Germinal centers (GC) are the sites of B cell clonal expansion, somatic hypermutation and clonal selection, a process that leads to the production of antibodies of higher affinity [1](#ref-0001). Efforts have been made to understand the kinetic of events controlling the GC and the production of specific antibodies in protective as well in pathogenic responses, such as autoimmunity and allergy. The ability of newly mutated GC clones to capture and present antigen to T follicular helper cells (Tfh) in the light zone of the GC is crucial for clonal survival and selection. Tfh cells produce IL-21, a key cytokine for the GC reaction and antibody responses [2](#ref-0002). However, it was not understood how IL-21 acts independently on T and B cells to mediate the GC reaction. In this study Quast and colleagues [3](#ref-0003) contribute to elucidate the specific role of IL-21 on the GC reaction and how IL-21 bioavailability affects the outcome of the GC response. They demonstrate that IL-21 influences Tfh cell differentiation and expansion early, before the GC establishment, as well later during GC development, through both autocrine and paracrine mechanisms, regardless of cognate T-B cell interactions.

RNA-binding proteins (RBPs) govern the lifespan of nearly all transcripts and play key roles in adaptive responses in microbes. A robust approach to examine protein-RNA interactions involves irradiating cells with UV light to form covalent adducts between RBPs and their cognate RNAs. Combined with RNA or protein purification, these procedures can provide global RBP censuses or transcriptomic maps for all target sequences of a single protein in living cells. Recent development of novel methods has quickly populated the RBP landscape in microorganisms. Here, we provide an overview of prominent UV cross-linking techniques which have been applied to investigate RNA interactomes in microbes. By assessing their advantages and caveats, this technical evaluation intends to guide the selection of appropriate methods and experimental design as well as to encourage the use of complementary UV-dependent techniques to inspect RNA-binding activity.

Economical uranium adsorption from seawater remains a crucial task for energy and environmental safety. Aiming for improving the mass transfer rate of uranium adsorption. Herein, a novel 2D porous aromatic framework(PAF) based on nucleophilic substitution of 2,5-dichloro benzonitrile was synthesized, with an ordered prous structure, excellent stability and selectivity of uranium extraction from seawater. PAF shows excellent uranium adsorption capacity of 637 mg/g and 3.22 mg/g in simulated and real seawater because of highly accessible pores on the walls of open channels. In addition, benefiting from the super-hydrophilicity due to the presence of amidoxime groups attributes high selectivity and ultrafast kinetics with an uptake rate of 0.43±0.03 mg/g.day and allowing half-saturation within 1.35±0.09 day. This strategy demonstrates a potential of PAF not only in uranium trap but also possess a power to monitor water quality. This technique can be extended in other applications by sensible planning target ligands

A document by Martha Zillig. Click on the document to view its contents.

The genomics revolution continues to change how ecologists and evolutionary biologists study the evolution and maintenance of biodiversity. It is now easier than ever to generate large molecular data sets consisting of hundreds to thousands of independently evolving nuclear loci to estimate a suite of evolutionary and demographic parameters. However, any inferences will be incomplete or inaccurate if incorrect taxonomic identities and perpetuated throughout the analytical pipeline. Due to decades of research and comprehensive online databases, sequencing of mitochondrial DNA (mtDNA), chloroplast DNA (cpDNA) and select nuclear genes can provide researchers with a cost effective and simple means to verify the species identity of samples prior to subsequent phylogeographic and population genomic analysis. The addition of these sequences to genomic studies can also shed light on other important evolutionary questions such as explanations for gene tree-species tree discordance, species limits, sex-biased dispersal patterns, and mtDNA introgression. Although the mtDNA and cpDNA genomes often should not be used exclusively to make historical inferences given their well-known limitations, the addition of these data to modern genomic studies adds little cost and effort while simultaneously providing a wealth of useful data that can have significant implications for both basic and applied research.

