Nab-paclitaxel plus S-1 versus nab-paclitaxel plus gemcitabine in patients with advanced pancreatic cancer: a multicenter, randomized, phase II study.

BACKGROUND: Encouraging antitumor activity of nab-paclitaxel plus S-1 (AS) has been shown in several small-scale studies. This study compared the efficacy and safety of AS versus standard-of-care nab-paclitaxel plus gemcitabine (AG) as a first-line treatment for advanced pancreatic cancer (PC). METHODS: In this multicenter, randomized, phase II trial, eligible patients with unresectable, locally advanced, or metastatic PC were recruited and randomly assigned (1:1) to receive AS (nab-paclitaxel 125 mg/m2 on days 1 and 8; S-1 twice daily on days 1 through 14) or AG (nab-paclitaxel 125 mg/m2 on days 1 and 8; gemcitabine 1000 mg/m2 on days 1 and 8) for 6 cycles. The primary endpoint was progression-free survival (PFS). RESULTS: Between July 16, 2019, and September 9, 2022, 62 patients (AS, n = 32; AG, n = 30) were treated and evaluated. With a median follow-up of 8.36 months at preplanned interim analysis (data cutoff, March 24, 2023), the median PFS (8.48 vs 4.47 months; hazard ratio [HR], 0.402; P = .002) and overall survival (OS; 13.73 vs 9.59 months; HR, 0.226; P < .001) in the AS group were significantly longer compared to the AG group. More patients had objective response in the AS group than AG group (37.50% vs 6.67%; P = .005). The most common grade 3-4 adverse events were neutropenia and leucopenia in both groups, and gamma glutamyl transferase increase was observed only in the AG group. CONCLUSION: The first-line AS regimen significantly extended both PFS and OS of Chinese patients with advanced PC when compared with the AG regimen, with a comparable safety profile. (ClinicalTrials.gov Identifier: NCT03636308).

Development of a stable genetic transformation system in Erigeron breviscapus: a case study with EbYUC2 in relation to leaf number and flowering time.

MAIN CONCLUSION: A stable genetic transformation system for Erigeron breviscapus was developed. We cloned the EbYUC2 gene and genetically transformed it into Arabidopsis thaliana and E. breviscapus. The leaf number, YUC2 gene expression, and the endogenous auxin content in transgenic plants were significantly increased. Erigeron breviscapus is a prescription drug for the clinical treatment of cardiovascular and cerebrovascular diseases. The rosette leaves have the highest content of the major active compound scutellarin and are an important component in the yield of E. breviscapus. However, little is known about the genes related to the leaf number and flowering time of E. breviscapus. In our previous study, we identified three candidate genes related to the leaf number and flowering of E. breviscapus by combining resequencing data and genome-wide association study (GWAS). However, their specific functions remain to be characterized. In this study, we cloned and transformed the previously identified full-length EbYUC2 gene into Arabidopsis thaliana, developed the first stable genetic transformation system for E. breviscapus, and obtained the transgenic plants overexpressing EbYUC2. Compared with wild-type plants, the transgenic plants showed a significant increase in the number of leaves, which was correlated with the increased expression of EbYUC2. Consistently, the endogenous auxin content, particularly indole-3-acetic acid, in transgenic plants was also significantly increased. These results suggest that EbYUC2 may control the leaf number by regulating auxin biosynthesis, thereby laying a foundation for revealing the molecular mechanism governing the leaf number and flowering time of E. breviscapus.

Pharmacologically significant constituents collectively responsible for anti-sepsis action of XueBiJing, a Chinese herb-based intravenous formulation.

