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Objective: The inflammatory response is integral to all stages of ischemic stroke. Unlike conventional reperfusion therapies, anti-inflammatory strategies offer a broader therapeutic window for treating ischemic stroke due to their capacity to attenuate inflammation. Astrocytes, once activated in ischemic conditions, significantly contribute to the production of inflammatory cytokines and exacerbate brain damage. While the neuroprotective effects of baicalin in post-stroke patients have been recognized, its role in modulating astrocyte activity and reducing inflammation remains under debate. This study aims to evaluate the impact of baicalin on astrocyte activation following ischemic stroke., Methods: A model of ischemia/reperfusion (I/R) injury was induced in wild-type mice through transient middle cerebral artery occlusion (tMCAO). Mice were randomized into groups receiving either baicalin or saline. The expression levels of inflammatory markers-interleukin (IL)-6, IL-1β, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-alpha (TNF-α)-were quantified using enzyme-linked immunosorbent assay (ELISA). Additionally, western blot analysis was employed to assess glial fibrillary acidic protein (GFAP) expression., Results: Baicalin administration significantly mitigated neurological deficits in mice post-tMCAO. It reduced the activation of astrocytes and the production of pro-inflammatory cytokines such as IL-6, IL-1β, TNF-α, and MCP-1, observed both in vivo and in vitro. In vitro studies also indicated a suppression of NF-κB activation., Conclusion: Baicalin effectively prevents ischemic brain damage by curtailing neuroinflammation and astrocyte activation. These findings advance the understanding of baicalin's mechanistic role in mitigating brain ischemia and support further investigation into its therapeutic potential., 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 © 2025 Elsevier B.V. All rights reserved.)

Parkinson's disease is the second most common neurodegenerative disease, characterized by substantial loss of dopaminergic (DA) neurons, the formation of Lewy bodies (LBs) in the substantia nigra, and pronounced neuroinflammation. The nucleotide-binding domain like leucine-rich repeat- and pyrin domain-containing protein 3 (NLRP3) inflammasome is one of the pattern recognition receptors (PRRs) that function as intracellular sensors in response to both pathogenic microbes and sterile triggers associated with Parkinson's disease. These triggers include reactive oxygen species (ROS), misfolding protein aggregation, and potassium ion (K + ) efflux. Upon activation, it recruits and activates caspase-1, then processes the pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18, which mediate neuroinflammation in Parkinson's disease. In this review, we provide a comprehensive overview of NLRP3 inflammasome, detailing its structure, activation pathways, and the factors that trigger its activation. We also explore the pathological mechanisms by which NLRP3 contributes to Parkinson's disease and discuss potential strategies for targeting NLRP3 as a therapeutic approach., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of this review., (Copyright © 2025. Published by Elsevier Inc.)

Background: Lung adenocarcinoma (LUAD) is a sub-type of non-small cell lung cancer (NSCLC) that is often associated with genetic alterations, including the Kirsten rat sarcoma viral oncogene homolog ( KRAS ) mutation. The KRAS mutation is particularly challenging to treat due to resistance to targeted therapies. This study aims to develop a predictive model for the KRAS mutation in patients with LUAD by integrating clinical, dual-energy spectral computed tomography (DESCT), and radiomics features., Methods: A total of 172 patients with LUAD were retrospectively enrolled and divided into a developing cohort (n=120) and a validation cohort (n=52). Clinical, DESCT and radiomics features were extracted and analyzed. Four predictive models were constructed: clinical, DESCT, radiomics, and combined clinical-DESCT-radiomics (C-S-R) model. The performance of these models was evaluated by the receiver operating characteristic curves. A nomogram incorporating clinical, DESCT, radiomics features with R-score was developed in the validation cohort., Results: In this study, 8.7% (15/172) of the patients showed KRAS mutation. The C-S-R model demonstrated the best performance, with an area under the curve (AUC) of 0.92 in the developing cohort and 0.87 in the validation cohort. The C-S-R model was not superior to radiomics model (P=0.28), but it was significantly better than DESCT model (P=0.01)., Conclusions: This study suggests that integrating clinical, DESCT, and radiomics features can enhance the prediction of KRAS mutation in patients with LUAD., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-694/coif). Y.M.W. is an employee of GE Healthcare China company. The other authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Objective To reveal the spatial distribution patterns of key pollutants in the Huaihe River Basin and quantify the risks and burdens of non-gastrointestinal cancers by the grade of pollution,providing targets and data support for enhanced management of water pollution in the Huaihe River Basin. Methods Surface water quality data of the Huaihe River Basin were obtained from the National Surface Water Environmental Quality Monitoring Network(2021).Incidence data of seven cancers were extracted from the 2019 Annual Report of the China Cancer Registry.Random forest and SHapley Additive exPlanations were employed to select key pollutants,and pollution was graded based on the spatial analysis of the Huaihe River Basin.The cancer risks and population attributable fractions were calculated under pollution grades. Results Five key pollutants linked to cancers were identified,including total nitrogen,total phosphorus,chemical oxygen demand,biochemical oxygen demand after 5 days,and arsenic.Pollution was graded into three levels regarding the combined effects of pollutants.Compared with the low pollution areas,high pollution areas showed increased risks of lung cancer( RR =1.26,95% CI :1.06-1.50),breast cancer(female)( RR =1.46,95% CI :1.21-1.77),pancreatic cancer( RR =1.46,95% CI :1.06-2.01),brain cancer( RR =1.44,95% CI :1.05-1.98),and gallbladder cancer( RR =1.60,95% CI :1.03-2.50).The grade of pollution contributed to more than 5% of cases for most cancers above. Conclusions The potential cancer risks and burdens attributed to surface water pollution cannot be overlooked.Addressing this challenge necessitates close collaboration of various stakeholders to strengthen policy development,enhance environmental governance,and implement public health interventions.

