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BackgroundRheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic and symmetrical polyarthritis. RA patients often experience inflammatory reaction and hypercoagulable state, which together affect the self-perception of patient (SPP). Currently, inhibiting inflammation and hypercoagulable state are common treatment methods for alleviating RA symptoms. Xinfeng Capsules (XFC) has a long history of treating RA, and can effectively improve the inflammatory response and hypercoagulable state of RA. However, the potential mechanisms have not yet been determined.Purpose and study designThis study elucidated the action mechanism of XFC in RA inflammation and hypercoagulability through the lncDSCR9/RPLP2/PI3K/AKT axis.ResultsClinical observations indicated that there was a strong link between XFC therapy and improvements in inflammatory and coagulation biomarkers, as well as SPP among RA patients. The subsequent network pharmacology analysis results identified the PI3K/AKT signaling pathway as a potential mediator for XFC treatment of RA. Furthermore, clinical validation and sequencing results revealed that lncRNA DSCR9 expression (a gene implicated in inflammation and coagulation) was negatively correlated with clinical markers of inflammation and coagulation, while positively correlated with SF-36 indicators. Notably, XFC treatment remarkably upregulated lncRNA DSCR9 expression and downregulated PI3K and AKT expressions, showing opposite expression trends to the untreated cases.The regulatory effect of XFC on the lncRNA DSCR9/RPLP2/PI3K/AKT axis in RA was investigated using techniques such as RNA pull-down assay, Western blot analysis, RT-PCR, and EdU assay. Moreover, the administration of the PI3K/AKT agonist RMH can counteract the effects of XFC on p-PI3K, p-AKT, inflammation, and hypercoagulability, reinforcing the role of pathway. Finally, animal studies utilizing HE staining and transmission electron microscopy (TEM) demonstrated that XFC notably decreased PI3K and AKT expressions in adjuvant-induced arthritis (AA) rats, mitigated inflammation and hypercoagulability, and enhanced the ultrastructure of synovial cells. These findings underscored the potential mechanisms of XFC in the treatment of RA.ConclusionRegulating the lncRNA DSCR9/RPLP2/PI3K/AKT axis may be an important mechanism by which XFC improved RA inflammatory response and hypercoagulable state.

The coexistence of microorganisms in complex soil environments greatly affects the environmental behavior and ecological effects of microplastics (MPs). However, relevant studies are sparse, and internal mechanisms remain unclear. Herein, arbuscular mycorrhizal fungi (AMF), a common symbiotic microorganism in the soil–plant system, was proved to significantly affect MPs absorption and migration with a “size effect”. Specifically, the existence of AMF accelerated small-sized MPs (0.5 μm) uptake but slowed large-sized MPs (2 μm) uptake in lettuce. The content of 0.5 μm MPs absorbed by plants with AMF was 1.26 times that of the non-AMF group, while the content of 2 μm MPs was only 77.62 % that of non-AMF group. Additionally, the different effects of microorganisms on the intake content of MPs with different particle sizes in plants also led to different toxic effects of MPs on lettuce, that is, AMF exacerbated small-size MPs toxicity in lettuce (e.g., reduced plant biomass, photosynthesis, etc), and it weakened large-sized MPs toxicity (e.g., increased plant height, antioxidant enzyme activity, etc). The above phenomenon mainly because of the change in AMF on the plant root structure, which can be visually observed through the intraradical and extraradical hyphae. The symbiotic structure (hyphae) formed by AMF and host plants root could enhance the absorption pathway for small-sized MPs in lettuce, although not for large-sized MPs. Additionally, the effects of AMF varied with the soil environment of differently sized MPs, which promoted the migration of small-particle MPs to plants but aggravated large-particle MPs fixation at the soil interface. These findings could deepen the understanding of MPs pollution in terrestrial systems and provide theoretical basis and technical support to accurately assess soil MPs pollution.

PurposeThis study aimed to investigate the impact of paternal age > 40 years on clinical pregnancy and perinatal outcomes among patients undergoing in vitro fertilization treatment.MethodsWe selected 75 male patients (aged > 40 years) based on predefined inclusion and exclusion criteria. Propensity score matching was performed in a 1:3 ratio, resulting in a control group (aged ≤ 40 years) of 225 individuals. Various statistical tests, including the Mann-Whitney U test, Chi-square test, Fisher’s exact test, and binary logistic regression, were used to analyze the association between paternal age and clinical outcomes.ResultsWe found no statistically significant differences in semen routine parameters, clinical pregnancy outcomes, and perinatal outcomes between paternal aged > 40 and ≤ 40 years. However, in the subgroup analysis, the live birth rate significantly decreased in those aged ≥ 45 compared to those aged 41–42 and 43–44 years (31.25% vs. 69.23% and 65%, respectively; all p < 0.05). Additionally, the clinical pregnancy rate was significantly lower among those aged ≥ 45 than among those aged 41–42 (43.75% vs. 74.36%; p=0.035).ConclusionPaternal age ≥ 45 years was associated with lower live birth and clinical pregnancy rates.

Abstract The continued miniaturization of chips demands highly thermally conductive materials and effective thermal management strategies. Particularly, the high‐field transport of the devices built with 2D materials is limited by self‐heating. Here a systematic control of heat flow in single‐side fluorinated graphene (FG) with varying degrees of fluorination is reported, revealing a superior room‐temperature thermal conductivity as high as 128 W m−1 K−1. Monolayer graphene/FG lateral heterostructures with seamless junctions are approached for device fabrication. Efficient in‐plane heat removal paths from graphene channel to side FG are created, contributing significant reduction of the channel peak temperature and improvement in the current‐carrying capability and power density. Molecular dynamics simulations indicate that the interfacial thermal conductance of the heterostructure is facilitated by the high degree of overlap in the phonon vibrational spectra. The findings offer novel design insights for efficient heat dissipation in micro‐ and nanoelectronic devices.