Introduction: Delayed enhancement - magnetic resonance imaging (DE-MRI) has demonstrated that nonischemic cardiomyopathy is mainly characterized by intramural or epicardial fibrosis whereas global endomyocardial fibrosis suggests cardiac involvement in autoimmune rheumatic diseases or amyloidosis. Conduction disorders and sudden cardiac death are important manifestations of autoimmune rheumatic diseases with cardiac involvement but the substrates of ventricular arrhythmias in autoimmune rheumatic diseases have not been fully elucidated. Methods and Results: 20 patients with autoimmune rheumatic diseases presenting with ventricular tachycardia (VT) (n=11) or frequent ventricular extrasystoles (n=9) underwent DE-MRI and / or endocardial electroanatomical mapping of the left ventricle (LV). 10 patients with autoimmune rheumatic diseases underwent VT ablation. Global endomyocardial fibrosis without myocardial thickening and unrelated to coronary territories was detected by DE-MRI or electroanatomical voltage mapping in 9 of 20 patients with autoimmune rheumatic diseases. In the other patients with autoimmune rheumatic diseases, limited regions of predominantly epicardial (n = 4) and intramyocardial (n = 5) fibrosis or only minimal fibrosis (n = 2) were found using DE-MRI. Endocardial low-amplitude diastolic potentials and pre-systolic Purkinje or fascicular potentials, mostly within fibrotic areas, were identified as the targets of successful VT ablation in 7 of 10 patients with autoimmune rheumatic diseases. Conclusion: Global endomyocardial fibrosis can be a tool to diagnose severe cardiac involvement in autoimmune rheumatic diseases and may serve as the substrate of ventricular arrhythmias in a substantial part of patients.

Introduction: Antitachycardia pacing (ATP) is used to terminate ventricular tachycardia (VT) by delivering rapid, low energy pacing to the right ventricle (RV). Unfortunately, ATP is not effective against all VT episodes and can result in adverse outcomes, such as VT acceleration and degeneration into ventricular fibrillation (VF). Improving ATP is therefore desirable. Our objective was to compare the efficacy and safety of ATP delivered at the His bundle to traditional ATP. Methods: Six dogs were anesthetized and pacing leads were implanted in the RV and His bundle. The lateral anterior descending artery (LAD) was occluded for 2 hours to create an ischemic injury. In a study 4-7 days later, a 128-electrode sock was placed snugly around the ventricles and VT was induced using rapid pacing. ATP was delivered from either the His bundle or RV lead, then attempted at the other location if unsuccessful. Success rates and instances of VT acceleration and degeneration into VF were calculated. Results: We induced 83 runs of VT and attempted ATP 128 times. RV ATP was successful in 36% of attempts; His ATP was successful in 38% of attempts. RV ATP resulted in significantly more adverse outcomes. RV and His ATP induced VT acceleration in 9% and 3% of trains respectively, and induced degeneration into VF in 5% and 1% of trains, respectively. Conclusion: His bundle ATP is safer, but not significantly more effective, than RV ATP.

Background: eHealth CF-CBT is the first digital mental health intervention for depression/anxiety in adults with cystic fibrosis (awCF); an 8-session therapist-guided internet-delivered program that was developed in English and Dutch with stakeholder input and evaluation indicating high acceptability and usability. Methods: Dutch eHealth CF-CBT was piloted in awCF with mild-moderate symptoms of depression and/or anxiety. Feasibility, usability, acceptability, and preliminary efficacy were assessed, measuring pre-post changes in depression (PHQ-9), anxiety (GAD-7), perceived stress (PSS) and health-related quality of life (CFQ-R). Results: All participants (n=10, 7 female, mean age 29 (range 21-43), mean FEV1 71%pred (range 31-115)) completed all sessions. Patient-rated feasibility, usability and acceptability of eHealth CF-CBT was positive on validated scales, as were qualitative assessments of content and format. GAD-7 improved in 90% of participants; in 50% by ≥ the minimally important difference (MID) of 4 points. PHQ-9 improved in 90%; 40% by ≥ the MID of 5. PSS improved in 80%. CFQ-R improved in the domain Health Perceptions (70%). Conclusions: eHealth CF-CBT demonstrated feasibility, usability, acceptability and promising preliminary efficacy in this pilot trial with Dutch awCF with mild to moderate symptoms of depression and anxiety.

