Longitudinal Multi-omics Reveals Subset-Specific Mechanisms Underlying Irritable Bowel Syndrome.

The gut microbiome has been implicated in multiple human chronic gastrointestinal (GI) disorders. Determining its mechanistic role in disease has been difficult due to apparent disconnects between animal and human studies and lack of an integrated multi-omics view of disease-specific physiological changes. We integrated longitudinal multi-omics data from the gut microbiome, metabolome, host epigenome, and transcriptome in the context of irritable bowel syndrome (IBS) host physiology. We identified IBS subtype-specific and symptom-related variation in microbial composition and function. A subset of identified changes in microbial metabolites correspond to host physiological mechanisms that are relevant to IBS. By integrating multiple data layers, we identified purine metabolism as a novel host-microbial metabolic pathway in IBS with translational potential. Our study highlights the importance of longitudinal sampling and integrating complementary multi-omics data to identify functional mechanisms that can serve as therapeutic targets in a comprehensive treatment strategy for chronic GI diseases. VIDEO ABSTRACT.

Modulating the sEH/EETs Axis Restrains Specialized Proresolving Mediator Impairment and Regulates T Cell Imbalance in Experimental Periodontitis.

Epoxyeicosatrienoic acids (EETs) and other epoxy fatty acids are short-acting lipids involved in resolution of inflammation. Their short half-life, due to its metabolism by soluble epoxide hydrolase (sEH), limits their effects. Specialized proresolving mediators (SPMs) are endogenous regulatory lipids insufficiently synthesized in uncontrolled and chronic inflammation. Using an experimental periodontitis model, we pharmacologically inhibited sEH, examining its impact on T cell activation and systemic SPM production. In humans, we analyzed sEH in the gingival tissue of periodontitis patients. Mice were treated with sEH inhibitor (sEHi) and/or EETs before ligature placement and treated for 14 d. Bone parameters were assessed by microcomputed tomography and methylene blue staining. Blood plasma metabololipidomics were carried out to quantify SPM levels. We also determined T cell activation by reverse transcription-quantitative PCR and flow cytometry in cervical lymph nodes. Human gingival samples were collected to analyze sEH using ELISA and electrophoresis. Data reveal that pharmacological sEHi abrogated bone resorption and preserved bone architecture. Metabololipidomics revealed that sEHi enhances lipoxin A4, lipoxin B4, resolvin E2, and resolvin D6. An increased percentage of regulatory T cells over Th17 was noted in sEHi-treated mice. Lastly, inflamed human gingival tissues presented higher levels and expression of sEH than did healthy gingivae, being positively correlated with periodontitis severity. Our findings indicate that sEHi preserves bone architecture and stimulates SPM production, associated with regulatory actions on T cells favoring resolution of inflammation. Because sEH is enhanced in human gingivae from patients with periodontitis and connected with disease severity, inhibition may prove to be an attractive target for managing osteolytic inflammatory diseases.

Ancient West African foragers in the context of African population history.

Our knowledge of ancient human population structure in sub-Saharan Africa, particularly prior to the advent of food production, remains limited. Here we report genome-wide DNA data from four children-two of whom were buried approximately 8,000 years ago and two 3,000 years ago-from Shum Laka (Cameroon), one of the earliest known archaeological sites within the probable homeland of the Bantu language group1-11. One individual carried the deeply divergent Y chromosome haplogroup A00, which today is found almost exclusively in the same region12,13. However, the genome-wide ancestry profiles of all four individuals are most similar to those of present-day hunter-gatherers from western Central Africa, which implies that populations in western Cameroon today-as well as speakers of Bantu languages from across the continent-are not descended substantially from the population represented by these four people. We infer an Africa-wide phylogeny that features widespread admixture and three prominent radiations, including one that gave rise to at least four major lineages deep in the history of modern humans.

Inositol pyrophosphates inhibit Akt signaling, thereby regulating insulin sensitivity and weight gain.