Sepsis, a life-threatening health issue, lacks effective medicine targeting the septic response. In China, treatment combining the intravenous herbal medicine XueBiJing with conventional procedures reduces the 28-day mortality of critically ill patients by modulating septic response. In this study, we identified the combined active constituents that are responsible for the XueBiJing's anti-sepsis action. Sepsis was induced in rats by cecal ligation and puncture (CLP). The compounds were identified based on their systemic exposure levels and anti-sepsis activities in CLP rats that were given an intravenous bolus dose of XueBiJing. Furthermore, the identified compounds in combination were assessed, by comparing with XueBiJing, for levels of primary therapeutic outcome, pharmacokinetic equivalence, and pharmacokinetic compatibility. We showed that a total of 12 XueBiJing compounds, unchanged or metabolized, circulated with significant systemic exposure in CLP rats that received XueBiJing. Among these compounds, hydroxysafflor yellow A, paeoniflorin, oxypaeoniflorin, albiflorin, senkyunolide I, and tanshinol displayed significant anti-sepsis activities, which involved regulating immune responses, inhibiting excessive inflammation, modulating hemostasis, and improving organ function. A combination of the six compounds, with the same respective doses as in XueBiJing, displayed percentage survival and systemic exposure in CLP rats similar to those by XueBiJing. Both the combination and XueBiJing showed high degrees of pharmacokinetic compatibility regarding interactions among the six active compounds and influences of other circulating XueBiJing compounds. The identification of XueBiJing's pharmacologically significant constituents supports the medicine's anti-sepsis use and provides insights into a polypharmacology-based approach to develop medicines for effective sepsis management.

The propagation behavior of reaction wave for Ni/Al clad particle composites under shock loading.

Prior studies indicate that the reaction wave can propagate from the impact surface, but the possibility and the influencing factors of the reaction wave formation are still unclear. This work investigates the propagation behavior of the shock-induced reaction wave for Ni/Al clad particle composites with varying stoichiometry (from 0.5 to 0.75 of the Ni mole fraction) through molecular dynamics simulations. It is found that the solid-state reaction processes with or without wave propagation strongly depend on the conjunction of stoichiometry and shock intensity. Within the cases of wave propagation, the calculated propagation velocity (in the range of 135-170 m/s) increases linearly or exponentially with the Ni mole fraction. Furthermore, the thermodynamic criteria for the reaction wave formation, including Al melting at the collision surface and higher temperature gradient, are established by analysis of the shock-induced high-entropy layer. In addition, microstructural characterization reveals the intrinsic mechanisms of the propagation of the reaction wave and the formation of additional reaction wave, namely, the dissolution of Ni into Al and the coalescence of reaction zones. Apart from the propagation behavior, the initial stoichiometry influences the crystallization-dissolution of B2-NiAl during reaction processes, notably through an exponential growth relationship between maximum crystallinity and the Ni mole fraction. These findings may provide a physical basis for improving traditional reaction rate models to break through phenomenological understanding.

Brain natriuretic peptide as a predictive marker of mortality in sepsis: an updated systematic review and meta-analysis.

INTRODUCTION: Early identification of patients with sepsis at high risk of death remains a challenge, and whether brain natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) has a prognostic effect on patients with sepsis is controversial. Here, we clarified the prognostic value of BNP and NT-proBNP and sought to establish suitable cutoff values and intervals. METHODS: We searched five databases to identify studies that met the inclusion criteria. The primary outcomes were the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), area under the curve (AUC), and corresponding 95% credible interval (95% CI) of BNP and NT-proBNP. The secondary outcomes were the sensitivity and specificity of BNP or NT-proBNP in subgroup analyses. RESULTS: Forty-seven studies were included in our meta-analysis. The pooled sensitivity of NT-proBNP (0.77 [0.68, 0.84]) was weaker than that of BNP (0.82 [0.76, 0.87]), the pooled specificity of NT-proBNP (0.70 [0.60, 0.77]) was less than that of BNP (0.77 [0.71, 0.82]), and the AUC of BNP (0.87 [0.83-0.89]) was greater than that of NT-proBNP (0.80 (0.76-0.83]). The results of the subgroup analysis showed that the cutoff range of 400-800 pg/mL for BNP had high sensitivity (0.86 [0.74-0.98]) and specificity (0.87 [0.81-0.93]) and was probably the most appropriate cutoff range. CONCLUSIONS: Elevated levels of BNP and NT-proBNP were significantly related to the mortality of patients with sepsis and had a moderate prognostic value in predicting the mortality of patients with sepsis. In addition, our meta-analysis preliminarily established appropriate cutoff values for BNP and NT-proBNP.

