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Xian-Ping Yang,1,* Ying-Yao Liu,2,* Cai-Yun Zhang,3 Kai-Kai Huang,1 Shan-Shan Han,1 Bao-Ying Liang,1 Ying Lin1 1Department of Dermatology, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, Guangdong, People’s Republic of China; 2The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 3Department of Dermatology, Dongguan Traditional Chinese Medicine Hospital, Dongguan, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ying Lin, Department of Dermatology, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), No. 111 Dade Road, Guangzhou, Guangdong, 510120, People’s Republic of China, Email lin19791226@gzucm.edu.cnAim: Atopic dermatitis (AD) often accompanies skin infections, and bacterial skin infections often cause persistent and worsening symptoms. In this study, we explored the key changes in the microbiota of AD patients, as well as the effects of different ages and the severity of rash on changes in the microbiota.Patients and Methods: A total of 95 AD patients and 77 healthy volunteers were recruited. The AD patients were divided into three groups based age and three groups according to the EASI score. Microorganisms collected from the skin were analyzed through 16S rRNA gene sequencing, revealing species diversity via α and β diversity analyses. Species compositions were compared at the phylum and genus levels. The significance of skin microbiota at the genus level was assessed using the random forest algorithm. Finally, the impact of relationships between different microbial communities on the microbial community composition and the pathogenesis of AD was explored using Pearson correlation coefficients.Results: The species diversity of the skin microbiota in the AD group significantly decreased. Compared with that in the healthy volunteers (HV) group, the bacterial diversity in the two groups of samples significantly differed. Staphylococcus dominated the bacterial communities, and as AD symptoms gradually worsened, the abundance of Staphylococcus gradually increased. Among all bacterial genera with a relative abundance greater than 1%, Staphylococcus showed a negative correlation with other genera, and showed significant consistency in specimens from different age groups.Conclusion: Changes in the abundance of Staphylococcus in the skin bacterial colonies are the main cause of AD. Brevundimonas, Paracoccus, Corynebacterium, and Veillonella may serve as characteristic biomarkers for AD. These results indicate that altering the microbiota composition of the skin may aid in the treatment of AD.Keywords: atopic dermatitis, skin bacterial colony, 16S rRNA gene sequencing

Superconductors with kagome lattices have been identified for over 40 years, with a superconducting transition temperature Tc up to 7 K. Recently, certain kagome superconductors have been found to exhibit an exotic charge order, which intertwines with superconductivity and persists to a temperature being one order of magnitude higher than Tc. In this work, we use scanning tunneling microscopy to study the charge order in kagome superconductor RbV3Sb5. We observe both a 2×2 chiral charge order and nematic surface superlattices (predominantly 1×4). We find that the 2×2 charge order exhibits intrinsic chirality with magnetic field tunability. Defects can scatter electrons to introduce standing waves, which couple with the charge order to cause extrinsic effects. While the chiral charge order resembles that discovered in KV3Sb5, it further interacts with the nematic surface superlattices that are absent in KV3Sb5 but exist in CsV3Sb5.

Yue Ding,1,&ast; Lei Fang,2,&ast; Xiao-Ping Yang,3 Qi Zou1 1Department of General Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, People’s Republic of China; 2Department of Radiology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, People’s Republic of China; 3Department of Hepatobiliary Pancreatic Surgery, First Hospital of Ningbo City, Ningbo, 315010, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qi ZouDepartment of General Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, People’s Republic of ChinaTel +86 18918355163Fax +86 021-68035001Email zouqi_abc@163.comXiao-Ping YangDepartment of Hepatobiliary Pancreatic Surgery, First Hospital of Ningbo City, No. 59 of Liuting Street, Haishu District, Ningbo, 315010, People’s Republic of ChinaTel +86 18757177966Fax +86 0574-87085588Email yangxp_dr@163.comBackground: RNA binding proteins (RBPs) are now under discussion as novel promising bio-markers for patients with colon cancer. The purpose of our study is to identify several RBPs related to the progression and prognosis of colon cancer and to further investigate the mechanism of their influence on tumor progression.Methods: The transcriptome data of colon cancer and clinical characteristics were downloaded from The Cancer Genome Atlas (TCGA) database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and Gene Set Enrichment Analysis (GSEA) were performed to elucidate the gene functions and relative pathways. Cox and Lasso regression analyses were used to analyze the effect of immune genes on the prognosis of colon cancer. An immune risk scoring model was constructed based on the statistical correlation between hub immune genes and survival. Meanwhile, multivariate Cox regression analysis was utilized to investigate whether the immune gene risk score model was an independent factor for predicting the prognosis of colon cancer. A nomogram was constructed to comprehensively predict the survival rate of colon cancer. P < 0.05 was considered statistically significant.Results: The results showed that 473 RBPs exhibited differential expression between normal and colon cancer tissues (P < 0.05). Univariate Cox regression analysis revealed 25 RBPs statistically correlated with colon cancer-related survival risk (P < 0.05). In addition, a 10-RBPs based risk scoring model was constructed through multivariate Cox regression analysis. A K–M curve indicated that high-risk patients were associated with poor outcomes (P < 0.001). A ROC curve indicated that the immune risk score model was reliable in predicting survival risk (5-year overall survival (OS), area under curve (AUC) = 0.782). Our model showed satisfying AUC and survival correlation in the validation dataset (5-year OS, AUC = 0.744). Furthermore, multivariate Cox regression analysis confirmed that the immune risk score model was an independent factor for predicting the prognosis of colon cancer. Finally, we found that 10-RBPs and risk scores were significantly associated with clinical factors and prognosis and were involved in multiple oncogenic pathways.Conclusion: Collectively, RBPs play an essential role in the progression and prognosis of colon cancer by regulating multiple biological pathways. Furthermore, the RBP risk score was an independent predictive factor of colon cancer, indicating poor survival.Keywords: RNA binding proteins, RBPs, colon cancer, prognosis, risk model

