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IntroductionGoose astrovirus (GAstV) is a newly emerging pathogen that is currently widespread among geese, causing visceral gout and leading to substantial gosling mortalities, posing a severe threat to the waterfowl industry. GAstV II is the predominant epidemic strain, characterized by its high morbidity and mortality rate. Consequently, there is an urgent necessity to develop an effective diagnostic approach to control the dissemination of GAstV II, particularly in clinical farms with limited laboratory resources.MethodsIn this study, a novel multi-enzyme isothermal rapid amplification (MIRA) and lateral flow dipstick (LFD) combined assay was developed. Different primers designed specific targeting a highly conserved region within the viral RdRp gene for the detection of GAstV II. Primers optimized and MIRA-LFD assay analyzed its performance regarding limits of detection, specificity, and efficiency of detection.ResultsThe developed MIRA amplification is conducted at a constant temperature and accomplished within 10 minutes. Subsequent naked-eye observation of the LFD strips merely takes 5 minutes. The established MIRA-LFD method exhibits high specificity, with no cross-reaction with other pathogens and attains a detection sensitivity of 1 copy/μl, which is consistent with the reverse transcription quantitative PCR (RT-qPCR) assay. Further evaluation with clinical samples indicates that the accuracy of this MIRA-LFD method correlates well with RT-qPCR for the detection of GAstV II. ConclusionIn summary, the convenience, sensitivity, and rapidity of this newly developed detection method offer a significant advantage for on-site diagnosis of GAstV II.

BackgroundThe present study aimed to investigate the drug–drug interaction and initial dosage optimization of aripiprazole in patients with schizophrenia based on population pharmacokinetics.Research design and methodsA total of 119 patients with schizophrenia treated with aripiprazole were included to build an aripiprazole population pharmacokinetic model using nonlinear mixed effects.ResultsThe weight and concomitant medication of fluoxetine influenced aripiprazole clearance. Under the same weight, the aripiprazole clearance rates were 0.714:1 in patients with or without fluoxetine, respectively. In addition, without fluoxetine, for the once-daily aripiprazole regimen, dosages of 0.3 and 0.2 mg kg−1 day−1 were recommended for patients with schizophrenia weighing 40–95 and 95–120 kg, respectively, while for the twice-daily aripiprazole regimen, 0.3 mg kg−1 day−1 was recommended for those weighing 40–120 kg. With fluoxetine, for the once-daily aripiprazole regimen, a dosage of 0.2 mg kg−1 day−1 was recommended for patients with schizophrenia weighing 40–120 kg, while for the twice-daily aripiprazole regimen, 0.3 and 0.2 mg kg−1 day−1 were recommended for those weighing 40–60 and 60–120 kg, respectively.ConclusionThis is the first investigation of the effects of fluoxetine on aripiprazole via drug–drug interaction. The optimal aripiprazole initial dosage is recommended in patients with schizophrenia.

BackgroundThe appropriate initial dosage of tacrolimus is undefined in Chinese pediatric lung transplant patients with normal hematocrit values. The purpose of this study is to optimize the initial dose of tacrolimus in Chinese children who are undergoing lung transplantation and have normal hematocrit levels.MethodsThe present study is based on a published population pharmacokinetic model of tacrolimus in lung transplant patients and uses the Monte Carlo simulation to optimize the initial tacrolimus dosage in Chinese children with lung transplantation within normal hematocrit levels.ResultsWithin normal hematocrit levels, for children with lung transplantation who do not carry the CYP3A5*1 gene and have no coadministration with voriconazole, it is recommended to administer tacrolimus at a dosage of 0.02 mg/kg/day, divided into two doses, for children weighing 10–32 kg, and a dosage of 0.03 mg/kg/day, also divided into two doses, for children weighing 32–40 kg. For children with lung transplantation who carry the CYP3A5*1 gene and have no coadministration with voriconazole, tacrolimus dosages of 0.02, 0.03, and 0.04 mg/kg/day split into two doses are recommended for children weighing 10–15, 15–32, and 32–40 kg, respectively. For children with lung transplantation who do not carry the CYP3A5*1 gene and have coadministration with voriconazole, tacrolimus dosages of 0.01 and 0.02 mg/kg/day split into two doses are recommended for children weighing 10–17 and 17–40 kg, respectively. For children with lung transplantation who carry the CYP3A5*1 gene and have coadministration with voriconazole, a tacrolimus dosage of 0.02 mg/kg/day split into two doses is recommended for children weighing 10–40 kg.ConclusionsIt is the first time to optimize the initial dosage of tacrolimus in Chinese children undergoing lung transplantation within normal hematocrit.

