Clinical Significance of Plasma D-Dimer and Fibrinogen in Outcomes after Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: There is increasing evidence on the prognostic significance of D-dimer and fibrinolysis in stroke. However, the systematic analysis of their relationship with adverse outcomes after stroke is lacking. Herein, we comprehensively assessed the correlation of D-dimer and fibrinolysis with stroke outcomes through meta-analysis. METHODS: Studies for systematic literature review were retrieved from PubMed, EMBASE, and Cochrane Library databases. The association of D-dimer and fibrinolysis with outcomes of stroke patients was expressed as an odds ratio (OR) with 95% confidence intervals (95% CI). RESULTS: Totally, 52 studies comprising 21,473 stroke patients were included. The results showed that the high D-dimer level was significantly associated with peripheral venous thrombosis after stroke (OR 1.03, 95% CI 1.01-1.05), poor outcome (MRS >2) after stroke (OR 1.731, 95% CI 1.464-2.048), death after stroke (OR 2.367, 95% CI 1.737-3.224), stroke recurrence (OR 1.229, 95% CI 1.113-1.358), and early neurologic deterioration (NIHSS >4) (OR 1.791, 95% CI 1.117-2.870). Moreover, high fibrinogen level was significantly associated with poor outcome (MRS >2) after stroke (OR 1.650, 95% CI 1.314-2.071), death after stroke (OR 1.310, 95% CI 1.128-1.520), stroke recurrence (OR 1.228, 95% CI 1.166-1.422), early neurologic deterioration (NIHSS >4) (OR 2.381, 95% CI 1.156-4.904), and coronary events after stroke (OR 1.427, 95% CI 1.232-1.653). CONCLUSION: Fibrinogen and D-dimer may be associated with adverse outcomes in patients with stroke, suggesting that they may serve as possible biomarkers for post-stroke adverse outcomes.

Characterization of oxidative stress-induced cgahp, a gene coding for alkyl hydroperoxide reductase, from industrial importance Corynebacterium glutamicum.

Alkyl hydroperoxide reductase (Ahp), comprised of four different subunits AhpC, AhpD, AhpE, and AhpF, is a thiol-based antioxidative enzyme with the ability to protect bacteria against oxidative stress. Functionally, AhpC and AhpE considered as peroxidases directly detoxify peroxides, while AhpD and AhpF as oxidoreductases restore oxidized peroxidases to their reduced form. Corynebacterium glutamicum ncgl0877 encodes a putative Ahp with a unique Cys-Pro-Phe-Cys (C-P-G-C) active-site motif, similar with those of the thiol-disulfide oxidoreductases such as thioredoxin (Trx), mycoredoxin-1 (Mrx1) and AhpD. However, its physiological and biochemical functions remain unknown in C. glutamicum. Here, we report that NCgl0877, designated CgAhp, is involved in the protection against organic peroxide (OP) stress. The cgahp-deleted strain is notably more sensitive to OP stress. The cgahp expression is controlled by a MarR-type transcriptional repressor OasR (organic peroxide- and antibiotic-sensing regulator). The physiological role of CgAhp in resistance to OP stresses is corroborated by its induced expression under stresses. Although CgAhp has a weak peroxidase activity toward OP, it mainly supports the OP-scavenging activity of the thiol-dependent peroxidase preferentially linked to the dihydrolipoamide dehydrogenase (Lpd)/dihydrolipoamide succinyltransferase (SucB)/NADH system. The C-P-G-C motif of CgAhp is essential to maintain the reductase activity. In conclusion, our study identifies CgAhp, behaving like AhpD, as a key disulfide oxidoreductase involved in the oxidative stress tolerance and the functional electron donor for peroxidase.

Implications of frailty in acute ischemic stroke receiving endovascular treatment: systematic review and meta-analysis.

