Source-specific probabilistic health risk assessment of dust PAHs in urban parks based on positive matrix factorization and Monte Carlo simulation.

Understanding the health risks of polycyclic aromatic hydrocarbons (PAHs) in dust from city parks and prioritizing sources for control are essential for public health and pollution management. The combination of Source-specific and Monte Carlo not only reduces management costs, but also improves the accuracy of assessments. To evaluate the sources of PAHs in urban park dust and the possible health risks caused by different sources, dust samples from 13 popular parks in Kaifeng City were analyzed for PAHs using gas chromatograph-mass spectrometer (GC-MS). The results showed that the surface dust PAH content in the study area ranged from 332.34 µg·kg-1 to 7823.03 µg·kg-1, with a mean value of 1756.59 µg·kg-1. Nemerow Composite Pollution Index in the study area ranged from 0.32 to 14.41, with a mean of 2.24, indicating that the overall pollution warrants attention. Four pollution sources were identified using the positive matrix factorization (PMF) model: transportation source, transportation-coal and biomass combustion source, coke oven emission source, and petroleum source, with contributions of 33.74%, 25.59%, 22.14%, and 18.54%, respectively. The Monte Carlo cancer risk simulation results indicated that park dust PAHs pose a potential cancer risk to all three populations (children, adult male and adult female). Additionally, the cancer risk for children was generally higher than that for adult males and females, with transportation sources being the main contributor to the carcinogenic risk. Lastly, sensitivity analyses results showed that the toxic equivalent concentration (CS) is the parameter contributing the most to carcinogenic risk, followed by Exposure duration (ED).

Penfluridol regulates p62 / Keap1 / Nrf2 signaling pathway to induce ferroptosis in osteosarcoma cells.

The cure rate for patients with osteosarcoma (OS) has stagnated over the past few decades. Penfluridol, a first-generation antipsychotic, has demonstrated to prevent lung and esophageal malignancies from proliferation and metastasis. However, the effect of penfluridol on OS and its underlying molecular mechanism remains unclear. This study revealed that penfluridol effectively inhibited cell proliferation and migration, and induced G2/M phase arrest in OS cells. In addition, penfluridol treatment was found to increased reactive oxygen species (ROS) levels in OS cells. Combined with the RNA-Seq results, the anti-OS effect of penfluridol was hypothesized to be attributed to the induction of ferroptosis. Western blot results showed that penfluridol promoted intracellular Fe2+ concentration, membrane lipid peroxidation, and decreased intracellular GSH level to induce ferroptosis. Further studies showed that p62/Keap1/Nrf2 signaling pathway was implicated in penfluridol-induced ferroptosis in OS cells. Overexpression of p62 effectively reversed penfluridol-induced ferroptosis. In vivo, penfluridol effectively inhibited proliferation and prolonged survival in xenograft tumor model. Therefore, penfluridol is a promising drug targeting OS in the future.

[Source Apportionment and Health Risk Assessment of Heavy Metals in Dust Around Bus Stops in Kaifeng City Based on APCS-MLR Model].