The nephrite jade deposits of different tectonic units in China exert significant commercial quality, which have attracted wide attention. However, these deposits have not been systematically summarized to date. Here, we investigate the major nephrite jade deposits in China to decipher their gemological and mineralogical characteristics, spatial-temporal distribution, and mineralization processes as well as to identify their geological settings and gemological properties, via integrating published geochronology, major and trace elements as well as H-O isotopes. The compiled data suggest that the major nephrite jade deposits in China can also be generally divided into green jade-type (GJ-type) and white jade-type (WJ-type) which covers different species, but most of them belong to the latter. The GJ-type nephrite deposits predominantly occur in ophiolite/ophiolitic mélange suites or are embedded into ultramafic serpentine jade orebodies. This type of nephrite jade mainly formed through the late auto-metamorphic metasomatism of serpentine or the spontaneous crystallization/precipitation along suture/shear zones that acted as pathways to migrate Ca-rich fluids during orogeny. In contrast, the orebodies of WJ-type nephrite jade are usually hosted at the contact zones between the dolomitic marbles and intermediate-felsic or mafic intrusive rocks, which were produced through metamorphism-metasomatism during post continent-continent collision, such as the Kunlun orogenic belt with about ∼1,300 km Hetian nephrite belt, and the eastern nephrite jade deposits along the Pacific Ocean. Our study highlights that the nephrite jade deposits in China originally formed during multiple tectonic stages related to the interactions between hydrothermal fluids and metamorphism under subduction accretion- and collision orogenesis-related settings. In addition, this study also provides insights into the genetic discrimination, mineral exploration, and occurrence characteristics of nephrite jade deposits as well as the evaluation and identification of nephrite jade quality.

Dapagliflozin has been used to treat patients with type 1 diabetes mellitus; however, the actual drug efficacy of dapagliflozin on glycated hemoglobin (HbA1c) and whether there is a rebound from dapagliflozin efficacy on HbA1c remain unknown. The present study aimed to explore the actual therapeutic effect and rebound situation of dapagliflozin on HbA1c in type 1 diabetes mellitus patients. A total of 1,594 type 1 diabetes mellitus patients were enrolled for analysis using a non-linear mixed effect model from randomized controlled trials from published literature works including two 5 mg/day dapagliflozin dosage groups and three 10 mg/day dapagliflozin dosage groups. The change rate of HbA1c from a baseline value was chosen as a dapagliflozin pharmacodynamic evaluation index. After deducting control group effects, the therapeutic effect of 5 and 10 mg/day dapagliflozin on HbA1c in type 1 diabetes mellitus patients had no significant difference. In addition, the actual maximal efficacy (AEmax) of dapagliflozin on HbA1c was -6.24% at week 9. When it reached the AEmax, the dapagliflozin pharmacodynamic rebound on HbA1c occurred, and when the treatment was continued for 0.5 and 1 year, the actual efficacies were -4.70% (75% AEmax) and -3.27% (52% AEmax), respectively. This was the first time to clarify the actual therapeutic effect and rebound situation of dapagliflozin on HbA1c in type 1 diabetes mellitus patients, providing a reference value for clinical practices.

