M1-type polarized macrophage contributes to brain damage through CXCR3.2/CXCL11 pathways after RGNNV infection in grouper.

The vertebrate central nervous system (CNS) is the most complex system of the body. The CNS, especially the brain, is generally regarded as immune-privileged. However, the specialized immune strategies in the brain and how immune cells, specifically macrophages in the brain, respond to virus invasion remain poorly understood. Therefore, this study aimed to examine the potential immune response of macrophages in the brain of orange-spotted groupers (Epinephelus coioides) following red-spotted grouper nervous necrosis virus (RGNNV) infection. We observed that RGNNV induced macrophages to produce an inflammatory response in the brain of orange-spotted grouper, and the macrophages exhibited M1-type polarization after RGNNV infection. In addition, we found RGNNV-induced macrophage M1 polarization via the CXCR3.2- CXCL11 pathway. Furthermore, we observed that RGNNV triggered M1 polarization in macrophages, resulting in substantial proinflammatory cytokine production and subsequent damage to brain tissue. These findings reveal a unique mechanism for brain macrophage polarization, emphasizing their role in contributing to nervous tissue damage following viral infection in the CNS.

Development and external validation of a novel score for predicting postoperative 30­day mortality in tumor craniotomy patients: A cross­sectional diagnostic study.

The identification of patients with craniotomy at high risk for postoperative 30-day mortality may contribute to achieving targeted delivery of interventions. The present study aimed to develop a personalized nomogram and scoring system for predicting the risk of postoperative 30-day mortality in such patients. In this retrospective cross-sectional study, 18,642 patients with craniotomy were stratified into a training cohort (n=7,800; year of surgery, 2012-2013) and an external validation cohort (n=10,842; year of surgery, 2014-2015). The least absolute shrinkage and selection operator (LASSO) model was used to select the most important variables among the candidate variables. Furthermore, a stepwise logistic regression model was established to screen out the risk factors based on the predictors chosen by the LASSO model. The model and a nomogram were constructed. The area under the receiver operating characteristic (ROC) curve (AUC) and calibration plot analysis were used to assess the model's discrimination ability and accuracy. The associated risk factors were categorized according to clinical cutoff points to create a scoring model for postoperative 30-day mortality. The total score was divided into four risk categories: Extremely high, high, intermediate and low risk. The postoperative 30-day mortality rates were 2.43 and 2.58% in the training and validation cohort, respectively. A simple nomogram and scoring system were developed for predicting the risk of postoperative 30-day mortality according to the white blood cell count; hematocrit and blood urea nitrogen levels; age range; functional health status; and incidence of disseminated cancer cells. The ROC AUC of the nomogram was 0.795 (95% CI: 0.764 to 0.826) in the training cohort and it was 0.738 (95% CI: 0.7091 to 0.7674) in the validation cohort. The calibration demonstrated a perfect fit between the predicted 30-day mortality risk and the observed 30-day mortality risk. Low, intermediate, high and extremely high risk statuses for 30-day mortality were associated with total scores of (-1.5 to -1), (-0.5 to 0.5), (1 to 2) and (2.5 to 9), respectively. A personalized nomogram and scoring system for predicting postoperative 30-day mortality in adult patients who underwent craniotomy were developed and validated, and individuals at high risk of 30-day mortality were able to be identified.

Evolution of drought characteristics and propagation from meteorological to agricultural drought under the influences of climate change and human activities.