BACKGROUND: Frailty is a state of cumulative degeneration of bodily functions that is consistently associated with poor outcomes in older people following illness. Combined stroke intervention and frailty may yield additive and synergistic effects adults with stroke. OBJECTIVE: To evaluate the safety and efficacy of endovascular therapy (EVT) in frail patients. METHODS: We conducted a systematic review of the relationship between debilitation and acute ischemic stroke (AIS) after EVT. Until August 2022, researchers have searched three databases (Pubmed, EMBASE and Cochrane). Random-effects meta-analysis, combined ratio (OR) and 95% confidence interval (95%CI) were used to assess efficacy values. The I2 statistic was used to assess heterogeneity. Comprehensive meta-analysis software was used for meta-analysis. RESULTS: We ultimately included eight studies including 3662 non-overlapping participants. Four studies used the Clinical Frailty Scale (CFS), two studies used the Hospital Frailty Risk Score (HFRS), a study used frailty index and a study used the comprehensive geriatric assessment (CGA). Frailty prevalence: 35%; 95% CI, 0.27-0.43; low quality evidence, downgraded due to heterogeneity, bias. Random effects showed that poor functional outcome (5 studies, OR 1.956, 95% CI 1.256-3.048) and mortality (9 studies, OR 2.320, 95% CI 1.680-3.205) was significantly associated with frailty. In adjusted analyses, poor functional outcome (4 studies, ORadj 1.189, 95% CI 1.043-1.357), and mortality (3 studies, ORadj 1.036, 95% CI 1.008-1.065) were significantly associated with frailty. CONCLUSION: Pre-stroke frailty is an important predictor of poor prognosis assessed by EVT and can be added to the classical predictors of stroke outcome. Routine assessment of pre-stroke frailty can help patients to make decisions about the efficacy of their choice of EVT.

Efficacy of desferrioxamine mesylate in intracerebral hematoma: a systemic review and meta-analysis.

BACKGROUND: Previous meta-analysis had concluded that desferrioxamine mesylate (DFO) could effectively treat intracerebral hematoma (ICH) in animal models. We hope to confirm that DFO could treat ICH patients effectively through the systemic review and meta-analysis of clinical researches. METHOD: Data extraction included hematoma volume (HV), reduction of National Institute of Health Stroke Scale (NIHSS) scores, and relative perihematomal edema (RPHE). The standard mean difference (SMD) and 95% confidence interval (95%CI) were calculated by fixed effects model. I-square (I2) statistic was used to test the heterogeneity. All p values were two-side with a significant level at 0.05. RESULTS: Five randomized controlled trials were included in the meta-analysis, which included 239 patients. At 7 days after onset, there was significant difference of RPHE development (- 1.87 (- 2.22, - 1.51) (I2 = 0, p = 0.639)) and significant difference of HV absorption (- 0.71 (- 1.06, 0.36) (I2 = 17.5%, p = 0.271)) between DFO and control groups. There was significant difference of reduction of NHISS scores (0.25 (0.05, 0.46) (I2 = 0, p = 0.992)) between DFO and control groups at 30 days after onset. CONCLUSION: DFO reduced HV and perihematomal edema in ICH patients at 7 days after onset and improve neurological function at 30 days after onset efficiently and safely. DFO might be a new route of improving treatment of ICH.

Can Artificial Intelligence Be Applied to Diagnose Intracerebral Hemorrhage under the Background of the Fourth Industrial Revolution? A Novel Systemic Review and Meta-Analysis.

Aim: We intended to provide the clinical evidence that artificial intelligence (AI) could be used to assist doctors in the diagnosis of intracerebral hemorrhage (ICH). Methods: Studies published in 2021 were identified after the literature search of PubMed, Embase, and Cochrane. Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used to perform the quality assessment of studies. Data extraction of diagnosis effect included accuracy (ACC), sensitivity (SEN), specificity (SPE), positive predictive value (PPV), negative predictive value (NPV), area under curve (AUC), and Dice scores (Dices). The pooled effect with its 95% confidence interval (95%CI) was calculated by the random effects model. I-Square (I 2) was used to test heterogeneity. To check the stability of the overall results, sensitivity analysis was conducted by recalculating the pooled effect of the remaining studies after omitting the study with the highest quality or the random effects model was switched to the fixed effects model. Funnel plot was used to evaluate publication bias. To reduce heterogeneity, recalculating the pooled effect of the remaining studies after omitting the study with the lowest quality or perform subgroup analysis. Results: Twenty-five diagnostic tests of ICH via AI and doctors with overall high quality were included. Pooled ACC, SEN, SPE, PPV, NPV, AUC, and Dices were 0.88 (0.83∼0.93), 0.85 (0.81∼0.89), 0.90 (0.88∼0.92), 0.80 (0.75∼0.85), 0.93 (0.91∼0.95), 0.84 (0.80∼0.89), and 0.90 (0.85∼0.95), respectively. There was no publication bias. All of results were stable as revealed by sensitivity analysis and were accordant as outcomes via subgroups analysis. Conclusion: Under the background of the fourth industrial revolution, AI might be an effective and efficient tool to assist doctors in the clinical diagnosis of ICH.

