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Xue Fang Li,1 Shi Rong Liu,2 Jin Jin Li,1 Ning Liu,2 Hui Min Li,3 An Ning Ge,4 Liang Liang Wang,5 Xie Min Dong,1 Hui Wang,1 Ju Liu,1 Lin Zhang,1 Hao Dong Zhang,1 Wei Gou1 1Department of Metabolic Liver Disease, Qingdao Sixth People’s Hospital, Qingdao City, Shandong Province, People’s Republic of China; 2Infectious Diseases department, People’s Hospital of Qu fu City, Qufu City, Shandong Province, People’s Republic of China; 3Infection Department, Jiaozhou Branch of Shanghai East Hospital Tongji University, Qingdao City, Shandong Province, People’s Republic of China; 4Department of Infectious Diseases, People’s Hospital of Rizhao City, Rizhao City, Shandong Province, People’s Republic of China; 5Medical Intervention Department, Qingdao Sixth People’s Hospital, Qingdao City, Shandong Province, People’s Republic of ChinaCorrespondence: Wei Gou, Department of Metabolic Liver Disease, Qingdao Sixth People’s Hospital, Qingdao City, Shandong Province, People’s Republic of China, Tel +86-15666687727, Fax +86-532-81636699, Email gouwei@qdu.edu.cnObjective: To investigate the risk factors for the development of portal hypertension in patients with decompensated cirrhosis and analyze their prognosis.Methods: Patients with decompensated cirrhosis who were admitted to our hospital and Qu fu People’s Hospital from June 2022 to June 2023 were included in this study. Among them, there were 45 male and 15 female patients, with a median age of 56 (range: 35– 77) years. A comparative analysis was performed between Group A (hepatic venous pressure gradient, HVPG < 16 mmHg) and Group B (HVPG ≥ 16 mmHg) patients, along with various clinical outcomes. Multivariate analysis was conducted to explore the risk factors influencing the occurrence of portal hypertension and adverse prognosis in patients with cirrhosis.Results: In Group A patients with portal hypertension, we observed lower levels of aspartate aminotransferase, laminin, serum hyaluronic acid, type III procollagen N-terminal peptide, total bile acids, and cholylglycine acid compared to Group B. On the other hand, levels of alanine aminotransferase, white blood cells, and serum albumin were higher in Group A than in Group B. These differences between the groups were statistically significant (P < 0.05). Multivariate analysis of the aforementioned risk factors indicated that low white blood cell count, high cholylglycine acid levels, and high serum hyaluronic acid levels were identified as independent risk factors for the occurrence of difficult-to-control complications in decompensated portal hypertension among patients with liver cirrhosis (P < 0.05).Conclusion: Liver cirrhosis patients with portal hypertension and multiple risk factors like low white blood cell count and high liver transaminase levels should be cautious regarding the progression of portal hypertension when combined with splenomegaly, liver fibrosis, and bile stasis, as it often indicates a poor prognosis.Keywords: portal hypertension, white blood cells, glycine cholate, serum hyaluronic acid

The endogenous electric fields at the wound site had been found since 18th century, while its biological significance in wound healing, organ regeneration and development was unveiled until recent year. Here we summarized the mechanisms of the generation of endogenous electric fields and its significance in different biological events. Moreover, the ion flux behind the endogenous electric fields was introduced as well.

To overcome the limitations of conventional fuzzy logic control strategies, an adaptive fuzzy logic control based on a hybrid Taguchi genetic algorithm is proposed to control the vibration of the magneto-rheological suspension in order to promote ride comfort. A half-car model equipped with two telescopic magneto-rheological dampers is first developed. An adaptive fuzzy logic control based on a hybrid Taguchi genetic algorithm is then formulated on the basis of the developed model. The hybrid Taguchi genetic algorithm is applied to tune the linguistic variables and control rules of the fuzzy logic control. Finally, a road test is carried out to validate the proposed control scheme. For comparison purposes, a conventional fuzzy logic control is also implemented on the test car. The results show that the magneto-rheological suspension system with two control strategies can improve ride comfort, and the proposed control algorithm has better ride improvement than conventional fuzzy logic control. [ABSTRACT FROM PUBLISHER]

Background: Prostate cancer (PCa) is one of the most prevalent malignancies in males worldwide. Increasing research attention has focused on the PCa microenvironment, which plays a crucial role in tumor progression and therapy resistance. This review aims to provide a comprehensive overview of the key components of the PCa microenvironment, including immune cells, vascular systems, stromal cells, and microbiota, and explore their implications for diagnosis and treatment., Methods: Keywords such as "prostate cancer", "tumor microenvironment", "immune cells", "vascular system", "stromal cells", and "microbiota" were used for literature retrieval through online databases including PubMed and Web of Science. Studies related to the PCa microenvironment were selected, with a particular focus on those discussing the roles of immune cells, vascular systems, stromal cells, and microbiota in the development, progression, and treatment of PCa. The selection criteria prioritized peer-reviewed articles published in the last five years, aiming to summarize and analyze the latest research advancements and clinical relevance regarding the PCa microenvironment., Results: The PCa microenvironment is highly complex and dynamic, with immune cells contributing to immunosuppressive conditions, stromal cells promoting tumor growth, and microbiota potentially affecting androgen metabolism. Vascular systems support angiogenesis, which fosters tumor expansion. Understanding these components offers insight into the mechanisms driving PCa progression and opens avenues for novel therapeutic strategies targeting the tumor microenvironment., Conclusions: A deeper understanding of the PCa microenvironment is crucial for advancing diagnostic techniques and developing precision therapies. This review highlights the potential of targeting the microenvironment to improve patient outcomes, emphasizing its significance in the broader context of PCa research and treatment innovation., (© 2024. The Author(s).)

Mycoheterotrophic plants acquire nitrogen (N) directly from the soil and through their symbiotic fungi. The fungi-derived N has received considerable attention, but the contribution of soil-derived N has been largely overlooked. We investigated how the leafless, rootless, and almost mycoheterotrophic orchid Cymbidium macrorhizon obtains soil N by applying 15 N-labeled ammonium nitrate in its natural habitat, and tracking metabolite accumulation and mycorrhizal fungal association after N application. The decline of N in the rhizome from flowering to fruiting indicated a transfer of N from the rhizome to fruits. At current dose of N application (0.6 g NH 4 NO 3 each plant), only 1.5% of the plant's N was derived from fertilizer, resulting in a low nitrogen use efficiency of 0.27%. The majority of those newly absorbed N (88.89%) was found sank in the rhizome. Amino acids (or their derivatives) and alkaloids were predominant differentially accumulated nitrogenous metabolites after N application, with amino acids occurring in both fruits and the rhizome, and alkaloids primarily in the fruits. The addition of N did not alter the richness of mycorrhizal fungi, but did affect their relative abundance. Our findings suggest that Cymbidium macrorhizon uses very limited soil inorganic nitrogen in its natural habitat, and the root-like rhizome primarily stores N rather than absorbs its inorganic forms, offering new insights into how mycoheterotrophic plants utilize soil N, and the influence of nutrient availability on the orchid-fungi association., 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 GmbH. All rights reserved.)

