Trps1 predicts poor prognosis in advanced high grade serous ovarian carcinoma.

TRPS1 is aberrantly expressed in a variety of tumors, including breast, prostate, and gastric cancers, and is strongly associated with tumorigenesis or prognosis. However, the role of TRPS1 in high grade serous ovarian carcinoma (HGSC) is unknown. We investigated the relationship between TRPS1 expression and clinicopathology in HGSC patients. The tumor-related regulatory mechanisms of TRPS1 was explored through in vivo and vitro experiments. The results showed that TRPS1 was highly expressed in HGSC compared to normal tissues. It was also linked to the cell proliferation index Ki67 and poor prognosis. In vivo experiments showed that knockdown of TRPS1 could inhibit tumor growth. In vitro experiments, knockdown of TRPS1 inhibited the proliferation of ovarian cancer cells. TRPS1 exerted its regulatory role as a transcription factor, binding to the PSAT1 promoter and promoting the expression of PSAT1 gene. Meanwhile, PSAT1 was positively correlated with CCND1 expression. These results suggest that TRPS1 affects HGSC proliferation and cell cycle by regulating PSAT1 and thus CCND1 expression.

Season of delivery and risk of venous thromboembolism during hospitalization among pregnant women.

Background: Seasons were found to be related to the occurrences of venous thromboembolism (VTE) in hospitalized patients. No previous study has explored whether seasons were associated with VTE risk in pregnant women. This study aimed to investigate the relationships between the season of delivery and VTE risk during hospitalization among pregnant women. Methods: This is a multi-center retrospective cohort study of pregnant women. Participants were those who delivered at seven designated sites in Hubei Province, China, during the period from January 2017 to December 2022. They were categorized according to their season/month of delivery. Information on new-onset VTE during hospitalization was followed. Results: Approximately 0.28% (104/37,778) of the pregnant women developed new-onset VTE during hospitalization for delivery. After adjustment, compared with participants in the spring group, participants in the summer, autumn, and winter groups had an increased risk of VTE during hospitalization. The ORs were 2.59 [1.30, 5.15], 2.83 [1.43, 5.60], and 2.35 [1.17, 4.75] for the summer, autumn, and winter groups, respectively. Pregnant women in the combined group (summer + autumn + winter) had an increased risk of VTE during hospitalization than those in the spring group (OR, 2.59 [1.39, 4.85]). By restricting the analyses among pregnant women without in vitro fertilization, gestational diabetes mellitus, and preterm, the results still remained robust. Compared with participants who delivered in March, April, and May, participants who delivered in June, July, September, November, December, and February had a higher risk of VTE during hospitalization. Conclusion: This study demonstrated that pregnant women who delivered in summer, autumn, and winter had an increased VTE risk during hospitalization compared with those who delivered in spring.

Structural Characterization and Anticomplement Activity of an Acidic Heteropolysaccharide from Lysimachia christinae Hance.

A novel acidic heteropolysaccharide (LCP-90-1) was isolated and purified from a traditional "heat-clearing" Chinese medicine, Lysimachia christinae Hance. LCP-90-1 (Mw, 20.65 kDa) was composed of Man, Rha, GlcA, Glc, Gal, and Ara, with relative molar ratios of 1.00: 3.00: 11.62: 1.31: 1.64: 5.24. The backbone consisted of 1,4-α-D-GlcpA, 1,4-α-D-Glcp, 1,4-ß-L-Rhap, and 1,3,5-α-L-Araf, with three branches of ß-D-Galp-(1 → 4)-ß-L-Rhap-(1→, α-L-Araf-(1→ and α-D-Manp-(1→ attached to the C-5 position of 1,3,5-α-L-Araf. LCP-90-1 exhibited potent anticomplement activity (CH50: 135.01 ± 0.68 µg/mL) in vitro, which was significantly enhanced with increased glucuronic acid (GlcA) content in its degradation production (LCP-90-1-A, CH50: 28.26 ± 0.39 µg/mL). However, both LCP-90-1 and LCP90-1-A were inactivated after reduction or complete acid hydrolysis. These observations indicated the important role of GlcA in LCP-90-1 and associated derivatives with respect to anticomplement activity. Similarly, compared with LCP-90-1, the antioxidant activity of LCP-90-1-A was also enhanced. Thus, polysaccharides with a high content of GlcA might be important and effective substances of L. christinae.

