-AlOOH and CeO2@B2O3 was studied. Furthermore, the morpho-structural properties of the catalysts were characterized, and the effects of reaction time, reaction temperature, catalyst load, and the amount of cosolvent on the conversion of glucose to EMF were examined and optimized. Under the reaction conditions of 170 °C for 20 h, glucose, sucrose, cellobiose, inulin and starch were used as raw materials, and the EMF yield range was 9.2-27.7%. The results showed that the synergistic effect of γ-AlOOH and CeO2@B2O3 further causes the combination of multiple acid sites with different types and strength distributions. Particularly, the collaboration between weak, medium-strong, and strong acid, as well as between Lewis and Brønsted acidity, is of great significance for EMF generation. The reusability experiments showed that the combined catalytic system was easily separated and maintained catalytic activity for five successive reactions without further intermediate regeneration steps. This work provides a promising route for the catalytic conversion of biomass-derived carbohydrates into EMF.

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Water is one of the most important factors limiting vegetation recovery and agricultural development in arid and semi-arid areas. The reduction of ineffective soil evaporation can improve soil water use efficiency. As a kind of clay mineral, attapulgite (ATP) plays a critical role in limiting soil evaporation due to its hydrophilicity and adsorption. In this study, three typical soils with different textures (dark loessial soil, cultivated loess soil, and sandy soil) were selected from the arid and semi-arid area of the Loess Plateau, and five ATP additions (0%, 1%, 2%, 3% and 4%) were set for conducting soil evaporation experiments under natural conditions using micro-evaporators to investigate the effects of ATP addition on different soil evaporation processes and the characteristics of evaporation surface cracks. The results showed that the cumulative evaporation and evaporation loss ratio of the same soil decreased with the increases of ATP addition when the ATP addition was <3%. When ATP was added at 3%, the cumulative evaporation and evaporation loss ratio of dark loessial soil and sandy soil decreased, while those of cultivated loess soil increased. When ATP was added at 4%, the cumulative evaporation decreased and the evaporation loss ratio increased for dark loessial soil, the cumulative evaporation increased and the evaporation loss ratio decreased for sandy soil, and the cumulative evaporation and evaporation loss ratio decreased for cultivated loess soil. The average cumulative evaporation of different soils followed an order of dark loessial soil > cultivated loess soil > sandy soil. Soil water content of ATP treatment was consistently higher than that of control throughout the whole evaporation process in the same soil. Simulations of cumulative evaporation versus the square root of time indicated that the amount of water released from the ATP-treated soil samples at the end of evaporation was higher than that of the control. After the addition of ATP, the crack area density of dark loessial soil and cultivated loess soil increased significantly, and the crack area density of sandy soil increased with the increase of ATP addition. The crack area density of all three soils reached the maximum at 4% of ATP addition. In summary, ATP addition of 3% could minimize the ineffective evaporation of soil water.

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BACKGROUND: Mucosal-associated invariant T (MAIT) cells are systemically depleted in human immunodeficiency virus type 1 (HIV-1) infected patients and are not replenished even after successful combined antiretroviral therapy (cART). This study aimed to identify the mechanism underlying MAIT cell depletion. METHODS: In the present study, we applied flow cytometry, single-cell RNA sequencing and immunohistochemical staining to evaluate the characteristics of pyroptotic MAIT cells in a total of 127 HIV-1 infected individuals, including 69 treatment-naive patients, 28 complete responders, 15 immunological non-responders, and 15 elite controllers, at the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China. RESULTS: Single-cell transcriptomic profiles revealed that circulating MAIT cells from HIV-1 infected subjects were highly activated, with upregulation of pyroptosis-related genes. Further analysis revealed that increased frequencies of pyroptotic MAIT cells correlated with markers of systemic T-cell activation, microbial translocation, and intestinal damage in cART-naive patients and poor CD4+ T-cell recovery in long-term cART patients. Immunohistochemical staining revealed that MAIT cells in the gut mucosa of HIV-1 infected patients exhibited a strong active gasdermin-D (GSDMD, marker of pyroptosis) signal near the cavity side, suggesting that these MAIT cells underwent active pyroptosis in the colorectal mucosa. Increased levels of the proinflammatory cytokines interleukin-12 (IL-12) and IL-18 were observed in HIV-1 infected patients. In addition, activated MAIT cells exhibited an increased pyroptotic phenotype after being triggered by HIV-1 virions, T-cell receptor signals, IL-12 plus IL-18, and combinations of these factors, in vitro. CONCLUSIONS: Activation-induced MAIT cell pyroptosis contributes to the loss of MAIT cells in HIV-1 infected patients, which could potentiate disease progression and poor immune reconstitution.

