Impact of H2O on the Microscopic Oxidation Mechanism of Lollingite: Experimental and Theoretical Analyses.

Lollingite (FeAs2) is considered an arsenic-bearing mineral that is oxidized faster than arsenopyrite. The geometric configuration, chemical valence bond, and microscopic reaction of the oxidation on the surface of lollingite were systematically studied, which are of great significance for understanding the mechanism of oxidative dissolution. X-ray photoelectron spectroscopy (XPS) measurements and density functional theory (DFT) calculations were carried out to characterize the (101) surface oxidation process of lollingite under the O2/O2 + H2O conditions. XPS results confirmed that the participation of water molecules can promote the formation of abundant OH structures on the surface of lollingite, while the relative concentration of O, As(III), and Fe(III) increased. Moreover, the DFT results demonstrated that the (101) As-terminal plane of FeAs2 was the most stable surface with the lowest surface energy. H2O molecules were physically adsorbed onto the Fe atoms of the lollingite surface, while oxygen molecules can readily be adsorbed on the Fe-As2 site by chemical adsorption processes. The oxidation process of the lollingite surface with water includes the following mechanisms: adsorption, dissociation, formation of the hydrogen bond, and desorption. The dissociation of the H2O molecule into OH and H led to the hydroxylation of both Fe and As atoms and the formation of hydrogen bonding. The participation of H2O molecules can also reduce the reaction energy barrier and accelerate the oxidation reaction of the lollingite surface, especially as far as the water dissociation and formation of hydrogen bonds are concerned. According to PDOS data, there is considerable hybridization between the d orbitals of bonded Fe atoms and the p orbitals of O atoms, as well as between the p orbitals of bonded As atoms and the p orbitals of O atoms. Due to a strong propensity for orbital hybridization and bonding between the s orbitals of the H atoms in H2O molecules and the p orbitals of the O atoms on the (101) surface, water molecules have the ability to speed up the oxidation on the surface.

Endovascular Treatment of Ruptured or Symptomatic Thoracoabdominal and Pararenal Aortic Aneurysms Using Octopus Endograft Technique: Mid-Term Clinical Outcomes.

OBJECTIVE: To evaluate the effectiveness and safety of using off-the-shelf "Octopus" technique to treat ruptured or symptomatic thoracoabdominal aortic aneurysm (TAAA) and pararenal abdominal aortic aneurysm (PRAAA). METHODS AND RESULTS: All cases who underwent "Octopus" technique from May 2016 to May 2019 at our center were retrospectively analyzed. A total of 10 cases (8 males) were included. The mean age was 54.5±14.2 years (range: 31-80 years). Eight cases presented as aneurysm rupture or impending rupture accepted emergency repair. Technical success, defined by placement of all endografts as planned, was achieved in all cases. A total of 30 target visceral branches were successfully cannulated, 9 celiac arteries were covered intentionally. Intraoperative endoleak was observed in 6 patients, all of them were gutter leak. During hospital stay, there was no death, no side branch occlusion or spinal cord ischemia. Median follow-up was 30 months (range: 12-50 months). One patient died of lung cancer at 14-month follow-up. There was no secondary endoleak. The primary endoleak were found spontaneously resolved in 3 cases at 7 days, 3-month, and 1-year imaging. One persistent endoleak totally resolved after sealing of gutter spaces at 4-month follow-up. The other 2 persistent endoleak decreased during follow-up, which are still under observation. The branch patency rate was 90.3% (28/31). All the 3 occluded branches were renal arteries. Branch occlusion occurred in 2 cases at 1-month follow-up and 1 case at 2-year follow-up, but renal insufficiency was not observed in these cases. Obvious aneurysm sac shrinkage (≥5 mm) was observed in all cases. The aneurysm size shrunk from 7.6±1.9 to 5.5±1.4 cm. No spinal cord ischemia occurred during follow-up. CONCLUSION: Treatment of ruptured TAAA and PRAAA with "Octopus" technique is feasible and safe for high surgical risk patients in the absence of fenestrated and branched devices. The long-term clinical outcomes needed to be investigated.

Simultaneous stabilization/solidification of arsenic in acidic wastewater and tin mine tailings with synthetic multiple solid waste base geopolymer.