The miR-124-3p regulates the allergic airway inflammation and remodeling in an ovalbumin-asthmatic mouse model by inhibiting S100A4.

OBJECTIVE: Asthma is a chronic respiratory disease with an increasing incidence every year. microRNAs (miRNAs) have been demonstrated to have implications for asthma. However, limited information is available regarding the effect of miR-124-3p on this disease. Therefore, this study aimed to explore the possible effects of miR-124-3p and S100A4 on inflammation and epithelial-mesenchymal transition (EMT) in asthma using mouse models. METHOD: Ovalbumin was used to induce asthmatic mouse models. Lung injury in mouse models was assessed, and the bronchoalveolar lavage fluid of mice was collected to determine the number of eosinophilic granulocytes and assess inflammation. The expression levels of miR-124-3p, S100A4, E-cadherin, N-cadherin, Snail1, vimentin, and TGF-ß1/Smad2 signaling pathway-related proteins were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. In vitro experiments, cells were transfected with miR-124-3p mimics or inhibitors to test the expression of S100A4 by RT-qPCR and western blot analysis, and the mutual binding of miR-124-3p and S100A4 was validated by dual-luciferase reporter gene assay. RESULTS: Overexpression of miR-124-3p or inhibition of S100A4 expression attenuated bronchial mucus secretion and collagenous fibers and suppressed inflammatory cell infiltration. Additionally, upon miR-124-3p overexpression or S100A4 suppression, eosinophilic granulocytes were decreased, interleukin-4 (IL-4) and IL-13 expression levels were reduced in the bronchoalveolar lavage fluid, serum total IgE level was reduced, and the TGF-ß1/Smad2 signaling pathway was suppressed. Mechanically, a dual-luciferase reporter gene assay verified the binding relationship between miR-124-3p and S100A4. CONCLUSION: miR-124-3p can negatively target S100A4 to attenuate inflammation in asthmatic mouse models by suppressing the EMT process and the TGF-ß/smad2 signaling pathway.

Exploring the anticomplement components from Fagopyrum dibotrys for the treatment of H1N1-induced acute lung injury by UPLC-Triple-TOF-MS/MS.

In the present study, a procyanidins-enriched fraction (PCE) from the rhizome of Fagopyrum dibotrys was obtained by anticomplement activity-guided fractionation. PCE could alleviate H1N1-induced ALI in mice by reducing weight loss, decreasing lung index, and regulating cytokine levels in lung tissue. PCE contained 76.5 ± 1.1% procyanidins with a mean degree of polymerization (mDP) of 5.24 ± 0.16. Meanwhile, thirty-three chemical constituents, including 27 procyanidins and 6 other compounds, were recognized by UPLC-Triple-TOF-MS/MS. Among them, twenty recognized procyanidins were composed of (epi)catechin with B-type link, while the rest consisted of (epi)catechin gallate. Furthermore, six compounds were obtained by preparative HPLC on a C18 column (250 × 10.0 mm, 5 µm), and their structures were confirmed by mass spectrum (MS), nuclear magnetic resonance (NMR), and specific rotation. The structure-activity relationship analysis indicated that DP and galloylation were closely related to the anticomplement activity of procyanidins. The obtained results revealed that anticomplement procyanidins were one kind of the potentially effective materials of F. dibotrys against H1N1 influenza virus infection, and the in vivo efficacy of these compounds was worthy of further investigation.

First report of Fusarium oxysporum causing stem spots on Polygonatum odoratum in China.

