Contrasting effects of music therapy and aromatherapy on perioperative anxiety: A systematic review and meta-analysis.

INTRODUCTION: Music therapy and aromatherapy have been demonstrated effective for perioperative anxiety. However, the available studies have indicated discordant results about which adjunct treatment is better for perioperative anxiety. Therefore, we conducted this meta-analysis to explore the contrasting effects between them. METHODS: Six electronic databases were searched for clinical trials evaluating the efficacy of music therapy compared with aromatherapy in alleviating perioperative anxiety. The primary outcome was the postintervention anxiety level. Secondary outcomes included differences in blood pressure and heart rate before and after the intervention as well as pain scores at intraoperative and postoperative time points. The study protocol was registered on PROSPERO (CRD42021249737). RESULTS: Twelve studies (894 patients) were included. The anxiety level showed no statistically significant difference (SMD, 0.28; 95% CI: -0.12, 0.68; P =.17). The analysis of blood pressure and heart rate also did not identify statistically significant differences. Notably, the pain scores at the intraoperative time point suggested that aromatherapy was superior to music therapy (WMD, 0.29 cm; 95% CI: 0.05, 0.52; P =.02), while those at 4 hours after surgery indicated the opposite results (WMD, -0.48 cm; 95% CI: -0.60, -0.36; P <.001). CONCLUSION: Low-to-moderate quality evidence suggests that music therapy and aromatherapy have similar potential to relieve perioperative anxiety. The potential data indicates that the two therapies have different benefits in intervention duration and age distribution. More direct high-quality comparisons are encouraged in the future to verify this point.

Clinical features and prognosis of ANCA-associated vasculitis patients who were double-seropositive for myeloperoxidase-ANCA and proteinase 3-ANCA.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients with dual positivity for proteinase 3-ANCA (PR3-ANCA) and myeloperoxidase-ANCA (MPO-ANCA) are uncommon. We aimed to investigate these idiopathic double-positive AAV patients' clinical features, histological characteristics, and prognosis. We reviewed all the electronic medical records of patients diagnosed with AAV to obtain clinical data and renal histological information from January 2010 to December 2020 in a large center in China. Patients were assigned to the MPO-AAV group or PR3-AAV group or idiopathic double-positive AAV group by ANCA specificity. We explored features of idiopathic double-positive AAV. Of the 340 patients who fulfilled the study inclusion criteria, 159 (46.76%) were female, with a mean age of 58.41 years at the time of AAV diagnosis. Similar to MPO-AAV, idiopathic double-positive AAV patients were older and had more severe anemia, lower Birmingham Vasculitis Activity Score (BVAS) and C-reactive protein (CRP) levels, less ear, nose, and throat (ENT) involvement, higher initial serum creatinine and a lower estimated glomerular filtration rate (eGFR) when compared with PR3-AAV (P < 0.05). The proportion of normal glomeruli of idiopathic double-positive AAV was the lowest among the three groups (P < 0.05). The idiopathic double-positive AAV patients had the worst remission rate (58.8%) among the three groups (P < 0.05). The relapse rate of double-positive AAV (40.0%) was comparable with PR3-AAV (44.8%) (P > 0.05). Although there was a trend toward a higher relapse rate of idiopathic double-positive AAV (40.0%) compared with MPO-AAV (23.5%), this did not reach statistical significance (P > 0.05). The proportion of patients who progressed to ESRD was 47.1% and 44.4% in the idiopathic double-positive AAV group and MPO-AAV group respectively, without statistical significance. Long-term patient survival also varied among the three groups (P < 0.05). Idiopathic double-positive AAV is a rare clinical entity with hybrid features of MPO-AAV and PR3-AAV. MPO-AAV is the "dominant" phenotype in idiopathic double-positive AAV.

[Correlation Analysis between Neutrophil-to-lymphocyte Ratio 
and the Risk of Malnutrition in Stage IV Primary Lung Cancer].

