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Exposure to heat stress causes diminished work performance and leads to economic loss. In the last two decades, China has experienced both rapid economic development and environmental warming; however, the spatiotemporal variations of association between environmental heat and labor loss have been rarely investigated behind this double impact. Here, we evaluated the variation in China's heat-induced labor productivity loss and related economic cost from 2001 to 2019 and investigated the effect of economic development and regional warming. We found that decline in labor productivity because of heat stress increased significantly (p

Early flowering promotes early maturity, production, and the capacity to counteract biotic and abiotic stresses, making it an important agronomic trait in zucchini. The present study demonstrated that the zucchini inbred line ‘19’ consistently flowered early, taking significantly fewer days to bloom the first female flower (DFF) than the inbred line ‘113’. Genetic analysis revealed that DFF, an inheritable quantitative trait, is controlled by multiple genes. Based on the strategy of quantitative trait locus (QTL) sequencing (QTL-seq) combined with linkage analysis, three QTLs for DFF were identified on chromosomes 4, 11, and 20. This study used additional F2 populations grown under different environmental conditions for QTL mapping analysis of DFF with insertion/deletion (InDel) markers to validate these results. Using the composite interval mapping (CIM) method of R/qtl software, we only identified one major locus under all environmental conditions, located in a 117-kb candidate region on chromosome 20. Based on gene annotation, gene sequence alignment, and qRT-PCR analysis, we found that the Cp4.1LG20g08050 gene encoding a RING finger protein may be a candidate gene for the opposite regulation of early flowering in zucchini. In summary, these results lay a foundation for a better understanding of early flowering and improving early flowering-based breeding strategies in zucchini.

The objective of this study was to determine the role of SLC15A4 in the muramyl dipeptide (MDP)-mediated inflammatory response of bovine rumen epithelial cells (BRECs). First, changes in the mRNA expression of pro-inflammatory factor genes in BRECs following 10 μg mL–1 MDP treatments were examined. RT-qPCR results showed that the expression of pro-inflammatory factor (IL-1β, IL-6, and TNF-α) mRNAs were significantly increased under MDP stimulation (P

Abstract Background Spinal cord injury (SCI), which causes loss of sensory and motor function in the body below the level of injury, is a devastating disease of the central nervous system. SCI leads to severe secondary immunosuppression, called SCI-induced immunodeficiency syndrome (SCI-IDS), which is characterized by increased susceptibility to infection and further exacerbates neurological dysfunction. Several studies have suggested that SCI-IDS is an independent risk factor for poor neurological prognosis. SCI-IDS predominantly occurs following injury above the T5 levels and eventually leads to systemic immune failure, possibly via the sympathetic–adrenal medullary axis and the hypothalamic‒pituitary‒adrenal (HPA) axis. However, the mechanism remains unclear. Methods and objectives The concentrations of adrenocorticotropic hormone and cortisol in plasma, as well as changes in sympathetic activity (blood pressure and catecholamine levels in plasma), were assessed in rats in the high-level (T3) spinal cord injury (T3-SCI) group and the low-level (T10) spinal cord injury (T10-SCI) group. Second, the differential regulation of the gene network between the sympathetic–adrenal medullary axis and the HPA axis was explored by histology and multitissue transcriptomics, and the neuroendocrine–immune network associated with SCI-IDS was further elucidated. Results The spleen and thymus gland, which are secondary immune organs, were significantly atrophied in rats in the T3-SCI group, and the white pulp of the spleen was significantly atrophied. The level of cortisol, which is mediated by the adrenal glands, was markedly elevated, but norepinephrine levels were markedly decreased. There was no difference in adrenocorticotropic hormone expression between any of the groups. The transcriptome analysis results showed that the downregulated differentially expressed genes (DEGs) in the T3-SCI group were enriched in the GO term immunoregulation, indicating that splenic immune function was markedly impaired after high-level SCI. The upregulated DEGs in the hypothalamus (hub genes: Nod2, Serpine1, Cebpb, Nfkbil1, Ripk2, Zfp36, Traf6, Akap8, Gfer, Cxcl10, Tnfaip3, Icam1, Fcgr2b, Ager, Dusp10, and Mapkapk2) were significantly enriched in inflammatory pathways, and the downregulated genes (hub genes: Grm4, Nmu, P2ry12, rt1-bb1, Oprm1, Zfhx2, Gpr83, and Chrm2) were enriched in pathways related to inhibitory Gi-mediated G protein-coupled receptor (Gi-GPCR) neurons and neuropeptide changes. The upregulated genes in the adrenal glands (hub genes: Ciart, per2, per3, cry1, and cry2) were enriched in cortisol secretion and circadian rhythm changes, and the downregulated genes (hub genes: IL7r, rt1-bb, rt1-bb1, rt1-da, rt1-ba, cd74, cxcr3, vcam1, ccl5, bin1, and IL8) were significantly enriched in MHC-mediated immune responses. Conclusions To explore the possible mechanism underlying SCI-IDS, this study assessed the differential regulation of the gene network associated with neuroendocrine immunity after SCI. Progressive neuroinflammation spreads after injury, and neurotransmission through Gi-mediated G protein-coupled receptors in the HPA axis and neuropeptide production by the hypothalamus are inhibited. Disruption of the connection between the hypothalamus and the adrenal glands causes autonomous regulation of the adrenal glands, disturbance of circadian rhythm and finally hypercortisolemia, leading to general suppression of peripheral adaptive immunity. Neuraxial nerve inflammation caused by SCI persists indefinitely, blocking nerve repair; persistent system-wide immunosuppression in the periphery results in increased susceptibility to infection, leading to poor neurological prognosis.