Polygonatum odoratum (Mill.) Druce is a perennial herb in the Liliaceae family and it is one of the traditional Chinese medicinal plants. Modern pharmaceutical studies demonstrate that P. odoratum contains polysaccharides, saponins, alkaloids, flavonoids, volatile oil, and other active components (Jiang-Nan, et al., 2018). From May to June 2022, the stem spot disease was discovered on P. odoratum in the planting demonstration garden in Changsha (28°20N; 113°07E), Hunan province of China. The disease seriously retarded plant growth and was estimated to have affected approximately 40-50% of the plants, significant economic losses to growers. Plants had oval tan spots on the stems, which were light in the center and dark at the margin. The spots in the back expanded and joined together, where the disease was severe, and chlorosis was near the stem spot, while many leaves turned completely yellow and withered before falling to the ground. Finally, the whole plant faded to light green and dried up. In order to isolate pathogens, symptomatic stem samples (5×5 mm) were collected from the edges of the lesions and excised symptomatic tissues consisting of diseased and healthy parts were surface-sterilized with 2% solution of sodium hypochlorite (0.1% active ingredient of chlorine) for 1 min and 75% ethanol for 30 s. The samples were then washed thrice with sterile distilled water, air-dried on the sterile filter papers under aseptic conditions, and finally plated onto Potato Dextrose Agar (PDA) plates, which were incubated at 25 °C for 24 h to 36 h in the dark. Additionally, the emerging fungal hyphal tips were transferred to PDA and purified by the single-spore method. Next, forty plants with stem spots were isolated, and 8 cultures with the same appearance were obtained. Two strains coded hnxryzj and hnxryzj1 were randomly selected, for identification. With a mean radial growth rate of 7.5 mm/day, white and dense colonies were observed after 6 days of culture on PDA. After hnxryzj was cultured on SNA, microconidia were oval or ovate (9.25-14.8µm × 2.18-3.76µm), macroconidia were sickle-shaped and slightly curved, with 2-5 septa (21.52-23.49µm × 2.64-4.51µm (n = 50)). These morphological characteristics were consistent with the description of Fusarium oxysporum (Mirghasempour, et al., 2022) Furthermore, we amplified the partial region of the internal transcribed spacer (ITS) region, the translation elongation factors EF-1α, ß-tubulin, polymerase II largest subunit (RPB1) and RNA polymerase II second largest subunit (RPB2) genes from strain hnxryzj and hnxryzj1, based on the primer pairs ITS1/ITS4, EF728F/EF986R, Bt2a/Bt2b, RPB1-F5/RPB1-R8 and fRPB2-5F2/fRPB2-7cR (Li, et al., 2013, Xie, et al., 2022), and amplicons were sequenced by Tsingke Biotechnology Co. Ltd. By sequence alignment, the ITS, EF-1α, ß-tubulin , RPB1 and RPB2 of hnxryzj and hnxryzj1 were identical, respectively. The sequence alignment of hnxryzj and hnxryzj1 with the Fusarium ID database and NCBI shows the following results: the ITS region, EF-1α, RPB1 and RPB2 sequences of the strain hnxryzj (GenBank accession nos. ON872218, ON897740, OP467556 and OP467557) and hnxryzj1 (GenBank accession nos. OP071248, OP087208, OP467558 and OP467559) were 100% identical to those of F. oxysporum (GenBank accession nos. MZ890536, LC469784 , MT179509 and MW368380, respectively); whereas the ß-tubulin sequences of the strain hnxryzj (GenBank accession nos. ON897741) and hnxryzj1 (GenBank accession nos. OP087207) were 96.9% identical to those of F.oxysporum (CBS144135 GenBank accession nos. MH485136). Subsequently, a phylogenetic tree was established combining EF-1α, RPB1, and RPB2. Strains hnxryzj and hnxryzj1 were F.oxysporum (JW257006 GenBank accession nos. MZ921883, MZ921657 and MZ921752)(Torres-Cruz, et al., 2022), with bootstrap values 100%. The pathogenicity test was carried out by placing mycelial discs obtained from colonies that had been actively growing on PDA for 6 days. In the pathogenicity test, two sets (5 plants in each set) of potted plants, whose stems were wounded, were taken. In one set (5 plants), the PDA cakes with F. oxysporum (d=5mm, the same below) were inoculated on the stems scratched by an inoculation needle (sterilized) (the front of the colony was close to the wound of the stem). In the other set (5 plants), potted plants inoculated with the sterile PDA cakes were served as controls. In a 25 °C greenhouse, each treatment was given a 12h/12h light/dark cycl(Nabi, et al., 2019). The symptoms were observed, and the fungus cake was removed 5 days after inoculation. Then, after 18 days, typical symptoms of oval tan spots similar to original diseased plants in the field were found on the inoculated stems, and 32 days later, the inoculated plant died, while the control stems remained asymptomatic. In addition, F. oxysporum was isolated and identified from the inoculated, symptomatic stems, verifying Koch's postulates. Based on our knowledge, this is the first report of F. oxysporum causing stem spots on P. odoratum in China. Only one other study from China that root rot of Phyllostachys officinalis also resulted from F. oxysporum (Pang, et al., 2022). Furthermore, P. odoratum is an medicinal material in Hunan province. Therefore, comprehensive prevention and control methods are required.

