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Hong-Bin Liang,1,2 Wan-You He,2 Yan-Ping Liu,3 Han-Bing Wang1,2 1Graduate School of Guangdong Medical University, Zhanjiang, Guangdong Province, People’s Republic of China; 2Department of Anesthesiology, The First People’s Hospital of Foshan, Foshan, Guangdong Province, People’s Republic of China; 3College of Nursing, Shandong First Medical University (Shandong Academy of Medical Science), Jinan, Shandong Province, People’s Republic of ChinaCorrespondence: Han-Bing Wang, Department of Anesthesiology, The First People’s Hospital of Foshan, No. 81 North of Ling Nan Road, Foshan, Guangdong Province, People’s Republic of China, Email fswhbing@126.comAbstract: A negative correlation exists between attention and pain. The cognitive impairments linked to pain can significantly impede a patient’s healing process and everyday tasks, particularly for individuals experiencing persistent pain. Furthermore, it has been demonstrated that diversion can effectively decrease pain levels in individuals. The focus of this review is to analyze clinical trials and fundamental investigations regarding alterations in focus and persistent discomfort. Moreover, we investigated the common neuroanatomy associated with attention and pain. Furthermore, we examined the impact of various neuromodulators on the transmission of pain and processes related to attention, while also considering the potential neural mechanisms that contribute to the co-occurrence of pain and attention deficits. Further investigation in this field will enhance our comprehension of patient symptoms and the underlying pathophysiology, ultimately resulting in more objective approaches to treatment.Keywords: pain, attention deficit, brain, neuromodulator

Ming Zhang,1 Shuai-shuai Huang,1 Wen-yue He,1 Wei-juan Cao,2 Min-yi Sun,1 Ning-wei Zhu2 1Department of Pharmacy, Ningbo Yinzhou NO.2 Hospital, Ningbo, Zhejiang, 315100, People’s Republic of China; 2Department of Pharmacy, Zhejiang Pharmaceutical University, Ningbo, Zhejiang Province, 315100, People’s Republic of ChinaCorrespondence: Ning-wei Zhu, Email NingweiZhu@126.comIntroduction: Basic fibroblast growth factor (bFGF) shows great potential for preventing vascular dementia (VD). However, the blood‒brain barrier (BBB) and low bioavailability of bFGF in vivo limit its application. The present study investigated how nasal administration of bFGF-loaded nanoliposomes (bFGF-lips) affects the impaired learning and cognitive function of VD mice and the underlying mechanism involved.Methods: A mouse model of VD was established through repeated cerebral ischemia‒reperfusion. A Morris water maze (MWM) and novel object recognition (NOR) tests were performed to assess the learning and cognitive function of the mice. Hematoxylin and eosin (HE) staining, Nissl staining and TUNEL staining were used to evaluate histopathological changes in mice in each group. ELISA and Western blot analysis were used to investigate the molecular mechanism by which bFGF-lips improve VD incidence.Results: Behavioral and histopathological analyses showed that cognitive function was significantly improved in the bFGF-lips group compared to the VD and bFGF groups; in addition, abnormalities and the apoptosis indices of hippocampal neurons were significantly decreased. ELISA and Western blot analysis revealed that bFGF-lips nasal administration significantly increased the concentrations of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), bFGF, B-cell lymphoma 2 (Bcl-2), phosphorylated protein kinase B (PAKT), nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H quinone oxidoreductase 1 (NQO1) and haem oxygenase-1 (HO-1) in the hippocampus of bFGF-lips mice compared with the VD and bFGF groups. Furthermore, the concentrations of malondialdehyde (MDA), caspase-3 and B-cell lymphoma 2-associated X (Bax) were clearly lower in the bFGF-lips group than in the VD and bFGF groups.Conclusion: This study confirmed that the nasal administration of bFGF-lips significantly increased bFGF concentrations in the hippocampi of VD mice. bFGF-lips treatment reduced repeated I/R-induced neuronal apoptosis by regulating apoptosis-related protein concentrations and activating the phosphatidylinositol-3-kinase (PI3K)/(AKT)/Nrf2 signaling pathway to inhibit oxidative stress.Keywords: bFGF, nanoliposomes, vascular dementia, nasal administration, oxidative stress, neuronal apoptosis

Yizhou Zeng, Xiaofang Tian, Quan Wang, Weiyang He, Jing Fan, Xin Gou Department of Urinary Surgery, The First Affiliated Hospital of Chongqing Medical University, Yuzhong District, Chongqing, China Aim: The mammalian target of rapamycin (mTOR) pathway is a critical target for cancer treatment and the mTOR inhibitor everolimus (RAD001) has been approved for treatment of renal cell carcinoma (RCC). However, the limited efficacy of RAD001 has led to the development of drug resistance. Autophagy is closely related to cell survival and death, which may be activated under RAD001 stimulation. The aim of the present study was to identify the underlying mechanisms of RAD001 resistance in RCC cells through cytoprotective autophagy involving activation of the extracellular signal-regulated kinase (ERK) pathway. Methods and results: RAD001 strongly induced autophagy of RCC cells in a dose- and time-dependent manner, as confirmed by Western blot analysis. Importantly, suppression of autophagy by the pharmacological inhibitor chloroquine effectively enhanced RAD001-induced apoptotic cytotoxicity, as demonstrated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Western blot analysis, indicating a cytoprotective role for RAD001-induced autophagy. In addition, as was shown by the MTT assay, flow cytometry, and Western blot analysis, RAD001 robustly activated ERK, but not c-Jun N-terminal kinase and p38. Activation of ERK was inhibited by the pharmacological inhibitor selumetinib (AZD6244), which effectively promoted RAD001-induced cell death. Moreover, employing AZD6244 markedly attenuated RAD001-induced autophagy and enhanced RAD001-induced apoptosis, which play a central role in RAD001-induced cell death. Furthermore, RAD001-induced autophagy is regulated by ERK-mediated phosphorylation of Beclin-1 and B-cell lymphoma 2, as confirmed by Western blot analysis. Conclusion: These results suggest that RAD001-induced autophagy involves activation of the ERK, which may impair cytotoxicity of RAD001 in RCC cells. Thus, inhibition of the activation of ERK pathway-mediated autophagy may be useful to overcome chemoresistance to RAD001. Keywords: apoptosis, autophagy, everolimus, ERK, renal cancer, selumetinib

