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Shu-Jie Pang,1,&ast; Zhe Sun,1,&ast; Wen-Feng Lu,1,&ast; Hui Si-Ma,1 Zhi-Peng Lin,2 Yang Shi,1 Ying-Cheng Yang,1 Xi-Jun Zhao,1 Guang-Shun Yang,1 Guang-Zhi Jin,3 Ning Yang1 1Department V of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, People’s Republic of China; 2Department of Hepatobiliary Surgery, The 940th Hospital of CPLA Joint Logistics Support Force, Lanzhou, 730050, People’s Republic of China; 3Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200336, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ning Yang, Department V of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, People’s Republic of China, Tel +86 21 81877591, Fax +86 21 6556 6851, Email lancet00@163.com Guang-Zhi Jin, Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200336, People’s Republic of China, Email jgzhi@hotmail.comBackground: RBM10ʹs function in hepatocellular carcinoma (HCC) has rarely been addressed. We intend to explore the prognostic significance and therapeutic meaning of RBM10 in HCC in this study.Methods: Multiple common databases were integrated to analyze the expression status and prognostic meaning of RBM10 in HCC. The relationship between RBM10 mRNA level and clinical features was also assessed. Multiple enrichment analyses of the differentially expressed genes between RBM10 high- and low- transcription groups were constructed by using R software (version 4.0.2). A Search Tool for Retrieval of Interacting Genes database was used to construct the protein–protein interaction network between RBM10 and other proteins. A tumor immune estimation resource database was employed to identify the relationship between RBM10 expression and immune cell infiltrates. The prognostic value of RBM10 expression was validated in our HCC cohort by immunohistochemistry test.Results: The transcription of RBM10 mRNA was positively correlated with tumor histologic grade (p < 0.001), T classification (p < 0.001), and tumor stage (p < 0.001). High transcription of RBM10 in HCC predicted a dismal overall survival (p = 0.0037) and recurrence-free survival (p < 0.001). Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and Gene Set Enrichment Analysis all revealed that RBM10 was involved in the regulation of cell cycle, DNA replication, and immune-related pathways. Tumor immune estimation analysis revealed that RBM10 transcription was positively related to multiple immune cell infiltrates and the expressions of PD-1 and PD-L1.Conclusion: RBM10 was demonstrated to be a dismal prognostic factor and a potential biomarker for immune therapy in HCC in that it may be involved in the immune-related signaling pathways.Keywords: RBM10, hepatocellular carcinoma, prognosis, differentially expressed gene, integrated bioinformatics analysis

Yang Han,1 Bo Tang,2 Xian-Miao Li,3 Guo-Song-Rui Yang,4 Li Yang4 1Department of Finance and Accounting, School of Economics and Management, Anhui University of Science and Technology, Huainan, 232001, People’s Republic of China; 2Department of Management, Birmingham Business School, University of Birmingham, Birmingham, B15 2TT, UK; 3Department of Business and Administration, School of Economics and Management, Anhui University of Science and Technology, Huainan, 232001, People’s Republic of China; 4Department of Management Science and Engineering, School of Economics and Management, Anhui University of Science and Technology, Huainan, 232001, People’s Republic of ChinaCorrespondence: Yang Han, Department of Finance and Accounting, School of Economics and Management, Anhui University of Science and Technology, No. 168 of Taifeng Street, Shannan District, Huainan, 232001, People’s Republic of China, Tel +86 15375052657, Email yanghan3134hes@163.comBackground: This study aims to investigate how a team can be resilient in the face of crisis and adversity.Methods: This empirical study adopted a quantitative research method. The data were collected by questionnaire survey, and the stats analysis package in R language and AMOS 23 were used for empirical analysis of 98 teams. Based on complex adaptive system theory and conservation of resources theory, this study was constructed the theoretical framework of “environmental influence — team exchange — team resilience” with informational team faultline (ITF) as independent variable, team leader member exchange (TLMX) and team member exchange (TMX) as mediating and moderating variables, and team resilience as dependent variable in the context of Chinese culture.Results: We found that the ITF had a significant negative effect on the team resilience. TLMX and TMX played partial mediating role between ITF and team resilience. In addition, TLMX and TMX played moderating role between ITF and team resilience, that is, weakening the negative influence of ITF on team resilience.Conclusion: This study contributes to clarify the mechanism of the influence of ITF on team resilience, and provide reference for team leaders to improve team resilience in the face of adversity.Keywords: informational team faultline, team leader member exchange, team member exchange, team resilience, Chinese culture context

Contents Microbial environment is one of the important factors that affect the quality of preserved semen. Iodine methionine ( IM), participating in the production and activation of metabolic enzymes, is a new type of amino acid chelate. To date, there has been no report to evaluate the effects of IM on boar semen preservation at 17°C. This study was designed to investigate the effects of IM on boar sperm quality and reproductive performance during liquid storage at 17°C and its antibacterial effect. Semen samples collected from six Yorkshire boars were diluted with basic liquid containing different concentrations of IM (0, 20, 40, 80, 160 and 320 μM). Subsequently, sperm motility, plasma membrane integrity and acrosome integrity were determined. After 6 days of preservation, the difference in microbial composition between control group and 80 μM IM group was compared using 16S rDNA sequencing, and the effects of IM on reproductive performance were also compared and analysed between the two groups. The results demonstrated that 20, 40 and 80 μM IM improved boar sperm motility, plasma membrane integrity and acrosome integrity. 80 μM IM was the optimum concentration. Conversely, 160 and 320 μM IM resulted in deleterious consequences to boar sperm quality compared to the control group and other treatment groups ( p < .05). After 6 days of preservation, sperm motility, plasma membrane integrity and acrosome integrity were 56.0%, 51.8% and 59.4%, respectively. There was no significant difference in non-return rate between the two groups ( p > .05). But the litter size of 80 μM IM group was significantly higher than that of control group ( p < .05). 80 μM IM inhibited proliferation of the phylum Proteobacteria and the genus Staphylococcus as well as Pseudomonas ( p < .05). Further studies are required to understand the antibacterial mechanism of IM in liquid-preserved boar semen. [ABSTRACT FROM AUTHOR]

Objectives The aim was to compare the change in dental caries status in two different intervention groups of the Children's Oral Health Promotion Programme ( COHPP). Methods A longitudinal study among 500 children who had participated into the COHPP for 6 years was conducted in Pyongyang, Democratic People's Republic of Korea ( DPRK). Children in Group I received intensified school-based intervention and were clinically examined at the age of 7 years in 2007 ( n = 250), 10 years in 2010 ( n = 250) and 13 years in 2013 ( n = 242). Children in Group II ( n = 250) joined the programme at the age of 4 years in kindergarten in 2007, were provided with early preschool-based intervention and were clinically examined at the age of 7 years in 2010 and 10 years in 2013. Results Both the prevalence and the mean number of dt + DT decreased significantly in both groups during the follow-up. This was due to decrease in the number of dt, whereas the number of DT remained relatively constant. Poisson regression showed that the association between the group status and the change in the number of dt + DT was statistically significant when adjusted for gender but disappeared when the school was included in the analysis. Conclusions The decrease in dental caries may be partly due to the exfoliation of deciduous teeth and dental treatment received. However, the study gave some reference emphasizing the early starting of the prevention. [ABSTRACT FROM AUTHOR]

Adipose tissue dysfunction underpins the association of obesity with type 2 diabetes. Adipogenesis is required for the maintenance of adipose tissue function. It involves the commitment and subsequent differentiation of preadipocytes and is coordinated by autocrine, paracrine, and endocrine factors. We previously reported that fibroblast growth factor-1 (FGF-1) primes primary human preadipocytes and Simpson Golabi Behmel syndrome (SGBS) preadipocytes and increases adipogenesis through a cascade involving extracellular signal-related kinase 1/2 (ERK1/2). Here, we aimed to use the FGF-1 system to identify novel adipogenic regulators. Expression profiling revealed bone morphogenetic protein (BMP) and activin membrane-bound inhibitor (BAMBI) as a putative FGF-1 effector. BAMBI is a transmembrane protein and modulator of paracrine factors that regulate adipogenesis, including transforming growth factor (TGF) superfamily members (TGF-β and BMP) and Wnt. Functional investigations established BAMBI as a negative regulator of adipogenesis and modulator of the anti- and proadipogenic effects of Wnt3a, TGF-β1, and BMP-4. Further studies showed that BAMBI expression levels are decreased in a mouse model of diet-induced obesity. Collectively, these findings establish BAMBI as a novel, negative regulator of adipogenesis that can act as a nexus to integrate multiple paracrine signals to coordinate adipogenesis. Alterations in BAMBI may play a role in the (patho)physiology of obesity, and manipulation of BAMBI may present a novel therapeutic approach to improve adipose tissue function. [ABSTRACT FROM AUTHOR]

