Clinical application of dual-layer spectral CT multi-parameter feature to predict microvascular invasion in hepatocellular carcinoma.

OBJECTIVE: This study aimed to investigate the feasibility of using dual-layer spectral CT multi-parameter feature to predict microvascular invasion of hepatocellular carcinoma. METHODS: This retrospective study enrolled 50 HCC patients who underwent multiphase contrast-enhanced spectral CT studies preoperatively. Combined clinical data, radiological features with spectral CT quantitative parameter were constructed to predict MVI. ROC was applied to identify potential predictors of MVI. The CT values obtained by simulating the conventional CT scans with 70 keV images were compared with those obtained with 40 keV images. RESULTS: 50 hepatocellular carcinomas were detected with 30 lesions (Group A) with microvascular invasion and 20 (Group B) without. There were significant differences in AFP,tumer size, IC, NIC,slope and effective atomic number in AP and ICrr in VP between Group A ((1000(10.875,1000),4.360±0.3105, 1.7750 (1.5350,1.8825) mg/ml, 0.1785 (0.1621,0.2124), 2.0362±0.2108,8.0960±0.1043,0.2830±0.0777) and Group B (4.750(3.325,20.425),3.190±0.2979,1.4700 (1.4500,1.5775) mg/ml, 0.1441 (0.1373,0.1490),1.8601±0.1595, 7.8105±0.7830 and 0.2228±0.0612) (all p < 0.05). Using 0.1586 as the threshold for NIC, one could obtain an area-under-curve (AUC) of 0.875 in ROC to differentiate between tumours with and without microvascular invasion. AUC was 0.625 with CT value at 70 keV and improved to 0.843 at 40 keV. CONCLUSION: Dual-layer spectral CT provides additional quantitative parameters than conventional CT to enhance the differentiation between hepatocellular carcinoma with and without microvascular invasion. Especially, the normalized iodine concentration (NIC) in arterial phase has the greatest potential application value in determining whether microvascular invasion exists, and can offer an important reference for clinical treatment plan and prognosis assessment.

Celastrol inhibits angiogenesis and the biological processes of MDA-MB-231 cells via the DEGS1/S1P signaling pathway.

Celastrol (Cel) shows potent antitumor activity in various experimental models. This study examined the relationship between Cel's antivascular and antitumor effects and sphingolipids. CCK-8 assay, transwell assay, Matrigel, PCR-array/RT-PCR/western blotting/immunohistochemistry assay, ELISA and HE staining were used to detect cell proliferation, migration and invasion, adhesion and angiogenesis, mRNA and protein expression, S1P production and tumor morphology. The results showed that Cel could inhibit proliferation, migration or invasion, adhesion and angiogenesis of human umbilical vein endothelial cells (HUVECs) and MDA-MB-231 cells by downregulating the expression of degenerative spermatocyte homolog 1 (DEGS1). Transfection experiments showed that downregulation of DEGS1 inhibited the above processes and sphingosine-1-phosphate (S1P) production of HUVECs and MDA-MB-231 cells, while upregulation of DEGS1 had the opposite effects. Coculture experiments showed that HUVECs could promote proliferation, migration and invasion of MDA-MB-231 cells through S1P/sphingosine-1-phosphate receptor (S1PR) signaling pathway, while Cel inhibited these processes in MDA-MB-231 cells induced by HUVECs. Animal experiments showed that Cel could inhibit tumor growth in nude mice. Western blotting, immunohistochemistry and ELISA assay showed that Cel downregulated the expression of DEGS1, CD146, S1PR1-3 and S1P production. These data confirm that DEGS1/S1P signaling pathway may be related to the antivascular and antitumor effects of cel.

Porous and Partially Dehydrogenated Fe2+ -Containing Iron Oxyhydroxide Nanosheets for Efficient Electrochemical Nitrogen Reduction Reaction (ENRR).