In order to reveal the influence of urban transportation systems on the quality of urban ecological environment, this study selected surface dust from bus stops, which is strongly disturbed by transportation, as the research object. The contents of eight heavy metals (V, Cr, Co, Ni, Cu, Zn, Cd, and Pb) in the dust were determined through inductively coupled plasma mass spectrometry (ICP-MS) and inductively coupled plasma atomic emission spectroscopy (ICP-ASE). The spatial distribution characteristics and pollution levels of the eight heavy metals in the dust were analyzed using the geo-accumulation index method. A combined qualitative (correlation analysis and principal component analysis) and quantitative (absolute principal component scores-multiple linear regression model (APCS-MLR)) method was used to explore the sources of heavy metals in surface dust near bus stops. The spatial distribution characteristics of heavy metals from different sources were elucidated using the Kriging interpolation method. The health risk assessment model proposed by the United States Environmental Protection Agency was used to evaluate the human health risks. The results showed that the average values of ω(V), ω(Cr), ω(Co), ω(Ni), ω(Cu), ω(Zn), ω(Cd), ω(Pb), and ω(As) in the bus stop surface dust were 68.36, 59.73, 5.81, 19.34, 40.10, 208.32, 1.01, and 49.46 mg·kg-1, respectively. The concentrations of heavy metals (Cd, Zn, Pb, Cu, and Cr) in the dust were all higher than the background values in the surrounding dust, exceeding them by 3.37, 2.70, 2.01, 1.95, and 1.28 times, respectively. The order of the geo-accumulation index for the eight heavy metals was Cd > Zn > Pb > Cu > Cr > V > Ni > Co, with Cd, Zn, Cu, and Pb in the dust indicating mild pollution levels and the others showing no pollution. The source analysis results showed that Cr, Co, and Ni were natural sources, whereas Cu, Zn, Pb, and Cd were traffic sources, and V was derived from a combination of industrial and natural sources. The APCS-MLR results indicated that the average contribution rates of the four sources were as follows:natural source (34.17 %), traffic source (29.84 %), industrial-natural mixed source (14.64 %), and unknown source (21.35 %). The spatial distribution map of the contribution rate of the traffic source was consistent with the trends of traffic volume and bus route density distribution. According to the health risk assessment, the cancer risk and non-cancer risk for children were both higher than those for adults. Cr was the main non-cancer factor, and Cd was the main cancer-causing factor. Natural and traffic sources contributed the most to non-cancer risk and cancer risk, respectively.

In-situ biosynthesized plant exudate gums­silver nanocomposites as corrosion inhibitors for mild steel in hydrochloric acid medium.

Natural gums due to availability, multifunctionality, and nontoxicity are multifaceted in application. In corrosion inhibition applications, their performance, in unmodified form is unsatisfactory because of high hydration rate, solubility issues, algal and microbial contamination, as well as thermal instability. This work attempts to enhance the inhibitive performance of Berlinia grandiflora (BEG) and cashew (CEG) exudate gums through various modification approaches. The potential of biogenic BEG and CEG gums-silver (Ag) nanocomposites (NCPs) for corrosion inhibition of mild steel in 1 M HCl is studied. The nanocomposites were characterized using the FTIR, UV-vis, and TEM techniques. The corrosion studies through the gravimetric and electrochemical (PDP, EIS, LPR, and EFM) analyses reveal moderate inhibition performance by the nanocomposites. Furthermore, the PDP results reveal that both inhibitors are mixed-type with maximum corrosion inhibition efficiencies (IEs) of 61.2 % and 54.2 % for BEG-Ag NCP and CEG-Ag NCP, respectively at an optimum concentration of 1.0 %. Modification of these inhibitors with iodide ion (KI) significantly increased the IE values to 90.1 % and 88.5 % for BEG-Ag NCP and CEG-Ag NCP at the same concentration. Surface observation of the uninhibited and inhibited steel samples using SEM/EDAX, 3D Surface profilometer, and AFM affirm that the modified nanocomposites are highly effective.

[Analysis of the Efficacy and Prognosis Factors of Acute Myeloid Leukemia with a Combination Therapy of Venetoclax].

OBJECTIVE: To explore the efficacy and prognosis factors of acute myeloid leukemia with a combination therapy of venetoclax. METHODS: A retrospective analysis was performed on the clinical data of AML patients treated with a combination therapy of venetoclax from March 2020 to April 2023 in the First Hospital of Lanzhou University. The efficacy, adverse reactions and survival were observed, and the influencing factors were analyzed. RESULTS: A total of 74 AML patients were included in this study, including 43 initially treated AML and 31 relapsed or refractory AML (R/R AML). The median age of 43 initially treated AML patients was 65 years old, the composite complete remission (cCR) rate was 67.4% (29/43), the objective response rate (ORR) was 72.1% (31/43), and the median overall survival (OS) was 17.3 months. The median age of 31 R/R AML patients was 51 years old, with a cCR rate of 38.7% (12/31), an ORR of 58.1% (18/31), and a median OS of 7.1 months. Sex, the blood cell count before VEN, gene mutation and prognosis stratification were related to whether to obtain cCR. Failure to obtain cCR was an independent risk factor for adverse outcomes. CONCLUSION: A combination therapy of venetoclax is safe and efficacious for AML. Its efficacy and survival are affected by molecular biology, cytogenetics and other factors.

[The Correlation of Gene Mutation and Clinical Characteristics in Patients with Myelodysplastic Syndrome and Prognostic Analysis].