Yi-Zheng Li,1,2 Yi Jiang,2 Han Lin,1 Xue-Ping Yang1 1Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2Department of Anesthesiology, Wenzhou Integrated Chinese and Western Hospital of Zhejiang Chinese Medical University, Wenzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Han LinDepartment of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 109 Western Xueyuan Road, Lucheng, Wenzhou, Zhejiang 325027, People’s Republic of ChinaTel +86 1 586 871 0831Email nanlinhannansh@gmail.comBackground: Post-anesthetic shivering incurs discomfort to patients or even exacerbates their condition. However, no ideal drug has been well established for preventing post-anesthetic shivering. Currently, subarachnoid and epidural dexmedetomidine have demonstrated to have an anti-shivering effect.Methods: An electronic search was conducted to identify randomized placebo-controlled trials reporting shivering and then compared subarachnoid and epidural dexmedetomidine with placebo in adults undergoing selective surgery. Data assessment and pooling were analyzed by Review Manager 5.3, STATA 15.0 and GRADE-pro 3.6 software.Results: Twenty-two studies (1389 patients) were subjected to this meta-analysis. The incidence of post-anesthetic shivering decreased from 20.10% in the placebo group to 10.30% in the dexmedetomidine group (RR, 0.48; 95% CI, 0.39–0.59; Z=6.86, P5 μg showed significantly superior anti-shivering effects than that of ≤5 μg. Subarachnoid and epidural dexmedetomidine increased the incidence of bradycardia, had no impact on nausea and vomiting, shortened the onset of block and lengthened the duration of block and analgesia. However, its effect on hypotension and sedation remained uncertain. The overall risk of bias was relatively low. The level of evidence was high, and the recommendation of voting results was strong.Conclusion: Dexmedetomidine as a subarachnoid and epidural adjunct drug could decrease the incidence of post-anesthetic shivering in a dose-dependent manner. However, caution should be taken in patients with original bradycardia.Keywords: dexmedetomidine, shivering, meta-analysis, subarachnoid, epidural

Yun-liang Wang,1,2,* Jin-feng Li,1,* Yu-tong Wang,3 Chun-yang Xu,2 Lin-lin Hua,2 Xiao-peng Yang,2 Shuang Geng,1 Shan-shan Wang,1 Zhen Wang,1 Hong-lei Yin1 1Neurology Department, 148th Hospital, Zibo, Shandong, 2Neurology Department, Second Affiliated Hospital of Zhengzhou University, Zhengzhou, 3Public Health Department, Henan University School of Medicine, Kaifeng, Henan, People’s Republic of China *These authors contributed equally to this work Abstract: Amyloid-β peptide (Aβ) toxicity in Alzheimer’s disease (AD) is associated with the c-Jun N-terminal kinase (JNK) signaling pathway. Curcumin may prevent Aβ fiber formation, slowing AD progression. A model of AD was established in 32 Sprague Dawley rats by injection of 10 μg Aβ1–40 into the right hippocampus. Saline was used in sham control (n=16). Sixteen AD model rats received 300 mg/kg curcumin and another 16 received saline daily for 7 days. Spatial learning and memory were assessed using a Morris water maze. Hippocampus neuron apoptosis and hippocampal levels of JNK-3 and p-JNK-3 were assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling, reverse transcription-polymerase chain reaction and Western blotting. Aβ1–40 injection induced slower spatial learning, memory deficit, neuronal apoptosis and increased JNK-3 expression and phosphorylation (all P

Two new sesquiterpenoids, polydactins A (1) and B (2) and a known sesquiterpene, 10alpha-hydroxycadin-4-en-15-al (3), were isolated from the soft coral Sinularia polydactyla (Ehreberg). Their structures were determined mainly by spectroscopic methods. Polydactin A (1) showed moderate cytotoxic activities against human oral epidermoid carcinoma cell lines (KB) and human breast carcinoma (MCF) tumour cell lines (in vitro). [ABSTRACT FROM AUTHOR]

BACKGROUND: Although the roles of interferon (IFN)-gamma and interleukin (IL)-4 in oral lichen planus (OLP) have been described extensively in past decades, the available results are controversial. Moreover, few studies have utilized simultaneous detection of cytokines in local tissues and saliva to determine whether salivary cytokines could reflect the fact of local lesions. METHODS: IFN-gamma and IL-4 were determined simultaneously in lesions and whole unstimulated saliva (WUS) from OLP patients with various clinical forms. RESULTS: In OLP lesions, both IFN-gamma and IL-4 in erythematous/ulcerated OLP were higher significantly than that in control specimens. In WUS, however, only IFN-gamma of erythematous/ulcerated OLP was increased compared with control. Remarkably, IFN-gamma and IL-4 in WUS showed a more significant correlation to those in local tissues of all subjects. CONCLUSION: These results indicate that both IFN-gamma and IL-4 may play more important role in pathogenesis of erythematous/ulcerated OLP, and changes of these proinflammatory cytokines in WUS may reflect the status of the OLP lesion. [ABSTRACT FROM AUTHOR]

