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P-type organic cathode materials typically exhibit high redox potentials and fast redox kinetics, presenting broad application prospects in aqueous zinc batteries (AZBs). However, most of the reported p-type organic cathode materials exhibit limited capacity (<100 mAh g -1 ), which is attributable to the low mass content ratio of oxidation-reduction active functional groups in these materials. Herein, we report a high-capacity p-type organic material, 5,12-dihydro-5,6,11,12-tetraazatetracene (DHTAT), for aqueous zinc batteries. Both experiments and calculation indicate the charge storage of DHTAT mainly involves the adsorption/desorption of ClO 4 - on the -NH- group. Benefitting from the high mass content ratio of the -NH- group in DHATA molecule, the DHATA electrode demonstrates a remarkable capacity of 224 mAh g -1 at a current density of 50 mA g -1 with a stable voltage of 1.12 V. Notably, after 5000 cycles at a high current density of 5 A g -1 , DHTAT retains 73 % of its initial capacity, showing a promising cycling stability. In addition, DHTAT also has good low-temperature performance and can stably cycle at -40 °C for 4000 cycles at 1 A g -1 , making it a competitive candidates cathode material for low-temperature batteries., (© 2024 Wiley-VCH GmbH.)

Background: Reliable quantification of the association between hypertension requiring medication and postoperative 30-day mortality in adult patients who undergo craniotomy for tumor resection is limited. We aimed to explore the associations between these factors., Materials and Methods: This work was a retrospective cohort study that used propensity score matching (PSM) among 18,642 participants from the American College of Surgeons National Surgical Quality Improvement Program database between 2012 and 2015. Hypertension requiring medication and postoperative 30-day mortality were the independent and dependent target variables, respectively. PSM was conducted via nonparsimonious multivariate logistic regression to balance the confounders. Robust estimation methods were used to investigate the association between hypertension requiring medication and postoperative 30-day mortality., Results: A total of 18,642 participants (52.6% male and 47.4% female) met our inclusion criteria; 7,116 (38.17%) participants with hypertension required medication and had a 3.74% mortality rate versus an overall mortality rate of 2.46% in the adult cohort of patients who underwent craniotomy for tumor resection. In the PSM cohort, the risk of postoperative 30-day mortality significantly increased by 39.0% among patients with hypertension who required medication (OR = 1.390, 95% confidence interval (CI): 1.071-1.804, p  = 0.01324) after adjusting for the full covariates. Compared with participants without hypertension requiring medication, those with hypertension requiring medication had a 34.0% greater risk of postoperative 30-day mortality after adjusting for the propensity score (OR = 1.340, 95% CI: 1.040-1.727, p  = 0.02366) and a 37.6% greater risk of postoperative 30-day mortality in the inverse probability of treatment weights (IPTW) cohort (OR = 1.376, 95% CI: 1.202, 1.576, p  < 0.00001)., Conclusion: Among U.S. adult patients undergoing craniotomy for tumor resection, hypertension requiring medication is a notable contributor to 30-day mortality after surgery, with odds ratios ranging from 1.34 to 1.39., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Hu, Zheng, Deng, Yang, Zhang, Li, Chen, Chen, Ji and Huang.)

In recent years, oleogel as a viscoelastic semi-solid to replace trans fatty acids and reduce saturated fatty acids in food has received more and more attention. Herein, an emulsion template method was used to produce soybean oil-based oleogels with seven different ester emulsifiers and soy protein isolate as oleogelators. The chemical and physical characteristics of oleogels produced via various crosslinking factors were comparatively examined. Results revealed that all oleogels generated β-type needle crystals and exhibited high oil-holding capacity (>80 %), among which glycerol monolaurate G2 and diacetyl tartaric acid ester of mono-diglycerides G6 exhibited the strongest oil-holding capacity (96.6 % and 96.2 %, respectively). Furthermore, all oleogels exhibited strong thixotropic recovery, high thermal stability, as well as high gel strength (G' > G''). Of these, G2 and G6 exhibited the highest thixotropic recovery rates at 74.54 % and 78.19 %, respectively. Additionally, in accelerated oxidation trials, the peroxide value and thiobarbituric acid reactive substances of all oleogels had low oxidation rates, indicating high oxidative stability. These results contribute to a better understanding of oleogels for formulating trans-free and low-saturated foodstuffs with desired physical and functional properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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.