Stabilization/Solidification (S/S) is considered as a feasible technology for the treatment of arsenic (As) in acidic wastewater (AW) and tin mine tailings (TMTs); however, high cost, high carbon footprint, and strict reaction conditions are the main limitations. Herein, a novel alkali-activated geopolymer material (AAGM) for S/S As was synthesized by combining AW, TMT, gypsum (GP), and metakaolin (MK). At room temperature, an initial As concentration of 3914 mg/L, a NaOH content of 4.98%, and an MK content of 20% decreased the As leaching concentration to 1.55 mg/L (<5 mg/L). The main S/S mechanisms of As included physical encapsulation of C-(A)-S-H and geopolymer structures, ion exchange of ettringite, and formation of Fe-As and Ca-As precipitates. Further studies showed that increasing initial As concentration and MK content facilitated the formation of Ca-As precipitates and C-(A)-S-H gels. The semi-dynamic leaching tests revealed that the leaching mechanism of As was surface wash-off. The effective diffusion coefficients of the samples were less than 10-13 cm2/s, and the respective leachability indexes were greater than 9, indicating that AAGM was effective in preventing the leaching of As. Therefore, this study provides a green and low cost solution for the synergistic utilization of AW, TMT, GP, and MK.

Integrating Machine Learning and Tumor Immune Signature to Predict Oncologic Outcomes in Resected Biliary Tract Cancer.

BACKGROUND: Improved methods are needed to predict outcomes in biliary tract cancers (BTCs). We aimed to build an immune-related signature and establish holistic models using machine learning. METHODS: Samples were from 305 BTC patients treated with curative-intent resection, divided into derivation and validation cohorts in a two-to-one ratio. Spatial resolution of T cell infiltration and PD-1/PD-L1 expression was assessed by immunohistochemistry. An immune signature was constructed using classification and regression tree. Machine learning was applied to develop prediction models for disease-specific survival (DSS) and recurrence-free survival (RFS). RESULTS: The immune signature composed of CD3+, CD8+, and PD-1+ cell densities and PD-L1 expression within tumor epithelium significantly stratified patients into three clusters, with median DSS varying from 11.7 to 80.8 months and median RFS varying from 6.2 to 62.0 months. Gradient boosting machines (GBM) outperformed rival machine-learning algorithms and selected the same 11 covariates for DSS and RFS prediction: immune signature, tumor site, age, bilirubin, albumin, carcinoembryonic antigen, cancer antigen 19-9, tumor size, tumor differentiation, resection margin, and nodal metastasis. The clinical-immune GBM models accurately predicted DSS and RFS, with respective concordance index of 0.776-0.816 and 0.741-0.781. GBM models showed significantly improved performance compared with tumor-node-metastasis staging system. CONCLUSIONS: The immune signature promises to stratify prognosis and allocate treatment in resected BTC. The clinical-immune GBM models accurately predict recurrence and death from BTC following surgery.

Comparative Analysis of Patch Angioplasty Versus Selective Primary Closure during Carotid Endarterectomy Performed at a Single Vascular Center in China.

BACKGROUND: One of the ongoing debates about carotid endarterectomy (CEA) is the closure technique of arterial wall in the operation. Current guidelines recommend routine patch closure (PAC); this recommendation is based on the evidence reported 10-20 years ago. Therefore, the exact role of PAC and primary closure (PRC) remains uncertain. The objectives of this study were to compare the perioperative and long-term outcomes of patients who underwent CEA with different closure techniques. METHODS: From January 2013 and December 2018, one senior vascular surgeon performed CEA for 126 patients in the First Affiliated Hospital, Sun Yat-sen University. The closure technique (PAC or PRC) was determined on the characteristics (diameter and level) of carotid arteries. Patient demographics and clinical data were retrospectively collected by two research fellows by reviewing the hospital medical records and relevant radiologic studies, as were carotid duplex reports, indications, intraoperative data, closure technique, and perioperative complications. Data of long-term outcomes were gathered by reviewing outpatient clinic visits and associated supplementary examinations. RESULTS: PRC was performed in 78 operations (61.9%), and PAC was performed in 48 operations (38.1%). There were no statistical differences in demographic and clinical data between the two groups. Carotid clamp time (P < 0.001) and operating time (P < 0.001) were significantly longer when performing PAC (P < 0.001), and intraoperative blood loss was significantly more when performing PAC than that of PRC (P < 0.001). The postoperative outcome and the follow-up results showed that there was no significant difference in the short-term and middle-term overall survival rate and restenosis-free survival rate between the two groups. CONCLUSIONS: There are no differences in postoperative and middle-term outcomes between PAC and selective PRC, whereas PRC technique can save operation time and shorten the intraoperative carotid clamp time. PRC can be safely applied in patients with a greater than 5 mm internal carotid artery (ICA).

