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Background: Acute Stanford Type A Aortic Dissection (ATAAD) is a critical medical emergency characterized by significant morbidity and mortality. This study aims to identify specific gene expression patterns and RNA modification associated with ATAAD., Methods: The GSE153434 dataset was obtained from the Gene Expression Omnibus (GEO) database. Differential expression analysis was conducted to identify differential expression genes (DEGs) associated with ATAAD. To validate the involvement of RNA modification in ATAAD, RNA modification-related genes (M6A, M1A, M5C, APA, A-to-I) were acquired from GeneCards, following by Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. A gene prediction signature consisting of key genes was established, and Real-time PCR was used to validate the gene expression in clinical samples. The patients were then divided into high and low-risk groups, and subsequent enrichment analysis, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), Gene Set Variation Analysis (GSVA), and assessments of immune infiltration. A co-expression network analysis (WGCNA) was performed to explore gene-phenotype relationships and identify key genes., Results: A total of 45 RNA modification genes were acquired. Six gene signatures (YTHDC1, WTAP, CFI, ADARB1, ADARB2, TET3) were developed for ATAAD diagnosis and risk stratification. Enrichment analysis suggested the potential involvement of inflammation and extracellular matrix pathways in the progression of ATAAD. The incorporation of pertinent genes from the GSE147026 dataset into the six-gene signature further validated the model's effectiveness. A significant upregulation in WTAP, ADARB2, and TET3 expression, whereas YTHDC1 exhibited a noteworthy downregulation in the ATAAD group., Conclusion: Six-gene signature could serve as an efficient model for predicting the diagnosis of ATAAD., Competing Interests: None., (© 2024 JGC All rights reserved; www.jgc301.com.)

Previous research has shown mixed results regarding the relationship between social class and children's prosocial behavior. The current study aims to further our understanding of these findings by exploring the relationship between social class and children's prosocial behavior in a moral context. Study 1 ( N = 833) found that when a target child pursued a morally negative goal and subsequently experienced misfortune, children from higher social class, compared to those from lower social class, experienced greater schadenfreude and exhibited less prosocial behavior. The relation between social class and prosocial behavior was mediated by schadenfreude. Study 2 ( N = 389) investigated whether the greater schadenfreude experienced by children from higher social class was due to a weaker empathic response to misfortune or a stronger sense of deservingness. The results revealed a sequential mediation effect of social class on prosocial behavior through deservingness and schadenfreude. These findings provide insight into the impact of social class on the development of children's moral judgment, emotions, and behavior. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Peroxymonosulfate (PMS)-based advanced oxidation processes (AOPs) are attractive approaches for solving the global problem of water pollution, due to the generation of highly-active reactive oxygen species (ROS). Therefore, highly-efficient PMS activation is crucial for promoting the catalytic degradation of environmental pollutants. Here, bimetallic CoGeO 2 (OH) 2 nanosheets with abundant surface hydroxyl groups (CGH) were synthesized via a simple hydrothermal route for PMS activation and degradation of various organic contaminants for the first time. The abundant surface hydroxyl groups (≡Co-OH/≡Ge-OH) could promptly initiate PMS to generate highly-active species: singlet oxygen ( 1 O 2 ), sulfate radicals (SO 4 · - ) and hydroxyl radicals (HO • ), while the asymmetric electron distribution among Co-O-Ge bonds derived from the higher electronegativity of Ge than Co further enhances the quick electron transfer to promote the redox cycle of Co 2+ /Co 3+ and Ge 2+ /Ge 4+ , thereby achieving an outstanding catalytic capability. The optimal catalyst exhibits nearly 100 % catalytic degradation performance of dyes (Methylene blue, Rhodamine B, Methyl orange, Orange II, Methyl green) and antibiotics (Norfloxacin, Bisphenol A, Tetracycline) over a wide pH range of 3-11 and under different coexisting anion conditions (Cl - , HCO 3 - , NO 3 - , HA), suggesting the excellent adaptability for practical usage. This study could potentially lead to novel perspectives on the remediation of water areas such as groundwater and deep-water areas., 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 Inc. All rights reserved.)

Objectives: To observe the effect of electroacupuncture on miR-142-5p and ADAMTS1/PI3K/AKT pathway in rats with ischemic stroke, so as to explore the regulatory mechanism of electroacupuncture on angiogenesis after ischemic stroke., Methods: This study was divided into two parts. The first part of the experiment：SD rats were randomly divided into sham operation group, model group and electroacupuncture group. There were 20 rats in each group. The middle cerebral artery occlusion (MCAO) rat model was prepared using a modified Longa's method. In the electroacupuncture group, "Shuigou" (GV26) was selected for electroacupuncture intervention (4 Hz/20 Hz) for 30 min each time. The rats in the electroacupuncture group were given electroacupuncture immediately after successful modeling, once a day for 4 times. Hunter score and TTC staining were used to observe the neurological deficits and infarct volumes respectively；HE staining was used to observe the cortical pathological changes；immunohistochemistry was used to determine the changes of cerebral microvascular density. Real-time quantitative PCR and Western blot were used to observe the miR-142-5p expression, mRNA and protein expression levels of ADAMTS1, VEGF, PI3K, AKT, eNOS in ischemic cortex. The second part of the experiment：The rats were randomly divided into electroacupuncture+control group and electroacupuncture+miR-142-5p Antagomir group with 8 rats in each group. MCAO model was established after injection. Electroacupuncture+control group was given 0.9% sodium chloride solution injected into the right ventricle.The rats in the electroacupuncture+miR-142-5p Antagomir group were injected with miR-142-5p inhibitor into the right ventricle 30 min before modeling. Rats in electroacupuncture+control group and electroacupuncture+miR-142-5p Antagomir group were all given the same electroacupuncture treatment. Real-time fluorescence quantitative PCR was used to observe the effect of miR-142-5p Antagomir on the expression of miR-142-5p and ADAMTS1 mRNA. The effect of miR-142-5p Antagomir on ADAMTS1 protein was observed by Western blot., Results: In the first part of the experiment, compared with the sham operation group, the Hunter score in the model group was significantly increased ( P <0.01)；the volume of cerebral infarction in the model group was significantly increased ( P <0.01)；the degree of brain edema and neuronal necrosis and the density of cerebral microvessels was increased；the cerebral microvascular density was significantly increased ( P <0.01)；the expression levels of miR-142-5p and the mRNA expression levels of VEGF, AKT and eNOS were significantly decreased ( P <0.01, P <0.05), and the protein expression levels of VEGF, p-AKT and eNOS were significantly down-regulated ( P <0.01), while the mRNA expression levels of ADAMTS1 and PI3K, and the protein expression levels of ADAMTS1 and p-PI3K were all up-regulated ( P <0.01, P <0.05) in the model group. Compared with the model group, after intervention, the Hunter score in the electroacupuncture group was decreased ( P <0.01), the volume of cerebral infarction was significantly decreased ( P <0.01)；the degree of brain edema and neuronal necrosis were alleviated；the cerebral microvascular density was significantly increased ( P <0.01)；the expression of miR-142-5p and the mRNA expression of VEGF, PI3K, AKT and eNOS were increased ( P <0.01), the protein expressions of VEGF, p-PI3K, p-AKT and eNOS were increased ( P <0.01, P <0.05), while the mRNA and protein expression of ADAMTS1 were decreased ( P <0.05, P <0.01). After injection of miR-142-5p inhibitor, compared with electroacupuncture+control group, the expression of miR-142-5p in electroacupuncture+miR-142-5p Antagomir group was decreased( P <0.05), while the mRNA and protein expression of ADAMTS1 were increased ( P <0.01, P <0.05)., Conclusions: Electroacupuncture at GV26 can improve the neurological damage of ischemic stroke rats, reduce the volume of cerebral infarction and promote angiogenesis. The mechanism may be associated with the function of electroacupuncture in promoting the expression of miR-142-5p, so as to inhibit the expression of its target gene ADAMTS1, mediate the up-regulation of VEGF expression, activate PI3K/AKT pathway, promote the release of eNOS, and participate in promoting angiogenesis in ischemic stroke rats.

Chronic itch often clinically coexists with anxiety symptoms, creating a vicious cycle of itch-anxiety comorbidities that are difficult to treat. However, the neuronal circuit mechanisms underlying the comorbidity of anxiety in chronic itch remain elusive. Here, we report anxiety-like behaviors in mouse models of chronic itch and identify γ-aminobutyric acid-releasing (GABAergic) neurons in the lateral septum (LS) as the key player in chronic itch-induced anxiety. In addition, chronic itch is accompanied with enhanced activity and synaptic plasticity of excitatory projections from the thalamic nucleus reuniens (Re) onto LS GABAergic neurons. Selective chemogenetic inhibition of the Re → LS circuit notably alleviated chronic itch-induced anxiety, with no impact on anxiety induced by restraint stress. Last, GABAergic neurons in lateral hypothalamus (LH) receive monosynaptic inhibition from LS GABAergic neurons to mediate chronic itch-induced anxiety. These findings underscore the potential significance of the Re → LS → LH pathway in regulating anxiety-like comorbid symptoms associated with chronic itch.