Organic-inorganic hybrid linear and nonlinear optical (NLO) materials have received increasingly wide spread attention in recent years. Herein, the first hybrid noncentrosymmetric (NCS) borophosphate, (C 5 H 6 N) 2 B 2 O(HPO 4 ) 2 (4PBP), is rationally designed and synthesized by a covalent-linkage strategy. 4-pyridyl-boronic acid (4 PB) is considered as a bifunctional unit, which may effectively improve the optical properties and stability of the resultant material. On the one hand, 4 PB units are covalently linked with PO 3 (OH) groups via strong B-O-P connections, which significantly enhances the thermal stability of 4PBP (decomposition at 321, vs lower 200 °C of most of hybrid materials). On the other hand, the planar π-conjugated C 5 H 6 N units and their uniform layered arrangements represent large structural anisotropy and hyperpolarizability, achieving the largest birefringence (0.156 @ 546 nm) in the reported borophosphates and a second-harmonic generation response (0.7 × KDP). 4PBP also exhibits a wide transparency range (0.27-1.50 µm). This work not only provides a promising birefringent material, but also offers a practical covalent-attachment strategy for the rational design of new high-performance optical materials., (© 2024 Wiley‐VCH GmbH.)

We assessed the prognostic utility of the new perinephric fat adherence risk score - Mayo Adhesive Probability (MAP), in patients of East Asian ethnicity undergoing either laparoscopic partial nephrectomy (LPN) or laparoscopic radical nephrectomy (LRN). A retrospective analysis of clinical data was carried out on 169 patients who either underwent LPN or LRN surgery. These patients were categorized into two groups, group A (0-2 points) and group B (3-4 points) using the new MAP score. The overall clinical data between these two groups was compared and potential risk factors were investigated using logistic regression analyses. The new MAP score yielded an area under the curve of 0.761 (95 % CI: 0.691-0.831), indicating its effectiveness. Group B had a significantly higher incidence of adherent perirenal fat (APF) during surgery (p<0.001) and had a greater average age (p<0.001). There was an increased prevalence of hypertension (p=0.009), type 2 diabetes mellitus (p<0.001), and MAFLD (p<0.001) in group B. Additionally, there were significant differences in posterior perinephric fat thickness (p<0.05), lateral perinephric fat thickness (p<0.001), and perinephric stranding (p<0.001) between the two groups. The new MAP score holds significance in predicting APF in people of East Asian ethnicity undergoing LPN or LRN, and there is a strong correlation between elevated MAP scores and risk factors such as MAFLD and advanced age.

Objective: In this study, we aimed to evaluate the combined diagnostic value of procalcitonin (PCT), C-reactive protein (CRP), and serum amyloid A (SAA) in sepsis caused by urinary tract infection., Method: A total of 80 patients with urosepsis who were hospitalized were included in the study group, and 80 patients with urinary tract infection without sepsis were included in the control group. We collected the PCT, SAA, and CRP levels of patients following admission. Subsequently, we conducted a comparative analysis to assess the specificity, accuracy, and sensitivity of combined diagnostic approaches in contrast to individual diagnostic methods for blood PCT, SAA, and CRP., Results: The levels of PCT, SAA, and CRP in the study group were significantly higher than those in the control group, and the differences were statistically significant (P < 0.01). Multi-factor logistic regression analysis revealed that the levels of PCT (P = 0.003) and SAA (P = 0.014) were associated with urosepsis. The sensitivity of PCT was 87.133% and the specificity was 93.066%, which were higher than that of SAA and CRP. The specificity of the combined detection of the three was 95.670%, which was higher than that of PCT, SAA, and CRP alone. Correlation analysis revealed that PCT had a significant positive correlation with CRP and SAA (P < 0.01), and a weak correlation with white blood cell count (WBC) and fibrinogen (FIB) (P = 0.03 for WBC, P = 0.04 for FIB)., Conclusion: PCT, SAA, and CRP indicators in patients with urosepsis are significantly elevated, and all three are valuable in the diagnosis of urosepsis. PCT alone has good diagnostic efficiency for urosepsis, and a certain correlation with other inflammatory factors. The diagnostic efficacy of the three indicators in combination is better than that of any one of the three, and is worthy of widespread clinical application., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The JASMONATE ZIM DOMAIN (JAZ) proteins are a key inhibitors of the jasmonic acid (JA) signaling pathway that play an important role in the regulation of plant growth and development and environmental stress responses. However, there is no systematic identification and functional analysis of JAZ gene family members in sugarcane. In this study, a total of 49 SsJAZ genes were identified from the wild sugarcane species Saccharum spontaneum genome that were unevenly distributed on 13 chromosomes. Phylogenetic analysis showed that all SsJAZ members can be divided into six groups, and most of the SsJAZ genes contained photoreactive and ABA-responsive elements. RNA-seq analysis revealed that SsJAZ1-1/2/3/4 and SsJAZ7-1 were significantly upregulated under drought stress. The transcript level of ScJAZ1 which is the homologous gene of SsJAZ1 in modern sugarcane cultivars was upregulated by JA, PEG, and abscisic acid (ABA). Moreover, ScJAZ1 can interact with three other JAZ proteins to form heterodimers. The spatial and temporal expression analysis showed that SsJAZ2-1/2/3/4 were highly expressed in different tissues and growth stages and during the day-night rhythm between 10:00 and 18:00. Overexpression of ScJAZ2 in Arabidopsis accelerated flowering through activating the expression of AtSOC1, AtFT, and AtLFY. Moreover, the transcription level of ScJAZ2 was about 30-fold in the early-flowering sugarcane variety than that of the non-flowering variety, indicating ScJAZ2 positively regulated flowering. This first systematic analysis of the JAZ gene family and function analysis of ScJAZ1/2 in sugarcane provide key candidate genes and lay the foundation for sugarcane breeding., 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 Masson SAS. All rights reserved.)

Acoustic behaviour plays a significant role in insect communications, but is rarely reported in their immature stages. Larvae of Lucanidae bear paired stridulatory organs on their thoracic legs, which could produce sounds as communicational signals. However, the species-specific differences on stridulatory organs and acoustic signals are far from fully investigated. In this study, the larval acoustic behaviours of three lucanid species, Lucanus dybowski, Prosopocoilus confucius and P. girafa were recorded and compared for the first time. The sound producing mechanism was described in detail based on video recordings, morphological observations, and acoustic analyses. The larvae of all three species are able to produce sounds by scraping the plectrum on the metatrochanter against the pars stridens on the mesocoxa during disturbance. The sounds exhibit species-specific differences in terms of acoustic parameters: the larvae of L. dybowski produce short-duration (140-200 ms), single-pulse and low-frequency (∼210 Hz) sounds; P. confucius produce long-duration (500-800 ms), triple-pulse and low-frequency (∼280 Hz) sounds; P. girafa produce long-duration (500-560 ms), double-pulse and low-frequency (∼260 Hz) sounds. The amounts and arrangements of the teeth on stridulatory organs also exhibit differences on specific level. The acoustic signals and stridulatory organs were compared using principal component analysis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Elemene, an active anticancer extract derived from Curcuma wenyujin, has well-documented anticarcinogenic properties. Nevertheless, the role of elemene in prostate cancer (PCa) and its underlying molecular mechanism remain elusive., Purpose: This study focuses on investigating the anti-PCa effects of elemene and its underlying mechanisms., Methods: Cell-based assays, including CCK-8, scratch, colony formation, cell cycle, and apoptosis experiments, to comprehensively assess the impact of elemene on PCa cells (LNCaP and PC3) in vitro. Additionally, we used a xenograft model with PC3 cells in nude mice to evaluate elemene in vivo efficacy. Targeted metabolomics analysis via HILIC-MS/MS was performed to investigate elemene potential target pathways, validated through molecular biology experiments, including western blotting and gene manipulation studies., Results: In this study, we discovered that elemene has remarkable anti-PCa activity in both in vitro and in vivo settings, comparable to clinical chemotherapeutic drugs but with fewer side effects. Using our established targeted metabolomics approach, we demonstrated that β-elemene, elemene's primary component, effectively inhibits glycolysis in PCa cells by downregulating 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) expression. Furthermore, we found that β-elemene accomplishes this downregulation by upregulating p53 and FZR1. Knockdown and overexpression experiments conclusively confirmed the pivotal role of PFKFB3 in mediating β-elemene's anti-PCa activity., Conclusion: This finding presents compelling evidence that elemene exerts its anti-PCa effect by suppressing glycolysis through the downregulation of PFKFB3. This study not only improves our understanding of elemene in PCa treatment but also provides valuable insights for developing more effective and safer therapies for PCa., 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 GmbH. All rights reserved.)