The design and development of efficient catalysts for electrochemical nitrogen reduction reaction (ENRR) under ambient conditions are critical for the alternative ammonia (NH3 ) synthesis from N2 and H2 O, wherein iron-based electrocatalysts exhibit outstanding NH3 formation rate and Faradaic efficiency (FE). Here, the synthesis of porous and positively charged iron oxyhydroxide nanosheets by using layered ferrous hydroxide as a starting precursor, which undergoes topochemical oxidation, partial dehydrogenated reaction, and final delamination, is reported. As the electrocatalyst of ENRR, the obtained nanosheets with a monolayer thickness and 10-nm mesopores display exceptional NH3 yield rate (28.5 µg h-1 mgcat. -1 ) and FE (13.2%) at a potential of -0.4 V versus RHE in a phosphate buffered saline (PBS) electrolyte. The values are much higher than those of the undelaminated bulk iron oxyhydroxide. The larger specific surface area and positive charge of the nanosheets are beneficial for providing more exposed reactive sites as well as retarding hydrogen evolution reaction. This study highlights the rational control on the electronic structure and morphology of porous iron oxyhydroxide nanosheets, expanding the scope of developing non-precious iron-based highly efficient ENRR electrocatalysts.

Effect of biochar with different particle sizes on the sorption-desorption characteristics of soil phosphorus.

The size of particles determines the adsorption reaction. In this study, three different particle sizes of biochar (0.25-1 mm, 0.075-0.25 mm, <0.075 mm) were produced from rapeseed straw (SBC) and chicken manure (MBC). The biochar was mixed with high phosphorus (P) soil and low P soil and then incubated for 30 days. We conducted isothermal P sorption and desorption experiments to evaluate the effects of biochar particle size on sorption-desorption characteristics of soil P, and analyzed soil properties associated with P sorption. The results showed that P sorption capacity of SBC and MBC in the water system was highest for the smallest particle size (<0.075 mm) (SBC: 43125 mg·kg-1, MBC: 20083 mg·kg-1), followed by the intermediate particle size (0.075-0.25 mm) (SBC: 37376 mg·kg-1, MBC: 13199 mg·kg-1) and the largest particle size (0.25-1 mm) (SBC: 27749 mg·kg-1, MBC: 12251 mg·kg-1). However, there was little difference in soil P sorption between the three particle sizes of the same biochar in the soil system. In comparison with no biochar treatment, the addition of SBC increased the Langmuir P sorption maximum (Smax) by 236.8%-755.7%, and decreased soil P desorption rate. The addition of MBC increased Smax, but the enhancement was less than that of SBC. Soil P desorption rate was increased by 7.2%-295.9%. Both SBC and MBC significantly increased the contents of soil total P, available P, and exchangeable calcium (Ca) and magnesium (Mg). The increases in Ca and Mg contents due to biochar addition was 64.0%-257.1% (SBC) and 39.1%-205.3% (MBC), respectively. The contents of soil exchangeable Ca and Mg were positively correlated with Smax. These results suggested that biochar particle size had little effect on soil P sorption, but the enrichment of Ca and Mg due to biochar addition played a critical role in regulating soil P sorption. The rapeseed straw biochar had a high adsorption capacity for soil P, making it suitable for improving the P fixation capacity of soil rich in P and reducing the loss of excess P. Chicken manure biochar could be used to improve the P availability of low P soils and increase the contents of available P.

CNT-MXene ultralight membranes: fabrication, surface nano/microstructure, 2D-3D stacking architecture, ion-transport mechanism, and potential application as interlayers for Li-O2 batteries.