Discrimination of the shape of motion-produced forms generated by random elements (i.e. second-order stimuli varying in element density and temporal correlation) was tested in four groups: (1) subjects with Prader-Willi syndrome (PWS), chromosome 15q deletion subtype; (2) subjects with PWS, uniparental maternal disomy (UPD) subtype; (3) equivalent non-PWS controls; and (4) normal controls. The performance of the normal controls exceeded that of all other groups (78% correct, P < 0.009). The PWS deletion (66%) and the equivalent control groups (59%) did not differ (P < 0.95). The UPD group performed significantly less well (38%, P < 0.04) than all the other groups. The performance of the PWS deletion and equivalent control groups is consistent with other data indicating that these populations encounter difficulty meeting the processing demands posed by second-order stimuli. The inferior performance of the UPD group may be attributed to receiving two active alleles of a maternally expressed gene influencing neural development. One candidate is the ubiquitin protein ligase gene (UBE3A), which is maternally expressed only and localized to the 15q region. Other possibilities include the requirement of a paternally expressed gene, residual mosaic trisomy 15 in the brain tissue or complex interactions including specific ratios of differentially spliced gene products. [ABSTRACT FROM AUTHOR]

A carbazolyl-based fluorescent metal-organic framework with deep-blue light emission and a high quantum yield (88%) has been screened out by changing the ratio of mixed ligands, named Cz-MOF-2, which was constructed by ZrO 4 (OH) 4 clusters, 3-(9-ethyl-9 H -carbazol-3-yl)-4-methylthieno[2,3- b ]thiophene-2,5-dicarboxylate (H 2 ECMTDC) and 3,4-dimethyl-dihydrothieno[2,3- b ]thiophene-2,5-dicarboxylate (H 2 DMTDC). Cz-MOF-2 has excellent sensitivity in fluorescent sensing of 2,6-dichloro-4-nitroaniline (DCN), nitrofurazone (NZF), and nitrofurantoin (NFT) with detection limits of 3.37 × 10 -7 , 1.64 × 10 -5 , and 1.76 × 10 -5 M, respectively. The quenching mechanisms involving electron transfer and competitive absorption were comprehensively elucidated through DFT calculations and UV absorption experiments. Cz-MOF-2 has been fabricated into a rapidly regenerated composite membrane with PVDF as a visualized fluorescent sensor for DCN. Furthermore, the carbazolyl groups covalently modified in the framework endowed Cz-MOF-2 with a suitable band gap (2.58 eV) for photocatalytic degradation of organic contaminants. It demonstrated superior photocatalytic efficiency compared to UiO-66 and NH 2 -UiO-66 in the degradation of tetracycline (TC), and the removal efficiency was up to 85% (20 mg of catalyst, 50 mL, 20 mg/L TC solution and 180 min) under simulated sunlight irradiation using a 300 W Xe lamp. Photoelectrochemical tests demonstrate that Cz-MOF-2 exhibits high photocurrent density and low charge transfer resistance, which provide evidence for the efficient charge separation capability. Radical trapping experiments and ESR detection have substantiated that · O 2 - and h + are the primary active species involved in this photocatalytic reaction. This work highlights the potential of MOFs in the targeted design and development of fluorescent sensors and photocatalysts for environmental detection and remediation.

The spine grapes (Vitis davidii Foëx.) are wild grape species that grow in southern China, and can be used for table grapes, juicing and winemaking. To systematically investigate the flavor profiles of spine grapes, flavonoids and volatile compounds were detected in five spine grape varieties (Seputao, Ziqiu, Miputao, Tianputao and Baiputao) using HPLC-QqQ-MS/MS and GC-MS. The content of flavonoids highly depended on the variety, such as the total concentrations of anthocyanins (91.43-328.85 mg/kg FW) and flavonols (33.90 to 83.16 mg/kg FW). The volatile compounds with higher odor active value were selected to describe the aroma of spine grapes. Hexanal, (E)-2-hexenal and (E, Z)-2,6-nonadienal contributed to the higher herbaceous flavor to Baiputao and Ziqiu. β-Damascenone and (E)-2-nonenal gave Baiputao a flavor with more floral, fruity and earthy. Their characteristic flavor compounds were subsequently revealed using multivariate statistical analysis. The results helped producers to further develop and utilize the spine grapes., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Interleaflet coupling-the influence of one leaflet on the properties of the opposing leaflet-is a fundamental plasma membrane organizational principle. This coupling is proposed to participate in maintaining steady-state biophysical properties of the plasma membrane, which in turn regulates some transmembrane signaling processes. A prominent example is antigen (Ag) stimulation of signaling by clustering transmembrane receptors for immunoglobulin E (IgE), FcεRI. This transmembrane signaling depends on the stabilization of ordered regions in the inner leaflet for sorting of intracellular signaling components. The resting inner leaflet has a lipid composition that is generally less ordered than the outer leaflet and that does not spontaneously phase separate in model membranes. We propose that interleaflet coupling can mediate ordering and disordering of the inner leaflet, which is poised in resting cells to reorganize upon stimulation. To test this in live cells, we first established a straightforward approach to evaluate induced changes in membrane order by measuring inner leaflet diffusion of lipid probes by imaging fluorescence correlation spectroscopy, by imaging fluorescence correlation spectroscopy (ImFCS), before and after methyl-α-cyclodexrin (mαCD)-catalyzed exchange of outer leaflet lipids (LEX) with exogenous order- or disorder-promoting phospholipids. We examined the functional impact of LEX by monitoring two Ag-stimulated responses: recruitment of cytoplasmic Syk kinase to the inner leaflet and exocytosis of secretory granules (degranulation). Based on the ImFCS data in resting cells, we observed global increase or decrease of inner leaflet order when outer leaflet is exchanged with order- or disorder-promoting lipids, respectively. We find that the degree of both stimulated Syk recruitment and degranulation correlates positively with LEX-mediated changes of inner leaflet order in resting cells. Overall, our results show that resting-state lipid ordering of the outer leaflet influences the ordering of the inner leaflet, likely via interleaflet coupling. This imposed lipid reorganization modulates transmembrane signaling stimulated by Ag clustering of IgE-FcεRI., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Biophysical Society. All rights reserved.)

Plants of the Asteraceae family have been cultivated worldwide for economic, medicinal, and ornamental purposes, including genera such as Aster , Helianthus , and Cosmos . Numerous studies examined their secondary metabolites; however, those of Aster × chusanensis , which is a natural hybrid species in South Korea, are unclear, and optimized propagation methods should be identified. We analyzed phenolic acid concentrations in each part of Aster × chusanensis through HPLC. Further, we investigated the growth characteristics and secondary metabolite concentrations under various growth temperatures using division propagation, followed by growing at 20, 25, and 30 °C in a growth chamber. Chlorogenic acid was the primary compound, which was particularly high in the leaves. The growth characteristics did not differ significantly between temperatures, and 30 °C was most efficient for phenolic acid biosynthesis. Our results provide valuable information on optimized propagation and secondary metabolite concentrations under different temperatures of Aster × chusanensis .

Keteleeria evelyniana Mast var. pendula Hsüeh, a typical plant species of extremely small population, is faced to be endangered. The complete chloroplast (cp) genome of K. evelyniana var. pendula has been assembled and annotated for the first time in this study. The complete genome in length was found to be 117,139 bp. The genome annotation revealed a total of 118 genes, including 34 transfer RNA (tRNA) genes, 4 ribosomal RNA (rRNA) genes, and 80 protein-coding genes. The maximum-likelihood phylogenetic tree supported that K. evelyniana var. pendula , K. fortune , K. evelyniana , and K. davidiana are clustered in one branch. This complete chloroplast genome helped us to understand the evolution of K. evelyniana var. pendula . These results laid the foundation for future studies on the conservation of this species., Competing Interests: No potential conflict of interest was reported by the authors., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

As the global population ages, the prevalence of Parkinson's disease (PD) is steadily on the rise. PD demonstrates chronic and progressive characteristics, and many cases can transition into dementia. This increases societal and economic burdens, emphasizing the need to find effective treatments. Among the widely recognized causes of PD is the abnormal accumulation of proteins, and autophagy dysfunction accelerates this accumulation. The resultant Lewy bodies are also commonly found in Alzheimer's disease patients, suggesting an increased potential for the onset of dementia. Additionally, the production of free radicals due to mitochondrial dysfunction contributes to neuronal damage and degeneration. The activation of astrocytes and the M1 phenotype of microglia promote damage to dopamine neurons. The drugs currently used for PD only delay the clinical progression and exacerbation of the disease without targeting its root cause, and come with various side effects. Thus, there is a demand for treatments with fewer side effects, with much potential offered by natural products. In this study, we reviewed a total of 14 articles related to herbal medicines and natural products and investigated their relevance to possible PD treatment. The results showed that the reviewed herbal medicines and natural products are effective against lysosomal disorder, mitochondrial dysfunction, and inflammation, key mechanisms underlying PD. Therefore, natural products and herbal medicines can reduce neurotoxicity and might improve both motor and non-motor symptoms associated with PD. Furthermore, these products, with their multi-target effects, enhance bioavailability, inhibit antibiotic resistance, and might additionally eliminate side effects, making them good alternative therapies for PD treatment.

