Untargeted metabolomics reveals intervention effects of wine-processed Schisandra chinensis polysaccharide on Alzheimer's disease mice.

Schisandra chinensis (Turcz.) Baill (SC) is a traditional sedative in China, with wide applications for treating various neurological disorders. Its polysaccharide component has been gaining increased attention for its potential in nerve protection. While raw SC is the primary focus of current research, its processed products are primarily utilized as clinical medicines. Notably, limited research exists on the mechanisms underlying the effects of wine-processed Schisandra chinensis polysaccharide (WSCP) in Alzheimer's Disease (AD). Therefore, this study seeks to assess the therapeutic impact of WSCP on AD mice and investigate the underlying mechanisms through biochemical and metabolomics analyses. The results demonstrate that WSCP exerts significant therapeutic effects on AD mice by enhancing learning and memory abilities, mitigating hippocampal neuronal damage, reducing abnormal amyloid-beta (Aß) deposition, and attenuating hyperphosphorylation of Tau. Biochemical analysis revealed that WSCP can increase SOD content and decrease MDA, IL-6, and TNF-α content in AD mice. Furthermore, serum metabolomic results showed that WSCP intervention can reverse metabolic disorders in AD mice. 43 endogenous metabolites were identified as potential biomarkers for WSCP treatment of AD, and the major metabolic pathways were Ala, Glu and Asp metabolism, TCA cycle. Overall, these findings will provide a basis for further development of WSCP.

Carbon trade-off and energy budgeting under conventional and conservation tillage in a rice-wheat double cropping system.

Amid rising energy crises and greenhouse gas (GHG) emissions, designing energy efficient, GHG mitigation and profitable conservation farming strategies are pertinent for global food security. Therefore, we tested a hypothesis that no-till with residue retaining could improve energy productivity (EP) and energy use efficiency (EUE) while mitigating the carbon footprint (CF), water footprint (WF) and GHG emissions in rice-wheat double cropping system. We studied two tillage viz., conventional and conservation, with/without residue retaining, resulting as CT0 (puddled-transplanted rice, conventional wheat -residue), CTR (puddled-transplanted rice, conventional wheat + residue), NT0 (direct seeded rice, zero-till wheat -residue), and NTR (direct seeded rice, zero-till wheat + residue). The overall results showed that the NTR/NT0 had 34% less energy consumption and 1.2-time higher EP as compared to CTR/CT0. In addition, NTR increased 19.8% EUE than that of CT0. The grain yield ranged from 8.7 to 9.3 and 7.8-8.5 Mg ha-1 under CT and NT system, respectively. In NTR, CF and WF were 56.6% and 17.9% lower than that of CT0, respectively. The net GHG emissions were the highest (7261.4 kg CO2 ha-1 yr-1) under CT0 and lowest (4580.9 kg CO2 ha-1 yr-1) under NTR. Notably, the carbon sequestration under NTR could mitigate half of the system's CO2-eq emissions. The study results suggest that NTR could be a viable option to offset carbon emissions and water footprint by promoting soil organic carbon sequestration, and enhancing energy productivity and energy use efficiency in the South Asian Indo-Gangetic Plains.

Serglycin secreted by late-stage nucleus pulposus cells is a biomarker of intervertebral disc degeneration.

Intervertebral disc degeneration is a natural process during aging and a leading cause of lower back pain. Here, we generate a comprehensive atlas of nucleus pulposus cells using single-cell RNA-seq analysis of human nucleus pulposus tissues (three males and four females, age 41.14 ± 18.01 years). We identify fibrotic late-stage nucleus pulposus cells characterized by upregulation of serglycin expression which facilitate the local inflammatory response by promoting the infiltration of inflammatory cytokines and macrophages. Finally, we discover that daphnetin, a potential serglycin ligand, substantially mitigates the local inflammatory response by downregulating serglycin expression in an in vivo mouse model, thus alleviating intervertebral disc degeneration. Taken together, we identify late-stage nucleus pulposus cells and confirm the potential mechanism by which serglycin regulates intervertebral disc degeneration. Our findings indicate that serglycin is a latent biomarker of intervertebral disc degeneration and may contribute to development of diagnostic and therapeutic strategies.