Pulmonary Vein Isolation-induced Vagal Nerve Injury and Gastric Motility DisordersBachir Lakkiss, MD; Marwan M. Refaat, MDDivision of Cardiology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, LebanonRunning Title: PVI-induced vagal nerve injury and gastric motility disordersWords: 665 (excluding the title page and references)Keywords: Heart Diseases, Cardiovascular Diseases, Cardiac Arrhythmias, Atrial Fibrillation, Catheter Ablation, Pulmonary Vein IsolationFunding: NoneDisclosures: NoneCorresponding Author:Marwan M. Refaat, MD, FACC, FAHA, FHRS, FRCPTenured Professor of MedicineTenured Professor of Biochemistry and Molecular GeneticsVan Dyck Medical Educator and Director of the Cardiovascular Fellowship ProgramDepartment of Internal Medicine, Cardiovascular Medicine/Cardiac ElectrophysiologyAmerican University of Beirut Faculty of Medicine and Medical CenterPO Box 11-0236, Riad El-Solh 1107 2020- Beirut, LebanonUS Address: 3 Dag Hammarskjold Plaza, 8th Floor, New York, NY 10017, USAOffice: +961-1-350000/+961-1-374374 Extension 5353 or Extension 5366 (Direct)Email: [email protected] fibrillation (AF) is the most prevalent heart rhythm abnormality worldwide. An estimated three to six million people in the United States have AF. It is expected that this number is likely to double by 2050, making AF a significant public health burden. (1) AF is a leading cause of stroke and thromboembolism and is associated with a reduced quality of life. (2) Furthermore, it is linked to an increased mortality in both men and women, with an OR for death of 1.5 in men and 1.9 in women. (3) Medical expenditures for AF are significant, ranging from an annual cost of $1,632 to $21,099, with acute care accounting for the largest cost component in addition to anticoagulation therapy, which accounted for almost one-third of these costs. (4) The four pillars of AF management include rhythm control, rate control, stroke prevention and risk factor management. (5, 6) While antiarrhythmic drugs are used in some patients for AF rhythm control, AF ablation using pulmonary vein isolation (PVI) is regarded as the major modality for rhythm control. (6)The vagal nerve provides most of the parasympathetic innervation to the abdominal organs, including the stomach, esophagus, and a significant portion of the intestines. It serves a major role in the regulation of gastric and esophageal motility, in addition to maintaining lower esophageal sphincter tone. (7-9) Due to the relatively close vicinity of the vagal nerve plexus located on the anterior surface of the esophagus and the left atrial posterior wall, the thermal energy utilized during ablation can result in uncommon but potentially fatal complications such as esophageal perforation and atrial-esophageal fistula formation. (10-12) In addition, radiofrequency ablation for AF is associated with non-fatal complications such as an increased risk of gastric motility disorders and acid reflux. (13, 14)In the current issue of the Journal of Cardiovascular Electrophysiology, Meininghaus et al. recruited 85 patients to assess the incidence of ablation-induced vagal nerve injury (VNI) using both cryoballoon and radiofrequency ablation. Although many cases of VNI induced by PVI have been documented previously, this is one of the first studies to utilize electrophysiologic measurements of gastric motility (EGG) using cutaneous electrodes to record the electrical activity of the stomach two days prior to and two days after the procedure. (15-17) Moreover, the authors have used endoscopy to detect lesions such as erosions, ulcers, and perforations in the esophagus one week prior to and within two days of the procedure.The findings from this study add to our understanding of one of the complications of PVI in patients with AF (13, 14). One of the key outcomes the researchers observed was the perceived direct link between VNI and preexisting esophageal vulnerability. The authors have found that patients who had preexisting esophagitis had an elevated risk of developing VNI. In addition, the authors identified that in patients in whom EGG showed VNI, the elevated risk of ablation-induced endoscopic pathology was present in the post-procedure endoscopy. Furthermore, another significant finding was the detection of VNI on EGG in approximately one-third of PVI patients, irrespective of energy source, whether high power short duration, or moderate power moderate duration. These findings did not corroborate other studies, which showed that titration of the duration of the ablation energy could prevent VNI in patients undergoing AF ablation. (18)Overall, the authors should be commended for their tremendous efforts in attempting to understand the intricate pathophysiology and the association of esophageal lesions, atrial-esophageal fistula formation, and vagal nerve injury following PVI using EGG. Certainly, the results of this study have tremendous clinical implications. EGG could have a very important role in the prevention of atrial-esophageal fistula formation in the future. The article had a few limitations, mainly that the results were from a single-center study. Further studies incorporating additional patients from different medical centers should be conducted to better understand the complex pathophysiology of vagal nerve injury and gastric motility disorders following PVI. Advances in esophageal protection technologies will help in decreasing esophageal lesions during PVI. (19-20)References1. Miyasaka Y, Barnes ME, Gersh BJ, Cha SS, Bailey KR, Abhayaratna WP, et al. Secular Trends in Incidence of Atrial Fibrillation in Olmsted County, Minnesota, 1980 to 2000, and Implications on the Projections for Future Prevalence. Circulation. 