BACKGROUND: Malnutrition is commonly associated with poor prognosis in patients with malignant tumors. The neutrophil-to-lymphocyte ratio (NLR) is an indicator of inflammation in the body and predicts the risk of malnutrition in a variety of diseases; however, its association with malnutrition in lung cancer patients is unclear. The aim of this study is to clarify the association between NLR and nutritional status in stage IV primary lung cancer and to further determine the optimal NLR cut-off that best predicts the risk of malnutrition. METHODS: A retrospective analysis of 209 patients admitted to the Department of Medical Oncology, Tianjin Medical University General Hospital with a primary diagnosis of stage IV lung cancer from May 2019 to February 2021 was performed, and the nutritional risk screening 2002 (NRS 2002) was used to examine their nutritional status. Patient demographic information, pathology, Karnofsky performance status (KPS) score, body mass index (BMI), comorbidities and clinical biochemical indicators were also included. The correlation between NLR and NRS 2002 was investigated. Receiver operating characteristic (ROC) curve was used to determine the best NLR cut-off predi cting malnutrition risk. Multivariable Logistic regression was used to assess the association between NLR and malnutrition risk. RESULTS: The rate of patients with stage IV primary lung cancer at nutritional risk was 36.36% (76/209). A significant positive correlation was observed between NLR values and NRS 2002 risk score (r=0.765, P<0.001). The ROC curve analysis indicated that an NLR of 3.94 was the optimal cut-off for predicting malnutrition risk (area under the curve=0.747, 95%CI: 0.678-0.815, P<0.001), which showed a sensitivity of 55%, a specificity of 86%, a positive predictive value of 68%, and a negative predictive value of 77%. Patients in the NLR>3.94 group had a significantly higher risk of malnutrition compared to those in the NLR≤3.94 group (69.49% vs 23.33%, P<0.001). Furthermore, NLR was identified as a risk factor for malnutrition in stage IV primary lung cancer patients. CONCLUSIONS: NLR is associated with the risk of malnutrition in stage IV primary lung cancer, and NLR can be used as one of the indicators for screening nutritional risk in patients with stage IV primary lung cancer.

[Multi-scenario Simulation of Construction Land Expansion and Its Impact on Ecosystem Carbon Storage in Beijing-Tianjin-Hebei Urban Agglomeration].

It is of great practical significance for regional sustainable development and ecological construction to quantitatively analyze the impact of construction land expansion on terrestrial ecosystem carbon storage and to explore the optimization scheme of simulating construction land expansion to improve future ecosystem carbon storage. Based on the land use and cover change (LUCC) and other geospatial data of the Beijing-Tianjin-Hebei Urban Agglomeration from 2000 to 2020, this study utilized the Integrated Valuation of Ecosystem Services and Tradeoffs (InVEST) model and the patch-generating land-use simulation (PLUS) model to assess and analyze the changes in ecosystem carbon stocks and spatial patterns regionally. In this study, we performed linear regression analysis to investigate the relationship between urban land expansion and changes in ecosystem carbon stocks for varying urban land proportion levels during two distinct time intervals, 2000-2010 and 2010-2020, which was conducted at a spatial resolution of 2 km. Three distinct urban land expansion scenarios were subjected to simulation to forecast the prospective land use pattern by 2030. Subsequently, we quantified the ramifications of these scenarios on ecosystem carbon stocks during the period from 2020 to 2030. The results were as follows:① In the Beijing-Tianjin-Hebei Urban Agglomeration, the ecosystem carbon stocks exhibited notable variations over the study period, with values of 2 088.02, 2 106.78, and 2 121.25 Tg recorded for the years 2000, 2010, and 2020, respectively, resulting in a cumulative carbon sequestration of 33.23 Tg C during the study duration. It is noteworthy that forest carbon storage emerged as the dominant contributor, with an increase from 1 010.17 Tg in 2000 to 1 136.53 Tg in 2020. Throughout the study period, the spatial distribution of carbon stocks displayed relative stability. Regions characterized by lower carbon content were concentrated in the vicinity of the Bohai Rim region and in proximity to cities such as Beijing, Tianjin, and Shijiazhuang, as well as rural settlements. In contrast, grid units with moderate and high carbon stocks were predominantly situated in the western Taihang Mountain and the northern Yanshan Mountain. Additionally, there was a tendency of increasing carbon stocks in the Taihang Mountain and Yanshan Mountain region, whereas those surrounding major urban centers such as Beijing, Tianjin, Shijiazhuang, and Tangshan experienced a notable decline in carbon stocks. Such reductions were most pronounced in regions undergoing urban land expansion during the study period. ② In grid units with an urban land proportion exceeding 10% at each level, a strong correlation was observed between urban land expansion and changes in carbon stocks during both the 2000-2010 and 2010-2020 periods. The changes in urban land proportion adequately explained the variations in carbon stocks. However, the explanatory power of urban land on carbon stocks decreased during the 2010-2020 period, indicating that other factors played a more substantial role in influencing carbon stocks during this time. The regression coefficients for both periods exhibited a fluctuating upward trend. In comparison to that during the 2000-2010 period, the impact of urban land expansion on carbon stocks was relatively smaller during 2010-2020, indicating a weakening influence. ③ In light of three distinct development scenarios, namely natural development (Scenario Ⅰ), a 15% reduction in the rate of urban land expansion (Scenario Ⅱ), and a 30% reduction in the rate of urban land expansion (Scenario Ⅲ), the projected ecosystem carbon stocks for the Beijing-Tianjin-Hebei Urban Agglomeration in the year 2030 were estimated to be 2 129.12, 2 133.55, and 2 139.10 Tg, respectively. These projections indicated an increase of 7.88, 12.30, and 17.85 Tg in comparison to the current carbon stocks. All scenarios demonstrated that the terrestrial ecosystem would play a role of carbon sink, particularly with the greatest carbon sink observed in the scenario with a 30% reduction in urban land expansion. The fit performance between urban land expansion and carbon stock changes during the 2020-2030 period was significantly better than that during the 2000-2010 and 2010-2020 periods, and the regression coefficients showed a fluctuating increase with an increase in urban land proportion. Across grid units with different urban land proportion levels, the regression coefficients exhibited the order of Scenario Ⅰ < Scenario Ⅱ < Scenario Ⅲ. In pursuit of the carbon peaking and carbon neutrality goals, the Beijing-Tianjin-Hebei Urban Agglomeration should prioritize scenarios with reduced rates of urban land expansion, especially in regions with higher urban land proportions.