The inositol pyrophosphate IP7 (5-diphosphoinositolpentakisphosphate), formed by a family of three inositol hexakisphosphate kinases (IP6Ks), modulates diverse cellular activities. We now report that IP7 is a physiologic inhibitor of Akt, a serine/threonine kinase that regulates glucose homeostasis and protein translation, respectively, via the GSK3ß and mTOR pathways. Thus, Akt and mTOR signaling are dramatically augmented and GSK3ß signaling reduced in skeletal muscle, white adipose tissue, and liver of mice with targeted deletion of IP6K1. IP7 affects this pathway by potently inhibiting the PDK1 phosphorylation of Akt, preventing its activation and thereby affecting insulin signaling. IP6K1 knockout mice manifest insulin sensitivity and are resistant to obesity elicited by high-fat diet or aging. Inhibition of IP6K1 may afford a therapeutic approach to obesity and diabetes.

Threespine Stickleback: A Model System For Evolutionary Genomics.

The repeated adaptation of oceanic threespine sticklebacks to fresh water has made it a premier organism to study parallel evolution. These small fish have multiple distinct ecotypes that display a wide range of diverse phenotypic traits. Ecotypes are easily crossed in the laboratory, and families are large and develop quickly enough for quantitative trait locus analyses, positioning the threespine stickleback as a versatile model organism to address a wide range of biological questions. Extensive genomic resources, including linkage maps, a high-quality reference genome, and developmental genetics tools have led to insights into the genomic basis of adaptation and the identification of genomic changes controlling traits in vertebrates. Recently, threespine sticklebacks have been used as a model system to identify the genomic basis of highly complex traits, such as behavior and host-microbiome and host-parasite interactions. We review the latest findings and new avenues of research that have led the threespine stickleback to be considered a supermodel of evolutionary genomics.

A novel vaccination strategy against Vibrio harveyi infection in Asian seabass (Lates calcarifer) with the aid of oxygen nanobubbles and chitosan.

Immersion vaccination, albeit easier to administer than immunization by injection, sometimes has challenges with antigen uptake, resulting in sub-optimal protection. In this research, a new strategy to enhance antigen uptake of a heat-inactivated Vibrio harveyi vaccine in Asian seabass (Lates calcarifer) using oxygen nanobubble-enriched water (ONB) and positively charged chitosan (CS) was explored. Antigen uptake in fish gills was assessed, as was the antibody response and vaccine efficacy of four different combinations of vaccine with ONB and CS, and two control groups. Pre-mixing of ONB and CS before introducing the vaccine, referred to as (ONB + CS) + Vac, resulted in superior antigen uptake and anti-V. harveyi antibody (IgM) production in both serum and mucus compared to other formulas. The integration of an oral booster (4.22 × 108 CFU/g, at day 21-25) within a vaccine trial experiment set out to further evaluate how survival rates post exposure to V. harveyi might be improved. Antibody responses were measured over 42 days, and vaccine efficacy was assessed through an experimental challenge with V. harveyi. The expression of immune-related genes IL1ß, TNFα, CD4, CD8, IgT and antibody levels were assessed at 1, 3, and 7-day(s) post challenge (dpc). The results revealed that antibody levels in the group (ONB + CS) + Vac were consistently higher than the other groups post immersion immunization and oral booster, along with elevated expression of immune-related genes after challenge with V. harveyi. Ultimately, this group demonstrated a significantly higher relative percent survival (RPS) of 63 % ± 10.5 %, showcasing the potential of the ONB-CS-Vac complex as a promising immersion vaccination strategy for enhancing antigen uptake, stimulating immunological responses, and improving survival of Asian seabass against vibriosis.

Immersion prime and oral boost vaccination with an inactivated Vibrio harveyi vaccine confers a specific immune response and protection in Asian seabass (Lates calcarifer).