2006;114(2):119-25. doi: doi:10.1161/CIRCULATIONAHA.105.595140.2. Jalloul Y, Refaat MM. IL-6 Rapidly Induces Reversible Atrial Electrical Remodeling by Downregulation of Cardiac Connexins. J Am Heart Assoc. 2019;8(16):e013638. Epub 2019/08/20. doi: 10.1161/jaha.119.013638. PubMed PMID: 31423871; PubMed Central PMCID: PMCPMC6759896.3. Benjamin EJ, Wolf PA, D’Agostino RB, Silbershatz H, Kannel WB, Levy D. Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation. 1998;98(10):946-52. Epub 1998/09/16. doi: 10.1161/01.cir.98.10.946. PubMed PMID: 9737513.4. Wodchis WP, Bhatia RS, Leblanc K, Meshkat N, Morra D. A review of the cost of atrial fibrillation. Value Health. 2012;15(2):240-8. Epub 2012/03/22. doi: 10.1016/j.jval.2011.09.009. PubMed PMID: 22433754.5. Lakkis B, Refaat MM. Is esophageal temperature management needed during cryoballoon ablation for atrial fibrillation? Journal of Cardiovascular Electrophysiology. 2022;33(12):2567-8. doi: https://doi.org/10.1111/jce.15725.6. Chung MK, Refaat M, Shen W-K, Kutyifa V, Cha Y-M, Di Biase L, et al. Atrial Fibrillation: JACC Council Perspectives. Journal of the American College of Cardiology. 2020;75(14):1689-713. doi: https://doi.org/10.1016/j.jacc.2020.02.025.7. Richards WG, Sugarbaker DJ. Neuronal control of esophageal function. Chest Surg Clin N Am. 1995;5(1):157-71. Epub 1995/02/01. PubMed PMID: 7743145.8. Hsu M, Safadi AO, Lui F. Physiology, Stomach. StatPearls. Treasure Island (FL): StatPearls PublishingCopyright © 2022, StatPearls Publishing LLC.; 2022.9. Goyal RK, Chaudhury A. Physiology of normal esophageal motility. J Clin Gastroenterol. 2008;42(5):610-9. Epub 2008/03/28. doi: 10.1097/MCG.0b013e31816b444d. PubMed PMID: 18364578; PubMed Central PMCID: PMCPMC2728598.10. Kapur S, Barbhaiya C, Deneke T, Michaud GF. Esophageal Injury and Atrioesophageal Fistula Caused by Ablation for Atrial Fibrillation. Circulation. 2017;136(13):1247-55. doi: doi:10.1161/CIRCULATIONAHA.117.025827.11. D’Avila A, Ptaszek LM, Yu PB, Walker JD, Wright C, Noseworthy PA, et al. Images in cardiovascular medicine. Left atrial-esophageal fistula after pulmonary vein isolation: a cautionary tale. Circulation. 2007;115(17):e432-3. Epub 2007/05/02. doi: 10.1161/circulationaha.106.680181. PubMed PMID: 17470703.12. Sánchez-Quintana D, Cabrera JA, Climent V, Farré J, Mendonça MCd, Ho SY. Anatomic Relations Between the Esophagus and Left Atrium and Relevance for Ablation of Atrial Fibrillation. Circulation. 2005;112(10):1400-5. doi: doi:10.1161/CIRCULATIONAHA.105.551291.13. Shah D, Dumonceau J-M, Burri H, Sunthorn H, Schroft A, Gentil-Baron P, et al. Acute Pyloric Spasm and Gastric Hypomotility: An Extracardiac Adverse Effect of Percutaneous Radiofrequency Ablation for Atrial Fibrillation. Journal of the American College of Cardiology. 2005;46(2):327-30. doi: https://doi.org/10.1016/j.jacc.2005.04.030.14. Park S-Y, Camilleri M, Packer D, Monahan K. Upper gastrointestinal complications following ablation therapy for atrial fibrillation. Neurogastroenterology & Motility. 2017;29(11):e13109. doi: https://doi.org/10.1111/nmo.13109.15. Choi SW, Kang SH, Kwon OS, Park HW, Lee S, Koo BS, et al. A case of severe gastroparesis: indigestion and weight loss after catheter ablation of atrial fibrillation. Pacing Clin Electrophysiol. 2012;35(3):e59-61. Epub 2010/10/05. doi: 10.1111/j.1540-8159.2010.02912.x. PubMed PMID: 20883511.16. Lakkireddy D, Reddy YM, Atkins D, Rajasingh J, Kanmanthareddy A, Olyaee M, et al. Effect of atrial fibrillation ablation on gastric motility: the atrial fibrillation gut study. Circ Arrhythm Electrophysiol. 2015;8(3):531-6. Epub 2015/03/17. doi: 10.1161/circep.114.002508. PubMed PMID: 25772541.17. Kuwahara T, Takahashi A, Takahashi Y, Kobori A, Miyazaki S, Takei A, et al. Clinical characteristics and management of periesophageal vagal nerve injury complicating left atrial ablation of atrial fibrillation: lessons from eleven cases. J Cardiovasc Electrophysiol. 2013;24(8):847-51. Epub 2013/04/05. doi: 10.1111/jce.12130. PubMed PMID: 23551640.18. KUWAHARA T, TAKAHASHI A, KOBORI A, MIYAZAKI S, TAKAHASHI Y, TAKEI A, et al. Safe and Effective Ablation of Atrial Fibrillation: Importance of Esophageal Temperature Monitoring to Avoid Periesophageal Nerve Injury as a Complication of Pulmonary Vein Isolation. Journal of Cardiovascular Electrophysiology. 2009;20(1):1-6. doi: https://doi.org/10.1111/j.1540-8167.2008.01280.x.19. D’Avila A, Ptaszek LM, Yu PB, Walker JD, Wright C, Noseworthy PA, Myers A, Refaat M, Ruskin JN: Left Atrial-Esophageal Fistula After Pulmonary Vein Isolation. Circulation May 2007; 115(17): e432-3.20. El Moheb MN, Refaat MM. Protecting the Esophagus During Catheter Ablation: Evaluation of a Novel Vacuum Suction-Based Retractor. J Cardiovasc Electrophysiol Jul 2020; 31 (7): 1670-1671.