Background: Cognitive dysfunction is the most severe non-motor symptom of Parkinson's disease (PD). Our previous study revealed that hydrogen sulfide (H 2 S) ameliorates cognitive dysfunction in PD, but the underlying mechanisms remain unclear. Hippocampal necroptosis plays a vital role in cognitive dysfunction, while the cGAS/STING pathway triggers necroptosis. To understand the mechanism underlying the inhibitory role of H 2 S in cognitive dysfunction of PD, we explored whether H 2 S reduces the enhancement of necroptosis and the activation of the cGAS/STING pathway in the hippocampus of the rotenone (ROT)-induced PD rat model., Method: Adult Sprague-Dawley (SD) rats were pre-treated with NaHS (30 or 100 μmol/kg/d, i.p.) for 7 days and then co-treated with ROT (2 mg/kg/d, s.i.) for 35 days. The Y-maze and Morris water maze (MWM) tests were used to assess the cognitive function. Hematoxylin-eosin (H&E) staining was used to detect the hippocampal pathological morphology. Western blotting analysis was used to measure the expressions of proteins. Enzyme-linked immunosorbent assay was used to determine the levels of inflammatory factors., Result: NaHS (a donor of H 2 S) mitigated cognitive dysfunction in ROT-exposed rats, according to the Y-maze and MWM tests. NaHS treatment also markedly down-regulated the expressions of necroptosis-related proteins (RIPK1, RIPK3, and MLKL) and decreased the levels of necroptosis-related inflammatory factors (IL-6 and IL-1β) in the hippocampus of ROT-exposed rats. Furthermore, NaHS treatment reduced the expressions of cGAS/STING pathway-related proteins (cGAS, STING, p-TBK1 Ser172 , p-IRF3 Ser396 , and p-P65 Ser536 ) and decreased the contents of pro-inflammation factors (INF-β and TNF-α) in the hippocampus of ROT-exposed rats., Conclusion: H 2 S attenuates the cGAS/STING pathway-triggered necroptosis in the hippocampus, which is related to H 2 S to attenuate cognitive dysfunction in PD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Our previous studies have reported that hydrogen sulfide (H 2 S) has ability to improve diabetes-associated cognitive dysfunction (DACD), but the exact mechanisms remain unknown. Recent research reveals that Warburg effect is associated with synaptic plasticity which plays a key role in cognition promotion. Herein, the present study was aimed to demonstrate whether hippocampal Warburg effect contributes to H 2 S-ameliorated DACD and further explore its potential mechanism. We found that H 2 S promoted the hippocampal Warburg effect and inhibited the OxPhos in the hippocampus of STZ-induced diabetic rats. It also improved the hippocampal synaptic plasticity in STZ-induced diabetic rats, as evidenced by the change of microstructures and the expression of different key-enzymes. Furthermore, inhibited hippocampal Warburg effect induced by DCA markedly abolished the improvement of H 2 S on synaptic plasticity in the hippocampus of STZ-induced diabetic rats. DCA blocked H 2 S-attenuated the cognitive dysfunction in STZ-induced diabetic rats, according to the Y-maze, Novel Objective Recognition, and Morris Water Maze tests. Collectively, these findings indicated that the hippocampal Warburg effect mediates H 2 S-ameliorated DACD by improving hippocampal synaptic plasticity., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Histone modifications (HMs) play various roles in growth, development, and resistance to abiotic stress. However, HMs have been systematically identified in a few plants, and identification of HMs in medicinal plants is very rare. Aquilaria sinensis is a typical stress-induced medicinal plant, in which HMs remain unexplored. We conducted a comprehensive study to identify HMs and obtained 123 HMs. To conduct evolutionary analysis, we constructed phylogenetic trees and analyzed gene structures. To conduct functional analysis, we performed promoter, GO, and KEGG analyses and ortholog analyses against AtHMs. Based on the expression profiles of different tissues and different layers of Agar-Wit, some HMs of A. sinensis (AsHMs) were predicted to be involved in the formation of agarwood, and their response to MeJA and NaCl stress was tested by qRT-PCR analysis. By analyzing the enrichment of H3K4me3, H3K27me3, and H4K5ac in the promoter regions of two key sesquiterpene synthase genes, AsTPS13/18, we hypothesized that AsHMs play important roles in the synthesis of agarwood sesquiterpenes. We confirmed this hypothesis by conducting RNAi transgenic interference experiments. This study provided valuable information and important biological theories for studying epigenetic regulation in the formation of agarwood. It also provided a framework for conducting further studies on the biological functions of HMs., Competing Interests: Declaration of competing interest There are no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Ingestion of perfluoroalkyl acids (PFAAs) via contaminated food contact materials (FCMs) is an important human exposure source. This study adopts a toxicity equivalent approach to evaluate the collective health risk of multiple PFAAs in FCMs. A comprehensive extraction and analysis of 21 PFAAs in FCMs was performed. Among the analyzed substances, 15 PFAAs were detected. Migration experiment using three food simulants revealed the migration range of seven PFAAs from FCMs into the simulant to be 0.47-46.7 ng/cm 2 . The hazard quotient results suggest minimal health risk, except for 9% of packaged samples where perfluorooctanoic acid (PFOA) poses a higher risk. Utilizing PFOA toxic equivalent concentrations, comprehensive risk calculations showed ∼77% of samples potentially posing elevated health risks due to PFAA exposure. This emphasizes the substantial contribution of PFAAs beyond PFOA and underscores the importance of considering them in related assessments. The aggregated risk assessment reflects actual exposure circumstances more accurately., (© 2024 Institute of Food Technologists.)

In their letter-to-the-editor entitled "Letter to the Editor: Incidence rate of occult lymph node metastasis in clinical T 1 - 2 N 0 M 0 small cell lung cancer patients and radiomic prediction based on contrast-enhanced CT imaging: a multicenter study", Prof. Chen et al. provided insightful comments and suggestions on our original study. We appreciate the authors' feedback and have conducted a preliminary exploration of the predictive value of serum tumor markers (TMs) for occult lymph node metastasis (OLM) in clinical T 1 - 2 N 0 M 0 (cT 1 - 2 N 0 M 0 ) small cell lung cancer (SCLC) patients. The results indicate that neuron-specific enolase (NSE), carbohydrate antigen 125 (CA125), and squamous cell carcinoma antigen (SCC) have potential predictive value for detecting OLM in cT 1 - 2 N 0 M 0 SCLC patients. Additionally, further exploration and confirmation through prospective, large-scale studies with robust external validation are needed., (© 2024. The Author(s).)

Background: Research has demonstrated that radiomics models are capable of forecasting the characteristics of lung cancer. Nevertheless, due to radiomics' poor interpretability, its applicability in clinical settings remains restricted. This investigation sought to verify the correlation between radiomics features (RFs) and the biological behavior of clinical stage IA adenocarcinomas., Methods: A retrospective analysis was conducted on patients diagnosed with clinical stage IA lung adenocarcinoma who underwent resection between May 2005 and December 2018. Detailed radiomics examination of the primary tumor was carried out utilizing preoperative computed tomography (CT) images. Subsequently, patients were grouped based on their RFs using consensus clustering, enabling comparison of tumor biological characteristics among the clusters. Survival disparities among the clusters were evaluated through Kaplan-Meier and Cox analyses., Results: A consensus cluster analysis was performed on 669 patients [median age, 58 years; interquartile range (IQR), 50-64 years, 257 males, 412 females], and three distinct clusters were identified. Cluster 2 was associated with radiological solid adenocarcinoma [119 of 324 (36.7%), P<0.001], larger tumors with median tumor size of 2.1 cm with IQR of 1.7 to 2.5 cm (P<0.001), central tumor [91 of 324 (28.1%), P=0.002], pleural invasion [87 of 324 (26.9%), P<0.001], occult lymph node metastasis (ONM) [106 of 324 (32.7%), P<0.001], and a higher frequency of metastasis or recurrence [62 of 324 (19.1%), P<0.001]. The frequency of histological grade 3 was the highest in Cluster 3 [8 of 34 (23.5%), P<0.001]. Cluster 1 was associated with pure ground glass nodules (pGGNs) [184 of 310 (59.4%), P<0.001], smaller tumors with median tumor size of 1.1 cm with IQR of 0.8 to 1.4 cm (P<0.001), no pleural invasion [276 of 310 (89.0%), P<0.001], histological grade 1 [114 of 248 (46.0%), P<0.001], ONM negative [292 of 310 (94.2%), P<0.001], and a lower rate of metastasis or recurrence [298 of 310 (96.1%), P<0.001]., Conclusions: Differences in tumor biological behavior were detected among consensus clusters based on the RFs of clinical stage IA adenocarcinoma., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-283/coif). The authors have no conflicts of interest to declare., (2024 Translational Lung Cancer Research. All rights reserved.)

