Immobilization of Perylenetetracarboxylic Dianhydride on Al2O3 for Efficiently Photocatalytic Sulfide Oxidation.

Perylenetetracarboxylic dianhydride (PTCDA) derivatives have received significant attention as molecule photocatalysts. However, the poor recyclability of molecule-type photocatalysts hinders their widespread applications. Herein, immobilization of PTCDA on Al2O3 was achieved by simply physical mixing, which not only dramatically improved their recyclability, but also surprisingly improved the reactivity. A mechanism study suggested that the photo-exited state (PTCDA*) of PTCDA could promote the oxidation of thioanisole to generate PTCDA•-, which sequentially reduces oxygen to furnish superoxide radicals to achieve the catalytic cycle. Herein, the immobilization support Al2O3 was able to facilitate the strong adsorption of thioanisole, thereby boosting the photocatalytic activity. This work provides a new insight that the immobilization of organic molecular photocatalysts on those supports with proper adsorption sites could furnish highly efficient, stable, and recyclable molecular-based heterogeneous photocatalysts.

LncRNA Gm15834 Aggravates Cardiac Hypertrophy by Interacting with Sam68 and Activating NF-κB Mediated Inflammation.

BACKGROUND: Cardiac hypertrophy is the common pathological process of multiple cardiovascular diseases. However, the molecular mechanisms of cardiac hypertrophy are unclear. Long non-coding RNA (lncRNA), a newly discovered type of transcript that has been demonstrated to function as crucial regulators in the development of cardiovascular diseases. This study revealed a novel regulatory pathway of lncRNA in cardiac hypertrophy. METHODS: The cardiac hypertrophy models were established by transverse aortic constriction (TAC) in mice and angiotensin II (Ang II) in HL-1 cardiomyocytes. Adeno-associated virus 9 (AAV9) in vivo and lncRNA Gm15834 and shRNA plasmids in vitro were used to overexpress and knock down lncRNA Gm15834. The myocardial tissue structure, cardiomyocyte area, cardiac function, protein expressions, and binding of lncRNA Gm15834 and Src-associated substrate during mitosis of 68 KDa (Sam68) were detected by hematoxylin and eosin (HE) staining, immunofluorescence staining, echocardiography, western blot and RNA immunoprecipitation (RIP), respectively. RESULTS: In cardiac hypertrophy models, inhibiting lncRNA Gm15834 could decrease Sam68 expression and nuclear factor kappa-B (NF-κB) mediated inflammatory activities in vivo and in vitro, but overexpressing lncRNA Gm15834 showed the opposite results. RIP experiments validated the binding activities between lncRNA Gm15834 and Sam68. Overexpression of Sam68 could counteract the anti-hypertrophy effects of lncRNA Gm15834 knockdown. Meanwhile, in vivo inhibition of lncRNA Gm15834 could inhibit Sam68 expression, reduce NF-κB mediated inflammatory activity and attenuate cardiac hypertrophy. CONCLUSION: Our study revealed a novel regulatory axis of cardiac hypertrophy, which comprised lncRNA Gm15834/Sam68/NF-κB/inflammation, shedding a new light for identifying therapy target of cardiac hypertrophy in clinic.

Genomic epidemiology reveals multiple mechanisms of linezolid resistance in clinical enterococci in China.