Background: Traditional Chinese medicine is widely used in the treatment of osteoarthritis. This study explores the therapeutic effect of Traditional Chinese Medicine (TCM) on osteoarthritis (OA), as well as the mechanism by which Spatholobi Caulis (SPC) improves the immune-Inflammatory response of OA. Methods: The clinical data mining techniques to evaluate the efficacy of Caulis spatholobi in treating OA, and elucidated its mechanism of action using network pharmacology, molecular docking, and cell experiments. The random walk model was applied to systematically evaluate the therapeutic efficacy of Chinese herbal medicine on OA. Results: The evaluation based on the clinical data mining showed that TCM is effective in improving ESR, CRP, C3, C4, and PLT. Data mining results showed significant OA treatment. Network analysis results showed that it may fight OA by targeting JUN, ESR1 and PPARG; molecular docking results showed good JUN, ESR1, PPARG and active component formononetin. Finally, in vitro experiments conducted the preliminary validation of formononetin for the core target of FLS. Cell proliferation was measured by CCK-8, and JUN, ESR1, PPARG protein, and mRNA expression was measured by quantitative real-time RCR at 48 h after drug intervention. Conclusion: The present study demonstrated that the SPC effectively relieved immune inflammation indicators in OA patients. Formononetin, the main active component of the chicken blood vine, acts to reduce the immune validation response in OA patients by reducing the expression of ESR1, JUN, and PPARG.

Abstract The dried rhizomes of Coptis chinensis hold significance in Chinese medicine. Monocropping C. chinensis under the shade of a manmade scaffold, the primary planting mode, poses a threat to the ecological balance. In recent years, the practice of C. chinensis–Cunninghamia lanceolata understory cultivation has gained prevalence in southwest China. However, there is no evidence to suggest that understory cultivation enhances the viability, yield, or isoquinoline alkaloid content of C. chinensis. This study examined the physiological properties, yield indicators, and isoquinoline alkaloid content to investigate variations in C. chinensis in response to understory cultivation. Transcriptome analysis was conducted to elucidate potential mechanisms driving these alterations. The results indicate that understory cultivation significantly enhances the viability, yield, and levels of epiberberine, palmatine, and berberine in C. chinensis while reducing coptisine content. Transcriptomic analyses identified 2062 upregulated and 1853 downregulated genes in the understory cultivation system. Pathways such as “phenylpropanoid biosynthesis,” “zeatin biosynthesis,” “photosynthesis,” “tyrosine metabolism,” “isoquinoline alkaloid biosynthesis,” and “starch and sucrose metabolism” exhibited significant enrichment of differentially expressed genes (DEGs). DEGs involved in these pathways were thoroughly analyzed. INV, BGL-2, BGL-4, SPS-2, AMY-3, Psb B, Psb R, Psb S, Psa D, Psa E, Psa H, Psa O, Pet C, Pet H, deta, and b exhibited significant positive correlations with plant fresh weight, aboveground fresh weight, and underground fresh weight. 6-OMT-2 and COMT1-3 displayed significant positive correlations with coptisine content, but negative correlations with epiberberine, palmatine, and berberine content. ZOG-1, ZOG-3, TAT, PPO, POD-13 and UGT 73C5-1 showed noteworthy positive correlations with berberine content. Conversely, MIFH, POD-4, POD-5, and POD-8 displayed significant positive correlations with epiberberine, palmatine, and berberine content. POD-5, and POD-7 were significantly negatively correlated with coptisine content. Furthermore, gene expression levels determined by qRT–PCR aligned with the transcriptomic sequencing results, confirming the reliability of the transcriptomic findings. The results of this study contribute evidence elucidating potential mechanisms through which C. chinensis responds to understory cultivation. Graphical Abstract

AbstractRheumatoid arthritis (RA) is a systemic and autoimmune disease that is mainly featured abnormal fibroblast-like synoviocyte (FLS) proliferation and inflammatory cell infiltration. Abnormal expression or function of long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) are closely related to human diseases, including RA. There has been increasing evidence showing that in the competitive endogenous RNA (ceRNA) networks, both lncRNA and circRNA are vital in the biological functions of cells. Nevertheless, the exact mechanism of ceRNA in RA remains to be investigated. Herein, we summarized the molecular potencies of lncRNA/circRNA-mediated ceRNA networks in RA, with emphasis on the phenotypic regulation of ceRNA in the progression of RA, including regulation of proliferation, invasion, inflammation and apoptosis, as well as the role of ceRNA in traditional Chinese medicine (TCM) in the treatment of RA. In addition, we also discussed the future direction and potential clinical value of ceRNA in the treatment of RA, which may provide potential reference value for clinical trials of TCM therapy for the treatment of RA.Key messagesLong noncoding RNA/circular RNA can work as the competitive endogenous RNA sponge and participate in the pathogenesis of rheumatoid arthritis.Traditional Chinese medicine and its agents have shown potential roles in the prevention and treatment of rheumatoid arthritis via competitive endogenous RNA.