Acetylshikonin promoting PI3K/Akt pathway and inhibiting SOX4 expression to delay intervertebral disc degeneration and low back pain.

This study investigated the molecular mechanism by which acetylshikonin inhibits SOX4 expression via the PI3K/Akt pathway to delay intervertebral disc degeneration (IVDD) and low back pain (LBP). Bulk RNA-seq, RT-qPCR, Western blot analysis, immunohistochemical staining, small interfering RNA (siSOX4), lentivirus (lentiv-SOX4hi ), and imaging techniques were used to assess SOX4 expression and validate its upstream regulatory pathway. Acetylshikonin and siSOX4 were injected into the IVD to measure IVDD. SOX4 expression significantly increased in degenerated IVD tissues. TNF-α increased SOX4 expression and apoptosis-related proteins in nucleus pulposus cells (NPCs). siSOX4 reduced TNF-α-induced NPCs apoptosis, while Lentiv-SOX4hi increased it. The PI3K/Akt pathway was significantly correlated with SOX4, and acetylshikonin upregulated PI3K/Akt pathway while inhibiting SOX4 expression. In the anterior puncture IVDD mouse model, SOX4 expression was upregulated, and acetylshikonin and siSOX4 delayed IVDD-induced LBP. Acetylshikonin delays IVDD-induced LBP by inhibiting SOX4 expression through the PI3K/Akt pathway. These findings offer potential therapeutic targets for future treatments.

Site-Specific Profiling of N-Glycans in Drosophila melanogaster.

BACKGROUND: Drosophila melanogaster is a well-studied and highly tractable genetic model system for deciphering the molecular mechanisms underlying various biological processes. Although being one of the most critical post-translational modifications of proteins, the understanding of glycosylation in Drosophila is still lagging behind compared with that of other model organisms. METHODS: In this study, we systematically investigated the site-specific N-glycan profile of Drosophila melanogaster using intact glycopeptide analysis technique. This approach identified the glycans, proteins, and their glycosites in Drosophila, as well as information on site-specific glycosylation, which allowed us to know which glycans are attached to which glycosylation sites. RESULTS: The results showed that the majority of N-glycans in Drosophila were high-mannose type (69.3%), consistent with reports in other insects. Meanwhile, fucosylated N-glycans were also highly abundant (22.7%), and the majority of them were mono-fucosylated. In addition, 24 different sialylated glycans attached with 16 glycoproteins were identified, and these proteins were mainly associated with developmental processes. Gene ontology analysis showed that N-glycosylated proteins in Drosophila were involved in multiple biological processes, such as axon guidance, N-linked glycosylation, cell migration, cell spreading, and tissue development. Interestingly, we found that seven glycosyltransferases and four glycosidases were N-glycosylated, which suggested that N-glycans may play a regulatory role in the synthesis and degradation of N-glycans and glycoproteins. CONCLUSIONS: To our knowledge, this work represents the first comprehensive analysis of site-specific N-glycosylation in Drosophila, thereby providing new perspectives for the understanding of biological functions of glycosylation in insects.

Health Status Recognition Method for Rotating Machinery Based on Multi-Scale Hybrid Features and Improved Convolutional Neural Networks.