A combined pre- and intra-operative nomogram in evaluation of degrees of liver cirrhosis predicts post-hepatectomy liver failure: a multicenter prospective study.

Background: Adequate evaluation of degrees of liver cirrhosis is essential in surgical treatment of hepatocellular carcinoma (HCC) patients. The impact of the degrees of cirrhosis on prediction of post-hepatectomy liver failure (PHLF) remains poorly defined. This study aimed to construct and validate a combined pre- and intra-operative nomogram based on the degrees of cirrhosis in predicting PHLF in HCC patients using prospective multi-center's data. Methods: Consecutive HCC patients who underwent hepatectomy between May 18, 2019 and Dec 19, 2020 were enrolled at five tertiary hospitals. Preoperative cirrhotic severity scoring (CSS) and intra-operative direct liver stiffness measurement (DSM) were performed to correlate with the Laennec histopathological grading system. The performances of the pre-operative nomogram and combined pre- and intra-operative nomogram in predicting PHLF were compared with conventional predictive models of PHLF. Results: For 327 patients in this study, histopathological studies showed the rates of HCC patients with no, mild, moderate, and severe cirrhosis were 41.9%, 29.1%, 22.9%, and 6.1%, respectively. Either CSS or DSM was closely correlated with histopathological stages of cirrhosis. Thirty-three (10.1%) patients developed PHLF. The 30- and 90-day mortality rates were 0.9%. Multivariate regression analysis showed four pre-operative variables [HBV-DNA level, ICG-R15, prothrombin time (PT), and CSS], and one intra-operative variable (DSM) to be independent risk factors of PHLF. The pre-operative nomogram was constructed based on these four pre-operative variables together with total bilirubin. The combined pre- and intra-operative nomogram was constructed by adding the intra-operative DSM. The pre-operative nomogram was better than the conventional models in predicting PHLF. The prediction was further improved with the combined pre- and intra-operative nomogram. Conclusions: The combined pre- and intra-operative nomogram further improved prediction of PHLF when compared with the pre-operative nomogram. Trial Registration: Clinicaltrials.gov Identifier: NCT04076631.

Circ-10720 as a ceRNA adsorbs microRNA-1238 and modulates ZEB2 to boost NSCLC development by activating EMT.

