Unraveling the mechanism of norfloxacin removal and fate of antibiotics resistance genes (ARGs) in the sulfur-mediated autotrophic denitrification via metagenomic and metatranscriptomic analyses.

The co-contamination of antibiotics and nitrogen has attracted widespread concerns due to its potential harm to ecological safety and human health. Sulfur-driven autotrophic denitrification (SAD) with low sludge production rate was adopted to treat antibiotics laden-organic deficient wastewater. Herein, a lab-scale sequencing batch reactor (SBR) was established to explore the simultaneous removal of nitrate and antibiotics, i.e. Norfloxacin (NOR), as well as microbial response mechanism of SAD sludge system towards NOR exposure. About 80.78 % of NOR was removed by SAD sludge when the influent NOR level was 0.5 mg/L, in which biodegradation was dominant removal route. The nitrate removal efficiency decreased slightly from 98.37 ± 0.58 % to 96.58 ± 1.03 % in the presence of NOR. Thiobacillus and Sulfurimonas were the most abundant sulfur-oxidizing bacteria (SOB) in SAD system, but Thiobacillus was more sensitive to NOR. The up-regulated genes related to Xenobiotics biodegradation and metabolism and CYP450 indicated the occurrence of NOR biotransformation in SAD system. The resistance of SAD sludge to the exposure of NOR was mainly ascribed to antibiotic efflux. And the effect of antibiotic inactivation was enhanced after long-term fed with NOR. The NOR exposure resulted in the increased level of antibiotics resistance genes (ARGs) and mobile genetic elements (MGEs). Besides, the enhanced ARG-MGE co-existence patterns further reveals the higher horizontal mobility potential of ARGs under NOR exposure pressures. The most enriched sulfur oxidizing bacterium Thiobacillus was a potential host for most of ARGs. This study provides a new insight for the treatment of NOR-laden wastewater with low C/N ratio based on the sulfur-mediated biological process.

Synergistic effects of adsorption and chemical reduction towards the effective Cr(VI) removal in the presence of the sulfur-doped biochar material.

In this study, the anaerobic sludge withdrawn from thickener in a sewage treatment plant served as the precursor for sludge-based biochar fabrication, which was further modified via sulfur (S) heteroatom doping (i.e., S-BC). The S atom doping resulted in the adjustment of the physicochemical properties towards the carbon material, endowment of abundant functional groups on biochar surface, and increasing the binding sites between biochar and Cr(VI). Compared to the primary biochar (i.e., biochar without heteroatomic doping, named BC), S-BC exhibited a rough surface and possessed remarkable advantages in ash content, specific surface area, and pore volume. The existence of graphene carbon crystal structure for S-BC was confirmed through S-BC by XRD and FTIR analysis. The studies of adsorption kinetics and isotherms showed that pseudo-second-order kinetics and the Langmuir model more fitted the Cr(VI) removal behavior in the presence of S-BC. Therefore, the chemisorption and monolayer adsorption were the primary mechanisms involved in the Cr(VI) removal process. Additionally, XPS analysis results illustrated the aqueous Cr(VI) was efficiently eliminated through the synergistic effect of chemisorption and reduction to Cr(III) in the presence of S-BC. Moreover, S-BC could still achieve the Cr(VI) eliminating efficiency of 85.31% undergoing five cycles with unchanged functional group and crystal structure via FTIR and XRD analysis. Thus, the results of this study may shed light on a new approach for simultaneous economical sludge disposal and the sustainable remediation of the Cr(VI)-contaminated wastewater.

NiCo layered double hydroxides/NiFe layered double hydroxides composite (NiCo-LDH/NiFe-LDH) towards efficient oxygen evolution in different water matrices.

