Cell Membrane Is Impaired, Accompanied by Enhanced Type III Secretion System Expression in Yersinia pestis Deficient in RovA Regulator

BACKGROUND: In the enteropathogenic Yersinia species, RovA regulates the expression of invasin, which is important for enteropathogenic pathogenesis but is inactivated in Yersinia pestis. Investigation of the RovA regulon in Y. pestis at 26 °C has revealed that RovA is a global regulator that contributes to virulence in part by the direct regulation of psaEFABC. However, the regulatory roles of RovA in Y. pestis at 37 °C, which allows most virulence factors in mammalian hosts to be expressed, are still poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: The transcriptional profile of an in-frame rovA mutant of Y. pestis biovar Microtus strain 201 was analyzed under type III secretion system (T3SS) induction conditions using microarray techniques, and it was revealed that many cell-envelope and transport/binding proteins were differentially expressed in the ΔrovA mutant. Most noticeably, many of the T3SS genes, including operons encoding the translocon, needle and Yop (Yersinia outer protein) effectors, were significantly up-regulated. Analysis of Yop proteins confirmed that YopE and YopJ were also expressed in greater amounts in the mutant. However, electrophoresis mobility shift assay results demonstrated that the His-RovA protein could not bind to the promoter sequences of the T3SS genes, suggesting that an indirect regulatory mechanism is involved. Transmission electron microscopy analysis indicated that there are small loose electron dense particle-like structures that surround the outer membrane of the mutant cells. The bacterial membrane permeability to CFSE (carboxyfluorescein diacetate succinimidyl ester) was significantly decreased in the ΔrovA mutant compared to the wild-type strain. Taken together, these results revealed the improper construction and dysfunction of the membrane in the ΔrovA mutant. CONCLUSIONS/SIGNIFICANCE: We demonstrated that the RovA regulator plays critical roles in the construction and functioning of the bacterial membrane, which sheds considerable light on the regulatory functions of RovA in antibiotic resistance and environmental adaptation. The expression of T3SS was upregulated in the ΔrovA mutant through an indirect regulatory mechanism, which is possibly related to the altered membrane construction in the mutant

Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke

Importance It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. Design, Setting, and Participants This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023.InterventionsEligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. Main Outcomes and Measures The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. Results Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. Conclusions and Relevance Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability.Trial RegistrationChiCTR.org.cn Identifier: ChiCTR210005172

Cloud-Edge-Terminal-Based Synchronized Decision-Making and Control System for Municipal Solid Waste Collection and Transportation

Due to dynamics caused by factors such as random collection and transportation requirements, vehicle failures, and traffic jams, it is difficult to implement regular waste collection and transportation schemes effectively. A challenge for the stable operation of the municipal solid waste collection and transportation (MSWCT) system is how to obtain the whole process data in real time, dynamically judge the process control requirements, and effectively promote the synchronization operation between multiple systems. Based on this situation, this study proposes a cloud-edge-terminal-based synchronization decision-making and control system for MSWCT. First, smart terminals and edge computing devices are deployed at key nodes of MSWCT for real-time collection and edge computing analysis of the whole process data. Second, we propose a collaborative analysis and distributed decision-making method based on the cloud-edge-terminal multi-level computing architecture. Finally, a “three-level and two-stage” synchronization decision-making mechanism for the MSWCT system is established, which enables the synchronization operation between various subsystems. With a real-world application case, the efficiency and effectiveness of the proposed decision-making and control system are evaluated based on real data of changes in fleet capacity and transportation costs

Cloud-Edge-Terminal-Based Synchronized Decision-Making and Control System for Municipal Solid Waste Collection and Transportation