Multiwalled carbon nanotubes (MWCNTs) have shown effectiveness in improving the suitability of MXenes for energy-related applications. However, the ability of individually dispersed MWCNTs to control the structure of MXene-based macrostructures is unclear. Here, the correlation among composition, surface nano- and microstructure, MXenes' stacking order, structural swelling, and Li-ion transport mechanisms and properties in individually dispersed MWCNT-Ti3C2 films was investigated. The compact surface microstructure of MXene film, characterized by prominent wrinkles, is dramatically changed as MWCNTs occupy MXene/MXene edge interfaces. The 2D stacking order is preserved up to 30 wt% MWCNTs despite a significant swelling of ∼400%. Such alignment is completely disrupted at 40 wt%, and a more pronounced surface opening and internal expansion of ∼770% are realized. Both 30 wt% and 40 wt% membranes show stable cycling performance under a significantly higher current density due to faster transport channels. Notably, for the 3D membrane, the overpotential during repeated Li deposition/dissolution reactions is further reduced by ∼50%. Ion-transport mechanisms in the absence and presence of MWCNTs are discussed. Furthermore, ultralight yet continuous hybrid films comprising up to ∼0.027 mg cm-2 Ti3C2 can be prepared using aqueous colloidal dispersions and vacuum filtration for specific applications. The potential application of such ultralight membranes as interlayers for Li-O2 batteries is briefly examined.

A Fluorescent Molecularly Imprinted Polymer-Coated Paper Sensor for On-Site and Rapid Detection of Glyphosate.

Due to the massive use and abuse of pesticides, practices which have led to serious threats to human health, the research community must develop on-site and rapid detection technology of pesticide residues to ensure food safety. Here, a paper-based fluorescent sensor, integrated with molecularly imprinted polymer (MIP) targeting glyphosate, was prepared by a surface-imprinting strategy. The MIP was synthesized by a catalyst-free imprinting polymerization technique and exhibited highly selective recognition capability for glyphosate. The MIP-coated paper sensor not only remained selective, but also displayed a limit of detection of 0.29 µmol and a linear detection range from 0.5 to 10 µmol. Moreover, the detection time only took about 5 min, which is beneficial for rapid detection of glyphosate in food samples. The detection accuracy of such paper sensor was good, with a spiked recovery rate of 92-117% in real samples. The fluorescent MIP-coated paper sensor not only has good specificity, which is helpful to reduce the food matrix interference and shorten the sample pretreatment time, but it also has the merits of high stability, low-cost and ease of operation and carrying, displaying great potential for application in the on-site and rapid detection of glyphosate for food safety.

Occurrence of bisphenol diglycidyl ethers and bisphenol analogs, and their associations with DNA oxidative damage in pregnant women.

Bisphenol diglycidyl ethers (BDGEs) and Bisphenol A and its analogs (bisphenols) may have the same exposure routes and coexposure phenomenon in sensitive populations such as pregnant women. Previous biomonitoring studies on BDGEs are limited. Levels of fifteen bisphenols, six BDGEs and the DNA oxidative damage biomarker 8-hydroxy-2-deoxyguanosine (8-OHdG) were measured in the urine of pregnant women recruited in south China (n = 358). We aimed to provide the occurrence of bisphenols and BDGEs in pregnant women, and to investigate the potential relationship between their exposure and oxidative stress. Bisphenol A, bisphenol S, bisphenol F, bisphenol AP and all BDGEs (except for BADGE·2HCl) were frequently detected. The total concentrations of all bisphenols and BDGEs were 0.402-338 and 0.104-32.5 ng/mL, with geometric means of 2.87 and 2.48 ng/mL, respectively. BFDGE was the most abundant chemical of BDGEs, with a median concentration of 0.872 ng/mL, followed by BADGE·H2O·HCl (0.297 ng/mL). Except for pre-pregnancy obesity, maternal age/height, employment, fasting in the morning and parity did not affect the urinary concentrations of BDGEs. Significant and weak correlations were observed between concentrations (unadjusted) of total bisphenols and BDGEs (r = 0.389, p < 0.01), indicating their similar sources and exposure routes. The biomarker 8-OHdG was detected in all samples, with concentrations ranging from 1.98 to 32.6 ng/mL (median: 9.96 ng/mL). Levels of 8-OHdG were positively correlated with urinary several bisphenol concentrations (adjusted ß range: 0.037-0.089, p < 0.05) but were not correlated with those of BDGEs. Further studies should focus on whether BDGEs and bisphenols exert combined effects on oxidative stress. Our study provided the first BDGEs exposure data in pregnant women and indicated that BDGEs exposure was highly prevalent in pregnant women as early as 2015 in south China.