This study extracted and purified a polysaccharide from Rehmanniae radix praeparata (RGP) with an average molecular weight. The structural characteristics of RGP and its iron (III) complex, RGP-Fe(III), were examined for their antioxidant properties and potential in treating iron deficiency anemia (IDA). Analysis revealed that RGP comprised Man, Rha, Gal, and Xyl, with a sugar residue skeleton featuring 1→3; 1→2, 3; and 1→2, 3, 4 linkages, among others. RGP-Fe(III) had a molecular weight of 4.39×10 4  Da. Notably, RGP-Fe(III) exhibited superior antioxidant activity compared to RGP alone. In IDA rat models, treatment with RGP-Fe(III) led to increased weight gain, restoration of key blood parameters including hemoglobin, red blood cells, and mean hemoglobin content, elevated serum iron levels, and decreased total iron-binding capacity. Histological examination revealed no observable toxic effects of RGP-Fe(III) on the liver and spleen. These findings suggest the potential of RGP-Fe(III) as a therapeutic agent for managing IDA and highlight its promising antioxidant properties., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Salt stress is a critical limiting factor for fruit yield and quality of apples. Brassinosteroids (BRs) play an important role in response to abiotic stresses. In the present study, application of 2,4- Epicastasterone on seedlings of Malus 'M9T337' and Malus domestica 'Gala3' alleviated the physiological effects, such as growth inhibition and leaf yellowing, induced by salt stress. Further analysis revealed that treatment with NaCl induced expression of genes involved in BR biosynthesis in 'M9T337' and 'Gala3'. Among which, the expression of BR biosynthetic gene MdBR6OX2 showed a three-fold upregulation upon salt treatment, suggesting its potential role in response to salt stress in apple. MdBR6OX2, belonging to the CYP450 family, contains a signal peptide region and a P450 domain. Expression patterns analysis showed that the expression of MdBR6OX2 can be significantly induced by different abiotic stresses. Overexpressing MdBR6OX2 enhanced the tolerance of apple callis to salt stress, and the contents of endogenous BR-related compounds, such as Typhastero (TY), Castasterone (CS) and Brassinolide (BL) were significantly increased in transgenic calli compared with that of wild-type. Extopic expression of MdBR6OX2 enhanced tolerance to salt stress in Arabidopsis. Genes associated with salt stress were significantly up-regulated, and the contents of BR-related compounds were significantly elevated under salt stress. Our data revealed that BR-biosynthetic gene MdBR6OX2 positively regulates salt stress tolerance in both apple calli and Arabidopsis., 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. Published by Elsevier Masson SAS.)

Objective: To evaluate the effect of stent implantation for vertebrobasilar artery stenosis，by using 3D arterial spin labeling (3D ASL) technique., Methods: A retrospective analysis was conducted on the clinical and 3D ASL data of 48 patients who underwent vertebral-basilar artery stenting. Post-labeling delay times (PLD) of 1.5 s and 2.5 s were chosen, and the average regional cerebral blood flow (rCBF) values were measured in nine brain regions of the posterior circulation: bilateral thalamus, bilateral occipital lobes, bilateral cerebellar hemispheres, midbrain, pons, and medulla. The 48 patients were divided into two groups based on the presence or absence of acute ischemic stroke in the posterior cerebral circulation region detected by diffusion-weighted imaging (DWI). The preoperative and postoperative rCBF results were statistically analyzed., Results: In the infarct group, there were significant increases in rCBF values of all nine brain regions at both PLD = 1.5 s and 2.5 s postoperatively compared to preoperatively. At PLD = 1.5 s, statistically significant differences in rCBF values between the preoperative and postoperative periods were found in the right thalamus, left cerebellum, midbrain, and pons regions (P < 0.05). At PLD = 2.5 s, statistically significant differences in rCBF values between the preoperative and postoperative periods were observed in the left occipital lobe, right cerebellum, midbrain, and pons regions (P < 0.05). When analyzing the rCBF values of the brain regions with recent infarcts in the infarct group, there was a significant increase in postoperative rCBF values compared to preoperative values (P < 0.05). After excluding the data from brain regions with recent infarcts, the CBF values in the remaining brain regions were also increased postoperatively, and some brain regions showed statistically significant differences in rCBF values between the preoperative and postoperative periods (P < 0.05). In the non-infarct group, there were no statistically significant differences in the preoperative and postoperative rCBF values in all brain regions at both PLD = 1.5 s and 2.5 s (P > 0.05)., Conclusion: The application of 3D ASL technology shows significant value in assessing the surgical efficacy of vertebral-basilar artery stenting, especially in patients with acute posterior circulation infarction., (Copyright © 2024. Published by Elsevier Inc.)

Objective: To investigate whether the child-centered treatment significantly increased satisfaction as revealed by CBCL scores and decreased duration of nasal endoscopy., Methods: A total of 206 pediatric patients were selected as study participants. Using a random number table, the participants were divided into the control group and the treatment group, with 103 cases in each group. The control group received routine nursing care, whereas the treatment group received child-centered health education nursing intervention. The differences between the two groups were observed in four aspects: examination compliance, child behavior checklist (CBCL) scores, the satisfaction level of the patient's family with the nurses in the endoscopy room, and the average duration of the nasal endoscopy., Results: Subsequent to the implementation of the intervention, it was observed that within the treatment group, the level of compliance among pediatric patients undergoing nasal endoscopy exhibited a statistically significant increase when compared to the control group; the CBCL scores of both groups were lower than those before nursing care, and those of the treatment group were statistically significantly lower than those of the control group; the satisfaction rate of the patient's family in two groups was 74 % and 90 %, respectively. The average duration of nasal endoscopy was statistically significantly lower in the treatment group than that in the control group., Conclusions: The implementation of a child-centered health education nursing intervention for pediatric patients undergoing nasal endoscopy has been shown to effectively mitigate instances of crying and screaming, enhance patient compliance, reduce examination duration, and elevate the overall satisfaction levels among their respective families., 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 B.V. All rights reserved.)

Background/purpose: Previous epidemiological studies have associated interstitial lung disease (ILD) with rheumatoid arthritis (RA), yet the causality of this relationship remains uncertain. This study aimed to investigate the genetic causal link between ILD and RA. Methods: Genome-wide association study (GWAS) statistics for ILD and RA were collected from public datasets. Relevant single-nucleotide polymorphisms (SNPs) were selected by executing quality control steps from the GWAS summary results. A two-sample bidirectional Mendelian randomization (MR) analysis was performed to assess the causal relationship between the two conditions. The MR analysis primarily used the inverse variance weighting (IVW), weighted median (WM), and MR-Egger regression methods. Sensitivity analyses, including MR-Egger, leave-one-out, and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO), were conducted to evaluate the heterogeneity and pleiotropy. Replication analyses using Asian datasets were also conducted to enhance the robustness of our findings. Results: In the European population, RA was found to increase the risk of ILD by 9.6% (OR: 1.096, 95% CI: 1.023-1.174, p = 0.009). Conversely, ILD was associated with a 12.8% increased risk of RA (OR: 1.128, 95% CI: 1.013-1.256, p = 0.029). Replication analyses from Asian GWAS further supported these findings, particularly the increased risk of ILD attributable to RA (OR: 1.33, 95% CI: 1.18-1.49, p -value <0.001). Conclusion: Our findings underscore the clinical importance of screening for ILD in RA patients and suggest that effective management of RA could significantly benefit ILD patients. The potential applicability of novel RA treatments to ILD warrants further exploration. Additionally, racial disparities in the manifestation of these diseases should not be overlooked, as they may offer new perspectives for targeted therapies in diverse populations., 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 Zhao, Zhang, Guo, Qiao, Song, Zhang, Zhang and Zhang.)

Background and Purpose: To investigate the effect of combining Endostar with concurrent chemoradiotherapy (ECCRT) compared to concurrent chemoradiotherapy (CCRT) on the regression rate of retropharyngeal lymph nodes (RLNs) and the relationship between regression rate of RLNs and prognosis of patients with locally advanced nasopharyngeal carcinoma (LANPC)., Methods: A total of 122 LANPC patients with RLNs metastasis were included. Metastatic RLNs were delineated both before and after treatment slice by slice on the magnetic resonance images cross-section. The regression rate of RLNs, adverse effects (AE) were evaluated. The median regression rate of RLNs was taken as the cut-off value, and the patients were furtherly divided into high regression rate (HRR) group and low regression rate (LRR) group, then survival times were evaluated., Results: The median regression rates of RLNs in the ECCRT and CCRT groups were 81% and 50%, respectively (P < 0.001). There was no statistically significant difference in the incidence of grade 3/4 AEs between the two groups, except for oral mucositis (ECCRT 26.23% vs. CCRT 44.26%, P = 0.037). The 3-year overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and locoregional failure-free survival (LRFFS) rates in the HRR and LRR groups were 85.48% and 86.67% (P = 0.983), 80.65% and 68.33% (P = 0.037), 83.87% and 85% (P = 0.704), 93.55% and 81.67% (P = 0.033), respectively., Conclusions: Patients in the ECCRT group had higher regression rates of RLNs and lower incidence of severe oral mucositis. Furthermore, patients in the HRR group had a better 3-year PFS and LRFFS rate than those in the LRR group., (© 2024. The Author(s).)