Asian seabass (Lates calcarifer) holds significant economic value in fish farming in the Asia-Pacific region. Vibriosis caused by Vibrio harveyi (Vh) is a severe infectious disease affecting intensive farming of this species, for which prevention strategies by vaccination have been developed. This study investigated an alternative approach to injectable vaccination to prevent vibriosis in Asian seabass juveniles. The strategy begins with an immersion prime vaccination with a heat-inactivated Vh vaccine, followed by two oral booster doses administered at 14- and 28-days post-vaccination (dpv). Expression of five immune genes TNFα, IL1ß, CD4, CD8, and IgM in the head kidney and spleen, along with investigation of anti-Vh antibody response (IgM) in both systemic and mucosal systems, was conducted on a weekly basis. The efficacy of the vaccines was assessed by a laboratory challenge test at 43 dpv. The results showed that the immunized fish displayed higher levels of mRNA transcripts of the immune genes after the immersion prime and the first oral booster dose compared to the control group. The expression levels peaked at 14 and 28 dpv and then declined to baseline at 35 and 42 dpv. Serum specific IgM antibodies were detected as early as 7 dpv (the first time point investigated) and exhibited a steady increase, reaching the first peak at 21 dpv, and a second peak at 35 dpv. Although the antibody levels gradually declined over subsequent weeks, they remained significantly higher than the control group throughout the experiment. A similar antibody response pattern was also observed in the mucosal compartment. The laboratory challenge test demonstrated high protection by injection with 1.65 × 104 CFU/fish, with a relative percent of survival (RPS) of 72.22 ± 7.86 %. In conclusion, our findings highlight the potential of an immersion prime-oral booster vaccination strategy as a promising approach for preventing vibriosis in Asian seabass.

Review of current perspectives and future outlook on bacterial disease prevention through vaccination in Asian seabass (Lates calcarifer).

Asian seabass, Lates calcarifer, is an important aquatic species in mariculture. Intensive farming of this species has faced episodes of bacterial diseases, including those due to vibriosis, scale drop, and muscle necrosis disease, big belly disease, photobacteriosis, columnaris, streptococcosis, aeromoniasis, and tenacibaculosis. Vaccination is one of the most efficient, non-antibiotic, and eco-friendly strategies for protecting fish against bacterial diseases, contributing to aquaculture expansion and ensuring food security. As of now, although numerous vaccines have undergone laboratory research, only one commercially available inactivated vaccine, suitable for both immersion and injection administration, is accessible for preventing Streptococcus iniae. Several key challenges in developing vaccines for Asian seabass must be addressed, such as the current limited understanding of immunological responses to vaccines, the costs associated with vaccine production, forms, and routes of vaccine application, and how to increase the adoption of vaccines by farmers. The future of vaccine development for the Asian seabass industry, therefore, is discussed with these key critical issues in mind. The focus is on improving our understanding of Asian seabass immunity, including maternal immunity, immunocompetence, and immune responses post-vaccination, as well as developing tools to assess vaccine effectiveness. The need for an alignment of fish vaccines with state-of-the-art vaccine technologies employed in human and terrestrial animal healthcare is also discussed. This review also discusses the necessity of providing locally-produced autogenous vaccines, especially for immersion and oral vaccines, to benefit small-scale fish farmers, and the potential benefits that might be extended through changes to current husbandry practices such as the vaccination of broodstock and earlier life stages of their off-spring.

Association Between Digitally Provided Education and 90-Day Return to Sexual Activity Following Total Knee Arthroplasty: A Randomized Controlled Trial.

BACKGROUND: Contemporary total knee arthroplasty patients have increased expectations of returning to predisease function, including sexual activity (SA). The purpose of this study was to determine whether patients using a digital care management platform (DCMP) were more likely to have a higher rate and frequency of return to SA. METHODS: We conducted an exploratory analysis of a prospective, multicenter, randomized controlled trial that enrolled patients undergoing total knee arthroplasty. A total of 304 patients were randomized to a DCMP (n = 119) providing preoperative and postoperative education regarding return to SA or standard postoperative care (control group; n = 185). Return to SA, assessed via questionnaire, patient-reported outcome measures, Timed Up and Go test, single leg stance, active range of motion and need for manipulation under anesthesia were assessed at 90 days postoperatively. RESULTS: More patients in the DCMP group returned to SA compared to control at 90 days (58.4 versus 39.6%, P = .018); however, the control group resumed SA sooner (33.1 versus 42.0 days, P = .023). Patients who returned to SA were younger (61.6 versus 65.9 year), more often men (56 versus 35%) (P < .001), higher performing on the Timed Up and Go and single leg stance tests (P < .001), and had greater active range of motion (P = .007). There were no differences in patient-reported outcome measures or need for manipulation under anesthesia between patients that returned to SA and those who did not. CONCLUSIONS: More patients using a DCMP resumed SA at 90 days; however, patients in the control group returned to SA sooner. Those who returned to SA were younger, possessed greater physical function, and were more often men.