Genomic Insights into High-Altitude Adaptation: A Comparative Analysis of Roscoea alpina and R. purpurea in the Himalayas.

Environmental stress at high altitudes drives the development of distinct adaptive mechanisms in plants. However, studies exploring the genetic adaptive mechanisms of high-altitude plant species are scarce. In the present study, we explored the high-altitude adaptive mechanisms of plants in the Himalayas through whole-genome resequencing. We studied two widespread members of the Himalayan endemic alpine genus Roscoea (Zingiberaceae): R. alpina (a selfing species) and R. purpurea (an outcrossing species). These species are distributed widely in the Himalayas with distinct non-overlapping altitude distributions; R. alpina is distributed at higher elevations, and R. purpurea occurs at lower elevations. Compared to R. purpurea, R. alpina exhibited higher levels of linkage disequilibrium, Tajima's D, and inbreeding coefficient, as well as lower recombination rates and genetic diversity. Approximately 96.3% of the genes in the reference genome underwent significant genetic divergence (FST ≥ 0.25). We reported 58 completely divergent genes (FST = 1), of which only 17 genes were annotated with specific functions. The functions of these genes were primarily related to adapting to the specific characteristics of high-altitude environments. Our findings provide novel insights into how evolutionary innovations promote the adaptation of mountain alpine species to high altitudes and harsh habitats.

The Identification and Gene Mapping of Spotted Leaf Mutant spl43 in Rice.

Our study investigates the genetic mechanisms underlying the spotted leaf phenotype in rice, focusing on the spl43 mutant. This mutant is characterized by persistent reddish-brown leaf spots from the seedling stage to maturity, leading to extensive leaf necrosis. Using map-based cloning, we localized the responsible locus to a 330 Kb region on chromosome 2. We identified LOC_Os02g56000, named OsRPT5A, as the causative gene. A point mutation in OsRPT5A, substituting valine for glutamic acid, was identified as the critical factor for the phenotype. Functional complementation and the generation of CRISPR/Cas9-mediated knockout lines in the IR64 background confirmed the central role of OsRPT5A in controlling this trait. The qPCR results from different parts of the rice plant revealed that OsRPT5A is constitutively expressed across various tissues, with its subcellular localization unaffected by the mutation. Notably, we observed an abnormal accumulation of reactive oxygen species (ROS) in spl43 mutants by examining the physiological indexes of leaves, suggesting a disruption in the ROS system. Complementation studies indicated OsRPT5A's involvement in ROS homeostasis and catalase activity regulation. Moreover, the spl43 mutant exhibited enhanced resistance to Xanthomonas oryzae pv. oryzae (Xoo), highlighting OsRPT5A's role in rice pathogen resistance mechanisms. Overall, our results suggest that OsRPT5A plays a critical role in regulating ROS homeostasis and enhancing pathogen resistance in rice.

A critical review on bioremediation technologies of metal(loid) tailings: Practice and policy.

Globally, most high-grade ores have already been exploited. Contemporary mining tends to focus on the extraction of lower-grade ores thereby leaving large stored tailings open to the environment. As a result, current mines have emerged as hotspots for the migration of metal(loid)s and resistance genes, thereby potentially contributing to a looming public health crisis. Therefore, the management and remediation of tailings are the most challenging issues in environmental ecology. Bioremediation, a cost-effective solution for the treatment of multi-element mixed pollution (co-contamination), shows promise for the restoration of mine tailings. This review focuses on the bioremediation technologies developed to untangle the issues of non-ferrous metal mine tailings. These technologies address the environmental risks of multi-element exposure to the ecosystem and human health risks. It provides a review and comparison of current bioremediation technologies used to mineralize metal(loid)s. The role of plant-microorganisms and their mechanisms in the remediation of tailings are also discussed. The importance of "treating waste with wastes" is crucial for advancing bioremediation technologies. This approach underscores the potential for waste materials to contribute to environmental cleanup processes. The concept of a circular economy is pertinent in this context, emphasizing recycling and reuse. There's an immediate need for international collaboration. Collaboration is needed in policy-making, funding, and data accessibility. Sharing data is essential for the growth of bioremediation globally.