Engineering robust non-noble metal electrocatalysts towards efficient impure water (e.g., seawater, wastewater) oxidation is a prospective approach to achieve carbon neutrality via accelerating green hydrogen energy development. Herein, a NiCo layered double hydroxides (LDH)/NiFe LDH composite (NiCo-LDH/NiFe-LDH) was developed for oxygen evolution reaction (OER) via a hydrothermal process-electrodeposition method. The optimal NiCo-LDH/NiFe-LDH-30 composite only needed an overpotential (η) of 240 mV to drive 100 mA/cm2 in alkalized freshwater, with a low Tafel slope of 16.6 mV/dec and good stability for over 90 h. Further analyses suggested that the strong interface interaction between NiCo-LDH and NiFe-LDH accelerated the oxygen gas bubble evolution and boosted interfacial charge transfer, and the formed built-in electric field and higher oxidation state species (metal oxyhydroxides) contributed to the high intrinsic catalytic activity. The NiCo-LDH/NiFe-LDH-30 composite also held excellent OER activities in different impure water environments, including alkaline 0.5 M NaCl solution (η100 = 333 mV), alkaline lake water (η100 = 345 mV), and alkaline wastewater treatment plant (WWTP) effluent (η100 = 320 mV). More importantly, the potential effects of Cl- and CO32- in impure water were revealed during the OER process. This work elaborates on the role of built-in electric field and the strong coupling interaction in composite catalysts, which pave the way for the design of cost-effective catalysts with excellent adaptability in different water environments.

Sulfur-decorated Fe/C composite synthesized from MIL-88A(Fe) for peroxymonosulfate activation towards tetracycline degradation: Multiple active sites and non-radical pathway dominated mechanism.

Peroxymonosulfate (PMS)-mediated advanced oxidation processes gain growing attention in degrading antibiotics (e.g., tetracycline (TC)) in wastewater for their high capacity and relatively low cost, while designing efficient catalysts for PMS activation remains a challenge. In this study, a sulfur-doped Fe/C catalyst (Fe@C-S) synthesized from iron metal-organic frameworks (Fe-MOFs) was developed for PMS activation towards TC removal. Under optimal conditions, the TC removal efficiency of Fe@C-S150/PMS system within 40 min was 91.2%. Meanwhile, the k value for Fe@C-S150/PMS system (0.2038 min-1) was 3.36-fold as high as the S-free Fe@C-based PMS system. Also, Fe@C-S150/PMS system showed high robustness in different water matrices. Further studies found that the TC degradation mechanism was mainly ascribed to the non-radical pathway (1O2 and electron transfer). Fe nanoparticles, S and CO groups on the catalyst all participated in the generation of reactive oxygen species (ROS). Besides, S species could enhance the Fe2+/Fe3+ redox cycle and accelerate the electron transfer process. This work highlights the critical role of S in enhancing the catalytic performance of Fe/C-based catalysts for PMS activation, which would provide meaningful insights into the design of high-performance PMS activators for the sustainable remediation of emerging contaminants-polluted water bodies.

Synthesis of bifunctional NiFe layered double hydroxides (LDH)/Mo-doped g-C3N4 electrocatalyst for efficient methanol oxidation and seawater splitting.

To boost the oxygen evolution reaction (OER) and methanol oxidation reaction (MOR) of pristine NiFe-layered double hydroxides (LDH), the NiFe-LDH/Mo-doped graphitic carbon nitride (NiFe-LDH/MoCN) heterojunction was synthesized herein through hydrothermal method. The establishment of built-in electric field in NiFe-LDH/MoCN heterojunction enhanced the electrochemical oxidation activities towards both seawater splitting and methanol oxidation, via the improving electrocatalyst surface wettability and conductivity. Almost 10-fold enhancement of turnover frequency (TOF) and electrochemical active surface area (ECSA) than pure NiFe-LDH implied more active sites to participate in catalytic reactions via Mo doping and the formation of heterostructure. Moreover, the local charge redistribution demonstrated in the NiFe-LDH/MoCN interface region may favor the adsorption of methanol and OH- in the seawater. The present work may expound the strong coupling interaction and the establishment of built-in electric field in the interface between NiFe-LDH and semiconductor to enhance both methanol oxidation and seawater oxidation for NiFe-LDH.

Assessing electrocardiogram changes after ischemic stroke with artificial intelligence.