Understanding the propagation of agricultural droughts (AD) is important to comprehensively assess drought events and develop early warning systems. The present study aims to assess the impacts of climate change and human activities on drought characteristics and propagation from meteorological drought (MD) to AD in the Yellow River Basin (YRB) over the 1950-2021 period using the Standardized Precipitation Evapotranspiration Index (SPEI) and Standardized Soil Moisture Index (SSMI). In total, the YRB was classified into three groups of catchments for spring wheat and four groups of catchments for winter wheat based on different human influence degrees (HId). In addition, the entire study period was divided into periods with natural (NP), low (LP), and high (HP) impacts of human activities, corresponding to 1950-1971, 1972-1995, and 1996-2021, respectively. The results demonstrated the significance and credibility of the application of the natural and human-impacted catchment comparison method for drought characteristics and propagation from meteorological to agricultural drought in the YRB. Winter wheat showed a more pronounced drying trend than spring wheat under both MD and AD. The results showed meteorological drought intensity (MDI) and agricultural drought intensity (ADI) intensified for spring and winter wheat in NP, with correspondingly a short propagation time, followed by those in the LP and HP in catchments minimally impacted by human activities. On the other hand, increases in the MDI and ADI, as well as in their times, for both spring and winter wheat were observed from the LP to the HP in all catchments. The MDI, ADI, and their propagation times for winter wheat generally showed greater fluctuations than those for spring wheat. Human activities increasingly prolonged the drought propagation time. In contrast, climate change insignificantly shortened the drought propagation time.

Diterpenoid honatisine overcomes temozolomide resistance in glioblastoma by inducing mitonuclear protein imbalance through disruption of TFAM-mediated mtDNA transcription.

BACKGROUND: Glioblastoma (GBM) represents as the most formidable intracranial malignancy. The systematic exploration of natural compounds for their potential applications in GBM therapy has emerged as a pivotal and fruitful avenue of research. PURPOSE: In the present study, a panel of 96 diterpenoids was systematically evaluated as a repository of potential antitumour agents. The primary objective was to discern their potency in overcoming resistance to temozolomide (TMZ). Through an extensive screening process, honatisine, a heptacyclic diterpenoid alkaloid, emerged as the most robust candidate. Notably, honatisine exhibited remarkable efficacy in patient-derived primary and recurrent GBM strains. Subsequently, we subjected this compound to comprehensive scrutiny, encompassing GBM cultured spheres, GBM organoids (GBOs), TMZ-resistant GBM cell lines, and orthotopic xenograft mouse models of GBM cells. RESULTS: Our investigative efforts delved into the mechanistic underpinnings of honatisine's impact. It was discerned that honatisine prompted mitonuclear protein imbalance and elicited the mitochondrial unfolded protein response (UPRmt). This effect was mediated through the selective depletion of mitochondrial DNA (mtDNA)-encoded subunits, with a particular emphasis on the diminution of mitochondrial transcription factor A (TFAM). The ultimate outcome was the instigation of deleterious mitochondrial dysfunction, culminating in apoptosis. Molecular docking and surface plasmon resonance (SPR) experiments validated honatisine's binding affinity to TFAM within its HMG-box B domain. This binding may promote phosphorylation of TFAM and obstruct the interaction of TFAM bound to heavy strand promoter 1 (HSP1), thereby enhancing Lon-mediated TFAM degradation. Finally, in vivo experiments confirmed honatisine's antiglioma properties. Our comprehensive toxicological assessments underscored its mild toxicity profile, emphasizing the necessity for a thorough evaluation of honatisine as a novel antiglioma agent. CONCLUSION: In summary, our data provide new insights into the therapeutic mechanisms underlying honatisine's selective inducetion of apoptosis and its ability to overcome chemotherapy resistance in GBM. These actions are mediated through the disruption of mitochondrial proteostasis and function, achieved by the inhibition of TFAM-mediated mtDNA transcription. This study highlights honatisine's potential as a promising agent for glioblastoma therapy, underscoring the need for further exploration and investigation.

A novel automatic segmentation method directly based on magnetic resonance imaging K-space data for auxiliary diagnosis of glioma.