Effect of comprehensive nursing intervention on wound pain and wound complications in patients with tonsillectomy: A meta-analysis.

To systematically evaluate the effects of comprehensive nursing interventions on wound pain and complications in patients after tonsillectomy, with a view to providing a reference basis for future post-tonsillectomy care. According to the developed literature search strategy, PubMed, Web of Science, Cochrane Library, Embase, Wanfang, China Biomedical Literature Database and China National Knowledge Infrastructure database were systematically searched, from database inception to October 2023, for randomised controlled trials (RCTs) of the application of comprehensive nursing interventions in patients undergoing tonsillectomy. Two researchers independently screened the literature, evaluated the risk of bias of the included studies and extracted data in strict accordance with the inclusion and exclusion criteria. RevMan 5.4 software was applied for data analysis. Overall, 18 RCTs involving 1954 patients were included, including 967 in the comprehensive nursing group and 987 in the conventional nursing group. The analyses revealed that compared with conventional nursing, patients who received comprehensive nursing interventions had lower postoperative wound pain scores (standardised mean difference [SMD]: -2.30, 95% confidence interval [CI]: -2.19 to -1.70, p < 0.00001), shorter hospital stays (SMD: -1.95, 95% CI: -2.39 to -1.51, p < 0.00001), incidence of postoperative haemorrhage (1.60% vs. 6.41%, odds ratio [OR]: 0.29, 95% CI: 0.12-0.70, p = 0.006) and complication rates (4.21% vs. 19.01%, OR: 0.19, 95% CI: 0.11-0.32, p < 0.00001) was lower. This study concludes as follows: comprehensive nursing intervention applied to tonsillectomy can significantly reduce patients' postoperative wound pain, shorten hospital stay, reduce postoperative bleeding and postoperative complications, which is worthy of being promoted and applied in the clinic.

Effects of clinical nursing pathway on surgical site wound infection in patients undergoing acute appendicitis surgery: A meta-analysis.

This study aimed to explore the impact of clinical nursing pathway applied to acute appendicitis surgery on patients' postoperative wound infections and complications. A computerised search of PubMed, Cochrane Library, Web of Science, EMBASE, Wanfang, Chinese Biomedical Literature Database and China National Knowledge Infrastructure was conducted and supplemented by a manual search, from database inception to October 2023, to collect randomised controlled trials (RCTs) on the application of clinical nursing pathways to acute appendicitis surgery. Literature screening, data extraction and quality assessment of the included literature were carried out independently by two researchers. RevMan 5.4 software was applied for data analysis. Twenty-one RCTs with a total of 2408 patients were finally included. The analysis revealed the implementation of clinical nursing pathway could effectively reduce the incidence of wound infection (OR = 0.26, 95% CI: 0.15-0.46, p < 0.001) and postoperative complications (OR = 0.20, 95% CI: 0.15-0.27, p < 0.001), as well as shorten the hospital length of stay (MD = -3.26, 95% CI: -3.74 to -2.79, p < 0.001) and accelerated the time to first ventilations (MD = -14.85, 95% CI: -21.56 to -8.13, p < 0.001), as well as significantly improved patient satisfaction (OR = 5.52, 95% CI: 3.52-8.65, p < 0.001) in patients undergoing surgery for acute appendicitis. The application of clinical nursing pathway in acute appendicitis surgery can significantly reduce postoperative wound infection and complications, and at the same time can shorten the hospital length of stay as well as improve the satisfaction of patients.

High SNHG expression may predict a poor lung cancer prognosis based on a meta-analysis.