Body-protective compound (BPC) 157 demonstrates protective effects against damage to various organs and tissues. For future clinical applications, we had previously established a solid-phase synthesis process for BPC157, verified its biological activity in different wound models, and completed preclinical safety evaluations. This study aimed to investigate the pharmacokinetics, excretion, metabolism, and distribution profiles of BPC157. After a single intravenous (IV) administration, single intramuscular (IM) administrations at three doses in successive increments along with repeated IM administrations, the elimination half-life (t1/2) of prototype BPC157 was less than 30 min, and BPC157 showed linear pharmacokinetic characteristics in rats and beagle dogs at all doses. The mean absolute bioavailability of BPC157 following IM injection was approximately 14%–19% in rats and 45%–51% in beagle dogs. Using [3H]-labeled BPC157 and radioactivity examination, we proved that the main excretory pathways of BPC157 involved urine and bile. [3H]BPC157 was rapidly metabolized into a variety of small peptide fragments in vivo, thus forming single amino acids that entered normal amino acid metabolism and excretion pathways. In conclusion, this study provides the first analysis of the pharmacokinetics of BPC157, which will be helpful for its translation in the clinic.

The aim of the present study is to investigate the quantitative effects of sodium–glucose cotransporter-2 (SGLT-2) inhibitors on the quality of life in heart failure (HF) patients. A total of 14,674 HF patients from two dapagliflozin and three empagliflozin studies is included for analysis via the nonlinear mixed-effect modeling (NONMEM) software, among which the change rate of the Kansas City Cardiomyopathy Questionnaire (KCCQ) score is used as the evaluation index. There is no significant difference in the pharmacodynamics influencing the quality of life in HF patients between the SGLT-2 inhibitors: 10 mg/day dapagliflozin and 10 mg/day empagliflozin. For the clinical summary score (CSS), total symptom score (TSS), and overall summary score (OSS), the Emax of the SGLT-2 inhibitors on the quality of life in HF patients is 3.74%, 4.43%, and 4.84%, respectively, and ET50 is 2.23, 4.37, and 7.15 weeks, respectively. In addition, the time duration of achieving 25%, 50%, 75%, and 80% Emax is 0.75, 2.23, 6.69, and 8.92 weeks for the CSS; 1.46, 4.37, 13.11, and 17.48 weeks for the TSS; and 2.39, 7.15, 21.45, and 28.6 weeks for the OSS, respectively. Therefore, to reach the plateau period (80% of Emax) of SGLT-2 inhibitors on the CSS, TSS, and OSS, 10 mg/day dapagliflozin (or 10 mg/day empagliflozin) is required to be taken for 8.92 weeks, 17.48 weeks, and 28.6 weeks, respectively. This is the first time that the quantitative effects of SGLT-2 inhibitors on the quality of life in HF patients are being explored.

Subcortical ischemic vascular disease (SIVD) is one of the important causes of cognitive dysfunction, altered amyloid-beta (Aβ) and cerebral perfusion may be involved in the pathophysiological mechanism of SIVD and are closely related to cognitive function. We aimed to investigate altered serum Aβ and cerebral perfusion in patients with SIVD and their correlation with cognitive function. Seventy-four healthy controls (HCs) and 74 SIVD patients, including 38 SIVD patients with no cognitive impairment (SIVD-NCI) and 36 SIVD patients with mild cognitive impairment (SIVD-MCI) underwent the measurement of serum Aβ40 and Aβ42 levels, pseudo-continuous arterial spin labeling MRI scanning, and cognitive evaluation. Compared to the healthy controls (HCs), the level of serum Aβ40 and Aβ40/42 ratio increased and Aβ42 decreased in SIVD patients. The serum Aβ40 level and Aβ40/42 ratio in patients with SIVD-MCI were significantly higher than those in the HCs and SIVD-NCI, and the level of Aβ42 in the SIVD-MCI was lower than the HCs. In addition, the serum Aβ40/42 ratio provided high diagnostic accuracy for SIVD and SIVD-MCI, it was further identified as an independent risk factor for cognitive impairment. Patients with SIVD-NCI and SIVD-MCI exhibited both increased and decreased cerebral blood flow (CBF) in regional. The Aβ40/42 ratio was associated with global CBF, while altered global and regional CBF was associated with cognitive deficits. In addition, white matter hyperintensities volume (WMHV) correlated with Aβ40/42 ratio, CBF, and cognition. The relationship between Aβ40/42 ratio and cognition was partially mediated by altered CBF. Based on these results, we conclude that the serum Aβ40/42 ratio may be a potential biomarker that can complement current methods for the prediction and diagnosis of cognitive impairment in SIVD patients. In addition, serum Aβ may play a role in cognitive function by regulating CBF, which provides new insights into the intervention, treatment, and prevention of cognitive impairment in SIVD.