OBJECTIVE: To explore the correlation between gene mutations and clinical characteristics, prognosis of myelodysplastic syndromes (MDS). METHODS: Clinical data of 131 patients with MDS were collected from the First Hospital of Lanzhou University from June 2015 to February 2023, which 19 of them developed into secondary acute myeloid leukemia (sAML) during follow-up time. Second generation sequencing technology was used to detect the mutation types of MDS disease-related genes, drawn gene maps, and analyzed their correlation and prognosis based on the clinical data of patients. RESULTS: The median age of 131 MDS patients was 58(17-86) years old. The ratio of male to female was 1.3∶1. A total of 148 gene mutations and 25 types were found in the center. U2AF1 and ASXL1 were often co-mutations with other genes, which were accompanied by 20q- and normal karyotype (NK) respectively. SETBP1 and SRSF2 were more common in patients over 60 years old, while NPM1 and WT1 under 60 years. Older patients had a higher the number of genetic mutations than younger patients. The incidence of SF3B1 and RUNX1 in males was higher than females and DNMT3A in females was higher than males. The number of gene mutations in sAML was higher than MDS (1.8 vs 1.0, P =0.006). The univariate and multivariate analysis showed that IPSS-R prognostic score≥3.5, TP53 were adverse factors for poor prognosis in MDS patients. Patients with monoallelic mutation（ma-TP53）and wild-type（wt-TP53） TP53 had OS better than biallelic mutation（bi-TP53）(P =0.003). The OS of MDS patients was better than sAML(P =0.01) and transplant patients was significantly better than nontransplant patients(P =0.036). CONCLUSION: Gene mutation is closely related to cytogenetic indexes and clinical features (peripheral blood cell count, sex, age). IPSS-R prognostic score and TP53 were risk factors affecting OS in MDS patients.

Trifluoperazine activates AMPK / mTOR / ULK1 signaling pathway to induce mitophagy in osteosarcoma cells.

Osteosarcoma is a prevalent kind of primary bone malignancy. Trifluoperazine, as an antipsychotic drug, has anti-tumor activity against a variety of cancers. Nevertheless, the impact of trifluoperazine on osteosarcoma is unclear. Our investigation aimed to explore the mechanism of trifluoperazine's effect on osteosarcoma. We found that trifluoperazine inhibited 143B and U2-OS osteosarcoma cell proliferation in a method based on the dose. Furthermore, it was shown that trifluoperazine induced the accumulation of reactive oxygen species (ROS) to cause mitochondrial damage and induced mitophagy in osteosarcoma cells. Finally, combined with RNA-seq results, we first demonstrated the AMPK/mTOR/ULK1 signaling pathway as a potential mechanism of trifluoperazine-mediated mitophagy in osteosarcoma cells and can be suppressed by AMPK inhibitor Compound C.

[Soil Heavy Metal Contamination, Sources, and Health Risk of Typical Drinking Water Sources in the Suspended Reach of the Lower Yellow River].

