Miracle-dz/UniFAR-FTUs huggingface dataset:
Combination of 2-tert-Butyl-1,4-Benzoquinone (TBQ) and ZnO Nanoparticles, a New Strategy To Inhibit Biofilm Formation and Virulence Factors of Chromobacterium violaceum

The combination of ZnO-NPs and TBQ (ZnO-TBQ) can compete with the inducer N-decanoyl-homoserine lactone (C10-HSL) by binding to CviR and downregulate genes related to the CviI/CviR system to interrupt the QS system of C. violaceum ATCC 12472. The downstream genes responding to cviR were also downregulated so that virulence factors and biofilm formation were inhibited. ABSTRACT Drug-resistant bacteria have been raising serious social problems. Bacterial biofilms and different virulence factors are the main reasons for persistent infections. As a conditioned pathogen, Chromobacterium violaceum has evolved a vast network of regulatory mechanisms to modify and fine-tune biofilm development, contributing to multidrug resistance. However, there are few therapies to combat drug-resistant bacteria. Quorum sensing (QS) inhibitors (QSIs) are a promising strategy to solve antibiotic resistance. Our previous work suggested that 2-tert-butyl-1,4-benzoquinone (TBQ) is a potent QSI. In this study, the combination of zinc oxide nanoparticles (ZnO-NPs) and TBQ (ZnO-TBQ) was investigated for the treatment of Chromobacterium violaceum ATCC 12472 infection. ZnO-NPs attach to cell walls or biofilms, and the local dissolution of ZnO-NPs can lead to increased Zn2+ concentrations, which could destroy metal homeostasis, corresponding to disturbances in amino acid metabolism and nucleic acid metabolism. ZnO-NPs significantly improved the efficiency of TBQ in inhibiting the QS-related virulence factors and biofilm formation of C. violaceum ATCC 12472. ZnO-TBQ effectively reduces the expression of genes related to QS, which is conducive to limiting the infectivity of C. violaceum ATCC 12472. Caenorhabditis elegans nematodes treated with ZnO-TBQ presented a significant improvement in the survival rate by 46.7%. Overall, the combination of ZnO-NPs and TBQ offers a new strategy to attenuate virulence factors and biofilm formation synergistically in some drug-resistant bacteria. IMPORTANCE The combination of ZnO-NPs and TBQ (ZnO-TBQ) can compete with the inducer N-decanoyl-homoserine lactone (C10-HSL) by binding to CviR and downregulate genes related to the CviI/CviR system to interrupt the QS system of C. violaceum ATCC 12472. The downstream genes responding to cviR were also downregulated so that virulence factors and biofilm formation were inhibited. Furthermore, ZnO-TBQ presents multiple metabolic disturbances in C. violaceum ATCC 12472, which results in the reduced multidrug resistance and pathogenicity of C. violaceum ATCC 12472. In an in vivo assay, C. elegans nematodes treated with ZnO-TBQ presented a significant improvement in the survival rate by 46.7% by limiting the infectivity of C. violaceum ATCC 12472. In addition, ZnO-TBQ inhibited the generation of virulence factors and biofilm formation 2-fold compared to either ZnO-NPs or TBQ alone. The combination of ZnO-NPs with TBQ offers a potent synergistic strategy to reduce multidrug resistance and pathogenicity.
Keratinocytes activated by IL‐4/IL‐13 express IL‐2Rγ with consequences on epidermal barrier function

Atopic dermatitis (AD) is a Th2‐type inflammatory disease characterized by an alteration of epidermal barrier following the release of IL‐4 and IL‐13. These cytokines activate type II IL‐4Rα/IL‐13Rα1 receptors in the keratinocyte. Whilst IL‐2Rγ, that forms type I receptor for IL‐4, is only expressed in haematopoietic cells, recent studies suggest its induction in keratinocytes, which questions about its role. We studied expression of IL‐2Rγ in keratinocytes and its role in alteration of keratinocyte function and epidermal barrier. IL‐2Rγ expression in keratinocytes was studied using both reconstructed human epidermis (RHE) exposed to IL‐4/IL‐13 and AD skin. IL‐2Rγ induction by type II receptor has been analyzed using JAK inhibitors and RHE knockout (KO) for IL13RA1. IL‐2Rγ function was investigated in RHE KO for IL2RG. In RHE, IL‐4/IL‐13 induce expression of IL‐2Rγ at the mRNA and protein levels. Its mRNA expression is also visualized in keratinocytes of lesional AD skin. IL‐2Rγ expression is low in RHE treated with JAK inhibitors and absent in RHE KO for IL13RA1. Exposure to IL‐4/IL‐13 alters epidermal barrier, but this alteration is absent in RHE KO for IL2RG. A more important induction of IL‐13Rα2 is reported in RHE KO for IL2RG than in not edited RHE. These results demonstrate IL‐2Rγ induction in keratinocytes through activation of type II receptor. IL‐2Rγ is involved in the alteration of the epidermal barrier and in the regulation of IL‐13Rα2 expression. Observation of IL‐2Rγ expression by keratinocytes inside AD lesional skin suggests a role for this receptor subunit in the disease.
Liver-restricted deletion of the biliary atresia candidate gene Pkd1l1 causes bile duct dysmorphogenesis and ciliopathy