In recent years, the prevalence and danger of organophosphorus flame retardants (OPFRs) have drawn attention from all around the world. This study examined twenty-five OPFRs observed in water and sediment samples from the Qiantang River in eastern China, as well as their occurrence, spatial distribution, possible origins, and ecological hazards. All the 25 OPFRs were detected in water and sediment samples. The levels of Σ 25 OPFRs in water and sediment were 35.5-192 ng/L and 8.84-48.5 ng/g dw, respectively. Chlorinated OPFRs were the main contributions in water, whereas alkyl-OPFRs were the most common congeners found in sediment. Spatial analysis revealed that sample locations in neighboring cities had somewhat higher water concentrations of OPFRs. Slowing down the river current and making the reservoir the main sink of OPFRs, the dam can prevent OPFRs from moving via the Qiantang River. Positive matrix factorization indicated that plasticizer in polyvinyl chloride, polyester resins, and polyurethane foam made the greatest contributions in water, whereas polyurethane foam and textile were the predominant source in sediment. Analysis of sediment-water exchange of OPFRs showed that twelve OPFRs in sediments can re-enter into the water body. The risk quotients showed the ecological risk was low to medium, but trixylyl phosphate exposures posed high ecological risk to aquatic organisms., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Human pharyngeal squamous cell carcinoma (HPSCC) is the most common malignancy in the head and neck region, characterized by high mortality and a propensity for metastasis. Fucoxanthin, a carotenoid isolated from brown algae, exhibits pharmacological properties associated with the suppression of tumor proliferation and metastasis. Nevertheless, its potential to inhibit HPSCC proliferation and metastasis has not been fully elucidated. This study represents the first exploration of the inhibitory effects of fucoxanthin on two human pharyngeal squamous carcinoma cell lines (FaDu and Detroit 562), as well as the mechanisms underlying those effects. The results showed dose-dependent decreases in the proliferation, migration, and invasion of HPSCC cells after fucoxanthin treatment. Further studies indicated that fucoxanthin caused a significant reduction in the expression levels of proteins in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway, as well as the downstream proteins matrix metalloproteinase (MMP)-2 and MMP-9. Specific activators of PI3K/AKT reversed the effects of fucoxanthin on these proteins, as well as on cell proliferation and metastasis, in FaDu and Detroit 562 cells. Molecular docking assays confirmed that fucoxanthin strongly interacted with PI3K, AKT, mTOR, MMP-2, and MMP-9. Overall, fucoxanthin, a functional food component, is a potential therapeutic agent for HPSCC.

Three Stemona alkaloids named stemotuberines A-C (1-3) with unique C 17 N frameworks, presumably formed by elimination of the C-11-C-15 lactone ring of the stichoneurine skeleton, were isolated from the roots of Stemona tuberosa. Their structures were elucidated by spectroscopic analysis, X-ray diffraction, and computational methods. Compounds 2 and 3 showed inhibition (IC 50 values of 37.1 and 23.2 μM, respectively) against LPS-induced nitric oxide production in RAW 264.7 cells. In addition, concern was expressed about the reported plant origin (S. sessilifolia) of the recently described alkaloids tuberostemonols O-R (4-7), which should be S. tuberosa. NMR calculations indicated structural misassignment of these compounds except for 6. Isolation of tuberostemonol P (5) from our material of S. tuberosa allowed for a close examination of the spectroscopic data leading to the revised structure 5a. Tuberostemonol R (7) was found to have identical 1 H and 13 C NMR data to the well-known alkaloid croomine, and therefore its structure including relative stereochemistry must be revised as 7a., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: This study aimed to explore the incidence of occult lymph node metastasis (OLM) in clinical T 1 - 2 N 0 M 0 (cT 1 - 2 N 0 M 0 ) small cell lung cancer (SCLC) patients and develop machine learning prediction models using preoperative intratumoral and peritumoral contrast-enhanced CT-based radiomic data., Methods: By conducting a retrospective analysis involving 242 eligible patients from 4 centeres, we determined the incidence of OLM in cT 1 - 2 N 0 M 0 SCLC patients. For each lesion, two ROIs were defined using the gross tumour volume (GTV) and peritumoral volume 15 mm around the tumour (PTV). By extracting a comprehensive set of 1595 enhanced CT-based radiomic features individually from the GTV and PTV, five models were constucted and we rigorously evaluated the model performance using various metrics, including the area under the curve (AUC), accuracy, sensitivity, specificity, calibration curve, and decision curve analysis (DCA). For enhanced clinical applicability, we formulated a nomogram that integrates clinical parameters and the rad&#95;score (GTV and PTV)., Results: The initial investigation revealed a 33.9% OLM positivity rate in cT 1 - 2 N 0 M 0 SCLC patients. Our combined model, which incorporates three radiomic features from the GTV and PTV, along with two clinical parameters (smoking status and shape), exhibited robust predictive capabilities. With a peak AUC value of 0.772 in the external validation cohort, the model outperformed the alternative models. The nomogram significantly enhanced diagnostic precision for radiologists and added substantial value to the clinical decision-making process for cT 1 - 2 N 0 M 0 SCLC patients., Conclusions: The incidence of OLM in SCLC patients surpassed that in non-small cell lung cancer patients. The combined model demonstrated a notable generalization effect, effectively distinguishing between positive and negative OLMs in a noninvasive manner, thereby guiding individualized clinical decisions for patients with cT 1 - 2 N 0 M 0 SCLC., (© 2024. The Author(s).)

Corticosterone (CORT) damages hippocampal neurons as well as induces neuroinflammation. The tricarboxylic acid cycle metabolite itaconate has an anti-inflammatory role. Necroptosis is a form of programmed cell death, also known as inflammatory cell death. Menin is a multifunctional scaffold protein, which deficiency aggravates neuroinflammation. In this study, we explored whether itaconate inhibits CORT-induced neuroinflammation as well as necroptosis and further investigated the mediatory role of Menin in this protective effect of itaconate by using an exposure of CORT to HT22 cells (a hippocampal neuronal cell line). The viability of HT22 cells was examined by the cell counting kit 8 (CCK-8). The morphology of HT22 cells was observed by transmission electron microscope (TEM). The expressions of necroptosis-related proteins (p-RIP1/RIP1, p-RIP3/RIP3, and p-MLKL/MLKL) were evaluated by western blotting. The contents of inflammatory factors were detected by an enzyme-linked immunosorbent assay (ELISA) kit. Our results showed that CORT increases the contents of pro-inflammatory factors (IL-1β, TNF-α) as well as decreases the contents of anti-inflammatory factors (IL-4, IL-10) in HT22 cells. We also found that CORT increases the expressions of necroptosis-related proteins (p-RIP1/RIP1, p-RIP3/RIP3, and p-MLKL/MLKL) and decreases the cell viability in HT22 cells, indicating that CORT induces necroptosis in HT22 cells. Itaconate improves CORT-induced neuroinflammation and necroptosis. Furthermore, itaconate upregulates the expression of Menin in CORT-exposed HT22 cells. Importantly, silencing Menin abolishes the antagonistic effect of itaconate on CORT-induced necroptosis and neuroinflammation. In brief, these results indicated that itaconate protects HT22 cells against CORT-induced neuroinflammation and necroptosis via upregulating Menin., (© 2024. The Author(s) under exclusive licence to University of Navarra.)