Sorafenib is one of the few effective first-line drugs approved for the treatment of advanced hepatocellular carcinoma (HCC). However, the development of drug resistance is common among individuals with HCC. Recent evidence indicated that the anticancer activity of sorafenib mainly relies on the induction of ferroptosis. Furthermore, in our study, genes that suppress ferroptosis, especially GPX4 and DHODH, were enriched in sorafenib-resistant cells and primary tissues and were associated with poor prognosis of HCC patients who received sorafenib treatment. Therefore, a new ferroptosis inducer comprising a multiplex small interfering RNA (multi-siRNA) capable of simultaneously silencing GPX4 and DHODH was created. Then, exosomes with high multi-siRNA loading and HCC-specific targeting were established by fusing the SP94 peptide and the N-terminal RNA recognition motif (RRM) of U1-A with the exosomal membrane protein Lamp2b. The results from the in vitro and in vivo experiments indicate that this tumor-targeting nano-delivery system (ExoSP94-lamp2b-RRM-multi-siRNA) could enhance sorafenib-induced ferroptosis and overcome sorafenib resistance. Taken together, HCC-targeted exosomes (ExoSP94-Lamp2b-RRM) could specifically deliver multi-siRNA to HCC tissues, enhance sorafenib-induced ferroptosis by silencing GPX4 and DHODH expression and consequently increase HCC sensitivity to sorafenib, which opens a new avenue for clinically overcoming sorafenib resistance from the perspective of ferroptosis.

Rock reinforcement is significant in maintaining the stability of excavated structures, such as tunnels and underground roadways. However, shear failure in the rock reinforcement system, especially the shear failure at the rock reinforcement bolt surface, induces a threat to the rock reinforcement system. To reveal the shear stress (SS) propagation mechanism in the rock reinforcement system, this article conducted a literature review. First, the investigation approaches that were used by previous researchers to study the SS propagation were summarized. The advantages and disadvantages of experimental tests, analytical simulation, and numerical simulation were compared and analyzed. Then, the SS propagation process in the rock reinforcement system was presented. Two typical SS propagation modes were explained. More attention was given to the SS propagation mode in which the maximum SS propagates from the external end of rock reinforcement bolts to the internal end of rock reinforcement bolts. After that, a discussion section was given. In the discussion section, the significance of the SS propagation was further emphasized. Moreover, the limitations in the analytical simulation and numerical simulation were indicated. It is concluded that when studying the SS propagation mechanism of rock reinforcement bolts, combining experimental tests, analytical simulation, and numerical simulation is a better choice. This study is beneficial for revealing the SS propagation mechanism of the rock reinforcement system.

This study investigated the development of lexical complexity, sentence complexity, accuracy, and fluency in the English writing of 22 Chinese university students from the perspective of Complex Dynamic Systems Theory (CDST). Compositions were assigned 30 times over the course of one academic year through Pigaiwang, an online platform that automatically evaluates writing. A modified retrodictive modeling approach was adopted. Specifically, a longitudinal cluster analysis was used to examine emergent prototypes. A moving correlation analysis and retrodictive interviews were conducted to study the signature dynamics that produce each prototype. At each collection, the 22 student compositions were classified into two clusters. One cluster contained those students who performed better than average in accuracy, but worse in the other three variables. The other cluster comprised those students with the opposite performance. Students moved continuously between the two clusters; and their change trajectories can be categorized into three prototypes: a continuously stable type, an initially variable and then stable type, and a continuously variable type. Case studies of three students representing the three emergent prototypes indicated that the signature dynamics for the three prototypes were related to dynamic interactions among different variables and dynamic changes in affect-related elements in the form of writing interests, motivation, and strategies. The initial conditions and the feedback from Pigaiwang acted as key control parameters in shaping the prototypes. The continuously variable prototype developed their writing proficiency to the greatest extent and had the most variability. Based upon the findings, implications for teaching L2 writing are discussed.

