Inhaled SARS-CoV-2 vaccine for single-dose dry powder aerosol immunization.

The COVID-19 pandemic has fostered major advances in vaccination technologies1-4; however, there are urgent needs for vaccines that induce mucosal immune responses and for single-dose, non-invasive administration4-6. Here we develop an inhalable, single-dose, dry powder aerosol SARS-CoV-2 vaccine that induces potent systemic and mucosal immune responses. The vaccine encapsulates assembled nanoparticles comprising proteinaceous cholera toxin B subunits displaying the SARS-CoV-2 RBD antigen within microcapsules of optimal aerodynamic size, and this unique nano-micro coupled structure supports efficient alveoli delivery, sustained antigen release and antigen-presenting cell uptake, which are favourable features for the induction of immune responses. Moreover, this vaccine induces strong production of IgG and IgA, as well as a local T cell response, collectively conferring effective protection against SARS-CoV-2 in mice, hamsters and nonhuman primates. Finally, we also demonstrate a mosaic iteration of the vaccine that co-displays ancestral and Omicron antigens, extending the breadth of antibody response against co-circulating strains and transmission of the Omicron variant. These findings support the use of this inhaled vaccine as a promising multivalent platform for fighting COVID-19 and other respiratory infectious diseases.

Lactic acid promotes nucleus pulposus cell senescence and corresponding intervertebral disc degeneration via interacting with Akt.

The accumulation of metabolites in the intervertebral disc is considered an important cause of intervertebral disc degeneration (IVDD). Lactic acid, which is a metabolite that is produced by cellular anaerobic glycolysis, has been proven to be closely associated with IVDD. However, little is known about the role of lactic acid in nucleus pulposus cells (NPCs) senescence and oxidative stress. The aim of this study was to investigate the effect of lactic acid on NPCs senescence and oxidative stress as well as the underlying mechanism. A puncture-induced disc degeneration (PIDD) model was established in rats. Metabolomics analysis revealed that lactic acid levels were significantly increased in degenerated intervertebral discs. Elimination of excessive lactic acid using a lactate oxidase (LOx)-overexpressing lentivirus alleviated the progression of IVDD. In vitro experiments showed that high concentrations of lactic acid could induce senescence and oxidative stress in NPCs. High-throughput RNA sequencing results and bioinformatic analysis demonstrated that the induction of NPCs senescence and oxidative stress by lactic acid may be related to the PI3K/Akt signaling pathway. Further study verified that high concentrations of lactic acid could induce NPCs senescence and oxidative stress by interacting with Akt and regulating its downstream Akt/p21/p27/cyclin D1 and Akt/Nrf2/HO-1 pathways. Utilizing molecular docking, site-directed mutation and microscale thermophoresis assays, we found that lactic acid could regulate Akt kinase activity by binding to the Lys39 and Leu52 residues in the PH domain of Akt. These results highlight the involvement of lactic acid in NPCs senescence and oxidative stress, and lactic acid may become a novel potential therapeutic target for the treatment of IVDD.

PHLDA2 overexpression facilitates senescence and apoptosis via the mitochondrial route in human nucleus pulposus cells by regulating Wnt/ß-catenin signalling pathway.

