The water lily genome and the early evolution of flowering plants.

Water lilies belong to the angiosperm order Nymphaeales. Amborellales, Nymphaeales and Austrobaileyales together form the so-called ANA-grade of angiosperms, which are extant representatives of lineages that diverged the earliest from the lineage leading to the extant mesangiosperms1-3. Here we report the 409-megabase genome sequence of the blue-petal water lily (Nymphaea colorata). Our phylogenomic analyses support Amborellales and Nymphaeales as successive sister lineages to all other extant angiosperms. The N. colorata genome and 19 other water lily transcriptomes reveal a Nymphaealean whole-genome duplication event, which is shared by Nymphaeaceae and possibly Cabombaceae. Among the genes retained from this whole-genome duplication are homologues of genes that regulate flowering transition and flower development. The broad expression of homologues of floral ABCE genes in N. colorata might support a similarly broadly active ancestral ABCE model of floral organ determination in early angiosperms. Water lilies have evolved attractive floral scents and colours, which are features shared with mesangiosperms, and we identified their putative biosynthetic genes in N. colorata. The chemical compounds and biosynthetic genes behind floral scents suggest that they have evolved in parallel to those in mesangiosperms. Because of its unique phylogenetic position, the N. colorata genome sheds light on the early evolution of angiosperms.

Interleukin-2 enhancer binding factor 2 negatively regulates the replication of duck hepatitis A virus type 1 by disrupting the RNA-dependent RNA polymerase activity of 3D polymerase.

The interaction between viral components and cellular proteins plays a crucial role in viral replication. In a previous study, we showed that the 3'-untranslated region (3'-UTR) is an essential element for the replication of duck hepatitis A virus type 1 (DHAV-1). However, the underlying mechanism is still unclear. To gain a deeper understanding of this mechanism, we used an RNA pull-down and a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry assay to identify new host factors that interact with the 3'-UTR. We selected interleukin-2 enhancer binding factor 2 (ILF2) for further analysis. We showed that ILF2 interacts specifically with both the 3'-UTR and the 3D polymerase (3Dpol) of DHAV-1 through in vitro RNA pull-down and co-immunoprecipitation assays, respectively. We showed that ILF2 negatively regulates viral replication in duck embryo fibroblasts (DEFs), and that its overexpression in DEFs markedly suppresses DHAV-1 replication. Conversely, ILF2 silencing resulted in a significant increase in viral replication. In addition, the RNA-dependent RNA polymerase (RdRP) activity of 3Dpol facilitated viral replication by enhancing viral RNA translation efficiency, whereas ILF2 disrupted the role of RdRP in viral RNA translation efficiency to suppress DHAV-1 replication. At last, DHAV-1 replication markedly suppressed the expression of ILF2 in DEFs, duck embryo hepatocytes, and different tissues of 1 day-old ducklings. A negative correlation was observed between ILF2 expression and the viral load in primary cells and different organs of young ducklings, suggesting that ILF2 may affect the viral load both in vitro and in vivo.

Interspecific barrier effect driven by heavy metals makes soil bacterial functional assembly more stochastic.

Residual heavy metals in soils will destroy microbial community stability and influence its aggregation. However, exploring microbial ecology under heavy-metal stress still requires a conjoint analysis of bacterial interspecies communication and the community diversity maintenance mechanism. In this study, soil samples were collected from a heavy-metal-contaminated site in China to investigate the ecological response of indigenous microbial communities through high-throughput sequencing. Results showed that bacterial taxa and functions generated unusual decoupling phenomena. There were no significant differences in the diversity of species with the increase in concentration of heavy metals (Hg, Se, and Cr), but the functional diversity was lost. Also, the average niche breadth of bacterial species increased from 1.70 to 2.28, but community stability declined and the species assembly was always a deterministic process (NST <0.5). After the bacterial functional assembly changed from a stochastic process to a deterministic process (NST <0.5), it was transformed into a stochastic process (NST >0.5) again under the stress of high-concentration heavy metals, indicating that the collective stress resistance of bacterial communities changed from positive mutation into passive functional propagation. The research results can provide new insight into understanding the adaptive evolution of communities and ecosystem restoration under the stress of soil heavy metals.