Oral mucosal lesions may persist years before diagnosis of inflammatory bowel disease (IBD) and subsequent primary sclerosing cholangitis (PSC). It may be that a dental practitioner may be the first clinician to suspect IBD. Suspect IBD; early referral and close collaboration with a gastroenterologist are recommended.

Error Augmentation training using a robotic interface is thought to promote motor recovery by enhancing proprioceptive feedback, which motivates and challenges patients to optimize their performance during training. Here, we investigated the effectiveness of robotic Error Augmentation training on motor recovery after a stroke, compared to standard robotic training in a null field. Post-stroke patients were randomly assigned to one of two groups: a study group (n=9) that was trained on a 3D robotic system applying Error Augmentation forces, and a control group (n=7) that carried out the same protocol in null field conditions. The robotic rehabilitation intervention was applied in addition to the standard rehabilitation protocol of the rehabilitation center. Error Augmentation training increased clinical scores compared to standard robotic training by 266% on the Motor Assessment Scale, and 88% on the Fugl-Meyer scale. The Motor Assessment Scale scores were significantly correlated with the Fugl-Meyer scores (p=0.03, r=0.541). There were more movement errors on the initial trials of the game sequence using the DeXtreme robotic device with Error Augmentation compared to trials with no force field. This difference vanished however after 10 trials. Error Augmentation training decreased the number of movement units and jerkiness compared to the control treatment. These findings suggest that Error Augmentation training may enhance motor performance possibly through motor adaptation.