Preparedness of medical education in China: Lessons from the COVID-19 outbreak.

The COVID-19 outbreak can be seen as a 'big test' for China; a summative assessment of its preparedness on multiple fronts, including medical education. Being intimately involved in the coordinated response, the First Affiliated Hospital of Sun Yat-sen University has been a first-hand witness to the strengths and weaknesses of the current medical education system in China. On the one hand, we believe that the distinguished contributions in disease containment efforts by healthcare professionals indicated that our medical education system has achieved its intended outcomes and is socially accountable. On the other hand, we have also identified three major issues that need to be addressed from an educational standpoint: insufficient emphasis on public health emergency preparedness; unsophisticated mechanisms for interdisciplinary cooperation; and inadequate guidance in medical ethics. Whilst these reflections might be seen in its summative form, we would suggest changing it to that of a formative process, where we learn from our assessment through observation and feedback of the gaps, upon which improvement of our present situation can be made. We hope that these lessons may be helpful to our colleagues in the rest of China and around the world, who are engaged in medical educational reform.

Homeobox protein MSX-1 inhibits expression of bone morphogenetic protein 2, bone morphogenetic protein 4, and lymphoid enhancer-binding factor 1 via Wnt/ß-catenin signaling to prevent differentiation of dental mesenchymal cells during the late bell stage.

Homeobox protein MSX-1 (hereafter referred to as MSX-1) is essential for early tooth-germ development. Tooth-germ development is arrested at bud stage in Msx1 knockout mice, which prompted us to study the functions of MSX-1 beyond this stage. Here, we investigated the roles of MSX-1 during late bell stage. Mesenchymal cells of the mandibular first molar were isolated from mice at embryonic day (E)17.5 and cultured in vitro. We determined the expression levels of ß-catenin, bone morphogenetic protein 2 (Bmp2), Bmp4, and lymphoid enhancer-binding factor 1 (Lef1) after knockdown or overexpression of Msx1. Our findings suggest that knockdown of Msx1 promoted expression of Bmp2, Bmp4, and Lef1, resulting in elevated differentiation of odontoblasts, which was rescued by blocking the expression of these genes. In contrast, overexpression of Msx1 decreased the expression of Bmp2, Bmp4, and Lef1, leading to a reduction in odontoblast differentiation. The regulation of Bmp2, Bmp4, and Lef1 by Msx1 was mediated by the Wnt/ß-catenin signaling pathway. Additionally, knockdown of Msx1 impaired cell proliferation and slowed S-phase progression, while overexpression of Msx1 also impaired cell proliferation and prolonged G1-phase progression. We therefore conclude that MSX-1 maintains cell proliferation by regulating transition of cells from G1-phase to S-phase and prevents odontoblast differentiation by inhibiting expression of Bmp2, Bmp4, and Lef1 at the late bell stage via the Wnt/ß-catenin signaling pathway.

[Kangle Decoction for erectile dysfunction with liver-qi stagnation and kidney deficiency].