BackgroundPoor sleep quality is related to depression. However, the investigation of the neural basis for poor sleep quality in individuals with major depression (MD) is limited.MethodsResting state functional and structural MRI data were derived from 114 MD individuals and 74 normal controls (NCs). Fractional amplitude of low-frequency fluctuation (fALFF) and gray matter volume (GMV) were used to measure function and structure of the brain. Pittsburgh Sleep Quality Index (PSQI) was performed to evaluate subjective sleep quality. Correlations were carried out to investigate links of PSQI score with brain imaging indices in MD and NCs, separately. We also examined the differences in fALFF and GMV of brain regions related to PSQI score between MD and NCs.ResultsIn contrast to NCs, MD individuals had higher PSQI score. The higher PSQI score was associated with lower fALFF and lower GMV in bilateral precuneus in MD individuals. Moreover, the MD individuals exhibited increased fALFF in bilateral precuneus compared with NCs. However, the correlation between subjective sleep quality and neuroimaging parameters was not significant in NCs.ConclusionThe implication of these findings is that the function and structure of precuneus provides a neural basis for subjective poor sleep quality in MD. Understanding this may lead to better intervention of depression and associated sleep complaints.

Evidence suggests the pivotal role of vitamin D in the pathophysiology of major depressive disorder (MDD) via its effects on the brain. Gender differences exist in both depression and vitamin D level. Our objective was to investigate the association between gender, vitamin D, clinical manifestations, and functional network connectivity in a large sample of MDD patients and healthy controls. Resting-state functional MRI data were collected from 122 patients and 119 controls, with independent component analysis adopted to examine large-scale inter- and intranetwork functional connectivity. Serum concentration of vitamin D (SCVD) and clinical manifestations were also assessed. MDD patients exhibited lower SCVD than controls in females but not males. Moreover, we identified a female-specific association between lower SCVD and poorer cognitive performance. Concurrently, MDD-related functional network connectivity changes were correlated with SCVD in females as well as depression and anxiety symptoms in female patients. Remarkably, MDD- and SCVD-related functional network connectivity alterations mediated the associations between SCVD and cognition in females. Aside from providing evidence for a female-specific neurobiological mechanism whereby low vitamin D might contribute to MDD and its associated clinical characteristics, our findings inform a novel conceptualization that adjuvant vitamin D supplementation therapy may yield clinical benefits in improving treatment outcomes in female patients with MDD.

Background: It has been reported that type 2 diabetes (T2DM) is associated with olfactory identification (OI) impairments and cognitive decline. However, the relationship between OI impairments and cognitive decline is largely unknown in T2DM patients.Methods: Sixty-eight T2DM patients and 68 healthy controls underwent 3D-T1 MRI scans, olfactory and cognitive assessments. The cortical thickness of olfaction-related brain regions, olfactory and cognitive scores were compared between groups. Correlation analyses were carried out among cognition, olfaction, and cortical thickness of olfaction-related brain regions.Results: First, the cognitive and olfactory test scores of T2DM patients were lower than healthy subjects. Second, higher olfactory scores were associated with increased cortical thickness in the left parahippocampal gyrus and bilateral insula in T2DM. Third, higher olfactory scores were associated with higher cognitive performance in T2DM. Fourth, some cognitive performances were related to cortical thickness in the left parahippocampal gyrus and left insula in T2DM.Conclusion: These findings indicated that olfactory dysfunction may be useful for future applications that attempt to predict cognitive decline or develop tailored therapies in T2DM patients.