Sleep-related disorders and lower urinary tract symptoms in middle-aged and elderly males: a cross-sectional study based on NHANES 2005-2008.

PURPOSE: Lower urinary tract symptoms (LUTS) and sleep disorders both commonly affect people's quality of life. This study aimed to explore the associations between sleep-related disorders and LUTS through epidemiological investigations. METHODS: Data were generated from the cross-sectional study called the National Health and Nutrition Examination Survey (NHANES) 2005-2008. Multivariable logistic regression models were conducted to investigate the relationships between sleep-related disorders and LUTS. RESULTS: A total of 2516 men were included in the study. Participants sleeping ≤ 6 h/night had higher odds ratios of LUTS (OR: 1.38; 95% CI 1.08, 1.77), daytime LUTS (OR: 1.26; 95% CI 1.03, 1.54), and nocturia (OR: 1.23; 95% CI 1.02, 1.49) than those sleeping 7-8 h/night. Participants who required > 30 min to fall asleep had an approximately 39% higher odds ratios of nocturia than those who fell asleep within 6 to 30 min (OR: 1.39; 95% CI 1.12, 1.73). Sleep problems were positively related to LUTS (OR: 1.42; 95% CI 1.11, 1.82), daytime LUTS (OR: 1.32; 95% CI 1.08, 1.61), urinary hesitancy (OR: 1.75; 95% CI 1.31, 2.34), and nocturia (OR: 1.52; 95% CI 1.26, 1.84). Obstructive sleep apnea (OSA) symptoms were positively associated with urinary incontinence (OR: 1.52; 95% CI 1.12, 2.08). In addition, participants with daytime sleepiness were at higher prevalence of LUTS (OR: 1.66; 95% CI 1.29, 2.15), daytime LUTS (OR: 1.44; 95% CI 1.16, 1.78), urinary hesitancy (OR: 1.95; 95% CI 1.45, 2.63), and nocturia (OR: 1.66; 95% CI 1.35, 2.05). CONCLUSION: The findings suggested that sleep-related disorders were associated with LUTS, daytime LUTS, urinary hesitancy, incomplete emptying, urinary incontinence, and nocturia in middle-aged and elderly males.

Nomogram predicting the efficacy of transurethral surgery in benign prostatic hyperplasia patients.

PURPOSE: This study aimed to develop and validate a nomogram for predicting the efficacy of transurethral surgery in benign prostatic hyperplasia (BPH) patients. METHODS: Patients with BPH who underwent transurethral surgery in the West China Hospital and West China Shang Jin Hospital were enrolled. Patients were retrospectively involved as the training group and were prospectively recruited as the validation group for the nomogram. Logistic regression analysis was utilized to generate nomogram for predicting the efficacy of transurethral surgery. The discrimination of the nomogram was assessed using the area under the receiver operating characteristic curve (AUC) and calibration plots were applied to evaluate the calibration of the nomogram. RESULTS: A total of 426 patients with BPH who underwent transurethral surgery were included in the study, and they were further divided into a training group (n = 245) and a validation group (n = 181). Age (OR 1.07, 95% CI 1.02-1.15, P < 0.01), the compliance of the bladder (OR 2.37, 95% CI 1.20-4.67, P < 0.01), the function of the detrusor (OR 5.92, 95% CI 2.10-16.6, P < 0.01), and the bladder outlet obstruction (OR 2.21, 95% CI 1.07-4.54, P < 0.01) were incorporated in the nomogram. The AUC of the nomogram was 0.825 in the training group, and 0.785 in the validation group, respectively. CONCLUSION: The nomogram we developed included age, the compliance of the bladder, the function of the detrusor, and the severity of bladder outlet obstruction. The discrimination and calibration of the nomogram were confirmed by internal and external validation.