Drought stress is one of the main environmental factors limiting plant growth and development. Plants adapt to changing soil moisture by modifying root architecture, inducing stomatal closure, and inhibiting shoot growth. The AP2/ERF transcription factor DREB2A plays a key role in maintaining plant growth in response to drought stress, but the molecular mechanism underlying this process remains to be elucidated. Here, it was found that overexpression of MdDREB2A positively regulated nitrogen utilisation by interacting with DRE cis-elements of the MdNIR1 promoter. Meanwhile, MdDREB2A could also directly bind to the promoter of MdSWEET12, which may enhance root development and nitrogen assimilation, ultimately promoting plant growth. Overall, this regulatory mechanism provides an idea for plants in coordinating with drought tolerance and nitrogen assimilation to maintain optimal plant growth and development under drought stress., (© 2024 John Wiley & Sons Ltd.)

Preservation and restoration of hand function after burn injuries are challenging yet imperative. This study aimed to assess the curative effect of a composite skin graft over an acellular dermal matrix (ADM) and a thick split-thickness skin graft (STSG) for treating deep burns on the hand. Patients who met the inclusion criteria at the First Affiliated Hospital of Wenzhou Medical University between September 2011 and January 2020 were retrospectively identified from the operative register. We investigated patient characteristics, time from operation to the start of active motion exercise, take rates of skin graft 7 days post-surgery, donor site recovery, complications and days to complete healing. Patients were followed up for 12 months to evaluate scar quality using the Vancouver Scar Scale (VSS) and hand function through total active motion (TAM) and the Jebsen-Taylor Hand Function Test (JTHFT). A total of 38 patients (52 hands) who received thin STSG on top of the ADM or thick STSG were included. The location of the donor sites was significantly different between Group A (thick STSG) and Group B (thin STSG + ADM) (p = 0.03). There were no statistical differences in age, gender, underlying disease, cause of burn, burn area, dominant hand, patients with two hands operated on and time from burn to surgery between the two groups (p > 0.05). The time from operation to the start of active motion exercise, take rates of skin graft 7 days post-surgery and days to complete healing were not significantly different between Group A and Group B (p > 0.05). The rate of donor sites requiring skin grafting was lower in Group B than in Group A (22.2% vs. 100%, p < 0.001). There were no statistically significant differences in complications between the groups (p = 0.12). Moreover, 12 months postoperatively, the pliability subscore in the VSS was significantly lower in Group A than in Group B (p = 0.01). However, there were no statistically significant differences in vascularity (p = 0.42), pigmentation (p = 0.31) and height subscores (p = 0.13). The TAM and JTHFT results revealed no statistically significant differences between the two groups (p = 0.22 and 0.06, respectively). The ADM combined with thin STSG is a valuable approach for treating deep and extensive hand burns with low donor site morbidity. It has a good appearance and function in patients with hand burns, especially in patients with limited donor sites., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Objective: To explore the effect of applying the online to offline teaching mode in the training of non-anesthesiology residents in department of anesthesiology., Trial Design: The randomized controlled trial was performed on non-anesthesiology residents from Affiliated Jiangning Hospital of Nanjing Medical University., Methods: All selected residents were randomly divided into the traditional teaching group (Group T) and the online to offline teaching group (Group O) by the random number table method. Traditional teaching mode was used in Group T, while the online to offline teaching mode was used in Group O. The training period lasted for two months. At the end of the training, theoretical and clinical skills were assessed for all residents, and students' satisfaction scores on teaching were investigated from the aspects of teaching mode, stimulating learning interest, improving learning process and teaching satisfaction. The teaching efficiency was compared and analyzed in the two groups., Results: In total, 39 cases in Group O and 38 cases in Group T were included in the statistical analysis. Compared with Group T, theory test scores, clinical skills test scores, and overall scores improved significantly in Group O (82.2 ± 8.1 vs. 91.3 ± 7.6; 85.1 ± 4.7 vs. 93.3 ± 5.4 and 83.4 ± 6.4 vs. 92.1 ± 6.7, respectively, p  < 0.01). Compared with Group T, scores on teaching mode, stimulating learning interest, improving learning process and teaching satisfaction were higher in Group O (81.1 ± 6.9 vs. 93.7 ± 5.2; 83.6 ± 5.8 vs. 91.6 ± 6.4; 82.4 ± 5.3 vs. 90.9 ± 4.8 and 82.1 ± 5.9 vs. 92.1 ± 5.5, respectively, p  < 0.01)., Conclusion: The online to offline teaching mode can improve the level of professional theory and clinical skill operation, and teaching satisfaction of the non-anesthesiology residents in department of anesthesiology, thus improving the teaching effectiveness., 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 Zhao, Zhang, Li, Liu, Peng, Wang, Wang and Yu.)

Posttransplant lymphoproliferative disease (PTLD) is a major therapeutic challenge that has been difficult to study using human cells because of a lack of suitable models for mechanistic characterization. Here, we show that ex vivo-differentiated B cells isolated from a subset of healthy donors can elicit pathologies similar to PTLD when transferred into immunodeficient mice. The primary driver of PTLD-like pathologies were IgM-producing plasmablasts with Epstein-Barr virus (EBV) genomes that expressed genes commonly associated with EBV latency. We show that a small subset of EBV + peripheral blood-derived B cells expressing self-reactive, nonmutated B cell receptors (BCRs) expand rapidly in culture in the absence of BCR stimulation. Furthermore, we found that in vitro and in vivo expansion of EBV + plasmablasts required BCR signaling. Last, treatment of immunodeficient mice with the BCR pathway inhibitor, ibrutinib, delays onset of PTLD-like pathologies in vivo. These data have implications for the diagnosis and care of transplant recipients who are at risk of developing PTLD.

'Human neural stem cells' jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research, is the first guideline for human neural stem cells (hNSCs) in China. This standard specifies the technical requirements, test methods, test regulations, instructions for use, labelling requirements, packaging requirements, storage requirements, transportation requirements and waste disposal requirements for hNSCs, which is applicable to the quality control for hNSCs. It was originally released by the China Society for Cell Biology on 30 August 2022. We hope that publication of the guideline will facilitate institutional establishment, acceptance and execution of proper protocols, and accelerate the international standardization of hNSCs for clinical development and therapeutic applications., (© 2023 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

Background: The clinical manifestations of nonclassical 11beta-hydroxylase deficiency are very similar to those of non-classical 21-hydroxylase deficiency. For this study, we investigated the relationship between the clinical and molecular features of congenital adrenal hyperplasia caused by 11beta-hydroxylase deficiency and reviewed the related literature, which are expected to provide assistance for the clinical diagnosis and analysis of congenital adrenal hyperplasia., Methods: Clinical data for 10 Chinese patients diagnosed with congenital adrenal hyperplasia in our hospital from 2018 to 2022 were retrospectively analyzed. We examined the effects of gene mutations on protease activity and constructed three-dimensional structure prediction models of proteins., Results: We describe 10 patients with 11beta-hydroxylase gene mutations (n = 5, 46,XY; n = 5, 46,XX), with 10 novel mutations were reported. Female patients received treatment at an early stage, with an average age of 2.08 ± 1.66 years, whereas male patients received treatment significantly later, at an average age of 9.77 ± 3.62 years. The most common CYP11B1 pathogenic variant in the Chinese population was found to be c.1360C > T. All mutations lead to spatial conformational changes that affect protein stability., Conclusions: Our study found that there was no significant correlation between each specific mutation and the severity of clinical manifestations. Different patients with the same gene pathogenic variant may have mild or severe clinical manifestations. The correlation between genotype and phenotype needs further study. Three-dimensional protein simulations may provide additional support for the physiopathological mechanism of genetic mutations., (© 2023. The Author(s).)

pH plays a crucial part in numerous chemical and physiological processes. In this work, a new perylene diimide derivative that acts as a pH-sensitive dye with Bay Area Carboxylic Acid functionality. The derivative utilizes the outstanding thermal, chemical and photochemical stability found in PDI materials and has remarkable UV-visible absorption and fluorescence emission qualities. Based on these properties, a fluorescent probe (PCA) was synthesised using a perylene tetracarbodiimide (PDI) backbone for the recognition of alkaline pH. In alkaline environments where the pH values are between 10 and 14, the fluorescence intensity significantly decreases, and a blue shift occurs, which is a standard feature of alkaline pH probes. The probe demonstrates exceptional sensing ability within the pH range of 10.00-14.00, with notable stability and reversibility. Encapsulation of the probe in a thin polymer film material enhances the pH sensing capability of the system. New sensor has been developed to detect basic amino acids by utilizing the probes' pH response characteristics. this sensor has also been applied to detect the concentration of arginine., 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 B.V. All rights reserved.)

Scope: To investigate the underlying mechanism of Astragaloside IV (AS-IV) in ameliorating diabetic nephropathy (DN) by regulating intestinal microbiota ecology and intestinal mucosal barrier., Methods and Results: Genetically db/db mice are used to establish DN mouse model to monitor the therapeutic effects of AS-IV and fecal microbiota transplantation (FMT) against DN. Supplementation with AS-IV dramatically attenuates several clinical indicators of DN in db/db mice. In addition, AS-IV markedly improves intestinal barrier function, modifies intestinal permeability, and reduces inflammation. Moreover, AS-IV treatment remarkably improves intestinal dysbiosis in db/db mice, characterized by an elevated abundance of Akkermansia, Ligilactobacillus, and Lactobacillus, indicating the fundamental role of the microbiome in DN progression. Furthermore, FMT derived from AS-IV-treated db/db mice is potentially efficient in antagonizing renal dysfunction, rebalancing gut microbiota, and improving intestinal permeability in recipient db/db mice. AS-IV-enriched Akkermansia muciniphila dramatically alleviates DN and intestinal mucosal barrier dysfunction in db/db mice. Intriguingly, AS-IV intervention dramatically diminishes ferroptosis in the kidney and colon tissues. CONCLUSION : Intestinal microbiome alterations and ferroptosis modulation by AS-IV may play instrumental roles in this mechanism, providing compelling evidence for the role of the gut-renal axis in DN., (© 2024 Wiley‐VCH GmbH.)