With the implementation of ecological protection and a high-quality development strategy in the Yellow River Basin, the environmental conditions around the Yellow River have attracted wide attention from scholars. In this study, the soil of drinking water sources(Heichi and Liuchi) in the typical suspended reach of the lower reaches of the Yellow River was selected as the research object. The geo-accumulation index and pollution load index were used to analyze the pollution characteristics of seven heavy metals(Cr, Ni, Cu, Zn, Cd, Pb, and As), and correlation analysis, principal component analysis, and absolute factor score-multiple linear regression(APCS-MLR) were employed to reveal the sources of soil heavy metals from both qualitative and quantitative perspectives. The health risk assessment model recommended by the United States Environmental Protection Agency(USEPA) was used to analyze the impact of soil heavy metals on human health, and the contribution rate of pollution sources to health risks was analyzed by combining the APCS-MLR model. The results showed that the average values of ω(Cr), ω(Ni), ω(Cu), ω(Zn), ω(Cd), ω(Pb), and ω(As) in the soil around the water source were 60.27, 30.00, 35.14, 77.75, 0.38, 21.74, and 9.70 mg·kg-1, respectively. Except for As, the contents of Cr, Ni, Cu, Zn, Cd, and Pb were higher than the background values of soil elements in the fluvo-aquic soil area of the lower Yellow River, whereas the contents of Cu and Zn in the soil around Liuchi were significantly higher than those in Heichi. Both the geo-accumulation index and the single-factor index showed that the black pond and the willow pond were slightly polluted by heavy metals, and Cd was the main pollution factor. The pollution load index model showed that the number of non-polluted and mildly polluted samples in the study area accounted for 5% and 95% of the total samples, respectively, indicating that the study area was at a mild pollution level. The source apportionment showed that Cr, Ni, Cu, and As were mainly affected by parent materials. The analysis results of the APCS-MLR model showed that the soil pollutants in the study area were mainly from natural sources, traffic sources, agricultural sources, and unknown sources, and their contribution rates were 42.95%, 23.39%, 16.95%, and 16.71%, respectively. The health risk assessment showed that As was the main non-carcinogenic factor, and Ni was the main carcinogenic factor. The non-carcinogenic risk of heavy metals to adults and children was negligible, and there was a tolerable carcinogenic risk to the human body. For both adults and children, the non-carcinogenic and carcinogenic risk contribution rates of the four pollution sources were:natural sources>unknown sources>traffic sources>agricultural sources, among which natural sources contributed the most to non-carcinogenic and carcinogenic risks. Therefore, it is of great significance to study the characteristics, sources, and effects of soil pollution on human health around the water source area of the suspended reach of the lower reaches of the Yellow River, which is of great significance for the protection of water sources and provides theoretical support for the high-quality development of the ecological environment along the Yellow River.

VvBBX44 and VvMYBA1 form a regulatory feedback loop to balance anthocyanin biosynthesis in grape.

Anthocyanins are essential for the quality of perennial horticultural crops, such as grapes. In grapes, ELONGATED HYPOCOTYL 5 (HY5) and MYBA1 are two critical transcription factors that regulate anthocyanin biosynthesis. Our previous work has shown that Vitis vinifera B-box protein 44 (VvBBX44) inhibits anthocyanin synthesis and represses VvHY5 expression in grape calli. However, the regulatory mechanism underlying this regulation was unclear. In this study, we found that loss of VvBBX44 function resulted in increased anthocyanin accumulation in grapevine callus. VvBBX44 directly represses VvMYBA1, which activates VvBBX44. VvMYBA1, but not VvBBX44, directly modulates the expression of grape UDP flavonoid 3-O-glucosyltransferase (VvUFGT). We demonstrated that VvBBX44 represses the transcriptional activation of VvUFGT and VvBBX44 induced by VvMYBA1. However, VvBBX44 and VvMYBA1 did not physically interact in yeast. The application of exogenous anthocyanin stimulated VvBBX44 expression in grapevine suspension cells and tobacco leaves. These findings suggest that VvBBX44 and VvMYBA1 form a transcriptional feedback loop to prevent overaccumulation of anthocyanin and reduce metabolic costs. Our work sheds light on the complex regulatory network that controls anthocyanin biosynthesis in grapevine.

The use of the ratio of C-reactive protein to albumin for the diagnosis of pediatric septic arthritis.

Purpose: This study aimed to investigate the relationship between the ratio of c-reactive protein to albumin (CAR) and pediatric septic arthritis (PSA). Methods: Clinical and laboratory data were collected. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive ability of CAR in identifying PSA. Multivariable logistic regression analyses was performed to calculate adjusted odds ratio (OR) with 95% confidence interval (CI). Results: We included 305 patients with PSA (CAR ≤ 0.447, 182 patients; CAR > 0.447, 123 patients) between September 2013 and November 2022. ROC analysis showed that CAR performed best in diagnosing PSA, with an area under curve (AUC) value of 0.828. After adjusted for potential confounders, we found that high CAR was associated with PSA (OR = 6.85, 95% CI: 2.30-20.40, p = 0.001). In sensitivity analyses, subgroups analyses, and propensity score matching, the results remain stable. Conclusions: The CAR (>0.447) at admission was an independent risk factor for PSA. It is worthy to further investigate this association.

A postpartum enriched environment rescues impaired cognition and oxidative markers in aged mice with gestational inflammation.