Thermodynamic Modeling and Exergy Analysis of A Combined High-Temperature Proton Exchange Membrane Fuel Cell and ORC System for Automotive Applications.

A combined system consisting of a high-temperature proton exchange membrane fuel cell (HT-PEMFC) and an organic Rankine cycle (ORC) is provided for automotive applications in this paper. The combined system uses HT-PEMFC stack cathode exhaust gas to preheat the inlet gas and the ORC to recover the waste heat from the stack. The model of the combined system was developed and the feasibility of the model was verified. In addition, the evaluation index of the proposed system was derived through an energy and exergy analysis. The numerical simulation results show that the HT-PEMFC stack, cathode heat exchanger, and evaporator contributed the most to the total exergy loss of the system. These components should be optimized as a focus of future research to improve system performance. The lower current density increased the ecological function and the system efficiency, but reduced the system's net out-power. A higher inlet temperature and higher hydrogen pressures of the stack and the lower oxygen pressure helped improve the system performance. Compared to the HT-PEFC system without an ORC subsystem, the output power of the combined system was increased by 12.95%.

A Novel L-Phenylalanine Dipeptide Inhibits the Growth and Metastasis of Prostate Cancer Cells via Targeting DUSP1 and TNFSF9.

Prostate cancer (PCa) is a common malignant cancer of the urinary system. Drug therapy, chemotherapy, and radical prostatectomy are the primary treatment methods, but drug resistance and postoperative recurrence often occur. Therefore, seeking novel anti-tumor compounds with high efficiency and low toxicity from natural products can produce a new tumor treatment method. Matijin-Su [N-(N-benzoyl-L-phenylalanyl)-O-acetyl-L-phenylalanol, MTS] is a phenylalanine dipeptide monomer compound that is isolated from the Chinese ethnic medicine Matijin (Dichondra repens Forst.). Its derivatives exhibit various pharmacological activities, especially anti-tumor. Among them, the novel MTS derivative HXL131 has a significant inhibitory effect against prostate tumor growth and metastasis. This study is designed to investigate the effects of HXL131 on the growth and metastasis of human PCa cell lines PC3 and its molecular mechanism through in vitro experiments combined with proteomics, molecular docking, and gene silencing. The in vitro results showed that HXL131 concentration dependently inhibited PC3 cell proliferation, induced apoptosis, arrested cell cycle at the G2/M phase, and inhibited cell migration capacity. A proteomic analysis and a Western blot showed that HXL131 up-regulated the expression of proliferation, apoptosis, cell cycle, and migration-related proteins CYR61, TIMP1, SOD2, IL6, SERPINE2, DUSP1, TNFSF9, OSMR, TNFRSF10D, and TNFRSF12A. Molecular docking, a cellular thermal shift assay (CETSA), and gene silencing showed that HXL131 had a strong binding affinity with DUSP1 and TNFSF9, which are important target genes for inhibiting the growth and metastasis of PC3 cells. This study demonstrates that HXL131 exhibited excellent anti-prostate cancer activity and inhibited the growth and metastasis of prostate cancer cells by regulating the expression of DUSP1 and TNFSF9.

Prediction of Poor Outcome in Intracerebral Hemorrhage Based on Computed Tomography Markers.