The bromodomain is a highly conserved protein domain that specifically binds to acetylated lysine residues in histones, thereby activating transcription of target genes. Although some progress in Global Transcription Factor Group E (GTE) has been achieved in numerous animals and a few plant species, no systematic analysis of GTE gene families has been reported yet in sugarcane. In our study, 37 GTE and GTE-Like (GTEL) genes were characterized in the Saccharum spontaneum. All SsGTE/SsGTEL members were heterogeneously located on all chromosomes of the sugarcane genome and divided into five groups. Transcriptome data showed that SsGTEL3a was expressed at significantly higher levels under drought stress in drought-resistant varieties than in drought-sensitive varieties. Moreover, the overexpression of SsGTEL3a significantly improved the drought tolerance in Arabidopsis through improving the scavenging ability of reactive oxygen species. Additionally, an interaction between ScFAR1 and SsGTEL3a was identified, with ScFAR1 showing a positive response to drought stress in bacterium. In summary, this systematic analysis of GTE gene family in sugarcane and functional research of SsGTEL3a broadened deeper insight into their evolutionary dynamics and functional properties and provided new candidate genes for drought-resistant molecular breeding of sugarcane., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

The unprecedented global increase in the anthropogenic-derived nitrogen (N) input may have profound effects on phosphorus (P) dynamics and may potentially lead to enhanced eutrophication as demonstrated in short-term mesocosm experiments. However, the role of N-influenced P release is less well studied in large-scale ecosystems. To gain more insight into ecosystem effects, we conducted a five-year large-scale experiment in ten ponds (700-1000 m 2 each) with two types of sediments and five targeted total N concentrations (TN) by adding NH 4 Cl fertilizer (0.5, 1, 5, 10, and 25 mg N L -1 ). The results showed that: (ⅰ) The sediment P release increased significantly when TN exceeded 10-25 mg N L -1 . (ⅱ) The most pronounced sediment P release increase occurred in summer and from sediments rich in organic matter (OM Sed ). (ⅲ) TN, algal biomass, fish biomass, non-algal turbidity, sediment pH, and OM Sed were the dominant factors explaining the sediment P release, as suggested by piecewise structural equation modeling. We propose several mechanisms that may have stimulated P release, i.e. high ammonium input causes a stoichiometric N:P imbalance and induce alkaline phosphatase production and dissolved P uptake by phytoplankton, leading to enhanced inorganic P diffusion gradient between sediment and water; higher pelagic fish production induced by the higher phytoplankton production may have led increased sediment P resuspension through disturbance; low oxygen level in the upper sediment caused by nitrification and organic decomposition of the settled phytoplankton and, finally, long-term N application-induced sediment acidification as a net effect of ammonium hydrolysis, nitrification, denitrification; The mechanisms revealed by this study shed new light on the complex processes underlying the N-stimulated sediment P release, with implications also for the strategies used for restoring eutrophicated lakes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Objective: To investigate the effect of phorbol-12-myristate-13-ace-tate (TPA) on the proliferation and apoptosis of acute promyelocytic leukemia cell line NB4 and its molecular mechanism., Methods: The effect of different concentrations of TPA on the proliferation of NB4 cells at different time points was detected by CCK-8 assay. The morphological changes of NB4 cells were observed by Wright-Giemsa staining. The cell cycle and apoptosis of NB4 cells after TPA treatment were detected by flow cytometry. The mRNA expressions of NB4 cells after TPA treatment were analyzed by high-throughput microarray analysis and real-time quantitative PCR. Western blot was used to detect the protein expression of CDKN1A, CDKN1B, CCND1, MYC, Bax, Bcl-2, c-Caspase 3, c-Caspase 9, PIK3R6, AKT and p-AKT., Results: Compared with the control group, TPA could inhibit the proliferation of NB4 cells, induce the cells to become mature granulocyte-monocyte differentiation, and also induce cell G 1 phase arrest and apoptosis. Differentially expressed mRNAs were significantly enriched in PI3K/AKT pathway. TPA treatment could increase the mRNA levels of CCND1, CCNA1 , and CDKN1A , while decrease the mRNA level of MYC . It could also up-regulate the protein levels of CDKN1A, CDKN1B, CCND1, Bax, c-Caspase 3, c-Caspase 9, and PIK3R6, while down-regulate MYC, Bcl-2, and p-AKT in NB4 cells., Conclusion: TPA induces NB4 cell cycle arrest in G 1 phase and promotes its apoptosis by regulating PIK3/AKT signaling pathway.