Low back pain is a common clinical symptom of intervertebral disc degeneration (IVDD), which seriously affects the quality of life of the patients. The abnormal apoptosis and senescence of nucleus pulposus cells (NPCs) play important roles in the pathogenesis of IVDD. PHLDA2 is an imprinted gene related to cell apoptosis and tumour progression. However, its role in NPC degeneration is not yet clear. Therefore, this study was set to explore the effects of PHLDA2 on NPC senescence and apoptosis and the underlying mechanisms. The expression of PHLDA2 was examined in human nucleus pulposus (NP) tissues and NPCs. Immunohistochemical staining, magnetic resonance imaging imaging and western blot were performed to evaluate the phenotypes of intervertebral discs. Senescence and apoptosis of NPCs were assessed by SA-ß-galactosidase, flow cytometry and western blot. Mitochondrial function was investigated by JC-1 staining and transmission electron microscopy. It was found that the expression level of PHLDA2 was abnormally elevated in degenerated human NP tissues and NPCs. Furthermore, knockdown of PHLDA2 can significantly inhibit senescence and apoptosis of NPCs, whereas overexpression of PHLDA2 can reverse senescence and apoptosis of NPCs in vitro. In vivo experiment further confirmed that PHLDA2 knockdown could alleviate IVDD in rats. Knockdown of PHLDA2 could also reverse senescence and apoptosis in IL-1ß-treated NPCs. JC-1 staining indicated PHLDA2's knockdown impaired disruption of the mitochondrial membrane potential and also ameliorated superstructural destruction of NPCs as showed by transmission electron microscopy. Finally, we found the PHLDA2 knockdown promoted Collagen-II expression and suppressed MMP3 expression in NPCs by repressing wnt/ß-catenin pathway. In conclusion, the results of the present study showed that PHLDA2 promotes IL-1ß-induced apoptosis and senescence of NP cells via mitochondrial route by activating the Wnt/ß-catenin pathway, and suggested that therapy targeting PHLDA2 may provide valuable insights into possible IVDD therapies.

How the Listener's Attention Dynamically Switches Between Different Speakers During a Natural Conversation.

The neural mechanisms underpinning the dynamic switching of a listener's attention between speakers are not well understood. Here we addressed this issue in a natural conversation involving 21 triadic adult groups. Results showed that when the listener's attention dynamically switched between speakers, neural synchronization with the to-be-attended speaker was significantly enhanced, whereas that with the to-be-ignored speaker was significantly suppressed. Along with attention switching, semantic distances between sentences significantly increased in the to-be-ignored speech. Moreover, neural synchronization negatively correlated with the increase in semantic distance but not with acoustic change of the to-be-ignored speech. However, no difference in neural synchronization was found between the listener and the two speakers during the phase of sustained attention. These findings support the attenuation model of attention, indicating that both speech signals are processed beyond the basic physical level. Additionally, shifting attention imposes a cognitive burden, as demonstrated by the opposite fluctuations of interpersonal neural synchronization.

Silver Metal-Organic Framework Derived N-Doped Carbon Nanofibers for CO2 Conversion into ß-Oxopropylcarbamates.

Developing efficient heterogeneous catalysts for chemical fixation of CO2 to produce high-value-added chemicals under mild conditions is highly desired but still challenging. Herein, we first reported an approach to prepare a novel catalyst (Ag@NCNFs), featuring Ag nanoparticles (NPs) embedded within porous nitrogen-doped carbon nanofibers (NCNFs), via growing a Ag metal-organic framework on one-dimensional electrospun nanofibers followed by pyrolysis. Benefiting from the abundant nitrogen species and porous structure, Ag NPs is well dispersed in the obtained Ag@NCNFs. Catalytic studies indicated that Ag@NCNFs exhibited excellent catalytic activity for the three-component coupling reaction of CO2, secondary amines, and propargylic alcohols to generate ß-oxopropylcarbamates under mild conditions with a turnover number (TON) of 16.2, and it can be recycled and reused at least 5 times without an obvious decline in catalytic activity. The reaction mechanism was clearly clarified by FTIR, NMR, 13C isotope labeling, control experiments, and density functional theory calculations. The results suggest that Ag@NCNFs and 1,8-diazabicyclo[5.4.0]undec-7-ene can synergistically activate propargylic alcohol to react with CO2, and then the generated α-alkylidene cyclic carbonate was invaded by secondary amine to produce ß-oxopropylcarbamate. Importantly, to the best of our knowledge, this is the first experimental and theoretical investigation on this reaction.

Energy transfer from two luteins to chlorophylls in light-harvesting complex II study by using exciton models with phase correction.