Background: Accurate prediction of occult lymph node metastasis (ONM) is an important basis for determining whether lymph node (LN) dissection is necessary in clinical stage IA lung adenocarcinoma patients. The aim of this study is to determine the best machine learning algorithm for radiomics modeling and to compare the performances of the radiomics model, the clinical-radilogical model and the combined model incorporate both radiomics features and clinical-radilogical features in preoperatively predicting ONM in clinical stage IA lung adenocarcinoma patients., Methods: Patients with clinical stage IA lung adenocarcinoma undergoing curative surgery from one institution were retrospectively recruited and assigned to training and test cohorts. Radiomics features were extracted from the preoperative computed tomography (CT) images of the primary tumor. Seven machine learning algorithms were used to construct radiomics models, and the model with the best performance, evaluated using the area under the curve (AUC), was selected. Univariate and multivariate logistic regression analyses were performed on the clinical-radiological features to identify statistically significant features and to develop a clinical model. The optimal radiomics and clinical models were integrated to build a combined model, and its predictive performance was assessed using receiver operating characteristic curves, Brier score, and decision curve analysis (DCA)., Results: This study included 258 patients who underwent resection (training cohort, n=182; test cohort, n=76). Six radiomics features were identified. Among the seven machine learning algorithms, extreme gradient boosting (XGB) demonstrated the highest performance for radiomics modeling, with an AUC of 0.917. The combined model improved the AUC to 0.933 and achieved a Brier score of 0.092. DCA revealed that the combined model had optimal clinical efficacy., Conclusions: The superior performance of the combined model, based on XGB algorithm in predicting ONM in patients with clinical stage IA lung adenocarcinoma, might aid surgeons in deciding whether to conduct mediastinal LN dissection and contribute to improve patients' prognosis., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1578/coif). Y.M.W. is an employee of GE HealthCare China, Pudong New Town, Shanghai, China. The other authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Objective: Understanding HPV vaccination willingness and its influencing factors among female sex workers (FSWs) in entertainment venues in an urban area of Guangxi, China., Methods: From 15 August to 15 October 2022, FSWs in entertainment venues with commercial sex trade in an urban area of Guangxi were selected as the study subjects for the questionnaire survey using the method of intentional sampling. The questionnaire based on the information-motivation-behavior (IMB) skills model was used to collect the basic characteristics, HPV and HPV vaccine-related information and cognition, motivation to vaccinate, behavioral skills and willingness to vaccinate from the research targets. A multifactor logistic regression model was used to analyze the factors influencing the research targets' willingness to receive HPV vaccination., Results: Of the 921 research targets, 712 (77.31%) were willing to receive HPV vaccination. The higher the level of knowledge regarding HPV and HPV vaccine-related information, the higher the motivation for HPV vaccination. In addition, the higher the behavioral skills score, the higher the willingness of FSWs in entertainment venues to receive HPV vaccination (P<0.001). FSWs in entertainment venues with lower venue grades [OR(95% CI)=0.693 (0.539, 0.891), P=0.004] were more reluctant to receive HPV vaccination. Those who favored the effectiveness of the vaccine in preventing the disease [OR(95% CI)=2.144 (1.449, 3.174), P<0.001] and those who had heard of HPV vaccine [OR(95% CI)=2.105 (1.451, 3.054), P<0.001], were able to perceive the benefits of HPV vaccination [OR(95% CI)=1.134 (1.045, 1.230), P=0.002]. These individuals acquired greater behavioral skills i.e., self-decision making for HPV vaccination [OR(95% CI)=1.130 (1.008, 1.267), P=0.036] and self-efficacy [OR(95% CI)=1.135 (1.081, 1.191), P<0.001] and they were more willing to receive HPV vaccine., Conclusions: There was a relatively high HPV vaccination willingness among FSWs in entertainment venues in an urban area of Guangxi, China. Attention should be focused on introducing the benefits of primary prevention measures such as the HPV vaccine for individuals and behavioral skills for HPV vaccination in order to increase their willingness to be vaccinated thus increasing their HPV vaccination rate., (© 2024. The Author(s).)

Objectives: Patients with epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma (LUAD) can benefit from individualized targeted therapy. This study aims to develop, compare, analyse prediction models based on dual-energy spectral computed tomography (DESCT) and CT-based radiomic features to non-invasively predict EGFR mutation status in LUAD., Materials and Methods: Patients with LUAD (n = 175), including 111 patients with and 64 patients without EGFR mutations, were enrolled in the current study. All patients were randomly divided into a training dataset (122 cases) and validation dataset (53 cases) at a ratio of 7:3. After extracting CT-based radiomic, DESCT and clinical features, we built seven prediction models and a nomogram of the best prediction. Receiver operating characteristic (ROC) curves and the mean area under the curve (AUC) values were used for comparisons among the models to obtain the best prediction model for predicting EGFR mutations., Results: The best distinguishing ability is the combined model incorporating radiomic, DESCT and clinical features for predicting the EGFR mutation status with an AUC of 0.86 (95 % CI: 0.79-0.92) in the training group and an AUC value of 0.83 (95 % CI: 0.73, 0.96) in the validation group., Conclusions: Our study provides a predictive nomogram non-invasively with a combination of CT-based radiomic, DESCT and clinical features, which can provide image-based biological information for targeted therapy of LUAD with EGFR mutations., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

To evaluate the efficacy of one-step acellular dermis combined with autologous split thickness skin grafting in the treatment of burn or trauma wounds by a multicenter controlled study. In patients with extensive burns, it is even difficult to repair the wounds due to the shortage of autologous skin. The traditional skin grafting method has the disadvantages of large damage to the donor site, insufficient skin source and unsatisfactory appearance, wear resistance and elasticity of the wound tissue after skin grafting. One-step acellular dermis combined with autologous ultra-thin split thickness skin graft can achieve better healing effect in the treatment of burn and trauma wounds. A total of 1208 patients who underwent single-layer skin grafting and one-step composite skin grafting in the First Affiliated Hospital of Wannan Medical College, Wuhan Third People's Hospital and Lu 'an People's Hospital from 2019 to 2022 were retrospectively analysed. The total hospitalization cost, total operation cost, hospitalization days after surgery, wound healing rate after 1 week of skin grafting and scar follow-up at 6 months after discharge were compared and studied. The total cost of hospitalization and operation in the composite skin grafting group was significantly higher than those in the single-layer autologous skin grafting group. The wound healing rate after 1 week of skin grafting and the VSS score of scar in the follow-up of 6 months after discharge were better than those in the single-layer skin grafting group. One-step acellular dermis combined with autologous ultra-thin split thickness skin graft has high wound healing rate, less scar, smooth appearance and good elasticity in repairing burn and trauma wounds, which can provide an ideal repair method for wounds., (© 2023 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Background: We previously revealed that hydrogen sulfide (H 2 S) attenuates chronic stress-induced cognitive impairment, but the underlying mechanism needs to be further clarified. Growth differentiation factor 11 (GDF11) plays an important regulatory role in cognitive function and that hippocampal NLRP3/caspase-1-mediated pyroptosis contributes to the pathogenesis of cognitive impairment. Hence, this research aimed to explore whether promoting GDF11 levels and suppressing hippocampal NLRP3/caspase-1-mediated pyroptosis mediate H 2 S to alleviate chronic stress-induced cognitive impairment., Methods: Sprague-Dawley rats were subjected to unpredictable chronic mild stress lasting four weeks to establish an animal model of chronic stress-induced cognitive impairment. Behavioral performance was assessed by the Y-maze test and the novel object recognition test. The expression levels of proteins were analyzed by Western blot analysis. The levels of IL-1β and IL-18 in the hippocampus were measured by ELISA., Results: NaHS upregulated the expression of GDF11 in the hippocampus of chronic unpredictable mild stress (CUMS)-exposed rats. Silencing GDF11 blocked NaHS-improved cognitive impairment in CUMS-exposed rats, according to the Y-maze test and the novel object recognition test. Furthermore, NaHS mitigated NLRP3/caspase-1-mediated pyroptosis in the hippocampus of CUMS-exposed rats and this effect was reversed by silencing GDF11. Moreover, overexpression of GDF11 alleviated CUMS-induced cognitive impairment and NLRP3/caspase-1-mediated hippocampal pyroptosis., Conclusions: GDF11 mediates H 2 S to attenuate chronic stress-induced cognitive impairment via inhibiting hippocampal NLRP3/caspase-1-mediated pyroptosis., Competing Interests: Declaration of competing interest The authors declare that there are no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Antifouling biocides may cause adverse effects on non-target species. This study aims to determine the distribution, sources, and ecological risks of antifouling biocides in the surface waters of the Qiantang River and its estuary in eastern China. The concentrations of total antifouling biocides were ranged from 12.9 to 215 ng/L for all water samples. Atrazine, diuron and tributyltin were the major compounds in the water bodies of the study area. The acute and chronic toxicity criteria for tributyltin, diuron and atrazine were derived for freshwater and saltwater, respectively, based on the species sensitivity distribution approach. The freshwater and saltwater criteria were slightly different, and the toxicity to aquatic organisms could be summarized as tributyltin > diuron > atrazine. The graded ecological risk rating showed that the long-term risk of TBT was significant in coastal waters. The pollution of TBT in the Qiantang River deserves further attention., 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.)