Interferons (IFNs) are cytokines with potent antineoplastic and antiviral properties. IFNα has significant clinical activity in the treatment of myeloproliferative neoplasms (MPN), but the precise mechanisms by which it acts are not well understood. Here, we demonstrate that chromatin assembly factor 1 subunit B (CHAF1B), an Unc-51-like kinase 1 (ULK1)-interactive protein in the nuclear compartment of malignant cells, is overexpressed in patients with MPN. Remarkably, targeted silencing of CHAF1B enhances transcription of IFNα-stimulated genes and promotes IFNα-dependent antineoplastic responses in primary MPN progenitor cells. Taken together, our findings indicate that CHAF1B is a promising newly identified therapeutic target in MPN and that CHAF1B inhibition in combination with IFNα therapy might offer a novel strategy for treating patients with MPN., Significance: Our findings raise the potential for clinical development of drugs targeting CHAF1B to enhance IFN antitumor responses in the treatment of patients with MPN and should have important clinical translational implications for the treatment of MPN and possibly in other malignancies., (© 2023 The Authors; Published by the American Association for Cancer Research.)

MicroRNAs (miRNAs) are a class of non-coding single-stranded RNA molecules about 22 nucleotides in length and are encoded by endogenous genes, and are involved in the regulation of post-transcriptional gene expression in animals and plants. Many studies have shown that microRNAs regulate the development of skeletal muscle, mainly manifested in the activation of muscle satellite cells and biological processes such as proliferation, differentiation, and formation of muscle tubes. In this study, miRNA sequencing screening of longissimus dorsi (LD, mainly fast-twitch fibers) and soleus muscle (Sol, dominated by slow-twitch fibers) identified the miR-196b-5p as a differentially expressed and highly conserved sequence in different skeletal muscles. Studies of miR-196b-5p in skeletal muscle have not been reported. In this study, miR-196b-5p mimics and inhibitor were used in miR-196b-5p overexpression and interference experiments in C2C12 cells. The effect of miR-196b-5p on myoblast proliferation and differentiation was analyzed by western blotting, real-time quantitative RT-PCR, flow cytometry, immunofluorescence staining, and the target gene of miR-196b-5p was identified by bioinformatics prediction and analyzed by dual luciferase reporter assays. The results showed that overexpression of miR-196b-5p could significantly increase the mRNA and protein expression of Cyclin B, Cyclin D and Cyclin E (P<0.05); Cell cycle analysis showed that overexpression of miR-196b-5p significantly increased the proportion of cells in the S phase (P<0.05), indicating that miR-196b-5p could accelerate cell cycle progress. Results of EdU staining showed that overexpression of miR-196b-5p significantly promoted cell proliferation. Conversely, inhibition of miR-196b-5p expression could significantly reduce the proliferation capacity of myoblasts. Further, overexpression of miR-196b-5p could significantly increase the expression levels of myogenic marker genes MyoD, MoyG and MyHC (P<0.05), thereby promoting myoblast fusion and accelerating C2C12 cell differentiation. Bioinformatics predictions and dual luciferase experiments demonstrated that miR-196b-5p could target and inhibit the expression of the Sirt1 gene. Altering the Sirt1 expression could not rescue the effects of miR-196b-5p on the cell cycle, but could weaken the promoting effects of miR-196b-5p on myoblast differentiation, suggesting that miR-196b-5p promoted myoblast differentiation by targeting Sirt1.

Building metal-organic frameworks (MOFs) covalently modified by onium halides is a promising approach to develop efficient MOF-based heterogeneous catalysts for the cycloaddition of CO 2 to epoxides (CCE) into cyclic carbonates. Herein, we report a novel zirconium-based MOF covalently modified by methyl pyridinium bromide, Zr 6 O 4 (OH) 4 (MPTDC) 2.2 (N-CH 3 -MPTDC) 3.8 Br 3.8 ((Br-)CH3-Pyridinium-MOF-1), where MPTDC denotes 3-methyl-4-pyridin-4-yl-thieno[2,3- b ] thiophene-2,5-dicarboxylate. The structure and composition of this complex were fully characterized with PXRD, NMR, XPS, TEM and so on. CO 2 adsorption experiments show that (Br-)CH3-Pyridinium-MOF-1 has a higher affinity for CO 2 than its electrically neutral precursor, which should be attributed to the fact that charging frameworks containing pyridinium salt have stronger polarization to CO 2 . (Br-)CH3-Pyridinium-MOF-1 integrated reactive Lewis acid sites and Br - nucleophilic anions and exhibited efficient catalytic activity for CCE under ambient pressure in the absence of co-catalysts and solvents. Furthermore, (Br-)CH3-Pyridinium-MOF-1 was recycled after five successive cycles without substantial loss in catalytic activity. The corresponding reaction mechanism also was speculated.

Purpose: The epigenetic clock has been acknowledged as an indicator for molecular aging, but few studies have examined possible associations of DNA methylation (DNAm) age or age acceleration (AA) with symptom burden in individuals who are treated for cancer. This study explored the association of DNAm age or AA with psychoneurological (PN) symptoms, including cognitive impairment, fatigue, sleep disturbances, pain, and depressive symptoms, in breast cancer survivors over a 2-year period., Methods: We measured PN symptoms using reliable instruments and DNAm levels by Infinium HumanMethylation450K BeadChip (N = 72). DNAm age was calculated by the Horvath, Grim, and Hannum-based intrinsic and extrinsic age estimations. AA was defined by the residual regressing estimated epigenetic age on chronological age. Mixed regression models were fitted for AA and changes in AA to study the association over time. Separate linear regression models and a mixed-effects model were fitted for AA at each time point., Results: Horvath-AA, Grim-AA, and extrinsic epigenetic AA were significantly changed over time, while intrinsic epigenetic AA did not exhibit any temporal changes. Increased AA was associated with greater anxiety and fatigue, as well as worse cognitive memory, adjusting for race, BMI, income, chemotherapy, radiation therapy, and chronological age. Increased DNAm age was associated with greater anxiety over 2 years., Conclusion: Our findings suggest DNAm age and AA may be associated with PN symptoms over the course of cancer treatment and survivorship. Some PN symptoms may be amenable to preventive interventions targeted to epigenetic clocks that influence aging-associated processes., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Clinical pharmacists play a pivotal role in ensuring medication safety due to their detailed understanding of the medication-use process. This study aimed to propose the concept of pharmaceutical care pathway (PCP) in surgical care and design the work pattern and workflow in the healthcare systems of China., Setting: Data were collected from patients in the Department of Hepatobiliary Surgery of the First People's Hospital of Lianyungang in China between January 2019 and December 2019., Materials and Methods: The study was conducted using 346 patients in the control group and 363 in the intervention group. The control group was managed only by the clinical pathway (CP), while the intervention group was managed by the CP and PCP., Main Outcome Measure: Adverse drug reactions (ADRs), patient satisfaction, hospital expense, drug cost, length of stay, and prescription situations were documented., Results: Using PCP, the rational use of drugs increased from 56% in the control group to 94.2% in the intervention group. Further, 124 (35.8%) ADRs in the control group and 44 (12.1%) ADRs in the intervention group were assessed using the Karch and -Lasagna scale. The mean hospital expense was 21,949.12 ± 2,311.25 yuan in the control group and 17,566.25 ± 1,082.56 yuan in the intervention group. The mean drug cost was 6,250.69 ± 589.35 yuan and 4,894.22 ± 356.14 yuan (1 US$ = 6.37 yuan). The mean length of stay was 12.23 ± 2.51 days and 8.35 ± 1.32 days in the control and intervention groups, respectively. Patient satisfaction increased significantly., Conclusion: PCP reduced the length of stay for patients and drug-related adverse events, increased the rational use of drugs, cost-effectiveness, patient satisfaction, and consequently, improved the quality of service in surgery medicine.