Background and Aims: A recent multicenter genetic exploration of the biliary atresia splenic malformation syndrome identified mutations in the ciliary gene PKD1L1 as candidate etiologic contributors. We hypothesized that deletion of Pkd1l1 in developing hepatoblasts would lead to cholangiopathy in mice. Approach and Results: CRISPR-based genome editing inserted loxP sites flanking exon 8 of the murine Pkd1l1 gene. Pkd1l1 Fl/Fl cross-bred with alpha-fetoprotein-Cre expressing mice to generate a liver-specific intrahepatic Pkd1l1-deficient model (LKO). From embryonic day 18 through week 30, control (Fl/Fl) and LKO mice were evaluated with standard serum chemistries and liver histology. At select ages, tissues were analyzed using RNA sequencing, immunofluorescence, and electron microscopy with a focus on biliary structures, peribiliary inflammation, and fibrosis. Bile duct ligation for 5 days of Fl/Fl and LKO mice was followed by standard serum and liver analytics. Histological analyses from perinatal ages revealed delayed biliary maturation and reduced primary cilia, with progressive cholangiocyte proliferation, peribiliary fibroinflammation, and arterial hypertrophy evident in 7- to 16-week-old LKO versus Fl/Fl livers. Following bile duct ligation, cholangiocyte proliferation, peribiliary fibroinflammation, and necrosis were increased in LKO compared with Fl/Fl livers. Conclusions: Bile duct ligation of the Pkd1l1-deficient mouse model mirrors several aspects of the intrahepatic pathophysiology of biliary atresia in humans including bile duct dysmorphogenesis, peribiliary fibroinflammation, hepatic arteriopathy, and ciliopathy. This first genetically linked model of biliary atresia, the Pkd1l1 LKO mouse, may allow researchers a means to develop a deeper understanding of the pathophysiology of this serious and perplexing disorder, including the opportunity to identify rational therapeutic targets.
BCAT2 Shapes a Noninflamed Tumor Microenvironment and Induces Resistance to Anti‐PD‐1/PD‐L1 Immunotherapy by Negatively Regulating Proinflammatory Chemokines and Anticancer Immunity

To improve response rate of monotherapy of immune checkpoint blockade (ICB), it is necessary to find an emerging target in combination therapy. Through analyzing tumor microenvironment (TME)‐related indicators, it is validated that BCAT2 shapes a noninflamed TME in bladder cancer. The outcomes of multiomics indicate that BCAT2 has an inhibitory effect on cytotoxic lymphocyte recruitment by restraining activities of proinflammatory cytokine/chemokine‐related pathways and T‐cell‐chemotaxis pathway. Immunoassays reveal that secretion of CD8+T‐cell‐related chemokines keeps a robust negative correlation with BCAT2, generating a decreasing tendency of CD8+T cells around BCAT2+ tumor cells from far to near. Cotreatment of BCAT2 deficiency and anti‐PD‐1 antibody has a synergistic effect in vivo, implying the potential of BCAT2 in combination therapy. Moreover, the value of BCAT2 in predicting efficacy of immunotherapy is validated in multiple immunotherapy cohorts. Together, as a key molecule in TME, BCAT2 is an emerging target in combination with ICB and a biomarker of guiding precision therapy.
Correction to: Larvae Crowding Increases Development Rate, Improves Disease Resistance, and Induces Expression of Antioxidant Enzymes and Heat Shock Proteins in Mythimna separata (Lepidoptera: Noctuidae)