Diabetic cardiomyopathy (DCM) is a prevalent cardiovascular complication of diabetes mellitus, characterized by high morbidity and mortality rates worldwide. However, treatment options for DCM remain limited. For decades, a substantial body of evidence has suggested that the inflammatory response plays a pivotal role in the development and progression of DCM. Notably, DCM is closely associated with alterations in inflammatory cells, exerting direct effects on major resident cells such as cardiomyocytes, vascular endothelial cells, and fibroblasts. These cellular changes subsequently contribute to the development of DCM. This article comprehensively analyzes cellular, animal, and human studies to summarize the latest insights into the impact of inflammation on DCM. Furthermore, the potential therapeutic effects of current anti-inflammatory drugs in the management of DCM are also taken into consideration. The ultimate goal of this work is to consolidate the existing literature on the inflammatory processes underlying DCM, providing clinicians with the necessary knowledge and tools to adopt a more efficient and evidence-based approach to managing this condition., 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. They also have no vested interests in any product, service, or company that may have influenced the positions presented in the manuscript or in its review., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The aim of this study was to validate the diagnostic efficacy of acoustic attenuation imaging (ATI) and ultrasonic shear wave elastography (SWE) in classifying nonalcoholic fatty liver disease (NAFLD). A total of 100 patients with NAFLD were recruited from our hospital between January 2021 and December 2022. Patient demographics and clinical data were collected, and 2-dimensional ultrasound was used to screen patients based on liver echo characteristics. Patients without liver space-occupying lesions underwent routine ultrasound examinations. Imaging or serology was used to confirm the presence of fatty liver in patients or healthy individuals. Patients with alcoholic liver disease (alcohol equivalent content < 20 g/day for women, <30 g/day for men), as well as those with lenticular degeneration, total parenteral nutrition, autoimmune liver disease, drug-induced hepatitis, and viral hepatitis, were excluded from the study. Out of the 100 included patients, 24 had normal liver, 21 had mild fatty liver, 30 had moderate fatty liver, and 25 had severe fatty liver. There were age differences between the normal group and patients with mild fatty liver, and the average body mass index (BMI) varied across the 4 groups. As the severity of the disease increased, the average BMI also increased (P < .05). The ATI scores and SWE scores differed significantly among the different groups (P < .05), with both scores showing an upward trend as the fatty liver condition worsened. Correlation analysis revealed positive correlations between ATI and SWE scores and the degree of fatty liver (P < .05), positive correlations with BMI (P < .05), and negative correlations with high-density lipoprotein cholesterol expression (P < .05). The area under the curve (AUC) for the ATI score in diagnosing different degrees of fatty liver was > 0.750, and the AUC for the SWE score was also > 0.750. The AUC for SWE score in diagnosing different degrees of fatty liver ranged from 1.01 to 4.57, while the combined AUC for ATI and SWE scores was > 0.850, with respective cutoff values of 3.62, 5.72, and 7.57 based on the maximum approximate entry index. The combination of ATI and SWE has a significant impact on the grading diagnosis of NAFLD, and its application can be extended to clinical practice., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Ethnopharmacological Relevance: The rhizome of Curcuma wenyujin Y.H. Chen & C. Ling, also known as Wen-E-Zhu, has been used for cancer treatment since ancient times, with roots dating back to the Song Dynasty. Elemene (EE), a sesquiterpene extract with potent anticancer properties, is extracted from Wen-E-Zhu, with β-elemene (BE) being its main active compound, along with trace amounts of β-caryophyllene (BC), γ-elemene and δ-elemene isomers. EE has demonstrated broad-spectrum anti-cancer effects and is commonly used in clinical treatments for various types of malignant cancers, including lung cancer. Studies have shown that EE can arrest the cell cycle, inhibit cancer cell proliferation, and induce apoptosis and autophagy. However, the exact mechanism of its anti-lung cancer activity remains unclear and requires further research and investigation., Aim of the Study: In this study, the possible mechanism of EE and its main active components, BE and BC, against lung adenocarcinoma was investigated by using A549 and PC9 cell lines., Materials and Methods: The subcutaneous tumor model of nude mice was constructed to evaluate the efficacy of EE in vivo, then the in vitro half-inhibitory concentration (IC 50 ) of EE and its main active components, BE and BC, on A549 and PC9 cells at different concentrations were determined by CCK-8. Flow cytometry was used to detect the apoptosis and cycle of A549 and PC9 cells treated with different concentrations of BE and BC for 24 h. Non-targeted metabolomics analysis was performed on A549 cells to explore potential target pathways, which were subsequently verified through kit detection and western blot analysis., Results: Injection of EE in A549 tumor-bearing mice effectively suppressed cancer growth in vivo. The IC 50 of EE and its main active components, BE and BC, was around 60 μg/mL. Flow cytometry analysis showed that BE and BC blocked the G 2 /M and S phases of lung adenocarcinoma cells and induced apoptosis, leading to a significant reduction in mitochondrial membrane potential (MMP). Results from non-targeted metabolomics analysis indicated that the glutathione metabolism pathway in A549 cells was altered after treatment with the active components. Kit detection revealed a decrease in glutathione (GSH) levels and an increase in the levels of oxidized glutathione (GSSG) and reactive oxygen (ROS). Supplementation of GSH reduced the inhibitory activity of the active components on lung cancer and also decreased the ROS content of cells. Analysis of glutathione synthesis-related proteins showed a decrease in the expression of glutaminase, cystine/glutamate reverse transporter (SLC7A11), and glutathione synthase (GS), while the expression of glutamate cysteine ligase modified subunit (GCLM) was increased. In the apoptosis-related pathway, Bax protein and cleaved caspase-9/caspase-9 ratio were up-regulated and Bcl-2 protein was down-regulated., Conclusions: EE, BE, and BC showed significant inhibitory effects on the growth of lung adenocarcinoma cells, and the mechanism of action was linked to the glutathione system. By down-regulating the expression of proteins related to GSH synthesis, EE and its main active components BE and BC disrupted the cellular redox system and thereby promoted cell apoptosis., 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.)

The pseudobulb is a storage organ for water and nutrients that plays a crucial role in the growth and survival of epiphytic orchids. However, the role of water and metabolites in pseudobulb during adaptation to environmental stress are rarely detected through control experiments. In the present study, water-related physiological traits and metabolite changes in the pseudobulbs at the flowering stage and full leaf expansion stage for Pleione aurita were investigated after drought stress and recovery treatments. We found that the composition of non-structural carbohydrates (starch vs. soluble sugar) varied over the lifetime of pseudobulbs, and older pseudobulbs stored more water, whereas younger pseudobulbs stored more dry matter. When plants were subjected to drought stress and subsequent recovery, multiple metabolites in the pseudobulbs including non-structural carbohydrates, flavonoids, phenolic acids, as well as amino acids and their derivatives responded positively to these water level fluctuations. For those metabolites that differently accumulated in both stress and recovery processes, old pseudobulbs contained a higher number of these key metabolites than did the connected younger pseudobulbs. In addition, young and old pseudobulbs use different metabolic pathways to both respond and recover to drought. These results indicate that orchid pseudobulbs cope with water level fluctuations by mobilizing metabolite reserves and that pseudobulbs of different ages exhibit different physiological and metabolic responses to drought stress. These findings broadens our understanding of the role pseudobulbs play in the survival of orchids growing in epiphytic habitats., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Metabolic reprogramming of cancer cells is a hallmark of cancer, in which the polar metabolites involving aerobic glycolysis, pentose phosphate pathway (PPP), tricarboxylic acid (TCA) cycle, and glutaminolysis play a crucial role in the occurrence and development of cancer. Therefore, targeted analysis of the polar metabolites in these pathways is of great value for understanding cancers, finding diagnostic biomarkers, and identifying therapeutic targets. However, it is still challenging to directly determine polar metabolites in these pathways without derivatization due to their diverse chemical properties, isomers, and strong polarity. Herein, a highly selective and sensitive HILIC-MS/MS method was developed for direct determination of the polar metabolites in aerobic glycolysis, PPP, TCA cycle, and glutaminolysis pathways. Without derivatization, 19 polar metabolites and their isomers with carbonyl, carboxyl, or phosphoryl groups in human plasma and cell extracts of prostate cancer (PC) were determined with strong retention and high resolution. This method has been widely verified by measuring linearity, precision, sensitivity, repeatability, matrix effect, and accuracy. The analysis of plasma samples by HILIC-MS/MS revealed distinct PC-specific metabolic signatures compared to a healthy control. In addition, this method could also be used to screen the targets of metabolic inhibitors at the cellular level. We conclude that the developed HILIC-MS/MS method provides a valuable means to study the cancer metabolic reprogramming or energy metabolism in living organisms., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Chronic refractory wounds were common and the treatments were complicated for burn and plastic surgeons. This study was to investigate the bacterial distribution characteristics and bacterial drug resistance of chronic refractory wound secretions., Methods: The authors retrospectively analyzed 425 patients with chronic refractory wound infection. The results of bacterial culture of wound secretions and drug sensitivity test were retrospectively analyzed. Further, the location area of the wound was divided into 4 regions, and the difference of the bacterial culture results between different regions was analyzed., Results: The wound secretions were cultured into 401 bacterial strains, including 206 gram-positive bacteria strains, accounting for 51.4%, with the highest detection rate of Staphylococcus aureus at 26.2% (105/401). There were 195 gram-negative bacteria strains, accounting for 48.6%, with the highest detection rate of Pseudomonas aeruginosa at 14.2% (57/401). There were 6 fungal strains. The proportion of gram-negative bacteria in the III region of the wound zone was significantly greater than that in the other 3 regions., Conclusions: The detection rate of gram-positive bacteria and gram-negative bacteria of chronic refractory wound secretions is not much different. However, in the area close to the perineum (III region), gram-negative bacteria is significantly higher, which has a certain reference value for the use of antibiotics in clinical practice., Level of Evidence: Level 4., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by Mutaz B. Habal, MD.)