Sculpting Electrochemically Growing or Grown Microarchitectures.

Microarchitectures with complex interior structures are important for many applications. However, engineering complex interior structures within microarchitectures are challenging. This article reports the introduction of electrochemical sculpting processes to carve the microarchitectures during or after their electrochemical growing process to design the interior structure of the microarchitectures. The electrochemical growing and sculpting process tangle together under the constant voltage electrodeposition mode with their strength depending on the ion concentration gradient and the voltage value. The unique thawing process of the frozen electrolyte is used to create the desired sharp ion concentration gradient, and has the potential to control the strength of the sculpting and the growing processes. How to completely decouple the growing and the sculpting process is further studied to gain more accurate control over the interior structures of the microarchitectures. It is revealed that the sculpting process can be exclusively applied onto the electrochemically grown microarchitectures simply by reversing the electric field without triggering any growing processes. Microarchitectures with complex interior structures, including micropyramids with a single cavity exclusively at the outward or every apex to multi-walled hollow pyramids with designable wall numbers and inter-wall distances are prepared as examples.

Characterization of ectomycorrhizal fungal communities associated with tree species on an iron tailings deposit undergoing restoration.

Vegetation restoration is an effective method to improve the ecological environment of mine tailings, which has a profound impact on the potential ecological functions of soil fungal communities; yet, little is known about its beneficial effect on soil ectomycorrhizal fungal community. In this study, the responses of soil characteristics and soil ectomycorrhizal fungal community diversity and structure to different revegetation, as well as the contribution of soil factors to soil ectomycorrhizal community were investigated in Liaoning Province, China. As we anticipated, the presence of vegetation significantly improved most soil properties we studied. What's more, compared to Korean pine (Pinus koraiensis Sieb. et Zucc.), Chinese poplar (Populus simonii Carr), and black locust (Robinia pseudoacacia L) could better improve soil total carbon, total nitrogen, total phosphorus, and available phosphorus. In addition, soil ectomycorrhizal fungal community diversity in black locust was greater than Korean pine and Populus simonii. Nonmetric multidimensional scaling analyses indicated that soil ectomycorrhizal community significantly differed depending on different revegetation types. Thus, these results indicated that black locust could be a suitable species for the revegetation of iron mine tailings. The study provided theoretical basis for ecological restoration of iron mine tailings using local plant species.

Apelin is associated with clinicopathological parameters and prognosis in breast cancer patients.