Cardiac remodelling mainly manifests as excessive myocardial hypertrophy and fibrosis, which are associated with heart failure. Gentianella acuta (G. acuta) is reportedly effective in cardiac protection; however, the mechanism by which it protects against cardiac remodelling is not fully understood. Here, we discuss the effects and mechanisms of G. acuta in transverse aortic constriction (TAC)-induced cardiac remodelling in rats. Cardiac function was analysed using echocardiography and electrocardiography. Haematoxylin and eosin, Masson's trichrome, and wheat germ agglutinin staining were used to observe pathophysiological changes. Additionally, real-time quantitative reverse transcription polymerase chain reaction and western blotting were used to measure protein levels and mRNA levels of genes related to myocardial hypertrophy and fibrosis. Immunofluorescence double staining was used to investigate the co-expression of endothelial and interstitial markers. Western blotting was used to estimate the expression and phosphorylation levels of the regulatory proteins involved in autophagy and endothelial-mesenchymal transition (EndMT). The results showed that G. acuta alleviated cardiac dysfunction and remodelling. The elevated levels of myocardial hypertrophy and fibrosis markers, induced by TAC, decreased significantly after G. acuta intervention. G. acuta decreased the expression of LC3 II and Beclin1, and increased p62 expression. G. acuta upregulated the expression of CD31 and vascular endothelial-cadherin, and prevented the expression of α-smooth muscle actin and vimentin. Furthermore, G. acuta inhibited the PI3K/Akt/FOXO1/3a pathway and activated the Notch signalling. These findings demonstrated that G. acuta has cardioprotective effects, such as alleviating myocardial fibrosis, inhibiting hypertrophy, reducing autophagy, and blocking EndMT by regulating the PI3K/Akt/FOXO1/3a and Notch signalling pathways., Competing Interests: Conflict of interest statement We declare that there are no financial and personal relationships with other people or organizations that can inappropriately influence our work. There is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

It is well known that the role of gut microbiota in drug metabolism, especially in oral difficult absorbable drugs. Understanding the gut microbiota could enable us to understand drugs in new ways. The purpose of the study was to investigate explore the metabolites of the anti-prostate cancer drug Abiraterone by examining gut microbiota metabolism and hepatic metabolism in vitro . In this study, five metabolites (M1, M2, M3, M4 and M5) of Abiraterone were discovered using LC/MS n -IT-TOF. Four isomeric metabolites M1-M4 were found in liver microsome. M5 was found in the intestinal contents of Sprague-Dawley rats with a molecular weight of 388.31. Among them, M4 was found to be Abiraterone N-Oxide by comparison with the standard sample. After further comparing the metabolic behavior of Abiraterone in rat gut microbiota and liver microsomes, we delineated the possible metabolic pathways of Abiraterone. In conclusion, Abiraterone is metabolized specifically in liver microsomes and gut microbiota. This study can provide a theoretical basis for elucidating the metabolic mechanism of Abiraterone and guide its rational application in clinic., 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 Keranmu, Yang, Wahafu, Han, Yang and Xing.)

Introduction: Yoga has been shown to reduce pain and improve function in populations with chronic low back pain (cLBP), yet the underlying molecular mechanisms remain elusive. This study examined the feasibility and acceptability of a yoga research protocol, including recruitment, retention, and data collection, and investigated the preliminary effects of yoga on psychological and neurophysiological functions, including gene expression and DNA methylation profiles, in participants with cLBP., Methods: A one-arm trial was conducted with 11 participants with cLBP who enrolled in a 12-week yoga intervention. Data on subjective pain characteristics, quantitative sensory testing, and blood for analysis of differentially expressed genes and CpG methylation was collected prior to the start of the intervention and at study completion., Results: Based on pre-determined feasibility and acceptability criteria, the yoga intervention was found to be feasible and highly acceptable to participants. There was a reduction in pain severity, interference, and mechanical pain sensitivity post-yoga and an increase in emotion regulation and self-efficacy. No adverse reactions were reported. Differential expression analysis demonstrated that the yoga intervention induced increased expression of antisense genes, some of which serve as antisense to known pain genes. In addition, there were 33 differentially hypomethylated positions after yoga (log2 fold change ≥ 1), with enrichment of genes involved in NIK/NF-kB signaling, a major pathway that modulates immune function and inflammation., Discussion/conclusions: The study supports the feasibility and acceptability of the proposed protocol to test a specific mechanism of action for yoga in individuals with cLBP. These results also support the notion that yoga may operate through our identified psychological and neurophysiologic pathways to influence reduced pain severity and interference., (© 2022. The Author(s).)

We investigated the decomposition characteristics of Eragrostis minor , mosses, and leaves of Artemisia ordosica with litterbag method in the sand-binding revegetation area, southeastern edge of the Tengger Desert, and further examined their effects on soil microbial communities using the Illumina MiSeq sequencing method. The results showed that the decomposition duration and litter types significantly affected litter decomposition rate. Mosses had the lowest decomposition rate, with a mass loss ratio of only 15.4% after decomposition for 13 months. The average decomposition rates of E. minor and leaves of A. ordosica were 4.9 and 3.4-fold of that of mosses, respectively. During decomposition for 11 months, the dominant bacterial phyla were Actinomycota and Proteobacteria, while that of the fungal community was Ascomycota. Moss decomposition significantly increased the relative abundance of Bacteroidetes and Chloroflexi, but remarkedly decreased the abundance of Basidiomycetes. The diversity and richness of bacterial and fungal communities significantly increased after litter decomposition. The compositional changes of fungal community were significant among litters, but that of bacterial community was not. There was a negative correlation between decomposition rate and the diversity and richness of bacterial and fungal communities. Plant polysaccharides, total phosphorus, soil pH, microbial biomass nitrogen, and soil ammonium content were the main factors affecting microbial community structure. Litter decomposition changed the composition and interspecific similarity within microbial communities, as well as increased the diversity and richness of soil microbial communities, and thus would promote the restoration of soil habitat.