Watermelon Fusarium wilt, caused by Fusarium oxysporum f. sp. niveum (FON), is one of the most important diseases, and has become a major limiting factor to watermelon production worldwide. Previous research has found that the improved biocontrol agent, F1-35, had a high control efficiency to watermelon Fusarium wilt. In this study, the control efficiency of F1-35 to watermelon Fusarium wilt was firstly tested, and the control efficiency was 61.7%. Then, we investigated the mode of action of F1-35 in controlling watermelon Fusarium wilt. Using a pairing assay, we found that F1-35 did not inhibit the normal growth of FON. To know more about the interaction between F1-35 and watermelon root, the protein expressions of roots after 12, 24, and 48 h post-inoculation were examined. A total of 1109 differentially expressed proteins were obtained. KEGG analysis found that the most differentially expressed proteins occurred in alpha-linolenic acid metabolism, cysteine and methionine metabolism, plant-pathogen interaction, and the MAPK signaling pathway to the plant. A further analysis of differentially expressed proteins showed that F1-35 triggered the jasmonic acid and ethylene pathways in watermelon. To validate our results, the qRT-PCR was used to analyze the gene expression levels of PAL , LOX1 , and CTR1 . The gene expression results showed that those genes, which were positive correlated with the JA pathway, were up-expressed, including PAL and LOX1 , and the negative associated gene, CTR1 , was down-expressed. In conclusion, the improved biocontrol agent, F1-35, improves the resistance of watermelons to FON by triggering the JA and ET pathways.

Neuromorphic electronics, which use artificial photosensitive synapses, can emulate biological nervous systems with in-memory sensing and computing abilities. Benefiting from multiple intra/interactions and strong light-matter coupling, two-dimensional heterostructures are promising synaptic materials for photonic synapses. Two primary strategies, including chemical vapor deposition and physical stacking, have been developed for layered heterostructures, but large-scale growth control over wet-chemical synthesis with comprehensive efficiency remains elusive. Here we demonstrate an interfacial coassembly heterobilayer films from perylene and graphene oxide (GO) precursors, which are spontaneously formed at the interface, with uniform bilayer structure of single-crystal perylene and well-stacked GO over centimeters in size. The planar heterostructure device exhibits an ultrahigh specific detectivity of 3.1 × 10 13 Jones and ultralow energy consumption of 10 -9  W as well as broadband photoperception from 365 to 1550 nm. Moreover, the device shows outstanding photonic synaptic behaviors with a paired-pulse facilitation (PPF) index of 214% in neuroplasticity, the heterosynapse array has the capability of information reinforcement learning and recognition., (© 2022. The Author(s).)

When the human brain learns multiple related or continuous tasks, it will produce knowledge sharing and transfer. Thus, fast and effective task learning can be realized. This idea leads to multi-task learning. The key of multi-task learning is to find the correlation between tasks and establish a fast and effective model based on these relationship information. This paper proposes a multi-task learning framework based on stochastic configuration networks. It organically combines the idea of the classical parameter sharing multi-task learning with that of constraint sharing configuration in stochastic configuration networks. It organically combines the idea of the classical parameter sharing multi-task learning with that of constraint sharing configuration in stochastic configuration neural networks. Moreover, it provides an efficient multi-kernel function selection mechanism. The convergence of the proposed algorithm is proved theoretically. The experiment results on one simulation data set and four real life data sets verify the effectiveness of the proposed algorithm., 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 Dong, Kong and Zhang.)

Almost all genomes have orphan genes, the majority of which are not functionally annotated. There is growing evidence showed that orphan genes may play important roles in the environmental stress response of Physcomitrium patens. We identified PpARDT (ABA-responsive drought tolerance) as a moss-specific and ABA-responsive orphan gene in P. patens. PpARDT is mainly expressed during the gametophytic stage of the life cycle, and the expression was induced by different abiotic stresses. A PpARDT knockout (Ppardt) mutant showed reduced dehydration-rehydration tolerance, and the phenotype could be rescued by exogenous ABA. Meanwhile, transgenic Arabidopsis lines exhibiting heterologous expression of PpARDT were more sensitive to exogenous ABA than wild-type (Col-0) plants and showed enhanced drought tolerance. These indicate that PpARDT confers drought tolerance among land plants potentially by enhancing ABA response. Further, we identified genes encoding abscisic acid receptor PYR/PYL family proteins, and ADP-ribosylation factors (Arf) as hub genes associated with the Ppardt phenotype. Given the lineage-specific characteristics of PpARDT, our results provide insights into the roles of orphan gene in shaping lineage-specific adaptation possibly by recruiting common pre-existed pathway components., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: We aimed to construct the lncRNA-associated competing endogenous RNA (ceRNA) network and distinguish feature lncRNAs associated with tendinopathy., Methods: We downloaded the gene profile of GSE26051 from the Gene Expression Omnibus (GEO), including 23 normal samples and 23 diseased tendons. Differentially expressed mRNAs (DEmRNAs) and differentially expressed lncRNAs (DElncRNAs) were identified, and functional and pathway enrichment analyses were performed. Protein-protein interaction (PPI) network was constructed and further analyzed by module mining. Moreover, a ceRNA regulatory network was constructed based on the identified lncRNA-mRNA coexpression relationship pairs and miRNA-mRNA regulation pairs., Results: We identified 1117 DEmRNAs and 57 DElncRNAs from the GEO data. The downregulated DEmRNAs were particularly associated with muscle contraction and muscle filament, while the upregulated ones were linked to extracellular matrix organization and cell adhesion. From the PPI network, 11 modules were extracted. Genes in MCODE 2 (such as TPM4) were significantly involved in cardiomyopathy, and genes in MCODE 4 (such as COL4A3 and COL4A4) were involved in focal adhesion, ECM-receptor interaction, and PI3K-Akt signaling pathway. The ceRNA network contained 7 lncRNAs (MIR133A1HG, LINC01405, PRKCQ-AS1, C10orf71-AS1, MBNL1-AS1, HOTAIRM1, and DNM3OS), 63 mRNAs, and 41 miRNAs. Downregulated lncRNA MIR133A1HG could competitively bind with hsa-miR-659-3p and hsa-miR-218-1-3p to regulate the TPM3. Meanwhile, MIR133A1HG could competitively bind with hsa-miR-1179 to regulate the COL4A3. Downregulated C10orf71-AS1 could competitively bind with hsa-miR-130a-5p to regulate the COL4A4., Conclusions: Seven important lncRNAs, particularly MIR133A1HG and C10orf71-AS1, were found associated with tendinopathy according to the lncRNA-associated ceRNA network., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Bing-Zhe Huang et al.)