INTRODUCTION: Previous studies have shown that gestational inflammation can accelerate age-associated cognitive decline (AACD) in maternal mice; enriched environments (EEs) have been reported to protect normally aging mice from AACD and improve mitochondrial function. However, it is unclear whether the nitrosative stress-related proteins tet methylcytosine dioxygenase 1 (TET1) and S-nitrosoglutathione reductase (GSNOR) are involved in the accelerated aging process of gestational inflammation and whether EEs can slow this process. METHODS: In this study, CD-1 female mice on the 15th day of pregnancy were injected with bacterial lipopolysaccharide (50 µg/kg; LPS group) or an equivalent amount of normal saline (CON group) from the abdominal cavity for 4 consecutive days. Twenty-one days after delivery, half of the LPS-treated mice were randomly selected for EE until the end of the behavioral experiment (LPS-E group). When the female rats were raised to 6 months and 18 months of age, the Morris water maze (MWM) was used to detect spatial learning and memory ability; RT-PCR and Western blots were used to measure the mRNA and protein levels of hippocampal TET1 and GSNOR. RESULTS: As for the control group, compared with 6-month-old mice, the spatial learning and memory ability of 18-month-old mice decreased, and the hippocampal TET1 and GSNOR mRNA and protein levels were decreased. Gestational inflammation exacerbated these age-related changes, but an EE alleviated the effects. Pearson's correlation analysis indicated that performance during the learning and memory periods in the MWM correlated with the levels of hippocampal TET1 and GSNOR. CONCLUSIONS: Our findings suggest that gestational inflammation accelerates age-related learning and memory impairments and that postpartum EE exposure could alleviate these changes. These effects may be related to hippocampal TET1 and GSNOR expression.

Clinicopathologic and Genomic Features in Triple-Negative Breast Cancer Between Special and No-Special Morphologic Pattern.

Background: Triple-negative breast cancer (TNBC) is refractory and heterogeneous, comprising various entities with divergent phenotype, biology, and clinical presentation. As an aggressive subtype, Chinese TNBC patients with special morphologic patterns (STs) were restricted to its incidence of 10-15% in total TNBC population. Methods: We recruited 89 patients with TNBC at Guangdong Provincial People's Hospital (GDPH) from October 2014 to May 2021, comprising 72 cases of invasive ductal carcinoma of no-special type (NSTs) and 17 cases of STs. The clinical data of these patients was collected and statistically analyzed. Formalin-fixed, paraffin-embedded (FFPE) tumor tissues and matched blood samples were collected for targeted next-generation sequencing (NGS) with cancer-related, 520- or 33-gene assay. Immunohistochemical analysis of FFPE tissue sections was performed using anti-programmed cell death-ligand 1(PD-L1) and anti-androgen receptor antibodies. Results: Cases with NSTs presented with higher histologic grade and Ki-67 index rate than ST patients (NSTs to STs: grade I/II/III 1.4%, 16.7%,81.9% vs 0%, 29.4%, 58.8%; p<0.05; Ki-67 ≥30%: 83.3% vs. 58.8%, p<0.05), while androgen receptor (AR) and PD-L1 positive (combined positive score≥10) rates were lower than of STs cases (AR: 11.1% vs. 47.1%; PD-L1: 9.6% vs. 33.3%, p<0.05). The most commonly altered genes were TP53 (88.7%), PIK3CA (26.8%), MYC (18.3%) in NSTs, and TP53 (68.8%), PIK3CA (50%), JAK3 (18.8%), KMT2C (18.8%) in STs respectively. Compared with NSTs, PIK3CA and TP53 mutation frequency showed difference in STs (47.1% vs 19.4%, p=0.039; 64.7% vs 87.5%, p=0.035). Conclusions: In TNBC patients with STs, decrease in histologic grade and ki-67 index, as well as increase in PD-L1 and AR expression were observed when compared to those with NSTs, suggesting that TNBC patients with STs may better benefit from immune checkpoint inhibitors and/or AR inhibitors. Additionally, lower TP53 and higher PIK3CA mutation rates were also found in STs patients, providing genetic evidence for deciphering at least partly potential mechanism of action.

Anoctamin 5 promotes osteosarcoma development by increasing degradation of Nel-like proteins 1 and 2.