BACKGROUND: Circular RNAs (circRNAs) are critical regulators in the progression of tumors. This experimental design aimed to explore the mechanism of circ-10720 in non-small cell lung cancer (NSCLC). METHODS: We used RT-qPCR to measure circ-10720 expression in clinical samples and analyzed its relationship with the clinicopathological characteristics of NSCLC patients. The expression levels of microRNA-1238 (miR-1238) and Zinc Finger E-box-binding Homeobox 2 (ZEB2) in clinical samples were detected by RT-qPCR. NSCLC cells were transfected with relevant plasmids or sequences. Circ-10720, miR-1238, and ZEB2 expressions in cells were analyzed via RT-qPCR or western blot. Cell proliferation, apoptosis, migration, and invasion were assessed with CCK-8, flow cytometry, and transwell assay, respectively. The protein expression of ZEB2 and epithelial-mesenchymal transition (EMT)-related markers (E-cadherin, Vimentin, N-cadherin) were detected via western blot. Xenograft assay was used to determine the effect of circ-10720 on NSCLC in vivo. Circ-10720 and ZEB2 expressions in tumors were detected using RT-qPCR or Western blot. Immunohistochemistry was used to evaluate E-cadherin and N-cadherin expression in tumors. Finally, the binding relationship between miR-1238 with circ-10720 or ZEB2 was verified by the bioinformatics website, dual luciferase reporter assay, RNA pull-down assay, and RIP assay. RESULTS: Circ-10720 was upregulated in NSCLC and correlated with TNM stage of NSCLC patients. MiR-1238 was lowly expressed but ZEB2 was highly expressed in NSCLC. Circ-10720 silencing suppressed the proliferation, metastasis, and EMT of NSCLC cells. Mechanically, circ-10720 was a competitive endogenous RNA (ceRNA) for miR-1238, and ZEB2 was a target of miR-1238. circ-10720-modulated ZEB2 via competitively binding with miR-1238 to control NSCLC progression. In addition, circ-10720 knockdown suppressed tumor growth in vivo. CONCLUSIONS: Circ-10720 acts as a ceRNA to adsorb miR-1238 and modulate ZEB2 to facilitate the proliferation, migration, invasion, and EMT of NSCLC cells.

A Paternò-Büchi Reaction of Aromatics with Quinones under Visible Light Irradiation.

Reported herein is a Paternò-Büchi reaction of aromatic double bonds with quinones under visible light irradiation. The reactions of aromatics with quinones exposed to blue LED irradiation yielded oxetanes at -78 °C, which was attributed to both the activation of double bonds in aromatics and the stabilization of oxetanes by thiadiazole, oxadiazole, or selenadiazole groups. The addition of Cu(OTf)2 to the reaction system at room temperature resulted in the formation of diaryl ethers via the copper-catalyzed ring opening of oxetanes in situ. Notably, the substrate scope was extended to general aromatics.

GSDMD/Drp1 signaling pathway mediates hippocampal synaptic damage and neural oscillation abnormalities in a mouse model of sepsis-associated encephalopathy.

BACKGROUND: Gasdermin D (GSDMD)-mediated pyroptotic cell death is implicated in the pathogenesis of cognitive deficits in sepsis-associated encephalopathy (SAE), yet the underlying mechanisms remain largely unclear. Dynamin-related protein 1 (Drp1) facilitates mitochondrial fission and ensures quality control to maintain cellular homeostasis during infection. This study aimed to investigate the potential role of the GSDMD/Drp1 signaling pathway in cognitive impairments in a mouse model of SAE. METHODS: C57BL/6 male mice were subjected to cecal ligation and puncture (CLP) to establish an animal model of SAE. In the interventional study, mice were treated with the GSDMD inhibitor necrosulfonamide (NSA) or the Drp1 inhibitor mitochondrial division inhibitor-1 (Mdivi-1). Surviving mice underwent behavioral tests, and hippocampal tissues were harvested for histological analysis and biochemical assays at corresponding time points. Haematoxylin-eosin staining and TUNEL assays were used to evaluate neuronal damage. Golgi staining was used to detect synaptic dendritic spine density. Additionally, transmission electron microscopy was performed to assess mitochondrial and synaptic morphology in the hippocampus. Local field potential recordings were conducted to detect network oscillations in the hippocampus. RESULTS: CLP induced the activation of GSDMD, an upregulation of Drp1, leading to associated mitochondrial impairment, neuroinflammation, as well as neuronal and synaptic damage. Consequently, these effects resulted in a reduction in neural oscillations in the hippocampus and significant learning and memory deficits in the mice. Notably, treatment with NSA or Mdivi-1 effectively prevented these GSDMD-mediated abnormalities. CONCLUSIONS: Our data indicate that the GSDMD/Drp1 signaling pathway is involved in cognitive deficits in a mouse model of SAE. Inhibiting GSDMD or Drp1 emerges as a potential therapeutic strategy to alleviate the observed synaptic damages and network oscillations abnormalities in the hippocampus of SAE mice.

Pharmacokinetic/pharmacodynamic evaluation of gamithromycin against rabbit pasteurellosis.