OBJECTIVE: To observe the clinical efficacy of Kangle Decoction in the treatment of erectile dysfunction (ED) with liver-qi stagnation and kidney deficiency. METHODS: A total of 79 ED patients with liver-qi stagnation and kidney deficiency were randomly assigned to an experimental group (aged ï¼»36.62±8.05ï¼½ yr and with a disease course of ï¼»18.15±6.41ï¼½ mo) and a control group (aged ï¼»37.44±8.10ï¼½ yr and with a disease course of ï¼»17.51±6.79ï¼½ mo), the former treated orally with Kangle Decoction at 0.5 dose bid while the latter with Cialis at 10 mg qd alt, both for 8 weeks. Before treatment, after 4 and 8 weeks of medication, and at 4 weeks after drug withdrawal, we obtained the scores of the patients in the International Index of Erectile Function-5 (IIEF-5), Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), and Short-Form Psychological and Interpersonal Relationship Scales (SF-PAIRS), and compared the indexes between the two groups of patients. RESULTS: The IIEF-5 score was dramatically increased in both the treatment and control groups after 4 weeks (13.40±2.42 and 16.00±2.68) and 8 weeks of medication (18.60±3.50 and 18.59±3.80) and at 4 weeks after drug withdrawal (17.00±3.05 and 13.95±2.61) as compared with the baseline (10.78±2.28 and 10.77±2.33) (P<0.05 ), even higher in the treatment than in the control group after drug withdrawal (P<0.05 ). The EDITS scores in the treatment and control groups were (28.88±3.31 and 28.90±3.31) after 4 weeks of intervention, (29.68±3.30 and 29.13±3.32) after 8 weeks of intervention, and (29.20±2.92 and 26.82±3.23) at 4 weeks after drug withdrawal, all significantly higher in the former than in the latter group after drug withdrawal (P<0.05 ). The sexual self-confidence score (SSCS), sexual spontaneity score (SSS), and sexual time-concern score (STCS) were all improved in the treatment and control groups after medication as compared with the baseline (P<0.05 ), even higher in the former than in the latter group after drug withdrawal (P<0.05 ). CONCLUSIONS: Kangle Decoction has a definite efficacy in the treatment of ED with liver-qi stagnation and kidney deficiency, with few adverse reactions and long-term post-withdrawal effect, and therefore deserves a wide clinical application.

Structure design of and experimental research on a two-stage laval foam breaker for foam fluid recycling.

Environmental, economical and efficient antifoaming technology is the basis for achievement of foam drilling fluid recycling. The present study designed a novel two-stage laval mechanical foam breaker that primarily uses vacuum generated by Coanda effect and Laval principle to break foam. Numerical simulation results showed that the value and distribution of negative pressure of two-stage laval foam breaker were larger than that of the normal foam breaker. Experimental results showed that foam-breaking efficiency of two-stage laval foam breaker was higher than that of normal foam breaker, when gas-to-liquid ratio and liquid flow rate changed. The foam-breaking efficiency of normal foam breaker decreased rapidly with increasing foam stability, whereas the two-stage laval foam breaker remained unchanged. Foam base fluid would be recycled using two-stage laval foam breaker, which would reduce the foam drilling cost sharply and waste disposals that adverse by affect the environment.

[Sertraline hydrochloride combined with four-spot caressing for primary premature ejaculation].

OBJECTIVE: To investigate the clinical effectiveness of sertraline hydrochloride combined with four-spot caress in the treatment of primary premature ejaculation (PE). METHODS: We randomly assigned 90 primary PE patients to three groups of equal number. The patients in group A (aged [28.1 ± 5.2] yr and with a disease course of [3.1 ± 1.9] yr) were treated with oral sertraline hydrochloride at 50 mg qd, those in B (aged [27.8 ± 4.1] yr and with a disease course of [3.2 ± 2.0] yr) by four-spot caressing (caressing the tongue, breasts, and vulva prior to intercourse), and those in C (aged [27.1 ± 4.7] yr and with a disease course of [3.1 ± 2.0] yr) by the combination of oral sertraline hydrochloride and four-spot caressing, all for 12 weeks. Before and after 4, 8, and 12 weeks of treatment, we obtained the intravaginal ejaculatory latency time (IELT) and Chinese Index of Sexual Function for Premature Ejaculation-5 (CIPE-5) scores and compared them among the three groups of patients. RESULTS: The IELT was dramatically prolonged in groups A, B, and C after 4 weeks ([1.08 ± 0.29], [0.93 ± 0.28] and [1.21 ± 0.27] min), 8 weeks ([1.43 ± 0.30], [1.20 ± 0.33] and [1.72 ± 0.42] min) and 12 weeks of treatment ([2.12 ± 0.63], [1.90 ± 0.65] and [2.67 ± 0.82] min) as compared with the baseline ([0.63 ?0.14] , [0.60 ?0.14] and [0.62 ?0.11] min) (P < 0.05), even longer in group C than in A and B (P < 0.05). The CIPE-5 scores were markedly improved in groups A, B and C after 4 weeks ([15.17 ± 1.74], [14.57 ± 1.94] and [15.60 ± 1.63] min), 8 weeks ([17.13 ± 1.63], [16.37 ± 1.97] and [18.00 ± 1.05] min) and 12 weeks of intervention ([18.93 ± 1.57], [18.53 ± 1.67] and [20.00 ± 1.46] min ) as compared with the baseline ([12.57 ± 2.05], [13.20 ± 2.51] and [13.07 ± 2.01] min) (P < 0.05), even higher in group C than in A and B (P < 0.05). CONCLUSION: Sertraline hydrochloride combined with four-spot caressing, with its definite efficacy and rare adverse reactions, deserves wide clinical application in the treatment of primary PE.