OBJECTIVE: Ischemic stroke (IS) with subsequent cerebrocardiac syndrome (CCS) has a poor prognosis. We aimed to investigate electrocardiogram (ECG) changes after IS with artificial intelligence (AI). METHODS: We collected ECGs from a healthy population and patients with IS, and then analyzed participant demographics and ECG parameters to identify abnormal features in post-IS ECGs. Next, we trained the convolutional neural network (CNN), random forest (RF) and support vector machine (SVM) models to automatically detect the changes in the ECGs; Additionally, We compared the CNN scores of good prognosis (mRS ≤ 2) and poor prognosis (mRS > 2) to assess the prognostic value of CNN model. Finally, we used gradient class activation map (Grad-CAM) to localize the key abnormalities. RESULTS: Among the 3506 ECGs of the IS patients, 2764 ECGs (78.84%) led to an abnormal diagnosis. Then we divided ECGs in the primary cohort into three groups, normal ECGs (N-Ns), abnormal ECGs after the first ischemic stroke (A-ISs), and normal ECGs after the first ischemic stroke (N-ISs). Basic demographic and ECG parameter analyses showed that heart rate, QT interval, and P-R interval were significantly different between 673 N-ISs and 3546 N-Ns (p < 0.05). The CNN has the best performance among the three models in distinguishing A-ISs and N-Ns (AUC: 0.88, 95%CI = 0.86-0.90). The prediction scores of the A-ISs and N-ISs obtained from the all three models are statistically different from the N-Ns (p < 0.001). Futhermore, the CNN scores of the two groups (mRS > 2 and mRS ≤ 2) were significantly different (p < 0.05). Finally, Grad-CAM revealed that the V4 lead may harbor the highest probability of abnormality. CONCLUSION: Our study showed that a high proportion of post-IS ECGs harbored abnormal changes. Our CNN model can systematically assess anomalies in and prognosticate post-IS ECGs.

Revealing the mechanisms of polypyrrole (Ppy) enhancing methane production from anaerobic digestion of waste activated sludge (WAS).

Anaerobic digestion (AD) is a promising method for treating waste activated sludge (WAS), but the low methane yield limits its large-scale application. The addition of conductive nanomaterials has been demonstrated to enhance the activity of AD via promoting the direct interspecies electron transfer (DIET). In this study, novel conductive polypyrrole (Ppy) was prepared to effectively improve the AD performance of WAS. The results showed that the accumulative methane production was enhanced by 27.83% by Ppy, with both acidogenesis and methanogenesis being efficiently accelerated. The microbial community analysis indicated that the abundance of bacteria associated with acidogenesis process was significantly elevated by Ppy. Further investigation by metatranscriptomics revealed that fadE and fadN genes (to express the key enzymes in fatty acid metabolism) were highly expressed in the Ppy-driven AD, suggesting that Ppy promoted electron generation during acid production. For methanogenesis metabolism, genes related to acetate utilization and CO2 utilization methanogenesis were also up-regulated by Ppy, illustrating that Ppy facilitates the utilization of acetate and electrons by methanogenic archaea, thus potentially promoting the methanogenesis through DIET.

Comparative effects of left bundle branch area pacing, His bundle pacing, biventricular pacing in patients requiring cardiac resynchronization therapy: A network meta-analysis.

BACKGROUND: The comparative effects of different types of cardiac resynchronization therapy (CRT) delivered by biventricular pacing (BVP), His bundle pacing (HBP), and left bundle branch area pacing (LBBAP) remain inconclusive. HYPOTHESIS: HBP and LBBAP may be advantageous over BVP for CRT. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched for studies that reported the effects after BVP, HBP, and LBBAP for CRT. The effects between groups were compared by a frequentist random-effects network meta-analysis (NMA), by which the mean differences (MDs) and 95% confidence intervals (CIs) were calculated. RESULTS: Six articles involving 389 patients remained for the final meta-analysis. The mean follow-up of these studies was 8.03 ± 3.15 months. LBBAP resulted in a greater improvement in LVEF% (MD = 7.17, 95% CI = 4.31 to 10.04), followed by HBP (MD = 4.06, 95% CI = 1.09 to 7.03) compared with BVP. HBP resulted in a narrower QRS duration (MD = 31.58 ms, 95% CI = 12.75 to 50.40), followed by LBBAP (MD = 27.40 ms, 95% CI = 10.81 to 43.99) compared with BVP. No significant differences of changes in LVEF improvement and QRS narrowing were observed between LBBAP and HBP. The pacing threshold of LBBAP was significantly lower than those of BVP and HBP. CONCLUSION: The NMA first found that LBBAP and HBP resulted in a greater LVEF improvement and a narrower QRS duration compared with BVP. Additionally, LBBAP resulted in similar clinical outcomes but with lower pacing thresholds, and may therefore offer advantages than does HBP for CRT.