BACKGROUND: Gamithromycin is an effective therapy for bovine and swine respiratory diseases but not utilized for rabbits. Given its potent activity against respiratory pathogens, we sought to determine the pharmacokinetic profiles, antimicrobial activity and target pharmacokinetic/pharmacodynamic (PK/PD) exposures associated with therapeutic effect of gamithromycin against Pasteurella multocida in rabbits. RESULTS: Gamithromycin showed favorable PK properties in rabbits, including high subcutaneous bioavailability (86.7 ± 10.7%) and low plasma protein binding (18.5-31.9%). PK analysis identified a mean plasma peak concentration (Cmax) of 1.64 ± 0.86 mg/L and terminal half-life (T1/2) of 31.5 ± 5.74 h after subcutaneous injection. For P. multocida, short post-antibiotic effects (PAE) (1.1-5.3 h) and post-antibiotic sub-inhibitory concentration effects (PA-SME) (6.6-9.1 h) were observed after exposure to gamithromycin at 1 to 4× minimal inhibitory concentration (MIC). Gamithromycin demonstrated concentration-dependent bactericidal activity and the PK/PD index area under the concentration-time curve over 24 h (AUC24h)/MIC correlated well with efficacy (R2 > 0.99). The plasma AUC24h/MIC ratios of gamithromycin associated with the bacteriostatic, bactericidal and bacterial eradication against P. multocida were 15.4, 24.9 and 27.8 h in rabbits, respectively. CONCLUSIONS: Subcutaneous administration of 6 mg/kg gamithromycin reached therapeutic concentrations in rabbit plasma against P. multocida. The PK/PD ratios determined herein in combination with ex vivo activity and favorable rabbit PK indicate that gamithromycin may be used for the treatment of rabbit pasteurellosis.

Hypomethylation-associated LINC00987 downregulation induced lung adenocarcinoma progression by inhibiting the phosphorylation-mediated degradation of SND1.

DNA methylation, an epigenetic regulatory mechanism dictating gene transcription, plays a critical role in the occurrence and development of cancer. However, the molecular underpinnings of LINC00987 methylation in the regulation of lung adenocarcinoma (LUAD) remain elusive. This study investigated LINC00987 expression in LUAD patients through analysis of The Cancer Genome Atlas data sets. Quantitative real-time polymerase chain reaction (RT-qPCR) and fluorescence in situ hybridization assays were used to assess LINC00987 expression in LUAD. The bisulfite genomic sequence PCR (BSP) assay was used to determine the methylation levels of the LINC00987 promoter. The interaction between LINC00987 and SND1 was elucidated via immunoprecipitation and RNA pull-down assays. The functional significance of LINC00987 and SND1 in Calu-3 and NCI-H1688 cells was evaluated in vitro through CCK-8, EdU, Transwell, flow cytometry, and vasculogenic mimicry (VM) tube formation assays. LINC00987 expression decreased in LUAD concomitant with hypermethylation of the promoter region, while hypomethylation of the LINC00987 promoter in LUAD tissues correlated with tumor progression. Treatment with 5-Aza-CdR augmented LINC00987 expression and inhibited tumor growth. Mechanistically, LINC00987 overexpression impeded LUAD progression and VM through direct binding with SND1, thereby facilitating its phosphorylation and subsequent degradation. Additionally, overexpression of SND1 counteracted the adverse effects of LINC00987 downregulation on cell proliferation, apoptosis, cell migration, invasion, and VM in LUAD in vitro. In conclusion, this pioneering study focuses on the expression and function of LINC00987 and reveals that hypermethylation of the LINC00987 gene may contribute to LUAD progression. LINC00987 has emerged as a potential tumor suppressor gene in tumorigenesis through its binding with SND1 to facilitate its phosphorylation and subsequent degradation.

Precise Synthesis of Diastereomers of Spiro-oxindole Derivatives through Dynamic Covalent Transformation.

In this study, [1+2+2] cyclization of tryptamine-derived isocyanides with 3-ylideneoxindoles was systematically investigated. A series of structurally complex spiro-oxindole derivatives were obtained. Characteristic dynamic covalent chemistry was observed and confirmed by experiments and density functional theory calculation. Through the regulation of the solvent, temperature, and time, the precise and stereodivergent synthesis of spiro-oxindoles was achieved.

The impact of virtual reality on student engagement in the classroom-a critical review of the literature.

Objective: The purpose of this review is to identify the impact of virtual reality (VR) technology on student engagement, specifically cognitive engagement, behavioral engagement, and affective engagement. Methods: A comprehensive search of databases such as Google, Scopus, and Elsevier was conducted to identify English-language articles related to VR and classroom engagement for the period from 2014 to 2023. After systematic screening, 33 articles were finally reviewed. Results: The use of VR in the classroom is expected to improve student engagement and learning outcomes, and is particularly effective for students with learning disabilities. However, introducing VR into middle school education poses several challenges, including difficulties in the education system to keep up with VR developments, increased demands on students' digital literacy, and insufficient proficiency of teachers in using VR. Conclusion: To effectively utilize VR to increase student engagement, we advocate for educational policymakers to provide training and technical support to teachers to ensure that they can fully master and integrate VR to increase student engagement and instructional effectiveness.