Background: Breast cancer survivors (BCS) often report poor sleep quality and wakefulness throughout the night as the greatest challenges experienced during and posttreatment., Objectives: This study aimed to elucidate characteristics of sleep disturbances and determine potential predictors that affect sleep disturbances in BCS for 2 years postchemotherapy., Methods: This is a secondary analysis of data from the EPIGEN study, which longitudinally examined sociodemographic and cancer-related factors, lifestyle, symptom characteristics, and epigenetic factors at baseline prior to chemotherapy (T1), the midpoint (T2), 6-month (T3), 1-year (T4), and 2-year (T5) time points postchemotherapy. Temporal lifestyle changes, symptom characteristics, and epigenetic factors were explored using linear mixed-effects models with a random intercept. A linear regression model was fitted to identify significant predictors of sleep disturbances at each time point., Results: In 74 BCS with an average age of 51 years and 70% non-Hispanic White, BCS experienced severe sleep disturbances at T2, which gradually improved over time. Significant temporal changes in midsleep awakenings, early awakenings, and fatigue at work were observed, with disturbances being elevated at T2. Anxiety (T1, T2, and T4), fatigue (T3 and T4), and perceived stress (T3) were significant predictors after adjusting for radiation therapy, surgery, and adjuvant endocrine therapy., Discussion: This study highlights that predictors of sleep disturbances change over time, with anxiety being a factor earlier in the treatment trajectory (prechemotherapy) and continuing over time with fatigue and perceived stress being involved later in the treatment trajectory. Our results indicate that symptom management strategies to address sleep disturbances should be tailored to the temporal factors that may change in severity during active treatment and early survivorship period. Findings gained from this study on sleep disturbance patterns and the potential risk factors can be incorporated into clinical practice in planning education and developing interventions., Competing Interests: The authors have no conflicts of interest to report., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Depressive symptoms are highly prevalent in breast cancer patients. These symptoms can contribute to lower treatment adherence, increased healthcare charges, and higher mortality rates. Growing evidence suggests that genetic variations may be associated with depressive symptom susceptibility., Objective: To comprehensively review current findings on the association of genetic variations with depressive symptoms in breast cancer patients., Methods: A literature search was conducted using keywords such as gene variation, single-nucleotide polymorphism, depression/depressive symptoms, and breast cancer. Four hundred articles were retrieved from PubMed, Web of Science, CINAHL, and PsycINFO, yielding 9 full-text, data-based articles. The study quality was assessed using the STrengthening the REporting of Genetic Association studies guideline., Results: Genetic polymorphisms in brain-derived neurotrophic factor (BDNF), interferon γ receptor 1 (IFNGR1), interleukin-6 (IL-6), tumor necrosis factor α (TNFA), and IL-1B were found to be associated with depressive symptoms among breast cancer patients. The role of serotonin transporter gene linked promotor region (5-HTTLPR) functional polymorphisms on depressive symptoms was inconclusive. The overall quality of reporting results and methods was medium., Conclusions: This is the first review of genetic variations related to differences in levels of depressive symptoms among breast cancer patients. Genetic polymorphisms in inflammatory, neuronal system, and signal transduction pathways can influence the susceptibility. However, more research regarding this topic is needed to further clarify genetic risk factors., Implications for Practice: Healthcare providers may determine patients at higher risk of developing depression and symptom outcomes if genetic biomarkers with good sensitivity/specificity are provided. This knowledge can potentially help the development of personalized treatment and decision making for those patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: To evaluate whether a nurse-supervised rehabilitation programmes could improve respiratory functions and systematic inflammation in children with asthma., Background: Children with asthma always suffer from poor life quality, and physical training and pulmonary rehabilitation could be beneficial to asthma., Design: A retrospective, observational, single-centre cohort analysis., Method: Baseline characteristics between the nurse-supervised rehabilitation programme and usual-care groups were matched by propensity-score matching (PSM) in a 1:1 ratio. We compared the lung function and inflammatory markers between groups., Results: Among 52 pairs of children, differences in lung function were improved in the nurse-supervised rehabilitation group compared with those in usual-care group, including the oxygen saturation, forced expiratory volume in 1 second, forced expiratory flow of 25%-75% and peak expiratory flow (all P < 0.05). Two asthma-related inflammatory markers (hypersensitive C-reactive protein and immunoglobulin E) also significantly decreased in the nurse-supervised rehabilitation group (both P < 0.001)., Conclusions: The results indicate that the nurse-supervised rehabilitation programme might be effective in improving symptom control, respiratory functions and systemic inflammation in children with asthma. The study suggests that the NSR for asthma merits further research., (© 2021 John Wiley & Sons Australia, Ltd.)

Pochonia chlamydosporia is a fungal parasite of nematode eggs. Studies have shown that some strains of Pochonia chlamydosporia can promote plant growth and induce plants' systemic resistance to root-knot nematodes by colonizing in their roots. This study aimed to verify the effect of the PC-170 strain on tomato growth and systemic resistance. Split-root experiments were conducted to observe the systemic resistance induced by PC-170. To explore the defense pathway that was excited due to the colonization by PC-170, we tested the expression of marker genes for defense pathways, and used mutant lines to verify the role of plant defense pathways. Our results showed that PC-170 can colonize roots, and promotes growth. We found a role for jasmonic acid (JA) in modulating tomato colonization by PC-170. PC-170 can activate tomato defense responses to reduce susceptibility to infection by the root-knot nematode Meloidogyne incognita , and induced resistance to some pathogens in tomatoes. The marker genes of the defense pathway were significantly induced after PC-170 colonization. However, salicylic acid (SA)- and jasmonic acid (JA)-dependent defenses in roots were variable with the invasion of different pathogens. Defense pathways play different roles at different points in time. SA- and JA-dependent defense pathways were shown to cross-communicate. Different phytohormones have been involved in tomato plants' responses against different pathogens. Our study confirmed that adaptive JA signaling is necessary to regulate PC-170 colonization and induce systemic resistance in tomatoes.

Significance: Approximately 6.5 million people in the United States suffer from chronic wounds. The chronic wound population is typically older and is characterized by a number of comorbidities associated with inflammation. In addition to experiencing wound-related pain, individuals with chronic wounds commonly experience multiple concurrent psychoneurological symptoms such as fatigue and depression, which delay wound healing. However, these distressing symptoms have been relatively overlooked in this population, although their adverse effects on morbidity are well established in other chronic disease populations. Recent Advances: Inflammation is involved in multiple pathways, which activate brain endothelial and innate immune cells that release proinflammatory cytokines, which produce multiple symptoms known as sickness behaviors. Inflammation-based activation of the kynurenine (KYN) pathway and its metabolites is a mechanism associated with chronic illnesses. Critical Issues: Although putative humoral and neuronal routes have been identified, the specific metabolic variations involved in sickness behaviors in chronic wound patients remain unclear. To improve health outcomes in the chronic wound population, clinicians need to have better understanding of the mechanisms underlying sickness behaviors to provide appropriate treatments. Future Directions: This article presents a synthesis of studies investigating associations between inflammation, metabolic pathways, and sickness behaviors in multiple chronic diseases. The presentation of a theoretical framework proposes a mechanism underlying sickness behaviors in the chronic wound population. By mediating the immune system response, dysregulated metabolites in the KYN pathway may play an important role in sickness behaviors in chronic inflammatory conditions. This framework may guide researchers in developing new treatments to reduce the disease burden in the chronic wound population.

Objectives: Fatigue is one of the most common symptoms associated with chronic noncommunicable diseases, and it may also increase cognitive impairment. However, associations between fatigue and cognitive impairment in chronic illnesses remain unclear. Therefore, the purpose of this systematic review was to examine research that investigated associations between level of fatigue and cognitive status., Methods: PubMed/Medline, PsycINFO, CINAHL, and Cochrane Database were searched for articles published between 2012 and 2018 using search terms fatigue, cognition, and various iterations of these terms. Study quality was assessed by the Joanna Briggs Institute Critical Appraisal Checklist tool., Results: Of 1799 citations, 10 studies in samples of individuals with cancer, multiple sclerosis, neurosarcoidosis, and chronic fatigue syndrome met the inclusion criteria. Fatigue was found to be significantly correlated with cognitive impairment in one cancer-related study ( r  = -.480, p  < .001), one multiple sclerosis study ( β = -0.52, p  < .0001), and two chronic fatigue syndrome studies ( r  = 0.397, p  < .001; r  = 0.388, p  < .001)., Discussion: There is insufficient evidence examining the relationship between fatigue and cognitive impairment in patients with chronic illnesses. As a result, more studies are needed that examine potential relationships between these two symptoms in order to develop effective treatments for individuals living with a chronic noncommunicable disease.

Objective: This study aimed to investigate the reversal effect of verapamil (VER) on the chemoresistance to cisplatin of esophageal squamous cell carcinoma (ESCC) cells., Patients and Methods: The reversal effect of VER on cisplatin resistance in ESCC cells was evaluated via CCK-8 assay, colony formation assessment, and flow cytometry. The key genes that mediate this effect were screened via high-throughput transcriptome se¬quencing. The mRNA and protein expression levels of potassium calcium-activated channel subfamily M alpha 1 (KCNMA1) in ESCC cells were examined via quantitative real-time PCR and Western blot analysis, respectively. The protein expressions of KCNMA1 in tissue samples from patients with either positive or negative responses to the therapeutic regimen of VER were determined via immunohistochemistry assay. Cell models with KCNMA1 knockdown and overexpression were es¬tablished to examine the role of KCNMA1 in mediating the reversal effect of VER on the chemoresistance to cisplatin of ESCC cells., Results: Results revealed that VER significantly decreased the 50% inhibitory concentration of cisplatin, inhibited colony formation, and induced apoptosis in ESCC cells. The curative effects of VER combined with chemotherapeutic drugs in KCNMA1-positive patients were better than those in KCNMA1-negative patients. KCNMA1 upregulation enhanced the reversal effect of VER on the chemoresistance to cisplatin of ESCC cells., Conclusions: KCNMA1 facilitated the reversal effect of VER on cisplatin resistance in ESCC cells.