INTRODUCTION: Intracerebral hemorrhage (ICH) is the most fatal type of stroke worldwide. Herein, we aim to develop a predictive model based on computed tomography (CT) markers in an ICH cohort and validate it in another cohort. METHODS: This retrospective observational cohort study was conducted in 3 medical centers in China. The values of CT markers, including hypodensities, hematoma density, blend sign, black hole sign, island sign, midline shift, baseline hematoma volume, and satellite sign, in predicting poor outcome were analyzed by logistic regression analysis. A nomogram was developed based on the results of multivariate logistic regression analysis in development cohort. Area under curve (AUC) and calibration plot were used to assess the accuracy of nomogram in this development cohort and validate in another cohort. RESULTS: A total of 1,498 patients were included in this study. Multivariate logistic regression analysis indicated that hypodensities, black hole sign, island sign, midline shift, and baseline hematoma volume were independently associated with poor outcome in development cohort. The AUC was 0.75 (95% confidence interval [CI]: 0.73-0.76) in the internal validation with development cohort and 0.74 (95% CI: 0.72-0.75) in the external validation with validation cohort. The calibration plot in development and validation cohort indicated that the nomogram was well calibrated. CONCLUSIONS: CT markers of hypodensities, black hole sign, and island sign might predict poor outcome of ICH patients within 90 days.

A novel model for predicting the outcome of intracerebral hemorrhage: Based on 1186 Patients.

OBJECTIVE: To establish a model for predicting the outcome according to the clinical and computed tomography(CT) image data of patients with intracerebral hemorrhage(ICH). METHODS: The clinical and CT image data of the patients with ICH in Qinghai Provincial People's Hospital and Xuzhou Central Hospital were collected. The risk factors related to the poor outcome of the patients were determined by univariate and multivariate logistic regression analysis. To determine the effect of factors related to poor outcome, the nomogram model was made by software of R 3.5.2 and the support vector machine operation was completed by software of SPSS Modelor. RESULTS: A total of 8265 patients were collected and 1186 patients met the criteria of the study. Age, hospitalization days, blend sign, intraventricular extension, subarachnoid hemorrhage, midline shift, diabetes and baseline hematoma volume were independent predictors of poor outcome. Among these factors, baseline hematoma volume๥20ml (odds ratio:13.706, 95% confidence interval:9.070-20.709, p < 0.001) was the most significant factor for poor outcome, followed by the volume among 10ml-20ml (odds ratio:11.834, 95% confidence interval:7.909-17.707, p < 0.001). It was concluded that the highest percentage of weight in outcome was baseline hematoma volume (25.0%), followed by intraventricular hemorrhage (23.0%). CONCLUSION: This predictive model might accurately predict the outcome of patients with ICH. It might have a wide range of application prospects in clinical.

Raddeanin a Suppresses Glioblastoma Growth by Inducing ROS Generation and Subsequent JNK Activation to Promote Cell Apoptosis.

BACKGROUND/AIMS: Raddeanin A (RA), an active pharmacological ingredient from Anemone raddeana Regel, plays an important role in tumor suppression. In this study, we assessed the potentially therapeutic effect of RA on glioblastoma and its underlying mechanisms. METHODS: Cell viability was examined using the MTT assay. Invasive and migratory capacities were examined using Transwell and wound healing assays. Apoptosis was determined by Hoechst staining, flow cytometry, DCFH-fluorescent probe and immunohistochemical staining. Autophagy was detected by transmission electron microscopy and western blotting. A U251 glioma xenograft model was established to evaluate the effect of RA in vivo. RESULTS: The data demonstrated that RA inhibited viability, and abrogated the invasive/migratory abilities of glioblastoma cells. In addition, RA induced apoptosis by reactive oxygen species (ROS)/ Jun N-terminal kinase (JNK) signaling in glioblastoma. Conversely, the antioxidant N-Acetyl-L-cysteine (NAC) and pan-caspase inhibitor z-VAD-fmk attenuated RA-induced apoptosis by scavenging ROS and inactivating caspase-3. Furthermore, the inhibition of autophagy by 3-MA exacerbated apoptosis through ROS generation and JNK phosphorylation. In vivo, RA exhibited a curative effect on U251-derived xenografts in nude mice. CONCLUSIONS: The results of this study suggest that RA suppressed the growth of glioblastoma, thus serving as a promising and potential strategy for glioblastoma chemotherapy.