Is There a Change in Anxiety and Depression Following Total Knee Arthroplasty?

BACKGROUND: The primary purpose of this study was to investigate whether anxiety and depression change following total knee arthroplasty (TKA). A secondary objective was to explore the association between preoperative variables and changes in anxiety and depression. METHODS: This was a prospective, multicenter, cohort study. Participants (n = 1,852, age 64 ± 8.7 years, a body mass index of 31.3, a modified Comorbidity Index of 1.0 ± 1.3, and 61.7% were women) completed the EuroQol 5-dimension 5-level preoperatively and at 1- and 3-month postoperatively. Fulfillment of physical activity expectations and preparedness to resume activities was assessed at 3 months. The anxiety or depression dimension was analyzed using the Paretian classification profile changes and compared with the sign Fisher's exact test. Logistic regressions were used to analyze the relationship between patient characteristics, preoperative anxiety or depression, activity expectations, preparedness to resume activities, and changes in anxiety/depression. RESULTS: The percentage of patients reporting Level 1 (no anxious or depressed feelings) significantly (P < .0001) increased from preoperative (62.2%) to 3 months (77.1%) postoperative, while levels 2 to 5 (slightly through extremely anxious or depressed) all decreased. The percentage of worsening anxiety and depression was significantly (P < .0001) greater in patients who did not feel they were well prepared to resume activities of daily living (17.7 versus 4.4%) and physical recreation (12.9 versus 3.9%). Preoperative anxiety and depression (odds ratio [OR] 52.27, 95% confidence interval [CI]: 34.98, 80.67), EuroQol 5-dimension 5-level (OR: 2.55, 95% CI: 1.04, 6.34), activity of daily living (OR: 1.57, 95% CI: 1.19, 2.06), and body mass index (OR: 1.05, 95% CI: 1.02, 1.08) were significant (P < .05) predictors of an improving Paretian change profile at 3 months postoperative. CONCLUSIONS: Anxiety and depression decrease following TKA, and these changes appear heavily dependent on a patient's preoperative psychological well-being and postoperative preparedness to resume daily activities. Physicians' awareness of preoperative patient psychological well-being and management of patient preparedness and expectations to resume physical activity may modulate postoperative anxiety and depression.

Integration of multiomics data shows down regulation of mismatch repair and tubulin pathways in triple-negative chemotherapy-resistant breast tumors.

BACKGROUND: Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype. Patients with TNBC are primarily treated with neoadjuvant chemotherapy (NAC). The response to NAC is prognostic, with reductions in overall survival and disease-free survival rates in those patients who do not achieve a pathological complete response (pCR). Based on this premise, we hypothesized that paired analysis of primary and residual TNBC tumors following NAC could identify unique biomarkers associated with post-NAC recurrence. METHODS AND RESULTS: We investigated 24 samples from 12 non-LAR TNBC patients with paired pre- and post-NAC data, including four patients with recurrence shortly after surgery (< 24 months) and eight who remained recurrence-free (> 48 months). These tumors were collected from a prospective NAC breast cancer study (BEAUTY) conducted at the Mayo Clinic. Differential expression analysis of pre-NAC biopsies showed minimal gene expression differences between early recurrent and nonrecurrent TNBC tumors; however, post-NAC samples demonstrated significant alterations in expression patterns in response to intervention. Topological-level differences associated with early recurrence were implicated in 251 gene sets, and an independent assessment of microarray gene expression data from the 9 paired non-LAR samples available in the NAC I-SPY1 trial confirmed 56 gene sets. Within these 56 gene sets, 113 genes were observed to be differentially expressed in the I-SPY1 and BEAUTY post-NAC studies. An independent (n = 392) breast cancer dataset with relapse-free survival (RFS) data was used to refine our gene list to a 17-gene signature. A threefold cross-validation analysis of the gene signature with the combined BEAUTY and I-SPY1 data yielded an average AUC of 0.88 for six machine-learning models. Due to the limited number of studies with pre- and post-NAC TNBC tumor data, further validation of the signature is needed. CONCLUSION: Analysis of multiomics data from post-NAC TNBC chemoresistant tumors showed down regulation of mismatch repair and tubulin pathways. Additionally, we identified a 17-gene signature in TNBC associated with post-NAC recurrence enriched with down-regulated immune genes.