Background: In addition to their established action of synthetic lethality in tumor cells, poly(ADP-ribose) polymerase inhibitors (PARPis) also orchestrate tumor immune microenvironment (TIME) that contributes to suppressing tumor growth. However, it remains not fully understood whether and how PARPis trigger tumor-targeting immune responses., Methods: To decode the immune responses reshaped by PARPis, we conducted T-cell receptor (TCR) sequencing and immunohistochemical (IHC) analyses of paired clinical specimens before and after niraparib monotherapy obtained from a prospective study, as well as ID8 mouse ovarian tumors. To validate the induction of immunogenic cell death (ICD) by PARPis, we performed immunofluorescence/IHC staining with homologous recombination deficiency tumor cells and patient-derived xenograft tumor tissues, respectively. To substantiate that PARPis elicited tumor cell pyroptosis, we undertook comprehensive assessments of the cellular morphological features, cleavage of gasdermin (GSDM) proteins, and activation of TNF-caspase signaling pathways through genetic downregulation/depletion and selective inhibition. We also evaluated the critical role of pyroptosis in tumor suppression and immune activation following niraparib treatment using a syngeneic mouse model with implanting CRISPR/Cas9 edited Gsdme -/ - ID8 tumor cells into C57BL/6 mice., Results: Our findings revealed that PARPis augmented the proportion of neoantigen-recognized TCR clones and TCR clonal expansion, and induced an inflamed TIME characterized by increased infiltration of both innate and adaptive immune cells. This PARPis-strengthened immune response was associated with the induction of ICD, specifically identified as pyroptosis, which possessed distinctive morphological features and GSDMD/E cleavage. It was validated that the cleavage of GSDMD/E was due to elevated caspase 8 activity downstream of the TNFR1, rather than FAS and TRAIL-R. On PARP inhibition, the NF-κB signaling pathway was activated, leading to increased secretion of TNF-α and subsequent initiation of the TNFR1-caspase 8 cascade. Impeding pyroptosis through the depletion of Gsdme significantly compromised the tumor-suppressing effects of PARP inhibition and undermined the anti-immune response in the syngeneic ID8 mouse model., Conclusions: PARPis induce a specific type of ICD called pyroptosis via TNF-caspase 8-GSDMD/E axis, resulting in an inflamed TIME and augmentation of tumor-targeting immune responses. These findings deepen our understanding of PARPis activities and point toward a promising avenue for synergizing PARPis with immunotherapeutic interventions., Trial Registration Number: NCT04507841., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aims: Distinctive gut microbial profiles have been observed between patients with Wilson disease (WD) and healthy individuals. Despite this, the exact relationship and influence of gut microbiota on the advancement of WD-related liver damage remain ambiguous. This research seeks to clarify the gut microbiota characteristics in both human patients and mouse models of WD, as well as their impact on liver injury., Methods: Gut microbial features in healthy individuals, patients with WD, healthy mice and mice with early- and late-stage WD were analysed using 16S rRNA gene sequencing. Additionally, WD-afflicted mice underwent treatment with either an antibiotic cocktail (with normal saline as a control) or healthy microbiota (using disease microbiota as a control). The study assessed gut microbiota composition, hepatic transcriptome profiles, liver copper concentrations and hepatic pathological injuries., Results: Patients with hepatic WD and mice with WD-related liver injury displayed altered gut microbiota composition, notably with a significant reduction in Lactobacillus abundance. Additionally, the abundances of several gut genera, including Lactobacillus, Veillonella and Eubacterium coprostanoligenes, showed significant correlations with the severity of liver injury in patients with WD. In WD mice, antibiotic treatment or transplantation of healthy microbiota altered the gut microbial structure, increased Lactobacillus abundance and modified the hepatic transcriptional profile. These interventions resulted in reduced hepatic copper concentration and alleviation of WD-related liver injury., Conclusions: Individuals and mice with pronounced WD-related liver injury exhibited shifts in gut microbial composition. Regulating gut microbiota through healthy microbiota transplantation emerges as a promising therapeutic approach for treating WD-related liver injury., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A nematic phase breaks the point-group symmetry of the crystal lattice and is known to emerge in correlated materials. Here we report the observation of an intra-unit-cell nematic order and associated Fermi surface deformation in the kagome metal ScV 6 Sn 6 . Using scanning tunnelling microscopy and scanning tunnelling spectroscopy, we reveal a stripe-like nematic order breaking the crystal rotational symmetry within the kagome lattice itself. Moreover, we identify a set of Van Hove singularities adhering to the kagome-layer electrons, which appear along one direction of the Brillouin zone and are annihilated along other high-symmetry directions, revealing rotational symmetry breaking. Via detailed spectroscopic maps, we further observe an elliptical deformation of the Fermi surface, which provides direct evidence for an electronically mediated nematic order. Our work not only bridges the gap between electronic nematicity and kagome physics but also sheds light on the potential mechanism for realizing symmetry-broken phases in correlated electron systems., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The interplay of topology, magnetism, and correlations gives rise to intriguing phases of matter. In this study, through state-of-the-art angle-resolved photoemission spectroscopy, density functional theory, and dynamical mean-field theory calculations, we visualize a fourfold degenerate Dirac nodal line at the boundary of the bulk Brillouin zone in the antiferromagnet YMn 2 Ge 2 . We further demonstrate that this gapless, antiferromagnetic Dirac nodal line is enforced by the combination of magnetism, space-time inversion symmetry, and nonsymmorphic lattice symmetry. The corresponding drumhead surface states traverse the whole surface Brillouin zone. YMn 2 Ge 2 thus serves as a platform to exhibit the interplay of multiple degenerate nodal physics and antiferromagnetism. Interestingly, the magnetic nodal line displays a d-orbital dependent renormalization along its trajectory in momentum space, thereby manifesting Hund's coupling. Our findings offer insights into the effect of electronic correlations on magnetic Dirac nodal lines, leading to an antiferromagnetic Hund nodal line., (© 2024. The Author(s).)