Rotating machinery is susceptible to harsh environmental interference, and fault signal features are challenging to extract, leading to difficulties in health status recognition. This paper proposes multi-scale hybrid features and improved convolutional neural networks (MSCCNN) health status identification methods for rotating machinery. Firstly, the rotating machinery vibration signal is decomposed into intrinsic modal components (IMF) using empirical wavelet decomposition, and multi-scale hybrid feature sets are constructed by simultaneously extracting time-domain, frequency-domain and time-frequency-domain features based on the original vibration signal and the intrinsic modal components it decomposes. Secondly, using correlation coefficients to select features sensitive to degradation, construct rotating machinery health indicators based on kernel principal component analysis and complete health state classification. Finally, a convolutional neural network model (MSCCNN) incorporating multi-scale convolution and hybrid attention mechanism modules is developed for health state identification of rotating machinery, and an improved custom loss function is applied to improve the superiority and generalization ability of the model. The bearing degradation data set of Xi'an Jiaotong University is used to verify the effectiveness of the model. The recognition accuracy of the model is 98.22%, which is 5.83%, 3.30%, 2.29%, 1.52%, and 4.31% higher than that of SVM, CNN, CNN + CBAM, MSCNN, and MSCCNN + conventional features, respectively. The PHM2012 challenge dataset is used to increase the number of samples to validate the model effectiveness, and the model recognition accuracy is 97.67%, which is 5.63%, 1.88%, 1.36%, 1.49%, and 3.69% higher compared to SVM, CNN, CNN + CBAM, MSCNN, and MSCCNN + conventional features methods, respectively. The MSCCNN model recognition accuracy is 98.67% when validated on the degraded dataset of the reducer platform.

Development of a fast and robust liquid chromatography-mass spectrometry-based metabolomics analysis method for neonatal dried blood spots.

Dried blood spot (DBS) samples have been widely used in many fields including newborn screening, with the advantages in transportation, storage and non-invasiveness. The DBS metabolomics research of neonatal congenital diseases will greatly expand the understanding of the disease. In this study, we developed a liquid chromatography-mass spectrometry-based method for neonatal metabolomics analysis of DBS. The influences of blood volume and chromatographic effects on the filter paper on metabolite levels were studied. The levels of 11.11 % metabolites were different between 75 µL and 35 µL of blood volumes used for DBS preparation. Chromatographic effects on the filter paper occurred in DBS prepared with 75 µL whole blood and 6.67 % metabolites had different MS responses when central disks were compared with outer disks. The DBS storage stability study showed that compared with - 80 °C storage, storing at 4 °C for 1 year had obvious influences on more than half metabolites. Storing at 4 °C and - 20 °C for short term (< 14 days) and - 20 °C for longer term (1 year) had less influences on amino acids, acyl-carnitines and sphingomyelins, but greater influences on partial phospholipids. Method validation showed that this method has a good repeatability, intra-day and inter-day precision and linearity. Finally, this method was applied to investigate metabolic disruptions of congenital hypothyroidism (CH), metabolic changes of CH newborns were mainly involved in amino acid metabolism and lipid metabolism.

Humoral immunity and transcriptome differences of COVID-19 inactivated vacciane and protein subunit vaccine as third booster dose in human.

Under the background of the severe human health and world economic burden caused by COVID-19, the attenuation of vaccine protection efficacy, and the prevalence and immune escape of emerging variants of concern (VOCs), the third dose of booster immunization has been put on the agenda. Systems biology approaches can help us gain new perspectives on the characterization of immune responses and the identification of factors underlying vaccine-induced immune efficacy. We analyzed the antibody signature and transcriptional responses of participants vaccinated with COVID-19 inactivated vaccine and protein subunit vaccine as a third booster dose. The results from the antibody indicated that the third booster dose was effective, and that heterologous vaccination with the protein subunit vaccine as a booster dose induced stronger humoral immune responses than the homologous vaccination with inactivated vaccine, and might be more effective against VOCs. In transcriptomic analysis, protein subunit vaccine induced more differentially expressed genes that were significantly associated with many important innate immune pathways. Both the homologous and heterologous boosters could increase the effectiveness against COVID-19, and compared with the inactivated vaccine, the protein subunit vaccine, mediated a stronger humoral immune response and had a more significant correlation with the innate immune function module, which provided certain data support for the third booster immunization strategy.