Background: Neuroblastoma (NB), characterized by its marked heterogeneity, is the most common extracranial solid tumor in children. The status and functionality of mitochondria are crucial in regulating NB cell behavior. While the significance of mitochondria-related genes (MRGs) in NB is still missing in key knowledge., Materials and Methods: This study leverages consensus clustering and machine learning algorithms to construct and validate an MRGs-related signature in NB. Single-cell data analysis and experimental validation were employed to characterize the pivotal role of FEN1 within NB cells., Results: MRGs facilitated the classification of NB patients into 2 distinct clusters with considerable differences. The constructed MRGs-related signature and its quantitative indicators, mtScore and mtRisk, effectively characterize the MRGs-related patient clusters. Notably, the MRGs-related signature outperformed MYCN in predicting NB patient prognosis and was adept at representing the tumor microenvironment (TME), tumor cell stemness, and sensitivity to the chemotherapeutic agents Cisplatin, Topotecan, and Irinotecan. FEN1, identified as the most contributory gene within the MRGs-related signature, was found to play a crucial role in the communication between NB cells and the TME, and in the developmental trajectory of NB cells. Experimental validations confirmed FEN1's significant influence on NB cell proliferation, apoptosis, cell cycle, and invasiveness., Conclusion: The MRGs-related signature developed in this study offers a novel predictive tool for assessing NB patient prognosis, immune infiltration, stemness, and chemotherapeutic sensitivity. Our findings unveil the critical function of FEN1 in NB, suggesting its potential as a therapeutic target., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Tan, Jin, Li, Yang, Jia, Xia, Gong, Dong and Zhao.)

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., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled, “Diterpenoid honatisine overcomes temozolomide resistance in glioblastoma by inducing mitonuclear protein imbalance through disruption of TFAM-mediated mtDNA transcription”., (Copyright © 2023. Published by Elsevier GmbH.)

The circulatory system is a closed conduit system throughout the body and consists of two parts as follows: the cardiovascular system and the lymphatic system. Hematological malignancies usually grow and multiply in the circulatory system, directly or indirectly affecting its function. These malignancies include multiple myeloma, leukemia, and lymphoma. O -linked β-N-acetylglucosamine ( O -GlcNAc) transferase (OGT) regulates the function and stability of substrate proteins through O -GlcNAc modification. Abnormally expressed OGT is strongly associated with tumorigenesis, including hematological malignancies, colorectal cancer, liver cancer, breast cancer, and prostate cancer. In cells, OGT can assemble with a variety of proteins to form complexes to exercise related biological functions, such as OGT/HCF-1, OGT/TET, NSL, and then regulate glucose metabolism, gene transcription, cell proliferation, and other biological processes, thus affecting the development of hematological malignancies. This review summarizes the complexes involved in the assembly of OGT in cells and the role of related OGT complexes in hematological malignancies. Unraveling the complex network regulated by the OGT complex will facilitate a better understanding of hematologic malignancy development and progression.

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., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Liu et al.)

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., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-946/coif). Y.X.J.W. serves as the Editor-In-Chief of Quantitative Imaging in Medicine and Surgery. D.L. serves as an unpaid editorial board member of Quantitative Imaging in Medicine and Surgery. The other authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

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 IC 50 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Su, Cao, Ma, Li, Li, Liu, Chen, Chen, Li, Cui and Huang.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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., (© 2023. BioMed Central Ltd., part of Springer Nature.)

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., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Zhou, Li, Lao, Wang, Zhang, Dai and Fan.)

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.

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-1β, 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Chen, Zhang, Huang, Yang, Li, Wang, Meng and Huang.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

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 β-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)-(+)-β-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., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

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 3 m ×3 m 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.

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 β-amyloid (Aβ) 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., (© 2022 John Wiley & Sons Ltd.)

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) × 10 9 /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 × 10 9 /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 × 10 9 /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., (© 2022. The Author(s).)

PPARγ agonists have been proven to be neuroprotective in vitro and in vivo models of Alzheimer's disease (AD). In the present study, we identified ligustrazine piperazine derivative (LPD) as a novel PPARγ agonist, which was detected by a dual-luciferase reporter assay system. LPD treatment dose-dependently reduced Aβ40 and Aβ42 levels in PC12 cells stably transfected with APP695swe and PSEN1dE9. Intragastric administration of LPD for 3 months dose-dependently reversed cognitive deficits in APP/PS1 mice. LPD treatment substantially decreased hippocampal Aβ plaques in APP/PS1 mice and decreased the levels of Aβ40 and Aβ42 in vivo and in vitro. Moreover, LPD treatment induced mitophagy in vivo and in vitro and increased brain 18 F-FDG uptake in APP/PS1 mice. LPD treatment significantly increased OCR, ATP production, maximal respiration, spare respiratory capacity, and basal respiration in APP/PS1 cells. Mechanistically, LPD treatment upregulated PPARγ, PINK1, and the phosphorylation of Parkin (Ser65) and increased the LC3-II/LC3-I ratio but decreased SQSTM1/p62 in vivo and in vitro. Importantly, all these protective effects mediated by LPD were abolished by cotreatment with the selective PPARγ antagonist GW9662. In summary, LPD could increase brain glucose metabolism and ameliorate cognitive deficits through PPARγ-dependent enhancement of mitophagy in APP/PS1 mice., (© 2022. The Author(s).)