BackgroundFOXP3, as a tumour suppressor gene, has a vital function in inhibiting the metastasis of breast cancer cells, but the mechanisms by which it inhibits metastasis have not been fully elucidated. This study intended to explore a new mechanism by which FOXP3 inhibits breast cancer metastasis.MethodsBioinformatic analysis was performed to identify potential downstream molecules of FOXP3. The function of FOXP3 in inhibiting MTA1 expression at the mRNA and protein levels was verified by real-time PCR and Western blot analysis. The interaction between FOXP3 and the MTA1 promoter was verified by transcriptomic experiments. In vitro and in vivo experiments were used to determine whether the regulation of MTA1 by FOXP3 affected the invasion and migration of breast cancer cells. Immunohistochemistry was adopted to explore the correlation between the expression levels of FOXP3 and MTA1 in breast cancer samples.ResultsBioinformatics-based sequencing suggested that MTA1 is a potential downstream molecule of FOXP3. FOXP3 downregulated the expression of MTA1 in breast cancer cells by directly inhibiting MTA1 promoter activity. Importantly, FOXP3’s regulation of MTA1 affected the ability of breast cancer cells to invade and metastasize in vitro and in vivo. Moreover, analysis of clinical specimens showed a significant negative correlation between the expression levels of FOXP3 and MTA1 in breast cancer.ConclusionWe systematically explored a new mechanism by which FOXP3 inhibits breast cancer metastasis via the FOXP3-MTA1 pathway.

The development of an effective pharmacological countermeasure is needed to reduce the morbidity and mortality in high-dose ionizing radiation-induced acute damage. Genistein has shown bioactivity in alleviating radiation damage and is currently synthesized by chemosynthetic methods. Due to concerns about chemical residues and high costs, the clinical application of genistein is still a major challenge. In this study, we aimed to establish an efficient method for the extraction of genistein from Fructus sophorae. The effects of extracted genistein (FSGen) on preventing intestinal injury from radiation were further investigated in this study. C57/BL mice were exposed to 7.5 Gy whole body irradiation with and without FSGen treatments. Histological analysis demonstrated significant structural and functional restitution of the intestine and bone marrow in FSGen-pretreated cohorts after irradiation. Through mRNA expression, protein expression, and small interfering RNA analyses, we demonstrated that FSGen protects IEC-6 cells against radiation damage by upregulating the Rassf1a and Ercc1 genes to effectively attenuate DNA irradiation damage. Together, our data established an effective method to extract genistein from the Fructus sophorae plant with high purity, and validated the beneficial roles of the FSGen in protecting the radiation damage. These results promise the future applications of Fructus sophorae extracted genistein in the protection of radiation related damages.

Background: Previous neuroimaging studies have demonstrated brain abnormalities in patients with hepatic diseases. However, the identified liver–brain associations are largely limited to disease-affected populations, and the nature and extent of such relations in healthy subjects remain unclear. We hypothesized that serum liver function markers within a normal level would affect brain properties.Method: One hundred fifty-seven healthy young adults underwent structural, resting-state functional, and arterial spin labeling MRI scans. Gray matter volume (GMV), regional homogeneity (ReHo), and cerebral blood flow (CBF) analyses were performed to assess brain structure, function, and perfusion, respectively. Peripheral venous blood samples were collected to measure serum liver function markers. Correlation analyses were conducted to test potential associations between liver function markers and brain imaging parameters.Results: First, serum proteins showed relations to brain structure characterized by higher albumin associated with increased GMV in the parahippocampal gyrus and amygdala and lower globulin and a higher albumin/globulin ratio with increased GMV in the olfactory cortex and parahippocampal gyrus. Second, serum bilirubin was linked to brain function characterized by higher bilirubin associated with increased ReHo in the precuneus, middle cingulate gyrus, inferior parietal lobule, and supramarginal gyrus and decreased ReHo in the caudate nucleus. Third, serum alanine transaminase (ALT) was related to brain perfusion characterized by higher ALT associated with increased CBF in the superior frontal gyrus and decreased CBF in the middle occipital gyrus, angular gyrus, precuneus, and middle temporal gyrus. More importantly, we found that CBF in the superior frontal gyrus was a significant mediator of the association between serum ALT level and working memory performance.Conclusion: These findings may not only expand existing knowledge about the relationship between the liver and the brain but also have clinical implications for studying brain impairments secondary to liver diseases as well as providing potential neural targets for their diagnosis and treatment.