BACKGROUND: Infections caused by linezolid-resistant enterococci (LRE) are clinically difficult to treat and threaten patient health. However, there is a lack of studies on long time-span LRE strains in China. For this reason, our study comprehensively revealed the resistance mechanisms of LRE strains collected in a Chinese tertiary care hospital from 2011 to 2022. METHODS: Enterococcal strains were screened and verified after retrospective analysis of microbial data. Subsequently, 65 LRE strains (61 Enterococcus faecalis and 4 Enterococcus faecium, MIC ≥ 8 µg/ml), 1 linezolid-intermediate Enterococcus faecium (MIC = 4 µg/ml) and 1 linezolid-susceptible Enterococcus faecium (MIC = 1.5 µg/ml) were submitted for whole-genome sequencing (WGS) analysis and bioinformatics analysis. RESULTS: The optrA gene was found to be the most common linezolid resistance mechanism in our study. We identified the wild-type OptrA and various OptrA variants in 98.5% of LRE strains (61 Enterococcus faecalis and 3 Enterococcus faecium). We also found one linezolid-resistant Enterococcus faecium strain carried both optrA and cfr(D) gene, while one linezolid-resistant Enterococcus faecium only harbored the poxtA gene. Most optrA genes (55/64) were located on plasmids, with impB-fexA-optrA, impB-fexA-optrA-erm(A), fexA-optrA-erm(A), and fexA-optrA segments. A minority of optrA genes (9/64) were found on chromosomes with the Tn6674-like platform. Besides, other possible linezolid resistance-associated mechanisms (mutations in the rplC and rplD genes) were also found in 26 enterococcal strains. CONCLUSIONS: Our study suggested that multiple mechanisms of linezolid resistance exist among clinical LRE strains in China.

Giant Spin-Orbit Torque in Antiferromagnetic-Coupled Pt/[Co/Gd]N Multilayers with Suppressed Spin Dephasing and Robust Thermal Stability.

Manipulating magnetization via power-efficient spin-orbit torque (SOT) has garnered significant attention in the field of spin-based memory and logic devices. However, the damping-like SOT efficiency (ξDL) in heavy metal (HM)/ferromagnetic metal (FM) bilayers is relatively small due to the strong spin dephasing accompanied by additional spin polarization decay. Furthermore, the perpendicular magnetic anisotropy (PMA) originating from the HM/FM interface is constrained by the thickness of FM, which is unfavorable for thermal stability in practical applications. Consequently, it is valuable to develop systems that not only exhibit large ξDL but also balance thermal stability. In this work, we designed antiferromagnetic-coupled [Co/Gd]N multilayers, where staggered Co and Gd magnetic moments effectively suppress the spin dephasing and additional spin polarization decay. The ordered Co-Gd arrangements along the out-of-plane direction provide bulk PMA, endowing Pt/[Co/Gd]N high thermal stability. The SOT of Pt/[Co/Gd]N was systematically studied with N, demonstrating a significantly large ξDL of up to 0.66. The ξDL of Pt/[Co/Gd]N is greater than those of Pt/Co and Pt/ferrimagnetic alloys. This significant enhancement relies on the effective suppression of spin dephasing in [Co/Gd]N. Our work highlights that the antiferromagnetic-coupled [Co/Gd]N multilayer is a promising candidate for low-consumption and high-density spintronic devices.

Greater prosociality toward other human drivers than autonomous vehicles: Human drivers' discriminatory behavior in mixed traffic.

The development of autonomous vehicles (AVs) has rapidly evolved in recent years, aiming to gradually replace humans in driving tasks. However, road traffic is a complex environment involving numerous social interactions. As new road users, AVs may encounter different interactive situations from those of human drivers. This study therefore investigates whether human drivers show distinct degrees of prosociality toward AVs or other human drivers and whether AV behavioral patterns exert a relevant influence. Sixty-two drivers participated in the driving simulation experiment and interacted with other human drivers and different kinds of AVs (conservative, human-like, aggressive). The results show that human drivers are more willing to yield to other human drivers than to all kinds of AVs. Their braking reaction time is longer when yielding to AVs and their distance to AVs is shorter when choosing not to yield. AVs of different behavioral patterns do not significantly differ in yielding rate, but the braking reaction time of human-like AVs is longer than conservative AVs and shorter than aggressive AVs. These findings suggest that human drivers show more prosocial behaviors toward other human drivers than toward AVs. And human drivers' yielding behavior changes as the behavioral patterns of AVs changes. Accordingly, this study improves the understanding of how human drivers interact with nonliving road users such as AVs and how the former accept AVs with different driving styles on the road.

Can Human Growth Hormone Accelerate Tendon and Ligament Injury Recovery?