Prediction of Hematoma Expansion in Intracerebral Hemorrhage in 24 Hours by Machine Learning Algorithm.

OBJECTIVE: The significance of noncontrast computer tomography (CT) image markers in predicting hematoma expansion (HE) following intracerebral hemorrhage (ICH) within different time intervals in the initial 24 hours after onset may be uncertain. Hence, our objective was to examine the predictive value of clinical factors and CT image markers for HE within the initial 24 hours using machine learning algorithms. METHODS: Four machine learning algorithms, including extreme gradient boosting (XGBoost), support vector machine, random forest, and logistic regression, were employed to assess the predictive efficacy of HE within every 6-hour interval during the first 24 hours post-ICH. The area under the receiver operating characteristic curves was utilized to appraise predictive performance across various time periods within the initial 24 hours. RESULTS: A total of 604 patients were included, with 326 being male, and 112 experiencing hematoma expansion (HE). The findings from machine learning algorithms revealed that computed tomography (CT) image markers, baseline hematoma volume, and other factors could accurately predict HE. Among these algorithms, XGBoost demonstrated the most robust predictive model results. XGBoost's accuracy at different time intervals was 0.89, 0.82, 0.87, and 0.94, accompanied by F1-scores of 0.89, 0.80, 0.87, and 0.93, respectively. The corresponding area under the curve was 0.96, affirming the precision of the predictive capability. CONCLUSIONS: Computed tomography (CT) imaging markers and clinical factors could effectively predict HE within the initial 24 hours across various time periods by machine learning algorithms. In the expansive landscape of big data and multimodal cerebral hemorrhage, machine learning held significant potential within the realm of neuroscience.

Safety and efficacy of intravenous thrombolysis before mechanical thrombectomy in patients with atrial fibrillation.

BACKGROUND: Intravenous thrombolysis (IVT) before endovascular thrombectomy (EVT) is the standard treatment for patients with acute ischemic stroke caused by large vessel occlusion (AIS-LVO). However, the efficacy and safety of IVT before EVT in AIS-LVO patients with atrial fibrillation (AF) remains controversial. Thus, this study aims to assess the benefit of IVT plus EVT and direct EVT alone in AIS-LVO patients with AF. METHOD: Relevant studies that evaluated the outcomes of IVT plus EVT versus direct EVT alone in AIS-LVO patients with AF were systematically searched in PubMed, Embase, and Cochrane Library from inception to August 10, 2023. The outcomes included successful reperfusion (score of 2b to 3 for thrombolysis in cerebral infarction), symptomatic intracerebral hemorrhage (sICH), good clinical outcome (modified Rankin scale score ≤ 2) at 3 months, and 3-month mortality. RESULT: Eight eligible observational studies involving 6998 (3827 in the IVT plus EVT group and 3171 in the direct EVT group) patients with AIS-LVO complicated by AF were included. Compared with direct EVT, IVT plus EVT resulted in better 3-month clinical outcomes (odds ratio [OR] 1.27, 95% confidence interval [CI] 1.05-1.54) and lower 3-month mortality (OR 0.78, 95% CI 0.68-0.88). However, the incidence of sICH (OR 1.26, 95% CI 0.91-1.75) and the rate of successful reperfusion (OR 0.98, 95% CI 0.83-1.17) were not significantly different between treatment modalities. CONCLUSION: IVT plus EVT leads to better functional outcomes and lower mortality in AIS-LVO patients with AF. Withholding IVT plus EVT from patients with AF alone may not be justified.

Real-world safety and efficacy endovascular treatment versus standard medical treatment for basilar artery occlusion: A systematic review and meta-analysis.