Phenformin, a biguanide compound, has attracted increased attention due to its prominent antitumor activity. As a multi‑target agent, the antitumor effects of phenformin involve a wide range of factors, including inhibition of mitochondrial complex I, activation of AMP‑activated protein kinase, impact on the tumor microenvironment, suppression of cancer stem cells and others. In addition, phenformin has been shown to markedly augment the effectiveness of various clinical treatment methods, including radiotherapy, chemotherapy, targeted therapy and immunotherapy. It is noteworthy that breakthrough progress has been made in the treatment of cancer with phenformin with application in clinical trials for the treatment of melanoma. Phenformin not only reduces the lesion area of patients, but also enhances the efficacy of dalafinib/trimetinib. In the present review, the novel breakthroughs in the antitumor effects and mechanisms of phenformin were discussed. In addition, the current review focuses on the clinical development value of phenformin, striving to provide new insights into the future research direction of phenformin in the field of tumor treatment.

Ethnopharmacological Relevance: Dichroa febrifuga Lour., a toxic but extensively used traditional Chinese medicine with a remarkable effect, is commonly called "Changshan" in China. It has been used to treat malaria and many other parasitic diseases., Aim of the Review: The study aims to provide a current overview of the progress in the research on traditional use, phytochemistry, pharmacological activities, toxicology, and methods of toxicity reduction of D. febrifuga. Additionally, further research directions and development prospects for the plant were put forward., Materials and Methods: The article uses "Dichroa febrifuga Lour." "D. febrifuga" as the keyword and all relevant information on D. febrifuga was collected from electronic searches (Elsevier, PubMed, ACS, CNKI, Google Scholar, and Baidu Scholar), doctoral and master's dissertations and classic books about Chinese herbs., Results: 30 chemical compounds, including alkaloids, terpenoids, flavonoids and other kinds, were isolated and identified from D. febrifuga. Modern pharmacological studies have shown that these components have a variety of pharmacological activities, including anti-malarial activities, anti-inflammatory activities, anti-tumor activities, anti-parasitic activities and anti-oomycete activities. Meanwhile, alkaloids, as the material basis of its efficacy, are also the source of its toxicity. It can cause multiple organ damage, including liver, kidney and heart, and cause adverse reactions such as nausea and vomiting, abdominal pain and diarrhea. In the current study, the toxicity can be reduced by modifying the structure of the compound, processing and changing the dosage forms., Conclusions: There are few studies on the chemical constituents of D. febrifuga, so the components and their structure characterization contained in it can become the focus of future research. In view of the toxicity of D. febrifuga, there are many methods to reduce it, but the safety and rationality of these methods need further study., 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.)

Biomolecular condensates have been proposed to mediate cellular signaling transduction. However, the mechanism and functional consequences of signal condensates are not well understood. Here we report that LATS2, the core kinase of the Hippo pathway, responds to F-actin cytoskeleton reduction and forms condensates. The proline-rich motif (PRM) of LATS2 mediates its condensation. LATS2 partitions with the main components of the Hippo pathway to assemble a signalosome for LATS2 activation and for its stability by physically compartmentalizing from E3 ligase FBXL16 complex-dependent degradation, which in turn mediates yes-associated protein (YAP)-transcriptional coactivator with PDZ-binding motif (TAZ) recruitment and inactivation. This oncogenic FBXL16 complex blocks LATS2 condensation by binding to the PRM region to promote its degradation. Disruption of LATS2 condensation leads to tumor progression. Thus, our study uncovers that the signalosomes assembled by LATS2 condensation provide a compartmentalized and reversible platform for Hippo signaling transduction and protein stability, which have potential implications in cancer diagnosis and therapeutics., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objective: To investigate the expression of the precursor of brain-derived neurotrophic factor (proBDNF) and its high-affinity receptor p75NTR in neurons of emotion-related brain areas (prefrontal cortex, hippocampus, and amygdala) in rats with post-stroke depression (PSD), and to explore the expression levels of proBDNF and p75NTR in neurons of emotion-related brain areas by injecting tissue plasminogen activator (t-PA) into the lateral ventricle of PSD rats, this significantly improved the stress-induced depression-like behavior,thus further validating the above results., Methods: Rats were randomly divided into four groups: a normal control group (n = 8), a depression group (n = 8), a stroke group (n = 8), and a PSD group (n = 8). The rat model of stroke was established by thread embolism, and the PSD animal model was induced by chronic unpredictable mild stress (CUMS) and solitary feeding. Behavioral tests were conducted, including weight measurement, open field tests, and sucrose preference tests. Immunofluorescence double labeling was used to detect the expression of proBDNF and p75NTR in neurons of emotion-related brain regions in the PSD rat model. Four weeks after CUMS treatment, the PSD group was selected. Rats were infused with t-PA (3 μg dissolved in 6 μL saline, Boehringer Ingelheim), proBDNF (3 μg dissolved in 6 μL saline, Abcam), or equal-volume NS once per day for 7 consecutive days using the syringe pump connecting to injection needles. After 7 days of continuous administration, animal behavior was assessed through scoring, and the expression of proBDNF and p75NTR in the emotion-related brain regions of the PSD rat model was detected using immunofluorescence double labeling., Results: Compared with the normal control group and the stroke group, the body weight, sucrose water consumption, and vertical movement distance in the PSD group were significantly lower (P < 0.05). In contrast, when compared with the proBDNF injection group and saline injection group, the weight, sucrose water consumption, field horizontal movement, and vertical movement distance of the t-PA injection group significantly increased after PSD lateral ventricle intubation.Double immunofluorescence revealed a higher neuronal expression of proBDNF as well as p75NTR in the prefrontal cortex and hippocampus of PSD rats compared to control animals (P < 0.05). In the amygdala, the expression levels of proBDNF and P75NTR were significantly reduced in the PSD group compared to the control group (P < 0.05). The results of the expression levels of proBDNF and P75NTR in the emotion-related brain regions of PSD rats injected with t-PA showed that proBDNF and P75NTR was significantly reduced in the prefrontal cortex, hippocampus, and amygdala of PSD rats compared to those of the NS and proBDNF groups (P < 0.05)., Conclusions: The increased expression of the brain-derived neurotrophic factor precursor proBDNF and its receptor p75NTR in neurons of emotion-related brain regions may play an important role in the pathogenesis of PSD.t-PA reduced the expression of proBDNF and its receptor p75NTR in neurons emotion-related brain regions and significantly improved the stress-induced depression-like behavior. Therefore, it is reasonable to assume that exogenous injection of t-PA may alleviate the depressive symptoms of PSD patients.Reducing the expression of proBDNF by injecting t-PA may provide a novel therapeutic approach for the treatment of stress-related mood disorders., 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 B.V.)