PURPOSE: Apelin has been shown to be a novel angiogenic factor in various cancers. However, there is limited information regarding the role of apelin in breast cancer. The aim of the present study is to examine associations between apelin, clinicopathological variables, and clinical outcome in breast cancer patients. METHODS: In this study, we began by investigating the apelin expression in breast cancer with long-term follow-up using immunohistochemistry. We then analyzed the relationship between apelin expression and microvessel density (MVD), lymphatic vessel density (LVD), lymph node status as well as other established clinicopathological parameters. The relationship between apelin expression and prognosis was also studied. In addition, we compared the apelin and its ligant APJ expression between 30 breast cancer samples and normal breast tissues adjacent to the breast tumors using western blot (WB) and RT-PCR. RESULTS: Apelin protein expression was detected in the cytoplasm of the breast carcinoma cells at various intensities. Apelin expression was positive in 59.2% (84/142) of the breast cancer patients and apelin expression was significantly correlated with tumor size (p = 0.030), stage (p = 0.000), histological type (p = 0.009), MVD (p = 0.000), LVD (p = 0.000), and lymph node metastasis (p = 0.041). Survival curves determined by the Kaplan-Meier method and univariate analysis demonstrated that high expression of apelin was associated with both worse disease-free survival (p < 0.001) and overall survival (p < 0.001). Interestingly, a significant difference in apelin and APJ expression by WB as well as RT-PCR was observed between normal breast tissues adjacent to the breast tumors and breast cancer tissues. CONCLUSIONS: Our results showed apelin expression was associated with tumor size, stage, histological type, MVD, LVD, lymph node metastasis and poor prognosis. The presence of apelin may be a new prognostic factor and potential therapeutic target for breast cancer.

Study on the differences of phyllosphere microorganisms between poplar hybrid offspring and their parents.

The females and males of dioecious plants have evolved sex-specific characteristics in terms of their morphological and physiological properties. However, the differentiation of phyllosphere microorganism of dioecious plants between parents and hybrid offspring remain largely unexplored. Here, the phyllosphere bacterial and fungal community diversity and composition of female (Populus nigra 'DH5' (PNDH5)), male (P. simonii 'DH4' (PSDH4)), and the hybrid offspring (P. simonii × P. nigra 'DH1' (PSPNDH1), P. simonii × P. nigra 'DH2' (PSPNDH2), P. simonii × P. nigra 'DH3' (PSPNDH3)) were investigated using 16S rDNA/ITS rDNA gene-based Illumina NovaSeq 6000 sequencing. There was considerable variation of plant height, diameter at breast height, leaf area, length of petioles, leaf moisture content, and starch among different samples, and PSDH2 owned the highest plant height, diameter at breast height, and length of petioles. No distinct differences of phyllosphere bacterial community diversity were observed among PSDH4, PNDH5, PSPNDH1, PSPNDH2, and PSPNDH3; while, PSPNDH2 owned the highest fungal Pielou_e index, Shannon index, and Simpson index. Firmicutes and Ascomycota were the predominant phyllosphere bacterial and fungal community at the phylum level, respectively. Bacilli and Gammaproteobacteria were the two most dominant bacterial classes regardless of parent and the hybrid offspring. The predominant phyllosphere fungal community was Dothideomycetes at the class level. The NMDS demonstrated that phyllosphere microbial community obviously differed between parents and offspring, while the phyllosphere microbial community presented some similarities under different hybrid progeny. Also, leaf characteristics contributed to the differentiation of phyllosphere bacterial and fungal communities between parents and hybrid offspring. These results highlighted the discrimination of phyllosphere microorganisms on parent and hybrid offspring, which provided clues to potential host-related species in the phyllosphere environment.

New Phenolic Glycosides and Lignans from the Roots of Lilium dauricum.

Three new phenolic glycosides, carvacrol-2-O-ß-D-apiofuranosyl-(1 → 6)-ß-D-glucopyranoside (1: ), 1-methyl-3-isopropylphenol-4-O-ß-D-apiofuranosyl-(1 → 6)-ß-D-glucopyranoside (2: ), p-methoxythymol-5-O-ß-D-apiofuranosyl-(1 → 6)-ß-D-glucopyranoside (3: ), and a pair of new 8-O-4' neolignan enantiomers (5A: /5B: ), together with 26 known compounds (4, 6:  - 30: ) were isolated from the roots of Lilium dauricum. The structures of the new compounds were elucidated based on extensive spectroscopic and chemical methods, and the absolute configurations of 5A: and 5B: were established by electronic circular dichroism analysis. Nine compounds (1, 3, 4, 8, 9, 17, 25, 29,: and 30: ) exhibited potent α-glucosidase inhibitory activity with IC50 values ranging from 73.4 µM to 988.2 µM. Besides, compound 19: displayed strong anticomplementary activity (CH50: 71.6 µM).