UPLC-MS based integrated plasma proteomic and metabolomic profiling of TSC-RAML and its relationship with everolimus treatment.

Aim: To profile the plasma proteomics and metabolomics of patients with renal cysts, sporadic angiomyolipoma (S-AML) and tuberous sclerosis complex related angiomyolipoma (TSC-RAML) before and after everolimus treatment, and to find potential diagnostic and prognostic biomarkers as well as reveal the underlying mechanism of TSC tumorigenesis. Materials and Methods: We retrospectively measured the plasma proteins and metabolites from November 2016 to November 2017 in a cohort of pre-treatment and post-treatment TSC-RAML patients and compared them with renal cyst and S-AML patients by ultra-performance liquid chromatography-mass spectrometer (UPLC-MS). The tumor reduction rates of TSC-RAML were assessed and correlated with the plasma protein and metabolite levels. In addition, functional analysis based on differentially expressed molecules was performed to reveal the underlying mechanisms. Results: Eighty-five patients with one hundred and ten plasma samples were enrolled in our study. Multiple proteins and metabolites, such as pre-melanosome protein (PMEL) and S-adenosylmethionine (SAM), demonstrated both diagnostic and prognostic effects. Functional analysis revealed many dysregulated pathways, including angiogenesis synthesis, smooth muscle proliferation and migration, amino acid metabolism and glycerophospholipid metabolism. Conclusion: The plasma proteomics and metabolomics pattern of TSC-RAML was clearly different from that of other renal tumors, and the differentially expressed plasma molecules could be used as prognostic and diagnostic biomarkers. The dysregulated pathways, such as angiogenesis and amino acid metabolism, may shed new light on the treatment of TSC-RAML.

Quantitative proteomics identifies and validates urinary biomarkers of rhabdomyosarcoma in children.

BACKGROUND: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma with poor prognosis in children. The 5-year survival rate for early RMS has improved, whereas it remains unsatisfactory for advanced patients. Urine can rapidly reflect changes in the body and identify low-abundance proteins. Early screening of tumor markers through urine in RMS allows for earlier treatment, which is associated with better outcomes. METHODS: RMS patients under 18 years old, including those newly diagnosed and after surgery, were enrolled. Urine samples were collected at the time points of admission and after four cycles of chemotherapy during follow-up. Then, a two-stage workflow was established. (1) In the discovery stage, differential proteins (DPs) were initially identified in 43 RMS patients and 12 healthy controls (HCs) using a data-independent acquisition method. (2) In the verification stage, DPs were further verified as biomarkers in 54 RMS patients and 25 HCs using parallel reaction monitoring analysis. Furthermore, a receiver operating characteristic (ROC) curve was used to construct the protein panels for the diagnosis of RMS. Gene Ontology (GO) and Ingenuity Pathway Analysis (IPA) software were used to perform bioinformatics analysis. RESULTS: A total of 251 proteins were significantly altered in the discovery stage, most of which were enriched in the head, neck and urogenital tract, consistent with the most common sites of RMS. The most overrepresented biological processes from GO analysis included immunity, inflammation, tumor invasion and neuronal damage. Pathways engaging the identified proteins revealed 33 common pathways, including WNT/ß-catenin signaling and PI3K/AKT signaling. Finally, 39 proteins were confirmed as urinary biomarkers for RMS, and a diagnostic panel composed of 5 candidate proteins (EPS8L2, SPARC, HLA-DRB1, ACAN, and CILP) was constructed for the early screening of RMS (AUC: 0.79, 95%CI = 0.66 ~ 0.92). CONCLUSIONS: These findings provide novel biomarkers in urine that are easy to translate into clinical diagnosis of RMS and illustrate the value of global and targeted urine proteomics to identify and qualify candidate biomarkers for noninvasive molecular diagnosis.