Objective To compare the surgical safety of elderly hospitalized patients in different age groups undergoing general surgery,and provide references for preoperative evaluation and treatment decision-making.Methods The inpatients ≥ 60 years old in the department of general surgery were selected from a national multi-center survey conducted from January to June in 2015 and from January to June in 2016.The patient characteristics and postoperative outcomes were described,and the risk factors for adverse postoperative outcomes of patients in different age groups were explored.Results The elderly patients (≥75 years old) accounted for 17.33%.The non-elderly patient (< 75 years old) group and the elderly patient (≥75 years old) group had significant differences in the proportions of patients with three or more chronical diseases (13.18% vs .5.36%, P <0.001),emergency surgery (16.64% vs .7.62%, P <0.001),American Society of Anesthesiologists score≥3 (48.68% vs .27.28%, P <0.001),and postoperative return to the intensive care unit(33.64% vs .12.00%, P <0.001).The occurrence of postoperative infectious complications showed no significant difference between the two age groups (7.29% vs .6.40%, P =0.410),while severe complications differed between the two groups (6.51% vs .2.60%, P <0.001).Besides,emergency surgery was a common independent risk factor for the two age groups.Conclusions Advanced age is not a contraindication to surgery of elderly patients.With consideration to patient's physical conditions and available surgical resources,elderly patients can still benefit from surgery.

Multidrug-resistant tuberculosis (MDR-TB) has become one of the major challenges in the global tuberculosis (TB) control.Despite years of efforts on MDR-TB control,the treatment success rates in China have increased slowly,which indicates possible deficiencies in the management of prevention and control work.Therefore,it is necessary to analyze the current status of MDR-TB prevention and treatment based on the patient pathway.This review summarizes the current drop-out situation of MDR-TB patients in the diagnosis and treatment pathway and the factors affecting patients' outcomes in the whole pathway,so as to provide a scientific reference for the prevention and control of MDR-TB.

Superconductivity in the cuprates is found to be intertwined with charge and spin density waves. Determining the interactions between the different types of order is crucial for understanding these important materials. Here, we elucidate the role of the charge density wave (CDW) in the prototypical cuprate La 1.885 Sr 0.115 CuO 4 , by studying the effects of large magnetic fields (H) up to 24 Tesla. At low temperatures (T), the observed CDW peaks reveal two distinct regions in the material: a majority phase with short-range CDW coexisting with superconductivity, and a minority phase with longer-range CDW coexisting with static spin density wave (SDW). With increasing magnetic field, the CDW first grows smoothly in a manner similar to the SDW. However, at high fields we discover a sudden increase in the CDW amplitude upon entering the vortex-liquid state. Our results signify strong coupling of the CDW to mobile superconducting vortices and link enhanced CDW amplitude with local superconducting pairing across the H - T phase diagram., (© 2023. The Author(s).)

Objectives: Our previous study has demonstrated that hydrogen sulfide (H 2 S), a novel gasotransmitter, attenuates excessive autophagy and depressive-like behaviors in chronic restraint stress (CRS)-exposed rats, but the underlying molecular mechanism remains to be elucidated. Silent information regulator 1 (SIRT1), a deacetylase at the consumption of NAD+ plays an important regulatory role in depression. Hence, this study aimed to investigate whether SIRT1 mediates the protective effect of H 2 S on CRS-induced depressive-like behaviors by regulating hippocampal autophagy., Methods: Adult male Sprague-Dawley (SD) rats were subjected to CRS (6 h × 28 days) to induce depression-like behavior. Rats were injected with sodium hydrosulfate (NaHS, 100 μmol/kg/d, i.p.), as a donor of H 2 S, alone or in combination with Sirtinol (a SIRT1 inhibitor; 10 nmol, i.c.v.) during CRS process. The depression-like characteristics of rats were assessed by the novelty-suppressed feeding test (NSFT), tail suspension test (TST), forced swimming test (FST) and open field test (OFT). The number of hippocampal autophagosomes was detected by transmission electron microscopy. The expressions of hippocampal autophagy-related proteins were measured by western blotting analysis., Results: Sirtinol blocked the inhibitory effect of H 2 S on depressive-like behaviors in CRS-exposed rats according to NSFT, TST, FST and OFT. In addition, sirtinol reversed the protective response of H 2 S to CRS-induced excessive autophagy, as proved by the increases in the number of autophagosomes and the expression of Beclin-1 as well as a decrease in the expression of P62 in the hippocampus., Conclusion: These results indicated that SIRT1 contributes to the antidepressant-like function of H 2 S during CRS via reducing hippocampal autophagy., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that caused a global outbreak of coronavirus disease 2019 (COVID-19) pandemic. To elucidate the mechanism of SARS-CoV-2 replication and immunogenicity, we performed a comparative transcriptome profile of mRNA and long non-coding RNAs (lncRNAs) in human lung epithelial cells infected with the SARS-CoV-2 wild-type strain (8X) and the variant with a 12-bp deletion in the E gene (F8). In total, 3,966 differentially expressed genes (DEGs) and 110 differentially expressed lncRNA (DE-lncRNA) candidates were identified. Of these, 94 DEGs and 32 DE-lncRNAs were found between samples infected with F8 and 8X. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyzes revealed that pathways such as the TNF signaling pathway and viral protein interaction with cytokine and cytokine receptor were involved. Furthermore, we constructed a lncRNA-protein-coding gene co-expression interaction network. The KEGG analysis of the co-expressed genes showed that these differentially expressed lncRNAs were enriched in pathways related to the immune response, which might explain the different replication and immunogenicity properties of the 8X and F8 strains. These results provide a useful resource for studying the pathogenesis of SARS-CoV-2 variants., 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 Sun, Sun, Zhu, Li, Xu, Lu, Tang, Wu, Li, Yao and Jiang.)

Background: Acute pancreatitis (AP) is a complex and heterogeneous disease. We aimed to design and validate a prognostic nomogram for improving the prediction of short-term survival in patients with AP., Methods: The clinical data of 632 patients with AP were obtained from the Medical Information Mart for Intensive Care (MIMIC)-IV database. The nomogram for the prediction of 30-day, 60-day and 90-day survival was developed by incorporating the risk factors identified by multivariate Cox analyses., Results: Multivariate Cox proportional hazard model analysis showed that age (hazard ratio [HR]=1.06, 95% confidence interval [95% CI] 1.03-1.08, P<0.001), white blood cell count (HR=1.03, 95% CI 1.00-1.06, P=0.046), systolic blood pressure (HR=0.99, 95% CI 0.97-1.00, P=0.015), serum lactate level (HR=1.10, 95% CI 1.01-1.20, P=0.023), and Simplified Acute Physiology Score II (HR=1.04, 95% CI 1.02-1.06, P<0.001) were independent predictors of 90-day mortality in patients with AP. A prognostic nomogram model for 30-day, 60-day, and 90-day survival based on these variables was built. Receiver operating characteristic (ROC) curve analysis demonstrated that the nomogram had good accuracy for predicting 30-day, 60-day, and 90-day survival (area under the ROC curve: 0.796, 0.812, and 0.854, respectively; bootstrap-corrected C-index value: 0.782, 0.799, and 0.846, respectively)., Conclusion: The nomogram-based prognostic model was able to accurately predict 30-day, 60-day, and 90-day survival outcomes and thus may be of value for risk stratification and clinical decision-making for critically ill patients with AP., Competing Interests: Conflicts of interest: The authors report that there are no competing interests to declare., (Copyright: © World Journal of Emergency Medicine.)