7-dehydrocholesterol (7-DHC) is a key intermediate product used for biosynthesis of molting hormone. This is achieved through a series of hydroxylation reactions catalyzed by the Halloween family of cytochrome P450s. Neverland is an enzyme catalyzes the first reaction of the ecdysteroidogenic pathway, which converts dietary cholesterol into 7-DHC. However, research on the physiological function of neverland in orthopteran insects is lacking. In this study, neverland from Locusta migratoria (LmNvd) was cloned and analyzed. LmNvd was mainly expressed in the prothoracic gland and highly expressed on days 6 and 7 of fifth instar nymphs. RNAi-mediated silencing of LmNvd resulted in serious molting delays and abnormal phenotypes, which could be rescued by 7-DHC and 20-hydroxyecdysone supplementation. Hematoxylin and eosin staining results showed that RNAi-mediated silencing of LmNvd disturbed the molting process by both promoting the synthesis of new cuticle and suppressing the degradation of the old cuticle. Quantitative real-time PCR results suggested that the mRNA expression of E75 early gene and chitinase 5 gene decreased and that of chitin synthase 1 gene was markedly upregulated after knockdown of LmNvd. Our results suggest that LmNvd participates in the biosynthesis process of molting hormone, which is involved in regulating chitin synthesis and degradation in molting cycles., (Copyright © 2023. Published by Elsevier Inc.)

Heat shock protein 20 (Hsp20) is a small molecule heat shock protein that plays an important role in plant growth, development, and stress resistance. Little is known about the function of Hsp20 family genes in apple (Malus domestica). Here, we performed a genome-wide analysis of the apple Hsp20 gene family, and a total of 49 Hsp20s genes were identified from the apple genome. Phylogenetic analysis revealed that the 49 genes were divided into 11 subfamilies, and MdHsp18.2b, a member located in the CI branch, was selected as a representative member for functional characterization. Treatment with NaCl and Botryosphaeria dothidea (B. dothidea), the causal agent of apple ring rot disease, significantly induced MdHsp18.2b transcription level. Further analysis revealed that overexpressing MdHsp18.2b reduced the resistance to salt stress but enhanced the resistance to B. dothidea infection in apple calli. Moreover, MdHsp18.2b positively regulated anthocyanin accumulation in apple calli. Physiology assays revealed that MdHsp18.2b promoted H 2 O 2 production, even in the absence of stress factors, which might contribute to its functions in response to NaCl and B. dothidea infection. Hsps usually function as homo- or heterooligomers, and we found that MdHsp18.2b could form a heterodimer with MdHsp17.9a and MdHsp17.5, two members from the same branch with MdHsp18.2b in the phylogenetic tree. Therefore, we identified 49 Hsp20s genes from the apple genome and found that MdHsp18.2b was involved in regulating plant resistance to salt stress and B. dothidea infection, as well as in regulating anthocyanin accumulation in apple calli., (© 2024 Scandinavian Plant Physiology Society.)

Herein, the preparation process, morphology, structure, and magnetic properties of La 1.85 Sr 0.15 CuO 4 (LSCO) cobweb-like nanofibers are reported. LSCO nanofibers with a regular grain size distribution are successfully prepared via electrospinning, followed by calcination. We conducted morphology analysis and elemental distribution using electron microscopy and energy-dispersive X-ray spectroscopy (EDS), respectively. Additionally, magnetic property testing was performed using a vibrating sample magnetometer (VSM) to confirm the superconducting properties of the samples. Interestingly, our samples exhibited a superconducting transition temperature, Tc, of 25.21 K, which showed some disparity compared to similar works. Furthermore, we observed a ferromagnetic response at low temperatures in the superconducting nanofibers. We attribute these phenomena to the effects generated by surface states of nanoscale superconducting materials.

Alterations in circadian sleep patterns constitute a salient manifestation in major depressive disorder. GW117, an emergent antidepressant, functions as an agonist for melatonin 1 and melatonin 2 (MT1/MT2) receptors, in tandem with antagonism of the serotonin (5-HT) 2C receptor. The present investigation is dedicated to elucidating the role and underlying mechanisms by which GW117 ameliorates circadian sleep disruptions. Utilizing an adapted chronic unpredictable mild stress protocol, we induced a depressive-like phenotype and perturbed circadian rhythms in rodent models. Our methodological approach integrated quantitative polymerase chain reaction (qPCR) in real-time, enzyme-linked immunosorbent assay (ELISA), and immunoblotting techniques to probe alterations in the expression of core circadian genes and homeostatic sleep markers. The impact of GW117 was assessed across various dosages (10, 20, and 40 mg/kg) on these molecular signatures. In a parallel examination, we evaluated the influence of GW117 (administered at 15, 40, and 60 mg/kg) on the sleep patterns of healthy mice. The results showed that GW117 significantly improved sleep-wake circadian rhythms, altered sleep architecture, and shortened sleep latency. Furthermore, GW117 increased the expression of several clock genes in the hypothalamus of chronic unpredictable mild stress model rats and normal mice. It also regulated circadian biomarkers, including melatonin and cortisol. Based on our findings, we propose that the beneficial effects of GW117 on sleep rhythms may be due to the melatonin system-mediated activation of the Wnt/β-catenin signaling pathway., Competing Interests: Declaration of Competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Main Conclusion: The divergence of subsect. Gerardianae was likely triggered by the uplift of the Qinghai-Tibetan Plateau and adjacent mountains. Pinus bungeana might have probably experienced expansion since Last Interglacial period. Historical geological and climatic oscillations have profoundly affected patterns of nucleotide variability, evolutionary history, and species divergence in numerous plants of the Northern Hemisphere. However, how long-lived conifers responded to geological and climatic fluctuations in East Asia remain poorly understood. Here, based on paternally inherited chloroplast genomes and maternally inherited mitochondrial DNA markers, we investigated the population demographic history and molecular evolution of subsect. Gerardianae (only including three species, Pinus bungeana, P. gerardiana, and P. squamata) of Pinus. A low level of nucleotide diversity was found in P. bungeana (π was 0.00016 in chloroplast DNA sequences, and 0.00304 in mitochondrial DNAs). The haplotype-based phylogenetic topology and unimodal distributions of demographic analysis suggested that P. bungeana probably originated in the southern Qinling Mountains and experienced rapid population expansion since Last Interglacial period. Phylogenetic analysis revealed that P. gerardiana and P. squamata had closer genetic relationship. The species divergence of subsect. Gerardianae occurred about 27.18 million years ago (Mya) during the middle to late Oligocene, which was significantly associated with the uplift of the Qinghai-Tibetan Plateau and adjacent mountains from the Eocene to the mid-Pliocene. The molecular evolutionary analysis showed that two chloroplast genes (psaI and ycf1) were under positive selection, the genetic lineages of P. bungeana exhibited higher transition and nonsynonymous mutations, which were involved with the strongly environmental adaptation. These findings shed light on the population evolutionary history of white pine species and provide striking insights for comprehension of their species divergence and molecular evolution., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Medullary thyroid carcinoma (MTC) presents a distinct biological context from other thyroid cancers due to its specific cellular origin. This heterogeneous and rare tumor has a high prevalence of advanced diseases, making it crucial to address the limited therapeutic options and enhance complex clinical management. Given the high clinical accessibility of methylation information, we construct the largest MTC methylation cohort to date., Experimental Design: Seventy-eight fresh-frozen MTC samples constituted our methylation cohort. The comprehensive study process incorporated machine learning, statistical analysis, and in vitro experiments., Results: Our study pioneered the identification of a three-class clustering system for risk stratification, exhibiting pronounced epigenomic heterogeneity. The elevated overall methylation status in MTC-B, combined with the "mutual exclusivity" of hypomethylated sites displayed by MTC-A and MTC-C, distinctively characterized the MTC-specific methylation pattern. Integrating with the transcriptome, we further depicted the features of these three clusters to scrutinize biological properties. Several MTC-specific aberrant DNA methylation events were emphasized in our study. NNAT expression was found to be notably reduced in poor-prognostic MTC-C, with its promoter region overlapping with an upregulated differentially methylated region. In vitro experiments further affirmed NNAT's therapeutic potential. Moreover, we built an elastic-net logistic regression model with a relatively high AUC encompassing 68 probes, intended for future validation and systematic clinical application., Conclusions: Conducting research on diseases with low incidence poses significant challenges, and we provide a robust resource and comprehensive research framework to assist in ongoing MTC case inclusion and facilitate in-depth dissection of its molecular biological features., (©2023 American Association for Cancer Research.)

The copper-catalyzed enantioselective allylation reaction of N -aryl aldimines has been developed using a combination of Cu(OAc) 2 and SPINOL-based phosphonamidite. This protocol significantly broadens the substrate scope, such that imines bearing various ortho -substituents on the N -aryl were converted smoothly into homoallylic amines in up to 99% yield and 98% ee. Taking advantage of the diversity of the N -aryl motif, three kinds of N -heterocyclic compounds were constructed, respectively, from the corresponding homoallylic amines in merely one step.