Background: The use of segmentation architectures in medical imaging, particularly for glioma diagnosis, marks a significant advancement in the field. Traditional methods often rely on post-processed images; however, key details can be lost during the fast Fourier transformation (FFT) process. Given the limitations of these techniques, there is a growing interest in exploring more direct approaches. The adaption of segmentation architectures originally designed for road extraction for medical imaging represents an innovative step in this direction. By employing K-space data as the modal input, this method completely eliminates the information loss inherent in FFT, thereby potentially enhancing the precision and effectiveness of glioma diagnosis. Methods: In the study, a novel architecture based on a deep-residual U-net was developed to accomplish the challenging task of automatically segmenting brain tumors from K-space data. Brain tumors from K-space data with different under-sampling rates were also segmented to verify the clinical application of our method. Results: Compared to the benchmarks set in the 2018 Brain Tumor Segmentation (BraTS) Challenge, our proposed architecture had superior performance, achieving Dice scores of 0.8573, 0.8789, and 0.7765 for the whole tumor (WT), tumor core (TC), and enhanced tumor (ET) regions, respectively. The corresponding Hausdorff distances were 2.5649, 1.6146, and 2.7187 for the WT, TC, and ET regions, respectively. Notably, compared to traditional image-based approaches, the architecture also exhibited an improvement of approximately 10% in segmentation accuracy on the K-space data at different under-sampling rates. Conclusions: These results show the superiority of our method compared to previous methods. The direct performance of lesion segmentation based on K-space data eliminates the time-consuming and tedious image reconstruction process, thus enabling the segmentation task to be accomplished more efficiently.

LuxS-deficiency reduces persistence of Cronobacter to low-moisture but contributes to virulence after rehydration.

Low-moisture foods (LMF) have arisen an increasing concern as vehicles of foodborne pathogens. Cronobacter genus, a class A pathogen in powdered infant formula (PIF), is crucial to the safety of LMF. Researchers have concentrated more on the bacterial survival caused by key hazardous factors, yet they often ignore the alteration of virulence properties in the surviving strains following rehydration of LMF mediated by the key factors. Our previous transcriptional profiling showed that luxS might participate in desiccation response. Herein, we further investigated the role of Cronobacter LuxS under desiccation stress by combining with the phenotypic and gene analysis between the Cronobacter parent and luxS mutant strains. Desiccation stress destructing assays confirmed that luxS can significantly enhance the resistance of Cronobacter towards desiccation. Our results also showed that cell hydrophobicity, aggregation, motility, the content of polysaccharide, and AI-2 synthesis pathway involved in luxS-mediated desiccation response. The luxS mutant strain exhibited higher swimming and swarming motility, more content of capsular polysaccharide, and more rapid of aggregation, but lower hydrophobicity than that of the wild-type strain, whereas desiccation stress would result in a opposite effect on these cell surface properties in ΔluxS during rehydration. Additionally, the comparation of gene expression profiles indicated that low moisture would trigger Cronobacter luxS to promote transport osmoprotectants by regulating the expression of proX, proW, and treC, and suppress the expression of cpsG associated with polysaccharide colanic acid. Notably, this study also discovered for the first time that the luxS-deficiency dramatically attenuated adhesion and invasion to intestinal and brain cells, but ΔluxS subjected to desiccation could aggravate the cell virulence instead. Therefore, thinking the alteration of toxicity caused by low-moisture, approach based on blocking the expression of the luxS gene to prevent Cronobacter in LMF needs to be adopted with caution.

Association between preoperative serum sodium and postoperative 30-day mortality in adult patients with tumor craniotomy.

BACKGROUND: Limited data exist regarding preoperative serum sodium (Na) and 30-day mortality in adult patients with tumor craniotomy. Therefore, this study investigates their relationship. METHODS: A secondary retrospective analysis was performed using data from the ACS NSQIP database (2012-2015). The principal exposure was preoperative Na. The outcome measure was 30-day postoperative mortality. Binary logistic regression modeling was conducted to explore the link between them, and a generalized additive model and smooth curve fitting were applied to evaluate the potential association and its explicit curve shape. We also conducted sensitivity analyses and subgroup analyses. RESULTS: A total of 17,844 patients (47.59% male) were included in our analysis. The mean preoperative Na was 138.63 ± 3.23 mmol/L. The 30-day mortality was 2.54% (455/17,844). After adjusting for covariates, we found that preoperative Na was negative associated with 30-day mortality. (OR = 0.967, 95% CI:0.941, 0.994). For patients with Na ≤ 140, each increase Na was related to a 7.1% decreased 30-day mortality (OR = 0.929, 95% CI:0.898, 0.961); for cases with Na > 140, each increased Na unit was related to a 8.8% increase 30-day mortality (OR = 1.088, 95% CI:1.019, 1.162). The sensitivity analysis and subgroup analysis indicated that the results were robust. CONCLUSIONS: This study shows a positive and nonlinear association between preoperative Na and postoperative 30-day mortality in adult patients with tumor craniotomy. Appropriate preoperative Na management and maintenance of serum Na near the inflection point (140) may reduce 30-day mortality.