PLK1 and Smad4 are two important factors in prostate cancer initiation and progression. They have been reported to play the opposite role in Pten-deleted mice, one is an oncogene, the other is a tumor suppressor. Moreover, they could reversely regulate the PI3K/AKT/mTOR pathway and the activation of MYC. However, the connections between PLK1 and Smad4 have never been studied. Here, we showed that PLK1 could interact with Smad4 and promote the ubiquitination and degradation of Smad4 in PCa cells. PLK1 and PELO could bind to different domains of Smad4 and formed a protein complex. PELO facilitated the degradation of Smad4 through cooperating with PLK1, thereby resulting in proliferation and metastasis of prostate cancer cell. Changes in protein levels of Smad4 led to the alteration of biological function that caused by PLK1 in prostate cancer cells. Further studies showed that PELO upregulation was positively associated with high grade PCa and knockdown of PELO expression significantly decreased PCa cell proliferation and metastasis in vitro and vivo. PELO knockdown in PCa cells could enhance the tumor suppressive role of PLK1 inhibitor. In addition, blocking the interaction between PELO and Smad4 by using specific peptide could effectively inhibit PCa cell metastasis ability in vitro and vivo. Overall, these findings identified a novel regulatory relationship among PLK1, Smad4 and PELO, and provided a potential therapeutic strategy for advanced PCa therapy by co-targeting PLK1 and PELO., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Hematopoietic stem and progenitor cells (HSPCs) possess the remarkable ability to regenerate the whole blood system in response to ablated stress demands. Delineating the mechanisms that maintain HSPCs during regenerative stresses is increasingly important. Here, it is shown that Hemgn is significantly induced by hematopoietic stresses including irradiation and bone marrow transplantation (BMT). Hemgn deficiency does not disturb steady-state hematopoiesis in young mice. Hemgn -/- HSPCs display defective engraftment activity during BMT with reduced homing and survival and increased apoptosis. Transcriptome profiling analysis reveals that upregulated genes in transplanted Hemgn -/- HSPCs are enriched for gene sets related to interferon gamma (IFN-γ) signaling. Hemgn -/- HSPCs show enhanced responses to IFN-γ treatment and increased aging over time. Blocking IFN-γ signaling in irradiated recipients either pharmacologically or genetically rescues Hemgn -/- HSPCs engraftment defect. Mechanistical studies reveal that Hemgn deficiency sustain nuclear Stat1 tyrosine phosphorylation via suppressing T-cell protein tyrosine phosphatase TC45 activity. Spermidine, a selective activator of TC45, rescues exacerbated phenotype of HSPCs in IFN-γ-treated Hemgn -/- mice. Collectively, these results identify that Hemgn is a critical regulator for successful engraftment and reconstitution of HSPCs in mice through negatively regulating IFN-γ signaling. Targeted Hemgn may be used to improve conditioning regimens and engraftment during HSPCs transplantation., (© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.)

The development and tissue-dependent color formation of the horticultural plant results in various color pattern flowers. Anthocyanins and carotenoids contribute to the red and yellow colors, respectively. In this study, quantitative real-time polymerase chain reaction (qRT-PCR) is used to analyze the expression profiles of anthocyanin and carotenoids biosynthesis genes in Cymbidium lowianum (Rchb.f.) Rchb.f. Appropriate reference gene selection and validation are required before normalization of gene expression in qRT-PCR analysis. Thus, we firstly selected 12 candidate reference genes from transcriptome data, and used geNorm and Normfinder to evaluate their expression stability in lip (divided into abaxial and adaxial), petal, and sepal of the bud and flower of C. lowianum . Our results show that the two most stable reference genes in different tissues of C. lowianum bud and flower are EF1δ and 60S , the most unstable reference gene is 26S . The expression profiles of the CHS and BCH genes were similar to FPKM value profiles after normalization to the two most stable reference genes, EF1δ and 60S , with the upregulated CHS and BCH expression in flower stage, indicating that the ABP and CBP were activated across the stages of flower development. However, when the most unstable reference gene, 26S , was used to normalize the qRT-PCR data, the expression profiles of CHS and BCH differed from FPKM value profiles, indicating the necessity of selecting stable reference genes. Moreover, CHS and BCH expression was highest in the abaxial lip and adaxial lip, respectively, indicating that the ABP and CBP were activated in abaxial and adaxial lip, respectively, resulting in a presence of red or yellow segments in abaxial and adaxial lip. This study is the first to provide reference genes in C. lowianum , and also provide useful information for studies that aim to understand the molecular mechanisms of flower color formation in C. lowianum .

Background: The treatment of sacral fractures accompanied by nerve injury is complex and often leads to an unsatisfactory prognosis and poor quality of life in patients., Objective: The present study aimed to investigate the clinical value of using 3.0T magnetic resonance contrast-enhanced three-dimensional (MR CE-3D) nerve view magnetic resonance neurography (MRN) in the diagnosis and management of a sacral fracture accompanied by a sacral plexus injury., Methods: Thirty-two patients with a sacral fracture accompanied by a sacral plexus injury, including 24 cases of Denis spinal trauma type II and 8 cases of type III, were enrolled in the study. All patients had symptoms or signs of lumbosacral nerve injury, and an MRN examination was performed to clarify the location and severity of the sacral nerve injury. Segmental localization of the sacral plexus was done to indicate the site of the injury as being intra-spinal (IS), intra-foraminal (IF), or extra-foraminal (EF), and the severity of the nerve injury was determined as being mild, moderate, or severe. Surgical nerve exploration was then conducted in six patients with severe nerve injury. The location and severity of the nerve injury were recorded using intra-operative direct vision, and the results were statistically compared with the MRN examination results., Results: MRN showed that 81 segments had mild sacral plexus injuries (8 segments of IS, 20 segments of IF, 53 segments of EF), 78 segments had moderate sacral plexus injuries (8 segments of IS, 37 segments of IF, and 33 segments of EF), and 19 segments had severe sacral plexus injuries (7 segments of IS, 9 segments of IF, and 3 segments of EF). The six patients who underwent surgery had the following intra-operative direct vision results: 3 segments of moderate injury (IF) and 20 segments of severe injury (7 segments of IS, 10 segments of IF, 3 segments of EF). There was no statistically significant difference in the results between the intra-operative direct vision and those of the MRN examination (p> 0.05)., Conclusion: MR CE-3D nerve view can clearly and accurately demonstrate the location and severity of sacral nerve injury accompanied by a sacral fracture, and has the potential for being the first choice of examination method for this kind of injury, which would be of important clinical value.

Increased urea is one of the common nitrogen forms polluting coastal waters and affecting nutrient dynamics. To investigate the effects of urea on sediment phosphorus (P) release, we carried out a 2-month mesocosm experiment with six targeted loadings of urea (0-0.6 mg N L -1 d -1 ). Results showed that: i) urea was rapidly transformed into ammonium and then nitrate (NO 3 - ). ii) When nitrogen occurred as urea or ammonium, minor P release was observed. iii) After urea were mostly converted to NO 3 - , P release became clearer. iv) NO 3 - had a dual effect by promoting P release through decreasing sediment pH and increasing alkaline phosphatase activity or by inhibiting P release through improving sediment oxidation. v) The overall effects of urea on P release depended on the ultimate NO 3 - concentrations, being prominent when NO 3 - ≥ 11 mg N L -1 . Our findings are of relevance when determining nitrogen reduction targets needed for combating eutrophication., (Copyright © 2021. Published by Elsevier Ltd.)

