Gα13 restricts nutrient driven proliferation in mucosal germinal centers.

Germinal centers (GCs) that form in mucosal sites are exposed to gut-derived factors that have the potential to influence homeostasis independent of antigen receptor-driven selective processes. The G-protein Gα13 confines B cells to the GC and limits the development of GC-derived lymphoma. We discovered that Gα13-deficiency fuels the GC reaction via increased mTORC1 signaling and Myc protein expression specifically in the mesenteric lymph node (mLN). The competitive advantage of Gα13-deficient GC B cells (GCBs) in mLN was not dependent on T cell help or gut microbiota. Instead, Gα13-deficient GCBs were selectively dependent on dietary nutrients likely due to greater access to gut lymphatics. Specifically, we found that diet-derived glutamine supported proliferation and Myc expression in Gα13-deficient GCBs in the mLN. Thus, GC confinement limits the effects of dietary glutamine on GC dynamics in mucosal tissues. Gα13 pathway mutations coopt these processes to promote the gut tropism of aggressive lymphoma.

Aberrant expansion of spontaneous splenic germinal centers induced by hallmark genetic lesions of aggressive lymphoma.

Unique molecular vulnerabilities have been identified in the aggressive MCD/C5 genetic subclass of diffuse large B-cell lymphoma (DLBCL). However, the premalignant cell-of-origin exhibiting MCD-like dependencies remains elusive. In this study, we examined animals carrying up to 4 hallmark genetic lesions found in MCD consisting of gain-of-function mutations in Myd88 and Cd79b, loss of Prdm1, and overexpression of BCL2. We discovered that expression of combinations of these alleles in vivo promoted a cell-intrinsic accumulation of B cells in spontaneous splenic germinal centers (GCs). As with MCD, these premalignant B cells were enriched for B-cell receptors (BCRs) with evidence of self-reactivity, displayed a de novo dependence on Tlr9, and were more sensitive to inhibition of Bruton's tyrosine kinase. Mutant spontaneous splenic GC B cells (GCB) showed increased proliferation and IRF4 expression. Mice carrying all 4 genetic lesions showed a >50-fold expansion of spontaneous splenic GCs exhibiting aberrant histologic features with a dark zone immunophenotype and went on to develop DLBCL in the spleen with age. Thus, by combining multiple hallmark genetic alterations associated with MCD, our study identifies aberrant spontaneous splenic GCBs as a likely cell-of-origin for this aggressive genetic subtype of lymphoma.

Coralline photosynthetic physiology across a steep light gradient.

Coralline algae (CA) are globally distributed and fulfil many important roles within coastal ecosystems. In this study, photosynthetically active radiation (PAR) measured for 616 days at 2 and 10 m in a temperate subtidal kelp forest in southern New Zealand provided context to photosynthesis vs. irradiance relationships for, and pigment concentrations of, an articulated coralline alga, Arthrocardia sp. and a crustose coralline species assemblage within the Hapalidiales order. The maximum photosynthetic rate Pmax of the Arthrocardia sp. (20.38 ± 2.38 µmol O2. gDW-1 h-1) was significantly higher than the Pmax of crustose coralline spp. (3.72 ± 0.74 µmol O2. gDW-1 h-1) at the same 2 m stratum. Pigment concentration of Arthrocardia sp. was significantly higher than that of crustose coralline spp. at the same depth, while pigment concentration of crustose coralline spp. at 2 and 10 m were not significantly affected by depth. The photosynthetic characteristics of these coralline algae represent a shade acclimated organism with low saturation irradiance (all Ek < 100 µmol photons m-2 s-1). Despite sevenfold difference in average daily dose between 2 and 10 m there was no significant effect of depth on the photosynthetic performance of crustose coralline algae measured. The lack of evidence for acclimation to low light could be because periods of clear water provide enough light to maintain photosynthesis, lower energetic requirements of species found at depth or constraints on the synthesis of photosynthetic pigments at greater depth.

Toward enhanced visible-light photocatalytic dye degradation and reusability of La3+ substituted ZnFe2O4 nanostructures.