Energetic metal-organic complexes have been involved in nanothermites as novel oxidants. However, the existing preparation methods often lead to mixing inhomogeneity and small contact area of ingredients, the reactivity and functionality of the novel energetic nanocomposites are still limited. In this work, spray crystallization (SC) method was used to prepare novel energetic nanocomposites, the high-energy metal-organic complex [Ni(CHZ)3](ClO4)2 (CHZ = 1,3-diaminourea) was composited with nano-aluminum (n-Al). Results showed that n-Al/[Ni(CHZ)3](ClO4)2 energetic nanocomposites prepared by SC method increased heat release to 2977.6 J/g and peak pressure to 3.91 MPa with higher pressurization rate (1324.06 MPa/s), decreased sensitivity thresholds (>100 mJ) to electrostatic discharge (ESD) and enhanced detonation ability compared with [Ni(CHZ)3](ClO4)2 alone and physically mixed (PM) n-Al/[Ni(CHZ)3](ClO4)2. These results proved that it is significant to introduce energetic metal-organic complexes with inherent high energy in new-concept n-Al/energetic metal-organic complexes nanocomposites through SC method for a better performance of its application.

Abstract Background To explore the potential of histogram analysis (HA) of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in the identification of extramural venous invasion (EMVI) in rectal cancer patients. Methods This retrospective study included preoperative images of 194 rectal cancer patients at our hospital between May 2019 and April 2022. The postoperative histopathological examination served as the reference standard. The mean values of DCE-MRI quantitative perfusion parameters (K trans , K ep and V e ) and other HA features calculated from these parameters were compared between the pathological EMVI-positive and EMVI-negative groups. Multivariate logistic regression analysis was performed to establish the prediction model for pathological EMVI-positive status. Diagnostic performance was assessed and compared using the receiver operating characteristic (ROC) curve. The clinical usefulness of the best prediction model was further measured with patients with indeterminate MRI-defined EMVI (mrEMVI) score 2(possibly negative) and score 3 (probably positive). Results The mean values of K trans and V e in the EMVI-positive group were significantly higher than those in the EMVI-negative group (P = 0.013 and 0.025, respectively). Significant differences in K trans skewness, K trans entropy, K trans kurtosis, and V e maximum were observed between the two groups (P = 0.001,0.002, 0.000, and 0.033, respectively). The K trans kurtosis and K trans entropy were identified as independent predictors for pathological EMVI. The combined prediction model had the highest area under the curve (AUC) at 0.926 for predicting pathological EMVI status and further reached the AUC of 0.867 in subpopulations with indeterminate mrEMVI scores. Conclusions Histogram Analysis of DCE-MRI K trans maps may be useful in preoperative identification of EMVI in rectal cancer, particularly in patients with indeterminate mrEMVI scores.