Background: Lack of motivation and behavioral abnormalities are the hallmarks of postpartum depression (PPD). Severe uterine contractions during labor are pain triggers for psychiatric disorders, including PPD in women during the puerperium. Creating biomarkers to monitor PPD may help in its early detection and treatment. It has been suggested that uterine contraction-induced labor pain plays a role in the emergence of this syndrome. Therefore, abnormal electroencephalography (EEG) patterns during the first stage of labor may provide useful information. Here, we propose that aberrant EEG patterns caused by painful uterine contractions may be predictive markers for PPD., Methods: This study is a single-centre prospective cohort planned for 331 parturients for vaginal delivery in the maternity ward of Zhujiang Hospital from 2022 to 2023. At baseline, online or paper-based questionnaires, including the Edinburgh Postnatal Depression Scale (EPDS) and demographic data, will be collected when the parturient is admitted to labor. EEG, electrocardiography (ECG) and electrohysterography (EHG) signals will be monitored and recorded during the first stage of labor in the ward. Follow-up will be taken at the postpartum timepoints of day 3, day 42, and 3, 6 and 12 months, respectively. Power spectral density and functional connections will be quantified. The connections between PPD severity and EEG measurements as a function of time will be assessed using linear mixed-effects models. Maternal age, parity, and whether oxytocin is used during labor, all have an impact on the incidence of PPD, hence a stratified analysis will be carried out., Discussion: We expect EEG changes caused by painful uterine contractions in the first labor may predict early PPD. The results from this study may act as a predictor for the development of PPD which may enhance long-term quality of life for the parturient and her offspring., Trial Registration: Name of registry: EEG Alterations of Uterine Contractions in the First Stage of Labor Predicting PPD., Trial Registration Number: NCT05217251; registration date on the ClinicalTrial.gov platform: February, 1/2022., Competing Interests: Declarations. Ethics approval and consent to participate: This study is conducted in accordance with the Declaration of Helsinki and national and international standards of GCP. Potential participants receive detailed written and oral information on the study procedures and all participants provide written informed consent. The study protocol is registered at the Human Research Ethics Committee at Zhujiang Hospital of Southern Medical University with trial registration number No.2021-KY-160–03. In addition, the study protocol is registered at ClinicalTrial.gov with trial registration number NCT05217251. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Postharvest spoilage of fruits accounts for significant losses ranging between 20 %-30 %, leading to considerable resource wastage and economic downturns. The development of an effective fresh-keeping packaging material is of paramount importance. This study introduces an innovative on-demand removable active fruit fresh-keeping film (GPP), created by embedding a GP (gallic acid-phycocyanin) fiber mesh hydrogel with functional properties into a polyvinyl alcohol (PVA) matrix. The resultant GPP hydrogel-based film demonstrates outstanding UV and water vapor barrier capabilities, mechanical stability, resistance to external mechanical stress, universal surface adhesion, antibacterial efficacy, and on-demand removal attributes, while being devoid of potential toxicity hazards. Utilizing grapes and blueberries as representative fruits, it is shown that the GPP hydrogel film significantly preserves the fruits' hardness, pH, total soluble solids content (TSS), and minimizes the rate of weight loss, thereby prolonging the shelf life to 13 days for grapes and 20 days for blueberries at ambient temperature. These results underscore the potential of this hydrogel-based film as an invaluable material for fruit preservation within the food industry., 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. The following are the supplementary data related to this article. Supplementary data to this article can be found online at https://doi.org/10.1016/j.foodchem.2024.141404., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Van der Waals (vdW) crystals with strong spin-orbit coupling (SOC) provide great opportunities for exploring unconventional 2D superconductors, wherein new pairing states emerge due to the interplay of SOC with crystalline symmetries, electronic correlations, quenched disorders and external modulation forces, etc. Here, a distinct mirror-symmetry protected Ising pairing state with unprecedented Γ- and M-valley symmetries in natural vdW heterostructures (vdWH) of interweaving tetragonal SnSe and trigonal 1H-TaSe 2 monolayers is reported, in which the unidirectional lattice interlocking effectively suppresses the K-valley Ising pairing mechanism by incommensurate charge-density-wave (CDW) transitions. In the 2D limit of an TaSe 2 /SnSe bilayer with intact basal mirror symmetry (M z ), the mirror-symmetric vdWH Ising superconductors show anomalous in-plane magnetic field B ‖ -controlled enhancements in the critical temperature T c , which is completely absent for multilayer vdWHs with broken M z induced by orthorhombic stacking between nearest-neighbour TaSe 2 monolayers. The experimental observations consistently reveal a mirror symmetry-protected type-III Ising state in the inversion asymmetric lattice of 1H-TaSe 2 , which is predicted to be a mixture of spin-singlet and spin-triplet states., (© 2024 Wiley‐VCH GmbH.)

Obesity is acknowledged as a significant risk factor for various metabolic diseases, and the inhibition of human pancreatic lipase (hPL) can impede lipid digestion and absorption, thereby offering potential benefits for obesity treatment. Anthraquinones is a kind of natural and synthetic compounds with wide application. In this study, the inhibitory effects of 31 anthraquinones on hPL were evaluated. The data shows that AQ7, AQ26, and AQ27 demonstrated significant inhibitory activity against hPL, and exhibited selectivity towards other known serine hydrolases. Then the structure-activity relationship between anthraquinones and hPL was further analysed. AQ7 was found to be a mixed inhibition of hPL through inhibition kinetics, while AQ26 and AQ27 were effective non-competitive inhibition of hPL. Molecular docking data revealed that AQ7, AQ26, and AQ27 all could associate with the site of hPL. Developing hPL inhibitors for obesity prevention and treatment could be simplified with this novel and promising lead compound.

Nanozymes, a revolutionary category of engineered artificial enzymes based on nanomaterials, have been developed to overcome the inherent limitations of natural enzymes, such as the high cost associated with storage and their fragility. Carbon dots (CDs) have emerged as compelling candidates for various applications due to their versatile properties. Particularly noteworthy are CDs with a range of surface functional groups that exhibit enzyme-like behavior, combining exceptional performance with catalytic capabilities. This review explores the methodologies used for synthesizing CDs with enzyme mimicking capabilities, highlighting potential avenues such as doping and hybrid nanozymes to enhance their catalytic efficacy. Moreover, a comprehensive overview of CDs that mimick the activities of various oxidoreductases-like peroxidase, catalase, oxidase/laccase, and superoxide dismutase-like is provided. The focus is on the in-depth exploration of the mechanisms, advancements and practical applications of each oxidoreductase-like function exhibited by CD nanozymes. Drawing upon these exhaustive summaries and analyses, the review identifies the prevailing challenges that hinder the seamless integration of CDs into real-world applications and offers forward-looking perspectives for future directions., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Objective: To investigate the therapeutic effects and mechanisms of Ultrasound-targeted microbubble destruction (UTMD) technology combined with CoQ10 loaded PEGylated nanoliposomes (CoQ10-PEG-lips) on diabetic cardiomyopathy (DCM) in rats. Methods: CoQ10-PEG-lips were prepared using the thin-film dispersion method combined with ultrasonic hydration, followed by quality assessment. Sixty healthy and clean male SD rats were selected, and 50 were randomly chosen using a random number table to establish a type 1 diabetes mellitus (DM) model via a single intraperitoneal injection of streptozotocin. The remaining 10 rats were assigned as the normal control group. A total of 47 rats successfully developed the DM model, and 40 were selected using the random number table method. Based on different intervention methods, these rats were then randomly divided into DM model group, CoQ10 solution group, CoQ10-PEG-Lips group, and CoQ10-PEG-Lips+UTMD group ( n =10 per group). Normal control group and DM model group rats were injected with 1 ml of normal saline through caudal vein. CoQ10 solution group and CoQ10-PEG-Lips group were injected with 1 ml of CoQ10 solution or CoQ10-PEG-Lips solution containing 10 mg/kg of CoQ10 through caudal vein, respectively. Rats in the CoQ10-PEG-Lips+UTMD group were injected with 1 ml of CoQ10-PEG-Lips solution containing 10 mg/kg of CoQ10+100 mg of freeze-dried ultrasound microbubble powder through caudal vein and were given UTMD treatment at the same time, with the intervention given twice a week. After 12 weeks of intervention, cardiac function indexes [left ventricular end-systolic diameter (LVEDs), left ventricular end-diastolic diameter (LVEDd), and left ventricular ejection fraction (LVEF)]of each group were measured by ultrasonic cardiac function detection in vivo. Simultaneously, ex-vivo histopathological examination was conducted to assess myocardial cell morphology, cross-sectional area, collagen volume fraction (CVF), and apoptosis index (AI) in each group. Additionally, molecular biology techniques were employed to measure oxidative stress-related indicators and the expression of apoptosis-related pathway proteins. Results: The prepared CoQ10-PEG-lips had a well-rounded morphology, good dispersibility, and a high encapsulation efficiency of 87.45%±3.23%. After 12 weeks of intervention, the myocardial cell morphology in the CoQ10-PEG-Lips+UTMD group was intact, with orderly arrangement, closely resembling that of the normal control group. There were no statistically significant differences between the two groups in terms of LVEDs [(1.53±0.07) mm vs (1.42±0.04) mm], LVEDd [(2.93±0.15) mm vs (2.81±0.05) mm], or LVEF (80.76%±3.42% vs 84.60%±2.10%) (all P >0.05). Similarly, there were no significant differences between the two groups in myocardial cell cross-sectional area, CVF, or AI (all P >0.05). The CoQ10-PEG-Lips+UTMD group showed statistically significant differences in the above-mentioned indicators compared to the DM group, CoQ10 solution group, and CoQ10-PEG-Lips group (all P <0.05). In the CoQ10-PEG-Lips+UTMD group, the levels of myocardial superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and the expression of the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) were significantly higher compared to the DM model group, CoQ10 solution group, and CoQ10-PEG-Lips group (all P <0.05), while malondialdehyde levels and the expression of Bcl-2-associated X protein (Bax) and caspase-3 were lower (all P <0.05). Conclusions: Using PEG-lips to encapsulate the poorly soluble drug CoQ10 in combination with UTMD technology enables targeted delivery of the drug to the myocardium, which can help reduce myocardial cell damage, fibrosis, and apoptosis caused by diabetes mellitus (DM) by inhibiting oxidative stress damage and the Bcl-2/Bax/caspase-3 apoptosis signaling pathway, ultimately improving cardiac function in DCM rats.