Dynamic assessment of serum chromogranin A and treatment response with abiraterone acetate in metastatic castration-resistant prostate cancer.

OBJECTIVE: Elevated serum chromogranin A (CGA) is associated with intrinsic or treatment-related neuroendocrine differentiation (NED) in men with metastatic castration-resistant prostate cancer (mCRPC). Fluctuations in serum CGA during treatment of mCRPC have had conflicting results. We analyzed the impact of (i) rising serum CGA and (ii) baseline CGA/PSA ratio during treatment to identify associations with abiraterone acetate (AA) therapy. METHODS: Between June 2013 and August 2015, 92 men with mCRPC were enrolled in a prospective trial with uniform serum CGA processing performed before initiating abiraterone acetate/prednisone (AA/P) and serially after 12 weeks of AA/P treatments. Serum CGA was measured using a homogenous automated immunofluorescent assay. Patients receiving proton pump inhibitors or with abnormal renal function were excluded due to possible false elevations of serum CGA (n = 21 excluded), therefore 71 patients were analyzed. All patients underwent a composite response assessment at 12-weeks. Kaplan-Meier estimates and Cox Regression models were used to calculate the association with time-to-treatment failure analyses and overall survival. RESULTS: An increase in chromogranin was associated with a lower risk of treatment failure (hazard ratio [HR]: 0.52, p = 0.0181). The median CGA/PSA ratio was 7.8 (2.6-16.0) and an elevated pretreatment CGA/PSA ratio above the median was associated with a lower risk of treatment failure (HR: 0.54 p value = 0.0185). An increase in CGA was not found to be associated with OS (HR: 0.71, 95% CI: 0.42-1.21, p = 0.207). An elevated baseline CGA/PSA ratio was not associated with OS (HR: 0.62, 95% CI: 0.37-1.03, p = 0.062). An increase in PSA after 12 weeks of treatment was associated with an increased risk of treatment failure (HR: 4.14, CI: 2.21-7.73, p = < 0.0001) and worse OS (HR: 2.93, CI: 1.57-4.45, p = < 0.0001). CONCLUSIONS: We show that an increasing chromogranin on AA/P and an elevated baseline CGA/PSA in patients with mCRPC were associated with a favorable response to AA/P with no changes in survival. There may be limited clinical utility in serum CGA testing to evaluate for lethal NED as AA/P did not induce lethal NED in this cohort. This highlights that not all patients with an increasing CGA have a worse OS.

Integrative multi-omics profiling reveals cAMP-independent mechanisms regulating hyphal morphogenesis in Candida albicans.