Feasibility of low-intensity ultrasound treatment with hydroxylamine to accelerate the initiation of partial nitrification and allow operation under intermittent aeration.

Partial nitrification is a key aspect of efficient nitrogen removal, although practically it suffers from long start-up cycles and unstable long-term operational performance. To address these drawbacks, this study investigated the effect of low intensity ultrasound treatment combined with hydroxylamine (NH2OH) on the performance of partial nitrification. Results show that compared with the control group, low-intensity ultrasound treatment (0.10 W/mL, 15 min) combined with NH2OH (5 mg/L) reduced the time required for partial nitrification initiation by 6 days, increasing the nitrite accumulation rate (NAR) and ammonia nitrogen removal rate (NRR) by 20.4% and 6.7%, respectively, achieving 96.48% NRR. Mechanistic analysis showed that NH2OH enhanced ammonia oxidation, inhibited nitrite-oxidizing bacteria (NOB) activity and shortened the time required for partial nitrification initiation. Furthermore, ultrasonication combined with NH2OH dosing stimulated EPS (extracellular polymeric substances) secretion, increased carbonyl, hydroxyl and amine functional group abundances and enhanced mass transfer. In addition, 16S rRNA gene sequencing results showed that ultrasonication-sensitive Nitrospira disappeared from the ultrasound + NH2OH system, while Nitrosomonas gradually became the dominant group. Collectively, the results of this study provide valuable insight into the enhancement of partial nitrification start-up during the process of wastewater nitrogen removal.

Molecular evidence for potential transovarial transmission of Jingmen tick virus in Haemaphysalis longicornis fed on cattle from Yunnan Province, China.

Jingmen tick virus (JMTV) is a novel tick-borne virus first identified from Jingmen city, Hubei Province of China in 2010. It has been proved that JMTV can cause human diseases and is widely distributed both inside and outside of China. However, the survival mode and transmission characteristics of JMTV still need further research, particularly in terms of transovarial transmission. In this study, an investigation was conducted to explore the presence of JMTV from engorged female ticks to their offspring. All engorged female adult ticks were collected from domestic cattle and allowed to lay eggs in appropriate humidity and temperature conditions. Maternal ticks, eggs and larvae were screened for JMTV RNA through real-time polymerase chain reaction (RT-PCR) and nested PCR methods. The results revealed the positive rate of 10.53% (10/95) in engorged ticks, 9.09% (2/22) in eggs and 8% (4/50) in larvae pools, respectively. Phylogenetic analysis confirmed that sequences from eggs and larvae had closer relationship with those isolates from maternal engorged ticks with more than 99.7% homology and JMTV manifested with evolutional conservatism. Our study has identified for the first time that JMTV could be transmitted from mother generation to offspring of Haemaphysalis Longicornis. Nonetheless, the efficiency of transovarial transmission in JMTV and the significance of ticks as amplification hosts still need to be further illustrated.

Body Mass Index and Cancer Risk: An Umbrella Review of Meta-Analyses of Observational Studies.

Increasing evidence indicates that obesity is a risk factor for various tumors. We aimed to clarify the evidence for an association between body mass index (BMI) and cancer risk based on existing systematic reviews and meta-analyses. Eighteen studies were included in this umbrella review after searching PubMed, Embase and Web of science. The results revealed that underweight was inversely associated with the incidence of brain tumors and positively related to the risk of esophageal and lung cancer. Overweight enhances the incidence of brain tumors, kidney cancer, endometrial cancer, ovarian cancer, multiple myeloma, bladder cancer and liver cancer. Obesity was related to the increased incidence of brain tumors, cervical cancer, kidney cancer, endometrial cancer, esophageal cancer, gastric cancer, ovarian cancer, multiple myeloma, gallbladder cancer, bladder cancer, colorectal cancer, liver cancer, thyroid cancer and Hodgkin's lymphoma. Moreover, dose-response analysis was conducted by 10 studies, and the results demonstrated that each 5 Kg/m2 increase in BMI was associated with a 1.01- to 1.13-fold increased risk of general brain tumors, multiple myeloma, bladder cancer, pancreatic cancer, breast cancer, and non-Hodgkin's lymphoma. Every 1 Kg/m2 increase in BMI was linked to 6% and 4% increases in the risk of kidney cancer and gallbladder cancer, respectively.