Purpose: To explore the effect of narrative medicine teaching practice on the narrative ability and empathy ability of dental interns and establish an effective narrative medicine teaching system., Methods: From June 2022 to May 2023, atotal of 34 dental undergraduate students participating in clinical practice were divided into two groups, with 14 students in experimental group and 20 in control group. During clinical internships, the experimental group took narrative medicine into practice including theoretical lectures, close reading, parallel chart, seminars and so on. Interpersonal Reactivity Index(IRI) was used to evaluate the empathy of the students in the two groups, and a questionnaire survey was conducted on the narrative medicine practice of the experimental group. SPSS 12.0 software package was used for data analysis., Results: The total score and module scores of empathy scale in the experimental group did not change significantly after the practice compared with before the practice. The score of "personal distress" module in the control group decreased significantly after the practice (P＜0.05), indicating that students in the control group who did not receive narrative education had a decrease in empathy after clinical practice. The questionnaire and parallel charts reflected that the interns' narrative ability and the understanding for medical psycho-social factors of experimental group students had been enhanced., Conclusions: Narrative medicine practice is helpful to improve narrative ability and empathy ability, cultivate professional quality and ease the doctor-patient relationship. It should be continuously promoted during the dental undergraduate teaching and dentist's practicing career.

Exploring the physical fractions of organic carbon and influencing mechanisms in grassland, forest, and farmland soils in wind erosion area can provide scientific basis for carbon sequestration, land utilization, wind prevention measure making, and fertility restoration of sloping farmland in the region. We examined the differentiation of aggregate organic carbon and density fractionation organic carbon in 0-15 cm soil layer across grassland, forest, and sloping farmland with 350 m long and 5° slope gradient in the wind erosion area of Meilisi District, Qiqihar, Heilongjiang, as well as the sloping farmland in the downhill section, middle section, and uphill section with every 100 m apart from the bottom to the top. The results showed that soil aggregates >2 mm were all destroyed across grassland, forest, and farmland soils, while the percentage of aggregates <0.053 mm was significantly higher than that of other sizes. The percentage of various soil aggregates, organic carbon content from density fractionations, and the proportion of organic carbon in the heavy fraction aggregates in farmland were significantly lower than that in grassland and forest soils. Soil aggregates in the uphill section of farmland were completely destroyed, and organic carbon content in various size aggregates and density fractionations gradually decreased with increasing slope. The proportion of organic carbon in the heavy fraction aggregates decreased, but that in light fraction aggregates increased gradually. Soil organic carbon and available potassium were key factors affecting aggregate stability, aggregate organic carbon content, and organic carbon content in density fractionations, while the loss of organic carbon in aggregate led to a decrease in aggregate stability. In summary, compared with grassland and forest soils, the stability of soil aggregates, the aggregate organic carbon content, the organic carbon content in density fractionations, and the proportion of organic carbon in heavy fraction aggregates in farmland all decreased in the wind erosion area of Northeast China. With the increases of slope, the aggregate organic carbon content, the organic carbon content in density fractionations, and the proportion of organic carbon in the heavy fraction aggregates in sloping farmland all decreased. Planting trees, conserving and expanding grassland area, and increasing the application of organic materials in sloping farmland in wind erosion area are effective approaches to stabilize and increase carbon storage, improve soil structure, and enhance soil quality.

Quantum materials exhibit dissipationless topological edge state transport with quantized Hall conductance, offering notable potential for fault-tolerant computing technologies. However, the development of topological edge state-based computing devices remains a challenge. Here we report the selective and quasi-continuous ferroelectric switching of topological Chern insulator devices, showcasing a proof-of-concept demonstration in noise-immune neuromorphic computing. We fabricate this ferroelectric Chern insulator device by encapsulating magic-angle twisted bilayer graphene with doubly aligned h-BN layers and observe the coexistence of the interfacial ferroelectricity and the topological Chern insulating states. The observed ferroelectricity exhibits an anisotropic dependence on the in-plane magnetic field. By tuning the amplitude of the gate voltage pulses, we achieve ferroelectric switching between any pair of Chern insulating states in the presence of a finite magnetic field, resulting in 1,280 ferroelectric states with distinguishable Hall resistance levels on a single device. Furthermore, we demonstrate deterministic switching between two arbitrary levels among the record-high number of ferroelectric states. This unique switching capability enables the implementation of a convolutional neural network resistant to external noise, utilizing the quantized Hall conductance levels of the Chern insulator device as weights. Our study provides a promising avenue towards the development of topological quantum neuromorphic computing, where functionality and performance can be drastically enhanced by topological quantum materials., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objectives: To develop an interactive, non-invasive artificial intelligence (AI) system for malignancy risk prediction in cystic renal lesions (CRLs)., Methods: In this retrospective, multicenter diagnostic study, we evaluated 715 patients. An interactive geodesic-based 3D segmentation model was created for CRLs segmentation. A CRLs classification model was developed using spatial encoder temporal decoder (SETD) architecture. The classification model combines a 3D-ResNet50 network for extracting spatial features and a gated recurrent unit (GRU) network for decoding temporal features from multi-phase CT images. We assessed the segmentation model using sensitivity (SEN), specificity (SPE), intersection over union (IOU), and dice similarity (Dice) metrics. The classification model's performance was evaluated using the area under the receiver operator characteristic curve (AUC), accuracy score (ACC), and decision curve analysis (DCA)., Results: From 2012 to 2023, we included 477 CRLs (median age, 57 [IQR: 48-65]; 173 men) in the training cohort, 226 CRLs (median age, 60 [IQR: 52-69]; 77 men) in the validation cohort, and 239 CRLs (median age, 59 [IQR: 53-69]; 95 men) in the testing cohort (external validation cohort 1, cohort 2, and cohort 3). The segmentation model and SETD classifier exhibited excellent performance in both validation (AUC = 0.973, ACC = 0.916, Dice = 0.847, IOU = 0.743, SEN = 0.840, SPE = 1.000) and testing datasets (AUC = 0.998, ACC = 0.988, Dice = 0.861, IOU = 0.762, SEN = 0.876, SPE = 1.000)., Conclusion: The AI system demonstrated excellent benign-malignant discriminatory ability across both validation and testing datasets and illustrated improved clinical decision-making utility., Critical Relevance Statement: In this era when incidental CRLs are prevalent, this interactive, non-invasive AI system will facilitate accurate diagnosis of CRLs, reducing excessive follow-up and overtreatment., Key Points: The rising prevalence of CRLs necessitates better malignancy prediction strategies. The AI system demonstrated excellent diagnostic performance in identifying malignant CRL. The AI system illustrated improved clinical decision-making utility., (© 2024. The Author(s).)

'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.)

Quantum spin liquids (QSLs) are in a quantum disordered state that is highly entangled and has fractional excitations. As a highly sought-after state of matter, QSLs were predicted to host spinon excitations and to arise in frustrated spin systems with large quantum fluctuations. Here we report on the experimental observation and theoretical modeling of QSL signatures in monolayer 1T-NbSe 2 , which is a newly emerging two-dimensional material that exhibits both charge-density-wave (CDW) and correlated insulating behaviors. By using scanning tunneling microscopy and spectroscopy (STM/STS), we confirm the presence of spin fluctuations in monolayer 1T-NbSe 2 by observing the Kondo resonance as monolayer 1T-NbSe 2 interacts with metallic monolayer 1H-NbSe 2 . Subsequent STM/STS imaging of monolayer 1T-NbSe 2 at the Hubbard band energy further reveals a long-wavelength charge modulation, in agreement with the spinon modulation expected for QSLs. By depositing manganese-phthalocyanine (MnPc) molecules with spin S = 3/2 onto monolayer 1T-NbSe 2 , new STS resonance peaks emerge at the Hubbard band edges of monolayer 1T-NbSe 2 . This observation is consistent with the spinon Kondo effect induced by a S = 3/2 magnetic impurity embedded in a QSL. Taken together, these experimental observations indicate that monolayer 1T-NbSe 2 is a new promising QSL material., (© 2024. The Author(s).)