BACKGROUND: Studies involving human fibroblasts and use of human growth hormone (HGH) administration for injury recovery are limited. It is plausible that if the administration of HGH to human cells increased cellular proliferation and differentiation, then HGH might be able to assist in accelerating recovery from injury. HYPOTHESIS: HGH will increase proliferation and differentiation of human tendon and ligament fibroblasts in vitro based on both a single-dose and a sustained-dose model of HGH administration. STUDY DESIGN: Basic science cellular study. METHODS: Human tendon and ligament tissue were harvested from 24 patients. Tissue samples were digested with type I collagenase to isolate the target cell types. HGH was administered directly to isolated cells at doses ranging from 100 pg/mL to 10 µg/mL, either in a single-dose or a sustained-dose model. Proliferation was analyzed at days 4 and 7. Differentiation of ligament and tendon fibroblasts was assessed at day 14. RESULTS: Administration of a single-dose of HGH to both cell types demonstrated similar or inferior cellular proliferation compared with controls after 7 days. For the sustained-dosing model of ligament fibroblasts, only the 100 ng/mL concentration demonstrated at least statistically similar or improved proliferation compared with controls. When examining the 100 ng/mL HGH concentration with larger sample sizes, cellular proliferation was not improved over controls for any cell type for the single- or sustained-dosing models. Proliferation for tendon fibroblasts was either similar or inferior to the control group at all concentrations of HGH. There was no clear dose-response relationship demonstrating enhanced collagen production with administration of HGH to suggest it enhances injury recovery. CONCLUSION: HGH administered to human tendon and ligament fibroblasts does not appear to positively affect cellular proliferation and differentiation. CLINICAL RELEVANCE: This study does not support the use of HGH for accelerating recovery from injury.

MicroRNA-200c Release from Gelatin-Coated 3D-Printed PCL Scaffolds Enhances Bone Regeneration.

The fabrication of clinically relevant synthetic bone grafts relies on combining multiple biodegradable biomaterials to create a structure that supports the regeneration of defects while delivering osteogenic biomolecules that enhance regeneration. MicroRNA-200c (miR-200c) functions as a potent osteoinductive biomolecule to enhance osteogenic differentiation and bone formation; however, synthetic tissue-engineered bone grafts that sustain the delivery of miR-200c for bone regeneration have not yet been evaluated. In this study, we created novel, multimaterial, synthetic bone grafts from gelatin-coated 3D-printed polycaprolactone (PCL) scaffolds. We attempted to optimize the release of pDNA encoding miR-200c by varying gelatin types, concentrations, and polymer crosslinking materials to improve its functions for bone regeneration. We revealed that by modulating gelatin type, coating material concentration, and polymer crosslinking, we effectively altered the release rates of pDNA encoding miR-200c, which promoted osteogenic differentiation in vitro and bone regeneration in a critical-sized calvarial bone defect animal model. We also demonstrated that crosslinking the gelatin coatings on the PCL scaffolds with low-concentration glutaraldehyde was biocompatible and increased cell attachment. These results strongly indicate the potential use of gelatin-based systems for pDNA encoding microRNA delivery in gene therapy and further demonstrate the effectiveness of miR-200c for enhancing bone regeneration from synthetic bone grafts.

Triptolide attenuates cardiac remodeling by inhibiting pyroptosis and EndMT via modulating USP14/Keap1/Nrf2 pathway.