In light-harvesting complex II of plants, the two lutein pigments (LUT1 and LUT2) are always paired and an energy transfer pathway between them is believed to exist. However, it remains unclear whether this pathway is essential for the energy transfer between carotenoids and chlorophylls. In this work, we performed hybrid quantum mechanics/molecular mechanics simulations with Frenkel exciton models to investigate this energy transfer. The results show that the energy transfer pathways between the S2 state of LUT1 and CLAs are not affected by LUT2 S2. The energy transfer between LUT and chlorophyll-a (CLA) also follows a resonance mechanism. The two LUTs have different energy transfer pathways according to their energy gaps and coupling strengths with each CLA. The present work sheds light on the energy transfer pathways involved in the two LUTs.

Neural synchrony underlies the positive effect of shared reading on children's language ability.

Although it is well recognized that parent-child shared reading produces positive effects on children's language ability, the underlying neurocognitive mechanisms are not well understood. Here, we addressed this issue by measuring brain activities from mother-child dyads simultaneously during a shared book reading task using functional near infrared spectroscopy hyperscanning. The behavioral results showed that the long-term experience of shared reading significantly predicted children's language ability. Interestingly, the prediction was moderated by children's age: for older children over 30 months, the more the shared reading experience, the better the language performance; for younger children below 30 months, however, no significant relationship was observed. The brain results showed significant interpersonal neural synchronization between mothers and children at the superior temporal cortex, which was closely associated with older children's language ability through the mediation of long-term experience of shared reading. Finally, the results showed that the instantaneous quality of shared reading contributed to children's language ability through enhancing interpersonal neural synchronization and increasing long-term experience. Based on these findings, we tentatively proposed a theoretical model for the relationship among interpersonal neural synchronization, shared reading and children's language ability. These findings will facilitate our understanding on the role of shared reading in children's language development.

Biasing the neurocognitive processing of videos with the presence of a real cultural other.

In the digital age, while short videos present vital events with powerful information, the presence of cultural cues may bias our processing of videos of foreign cultures. However, the underlying neurocognitive processes remain unclear. In this study, we hypothesized that cultural cues might bias video processing by either enhancing cultural perspective-taking or shifting cultural self-schema. To test these hypotheses, we used a novel paradigm in which the cultural cue was a real cultural other (the priming participants) who watched American/Chinese videos together with the primed participants. The results showed that when the cue was present, the right temporoparietal junction (rTPJ) response to videos with other cultural content was shifted, showing a priming effect. Moreover, the activity pattern in the rTPJ was more congruent with the primed culture than with the original culture, reflecting a neural biasing effect. Finally, intersubject representational similarity analysis indicated that the neural biasing effect in the rTPJ was more closely associated with cultural perspective-taking than with cultural self-schema. In summary, these findings support the perspective-taking hypothesis, suggesting that cultural cues can significantly bias our cultural mindset by altering cultural perspective-taking when we are exposed to culture-relevant naturalistic stimuli.

Neurocomputational mechanisms of young children's observational learning of delayed gratification.

The ability to delay gratification is crucial for a successful and healthy life. An effective way for young children to learn this ability is to observe the action of adult models. However, the underlying neurocomputational mechanism remains unknown. Here, we tested the hypotheses that children employed either the simple imitation strategy or the goal-inference strategy when learning from adult models in a high-uncertainty context. Results of computational modeling indicated that children used the goal-inference strategy regardless of whether the adult model was their mother or a stranger. At the neural level, results showed that successful learning of delayed gratification was associated with enhanced interpersonal neural synchronization (INS) between children and the adult models in the dorsal lateral prefrontal cortex but was not associated with children's own single-brain activity. Moreover, the discounting of future reward's value obtained from computational modeling of the goal-inference strategy was positively correlated with the strength of INS. These findings from our exploratory study suggest that, even for 3-year-olds, the goal-inference strategy is used to learn delayed gratification from adult models, and the learning strategy is associated with neural interaction between the brains of children and adult models.

Overexpressed ski efficiently promotes neurorestoration, increases neuronal regeneration, and reduces astrogliosis after traumatic brain injury.