Femoral neck system vs. cannulated screws on treating femoral neck fracture: a meta-analysis and system review.

Objective: This meta-analysis aimed to compare the relative safety and efficacy of cannulated compression screw (CCS) and femoral neck system (FNS) in treating patients with femoral neck fractures and to provide evidence-based medical evidence for FNS in treating femoral neck fractures. Methods: PubMed, Embase, Cochrane, and China National Knowledge Infrastructure databases were searched to collect outcomes related to femoral neck fractures treated with FNS and CCS, including time to fracture healing, incidence of non-union, incidence of osteonecrosis of the femoral head, incidence of failure of internal fixation, rate of femoral neck shortening, Harris hip score, Barthel index, operative time, intraoperative blood loss, fluoroscopy frequency, and complications. A meta-analysis was performed using RevManv5.4 (The Cochrane Collaboration) and Stata v14.0 software. Results: This analysis included 21 studies involving 1,347 patients. The results showed that FNS was superior to CCS in terms of fracture healing time [mean difference (MD) = -0.75, 95% CI = (-1.04, -0.46), P < 0.05], incidence of bone non-union [odds ratio (OR) = 0.53, 95% CI = (0.29, 0.98), P = 0.04], incidence of osteonecrosis of the femoral head [OR = 0.49, 95% CI = (0.28, 0.86), P = 0.01], incidence of internal fixation failure [OR = 0.30, 95% CI = (0.18, 0.52), P < 0.05], rate of femoral neck shortening [OR = 0.38, 95% CI = (0.27, 0.54), P > 0.05], Harris hip score [MD = 3.31, 95% CI = (1.99, 4.63), P < 0.001], Barthel index [MD = 4.31, 95% CI = (3.02, 5.61), P < 0.05], intraoperative bleeding [MD = 14.72, 95% CI = (8.52, 20.92), P < 0.05], fluoroscopy frequency [OR = 0.53, 95% CI = (0.29, 0.98), P = 0.04], and complications [OR = 0.31, 95% CI = (0.22, 0.45), P < 0.05]. The difference between FNS and CCS in operative time was not statistically significant [MD = -2.41, 95% CI = (-6.88, 2.05), P = 0.29]. Conclusion: FNS treatment of femoral neck fracture can shorten the fracture healing time; reduce the incidence and translucent rate of bone non-union, osteonecrosis of the femoral head, and internal fixation failure; reduce intraoperative blood loss and postoperative complications; and improve hip joint function and activity. We are confident in the findings that FNS, an effective and safe procedure for internal fixation of femoral neck fractures, is superior to CCS.

The complete mitochondrial genome of Allogalathea elegans (Adams & White, 1848) (Decapoda: Galatheidae).

The genus Allogalathea belongs to the subfamily Galatheoidea of the family Galatheidae. Here, we report a mitogenome of Allogalathea elegans (Adams & White, 1848). In this study, we obtained the complete mitochondrial genome of Allogalathea elegans by sequencing, which was 16,263 bp in length. The mitogenome contained 37 genes, including the typical set of 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, and 2 Ribosomal RNA (rRNA) genes. The nucleotides A, C, G, and T distribution was 36.40%, 19.44%, 9.09%, and 35.07%, respectively. The length of the total protein-coding genes was 11,172 bp, which accounts for 68.69% of the whole mitochondrial genome. The phylogenetic result generated by IQ-Tree based on 13 PGCs showed that the infraorder Anomura is monophyletic, and the infraorder Anomura is a sister group of the infraorder Glypheidea. The discovery of the complete mitochondrial genome of A. elegans would help to conduct in-depth research on the infraorder Anomura.