Long-term outcomes of left bundle branch area pacing versus biventricular pacing in patients with heart failure and complete left bundle branch block.

Left bundle branch area pacing (LBBAP) has developed in an effort to improve cardiac resynchronization therapy (CRT). We aimed to compare the long-term clinical outcomes between LBBAP and biventricular pacing (BIVP) in patients with heart failure (HF) and complete left bundle branch block (CLBBB). Consecutive patients with HF and CLBBB requiring CRT received either LBBAP or BIVP were recruited at the Second Affiliated Hospital of Nanchang University from February 2018 to May 2019. We assessed their implant parameters, electrocardiogram (ECG), clinical outcomes at implant and during follow-up at 1, 3, 6, 12, and 24 months. Forty-one patients recruited including 21 for LBBAP and 20 for BIVP. Mean follow-up duration was 23.71 ± 4.44 months. LBBAP produced lower pacing thresholds, shorter procedure time and fluoroscopy duration compared to BIVP. The QRS duration was significantly narrower after LBBAP than BIVP (129.29 ± 31.46 vs. 156.85 ± 26.37 ms, p = 0.005). Notably, both LBBAP and BIVP significantly improved LVEF, LVEDD, NYHA class, and BNP compared with baseline. However, LBBAP significantly lowered BNP compared with BIVP (416.69 ± 411.39 vs. 96.07 ± 788.71 pg/ml, p = 0.007) from baseline to 24-month follow-up. Moreover, patients who received LBBAP exhibited lower number of hospitalizations than those in the BIVP group (p = 0.019). In addition, we found that patients with moderately prolonged left ventricular activation time (LVAT) and QRS notching in limb leads in baseline ECG respond better to LBBAP for CLBBB correction. LBBAP might be a relative safe and effective resynchronization therapy and as a supplement to BIVP for patients with HF and CLBBB.

Development and validation of a deep learning model to screen hypokalemia from electrocardiogram in emergency patients.

BACKGROUND: A deep learning model (DLM) that enables non-invasive hypokalemia screening from an electrocardiogram (ECG) may improve the detection of this life-threatening condition. This study aimed to develop and evaluate the performance of a DLM for the detection of hypokalemia from the ECGs of emergency patients. METHODS: We used a total of 9908 ECG data from emergency patients who were admitted at the Second Affiliated Hospital of Nanchang University, Jiangxi, China, from September 2017 to October 2020. The DLM was trained using 12 ECG leads (lead I, II, III, aVR, aVL, aVF, and V1-6) to detect patients with serum potassium concentrations <3.5 mmol/L and was validated using retrospective data from the Jiangling branch of the Second Affiliated Hospital of Nanchang University. The blood draw was completed within 10 min before and after the ECG examination, and there was no new or ongoing infusion during this period. RESULTS: We used 6904 ECGs and 1726 ECGs as development and internal validation data sets, respectively. In addition, 1278 ECGs from the Jiangling branch of the Second Affiliated Hospital of Nanchang University were used as external validation data sets. Using 12 ECG leads (leads I, II, III, aVR, aVL, aVF, and V1-6), the area under the receiver operating characteristic curve (AUC) of the DLM was 0.80 (95% confidence interval [CI]: 0.77-0.82) for the internal validation data set. Using an optimal operating point yielded a sensitivity of 71.4% and a specificity of 77.1%. Using the same 12 ECG leads, the external validation data set resulted in an AUC for the DLM of 0.77 (95% CI: 0.75-0.79). Using an optimal operating point yielded a sensitivity of 70.0% and a specificity of 69.1%. CONCLUSIONS: In this study, using 12 ECG leads, a DLM detected hypokalemia in emergency patients with an AUC of 0.77 to 0.80. Artificial intelligence could be used to analyze an ECG to quickly screen for hypokalemia.

Overexpression of the Apple (Malus × domestica) MdERF100 in Arabidopsis Increases Resistance to Powdery Mildew.