[Guideline for clinical comprehensive evaluation of Chinese patent medicine (2022 version)].

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.

Current status and quality of radiomic studies for predicting KRAS mutations in colorectal cancer patients: A systematic review and meta­analysis.

PURPOSE: The purpose of this study was to evaluate the methodological quality of radiomics-based studies for noninvasive, preoperative prediction of Kirsten rat sarcoma (KRAS) mutations in patients with colorectal cancer; furthermore, we systematically evaluate the diagnostic accuracy of predicting models. METHODS: We systematically searched PubMed, Embase, Cochrane Library and Web of Science databases up to 20 April 2022 for eligible studies. The methodological quality of included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) and Radiomics Quality Score (RQS) tools. A meta-analysis of studies on the prediction of KRAS status in colorectal cancer patients was performed. RESULT: Twenty-nine studies were identified in the systematic review, including three studies on the prediction of KRAS status in colorectal cancer liver metastases. All studies had an average RQS score of 9.55 (26.5% of the total score), ranging from 3 to 17. Most studies demonstrated a low or unclear risk of bias in the domains of QUADAS-2. Nineteen studies were included in the meta-analysis, mostly imaged with magnetic resonance imaging (MRI), followed by computed tomography (CT), positron emission tomography-CT (PET/CT). With pooled sensitivity, specificity and area under the curve (AUC) of the training cohorts were 0.80(95% confidence interval(CI), 0.75-0.84), 0.80(95% CI, 0.74-0.85) and 0.87(95% CI, 0.84-0.90),respectively. The pooled sensitivity, specificity, and AUC for the validation cohorts (13 studies) were 0.78(95% CI, 0.71-0.84), 0.84(95% CI, 0.74-0.90), and 0.86(95% CI, 0.83-0.89), respectively. CONCLUSION: Radiomics is a potential noninvasive technology that has a moderate preoperative diagnosis and prediction effect on KRAS mutations. However, it has not been implemented as a clinical decision-making tool. Future researchers should pay more attention to the methodological quality of the study and further externally validate the model using multicenter datasets.

[18F]FAPI-42 PET/CT in differentiated thyroid cancer: diagnostic performance, uptake values, and comparison with 2-[18F]FDG PET/CT.

PURPOSE: This study aimed to assess the diagnostic performance of [18F]FAPI-42 PET/CT and compare it with that of 2-[18F]FDG PET/CT in patients with differentiated thyroid cancer (DTC) with biochemical elevations in Tg or anti-Tg antibodies. METHODS: A total of 42 patients with DTC with biochemical elevations in Tg or anti-Tg antibodies underwent [18F]FAPI-42 PET/CT as part of this study; of which, 11 additionally underwent 2-[18F]FDG PET/CT within 7 days. Images were semi-quantitatively and visually interpreted, and the quantity, location, and uptake values of lesions were noted. The diagnostic capacity of [18F]FAPI-42 PET/CT and biomarkers affecting the uptake of [18F]FAPI-42 were evaluated. In addition, the diagnostic performance and uptake of [18F]FAPI-42 and 2-[18F]FDG were compared, and the correlation between lesion diameter and quantitative parameters was investigated. RESULTS: A total of 161 lesions were detected in 27 (64%) patients on [18F]FAPI-42 PET/CT. FAPI-positive local recurrence showed the highest uptake intensity, followed by lymphatic, other site-associated (bone and pleura), and pulmonary lesions (mean SUVmax, 4.7 versus 3.7 versus 3.0 versus 2.2, respectively; P < 0.0001). The levels of TSH, Tg, and Tg-Ab did not affect the uptake value of lesions (median SUVmax: 2.4 versus 3.2, P = 0.56; 2.9 versus 2.4, P = 0.0935; 2.8 versus 2.6, P = 0.0525, respectively). A total of 90 positive lesions were detected in 7 patients using both modalities. All positive lesions showed statistically higher uptake of 2-[18F]FDG than that of [18F]FAPI-42 (SUVmax, 2.6 versus 2.1; P = 0.026). However, the SUVmax of [18F]FAPI-42 was higher than that of 2-[18F]FDG in local recurrences and lymphatic lesions (SUVmax, 4.2 versus 2.9 and 3.9 versus 3.4, respectively; P > 0.05). CONCLUSION: [18F]FAPI-42 can be used for detecting lesions and reflecting FAP expression during local recurrence and metastasis in patients with DTC with biochemical elevations in Tg or anti-Tg antibodies. The diagnostic performance of [18F]FAPI-42 PET/CT is comparable with that of 2-[18F]FDG PET/CT in such patients.