Abstract Background Chinese medicine usually acts as "multi-ingredients, multi-targets and multi-pathways" on complex diseases, and these action modes reflect the coordination and integrity of the treatment process with traditional Chinese medicine (TCM). System pharmacology is developed based on the cross-disciplines of directional pharmacology, system biology, and mathematics, has the characteristics of integrity and synergy in the treatment process of TCM. Therefore, it is suitable for analyzing the key ingredients and mechanisms of TCM in treating complex diseases. Intracerebral Hemorrhage (ICH) is one of the leading causes of death in China, with the characteristics of high mortality and disability rate. Bring a significant burden on people and society. An increasing number of studies have shown that Chinese medicine prescriptions have good advantages in the treatment of ICH, and Ditan Decoction (DTT) is one of the commonly used prescriptions in the treatment of ICH. Modern pharmacological studies have shown that DTT may play a therapeutic role in treating ICH by inhibiting brain inflammation, abnormal oxidative stress reaction and reducing neurological damage, but the specific key ingredients and mechanism are still unclear. Methods To solve this problem, we established PPI network based on the latest pathogenic gene data of ICH, and CT network based on ingredient and target data of DTT. Subsequently, we established optimization space based on PPI network and CT network, and constructed a new model for node importance calculation, and proposed a calculation method for PES score, thus calculating the functional core ingredients group (FCIG). These core functional groups may represent DTT therapy for ICH. Results Based on the strategy, 44 ingredients were predicted as FCIG, results showed that 80.44% of the FCIG targets enriched pathways were coincided with the enriched pathways of pathogenic genes. Both the literature and molecular docking results confirm the therapeutic effect of FCIG on ICH via targeting MAPK signaling pathway and PI3K-Akt signaling pathway. Conclusions The FCIG obtained by our network pharmacology method can represent the effect of DTT in treating ICH. These results confirmed that our strategy of active ingredient group optimization and the mechanism inference could provide methodological reference for optimization and secondary development of TCM.

As an essential component of ammunition, pyrotechnics can control ignition with high reliability. However, due to limits of fabrication technology, traditional pyrotechnics are bulky. To achieve both functionality and miniaturization, MEMS pyrotechnics integrate initiator, safety-and-arming (S&A) device and lead charge and keep all components within a small size. MEMS S&A devices, as the core component to ensure system safety, are difficult to achieve active and rapid response to control signals with high safety and reliability. In order to overcome the difficulty, we propose the design and characterization of a MEMS pyrotechnic with a double-layer barrier S&A device. The MEMS pyrotechnic is a high-integrated device with an overall size of 13.4 × 8.5 × 5.2 mm3. The initiator is a NiCr bridge foil covered with an Al/CuO energetic film, which can generate flame when ignited by an excitation voltage. To match the flame energy, lead styphnate is chosen in this study as the lead charge. The S&A device contains four semi-circular barriers, which are directly driven by V-shape electro-thermal actuators to gain active control of the pyrotechnics' ignition condition with rapid response. To improve the system's reliability, the four barriers are axisymmetrically placed in two layers, two barriers for each layer, to constitute a double-layer structure with a thickness of 100 μm. The ignition test results show that the S&A device can prevent the initiator from detonating the lead charge in safety condition. In arming condition, the lead charge will be detonated.

ABSTRACT: Objectives: Here, we report the complete genome of strain WB, isolated from the rhizosphere of a healthy watermelon from a Fusarium wilt diseased field, which possesses antifungal activity against Fusarium oxysporum f. sp. niveum (Fon) and reduces the incidence of Fusarium wilt in watermelon. Methods: Genome sequences were determined using the Illumina HiSeq and PacBio platforms. Genome assembly was performed by Unicycler software. Gene clusters responsible for secondary metabolite biosynthesis were predicted using antiSMASH. Results: The size of the genome was 3 896 799 base pairs, and there were 3977 coding DNA sequences (CDSs). The G+C content of the circular genome was 46.65%, and there were 27 rRNAs and 86 tRNAs. Strain WB was finally designated Bacillus velezensis based on phylogenomic analyses. In addition, 13 gene clusters were related to the synthesis of antimicrobial secondary metabolites, including surfactin, fengycin, iturin, bacillibactin, bacilysin, bacillaene, and butirosin. Conclusion: The complete genome sequence of strain WB reported here will be a valuable reference for studying the biocontrol mechanisms of Fusarium wilt in watermelon.