APETALA2/ETHYLENE RESPONSIVE FACTOR (AP2/ERF) transcription factors play important roles in plant development and stress response. Although AP2/ERF genes have been extensively investigated in model plants such as Arabidopsis thaliana, little is known about their role in biotic stress response in perennial fruit tree crops such as apple (Malus × domestica). Here, we investigated the role of MdERF100 in powdery mildew resistance in apple. MdERF100 localized to the nucleus but showed no transcriptional activation activity. The heterologous expression of MdERF100 in Arabidopsis not only enhanced powdery mildew resistance but also increased reactive oxygen species (ROS) accumulation and cell death. Furthermore, MdERF100-overexpressing Arabidopsis plants exhibited differential expressions of genes involved in jasmonic acid (JA) and salicylic acid (SA) signaling when infected with the powdery mildew pathogen. Additionally, yeast two-hybrid and bimolecular fluorescence complementation assays confirmed that MdERF100 physically interacts with the basic helix-loop-helix (bHLH) protein MdbHLH92. These results suggest that MdERF100 mediates powdery mildew resistance by regulating the JA and SA signaling pathways, and MdbHLH92 is involved in plant defense against powdery mildew. Overall, this study enhances our understanding of the role of MdERF genes in disease resistance, and provides novel insights into the molecular mechanisms of powdery mildew resistance in apple.

Expression of neuronal protein synuclein gamma gene as a novel marker for breast cancer prognosis.

Synucleins are emerging as central players in the fundamental neural processes and in the formation of pathologically insoluble deposits characteristic of neurodegenerative diseases. However, synuclein gamma (SNCG), previously identified as a breast cancer specific gene (BCSG1), is also highly expressed in breast carcinomas, but not expressed in normal or benign breast tissues. We analyzed SNCG gene expression in 93 clinical breast specimens and associated it with clinical outcome. Overall SNCG mRNA expression was detectable in 36% breast cancers. However, 81% of stage III/IV breast cancers were positive for SNCG expression, while only 15% of stage I/II breast cancers were positive for SNCG expression. In contrast, SNCG was undetectable in benign breast lesions. Expression of SNCG in the primary tumor also significantly associated with lymph node involvement and metastasis. There was no significant correlation between SNCG gene expression and age, menstruation, and status of ER, PR, PCNA, and HER-2. Patients whose tumors expressed SNCG had a significantly shorter DFS and a high probability of death when compared with those whose tumors did not express SNCG. The hazard ratio of metastasis or recurrence according to the SNCG status was 4.515 (95% CI, 1,188-17.154; P = 0.027). Cox multivariate analysis showed that SNCG had independent prognostic significance above and beyond conventional variables. This study suggests that the expression of SNCG is an independent predictive marker for recurrence and metastasis in breast cancer progression. SNCG is expected to be a useful marker for breast cancer progression and a potential target for breast cancer treatment.

[The effect of breast cancer specific gene 1 in the prognosis of breast cancer].

OBJECTIVE: To detect breast cancer specific gene 1 (BCSG1) expression in different breast tissue, analysis its correlation with clinical parameters and evaluate the prognosis of breast cancer. METHODS: The expression of BCSG1 was detected by reverse transcription-polymerase chain reaction (RT-PCR) in surgical specimens from 84 cases of breast disease patients selected randomly at XinHua Hospital affiliated with Shanghai Second Medical University from September 1999 to December 2002. Of 84 cases, 72 case were breast cancer. Statistic analysis BCSG1 gene expression correlation with clinical parameters of breast cancer. 72 breast cancers were followed up (4 - 43 months) to set up independent prognosis factor by survival analysis. RESULTS: BCSG1 was undetectable in all benign breast lesions, while was detectable in 36.1% of all breast cancer samples (26/72), in which 79.2% of stage III/IV cases were positive (19/24). The expression of BCSG1 was tightly correlated with the stage (P = 0.000) and the size of tumor (P = 0.007). Both ER (P = 0.027) and BCSG1 (P = 0.001) were the independent prognosis factor of breast cancer. CONCLUSION: BCSG1 is one of independent tumor marker of breast cancer, the expression of BCSG1 is closely correlated to the stage of breast cancer and the tumor size. Maybe, BCSG1 is a new prognosis factor of breast cancer.