[Distribution, combination, and evolution of syndromic etiologies of erectile dysfunction].

OBJECTIVE: To explore the distribution, combination and evolution of various syndromic etiologies of erectile dysfunction (ED) based on the syndrome etiology theory. METHODS: Using the ED Syndromic Etiology Scale, we collected the clinical data on the Chinese medicine diagnoses of 297 cases of ED, extracted the core syndromic etiologies by analysis of principal components and factors, and analyzed the patterns of distribution, combination, and evolution of ED syndromic etiologies according to the general information of the patients. RESULTS: Through analysis of principal components and factors, 9 core syndromic etiologies were extracted, i. e. , liver constraint with qi stagnation, kidney yin deficiency, damp-heat, liver constraint transforming into liver-fire, blood stasis, kidney yang deficiency, heart-spleen paired deficiency, qi-yin paired deficiency, and phlegm-damp. Each of these syndrome etiologies exhibited its own specific distribution patterns. Of the total number of cases studied, 51.52% had 2 or 3 core syndromic etiologies and 36.03% had only one. CONCLUSION: In the early stage of ED, its syndromic etiologies are usually liver constraint with qi stagnation, kidney yin deficiency, damp-heat, liver constraint transforming into liver-fire, and blood stasis. With the natural progres- sion of the disease, its syndromic etiologies gradually evolve into kidney yang deficiency, heart-spleen paired deficiency, qi-yin paired deficiency, phlegm-damp, and blood stasis, and finally into yin-yang deficiency of the heart, spleen and kidneys, combined with phlegm-damp and blood stasis.

Foxtail millet [Setaria italica (L.) P. Beauv.] grown under nitrogen deficiency exhibits a lower folate contents.

Foxtail millet [Setaria italica (L.) P. Beauv.], as a rich source of folates, has been cultivated on arid infertile lands, for which N deficiency is one of the major issues. Growing environments might have a significant influence on cereal folate levels. However, little is known whether N deficiency modulates cereal folate levels. In order to obtain enriched folate foxtail millet production in nutrient-poor soil, we conducted a study investigating the content of folate derivatives of 29 diverse foxtail millet cultivars under two N regimes (0 and 150 kg N ha-1) for 2 years to explore folate potential grown under low N. The contents of total folate and most derivatives were reduced by N deficiency. The effect on total folate content caused by N was stronger than cultivar genotype did. Folate content of enriched folate cultivars was prone to be reduced by N deficiency. Structural equation models (SEMs) revealed that N fertilization had a positive indirect effect on grain folate content through influencing plant N and K accumulation. Collectively, the results indicate much more attention should be paid to N management when foxtail millet is cultivated in infertile soil, to improve foxtail millet folate contents.

[Differential expressions of microRNA between young and senescent endothelial cells].