Anoctamin 5 (ANO5) is a member of the Anoctamin (ANO) family of calcium-activated chloride channels. Although ANO5 expression is upregulated in various cancers, its role in osteosarcoma remains largely unknown. In this study, bioinformatics analysis, western blot, and immunohistochemical staining revealed that ANO5 was upregulated in osteosarcoma cell lines and osteosarcoma tissues, and ANO5 expression was positively associated with tumor size, tumor grade, and metastasis. Functional experiments demonstrated that inhibition of ANO5 decreased, while ANO5 overexpression increased, osteosarcoma cell proliferation and mobility in vitro. Immunoprecipitation, western blot, and confocal microscopy experiments showed that ANO5 bound to and promoted the degradation of Nel-like proteins 1 (NELL1) and 2 (NELL2). Moreover, a subcutaneous tumor transplantation model revealed that ANO5 knockdown reduced osteosarcoma cell proliferation and increased NELL1 and NELL2 expression in vivo. Finally, rescue experiments showed that knockdown of NELL1 or NELL2 reversed the inhibitory effects of ANO5 knockdown on osteosarcoma cell proliferation and migration. These results demonstrated that upregulation of ANO5 promoted osteosarcoma development by decreasing the stability of the NELL1 and NELL2 proteins and that ANO5 may be an effective target for the treatment of osteosarcoma.

Treatment of Recurrent Axillary Osmidrosis: Trimming and Electrocoagulation of Apocrine Glands Under Direct Vision Through Double Incisions.

OBJECTIVE: The aim of this study was to explore the clinical effect of treatment for recurrent axillary osmidrosis (AO) after small-incision minimally invasive surgery by trimming and electrocoagulation of apocrine glands under direct vision through double incisions parallel to axillary creases. METHODS: This was a retrospective study. From September 2012 to January 2019, 75 axillae in 48 cases of recurrent AO after small-incision minimally invasive surgery were treated using trimming and electrocoagulation of apocrine glands under direct vision through double incisions parallel to axillary creases. Patient data, such as sex, age, original surgery method, the severity of underarm malodor before and after the operation, and occurrence of complications, were collected and analyzed. RESULTS: For the follow-up of at least 12 months after the surgery, all patients' underarm malodor disappeared or was significantly reduced. Patients with preoperative severity of grade I did not show a recurring AO, whereas the recurrence rate of grade II and grade III AO was 7.9% and 14.3%, respectively. Furthermore, the AO recurrence rate was 9.1% for those younger than 18 years and 6.2% in those 18 years or older. Subcutaneous hematomas appeared on 3 axillae (4.0%), and the contraction of subdermal fibrotic bands appeared on 5 axillae (6.7%). CONCLUSIONS: Patients with recurring AO after small-incision minimally invasive surgery achieved good treatment results by trimming and electrocoagulation of apocrine glands under direct vision through double incisions parallel to axillary creases.

A four-oil intravenous lipid emulsion improves markers of liver function, triglyceride levels and shortens length of hospital stay in adults: a systematic review and meta-analysis.

Clinical trials have reported that a four-oil intravenous lipid emulsion (SMOFlipid) play a positive role in immune function, but showed inconsistent outcomes compared to other lipid emulsions. A systematic review and meta-analysis was conducted to evaluate the effect of SMOFlipid on liver function, triglycerides (TG), inflammatory markers, and clinical outcomes in hospitalized adults after short-term use compared to others. A search of the PubMed, Medline, Embase, China National Knowledge Infrastructure, and Wanfang databases was performed to identify the included randomized controlled trials. Trials with adults who were administrated a short-term course of SMOFlipid were included. A meta-analysis on liver function markers, TG, inflammatory markers, and clinical outcomes was conducted. A total of 18 randomized controlled trials with 1188 patients were included. Compared to other lipid emulsions, SMOFlipid was associated with a significant reduction in ALT, AST, γ-glutamyltransferase, total bilirubin, TG, C-reactive protein and length of hospital stay. No effect on serum interleukin-6 levels or adverse events were observed. For adult patients, our meta-analysis indicated that SMOFlipid may be beneficial to the liver and prone to prevent hyperlipidemia. The SMOFlipid also shortened length of hospital stay.

Optimizing the CRISPR/Cas9 system for genome editing in grape by using grape promoters.