Abstract Background Exertional heatstroke (EHS), a fatal illness, pronounces multiple organ dysfunction syndrome (MODS) and high mortality rate. Currently, no ideal factor prognoses EHS. Decreased monocyte human leukocyte‐DR antigen (mHLA‐DR) has been observed in critically ill individuals, particularly in those with sepsis. While most research focus on the pro‐inflammatory response exploration in EHS, there are few studies related to immunosuppression, and no report targeted on mHLA‐DR in EHS. The present study tried to explore the prognostic value of mHLA‐DR levels in EHS patients. Methods This was a single‐center retrospective study. Clinical data of EHS patients admitted to the intensive care unit of the General Hospital of Southern Theatre Command between January 1, 2008, and December 31, 2020, were recorded and analyzed. Results Seventy patients with 54 survivors and 16 nonsurvivors were ultimately enrolled. Levels of mHLA‐DR in the nonsurvivors (41.8% [38.1–68.1]%) were significantly lower than those in the survivors (83.1% [67.6–89.4]%, p

IntroductionSouthern blight, caused by Sclerotium rolfsii, poses a serious threat to the cultivation of Coptis chinensis, a plant with significant medicinal value. The overreliance on fungicides for controlling this pathogen has led to environmental concerns and resistance issues. There is an urgent need for alternative, sustainable disease management strategies.MethodsIn this study, Bacillus velezensis LT1 was isolated from the rhizosphere soil of diseased C. chinensis plants. Its biocontrol efficacy against S. rolfsii LC1 was evaluated through a confrontation assay. The antimicrobial lipopeptides in the fermentation liquid of B. velezensis LT1 were identified using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF-MS). The effects of B. velezensis LT1 on the mycelial morphology of S. rolfsii LC1 were examined using scanning electron microscopy (SEM) and transmission electron microscopy (TEM).ResultsThe confrontation assay indicated that B. velezensis LT1 significantly inhibited the growth of S. rolfsii LC1, with an inhibition efficiency of 78.41%. MALDI-TOF-MS analysis detected the presence of bacillomycin, surfactin, iturin, and fengycin in the fermentation liquid, all known for their antifungal properties. SEM and TEM observations revealed that the mycelial and cellular structures of S. rolfsii LC1 were markedly distorted when exposed to B. velezensis LT1.DiscussionThe findings demonstrate that B. velezensis LT1 has considerable potential as a biocontrol agent against S. rolfsii LC1. The identified lipopeptides likely contribute to the antifungal activity, and the morphological damage to S. rolfsii LC1 suggests a mechanism of action. This study underscores the importance of exploring microbial biocontrol agents as a sustainable alternative to chemical fungicides in the management of plant diseases. Further research into the genetic and functional aspects of B. velezensis LT1 could provide deeper insights into its biocontrol mechanisms and facilitate its application in agriculture.

Two new meroterpenoids, aspergienynes O and P (1 and 2), one new natural compound, aspergienyne Q (3), and a new α-pyrone derivative named 3-(4-methoxy-2-oxo-2H-pyran-6-yl)butanoic acid (4) were isolated from the mangrove endophytic fungal strain Aspergillus sp. GXNU-Y85, along with five known compounds (5–9). The absolute configurations of those new isolates were confirmed through extensive analysis using spectroscopic data (HRESIMS, NMR, and ECD). The pharmacological study of the anti-proliferation activity indicated that isolates 5 and 9 displayed moderate inhibitory effects against HeLa and A549 cells, with the IC50 values ranging from 16.6 to 45.4 μM.

Objective: To explore the efficacy of long-term traditional Chinese medicine (TCM) treatment on the occurrence of extra-articular lesions in rheumatoid arthritis (RA) patients. Methods: Our retrospective cohort study included patients diagnosed with RA between January 2018 to December 2019. Patients were divided into TCM treatment group and control group according to whether they received TCM treatment for more than three months. Propensity score matching (PSM) was used to balance covariates between groups. The occurrence time of extra-articular lesions, including interstitial lung disease, Sjögren's syndrome, and anemia, was calculated for both groups after PSM. Additionally, clinical indicators that may affect the occurrence of extra-articular lesions in RA were included in Cox multivariate regression analysis to explore prognostic factors related to RA. Results: A total of 883 RA patients were initially included in our study, with 481 in the TCM treatment group and 279 in the control group. TCM treatment improved all clinical indicators of RA patients, and there was a higher degree of support, confidence, and lift between TCM treatment and the improvement of clinical indicators. There was no significant difference in the rate of extra-articular lesions occurrence between the two groups. After PSM, the median occurrence time of interstitial lung disease, Sjögren's syndrome and anemia in the TCM treatment group were 30.767, 21.370 and 31.970 months, respectively. While in the control group, it was 15.911, 14.667 and 11.825 months, respectively. Cox multivariate regression analysis indicated that TCM treatment was a protective factor for the occurrence of extra-articular lesions in RA, while abnormally high level of IgG was an independent factor for interstitial lung disease and C4 was an independent factor for Sjögren's syndrome. Moreover, a longer duration of TCM usage was associated with a later occurrence of extra-articular lesions. Conclusion: Long-term TCM treatment not only positively affects the occurrence time of extra-articular lesions in RA patients, but also helps reduce the risk of extra-articular lesions occurrence. TCM can be applied flexibly throughout the treatment process for RA patients.

Innovation is a key factor for product development. Identifying innovative opportunities is the first step in innovative product design. Traditional methods of identifying innovative opportunities, such as market surveys and brainstorming, are limited by product users’ and designers’ experiences and lack systematic approaches to generate breakthrough innovations. This paper proposes a method to identify innovative opportunities based on product scenario evolution. The method models a product scenario based on product scenario elements, states, and behaviors. A Type II hierarchical function model is constructed based on the transformation and abstraction hierarchy of the product function model to identify target elements for the scenario evolution. Based on the theory of basic element extension and needs evolution characteristics, the method of extending target scenario elements is proposed. Based on the new scenario element sets and their impact, diffusion, identification, and evaluation methods are proposed for innovation opportunities. Potential opportunities are explored for product innovation from a scenario evolutionary perspective, which updates knowledge and technology reserves and finds new market opportunities for industries. The feasibility and effectiveness of the method are verified using the innovative design of a polyethylene (PE) pipeline hot-melt welding machine.