Traumatic brain injury (TBI) survivors suffer from long-term disability and neuropsychiatric sequelae due to irreparable brain tissue destruction. However, there are still few efficient therapies to promote neurorestoration in damaged brain tissue. This study aimed to investigate whether the pro-oncogenic gene ski can promote neurorestoration after TBI. We established a ski-overexpressing experimental TBI mouse model using adenovirus-mediated overexpression through immediate injection after injury. Hematoxylin-eosin staining, MRI-based 3D lesion volume reconstruction, neurobehavioral tests, and analyses of neuronal regeneration and astrogliosis were used to assess neurorestorative efficiency. The effects of ski overexpression on the proliferation of cultured immature neurons and astrocytes were evaluated using imaging flow cytometry. The Ski protein level increased in the perilesional region at 3 days post injury. ski overexpression further elevated Ski protein levels up to 14 days post injury. Lesion volume was attenuated by approximately 36-55% after ski overexpression, with better neurobehavioral recovery, more newborn immature and mature neurons, and less astrogliosis in the perilesional region. Imaging flow cytometry results showed that ski overexpression elevated the proliferation rate of immature neurons and reduced the proliferation rate of astrocytes. These results show that ski can be considered a novel neurorestoration-related gene that effectively promotes neurorestoration, facilitates neuronal regeneration, and reduces astrogliosis after TBI.

Neurocomputations on dual-brain signals underlie interpersonal prediction during a natural conversation.

Prediction on the partner's speech plays a key role in a smooth conversation. However, previous studies on this issue have been majorly conducted at the single-brain rather than dual-brain level, leaving the interpersonal prediction hypothesis untested. To fill this gap, this study combined a neurocomputational modeling approach with a natural conversation paradigm in which two salespersons persuaded a customer to buy their product with their haemodynamic signals being collected using functional near-infrared spectroscopy hyperscanning. First, the results showed a cognitive hierarchy in a natural conversation, with the lower-level process (i.e., pragmatic representation of the persuasion) in the salesperson interacting with the higher-level process (i.e., value representation of the product) in the customer. Next, we found that the right dorsal lateral prefrontal cortex (rdlPFC) and temporoparietal junction (rTPJ) were associated with the representation of the product's value in the customer, while the right inferior frontal cortex (rIFC) was associated with the representation of the pragmatic processes in the salesperson. Finally, neurocomputational modeling results supported the prediction of the salesperson's lower-level brain activity based on the customer's higher-level brain activity. Moreover, the updating weight of the prediction model based on the neural computation between the rIFC of the salesperson and the rTPJ of the customer was closely associated with the interaction context, whereas that based on the rIFC-rdlPFC was not. In summary, these findings provide initial support for the interpersonal prediction hypothesis at the dual-brain level and reveal a hierarchy for the interpersonal prediction process.

Phospholipase iPLA2ß averts ferroptosis by eliminating a redox lipid death signal.

Ferroptosis, triggered by discoordination of iron, thiols and lipids, leads to the accumulation of 15-hydroperoxy (Hp)-arachidonoyl-phosphatidylethanolamine (15-HpETE-PE), generated by complexes of 15-lipoxygenase (15-LOX) and a scaffold protein, phosphatidylethanolamine (PE)-binding protein (PEBP)1. As the Ca2+-independent phospholipase A2ß (iPLA2ß, PLA2G6 or PNPLA9 gene) can preferentially hydrolyze peroxidized phospholipids, it may eliminate the ferroptotic 15-HpETE-PE death signal. Here, we demonstrate that by hydrolyzing 15-HpETE-PE, iPLA2ß averts ferroptosis, whereas its genetic or pharmacological inactivation sensitizes cells to ferroptosis. Given that PLA2G6 mutations relate to neurodegeneration, we examined fibroblasts from a patient with a Parkinson's disease (PD)-associated mutation (fPDR747W) and found selectively decreased 15-HpETE-PE-hydrolyzing activity, 15-HpETE-PE accumulation and elevated sensitivity to ferroptosis. CRISPR-Cas9-engineered Pnpla9R748W/R748W mice exhibited progressive parkinsonian motor deficits and 15-HpETE-PE accumulation. Elevated 15-HpETE-PE levels were also detected in midbrains of rotenone-infused parkinsonian rats and α-synuclein-mutant SncaA53T mice, with decreased iPLA2ß expression and a PD-relevant phenotype. Thus, iPLA2ß is a new ferroptosis regulator, and its mutations may be implicated in PD pathogenesis.