Spatiotemporal mode-locked (STML) fiber lasers have become a new platform for investigating nonlinear phenomena. In this work, spatiotemporal dual-periodic soliton pulsation (SDSP) is firstly observed in an STML fiber laser. It is found that in the SDSP, the long-period pulsations (LPPs) of different transverse modes are synchronous, while the short-period pulsations (SPPs) exhibit asynchronous modulations. The numerical simulation confirms the experimental results and further reveals that the proportion of transverse mode components can manipulate the periods of the LPP and SPP but does not affect the synchronous and asynchronous pulsations of different transverse modes. The obtained results bring the study of spatiotemporal dissipative soliton pulsation into the multi-period modulation stage, which helps to understand the complex spatiotemporal dynamics in STML fiber lasers and discover new dynamics in high-dimensional nonlinear systems.

Objective: This study explored the potential molecular mechanisms of ursolic acid (UA) in bladder cancer treatment using network pharmacology and molecular docking., Methods: The Traditional Chinese Medicine Systems Pharmacology and UniProt databases were used to screen potential targets of UA. Relevant bladder cancer target genes were extracted using the GeneCards database. All data were pooled and intercrossed to obtain common target genes of UA and bladder cancer. Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed. Molecular docking was conducted to verify the possible binding conformation between UA and bladder cancer cells. Then, in vitro experiments were performed to further validate the predicted results., Results: UA exerts anti-tumor effects on bladder cancer through multiple targets and pathways. Molecular docking indicated that UA undergoes stable binding with the proteins encoded by the top six core genes ( STAT3, VEGFA, CASP3, TP53, IL1B, and CCND1 ). The in vitro experiments verified that UA can induce bladder cancer cell apoptosis by regulating the PI3K/Akt signaling pathway., Conclusions: Our study illustrated the potential mechanism of UA in bladder cancer based on network pharmacology and molecular docking. The results will provide scientific references for follow-up studies and clinical treatment., Competing Interests: Declaration of conflicting interestsThe authors declare that they have no conflicts of interest.

Multimode fiber lasers have become a new platform for investigating nonlinear phenomena since the report on spatiotemporal mode-locking. In this work, the multimode soliton pulsation with a tunable period is achieved in a spatiotemporal mode-locked fiber laser. It demonstrates that the pulsation period drops while increasing the pump power. Moreover, it is found that different transverse modes have the same pulsation period, asynchronous pulsation evolution and different dynamical characteristics through the spatial sampling technique and the dispersive Fourier transform technique. To further verify the experimental results, we numerically investigate the influences of the gain and the loss on the pulsation properties. It is found that within a certain parameter range, the pulsation period drops and rises linearly with the increase of the gain and the loss, respectively. The obtained results contribute to understanding the formation and regulating of soliton pulsations in fiber lasers.

Background: To date, the clinical management of advanced hepatocellular carcinoma (HCC) patients remains challenging and the mechanisms of E2F transcription factor 1 (E2F1) underlying HCC are obscure. Materials and Methods: Our study integrated datasets mined from several public databases to comprehensively understand the deregulated expression status of E2F1. Tissue microarrays and immunohistochemistry staining was used to validate E2F1 expression level. The prognostic value of E2F1 was assessed. In-depth subgroup analyses were implemented to compare the differentially expressed levels of E2F1 in HCC patients with various tumor stages. Functional enrichments were used to address the predominant targets of E2F1 and shedding light on their potential roles in HCC. Results: We confirmed the elevated expression of E2F1 in HCC. Subgroup analyses indicated that elevated E2F1 level was independent of various stages in HCC. E2F1 possessed moderate discriminatory capability in differentiating HCC patients from non-HCC controls. Elevated E2F1 correlated with Asian race, tumor classification, neoplasm histologic grade, eastern cancer oncology group, and plasma AFP levels. Furthermore, high E2F1 correlated with poor survival condition and pooled HR signified E2F1 as a risk factor for HCC. Enrichment analysis of differentially expressed genes, coexpressed genes, and putative targets of E2F1 emphasized the importance of cell cycle pathway, where CCNE1 and CCNA2 served as hub genes. Conclusions: We confirmed the upregulation of E2F1 and explored the prognostic value of E2F1 in HCC patients. Two putative targeted genes ( CCNE1 and CCNA2 ) of E2F1 were identified for their potential roles in regulating cell cycle and promote antiapoptotic activity in HCC patients.

Background: Medical students applying to residency, including those from underrepresented groups, strongly value cultural fit and program diversity. Program websites and social media are thus an influential information source for prospective applicants and recruitment tool for residencies. We evaluated whether and how integrated plastic surgery residency program websites and social media display commitments to diversity online., Methods: We evaluated program websites for 8 predetermined diversity elements, (1) nondiscrimination and (2) diversity statements, (3) community resources, (4) faculty and (5) resident biographies, (6) faculty and (7) resident photographs, and (8) resident resources, and assessed Instagram accounts for diversity-related images, captions, and hashtags. Our analysis used Mann-Whitney U , chi-squared, and t tests; significance level was P < 0.05., Results: We reviewed 82 program websites with a mean of 3.4 ± 1.4 diversity elements. Resident (n = 76, 92.7%) and faculty photographs (n = 65, 79.3%) and resident biographies (n = 43, 52.4%) were the most common. Seventy programs (85.4%) had Instagram accounts, the majority of which (n = 41, 58.6%) shared content related to diversity in race, ethnicity, gender, and/or sexual orientation. Programs located in smaller cities were more likely to have ≥4 website diversity elements ( P = 0.014) and mention diversity on Instagram ( P = 0.0037). Programs with women chairs/chiefs were more likely to mention diversity on Instagram ( P = 0.007)., Conclusions: In the age of virtual recruitment, program websites and social media should provide sufficient information, described in our diversity element checklist, to help prospective applicants determine fit from a diversity perspective. Residents, who often contribute to program social media, and women chairs/chiefs may be critical to driving diversity promotion., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Liver fibrosis (LF) is an important reparative process in response to acute or chronic hepatic injury, which has the potential to advance towards cirrhosis and hepatocellular carcinoma. Dietary naringin consumption contributes to protection against LF in animal studies, while the exact protective mechanism of naringin remains unclear. This study aimed to investigate the molecular mechanisms behind the potential protective effect of naringin against TAA-induced LF in zebrafish. In this study, we utilized zebrafish to create the LF model and investigate the therapeutic mechanism of naringin. Firstly, we evaluated the changes in hepatic fibrosis and lipid accumulation in the liver following naringin treatment with oil red O, Nile red, and Sirius red and immunohistochemistry. In addition, we employed an ROS probe to directly measure oxidative stress and monitor inflammatory cell migration in a zebrafish transgenic line. Morpholino was used in the knockdown of IDO1 in order to verify its vital role in LF. Our findings demonstrated that naringin exhibited anti-inflammatory and anti-fibrotic action in conjunction with a reversal in lipid accumulation, oxidative stress and suppression of macrophage infiltration and activation of hepatic stellate cells. Furthermore, the results showed that the antifibrotic effect of naringin was removed upon IDO1 knockdown, proving that naringin exerts a protective effect by regulating IDO1. Naringin demonstrates remarkable protective effects against LF, effectively counteracting inflammation and hepatic steatosis in zebrafish liver. These findings suggest that naringin may function as an effective IDO1 inhibitor, holding the potential for clinical translation as a therapeutic agent for the treatment of LF.