The efficacy of the CRISPR/Cas9 system in grapevine (Vitis vinifera L.) has been documented, but the optimization of this system, as well as CRISPR/Cas9-mediated multiplex genome editing, has not been explored in this species. Herein, we identified four VvU3 and VvU6 promoters and two ubiquitin (UBQ) promoters in grapevine and demonstrated that the use of the identified VvU3/U6 and UBQ2 promoters could significantly increase the editing efficiency in grape by improving the expression of sgRNA and Cas9, respectively. Furthermore, we conducted multiplex genome editing using the optimized CRISPR/Cas9 vector that contained the conventional multiple sgRNA expression cassettes or the polycistronic tRNA-sgRNA cassette (PTG) by targeting the sugar-related tonoplastic monosaccharide transporter (TMT) family members TMT1 and TMT2, and the overall editing efficiencies were higher than 10%. The simultaneous editing of TMT1 and TMT2 resulted in reduced sugar levels, which indicated the role of these two genes in sugar accumulation in grapes. Moreover, the activities of the VvU3, VvU6, and UBQ2 promoters in tobacco genome editing were demonstrated by editing the phytoene desaturase (PDS) gene in Nicotiana benthamiana leaves. Our study provides materials for the optimization of the CRISPR/Cas9 system. To our knowledge, our simultaneous editing of the grape TMT family genes TMT1 and TMT2 constitutes the first example of multiplex genome editing in grape. The multiplex editing systems described in this manuscript expand the toolbox of grape genome editing, which would facilitate basic research and molecular breeding in grapevine.

Changed signals of blood adenosine and cytokines are associated with parameters of sleep and/or cognition in the patients with chronic insomnia disorder.

OBJECTIVES: This study aimed to investigate whether plasma levels of adenosine, adenosine deaminase (ADA), and certain cytokines change in patients with chronic insomnia disorder (CID), and if so, whether these alterations are associated with poor sleep quality and cognitive dysfunction. METHODS: Fifty-five CID patients were selected for the study, along with fifty-five healthy controls (HC) matched to the patients according to their basic data. All subjects completed sleep, emotion, and cognition assessments, with some CID patients also completing an overnight polysomnography. The plasma level of adenosine was measured using liquid chromatography-tandem mass spectrometry, while ADA level was quantified using a quantitative sandwich enzyme-linked immunosorbent assay. Levels of cytokines, including IL-1ß, IL-2, IL-4, IL-6, IL-10, IL-12, TNF-α, and IFN-γ, were measured using Luminex liquid chip technology. RESULTS: CID patients had a lower adenosine level, and higher levels of ADA and some of the cytokines (IL-1ß, IL-2, IL-6, IL-10 and TNF-α) compared with controls. In the CID group, plasma concentrations of adenosine were negatively correlated with Pittsburgh Sleep Quality Index scores, while concentrations of IL-1ß, IL-6 and TNF-α were positively correlated with these scores. Concentrations of IL-1ß and TNF-α were negatively correlated with scores on the Chinese-Beijing Version of the Montreal Cognitive Assessment. Moreover, levels of IL-1ß, TNF-α, IL-6, and IL-2 were positively correlated with memory test errors by CID patients after controlling for confounding factors. CONCLUSIONS: The reduced adenosine and elevated cytokine levels of CID patients were associated with the severity of insomnia and/or cognitive dysfunction.

Clinical Value of Prognostic Nutritional Index in Prediction of the Presence and Severity of Neonatal Sepsis.

PURPOSE: The prognostic nutritional index (PNI) is a common indicator of nutritional and inflammatory status and is associated with various diseases such as cancer, cardiovascular diseases and infectious diseases. However, to date, no study has concentrated on the role of PNI in assessing and predicting the presence and severity of neonatal sepsis. Therefore, the present study aimed to explore the association of the PNI with the presence and severity of neonatal sepsis. MATERIALS AND METHODS: A total of 1196 neonates with suspected sepsis were enrolled in this study and their complete clinical and laboratory data were collected. PNI was calculated as serum albumin (g/L) + 5 × total lymphocyte count (109/L). Multivariate logistic regression analysis was performed to identify the risk factors for the presence and severity of neonatal sepsis. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive value of PNI. All statistical analyses were performed using the statistical package SPSS 24.0. RESULTS: PNI was lower in neonates with sepsis and decreased significantly with the severity of sepsis. The correlation analysis demonstrated that the PNI was negatively correlated with the levels of the inflammatory marker procalcitonin (PCT) and C-reactive protein (CRP), and the length of hospital stay. Multivariate logistic regression analysis revealed that the PNI was independently and inversely associated with the presence and severity of neonatal sepsis. The area under the ROC curve of the PNI was 0.64 (95% confidence interval (CI): 0.61-0.67, P < 0.001) for severe sepsis and 0.69 (95% CI: 0.60-0.78, P < 0.001) for septic shock. In addition, our data revealed that PNI was also independently correlated with the length of hospital stay. CONCLUSION: PNI is an independent predictor for the presence and severity of neonatal sepsis.