Background: Polycystic Ovary Syndrome (PCOS) is a highly prevalent, complex, heterogeneous, polygenic endocrine disorder characterized by metabolic and reproductive dysfunction that affects 8-13% of women of reproductive age worldwide. The pathogenesis of PCOS has not been fully clarified and includes genetics, obesity, and insulin resistance (IR). Oxidative stress (OS) of PCOS is independent of obesity. It can induce IR through post-insulin receptor defects, impair glucose uptake in muscle and adipose tissue, and exacerbate IR by reducing insulin secretion from pancreatic β-cells., Objective: To investigate the effects of Calorie Restricted Diet (CRD), High Protein Diet (HPD), and High Protein and High Dietary Fiber Diet (HPD+HDF) on body composition, insulin resistance, and oxidative stress in overweight/obese PCOS patients., Methods: A total of 90 overweight/obese patients with PCOS were selected to receive an 8- week medical nutrition weight loss intervention at our First Hospital of Peking University, and we randomly divided them into the CRD group (group A), the HPD group (group B), and the HPD+HDF group (group C), with 30 patients in each group. We measured their body composition, HOMA-IR index, and oxidative stress indicators. The t-test, Mann-Whitney U test, analysis of variance (ANOVA), and Kruskal-Wallis H test were used to compare the efficacy of the three methods., Results: After eight weeks, the body weights of the three groups decreased by 6.32%, 5.70% and 7.24%, respectively, and the Visceral Fat Area (VFA) values decreased by 6.8 cm 2 , 13.4 cm 2 and 23.45 cm 2 , respectively, especially in group C ( p <0.05). The lean body mass (LBM), also known as the Fat-Free Mass (FFM) values of group B and group C after weight loss, were higher than that of group A ( p <0.05). After weight loss, the homeostatic model assessment of insulin resistance (HOMA-IR) index and malondialdehyde (MDA) were decreased. Superoxide dismutase (SOD) was increased in all three groups ( p <0.05), and the changes in SOD and MDA in group B and group C were more significant ( p <0.05). HOMA-IR index positively correlated with body mass index (BMI) (r=0.195; p <0.05); MDA positively correlated with percent of body fat (PBF) (r=0.186; p <0.05) and HOMA-IR index (r=0.422; p <0.01); SOD positively correlated with LMI/FFMI (r=0.195; p <0.05), negatively correlated with HOMA-IR index (r=-0.433; p <0.01)., Conclusion: All three diets were effective in reducing the body weight of overweight/obese patients with PCOS by more than 5% within 8 weeks and could improve both insulin resistance and oxidative stress damage. Compared with CRD, HPD and HPD+HDF diets could better retain lean body mass and significantly improve oxidative stress damage., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: In the event of a large-scale radiological accident, rapid and high-throughput biodosimetry is the most vital basis in medical resource allocation for the prompt treatment of victims. However, the current biodosimeter is yet to be rapid and high-throughput. Studies have shown that ionizing radiation modulates expressions of circular RNAs (circRNAs) in healthy human cell lines and tumor tissue. circRNA expressions can be quantified rapidly and high-throughput. However, whether circRNAs are suitable for early radiation dose classification remains unclear., Methods: We employed transcriptome sequencing and bioinformatics analysis to screen for radiation-differentially expressed circRNAs in the human lymphoblastoid cell line AHH-1 at 4 h following exposure to 0, 2, and 5 Gy 60 Co γ-rays. The dose-response relationships between differentially expressed circRNA expressions and absorbed doses were investigated using real-time polymerase chain reaction and linear regression analysis at 4 h, 24 h, and 48 h post-exposure to 0, 2, 4, 6, and 8 Gy. Six distinct dose classification models of circRNA panels were established and validated by receiver operating characteristic (ROC) curve analysis., Results: A total of 11 radiation-differentially expressed circRNAs were identified and validated. Based on dose-response effects, those circRNAs changed in a dose-responsive or dose-dependent manner were combined into panels A through F at 4 h, 24 h, and 48 h post-irradiation. ROC curve analysis showed that panels A through C had the potential to effectively classify exposed and non-exposed conditions, which area under the curve (AUC) of these three panels were all 1.000, and the associate p values were .009. Panels D through F excellently distinguished between different dose groups (AUC = 0.963-1.000, p  < .05). The validation assay showed that panels A through F demonstrated consistent excellence in sensitivity and specificity in dose classification., Conclusions: Ionizing radiation can indeed modulate the circRNA expression profile in the human lymphoblastoid cell line AHH-1. The differentially expressed circRNAs exhibit the potential for rapid and high-throughput dose classification.

Newcastle disease (ND) and infectious bursal disease (IBD) are two viral infectious diseases that are extremely damaging to the poultry industry and are widespread throughout the world. It is necessary to develop a safe and effective vaccine against IBD and ND because vaccination is an effective preventive measure. It has been discovered that recombinant proteins expressed by an expression system in which a fragment of mammalian Immunoglobulin G (IgG) Fragment crystallizable (Fc) is linked to a segment of a gene have antibody-like properties that increase the exogenous protein's serum half-life. Heavy chain constant region 3 and heavy chain constant region 4 (CH3-CH4) of Avian Immunoglobulin Y (IgY) is structurally very similar to mammalian Ig G Fc. In this study, a bivalent vaccine rClone30-VP2L-CH3-CH4-GMCSF was developed by using NDV rClone30-chGM-CSF vector to produce VP2L-CH3-CH4 fusion protein. The vaccine has been given to 14-day-old specific pathogen free (SPF) free chickens to test whether it has the potential to prevent IBD and ND. Anti-IBDV and anti-NDV antibody levels in serum were evaluated using ELISA and HI, respectively, and the contents of CD4 + T, CD8 + T, and B cells in leukocytes were determined via flow cytometry. The contents and mRNA transcription levels of four inflammatory factors, IL-1β, IL-4, IFN-γ and chGM-CSF, were detected by ELISA and real-time PCR respectively. The results showed that after vaccination with the rClone30-VP2L-CH3-CH4-GMCSF vaccine, the levels of anti NDV and anti IBDV antibodies in chickens were significantly higher than those of the rClone30 vaccine and commercial vaccines. Meanwhile, the contents and transcription levels of inflammatory factors in chickens inoculated with rClone30-VP2L-CH3-CH4-GMCSF were significantly increased, and the proliferation response of B cells, CD4 + and CD8 + T cells was also stronger. However, the rClone30-VP2L-CH3-CH4-GMCSF vaccine had no significant advantage over the rClone30-VP2L-GMCSF vaccine in any of the above-mentioned features. In summary, rClone30-VP2L-CH3-CH4-GMCSF can stimulate the body to produce a stronger immune response, showing its potential to be considered as vaccine against IBD and ND, but the addition of CH3-CH4 did not improve the vaccine's immune effect as expected. The research lays the foundation for developing vaccines for other infectious viral diseases and avoids a unrealistic vaccine optimization method., 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.)

Rationale: Primary hepatic yolk sac tumors (YSTs) are rare in adults. Liver resection is an acknowledged treatment modality for primary hepatic YST. Liver transplantation may offer a possible cure for unresectable cases., Patient Concerns: We present a case of a 31-year-old woman with an abdominal mass who had abnormally elevated alpha-fetoprotein (AFP) levels (31,132 ng/mL; normal: 0-7 ng/mL). Contrast-enhanced computed tomography (CT) revealed large tumors located in both lobes of the liver, with arterial enhancement and venous washout. Fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT indicated increased 18F-FDG uptake (maximum standardized uptake value, 24.4) in the liver tumors and left middle intra-abdominal nodule., Diagnoses: The diagnosis was primary hepatic YST with metastasis to the greater omentum., Interventions: The patient underwent orthotopic liver transplantation and intra-abdominal nodule resection after transarterial chemoembolization (TACE) as a bridge. Intraoperatively, an intra-abdominal nodule was confirmed in the greater omentum. Histopathological examination of the liver tumors revealed Schiller-Duval bodies. The tropomyosin receptor kinase (TRK) inhibitor larotrectinib was administered, followed by four cycles of chemotherapy with bleomycin, etoposide, and cisplatin based on the next-generation sequencing results., Outcomes: The AFP level decreased to within the normal range. No evidence of tumor collapse was observed during the 34-month follow-up period., Lessons: This case suggests that multimodal therapy dominated by liver transplantation, including preoperative TACE, postoperative adjuvant chemotherapy, and TRK inhibitors, is an effective treatment modality for unresectable primary hepatic YST., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Most cancer patients suffer from the pain of chemotherapy-induced nausea and vomiting (CINV). This meta-analysis was performed to evaluate the efficacy and safety of a regimen consisting of aprepitant, dexamethasone, and 5-HT3 receptor antagonists in the prevention and treatment of CINV., Methods: A systematic literature search was conducted across multiple databases, including PubMed, EMbase, Cochrane Library, MEDLINE, CENTRAL, HEED, CNKI, Wanfang, and VIP, to identify randomized controlled trials (RCTs) investigating the use of triple therapy (aprepitant, 5-HT3 receptor antagonist, and dexamethasone) to prevent and treat CINV. Meta-analysis was performed using RevMan 5.4 and Stata17 software, employing either a fixed-effect or random-effect model based on statistical heterogeneity., Results: A meta-analysis of 23 randomized controlled trials (RCTs) involving 7956 patients was conducted. Efficacy: Results showed significantly improved complete responses (CRs) for CINV in the test group versus the control group in the overall, acute, and delayed phases. Furthermore, in the test group, substantial alleviation of nausea symptoms was observed in the delayed and overall phases but not in the acute phase. Safety: There was no statistically significant difference in the incidence of febrile neutropenia, diarrhea, anorexia, and headache between the 2 groups. The incidence of fatigue and hiccups in the test group was higher than that in the control group; however, the incidence of constipation was significantly lower., Conclusions: Aprepitant-containing triple therapy is highly effective in the prevention and treatment of CINV, with reliable medication safety., Competing Interests: This work was financially supported by 2021 Shandong Provincial Medical Association Clinical Research Funding-Qilu Special Project (no. YXH2022ZX02062), and there are no conflicts of interest to disclose. The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Twelve previously undescribed and four known lanostane triterpenoids were isolated from the fruiting bodies of Ganoderma calidophilum. The structures of undescribed compounds, ganodecalones H-S (1-12), were elucidated by extensive spectroscopic analysis as well as ECD and NMR calculations. Compound 4 showed significant inhibitory activity against human leukaemia cell line K562, gastric cancer cell line SGC-7901, and cervical cancer cell line HeLa with IC 50 values of 13.10 ± 0.19, 17.26 ± 4.75, and 4.36 ± 0.58 μM, respectively. Compound 16 exhibited inhibitory potency against protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase with IC 50 values of 30.2 ± 0.13 μM and 120.6 ± 0.14 μM, respectively. The binding sites and interactions of 16 with PTP1B and α-glucosidase were revealed using molecular docking simulations., 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.)