Survivin antisense oligodeoxynucleotide inhibits growth of gastric cancer cells.

AIM: To investigate the effect of transfected survivin antisense oligonucleotide (ASODN) on proliferation and apoptosis of gastric cancer cells. METHODS: The authors designed ASODNs targeting different regions of survivin mRNA, including surviving ASODN1, ASODN2 and ASODN3. ASODNs were transfected into gastric cancer cell line SGC 7901, cell growth was detected by MTT assay. Cells exposed to the potent oligonucleotide were also examined for apoptosis induction by FCM and fluorescence microscopy. Semiquantitive RT-PCR and Western blot examinations were carried for expression of survivin mRNA and protein. RESULTS: ASODN3 caused a statistically significant reduction of cell viability to 60.6% (+/-2.9%) (P<0.01), while ASODN1 and ASODN2 had no such changes (P>0.05). The cell growth was also significantly inhibited by ASODN3, compared with reversal and scrambled sequence. A significant loss of survivin mRNA was presented in ASODN3 treated cells and this was not seen in treatment with sense ODN or scramble ODN. Protein level was significantly decreased 48 h after survivin ASODN trasfected by approximately 2-fold decrease compared with untreated controls. However, ASODN3 did not induce significant apoptosis response until 48 h after transfection (P>0.05). CONCLUSION: ASODN3, which targets translation initiation part, can be identified as a most potent antisense compound. Srvivin ASODN3 may provide a novel approach to therapy of gastric cancer.

Ets1 as a marker of malignant potential in gastric carcinoma.

AIM: Ets1 proto-oncogene is a transcription factor involved in the activation of several genes of tumor invasion and metastasis. We aimed to determine the relationship between the extent and intensity of Ets1 expression and patients' clinicopathological factors in gastric carcinoma. METHODS: Immunohistochemical analysis was performed for gastric tumor paraffin-embedded sections, followed by image analysis. RESULTS: Ets1 was not expressed in the normal gastric epithelium and its surrounding cells. The percentage of Ets1 expressing cells detected increased significantly in both epithelial tumor and stromal cells from high T classification, lymph node metastasis positive, clinical advanced-stage groups (P<0.001). The level of Ets1 staining in epithelial tumor cells also reflected the degree of cell differentiation. The percentage of epithelial and stromal cells expressing Ets1 was significantly correlated with the presence of lymph node metastasis (P=0.014 and P<0.001 respectively). Ets1 expression was not observed in tissue samples from patients with benign gastric ulcers. CONCLUSION: Ets1 protein expression in epithelial tumor cells reflects the degree of differentiation, and the percentage of Ets1 positive tumor and stromal cells correlates with lymph node metastasis. Thus Ets1 is a valuable marker of malignant potential in terms of invasiveness and metastasis of gastric carcinoma. It is also possible that inhibition of Ets1 is a potential avenue for therapy in gastric cancer.

Stage-specific expression of breast cancer-specific gene gamma-synuclein.

Gamma-synuclein (SNCG), also referred as breast cancer-specific gene 1, is the third member of a neuronal protein family synuclein. SNCG is highly expressed in human-infiltrating breast carcinomas but not expressed in normal or benign breast tissues. To evaluate the clinical relevance of SNCG expression in breast cancer progression and its correlation with clinical parameters, we analyzed SNCG expression in 79 clinical breast specimens from primary breast cancer, hyperplasia, and fibroadenoma patients by reverse transcription-PCR. The status of estrogen receptor, progesterone receptor, proliferating cell nuclear antigen, and C-erBb2 was also analyzed by immunohistochemistry. Overall SNCG mRNA expression was detectable in 38.8% of breast cancers. However, 79% of stage III/IV breast cancers were positive for SNCG expression, whereas only 15% of stage I/II breast cancers were positive for SNCG expression. In contrast, the expression of SNCG was undetectable in all benign breast lesions. The expression of SNCG was strongly correlated to the stage of breast cancer (P=0.000). This study suggests that the expression of SNCG is stage specific for breast cancer. SNCG is expected to be a useful marker for breast cancer progression and a potential target for breast cancer treatment.