BACKGROUND: An increasing number of small nucleolar RNA host genes (SNHGs) have been revealed to be dysregulated in lung cancer tissues, and abnormal expression of SNHGs is significantly correlated with the prognosis of lung cancer. The purpose of this study was to conduct a meta-analysis to explore the correlation between the expression level of SNHGs and the prognosis of lung cancer. METHODS: A comprehensive search of six related databases was conducted to obtain relevant literature. Relevant information, such as overall survival (OS), progression-free survival (PFS), TNM stage, lymph node metastasis (LNM), and tumor size, was extracted. Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled to evaluate the relationship between SNHG expression and the survival outcome of lung cancers. Sensitivity and publication bias analyses were performed to explore the stability and reliability of the overall results. RESULTS: Forty publications involving 2205 lung cancer patients were included in this meta-analysis. The pooled HR and 95% CI values indicated a significant positive association between high SNHG expression and poor OS (HR: 1.890, 95% CI: 1.595-2.185), disease-free survival (DFS) (HR: 2.31, 95% CI: 1.57-3.39) and progression-free survival (PFS) (HR: 2.01, 95% CI: 0.66-6.07). The pooled odds ratio (OR) and 95% CI values indicated that increased SNHG expression may be correlated with advanced TNM stage (OR: 1.509, 95% CI: 1.267-1.799), increase risk of distant lymph node metastasis (OR: 1.540, 95% CI: 1.298-1.828), and large tumor size (OR: 1.509, 95% CI: 1.245-1.829). Sensitivity analysis and publication bias results showed that each result had strong reliability and robustness, and there was no significant publication bias or other bias. CONCLUSION: Most SNHGs are upregulated in lung cancer tissues, and high expression of SNHGs predicts poor survival outcomes in lung cancer. SNHGs may be potential prognostic markers and promising therapeutic targets.

[Chemical constituents of Helleborus thibetanus].

The chemical constituents of Helleborus thibetanus were isolated and purified by silica gel column chromatography, Sephadex LH-20 gel column chromatography, and semi-preparative RP-HPLC, and the structures of all compounds were identified by modern spectrographic technology(MS, NMR). The MTT method was used to measure the cytotoxicity of compounds 1-8. Twelve compounds were isolated from the roots and rhizomes of H. thibetanus and were identified as(25R)-22ß,25-expoxy-26-[(O-ß-D-glucopyranosyl)oxy]-1ß,3ß-dihydroxyfurosta-5-en(1), ß-sitosterol myristate(2), ß-sitosterol lactate(3), ß-sitosterol 3-O-ß-D-glucopyrannoside(4), 4,6,8-trihydroxy-3,4-dihydronaphthalen-1(2H)-one(5), 1,3,5-trimethoxybenzene(6), 7,8-dimethylbenzo pteridine-2,4(1H,3H)-dione(7), 1H-indole-3-carboxylic acid(8), p-hydroxy cinnamic acid(9), lauric acid(10), n-butyl α-L-arabinofuranoside(11) and methyl-α-D-fructofuranoside(12), respectively. Among them, compound 1 is a new compound and named thibetanoside L; compounds 2, 5-8, 11 are first isolated from the family Ranunculaceae; compound 12 is isolated from the genus Helleborus for the first time. The results of MTT assay showed that the IC_(50) values of compounds 1-8 against HepG2 and HCT116 cells were greater than 100 µmol·L~(-1).

Rare case of p16-positive oropharyngeal cancer metastasis to the orbit.

We describe a case of a man in his 70s who was diagnosed with a p16-positive base of tongue squamous cell carcinoma (SCC) and presented with deteriorating vision and exophthalmos. Imaging revealed medial rectus hypertrophy, and surgery confirmed metastatic p16-positive SCC. Literature reveals that orbital metastasis from any malignancy is a rare occurrence, and even that of p16-positive oropharyngeal SCC has only been reported once in English literature previously. The case highlights the importance of maintaining a wide differential and not being narrowed into a diagnosis or treatment, and given the increasing incidence of human papillomavirus-related cancers, it is important to preserve a high index of suspicion.

Epigenetic insights into an epimutant colorless non-ripening: from fruit ripening to stress responses.

