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Our understanding of the lunar farside from orbital remote sensing is limited by the lack of ground-truth constraints from returned samples. China's Chang'e-6 (CE-6) mission plans to land at the southern rim of the Apollo basin in the South Pole-Aitken basin on the lunar farside and return ∼2 kg samples. In this study, we conduct analyses on the local geological context of the CE-6 candidate landing regions, with a focus on the non-mare ejecta. The CE-6 candidate landing region has been divided into three subunits. According to our analyses, the northeastern subunit is adjacent to the lowest elevation (and one of the highest excavation depth) of this region where the materials from the deepest crust may exist. The northwestern subunit is affected by the magnesian ejecta from young crater. Returning these non-mare ejecta will provide key insights into the magnesian lithologies that occurred in the lunar farside, whose petrogenesis is long debated. As for the southern light plains unit, a topographic positive feature (unofficially termed as Mons White) located at the west of the light plains is identified in this work. Three scenarios were proposed for its origin: (1) A volcanic complex built on special magmatism in the SPA basin; (2) Remnants of the central uplift of an ancient impact basin; (3) Target surface folded and uplifted by the Apollo basin impact event. Gradual lithological variations in the Mons White are discovered. The White crater has likely ejected materials with these gradual lithologies into the CE-6 candidate landing regions. The Orientale basin ejecta also exists on the light plains. These non-mare materials, if could be sampled by the CE-6 mission, will significantly help refine the lunar chronostratigraphic system from the pre-Nectarian/Aitkenian to the late Imbrian. Thus, we suggest that landing on the southern light plains will achieve the maximum scientific outcomes for the CE-6 mission, from a perspective of sample diversity. • We conduct analyses on the local geological context of the CE-6 candidate landing regions. • The northeastern subregion is adjacent to the Chawla crater where deep-seated materials may exist. • The northwestern subunit is affected by the magnesian ejecta from young crater. • A topographic positive feature located at the west of the candidate landing region is identified. • Three scenarios were proposed for the origin of the topographic positive feature. [ABSTRACT FROM AUTHOR]

Escherichia coli infections can result in lung injury, which may be closely linked to the induction of interferon secretion. The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is one of most important pathways that regulate interferon production. Thus, the present study aimed to dissect whether E. coli infections can regulate interferon production and the underlying mechanisms. For this aim, two lung cell lines, a human bronchial epithelial cell line transformed with Ad12-SV40 2B (BEAS-2b) and a human fetal lung fibroblast (HFL1) cell line, were used. The effects of E. coli infections on interferon production were studied using qRT-PCR, Western blot, and siRNA knockdown assays. E. coli infections remarkably promoted the expression levels of IFN-α, IFN-β, and ISGs. Major components of the JAK/STAT pathway, including JAK1, STAT1, and STAT2, were demonstrated to be regulated by E. coli infections. Importantly, knockdown of JAK1, STAT1, and STAT2 abolished the induction of IFN-α, IFN-β, and ISGs by E. coli. Therefore, experiments in the present study demonstrated that E. coli infections remarkably promoted interferon production in lung cells, which was closely regulated by the JAK/STAT signaling pathway. The findings in the present study are useful for further understanding the pathogenesis of E. coli infections in the lung and finding novel therapies to treat E. coli-induced lung injury. [ABSTRACT FROM AUTHOR]

An integrated full-bridge inverter circuit with fewer components and lower volume is proposed. The conventional light sintering system uses several independent power supplies, each having an input voltage source and inverting component. However, the structure of the proposed circuit comprises only one full-bridge inverter with two separated transformers for applying independent dc trigger and simmer output voltages. The separated transformers are considered to have the same operation switching frequency because of the integrated inverter part. When designing the system, we considered not only matching the switching frequency but also turning-on of the xenon flash lamp. Some of the considerations are as follows: no-load characteristic of the lamp at the initial moment, voltage-boosting effect of the parasitic inductance and capacitance, additional simmer output current path for continuous conduction, and dc trigger turn-off moment when the 15-kV trigger output voltage changes the lamp impedance. Here, the successful results of the aforementioned considerations for applying the light sintering technology are presented. The simulation and no-load experiment waveforms are consistent with the analysis of the effects of the parasitic inductance and capacitance. In addition, the waveforms show 15- and 1.0-kV stable output voltages for the dc trigger and simmer power supplies, respectively. Finally, the xenon flash lamp load is tested, and the integrated system is observed to be functional for single or series-connected lamps. [ABSTRACT FROM AUTHOR]