Fingerprint construction of optical transmitters based on the characteristic of electro-optic chaos for secure authentication.

In this paper, an optical transmitter authentication method using hardware fingerprints based on the characteristic of electro-optic chaos is proposed. By means of phase space reconstruction of chaotic time series generated by an electro-optic feedback loop, the largest Lyapunov exponent spectrum (LLES) is defined and used as the hardware fingerprint for secure authentication. The time division multiplexing (TDM) module and the optical temporal encryption (OTE) module are introduced to combine chaotic signal and the message to ensure the security of the fingerprint. Support vector machine (SVM) models are trained to recognize legal and illegal optical transmitters at the receiver. Simulation results show that LLES of chaos has the fingerprint characteristic and is highly sensitive to the time delay of the electro-optic feedback loop. The trained SVM models can distinguish electro-optic chaos generated by different feedback loops with a time delay difference of only 0.03ns and have a good anti-noise ability. Experimental results show that the recognition accuracy of the authentication module based on LLES can reach 98.20% for both legal and illegal transmitters. Our strategy can improve the defense ability of optical networks against active injection attacks and has high flexibility.

A novel nonreversible heat-induced low-molecular-weight gel based on naturally-occurring self-assembled fupenzic acid for tumor therapy.

Herein, a nonreversible heat-induced supramolecular gel based on natural products was reported for the first time. This natural triterpenoid, fupenzic acid (FA), isolated from the roots of Rosa laevigata, was discovered to be capable of forming supramolecular gel spontaneously in 50 % ethanol-water solution induced by heating. Distinguished from the common thermosensitive gels, the FA-gel showed a distinctive nonreversible phase transition from the liquid to gel state upon heating. In this work, the entire gelation process of FA-gel induced by heating was recorded digitally by microrheology monitor. And a unique heat-induced gelation mechanism based on self-assembled FA has been proposed by using various experimental methods and molecular dynamics (MD) simulation. Its excellent injectability and stability were also demonstrated. Furthermore, the FA-gel had been evaluated to exhibit better anti-tumor activity and higher biosafety comparing with its equivalent free-drug, which opened up a new possibility to reinforce antitumor efficacy by using natural product gelator originated from traditional Chinese medicine (TCM) without any complicated chemical modifications.

Intranasal 15d-PGJ2 inhibits the growth of rat lactotroph pituitary neuroendocrine tumors by inducing PPARγ-dependent apoptotic and autophagic cell death.

PPARγ agonists have been reported to induce cell death in pituitary neuroendocrine tumor (PitNET) cell cultures. However, the therapeutic effects of PPARγ agonists in vivo remain unclear. In the present study, we found that intranasal 15d-PGJ2, an endogenous PPARγ agonist, resulted in growth suppression of Fischer 344 rat lactotroph PitNETs induced by subcutaneous implantation with a mini-osmotic pump containing estradiol. Intranasal 15d-PGJ2 reduced the volume and weight of the pituitary gland and the level of serum prolactin (PRL) in rat lactotroph PitNETs. 15d-PGJ2 treatment attenuated pathological changes and significantly decreased the ratio of PRL/pituitary-specific transcription factor 1 (Pit-1) and estrogen receptor α (ERα)/Pit-1 double-positive cells. Moreover, 15d-PGJ2 treatment induced apoptosis in the pituitary gland characterized by an increased ratio of TUNEL-positive cells, cleavage of caspase-3, and elevated activity of caspase-3. 15d-PGJ2 treatment decreased the levels of cytokines, including TNF-α, IL-1ß, and IL-6. Furthermore, 15d-PGJ2 treatment markedly increased the protein expression of PPARγ and blocked autophagic flux, as evidenced by the accumulation of LC3-II and SQSTM1/p62 and the decrease in LAMP-1 expression. Importantly, all these effects mediated by 15d-PGJ2 were abolished by cotreatment with the PPARγ antagonist GW9662. In conclusion, intranasal 15d-PGJ2 suppressed the growth of rat lactotroph PitNETs by inducing PPARγ-dependent apoptotic and autophagic cell death. Therefore, 15d-PGJ2 may be a potential new drug for lactotroph PitNETs.