High population density (crowding) becomes a stress factor in insects. The oriental armyworm, Mythimna separata (Walker), displays gregarious and solitary phases at high and low population densities, respectively. In this study, we compared life history, disease resistance, and induction of antioxidant enzymes and heat shock protein (HSPs) in two phases of M. separata larvae. Results showed that gregarious larvae had a faster growth rate and lower pupal weight compared to solitary larvae. Furthermore, gregarious individuals exhibited higher survival rates than solitary individuals after Beauveria bassiana infection. The gregarious larvae had higher malondialdehyde content compared to solitary ones, but no differences in total antioxidant capacity were observed between the two larval phases before or after infection. Superoxide dismutase and glutathione peroxidase activities were significantly lower in gregarious M. separata larvae than solitary individuals before infection, but no difference was detected in two phases after infection. However, peroxidase and catalase activities in the two phases showed no difference either before or after infection. Hsp19.8 and Hsp90 expression in gregarious larvae were up-regulated when compared to solitary individuals before or after infection. CuZnSOD expression was not different between the two phases before infection, but it was up-regulated in gregarious ones compared to solitary ones after infection. However, expression of other stress-related genes in gregarious larvae was either repressed or unchanged when compared to solitary individuals before or after infection. Thus, larval crowding changed life history, improved disease resistance of M. separata larvae, and induced variable response of antioxidant enzymes and HSPs to fungal infection.
Mid‐ to Long‐term Follow‐up of Severe Acetabular Bone Defect after Revision Total Hip Arthroplasty Using Impaction Bone Grafting and Metal Mesh

In revision total hip arthroplasty (THA), reconstruction of severe acetabular bone defect continues to be problematic for orthopedic surgeons. This study reports the mid‐ to long‐term survivorship, radiological outcomes, and complications of impaction bone grafting (IBG) and metal mesh with a cemented acetabular component in the reconstruction of severe acetabular bone defects in revision THA.
Characterization of Exhaustion Disorder and Identification of Outcomes that Matter to Patients: Qualitative Content Analysis of a Swedish National Online Survey.

BACKGROUND Fatigue is a common presenting problem in healthcare settings, often attributed to chronic psychosocial stress. Understanding of fatigue and development of evidence-based treatments is hampered by a lack of consensus regarding diagnostic definitions and outcomes to be measured in clinical trials. This study aimed to map outcome domains of importance to the Swedish diagnosis stress-induced exhaustion disorder (ED; ICD-10, code F43.8A). METHODS An online survey was distributed nationwide in Sweden to individuals who reported to have been diagnosed with ED and to healthcare professionals working with ED patients. To identify outcome domains, participants replied anonymously to four open-ended questions about symptoms and expectations for ED-treatment. Qualitative content analysis was conducted of a randomized subsample of respondents, using a mathematical model to determine data saturation. RESULTS 670 participants (573 with reported ED, 97 healthcare professionals) completed the survey. Qualitative content analysis of answers supplied by 105 randomized participants identified 87 outcomes of importance to ED encompassing physical, cognitive, and emotional symptoms as well as functional disability. Self-rating scales indicated that many ED participants, beyond reporting fatigue, also reported symptoms of moderate to severe depression, anxiety, insomnia, poor self-rated health, and sickness behavior. CONCLUSIONS This study presents a map of outcome domains of importance for ED. Results shed light on the panorama of issues that individuals with ED deal with and can be used as a step to further understand the condition and to reach consensus regarding outcome domains to measure in clinical trials of chronic stress and fatigue. This article is protected by copyright. All rights reserved.
Astrocytic Kir4.1 channels regulate locomotion by orchestrating neuronal rhythmicity in the spinal network

Neuronal rhythmogenesis in the spinal cord is correlated with variations in extracellular K+ levels ([K+]e). Astrocytes play important role in [K+]e homeostasis and compute neuronal information. Yet it is unclear how neuronal oscillations are regulated by astrocytic K+ homeostasis. Here we identify the astrocytic inward‐rectifying K+ channel Kir4.1 (a.k.a. Kcnj10) as a key molecular player for neuronal rhythmicity in the spinal central pattern generator (CPG). By combining two‐photon calcium imaging with electrophysiology, immunohistochemistry and genetic tools, we report that astrocytes display Ca2+ transients before and during oscillations of neighboring neurons. Inhibition of astrocytic Ca2+ transients with BAPTA decreases the barium‐sensitive Kir4.1 current responsible of K+ clearance. Finally, we show in mice that Kir4.1 knockdown in astrocytes progressively prevents neuronal oscillations and alters the locomotor pattern resulting in lower motor performances in challenging tasks. These data identify astroglial Kir4.1 channels as key regulators of neuronal rhythmogenesis in the CPG driving locomotion.
A graph-valued Markov process as rings-allowed polymerization model: subcritical behavior