Microbial pathogens grow in a wide range of different morphologies that provide distinct advantages for virulence. In the fungal pathogen Candida albicans, adenylyl cyclase (Cyr1) is thought to be a master regulator of the switch to invasive hyphal morphogenesis and biofilm formation. However, faster growing cyr1Δ/Δ pseudorevertant (PR) mutants were identified that form hyphae in the absence of cAMP. Isolation of additional PR mutants revealed that their improved growth was due to loss of one copy of BCY1, the negative regulatory subunit of protein kinase A (PKA) from the left arm of chromosome 2. Furthermore, hyphal morphogenesis was improved in some of PR mutants by multigenic haploinsufficiency resulting from loss of large regions of the left arm of chromosome 2, including global transcriptional regulators. Interestingly, hyphal-associated genes were also induced in a manner that was independent of cAMP. This indicates that basal protein kinase A activity is an important prerequisite to induce hyphae, but activation of adenylyl cyclase is not needed. Instead, phosphoproteomic analysis indicated that the Cdc28 cyclin-dependent kinase and the casein kinase 1 family member Yck2 play key roles in promoting polarized growth. In addition, integrating transcriptomic and proteomic data reveals hyphal stimuli induce increased production of key transcription factors that contribute to polarized morphogenesis.

Transpyloric Feeding is Associated With Improved Oxygenation Compared With Gastric Feeding Among Nonintubated Extremely Low Birth Weight Infants.

OBJECTIVE: To study the impact of transpyloric (TP) feed initiation on short-term oxygenation and manual oxygen blender titration among extremely low birth weight infants. STUDY DESIGN: This retrospective study evaluated several measures of oxygenation among extremely low birth weight infants receiving positive pressure respiratory support for 96 hours before and after TP tube placement in a single neonatal intensive care unit during the years 2017- 2020. The measures included the achieved oxygen saturation (SpO2), the baseline fraction of inspired oxygen (FiO2), the SpO2/FiO2 ratio, the number and severity of hypoxemic episodes and the frequency of manual oxygen titrations (titration index) and were analyzed using an interrupted time series regression approach. RESULTS: A total of 56 infants were evaluated. No significant differences were observed in any oxygenation measures during TP vs gastric feeding among 14 intubated infants. However, among 42 nonintubated patients, significant improvements were observed in the median SpO2/FiO2 ratios (P = .001), median titration index (P = .05), median number of hypoxemic episodes (P = .02), and median severity of hypoxemic episodes (P = .008) after TP tube placement. CONCLUSIONS: The transition from gastric to TP tube feeding was temporally associated with acute improvement in oxygenation for nonintubated infants, but not for intubated infants.

Knowledge-guided analysis of "omics" data using the KnowEnG cloud platform.

We present Knowledge Engine for Genomics (KnowEnG), a free-to-use computational system for analysis of genomics data sets, designed to accelerate biomedical discovery. It includes tools for popular bioinformatics tasks such as gene prioritization, sample clustering, gene set analysis, and expression signature analysis. The system specializes in "knowledge-guided" data mining and machine learning algorithms, in which user-provided data are analyzed in light of prior information about genes, aggregated from numerous knowledge bases and encoded in a massive "Knowledge Network." KnowEnG adheres to "FAIR" principles (findable, accessible, interoperable, and reuseable): its tools are easily portable to diverse computing environments, run on the cloud for scalable and cost-effective execution, and are interoperable with other computing platforms. The analysis tools are made available through multiple access modes, including a web portal with specialized visualization modules. We demonstrate the KnowEnG system's potential value in democratization of advanced tools for the modern genomics era through several case studies that use its tools to recreate and expand upon the published analysis of cancer data sets.

Synthetic peptides derived from predicted B cell epitopes of nervous necrosis virus (NNV) show antigenicity and elicit immunogenic responses in Asian seabass (Lates calcarifer).