In the present study, six new cucurbitane type compounds, including three triterpenoids hemsleyacins P-R (6-7, 13) and three cucurbitane-type triterpenoid glycosides hemsleyaosides L-N (15-17), along with seventeen known cucurbitacin analogues were separated from the root tuber of Hemsleya penxianensis and elucidated based on NMR and HRESIMS. Then, 23 analogues of three types, namely, polyhydroxy-type (I) (1-7), monohydroxy-type (II) (8-13), and glycosides-type (III) (14-23), were assessed for their antitumor activity and structure-activity relationship analysis (SAR). We determined temozolomide (TMZ)-resistant GBM cell was the most sensitive to the tested compounds, and found hemsleyaoside N (HDN) displayed the best antineoplastic potency. Furthermore, we confirmed the anti-glioma activity of HDN in patient-derived recurrent GBM strains, GBM organoid (GBO) and orthotopic nude mouse models. Investigations exploring the mechanism made clear that HDN induced synchronous activation of UPR and MAPK signaling, which triggered deadly ER stress and apoptosis. Taken together, the potent antitumor activity of HDN warrants further comprehensive evaluation as a novel anti-glioma agent., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Pituitary adenoma (PA) includes invasive pituitary adenoma (IPA) and noninvasive pituitary adenoma (NIPA), which are associated with the endocrine system. The gut microbiome plays an important role in human metabolism, but the association between the gut microbiome and pituitary adenoma remains unclear. A total of 44 subjects were enrolled in this study. Of these, 29 PA patients were further divided into IPA patients ( n = 13) and NIPA patients ( n = 16), while 15 healthy age-matched subjects were defined as control subjects. We collected faecal samples and characterized the gut microbial profiles by metagenomic sequencing using the Illumina X-ten platform. PLS-DA showed different microbial clusters among the three groups, and slightly different microbial ecological networks were observed. LEfSe analysis revealed significant alterations in the microbial community among PA patients. In particular, the enrichment of Clostridium innocuum, along with the reduced abundance of Oscillibacter sp. 57&#95;20 and Fusobacterium mortiferum, were observed both in the IPA and NIPA groups compared to the control group. Moreover, PA patients could be effectively classified based on these bacteria using a support vector machine algorithm. In summary, this study demonstrated significant differences in the gut microbiome between PA patients and healthy controls. Future mechanistic experiments are needed to determine whether such alterations are a cause or consequence of pituitary adenoma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hu, Yang, Chen, Meng, Zhang, Li, Li and Huang.)

Solid-state lithium metal batteries (SSLMBs) promise high energy density and high safety by employing high-capacity Li metal anode and solid-state electrolytes. However, the construction of the composite Li metal electrode is a neglected but important subject when the extensive research focuses on the interface between the solid electrolyte Li 6.4 La 3 Zr 1.4 Ta 0.6 O 12 and Li metal anode. Here, an electronic-ionic conducting composite Li metal anode consisting of Li-Al alloy and LiF is constructed to achieve the stable electronic-ionic transport channel and the intimate interface contact, which can realize the uniform Li deposition and the efficiency utilization of lithium in composite Li metal electrode. Therefore, the symmetric battery with composite Li metal electrode exhibits the high critical current density with 1.2 mA cm -2 and stable cycle for 1500 h at 0.3 mA cm -2 , 25 °C. Moreover, the SSLMBs matched with LiFePO 4 and LiNi 0.8 Co 0.1 Mn 0.1 O 2 achieve the outstanding electrochemical performance, verifying the feasibility of composite Li metal electrode in various SSLMBs systems., (© 2022 Wiley-VCH GmbH.)

The cerebral ischemic microvascular response and collateral circulation compensatory capacity are important for the outcome of ischemic stroke. Here, we sought to evaluate the effect of a linarin derivate 4'-benzylapigenin-7- β -rutinoside (BLR) on neurological function and cerebral blood flow restoration in ischemic stroke. A mouse model of middle cerebral artery occlusion (30 min) with reperfusion (24 h) was used to mimic ischemic stroke in vivo , and 2,3,5-triphenyltetrazolium chloride (TTC) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays, and immunofluorescence microscopy were used to assess the protective effects of BLR on infarct volume, neurological function, neuronal apoptosis, and inflammatory damage. Cerebral blood flow was assayed by laser speckle contrast imaging. Double immunostaining of GFAP-collagen IV and brain lucidification were performed to determine the protective effects of BLR on the disruption of brain vasculature. Differential gene expression was assessed by RNA sequencing. Coimmunoprecipitation and western blotting were used to explore the mechanism of BLR-induced neuroprotection. The results of in vivo experiments showed that BLR administration after reperfusion onset reduced infarct volume, improved neurological function, and decreased the neural cell apoptosis and inflammatory response in the ischemic brain, which was accompanied by increased cerebral blood flow and reduced detachment of astrocyte endfeet from the capillary basement membrane. The RNA sequencing data showed that BLR promoted the upregulation of extracellular matrix and angiogenesis pathway-related genes; in particular, BLR significantly increased the expression of the chondroitin sulfate proteoglycan 4 (CSPG4) gene, enhanced the membrane location of CSPG4, and promoted its downstream signaling protein expression, which is associated with KDEL receptor (KDELR) activation. In addition, activated KDELR further increased the phosphorylation of mitogen-activated protein kinases after BLR treatment. Taken together, our data showed that BLR could protect against ischemic brain injury and may serve as a new promising therapeutic candidate drug for ischemic stroke, and that KDELR might act as both a sensor and effector to activate CSPG4 to increase cerebral blood flow., Competing Interests: The authors declare that they have no known conflicts of interest associated with this publication., (Copyright © 2022 Cong Xie et al.)