Interlocking detachable coil embolization for giant tandem bronchial aneurysms: A case report.

RATIONALE: Bronchial artery aneurysm (BAA) is a rare disease that can be life-threatening if it ruptures. Tandem connections of multiple aneurysms are even rarer and more challenging to manage. PATIENT CONCERNS: A 46-year-old woman presented to the hospital with intermittent hemoptysis for a week. A bronchial artery computed tomographic angiography scan revealed 2 BAAs associated with bronchial artery-to-pulmonary artery fistulas in the left lung. Three-dimensional CT reconstruction showed 2 bronchial aneurysms in tandem and 1 aneurysm adjacent to the descending aorta. DIAGNOSES: Giant tandem bronchial aneurysms were confirmed using computerized tomographic angiography. INTERVENTIONS: Nine interlocking detachable coils and 11 standard pushable coils were introduced into aneurysms for embolization. OUTCOMES: There was no episodes of hemoptysis. CT angiography indicated that the coils were closely knit and in their proper position 1 month later; at follow-up, the patient had no adverse effects and no recurrence of hemoptysis. LESSONS: BAA is a rare disease that can be life-threatening if it ruptures. It should be treated aggressively to determine the presence of symptoms.

Correlation of transrenal DNA with non-small-cell lung cancer in noninvasive disease monitoring.

Background: The study aims to use noninvasive transrenal DNA in advanced non-small-cell lung cancer (NSCLC) patients for treatment monitoring and prognosis. Methods: Urine specimens were collected longitudinally for 103 late-stage NSCLC patients. Detection of targetable mutations in transrenal DNA was achieved by digital droplet PCR. Patients' overall survival outcomes were correlated with levels of transrenal DNA. Results: Corresponding patients' matched tumor results demonstrated concordance rate of 95.6% with transrenal DNA. A significant decline in levels was observed after treatment initiation. We observed changes in transrenal DNA levels to be significantly associated with survival for patients (p < 0.0001). Conclusion: Our results demonstrated strong predictive values of transrenal DNA to better identify patients with poorer survival outcomes and may further complement disease management.

Primary hepatic neuroendocrine tumor - 18F-fluorodeoxyglucose positron emission tomography/computed tomography findings: A case report.

BACKGROUND: Primary hepatic neuroendocrine tumors (PHNETs) are rare hepatic tumors. Their diagnosis, which is based on radiological findings, is difficult. CASE SUMMARY: We present a case of PHNET in a 79-year-old man with no clinical symptoms. Computed tomography (CT) and 2-Deoxy-2-[fluorine-18] fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT) were performed for further evaluation. A hypoattenuating mass with rim-like enhancement in segment 6 of the liver was detected on contrast-enhanced CT imaging. Increased uptake was also observed on 18F-FDG PET/CT. Histopathological and immunohistochemical examinations, which revealed a grade 2 neuroendocrine tumor (NET), confirmed the diagnosis. CONCLUSION: Diagnosing PHNET is challenging, and must be distinguished from other liver tumors. Metastatic NETs should be excluded.

The combination of contrast-enhanced ultrasonography with blue dye for sentinel lymph node detection in clinically negative node breast cancer.