Interleukin-22 facilitates the interferon-λ-mediated production of tripartite motif protein 25 to inhibit replication of duck viral hepatitis A virus type 1.

The innate immune system provides a defense against invading pathogens by inducing various interferon (IFN)-stimulated genes (ISGs). We recently reported that tripartite motif protein 25 (TRIM25), an important ISG, was highly upregulated in duck embryo hepatocyte cells (DEFs) after infection with duck viral hepatitis A virus type 1 (DHAV-1). However, the mechanism of upregulation of TRIM25 remains unknown. Here we reported that interleukin-22 (IL-22), whose expression was highly facilitated in DEFs and various organs of 1-day-old ducklings after DHAV-1 infection, highly enhanced the IFN-λ-induced production of TRIM25. The treatment with IL-22 neutralizing antibody or the overexpression of IL-22 highly suppressed or facilitated TRIM25 expression, respectively. The phosphorylation of signal transducer and activator of transcription 3 (STAT3) was crucial for the process of IL-22 enhancing IFN-λ-induced TRIM25 production, which was suppressed by WP1066, a novel inhibitor of STAT3 phosphorylation. The overexpression of TRIM25 in DEFs resulted in a high production of IFNs and reduced DHAV-1 replication, whereas the attenuated expression of IFNs and facilitated replication of DHAV-1 were observed in the RNAi group, implying that TRIM25 defended the organism against DHAV-1 propagation by inducing the production of IFNs. In summary, we reported that IL-22 activated the phosphorylation of STAT3 to enhance the IFN-λ-mediated TRIM25 expression and provide a defense against DHAV-1 by inducing IFN production.

Applications of sulfonyl hydrazides in radical cyclization of alkenes.

Radical cyclization is regarded as a powerful and promising strategy for the assembly of diverse important cyclic structures because of its high atom- and step-economy. As excellent radical acceptors, alkenes offer two potential directions, pushing the research domain of radical cyclization. In this context, as a radical precursor, sulfonyl hydrazide plays an important role in accomplishing radical cyclization of alkenes in a facile and efficient way. This review focuses on the applications of sulfonyl hydrazides in radical cyclization of alkenes, which generally has two radical conversion modes, sulfonyl radicals and sulfoxide radicals. In particular, the section of sulfonyl radicals consists of eight parts containing aromatic rings, alkenes, alkynes, cyanides, aldehydes, carboxylic acids, amides, and small ring compounds, according to the objects of cyclization after addition with alkenes. Within each category, representative instances are presented and discussed in terms of their general mechanistic perspectives when needed.

A transfer learning nomogram for predicting prostate cancer and benign conditions on MRI.