In previous papers, random tree-type partitions of a finite set as a stochastic model for acyclic polymerization were studied. In this paper, the model is extended one important step further by allowing rings formation. The main result is that, in the subcritical domain, the asymptotic behavior of the process remains essentially the same as in the acyclic case despite the fact that cycles are not excluded.
Band gap ion mass filter

Ions in a plasma may be radially separated according to mass using a combination of an axial magnetic field and either a radial or azimuthal electric field. The separation is qualitatively different from that obtained by a plasma centrifuge and the characteristics of confined and unconfined ion orbits are analogous to the phenomenon of band gaps in semiconductors.
African Easterly Wave Dynamics in a Mesoscale Numerical Model: The Upscale Role of Convection

AbstractTo examine the dynamical role of convection in African easterly wave (AEW) life cycles the Weather Research and Forecasting (WRF) model is used to simulate the evolution of a single AEW from September 2004. The model simulations are validated against corresponding numerical weather prediction analyses and the mean fields closely resemble composite structures from previous studies. A potential vorticity (PV) thinking approach is used to highlight the interactions between dynamics and convection.Organized deep convection embedded within the AEW has a large contribution to the synoptic-scale mean PV and energetics of the AEW. The PV tendency is maximized in the lower troposphere, consistent with the vertical gradient in diabatic heating rates in the areas of convection. By examining terms in the Lorenz energy cycle, it is shown that diabatic heating associated with convection is as important as adiabatic energy conversion in producing eddy available potential energy of the synoptic AEW, implying that.
Conversion of Adjustable Gastric Banding to Stapling Bariatric Procedures

Supplemental Digital Content is available in the text Objective: The aim of this study was to compare the safety of single- versus two-stage conversion of adjustable gastric band (AGB) to gastric bypass (RYGB) or sleeve gastrectomy (SG). Summary Background Data: AGB patients often present for conversion to RYGB or SG. The impact of single- or two-stage approach of such conversion remains unclear. Methods: A statewide database was used to identify all patients who underwent AGB removal and concurrent (single-stage) or interval (two-stage) RYGB or SG. Propensity score matching schemes were constructed to account for differences in baseline comorbidities and demographics, allowing for matched pairs available for comparisons. Results: A total of 4330 patients underwent AGB conversion. Complications, readmissions, and ED visits were noted in 394 (9.1%), 278 (6.42%), and 589 (13.6%) patients, respectively. Three hundred sixty-seven matched pairs underwent RYGB; single-stage patients experienced shorter length of stay (LOS) (median difference −1 d, P < 0.0001), less complications [risk difference (RD): −8.4%, 95% confidence interval (CI), −13.4% to −3.5%], readmissions (RD: −5.2%, 95% CI, −9.6% to −0.8%), and ED visits (RD: −5.7%, 95% CI, −11.3% to −0.2%). Eight hundred seventy-five matched pairs underwent SG; single-stage patients experienced improved outcomes in all measures examined. For single-stage procedures (809 pairs), RYGB was associated with longer LOS, and more complications (RD: 3.3%, 95% CI, 0.9%–5.8%), with similar readmissions, and ED visits. Conclusions: AGB conversion procedures have low morbidity. Single-stage conversion is associated with lower morbidity compared with the two-stage approach. Conversion to SG seems to be safer than RYGB.
Spectral features in solar hard X-ray and radio events and particle acceleration.

Hard x-ray and radio intensities of two major solar outbursts are found to anticorrelate in time with their spectral indices, which, furthermore, are in satisfactory correlation with each other. The radio emission must be synchrotron radiation from the same electron population that causes the x-ray bremsstrahlung. A delay of temporal features, increasing with energy, is clearly observed in one of the x-ray events. The observations are interpreted with a simple model, which assumes ion-acoustic instability in a current sheet, transformation of turbulence energy into Langmuir waves, and their escape into the ambient plasma where they accelerate particles. A power-law index of the electron energy distribution is derived for acceleration being balanced by escape of particles. Anticorrelation of intensity and spectral index then follows naturally from variations of spectral wave energy density or the dimension of the acceleration region. The finite collision time in the acceleration region and its increase with energy introduce a perturbation which can explain the observed drift of temporal features. (AIP)
Prognostic value of the nodal yield in oral squamous cell carcinoma: a systematic review and meta-analysis