Introduction and Objectives: Radical resection remains the only curative treatment for liver tumors. Although associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) can increase the resection rate, huge controversy exists for high reported mortality and morbidity. This study was to evaluate the efficacy and safety of modified ALPPS procedure., Patients and Methods: Patients who were performed ALPPS in single-center in recent 5 years were retrospectively reviewed. The modified strategy included strict patient selection, precise future liver remnant (FLR) assessment and operation planning, and usage of minimally invasive methods. Data including clinical records, functional FLR increase, complications, and overall survival (OS) were analyzed., Results: Sixty patients underwent modified ALPPS procedure and recovered well. No severe complications happened after the 1-stage operation, and the increasing FLR was 179.3 cm 3 (±72.4 cm 3 ), with similar functional FLR increase. The OS was 20.0 months (±4.5month)., Conclusions: ALPPS could be a feasible treatment for complex liver tumors by risk-reduced modification. It could be expected to provide long-term survival for patients without enough FLR., (Copyright © 2020 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Intrahepatic cholangiocarcinoma (ICC) is the second most common tumor in primary liver cancer, but the prognostic factors associated with long-term outcomes after surgical resection remain poorly defined. This study aimed to develop a novel prognostic classifier for patients with ICC after surgery., Methods: Using a proteomics approach, we screened tumor markers that up-regulated in ICC tissues, and narrowed down by bioinformatics analysis, western blot and immunohistochemistry. Prognostic markers were identified using Cox regression analyses in primary training cohort and the predictive models for time to recurrence (TTR) were established. The predictive accuracy of predictive model was validated in external validation cohort and prospective validation cohort. MTT assay, clonal formation assay and trans-well assays were used to verify the effect on the proliferation and migration in ICC cell line., Results: Triosephosphate isomerise (TPI1) was significantly up-regulated in ICC tissues and Kaplan-Meier analysis reveals that higher TPI1 expression was strongly correlated with higher recurrence rate of ICC patients. In the primary training cohort, mean TTR was significantly longer (p < 0.0001) than in the low-risk group (26.9 months for TTR, 95% CI 22.4-31.5) than in the high-risk group (14.5 months for TTR, 95% CI 10.6-18.4). Similar results were observed in two validation cohorts. In addition, a nomogram to predict recurrence was developed. Moreover, Knockdown of TPI1 by shRNA inhibited ICC cell growth, colony information, migration, invasion in vitro., Conclusions: Current prognostic models were accurate in predicting recurrence for ICC patients after surgical resection.

Living matter often exhibits multimode transport that switches between an active, self-propelled motion and a seemingly passive, random motion. Here, we investigate an exactly solvable model of multimode active matter, such as living cells and motor proteins, which alternatingly undergoes active and passive motion. Our model study shows that the reversible transition between a passive mode and an active mode causes super-Gaussian transport dynamics, observed in various experiments. We find the non-Gaussian character of the matter's displacement distribution is essentially determined by the population ratio between active and passive motion. Interestingly, under a certain population ratio of the active and passive modes, the displacement distribution changes from sub-Gaussian to super-Gaussian as time increases. The mean-square displacement of our model exhibits transient superdiffusive dynamics, yet recovers diffusive behavior at both the short- and long-time limits. We finally generalize our model to encompass complex, multimode active matter in an arbitrary spatial dimension.

Autophagy is associated with the cytoprotection of physiological processes against inflammation and oxidative stress. Salvia miltiorrhiza possesses cardiovascular protective actions and has powerful anti-oxidative and anti-inflammatory effects; however, whether and how Salvia miltiorrhiza-derived microRNAs (miRNAs) protect vascular smooth muscle cells (VSMCs) by inducing autophagy across species are unknown. We first screened and identified Sal-miR-58 from Salvia miltiorrhiza as a natural autophagy inducer. Synthetic Sal-miR-58 suppresses chronic angiotensin II (Ang II) infusion-induced abdominal aortic aneurysm (AAA) formation in mice, as well as induces autophagy in VSMCs and attenuates the inflammatory response elicited by Ang II in vivo and in vitro. Mechanistically, Sal-miR-58 downregulates Krüppel-like factor 3 (KLF3) expression through direct binding to the 3' UTR of KLF3, which in turn relieves KLF3 repression of E3 ubiquitin ligase neural precursor cell-expressed developmentally downregulated 4-like (NEDD4L) expression, whereas NEDD4L upregulation increases the ubiquitination and degradation of the platelet isoform of phosphofructokinase (PFKP), subsequently leading to a decrease in the activation of Akt/mammalian target of rapamycin (mTOR) signaling and facilitating VSMC autophagy induced by Sal-miR-58 in the context of chronic Ang II stimulation and aneurysm formation. Our results provide the first evidence that plant-derived Sal-miR-58 induces autophagy and attenuates inflammation in VSMCs through cross-species modulation of the KLF3/NEDD4L/PFKP regulatory pathway., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

The inflammation and proliferation of vascular smooth muscle cells (VSMCs) are the basic pathological feature of proliferative vascular diseases. Tanshinone ⅡA (Tan ⅡA), which is the most abundant fat-soluble element extracted from Salvia miltiorrhiza, has potent protective effects on the cardiovascular system. However, the underlying mechanism is still not fully understood. Here, we show that Tan ⅡA significantly inhibits neointimal formation and decreases VSMC inflammation by upregulating the expression of KLF4 and inhibiting the activation of NFκB signaling. Using a microRNA array analysis, we found that miR-712-5p expression is significantly upregulated in tumor necrosis factor alpha (TNF-α)-treated VSMCs. Loss- and gain-of-function experiments revealed that transfection of miR-712-5p mimic promotes, whereas depletion of miR-712-5p suppresses TNF-α-induced VSMC inflammation, leading to amelioration of intimal hyperplasia induced by carotid artery ligation. Moreover, depletion of miR-712-5p by its antagomir largely abrogates TNF-α-induced VSMC proliferation. Our findings suggest that miR-712-5p mediates the stimulatory effect of TNF-α on VSMC inflammation, and that Tan ⅡA inhibits VSMC inflammation and proliferation in vivo and in vitro by suppression of miR-712-5p expression. Targeting miR-712-5p may be a novel therapeutic strategy to prevent proliferative vascular diseases., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Adipogenesis, a differentiation process that transitions preadipocytes to adipocytes, is key to understanding the biology of fat accumulation and obesity. During this process, there many crucial transcription factors, such as PPARγ and the C/EBP family. Here we show a transcription factor in preadipocytes --- Sox5, that has a function in porcine adipogenesis. In our porcine subcutaneous-derived preadipocyte differentiation model, we found Sox5 expression displayed a significant upregulation after initial induction and decreased afterwards, which resembles the PPARγ expression pattern. siRNA knockdown of Sox5 in porcine preadipocytes significantly promoted cell growth and accelerated cell cycle progression. After inducing differentiation, knockdown of Sox5 notably down-regulated the expression of adipogenic marker genes: PPARγ, aP2, FAS and impaired lipid accumulation. Mechanistically, the deletion of Sox5 down-regulated the BMP R-Smads signal pathway, a crucial signal pathway for controlling preadipocyte fate commitment and adipogenesis. After using BMP4 recombinant protein to activate the BMP R-Smads signal, Sox5 function was partially rescued. In conclusion, our findings uncovered a function of Sox5 in porcine adipogenesis and reveal an interaction between Sox5 and BMP signaling., 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 Inc. All rights reserved.)

Objective: Abnormal proliferation and migration of vascular smooth muscle cells ( VSMCs) are essential for vascular remodeling. Natural compounds with diterpene chinone or phenolic acid structure from Salvia miltiorrhiza, an eminent medicinal herb widely used to treat cardiovascular diseases in China, can effectively attenuate vascular remodeling induced by vascular injury. However, it remains unknown whether Salvia miltiorrhiza -derived miRNAs can protect VSMCs from injury by environmental stimuli. Here, we explored the role and underlying mechanisms of Salvia miltiorrhiza -derived Sal-miR-1 and 3 in the regulation of VSMC migration and monocyte adhesion to VSMCs induced by thrombin. Methods: A mouse model for intimal hyperplasia was established by the ligation of carotid artery and the injured carotid arteries were in situ-transfected with Sal-miR-1 and 3 using F-127 pluronic gel. The vascular protective effects of Sal-miR-1 and 3 were assessed via analysis of intimal hyperplasia with pathological morphology. VSMC migration and adhesion were analyzed by the wound healing, transwell membrane assays, and time-lapse imaging experiment. Using loss- and gain-of-function approaches, Sal-miR-1 and 3 regulation of OTUD7B/KLF4/NMHC IIA axis was investigated by using luciferase assay, co-immunoprecipitation, chromatin immunoprecipitation, western blotting, etc. Results: Salvia miltiorrhiza- derived Sal-miR-1 and 3 can enter the mouse body after intragastric administration, and significantly suppress intimal hyperplasia induced by carotid artery ligation. In cultured VSMCs, these two miRNAs inhibit thrombin-induced the migration of VSMCs and monocyte adhesion to VSMCs. Mechanistically, Sal-miR-1 and 3 abrogate OTUD7B upregulation by thrombin via binding to the different sites of the OTUD7B 3'UTR. Most importantly, OTUD7B downregulation by Sal-miR-1 and 3 attenuates KLF4 protein levels via decreasing its deubiquitylation, whereas decreased KLF4 relieves its repression of transcription of NMHC IIA gene and thus increases NMHC IIA expression levels. Further, increased NMHC IIA represses VSMC migration and monocyte adhesion to VSMCs via maintaining the contractile phenotype of VSMCs. Conclusions: Our studies not only found the novel bioactive components from Salvia miltiorrhiza but also clarified the molecular mechanism underlying Sal-miR-1 and 3 inhibition of VSMC migration and monocyte adhesion to VSMCs. These results add important knowledge to the pharmacological actions and bioactive components of Salvia miltiorrhiza . Sal-miR-1 and 3-regulated OTUD7B/KLF4/NMHC IIA axis may represent a therapeutic target for vascular remodeling., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