CHRDL2 promotes osteosarcoma cell proliferation and metastasis through the BMP-9/PI3K/AKT pathway.

Various studies demonstrated that bone morphogenetic proteins (BMPs) and their antagonists contribute to the development of cancers. Chordin-like 2 (CHRDL2) is a member of BMP antagonists. However, the role and its relative mechanism of CHRDL2 in osteosarcoma remains unclear. In the present study, we demonstrated that the expression of CHRDL2 was significantly upregulated in osteosarcoma tissues and cell lines compared with adjacent tissues and human normal osteoblast. Inhibition of CHRDL2 decreased the proliferation and colony formation of osteosarcoma cells in vitro, as well as the migration and invasion. CHRDL2 overexpression induced the opposite effects. CHRDL2 can bind with BMP-9, thus decreasing BMP-9 expression and the combination to its receptor protein kinase ALK1. It was predicted that BMP-9 regulates PI3K/AKT pathways using gene set enrichment analysis. Inhibition of CHRDL2 decreased the activation of PI3K/AKT pathway, while overexpression of CHRDL2 upregulated the activation. Increasing the expression of BMP-9 reversed the effects of CHRDL2 overexpression on the activation of PI3K/AKT pathway, as well as the proliferation and metastasis of osteosarcoma cells. Take together, our present study revealed that CHRDL2 upregulated in osteosarcoma tissues and cell lines, and promoted osteosarcoma cell proliferation and metastasis through the BMP-9/PI3K/AKT pathway. CHRDL2 maybe an oncogene in osteosarcoma, as well as novel biomarker for the diagnosis of osteosarcoma.

Short-term and mid-term effects of radiofrequency ablation in mitral valve surgery in patients with different left atrial sizes.

BACKGROUND: To evaluate the efficacy of atrial fibrillation radiofrequency ablation (AFRA) in patients with chronic valvular atrial fibrillation (AF) with different left atrial sizes [left atrial diameter (LAD) >45 or ≤45 mm]. METHODS: Between May 2016 and January 2019, 264 patients who underwent cardiac operations with modified bipolar AFRA in the Department of Cardiovascular Surgery, PLA General Hospital, were enrolled. The clinical data of the patients were analysed, and inclusion and exclusion criteria were implemented. A propensity score was given for two groups of different left atrial sizes: group A (75 patients with LAD >45 mm) and group B (75 patients with LAD ≤45 mm). Preoperative general data, operative indicators, postoperative mortality, complications, and sinus rhythm recovery were analysed and compared between the two groups. RESULTS: The rates of sinus rhythm recovery in group A (LAD >45 mm) at 1 week, 6 months, 1 year, and 2 years after surgery were 84.0%, 81.33%, 73.33%, and 69.33%, respectively, compared with 90.67.0%, 88.00%, 86.67%, and 84.00% at 1 week, 6 months, 1 year, and 2 years after surgery, respectively, in group B (LAD ≤45 mm). The difference between the two groups was statistically significant at the two points in time of 1 year, and 2 years (P<0.05). Warfarin anticoagulation, the standard therapy, was applied after surgery. No new cerebrovascular events occurred in either group during short- and medium-term postoperative follow-up. CONCLUSIONS: Mitral valve surgery using improved Cox-Maze IV bipolar radiofrequency ablation was effective in treating chronic long-term persistent valvular AF and had an excellent sinus rhythm recovery rate. However, the larger the LAD, the less likely a patient was to maintain sinus rhythm as time passed after surgery.