Background: Cardiac remodeling is a common pathological feature in many cardiac diseases, characterized by cardiac hypertrophy and fibrosis. Triptolide (TP) is a natural compound derived from Tripterygium wilfordii Hook F. However, the related mechanism of it in cardiac remodeling has not been fully understood. Methods and results: Transverse aortic constriction (TAC)-induced cardiac hypertrophic mouse model and angiotensin II (Ang II)-induced cardiomyocytes hypertrophic model were performed. Firstly, the results indicate that TP can improve cardiac function, decreased cardiomyocyte surface area and fibrosis area, as well as lowered the protein expressions of brain natriuretic peptide (BNP), ß-major histocompatibility complex (ß-MHC), type I and III collagen (Col I and III). Secondly, TP suppressed cardiac pyroptosis, and decreased the levels of Interleukin-1ß (IL-1ß), Interleukin-18 (IL-18) by Enzyme-linked immunosorbent assay (ELISA), and pyroptosis-associated proteins. Furthermore, TP enhanced the expressions of Nuclear factor erythroid 2-related factor 2 (Nrf2) and Heme oxygenase 1 (HO-1). Interestingly, when Nrf2 was silenced by siRNA, TP lost its properties of reducing pyroptosis and cardiac hypertrophy. In addition, in the Transforming Growth Factor ß1 (TGF-ß1)-induced primary human coronary artery endothelial cells (HCAEC) model, TP was found to inhibit the process of endothelial-to-mesenchymal transition (EndMT), characterized by the loss of endothelial-specific markers and the gain of mesenchymal markers. This was accompanied by a suppression of Slug, Snail, and Twist expression. Meanwhile, the inhibitory effect of TP on EndMT was weakened when Nrf2 was silenced by siRNA. Lastly, potential targets of TP were identified through network pharmacology analysis, and found that Ubiquitin-Specific Protease 14 (USP14) was one of them. Simultaneously, the data indicated that decrease the upregulation of USP14 and Kelch-like ECH-Associated Protein 1 (Keap1) caused by cardiac remodeling. However, Keap1 was decreased and Nrf2 was increased when USP14 was silenced. Furthermore, CoIP analysis showed that USP14 directly interacts with Keap1. Conclusion: TP can observably reduce pyroptosis and EndMT by targeting the USP14/Keap1/Nrf2 pathway, thereby significantly attenuating cardiac remodeling.

Multicenter comparative genomic study of Klebsiella oxytoca complex reveals a highly antibiotic-resistant subspecies of Klebsiellamichiganensis.

BACKGROUND: The Klebsiella oxytoca complex is an opportunistic pathogen that has been recently identified as an actual complex. However, the characteristics of each species remain largely unknown. We aimed to study the clinical prevalence, antimicrobial profiles, genetic differences, and interaction with the host of each species of this complex. METHODS: One hundred and three clinical isolates of the K. oxytoca complex were collected from 33 hospitals belonging to 19 areas in China from 2020 to 2021. Species were identified using whole genome sequencing based on average nucleotide identity. Clinical infection characteristics of the species were analyzed. Comparative genomics and pan-genome analyses were performed on these isolates and an augmented dataset, including 622 assemblies from the National Center for Biotechnology Information. In vitro assays evaluating the adhesion ability of human respiratory epithelial cells and survivability against macrophages were performed on randomly selected isolates. RESULTS: Klebsiella michiganensis (46.6%, 48/103) and K. oxytoca (35.92%, 37/103) were the major species of the complex causing human infections. K. michiganensis had a higher genomic diversity and larger pan-genome size than did K. oxytoca. K. michiganensis isolates with blaoxy-5 had a higher resistance rate to various antibiotics, antimicrobial gene carriage rate, adhesion ability to human respiratory epithelial cells, and survival rate against macrophages than isolates of other species. CONCLUSION: Our study revealed the genetic diversity of K. michiganensis and firstly identified the highly antimicrobial-resistant profile of K. michiganensis carrying blaoxy-5.

Biomimetic Therapeutics for Bone Regeneration: A Perspective on Antiaging Strategies.

Advances in modern medicine and the significant reduction in infant mortality have steadily increased the population's lifespan. As more and more people in the world grow older, incidence of chronic, noncommunicable disease is anticipated to drastically increase. Recent studies have shown that improving the health of the aging population is anticipated to provide the most cost-effective and impactful improvement in quality of life during aging-driven disease. In bone, aging is tightly linked to increased risk of fracture, and markedly decreased regenerative potential, deeming it critical to develop therapeutics to improve aging-driven bone regeneration. Biomimetics offer a cost-effective method in regenerative therapeutics for bone, where there are numerous innovations improving outcomes in young models, but adapting biomimetics to aged models is still a challenge. Chronic inflammation, accumulation of reactive oxygen species, and cellular senescence are among three of the more unique challenges facing aging-induced defect repair. This review dissects many of the innovative biomimetic approaches research groups have taken to tackle these challenges, and discusses the further uncertainties that need to be addressed to push the field further. Through these research innovations, it can be noted that biomimetic therapeutics hold great potential for the future of aging-complicated defect repair.