Purpose: Financial toxicity (FT) is a significant concern for patients with cancer. We reviewed prospectively collected data to explore associations with FT among patients undergoing concurrent, definitive chemoradiation therapy (CRT) within a diverse, urban, academic radiation oncology department., Methods and Materials: Patients received CRT in 1 of 3 prospective trials. FT was evaluated before CRT (baseline) and then weekly using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Core-30 questionnaire. Patients were classified as experiencing FT if they answered ≥2 on a Likert scale question (1-4 points) asking if they experienced FT. Rate of change of FT was calculated using linear regression; worsening FT was defined as increase ≥1 point per month. χ 2 , t tests, and logistic regression were used to assess predictors of FT., Results: Among 233 patients, patients attended an average of 9 outpatient and 4 radiology appointments over the 47 days between diagnosis and starting CRT. At baseline, 52% of patients reported experiencing FT. Advanced T stage (odds ratio, 2.47; P  = .002) was associated with baseline FT in multivariate analysis. The mean rate of FT change was 0.23 Likert scale points per month. In total, 26% of patients demonstrated worsening FT during CRT. FT at baseline was not associated with worsening FT ( P  = .98). Hospitalization during treatment was associated with worsening FT (odds ratio, 2.30; P  = .019) in multivariate analysis., Conclusions: Most patients reported FT before CRT. These results suggest that FT should be assessed (and, potentially, addressed) before starting definitive treatment because it develops early in a patient's cancer journey. Reducing hospitalizations may mitigate worsening FT. Further research is warranted to design interventions to reduce FT and avoid hospitalizations., (© 2022 The Authors.)

Objective To investigate the patterns of perioperative blood transfusion in patients with blood loss during major cardiac surgery,so as to provide data reference for rational and standardized blood use.Methods The adult patients(aged 18 years or above)who underwent vascular surgery,coronary artery bypass grafting surgery,heart valve surgery or surgery for congenital heart disease in a national multicenter(four large hospitals)survey in China,2015-2016 were included in this study.We described their baseline characteristics,postoperative outcomes,and in particular,bleeding and patterns of perioperative blood transfusion(autologous and allogeneic,the latter including red blood cells,plasma,and platelet,or a combination of these components).Results Autologous blood transfusion in operation accounted for the highest proportion(58.84%)in patients undergoing heart valve surgery.The patients undergoing vascular surgery had the largest autologous blood transfusion volume(722 ml)and the highest intraoperative transfusion proportion of allogeneic blood(53.28%),especially that of platelet(39.34%).Compared with the transfusion of red blood cells,the transfusion of other blood components showed concentrated time distribution,and the proportion of plasma transfusion was the highest one day post operation.With the increase in bleeding volume,combined transfusion presented increased proportion and became the dominant transfusion pattern.Conclusions The blood transfusion patterns varied significantly depending on different types of cardiac surgery,different perioperative stages,and different bleeding volumes.It is necessary to formulate the targeted transfusion practice scheme on the basis of understanding the current situation,so as to make better use of blood resources and improve the safety of transfusion.

This study aimed to evaluate the value of the deep learning image reconstruction (DLIR) algorithm (GE Healthcare’s TrueFidelity™) in improving the image quality of low-dose computed tomography (LDCT) of the chest. First, we retrospectively extracted raw data of chest LDCT from 50 patients and reconstructed them by using model-based adaptive statistical iterative reconstruction-Veo at 50% (ASIR-V 50%) and DLIR at medium and high strengths (DLIR-M and DLIR-H). Three sets of images were obtained. Next, two radiographers measured the mean CT value/image signal and standard deviation (SD) in Hounsfield units at the region of interest (ROI) and calculated the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). Two radiologists subjectively evaluated the image quality using a 5-point Likert scale. The differences between the groups of data were analyzed through a repeated measures ANOVA or the Friedman test. Last, our result show that the three reconstructions did not differ significantly in signal (p > 0.05) but had significant differences in noise, SNR, and CNR (p < 0.001). The subjective scores significantly differed among the three reconstruction modalities in soft tissue (p < 0.001) but not in lung tissue (p > 0.05). DLIR-H had the best noise reduction ability and improved SNR and CNR without distorting the image texture, followed by DLIR-M and ASIR-V 50%. In summary, DLIR can provide a higher image quality at the same dose, enhancing the physicians’ diagnostic confidence and improving the diagnostic efficacy of LDCT for lung cancer screening.

Objectives: Present study aimed to illustrate the role of miR-144-3p in rheumatoid arthritis (RA)., Methods: N1511 chondrocytes were stimulated by interleukin (IL)-1β to mimic RA injury model in vitro. Rats were subjected to injection of type II collagen to establish an in vivo RA model, and the arthritis index score was calculated. Cell viability was determined by Cell Counting Kit-8. The expression of cartilage extracellular matrix proteins (collagen II and aggrecan) and matrix metalloproteinase protein were determined by quantitative real-time polymerase chain reaction and western blots. Cell apoptosis was measured by flow cytometry. Enzyme-linked immunosorbent assay was applied to test the secretion of pro-inflammatory cytokines (IL-1β and tumour necrosis factor-α). Tissue injury and apoptosis were detected by haematoxylin-eosin staining and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling assay staining. Interaction of miR-144-3p and bone morphogenetic protein 2 (BMP2) was verified by dual-luciferase assay., Results: miR-144-3p was dramatically increased in IL-1β-induced N1511 cells. miR-144-3p depletion elevated cell viability, suppressed apoptosis, pro-inflammatory cytokine releasing, and extracellular matrix loss in IL-1β-induced N1511 cells. Moreover, miR-144-3p targeted BMP2 to modulate its expression negatively. Activation of phosphatidylinositol 3-kinase (PI3K)/Akt signalling compromised inhibition of BMP2 induced aggravated N1511 cell injury with IL-1β stimulation. Inhibition of miR-144-3p alleviated cartilage injury and inflammatory in RA rats., Conclusion: Collectively, miR-144-3p could aggravate chondrocyte injury inflammatory response in RA via BMP2/PI3K/Akt axis., (© Japan College of Rheumatology 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Arecoline, a major alkaloid of the areca nut, has potential toxicity to the nervous system. Our previous study reveals that the neurotoxicity of arecoline involves in inhibited endogenous hydrogen sulfide (H 2 S) generation. Therefore, the present study investigated whether exogenous H 2 S protects against arecoline-induced neurotoxicity and further explore the underlying mechanisms focusing on leptin/leptin receptor signaling pathway. The cell viability was measured by CCK-8 kit. The apoptosis were detected by Hoechst 33258 and Annexin V/PI (propidium iodide) staining. The protein expressions were determined by Western blot analysis. Our results demonstrated that NaHS, an exogenous H 2 S donor, significantly increases the cell viability, decreases apoptosis ratio, and reduces caspase-3 activity as well as Bax/Bcl-2 ratio in PC12 cells exposed to arecoline, indicating the protection of H 2 S against arecoline-induced cytotoxicity and apoptosis. Also, NaHS attenuated arecoline-induced endoplasmic reticulum (ER) stress, as evidenced by the decreases in the expressions of glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), and Cleaved caspase-12. Meanwhile, NaHS promoted leptin/leptin receptor signaling pathway in arecoline-exposed PC12 cells, as illustrated by upregulations of leptin and leptin receptor expressions. Furthermore, leptin tA, an antagonist of leptin receptor, obviously abolished the inhibitory effects of NaHS on arecoline-induced cytotoxicity, apoptosis, and ER stress in arecoline-exposed PC12 cells. Taken together, these results suggested that H 2 S prevents arecoline-induced neurotoxicity via enhancing the leptin/leptin receptor signaling pathway., (© 2022 International Federation for Cell Biology.)