The present work focused on the synthesis of novel ZnLaxFe2-xO4 catalysts (x = 0, 0.01, 0.03, 0.05) and their utilization for the photocatalytic degradation of Rhodamine B dye. Structurally, the band gap energy of the catalysts tended to decrease (1.94-1.70 eV) with increasing the amount of La3+ dopant. ZnLa0.05Fe1.95O4 had an average particle size (40 nm), high surface area (41.07 m2 g-1) and large pore volume (0.186 cm3 g-1). Moreover, the effect of doping ratio, reaction time, H2O2 concentration, catalyst loading on the treatment performance of La3+ substituted ZnFe2O4 nanocomposites was investigated. ZnLa0.05Fe1.95O4/H2O2 system exhibited the highest degradation efficiency of 99.5% and nonlinear pseudo first-order kinetic reaction rate (14.8 × 10-3 min-1) in the presence of visible light irradiation. The key role of reactive oxygen species involving •O2- and •OH radicals was well explained through the scavenger study. A plausible mechanism of the degradation of Rhodamine B dye was also proposed. Due to two advantageous points including high recyclability (up to 4 cycles) and stability, La3+ substituted ZnFe2O4 nanocomposites can be an effective and competitive catalyst for the visible light-driven photodegradation of toxic dyes in the real wastewaters.

Semisynthesis and biological evaluation of a focused library of unguinol derivatives as next-generation antibiotics.

In this study, we report the semisynthesis and in vitro biological evaluation of thirty-four derivatives of the fungal depsidone antibiotic, unguinol. Initially, the semisynthetic modifications were focused on the two free hydroxy groups (3-OH and 8-OH), the three free aromatic positions (C-2, C-4 and C-7), the butenyl side chain and the depsidone ester linkage. Fifteen first-generation unguinol analogues were synthesised and screened against a panel of bacteria, fungi and mammalian cells to formulate a basic structure activity relationship (SAR) for the unguinol pharmacophore. Based on the SAR studies, we synthesised a further nineteen second-generation analogues, specifically aimed at improving the antibacterial potency of the pharmacophore. In vitro antibacterial activity testing of these compounds revealed that 3-O-(2-fluorobenzyl)unguinol and 3-O-(2,4-difluorobenzyl)unguinol showed potent activity against both methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MIC 0.25-1 µg mL-1) and are promising candidates for further development in vivo.

Identifying the Transcriptional Response of Cancer and Inflammation-Related Genes in Lung Cells in Relation to Ambient Air Chemical Mixtures in Houston, Texas.

Atmospheric pollution represents a complex mixture of air chemicals that continually interact and transform, making it difficult to accurately evaluate associated toxicity responses representative of real-world exposure. This study leveraged data from a previously published article and reevaluated lung cell transcriptional response induced by outdoor atmospheric pollution mixtures using field-based exposure conditions in the industrialized Houston Ship Channel. The tested hypothesis was that individual and co-occurring chemicals in the atmosphere relate to altered expression of critical genes involved in inflammation and cancer-related processes in lung cells. Human lung cells were exposed at an air-liquid interface to ambient air mixtures for 4 h, with experiments replicated across 5 days. Real-time monitoring of primary and secondary gas-phase pollutants, as well as other atmospheric conditions, was simultaneously conducted. Transcriptional analysis of exposed cells identified critical genes showing differential expression associated with both individual and chemical mixtures. The individual pollutant identified with the largest amount of associated transcriptional response was benzene. Tumor necrosis factor (TNF) and interferon regulatory factor 1 (IRFN1) were identified as key upstream transcription factor regulators of the cellular response to benzene. This study is among the first to measure lung cell transcriptional responses in relation to real-world, gas-phase air mixtures.

Autophagy: A Novel Mechanism Involved in the Anti-Inflammatory Abilities of Probiotics.