PURPOSE: We acknowledge that between endovascular treatment (EVT) has emerged as a promising therapeutic approach, with some evidence of benefits observed in clinical trials. However, there remains a significant gap in the evidence regarding the real-world application and effectiveness of EVT.The objective of this study was to comprehensively evaluate the safety and efficacy differences between EVT and standard medical treatment (SMT) in patients with basilar artery occlusion(BAO). METHODS: Real-world studies (RWSs) on patients with BAO who underwent EVT and SMT were identified through searches in EMBASE, PubMed, and Cochrane Library databases. The efficacy outcomes included good clinical outcomes [defined as modified Rankin Scale (mRS) scores of 0-3 at 90 days], excellence clinical outcomes (defined as mRS scores of 0-2 at 90 days), 90-day mortality rate, and reperfusion status. The safety outcome was symptomatic intracranial hemorrhage (sICH). Subgroup analysis was conducted based on study type (prospective and retrospective studies). The relationship between EVT and SMT with the prognosis of BAO patients was expressed using odds ratios (OR) with a 95% confidence interval (95% CI). RESULTS: The seven studies involved a total of 2885 patients. After conducting sensitivity analysis and excluding articles with high heterogeneity, EVT demonstrated a significant association with good clinical outcomes at 90 days (OR=4.01, 95% CI: 2.60-6.19) and excellence clinical outcomes at 90 days (OR=5.70, 95% CI: 3.18-10.22) compared to SMT. Additionally, EVT showed a lower correlation with 90-day mortality rate compared to the SMT group (OR=0.35, 95% CI: 0.25-0.47). Subgroup analysis based on study type revealed that EVT had higher rates of successful reperfusion (retrospective study group: OR=7.97, 95% CI: 4.83-13.15; prospective study group: OR=51.57, 95% CI: 29.76-89.38) than the SMT group in both subgroups. The presence of sICH was not statistically significant in the retrospective study group (OR=1.20, 95% CI: 0.58-2.48) and showed high heterogeneity. However, in the prospective study group, EVT exhibited a higher risk of bleeding compared to SMT (OR=11.42, 95% CI: 2.65-49.20). CONCLUSIONS: In summary, our real-world study aligns with the conclusions of recently published randomized controlled trials research. When comparing EVT and SMT in the treatment of BAO, EVT shows a higher correlation with favorable clinical outcomes, higher rates of successful reperfusion, and lower mortality rates. However, it does come with an increased risk of sICH.

Intravenous thrombolysis in acute ischemic stroke patients with pre-stroke disability: A systematic review and meta-analysis.

BACKGROUND: Intravenous thrombolysis (IVT), which is safe and effective, is the first-line therapy for acute ischemic stroke (AIS). However, its benefit for AIS patients with pre-stroke disability (PSD) is controversial. OBJECTIVE: We determined the association of PSD with the safety and efficacy of IVT among patients with AIS. METHODS: We searched PubMed, Embase, and the Cochrane Library from inception to May 23, 2022. The articles focusing on outcomes of AIS patients with PSD receiving IVT were retrieved. We used the random-effects model to pool outcomes including mortality, 24 h NIHSS improvement, symptomatic intracerebral hemorrhage (sICH), favorable functional outcome (FFO), the favorable outcome, and mortality prevalence. RESULTS: Ten studies (including 245,773 participants) that reported the outcomes of AIS patients with PSD undergoing IVT were included. In unadjusted analyses, PSD was associated with mortality (10 studies; odds ratio [OR] 1.739, 95% confidence interval [CI], 1.336-2.407), FFO (7 studies; OR 1.057, 95% CI, 1.015-1.100), 24 h NIHSS improvement (5 studies; OR .840, 95% CI, .819-.917, p = .000), and sICH (9 studies; OR .773, 95% CI, .481-1.243). In adjusted analyses, PSD was associated with mortality (seven studies; ORadj 1.789, 95% CI, 1.413-2.264), FFO (five studies; ORadj 1.087, 95% CI, 1.002-1.179), 24 h NIHSS improvement (five studies; ORadj .837, 95% CI, .799-.876), and sICH (five studies; ORadj .857, 95% CI, .725-1.012). The prevalence of FFO and mortality in patients with pre-stroke modified Rankin Scale scores of 2-5 were 49% (0.42-0.56) and 37% (0.21-0.53), respectively. CONCLUSIONS: Patients with PSD undergoing IVT had a higher mortality rate than those without PSD. Meanwhile, PSD was associated with FFO, and there was no significant difference in sICH and 24 h NIHSS improvement. High-quality data are needed to clarify the benefits of administering IVT in these patients.