BACKGROUND: Deep learning has been used to detect or characterize prostate cancer (PCa) on medical images. The present study was designed to develop an integrated transfer learning nomogram (TLN) for the prediction of PCa and benign conditions (BCs) on magnetic resonance imaging (MRI). METHODS: In this retrospective study, a total of 709 patients with pathologically confirmed PCa and BCs from two institutions were included and divided into training (n = 309), internal validation (n = 200), and external validation (n = 200) cohorts. A transfer learning signature (TLS) that was pretrained with the whole slide images of PCa and fine-tuned on prebiopsy MRI images was constructed. A TLN that integrated the TLS, the Prostate Imaging-Reporting and Data System (PI-RADS) score, and the clinical factor was developed by multivariate logistic regression. The performance of the TLS, clinical model (CM), and TLN were evaluated in the validation cohorts using the receiver operating characteristic (ROC) curve, the Delong test, the integrated discrimination improvement (IDI), and decision curve analysis. RESULTS: TLS, PI-RADS score, and age were selected for TLN construction. The TLN yielded areas under the curve of 0.9757 (95% CI, 0.9613-0.9902), 0.9255 (95% CI, 0.8873-0.9638), and 0.8766 (95% CI, 0.8267-0.9264) in the training, internal validation, and external validation cohorts, respectively, for the discrimination of PCa and BCs. The TLN outperformed the TLS and the CM in both the internal and external validation cohorts. The decision curve showed that the TLN added more net benefit than the CM. CONCLUSIONS: The proposed TLN has the potential to be used as a noninvasive tool for PCa and BCs differentiation.

Oleanolic acid inhibits mercury chloride induced-liver ferroptosis by regulating ROS/iron overload.

Mercury chloride can cause severe liver injury, which involves multiple mechanisms. Ferroptosis plays an important role in regulating the development and progression of liver pathology. Oleanolic acid (OA), a triterpenoid compound widely exists in fruits, has liver protective properties. In this study, we investigated the role of ferroptosis in mercury chloride-induced liver injury and the intervention effect of OA, and clarified the potential mechanism. We found that mercury chloride-induced oxidative stress in liver tissues and cells, leading to lipid peroxidation and iron overload, thereby reducing the expression levels of GPX4 and SLC7A11, and increasing the expression level of TRF1, OA pretreatment improved the changes of GPX4, SLC7A11 and TRF1 induced by mercury chloride, which were related to its inhibition of oxidative stress. Furthermore, We pretreated cells with OA, VC, and Fer-1, respectively and found that VC pretreatment reduced oxidative stress and significantly reversed the gene and protein expressions of GPX4, SLC7A11, and TRF1 in mercury chloride-exposed cells (P < 0.05, vs. HgCl2 group), however, the protein expression level of GPX4 in OA pre-treatment group was lower than that in VC pre-treatment group (P < 0.05). Fer-1 pretreatment decreased the level of iron ions in cells, increased the gene and protein expression levels of GPX4 and SLC7A11, and decreased the gene and protein expression levels of TRF1 (P < 0.05, vs. HgCl2 group), however, the protein expression levels of GPX4 and SLC7A11 in OA pre-treatment group were lower than those in Fer-1 pre-treatment group (P < 0.05). Moreover, vivo experiments also demonstrated that pre-treatment with OA, VC, and Fer-1 reversed the changes in gene expression levels of Nrf2 and SOD1, and protein expression of GPX4 induced by mercury chloride (P < 0.05, vs. HgCl2 group), meanwhile, the difference was not statistically significant among OA, VC, and Fer-1 pretreatment. The improvement effect of OA pretreatment on the change in TFR1 protein expression caused by mercury chloride was similar to that of Fer-1 and VC, however, the intervention effect of OA on SLC7A11 protein expression was not as good as Fer-1 and VC pre-treatment. To sum up, all these results suggest that ferroptosis is involved in mercury chloride-induced liver injury, OA pretreatment alleviated mercury chloride-induced ferroptosis by inhibiting ROS production and iron ion overload, and then alleviate the liver injury.

Three-Dimensional Droplet Manipulation with Electrostatic Levitation.

An active and precise method for three-dimensional (3D) droplet manipulation is introduced. By modulating the local electrostatic force acting on droplets in carrier oil between needle plate electrodes, the vertical motion of droplets can be controlled, including the droplet levitation at the interface between the carrier oil and the air. Levitated droplets can be translated horizontally with high efficiency by the motion of the needle electrode. With controllable local deformation on the flexible plate electrode, selective manipulation can be realized for multiple droplets. Applying the manipulation method proposed, a platform is built and various droplet handling, such as transport, merging, and mixing, is performed effectively. Complex droplet transport trajectories are achieved by moving the needle electrode. The droplet transport velocity can reach up to 37 mm/s. The introduced method has fundamental advantages of avoiding cross-contamination between droplets, enhancing the flexibility, eliminating the transport track constraint, and lowering costs with straightforward and precise droplet manipulation.