Objective: To compare rib fracture detection and classification by radiologists using CT images with and without a deep learning model., Materials and Methods: A total of 8529 chest CT images were collected from multiple hospitals for training the deep learning model. The test dataset included 300 chest CT images acquired using a single CT scanner. The rib fractures were marked in the bone window on each CT slice by experienced radiologists, and the ground truth included 861 rib fractures. We proposed a heterogeneous neural network for rib fracture detection and classification consisting of a cascaded feature pyramid network and a classification network. The deep learning-based model was evaluated based on the external testing data. The precision rate, recall rate, F1-score, and diagnostic time of two junior radiologists with and without the deep learning model were computed, and the Chi-square, one-way analysis of variance, and least significant difference tests were used to analyze the results., Results: The use of the deep learning model increased detection recall and classification accuracy (0.922 and 0.863) compared with the radiologists alone (0.812 vs. 0.850). The radiologists achieved a higher precision rate, recall rate, and F1-score for fracture detection when using the deep learning model, at 0.943, 0.978, and 0.960, respectively. When using the deep learning model, the radiologist's reading time was decreased from 158.3 ± 35.7 s to 42.3 ± 6.8 s., Conclusion: Radiologists achieved the highest performance in diagnosing and classifying rib fractures on CT images when assisted by the deep learning model., (© 2021. ISS.)

Inspired by the 2D bilayer lipid membranes in nature, a unique supramolecular "push-pull" synergetic strategy toward self-assembled 2D organic crystals (2DOCs) is proposed in this work, which can effectively suppress the interlayer 3D stacking while maintaining the assembly of the intralayer for 2D growth. For this purpose, a model molecule PF-Py consisting of a planar supramolecular "attractor" and a nonplanar steric "repellor" is designed for the solution self-assembly process. Well-defined 2DOCs including crystal nanosheets and millimeter-sized crystal films with layered amphiphile-like packing are obtained, which is analogical to the cell membranes of living organisms. Thanks to the special packing mode, the 2DOCs have fascinating integrated photoelectric property, with high mobility of 7.8 × 10 -2 cm 2 V -1 s -1 , high crystalline state photoluminescence quantum yield of 55%, and superior deep-blue laser characteristics with a low threshold of 5.51 µJ cm -2 . This supramolecular synergetic strategy advances the design of 2D organic semiconductor crystals for high performance optoelectronics., (© 2021 Wiley-VCH GmbH.)

Background: Due to the diversity of the ingredients, the complexity of the mechanism of action, the uncertainty of the effective ingredients, coupled with the multiple species and multiple growing areas, the quality control (QC) of Traditional Chinese Medicines (TCMs) is challenging. Discovering and identifying effective compounds from the complex extracts of TCMs and then establishing a scientific QC method is the key to the holistic QC of TCMs., Purpose: To develop an anti-lung-cancer-guided spectrum-effect relationship approach for the discovery of QC markers of the rhizome of Curcuma wenyujin (WEZ) and establish a bioactive compounds-based holistic QC method., Methods: The chemical profiling of the volatile oil (WVO) from 42 batches of WEZ collected from different growing areas was performed by GC-MS. The anti-lung cancer activity of different WVO samples was determined by CCK-8 assay against human lung cancer cells (A549). The apoptosis and cell cycle analysis under different concentrations of WVO were detected by flow cytometry. SIMCA-P software was used to perform multivariate statistical analysis on the chemical composition of different WVO samples and to find the different components. Active compounds were screened using a PLSR model of the spectrum-effect relationship. Bioactive compounds-based fingerprint and quantification of the leading bioactive compounds were developed by GC-MS and GC-FID, respectively., Results: Seventy-eight compounds were detected in WVO and 54 were successfully identified. The multivariate statistical analysis uncovered that WVO components and the anti-A549 activity of WVO at the concentration of 60 nl/ml differ greatly according to the origin of the plant. The WVO at the concentration of 60 nl/ml (IC 50 ) increased A549 cells apoptosis significantly with late and early apoptosis of 15.61% and 7.80%, and the number of cells in the G2/M phase were also increased significantly under this concentration. The spectrum-effect relationship analysis revealed that 44 compounds were positively correlated with their activities, and the result was verified by A549 cell viability assay. Sixteen positively correlated compounds were further selected as QC markers according to their relative amount > 0.5% and anticancer activity. Finally, the 16 QC markers-based GC-MS fingerprint was established to holistically control the quality of WEZ, and a GC-FID method was developed for the quantification of leading bioactive compounds, β-elemene and β-caryophyllene., Conclusion: Based on an anti-lung-cancer-guided spectrum-effect relationship approach, the bioactive compounds-based holistic QC method was successfully developed for WEZ, which could provide a valuable reference for the QC of TCMs., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Ethnopharmacological Relevance: Herbal medicines (HMs) often exert integration effects, including synergistic, additive and antagonistic effects, in such ways that they act on multiple targets and multiple pathways on account of their multiple components. Turmeric, made from the rhizome of Curcuma longa L., is a well-known HM prescribed in the polyherbal formulas for cancer treatment in traditional Chinese medicines (TCMs). However, neither the multiple anticancer compounds of turmeric nor the integration effects of these components are fully known., Aim of the Study: This work aims to develop a systematic approach to reveal the integration effect mechanisms of multiple anticancer compounds in turmeric against prostate cancer PC3 cells., Materials and Methods: Combination index and omics technologies were applied to profile the integration effect mechanisms of bioactive compounds in proportions naturally found in turmeric. PC3 cell line (a prostate cancer cell line) fishing and high resolution mass spectrometry were employed to screen and identify the anticancer compounds from turmeric. The combinations which contain different cell-bound compounds in natural proportions were prepared for further evaluation of anti-cancer activity by using cell viability assays, and assessment of cell apoptosis and cell cycle analysis. Combination index analysis was applied to study the integration effects of the anticancer compounds in their natural proportions. Finally, quantitative glycoproteomics/proteomics and Western blot were implemented to reveal the potential synergistic effect mechanisms of the anticancer compounds based on their natural proportions in turmeric., Results: Three curcuminoids (curcumin, CUR; demethoxycurcumin, DMC; bisdemethoxycurcumin, BDMC) in turmeric were discovered and shown to possess significant synergistic anticancer activities. Combination index analysis revealed an additive effect of CUR combined with DMC or BDMC and a slight synergistic effect of DMC combined with BDMC in natural proportions in turmeric, while a combination of all three curcuminoids (CUR, DMC and BDMC) at a ratio of 1:1:1 yielded superior synergistic effects. Interestingly, the presence of BDMC and DMC are essential for synergistic effect. Glycoproteomics and proteomics demonstrated that different curcuminoids regulate various protein pathways, such as ribosome, glycolysis/gluconeogenesis, biosynthesis of amino acids, and combination of CUR + DMC + BDMC showed the most powerful effects on down-regulation of protein expression., Conclusions: Our analytical approach provides a systematic understanding of the holistic activity and integration effects of the anti-cancer compounds in turmeric and three curcuminoids of turmeric showed a synergistic effect on PC3 cells., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Cetoniinae is one of the showiest scarab groups, exhibiting bright-metallic body colors, and usually attract great attention from entomologists and amateur collectors. Larvae of Cetoniinae show dramatically diversity on morphology and living habits. Although being considered one of the best-studied groups of Scarabaeidae, larvae have been described for less than 5% species to the known Cetoniinae. In this study, the final instar larva of Lasiotrichius succinctus hananoi was described using scanning electron microscopy. The larvae are peculiar for bearing a haptomeral process dividing 10 spines into two groups: six on the left side, four on the right side, different from the previous descriptions on L. succinctus (Pallas, 1781). The morphological differences under SEM imply the further requirement of taxonomic revision in Lasiotrichius. Both advantage and disadvantage of SEM utilizing in larval descriptions were briefly discussed., (© 2020 Wiley Periodicals LLC.)