A Metagenomic Investigation of Potential Health Risks and Element Cycling Functions of Bacteria and Viruses in Wastewater Treatment Plants.

The concentration of viruses in sewage sludge is significantly higher (10-1000-fold) than that found in natural environments, posing a potential risk for human and animal health. However, the composition of these viruses and their role in the transfer of pathogenic factors, as well as their role in the carbon, nitrogen, and phosphorus cycles remain poorly understood. In this study, we employed a shotgun metagenomic approach to investigate the pathogenic bacteria and viral composition and function in two wastewater treatment plants located on a campus. Our analysis revealed the presence of 1334 amplicon sequence variants (ASVs) across six sludge samples, with 242 ASVs (41.22% of total reads) identified as pathogenic bacteria. Arcobacter was found to be the most dominant pathogen accounting for 6.79% of total reads. The virome analysis identified 613 viral genera with Aorunvirus being the most abundant genus at 41.85%. Approximately 0.66% of these viruses were associated with human and animal diseases. More than 60% of the virome consisted of lytic phages. Host prediction analysis revealed that the phages primarily infected Lactobacillus (37.11%), Streptococcus (21.11%), and Staphylococcus (7.11%). Furthermore, our investigation revealed an abundance of auxiliary metabolic genes (AMGs) involved in carbon, nitrogen, and phosphorus cycling within the virome. We also detected a total of 113 antibiotic resistance genes (ARGs), covering major classes of antibiotics across all samples analyzed. Additionally, our findings indicated the presence of virulence factors including the clpP gene accounting for approximately 4.78%, along with toxin genes such as the RecT gene representing approximately 73.48% of all detected virulence factors and toxin genes among all samples analyzed. This study expands our understanding regarding both pathogenic bacteria and viruses present within sewage sludge while providing valuable insights into their ecological functions.

The role of the transcriptional repressor CssR in Corynebacterium glutamicum in response to phenolic compounds.

The cssR gene (ncgl1578) of Corynebacterium glutamicum encodes a repressor of the TetR (tetracycline regulator) family. Its role in the stress response to antibiotics/heavy metals has been investigated, but how CssR functions in response to phenolic compounds in C. glutamicum has been rarely studied. In this study, we applied transcriptomic analysis, ß-galactosidase analysis, qRT-PCR, and EMSAs to analyze the target genes and functions of CssR in response to phenolic compounds. Consistent with the upregulation of genes involved in the degradation of phenolic compounds, the ΔcssR mutant was more resistant to various phenolic compounds than was the wild-type strain. Furthermore, the addition of phenolic compounds induced the expression of corresponding genes (ncgl0283, ncgl1032, ncgl1111, ncgl2920, ncgl2923, and ncgl2952) in vivo. However, the DNA binding activity of CssR to the promoter of phenolic compound-degrading genes was undetected in vitro. Additionally, we also found that CssR indirectly negatively regulates the expression of cell wall/membrane/envelope biogenesis-related genes, which may enhance resistance to stress caused by phenolic compounds. Together, our findings demonstrate that CssR is a key regulator that copes with stress conditions induced by phenolic compounds, thus greatly expanding our understanding of the functions of TetR family transcription factors.

Research on trajectory tracking and body attitude control of autonomous ground vehicle based on differential steering.