The Controlling Nutritional Status (CONUT) Score and Prognosis in Malignant Tumors: A Systematic Review and Meta-Analysis.

Increasing evidences indicate that the controlling nutritional status (CONUT) score is associated with cancer prognosis. This study was conducted to investigate the prognostic significance of pretreatment CONUT score on patients with various malignant tumors. The correlation between CONUT score and clinical outcomes of tumor patients were studied by electronic literature retrieval. Pooled hazard ratios (HR), odds ratios (OR) and 95% confidence intervals (95% CI) were calculated to clarify the conclusion. Subgroup analysis were conducted in line with cancer type, cancer stage, treatment, sample size and cut-off value. A total of 62 studies involving 25224 patients were included in this study. Pooled analysis showed that higher CONUT scores were associated with shorter overall survival (HR 1.62, 95% CI 1.45-1.79, p < 0.001), cancer-specific survival (HR 1.80, 95% CI 1.48-2.13, p < 0.001), progress/recurrence-free survival (HR 1.54, 95% CI 1.23-1.85, p < 0.001) and disease-free survival (HR 1.56, 95% CI 1.39-1.74, p < 0.001). In addition, high CONUT score was correlated to higher incidence of postoperative complications (OR 1.64, 95% CI 1.38-1.95, p < 0.001) and mortality (OR 4.22, 95% CI 2.22-8.02, p < 0.001). Consequently, the pretreatment CONUT score is a valuable indicator to predict the clinical outcomes of patients with various malignant tumors.

Second Malignant Tumors and Non-Tumor Causes of Death for Patients With Penile Cancer During Their Survivorship.

BACKGROUND: The aim was to evaluate the causes of death for patients with localized, regional and metastatic penile cancer (PeCa) after diagnosis. METHODS: PeCa patients diagnosed during 2004-2018 in the Surveillance, Epidemiology, and End Results program database were identified. Causes of deaths including PeCa, second malignant tumors (SMTs) and non-tumor diseases were analyzed, as well as the standardized mortality ratio (SMR) of each cause. RESULTS: For localized PeCa, 800 of 2155 patients died during the follow-up. 24.9% of all deaths were due to PeCa. 18.0% and 57.1% deaths were due to SMTs and non-tumor causes. Main SMTs included cancers of lung and bronchus (n = 40) and skin (n = 11) with significantly increased SMRs of 1.71 (1.22-2.33) and 4.82 (2.41-8.63). Mortality risks of other SMTs were mostly similar with the general populations. Main causes of non-tumor diseases included diseases of heart [n = 172, SMR: 1.66 (1.42-1.93)], COPD and allied cond [n = 38, SMR: 1.63 (1.15-2.24)], and cerebrovascular diseases [n = 33, SMR: 1.71 (1.17-2.4)]. For regional PeCa, 679 of 1310 patients died including 43.5% PeCa, 14.8% SMTs and 26.6% non-tumor causes. The mortality risks of cancers from lung and bronchus [SMR: 2.41 (1.53-3.62)], skin [SMR: 6.41 (2.35-13.95)] and testis [SMR: 149.35 (18.09-539.5)] were significantly increased. Main non-tumor causes of death included diseases of heart [n = 71, SMR: 1.77 (1.38-2.23)], COPD and allied cond [n = 17, SMR: 1.85 (1.08-2.95)] and diabetes mellitus [n = 16, SMR: 3.62 (2.07-5.88)]. For distant diseases, 109 of 132 patients died including 76 (69.7%) died for PeCa itself, 24 (22.0%) died for SMTs and 9 (8.3%) died for non-tumor diseases. The majority of PeCa deaths (67.1%) and SMTs deaths (79.2%) occurred within 1 year after the diagnosis of PeCa. CONCLUSIONS: We firstly analyzed the SMTs and non-tumor causes of death and morality risks of each cause for PeCa patients, which provided valuable information for PeCa patients on disease prevention and health care during their survivorship.