Objective: There is limited evidence to clarify the specific relationship between pre-operative blood urea nitrogen (BUN) and post-operative 30-day mortality in patients undergoing craniotomy for tumors. Therefore, we aimed to investigate this relationship in detail., Methods: Electronic medical records of 18,642 patients undergoing craniotomy for tumors in the ACS NSQIP from 2012 to 2015 were subjected to secondary retrospective analysis. The principal exposure was pre-operative BUN. Outcome measures were post-operative 30-day mortality. We used binary logistic regression modeling to evaluate the association between them and conducted a generalized additive model and smooth curve fitting (penalized spline method) to explore the potential relationship and its explicit curve shape. We also conducted sensitivity analyses to ensure the robustness of the results and performed subgroup analyses., Results: A total of 16,876 patients were included in this analysis. Of these, 47.48% of patients were men. The post-operative 30-day mortality of the included cases was 2.49% (420/16,876), and the mean BUN was 16.874 ± 6.648 mg/dl. After adjusting covariates, the results showed that pre-operative BUN was positively associated with post-operative 30-day mortality (OR = 1.020, 95% CI: 1.004, 1.036). There was also a non-linear relationship between BUN and post-operative 30-day mortality, and the inflection point of the BUN was 9.804. For patients with BUN < 9.804 mg/dl, a 1 unit decrease in BUN was related to a 16.8% increase in the risk of post-operative 30-day mortality (OR = 0.832, 95% CI: 0.737, 0.941); for patients with BUN > 9.804 mg/dl, a 1 unit increase in BUN was related to a 2.8% increase in the risk of post-operative 30-day mortality (OR = 1.028, 95% CI: 1.011, 1.045). The sensitivity analysis proved that the results were robust. The subgroup analysis revealed that all listed subgroups did not affect the relationship between pre-operative BUN and post-operative 30-day mortality ( P > 0.05)., Conclusion: Our study demonstrated that pre-operative BUN (mg/dl) has specific linear and non-linear relationships with post-operative 30-day mortality in patients over 18 years of age who underwent craniotomy for tumors. Proper pre-operative management of BUN and maintenance of BUN near the inflection point (9.804 mg/dl) could reduce the risk of post-operative 30-day mortality in these cases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Hu, Li, Han, Chen, Zhang, Li, Huang and Zhang.)

RIOK2 is an atypical kinase implicated in multiple human cancers. Although recent studies establish the role of RIOK2 in ribosome maturation and cell cycle progression, its biological functions remain poorly elucidated, hindering the potential to explore RIOK2 as a therapeutic target. Here, we report the discovery of CQ211 , the most potent and selective RIOK2 inhibitor reported so far. CQ211 displays a high binding affinity ( K d = 6.1 nM) and shows excellent selectivity to RIOK2 in both enzymatic and cellular studies. It also exhibits potent proliferation inhibition activity against multiple cancer cell lines and demonstrates promising in vivo efficacy in mouse xenograft models. The crystal structure of RIOK2- CQ211 sheds light on the molecular mechanism of inhibition and informs the subsequent optimization. The study provides a cell-active chemical probe for verifying RIOK2 functions, which may also serve as a leading molecule in the development of therapeutic RIOK2 inhibitors.

Esophageal squamous cell carcinoma (ESCC) is a cancer type with limited treatment options. The present study aimed to screen for small molecules that may inhibit ESCC cell viability. The small‑molecule‑perturbed signatures were extrapolated from the library of integrated network‑based cellular signatures (LINCS) database. Since LINCS does not include small‑molecule‑perturbed signatures of ESCC cells, it was hypothesized that non‑ESCC cell lines that display transcriptome profiles similar to those of ESCC may have similar small‑molecule‑perturbated responses to ESCC cells and that identifying small molecules that inhibit the viability of these non‑ESCC cells may also inhibit the viability of ESCC cells. The transcriptomes of >1,000 cancer cell lines from the Cancer Cell Line Encyclopedia database were analyzed and 70 non‑ESCC cell lines exhibiting similar transcriptome profiles to those of ESCC cells were identified. Among them, six cell lines with transcriptome signatures upon drug perturbation were available in the LINCS, which were used as reference signatures. A total of 20 ESCC datasets were analyzed and 522 downregulated and 461 upregulated differentially expressed genes (DEGs) that were consistently altered across >50% of the datasets were identified. These DEGs together with the reference signatures were then used as inputs of the ZhangScore method to score small molecules that may reverse transcriptome alterations of ESCC. Among the top‑ranked 50 molecules identified by the ZhangScore, four candidates that may inhibit ESCC cell viability were experimentally verified. Furthermore, 2‑[(aminocarbonyl)amino]‑5‑(4‑fluorophenyl)‑3‑-thiophenecarboxamide (TPCA‑1), an inhibitor of the NF‑κB pathway, was able to preferentially inhibit the viability of ESCC cells compared with non‑tumorigenic epithelial Het‑1A cells. Mechanistically, TPCA‑1 induced ESCC KYSE‑450 cell apoptosis by inhibiting the phosphorylation of inhibitor of NF‑κB kinase subunit β, leading to IκBα stabilization and NF‑κB signaling pathway inhibition. Collectively, these results demonstrated that LINCS‑based drug repositioning may facilitate drug discovery and that TPCA‑1 may be a promising candidate molecule in the treatment of ESCC.