IntroductionSclerotium rolfsii Sacc. is a globally dispersed pathogenic fungus that causes southern blight disease in many crops and Chinese herbal medicine. The high degree of variation and diversity in the fungi altered population genetic structure. Therefore, the important factors of variation within the pathogen population should be considered during the development of management strategies for the disease.MethodsIn this study, S. rolfsii isolates from 13 hosts in 7 provinces of China were collected and analyzed to identify their morphological features and perform molecular characterization. To develop EST-SSR primers, transcriptome sequencing was performed on isolated CB1, and its SSR loci were comprehensively analyzed. In addition, we analyzed the polymorphisms among different populations based on screened EST-SSR primers.ResultsThe results showed that all of these clean reads with total 36,165,475 assembled bases were clustered into 28,158 unigenes, ranged from 201 bp to 16,402 bp on the length, of which the average length was 1,284 bp. Of these, the SSR sequence appeared at an average interval of 15.43 kB, and the frequency of SSR was 0.0648 SSR/kB. Polymorphism of 9 primers was observed among 22 populations, and was verified by the Shannon’s index (average = 1.414) and polymorphic information index (> 0.50). The genetic diversity analysis revealed diversity in all host populations and geographical populations. Further, molecular variance analysis (AMOVA) showed that the differences between groups were mainly related to geographical location. Based on cluster analysis, the 7 populations were roughly divided into 3 groups, and the results were highly consistent with those based on the geographical location, ultimately aligning with the results of STRUCTURE analysis.DiscussionThe findings build on current knowledge of the distribution of S. rolfsii in the southwest area of China, adding value to current knowledge base on the population structure and genetic diversity of S. rolfsii, specifically in the context of Chinese herbal medicine cultivation in China. Overall, our findings may provide valuable information for breeding of crops with enhanced resistance toward S. rolfsii.

IntroductionThe ecological balance of the plant microbiome, as a barrier against pathogens, is very important for host health. Coptis chinensis is one of the important medicinal plants in China. In recent years, Illumina Miseq high-throughput sequencing technology was frequently used to analyze root rot pathogens and the effects of root rot on rhizosphere microorganisms of C. chinensis. But the effects of root rot infection on rhizosphere microecological balance of C. chinensis have received little attention.MethodsIn this study, Illumina Miseq high-throughput sequencing technology was applied to analyze the impact on microbial composition and diversity of C. chinensis by root rot.ResultsThe results showed that root rot infection had significant impact on bacterial α-diversity in rhizome samples, but had no significant effect on that in leaf samples and rhizosphere soil samples, while root rot infection exhibited significant impact on the fungal α-diversity in leaf samples and rhizosphere soil samples, and no significant impact on that in rhizome samples. PCoA analysis showed that the root rot infection had a greater impact on the fungal community structure in the rhizosphere soil, rhizome, and leaf samples of C. chinensis than on the bacterial community structure. Root rot infection destroyed the microecological balance of the original microbiomes in the rhizosphere soil, rhizome, and leaf samples of C. chinensis, which may also be one of the reasons for the serious root rot of C. chinensis.DiscussionIn conclusion, our findings suggested that root rot infection with C. chinensis disrupts microecological balance of rhizosphere soil and endophytic microbiomes. The results of this study can provide theoretical basis for the prevention and control of C. chinensis root rot by microecological regulation.

IntroductionThe lack of systematic investigations of arbuscular mycorrhizal fungi (AMF) community composition is an obstacle to AMF biotechnological applications in antimony (Sb)- and arsenic (As)-polluted soil.MethodsMorphological and molecular identification were applied to study the AMF community composition in Sb- and As-contaminated areas, and the main influencing factors of AMF community composition in Sb- and As-contaminated areas were explored.Results(1) A total of 513,546 sequences were obtained, and the majority belonged to Glomeraceae [88.27%, 193 operational taxonomic units (OTUs)], followed by Diversisporaceae, Paraglomeraceae, Acaulosporaceae, Gigasporaceae, and Archaeosporaceae; (2) the affinity between AMF and plants was mainly related to plant species (F = 3.488, p = 0.022 < 0.050), which was not significantly correlated with the total Sb (TSb) and total As (TAs) in soil; (3) the AMF spore density was mainly related to the available nitrogen, available potassium, and total organic carbon; (4) The effect of soil nutrients on AMF community composition (total explanation: 15.36%) was greater than that of soil Sb and As content (total explanation: 5.80%); (5) the effect of TAs on AMF community composition (λ = −0.96) was more drastic than that of TSb (λ = −0.21), and the effect of As on AMF community composition was exacerbated by the interaction between As and phosphorus in the soil; and (6) Diversisporaceae was positively correlated with the TSb and TAs.DiscussionThe potential impact of As on the effective application of mycorrhizal technology should be further considered when applied to the ecological restoration of Sb- and As-contaminated areas.