BackgroundSleep disturbance is common in patients with major depressive disorder (MDD), but the exploration of its neural underpinnings is limited by subjective sleep measurement and single-modality neuroimaging analyses.MethodsNinety six patients with MDD underwent polysomnography examinations and multi-modal magnetic resonance imaging (MRI) scans. According to sleep efficiency, patients were subdivided into well-matched normal sleep efficiency (NSE, N = 42; 14 men; aged 43 ± 10 years) and low sleep efficiency (LSE, N = 54; 23 men; aged 45 ± 12 years) groups. Inter-group differences in brain structure and function were examined by applying voxel-based morphometry (VBM), regional homogeneity (ReHo) and functional connectivity strength (FCS), and tract-based spatial statistics (TBSS) approaches to structural, functional, and diffusion MRI data, respectively.ResultsThere was no significant difference in gray matter volume (GMV) between the NSE and LSE groups. Compared with the NSE group, the LSE group showed increased axial diffusivity in the left superior and posterior corona radiata, and left posterior limb and retrolenticular part of internal capsule. In addition, the LSE group exhibited decreased ReHo in the bilateral lingual gyri and right postcentral gyrus yet increased FCS in the left angular gyrus relative to the NSE group. Moreover, validation analyses revealed that these results remained after adjusting for the medication effect.ConclusionOur data indicate that preserved gray matter morphology, impaired white matter integrity, and decreased local synchronization degree yet increased FCS are specific to low SE in MDD patients. These findings of disassociation between structural and functional alterations might provide insights into the neural mechanisms of sleep disturbance in depression.

Traditional Chinese Medicines (TCMs) have been used for more than 3,000 years. However, most TCMs are used based on previous experience, and their exact mechanisms are still unclear. Proteomics, as a major component of systems biology, is an appropriate tool that could bring breakthroughs in the study of pharmacological mechanisms of TCMs. Researchers made substantial progress by using the proteomics approach to investigate the mechanism of TCMs. In this review, we summarize the current applications of proteomics in the mechanistic study of TCMs. Proteomics technologies and strategies that might be used in the future to enhance the study of TCMs are also discussed.

Gardeniae Fructus (GF) and carbonized GF (GFC) have been shown to exert a gastrointestinal protective effect and are frequently used in clinical practice for the treatment of hemorrhage and brown stool. In this study, we employed a combination of pharmacological methods and metabolomics in a rat model of ethanol-induced acute stomach ulcer to investigate the gastroprotective effect of GF and GFC water extracts and the potential mechanism involved in this process. The levels of nitric oxide (NO) and interleukin 6 (IL-6) in the plasma of rats were determined. The results showed that both GF and GFC reduced the ethanol-induced gastric lesions and expression of NO and IL-6 in these rats. Of note, 16 and 11 feature metabolites were filtered and identified in the GF and GFC groups, respectively. Both GF and GFC act by restoring the biosynthesis of valine, leucine, and isoleucine, and the metabolism of glycerophospholipids. Moreover, histological evaluation revealed that heat processing of GF to create GFC enhanced the gastric mucosa protective effect. Furthermore, heat processing converted the main pathway from alanine, aspartate, and glutamate metabolism, associated with GF, to histidine metabolism, associated with GFC. GF and GFC ameliorated gastric mucosa lesions in rats via reductions in NO production and inflammatory cytokine secretion, and the induction of prostaglandin E2.