Abstract Background Chinese herbal medicine (CHM) is characterized by “multi- compounds, multi-targets and multi-pathway”, which has advanced benefits for preventing and treating complex diseases, but there still exists unsolved issues, mainly include unclear material basis and underlying mechanism of prescription. Integrated pharmacology is a hot cross research area based on system biology, mathematics and poly-pharmacology. It can systematically and comprehensively investigate the therapeutic reaction of compounds or drugs on pathogenic genes network, and is especially suitable for the study of complex CHM systems. Intracerebral Hemorrhage (ICH) is one of the main causes of death among Chinese residents, which is characterized with high mortality and high disability rate. In recent years, the treatment of ICH by CHM has been deeply researched. Xue Fu Zhu Yu Decoction (XFZYD), one of the commonly used prescriptions in treating ICH at clinic level, has not been clear about its mechanism. Methods Here, we established a strategy, which based on compounds-targets, pathogenetic genes, network analysis and node importance calculation. Using this strategy, the core compounds group (CCG) of XFZYD was predicted and validated by in vitro experiments. The molecular mechanism of XFZYD in treating ICH was deduced based on CCG and their targets. Results The results show that the CCG with 43 compounds predicted by this model is highly consistent with the corresponding Compound-Target (C-T) network in terms of gene coverage, enriched pathway coverage and accumulated contribution of key nodes at 89.49%, 88.72% and 90.11%, respectively, which confirmed the reliability and accuracy of the effective compound group optimization and mechanism speculation strategy proposed by us. Conclusions Our strategy of optimizing the effective compound groups and inferring the mechanism provides a strategic reference for explaining the optimization and inferring the molecular mechanism of prescriptions in treating complex diseases of CHM.

Background: Drug-induced liver injury (DILI) is a potentially serious adverse drug reaction. Due to the lack of definite etiology, specific clinical manifestations, and diagnostic methods, its prediction and diagnosis are challenging. Elderly individuals are deemed to be at high risk for DILI due to abnormal pharmacokinetics, aging tissue repair function, comorbidities, and taking multiple drugs. This study aimed to identify the clinical characteristics and explore the risk factors associated with the severity of illness in elderly patients with DILI.Methods: In the present study, the clinical characteristics at the time of liver biopsy of consecutive patients with biopsy-proven DILI who presented at our hospital from June 2005 to September 2022 were evaluated. Hepatic inflammation and fibrosis were assessed according to the Scheuer scoring system. The presence of autoimmunity was considered if IgG level >1.1 × ULN (1826 mg/dL), or high titer (>1:80) of ANA, or SMA.Results: In total, 441 patients were enrolled, and the median age was 63.3 years (IQR, 61.0–66.0); 122 (27.7%), 195 (44.2%), or 124 (28.1%) were classified as having minor, moderate, or severe hepatic inflammation, respectively; and 188 (42.6%), 210 (47.6%) or 43 (9.8%) patients presented minor, significant fibrosis or cirrhosis, respectively. Female sex (73.5%) and the cholestatic pattern (47.6%) were dominant in elderly DILI patients. Autoimmunity existed in 201 patients (45.6%). Comorbidities were not directly associated with the severity of DILI. PLT (OR: 0.994, 95% CI: 0.991–0.997; p < 0.001), AST (OR: 1.001, 95% CI: 1.000–1.003, p = 0.012), TBIL (OR: 1.006, 95% CI: 1.003–1.010, p < 0.001), and autoimmunity (OR: 1.831, 95% CI: 1.258–2.672, p = 0.002) were associated with the degree of hepatic inflammation. Meanwhile, PLT (OR: 0.990, 95% CI: 0.986–0.993, p < 0.001), TBIL (OR: 1.004, 95% CI: 1.000–1.007, p = 0.028), age (OR: 1.123, 95% CI: 1.067–1.183, p < 0.001), and autoimmunity (OR: 1.760, 95% CI: 1.191–2.608, p = 0.005) were associated with the stage of hepatic fibrosis.Conclusion: This study revealed that the presence of autoimmunity represents a more serious illness state of DILI, deserving more intensive monitoring and progressive treatment.