Streptomycetes have a strong ability to produce a vast array of bioactive natural products (NPs) widely used in agriculture and veterinary/human medicine. The recently developed CRISPR/Cas9-based genome editing tools have greatly facilitated strain improvement for target NP overproduction as well as novel NP discovery in Streptomyces . However, CRISPR/Cas9 shows high toxicity to the host, limiting its application in many Streptomyces strains with a low DNA transformation efficiency. In this study, we developed a low-toxicity CRISPR/Cas9 D10A nickase (nCas9)-based genome editing tool in the model strain Streptomyces coelicolor M145. We showed that in the presence of both targeting sgRNA and Cas proteins, utilization of nCas9 instead of Cas9 significantly reduced the toxicity to the host and greatly enhanced cell survival. Using this tool, we achieved deletion of single genes and gene clusters with efficiencies of 87-100 and 63-87%, and simultaneous deletion of two genes or gene clusters with efficiencies of 47 and 43%, respectively. The editing efficiency of nCas9 is comparable to that of the Cas9-mediated editing tool. Finally, the nCas9-based editing tool was successfully applied for genome editing in the industrial rapamycin-producing strain Streptomyces rapamycinicus , in which CRISPR/Cas9 cannot work well. We achieved the deletion of three tested genes with an efficiency of 27.2-30%. Collectively, the CRISPR/nCas9-based editing tool offers a convenient and efficient genetic modification system for the engineering of streptomycetes, particularly those with low DNA transformation efficiency.

Conjugative plasmids play a vital role in bacterial evolution and promote the spread of antibiotic resistance. They usually cause fitness costs that diminish the growth rates of the host bacteria. Compensatory mutations are known as an effective evolutionary solution to reduce the fitness cost and improve plasmid persistence. However, whether the plasmid transmission by conjugation is sufficient to improve plasmid persistence is debated since it is an inherently costly process. Here, we experimentally evolved an unstable and costly mcr-1 plasmid pHNSHP24 under laboratory conditions and assessed the effects of plasmid cost and transmission on the plasmid maintenance by the plasmid population dynamics model and a plasmid invasion experiment designed to measure the plasmid's ability to invade a plasmid-free bacterial population. The persistence of pHNSHP24 improved after 36 days evolution due to the plasmid-borne mutation A51G in the 5'UTR of gene traJ . This mutation largely increased the infectious transmission of the evolved plasmid, presumably by impairing the inhibitory effect of FinP on the expression of traJ . We showed that increased conjugation rate of the evolved plasmid could compensate for the plasmid loss. Furthermore, we determined that the evolved high transmissibility had little effect on the mcr-1 -deficient ancestral plasmid, implying that high conjugation transfer is vital for maintaining the mcr-1 -bearing plasmid. Altogether, our findings emphasized that, besides compensatory evolution that reduces fitness costs, the evolution of infectious transmission can improve the persistence of antibiotic-resistant plasmids, indicating that inhibition of the conjugation process could be useful to combat the spread of antibiotic-resistant plasmids. IMPORTANCE Conjugative plasmids play a key role in the spread of antibiotic resistance, and they are well-adapted to the host bacteria. However, the evolutionary adaptation of plasmid-bacteria associations is not well understood. In this study, we experimentally evolved an unstable colistin resistance ( mcr-1 ) plasmid under laboratory conditions and found that increased conjugation rate was crucial for the persistence of this plasmid. Interestingly, the evolved conjugation was caused by a single-base mutation, which could rescue the unstable plasmid from extinction in bacterial populations. Our findings imply that inhibition of the conjugation process could be necessary for combating the persistence of antibiotic-resistance plasmids., Competing Interests: The authors declare no conflict of interest.

Noninvasive wound closure remains a challenge in the field of wound healing. In this study, we report the development of a cross-linked P-GL hydrogel constructed from polyvinyl alcohol (PVA) and GL (a hydrogel consisting of gallic acid and lysozyme) that effectively promotes wound closure and healing. The P-GL hydrogel exhibited a unique lamellar and tendon-like fibrous network structure, providing good thermo-sensitivity and tissue adhesiveness up to 60 MPa, as well as retaining autonomous self-healing and acid resistance capacities. In addition, the P-GL hydrogel exhibited sustained release characteristics lasting >100 h, excellent biocompatibility both in vitro and in vivo, as well as good antibacterial activity and mechanical properties. The in vivo full-thickness skin wounds model revealed the positive wound closure and healing therapeutic effects of the P-GL hydrogels were confirmed, showing a promising potential as a noninvasive wound closure and healing bio-adhesive hydrogel., 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.)

Subarachnoid hemorrhage (SAH) is a severe acute cerebrovascular event that not only impairs the central nervous system but also negatively affects various other organs, including the heart. The underlying mechanisms, however, remain unclear. In this study, we discovered that mice with SAH exhibited significant cardiac injuries, such as extended QT and QTc intervals, cardiac fibrosis, and reduced cardiac ejection fractions. This phenomenon was accompanied by increased galectin-3 expression in the cardiac ventricle and can be reversed by galectin-3 inhibitor TD139. Interestingly, we also observed increased co-expression of galectin-3 in macrophage within the heart tissue of SAH mice. Additionally, when macrophage activation was suppressed using the beta-blocker propranolol, cardiac function improved, and galectin-3 expression in the cardiac tissue decreased. Collectively, our findings offer new insights into the role of galectin-3 in SAH-related cardiac dysfunction and suggest a macrophage-galectin-3 axis as a potential therapeutic strategy., Competing Interests: Declaration of Competing Interest All authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)

During a 2020 routine epidemiological investigation of carbapenem-resistant Enterobacterales at a local food market in Guangzhou, China, two Escherichia coli ST410 isolates coproducing NDM-5 and OXA-181 were obtained from environmental samples. Antimicrobial susceptibility testing, whole-genome sequencing, and conjugation assays were applied to identify their resistance phenotypes, phylogenetic relatedness, and genetic characteristics. Phylogenetic analysis showed that the two isolates were clonally related with only one core-genome single-nucleotide polymorphism (SNP) difference and clustered into a branch with 87 E. coli ST410 isolates deposited in GenBank. These 89 ST410 isolates were closely related (≤51 SNPs), and most were from humans in Southeast Asian countries ( n  = 47). A Vietnamese clinical isolate collected in 2017 showed the strongest epidemiological link (seven SNPs) to the two ST410 isolates detected in this study. Complete-genome analysis revealed that the carbapenem resistance determinants bla NDM-5 and bla OXA-181 were located on an IncF1:A1:B49-IncQ1 plasmid and IncX3 plasmid, respectively. Conjugation experiments confirmed that the IncX3 plasmid was self-transmissible while the IncF1:A1:B49-IncQ1 plasmid was nonconjugative. BLASTn analysis indicated that the two plasmids showed high similarity to other bla NDM-5 -bearing IncF1:A1:B49-IncQ1 and bla OXA-181 -bearing IncX3 plasmids from other countries. Altogether, the high similarity of the core genomes and plasmids between the ST410 isolates found in this study and those human source isolates from foreign countries suggested the clonal spread of E. coli ST410 strains and horizontal transmission of bla OXA-181 -bearing IncX3 plasmids across Southeast Asian countries. Stringent sanitary management of food markets is important to prevent the dissemination of high-risk clones to the public. IMPORTANCE This is the first report of an Escherichia coli ST410 clone that coproduces NDM-5 and OXA-181 in China. The high similarity of the core genomes and plasmids between the ST410 isolates characterized in this study and human source isolates from foreign countries strongly suggests that this ST410 lineage is an international high-risk clone, highlighting the need for continuous global surveillance of ST410 clones., Competing Interests: The authors declare no conflict of interest.

Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.

The global Calcium (Ca) cycle is closely coupled to the carbon cycle, and Ca isotopes have potential in tracing it. Even though groundwater is one of the main reservoirs of Ca at the Earth's surface, few data are available for groundwater, and the behavior of Ca and its isotopes in geothermal systems remains unknown. Here we analysed the stable Ca and radiogenic Sr isotope compositions of thermal waters distributed along the Jinsha and Yalong river valleys in the southeastern Tibetan Plateau. The Ca isotopic composition of the thermal water ranges from 0.45 to 2.16 ‰ (δ 44/40 Ca values relative to SRM 915a). The thermal waters collected from carbonate aquifers have higher δ 44/40 Ca values than bedrocks, which was attributed to secondary carbonate precipitation accompanied by CO 2 degassing. In contrast, δ 44/40 Ca values in thermal waters collected from clastic and igneous rocks are similar to bedrock. Despite some thermal waters undergoing secondary silicates formation and CaNa ion exchange, such processes maybe not play a significant role in governing the Ca isotopic composition of these thermal waters. This suggests that Ca isotopes can be used to trace secondary carbonate precipitation driven by CO 2 degassing (e.g. travertine) in geothermal systems located in tectonically active 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 © 2023 Elsevier B.V. All rights reserved.)