Upregulation of Hsp27 via further inhibition of histone H2A ubiquitination confers protection against myocardial ischemia/reperfusion injury by promoting glycolysis and enhancing mitochondrial function.

Research suggests that ischemic glycolysis improves myocardial tolerance to anoxia and low-flow ischemia. The rate of glycolysis during ischemia reflects the severity of the injury caused by ischemia and subsequent functional recovery following reperfusion. Histone H2AK119 ubiquitination (H2Aub) is a common modification that is primarily associated with gene silencing. Recent studies have demonstrated that H2Aub contributes to the development of cardiovascular diseases. However, the underlying mechanism remains unclear. This study identified Hsp27 (heat shock protein 27) as a H2Aub binding protein and explored its involvement in mediating glycolysis and mitochondrial function. Functional studies revealed that inhibition of PRC1 (polycomb repressive complex 1) decreased H2Aub occupancy and promoted Hsp27 expression through inhibiting ubiquitination. Additionally, it increased glycolysis by activating the NF-κB/PFKFB3 signaling pathway during myocardial ischemia. Furthermore, Hsp27 reduced mitochondrial ROS production by chaperoning COQ9, and suppressed ferroptosis during reperfusion. A delivery system was developed based on PCL-PEG-MAL (PPM)-PCM-SH (CWLSEAGPVVTVRALRGTGSW) to deliver PRT4165 (PRT), a potent inhibitor of PRC1, to damaged myocardium, resulting in decreased H2Aub. These findings revealed a novel epigenetic mechanism connecting glycolysis and ferroptosis in protecting the myocardium against ischemia/reperfusion injury.

Charge Density Modulation of Pyrene-Related Small Molecules by Nitrogen Heteroatoms Precisely Regulates Photocatalytic Generation of Hydrogen.

Organic semiconductor materials hold promising applications in photocatalytic hydrogen evolution due to their high modifiability and wide range of light absorption capability. In this study, we present an effective strategy for promoting the separation of photoexcited electrons from organic conjugated centers to active sites by modifying different nitrogen-containing groups on pyrene molecules. Building on this foundation, the well-designed catalyst Py-m-2N has demonstrated good performance by achieving a photocatalytic hydrogen evolution rate of 48.86 mmol g-1 h-1, even in the absence of the precious metal platinum cocatalyst. This achievement places the pyrene-based photocatalyst ahead of the majority of its organic counterparts. Our comprehensive characterization and density functional theory calculations reveal that the nitrogen atom not only serves as an active site for hydrogen production but also plays a pivotal role in efficiently accumulating bulk-phase electrons. This electron enrichment process enhances the transport of photoexcited electrons from the light-absorbing pyrene units to the active nitrogen sites. This work provides inspiration for the future design of effective nitrogen-atom-modified organic semiconductor photocatalysts at the molecular level.

CaCO 3 Nanoparticles Delivering MicroRNA-200c Suppress Oral Squamous Cell Carcinoma.