Moyamoya syndrome may result from psoriasis: Four case reports.

BACKGROUND: Moyamoya syndrome (MMS) is a group of diseases that involves more than one underlying disease and is accompanied by moyamoya vascular phenomena. Psoriasis is a chronic immune skin disease closely linked to high blood pressure and heart disease. However, psoriasis-related MMS has not been reported. CASE SUMMARY: We collected data on patients with stroke due to MMS between January 2017 and December 2019 and identified four cases of psoriasis. Case histories, imaging, and hematological data were collected. The average age of the initial stroke onset was 58.25 ± 11.52 years; three cases of hemorrhagic and one case of ischemic stroke were included. The average duration from psoriasis confirmation to the initial MMS-mediated stroke onset was 17 ± 3.56 years. All MMS-related stenoses involved the bilateral cerebral arteries: Suzuki grade III in one case, grade IV in two cases, and grade V in one case. Abnormally elevated plasma interleukin-6 levels were observed in four patients. Two patients had abnormally elevated immunoglobulin E levels, and two had thrombocytosis. All four patients received medication instead of surgery. With an average follow-up time of 2 years, two causing transient ischemic attacks occurred in two patients, and no hemorrhagic events occurred. CONCLUSION: Psoriasis may be a potential risk factor for MMS. Patients with psoriasis should be screened for MMS when they present with neurological symptoms.

TGF-ß downstream of Smad3 and MAPK signaling antagonistically regulate the viability and partial epithelial-mesenchymal transition of liver progenitor cells.

BACKGROUND: Liver progenitor cells (LPCs) are a subpopulation of cells that contribute to liver regeneration, fibrosis and liver cancer initiation under different circumstances. RESULTS: By performing adenoviral-mediated transfection, CCK-8 analyses, F-actin staining, transwell analyses, luciferase reporter analyses and Western blotting, we observed that TGF-ß promoted cytostasis and partial epithelial-mesenchymal transition (EMT) in LPCs. In addition, we confirmed that TGF-ß activated the Smad and MAPK pathways, including the Erk, JNK and p38 MAPK signaling pathways, and revealed that TGFß-Smad signaling induced growth inhibition and partial EMT, whereas TGFß-MAPK signaling had the opposite effects on LPCs. We further found that the activity of Smad and MAPK signaling downstream of TGF-ß was mutually restricted in LPCs. Mechanistically, we found that TGF-ß activated Smad signaling through serine phosphorylation of both the C-terminal and linker regions of Smad2 and 3 in LPCs. Additionally, TGFß-MAPK signaling inhibited the phosphorylation of Smad3 but not Smad2 at the C-terminus, and it reinforced the linker phosphorylation of Smad3 at T179 and S213. We then found that overexpression of mutated Smad3 at linker phosphorylation sites intensifies TGF-ß-induced cytostasis and EMT, mimicking the effects of MAPK inhibition in LPCs, whereas mutation of Smad3 at the C-terminus caused LPCs to blunt TGF-ß-induced cytostasis and partial EMT. CONCLUSION: These results suggested that TGF-ß downstream of Smad3 and MAPK signaling were mutually antagonistic in regulating the viability and partial EMT of LPCs. This antagonism may help LPCs overcome the cytostatic effect of TGF-ß under fibrotic conditions and maintain partial EMT and progenitor phenotypes.

Comparison of Machine Learning Models Using Diffusion-Weighted Images for Pathological Grade of Intrahepatic Mass-Forming Cholangiocarcinoma.