Contribution of Constituents in Rosemary-Magnolia Compound Essential Oil to Antibacterial, Antioxidant and Cytotoxicity Bioactivities Revealed by Grey Correlation Analysis.

The compound of essential oils (EOs) is a key approach to achieving the superimposed efficacy of plant EOs. In this article, grey correlation analysis was applied for the first time to explore the compound ratios and contribution between constituents and the bioactivity of the compound EOs. There were 12 active constituents shared in rosemary and magnolia EOs prepared by negative pressure distillation. With different proportions, these two EOs were blended and analyzed for the antioxidant, bacteriostatic and antitumor effects. According to the results of the inhibition circle, minimum bactericidal and inhibitory concentration, the most obvious inhibition effect of the compound EOs on different strains of bacteria was shown in Staphylococcus aureus. The results of antioxidant test showed that single EO from rosemary had the best antioxidant effect, and its EO content was directly proportional to the antioxidant effect. The cytotoxicity results showed that, there was a significant difference in the lethality of the compound EOs between tumor cells Mcf-7 (human breast cancer cells) and SGC-7901 cells (human gastric cancer cells). Furthermore, single EO from magnolia had an obvious inhibitory effect on the growth of Mcf-7 cells and SGC-7901 cells, and the cell lethality rate was as high as 95.19 % and 97.96 %, respectively. As the results of grey correlation analysis, the constituents with the maximal correlation of inhibitory effects on bacteria were as follows: S. aureus - Terpinolene (0.893), E. coli - Eucalyptol (0.901), B. subtilis - α-Pinene (0.823), B. cereus - Terpinolene (0.913) and Salmonella - α-Phellandrene (0.855). For the ABTS and DPPH scavenging effects, the constituents with the maximal correlation were (-)-Camphor (0.860) and ß-Pinene (0.780), respectively. In terms of the effects of the active constituents of compound EOs on the inhibitory activities of tumor cells Mcf-7 and SGC-7901, the three active constituents of γ-Terpinene, (R)-(+)-ß-Citronellol and (-)-Camphor were in the top three, and their correlation were Mcf-7 (0.833, 0.820, 0.795) and SGC-7901 (0.797, 0.766, 0.740). Our study determined the contribution degree of active constituents in the antibacterial, antioxidant, and antitumor bioactivities of rosemary-magnolia compound EOs, and also provided new insights for the research of EOs combination formulations.

Discovery of 3,5-diaryl-1H-pyrazol-based ureas as potent RET inhibitors.

Rearranged during transfection (RET) is a promising target for antitumor drug development. Multikinase inhibitors (MKI) have been developed for RET-driven cancers but displayed limited efficacy in disease control. Two selective RET inhibitors were approved by FDA in 2020 and proved potent clinical efficacy. However, the discovery of novel RET inhibitors with high target selectivity and improved safety is still highly desirable. Herein, we reported a class of 3,5-diaryl-1H-pyrazol-based ureas as new RET inhibitors. The representative compounds 17a/b displayed high selectivity to other kinases, and potently inhibited isogenic BaF3-CCDC6-RET cells harboring wild-type, or gatekeeper mutation (V804M). They also displayed moderate potency against BaF3-CCDC6-RET-G810C with solvent-front mutation. Compound 17b showed better pharmacokinetics properties and demonstrated promising oral in vivo antitumor efficacy in a BaF3-CCDC6-RET-V804M xenograft model. It may be utilized as a new lead compound for further development.

Three-wave differential locking scheme in a 12-m-perimeter large-scale passive laser gyroscope.