Lead absorption capacity in different parts of plants and its influencing factors: a systematic review and meta-analysis.

People pose a serious risk by plants contaminated with lead in soil. However, the strength of lead enrichment capacity in root, stem, and leaf of the plant is still controversial. Therefore, a meta-analysis was conducted to investigate the ability of lead enrichment of root, stem, and leaf and the main influencing factors for lead absorption. The results of this study indicated that all parts of plant can significantly accumulate lead. Concentrations of lead followed an order of root > stem > leaf. Alkaline soil was conducive to the absorption of lead. When the lead concentration in the soil was higher than 20 mg/kg, the lead absorption in root was more. Lead is absorbed most in trees and least in Gramineae. It is argued that this study is beneficial to select plants suitable for absorption of lead from polluted soil. This study also can help to clarify the influencing factors for lead enrichment in different parts of the plant.

Cost-effectiveness analysis of dasatinib versus imatinib in pediatric philadelphia chromosome-positive acute lymphoblastic leukemia patients in China.

BACKGROUND: Dasatinib and imatinib are the recommended tyrosine kinase inhibitors (TKIs) for treating pediatric Philadelphia-positive acute lymphoblastic leukemia (Ph + ALL), and the one which has been approved indication in China is imatinib. Recently, clinical demand for Ph + ALL treatment is becoming unmet gradually with the increasing resistance of imatinib. There are some studies reporting the better efficacy and comparative safety of dasatinib compared with imatinib, but no economic comparison has been published. This study aims to supplement economic evidence by comparing the cost-effectiveness between imatinib and dasatinib in treating pediatric patients with Ph+ ALL in China, and to help clinical rational drug use via multi-dimensional value assessment. METHODS: A decision tree model combined with a 10-year Markov model were established based on the disease progression. The parameters were collected from published literatures and our hospital's electronic medical records. From the health system perspective, the incremental cost-effectiveness ratio (ICER) between the two treatment groups was calculated through cost-effectiveness analysis and then compared with the willingness-to-pay (WTP) threshold. The set WTP threshold in this study was 1 times per capita gross domestic product (GDP) of China, as recommended by the World Health Organization. Direct medical costs and quality-adjusted life years (QALYs) were calculated and discounted at 5%. The sensitivity analyses were conducted to assess the uncertainty and robustness of the results. RESULTS: The total costs were CNY 1,020,995.35 and CNY 1,035,788.50 in imatinib group and dasatinib group during the 10-year simulation, and the total QALYs were 2.59 and 4.84. Compared with the imatinib treatment group, the ICER was around CNY 6,575.78/ QALY, which was less than the set threshold CNY 70,892/ QALY. The sensitive analyses indicated the robustness of the results. CONCLUSIONS: The cost-effectiveness analysis shows the potential cost-effective advantages of adding dasatinib comparing with adding imatinib for pediatric Ph + ALL patients in China under the set WTP threshold, which indicates that those patients could achieve more QALYs by paying acceptable fee.

Constructing Fast Transmembrane Pathways in a Layered Double Hydroxide Nanosheets/Nanoparticles Composite Film for an Inorganic Anion-Exchange Membrane.