BACKGROUND/AIMS: Deregulation of the complex interaction among host genetics, gut microbiota and environmental factors on one hand and aberrant immune responses on the other hand, are known to be associated with the development of inflammatory bowel disease. Recent studies provided strong evidence that autophagy plays a key role in the etiology of Crohn's disease (CD). Probiotics may exhibit many therapeutic properties, including anti-inflammatory abilities. While successful results have been obtained in ulcerative colitis patients, probiotics remain inefficient in CD for unknown reason. It remains therefore important to better understand their molecular mechanisms of action. METHODS: The activation of autophagy was examined by stimulating bone marrow-derived dendritic cells by the bacteria, followed by confocal microscopy and western blot analysis. The impact of blocking in vitro autophagy was performed in peripheral blood mononuclear cells using 3-methyl adenine or bafilomycin followed by cytokine secretion measurement by ELISA. The role of autophagy in the anti-inflammatory capacities of the bacterial strains was evaluated in vivo using an acute trinitrobenzene sulfonic acid-induced murine model of colitis. The impact of BMDC was evaluated by adoptive transfer, notably using bone marrow cells derived from autophagy-related 16-like 1-deficient mice. RESULTS: We showed that selected lactobacilli and bifidobacteria are able to induce autophagy activation in BMDCs. Blocking in vitro autophagy abolished the capacity of the strains to induce the release of the anti-inflammatory cytokine interleukin-10, while it exacerbated the secretion of the pro-inflammatory cytokine interleukin-1ß. We confirmed in the TNBS-induced mouse model of colitis that autophagy is involved in the protective capacity of these selected strains, and showed that dendritic cells are involved in this process. CONCLUSION: We propose autophagy as a novel mechanism involved in the regulatory capacities of probiotics.

Prior hypoxia prevents downregulation of ACE-2 by hyperoxia in fetal human lung fibroblasts.

UNLABELLED: Purpose/Aim of Study: The renin angiotensin system is involved in experimentally induced lung fibrosis. Angiotensin (ANG)-II is profibrotic. Angiotensin converting enzyme-2 (ACE-2) cleaves ANG-II and is thus protective. ACE-2 has recently been reported to be significantly decreased under hyperoxic conditions. Hyperoxia is linked to Bronchopulmonary Dysplasia and lung fibrosis. Fetal lung cells normally do not undergo fibrotic changes with physiologic hypoxemia. We hypothesized that hypoxia prior to hyperoxic exposure in fetal lung fibroblasts (IMR-90 cell line) might be protective by preventing ACE-2 downregulation. MATERIALS AND METHODS: IMR-90 cells were exposed to hypoxia (1%O2/99%N2) followed by hyperoxia (95%O2/5%CO2) or normoxia (21%O2) in vitro. Cells and culture media were recovered separately for assays of ACE-2, TNF-α-converting enzyme (TACE), αSmooth muscle actin (αSMA)-myofibroblast marker-, N-cadherin, and ß-catenin immunoreactive protein. RESULTS: ACE-2 significantly increased when IMR-90 were hypoxic prior to hyperoxic exposure with no recovery. In contrast to hyperoxia alone, ACE-2 did not decrease when IMR-90 were hypoxic prior to hyperoxic exposure with recovery. TACE/ADAM17 protein and mRNA were significantly decreased under these conditions. αSMA N-cadherin, and ß-catenin proteins were significantly decreased with or without normoxic recovery. CONCLUSIONS: Hypoxia prior to hyperoxic exposure of fetal lung fibroblasts prevented ACE-2 downregulation and decreased ADAM17/TACE protein and mRNA. αSMA, N-cadherin, and ß-catenin were also significantly decreased under these conditions.

Pathogenic/likely pathogenic mutations identified in Vietnamese children diagnosed with autism spectrum disorder using high-resolution SNP genotyping platform.

Among the most prevalent neurodevelopmental disorders, Autism Spectrum Disorder (ASD) is highly diverse showing a broad phenotypic spectrum. ASD also couples with a broad range of mutations, both de novo and inherited. In this study, we used a proprietary SNP genotyping chip to analyze the genomic DNA of 250 Vietnamese children diagnosed with ASD. Our Single Nucleotide Polymorphism (SNP) genotyping chip directly targets more than 800 thousand SNPs in the genome. Our primary focus was to identify pathogenic/likely pathogenic mutations that are potentially linked to more severe symptoms of autism. We identified and validated 23 pathogenic/likely pathogenic mutations in this initial study. The data shows that these mutations were detected in several cases spanning multiple biological pathways. Among the confirmed SNPs, mutations were identified in genes previously known to be strongly associated with ASD such as SLCO1B1, ACADSB, TCF4, HCP5, MOCOS, SRD5A2, MCCC2, DCC, and PRKN while several other mutations are known to associate with autistic traits or other neurodevelopmental disorders. Some mutations were found in multiple patients and some patients carried multiple pathogenic/likely pathogenic mutations. These findings contribute to the identification of potential targets for therapeutic solutions in what is considered a genetically heterogeneous neurodevelopmental disorder.