Large-scale laser gyroscopes with sufficiently high sensitivity for measurement of the rotation rate of the Earth Ω E are inertial sensors with the capability to provide Earth orientation parameters, i.e., rotation rate and polar motion in near real time. Larger-scale passive resonant gyroscopes (PRGs) theoretically have a lower shot-noise limit. However, the cavity perimeter fluctuations and laser frequency noise become challenges in a passive gyro. In this paper, we introduce a three-wave differential locking scheme for large-scale PRGs, resulting in an in situ measurement of the cavity perimeter with nanometer resolution. Furthermore, the laser frequency noise is effectively suppressed with an additional gain of 30 dB by a double-stage locking system, based on the three-wave differential locking scheme. Finally, the rotation rate resolution of our 3m×3m gyroscope improves to 1.1×10-9 r a d/s over 200 s. The simplicity, robustness, and effectiveness of the locking scheme are important to the long-term operation of large-scale PRGs aiming for applications in the geosciences.

Increasing brain glucose uptake by Gypenoside LXXV ameliorates cognitive deficits in a mouse model of diabetic Alzheimer's disease.

We have previously reported that Gypenoside LXXV (GP-75), a novel natural PPARγ agonist isolated from Gynostemma pentaphyllum, ameliorated cognitive deficits in db/db mice. In this study, we further investigated the beneficial effects on cognitive impairment in APP/PS1 mice and a mouse model of diabetic AD (APP/PS1xdb/db mice). Interestingly, intragastric administration of GP-75 (40 mg/kg/day) for 3 months significantly attenuated cognitive deficits in APP/PS1 and APP/PS1xdb/db mice. GP-75 treatment markedly reduced the levels of glucose, HbA1c and insulin in serum and improved glucose tolerance and insulin sensitivity in APP/PS1xdb/db mice. Notably, GP-75 treatment decreased the ß-amyloid (Aß) burden, as measured by 11 C-PIB PET imaging. Importantly, GP-75 treatment increased brain glucose uptake as measured by 18 F-FDG PET imaging. Moreover, GP-75 treatment upregulated PPARγ and increased phosphorylation of Akt (Ser473) and GLUT4 expression levels but decreased phosphorylation of IRS-1 (Ser616) in the hippocampi of both APP/PS1 and APP/PS1xdb/db mice. Furthermore, GP-75-induced increases in GLUT4 membrane translocation in primary hippocampal neurons from APP/PS1xdb/db mice was abolished by cotreatment with the selective PPARγ antagonist GW9662 or the PI3K inhibitor LY294002. In summary, GP-75 ameliorated cognitive deficits in APP/PS1 and APP/PS1xdb/db mice by enhancing glucose uptake via activation of the PPARγ/Akt/GLUT4 signaling pathways.

[Research Progress in the Regulation of Follicle Development by Melatonin].

Melatonin,an endocrine hormone synthesized by the pineal gland,plays an important role in the reproduction.The growth and development of follicles is the basis of female mammalian fertility.Follicles have a high concentration of melatonin.Melatonin receptors exist on ovarian granulosa cells,follicle cells,and oocytes.It regulates the growth and development of these cells and the maturation and atresia of follicles,affecting female fertility.This paper reviews the protective effects and regulatory mechanisms of melatonin on the development of ovarian follicles,granulosa cells,and oocytes and makes an outlook on the therapeutic potential of melatonin for ovarian injury,underpinning the clinical application of melatonin in the future.

The role of symbiotic fungi in the life cycle of Gastrodia elata Blume (Orchidaceae): a comprehensive review.

Gastrodia elata Blume, a fully mycoheterotrophic perennial plant of the family Orchidaceae, is a traditional Chinese herb with medicinal and edible value. Interestingly, G. elata requires symbiotic relationships with Mycena and Armillaria strains for seed germination and plant growth, respectively. However, there is no comprehensive summary of the symbiotic mechanism between fungi and G. elata. Here, the colonization and digestion of hyphae, the bidirectional exchange of nutrients, the adaptation of fungi and G. elata to symbiosis, and the role of microorganisms and secondary metabolites in the symbiotic relationship between fungi and G. elata are summarized. We comprehensively and deeply analyzed the mechanism of symbiosis between G. elata and fungi from three perspectives: morphology, nutrition, and molecules. The aim of this review was to enrich the understanding of the mutualistic symbiosis mechanisms between plants and fungi and lay a theoretical foundation for the ecological cultivation of G. elata.