Anion-exchange membranes (AEMs) with high conductivity are crucial for realizing next-generation energy storage and conversion systems in an alkaline environment, promising a huge advantage in cost reduction without using precious platinum group metal catalysts. Layered double hydroxide (LDH) nanosheets, exhibiting a remarkably high hydroxide ion (OH-) conductivity approaching 10-1 S cm-1 along the in-plane direction, may be regarded as an ideal candidate material for the fabrication of inorganic solid AEMs. However, two-dimensional anisotropy results in a substantially low conductivity of 10-6 S cm-1 along the cross-plane direction, which poses a hurdle to achieve fast ion conduction across the membrane comprising restacked nanosheets. In the present work, a composite membrane was prepared based on mixing/assembling micron-sized LDH nanosheets with nanosized LDH platelets (nanoparticles) via a facile vacuum filtration process. The hybridization with nanoparticles could alter the orientation of LDH nanosheets and reduce the restacking order, forming diversified fast ion-conducting pathways and networks in the composite membrane. As a result, the transmembrane conductivity significantly improved up to 1000-fold higher than that composed of restacked nanosheets only, achieving a high conductivity of 10-2 to 10-1 S cm-1 in both in-plane and cross-plane directions.

Triptolide Inhibits the Biological Processes of HUVECs and HepG2 Cells via the Serine Palmitoyltransferase Long Chain Base Subunit 2/Sphingosine-1-Phosphate Signaling Pathway.

Triptolide (TP) has demonstrated innumerous biological effects and pharmacological potential against different cancer types. Hepatocellular carcinoma has a high incidence in men, and its incidence is increasing year by year. Studies have shown that angiogenesis plays an important role in the formation of tumors and that angiogenesis is closely related to tumor growth and metastasis. Deregulation of sphingolipids signaling has been associated with several pathological conditions, including cancer. In the present study, we aimed at exploring the potential molecular mechanism of TP's antivascular and antitumor effects in vitro from the perspective of sphinolipids. Human umbilical vein endothelial cells (HUVECs) and HepG2 cells were, respectively, treated with different concentrations of TP and transfected. Then, the effect of HUVECs on HepG2 cells was investigated using a three-dimensional coculture model system. CCK-8 assay was performed for cell proliferation. Cell migration and invasion abilities were assessed using the transwell assay. Cell adhesion and tube formation were detected by Matrigel. RT-PCR and western blotting were used to detect the mRNA and protein expression. The S1P production was measured via ELISA assay. Our results showed that TP inhibited HUVECs and HepG2 cells proliferation, migration, invasion, adhesion, angiogenesis, and serine palmitoyltransferase long chain base subunit 2 (SPTLC2) expression; upregulating SPTLC2 facilitated the proliferation, migration, invasion, adhesion, angiogenesis, and sphingosine-1-phosphate (S1P) production of HUVECs and HepG2 cells, while interfering with SPTLC2 expression inhibited them; HUVECs facilitated the proliferation, migration, invasion, S1P production, S1PR1, and S1PR2 expression of HepG2 cells, while S1PR3 expression was decreased. In conclusion, SPTLC2 may be associated with the antivascular and antitumor effects of TP, and SPTLC2 is expected to become a new marker for tumor therapy. HUVECs can promote the proliferation, migration, and invasion of HepG2 cells, which may be related to the S1P/sphingosine-1-phosphate receptor (S1PR) signaling pathway.

Artificial intelligence with magnetic resonance imaging for prediction of pathological complete response to neoadjuvant chemoradiotherapy in rectal cancer: A systematic review and meta-analysis.