Mucoadhesive hydrogels with multifunctional properties such as gastric acid resistance and sustained drug release in the intestinal tract are highly desirable for the oral treatment of inflammatory bowel diseases (IBDs). Polyphenols are proven to have great efficacies compared with the first-line drugs for IBD treatments. We recently reported that gallic acid (GA) was capable of forming a hydrogel. However, this hydrogel is prone to easy degradation and poor adhesion in vivo . To tackle this problem, the current study introduced sodium alginate (SA) to form a gallic acid/sodium alginate hybrid hydrogel (GAS). As expected, the GAS hydrogel showed excellent antiacid, mucoadhesive, and sustained degradation properties in the intestinal tract. In vitro studies demonstrated that the GAS hydrogel significantly alleviated ulcerative colitis (UC) in mice. The colonic length of the GAS group (7.75 ± 0.38 cm) was significantly longer than that of the UC group (6.12 ± 0.25 cm). The disease activity index (DAI) value of the UC group was (5.5 ± 0.57), which was markedly higher than that of the GAS group (2.5 ± 0.65). The GAS hydrogel also could inhibit the expression of inflammatory cytokines, regulating macrophage polarization and improving the intestinal mucosal barrier functions. All these results indicated that the GAS hydrogel was an ideal candidate for oral treatment of UC.

The current antibacterial wound dressings with antibiotic substances or metal bactericidal agents may lead to severe multidrug resistance and poor biocompatibilities. Herein, we report an inherent antibacterial hydrogel constructed by only two naturally small molecules gallic acid (GA) and diammonium glycyrrhizinate (DG) for promoting Staphylococcus aureus (S. aureus)-infected wound healing. The resultant GAD hydrogel can be fabricated by co-assembly of these two materials through simple steps. Thanks to the incorporation of GA and DG, GAD hydrogel enabled a strong mechanical performance and great self-healing property with a sustained-release of drugs into skin wounds. Moreover, the cell viability assays showed that GAD hydrogel had good cytocompatibility by promoting cell proliferation and migration. In addition, GAD hydrogel had broad antibacterial efficiency against both Gram-positive and Gram-negative bacteria. Taken together, GAD hydrogel is a promising dressing to accelerate bacterial-infected wound healing through reconstructing an intact and thick epidermis without antibiotics or cytokines., 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 © 2022 Elsevier B.V. All rights reserved.)

Wound healing remains a critical challenge due to its vulnerability to bacterial infection and the complicated inflammatory microenvironment. Herein, we report a novel antibacterial hydrogel constructed only by gallic acid (GA) and phycocyanin (PC), which is expected for the treatment of bacteria-infected wounds. These GA/PC hydrogels (GP) was found to coassemble into fibrous networks with a diameter of around 2 μm mainly through noncovalent interactions of hydrogen bonds, van der Waals force, and π interaction. Notably, these GP hydrogels showed excellent rheological properties (i.e., storage modulus of more than 9.0 × 10 4 Pa) and outstanding biocompatibility and antibacterial activities. Thanks to the incorporation of GA and PC, the GP hydrogels enabled adherence to the moist wound tissue and achieved a sustained release of GA and PC into the wound skin, therefore effectively attenuating inflammation and accelerating wound healing both in normal mice and bacteria-infected mice through regulating the expression of the tight junction protein and the alleviation of oxidative stress. Considering these results, these GP hydrogels are demonstrated to be a promising candidate for bacteria-infected wound healing.

Colistin is a last-line antibiotic against Gram-negative pathogens. However, the emergence of colistin resistance has substantially reduced the clinical effectiveness of colistin. In this study, synergy between colistin and capric acid was examined against twenty-one Gram-negative bacterial isolates (four colistin-susceptible and seventeen colistin-resistant). Checkerboard assays showed a synergistic effect against all colistin-resistant strains [(FICI, fractional inhibitory concentration index) = 0.02-0.38] and two colistin-susceptible strains. Time-kill assays confirmed the combination was synergistic. We suggest that the combination of colistin and capric acid is a promising therapeutic strategy against Gram-negative colistin-resistant strains.

The purpose of this study is to provide a new strategy for constructing a temperature-controlled hydrogel as a promising agent for wound healing using natural products through physical co-assembly. Herein, the temperature-controlled physically assembled hydrogel consisting of gallic acid and lysozyme (GL) could be co-assembled into a regular fibrous structure accompanied by strong blue fluorescence with three-dimensional networks at micron levels through hydrophobic interactions, π-π interactions and hydrogen bonding. This GL hydrogel has excellent temperature sensitivity and self-healing properties, as proved by cycle high-low temperature tests. In addition, it possesses stable rheological properties, great sustained release ability, and could realize the spatiotemporal delivery of gallic acid and lysozyme. Biocompatibility and antibacterial tests proved that this well-assembled GL hydrogel has no cytotoxicity but excellent antibacterial activity. Both in vitro and in vivo experiments demonstrated that the GL hydrogel has excellent anti-inflammation efficiency and promotes the healing of chronic wounds by suppressing the expression of pro-inflammatory related genes. Tests using an E. coli -infected wound model confirmed that the GL hydrogel could terminate the inflammatory phase early and ultimately promote the healing of wounds infected by E. coli . This study provides a promising strategy for the effective treatment of wounds through a physical self-assembled hydrogel.

N 6 -methyladenosine (m 6 A) is one of the major epigenetic modifications in eukaryotes. Although increasing functions of m 6 A have been identified in insects, its role in Plutella xylostella L. for host plant adaptation remains unclear. In the current study, we show that the m 6 A content of P. xylostella was relatively low in different developmental stages and tissues, with no significant differences. Two RNA methyltransferase genes, PxMETTL3 (methyltransferase-like 3) and PxMETTL14 (methyltransferase-like 14), were identified and characterized. PxMETTL3 could be transcribed into two transcripts, and PxMETTL14 had only one transcript; both of these genes were highly expressed in egg and adult stages and reproductive tissues. The CRISPR/Cas9-mediated knockout of PxMETTL3 (Δ PxMETTL3-2 ) or PxMETTL14 (Δ PxMETTL14-14 ) confirmed their function in m 6 A installation into RNA. Furthermore, upon transfer from an artificial diet to the host plant, the mutant strains were affected in terms of larval and pupal weight or adult emergence rate, while the wildtype (WT) strain did not exhibit any difference. In addition, the fecundity and egg hatching rate of the WT strain decreased significantly, whereas only the Δ PxMETTL14-14 mutant strain displayed significantly decreased fecundity. There seemed to be a tradeoff between the stress adaptation and reproduction in P. xylostella mediated by m 6 A modification. During host transfer, the expression of PxMETTL14 was consistent with the change in m 6 A content, which implied that PxMETTL14 could respond to host plant defense effectively, and may regulate m 6 A content. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the differentially expressed transcripts with changes in m 6 A levels revealed that the potential functions of m 6 A-related genes may be involved in steroid biosynthesis for larval performance and metabolic pathways for adult reproduction. Overall, our work reveals an epigenetic regulation mechanism for the rapid adaptation of P. xylostella to variations in the host environment.