Objective: To investigate the effect of exposure to occupational hazard factors on serum bilirubin in workers. Methods: In April 2019, using cluster sampling method 5 433 workers exposed to occupational hazard factors from July 2017 to March 2019 were screened out by questionnaire and laboratory test, the date of serum bilirubin were used by the logistic regression analysis of single factor card test and wilcoxon band symbol rank and test. Results: The bilirubin decreases with age, is higher in male than in female, the han is higher than the uygur, and the unmarried workers is higher than the married one, there was significant difference in the levels of bilirubin between different genders, ages, ethnic groups and marriages ( P <0.01) . There were statistically significant differences in bilirubin among the occupational hazard factors ( P <0.01) , the bilirubin level is highest in the exposure to physical factors, followed by chemical factors and dust. The multivariate logistic regression analysis showed that the dust was the main factor affecting bilirubin ( OR (dusr/TBIL)=2.080, 95% CI : 1.542~2.807, P <0.01) . Abnormal alanine aminotransferase (ALT) and alanine aminotransferase (AST) are consistent with elevated bilirubin. Conclusion: Exposure to occupational hazard factors may lead to elevated serum bilirubin and abnormal liver function transaminase, the prevention and control of occupational hazards and cccupational health monitoring should be strengthened.

Objective: To compare the efficacy and safety of standard-dose (SD) daptomycin with those of high-dose (HD) daptomycin in complicated skin and soft tissue infections (cSSTIs) in an Asian population., Materials and Methods: Patients from three medical centers diagnosed with cSSTIs were screened in the clinical information system. Patients included in the analysis were divided into two groups: those who received daptomycin at doses ≥ 6 mg/kg (HD group) and those receiving 4 mg/kg (SD group). The demographics and clinical treatment information were analyzed., Results: Overall, 155 patients were recruited, including 108 patients in the SD group and 47 patients in the HD group. The rate of healthcare-associated infections was higher in the HD group (61.70% vs. 37.04%), demonstrating a statistically significant difference (P = 0.005). Compared with the SD group, the HD group had statistically significant early clinical stabilization (72.34% vs 52.78%, P = 0.023). The results of the multivariate analysis indicated that HD daptomycin was an independent effector for early clinical stabilization (HR=0.394, P < 0.001). The rate of drug-related adverse events was equally distributed in the HD and SD groups (36.17% vs. 26.85%, P = 0.243)., Conclusion: Compared with SD daptomycin, HD daptomycin increased the rate of early clinical stabilization in Asian patients with cSSTIs, whereas the incidence of adverse events did not increase., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

During human erythroid maturation, Hsp70 translocates into the nucleus and protects GATA-1 from caspase-3 cleavage. Failure of Hsp70 to localize to the nucleus was found in Myelodysplastic syndrome (MDS) erythroblasts and can induce dyserythropoiesis, with arrest of maturation and death of erythroblasts. However, the mechanism of the nuclear trafficking of Hsp70 in erythroblasts remains unknown. Here, we found the hematopoietic transcriptional regulator, EDAG, to be a novel binding partner of Hsp70 that forms a protein complex with Hsp70 and GATA-1 during human normal erythroid differentiation. EDAG overexpression blocked the cytoplasmic translocation of Hsp70 induced by EPO deprivation, inhibited GATA-1 degradation, thereby promoting erythroid maturation in an Hsp70-dependent manner. Furthermore, in myelodysplastic syndrome (MDS) patients with dyserythropoiesis, EDAG is dramatically down-regulated, and forced expression of EDAG has been found to restore the localization of Hsp70 in the nucleus and elevate the protein level of GATA-1 to a significant extent. In addition, EDAG rescued the dyserythropoiesis of MDS patients by increasing erythroid differentiation and decreasing cell apoptosis. This study demonstrates the molecular mechanism of Hsp70 nuclear sustaining during erythroid maturation and establishes that EDAG might be a suitable therapeutic target for dyserythropoiesis in MDS patients., (© 2020 Federation of American Societies for Experimental Biology.)

Two spirocyclic aromatic hydrocarbon derivatives were prepared to clarify the molecular geometry effects on the regulation of the crystalline morphologies and photophysical behaviors of organic nanocrystals. Due to the different structural symmetry of a spiro-center, distinguishing nanocrystal morphologies with unique crystallization-enhanced/quenched emission was achieved.

Objective: In cervical carcinoma (CC), microRNAs (miRNAs) were reported to be involved in its development. In this study, we explored how miR-377-3p regulates cell metastasis and epithelial-mesenchymal transition (EMT) in CC., Patients and Methods: Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), Dual-Luciferase Assay, transwell assays, and Western blot analysis were performed to explore the dysregulation of miR-377-3p., Results: MiR-377-3p expression was decreased in CC, and the downregulation of miR-377-3p could predict poor prognosis in CC patients. Moreover, miR-377-3p overexpression repressed cell invasion and migration in CC. Similarly, miR-377-3p overexpression also inhibited EMT in CC cells. Furthermore, miR-377-3p directly targeted SGK3 in CC cells. SGK3 silence had the same function as miR-377-3p overexpression in CC. Especially, the upregulation of SGK3 abolished the inhibitory action of miR-377-3p in CC., Conclusions: Taken together, miR-377-3p inhibited cell metastasis and EMT by suppressing SGK3 expression. Moreover, the high miR-377-3p expression could predict good prognosis of CC patients.

The stems of Dendrobium officinale, a well-known and expensive food material and herbal medicine in Asia, has recently suffered adulterants and counterfeits by using lower-price confusing Dendrobium species such as D. devonianum or D. transparens in the herbal market. However, robust methods that could authenticate D. officinale from its confusing species effectively are still lacking, especially for the dried samples. This study committed to discover specific peptides biomarkers for the authentication of D. officinale from the other two Dendrobium species using label-free proteomics by nanoLC LTQ Orbitrap mass spectrometry. Multivariate statistical analysis was applied to visualize the difference between the three Dendrobium species. As a result, 29 peptides among a total of 343 measurable peptides were selected to be potential biomarkers for the classification of these Dendrobium species. The validation of the representative peptide biomarkers was carried out by the synthesized peptides and 3 peptide biomarkers were found significant for the authentication of D. officinale. Further analysis showed that peptide ALGLELDLSER may also be a biomarker for the discrimination of the D. officinale originated from different geographical regions., 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 © 2020 Elsevier B.V. All rights reserved.)

Dayan lignite was subjected to thermal dissolution sequentially with cyclohexane, acetone, and methanol. Each thermal dissolution extract was subjected to further separation/enrichment using column chromatography, which was sequentially eluted with petroleum ether, a mixture of ethyl acetate and petroleum ether (vol:vol = 1:1), and ethyl acetate. The three thermal dissolution extracts and nine enrichment subfractions were characterized by an Orbitrap mass spectrometry equipped with an atmospheric pressure chemical ionization ion source. The mass spectrometry data were also statistically analyzed by principal component analysis, which can reduce the dimensionality of data and classify multiple samples according to principal components. Identified compounds in the extracts and subfractions are classified into eight classes according to the heteroatom distribution. Hydrocarbon class is mainly presented in the petroleum ether fraction, and oxygen class, nitrogen class, and oxygen-nitrogen class are distributed in both petroleum ether/ethyl acetate and ethyl acetate subfractions. The combination of different analytical methods enhances the understanding of coal at the molecular level and provides important data for downstream refining processes., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)