PURPOSE: The aim of this prospective study was to evaluate the value of the combination of contrast-enhanced ultrasonography (CEUS) and blue dye (BD) for SLN detection in patients with clinically negative node breast cancer. METHODS: Patients with clinically negative node breast cancer were randomized into two cohorts for SLN biopsy (SLNB): the combination method cohort using CEUS and BD together, and the single BD method cohort. Standard axillary lymph node dissection was performed if any of the SLNs confirmed positive by pathology. The identification rate, the number of SLNs removed and recurrence-free survival (RFS) rates were evaluated between two cohorts. In addition, we assessed the sensitivity, specificity, accuracy, false-negative rate of CEUS for diagnosis of SLNs based on patterns of CEUS enhancement. RESULTS: 144 consecutive patients with clinically negative node breast cancer were randomized into two cohorts. Each cohort consisted of 72 cases. In the combination method cohort, contrast-enhanced lymphatic vessels were clearly visualized and SLNs were accurately localized in 72 cases. The identification rate and the mean number of SLNs detected by the combination method were 100% (72/72) and 3.26 (1-9), respectively. In contrast, in the single BD method cohort, SLNs in 69 cases were successfully identified. The identification rate and the mean number of SLNs using BD alone were 95.8% (69/72) and 2.21 (1-4), respectively. According to patterns of CEUS enhancement, the sensitivity, specificity, accuracy, and the FNR of CEUS for SLN diagnosis were 69.2%, 96.6%, 91.7%, and 30.8%, respectively. After a median follow-up of 50 months for the combination method cohort and 51 months for the blue dye alone cohort, five patients in the combination method cohort and nine in the blue dye alone cohort had recurrence. RFS rates showed no significant difference (P = 0.26) between two cohorts. CONCLUSION: The combination of CEUS and BD is more effective than BD alone for SLNB in clinically negative node patients with an identification rate as high as 100%. Use of BD and CEUS in combination may provide the possibility of a non-radioactive alternative method for SLNB in centers without access to radioisotope.

The Ribosomal Protein L28 Gene Induces Sorafenib Resistance in Hepatocellular Carcinoma.

BACKGROUND: Sorafenib is the first molecular-targeted drug for the treatment of advanced hepatocellular carcinoma (HCC). However, its treatment efficiency decreases after a short period of time because of the development of drug resistance. This study investigates the role of key genes in regulating sorafenib-resistance and elucidates the mechanism of drug resistance in hepatocellular carcinoma. METHODS: The HCC HepG2 cells were used to generate a sorafenib-resistant cell model by culturing the cells in gradually increasing concentration of sorafenib. RNA microarray was applied to profile gene expression and screen key genes associated with sorafenib resistance. Specific targets were knockdown in sorafenib-resistant HepG2 cells for functional studies. The HCC model was established in ACI rats using Morris hepatoma3924A cells to validate selected genes associated with sorafenib resistance in vivo. RESULTS: The HepG2 sorafenib-resistant cell model was successfully established. The IC50 of sorafenib was 9.988µM in HepG2 sorafenib-resistant cells. A total of 35 up-regulated genes were detected by expression profile chip. High-content screening technology was used and a potential drug-resistance related gene RPL28 was filtered out. After knocking down RPL28 in HepG2 sorafenib-resistant cells, the results of cell proliferation and apoptosis illustrated that RPL28 is the key gene involving in drug resistance. Furthermore, it was found that both RNA and protein expression of RPL28 increased in HepG2 sorafenib-resistant specimens of Morris Hepatoma rats. In addition, the expression of proliferative protein Ki-67 increased in sorafenib-resistant cells. CONCLUSION: Our study suggested that RPL28 is a key gene inducing sorafenib resistance in HCC and could be a potential target for the treatment of drug-resistant HCC.

Diffusion capacity abnormalities for carbon monoxide in patients with COVID-19 at 3-month follow-up.