Utilization and cost of diagnostic methods for sexually transmitted infection screening among insured American youth, 2008.

BACKGROUND: Private sector utilization and cost information on testing for sexually transmitted infections (STIs) in the United States is limited. METHODS: We used current procedural terminology codes for tests for HIV, human papillomavirus (HPV), genital herpes simplex virus type 2, hepatitis B virus, chlamydia, gonorrhea, trichomoniasis, and syphilis. We extracted outpatient claims for persons aged 15 to 24 years in 2008 from the MarketScan database. Utilization was measured as the number of claims per 100,000 enrollees for tests specific to a given infection. We estimated claims rates and average costs by sex, compared these with Centers for Medicare and Medicaid Services (CMS) fees, and estimated the overall total cost of STI testing. RESULTS: The claims rate for HPV was higher than for any other STI (P < 0.001) at 18,085/100,000, whereas that for trichomoniasis was lower than all other STIs (P < 0.001) at 517/100,000. Claims rates for females were higher than for males (P < 0.001) for all STIs. Average costs were as follows: $24 (HIV), $34 (HPV), $29 (hepatitis B virus), $25 (herpes simplex virus type 2), $43 (chlamydia), $42 (gonorrhea), $28 (trichomoniasis), and $24 (syphilis). Costs exceeded CMS fees for 67 of 78 current procedural terminologies by an average of 40%. The estimated total cost for all STIs was $403.1 million for the privately insured population aged 15 to 24 years. CONCLUSIONS: We found that the utilization rates and many test costs varied by sex. Private insurers typically paid more than the CMS fee schedule for testing.

Structural evolution of in-plane hybrid graphene/hexagonal boron nitride heterostructure upon heating.

In-plane hybrid graphene/hexagonal boron nitride (h-BN) heterostructure (graphene/hBN/graphene) is studied via molecular dynamics simulation. The initial configuration (6400-atom graphene/6200-atom h-BN/6400-atom graphene) is heated up from 50 K to 7500 K via Tersoff potential. To study the structural evolution, some thermal dynamics quantities are calculated such as the coordination number, the total energy per atom, the heat capacity, the angular distribution, and the distribution of rings. Some main results are calculated and presented as follows: i) The sudden increase of total energy per atom at the melting point (5500 K) exhibits the first order phase transition from the crystalline state to a liquid state of the hybrid graphene/h-BN/graphene heterostructure; ii) The heat capacity shows two peaks. The first peak (at 5500 K) represents the phase transition from the crystalline to a liquid states while the second one (at 6300 K) represents the formation of gaseous atoms of B and N in the h-BN sheet; iii) The coordination number of three decreases dramatically at temperature of 5500 K (about 10% lefts for each type of atoms) leading to the formation of the first peak in the graph of the heat capacity. The coordination number of zero for B and N in the h-BN layer increases significantly (over 55%) at 6300 K causing the formation of the second peak in the graph of the heat capacity; iv) The influence of the relative number of atoms of h-BN to graphene in the hybrid graphene/h-BN/graphene heterostructure on the structural evolution upon heating is considered as follows. The number of atoms in the graphene sheets remains constant (6400 atoms per sheet) while the one of the h-BN sheet varies in size (780, 1560, 3120, 4680, 5490, 5880, 6080, and 6200 atoms). The results show that although the phase transition is still the first order type, the phase transition temperature decreases as the size of the h-BN layer in the hybrid heterostructure increases.

Equestrian-Related Musculoskeletal Injuries Presenting to a Chiropractic Practice: A Retrospective Chart Review of 19 Patients.