MicroRNA (miR)-200c suppresses the initiation and progression of oral squamous cell carcinoma (OSCC), the most prevalent head and neck cancer with high recurrence, metastasis, and mortality rates. However, miR-200c -based gene therapy to inhibit OSCC growth and metastasis has yet to be reported. To develop an miR-based gene therapy to improve the outcomes of OSCC treatment, this study investigates the feasibility of plasmid DNA encoding miR-200c delivered via non-viral CaCO 3 -based nanoparticles to inhibit OSCC tumor growth. CaCO 3 -based nanoparticles with various ratios of CaCO 3 and protamine sulfate (PS) were utilized to transfect pDNA encoding miR-200c into OSCC cells and the efficiency of these nanoparticles was evaluated. The proliferation, migration, and associated oncogene production, as well as in vivo tumor growth for OSCC cells overexpressing miR-200c were also quantified. It was observed that, while CaCO 3 -based nanoparticles improve transfection efficiencies of pDNA miR-200c , the ratio of CaCO 3 to PS significantly influences the transfection efficiency. Overexpression of miR-200c significantly reduced proliferation, migration, and oncogene expression of OSCC cells, as well as the tumor size of cell line-derived xenografts (CDX) in mice. In addition, a local administration of pDNA miR-200c using CaCO 3 delivery significantly enhanced miR-200c transfection and suppressed tumor growth of CDX in mice. These results strongly indicate that the nanocomplexes of CaCO 3 /pDNA miR-200c may potentially be used to reduce oral cancer recurrence and metastasis and improve clinical outcomes in OSCC treatment. (227 words).

The effect of prenatal stress on offspring depression susceptibility in relation to the gut microbiome and metabolome.

Prenatal stress (PS) increases offspring susceptibility to depression, but the underlying mechanism remains unclear. Our previous results showed that PS can affect depression-like behavior in offspring through neurotransmitters and neuroinflammatory substances in the hippocampus and frontal cortex. In recent years there has been increasing evidence for a role of the gut microbiome in depression. The brain-gut axis theory suggests there is a need to further explore the mechanism involving the gut microbiome in the susceptibility of offspring to depression caused by PS. In the present study we used a stress model relevant to depression in which pregnant female rats undergo prenatal restraint stress and the offspring show susceptibility to depression. High-resolution gene sequencing for 16S ribosomal RNA markers and non-targeted metabolomic analysis were used to evaluate the fecal microbiome and the availability of metabolites, respectively. PS was found to induce depressive-like behavior in susceptible offspring (PS-S), as detected by the sucrose preference and forced swimming tests, as well as altering Alpha and Beta diversity. The different microbiota between the PS-S and control groups were mainly involved in membrane transport, carbohydrate metabolism, amino acid metabolism, and replication and repair pathways. In total, 237 and 136 important differential metabolites with significant influence on modeling analysis were obtained under positive and negative modes, respectively. The main canonical pathways found to be altered were glycerophospholipid metabolism and glycerolipid metabolism. These results suggest that gut microbiota might contribute to the onset of PS-induced depression-like behavior by affecting the glycerophospholipid and glycerolipid metabolic pathways.

Super-enhancer-driven lncRNA Snhg7 aggravates cardiac hypertrophy via Tbx5/GLS2/ferroptosis axis.

Long non-coding RNAs (lncRNAs) are expressed aberrantly in cardiac disease, but their roles in cardiac hypertrophy are still unknown. Here we sought to identify a specific lncRNA and explore the mechanisms underlying lncRNA functions. Our results revealed that lncRNA Snhg7 was a super-enhancer-driven gene in cardiac hypertrophy by using chromatin immunoprecipitation sequencing (ChIP-seq). We next found that lncRNA Snhg7 induced ferroptosis by interacting with T-box transcription factor 5 (Tbx5), a cardiac transcription factor. Moreover, Tbx5 bound to the promoter of glutaminase 2 (GLS2) and regulated cardiomyocyte ferroptosis activity in cardiac hypertrophy. Importantly, extra-terminal domain inhibitor JQ1 could suppress super-enhancers in cardiac hypertrophy. Inhibition of lncRNA Snhg7 could block the expressions of Tbx5, GLS2 and levels of ferroptosis in cardiomyocytes. Furthermore, we verified that Nkx2-5 as a core transcription factor, directly bound the super-enhancer of itself and lncRNA Snhg7, increasing both of their activation. Collectively, we are the first to identify lncRNA Snhg7 as a novel functional lncRNA in cardiac hypertrophy, might regulate cardiac hypertrophy via ferroptosis. Mechanistically, lncRNA Snhg7 could transcriptionally regulate Tbx5/GLS2/ferroptosis in cardiomyocytes.

In Vitro Activities of Aztreonam-Avibactam, Eravacycline, Cefoselis, and Other Comparators against Clinical Enterobacterales Isolates: a Multicenter Study in China, 2019.