Ethnopharmacological relevance: This study determines whether traditional Chinese medicine (TCM) treatment is associated with the risk of recurrent exacerbation in patients with rheumatoid arthritis (RA). Materials and methods: In this retrospective study, we selected 1383 patients who were diagnosed with RA between 2013 and 2021 from the medical record information management system of the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine. Then, patients were classified into TCM users and non-TCM users. Gender, age, recurrent exacerbation, TCM, death, surgery, organ lesions, Chinese patent medicine, external medicine, and non-steroidal anti-inflammatory drugs were adjusted one TCM user-to-one non-TCM user with propensity score matching to reduce selection bias and confusion using propensity score matching (PSM). A Cox regression model was used to compare the hazard ratio of the risk of recurrent exacerbation and the Kaplan Meier curve of recurrent exacerbation proportion between the two groups. Results: Most of the tested clinical indicators in this study improved in patients, which was correlated with the use of TCM, with a statistical significance. TCM was preferred in female and younger (

The microorganisms that co-exist between soil and rice systems in heavy metal-contaminated soil environments play important roles in the heavy metal pollution states of rice, as well as in the growth of the rice itself. In this study, in order to further examine the effects of soil microorganisms on the mercury (Hg) uptake of rice plants and determine potential soil phytoremediation agents, an enriched 199Hg isotope was spiked in a series of pot experiments to trace the absorption and migration of Hg and rice growth in the presence of arbuscular mycorrhizal fungi (AMF). It was observed that the AMF inoculations significantly reduced the Hg concentration in the rice. The Hg concentration in rice in the AMF inoculation group was between 52.82% and 96.42% lower than that in the AMF non-inoculation group. It was also interesting to note that the presence of AMF tended to cause Hg (especially methyl-Hg (Me199Hg)) to migrate and accumulate in the non-edible parts of the rice, such as the stems and leaves. Under the experimental conditions selected in this study, the proportion of Me199Hg in rice grains decreased from 9.91% to 27.88%. For example, when the exogenous Hg concentration was 0.1 mg/kg, the accumulated methyl-Hg content in the grains of the rice in the AMF inoculation group accounted for only 20.19% of the Me199Hg content in the rice plants, which was significantly lower than that observed in the AMF non-inoculated group (48.07%). AMF also inhibited the absorption of Hg by rice plants, and the decrease in the Hg concentration levels in rice resulted in significant improvements in growth indices, including biomass and micro-indexes, such as antioxidant enzyme activities. The improvements occurred mainly because the AMF formed symbiotic structures with the roots of rice plants, which fixed Hg in the soil. AMF also reduce the bioavailability of Hg by secreting a series of substances and changing the physicochemical properties of the rhizosphere soil. These findings suggest the possibility of using typical co-existing microorganisms for the remediation of soil heavy metal contamination and provide valuable insights into reducing human Hg exposure through rice consumption.

IntroductionThe bulb of Fritillaria hupehensis, a traditional cough and expectorant medicine, is usually harvested from June to September according to traditional cultivation experience, without practical scientific guidance. Although steroidal alkaloid metabolites have been identified in F. hupehensis, the dynamic changes in their levels during bulb development and their molecular regulatory mechanisms are poorly understood.MethodsIn this study, integrative analyses of the bulbus phenotype, bioactive chemical investigations, and metabolome and transcriptome profiles were performed to systematically explore the variations in steroidal alkaloid metabolite levels and identify the genes modulating their accumulation and the corresponding regulatory mechanisms.ResultsThe results showed that weight, size, and total alkaloid content of the regenerated bulbs reached a maximum at IM03 (post-withering stage, early July), whereas peiminine content reached a maximum at IM02 (withering stage, early June). There were no significant differences between IM02 and IM03, indicating that regenerated bulbs could be harvested appropriately in early June or July. Peiminine, peimine, tortifoline, hupehenine, korseveramine, delafrine, hericenone N-oxide, korseveridine, puqiedinone, pingbeinone, puqienine B, puqienine E, pingbeimine A, jervine, and ussuriedine levels were upregulated in IM02 and IM03, compared with IM01 (vigorous growth stage, early April). The Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that the accumulation of steroidal alkaloid metabolites mainly occurred prior to IM02. HMGR1, DXR, CAS1, CYP 90A1, and DET2 may play a positive role in peiminine, peimine, hupehenine, korseveramine, korseveridine, hericenone N-oxide, puqiedinone, delafrine, tortifoline, pingbeinone, puqienine B, puqienine E, pingbeimine A, jervine, and ussuriedine biosynthesis, whereas the downregulation of FPS1, SQE and 17-DHCR may lead to a reduction in peimisine levels. Weighted gene correlation network analysis showed that CYP 74A2-1, CYP 74A2-2, CYP 71A26-1, CYP 71A26-2, and CYP74A were negatively correlated with peiminine and pingbeimine A, whereas CYP R and CYP707A1 were positively correlated. . CYP 74A2-1 and CYP 74A2-2 may play a negative role in peimine and korseveridine biosynthesis, whereas CYP R plays a positive role. In addition, the highly expressed C2H2, HSF, AP2/ERF, HB, GRAS, C3H, NAC, MYB-related transcription factors (TFs), GARP-G2-like TFs, and WRKY may play positive roles in the accumulation of peiminine, peimine, korseveridine, and pingbeimine A.DiscussionThese results provide new insights into scientific harvesting of F. hupehensis.