The epigenetic machinery has received extensive attention due to its involvement in plant growth, development, and adaptation to environmental changes. Recent studies often highlight the epigenetic regulatory network by discussing various epigenetic mutants across various plant species. However, a systemic understanding of essential epigenetic regulatory mechanisms remains limited due to a lack of representative mutants involved in multiple biological processes. Colorless Non-ripening (Cnr), a spontaneous epimutant isolated from a commercial population, was initially characterized for its role in fruit ripening regulation. Cnr fruits exhibit an immature phenotype with yellow skin, attributed to hypermethylation of the SQUAMOSA PROMOTER BINDING PROTEIN-LIKE-CNR (SlSPL-CNR) promoter, resulting in the repression of gene expression. In addition to DNA methylation, this process also involves histone modification and microRNA, integrating multiple epigenetic regulatory factors. Interestingly, knockout mutants of SlSPL-CNR display phenotypical distinctions from Cnr in fruit ripening, indicating complex genetic and epigenetic control over the non-ripening phenotype in Cnr fruits. Accumulating evidence suggests that Cnr epimutation is pleiotropic, participating in various biological processes such as Cd stress, Fe deficiency, vivipary, and cell death. Therefore, the Cnr epimutant serve as an excellent model for unveiling how epigenetic mechanisms are involved in diverse biological processes. This review paper focuses on recent research advances regarding the Cnr epimutant, delving into its complex genetic and epigenetic regulatory mechanisms, with the aim of enhancing our understanding and facilitating the development of high-quality, high-yield crops through epigenetic modification.

Transorbital and endonasal resection of a rare orbital ectopic atypical meningioma.

A female patient in her early 20s presented with increasing proptosis of her left eye over 2 months. She had no other signs of diplopia, pain or visual loss on initial presentation. Subsequent imaging of her orbits revealed a medial rectus tumour. A transorbital open biopsy of this tumour was non-diagnostic/inconclusive, hence a combined transorbital and endonasal resection of this tumour was performed. Histopathology of the resected tumour revealed an unusual inflammatory-rich spindle cell neoplasm, which was determined to be a primary orbital ectopic atypical meningioma. These tumours are exceedingly rare, with only case reports/series reported in the literature. Complete surgical resection with margins is the proposed treatment. The role of radiotherapy is still controversial. More studies are required to improve our knowledge of this condition.

Characterization and In vivo Evaluation of Polymorphic Valnemulin Hydrogen Fumarate.

AIMS: In the present study, a valnemulin hydrogen fumarate prodrug was characterized, its stability was compared with valnemulin hydrochloride, and the efficacy was evaluated in Actinobacillus pleuropneumoniae-induced pneumonia in mice. METHOD: Optical microscopy, X-ray powder diffraction, infrared spectroscopy, and hydrogen nuclear magnetic resonance spectroscopy were used to study the physical and chemical properties of the prodrug. The thermal stability was investigated in comparison with valnemulin hydrochloride to improve the preparation process of valnemulin hydrogen fumarate soluble powder and maximize its drug effect. Additionally, the efficacy of valnemulin hydrogen fumarate was evaluated in a challenge-treatment trial in mice using an in vitro antimicrobial susceptibility test. RESULTS: The valnemulin hydrogen fumarate had high crystallinity. After light irradiation for 20 days, valnemulin hydrogen fumarate did not degrade, whereas valnemulin hydrochloride did. These results showed that the valnemulin hydrogen fumarate was stable. At the same dose in drinking water, the valnemulin hydrogen fumarate was more effective than the reference drug (tiamulin fumarate) in an Actinobacillus pleuropneumoniae challenge-treatment trial. CONCLUSION: Valnemulin hydrogen fumarate shows excellent potential for application as a veterinary drug.

A comprehensive analysis of hepatopancreas metabolomics and transcriptomics provides insights into the growth of three-year-old crabs (Eriocheir sinensis) under low temperature.