Aztreonam-avibactam, eravacycline, and cefoselis are three novel antimicrobial agents for the treatment of serious infections caused by Gram-negative bacteria. We evaluated the in vitro activities of the above-mentioned three antimicrobial agents against clinical Enterobacterales isolates. A total of 1,202 Enterobacterales isolates, including 10 genera or species, were collected from 26 hospitals that cover seven regions of China. The susceptibilities of the 30 antimicrobial agents were interpreted based on the combination of U.S. Food and Drug Administration and Clinical and Laboratory Standards Institute guidelines. The results indicated that all Enterobacterales isolates showed high susceptibility to aztreonam-avibactam (98.25%), eravacycline (85.69%), and cefoselis (62.73%). The first two antimicrobial agents also demonstrated potent activities against multidrug-resistant and carbapenem-resistant Enterobacterales independent of antimicrobial resistance mechanisms. The rates of susceptibility to aztreonam-avibactam, eravacycline, and cefoselis were lowest in Morganella spp. (84.42%), Proteus spp. (33.65%), and Escherichia coli (40.14%), respectively. In general, the lower rates of susceptibility to eravacycline and cefoselis were in the older inpatient group. The strains isolated from urinary tract exhibited the lowest rate of susceptibility (78.97%) to eravacycline, and the lowest rate of susceptibility (45.83%) to cefoselis was observed in nervous system specimens. The strains isolated from intensive care unit (ICU) wards showed significantly reduced susceptibility to cefoselis compared with those isolated from non-ICU wards. The MIC values of aztreonam-avibactam and ceftazidime-avibactam have poor consistency (weighted kappa = 0.243), as did eravacycline and tigecycline (weighted kappa = 0.478). Cefoselis and cefepime showed highly similar activities against Enterobacterales (weighted kappa = 0.801). Our results support the clinical development of aztreonam-avibactam, eravacycline, and cefoselis to treat infections caused by Enterobacterales. IMPORTANCE Infections caused by multidrug-resistant (MDR) Enterobacterales, especially carbapenem-resistant Enterobacterales (CRE), have been a challenging clinical problem due to the limited therapeutic options. Therefore, the need to develop novel antimicrobial agents and evaluate their activities against Enterobacterales in vitro is urgent. Our results show that the novel antimicrobial agents aztreonam-avibactam and eravacycline retain activities against MDR and CRE isolates, including carbapenemase producers and non-carbapenemase producers. Further analysis combined with clinical information on the strains tested revealed that no significant differences were observed in susceptibility rates of strains with different demographic parameters to aztreonam-avibactam. Age, specimen source, and department were associated with the susceptibility of strains to eravacycline and cefoselis (P ≤ 0.01). Compared with ceftazidime-avibactam, aztreonam-avibactam has its advantages and limitations against Enterobacterales. The potent activity of eravacycline against Enterobacterales was higher than that of tigecycline. Cefoselis and cefepime showed a highly consistent activity against Enterobacterales.

Genome-wide by environment interaction studies of maternal smoking and educational score in UK biobank.

PURPOSE: This study aimed to investigate the associations between maternal smoking (MS) and education score in adult offspring. METHODS: To better understand this link, we performed a two-stage genome-wide by environment interaction studies (GWEIS) of MS and offspring education score in UK Biobank cohort. Specifically, 276 996 subjects from England were enrolled in the discovery study, while 24 355 subjects from Scotland and 14 526 subjects from Wales were enrolled in the replication study. GWEIS were conducted by PLINK 2.0 with MS used as an environmental risk factor. RESULTS: Significant GWEIS associations ( P  < 0.0001) between MS and offspring education score in both the discovery cohort and two replicate cohorts (Scotland population and Wales population) were identified. GWEIS identified 2 independent significant single nucleotide polymorphism-MS interaction, with one variant located in the chromosomal 16 (rs72768988, Position: 22,768,798, P  = 1.22 × 10 -8 , ß = 6.7662) and the other one located in 2q32.3 region (2 : 196424612_GT_G, Position: 196 424 612, 3.60 × 10 -9 , ß = -0.4721). CONCLUSION: Our results suggested 2q32.3 region and HECW2 gene could negatively moderate the influence of MS on offspring's educational status.