Genomic G-quadruplex folding triggers a cytokine-mediated inflammatory feedback loop to aggravate inflammatory diseases.

DNA G-quadruplex is a non-canonical secondary structure that could epigenetically regulate gene expression. To investigate the regulating role of G-quadruplex, we devised an integrating method to perform the algorithm profiling and genome-wide analysis for the dynamic change of genomic G-quadruplex and RNA profiles in rat nucleus pulposus cells by inducing G-quadruplex folding with multiple stabilizers. A group of genes potentially regulated by G-quadruplex and involved in the inflammation process has been identified. We found that G-quadruplex folding triggers inflammation response by upregulating inflammatory cytokines, which could promote G-quadruplex folding in a manner of positive feedback loop. Moreover, we confirmed that G-quadruplex is a marker indicating elevated inflammatory status and G-quadruplex folding facilitates the development of inflammatory diseases using in vivo intervertebral disc degeneration models. The crosstalk between G-quadruplex and inflammatory cytokines plays a vital role in regulating inflammation-derived diseases, which may provide new insights into the blocking target.

[Comparison between macroscopic identification and DNA barcoding identification of Amomi Fructus].

This study aims to explore the consistency between macroscopic identification and DNA barcoding identification of Amomi Fructus. With the DNA barcoding identification results, we evaluated the reliability of identifying Amomi Fructus quality by combining macroscopic traits with main volatile chemical components. Thirteen batches of Amomi Fructus samples were collected for identification. Firstly, the morphological and sensory characteristics of each sample were observed and recorded according to the standard in Chinese Pharmacopoeia(2020 edition). The 100-fruit weight, longitudinal diameter, transverse diameter, and longitudinal diameter-to-transverse diameter ratio were measured, which correspond to large, solid, and full kernel representing good quality in the sensory evaluation. The odor value detected by electronic nose and major volatile components(borneol, camphor, limonene, and borneol acetate) correspond to the sensory evaluation of strong odor representing good quality. Secondly, DNA barcoding was employed to identify the 13 batches of samples. Finally, clustering analysis was performed for the main volatile components and macroscopic traits, and the identification results were compared with those of DNA barcoding. Except two batches of samples(No.6 and No.10), the macroscopic identification showed the results consistent with those of DNA barcoding, with an identification rate of 84.62%. The clustering results of the content of four volatile chemical components and macroscopic traits were also consistent with the DNA barcoding identification results. DNA barcoding can verify the results of macroscopic identification and provide a scientific basis for the inheritance and development of macroscopic identification. Moreover, the combination of macroscopic traits and chemical components demonstrates higher accuracy in the quality evaluation of Chinese medicinal materials.

Identification of Nutmeg With Different Mildew Degree Based on HPLC Fingerprint, GC-MS, and E-Nose.

Nutmeg (Myristicae Semen), the so-called Rou-Dou-Kou in Chinese, is one kind of Chinese herbal medicines (CHMs) as well as a globally popular spice. Hence, its stable quality and safe application attract more attention. However, it is highly prone to mildew during storage due to its rich volatile components and fatty oil. Therefore, in this study, an electronic nose (E-nose) was introduced to attempt to reliably and rapidly identify nutmeg samples with different degrees of mildew. Meanwhile, the chemical composition and volatile oil were analyzed using HPLC fingerprint and GC-MS, respectively, which could support and validate the result of E-nose. The results showed that the cluster results of HPLC fingerprint and GC-MS were generally consistent with E-nose, and they all clustered into two categories. Additionally, a discriminant model was established, which divided the samples into three categories: mildew-free, mildew-slight, and mildew, and a high DPR was obtained, which indicates that the E-nose could be a novel and promising approach for the establishment of a quality evaluation system to identify CHMs with different degrees of mildew rapidly, especially to identify early mildew.