Low water temperature is a critical environmental factor limiting the size of cultivated aquatic individuals. However, it has found that a proportion of Eriocheir sinensis cultured in low water temperature with high-altitude can mature into three-year-old crabs, which present larger body size than conventional two-year-old crabs. Based on integrated transcriptomic and metabolomic analysis, the significantly difference focuses on metabolic pathways involving glycine, serine, and threonine metabolism, amino sugar and nucleotide sugar metabolism, cysteine and methionine metabolism, pantothenate and CoA biosynthesis, arginine and proline metabolism, and vitamin digestion and absorption. It revealed that the growth performance of three-year-old crabs is mainly regulated by improving its antioxidant defense to maintain physical fitness, while reducing protein consumption by intensifying energy supplement ability and enhancing the ability to digest and absorb nutrients at low temperature. This study provides new insights on the molecular and metabolic pathways that control E. sinensis growth at high-altitude and low water temperature, laying the theoretical basis for further artificial three-year-old crabs breeding.

Anesthesia, Anesthetics, and Postoperative Cognitive Dysfunction in Elderly Patients.

Postoperative cognitive dysfunction (POCD) remains a major issue that worsens the prognosis of elderly surgery patients. This article reviews the current research on the effect of different anesthesia methods and commonly utilized anesthetics on the incidence of POCD in elderly patients, aiming to provide an understanding of the underlying mechanisms contributing to this condition and facilitate the development of more reasonable anesthesia protocols, ultimately reducing the incidence of POCD in elderly surgery patients.

The sexually divergent cFos activation map of fear extinction.

Objective: Post-traumatic stress disorder (PTSD) is a neuropsychiatric disorder that can develop after experiencing or witnessing a traumatic event. Exposure therapy is a common treatment for PTSD, but it has varying levels of efficacy depending on sex. In this study, we aimed to compare the sexual dimorphism in brain activation during the extinction of fear conditioning in male and female rats by detecting the c-fos levels in the whole brain. Methods: Thirty-two rats (Male: n = 16; Female: n = 16) were randomly separated into the extinction group as well as the non-extinction group, and fear conditioning was followed by extinction and non-extinction, respectively. Subsequently, brain sections from the sacrificed animal were performed immunofluorescence and the collected data were analyzed by repeated two-way ANOVAs as well as Pearson Correlation Coefficient. Results: Our findings showed that most brain areas activated during extinction were similar in both male and female rats, except for the reuniens thalamic nucleus and ventral hippocampi. Furthermore, we found differences in the correlation between c-fos activation levels and freezing behavior during extinction between male and female rats. Specifically, in male rats, c-fos activation in the anterior cingulate cortex was negatively correlated with the freezing level, while c-fos activation in the retrosplenial granular cortex was positively correlated with the freezing level; but in female rats did not exhibit any correlation between c-fos activation and freezing level. Finally, the functional connectivity analysis revealed differences in the neural networks involved in extinction learning between male and female rats. In male rats, the infralimbic cortex and insular cortex, anterior cingulate cortex and retrosplenial granular cortex, and dorsal dentate gyrus and dCA3 were strongly correlated after extinction. In female rats, prelimbic cortex and basolateral amygdala, insular cortex and dCA3, and anterior cingulate cortex and dCA1 were significantly correlated. Conclusion: These results suggest divergent neural networks involved in extinction learning in male and female rats and provide a clue for improving the clinical treatment of exposure therapy based on the sexual difference.

Five new secondary metabolites from Aster tataricus.

Aster tataricus L.f. is highly valued for its rich reserves of bioactive compounds. Our research focused on the identification of previously unreported compounds found within the ethanol extract of A. tataricus. Through meticulous spectroscopic analyses and computational methods like NMR calculations and ECD, we successfully elucidated the structures of five novel compounds termed tatarisides A-E (1-5), alongside two known compounds (6, 7). The anti-inflammatory assays conducted yielded noteworthy results, particularly in relation to compounds 1 and 5. These compounds exhibited significant potential in inhibiting the release of NO in LPS-induced RAW 264.7 cells, as evidenced by their respective IC50 values of 17.81 ± 1.25 µM and 13.32 ± 0.84 µM. The discovery of these new compounds adds to the existing knowledge of A. tataricus's chemical composition and potential applications.