This paper describes the design and manufacture of a 5.4 kJ/s three-phase resonant converter based on a 22 and 44 V lithium polymer (LiPo) battery as a high density power supply. Using the low LiPo battery input voltage generates a relatively high current that causes problems such as a large current burden on the used components and high peak-to-peak noise when the switch is turned off. To resolve such problems, the three-phase resonant converter in this work is used to handle the high input current. In the three-phase inverter structure, the amount of current flowing in a single switch is smaller than that of a single-phase current. In addition, the delta-star structure is intentionally introduced to reduce the turns ratio which helps to decrease the current on the transformer's primary side when the same output power is required. Furthermore, components such as series and parallel resonant capacitors are placed on the secondary side of the transformer, which have a high voltage and low current. These voltage and current conditions of the secondary side are more appropriate for commercialized film capacitors, which normally use series and parallel resonant capacitors because the film capacitors have been manufactured with high voltage and low current rated capacity. In terms of the design procedure, the used delta-star three-phase resonant circuit is redrawn on the secondary side of the transformer as a single-phase resonant equivalent circuit for the three-phase resonant converter design. Based on the simplified design, the operating mode and simulation of the 22 and 44 V LiPo battery-based chargers were analyzed, and the comparison of the resistor and capacitor load test results for the two chargers verifies both the aforementioned features and the performance of the proposed chargers using 300 and 150 A of the LiPo battery. The advantages are confirmed, and the capacitor bank is charged to 600 V for 80 ms, achieving power efficiencies of 82 and 92.5% for the 22 and 44 V based capacitor chargers, respectively. [ABSTRACT FROM AUTHOR]

Helicobacter pylori infection has become a threat to the world populations. This leads to an urgent need of an efficient and convenient approach to accurately diagnose H. pylori infection. Saliva-based diagnoses are particularly welcomed for their efficiency and convenience. Aiming at saliva sample analysis, we proposed a CRISPR/Cas12a-assisted array, which had integrated H. pylori concentration detection and genotype screening functions. Single-nucleotide variations (SNVs) could be distinguished using the screening array with different probes, and an isothermal cycling strategy was combined with the trans -cleavage activity of Cas12a for signal amplification to improve accuracy of the diagnosis. As a demonstration, the SNV screening array was fabricated by utilizing the hybridization efficiency difference caused by mismatched bases. The array was able to successfully distinguish between ten H. pylori genotypes, and combined with the successful SDA biosensing, it had a LOD of as low as 60 fM. It was also able to diagnose H. pylori infection in saliva samples from infected patients. Together, the developed array has a potential in large-scale clinical screening and is a promising tool for the diagnosis and prevention of H. pylori infection-related diseases. [Display omitted] • A CRISPR/Cas12a assisted array is designed for the identification of H. pylori. • This strategy was capable of target DNA analysis and genotype classification. • An SDA strategy is designed to improve the sensitivity for accurate diagnosis. • H. pylori in saliva samples are analyzed via the proposed array. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is one of the world's most deadly infectious diseases resulting in nearly 1.3 million deaths annually and infecting nearly one-quarter of the population. para -Aminosalicylic acid (PAS), an important second-line agent for treating drug-resistant Mycobacterium tuberculosis , has moderate bioavailability and rapid clearance that necessitate high daily doses of up to 12 g per day, which in turn causes severe gastrointestinal disturbances presumably by disruption of gut microbiota and host epithelial cells. We first synthesized a series of alkyl, acyloxy and alkyloxycarbonyloxyalkyl ester prodrugs to increase the oral bioavailability and thereby prevent intestinal accumulation as well as undesirable bioactivation by the gut microbiome to non-natural folate species that exhibit cytotoxicity. The pivoxyl prodrug of PAS was superior to all of the prodrugs examined and showed nearly quantitative absorption. While the conceptually simple prodrug approach improved the oral bioavailability of PAS, it did not address the intrinsic rapid clearance of PAS mediated by N-acetyltransferase-1 (NAT-1). Thus, we next modified the PAS scaffold to reduce NAT-1 catalyzed inactivation by introduction of groups to sterically block N -acetylation and fluorination of the aryl ring of PAS to attenuate N -acetylation by electronically deactivating the para -amino group. Among the mono-fluorinated analogs prepared, 5-fluoro-PAS, exhibited the best activity and an 11-fold decreased rate of inactivation by NAT-1 that translated to a 5-fold improved exposure as measured by area-under-the-curve (AUC) following oral dosing to CD-1 mice. The pivoxyl prodrug and fluorination at the 5-position of PAS address the primary limitations of PAS and have the potential to revitalize this second-line TB drug. [Display omitted] • p -Aminosalicylic acid (PAS), a potent anti-tubercular agent, has limiting oral bioavailability. • Prodrugs and structural analogs improve pharmacokinetic properties of drugs. • Pivoxyl PAS prodrug quantitatively improves oral bioavailability of PAS. • PAS analogs show a 5 to 430-fold improvement in oral bioavailability, but result in a loss of potency. • Increased exposures of 5-Fluoro PAS and N-Methyl PAS are due to poor substrate specificities towards N-acetyl transferase 1. [ABSTRACT FROM AUTHOR]