The structural revision of four Stemona alkaloids from Stemona tuberosa is reported. The misassignment of the tuberostemonine O structure ( 1 ) was recognized when a new alkaloid, tuberostemonine P, was isolated and unambiguously assigned structure 1 in this work. Reinvestigation of the spectroscopic data and NMR calculations led to the revised structure 1a for tuberostemonine O. The structural misassignment of dehydrocroomine A as 2 was corrected by reinterpreting the X-ray crystal structure, which was consistent with 2a . The structural reassignments of dehydrocroomine B ( 3 to 3a ) and dehydrocroomine ( 4 to 4a ) were confirmed by X-ray crystallography and NMR calculations, respectively.

Aquilaria sinensis is an important non-timber tree species for producing high-value agarwood, which is widely used as a traditional medicine and incense. Agarwood is the product of Aquilaria trees in response to injury and fungal infection. The APETALA2/ethylene responsive factor ( AP2/ERF ) transcription factors (TFs) play important roles in plant stress responses and metabolite biosynthesis. In this study, 119 AsAP2/ERF genes were identified from the A. sinensis genome and divided into ERF, AP2, RAV, and Soloist subfamilies. Their conserved motif, gene structure, chromosomal localization, and subcellular localization were characterized. A stress/defense-related ERF-associated amphiphilic repression (EAR) motif and an EDLL motif were identified. Moreover, 11 genes that were highly expressed in the agarwood layer in response to whole-tree agarwood induction technique (Agar-Wit) treatment were chosen, and their expression levels in response to methyl jasmonate (MeJA), salicylic acid (SA), or salt treatment were further analyzed using the quantitative real time PCR (qRT-PCR). Among the 11 genes, eight belonged to subgroup B-3. All 11 genes were significantly upregulated under salt treatment, while eight genes were significantly induced by both MeJA and SA. In addition, the gene clusters containing these upregulated genes on chromosomes were observed. The results obtained from this research not only provide useful information for understanding the functions of AP2/ERF genes in A. sinensis but also identify candidate genes and gene clusters to dissect their regulatory roles in agarwood formation for future research.

Ethnopharmacological Relevance: The AnluoHuaxian pill (AHP) is a widely used patented medicine for chronic hepatitis B (CHB) patients with advanced fibrosis or cirrhosis that has been used in China for more than 15 years. However, data are lacking on whether monotherapy with AHP can be effective in CHB patients with alanine aminotransferase (ALT) levels less than 2 times the upper limit of normal (ALT<2ULN) and early liver fibrosis (F ≤ 2)., Aim of the Study: We aimed to investigate whether monotherapy with AHP improves liver histology in these patients., Materials and Methods: In this double-blind, randomized, placebo-controlled trial, 270 CHB patients with ALT<2ULN and F ≤ 2 were treated in 12 hospitals in China. The patients were randomly assigned to an intervention (AHP) group and a placebo group at a ratio of 2:1. Of these 270 enrolled patients, 147 had paired liver biopsies. The primary end point was histological change after 48 weeks of treatment., Results: Per-protocol analysis revealed that the rate of histologic improvement in liver fibrosis patients in the AHP group was significantly higher than that in the placebo group (37.7% vs. 19.5%, P = 0.035) after 48 weeks of treatment, which was consistent with results from intention-to-treat and sensitivity analyses. Moreover, after adjusting for baseline characteristics, AHP was superior to placebo with respect to improving liver fibrosis (odds ratio [OR] = 2.58, 95% confidence interval [CI]: (1.01, 6.63),P = 0.049) and liver histology (OR = 3.62, 95% CI: (1.42, 9.20),P = 0.007). In noninvasive measurement of liver fibrosis (FibroScan®), the level of liver stiffness measurement (LSM) had decreased significantly at 48 weeks (5.1 kPa) compared with that at baseline (5.7 kPa) (P = 0.008) in the AHP group, whereas it did not decrease significantly in the placebo group. Cirrhosis developed in one patient in the placebo group but in no patients in the AHP group. No serious side effects occurred in the AHP-treated patients., Conclusions: Treatment of CHB patients who had ALT<2ULN and F ≤ 2 with the traditional Chinese medicine AHP for 48 weeks improves liver fibrosis. However, due to the short duration of treatment and the limited sample size of liver pathology, the long-term benefits of AHP in reducing fibrosis and the risk of cirrhosis and hepatocellular carcinoma in these patients need to be further studied in the future., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

We report results of low-temperature heat-capacity, magnetocaloric-effect, and neutron-diffraction measurements of TmVO 4 , an insulator that undergoes a continuous ferroquadrupolar phase transition associated with local partially filled 4 f orbitals of the thulium (Tm[Formula: see text]) ions. The ferroquadrupolar transition, a realization of Ising nematicity, can be tuned to a quantum critical point by using a magnetic field oriented along the c axis of the tetragonal crystal lattice, which acts as an effective transverse field for the Ising-nematic order. In small magnetic fields, the thermal phase transition can be well described by using a semiclassical mean-field treatment of the transverse-field Ising model. However, in higher magnetic fields, closer to the field-tuned quantum phase transition, subtle deviations from this semiclassical behavior are observed, which are consistent with expectations of quantum fluctuations. Although the phase transition is driven by the local 4 f degrees of freedom, the crystal lattice still plays a crucial role, both in terms of mediating the interactions between the local quadrupoles and in determining the critical scaling exponents, even though the phase transition itself can be described via mean field. In particular, bilinear coupling of the nematic order parameter to acoustic phonons changes the spatial and temporal fluctuations of the former in a fundamental way, resulting in different critical behavior of the nematic transverse-field Ising model, as compared to the usual case of the magnetic transverse-field Ising model. Our results establish TmVO 4 as a model material and electronic nematicity as a paradigmatic example for quantum criticality in insulators.

Five Lycopodium alkaloids featuring novel C 17 N 2 ( 1 and 2 ), C 29 N 3 ( 3 and 4 ), and C 15 N 2 ( 5 ) skeletons were isolated from Lycopodium japonicum . Compound 1 is the first natural product containing a 3-aza[3.3.3]propellane motif. The structures of these compounds were elucidated by spectroscopic analysis, X-ray crystallography, and computational methods. Compounds 1 and 3-5 significantly inhibited TGF-β 1 -induced fibronectin deposition in HK-2 cells at a nontoxic concentration of 20 μM.