Purpose: The purpose of this study was to evaluate the diagnostic accuracy of artificial intelligence (AI) models with magnetic resonance imaging(MRI) in predicting pathological complete response(pCR) to neoadjuvant chemoradiotherapy (nCRT) in patients with rectal cancer. Furthermore, assessed the methodological quality of the models. Methods: We searched PubMed, Embase, Cochrane Library, and Web of science for studies published before 21 June 2022, without any language restrictions. The Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) and Radiomics Quality Score (RQS) tools were used to assess the methodological quality of the included studies. We calculated pooled sensitivity and specificity using random-effects models, I2 values were used to measure heterogeneity, and subgroup analyses to explore potential sources of heterogeneity. Results: We selected 21 papers for inclusion in the meta-analysis from 1562 retrieved publications, with a total of 1873 people in the validation groups. The meta-analysis showed that AI models based on MRI predicted pCR to nCRT in patients with rectal cancer: a pooled area under the curve (AUC) 0.91 (95% CI, 0.88-0.93), sensitivity of 0.82(95% CI,0.71-0.90), pooled specificity 0.86(95% CI,0.80-0.91). In the subgroup analysis, the pooled AUC of the deep learning(DL) model was 0.97, the pooled AUC of the radiomics model was 0.85; the pooled AUC of the combined model with clinical factors was 0.92, and the pooled AUC of the radiomics model alone was 0.87. The mean RQS score of the included studies was 10.95, accounting for 30.4% of the total score. Conclusions: Radiomics is a promising noninvasive method with high value in predicting pathological response to nCRT in patients with rectal cancer. DL models have higher predictive accuracy than radiomics models, and combined models incorporating clinical factors have higher diagnostic accuracy than radiomics models alone. In the future, prospective, large-scale, multicenter investigations using radiomics approaches will strengthen the diagnostic power of pCR. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021285630.

A multi­omics study of diagnostic markers and the unique inflammatory tumor micro­environment involved in tuberous sclerosis complex­related renal angiomyolipoma.

Tuberous sclerosis complex (TSC) is a rare disease that threatens multiple organs in the human body. TSC­associated renal angiomyolipoma (TSC­RAML) has potentially life­threatening complications and a generally poor prognosis. The present study aimed to find plasma proteomic diagnostics and disease­associated markers, and explore the tumor microenvironment using multi­omics. To achieve this goal, the plasma proteomics as well as tissue proteomics, bulk and single­cell RNA transcriptome from patients with TSC­RAML were examined and analyzed. The results suggested that plasma proteins such as MMP9 and C­C motif chemokine ligand 5 were able to differentiate TSC­RAML from sporadic angiomyolipoma and renal cyst. A correlation analysis revealed that plasma proteomics were associated with lymphangioleiomyomatosis, TSC­RAML grading and whole­body disease burden. Tissue proteomics of participants with TSC­RAML revealed disturbed small molecule catabolic process, mitochondrial matrix component and actin binding function. Bulk and single­cell RNA sequencing suggested a greater number of tumor­like cells, fibroblasts and mononuclear macrophages within the tumor microenvironment. The above results indicated that TSC­RAML exhibited a characteristic and disease­associated plasma proteomic profile. The unique microenvironment, made up of fibroblasts and mono­macrophages, may promote tumorigenesis and TSC­RAML progression.

A Comprehensive 2D-LC/MS/MS Profile of the Normal Human Urinary Metabolome.

Profiling bodily fluids is crucial for monitoring and discovering metabolic markers of disease. In this study, a comprehensive analysis approach based on 1D-LC-MS/MS and 2D-LC-MS/MS was applied to profile normal human urine metabolites from 348 children and 315 adults. A total of 2357 metabolites were identified, including 1831 endogenous metabolites and 526 exogenous ones. In total, 1005 metabolites were identified in urine for the first time. The urinary metabolites were mainly involved in amino acid metabolism, small molecule biochemistry, lipid metabolism and cellular compromise. The comparison of adult's and children's urine metabolomes showed adults urine had more metabolites involved in immune response than children's, but the function of binding of melatonin, which belongs to the endocrine system, showed a higher expression in children. The urine metabolites detected by the 1D-LC-MS/MS method were mainly related to amino acid metabolism and lipid metabolism, and the 2D-LC-MS/MS method not only explored metabolites from 1D-LC-MS/MS but also metabolites related to cell signaling, cell function and maintenance, etc. Our analysis comprehensively profiled and functionally annotated the metabolome of normal human urine, which would benefit the application of urinary metabolome to clinical research.