The prognostic value of the Controlling Nutritional Status score on patients undergoing nephrectomy for upper tract urothelial carcinoma or renal cell carcinoma: a systematic review and meta-analysis.

In recent years, the controlling nutritional status (CONUT) score has increasingly became an effective indicator associated with tumor prognosis. This study was conducted to synthesise data on the prognostic value of CONUT score on patients with upper tract urothelial carcinoma (UTUC) or renal cell carcinoma (RCC) undergoing nephrectomy. We designed and performed a systematic analysis of studies that verified the correlation between preoperative CONUT score and prognosis for UTUC and RCC using PubMed, Web of Science and Embase. The conclusion was clarified by pooled hazard ratios (HR) and 95% confidence intervals (95% CI). Subgroup analysis were further conducted in accordance with different primary tumor. Six studies involving 3529 patients were included in this evidence synthesis, which revealed that the CONUT score had a potential role to predict the survival of UTUC and RCC patients accepting surgery. Pooled analysis showed that the overall survival (OS, HR 2·32, p < 0·0001), cancer-specific survival (CSS, HR 2·68, p < 0·0001) and disease-free survival (DFS, HR 1·62, p < 0·00001) were inferior in the high CONUT score group when compared with low score group. Subgroup analysis revealed that this result was in line with UTUC (OS: HR 1·86, p = 0·02; CSS: HR 2·24, p = 0·01; DFS: HR 1·54, p < 0·00001) and RCC (OS: HR 3·05, p < 0·00001; CSS: HR 3·47, p < 0·00001; DFS: HR 2·21, p = 0·0005) patients respectively. Consequently, the CONUT score is a valuable preoperative index to predict the survival of patients with UTUC or RCC undergoing nephrectomy.

Salidroside prevents PM2.5-induced BEAS-2B cell apoptosis via SIRT1-dependent regulation of ROS and mitochondrial function.

PM2.5 is a harmful air pollutant currently threatening public health. It has been closely linked to increased morbidity of bronchial asthma and lung cancer worldwide. Salidroside (Sal), an active component extracted from Rhodiola rosea, has been reported to ameliorate the progression of asthma. However, there are few studies on the protective effect of salidroside on PM2.5-induced bronchial epithelial cell injury, and the related molecular mechanism is not clear. Here, we aimed to explore the protective effect and related mechanism of Sal on PM2.5 bronchial injury. We chose 50 µg/mL PM2.5 for 24 h as a PM2.5-induced cell damage model. After that BEAS-2B cells were pretreated with 40, 80, 160 µM Sal for 24 h and then exposed to 50 µg/mL PM2.5 for 24 h. We found that Sal pretreatment significantly inhibited the decrease of cell viability induced by PM2.5. Sal was effective in preventing PM2.5-induced apoptotic features, including Ca2+ overload, the cleavages of caspase 3, and the increases in levels of caspase 9 and Bcl-2-associated X protein (Bax), ultimately, Sal significantly inhibited PM2.5-induced apoptosis. Sal improved mitochondrial membrane potential, inhibited the release of cytochrome c from the mitochondria to cytoplasm. Sal alleviated ROS production, decreased the level of MDA, prevented the reduction of CAT, SOD and GSH-Px and increased the expression of NF-E2-related factor 2 (Nrf2), HO-1 and superoxide dismutase 1 (SOD1) in cells exposed to PM2.5. Furthermore, Sal improved the decrease of SIRT1 and PGC-1 α expression levels caused by PM2.5. In addition, inhibition of SIRT1 by EX527 (SIRT1 inhibitor) reversed the protective effects of Sal, including the decrease of ROS level, the increase of membrane potential level and the decrease of apoptosis level. Thus, Sal may be regarded as a potential drug to prevent PM2.5-induced apoptosis of bronchial epithelial cells and other diseases with similar pathological mechanisms.