OBJECTIVE: To explore the differential expressions of microRNA (miRNA) between young and senescent endothelial cells. METHODS: Young and senescent aorta endothelial cells (EC) were isolated and cultured in young and old male C57BL/6J mice. Immunostaining of VIII factor was performed to identify the endothelial cells. The method of diphenyl tetrazolium bromide (MTT) was employed to compare the cell growth. Microarray was used to detect the differential expression of microRNA between young and senescent endothelial cells and the microarray results were confirmed by real-time polymerase chain reaction (PCR). The expression of endothelial nitric oxide synthase (eNOS) was detected by Western blot. RESULTS: Primarily cultured endothelial cells were confirmed by the VIII immunostaining factor. Senescent ECs grew more rapidly than young ECs in lower serum ex vivo. Excluding gender difference, miR-135a, miR-182, miR-96, miR-31, miR-126-3p and miR-362-5p were up-regulated over 2 folds in young ECs, and miR-335-3p and miR-335-5p up-regulated over 2 folds in senescent ECs by miRNA microarray and RT-PCR. The up-regulation of miR335-3p in old ECs and the up-regulation of miR-135a, miR-96 in the young ECs might contribute to a lower expression of eNOS in senescent ECs. CONCLUSION: The expression of miRNAs changes with advancing age and may result in differential expressions of downstream genes.

[Serum sCD44v6 and sE-cadherin levels in patients with esophageal squamous cell carcinoma].

OBJECTIVE: To investigate the serum levels of sCD44v6 and sE-cadherin (sE-cad) in patients with esophageal squamous cell carcinoma. METHODS: The serum samples were collected from 65 cases of esophageal squamous cell carcinoma, 32 cases of erosive esophagitis and 35 healthy subjects. Serum sCD44v6 and sE-cad levels were measured by enzyme linked immunosorbent assay (ELISA). RESULTS: The mean levels of serum sCD44v6 and sE-cad in esophageal squamous cell carcinoma patients were significantly higher than those of erosive esophagitis patients and normal controls (both P<0.05). There was no significant difference in serum sCD44v6 and sE-cad levels between erosive esophagitis patients normal controls (P=0.566 and P=0.708, respectively). Serum sCD44v6 and sE-cad levels of esophageal cancer patients were not correlated with their clinicopathological features. Serum sCD44v6 level is not correlated with sE-cad level in squamous cell carcinoma patients(P=0.651). CONCLUSION: Serum sCD44v6 and sE-cad might be a potential marker for screening of esophageal squamous cell carcinoma.

Detecting anaplastic lymphoma kinase (ALK) gene rearrangements with next-generation sequencing remains a reliable approach in patients with non-small-cell lung cancer.

Next-generation sequencing (NGS) is rapidly becoming routine in clinical oncology practice to identify therapeutic biomarkers, including gene rearrangements in anaplastic lymphoma kinase (ALK). Our study investigated the concordance of ALK positivity evaluated by DNA-based NGS with orthogonal ALK testing methods such as fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), and RNA-based NGS (RNA-NGS). Thirty-eight patients with lung adenocarcinoma who were detected with ALK rearrangements using DNA-NGS and also had adequate tissue samples submitted for FISH, IHC, and RNA-NGS, were included in this study. Of the 38 patients, RNA samples from 3 patients failed quality control for RNA-NGS. The concordance of ALK positivity was calculated relative to DNA-NGS results. The concordance rates were 97.1% (34/35) for RNA-NGS, 94.7% (36/38) for IHC, and 97.4% (37/38) for FISH. DNA-NGS detected single ALK rearrangements in 14 (35.0%) patients and complex ALK rearrangements in 26 (65.0%). RNA-NGS detected only single transcripts of the primary ALK fusions. A novel LANCL1-ALK (L7:A20) detected using DNA-NGS was detected as EML4-ALK (E13:A20) transcripts using RNA-NGS. Interestingly, patients with single ALK rearrangements were more likely to be detected with atypical isolated red signals (p < 0.001), while patients with complex ALK rearrangements were more likely to be detected with atypical split red and green signals less than 2 signal diameters apart (p < 0.001). Our study highlights the reliability of NGS in the accurate detection of specific ALK fusion variants and concomitant mutations that are crucial for individualized treatment decisions in patients with lung cancer.

PgRNA kinetics predict HBsAg reduction in pregnant chronic hepatitis B carriers after treatment cessation.