Metallo-β-lactamases (MBLs) are zinc-dependent enzymes capable of hydrolyzing all bicyclic β-lactam antibiotics, posing a great threat to public health. However, there are currently no clinically approved MBL inhibitors. Despite variations in their active sites, MBLs share a common catalytic mechanism with carbapenems, forming similar reaction species and hydrolysates. We here report the development of 2-aminothiazole-4-carboxylic acids (AtCs) as broad-spectrum MBL inhibitors by mimicking the anchor pharmacophore features of carbapenem hydrolysate binding. Several AtCs manifested potent activity against B1, B2, and B3 MBLs. Crystallographic analyses revealed a common binding mode of AtCs with B1, B2, and B3 MBLs, resembling binding observed in the MBL-carbapenem product complexes. AtCs restored Meropenem activity against MBL-producing isolates. In the murine sepsis model, AtCs exhibited favorable synergistic efficacy with Meropenem, along with acceptable pharmacokinetics and safety profiles. This work offers promising lead compounds and a structural basis for the development of potential drug candidates to combat MBL-mediated antimicrobial resistance.

Lichen genus Endocarpon in biological soil crust form was chosen as a model to investigate the bacterial communities for the first time across four vertically distinct strata. Key bacterial microbiota in lichen thallus were discovered, which were gradually filtered and mainly derived from the crust soil, with clear host selection tendency. The study provided key information to better understand the homeostasis maintenance mechanism of the lichen symbiont and community assembly of desert lichen crust., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. iMeta published by John Wiley & Sons Australia, Ltd on behalf of iMeta Science.)

This study aims at evaluating two-phase and single-phase reactors for treating sulfate wastewater with low COD/SO 4 2- ratios. Additionally, a new process of gas stripping in an acidogenesis phase is proposed to reduce hydrogen sulfide (H 2 S) inhibition and enhance biomethanation. The two-phase performed better than the single-phase in terms of COD removal, CH 4 production and H 2 S resistance. After 30 days of stripping, the COD and sulfate degradation rates increased from 85.16% to 91.09% and from 49.39% to 63.07% in the two-phase, respectively. In contrast, without stripping, they were from 79.21% to 64.37% and from 50.26% to 53.15% in the single-phase, respectively. The microbial biodiversity was augmented via stripping, including norank&#95;f&#95;&#95;Spirochaetaceae, Petrimonas, Desulfurella and Blvii28&#95;wastewater-sludge&#95;group. Stripping operation enhanced the dissimilatory sulfate reduction, amino acid metabolism and possibly sulfate-dependent anaerobic ammonia oxidation (S-ANAMMOX). This study provides a promising strategy to improve sulfate reduction and reduce H 2 S inhibition under a low COD/SO 4 2- ratio., 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. Published by Elsevier Ltd.)

The beneficial microorganisms in food are diverse and complex in structure. These beneficial microorganisms can produce different and unique flavors in the process of food fermentation. The unique flavor of these fermented foods is mainly produced by different raw and auxiliary materials, fermentation technology, and the accumulation of flavor substances by dominant microorganisms during fermentation. The succession and metabolic accumulation of microbial flora significantly impacts the distinctive flavor of fermented foods. The investigation of the role of microbial flora changes in the production of flavor substances during fermentation can reveal the potential connection between microbial flora succession and the formation of key flavor compounds. This paper reviewed the evolution of microbial flora structure as food fermented and the key volatile compounds that contribute to flavor in the food system and their potential relationship. Further, it was a certain guiding significance for food industrial production., Competing Interests: 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., (© 2023 The Authors.)

Objective: To investigate the aplication of low contrast agent concentration and low tube voltage in coronary CTA on patients with high BMI (26kg/m 2 2 ) and ultra-high BMI (BMI>28kg/m 2 )., Methods: 60 patients with high BMI (26kg/m228kg/m 2 ) were randomly divided into two groups: double low group A (n=30, tube voltage = 70 KV), double low group B (n=30, tube voltage = 70 KV), processed by SAFIRE iterative reconstruction with 270 mgI/ml contrast agent. Conventional group a (n=30, tube voltage = 120 KV), conventional group b (n=30, tube voltage = 120 KV), with filtered back projection (FBP) and 370 mg I/ml contrast agent. the image excellent index (FOM), the effective radiation dose (ED), mean CT value, signal-to-noise ratio (SNR), and contrast-to-noise ratio(CNR) between corresponding groups were compared., Result: There was no significant difference in subjective scores of coronary artery image quality between the two high BMI subgroups (P>0.05).The ED of group A (1.103±0.101 mSv) was significantly lower than that of group a (4.663±0.412 mSv) (P<0.001).There was no significant difference in mean CT value, SNR and CNR between the two subgroups (P>0.05).The image excellent index (FOM) of group A was higher than that of group a (P<0.05).The total iodine content and iodine injection rate in group A were lower than those in group a (P<0.001).The difference of subjective scores of coronary artery image quality between the two ultra-high subgroups was significant. The mean CT value, SNR and CNR of group B were lower than those of group b (P<0.05). The images of 14 patients in group B could not meet the diagnosis demand., Conclusion: It is feasible to reduce the tube voltage to 70KV in patients with abdominal BMI with high BMI (26Kg/m 2 2 ). For patients with abdominal obesity with ultra-high BMI (BMI>28Kg/m 2 ), under the same conditions, the 70KV can not meet the daily diagnosis requirement., Competing Interests: The authors declare no conflicts of interest, financial or otherwise., (© 2023 Chen L et al.)

A variety of organometallic supramolecular architectures have been constructed over the past decades and their properties were also explored via different strategies. However, the synthesis of metalla-Russian doll is still a fascinating challenge. Herein, a series of new coordination supramolecular complexes, including a metalla-Russian doll, metalla[2]catenanes, and metallarectangles, were synthesized by using meticulously selected Cp*Rh (Cp* = η 5 -C 5 Me 5 ) building units (E1, E2, and E3) and three rigid anthracylpyridine ligands (L1, L2, and L3) via a self-assembly strategy. While the combination of the short ligand L1 and E1 or E2 generated two metallarectangles, the longer ligand L2 containing an alkynyl group resulted in two new [2]catenanes, most likely due to which the strong electron-donating effect of alkynyl groups causes self-accumulation. Interestingly, an unusual Russian doll assembly was obtained through the reaction of L3 and E3 based on sextuple π···π stacking interactions. Furthermore, the dynamic structural conversion between [2]catenanes and the corresponding metallarectangles could be observed through concentration-, solvent-, and guest-induced effects. The [2]catenane complexes 4b displayed efficient photothermal conversion efficiency in solution (20.2%), in comparison with other organometallic macrocycles. We believe that π···π stacking interactions generate active nonradiative pathways and promote radiative photodeactivation pathways. This study proves the versatility of half-sandwich building units, not only to build complicated supramolecular topologies but also in effective functional materials for various appealing applications.