In this study, we discovered a novel peptide, Gymepeptide A, with α-amylase inhibitory activity in the water extract of Gynura medica. The structure of Gymepeptide A was determined as CGDREETR using HR-MS, 1 H NMR, 13 C NMR, and 2D-NMR techniques. Notably, Gymepeptide A possesses a rare double arginine residue structure and exhibits strong α-amylase inhibitory activity. Enzyme dynamic assays, molecular docking experiments, and isothermal titration calorimetry indicated that the double arginine residue structure of Gymepeptide A interacts with amino acid residues in the nearby active site region of α-amylase through hydrogen bonds and van der Waals forces. This interaction effectively inhibits the hydrolysis activity of α-amylase. Furthermore, in vitro starch digestion tests revealed that Gymepeptide A significantly reduced the digestion rate of starch and the concentration of glucose produced after starch digestion. These findings highlight the great potential of Gymepeptide A in decreasing postprandial blood glucose levels., 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.)

Topology 1-3  and interactions are foundational concepts in the modern understanding of quantum matter. Their nexus yields three important research directions: (1) the competition between distinct interactions, as in several intertwined phases, (2) the interplay between interactions and topology that drives the phenomena in twisted layered materials and topological magnets, and (3) the coalescence of several topological orders to generate distinct novel phases. The first two examples have grown into major areas of research, although the last example remains mostly unexplored, mainly because of the lack of a material platform for experimental studies. Here, using tunnelling microscopy, photoemission spectroscopy and a theoretical analysis, we unveil a 'hybrid' topological phase of matter in the simple elemental-solid arsenic. Through a unique bulk-surface-edge correspondence, we uncover that arsenic features a conjoined strong and higher-order topology that stabilizes a hybrid topological phase. Although momentum-space spectroscopy measurements show signs of topological surface states, real-space microscopy measurements unravel a unique geometry of topologically induced step-edge conduction channels revealed on various natural nanostructures on the surface. Using theoretical models, we show that the existence of gapless step-edge states in arsenic relies on the simultaneous presence of both a non-trivial strong Z 2 invariant and a non-trivial higher-order topological invariant, which provide experimental evidence for hybrid topology. Our study highlights pathways for exploring the interplay of different band topologies and harnessing the associated topological conduction channels in engineered quantum or nano-devices., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The activation of YAP/TAZ, a pair of paralogs of transcriptional coactivators, initiates a dysregulated transcription program, which is a key feature of human cancer cells. However, it is not fully understood how YAP/TAZ promote dysregulated transcription for tumor progression. In this study, we employed the BioID method to identify the interactome of YAP/TAZ and discovered that YAP/TAZ interact with multiple components of SRCAP complex, a finding that was further validated through endogenous and exogenous co-immunoprecipitation, as well as immunofluorescence experiments. CUT&Tag analysis revealed that SRCAP complex facilitates the deposition of histone variant H2A.Z at target promoters. The depletion of SRCAP complex resulted in a decrease in H2A.Z occupancy and the oncogenic transcription of YAP/TAZ target genes. Additionally, the blockade of SRCAP complex suppressed YAP-driven tumor growth. In a genetically engineered lung adenocarcinoma mouse model and non-small cell lung cancer patients, SRCAP complex and H2A.Z deposition were found to be upregulated. This upregulation was statistically correlated with YAP expression, pathological stages, and poor survival in lung cancer patients. Together, our study uncovers that SRCAP complex plays a critical role in YAP/TAZ oncogenic transcription by coordinating H2A.Z deposition during cancer progression, providing potential targets for cancer diagnosis and prevention., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: This study aims to examine the effects of different preoperative waiting times on anxiety and pain levels in patients undergoing outpatient surgery for breast diseases, providing insights for clinical interventions during the perioperative phase., Methods: Patients who underwent outpatient surgery at a hospital breast center in Ningbo between January 2021 and December 2021 were selected. Their anxiety levels at the time when they entered the preoperative preparation room and when they ended the postoperative waiting period for the rapid frozen section procedure were assessed using the State Anxiety Inventory (S-AI) questionnaire, and their pain levels at the end of the postoperative waiting period were assessed using the short-form McGill Pain Questionnaire. The patients enrolled were divided into 3 groups according to the preoperative waiting time: <2 hours (T1 group), 2 to 4 hours (T2 group), and >4 hours (T3 group); there were 150 patients in each group, and the anxiety and pain levels were compared between the groups., Results: At the time of entering the preoperative preparation room, patients' S-AI score T1 = T2 ( P > 0.05), both T1 and T2 < T3 ( P < 0.05); however, at the time of the postoperative waiting period, patients' S-AI score was T1 < T2 < T3 ( P < 0.05), and the postoperative waiting period patients' short-form McGill Pain Questionnaire scores were T1 = T2 < T3 ( P < 0.05)., Conclusions: The perioperative anxiety and pain levels of patients undergoing outpatient breast surgery increased with the prolongation of preoperative waiting time; 4 hours was the critical time point for change, after which the anxiety and pain levels of patients increased significantly., Competing Interests: The authors disclose no conflict of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Exosomal microRNA (miRNA) is a potential biomarker for cancer diagnosis, metastasis, and treatment. In situ detection of exosomal miRNA is an attractive option due to its simplicity and high accuracy. However, in situ exosomal miRNA detection has encountered challenges because of the low target abundance of targets and limited probe permeability. Herein, a label-free and activatable biosensor was developed for in situ exosomal miRNA assays by utilizing hairpin-shaped nucleic acid probes and DNA-hosted silver nanoclusters (DNA-AgNCs). The probe is directly internalized into the exosomes, and then hybridized with the target miRNA-21. Subsequently, the DNA-AgNCs are pulled closer to the G-rich sequence, ultimately leading to in situ red fluorescence activation. The biosensor not only can detect exosomal miRNA-21 but also distinguish cancer cells from normal cells. Under optimal reaction conditions, the detection limit (LOD) of exosomal miRNA-21 is 1.53 × 10 7 particles per mL. Furthermore, DNA-AgNCs are used as label-free signal elements for in situ detection of exosomal miRNAs for the first time, expanding the application of nanomaterials in this field. This strategy does not require tedious RNA extraction steps and expensive instruments, and may develop into a non-invasive diagnostic tool for ovarian cancer.