The recent years' booming digital economy can not only benefit businesses, but also be an important way to improve people's wellbeing. This paper aimed to identify the relationship between the digital economy based on the “Broadband China” pilot policy and occupational health by applying DID method. The empirical results highlight that occupational health in the pilot cities of “Broadband China” are significantly improved compared with those in non-pilot cities, indicating that the digital economy can significantly improve occupational health. However, this effect varies across regions with different levels of economic development. Compared with developed areas, the digital economy has a more obvious effect on the improvement of occupational health in less developed areas, which indicates that this effect conforms to the law of diminishing marginal effect. Therefore, the digital economy should be continuously promoted to improve occupational health. Governments at all levels should strengthen the network infrastructure to provide a good basic environment for the development of the digital economy. At the same time, governments should introduce more detailed digital economy goals and programs according to the actual situation of their jurisdictions to fully release the economic and social benefits of the digital economy.

Heat resistance is a basic and crucial characteristic of energetic materials (EMs), and always accounted in development and application. Compared with the clear origin of the high heat resistance of EMs, the mechanism for the low heat resistance remains still unclear. This work reveals the mechanism by carrying reactive molecular dynamics simulations on heating six less thermally stable EMs of nitroforms and pentaerythritol tetranitrate (PETN), as well as a more thermally stable EM of 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) for comparison. Unexceptionally, all the nitroforms and PETN heated feature fast NO2 partition and further decomposition throng the oxidation of NO2 to form small fragments and final small stable product molecules, with fast heat release; while, the intermolecular reactions and the further clustering govern the initial steps in decomposing TATB. Therein the reactants also exhibit a rapid consumption; however, this fast consumption with clustering does not result in the low heat resistance of TATB. That is, some general indicators representative of thermostability, such as bond dissociation energy and the reactant consumption rate, are insufficient to assess it practically. Thus, the rapid fragmentation originally contributes to the low heat resistance. These insights are expected to present an overall perspective of understanding the thermal stability mechanism of EMs, and set a theoretical base and pave a way for designing EMs with desired heat resistance.

Fritillaria hupehensis, a well-known medicinal perennial herb, is used as an antitussive and an expectorant. Continuous cropping and monoculture cultivation usually negativly affect the growth of F. hupehensis. Compared with the monoculture system, the F. hupehensis-Magnolia officinalis intercropping system significantly increases the yield of F. hupehensis. However, changes in steroidal alkaloid metabolites (the most important bioactive components) and their molecular regulatory mechanisms in F. hupehensis intercropping system remain unclear. We performed comparative transcriptomic and metabolomic analyses of F. hupehensis bulbs grown in monocropping and intercropping systems. A total of 40 alkaloids were identified, including 26 steroidal alkaloids, 4 plumeranes, 3 phenolamines, 1 pyridine alkaloid, and 6 other alkaloids. The results showed that intercropping significantly increased the levels of peimine, peiminine, hupehenine, korseveridine, verticinone N-oxide, delafrine, tortifoline, pingbeinone, puqienine B, puqienine E, jervine, ussuriedine, hydroxymandelonitrile, N-feruloylputrescine, and N-benzylmethylene isomethylamine in F. hupehensis, but decreased the levels of indole, p-coumaroylputrescine, and N-benzylformamide. Transcriptome sequencing identified 11,466 differentially expressed unigenes in F. hupehensis under the intercropping system, of which 5,656 genes were up-regulated and 5,810 genes were down-regulated. We proposed a possible steroidal alkaloid biosynthesis pathway, in which 12 differentially expressed genes were identified. The higher expressions of these genes in the intercropping system positively correlated with the high accumulation of peimine, peiminine, and hupehenine, further validating our proposal. Moreover, the biological processes of oxidative phosphorylation and plant hormone signal transduction, cytochrome P450 enzymes, ATP-binding cassette transporters, and transcription factors may play pivotal roles in the regulation of steroidal alkaloid biosynthesis. This study revealed the underlying molecular mechanisms of intercropping in improving steroidal alkaloids in F. hupehensis at the transcriptome and metabolome levels. These findings provided a theoretical foundation for sustainable development of this ecological planting method.

Highly thermostable energetic materials (EMs) are highly desired for deep underground and space exploration, and therefore have attracted much attention. This work employs four typical traditional EMs composed of C, H, N and O atoms as example to clarify the origin of high heat resistance, by means of molecular dynamics simulations with the molecular reactive forcefield of ReaxFF. These EMs include 3,5-dinitro-N,N´-bis(2,4,6-trinitrophenyl)pyridine-2,6-diamine (PYX), 1,3,5-diamino-2,4,6-trinitrobenzene (TATB) and 2,2´,4,4´,6,6´-hexanitrostilbene (HNS), which are highly thermostable with decomposition temperature peaks > 600 K, and a less one of pentaerythritol tetranitrate (PETN) for comparison. It is found that the clustering in the decomposition of PYX, TATB and HNS retards the extraction of small product molecules from clusters, as well as heat release, and thereby roots for their high heat resistance; while, the clustering in the PETN decay is negligible and heat release and fragmentation proceed rapidly, facilitating to fast decomposition. Combining this finding with the well-known molecular stability, this work presents a perspective on the high heat resistance of traditional EMs. Based on it, a highly negative oxygen balance, a high C content and a high molecular stability are proposed as a strategy for designing and constructing new highly heat-resistant EMs.

Microplastics (MPs) are emerging as environmental pollutants and are widely distributed in aquatic environments. They are characterized by long life cycles, ease of migration, ability to adsorb other environmental pollutants, small size, and ease of ingestion by aquatic organisms, thereby threatening the growth, life, and health of aquatic organisms. MPs are biologically transferable and can accumulate in organisms at high trophic levels via food chains, thereby negatively impacting the ecological environment and human health. Moreover, the bioaccumulation of MPs is an important parameter for scientific risk assessments. This paper reviews the current status of MP pollution and its bioaccumulation in marine, freshwater, and other water environments. Furthermore, it proposes relevant recommendations for future research on the bioaccumulation of MPs in conjunction with previous studies to provide basic support for risk assessment and environmental management.