Stroke is a cerebrovascular event with cerebral blood flow interruption which is caused by occlusion or bursting of cerebral vessels. At present, the main methods in treating stroke are surgical treatment, statins, and recombinant tissue-type plasminogen activator (rt-PA). Relatively, traditional Chinese medicine (TCM) has widely been used at clinical level in China and some countries in Asia. Xiao-Xu-Ming decoction (XXMD) is a classical and widely used prescription in treating stroke in China. However, the material basis of effect and the action principle of XXMD are still not clear. To solve this issue, we designed a new system pharmacology strategy that combined targets of XXMD and the pathogenetic genes of stroke to construct a functional response space (FRS). The effective proteins from this space were determined by using a novel node importance calculation method, and then the key functional components group (KFCG) that could mediate the effective proteins was selected based on the dynamic programming strategy. The results showed that enriched pathways of effective proteins selected from FRS could cover 99.10% of enriched pathways of reference targets, which were defined by overlapping of component targets and pathogenetic genes. Targets of optimized KFCG with 56 components can be enriched into 166 pathways that covered 80.43% of 138 pathways of 1,012 pathogenetic genes. A component potential effect score (PES) calculation model was constructed to calculate the comprehensive effective score of components in the components-targets-pathways (C-T-P) network of KFCGs, and showed that ferulic acid, zingerone, and vanillic acid had the highest PESs. Prediction and docking simulations show that these components can affect stroke synergistically through genes such as MEK, NFκB, and PI3K in PI3K-Akt, cAMP, and MAPK cascade signals. Finally, ferulic acid, zingerone, and vanillic acid were tested to be protective for PC12 cells and HT22 cells in increasing cell viabilities after oxygen and glucose deprivation (OGD). Our proposed strategy could improve the accuracy on decoding KFCGs of XXMD and provide a methodologic reference for the optimization, mechanism analysis, and secondary development of the formula in TCM.

Background: Traditional Chinese medicine (TCM) has been widely used in the treatment of human diseases. However, the synergistic effects of multiple TCM prescriptions in the treatment of stroke have not been thoroughly studied.Objective of the study: This study aimed to reveal the mechanisms underlying the synergistic effects of these TCM prescriptions in stroke treatment and identify the active compounds.Methods: Herbs and compounds in the Di-Tan Decoction (DTD), Xue-Fu Zhu-Yu Decoction (XFZYD), and Xiao-Xu-Ming Decoction (XXMD) were acquired from the TCMSP database. SEA, HitPick, and TargetNet web servers were used for target prediction. The compound-target (C-T) networks of three prescriptions were constructed and then filtered using the collaborative filtering algorithm. We combined KEGG enrichment analysis, molecular docking, and network analysis approaches to identify active compounds, followed by verification of these compounds with an oxygen-glucose deprivation and reoxygenation (OGD/R) model.Results: The filtered DTD network contained 39 compounds and 534 targets, the filtered XFZYD network contained 40 compounds and 508 targets, and the filtered XXMD network contained 55 compounds and 599 targets. The filtered C-T networks retained approximately 80% of the biological functions of the original networks. Based on the enriched pathways, molecular docking, and network analysis results, we constructed a complex network containing 3 prescriptions, 14 botanical drugs, 26 compounds, 13 targets, and 5 pathways. By calculating the synergy score, we identified the top 5 candidate compounds. The experimental results showed that quercetin, baicalin, and ginsenoside Rg1 independently and synergistically increased cell viability.Conclusion: By integrating pharmacological and chemoinformatic approaches, our study provides a new method for identifying the effective synergistic compounds of TCM prescriptions. The filtered compounds and their synergistic effects on stroke require further research.

Perceived trustworthiness based on facial appearance plays an important role in interpersonal trust and cooperative behavior. Interpersonal trust behaviors involve both trustors and trustees. However, there is no clear conclusion on how the age of the two individuals affects interpersonal trust behaviors. Therefore, this study used the trust game task to explore the differences in trust behaviors between two different age groups in response to faces of different ages and analyzed whether such differences were apparent in the face processing stage. The behavioral results showed that only younger adults invested more money with older partners than younger ones; that is, younger adults trusted older faces more. The event-related potential (ERP) analyses showed that in the early stage of face processing, younger faces elicited more negative N170 than older faces; at the same time, older faces elicited more positive VPP than younger faces, and younger adults had more positive VPP than older adults. In the middle and late stages of face processing, younger faces elicited more negative FRN than older faces in younger adults but not in older adults. In addition, older faces elicited more positive LPP than younger faces in older adults but not in younger adults. The neural analyses suggested that age-related differences in facial trustworthiness judgments might occur in the later stages of face processing. Combining the behavioral and neural results, we found a dissociation between trustworthiness perceptions and trust behaviors in both younger and older adults, which may provide insight into how to prevent older adults from being deceived.