Pyrroloquinoline quinone (PQQ) is a bioactive compound that has attracted significant attention due to its potential health benefits. In this study, we developed a new magnetic molecularly imprinted nanoparticle (MMIN) for the selective extraction and determination of PQQ from food samples. The MMIN was synthesized using a surface molecular imprinting technique with PQQ as the template molecule, Fe 3 O 4 nanoparticles as the magnetic core, and methacrylic acid as the functional monomer. The MMIN exhibited high selectivity and affinity towards PQQ, allowing for efficient extraction and preconcentration of PQQ from complex food matrices. The extracted PQQ was then quantified using HPLC-DAD. The developed method showed good linearity ( R 2 = 0.9985) and low limits of detection (0.03 μg L -1 ). The accuracy and precision of the method were evaluated by analyzing spiked food samples, with average recoveries close to 89.8%. The MMIN also demonstrated good reusability, with negligible decrease in extraction efficiency after five cycles of use. Overall, the developed MMIN-based method provides a reliable and efficient approach for the analysis of PQQ in food samples.

Background: Echinacoside (ECH), a natural active compound, was found to exert neuroprotection in Parkinson's disease (PD). However, the underlying molecular mechanisms remain controversial., Purpose: This study aimed to explore the roles of ECH in PD and its engaged mechanisms., Conclusion: In vivo, MPTP was adapted to construct subacute PD mouse model to explore the regulation of ECH on NLRP3 inflammasome. In vitro, α-synuclein (α-syn)/MPP + was used to mediate the activation of NLRP3 inflammasome in BV2 cells, and the mechanism of ECH regulation of it was explored with molecular docking, immunofluorescence, Western blotting, and small molecule inhibitors., Conclusion: The activation of microglial NLRP3 inflammasome could be evoked by MPTP in vitro, but its toxic metabolite MPP + alone cannot trigger the activation of NLRP3 inflammasome in vitro, which requires α-synuclein (α-syn) priming. Exogenous α-syn could evoke microglial TLR2/NF-κB/NLRP3 axis, playing the priming role in MPP + -mediated NLRP3 inflammasome activation. ECH can suppress the upregulation of α-syn in MPTP-treated mice and BV2 microglia. It can also suppress the activation of the TLR2/NF-κB/NLRP3 axis induced by α-syn., Conclusion: ECH exerts neuroprotective effects by downregulating the TLR2/NF-κB/NLRP3 axis via reducing the expression of α-syn in the PD models., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest. All data were generated in-house, and no paper mill was used. All authors agree to be accountable for all aspects of work ensuring integrity and accuracy., (Copyright © 2023. Published by Elsevier GmbH.)

Purpose: To study the risk factors affecting amputation and survival in patients with diabetic foot (DF) and to construct a predictive model using the machine learning technique for DF foot amputation and survival and evaluate its effectiveness., Materials and Methods: A total of 200 patients with DF hospitalized in the First Affiliated Hospital of Shantou University Medical College in China were selected via cluster analysis screening, Kaplan-Meier survival calculation, amputation rate and Cox proportional hazards model investigation of risk factors associated with amputation and death. In addition, we constructed various models, including Cox proportional hazards regression analysis, the deep learning method convolution neural network (CNN) model, backpropagation (BP) neural network model, and backpropagation neural network prediction model after optimizing the genetic algorithm. The accuracy of the 4 prediction models for survival and amputation was assessed, and we evaluated the reliability of these computational models based on the size of the area under the ROC curve (AUC), sensitivity and specificity., Results: We found that the 1-year survival rate in patients with DF was 88.5%, and the 1-year amputation rate was 12.5%. Wagner's Classification of Diabetic Foot Ulcers grade, ankle-brachial index (ABI), low-density lipoprotein (LDL), and percutaneous oxygen partial pressure (TcPO2) were independent risk factors for amputation in patients with DF, while cerebrovascular disease, Sudoscan sweat gland function score, glycated hemoglobin (HbA1c) and peripheral artery disease (PAD) were independent risk factors for death in patients with DF. In addition, our results showed that in the case of amputation, the COX regression predictive model revealed an AUC of 0.788, sensitivity of 74.1% and specificity of 83.6%. The BP neural network predictive model identified an AUC of 0.874, sensitivity of 87.0% and specificity of 87.7%. An AUC of 0.909, sensitivity of 90.7% and specificity of 91.1% were found after optimizing the BP neural network prediction model via genetic algorithm. In the deep learning CNN model, the AUC, sensitivity and specificity were 0.939, 92.6%, and 95.2%, respectively. In the analysis of risk factors for death, the COX regression predictive model identified the AUC, sensitivity and specificity as 0.800, 74.1% and 85.9%, respectively. The BP neural network predictive model revealed an AUC, sensitivity and specificity of 0.937, 93.1% and 94.4%, respectively. Genetic algorithm-based optimization of the BP neural network predictive model identified an AUC, sensitivity and specificity of 0.932, 91.4% and 95.1%, respectively. The deep learning CNN model found the AUC, sensitivity and specificity to be 0.861, 82.8% and 89.4%, respectively., Conclusion: To identify risk factors for death, the BP neural network predictive model and genetic algorithm-based optimizing BP neural network predictive model have higher sensitivity and specificity than the deep learning method CNN predictive model and COX regression analysis.