ABSTRACT Objectives To systematically evaluate the prognostic value of the nodal yield in oral squamous cell carcinoma by meta-analysis. Methods The meta-analysis was adherence to PRISMA. We searched MEDLINE, Embase, and Cochrane for studies published up to 20 April 2022. We collected evidences from observational studies regarding nodal yield in oral squamous cell carcinoma, and investigated its prognostic value by the routine methods of meta-analysis. Results From seven studies, there was no significant impact of the lymph node yield on overall survival among patients with oral squamous cell carcinoma cases and <18 lymph nodes (hazard ratio (HR) = 1.019, 95% confidence interval (CI) = 0.786–1.320, p = 0.887), with significant heterogeneity (I2 = 80%). The pooled result indicated that a > 18-lymph node yield was a favorable prognostic factor (HR = 0.786, 95%CI = 0.646–0.956, p = 0.016; I2 = 39%). The lymph node yield was not associated with disease-specific survival (HR = 1.594, 95%CI = 0.996–2.552, p = 0.052; I2 = 81%) or disease-free survival (HR = 1.508, 95%CI = 0.924–2.460, p = 0.100; I2 = 41%). Conclusion A lymph node yield of ≥18 lymph nodes might be a favorable prognostic factor for the overall survival of patients with oral squamous cell carcinoma.
The relationship between high density lipoprotein cholesterol and sepsis: A clinical and genetic approach

Sepsis accounts for one in three hospital deaths. Higher concentrations of high‐density lipoprotein cholesterol (HDL‐C) are associated with apparent protection from sepsis, suggesting a potential therapeutic role for HDL‐C or drugs, such as cholesteryl ester transport protein (CETP) inhibitors that increase HDL‐C. However, these beneficial clinical associations might be due to confounding; genetic approaches can address this possibility. We identified 73,406 White adults admitted to Vanderbilt University Medical Center with infection; 11,612 had HDL‐C levels, and 12,377 had genotype information from which we constructed polygenic risk scores (PRS) for HDL‐C and the effect of CETP on HDL‐C. We tested the associations between predictors (measured HDL‐C, HDL‐C PRS, CETP PRS, and rs1800777) and outcomes: sepsis, septic shock, respiratory failure, and in‐hospital death. In unadjusted analyses, lower measured HDL‐C concentrations were significantly associated with increased risk of sepsis (p = 2.4 × 10−23), septic shock (p = 4.1 × 10−12), respiratory failure (p = 2.8 × 10−8), and in‐hospital death (p = 1.0 × 10−8). After adjustment (age, sex, electronic health record length, comorbidity score, LDL‐C, triglycerides, and body mass index), these associations were markedly attenuated: sepsis (p = 2.6 × 10−3), septic shock (p = 8.1 × 10−3), respiratory failure (p = 0.11), and in‐hospital death (p = 4.5 × 10−3). HDL‐C PRS, CETP PRS, and rs1800777 significantly predicted HDL‐C (p < 2 × 10−16), but none were associated with sepsis outcomes. Concordant findings were observed in 13,254 Black patients hospitalized with infections. Lower measured HDL‐C levels were significantly associated with increased risk of sepsis and related outcomes in patients with infection, but a causal relationship is unlikely because no association was found between the HDL‐C PRS or the CETP PRS and the risk of adverse sepsis outcomes.
New Monte Carlo Simulation Technique for Quasi-Ballistic Transport in Ultrasmall Metal Oxide Semiconductor Field-Effect Transistors

A new Monte Carlo simulation technique considering the uncertainty relation and the Pauli principle is proposed for analyzing a quasi-ballistic metal oxide semiconductor field-effect transistor (MOSFET). Instead of the conventional phase space that consists of continuous position and momentum, a discrete phase space represented by a complete basis set of the state vector is employed. The carrier dynamics in the device are analyzed using the Monte Carlo simulation framework, in which a possible transition among numerous probabilistic transitions between these discrete states is selected using random numbers. The technique is applied to a 90 nm MOSFET. Analysis shows how the phonon scattering disturbs the ballistic transport, and yields a result that the backscattered flux due to phonon scattering amounts to 27% of the original carrier flux injected from the source for the device.