Background: Idiopathic pulmonary fibrosis (IPF) is the interstitial lung disease with the highest incidence and mortality. The lack of specific markers results in limited treatment methods for IPF patients. Numerous prognostic signatures represented effective indexes in predicting the survival of patients in various diseases; however, little is investigated on their application in IPF. Methods: This study attempted to explore the clinical markers suitable for IPF by constructing a prognostic signature from the perspective of 7-methylguanosine (m7G). An m7G-related prognostic signature (m7GPS) was established based on the discovery cohort with the LASSO algorithm and was verified by internal and external validation cohorts. The area under the curve (AUC) values were utilized to assess the accuracy of m7GPS in predicting the prognosis of IPF patients and the ability of m7GPS in screening IPF patients. Kaplan-Meier curves and Cox regression analyses were used to identify the relationship of m7GPS with the prognosis of IPF individuals. Enrichment analyses, CIBERSORT algorithm, and weighted gene co-expression network analysis were applied to explore the underlying mechanisms and correlation of m7GPS in IPF. Results: The two m7G regulatory genes can divide IPF into subtypes 1 and 2, and subtype 2 demonstrated a poor prognosis for IPF patients ( p < 0.05). For the first time in this field, the m7GPS was constructed. m7GPS made it feasible to predict the 1-5 years survival status of IPF patients (AUC = 0.730-0.971), and it was an independent prognostic risk factor for IPF patients (hazard ratio > 1, p < 0.05). The conspicuous ability of m7GPS to screen IPF patients from the healthy was also revealed by an AUC value of 0.960. The roles of m7GPS in IPF may link to inflammation, immune response, and immune cell levels. Seven genes ( CYR61 , etc.) were identified as hub genes of m7GPS in IPF. Three drugs (ZM447439-1050, AZD1332-1463, and Ribociclib-1632) were considered sensitive to patients with high m7GPS risk scores. Conclusion: This study developed a novel m7GPS, which is a reliable indicator for predicting the survival status of IPF patients and is identified as an effective marker for prognosis and screening of IPF patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang and He.)

Background: Coronavirus disease 2019 (COVID-19) has been a public threat and healthcare concern caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. During the period of the pandemic of COVID-19, cancer patients should be paid more attention as more severe events are found in cancer patients infected with SARS-CoV-2. Basigin ( BSG ) is an essential factor for the infection and progression of COVID-19 and tumorigenesis of multiple tumors, which may serve as a novel target for the effective treatment against COVID-19 and multiple human cancers. Methods: A total of 19,020 samples from multiple centers were included in our research for the comprehensive investigation of the differences in BSG expression among human organs, cancer cells, cancer tissues, and normal tissues. Cox regression analysis and Kaplan-Meier curves were utilized to explore the prognosis factor of BSG in cancers. Correlation analyses were used to determine associations of BSG expression with tumor mutational burden, the immune microenvironment, etc. Gene set enrichment analysis was applied to explore the underlying mechanisms of BSG in cancers. Results: Compared with normal tissues, BSG expression was high in 13 types of cancers (cholangiocarcinoma, etc.) and low in colon adenocarcinoma and rectum adenocarcinoma. BSG expression was related to the prognosis of eight cancers (e.g., invasive breast carcinoma) ( p < 0.05). The gene also demonstrated a pronounced effect in identifying 12 cancers (cholangiocarcinoma, etc.) from their control samples (AUC >0.7). The BSG expression was associated with DNA methyltransferases, mismatch repair genes, immune infiltration levels, tumor mutational burden, microsatellite instability, neoantigen, and immune checkpoints, suggesting the potential of BSG as an exciting target for cancer treatment. BSG may play its role in several cancers by affecting several signaling pathways such as drug cytochrome metabolism P450 and JAK-STAT. Conclusion: BSG may be a novel biomarker for treating and identifying multiple human cancers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang and He.)

Programing self-assembly of naturally bioactive molecules has been a wide topic of great significance for biomedical uses. Despite the fact that plant-derived polyphenols with catechol or pyrogallol moieties have been widely studied to construct nanocomplexes or nanocoatings via self-polymerization, there is no report on the self-assembly of these polyphenols into therapeutic hydrogels for potential applications. Here, we reported that adding a very small amount of resveratrol (Res) into the gallic acid (GA) aqueous solution could trigger the quick self-assembly of GA to form a fibrous hydrogel within 5 min through hydrogen bonds and π-π interactions. The length of GA/Res (GR) fibrils in gels varied from 100 to 1000 microns, with a diameter of around 1 μm. Notably, these GR hydrogels showed excellent colloid stability, providing better slow release and outstanding biocompatibility. Also, in vivo experiments indicated the hydrogels had high antibacterial effects and excellent wound healing capabilities in a total skin defect model via regulating the expression of inflammatory factors ( IL -6, IL -1β, and TNF -α) due to the release of therapeutic agents (GA and Res) into the matrix. Overall, our results provide a new strategy to accelerate self-assembly of GA by adding Res to form hydrogels, which is further proved as a promising therapeutic carrier for wound healing.

We aimed to characterize NDM-5-producing Enterobacteriaceae from aquatic products in Guangzhou, China. A total of 196 intestinal samples of grass carp collected in 2019 were screened for carbapenemase genes. Characterization of bla NDM-5 positive isolates and plasmids was determined by antimicrobial susceptibility testing, conjugation experiments, Illumina HiSeq, and Nanopore sequencing. One Citrobacter freundii and six Escherichia coli strains recovered from seven intestinal samples were verified as bla NDM-5 carriers (3.57%, 7/196). The bla NDM-5 genes were located on the IncX3 ( n =5), IncHI2 ( n =1), or IncHI2-IncF ( n =1) plasmids. All bla NDM-5 -bearing plasmids were transferred by conjugation at frequencies of ~10 -4 -10 -6 . Based on sequence analysis, the IncHI2 plasmid pHNBYF33-1 was similar to other bla NDM-5 -carrying IncHI2 plasmids deposited in GenBank from Guangdong ducks. In all IncHI2 plasmids, bla NDM-5 was embedded in a novel transposon, Tn 7051 (IS 3000 -ΔIS Aba125 -IS 5 -ΔIS Aba125 - bla NDM-5 - ble MBL - trpF - tat -∆ dct -IS 26 -∆ umuD -∆IS Kox3 -IS 3000 ), which was identical to the genetic structure surrounding bla NDM-5 found in some IncX3 plasmids. The IncHI2-IncF hybrid plasmid pHNTH9F11-1 was formed by homologous recombination of the bla NDM-5 -carrying IncHI2 plasmid and a heavy-metal-resistant IncF plasmid through ∆Tn 1721 . To the best of our knowledge, this is the first report on the characterization of bla NDM-5 -bearing plasmids in fish in China. The IncHI2 plasmid pHNBYF33-1 may be transmitted from ducks, considering the common duck-fish freshwater aquaculture system in Guangdong. Tn 7051 is likely responsible for the transfer of bla NDM-5 from IncX3 to IncHI2 plasmids in Enterobacteriaceae , resulting in the expansion of transmission vectors of bla NDM-5 .

Melodicochinines A - D (1-4), four new monoterpene indole alkaloids (MIAs), along with 21 known ones, were isolated from the stems and twigs of Melodinus cochinchinensis. Their structures were elucidated on the basis of extensive spectroscopic analysis. A ubiquitin-rhodamine 110 assay showed that 11-methyloxytabersonine had potential inhibitory effect against ubiquitin-specific protease 7 (USP7)., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The widely used Air Quality Index (AQI) has been criticized due to its inaccuracy, leading to the development of the air quality health index (AQHI), an improvement on the AQI. However, there is currently no consensus on the most appropriate construction strategy for the AQHI., Objectives: In this study, we aimed to evaluate the utility of AQHIs constructed by different models and health outcomes, and determine a better strategy., Methods: Based on the daily time-series outpatient visits and hospital admissions from 299 hospitals (January 2016-December 2018), and mortality (January 2017-December 2019) in Guangzhou, China, we utilized cumulative risk index (CRI) method, Bayesian multi-pollutant weighted (BMW) model and standard method to construct AQHIs for different health outcomes. The effectiveness of AQHIs constructed by different strategies was evaluated by a two-stage validation analysis and examined their exposure-response relationships with the cause-specific morbidity and mortality., Results: Validation by different models showed that AQHI constructed with the BMW model (BMW-AQHI) had the strongest association with the health outcome either in the total population or subpopulation among air quality indexes, followed by AQHI constructed with the CRI method (CRI-AQHI), then common AQHI and AQI. Further validation by different health outcomes showed that AQHI constructed with the risk of outpatient visits generally exhibited the highest utility in presenting mortality and morbidity, followed by AQHI constructed with the risk of hospitalizations, then mortality-based AQHI and AQI. The contributions of NO 2 and O 3 to the final AQHI were prominent, while the contribution of SO 2 and PM 2.5 were relatively small., Conclusions: The BMW model is likely to be more effective for AQHI construction than CRI and standard methods. Based on the BMW model, the AQHI constructed with the outpatient data may be more effective in presenting short-term health risks associated with the co-exposure to air pollutants than the mortality-based AQHI and existing AQIs., (Copyright © 2021 Elsevier Inc. All rights reserved.)