Background: Neurocysticercosis (NCC), a predominant parasitic disease that affects the central nervous system and presents with diverse clinical manifestations, is a major contributor to acquired epilepsy worldwide, particularly in low-, middle-, and upper middle-income nations, such as China. In China, the Yunnan Province bears a significant burden of this disease., Objective: To describe the demographic, clinical, and radiological features as well as serum and cerebrospinal fluid antibodies to cysticercus in patients with NCC from Dali, Yunnan Province, China., Materials and Methods: This retrospective study included patients who were diagnosed with NCC at The First Affiliated Hospital of Dali University between January 2018 and May 2023 and were residing in Dali, Yunnan Province, China., Results: A total of 552 patients with NCC were included, of which 33.3% belonged to Bai ethnicity. The clinical presentation of NCC exhibited variability that was influenced by factors such as the number, location, and stage of the parasites. Epilepsy/seizure (49.9%) was the most prevalent symptom, with higher occurrence in the degenerative stage of cysts ( P < 0.001). Compared with other locations, cysticerci located in the brain parenchyma are more likely to lead to seizures/epilepsy (OR = 17.45, 95% CI: 7.96-38.25) and headaches (OR = 3.02, 95% CI: 1.23-7.41). Seizures/epilepsy are more likely in patients with cysts in the vesicular (OR = 2.71, 95% CI: 1.12-6.61) and degenerative (OR = 102.38, 95% CI: 28.36-369.60) stages than those in the calcified stage. Seizures was not dependent on the number of lesions. All NCC patients underwent anthelminthic therapy, with the majority receiving albendazole (79.7%)., Conclusion: This study provides valuable clinical insights into NCC patients in Dali and underscores the significance of NCC as a leading preventable cause of epilepsy., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Saudi Journal of Medicine & Medical Sciences.)

Objective: To compare the diagnostic value of cytobrush, ERCP-guided biopsy, SpyGlass direct visual impression and SpyGlass-guided biospy (SpyBite) in the differential diagnosis of benign and malignant bile duct strictures., Methods: The data of 1,008 patients who were clinically diagnosed with indeterminate biliary strictures and underwent ERCP-guided biopsy, cytobrush, SpyGlass direct visual impression or SpyBite at the First Affiliated Hospital of Nanchang University between January 2010 and December 2019 were collected and analyzed retrospectively. The final diagnose was determined by surgical pathological specimen or follow-up (Malignant stricture can be identified if the stricture showed malignant progression during one year of follow-up). The differential diagnostic value of the above endoscopic diagnostic methods was evaluated by means of sensitivity, specificity, accuracy, positive predictive value, negative predictive value, etc. and safety was evaluated by the incidence rate of adverse events., Results: In terms of sensitivity, standard biopsy group (48.6%) and SpyBite group (61.5%) were significantly higher than cytobrush group (32.0%), and visual impression group (100%) was significantly higher than any other group. As far as specificity was concerned, cytobrush group (99.0%), standard biopsy group (99.3%) and the SpyBite group (100%) were significantly higher than visual impression (55.6%), but there was no statistical difference among the three groups above. As far as accuracy was concerned, standard biopsy group (65.3%), and SpyBite group (80.0%) were significantly higher than cytobrush group (44.4%), and SpyBite group (80.0%) was significantly higher than visual impression group (54.8%). In terms of safety, visual impression group and SpyBite group were significantly higher than cytobrush group and standard biopsy group in post-ERCP cholangitis., Conclusion: SpyBite combined with SpyGlass-guided visual impression was better for differential diagnosis of benign and malignant bile duct strictures in terms of sensitivity and accuracy compared with conventional endoscopic diagnostic methods such as cytobrush and standard biopsy. Furthmore, the incidence rates of adverse events after SpyGlass examination was similar to those after conventional endoscopic diagnostic methods except for higher cholangitis, which could be controlled by antibiotics and might be avoided by adequate biliary drainage., 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 Zhu, Huang, Wang, Yang, Hong, Yang, Yu, Cao, He and Chen.)

Objective: Alzheimer's disease (AD), a prevalent neurodegenerative affliction that predominantly affects the elderly population, imposes a substantial burden on not only patients but also their families and society at large. Mitochondrial dysfunction plays an important role in its pathogenesis. In this study, we conducted a bibliometric analysis of research on mitochondrial dysfunction and AD over the past 10 years, with the aim of summarizing current research hotspots and trends in this field., Methods: On February 12, 2023, we searched for publications about mitochondrial dysfunction and AD in the Web of Science Core Collection database from 2013 to 2022. VOSview software, CiteSpace, SCImago, and RStudio were used to analyze and visualize countries, institutions, journals, keywords, and references., Results: The number of publications on mitochondrial dysfunction and AD were on the rise until 2021 and decreased slightly in 2022. The United States ranks first in the number of publications, H-index, and intensity of international cooperation in this research. In terms of institutions, Texas Tech University in the United States has the most publications. The Journal of Alzheimer's Disease has the most publications in this field of research, while Oxidative Medicine and Cellular Longevity have the highest number of citations. Mitochondrial dysfunction is still an important direction of current research. Autophagy, mitochondrial autophagy, and neuroinflammation are new hotspots. The article from Lin MT is the most cited by analyzing references., Conclusion: Research on mitochondrial dysfunction in AD is gaining significant momentum as it provides a crucial research avenue for the treatment of this debilitating condition. This study sheds light on the present research trajectory concerning the molecular mechanisms underlying mitochondrial dysfunction in AD., 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 Guo, Hassan, Chu, Yang, Wang, Zhu and Li.)