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Alkaline soil is widely distributed in China. Its rational utilization is an effective measure to solve land shortage and improve the environment. Alfalfa is characterized by strong salt and alkali tolerance and high yield and protein content. Nitrogen (N) and phosphorus (P) are the main nutrients for plant growth, and N metabolism is one of the primary forms of plant metabolism, which plays a vital role in quality and yield formation. The exploration of the effect of N and P on N metabolism and alfalfa growth will provide a theoretical basis for scientific fertilization for alfalfa in the alkaline soil of the Yinchuan Plain of the Hetao Basin. Therefore, a 2-year experiment of N and P addition was conducted. Six treatments were set up with a randomized block design, including without N (WN), medium N (MN), high N (HN), without P (WP), medium P (MP), and high P (HP). It was found that the MN and MP treatments increased plant height, stem diameter, stem/leaf, dry/fresh, and dry matter of alfalfa. The HN and HP treatments inhibited alfalfa biomass formation. The MN and MP treatments increased key products and enzymes of leaf N metabolism of alfalfa and promoted activities of leaf nitrate reductase (NR), glutamine synthase (GS), glutamate synthase (GOGAT), glutamic-oxalacetic transaminase (GOT), and glutamic-pyruvate transaminase (GPT), and inhibited activities of leaf protease of alfalfa. The MN and MP treatments increased contents of leaf N, P, ammonium nitrogen (NH4 +-N), nitrate nitrogen (NO3 --N), total chlorophyll, and protein and reduced leaf chlorophyll a/b and amino acid, results after HN and HP treatments were opposite. The correlation among leaf P, N, NO3 --N, amino acid, and protein reached significant levels (P < 0.01). It is suggested that MN and MP treatments can improve the yield and quality of alfalfa by increasing key products and enzymes of N metabolism and can be adopted to promote alfalfa production in the alkaline soil of the Yinchuan Plain of the Hetao Basin.

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BACKGROUND: Yindan Xinnaotong soft capsule (YDXNT) is a clinically effective herbal prescription used for the treatment of cardiovascular and cerebrovascular diseases. Since Chinese medicines (CMs) exert their effects via a "multiple-components and multiple-targets" mode, discovery of the active compounds with interactive effects may contribute to reveal their mechanisms of action. PURPOSE: This study aimed to establish an image-based fingerprint-efficacy screening strategy to identify active compounds with interaction effects from CM prescription, using YDXNT to inhibit microglia-mediated neuroinflammation as an instance. METHODS: A multi-component random content-oriented chemical library of YDXNT was constructed by uniform design, and their chemical fingerprint was profiled by liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) methods. Then the neuroinflammation activities of chemical library members of YDXNT were determined by image-based dual phenotypic quantification. Subsequently, fingerprint-efficacy correlation and random forest analysis were applied to predict the potentially active compounds with interactive effects. Finally, the interactive effects among the active compounds were confirmed by quantitative polymerase chain reaction (qPCR) and apoptosis analysis, and network pharmacology was applied to explore the possible mechanisms. RESULTS: Image-based fingerprint-efficacy correlation analysis revealed that six tanshinones (TNs) and four flavonoids (FAs) were potential anti-neuroinflammatory compounds. The inter-family of TNs and FAs possessed obvious interactive effects (combination index ≤ 0.825). Moreover, the combination of scutellarein and tanshinone I (2:1, w/w) was discovered as the possible interactive combinatorial components, which, comparing with individual scutellarein or tanshinone I, shown more powerful effects on anti-inflammatory and anti-apoptotic effects in lipopolysaccharide (LPS)-induced BV2 cells. Network pharmacology showed that the active compounds might suppress microglia-mediated neuroinflammation via multiple targets in the T cell receptor, Jak-STAT, and Toll-like receptor signaling pathways. CONCLUSION: The image-based fingerprint-efficacy strategy simplifies the screening process of efficacious component combinations in CMs for complex diseases, which also offers a promising approach to explore the integrative therapeutic mechanisms of CMs.

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