With the most active users of any social media platform in China, WeChat has become the preferred platform for public announcements and is widely used in the fields of medicine and nursing (Hong, Zhou, Fang, & Shi, 2017; Zeng, Deng, Wang, & Liu, 2016). The aim of this study was to evaluate the effect of WeChat messaging on bowel preparation for outpatient colonoscopy. A total of 150 outpatients scheduled for colonoscopy in a Grade III level A hospital were randomly assigned to the experimental group (n = 73) or the control group (n = 72). Both groups received routine guidance from the day of the scheduling appointment through the day of colonoscopy. In addition, the experimental group received colonoscopy-related information and individualized guidance daily through WeChat from the day of the appointment. After the colonoscopy, the diet and medication compliance, satisfaction, anxiety, and bowel cleanliness were compared. Post-intervention, there were significant differences in bowel cleanliness, satisfaction, diet and medication compliance, and anxiety between the two groups. WeChat messaging can help improve diet and medication compliance, patient satisfaction, and the success rate and thoroughness of colonoscopy, as well as alleviate the anxiety of patients scheduled for outpatient colonoscopy., Competing Interests: The authors declare that there is no conflict of interest related to this work., (Copyright © 2022 Society of Gastroenterology Nurses and Associates.)

Background: Painful diabetic neuropathy (PDN) is a frequent and troublesome complication of diabetes, with little effective treatment. PDN is characterized by specific spinal microglia-mediated neuroinflammation. Insulin-like growth factor 1 (IGF-1) primarily derives from microglia in the brain and serves a vital role in averting the microglial transition into the proinflammatory M1 phenotype. Given that epigallocatechin-3-gallate (EGCG) is a potent anti-inflammatory agent that can regulate IGF-1 signaling, we speculated that EGCG administration might reduce spinal microglia-related neuroinflammation and combat the development of PDN through IGF-1/IGF1R signaling., Methods: Type 1 diabetes mellitus (T1DM) was established by a single intraperitoneal (i.p.) injection of streptozotocin (STZ) in mice. The protein expression level of IGF-1, its receptor IGF1R, interleukin 1 β (IL-1 β ), tumor necrosis factor- α (TNF- α ), and inducible nitric oxide synthase (iNOS) was determined by Western blot or immunofluorescence., Results: The spinal IGF-1 expression markedly decreased along with the presence of pain-like behaviors, the spinal genesis of neuroinflammation (increased IL-1 β , TNF- α , and Iba-1 + microglia), and the intensified M1 microglia polarization (increased iNOS + Iba-1 + microglia) in diabetic mice. IGF-1 could colocalize with neurons, astrocytes, and microglia, but only microglial IGF-1 was repressed in T1DM mice. Furthermore, we found that i.t. administration of mouse recombinant IGF-1 (rIGF-1) as well as i.t. or i.p. treatment with EGCG alleviated the diabetes-induced pain-like behaviors, reduced neuroinflammation (suppressed IL-1 β , TNF- α , and Iba-1 + microglia), prevented the M1 microglia polarization (less iNOS + Iba-1 + microglia), and restored the microglial IGF-1 expression., Conclusions: Our data highlighted the importance of maintaining spinal IGF-1 signaling in treating microglia-related neuroinflammation in PDN. This study also provides novel insights into the neuroprotective mechanisms of EGCG against neuropathic pain and neuroinflammation through IGF-1 signaling, indicating that this agent may be a promising treatment for PDN in the clinical setting., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Xin Chen et al.)

Scrub typhus is an acute infectious disease in humans. A temporal, spatial and epidemiologic study was conducted to understand the characteristics of scrub typhus in Yunnan, to assist public health prevention and control measures. Based on the data on all cases reported in Yunnan during 2006-2017, we characterized the epidemiological features. Spatio-temporal patterns and Q-type cluster method were adopted to analyze the incidence of scrub typhus in Yunnan. In total, 27,838 scrub typhus cases were reported in Yunnan during 2006-2017. Of these, 49.53% (13,787) were male and 50.47% (14,051) were female (P > 0.05). Most patients were farmers (71.70%) (P < 0.05) and children aged 0-5 years (13.16%) (P < 0.01), which accounted for 84.86% of the total cases. An almost 20-fold increase in the number of patients was observed in 2017 (6,337 cases) compared to 2006 (307 cases). Baoshan and Lincang had the most cases accounting for 41.94%, while Diqing had the lowest incidence (only 3 cases). Sixteen municipalities infected were classified into three groups numbered in sequence. The incidence of scrub typhus in Yunnan is high and the annual incidence increased noticeably over time. Our results also indicate that surveillance and public education need to be focused on Baoshan, Lincang and Dehong., (© 2022. The Author(s).)

Introducing a weak covalent bond into an originally highly fluorescent molecule to create a non-fluorescent probe is able to provide a new way to detect some nucleophilic targets with enhanced sensitivity. Herein, this is the first time that a tetraphenylethene (TPE)-based probe (TPEONO 2 ) bearing a p -nitrobenzenesulfonyl moiety for the sensing of F - ions in aqueous solution via a cleavage reaction of the sulfonyl ester bond to induce aggregation-induced emission (AIE) has been reported.

Dexmedetomidine is an α2 adrenoceptor agonist and has cardioprotective effect,the mechanism of which is being studied.Increasing studies have proved the clinical value of dexmedetomidine in reducing postoperative complications and improving the prognosis of patients.Therefore,this review summarizes the cardiac protection mechanism of dexmedetomidine based on the existing studies and expounds the application of dexmedetomidine in the perioperative period of cardiovascular surgery.

Stroke accounts for a large proportion of morbidity and mortality burden in China. Moreover, there is a high prevalence of the leading risk factors for stroke, including hypertension and smoking. Understanding the underlying mechanisms and developing effective therapeutic interventions for patients with stroke is a key imperative. The pathophysiology of stroke involves a complex interplay between the immune and inflammatory mechanisms. Focal brain inflammation triggered by neuronal cell death and the release of factors such as damage-associated molecular patterns can further exacerbate neuronal injury; in addition, impairment of the blood-brain barrier, oxidative stress, microvascular dysfunction, and brain edema cause secondary brain injury. Immune cells, including microglia and other infiltrating inflammatory cells, play a key role in triggering focal and global brain inflammation. Anti-inflammatory therapies targeting the aforementioned mechanisms can alleviate primary and secondary brain injury in the aftermath of a stroke. Further experimental and clinical studies are required to explore the beneficial effects of anti-inflammatory drugs in stroke., (© 2022 S. Karger AG, Basel.)

During the pandemic of the coronavirus disease 2019, there exist quite a few studies on angiotensin-converting enzyme 2 ( ACE2 ) and SARS-CoV-2 infection, while little is known about ACE2 in hepatocellular carcinoma (HCC). The detailed mechanism among ACE2 and HCC still remains unclear, which needs to be further investigated. In the current study with a total of 6,926 samples, ACE2 expression was downregulated in HCC compared with non-HCC samples (standardized mean difference = -0.41). With the area under the curve of summary receiver operating characteristic = 0.82, ACE2 expression showed a better ability to differentiate HCC from non-HCC. The mRNA expression of ACE2 was related to the age, alpha-fetoprotein levels and cirrhosis of HCC patients, and it was identified as a protected factor for HCC patients via Kaplan-Meier survival, Cox regression analyses. The potential molecular mechanism of ACE2 may be relevant to catabolic and cell division. In all, decreasing ACE2 expression can be seen in HCC, and its protective role for HCC patients and underlying mechanisms were explored in the study.