Is the radiomic approach, utilizing diffusion-weighted imaging (DWI), capable of predicting the various pathological grades of intrahepatic mass-forming cholangiocarcinoma (IMCC)? Furthermore, which model demonstrates superior performance among the diverse algorithms currently available? The objective of our study is to develop DWI radiomic models based on different machine learning algorithms and identify the optimal prediction model. We undertook a retrospective analysis of the DWI data of 77 patients with IMCC confirmed by pathological testing. Fifty-seven patients initially included in the study were randomly assigned to either the training set or the validation set in a ratio of 7:3. We established four different classifier models, namely random forest (RF), support vector machines (SVM), logistic regression (LR), and gradient boosting decision tree (GBDT), by manually contouring the region of interest and extracting prominent radiomic features. An external validation of the model was performed with the DWI data of 20 patients with IMCC who were subsequently included in the study. The area under the receiver operating curve (AUC), accuracy (ACC), precision (PRE), sensitivity (REC), and F1 score were used to evaluate the diagnostic performance of the model. Following the process of feature selection, a total of nine features were retained, with skewness being the most crucial radiomic feature demonstrating the highest diagnostic performance, followed by Gray Level Co-occurrence Matrix lmc1 (glcm-lmc1) and kurtosis, whose diagnostic performances were slightly inferior to skewness. Skewness and kurtosis showed a negative correlation with the pathological grading of IMCC, while glcm-lmc1 exhibited a positive correlation with the IMCC pathological grade. Compared with the other three models, the SVM radiomic model had the best diagnostic performance with an AUC of 0.957, an accuracy of 88.2%, a sensitivity of 85.7%, a precision of 85.7%, and an F1 score of 85.7% in the training set, as well as an AUC of 0.829, an accuracy of 76.5%, a sensitivity of 71.4%, a precision of 71.4%, and an F1 score of 71.4% in the external validation set. The DWI-based radiomic model proved to be efficacious in predicting the pathological grade of IMCC. The model with the SVM classifier algorithm had the best prediction efficiency and robustness. Consequently, this SVM-based model can be further explored as an option for a non-invasive preoperative prediction method in clinical practice.

Synergistic effects of ceftazidime/avibactam combined with meropenem in a murine model of infection with KPC-producing Klebsiella pneumoniae.

OBJECTIVES: The emergence and expansion of carbapenem-resistant Klebsiella pneumoniae infections is a concern due to the lack of 'first-line' antibiotic treatment options. The ceftazidime/avibactam is an important clinical treatment for carbapenem-resistant K. pneumoniae infections but there is an increasing number of cases of treatment failure and drug resistance. Therefore, a potential solution is combination therapies that result in synergistic activity against K. pneumoniae carbapenemase: producing K. pneumoniae (KPC-Kp) isolates and preventing the emergence of KPC mutants resistant to ceftazidime/avibactam are needed in lieu of novel antibiotics. METHODS: To evaluate their synergistic activity, antibiotic combinations were tested against 26 KPC-Kp strains. Antibiotic resistance profiles, molecular characteristics and virulence genes were investigated by susceptibility testing and whole-genome sequencing. Antibiotic synergy was evaluated by in vitro chequerboard experiments, time-killing curves and dose-response assays. The mouse thigh model was used to confirm antibiotic combination activities in vivo. Additionally, antibiotic combinations were evaluated for their ability to prevent the emergence of ceftazidime/avibactam resistant mutations of blaKPC. RESULTS: The combination of ceftazidime/avibactam plus meropenem showed remarkable synergistic activity against 26 strains and restored susceptibility to both the partnering antibiotics. The significant therapeutic effect of ceftazidime/avibactam combined with meropenem was also confirmed in the mouse model and bacterial loads in the thigh muscle of the combination groups were significantly reduced. Furthermore, ceftazidime/avibactam plus meropenem showed significant activity in preventing the occurrence of resistance mutations. CONCLUSIONS: Our results indicated that the combination of ceftazidime/avibactam plus meropenem offers viable therapeutic alternatives in treating serious infections due to KPC-Kp.

Insights into the molecular mechanisms, structure-activity relationships and application prospects of polysaccharides by regulating Nrf2-mediated antioxidant response.

The occurrence and development of many diseases are closely related to oxidative stress. In this context, accumulating evidence suggests that Nrf2, as the master switch of cellular antioxidant signaling, plays a central role in controlling the expression of antioxidant genes. The core molecular mechanism of polysaccharides treatment of oxidative stress-induced diseases is to activate Keap1/Nrf2/ARE signaling pathway, promote nuclear translocation of Nrf2, and up-regulate the expression of antioxidant enzymes. However, recent studies have shown that other signaling pathways in which polysaccharides exert antioxidant effects, such as PI3K/Akt/GSK3ß, JNK/Nrf2 and NF-κB, have complex crosstalk with Keap1/Nrf2/ARE, may have direct effects on the nuclear translocation of Nrf2. This suggests a new strategy for designing polysaccharides as modulators of Nrf2-dependent pathways to target the antioxidant response. Therefore, in this work, we investigate the crosstalk between Keap1/Nrf2/ARE and other antioxidant signaling pathways of polysaccharides by regulating Nrf2-mediated antioxidant response. For the first time, the structural-activity relationship of polysaccharides, including molecular weight, monosaccharide composition, and glycosidic linkage, is systematically elucidated using principal component analysis and cluster analysis. This review also summarizes the application of antioxidant polysaccharides in food, animal production, cosmetics and biomaterials. The paper has significant reference value for screening antioxidant polysaccharides targeting Nrf2.