Grem1 accelerates nucleus pulposus cell apoptosis and intervertebral disc degeneration by inhibiting TGF-ß-mediated Smad2/3 phosphorylation.

Intervertebral disc degeneration (IVDD) is a main cause of low back pain, and inflammatory factors play key roles in its pathogenesis. Gremlin-1 (Grem1) was reported to induce an inflammatory response in other fields. This study aimed to investigate the mechanisms of Grem1 in the degenerative process of intervertebral discs. Dysregulated genes were determined by analyzing microarray profiles. The expression of Grem1 in 17 human disc samples (male:female = 9:8) and rat models (n = 5 each group) was measured by western blotting (WB), real-time quantitative PCR (RT-qPCR), and immunohistochemistry (IHC). The regulatory effects of Grem1 on apoptosis were examined using siRNAs, flow cytometry, immunofluorescence (IF), and WB. The therapeutic effect was evaluated by locally injecting specific Grem1 siRNA into IVDD rats. The expression of Grem1 was significantly increased in human degenerative intervertebral discs; furthermore, the expression of Grem1 positively correlated with the level of intervertebral disc degeneration. Grem1 was significantly overexpressed in tumor necrosis factor (TNF)-α-induced degenerative NP cells. Apoptosis in degenerative NP cells transfected with siRNA targeting Grem1 was significantly lower than that in the control group. Specific Grem1 siRNA markedly repressed the development of IVDD in surgery-induced IVDD rats. These results indicated that the expression of Grem1 was positively correlated with the severity of intervertebral disc degeneration, and Grem1 siRNA could inhibit Grem1-induced apoptosis and extracellular matrix alterations by mediating the TGF-ß/Smad signaling pathway. This study may provide a therapeutic strategy for alleviating inflammation-induced apoptosis associated with intervertebral disc degeneration.

[High-speed identification of odor changes and substance basis of Myristicae Semen mildew by electronic nose and HS-GC-MS].

This study adopted headspace-gas chromatography-mass spectrometry(HS-GC-MS) and electronic nose to detect volatile components from Myristicae Semen samples with varying degrees of mildew, aiming at rapidly identifying odor changes and substance basis of Myristicae Semen mildew. The experimental data were analyzed by electronic nose and principal component analysis(PCA). The results showed that Myristicae Semen samples were divided into the following three categories by electronic nose and PCA: mildew-free samples, slightly mildewy samples, and mildewy samples. Myristicae Semen samples with different degrees of mildew greatly varied in volatile components. The volatile components in the samples were qualitatively and quantitatively detected by HS-GC-MS, and 59 compounds were obtained. There were significant differences in the composition and content in Myristicae Semen samples with different degrees of mildew. The PCA results were the same as those by electronic nose. Among them, 3-crene, D-limonene, and other terpenes were important indicators for the identification of mildew. Bicyclo[3.1.0]hexane, 4-methylene-1-(1-methylethyl)-, terpinen-4-ol, and other alcohols were key substances to distinguish the degree of mildew. In the later stage of mildew, Myristicae Semen produced a small amount of hydroxyl and aldehyde compounds such as acetaldehyde, 2-methyl-propionaldehyde, 2-methyl-butyraldehyde, and formic acid, which were deduced as the material basis of the mildew. The results are expected to provide a basis for the rapid identification of Myristicae Semen with different degrees of mildew, odor changes, and the substance basis of mildew.

Perioperative Complications in 255 Patients Who Underwent Lateral Anterior Lumbar Interbody Fusion (LaLIF) Surgery.