Background: Pregenomic RNA (pgRNA) and hepatitis B core-related antigen (HBcrAg) play significant roles in predicting discontinuing treatment outcomes. However, their role in pregnancy has rarely been reported. We aimed to evaluate the performance of pgRNA and HBcrAg kinetics in predicting HBeAg seroconversion and HBsAg reduction postpartum in HBeAg-positive pregnant women. Methods: Pregnant HBeAg-positive patients receiving antiviral prophylaxis and ceasing treatment postpartum were included. PgRNA and HBcrAg levels were measured before treatment, at 32 weeks of gestation, and at treatment withdrawal postpartum. Other virological and biochemical parameters were regularly examined until 96 weeks postpartum. Results: Of 76 pregnant chronic hepatitis B (CHB) carriers with a median treatment duration of 18.1 weeks, HBeAg seroconversion and HBsAg reduction >0.3 log10 IU/mL at 96 weeks postpartum occurred in 8 (10.5%) and 13 (17.1%) patients, respectively. HBsAg correlated most strongly with pgRNA, while HBeAg correlated most strongly with HBcrAg. Multivariable regression analysis revealed that postpartum pgRNA decline and peak ALT levels were independent predictors of HBsAg reduction. The area under the curve of the regression model was 0.79 and reached as high as 0.76 through bootstrapping validation. The calibration plot showed that the nomogram had a performance similar to that of the ideal model. A decision tree was established to facilitate application of the nomogram. In addition, HBcrAg kinetics, as an independent predictor, performed poorly in predicting HBeAg seroconversion. Conclusions: Postpartum pgRNA decline together with peak ALT levels may identify patients with a higher probability of HBsAg reduction after treatment cessation postpartum among pregnant CHB carriers receiving antiviral prophylaxis.

Expression dynamics of periodic transcripts during cancer cell cycle progression and their correlation with anticancer drug sensitivity.

BACKGROUND: The cell cycle is at the center of cellular activities and is orchestrated by complex regulatory mechanisms, among which transcriptional regulation is one of the most important components. Alternative splicing dramatically expands the regulatory network by producing transcript isoforms of genes to exquisitely control the cell cycle. However, the patterns of transcript isoform expression in the cell cycle are unclear. Therapies targeting cell cycle checkpoints are commonly used as anticancer therapies, but none of them have been designed or evaluated at the alternative splicing transcript level. The utility of these transcripts as markers of cell cycle-related drug sensitivity is still unknown, and studies on the expression patterns of cell cycle-targeting drug-related transcripts are also rare. METHODS: To explore alternative splicing patterns during cell cycle progression, we performed sequential transcriptomic assays following cell cycle synchronization in colon cancer HCT116 and breast cancer MDA-MB-231 cell lines, using flow cytometry and reference cell cycle transcripts to confirm the cell cycle phases of samples, and we developed a new algorithm to describe the periodic patterns of transcripts fluctuating during the cell cycle. Genomics of Drug Sensitivity in Cancer (GDSC) drug sensitivity datasets and Cancer Cell Line Encyclopedia (CCLE) transcript datasets were used to assess the correlation of genes and their transcript isoforms with drug sensitivity. We identified transcripts associated with typical drugs targeting cell cycle by determining correlation coefficients. Cytotoxicity assays were used to confirm the effect of ENST00000257904 against cyclin dependent kinase 4/6 (CDK4/6) inhibitors. Finally, alternative splicing transcripts associated with mitotic (M) phase arrest were analyzed using an RNA synthesis inhibition assay and transcriptome analysis. RESULTS: We established high-resolution transcriptome datasets of synchronized cell cycle samples from colon cancer HCT116 and breast cancer MDA-MB-231 cells. The results of the cell cycle assessment showed that 43,326, 41,578 and 29,244 transcripts were found to be periodically expressed in HeLa, HCT116 and MDA-MB-231 cells, respectively, among which 1280 transcripts showed this expression pattern in all three cancer cell lines. Drug sensitivity assessments showed that a large number of these transcripts displayed a higher correlation with drug sensitivity than their corresponding genes. Cell cycle-related drug screening showed that the level of the CDK4 transcript ENST00000547281 was more significantly associated with the resistance of cells to CDK4/6 inhibitors than the level of the CDK4 reference transcript ENST00000257904. The transcriptional inhibition assay following M phase arrest further confirmed the M-phase-specific expression of the splicing transcripts. Combined with the cell cycle-related drug screening, the results also showed that a set of periodic transcripts, for example, ENST00000314392 (a dolichyl-phosphate mannosyltransferase polypeptide 2 isoform transcript), was more associated with drug sensitivity than the levels of their corresponding gene transcripts. CONCLUSIONS: In summary, we identified a panel of cell cycle-related periodic transcripts and found that the levels of transcripts of drug target genes showed different values for predicting drug sensitivity, providing novel insights into alternative splicing-related drug development and evaluation.