Purpose: Liver-directed therapy after transarterial chemoembolization (TACE) can lead to improvement in survival for selected patients with unresectable hepatocellular carcinoma (HCC). However, there is uncertainty in the appropriate application and modality of therapy in current clinical practice guidelines. The aim of this study was to develop a proof-of-concept, machine learning (ML) model for treatment recommendation in patients previously treated with TACE and select patients who might benefit from additional treatment with combination stereotactic body radiotherapy (SBRT) or radiofrequency ablation (RFA)., Methods: This retrospective observational study was based on data from an urban, academic hospital system selecting for patients diagnosed with stage I-III HCC from January 1, 2008, to December 31, 2018, treated with TACE, followed by adjuvant RFA, SBRT, or no additional liver-directed modality. A feedforward, ML ensemble model provided a treatment recommendation on the basis of pairwise assessments evaluating each potential treatment option and estimated benefit in survival., Results: Two hundred thirty-seven patients met inclusion criteria, of whom 54 (23%) and 49 (21%) received combination of TACE and SBRT or TACE and RFA, respectively. The ML model suggested a different consolidative modality in 32.7% of cases among patients who had previously received combination treatment. Patients treated in concordance with model recommendations had significant improvement in progression-free survival (hazard ratio 0.5; P = .007). The most important features for model prediction were cause of cirrhosis, stage of disease, and albumin-bilirubin grade (a measure of liver function)., Conclusion: In this proof-of-concept study, an ensemble ML model was able to provide treatment recommendations for HCC who had undergone prior TACE. Additional treatment in line with model recommendations was associated with significant improvement in progression-free survival, suggesting a potential benefit for ML-guided medical decision making., Competing Interests: Nitin OhriConsulting or Advisory Role: Merck, GenentechResearch Funding: Merck (Inst), RefleXion Medical (Inst), AstraZeneca Shalom KalnickiTravel, Accommodations, Expenses: Elekta Chandan GuhaConsulting or Advisory Role: Johnson & Johnson, Varian Medical Systems, Focused Ultrasound FoundationResearch Funding: Celldex, Johnson & Johnson, Myelo Therapeutics GmbH (Inst)Patents, Royalties, Other Intellectual Property: Montefiore Medical CenterOpen Payments Link: https://openpaymentsdata.cms.gov/physician/480201 N. Patrik BrodinResearch Funding: Varian Medical Systems (Inst)No other potential conflicts of interest were reported.

Due to the rapid evolution of antibiotic resistance in Staphylococcus aureus , antivirulence therapy may be a promising alternative for the effective control of the spread of resistant pathogens. The Chinese Materia Medica has been widely used for the treatment of diseases and production of health foods, and it remains a valuable resource for the discovery of compounds possessing antivirulence activity. Through a Caenorhabditis elegans infection model, an EtOAc-soluble fraction of 80% EtOH extract of Salvia miltiorrhiza Bunge (SMEA) was found to possess potential anti-infective activity against S. aureus . Then, several in vitro assays indicated that SMEA had robust antivirulence activity at the dose of 400 μg mL -1 , reducing hemolytic activity and α-hemolysin expression in S. aureus . Furthermore, at 100 mg kg -1 , SMEA reduced abscess formation in the main organs of mice challenged with S. aureus . In order to identify the bioactive components of SMEA and investigate the mechanisms underlying the antivirulence activity, SMEA was separated using bioassay-guided fractionation. As a result, eight compounds were identified in SMEA. Among them, tanshinone IIB (TNB) showed strong antivirulence activity both in vitro and in vivo . Furthermore, at 24 μg mL -1 , TNB significantly reduced the expression of RNAIII and psmα , indicating that the mechanism underlying TNB activity was related to the accessory gene regulator quorum sensing system. In conclusion, TNB's antivirulence properties make it a promising candidate for drug development against S. aureus infections.

Arecoline, the most abundant alkaloid of the areca nut, induces toxicity to neurons. Hydrogen sulfide (H 2 S) is an endogenous gas with neuroprotective effects. We recently found that arecoline reduced endogenous H 2 S content in PC12 cells. In addition, exogenously administration of H 2 S alleviated the neurotoxicity of arecoline on PC12 cells. Increasing evidence has demonstrated the neuroprotective role of improvement of autophagic flux. Therefore, the aim of the present work is to explore whether improvement of autophagic flux mediates the protection of H 2 S against arecoline-caused neurotoxicity. Transmission electron microscope (TEM) for observation of ultrastructural morphology. Western blotting was used to detect protein expression of the related markers. Functional analysis contained LDH release assay, Hoechst 33,258 nuclear staining and flow cytometry were used to detect cytotoxicity and apoptosis. In the present work, we found that arecoline disrupted autophagy flux in PC12 cells as evidenced by accumulation of autophagic vacuoles, increase in LC3II/LC3I, and upregulation of p62 expression in PC12 cells. Notably, we found that sodium hydrosulfide (NaHS), the donor of H 2 S improved arecoline-blocked autophagy flux in PC12 cells. Furthermore, we found that blocking autophagic flux by chloroquine (CQ), the inhibitor of autophagy flux, antagonized the inhibitory role of NaHS in arecoline-induced cytotoxicity apoptosis and endoplasmic reticulum (ER) stress. In conclusion, H 2 S improves arecoline-caused disruption of autophagic flux to exert its protection against the neurotoxicity of arecoline.

The emergence of antibiotic resistance in Staphylococcus aureus has necessitated the development of innovative anti-infective agents acting on novel targets. Alpha-hemolysin (Hla), a key virulence factor of S. aureus , is known to cause various cell damage and death. In this study, with bioassay-guided fractionation, a pair of unusual epimeric lignan trimers, ligustchuanes A and B ( 1 and 2 ), were isolated from the rhizomes of Ligusticum chuanxiong Hort, together with two known phthalides being identified by UPLC-QTOF-MS. To the best of our knowledge, trimers with rare C8-C9″-type neolignan and ferulic acid fragments have not been identified in any natural product. Both of them were isolated as racemic mixtures, and their absolute configurations were determined by comparing experimental and calculated ECD spectra after enantioseparation. Ligustchuane B exhibited an outstanding inhibitory effect on α -hemolysin expression in both MRSA USA300 LAC and MSSA Newman strains at concentrations of 3 and 6  μ M, respectively. Notably, a mouse model of infection further demonstrated that ligustchuane B could attenuate MRSA virulence in vivo ., 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 Wan, Ren, Jiang, Xu, Xu, Chen, Chen, Zheng, Yuan, Zhang and Xu.)

The improvement of the harvest period standards is critical in the quality control of Chinese medicinal materials. The present study statistically analyzed the harvest period standards of plant medicinal materials in the 2020 edition of Chinese Pharmacopoeia(Vol.Ⅰ) and put forward the existing problems and suggestions based on herbal records and modern research to provide references for the improvement of the standards. According to the statistical analysis, in 499 types of plant medicinal materials, harvest period standards are recorded under 486 types, accounting for 97.4%, and are lacking in the remaining. Only one medicinal material(Stellariae Radix) is recorded with the standard of the harvest year. The standards of the harvest season and phenological period are recorded under 233 types, accounting for 46.7%. For 237 types, only harvest season is specified, accounting for 47.5%, and for 15 types, only harvest phenological period is specified, accounting for 3.0%. Among 222 types mainly derived from cultivation and 51 types from wild resources and cultivation, only 11 types are recorded with harvest period of cultivated products. Only Stellariae Radix is recorded with the harvest period standards for the wild and cultivated products separately. The harvest period standards of plant medicinal materials with different medicinal parts have certain rules to follow. The main problems about the harvest period standards are discovered. Specifically, no harvest period standards are recorded under 13 types of plant medicinal materials. Almost all perennial cultivated medicinal materials are not recorded with harvest year standard. No phenological period standard is found under 250 types of plant medicinal materials. There is no clear distinction between the harvest period standards of cultivated and wild products. The evidence for harvest period standards of 26 types of plant medicinal materials that can be harvested all year round is insufficient. As a result, it is proposed to strengthen basic research in response to the above-mentioned problems and improve the harvest period standards as soon as possible to ensure the quality of Chinese medicinal materials.