PURPOSE: To investigate the perioperative complications of lateral anterior lumbar interbody fusion (LaLIF) surgery. METHODS: The participants were patients who underwent LaLIF surgery for degenerative lumbar diseases between April 2016 and November 2020. The collected data were classified into intraoperative and early-stage postoperative (1 month) complications. Intraoperative complications were subcategorized into nerve root injury, sympathetic chain injury, segmental artery injury, iliolumbar vein injury, peritoneum laceration, temporary psoas injury, endplate damage, and vertebral body fractures. Postoperative complications were subcategorized into surgical site infection, cage migration, cage subsidence and psoas major hematoma. RESULTS: In the 255 included patients, 39 complications (15.3%) were reported. One patient (0.4%) had residual neurological symptoms (numbness) at the last follow-up after conservative management. The most common complications were temporary psoas injury (3.9%), followed by sympathetic chain injury (2.7%) and endplate damage (2.0%). The most frequent postoperative complication was cage migration (1.6%), followed by cage subsidence (1.2%), and surgical site infection (0.8%). CONCLUSION: The complication rates for LaLIF are generally low and comparable to those for conventional OLIF and XLIF that have been reported in other studies. Almost all complications were transient after LaLIF. Severe complications can be avoided by using sufficient muscle relaxant, instruments with the required characteristics and vertical trajectories in multiple steps.

Transcriptome Analysis of Peripheral Blood Mononuclear Cells in SARS-CoV-2 Naïve and Recovered Individuals Vaccinated With Inactivated Vaccine.

The urgent approval of the use of the inactivated COVID-19 vaccine is essential to reduce the threat and burden of the epidemic on global public health, however, our current understanding of the host immune response to inactivated vaccine remains limited. Herein, we performed serum IgG antibody detection and transcriptomics analysis on 20 SARS-CoV-2 naïve individuals who received multiple doses of inactivated vaccine and 5 SARS-CoV-2 recovered individuals who received single dose of inactivated vaccine. Our research revealed the important role of many innate immune pathways after vaccination, identified a significant correlation with the third dose of booster vaccine and proteasome-related genes, and found that SARS-CoV-2 recovered individuals can produces a strong immune response to a single dose of inactivated vaccine. These results help us understand the reaction mechanism of the host's molecular immune system to the inactivated vaccine, and provide a basis for the choice of vaccination strategy.

Spin Hydrodynamic Generation in the Charged Subatomic Swirl.

Recently there have been significant interests in the spin hydrodynamic generation phenomenon from multiple disciplines of physics. Such phenomenon arises from global polarization effect of microscopic spin by macroscopic fluid rotation and is expected to occur in the hot quark-gluon fluid (the "subatomic swirl") created in relativistic nuclear collisions. This was indeed discovered in experiments which however revealed an intriguing puzzle: a polarization difference between particles and anti-particles. We suggest a novel application of a general connection between rotation and magnetic field: a magnetic field naturally arises along the fluid vorticity in the charged subatomic swirl. We establish this mechanism as a new way for generating long-lived in-medium magnetic field in heavy ion collisions. Due to its novel feature, this new magnetic field provides a nontrivial explanation to the puzzling observation of a difference in spin hydrodynamic generation for particles and anti-particles in heavy ion collisions.

The active fraction from the tuber of Bolboschoenus yagara inhibits melanoma B16 cells metastasis LPS-induced in vitro and in vivo.

This study was to identify anti-metastatic active fractions and compounds of Bolboschoenus yagara (B. yagara). The results indicated that 50 µg/mL ethyl acetate fraction (Et) can dramatically inhibit mouse melanoma B16 cells migration and invasion in vitro. In B16 cells pulmonary and hepatic metastasis assays, 50 µg/mL Et alleviated mouse lung and liver weights, the number of metastatic nodules and the levels of TNF-α and IL-6 in mouse serum and organs. Histological studies showed that Et fraction was able to prevent liver and lung metastasis. And the inhibition of 50 µg/mL Et fraction against hepatic metastasis was almost equivalent to that of 1 µM TAK242. In addition, fourteen compounds of Et were quantified by HPLC analysis, in which, isocoumarins, stilbenes and xanthones obviously abated LPS-modulated B16 cells migration and invasion.[Formula: see text].