Ursolic acid induces HL60 monocytic differentiation and upregulates C/EBPß expression by ERK pathway activation.

Ursolic acid (UA), a pentacyclic triterpenoid compound, is widely distributed in the plant kingdom and has a broad range of biological effects. This study was carried out for the first time to investigate the potential role of UA in the differentiation of human leukemia HL60 cells and the underlying mechanisms in it. UA could induce differentiation of HL60 cells into the monocytic lineage, as assessed by the morphological change, nitroblue tetrazolium reduction assay, and expression of CD14 and CD11b surface antigens. Moreover, UA activated the extracellular signal-regulated kinase (ERK) pathway in both dose-dependent and time-dependent manners. Inhibiting ERK pathway activation with PD98059 could significantly block the differentiation induced by UA. Consistent with the induced differentiation, the upregulation of CCAAT/enhancer-binding protein ß by UA was also eliminated by PD98059. Taken together, the results reported here show that UA can promote the monocytic differentiation of HL60 cells and increase the expression of CCAAT/enhancer-binding protein ß by activating the ERK pathway, suggesting that UA could be a potential candidate as a differentiation-inducing agent for the therapeutic treatment of leukemia.

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The evaluation of ecosystem service value is one of the important steps to improve ecosystem accounting methods and the existing accounting systems, and also one of the key techniques to accelerate the reform of ecological civilization system and to build a beautiful China. However, few literature have systematically distinguished the valuation methods of ecosystem services based on the purpose of valuation, which may lead to overestimation of ecosystem services value from the demand side and inconsistent measurement results among different departments. Based on the purpose of ecosystem accounting, we reviewed the valuation methods of ecosystem services. We started from the connotation and value of ecosystem services, illustrated the classification methods of ecosystem ser-vice value and concluded the approaches of ecosystem service economic units, with the aim to identify the extent to which ecosystem services were involved in system of national accounts (SNA). Then, we systematically sorted out the connotation, applicable scope and data demand of current ecosystem service valuation methods. From the perspective of ecosystem accounting, we discussed the valuation methods applicable to various types of ecosystem services. Finally, we analyzed the deficiency of the current relevant research and proposed some suggestions for the future research.

[Distribution Characteristics and Ecological Risk Assessment of Soil Heavy Metals in Typical Watersheds of the Qinghai-Tibet Plateau].

The Qinghai-Tibet Plateau is an extremely vulnerable area that is sensitive to human activities. In recent years, more and more human disturbances have been detected in this area. This study analyzed the spatial distribution and ecological risks of 7 heavy metals (Cr, Ni, Cu, Zn, As, Cd, and Pb) in two regions, namely the Bailong River and Yellow River and their two tributaries (BY region) in Gannan and the Yarlung Zangbo River and its two tributaries (YZ region) in Tibet. In terms of spatial distribution, concentrations of the seven heavy metals were higher in the east and lower in the west of the BY region. The average concentrations all exceeded the background value of the Qinghai-Tibet Plateau, especially for Cd (4.50 times) and As (2.83 times). High Pb concentrations were mainly found in water, urban and rural residential land, and industrial and construction land. In the YZ region, heavy metal concentrations were lower along the river, while high-altitude areas exhibited higher heavy metal concentrations. The average concentrations of Ni, Zn, As, and Cd exceeded the background values of the Qinghai-Tibet Plateau, especially that of Cd (3.13 times), which mostly exhibited high values in water coverage areas. The geo-accumulation index method and the potential ecological risk index method show that the degree of As and Cd pollution was relatively high in the BY region in Gannan, with the greatest potential ecological risk occurring in the water coverage area. In the YZ region in Tibet, the degree of Cd pollution was high, with the highest potential ecological risk also occurring in the water coverage area. This study provides significant guidance for the environmental protection, sustainable development, and utilization of soil under different types of land use in the Qinghai-Tibet Plateau.