The differential steering can be used not only as the backup system of steer-by-wire, but also as the only steering system. Because the differential steering is realized through the differential moment between the coaxial left and right driving wheels, the sharp reduction of the load on the inner driving wheel will directly lead to the failure of the differential steering when the four-wheel independent drive electric vehicle approaches the rollover. Therefore, this paper not only realizes the trajectory tracking of autonomous ground vehicle through the differential steering, but also puts forward the body attitude control to improve the handling stability. Firstly, the dynamic and kinematic models of differential steering autonomous ground vehicle (DSAGV) and its roll model are established, and the linear three-degree of freedom vehicle model is selected as the reference model to generate the ideal body roll angle. Secondly, a model predictive controller (MPC) is designed to control the DSAGV to track the given reference trajectory, and obtain the required differential moment and the resulting front-wheel steering angle. Then, a sliding mode controller (SMC) is adopted to control the DSAGV to track the ideal body roll angle, and obtain the required roll moment. The simulation results show that the proposed MPC and SMC can not only make the DSAGV realize the trajectory tracking, but also achieve the body attitude control.

Hierarchical control of differential steering for four-in-wheel-motor electric vehicle.

The purpose of this paper is to study the control of differential steering for four-in-wheel-motor electric vehicles. The so-called differential steering means that the front wheel steering is realized through the differential driving torque between the left and right front wheels. With the consideration of tire friction circle, a hierarchical control method is proposed to realize the differential steering and the constant longitudinal speed simultaneously. Firstly, the dynamic models of the front wheel differential steering vehicle, the front wheel differential steering system and the reference vehicle are established. Secondly, the hierarchical controller is designed. The upper controller is to obtain the resultant forces and resultant torque required by the front wheel differential steering vehicle tracking the reference model through the sliding mode controller. In the middle controller, the minimum tire load ratio is selected as the objective function. Combined with the constraints, the resultant forces and resultant torque are decomposed into the longitudinal and lateral forces of four wheels by the quadratic programming method. The lower controller provides the required longitudinal forces and tire sideslip angles for the front wheel differential steering vehicle model through the tire inverse model and the longitudinal force superposition scheme. Simulation results show that the hierarchical controller can guarantee the vehicle to track the reference model well on both of the high and low adhesion coefficient road with all of the tire load ratios smaller than 1. It can be drawn that the control strategy proposed in this paper is effective.

Mechanisms and biotechnological applications of transcription factors.

Transcription factors play an indispensable role in maintaining cellular viability and finely regulating complex internal metabolic networks. These crucial bioactive functions rely on their ability to respond to effectors and concurrently interact with binding sites. Recent advancements have brought innovative insights into the understanding of transcription factors. In this review, we comprehensively summarize the mechanisms by which transcription factors carry out their functions, along with calculation and experimental-based methods employed in their identification. Additionally, we highlight recent achievements in the application of transcription factors in various biotechnological fields, including cell engineering, human health, and biomanufacturing. Finally, the current limitations of research and provide prospects for future investigations are discussed. This review will provide enlightening theoretical guidance for transcription factors engineering.

New Guaiane-Type Sesquiterpenoids Biscogniauxiaols A-G with Anti-Fungal and Anti-Inflammatory Activities from the Endophytic Fungus Biscogniauxia Petrensis.

Seven undescribed guaiane-type sesquiterpenoids named biscogniauxiaols A-G (1-7) were isolated from the endophytic fungus Biscogniauxia petrensis on Dendrobium orchids. Their structures were determined by extensive spectroscopic analyses, electronic circular dichroism (EC) and specific rotation (SR) calculations. Compound 1 represented a new family of guaiane-type sesquiterpenoids featuring an unprecedented [5/6/6/7] tetracyclic system. A plausible biosynthetic pathway for compounds 1-7 was proposed. The anti-fungal, anti-inflammatory and multidrug resistance reversal activities of the isolates were evaluated. Compounds 1, 2 and 7 exhibited potent inhibitory activities against Candida albicans with MIC values ranging from 1.60 to 6.30 µM, and suppressed nitric oxide (NO) production with IC50 ranging from 4.60 to 20.00 µM. Additionally, all compounds (100 µg/mL) enhanced the cytotoxicity of cisplatin in cisplatin-resistant non-small cell lung cancer cells (A549/DDP). This study opened up a new source for obtaining bioactive guaiane-type sesquiterpenoids and compounds 1, 2, and 7 were promising for further optimization as multifunctional inhibitors for anti-fungal (C. albicans) and anti-inflammatory purposes.