We developed a facile, efficient method for synthesizing highly substituted 2-aminopyridines from unstable vinyl carbodiimides generated in situ in a one-pot transformation. A series of novel highly substituted 3-functionalized 2-aminopyridines were produced in good yields. Reaction mechanism studies, which included control experiments and density-functional theory (DFT) calculations, demonstrated that Rh and potassium carbonate played key roles in the cyclization step., (© 2022 Wiley-VCH GmbH.)

Background: The association between body mass index (BMI) and mortality is controversial. Thus, the purpose of our research was to survey the association between BMI and postoperative 30-day mortality in brain tumor patients undergoing craniotomy., Methods: This study analyzed data collected in a multicenter, cross-sectional study that consecutively and nonselectively collected data from a total of 18,642 patients undergoing craniotomy for tumors in the ACS NSQIP from 2012 to 2015. We constructed three linear and non-linear binomial logistic models (the inflection point was set at 18.5) to evaluate the association between BMI and postoperative 30-day mortality, respectively. We also conducted subgroup analyses. Additionally, we compared non-linear models with vs. without interaction with sex., Results: A total of 17,713 patients were included in this analysis. Of these, 47.38% were male. The postoperative 30-day mortality of the included cases was 2.39% (423/17,713), and the mean BMI was 28.41 ± 6.05 kg/m 2 . The linear logistic models suggested that after adjusting for the covariates, BMI was not associated with postoperative 30-day mortality (OR=0.999; 95% CI: 0.981, 1.017). The non-linear binomial logistic models suggested a nonlinear relationship between BMI and postoperative 30-day mortality. When BMI was < 18.5, we observed a stronger negative association between them after adjusting for covariates; the OR and 95% CI were 0.719, 0.576-0.896. When BMI was > 18.5, the relationship between them was not significant. We also found that a one-unit decrease in BMI for male patients with BMI < 18.5 kg/m 2 was related to a 34.6% increase in the risk of postoperative 30-day mortality (OR=0.654, 95% CI (0.472, 0.907). There was no significant association between them in male patients with BMI > 18.5 kg/m 2 or female patients., Conclusions: This study demonstrates a non-linear relationship between BMI and the risk of postoperative death. Preoperative underweight (BMI < 18.5 kg/m 2 ) would increase the risk of postoperative death in male patients (> 18 years old) undergoing craniotomy for brain tumors. Appropriate nutritional management prior to craniotomy for brain tumors may reduce the risk of postoperative 30-day mortality in underweight men., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Hu, Han, Li, Li, Zhang, Luo, Huang and Lan.)

Targeting the PPARγ might be a potential therapeutic strategy for diabetes-associated cognitive decline (DACD). In this study, Gypenoside LXXV (GP-75), a dammarane-type triterpene compound isolated from Gynostemma pentaphyllum, was found to be a novel PPARγ agonist using a dual-luciferase reporter assay system. However, whether GP-75 has protective effects against DACD remains unknown. Interestingly, intragastric administration of GP-75 (40 mg/kg/day) for 12 weeks significantly attenuated the cognitive deficit in db/db mice. GP-75 treatment significantly improved the glucose tolerance and lipid metabolism, and suppressed neuroinflammation. Notably, GP-75 treatment dramatically increased the uptake of glucose by the brain, as detected by 18 F-FDG PET. Incubation of primary cortical neurons with GP-75 significantly increased 2-deoxyglucose uptake. In addition, GP-75 treatment markedly increased the p-Akt (Ser 473)/total Akt levels and the expression levels of PPARγ and GLUT4, while decreasing the levels of p-IRS-1 (Ser 616)/total IRS-1. Importantly, all of these protective effects mediated by GP-75 were abolished by cotreatment with the PPARγ antagonist, GW9662. However, GP-75-mediated PPARγ upregulation was not affected by coincubation with the phosphatidylinositol 3-kinase inhibitor, LY294002. Collectively, GP-75 might be a novel PPARγ agonist that ameliorates cognitive deficit by enhancing brain glucose uptake via the activation of Akt/GLUT4 signaling in db/db mice., (© 2022 John Wiley & Sons Ltd.)

Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with an extremely low survival rate. New and effective approaches for treatment are therefore urgently needed. Here, we successfully developed M1-like macrophage-derived extracellular vesicles (M1EVs) that overcome multiple challenges via guidance from two macrophage-related observations in clinical specimens from GBM patients: enrichment of M2 macrophages in GBM; and origination of a majority of infiltrating macrophage from peripheral blood. To maximize the synergistic effect, we further functionalized the membranes of M1EVs with two hydrophobic agents (the chemical excitation source CPPO (C) and the photosensitizer Ce6 (C)) and loaded the hydrophilic hypoxia-activated prodrug AQ4N (A) into the inner core of the M1EVs. After intravenous injection, the inherent nature of M1-derived extracellular vesicles CCA-M1EVs allowed for blood-brain barrier penetration, and modulated the immunosuppressive tumor microenvironment via M2-to-M1 polarization, which increased hydrogen peroxide (H 2 O 2 ) levels. Furthermore, the reaction between H 2 O 2 and CPPO produced chemical energy, which could be used for Ce6 activation to generate large amounts of reactive oxygen species to achieve chemiexcited photodynamic therapy (CDT). As this reaction consumed oxygen, the aggravation of tumor hypoxia also led to the conversion of non-toxic AQ4N into toxic AQ4 for chemotherapy. Therefore, CCA-M1EVs achieved synergistic immunomodulation, CDT, and hypoxia-activated chemotherapy in GBM to exert a potent therapeutic effect. Finally, we demonstrated the excellent effect of CCA-M1EVs against GBM in cell-derived xenograft and patient-derived xenograft models, underscoring the strong potential of our highly flexible M1EVs system to support multi-modal therapies for difficult-to-treat GBM., (© 2022. The Author(s).)

Enhancing glucagon-like peptide 1 (GLP-1) signaling with a dipeptidyl peptidase IV (DPP-4) inhibitor might exert protective effects on Alzheimer's disease (AD). We found that intragastric administration of Gramcyclin A (10, 20 and 40 mg/kg), a novel DPP-4 inhibitor, for 3 months significantly reversed cognitive decline in APP/PS1/tau triple transgenic mice in a dose-dependent manner. Gramcyclin A treatment markedly reduced Aβ plaques as well as the insoluble and soluble forms of Aβ40 and Aβ42 in the hippocampus of APP/PS1/tau mice. Treatment with Gramcyclin A remarkedly decreased the level of microglia and suppressed neuroinflammation in the hippocampus of APP/PS1/tau mice. Moreover, Gramcyclin A treatment could increase brain glucose uptake in APP/PS1/tau mice, as detected by 18-fluoro-2-deoxyglucose ( 18 F-FDG) micro-positron emission tomography (micro-PET) imaging. Furthermore, Gramcyclin A significantly increased expression of glucagon-like peptide-1 (GLP-1), GLP-1R, proliferator-activated receptor gamma coactivator (PGC)-1α and glucose transporter 4 (GLUT4), and inhibited insulin receptor (IRS)-1 phosphorylation and tau hyperphosphorylation in the hippocampus of APP/PS1/tau mice. Collectively, Gramcyclin A conferred protective effects against AD via enhancing brain GLP-1-dependent glucose uptake. The DPP-4 inhibitor Gramcyclin A might be a potential therapeutic drug for AD., (© 2022 John Wiley & Sons Ltd.)

Unsubstituted pyridin-2-amine has a high quantum yield and is a potential scaffold for a fluorescent probe. However, the facile access to conjugated highly substituted aminopyridines and the study of their fluorescent properties is scarce. In this paper, synthesis and fluorescent properties of multisubstituted aminopyridines were studied based on a recently developed Rh-catalyzed coupling of vinyl azide with isonitrile to form a vinyl carbodiimide intermediate, following tandem cyclization with an alkyne. An aminopyridine substituted with an azide group as a potential probe was further designed, synthesized, and evaluated. The "clicking-and-probing" experiment of it on BSA protein showed the potential of aminopyridine as a scaffold of a biological probe.

Background: The identification of novel therapeutic candidates from natural products for the development of chemoresistant glioblastoma multiforme (GBM) treatment has been a highly significant and effective strategy., Purpose: Sesquiterpenes are a class of naturally occurring 15-carbon isoprenoid compounds, and several types of sesquiterpenes have the ability to induce growth inhibition and apoptosis in a variety of cancer cell lines. In the present study, 56 sesquiterpenes of five types, namely, eudesmane-type (I) (1-24), eremophilane-type (II) (25-32), cadinane-type (III) (33-41), guaiane-type (IV) (42-49), and oplopanone-type (V) (50-56), were screened for their antiglioma activity, structure-activity relationship analysis (SAR), and underlying mechanism based on patient-derived recurrent GBM strains, patient-derived GBM cell sphere, GBM organoid (GBO) models, and temozolomide (TMZ)-resistant GBM cell lines., Results: We found that compound 12 (oxyphyllanene B, OLB) showed the most potent antiglioma activity, and we confirmed that OLB could induce apoptosis in a time- and dose-dependent manner in TMZ-resistant GBM cells and GBOs. SAR announced that the presence of an α, β-unsaturated carbonyl moiety was likely to enhance cytotoxic activities. Mechanistic studies demonstrated that OLB induced abnormal changes in ER and mitochondria-associated membrane (MAM) networks, which triggered ER stress, mitochondrial dysfunction, and apoptosis. Furthermore, our findings suggested that OLB-triggered PACS2 activation might form a committed step to disrupt ER-mitochondria communication and showed for the first time that the expression levels of PACS2 might positively correlate with the progression and chemotherapy resistance of glioma., Conclusion: Our results indicated that OLB might be a promising candidate for treating TMZ-resistant GBM cells by activating PACS2, which triggered a crucial event to promote the disruption of ER-mitochondria communication and overcome chemotherapy resistance of GBM., (Copyright © 2021. Published by Elsevier GmbH.)