Compositional features analysis by machine learning in genome represents linear adaptation of monkeypox virus.

Introduction: The global headlines have been dominated by the sudden and widespread outbreak of monkeypox, a rare and endemic zoonotic disease caused by the monkeypox virus (MPXV). Genomic composition based machine learning (ML) methods have recently shown promise in identifying host adaptability and evolutionary patterns of virus. Our study aimed to analyze the genomic characteristics and evolutionary patterns of MPXV using ML methods. Methods: The open reading frame (ORF) regions of full-length MPXV genomes were filtered and 165 ORFs were selected as clusters with the highest homology. Unsupervised machine learning methods of t-distributed stochastic neighbor embedding (t-SNE), Principal Component Analysis (PCA), and hierarchical clustering were performed to observe the DCR characteristics of the selected ORF clusters. Results: The results showed that MPXV sequences post-2022 showed an obvious linear adaptive evolution, indicating that it has become more adapted to the human host after accumulating mutations. For further accurate analysis, the ORF regions with larger variations were filtered out based on the ranking of homology difference to narrow down the key ORF clusters, which drew the same conclusion of linear adaptability. Then key differential protein structures were predicted by AlphaFold 2, which meant that difference in main domains might be one of the internal reasons for linear adaptive evolution. Discussion: Understanding the process of linear adaptation is critical in the constant evolutionary struggle between viruses and their hosts, playing a significant role in crafting effective measures to tackle viral diseases. Therefore, the present study provides valuable insights into the evolutionary patterns of the MPXV in 2022 from the perspective of genomic composition characteristics analysis through ML methods.

[Effects of coal mine waste dump on soil seed bank and vegetation distribution pattern]. / ç ¤çŸ¿æŽ’çŸ¸åœºå¯¹å‘¨è¾¹åœŸå£¤ç§å­åº“åŠæ¤è¢«åˆ†å¸ƒæ ¼å±€çš„å½±å“.

Long-term occupation of coal gangue dumping sites (CGDS) may destroy ecological environment of nearby area. However, how the CGDS affects the distribution pattern of soil seed banks and vegetation in the nearby area is not clear. In this study, we investigated soil seed bank and vegetation at different distances from the second CGDS of Yangchangwan in Ningdong mining area, Lingwu, Ningxia. The results showed that soil seed bank was mainly distributed in 0-10 cm layer and decreased with increasing soil depth. Species richness of soil seed bank and vegetation first increased and then tended to be stable with increasing distance to the CGDS. The influence range of CGDS on soil seed banks was 300-500 m and was 100-300 m on aboveground vegetation. The CGDS did not affect the vertical distribution pattern of soil seed bank, but significantly affected the horizontal distribution pattern of soil seed banks and aboveground vegetation. The key area of vegetation restoration around the CGDS was between 100 m and 300 m.

The effects of initial and subsequent overweight or obesity on hypertension in the middle age.

The aims of our study were to examine whether initial or subsequent adiposity status had a greater effect on hypertension. We collected data in 1992 and again in 2007 from the same group of 597 individuals in the middle age. The subjects were classified into four groups: individuals with a normal body mass index (BMI) in 1992 and 2007 were in Group I; those with a normal BMI in 1992, but became overweight or obese in 2007 were in Group II; those who were overweight or obese in 1992, but had a normal BMI in 2007 were in Group III; and those who were overweight or obese in 1992 and 2007 were in Group IV. Their demographic data were recorded. The relationship between adiposity status and hypertension was analyzed using logistic regression model. The cumulative incidence of hypertension was 35.5%, 56.3%, 50.0%, and 65.1% for Group I to IV, respectively. Compared with Group I, after adjusted factors, the hazard ratio (HR) was 1.80 for Group II (P = .001), 1.40 for Group III (P = .150), and 2.31 for Group IV (P < .001). Adiposity status in 2007 could predict hypertension (OR = 2.5, P < .001), as opposed to the initial adiposity status (P = .148). Subsequently adiposity status could have major effects on hypertension. Our society is very short of public health resources, particularly in developing countries, we should pay more attention to current adiposity status and encourage middle-aged people to lose weight.