OBJECTIVE: To evaluate pulmonary function and clinical symptoms in coronavirus disease 2019 (COVID-19) survivors within 3 months after hospital discharge, and to identify risk factors associated with impaired lung function. METHODS AND MATERIAL: COVID-19 patients were prospectively followed-up with pulmonary function tests and clinical characteristics for 3 months following discharge from a hospital in Wuhan, China between January and February 2020. RESULTS: 647 patients were included. 87 (13%) patients presented with weakness, 63 (10%) with palpitations and 56 (9%) with dyspnoea. The prevalence of each of the three symptoms were markedly higher in severe patients than nonsevere patients (19% versus 10% for weakness, p=0.003; 14% versus 7% for palpitations, p=0.007; 12% versus 7% for dyspnoea, p=0.014). Results of multivariable regression showed increased odds of ongoing symptoms among severe patients (OR 1.7, 95% CI 1.1-2.6; p=0.026) or patients with longer hospital stays (OR 1.03, 95% CI 1.00-1.05; p=0.041). Pulmonary function test results were available for 81 patients, including 41 nonsevere and 40 severe patients. In this subgroup, 44 (54%) patients manifested abnormal diffusing capacity of the lung for carbon monoxide (D LCO) (68% severe versus 42% nonsevere patients, p=0.019). Chest computed tomography (CT) total severity score >10.5 (OR 10.4, 95% CI 2.5-44.1; p=0.001) on admission and acute respiratory distress syndrome (ARDS) (OR 4.6, 95% CI 1.4-15.5; p=0.014) were significantly associated with impaired D LCO. Pulmonary interstitial damage may be associated with abnormal D LCO. CONCLUSION: Pulmonary function, particularly D LCO, declined in COVID-19 survivors. This decrease was associated with total severity score of chest CT >10.5 and ARDS occurrence. Pulmonary interstitial damage might contribute to the imparied D LCO.

Additive Manufacturing for Automotive Applications: Mechanical and Weathering Durability of Vat Photopolymerization Materials.

In this study, the effect of the post-curing process as well as the long-term weathering behavior were studied for three different three-dimensional printable, pigmented (black), nonstabilized, ultraviolet (UV) cure resin formulations (A and B being thiol-ene chemistry, and C being acrylate chemistry). To study the effect of the post-cure process, the printed parts were post-cured using one of five different processes: no post-cure, UV-only, heat-only, UV+heat, and electron beam (EB) post-curing. Bulk tensile properties and nanohardness were measured for each of the systems and post-cure conditions. For weathering studies, the parts were post-cured using the recommended UV-only process and exposed using the ASTM D7869 exterior weathering protocol. The results show that the post-cure process had a significant effect on the final mechanical properties of the resins and was dependent on the underlying resin chemistry. Thermal post-curing was not as effective as UV curing for Resin C compared with the two other resins, which could both undergo thermal polymerization. In addition, Resin B showed the smallest change in mechanical properties before and after post-curing, regardless of the type of post-curing process. EB post-curing, even at very low dosages, that is, from 0.05 to 1 Mrad, resulted in considerable post-cure cross-linking to the point of embrittlement and a significant drop in percent elongation at break for dosages above 0.5 Mrad. Although Resins A and C outperformed Resin B in photooxidation performance, all three resins demonstrated that promising results considering no hindered amine light stabilizers were used in the formulations.

Reshaping the Cathodic Catalyst Layer for Anion Exchange Membrane Fuel Cells: From Heterogeneous Catalysis to Homogeneous Catalysis.

In anion exchange membrane fuel cells, catalytic reactions occur at a well-defined three-phase interface, wherein conventional heterogeneous catalyst layer structures exacerbate problems, such as low catalyst utilization and limited mass transfer. We developed a structural engineering strategy to immobilize a molecular catalyst tetrakis(4-methoxyphenyl)porphyrin cobalt(II) (TMPPCo) on the side chains of an ionomer (polyfluorene, PF) to obtain a composite material (PF-TMPPCo), thereby achieving a homogeneous catalysis environment inside ion-flow channels, with greatly improved mass transfer and turnover frequency as a result of 100 % utilization of the catalyst molecules. The unique structure of the homogeneous catalysis system comprising interconnected nanoreactors exhibits advantages of low overpotential and high fuel-cell power density. This strategy of reshaping of the catalyst layer structure may serve as a new platform for applications of many molecular catalysts in fuel cells.