Objective: The purpose of this study was to describe the types of equestrian-related musculoskeletal injuries and their management. Methods: We retrospectively reviewed the charts of 19 patients who presented with injuries from equestrian activities at a chiropractic practice from December 2000 to December 2020. Deidentified data were extracted from the charts and summarized. Results: Of the 19 patients, 42.3% presented with acute trauma, 38.5% had overuse injuries, and 19.2% had chronic injuries as a result of previous trauma. We found that 90% of overuse injuries and 18.2% of acute injuries led to chronic conditions that needed ongoing management. Conclusion: From this sample of patients, there was a high percentage of overuse and chronic injuries for patients who participated in equestrian activities.

Compression-induced hexa-to-tetra phase transition of confined germanene.

Via molecular dynamics (MD) simulations we find the existence of the new allotrope of two-dimensional (2D) germanene, i.e. 2D tetra-germanene (tetra-Ge) which contains entirely tetragons. We compress 2D hexa-germanene (hexa-Ge) step by step over a broad density range at constant temperature and hexa-tetra Ge phase transition occurs. We find that the compression of hexa-Ge at 2000 K (not far above the melting point of hexa-Ge) leads to the formation of tetra-Ge with the highest quality. Atomic structure of the obtained tetra-Ge at 300 K is analyzed in details. Although fraction of tetragons in the tetra-Ge is very high (larger than 0.99), some defects are found in addition to the skew tetragons. Due to containing almost entirely tetragons, tetra-Ge may exhibit new behaviors unlike those of the hexa-Ge. Subsequent studies in this direction for 2D tetra-Ge. In addition, first-principles calculations under density functional theory confirm the existence of stable tetra-Ge.

Case of Esophageal Actinomycosis Occurred after Endoscopic Mucosal Resection for Subepithelial Tumor.

Esophageal actinomycosis is a rare, chronic granulomatous disease caused by Actinomyces species. Endoscopy and biopsy are essential for making a diagnosis. This paper reports a case of esophageal actinomycosis that developed after an endoscopic mucosal resection (EMR) for a subepithelial tumor (SET). A 74-year-old male patient had a 3 cm flat, smooth elevation in the esophagus without symptoms. The SET was partially resected, and histology revealed "nonspecific degenerated mesenchymal tissue". Three months later, the patient exhibited a persistently large ulceration at the EMR site, and a biopsy revealed actinomycosis. CT of the chest and abdomen revealed no abnormal findings. Ampicillin treatment was administered for six months, and the ulceration on the esophageal SET improved.

Efficient and recyclable Nd3+-doped CoFe2O4 for boosted visible light-driven photocatalytic degradation of Rhodamine B dye.

Rare earth metal doping spinel ferrites offer excellent electronic, magnetic, and photocatalytic properties, but they have not been well explored for environmental mitigation. Herein, we report the facile fabrication of novel CoNd x Fe2-x O4 (x = 0-0.05) photocatalysts based on Nd3+ incorporated into CoFe2O4 for the degradation of Rhodamine B under visible light irradiation. The Nd3+ dopant considerably increased the specific surface area (35 m2 g-1) and enhanced the degradation performance (94.7%) of CoNd x Fe2-x O4 catalysts. Nd3+-doped CoFe2O4 played a role in the formation of radicals, including ˙OH, h+, and ˙O2 -. With high recyclability and performance, CoNd0.05Fe1.95O4 nanoparticles can be efficient and reusable photocatalysts for degrading organic dyes, including Rhodamine B from wastewaters.

Erratum: Closing the gap for cervical cancer research in Vietnam: current perspectives and future opportunities: a report from the 5th Gynecologic Cancer InterGroup (GCIG) Cervical Cancer Research Network (CCRN) Education Symposium.

This corrects the article on p. e88 in vol. 34, PMID: 37668081.

The psychometric properties of the Vietnamese Version of the Five Facet Mindfulness Questionnaire.