What Is Known and Objective: Corticosteroids are recommended by almost all international guidelines for the management of exacerbations of chronic obstructive pulmonary disease (COPD). Nevertheless, due to their side effects, there are still concerns regarding the use of systemic corticosteroids (SCs). The Global Initiative for Chronic Obstructive Lung Disease guideline states nebulized budesonide (NB) may be a suitable alternative to SCs for treating COPD exacerbations. We conducted this study to systematically compare the efficacies of NB and SCs by using a meta-analysis., Methods: PubMed, EMBASE and Cochrane Library databases were searched from database inception to 10 October 2019. Our main end points were change in pulmonary function and blood gas analysis. Secondary end points were numbers of exacerbations and hyperglycaemia., Results and Discussion: Of 645 identified studies, 6 were eligible and were included in our analysis (N = 867 participants). Compared with SCs, NB was non-inferior on the change in FEV 1 %predicted at 24 hours, 48-72 hours and 5-7 days; FEV 1 at 5-7 days; FEV 1 /FVC at 7 days. For blood gas analysis, our meta-analysis indicated that PaO 2 , PaCO 2 at 24 hours, 48-72 hours and 7-10 days and SaO 2 at 24 hours and 7-10 days showed a non-significant difference in both groups, whereas the SaO 2 was significant higher in NB group at 48-72 hours after treatment. Hyperglycaemia was less frequent with NB (odds ratio, 0.1; 95% CI, 0.01-0.85; P = .04)., What Is New and Conclusion: Based on our meta-analysis, NB was not inferior to SCs when used in the treatment of COPD exacerbations. However, additional well-designed prospective studies are needed to identify the optimal dose of nebulized budesonide and the effects of nebulized budesonide in outpatients, or patients in ICU settings., (© 2020 John Wiley & Sons Ltd.)

COVID-19 not only affects the physical health of Chinese people, but also their psychological health. This article mainly summarized the causes, clinical manifestations and preventive measures of COVID-19 impact on psychology of Chinese people, and presented two representative cases at the same time., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2020.)

The biological basis underlying cognitive dysfunction in women with early-stage breast cancer (BC) remains unclear, but could reflect gene expression changes that arise from the acquisition and long-term retention of soma-wide alterations in DNA methylation in response to chemotherapy. In this longitudinal study, we identified differences in peripheral methylation patterns present in women prior to treatment (T1) and 1 year after receiving chemotherapy (T4) and evaluated relationships among the differential methylation (DM) ratios with changes in cognitive function. A total of 58 paired (T1 and T4) blood specimens were evaluated. Methylation values were determined for DNA isolated from whole blood using a genome-wide array . Cognitive function was measured using the validated, computerized CNS Vital Signs platform. Relationships between methylation patterns and cognitive domain scores were compared using a stepwise linear regression analysis, with demographic variables as covariates. The symptom comparison analysis was restricted to 2,199 CpG positions showing significant methylation ratio changes between T1 and T4. The positions with DM were enriched for genes involved in the modulation of cytokine concentrations. Significant DM ratios were associated with memory domain (56 CpGs). Eight of the ten largest DM ratio changes associated with lack of memory improvement were localized to genes involved in either neural function ( ECE2, PPFIBP2 ) or signalling processes ( USP6NL, RIPOR2, KLF5, UBE2V1, DGKA, RPS6KA1 ). These results suggest that epigenetic changes acquired and retained for at least one year in non-tumour cells following chemotherapy may be associated with a lack of memory improvement following treatment in BC survivors.

Background: With improved survivorship rates for colorectal cancer (CRC), more CRC survivors are living with long-term disease and treatment side effects. Little research exists on CRC symptoms or symptom management guidelines to support these individuals after cancer treatments., Objectives: The aims of this study were to systematically review symptom experiences, risk factors, and the impact of symptoms and to examine the pooled frequency and severity of symptoms via meta-analyses in CRC survivors after cancer treatments., Methods: Relevant studies were systematically searched in 7 databases from 2009 to 2019. Meta-analysis was conducted for pooled estimates of symptom frequency and severity., Results: Thirty-five studies met the inclusion criteria. Six studies assessed multiple CRC symptoms, whereas 29 focused on a single symptom, including peripheral neuropathy, psychological distress, fatigue, body image distress, cognitive impairment, and insomnia. The pooled mean frequency was highest for body image distress (78.5%). On a scale of 0 to 100, the pooled mean severity was highest for fatigue (50.1). Gastrointestinal and psychological symptoms, peripheral neuropathy, and insomnia were also major problems in CRC survivors. Multiple factors contributed to adverse symptoms, such as younger age, female gender, and lack of family/social support. Symptoms negatively impacted quality of life, social and sexual functioning, financial status, and caregivers' physical and mental conditions., Conclusions: Colorectal cancer survivors experienced multiple adverse symptoms related to distinct risk factors. These symptoms negatively impacted patients and caregivers' well-being., Implications for Practice: Healthcare providers can use study findings to better assess and monitor patient symptoms after cancer treatments. More research is needed on CRC-specific symptoms and their effective management.

To explore the impacts of future climate change on spring phenology stages (first leaf storey expansion stage, spring flowering stage) of rubber tree in Hainan Island, we established a rubber tree spring phenology simulation model based on the crop clock model and developed a computer software RubberSP. The model simulation accuracy was examined with experimental observed phenology data. Five global climate models (GCMs) from the Coupled Model Intercomparison Project Phase 5 (CMIP5) were integrated using Bayesian Model averaging method (BMA) to predict the impacts of climate change on the spring phenology of rubber tree in 2020-2099 (relative to 1986-2017) under climate scenarios of RCP2.6, RCP4.5 and RCP8.5, respectively. The results showed that the RubberSP model had good simulation accuracy, with the determination coefficient (R 2 ) values ranging between 0.73-0.87, the root mean square error (RMSE) ranging from 3.26 to 4.15 d, and the normalized root mean square error (NRMSE) of 3.4%-7.4% between measured and simulated phenology stages. The uncertainty of a single GCM could be avoided by BMA method, which could better reflect the change trend of temperature. Temperature of Hainan Island in the end of 21 century, under the scenarios of RCP2.6, RCP4.5 and RCP8.5, would increase by more than 0.3, 1.0 and 2.5 ℃ compared with the baseline, respectively. The spring phenology stages would appear earlier and yield would increase in the future climate scenario. The time isoline of spring phenology stages would move forward to northwest, which indicated that most suitable area for rubber tree plantation in Hainan Island would expand to the northwest. The spatial difference of the first leaf storey expansion stage would be more evident, but not for spring flowering stage. The amplitude of rubber tree spring phenology variations was closely related to the increases of temperature under different RCP scenarios, with the most apparent change under RCP8.5 scenario and most mild change under RCP2.6 scenario.