Sepsis is a systemic inflammatory reaction caused by various infectious or noninfectious factors, which can lead to shock, multiple organ dysfunction syndrome, and death. It is one of the common complications and a main cause of death in critically ill patients. At present, the treatments of sepsis are mainly focused on the controlling of inflammatory response and reduction of various organ function damage, including anti-infection, hormones, mechanical ventilation, nutritional support, and traditional Chinese medicine (TCM). Among them, Xuebijing injection (XBJI) is an important derivative of TCM, which is widely used in clinical research. However, the molecular mechanism of XBJI on sepsis is still not clear. The mechanism of treatment of “bacteria, poison and inflammation” and the effects of multi-ingredient, multi-target, and multi-pathway have still not been clarified. For solving this issue, we designed a new systems pharmacology strategy which combines target genes of XBJI and the pathogenetic genes of sepsis to construct functional response space (FRS). The key response proteins in the FRS were determined by using a novel node importance calculation method and were condensed by a dynamic programming strategy to conduct the critical functional ingredients group (CFIG). The results showed that enriched pathways of key response proteins selected from FRS could cover 95.83% of the enriched pathways of reference targets, which were defined as the intersections of ingredient targets and pathogenetic genes. The targets of the optimized CFIG with 60 ingredients could be enriched into 182 pathways which covered 81.58% of 152 pathways of 1,606 pathogenetic genes. The prediction of CFIG targets showed that the CFIG of XBJI could affect sepsis synergistically through genes such as TAK1, TNF-α, IL-1β, and MEK1 in the pathways of MAPK, NF-κB, PI3K-AKT, Toll-like receptor, and tumor necrosis factor signaling. Finally, the effects of apigenin, baicalein, and luteolin were evaluated by in vitro experiments and were proved to be effective in reducing the production of intracellular reactive oxygen species in lipopolysaccharide-stimulated RAW264.7 cells, significantly. These results indicate that the novel integrative model can promote reliability and accuracy on depicting the CFIGs in XBJI and figure out a methodological coordinate for simplicity, mechanism analysis, and secondary development of formulas in TCM.

Traditional Chinese medicine (TCM) formulas treat complex diseases through combined botanical drugs which follow specific compatibility rules to reduce toxicity and increase efficiency. “Jun, Chen, Zuo and Shi” is one of most used compatibility rules in the combination of botanical drugs. However, due to the deficiency of traditional research methods, the quantified theoretical basis of herbal compatibility including principles of “Jun, Chen, Zuo and Shi” are still unclear. Network pharmacology is a new strategy based on system biology and multi-disciplines, which can systematically and comprehensively observe the intervention of drugs on disease networks, and is especially suitable for the research of TCM in the treatment of complex diseases. In this study, we systematically decoded the “Jun, Chen, Zuo and Shi” rules of Huanglian Jiedu Decoction (HJD) in the treatment of diseases for the first time. This interpretation method considered three levels of data. The data in the first level mainly depicts the characteristics of each component in single botanical drug of HJD, include the physical and chemical properties of component, ADME properties and functional enrichment analysis of component targets. The second level data is the characterization of component-target-protein (C-T-P) network in the whole protein-protein interaction (PPI) network, mainly include the characterization of degree and key communities in C-T-P network. The third level data is the characterization of intervention propagation properties of HJD in the treatment of different complex diseases, mainly include target coverage of pathogenic genes and propagation coefficient of intervention effect between target proteins and pathogenic genes. Finally, our method was validated by metabolic data, which could be used to detect the components absorbed into blood. This research shows the scientific basis of “Jun-Chen-Zuo-Shi” from a multi-dimensional perspective, and provides a good methodological reference for the subsequent interpretation of key components and speculation mechanism of the formula.