Remediation of mercury (Hg)-contaminated soil by mycorrhizal technology has drawn increasing attention because of its environmental friendliness. However, the lack of systematic investigations on arbuscular mycorrhizal fungi (AMF) community composition in Hg-polluted soil is an obstacle for AMF biotechnological applications. In this study, the AMF communities within rhizosphere soils from seven sites from three typical Hg mining areas were sequenced using an Illumina MiSeq platform. A total of 297 AMF operational taxonomic units (OTUs) were detected in the Hg mining area, of which Glomeraceae was the dominant family (66.96%, 175 OTUs). AMF diversity was significantly associated with soil total Hg content and water content in the Hg mining area. Soil total Hg showed a negative correlation with AMF richness and diversity. In addition, the soil properties including total nitrogen, available nitrogen, total potassium, total phosphorus, available phosphorus, and pH also affected AMF diversity. Paraglomeraceae was found to be negatively correlated to Hg stress. The wide distribution of Glomeraceae in Hg-contaminated soil makes it a potential candidate for mycorrhizal remediation.

Arbuscular mycorrhizal fungi (AMF) can form symbiotic relationships with most terrestrial plants and regulate the uptake and distribution of antimony (Sb) in rice. The effect of AMF on the uptake and transport of Sb in rice was observed using pot experiments in the greenhouse. The results showed that AMF inoculation increased the contact area between roots and metals by forming mycelium, and changed the pH and Eh of the root soil, leading to more Sb entering various parts of the rice, especially at an Sb concentration of 1,200 mg/kg. The increase in metal toxicity further led to a decrease in the rice chlorophyll content, which directly resulted in a 22.7% decrease in aboveground biomass, 21.7% in underground biomass, and 11.3% in grain biomass. In addition, the antioxidant enzyme results showed that inoculation of AMF decreased 22.3% in superoxide dismutase, 9.9% in catalase, and 20.7% in peroxidase compared to the non-inoculation groups, further verifying the negative synergistic effect of AMF inoculation on the uptake of Sb in rice. The present study demonstrated the effect of AMF on the uptake and transport of Sb in the soil–rice system, facilitating future research on the related mechanism in the soil–rice system under Sb stress.

To study the soil genetic diversity of bacteria and fungi in different vegetation successions (grassland, shrubbery, primary forest and secondary forest) from the karst area, the Polymerase Chain Reaction-Denaturing Gradient Gel Electrophoresis (PCR-DGGE) technology was applied. The results showed that: (1) the diversity of bacterial communities and the fungal communities in karst area were higher than non karst area in each vegetation succession. Compared with the survey from bacterial (the Shannon index was 2.97 in primary forest, 2.91 in secondary forest, 3.18 in shrubbery, 3.14 in grassland and 2.68 in non karst), fungal diversity between karst areas (the Shannon index was 3.56 in primary forest, 3.78 in secondary forest, 3.73 in shrubbery and 3.70 in grassland) and non karst areas (the Shannon index was 3.08) was more evident, which may be related to the alterations of the composition of plant community and the source of carbon in soil with the vegetation succession of karst ecosystem; (2) The comparation of bacterial diversity index and the richness comprehensively evaluated as follows: shrubbery > grassland > primary forest > nsecondary forest. The diversity index and the richness of fungal communities was as follows: secondary forest > shrubbery > grassland > primary forest. The results suggest that the fungal communities have been greatly changed via vegetation successions, but the diversity index and the richness of the bacterial communities have not been seriously affected. The results provide scientific basis for understanding karst surface ecosystem, which contributes to the future aim of protecting the karst from desertification.

Abstract In this paper, the synthesis of ultrasmall Na2FePO4F nanoparticles (≈3.8 nm) delicately embedded in porous N‐doped carbon nanofibers (denoted as Na2FePO4F@C) by electrospinning is reported. The as‐prepared Na2FePO4F@C fiber film tightly adherent on aluminum foil features great flexibility and is directly used as binder‐free cathode for sodium‐ion batteries, exhibiting admirable electrochemical performance with high reversible capacity (117.8 mAh g−1 at 0.1 C), outstanding rate capability (46.4 mAh g−1 at 20 C), and unprecedentedly high cyclic stability (85% capacity retention after 2000 cycles). The reaction kinetics and mechanism are explored by a combination study of cyclic voltammetry, ex situ structure/valence analyses, and first‐principles computations, revealing the highly reversible phase transformation of Na2FeIIPO4F ↔ NaFeIIIPO4F, the facilitated Na+ diffusion dynamics with low energy barriers, and the desirable pseudocapacitive behavior for fast charge storage. Pouch‐type Na‐ion full batteries are also assembled employing the Na2FePO4F@C nanofibers cathode and the carbon nanofibers anode, demonstrating a promising energy density of 135.8 Wh kg−1 and a high capacity retention of 84.5% over 200 cycles. The distinctive network architecture of ultrafine active materials encapsulated into interlinked carbon nanofibers offers an ideal platform for enhancing the electrochemical reactivity, electronic/ionic transmittability, and structural stability of Na‐storage electrodes.