Background: Aortic dissection (AD) is a fatal cardiovascular disorder without effective medications due to unclear pathogenic mechanisms. Bestrophin3 (Best3), the predominant isoform of bestrophin family in vessels, has emerged as critical for vascular pathological processes. However, the contribution of Best3 to vascular diseases remains elusive., Methods: Smooth muscle cell-specific and endothelial cell-specific Best3 knockout mice (Best3 SMKO and Best3 ECKO , respectively) were engineered to investigate the role of Best3 in vascular pathophysiology. Functional studies, single-cell RNA sequencing, proteomics analysis, and coimmunoprecipitation coupled with mass spectrometry were performed to evaluate the function of Best3 in vessels., Results: Best3 expression in aortas of human AD samples and mouse AD models was decreased. Best3 SMKO but not Best3 ECKO mice spontaneously developed AD with age, and the incidence reached 48% at 72 weeks of age. Reanalysis of single-cell transcriptome data revealed that reduction of fibromyocytes, a fibroblast-like smooth muscle cell cluster, was a typical feature of human ascending AD and aneurysm. Consistently, Best3 deficiency in smooth muscle cells decreased the number of fibromyocytes. Mechanistically, Best3 interacted with both MEKK2 and MEKK3, and this interaction inhibited phosphorylation of MEKK2 at serine153 and MEKK3 at serine61. Best3 deficiency induced phosphorylation-dependent inhibition of ubiquitination and protein turnover of MEKK2/3, thereby activating the downstream mitogen-activated protein kinase signaling cascade. Furthermore, restoration of Best3 or inhibition of MEKK2/3 prevented AD progression in angiotensin II-infused Best3 SMKO and ApoE -/- mice., Conclusions: These findings unveil a critical role of Best3 in regulating smooth muscle cell phenotypic switch and aortic structural integrity through controlling MEKK2/3 degradation. Best3-MEKK2/3 signaling represents a novel therapeutic target for AD., Competing Interests: Disclosures None.

Vascular calcification is caused by the deposition of calcium salts in the intimal or tunica media layer of the aorta, which increases the risk of cardiovascular events and all-cause mortality. However, the mechanisms underlying vascular calcification are not fully clarified. Recently it has been shown that transcription factor 21 (TCF21) is highly expressed in human and mouse atherosclerotic plaques. In this study we investigated the role of TCF21 in vascular calcification and the underlying mechanisms. In carotid artery atherosclerotic plaques collected from 6 patients, we found that TCF21 expression was upregulated in calcific areas. We further demonstrated TCF21 expression was increased in an in vitro vascular smooth muscle cell (VSMC) osteogenesis model. TCF21 overexpression promoted osteogenic differentiation of VSMC, whereas TCF21 knockdown in VSMC attenuated the calcification. Similar results were observed in ex vivo mouse thoracic aorta rings. Previous reports showed that TCF21 bound to myocardin (MYOCD) to inhibit the transcriptional activity of serum response factor (SRF)-MYOCD complex. We found that SRF overexpression significantly attenuated TCF21-induced VSMC and aortic ring calcification. Overexpression of SRF, but not MYOCD, reversed TCF21-inhibited expression of contractile genes SMA and SM22. More importantly, under high inorganic phosphate (3 mM) condition, SRF overexpression reduced TCF21-induced expression of calcification-related genes (BMP2 and RUNX2) as well as vascular calcification. Moreover, TCF21 overexpression enhanced IL-6 expression and downstream STAT3 activation to facilitate vascular calcification. Both LPS and STAT3 could induce TCF21 expression, suggesting that the inflammation and TCF21 might form a positive feedback loop to amplify the activation of IL-6/STAT3 signaling pathway. On the other hand, TCF21 induced production of inflammatory cytokines IL-1β and IL-6 in endothelial cells (ECs) to promote VSMC osteogenesis. In EC-specific TCF21 knockout (TCF21 ECKO ) mice, VD 3 and nicotine-induced vascular calcification was significantly reduced. Our results suggest that TCF21 aggravates vascular calcification by activating IL-6/STAT3 signaling and interplay between VSMC and EC, which provides new insights into the pathogenesis of vascular calcification. TCF21 enhances vascular calcification by activating the IL-6-STAT3 signaling pathway. TCF21 inhibition may be a new potential therapeutic strategy for the prevention and treatment of vascular calcification., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Objective: Diabetic kidney disease (DKD) has been reported as a main microvascular complication of diabetes mellitus. Although renal biopsy is capable of distinguishing DKD from Non Diabetic kidney disease(NDKD), no gold standard has been validated to assess the development of DKD.This study aimed to build an auxiliary diagnosis model for type 2 Diabetic kidney disease (T2DKD) based on machine learning algorithms., Methods: Clinical data on 3624 individuals with type 2 diabetes (T2DM) was gathered from January 1, 2019 to December 31, 2019 using a multi-center retrospective database. The data fell into a training set and a validation set at random at a ratio of 8:2. To identify critical clinical variables, the absolute shrinkage and selection operator with the lowest number was employed. Fifteen machine learning models were built to support the diagnosis of T2DKD, and the optimal model was selected in accordance with the area under the receiver operating characteristic curve (AUC) and accuracy. The model was improved with the use of Bayesian Optimization methods. The Shapley Additive explanations (SHAP) approach was used to illustrate prediction findings., Results: DKD was diagnosed in 1856 (51.2 percent) of the 3624 individuals within the final cohort. As revealed by the SHAP findings, the Categorical Boosting (CatBoost) model achieved the optimal performance 1in the prediction of the risk of T2DKD, with an AUC of 0.86 based on the top 38 characteristics. The SHAP findings suggested that a simplified CatBoost model with an AUC of 0.84 was built in accordance with the top 12 characteristics. The more basic model features consisted of systolic blood pressure (SBP), creatinine (CREA), length of stay (LOS), thrombin time (TT), Age, prothrombin time (PT), platelet large cell ratio (P-LCR), albumin (ALB), glucose (GLU), fibrinogen (FIB-C), red blood cell distribution width-standard deviation (RDW-SD), as well as hemoglobin A1C(HbA1C)., Conclusion: A machine learning-based model for the prediction of the risk of developing T2DKD was built, and its effectiveness was verified. The CatBoost model can contribute to the diagnosis of T2DKD. Clinicians could gain more insights into the outcomes if the ML model is made interpretable., 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 Liu, Duan, Huang, Zhang, Xiang, Niu, Zhou, Wang and Zhang.)

Objective: To investigate the long-term clinical efficacy and safety of "Fuyang Guben" (supporting yang and consolidating root) acupuncture-moxibustion therapy on perennial allergic rhinitis (PAR), and to explore its functioning mechanism., Methods: The patients with PAR were randomly divided into acupuncture + western medicine group ( n =30) and western medicine group ( n =30). In the western medicine group, fluticasone propionate nasal spray was administered, one spray in each nostril in one treatment, once a day, for 6 weeks. On the basis of the western medicine group, fuyangguben acupuncture-moxibustion therapy was supplemented. Acupuncture was applied to Shangxing (GV23), Yintang (GV24+), and bilateral Yingxiang (LI20), Shangyingxiang (EX-HN8), Sibai (ST2), Hegu (LI4) and Chize (LU5); warm needling was applied at Dazhui (GV14). The patients of this group received 30 min of acupuncture-moxibustion therapy 3 times weekly during the first 4 weeks and twice a week in the last 2 weeks, totally for 6 weeks. Before treatment, after treatment, in week 10, 18 and 30 of follow-up visits, the reflective total nasal symptom score (rTNSS), the total non-nasal symptom score (TNNSS), the total ophthalmic symptom score (TOSS), and the score of the rhinitis quality of life (RQLQ) scale were compared in the patients of the two groups separately. Using ELISA, the serum concentrations of total immunoglobulin E (IgE) and interleukin-4 (IL-4) were detected before and after treatment., Results: After treatment, the rTNSS, TNNSS, TOSS, as well as RQLQ score were lower in comparison with those before treatment in each group ( P <0.05).The rTNSS, TNNSS, TOSS and the score of RQLQ in the week 10, 18 and 30 of follow-up visits were reduced when compared with those before treatment in each group ( P <0.05), and these scores in the acupuncture + western medicine group were remarkably lower than those of the western medicine group ( P <0.05). After treatment, the serum contents of total IgE and IL-4 were significantly decreased when compared with those before treatment in the acupuncture + western medicine group ( P <0.05), and these indicators in the acupuncture + western medicine group were lower than those of the western medicine group ( P <0.05)., Conclusion: On the base of treatment with fluticasone propionate nasal spray, "Fuyang Guben" acupuncture-moxibustion therapy is safe and effective on PAR, presenting a remarkably long-term efficacy. The functioning mechanism may be related to the down-regulation of total IgE and IL-4 in serum.

Background/aims: To investigate the clinical situation, treatment methods, and clinical predictors of surgical intervention in children with magnetic foreign bodies in the digestive tract., Materials and Methods: From January 2019 to June 2022, we retrospectively analyzed the clinical data of 72 children who ingested magnetic foreign bodies inadvertently in our hospital, including their general information, admissions, clinical manifestations, and treatment methods, as well as pertinent literature and statistical data. Following software processing, univariate and multivariate logistic regression analyses were conducted to determine the independent risk factors of this study., Results: In this study, 16 patients (22.2%) were discharged smoothly following conservative treatment and 19 patients (26.4%) were cured by gastroscopy. The remaining 37 patients (51.4%) were underwent surgery, in which 26 cases developed gastrointestinal perforation. There were statistical differences between surgery group and non- surgery group in the days of eating by mistake, clinical manifestations (nausea and vomiting, intermittent abdominal pain, abdominal muscle tension) and movement trajectory by every 24-h radiograph (P < 0.01). Logistic regression analysis showed that intermittent abdominal pain and abdominal muscle tension were independent risk factors for surgical treatment., Conclusion: Magnetic foreign bodies seriously endanger children's health. This study offers a single-center basis for the choice of surgical opportunity for intestinal obstruction or perforation caused by magnetic foreign bodies. Clinicians need immediate surgical intervention if the child shows symptoms of abdominal pain or abdominal tension., (© 2023. The Author(s).)