More evidence, greater generalization? The relation between the prevalence of observed action and the strength of generalization depends on action properties.

Although group members may be diverse and have their own reasons for actions, people tend to generalize the actions of known members to unknown cases from the observer's perspective. Nevertheless, it is unclear whether action generalization is entirely determined by statistical evidence or is additionally constrained by prior knowledge or beliefs toward group members' actions. Given that people specifically believe that group members pursue common action goals, we hypothesized that action generalization is constrained by this belief. Accordingly, the extent of generalizing a goal underlying action does not always increase as the prevalence of the goal increases; instead, a strict monotonicity effect is observed for the action's movement. We found that the common goal is generalized to a new group member only when all sampled group members have this target property, revealing that the relation between the prevalence of goals and the strength of their generalization violates strict monotonicity (Studies 1a and 1b). In contrast, the more group members perform the same movement, the more likely this movement is to be generalized to an unknown group member, showing monotonic generalization of movements (Studies 3a, 3b, and 3c). Importantly, these dissociative generalizations are specific to entitative social groups (Studies 2, 4, and 6) and not due to differences in experimental tasks between studies. In shared experimental paradigms, when the goal status is available, the monotonic generalization of actions is not found; however, when the goal status is unavailable and the movement is still accessed, the monotonic generalization of actions is observed (Study 5). Thus, our findings highlight that the belief that group members pursue a common goal constrains action generalization to a greater extent than statistical evidence. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Exploring microRNAs in craniofacial regenerative medicine.

microRNAs (miRs) have been reported over the decades as important regulators in bone development and bone regeneration. They play important roles in maintaining the stem cell signature as well as regulating stem cell fate decisions. Thus, delivering miRs and miR inhibitors to the defect site is a potential treatment towards craniofacial bone defects. However, there are challenges in translation of basic research to clinics, including the efficiency, specificity, and efficacy of miR manipulation methods and the safety of miR delivery systems. In this review, we will compare miR oligonucleotides, mimics and antagomirs as therapeutic reagents to treat disease and regenerate tissues. Newer technology will be discussed as well as the efficiency and efficacy of using these technologies to express or inhibit miRs in treating and repairing oral tissues. Delivery of these molecules using extracellular vesicles and nanoparticles can achieve different results and depending on their composition will elicit specific effects. We will highlight the specificity, toxicity, stability, and effectiveness of several miR systems in regenerative medicine.

Event-related potential and behavioural evidence of goal-based expectations for consistent actions among group members.

PLACEHOLDER TEXT: ABSTRACT: People expect group members to act consistently. However, because actions are organized hierarchically, incorporating deep-level goals and shallow-level movements, it remains unclear what level of action is expected to be consistent among group members. We determined that these two levels of action representations can be dissociated in object-directed actions and measured the late positive potential (LPP), which indicates expectation. We found that participants identified a new agent's actions more quickly when this agent pursued a consistent goal while moving in a manner inconsistent with group members than when this agent pursued an inconsistent goal while moving in the same manner as group members. Moreover, this facilitation effect disappeared when the new agent was from a different group, revealing goal-based expectations for consistent actions among group members. The LPP amplitude during the action-expectation phase was greater for agents from the same group than for agents from a different group, suggesting that people implicitly generate clearer action expectations for group members than for other individuals. Additionally, the behavioural facilitation effect was observed when the goal of actions was clearly identifiable (i.e. performing rational actions to reach an external target) rather than when there was no clear association between actions and external targets (i.e. performing irrational actions). The LPP amplitude during the action-expectation phase was greater after observing rational actions than after observing irrational actions performed by two agents from the same group, and the expectation-related increase in LPP predicted the behavioural measurements of the facilitation effect. Hence, the behavioural and event-related potential evidence suggest that people implicitly expect group members to behave consistently according to goals rather than movements per se.