Clavipyrrine A (1), a novel polycyclic nitrogenous meroterpenoid with a pyrrolo[1,2-a]imidazole and a 10-membered carbocycle fused with an α,β-epoxy-γ-lactone, was isolated from Clitocybe clavipes, a basidiomycete. X-ray crystallography and spectroscopic analysis were used to fully elucidate its structure. The biosynthetic origin of the pyrrole unit in this nitrogenous meroterpenoid was identified by incorporating 15 N-labeled γ-aminobutyric acid. Compound 1 displayed promising anti-glioma activities and induced glioma cell apoptosis through inhibiting the JAK/STAT3 pathway and reinforcing SOCS1/3., (Copyright © 2021 Elsevier Inc. All rights reserved.)

In this work, a lithiophilic Ni-Al@LDH interlayer is engineered at the Li 6.4 La 3 Zr 1.4 Ta 0.6 O 12 (LLZTO) electrolyte and Li anode interface. The Ni-Al@LDH interlayer can significantly reduce the interfacial resistance as well as give excellent cycling performance both in a symmetric Li//Li cell and solid full lithium metal batteries.

Targeting the common molecular mechanism of type 2 diabetes mellitus and Alzheimer's disease (AD), including dysregulation of glucose metabolism, insulin resistance, and neuroinflammation, might be an efficient treatment strategy for AD. Previous studies have shown that 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), an endogenous PPARγ agonist, has anti-inflammatory, insulin sensitizing and anti-diabetic effects. However, whether 15d-PGJ2 has beneficial effects on AD remains to be elucidated. In the present study, we found that intranasal administration of 15d-PGJ2 (300 ng/30 μL/day) for 3 months significantly inhibited Aβ plaques, suppressed neuroinflammation, and attenuated cognitive deficits in APP/PS1 transgenic mice. Interestingly, 15d-PGJ2 treatment could increase brain glucose uptake, as detected by 18 F-FDG microPET imaging, and co-localization of GLUT4 and NeuN in the hippocampus of APP/PS1 mice. Furthermore, 15d-PGJ2 markedly increased the expression of PPARγ and PGC-1α, upregulated GLUT4, and decreased the phosphorylation of IRS-1 (Ser616) in the hippocampus of APP/PS1 mice. Importantly, co-administration of a PPARγ antagonist GW9662 abrogated these protective effects of 15d-PGJ2. Collectively, intranasal 15d-PGJ2 conferred protective effects against AD by activating PPARγ-dependent PGC-1α/GLUT4 signalling. The PPARγ agonist 15d-PGJ2 might be a potential therapeutic drug for AD., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Solid-state lithium-metal batteries (SSLMBs) using garnet Li 6.4 La 3 Zr 1.4 Ta 0.6 O 12 (LLZTO) as the solid electrolyte are expected to conquer the safety concerns of high energy Li batteries with organic liquid electrolytes owing to its nonflammable nature and good mechanical strength. However, the poor interfacial contact between the Li anode and LLZTO greatly restrains the practical applications of the electrolyte, because large polarization, dendritic Li formation and penetration can occur at the interfaces. Here, an effective method is proposed to improve the wettability of the LLZTO toward lithium and reduce the interfacial resistance by engineering universal lithiophilic interfacial layers. Thanks to the in-situ formed lithiophilic and ionic conductive Co/Li 2 O interlayers, the symmetric Li/CoO-LLZTO/Li batteries present much smaller overpotential, ultra-low areal specific resistance (ASR, 12.3 Ω cm 2 ), high critical current density (CCD, 1.1 mA cm -2 ), and outstanding cycling performance (1696 h at a current density of 0.3 mA cm -2 ) at 25 °C. Besides, the solid-state Li/CoO-LLZTO/LFP cells deliver an excellent electrochemical performance with a high coulombic efficiency of ~100% and a long cycling time over 185 times. Surprisingly, the high-voltage (4.6 V) solid state Li/CoO-LLZTO/Li 1.4 Mn 0.6 Ni 0.2 Co 0.2 O 2.4 (LMNC622) batteries can also realize an ultra-high specific capacity (232.5 mAh g -1 ) under 0.1 C at 25 °C. This work paves an effective way for practical applications of the dendrite-free SSLMBs., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2021 Science China Press. Published by Elsevier B.V. All rights reserved.)

The detection effect of the transient electromagnetic method is ambiguous in engineering applications due to the existence of interference sources, so explaining the influence of these fixed interference sources on is crucial. In this paper, the response characterisation of transient electromagnetic signals of fixed interference sources are thoroughly investigated. First, the secondary field generated by these interference sources is analyzed, and a typical fixed interference source is calculated. Then, a sensitivity analysis of the transient electromagnetic response curve is carried out. Finally, the mathematical superposition method for multiple field sources is proposed and verified. The results illustrate that the transient electromagnetic response curve of uniform full-space surrounding rock with a single fixed interference source has an apparent lifting phenomenon in the middle stage and presents an approximate horizontal change rule at the late stage. The transient electromagnetic response curves of multiple field sources separately illustrate the response characterisation of different field sources at different time stages. These research results can provide a valuable reference for the on-site interpretation of detection signals.