BACKGROUND: Although recent decades have witnessed a growing interest in mindfulness with the development of many mindfulness scales and their adaptation to different cultures, there has been no attempt at developing or adapting a mindfulness scale for Vietnamese people. To fill this gap and encourage the study of mindfulness in Vietnam, we adapted a 20-item short-form of the Five Facet Mindfulness Questionnaire (FFMQ-20) into Vietnamese, which we called the FFMQ-V, and examined its psychometric properties in a series of three independent studies. METHODS: In Study 1, using a college sample (N = 412) we conducted several exploratory factor analyses to elucidate the factor structure of the FFMQ-V. In Study 2, using an independent college sample (N = 344) we performed a confirmatory factor analysis (CFA) to test the goodness-of-fit for all obtained factor models from Study 1. In this study, we also examined the discriminant validities of the FFMQ-V by correlating mindfulness and other related psychological constructs, including acceptance, nonattachment, depression, anxiety, and stress. In Study 3, we replicated all data analyses in Study 2 using a community sample of young adults (N = 574). RESULTS: Across all Studies, our results indicated that the hierarchical five-factor model with method factors best captured the latent structure of the FFMQ-V. Our results also showed that the mindfulness facets met our expectations as they correlated positively with the acceptance and nonattachment and negatively with the depression, anxiety, and stress. CONCLUSIONS: In aggregate, our EFA and CFA results provided strong evidence for the hierarchical five-factor model with method factors in both community and college samples, suggesting that the FFMQ-V can be used to measure trait mindfulness of the Vietnamese young adults.

The COVID-19 Pandemic and Adolescents' Psychological Distress: A Multinational Cross-Sectional Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has continued for more than two years, and the impact of this pandemic on mental health has become one of the most important research topics in psychiatry and psychology. The aim of the present study was to assess psychological distress in adolescents across five countries (Sweden, Morocco, Serbia, Vietnam, and the United States of America) during the COVID-19 pandemic. METHODS: Using nonparametric analyses we examined the impact of COVID-19 on distress, measured by the Brief Symptom Inventory, in a sample of 4670 adolescents. RESULTS: Our results showed that the association between the COVID-19 impact and psychological distress in adolescents' lives was positive and moderate in Morocco and Serbia, positive and weak in Vietnam and the United States of America, and negative and weak in Sweden. We also found that female adolescents reported higher distress levels than male adolescents. CONCLUSIONS: COVID-19 impacted adolescents and their psychological distress differently depending on their residence.

Digital Omicron detection using unscripted voice samples from social media.

The success of artificial intelligence in clinical environments relies upon the diversity and availability of training data. In some cases, social media data may be used to counterbalance the limited amount of accessible, well-curated clinical data, but this possibility remains largely unexplored. In this study, we mined YouTube to collect voice data from individuals with self-declared positive COVID-19 tests during time periods in which Omicron was the predominant variant1,2,3, while also sampling non-Omicron COVID-19 variants, other upper respiratory infections (URI), and healthy subjects. The resulting dataset was used to train a DenseNet model to detect the Omicron variant from voice changes. Our model achieved 0.85/0.80 specificity/sensitivity in separating Omicron samples from healthy samples and 0.76/0.70 specificity/sensitivity in separating Omicron samples from symptomatic non-COVID samples. In comparison with past studies, which used scripted voice samples, we showed that leveraging the intra-sample variance inherent to unscripted speech enhanced generalization. Our work introduced novel design paradigms for audio-based diagnostic tools and established the potential of social media data to train digital diagnostic models suitable for real-world deployment.

Accelerated Synthesis of Graphene Oxide from Graphene.

Graphene oxide (GO) is an oxygenated functionalized form of graphene that has received considerable attention because of its unique physical and chemical properties that are suitable for a large number of industrial applications. Herein, GO is rapidly obtained directly from the oxidation of graphene using an environmentally friendly modified Hummers method. As the starting material consists of graphene flakes, intercalant agents are not needed and the oxidation reaction is enhanced, leading to orders of magnitude reduction in the reaction time compared to the conventional methods of graphite oxidation. With a superior surface area, the graphene flakes are quickly and more homogeneously oxidized since the flakes are exposed at the same extension to the chemical agents, excluding the necessity of sonication to separate the stacked layers of graphite. This strategy shows an alternative approach to quickly producing GO with different degrees of oxidation that can be potentially used in distinct areas ranging from biomedical to energy storage applications.