Complex disease is a cascade process which is associated with functional abnormalities in multiple proteins and protein-protein interaction (PPI) networks. One drug one target has not been able to perfectly intervene complex diseases. Increasing evidences show that Chinese herb formula usually treats complex diseases in the form of multi-components and multi-targets. The key step to elucidate the underlying mechanism of formula in traditional Chinese medicine (TCM) is to optimize and capture the important components in the formula. At present, there are several formula optimization models based on network pharmacology has been proposed. Most of these models focus on the 2D/3D similarity of chemical structure of drug components and ignore the functional optimization space based on relationship between pathogenetic genes and drug targets. How to select the key group of effective components (KGEC) from the formula of TCM based on the optimal space which link pathogenic genes and drug targets is a bottleneck problem in network pharmacology. To address this issue, we designed a novel network pharmacological model, which takes Lang Chuang Wan (LCW) treatment of systemic lupus erythematosus (SLE) as the case. We used the weighted gene regulatory network and active components targets network to construct disease-targets-components network, after filtering through the network attribute degree, the optimization space and effective proteins were obtained. And then the KGEC was selected by using contribution index (CI) model based on knapsack algorithm. The results show that the enriched pathways of effective proteins we selected can cover 96% of the pathogenetic genes enriched pathways. After reverse analysis of effective proteins and optimization with CI index model, KGEC with 82 components were obtained, and 105 enriched pathways of KGEC targets were consistent with enriched pathways of pathogenic genes (80.15%). Finally, the key components in KGEC of LCW were evaluated by in vitro experiments. These results indicate that the proposed model with good accuracy in screening the KGEC in the formula of TCM, which provides reference for the optimization and mechanism analysis of the formula in TCM.

Traditional Chinese medicine (TCM) with the characteristics of “multi-component-multi-target-multi-pathway” has obvious advantages in the prevention and treatment of complex diseases, especially in the aspects of “treating the same disease with different treatments”. However, there are still some problems such as unclear substance basis and molecular mechanism of the effectiveness of formula. Network pharmacology is a new strategy based on system biology and poly-pharmacology, which could observe the intervention of drugs on disease networks at systematical and comprehensive level, and especially suitable for study of complex TCM systems. Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, causing articular and extra articular dysfunctions among patients, it could lead to irreversible joint damage or disability if left untreated. TCM formulas, Danggui-Sini-decoction (DSD), Guizhi-Fuzi-decoction (GFD), and Huangqi-Guizhi-Wuwu-Decoction (HGWD), et al., have been found successful in controlling RA in clinical applications. Here, a network pharmacology-based approach was established. With this model, key gene network motif with significant (KNMS) of three formulas were predicted, and the molecular mechanism of different formula in the treatment of rheumatoid arthritis (RA) was inferred based on these KNMSs. The results show that the KNMSs predicted by the model kept a high consistency with the corresponding C-T network in coverage of RA pathogenic genes, coverage of functional pathways and cumulative contribution of key nodes, which confirmed the reliability and accuracy of our proposed KNMS prediction strategy. All validated KNMSs of each RA therapy-related formula were employed to decode the mechanisms of different formulas treat the same disease. Finally, the key components in KNMSs of each formula were evaluated by in vitro experiments. Our proposed KNMS prediction and validation strategy provides methodological reference for interpreting the optimization of core components group and inference of molecular mechanism of formula in the treatment of complex diseases in TCM.

Aim: The present study aimed to evaluate the combined value of locoregional extension patterns (LEPs) and circulating cell-free Epstein–Barr virus (cf EBV) DNA for risk stratification of locoregionally advanced nasopharyngeal carcinoma (LA-NPC) to better guide therapeutic strategies. Methods: A total of 7227 cases of LA-NPC were reviewed retrospectively and classified into six groups according to their LEP (ascending, descending, or mixed type) and pre-treatment cf EBV-DNA load (⩾ versus