Competing Interests: None declared.

Objective: The aim of this study was to compare the efficacy and safety of ultrasonic bone curette (UBC) and conventional surgical instruments in thoracic laminectomy decompression (TLD) for the treatment of thoracic spinal stenosis (TSS) by meta-analysis., Materials and Methods: Two authors independently searched Medline via PubMed, Embase, Cochrane Library, Web of Science, Wanfang Database, and China National Knowledge Infrastructure for the period from the establishment of the database until January 2023 to identify the studies on the safety and efficacy of UBC vs. conventional instruments for TSS. Data extraction and quality assessment were performed by two researchers independently. We used RevMan 5.4 software (Review Manager Web, The Cochrane Collaboration, Copenhagen, Denmark) to analyze the data., Results: Eight retrospective studies were included in the present work. This meta-analysis revealed that no significant differences in the preoperative JOA scores, the JOA scores at the last follow-up, the improvement rate of JOA scores, and the incidence of cerebrospinal fluid leakage/dura injury were detected between the two groups (p>0.05). However, there were significant differences in the operative time and intraoperative blood loss during single-level TLD [operative time: MD=-1.47, 95% CI (-1.86, -1.09), p<0.001; intraoperative blood loss: MD=-46.62, 95% CI (-53.83, -39.40), p<0.001], total operative time [MD=-56.88, 95% CI (-69.66, -44.10), p<0.001], total intraoperative blood loss [MD=-143.52, 95% CI (-212.49, -74.54), p<0.001], the incidence of neurological deterioration/nerve root injury [RR= 0.29, 95% CI (0.09, 0.91), p=0.03] between the groups., Conclusions: The application of UBC in TLD to treat TSS is safe and effective. UBC can significantly shorten operation time and reduce intraoperative blood loss compared to traditional surgical instruments. Moreover, it has the advantage of reducing perioperative nerve injury.

Background: Lacunes are the manifestations of lacunar infarction which can lead many patients to the clinical outcome of disability or dementia. However, the relationship between lacune burden, cognitive function and blood glucose fluctuation in patients with type 2 diabetes mellitus (T2DM) complicated with lacunes is not very clear., Aim: To explore the correlation between glucose variability, lacune burden and cognitive function in patients with lacunes complicated with T2DM., Methods: The clinical and imaging data of 144 patients with lacunes combined with T2DM were reviewed retrospectively. 72 h continuous glucose monitoring was performed. The Montreal Cognitive Assessment was used to assess cognitive function. The burden of lacunes was evaluated using magnetic resonance imaging performance. Multifactorial logistic regression analysis was used to study the affecting the lacune load and cognitive impairment in patients. To predict the value of patients' cognitive impairment with lacunes complicated with T2DM, a receiver operating characteristic (ROC) curve and a nomogram prediction model were constructed., Results: The standard deviation (SD) of the average blood glucose concentration, percentage coefficient of variation (%CV) and time of range (TIR) were significantly different between the low and the high load groups ( P < 0.05). The SD, %CV and TIR of the cognitive impairment group and non-cognitive impairment group were significantly different ( P < 0.05). SD (odds ratio (OR): 3.558, 95% confidence interval (CI): 1.268-9.978, P = 0.006), and %CV (OR: 1.192, 95%CI: 1.081-1.315, P < 0.05) were the risk factors for an increased infarct burden in lacunes patients complicated with T2DM. TIR (OR: 0.874, 95%CI: 0.833-0.928, P < 0.05) is a protective factor. In addition, an increased SD (OR: 2.506, 95%CI: 1.008-6.23, P = 0.003), %CV (OR: 1.163, 95%CI: 1.065-1.270, P < 0.05) were the risk factors for cognitive impairment in patients with lacunes complicated with T2DM, TIR (OR: 0.957, 95%CI: 0.922-0.994, P < 0.05) is a protective factor. A nomogram prediction model of the risk of cognitive impairment was established based on SD, %CV and TIR. Decision curve analysis and the internal calibration analysis were used for internal verification and showed that the model was clinical benefit. The area under the ROC curves for predicting cognitive impairment in patients with lacunes complicated with T2DM was drawn were %CV: 0.757 (95%CI :0.669-0.845, P < 0.05), TIR: 0.711 (95%CI: 0.623-0.799, P < 0.05)., Conclusion: Blood glucose variability is closely associated with the level of lacune burden and cognitive dysfunction in lacune patients combined with T2DM. %CV, TIR have a certain predictive effect in cognitive impairment in lacune patients., Competing Interests: Conflict-of-interest statement: We declare that we have no conflict of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Novel topological phases of matter are fruitful platforms for the discovery of unconventional electromagnetic phenomena. Higher-fold topology is one example, where the low-energy description goes beyond standard model analogs. Despite intensive experimental studies, conclusive evidence remains elusive for the multigap topological nature of higher-fold chiral fermions. In this Letter, we leverage a combination of fine-tuned chemical engineering and photoemission spectroscopy with photon energy contrast to discover the higher-fold topology of a chiral crystal. We identify all bulk branches of a higher-fold chiral fermion for the first time, critically important for allowing us to explore unique Fermi arc surface states in multiple interband gaps, which exhibit an emergent ladder structure. Through designer chemical gating of the samples in combination with our measurements, we uncover an unprecedented multigap bulk boundary correspondence. Our demonstration of multigap electronic topology will propel future research on unconventional topological responses.