Charge fluctuation drives anion rotation to enhance the conductivity of Na11M2PS12 (M = Si, Ge, Sn) superionic conductors.

Solid superionic conductors exhibit good battery safety and stability, promising to replace organic liquid electrolytes. However, a comprehensive understanding of the factors determining high ion mobility remains elusive. Experiments have confirmed that the Na11Sn2PS12 superionic conductor has high room temperature Na+-ion conductivity; excellent phase stability has been demonstrated in a solid-state electrolyte. The PS4 anion rotation exists in Na11M2PS12-type superionic conductors, but this rotation is affected by the isovalent cation substitutions of the M site. In combination with ab initio molecular dynamic simulations and joint time correlation analysis of the AIMD data, we show that the transport of Na+ ions is directly enhanced by the charge fluctuation in their tetrahedral MS4 anions that comprise the framework. The fundamental reason for the charge fluctuation is the material structure forming a micro-parallel capacitor with MS4 anions, which governs the differential capacitance. Our study provides a fundamental and comprehensive understanding of the structure-controlled charge transfer of Na11M2PS12-type material and can guide solid-state battery optimization and design.

Intermolecular resonance energy transfer between two lutein pigments in light-harvesting complex II studied by frenkel exciton models.

The energy transfer pathways in light-harvesting complex II are complicated and the discovery of the energy transfer between the two luteins revealed an unelucidated important role of carotenoids in the energy flow. This energy transfer between the two S2 states of luteins was for the first time investigated using Frenkel exciton models, using a hybrid scheme of molecular mechanics and quantum mechanics. The results show the energy flow between the two luteins under the Förster resonance energy transfer mechanism. The energy transfer caused by energy level resonance occurs in configurations with small energy gaps. This energy transfer pathway is particularly sensitive to conformation. Moreover, according to the statistical characteristics of the data of the energy gaps and coupling values between LUTs, we proposed stochastic exciton Hamiltonian models to facilitate clarification of the energy transfer among pigments in antenna complexes.

New insights into the alkoxy effects on auxiliary adsorption and inhibiting charge recombination in dye-sensitized solar cells with high open circuit voltage: a theoretical investigation.

Although introducing an alkoxy group is one of the most popular methods to suppress the interfacial charge recombination process of dye-sensitized solar cells, understanding of its effects is still limited and a microscopic picture of the alkoxy effects is lacking. Two ullazine dyes with distinct alkoxy chains at the donor part are used to investigate the effects of the alkoxy group on the adsorption, dye aggregation and charge recombination process in our study. Different from the usual assumption, we find that alkoxy chains can not only play a shielding role, but can also assist dye adsorption and inhibit the charge recombination process more effectively by covering the TiO2 surface. We also find that the existence of alkyl chains can well inhibit the aggregation of dyes and reduce intermolecular electron transfer. Furthermore, an important structural feature at the interface, the Ti-O interaction between the oxygen atom of the alkoxy group and the Ti atom of the surface is also found to contribute substantially to the interface stability. New insights into the effects of the alkoxy group on auxiliary adsorption and inhibiting charge recombination through reducing the recombination sites pave the way for rational design of sensitizers with high performance.

Interpersonal conflict increases interpersonal neural synchronization in romantic couples.