Background: Information available to date regarding the pregnancy outcomes of intrauterine insemination (IUI) without ovarian stimulation (OS) in infertile patients with unilateral tubal occlusion remains scarce. The objectives of this study were to investigate for couples affected by unilateral tubal occlusion (diagnosed via hysterosalpingography (HSG)/transvaginal real-time three-dimensional hysterosalpingo-contrast sonography (TVS RT-3D-HyCoSy)) and male infertility: (1) whether significant differences exist in pregnancy outcomes between IUI with or without OS cycles, and (2) whether the pregnancy outcomes of IUI without OS in women with unilateral tubal occlusion were similar to those of women with bilateral patent tubes., Methods: 258 couples affected by male infertility completed 399 IUI cycles. The cycles were divided into three groups: group A, IUI without OS in women with unilateral tubal occlusion; group B, IUI with OS in women with unilateral tubal occlusion; and group C, IUI without OS in women with bilateral patent tubes. The main outcome measures, including clinical pregnancy rate (CPR), live birth rate (LBR), and first trimester miscarriage rate, were compared between either groups A and B or groups A and C., Results: Although the number of dominant follicles > 16 mm were significantly higher in group B than that in group A (group B vs. group A: 1.6 ± 0.6 vs. 1.0 ± 0.2, P < 0.001), the CPR, LBR, and first trimester miscarriage rate were comparable between these two groups. When comparing group C to group A, the duration of infertility was significantly longer in group C than that in group A (group A vs. group C: 2.3 ± 1.2 (year) vs. 2.9 ± 2.1 (year), P = 0.017). Except for the first trimester miscarriage rate, which was significantly higher in group A (42.9%, 3/7) than that in group C (7.1%, 2/28) (P = 0.044), no significant differences were observed in the CPR and LBR in these two groups. After adjusting for female age, body mass index, and the duration of infertility, similar results were obtained between groups A and C., Conclusions: In couples affected by unilateral tubal occlusion (diagnosed via HSG/TVS RT-3D-HyCoSy) and male infertility, IUI without OS might be an alternative treatment strategy. However, when compared to patients with bilateral patent tubes, the patients with unilateral tubal occlusion showed a higher first trimester miscarriage rate following IUI without OS cycles. Further studies are warranted to clarify this relationship., (© 2023. The Author(s).)

Background: To investigate the use of flipped classroom pedagogy based on "Internet plus" in teaching viral hepatitis in the lemology course during the COVID-19 epidemic., Methods: This study included students from the clinical medicine general practitioner class at Nanjing Medical University's Kangda College, with the observation group consisting of 67 students from the 2020-2021 school year and the control group consisting of 70 students from the 2019-2020 school year. The observation group used "Internet plus" flipped classroom pedagogy, while the control group used conventional offline instruction. The theory course and case analysis ability scores from the two groups were compared and analyzed, and questionnaire surveys were administered to the observation group., Result: After the flipped classroom, the observation group had significantly higher theoretical test scores (38.62 ± 4.52) and case analysis ability scores (21.08 ± 3.58) than the control group (37.37 ± 2.43) (t = 2.024, P = 0.045) and (19.16 ± 1.15) (t = 4.254, P < 0.001), respectively. The questionnaire survey in the observation group revealed that the "Internet plus" flipped classroom pedagogy approach can help enhance students' enthusiasm to learn, clinical thinking ability, practical application ability, and learning efficiency, with satisfaction rates of 81.7%, 85.0%, 83.3%, and 78.8%, respectively; 89.4% of students expressed hope that whenever physical classes resumed, the offline courses could be combined with this pedagogy approach., Conclusion: The use of the "Internet plus" flipped classroom pedagogy technique for teaching viral hepatitis in a lemology course boosted students' theory learning ability as well as their case analysis ability. The majority of students were pleased with this type of instruction and hoped that whenever physical classes resumed, the offline courses may be integrated with the "Internet plus" flipped classroom pedagogical approach., (© 2023. The Author(s).)

Background: The failure of novel therapies effective in preclinical animal models largely reflects the fact that current models do not really mimic the pathological/therapeutic features of glioblastoma (GBM), in which the most effective temozolomide chemoradiotherapy (RT/TMZ) regimen can only slightly extend survival. How to improve RT/TMZ efficacy remains a major challenge in clinic., Methods: Syngeneic G422 TN -GBM model mice were subject to RT/TMZ, surgery, piperlongumine (PL), αPD1, glutathione. Metabolomics or transcriptomics data from G422 TN -GBM and human GBM were used for gene enrichment analysis and estimation of ROS generation/scavenging balance, oxidative stress damage, inflammation and immune cell infiltration. Overall survival, bioluminescent imaging, immunohistochemistry, and immunofluorescence staining were used to examine therapeutic efficacy and mechanisms of action., Results: Here we identified that glutathione metabolism was most significantly altered in metabolomics analysis upon RT/TMZ therapies in a truly refractory and reliable mouse triple-negative GBM (G422 TN ) preclinical model. Consistently, ROS generators/scavengers were highly dysregulated in both G422 TN -tumor and human GBM. The ROS-inducer PL synergized surgery/TMZ, surgery/RT/TMZ or RT/TMZ to achieve long-term survival (LTS) in G422 TN -mice, but only one LTS-mouse from RT/TMZ/PL therapy passed the rechallenging phase (immune cure). Furthermore, the immunotherapy of RT/TMZ/PL plus anti-PD-1 antibody (αPD1) doubled LTS (50%) and immune-cured (25%) mice. Glutathione completely abolished PL-synergistic effects. Mechanistically, ROS reduction was associated with RT/TMZ-resistance. PL restored ROS level (mainly via reversing Duox2/Gpx2), activated oxidative stress/inflammation/immune responses signature genes, reduced cancer cell proliferation/invasion, increased apoptosis and CD3 + /CD4 + /CD8 + T-lymphocytes in G422 TN -tumor on the basis of RT/TMZ regimen., Conclusion: Our findings demonstrate that PL reverses RT/TMZ-reduced ROS and synergistically resets tumor microenvironment to cure GBM. RT/TMZ/PL or RT/TMZ/PL/αPD1 exacts effective immune cure in refractory GBM, deserving a priority for clinical trials., (© 2023. The Author(s).)

Intricately interwoven topologies are continually being synthesized and are ultimately equally versatile and significant at the nanoscale level; however, reports concerning ravel structures, which are highly entwined new topological species, are extremely rare and fraught with tremendous synthesis challenges. To solve the synthesis problem, a tetrapodontic pyridine ligand L1 with two types of olefinic bond units and two Cp*M-based building blocks (E1, M=Rh; E2, M=Ir) featuring large conjugated planes was prepared to perform the self-assembly. Two unprecedented [5+10] icosanuclear molecular 4-ravels containing four crossings were obtained by parallel-displaced π⋅⋅⋅π interactions in a single-step strategy. Remarkably, reversible structural transformations between the 4-ravel and the corresponding metallocage could be realized by concentration changes and solvent- and guest-induced effects. X-ray crystallographic data and NMR spectroscopy provide full confirmation of these phenomena., (© 2023 Wiley-VCH GmbH.)

Objective: To investigate the mechanism underlying the effects of berberine (BBR) in the treatment of Alzheimer's disease (AD)., Methods: 3 × Tg AD mice were treated with BBR for 3 months, then the open field test (OFT), the novel object recognition test (NOR) and the Morris water maze (MWM) test were performed to assess behavioral performance. Hematoxylin-eosin (HE) staining, Nissl staining were used to examine histopathological changes. The pharmacological and molecular properties of BBR were obtained from the TCMSP database. BBR-associated AD targets were identified using the PharmMapper (PM), the comparative toxicogenomics database (CTD), DisGeNet and the human gene database (GeneCards). Core networks and BBR targets for the treatment of AD were identified using PPI network and functional enrichment analyses. AutoDock software was used to model the interaction between BBR and potential targets. Finally, RT-qPCR, western blotting were used to validate the expression of core targets., Results: Behavioral experiments, HE staining and Nissl staining have shown that BBR can improve memory task performance and neuronal damage in the hippocampus of AD mice. 117 BBR-associated targets for the treatment of AD were identified, and 43 genes were used for downstream functional enrichment analysis in combination with the results of protein-protein interaction (PPI) network analysis. 2,230 biological processes (BP) terms, 67 cell components (CC) terms, 243 molecular function (MF) terms and 118 KEGG terms were identified. ALB , EGFR , CASP3 and five targets in the PI3K-AKT signaling pathway including AKT1 , HSP90AA1 , SRC , HRAS , IGF1 were selected by PPI network analysis, validated by molecular docking analysis and RT-q PCR as core targets for further analysis. Akt1 mRNA expression levels were significantly decreased in AD mice and significantly increased after BBR treatment ( p  < 0.05). Besides, AKT and ERK phosphorylation decreased in the model group, and BBR significantly increased their phosphorylation levels., Conclusion: AKT1 , HSP90AA1 , SRC , HRAS , IGF1 and ALB , EGFR , CASP3 were core targets of BBR in the treatment of AD. BBR may exert a neuroprotective effect by modulating the ERK and AKT signaling pathways., 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 Wei, Yao, Zhang, Wen, Zhang, Luo, Cao and Li.)