Background: Depression has been linked to vitamin D deficiency. However, little attention was paid to the neural substrate underlying this association.Methods: Fifty patients with major depressive disorder (MDD) were enrolled in this study. High-resolution structural magnetic resonance imaging was performed to calculate total intracranial volume (TIV). Peripheral venous blood samples were collected to measure serum vitamin D concentration. Hamilton Rating Scale for Depression (HAMD) was used to assess severity of depression symptoms. The relationship among TIV, serum vitamin D concentration, and HAMD score was examined using correlation, linear regression, and mediation analyses.Results: In patients with MDD, HAMD score was negatively correlated with TIV and serum vitamin D concentration, and TIV was positively correlated with serum vitamin D concentration. Linear regression analyses showed that TIV and serum vitamin D concentration were significant predictors of HAMD score. Importantly, mediation analysis revealed that TIV significantly mediated the relationship between serum vitamin D concentration and HAMD score.Conclusion: Our findings suggest that TIV may serve as a potential neural biomarker for monitoring responses to adjuvant therapy of vitamin D in patients with MDD.

Gardeniae Fructus (GF), prepared GF (GFP), and carbonized GF (GFC) are widely used in China for the treatment of fever. However, the involved antipyretic mechanism has not been fully elucidated. In this study, rectal temperature and pyrogenic cytokines were used to evaluate the antipyretic effect of raw and processed GF in rats with dry-yeast-induced pyrexia. Reverse phase and hydrophilic interaction liquid chromatography and ultra-high-performance liquid chromatography/mass spectrometry were used to acquire the metabolomics profile of GF, GFP, and GFC in rats with pyrexia. The results showed that the rectal temperature of rats treated with GF, GFP, and GFC was suppressed after 6 h (P < 0.05), compared with that observed in pyrexia model rats. The enzyme-linked immunosorbent assay showed that the expression of tumor necrosis factor α and interleukin 6 were suppressed by GF, GFP, and GFC. Moreover, GFC suppressed the expression of interleukin 6 significantly (P < 0.01). Of note, 11, 15, and 25 feature metabolites were identified in the GF, GFP, and GFC groups. Pathway analysis showed that GF mainly regulated the biosynthesis of valine, leucine, and isoleucine. Notably, GFP was involved in glycerophospholipid metabolism, while GFC was linked to glycerophospholipid and sphingolipid metabolism. These results suggested that GF, GFP, and GFC maintained their antipyretic effect despite heat processing. However, heat processing altered endogenous feature metabolites and certain pathways of GF, GFP, and GFC in rats with yeast-induced pyrexia to exert an antipyretic effect.

The gall wasp, Leptocybe invasa (Hymenoptera; Eulophidae), is a devastating pest of eucalypt plantations in the Middle East, the Mediterranean basin, Africa, India, South-East Asia, and China. Heavy galling causes the leaves to warp and in extreme cases it may stunt the growth of the trees of Eucalyptus camaldulensis. However, the physiological mechanisms underlying how L. invasa inhibits the growth of plants of E. camaldulensis are unclear. Because the growth rate of plants is mainly dependent on photosynthesis that is largely correlated with hydraulic architecture, we speculate that galling of L. invasa depresses hydraulic conductance of stem and leaf. In the present study, we examined the effects of L. invasa galling on hydraulic architecture and photosynthetic parameters in E. camaldulensis plants. We found that galling of L. invasa significantly decreased stem hydraulic conductance (Kstem), midday leaf water potential (ψmd), minor vein density, and stomatal density (SD). Furthermore, the stomatal conductance (gs), chlorophyll content, CO2 assimilation rate (An) and photosynthetic electron flow were reduced in infected plants. Therefore, the galling of L. invasa not only declined the water supply from stem to leaves, but also restricted water transport within leaf. As a result, galled plants of E. camaldulensis reduced leaf number, leaf area, SD and gs to balance water supply and transpirational demand. Furthermore, galled plants had lower leaf nitrogen content, leading to decreases in chlorophyll content, CO2 assimilation rate and photosynthetic electron flow. These results indicate that the change in hydraulic architecture is responsible for the inhibition of growth rate in galled plants. [ABSTRACT FROM AUTHOR]