Previous studies on dual-brain social interaction have shown different patterns of interpersonal neural synchronization (INS) between conflictual and supportive interactions, but the role of emotion in the dual-brain mechanisms of such interactions is not well understood. Furthermore, little is known about how the dual-brain mechanisms are affected by relationship type (e.g., romantic relationship vs. friendship) and interaction mode (e.g., verbal vs. nonverbal). To elaborate on these issues, this study used functional near-infrared spectroscopy to collect hemodynamic signals from romantic couples and cross-sex friends while they were discussing conflictual, neutral, or supportive topics. For the couples but not the friends, INS between the sensorimotor cortex of both participants was greater when discussing the conflictual topic than when discussing the supportive topic. INS was positively correlated with the arousal level but not the valence level of communication contents. INS was also positively correlated with interpersonal physiological synchronization based on galvanic skin response, a physiological measure of arousal. Furthermore, the differences in INS between the conflictual and supportive topics were closely associated with verbal rather than nonverbal behaviors. Together, these findings suggest that it is the arousal level induced by verbal interactions during interpersonal conflicts that increases romantic couples' INS.

A method to protect the endometrium for microwave ablation treating types 1-3 uterine fibroids: a preliminary comparative study.

PURPOSE: To investigate the feasibility of percutaneous intrauterine instillation of chilled saline to protect the endometrium during microwave ablation (MWA) treating types 1-3 uterine fibroids. MATERIALS AND METHODS: Twenty-six patients with types 1-3 uterine fibroids were prospectively enrolled in an intrauterine saline instillation group (study group). The same number of patients with types 1-3 uterine fibroids who previously received MWA without endometrial protection were retrospectively included in a control group. Endometrial impairment was evaluated by hysteroscopy and magnetic resonance imaging (MRI). RESULTS: In the study group, hysteroscopy revealed an intact endometrium in 17 patients, congestion and reddening of the endometrium due to heat in 8 patients, and a burnt necrosis with a size < 1 cm on the functional layer of the endometrium in 1 patient. On MRI, in the study group, there were 17 (65.4%), 6 (23.1%), and 3 (11.5%) patients with grades 0, 1, and 2 endometrial impairment, respectively, but no grade 3 endometrial impairment. In the control group, there were 8 (30.8%), 8 (30.8%), 7 (26.9%), and 3 (11.5%) patients with grades 0, 1, 2, and 3 endometrial impairment, respectively. Endometrial impairment in the study group was significantly better than that in the control group (p = 0.006). One patient had puncture tunnel bleeding and no other complications occurred in the study group. CONCLUSION: Intraoperative percutaneous intrauterine instillation of chilled saline may be effective and safe in reducing the thermal damage to the endometrium caused by MWA for treating types 1-3 uterine fibroids.

Detection and Classification of Cotton Foreign Fibers Based on Polarization Imaging and Improved YOLOv5.

It is important to detect and classify foreign fibers in cotton, especially white and transparent foreign fibers, to produce subsequent yarn and textile quality. There are some problems in the actual cotton foreign fiber removing process, such as some foreign fibers missing inspection, low recognition accuracy of small foreign fibers, and low detection speed. A polarization imaging device of cotton foreign fiber was constructed based on the difference in optical properties and polarization characteristics between cotton fibers. An object detection and classification algorithm based on an improved YOLOv5 was proposed to achieve small foreign fiber recognition and classification. The methods were as follows: (1) The lightweight network Shufflenetv2 with the Hard-Swish activation function was used as the backbone feature extraction network to improve the detection speed and reduce the model volume. (2) The PANet network connection of YOLOv5 was modified to obtain a fine-grained feature map to improve the detection accuracy for small targets. (3) A CA attention module was added to the YOLOv5 network to increase the weight of the useful features while suppressing the weight of invalid features to improve the detection accuracy of foreign fiber targets. Moreover, we conducted ablation experiments on the improved strategy. The model volume, mAP@0.5, mAP@0.5:0.95, and FPS of the improved YOLOv5 were up to 0.75 MB, 96.9%, 59.9%, and 385 f/s, respectively, compared to YOLOv5, and the improved YOLOv5 increased by 1.03%, 7.13%, and 126.47%, respectively, which proves that the method can be applied to the vision system of an actual production line for cotton foreign fiber detection.

[Screening and expression analysis of transcription factors involved in genuineness of Codonopsis pilosula in Shanxi].