Background: With a nearly 89% 5-year survival rate for women with early-stage breast cancer, symptoms are a priority. Healthy lifestyle behaviors may be temporally associated with symptoms; however, evidence is lacking., Objective: This research examined temporal relationships among healthy lifestyle behaviors and symptoms in women diagnosed with breast cancer receiving chemotherapy., Methods: This research was part of a study (R01NR012667) approved by the institutional review board. Women (n = 76) providing written informed consent participated in this longitudinal study examining health-promoting lifestyle behaviors and symptoms (fatigue, anxiety, depression, and pain). Participants completed well-validated self-report questionnaires primarily at a clinic visit. Statistical methods included descriptive statistics, linear mixed-effects models, and pairwise comparisons using SAS 9.4; α was set at .05., Results: Lowest healthy lifestyle behavior scores for physical activity and highest scores for spiritual growth were reported. Significant changes in physical activity and stress management were noted. Fatigued patients had lower physical activity and nutrition scores than did patients without fatigue. Patients with anxiety had lower spiritual growth and interpersonal relation scores than did patients without anxiety. Relationships demonstrated temporal differences., Conclusions: Breast cancer survivors did not routinely engage in healthy lifestyle behaviors. Significant temporal changes in healthy lifestyle behaviors and symptoms and significant associations among healthy lifestyle behaviors, symptoms, and demographic and clinical factors were noted in this study., Implications for Practice: Knowing the temporal relationships among these variables provides insight that could be useful for nurses so they can encourage healthy lifestyle behaviors to mitigate symptoms throughout the cancer trajectory.

Aim: This study investigated the molecular mechanism underlying the involvement of miR-885 in the signaling pathways of VDR. Results: Based on their rs739837 genotype, the subjects were divided into a case group and a control group. Logistic regression was carried out to study the impact of rs739837 genotypes on the severity of asthma, and it was found that the minor allele (T) of rs739837 significantly increased the severity of asthma. Using a luciferase assay, VDR was confirmed as a miR-885 target, with a negative regulatory relationship established between VDR and miR-885. Conclusion: The findings of this study demonstrated that VDR is an miR-885 target, while the presence of rs739837 minor allele (T) in miR-885 interferes with the interaction between miR-885 and VDR to affect the severity of asthma.

We use 84 rainfall samples collected during June to September 2017 from the Dongkemadi basin, source region of the Yangtze River, China, to analyze the characteristics and influencing factors of stable isotopes in groundwater, and further discuss the groundwater recharge sources. The results showed that the range of groundwater δ 18 O values in this permafrost region varied from -15.3‰ to -12.5‰ (mean -14.0‰). The range of δ D values in groundwater varied from -108.9‰ to -91.7‰ (mean -100.2‰). Compared with local atmospheric precipitation, groundwater isotopes were relatively enriched. The slope and intercept of the groundwater line (GL) in the study area were both lower than of those of the global and local meteoric water lines (GMWL and LMWL), thus indicating that groundwater in the study area was subjected to evaporation during rainfall recharge of groundwater. The d -excess values of groundwater varied from 4.9‰ to 25.0‰ (mean 11.6‰), which was close to the average d -excess value determined for global average rainfall (10‰), but lower than that of rainfall in the study area (15.1‰). The influencing factors on the composition and variation of groundwater isotopes were different in different periods. The permafrost active layer was relatively thin during periods of increasing air temperature, and groundwater isotopes were significantly affected by air temperature. A temperature decrease during the latter part of the sampling period, when the thickness of the permafrost active layer was still increasing, further increased the retention time of infiltrating rainfall in the soil, thereby eventually leading to evaporation that strengthened the enrichment of heavy isotopes in the groundwater. According to the topographic characteristics of the Dongkemadi basin, the isotopic characteristics of the groundwater, and the factors influencing the isotopic composition, we conclude that rainfall was the main source of groundwater recharge. The results of this study provide a scientific basis for studying water cycle processes in the permafrost regions of the source region of the Yangtze River.

In this study, Cansjera rheedei J. F. Gmelin is an important role in the phylogeny and evolution of Opiliaceae plant. The chloroplast genome of C. rheedei is 144,306 bp in size, with an average GC content of 37.5%. The complete chloroplast genome has a typical quadripartite structure, including a large single copy (LSC) region (82,773 bp) and a small single copy (SSC) region (9745 bp), which were separated a pair of inverted repeats (IRs, 25,894 bp). This plastome contained 101 different genes, including 67 protein-coding genes (PCGs), 30 tRNA genes and four rRNA genes. The chloroplast genome of C. rheedei has completed that will be based on the phylogeny and genomic studies in the family Opiliaceae., Competing Interests: No potential conflict of interest was reported by the authors., (© 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Increased activity of the PI3K/AKT/mTOR pathway has been observed in chronic myeloid leukemia (CML). Morin, a kind of flavonoid, exhibits a significant anticancer activity by suppressing the PI3K/AKT signaling pathway. However, the effect of morin on CML and its underlying mechanisms is poorly understood. Here, we found that morin dose dependently inhibited the proliferation of CML cell lines K562 and KCL22 and induced their apoptosis, with a significant increase in cell apoptosis upon exposure of cells to 50 μmol/L morin. Moreover, morin significantly reduced CML xenograft growth in nude mice. Mechanically, morin attenuated phosphorylated AKT level by upregulating PTEN expression, thus leading to the inhibition of AKT signaling. Knockdown of PTEN by its siRNA completely abrogated morin-induced cell apoptosis, indicating that PTEN mediates the inductive effect of morin on CML cell apoptosis. More importantly, we found that miR-188-5p was significantly upregulated in CML patients and CML cell lines. Treating CML cells with morin markedly downregulated the miR-188-5p expression level. Further, we demonstrated that miR-188-5p repressed PTEN expression by directly targeting its 3'-UTR. miR-188-5p downregulation induced by morin enhanced CML cell apoptosis by relieving miR-188-5p repression of PTEN expression. In summary, morin exerts significant anticancer efficacy in CML by regulating the miR-188-5p/PTEN axis and thus repressing the PI3K/AKT signaling., (©2019 American Association for Cancer Research.)

Using 64 precipitation samples collected from June to September 2013 in the Dongkemadi Basin in the source region of the Yangtze River, the pH, conductivity, and main ionic concentration characteristics of precipitation were analyzed. The main ionic sources of precipitation and their relationships with atmospheric circulation were examined using factor analysis, correlation analysis, enrichment factor analysis, and backward trajectory analysis. The results showed that the range of precipitation pH values varied from 5.26 to 9.25 with a weighted average of 6.70, and conductivity ranged from 0.23 to 28.70 μS·cm -1 with a weighted average of 3.45 μS·cm -1 . The conductivity of precipitation was lower than for the Mt. Waliguan basin (China Global Atmosphere Watch baseline observatory). The total ionic concentrations in the precipitation ranged from 7.0 to 376.9 μeq·L -1 with a weighted average of 40.8 μeq·L -1 . The ranked order of ionic concentrations was HCO 3 - > NH 4 + > Ca 2+ > NO 3 - > SO 4 2- > Na + > Cl - > K + > Mg 2+ . HCO 3 - , NH 4 + ,Ca 2+ , and NO 3 - were the dominant ions, which accounted for 74.75% of the total ionic concentration. Fractional acidity (FA) analysis showed that 97.8% of the precipitation acidity was neutralized by alkaline constituents. Neutral factor (NF) analysis indicated that NH 4 + and Ca 2+ were the dominant neutralization constituents in the precipitation. The precipitation ions in this study area were mainly derived from terrestrial material, while input from marine sources was relatively low. Backward trajectory analysis revealed that the total ionic concentrations varied significantly between the different sources, which followed the order of local sources>westerly sources>monsoon sources. This indicates that different atmospheric circulation conditions and air mass sources have a significant influence on the chemical composition of precipitation in this area. To some extent, the chemical characteristics of precipitation could reflect the air quality and background values for remote areas due to the limited effect of human activities. The results of this study provide a scientific basis for the protection of water quality and the assessment of the impact of human activities on the atmospheric environment in the source region of the Yangtze River.

Even in the steady-state, the number of biomolecules in living cells fluctuates dynamically, and the frequency spectrum of this chemical fluctuation carries valuable information about the dynamics of the reactions creating these biomolecules. Recent advances in single-cell techniques enable direct monitoring of the time-traces of the protein number in each cell; however, it is not yet clear how the stochastic dynamics of these time-traces is related to the reaction mechanism and dynamics. Here, we derive a rigorous relation between the frequency-spectrum of the product number fluctuation and the reaction mechanism and dynamics, starting from a generalized master equation. This relation enables us to analyze the time-traces of the protein number and extract information about dynamics of mRNA number and transcriptional regulation, which cannot be directly observed by current experimental techniques. We demonstrate our frequency spectrum analysis of protein number fluctuation, using the gene network model of luciferase expression under the control of the Bmal 1a promoter in mouse fibroblast cells. We also discuss how the dynamic heterogeneity of transcription and translation rates affects the frequency-spectra of the mRNA and protein number., Competing Interests: The authors have declared that no competing interests exist.