Cyclohexene oxide CA, a derivative of zeylenone, exhibits anti-cancer activity in glioblastoma by inducing G0/G1 phase arrest through interference with EZH2.

Introduction: Due to its highly aggressiveness and malignancy, glioblastoma (GBM) urgently requires a safe and effective treatment strategy. Zeylenone, a natural polyoxygenated cyclohexenes compound isolated from Uvaria grandiflora, has exhibited potential biological activities in various human diseases, including tumors. Methods: We designed and synthesized a series of (+)-Zeylenone analogues and evaluated their anti-GBM roles through structural-activity analysis. Cell Counting Kit-8, TUNEL, transwell and flow cytometry were employed for investigating the anticancer effects of CA on GBM cells. Western blotting, molecular docking, qRT-PCR and ChIP assays were performed to reveal the underlying mechanisms by which CA regulates the GBM cell cycle. The nude mouse xenograft model, HE staining, immunohistochemistry and was used to evaluate the anticancer effect of CA in vivo. Results: We identified CA ((1R, 2R, 3S)-3-p-fluorobenzoyl-zeylenone) as having the lowest IC50 value in GBM cells. CA treatment significantly inhibited the malignant behaviors of GBM cells and induced G0/G1 phase arrest in vitro. Furthermore, we validated the molecular mechanism by which CA interferes with EZH2, attenuating the down-regulation of cyclin-dependent kinase inhibitors p27 and p16 by the PRC2 complex. By establishing orthotopic nude mice models, we further validated the inhibitory role of CA on tumorigenesis of GBM cells in vivo and its potential values to synergistically potentiate the anti-tumor effects of EZH2 inhibitors. Conclusion: Overall, this paper elucidated the anti-GBM effects and potential mechanisms of CA, and may provide a therapeutic drug candidate for GBM treatment.

Association between preoperative platelet and 30-day postoperative mortality of adult patients undergoing craniotomy for brain tumors: data from the American College of Surgeons National Surgical Quality Improvement Program database.

BACKGROUND: Evidence regarding the relationship between preoperative platelet and 30-day postoperative mortality of intracranial tumor patients undergoing craniotomy is still limited. Therefore, the present research was conducted to explore the link of the platelet and 30-day postoperative mortality. METHODS: Electronic medical records of 18,642 adult patients undergoing craniotomy for brain tumors from 2012 to 2015 in the American College of Surgeons National Surgical Quality Improvement Program, were subject to secondary retrospective analysis. A binary logistic regression model evaluated the independent association between preoperative platelet and 30-day postoperative mortality. A generalized additive model and smooth curve fitting was conducted to explore the exact shape of the curve between them. Additionally, We also conducted sensitivity analyses to test the robustness of the results, and performed subgroup analyses. RESULTS: Eighteen thousand sixty-three patients were included in this study analysis. Of these, 47.49% were male. The mean preoperative platelet value was (244.12 ± 76.77) × 109/L. The 30-day postoperative mortality of included participants was 2.5% (452/18,063). After adjusting covariates, the results showed that preoperative platelet was positively associated with 30-day postoperative mortality (OR = 0.999, 95%CI: 0.997, 1.000). There was also a nonlinear relationship between preoperative platelet and 30-day postoperative mortality, and the inflection point of the platelet was 236. The effect sizes (OR) on the right and left sides of the inflection point were 1.002 (1.000, 1.004) and 0.993 (0.990, 0.995), respectively. And sensitive analysis demonstrated the robustness of the results. Subgroup analysis showed a stronger association between preoperative platelet and 30-day postoperative mortality in non-emergency surgery patients when preoperative platelet value is less than 235 × 109/L. CONCLUSIONS: This research demonstrates a positive and non-linear relationship between preoperative platelet and 30-day postoperative mortality in U.S. adult brain tumor patients undergoing craniotomy. Preoperative platelet is strongly related to 30-day postoperative mortality when the platelet is less than 235 × 109/L. Proper preoperative management of platelet and maintenance of platelet near inflection point (235) could reduce risk of 30-day postoperative mortality in these cases.