Due to dynamics caused by factors such as random collection and transportation requirements, vehicle failures, and traffic jams, it is difficult to implement regular waste collection and transportation schemes effectively. A challenge for the stable operation of the municipal solid waste collection and transportation (MSWCT) system is how to obtain the whole process data in real time, dynamically judge the process control requirements, and effectively promote the synchronization operation between multiple systems. Based on this situation, this study proposes a cloud-edge-terminal-based synchronization decision-making and control system for MSWCT. First, smart terminals and edge computing devices are deployed at key nodes of MSWCT for real-time collection and edge computing analysis of the whole process data. Second, we propose a collaborative analysis and distributed decision-making method based on the cloud-edge-terminal multi-level computing architecture. Finally, a “three-level and two-stage” synchronization decision-making mechanism for the MSWCT system is established, which enables the synchronization operation between various subsystems. With a real-world application case, the efficiency and effectiveness of the proposed decision-making and control system are evaluated based on real data of changes in fleet capacity and transportation costs

Radix Rehmanniae and Corni Fructus against Diabetic Nephropathy via AGE-RAGE Signaling Pathway

Background and Aims. Radix Rehmanniae and Corni Fructus (RC) have been widely applied to treat diabetic nephropathy (DN) for centuries. But the mechanism of how RC plays the therapeutic role against DN is unclear as yet. Methods. The information about RC was obtained from a public database. The active compounds of RC were screened by oral bioavailability (OB) and drug-likeness (DL). Gene ontology (GO) analysis was performed to realize the key targets of RC, and an active compound-potential target network was created. The therapeutic effects of RC active compounds and their key signal pathways were preliminarily probed via network pharmacology analysis and animal experiments. Results. In this study, 29 active compounds from RC and 64 key targets related to DN were collected using the network pharmacology method. The pathway enrichment analysis showed that RC regulated advanced glycosylation end product (AGE-) RAGE and IL-17 signaling pathways to treat DN. The animal experiments revealed that RC significantly improved metabolic parameters, inflammation renal structure, and function to protect the kidney against DN. Conclusions. The results revealed the relationship between multicomponents and multitargets of RC. The administratiom of RC might remit the DM-induced renal damage through the AGE-RAGE signaling pathway to improve metabolic parameters and protect renal structure and function

Exploring the potential of open big data from ticketing websites to characterize travel patterns within the Chinese high-speed rail system

<div><p>Big data have contributed to deepen our understanding in regards to many human systems, particularly human mobility patterns and the structure and functioning of transportation systems. Resonating the recent call for ‘open big data,’ big data from various sources on a range of scales have become increasingly accessible to the public. However, open big data relevant to travelers within public transit tools remain scarce, hindering any further in-depth study on human mobility patterns. Here, we explore ticketing-website derived data that are publically available but have been largely neglected. We demonstrate the power, potential and limitations of this open big data, using the Chinese high-speed rail (HSR) system as an example. Using an application programming interface, we automatically collected the data on the remaining tickets (RTD) for scheduled trains at the last second before departure in order to retrieve information on unused transit capacity, occupancy rate of trains, and passenger flux at stations. We show that this information is highly useful in characterizing the spatiotemporal patterns of traveling behaviors on the Chinese HSR, such as weekend traveling behavior, imbalanced commuting behavior, and station functionality. Our work facilitates the understanding of human traveling patterns along the Chinese HSR, and the functionality of the largest HSR system in the world. We expect our work to attract attention regarding this unique open big data source for the study of analogous transportation systems.</p></div

Between-station correlation matrix of passenger flux between Nanjing and Shanghai from August 14 to September 3, 2016.

<p>The Pearson’s correlation coefficients are shown.</p

Time series of hourly remaining ticket data for all high-speed trains from Nanjing to Shanghai from November 22—December 26, 2016.

<p>Each curve represents a single day.</p

Retrieval of net passenger flux at stations using remaining ticket data.

<p>For a given scheduled train passing Station A, B and C sequentially, by enquiring into the numbers of remaining tickets for trips from Station A to B (n₁), and B to C (n₂), the net flux at station B can be calculated as their difference (Δn = n₁—n₂). Δn>0 represents outflow > inflow at station B, and vice versa.</p