A document by Carmen H. Li. Click on the document to view its contents.

1. High latitude ecosystems are experiencing the most rapid warming on earth, expected to trigger a diverse array of ecological responses. Climate warming affects the ecophysiology of fish, and fish close to the cold end of their thermal distribution are expected to increase somatic growth from increased temperatures and a prolonged growth season, which in turn affects maturation schedules, reproduction and survival, boosting population growth. Accordingly, fish species living in ecosystems close to their northern range edge should increase in numerical importance and possibly displace cold-water adapted species. 2. We aim to document if and how population level effects of warming mediated by individual level responses to increased temperatures, shift community structure and composition in high latitude ecosystems. 3. We studied 11 cool-water adapted freshwater fish populations in communities dominated by cold-water adapted species to investigate changes in the relative importance of cool-water fish during the last 30 years of rapid warming in high latitude lakes. In addition, we studied the individual level responses to warming to clarify the potential mechanisms underlying the population effects. 4. Our long-term series‘ (1991-2020) reveal a marked increase in numerical importance of the cool-water fish species, perch, in ten out of eleven populations, and in most fish communities the cool-water species is now dominant. Moreover, we show that climate warming affects population level processes via direct and indirect temperature effects on the individuals. Specifically, the increase in abundance arises from increased survival of 0+ individuals, faster juvenile growth and ensuing earlier maturation, all boosted by climate warming. 5. The speed and magnitude of the response to warming in these high latitude fish communities strongly suggest that cold-water fish will be displaced by fish adapted to warmer water. Consequently, management should focus on climate adaptation limiting future introductions and invasions of cool-water fish and mitigating harvesting pressure on cold-water fish.

A document by Ryuhei Jinushi. Click on the document to view its contents.