This study aims to mine the transcription factors that affect the genuineness of Codonopsis pilosula in Shanxi based on the transcriptome data of C. pilosula samples collected from Shanxi and Gansu, and then analyze the gene expression patterns, which will provide a theoretical basis for the molecular assisted breeding of C. pilosula. Gene ontology(GO) functional annotation, conserved motif prediction, and gene expression pattern analysis were performed for the differential transcription factors predicted based on the transcriptome data of C. pilosula from different habitats. A total of 61 differentially expressed genes(DEGs) were screened out from the transcriptome data. Most of the DEGs belonged to AP2/ERF-ERF family, with the conserved motif of [2X]-[LG]-[3X]-T-[3X]-[AARAYDRAA]-[3X]-[RG]-[2X]-A-[2X]-[NFP]. Forty-three of the DEGs showed significantly higher gene expression in C. pilosula samples from Shanxi than in the samples from Gansu, including 11 genes in the AP2/ERF-ERF family, 5 genes in the NAC fa-mily, 1 gene in the bHLH family, and 2 genes in the RWP-RK family, while 18 transcription factors showed higher expression levels in the samples from Gansu. GO annotation predicted that most of the DEGs were enriched in GO terms related to transcriptional binding activity(103), metabolic process(26), and stress response(23). The expression of transcription factor genes, CpNAC92, CpNAC100, CpbHLH128, and CpRAP2-7 was higher in the samples from Shanxi and in the roots of C. pilosula. CpNAC92, CpbHLH128, and CpRAP2-7 responded to the low temperature, temperature difference, and iron stresses, while CpNAC100 only responded to low temperature and iron stresses. The screening and expression analysis of the specific transcription factors CpNAC92, CpNAC100, CpbHLH128, and CpRAP2-7 in C. pilosula in Shanxi laid a theoretical foundation for further research on the mechanism of genuineness formation of C. pilosula.

[Correlation between drug-induced liver injury in rats caused by Xianling Gubao oral preparation and extraction process].

In light of the liver injury risk associated with the oral administration of Xianlin Gubao oral preparation, this study compared the differences in liver injury induced by two different extraction processes in rats and explored the correlation between hepatotoxicity and extraction process from the perspective of the differences in the content of the relevant components. Thirty male Sprague-Dawley(SD) rats were randomly divided into a normal group, tablet extract groups of different doses, and capsule extract groups of different doses, with 6 rats in each group. Each group received continuous oral administration for 4 weeks. The assessment of liver injury caused by different extracts was conducted by examining rat body weight, liver function blood biochemical indicators, liver coefficient, and liver pathological changes. In addition, a high-performance liquid chromatography(HPLC) method was established to simultaneously determine the content of icariin, baohuoside I, and bakuchiol in the extracts to compare the differences in the content of these three components under the two extraction processes. The results showed that both extracts caused liver injury in rats. Compared with the normal group, the tablet extract groups, at the studied dose, led to slow growth in body weight, a significant increase in triglyceride levels(P<0.05), a significant decrease in liver-to-brain ratio(P<0.05), and the appearance of hepatic steatosis. The capsule extract groups, at the studied dose, resulted in slow growth in body weight, a significant increase in aspartate aminotransferase levels(P<0.05), a significant decrease in body weight, liver weight, and liver-to-brain ratio(P<0.05), and the presence of hepatic steatosis and inflammatory cell infiltration. In comparison, the capsule extraction process had a higher risk of liver injury. Furthermore, based on the completion of the liquid chromatography method, the content of icariin and baohuoside Ⅰ in the capsule extract groups was 0.83 and 0.81 times that in the tablet extract groups, respectively, while the bakuchiol content in the capsule extract group was 29.80 times that in the tablet extract groups, suggesting that the higher risk of liver injury associated with the capsule extraction process may be due to its higher bakuchiol content. In summary, the differences in rat liver injury caused by the two extracts are closely related to the extraction process. This should be taken into consideration in the formulation production and clinical application.