Epidemiological studies have revealed that noise exposure was associated with an increased risk of type 2 diabetes mellitus (T2DM). However, the exact nature of that association remains to be elucidated. The present study is designed to examine the effects of chronic noise exposure on the development of T2DM in combination with a high-fat-diet (HFD) in mice. Here we show that chronic noise exposure at 85 dB SPL (4 h /day, below the safety limit for occupational noise exposure) exaggerated multiple metabolic abnormalities induced by HFD in C57BL/6J male mice, including worsened glucose intolerance, insulin resistance, fasting hyperglycemia and dyslipidemia. Furthermore, noise exposure exhibited a paradoxical impact on fat accumulation and circulating levels of free fatty acid, indicating a potential stimulating effect of noise on lipolysis. These results provide first in vivo supporting evidence for the causative role of noise exposure in diabetogenesis and pinpoint a noise-associated increase in blood free fatty acid levels as a possible mediator accelerating the effect of noise on the development of insulin resistance and T2DM.

Background: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic and symmetrical polyarthritis. RA patients often experience inflammatory reaction and hypercoagulable state, which together affect the self-perception of patient (SPP). Currently, inhibiting inflammation and hypercoagulable state are common treatment methods for alleviating RA symptoms. Xinfeng Capsules (XFC) has a long history of treating RA, and can effectively improve the inflammatory response and hypercoagulable state of RA. However, the potential mechanisms have not yet been determined. Purpose and study design: This study elucidated the action mechanism of XFC in RA inflammation and hypercoagulability through the lncDSCR9/RPLP2/PI3K/ AKT axis. Results: Clinical observations indicated that there was a strong link between XFC therapy and improvements in inflammatory and coagulation biomarkers, as well as SPP among RA patients. The subsequent network pharmacology analysis results identified the PI3K/AKT signaling pathway as a potential mediator for XFC treatment of RA. Furthermore, clinical validation and sequencing results revealed that lncRNA DSCR9 expression (a gene implicated in inflammation and coagulation) was negatively correlated with clinical markers of inflammation and coagulation, while positively correlated with SF-36 indicators. Notably, XFC treatment remarkably upregulated lncRNA DSCR9 expression and downregulated PI3K and AKT expressions, showing opposite expression trends to the untreated cases.The regulatory effect of XFC on the lncRNA DSCR9/ RPLP2/PI3K/AKT axis in RA was investigated using techniques such as RNA pulldown assay, Western blot analysis, RT-PCR, and EdU assay. Moreover, the administration of the PI3K/AKT agonist RMH can counteract the effects of XFC on p-PI3K, p-AKT, inflammation, and hypercoagulability, reinforcing the role of pathway. Finally, animal studies utilizing HE staining and transmission electron microscopy (TEM) demonstrated that XFC notably decreased PI3K and AKT expressions in adjuvant-induced arthritis (AA) rats, mitigated inflammation and hypercoagulability, and enhanced the ultrastructure of synovial cells. These findings underscored the potential mechanisms of XFC in the treatment of RA. Conclusion: Regulating the lncRNA DSCR9/RPLP2/PI3K/AKT axis may be an important mechanism by which XFC improved RA inflammatory response and hypercoagulable state. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the impact of paternal age > 40 years on clinical pregnancy and perinatal outcomes among patients undergoing in vitro fertilization treatment. Methods: We selected 75 male patients (aged > 40 years) based on predefined inclusion and exclusion criteria. Propensity score matching was performed in a 1:3 ratio, resulting in a control group (aged = 40 years) of 225 individuals. Various statistical tests, including the Mann-Whitney U test, Chi-square test, Fisher's exact test, and binary logistic regression, were used to analyze the association between paternal age and clinical outcomes. Results: We found no statistically significant differences in semen routine parameters, clinical pregnancy outcomes, and perinatal outcomes between paternal aged > 40 and = 40 years. However, in the subgroup analysis, the live birth rate significantly decreased in those aged = 45 compared to those aged 41-42 and 43-44 years (31.25% vs. 69.23% and 65%, respectively; all p < 0.05). Additionally, the clinical pregnancy rate was significantly lower among those aged = 45 than among those aged 41-42 (43.75% vs. 74.36%; p=0.035). Conclusion: Paternal age = 45 years was associated with lower live birth and clinical pregnancy rates. [ABSTRACT FROM AUTHOR]

BACKGROUND: Exertional heatstroke (EHS) is a life-threatening disease without ideal prognostic markers for predicting hospital mortality. METHODS: This is a single-center retrospective study. Clinical data from EHS patients admitted to the Intensive Care Unit (ICU) of the General Hospital of Southern Theatre Command between January 1, 2008, and December 31, 2020, were recorded and analyzed. Univariate and multivariate logistic regression were used to identify the factors for mortality. The prediction model was developed with the prognostic markers, and a nomogram was established. RESULTS: The study ultimately enrolled 156 patients, and 15 (9.6%) of patients died before discharge. The lymphocyte count (Lym) and percentage (Lym%) were significantly lower in nonsurvivors (P<0.05). The univariate and multivariate logistic regression analyses indicated that Lym% at the third day of admission (Lym% D3) (OR=0.609, 95%CI: 0.454-0.816) and hematocrit (HCT) (OR=0.908, 95%CI: 0.834-0.988) were independent protective factors for hospital mortality. A nomogram incorporating Lym% D3 with HCT was developed and demonstrated good discrimination and calibration ability. The comparison between the prediction model and scoring systems revealed that the prediction model had the largest area under the curve (AUC) (0.948, 95%CI: 0.900-0.977), with 100.00% sensitivity and 83.69% specificity, and a greater clinical net benefit. CONCLUSION: Severe EHS patients had a higher risk of experiencing prolonged lymphopenia. A nomogram based on Lym% D3 and HCT was developed to facilitate early identification and timely treatment of patients with potentially unfavorable prognoses. [ABSTRACT FROM AUTHOR]