Oleanolic acid (OA), a natural triterpenoid, which has the development prospects in anti-tumor therapy is a widely used hepatoprotective drug in China. It has been reported that OA can cause liver toxicity after higher doses or longer-term use. Therefore, the study aims to explore the possible hepatotoxicity mechanism based on liver metabolic profiles. Liver metabolic profiles were obtained from untargeted ultrahigh performance liquid chromatography (UHPLC)-Q Exactive Orbitrap mass spectrometry (MS) technique. It was found that altered bile acid, amino acid, and energy metabolism might be at least partly responsible for OA-induced hepatotoxicity. Bile acid metabolism, as the most important pathway, was verified by using UHPLC-TSQ-MS, indicating that conjugated bile acids were the main contributors to OA-induced liver toxicity. Our findings confirmed that increased bile acids were the key element of OA hepatotoxicity, which may open new insights for OA hepatotoxicity in-depth investigations, as well as provide a reference basis for more hepatotoxic drug mechanism research.

The effect of salt concentration on the processing and characteristics of turbot muscle was investigated in this study. The turbot muscle samples were salted with 1%, 5%, 10%, 15%, or 20% w/w salt at 4°C for 3 h. Low-field nuclear magnetic resonance was utilized to characterize water distribution and water holding capacity in the samples. Nuclear magnetic resonance transverse (T2) relaxation identified three water components (T21, T22, and T23) which all exhibited characteristics correlated with water holding capacity. Textural analysis indicated that hardness and elasticity increased with increasing salt concentration. Histological imaging showed that with the increase of salt concentration, the muscle fiber diameter and area increased first and then decreased. The porosity of salted samples was higher than that of fresh ones. It was shown that salting at lower salt concentrations would lead to partial degradation of the fibrin in the tissue samples and the swelling of proteins. In treated samples, 5% w/w salt was shown to produce the best results. This study provides theoretical basis for the development of salted turbot meat products.

Capsaicin, a kind of alkaloid from pepper cortex, has extensive anti-tumor activities. However, the anti-metastasis effects and mechanisms of capsaicin against hepatocellular carcinoma (HCC) have not been deeply studied so far. In the present work, the anti-metastasis effects of capsaicin were investigated in human hepatoma SMMC-7721 and HepG2 cells, and its mechanisms were explored using metabolomics-based approach. The results showed that capsaicin remarkably suppressed cell proliferation, migration, and invasion, and hampered cell-matrix adhesion in SMMC-7721 and HepG2 cells. Metabolomics approach revealed that 18 differential metabolites, and 5 metabolic pathways including glutathione metabolism, pyruvate metabolism, phenylalanine metabolism, glycine, serine and threonine metabolism, glycerophospholipid metabolism were implicated in the anti-HCC effects of capsaicin. A multi-level network further uncovered the possible molecular mechanisms of capsaicin in regulating these metabolites and metabolic pathways. This study revealed that metabolomics integrating with network-based approach can facilitate understanding of the anti-metastasis mechanisms of capsaicin against HCC.

BACKGROUND Stress hyperglycemia ratio (SHR) could provide accurate information on the acute status of hyperglycemia. The relationship between SHR and acute coronary syndrome (ACS) prognosis remains unclear. This study was conducted to identity the association between SHR and in-hospital outcomes in patients with ACS. METHODS A total of 12,010 patients were eventually enrolled in the study. The relationship between SHR and in-hospital major adverse cardiovascular events (MACEs) was then modeled by restricted cubic spline (RCS) curves, and all patients were divided into three groups according to the results. The multivariate logistic regression analysis was used to determine the associations between the SHR and in-hospital outcomes, described as odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses were also performed on different diseases. RESULTS The median age of this cohort was 63 (54, 71) years old, and 8942 (74.5%) were male. Group 1 was defined as SHR < 0.6 (n = 426), Group 2 was defined as SHR between 0.6 and 1 (n = 5821), and Group 3 was defined as SHR > 1 (n = 5763). Compared with Group 2, Group 1 (OR = 1.891, 95% CI: 1.028-3.479, P < 0.001) and Group 3 (OR = 1.868, 95% CI: 1.434-2.434, P < 0.001) had higher risks of suffering from in-hospital MACEs. SHR was associated with higher risks of in-hospital MACEs in the subgroups of DM [OR = 2.282, 95% CI: 1.477-3.524). CONCLUSIONS Both low and high SHR levels were independently associated with in-hospital MACEs. Young males with DM, hypertension, and decreased renal function had much higher risks of suffering from SHR-correlated MACEs. [ABSTRACT FROM AUTHOR]