Endothelial cell damage is an important pathological basis for the deterioration of acute ischemia stroke. Our previous studies have been exploring the mechanism of blood-brain barrier (BBB) endothelial cell injury in the early stage of cerebral ischemia. Exosomes act as an important intercellular player in neurovascular communication. However, the characteristic of exosomes derived from BBB endothelial cells in early ischemic stroke is poorly understood. We exposed cultured brain microvascular endothelial cells (bEnd.3) to 3 h oxygen glucose deprivation (OGD) to mimic early cerebral ischemia in vitro and compared miRome and surface protein contents of exosomes derived from bEnd.3 cells by miRNA sequencing and the proximity barcoding assay (PBA). A total of 346 differentially miRNA (159 upregulated and 187 downregulated) were identified via miRNA-Seq in bEnd.3 cells after exposure to OGD for 3 h. Moreover, Gene Ontology (GO) and KEGG pathway analyses showed that cell proliferation- and angiogenesis-associated miRNAs were significantly affected. The abnormal changes in top eight miRNAs were further verified by a quantitative polymerase chain reaction (qPCR). PBA experiments showed that the numbers of exosomes carrying the following proteins increased significantly under ischemia, including bFGF, CD146, EPHA2, ABCB5, and ITGB2. These proteins were related to angiogenesis, cell proliferation, and cell inflammation. The network analysis combining PBA data with miRNA-Seq data showed that 79 miRNAs were related to 24 membrane proteins and predicted that there were surface proteins associated with a variety of miRNA molecules, such as ITGA9, XIAP, ADAM1, ITGA2, ITGA3, PDPN, and ITGB1. Meanwhile, there were miRNAs related to various surface proteins including miR-410-3p, miR-378b, and miR-1960. Taken together, our data demonstrated for the first time the changes of exosomal miRNAs and surface protein profiles derived from ischemic microvascular endothelial cells, which may provide new therapeutic targets for BBB protection in ischemic stroke., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

A general synthesis of 4-hydroxylcarbazoles by domino vinylogous conjugate addition/cyclization/elimination/aromatization of easily prepared 3-nitroindoles with alkylidene azlactones under mild and transition-metal-free conditions has been developed. This method was also applicable to other nitrosubstituted benzofused heterocycles such as 3-nitrobenzothiophene, 2-nitrobenzothiophene, and 2-nitrobenzofuran. The valuable tetracyclic carbazole derivatives, such as 6 H -oxazolo[4,5- c ]carbazole and 3,6-dihydro-2 H -oxazolo[4,5- c ]carbazol-2-one, were readily prepared from the product, demonstrating synthetic utility of this method., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

The striking dominance of groundwater-related defects in the operational high-speed railway tunnels in China calls for swift and accurate detection and identification. Thus, it is a new attempt to detect the water-bearing defects at 5 to 10 meters via train-borne transient electromagnetic method in operating tunnels. Due to the short detection distance, the interaction between transmitting and receiving coils is more important than those normally used coils. Thus, numerical and experimental methods are combined to investigate the mutual induction. The influence of turns, current and coil size on the mutual induction and the impact of damping coefficient on the receiving system are manifested. To further verify these findings, full-scale model experiments are conducted. During these physical experiments, the detection results of different coil parameters including coil size, number of turns, and emission current are compared and analyzed. Then, a special effort to minimize the induction between transmitting and receiving coils is expended to acquire the suitable coils for close range detection in the tunnel context. Finally, in order to verify the availability of the detection system, different detection distances are conducted. It turns out that different detection distances have slight difference at the detection results, but they are still within the measuring range of the detection instrument. Obviously, these findings can provide theoretical support for the detection of water-bearing anomalies in operating tunnels and it also has reference significance for the detection of anomalies at close distance.

Estuaries are important in terms of biodiversity, biogeochemical function, and ecological balance due to their intense land-sea interactions. The sustainability of estuarine ecosystem function relies on a good understanding of the ecological processes related to microbial communities. However, microbial community assembly in such ecosystems is still not well understood. Here, based on 16S rRNA sequencing, we investigated the bacterioplankton community structure in the Pearl River Estuarine system during the wet and dry seasons. Results showed that there were significant seasonal and spatial variations in the bacterioplankton communities of the estuary, with seasonal variations being more remarkable. Multiple bacterioplankton with different abundances in the wet and dry seasons were observed, e.g., the class Actinobacteria and Oxyphotobacteria were enriched in the wet season, whereas Alphaproteobacteria and Saccharimonadia were more abundant in the dry season. Both variation partitioning and null model analysis revealed that environmental filtering dominated the bacterioplankton community assembly in the Pearl River Estuary. Water physical properties (e.g., salinity and temperature), nutrient content (e.g., nitrate), and upstream land use (e.g., urban land cover) together determined the distribution of the bacterioplankton composition in this highly urbanized estuarine ecosystem. These findings would help improve our understanding of the bacterioplankton communities in estuarine ecosystems and provide a theoretical foundation for estuarine ecological health management., (Copyright © 2021 Elsevier Inc. All rights reserved.)