Source, occurrence and risks of twenty antibiotics in vegetables and soils from facility agriculture through fixed-point monitoring and numerical simulation.

In this study, a universal method that combined fixed-point monitoring and numerical simulation was used to understand the source, fate and risks of antibiotics in environment. Results showed that the antibiotic concentration in vegetables, soil and manure from 53 fixed-point monitoring sampling sites were ND-18.47, ND-1438.50 and ND-24710.00 µg kg-1, respectively. There were positive correlations between the antibiotic concentrations of vegetables and soil as well as between soil and manure. The average Amountsoil/manure values were 1.48-46.02, indicating that antibiotics built up pseudo persistent residues in soil due to repeated fertilization. The modified level-III fugacity model showed that tetracyclines and fluoroquinolones tend to remain in soil given their sorption and mobility, while sulfonamides were highly distributed in plants, especially in leaves. Norfloxacin, ofloxacin, sulfadiazine, sulfamethoxazole and sulfisoxazole were found to be risk factors in facility agriculture and should be continuously monitored during agricultural production. Most importantly, we used the inversion method to determine the recommended maximum residue limits of antibiotics in soil. This will not only allow for better control of the amount of the antibiotics in the environment, but also act as a potential method to assess the risks of pollutants without maximum residue limits in the environment.

CXCL10 encoding synNotch T cells enhance anti-tumor immune responses without systemic side effect.

Modifying T cells to attack tumors using engineered chimeric receptors display powerful new therapeutic capabilities. Unfortunately, the effectiveness of therapeutic T cells is limited due to the inherent T cell responses: certain facets of endogenous response programs may be toxic, and the ability to overcome the immunosuppression in TME is deficient. Here we developed a Notch receptor based synNotch T cell platform that is able to response to target tumor cells and selectively lead to CXCL10 production. Further study showed that the administration of synNotch T cells significantly inhibited the tumor growth in a humanized murine model, accompanied by the increased infiltration of CD3+T cells and elevated level of CXCL10 and IFN-γ in the tumor site. A slightly increased level of CXCL10 and limited IFN-γ were found in the serum in mice received synNotch T cells, suggesting a high security of this treatment. Finally, we demonstrated that CXCL10 is sufficient and indispensable for the synNotch T cells induced anti-tumor effect. This study provided theoretical and experimental bases for the clinical implication of CXCL10 encoding synNotch T cells.

Differences in verbal and spatial working memory in patients with bipolar II and unipolar depression: an MSI study.

BACKGROUND: Depressive symptoms could be similarly expressed in bipolar and unipolar disorder. However, changes in cognition and brain networks might be quite distinct. We aimed to find out the difference in the neural mechanism of impaired working memory in patients with bipolar and unipolar disorder. METHOD: According to diagnostic criteria of bipolar II disorder of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and assessments, 13 bipolar II depression (BP II), 8 unipolar depression (UD) patients and 15 healthy controls (HC) were recruited in the study. We used 2-back tasks and magnetic source imaging (MSI) to test working memory functions and get the brain reactions of the participants. RESULTS: Compared with HC, only spatial working memory tasks accuracy was significantly worse in both UD and BP II (p = 0.001). Pearson correlation showed that the stronger the FCs' strength of MFG-IPL and IPL-preSMA, the higher accuracy of SWM task within left FPN in patients with UD (r = 0.860, p = 0.006; r = 0.752, p = 0.031). However, the FC strength of IFG-IPL was negatively correlated with the accuracy of SWM task within left FPN in patients with BP II (r = - 0.591, p = 0.033). CONCLUSIONS: Our study showed that the spatial working memory of patients with whether UD or BP II was impaired. The patterns of FCs within these two groups of patients were different when performing working memory tasks.