This study provides a comprehensive account of the various types of calcium oxalate crystals found in the genus Baccharis and assesses the exceptional value of crystal macropatterns for the taxonomy of the genus. The morphotype, occurrence and chemical composition of the crystals found in the stems and leaves are studied. The 44 species included in this study were selected based on a broad phylogeny-based sampling covering seven subgenera and 31 sections. These species were chosen to represent all the main phylogenetic lineages of Baccharis; thus, the sampling also represents a comprehensive coverage concerning evolutionary significance for such a large and environmentally and economically important plant group. The samples were analyzed by light microscopy, scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDS). Several morphotypes of crystals, including druses, crystal sand, styloids and prisms, were present. Based on their chemical composition, the crystals were classified as pure calcium oxalate, mixtures of oxalates and sulfates, and mixtures of oxalates, sulfates and silica. The crystal macropatterns observed in this study aid in the species identification and provide novel data for the taxonomy of Baccharis.

Brassica crops include various edible vegetable and plant oil crops, and their production is limited by low temperature beyond their tolerant capability. The key regulators of low-temperature resistance in Brassica remain largely unexplored. To identify post-transcriptional regulators of plant response to low temperature, we performed small RNA profiling, and found that 16 known miRNAs were responsive to cold treatment in Brassica rapa. The cold response of seven of those miRNAs were further confirmed by qRT-PCR and/or northern blotting analyses. In parallel, a genome-wide association study of 220 accessions of Brassica napus identified four candidate MIRNA genes, all of which were cold-responsive, at the loci associated with low temperature resistance. Specifically, these large-scale data analyses revealed a link between miR1885 and the plant response to low temperature in both B. rapa and B. napus. Using 5′ rapid amplification of cDNA ends approach, we validated that miR1885 can cleave its putative target transcripts, Bn.TIR.A09 and Bn.TNL.A03, in B. napus. Furthermore, overexpression of miR1885 in Semi-winter type B. napus decreased the mRNA abundance of Bn.TIR.A09 and Bn.TNL.A03, resulting in increased sensitivity to low temperature. Knocking down of miR1885 in Spring type B. napus led to increased mRNA abundance of its targets and improved rapeseed tolerance to low temperature. Together, our results suggested that the loci of miR1885 and its targets could be potential candidates for the molecular breeding of low temperature-tolerant Spring type Brassica crops.

The poly lactate co-glycolic acid (PLGA) nanoparticles of tubercular drugs have been demonstrated to have sustained release profile over seven days. There is no information on the location or mode of release of these nanoparticles in living system. Therefore, we have planned the study to explore the pharmacokinetics and biodistribution of PLGA rifampicin nanoparticles in healthy human volunteers. Rifampicin was labeled with 99mTc by indirect method and nanoparticles were prepared by a single emulsion evaporation method. To investigate the pharmacokinetics and biodistribution of nanoparticles, a single dose of 450 mg of rifampicin was administered orally to healthy human volunteers divided into two different groups. Following a single oral dosage of the rifampicin nanoformulation, the PK parameters were significantly different between the nanoparticle and conventional groups AUC (113.8 vs 58.6), MRT (16.2 vs 5.8) and Ke (0.04 vs 0.10). Also SPECT/CT images revealed bio-distrubution of nanoparticles in the distal portions of the intestine, which is consistent with our dosimetry analysis Significant difference in PK parameters and bio-distribution of nanoparticles in spleen and lymph nodes with maximum deposition were observed in large intestine. Nanoparticle distribution pattern may be advantageous for the treatment of intestinal or lymph node TB and has the potential to result in a lower dose of rifampicin nanoformulation for the treatment of pulmonary TB.

We study the ground state solutions for the following p\&q-Laplacain equation \[ \left\{ \begin{array}{ll} -\Delta_pu-\Delta_qu+V(x) (|u|^{p-2}u+|u|^{q-2}u)=\lambda K(x)f(u)+|u|^{q^*-2}u,~x\in\R^N, \\ u\in W^{1,p}(\R^N)\cap W^{1,q}(\R^N), \end{array} \right. \] where $\lambda>0$ is a parameter large enough, $\Delta_ru = \text{div}(|\nabla u|^{r-2}\nabla u)$ with $r\in\{p,q\}$ denotes the $r$ Laplacian operator, $1