Nervous necrosis virus (NNV) has spread throughout the world, affecting more than 120 freshwater and marine fish species. While vaccination effectively prevents disease outbreaks, the difficulty of producing sufficient viruses using cell lines continues to be a significant disadvantage for producing inactivated vaccines. This study, therefore, explored the application of synthetic peptides as potential vaccine candidates for the prevention of NNV in Asian seabass (Lates calcarifer). Using the epitope prediction tool and molecular docking, three predicted immunogenic B cell epitopes (30-32 aa) derived from NNV coat protein were selected and synthesised, corresponding to amino acid positions 5 to 34 (P1), 133 to 162 (P2) and 181 to 212 (P3). All the predicted peptides interact with Asian sea bass's MHC class II by docking. The antigenicity of these peptides was determined through ELISA and all peptides were able to react with NNV-specific antibodies. Subsequently, the immunogenicity of these synthetic peptides was investigated by immunisation of Asian seabass with individual peptides (30 µg/fish) and a peptide cocktail (P1+P2+P3, 10 µg each/fish) by intraperitoneal injection, followed by a booster dose at day 28 post-primary immunisation. There was a subset of immunised fish that were able to induce upregulation of immune genes (IL-1ß, TNFα, MHCI, MHCII ß, CD4, CD8, and IgM-like) in the head kidney and spleen post immunization. Importantly, antibodies derived from fish immunised with synthetic peptides reacted with whole NNV virions, and sera from P1 group could neutralise NNV in an in vitro assay. Taken together, these findings indicate that synthetic linear peptides based on predicted B cell epitopes exhibited both antigenic and immunogenic properties, suggesting that they could be potential vaccine candidates for the prevention of NNV in fish.

Immunological response of 35 and 42 days old Asian seabass (Lates calcarifer, Bloch 1790) fry following immersion immunization with Streptococcus iniae heat-killed vaccine.

Early disease prevention by vaccination requires understanding when fry fish develop specific immunity to a given pathogen. In this research, we explored the immune responses of Asian seabass (Lates calcarifer) at the stages of 35- and 42- days post-hatching (dph) to an immersive heat-killed Streptococcus iniae (Si) vaccine to determine whether fish can produce specific antibodies against the pathogen. The vaccinated fish of each stage (V35 and V42) were immersed with the Si vaccine at 107 CFU/ml for 3 h, whereas the control groups (C35 and C42) were immersed with tryptic soy broth (TSB) in the same manner. Specific antibodies were measured by enzyme-linked immunosorbent assay (ELISA) before and post-immunization (i.e., 0, 7, and 14 days post-immunization, dpi). Expression of innate (TNFα and IL-1ß) and adaptive (MHCI, MHCII, CD4, CD8, IgM-like, IgT-like, and IgD-like) immune-related genes were evaluated at the same time points with the addition of 1 dpi. The results showed that a subset of immunized fish from both V35 and V42 fry could elicit specific antibodies (IgM) against Si at 14 dpi. All tested innate and adaptive immune genes upregulated at 7 dpi among fish in V35 group. Interestingly, 42 dph fish appeared to respond to the Si vaccine faster than that of 35 dph, as a significant increase in transcripts was observed in CD4, IL-1ß, IgM-like, and IgD-like at 1 dpi; and specific antibody titers of some fish, although not all, were higher than a threshold (p = 0.05) since 7 dpi. In conclusion, this study reveals that 35-42 dph Asian seabass fry can elicit specific immunity to Si immersion vaccine, suggesting that early vaccination of 35 dph fry Asian seabass is feasible.

Arynes as synthetic linchpins towards the construction of diversely functionalized natural product skeletons.

Arynes are a privileged class of reactive intermediates in synthetic organic chemistry, and their unusual reactivities have been the subject of engrossing research interest. Recently, there are many reports on novel aryne-based synthetic innovations as a linchpin approach to accomplish the total synthesis of structurally diverse natural products or their derivatives in a racemic and enantiopure fashion. This review provides an overview of the literature on synthetic strategies, employing arynes as crucial intermediates to construct architecturally intriguing bioactive natural products/derivatives in a period of 2019 to 2022. This study highlights the need to investigate the effective synthesis and search for new biological uses of highly functionalized natural product skeletons.

Effect of the annealing temperature on structural, morphological, and nonlinear optical properties of TeO2 thin films used for efficient THz generation.

This paper reports the effect of annealing on T e O 2 films deposited using the thermal evaporation technique. T e O 2 films of 120 nm thickness were grown on a glass substrate at room temperature (RT) and annealed at 400°C and 450°C. The structure of the film and the influence of the annealing temperature on the crystalline phase change were examined using the X-ray diffraction method. Optical properties such as transmittance, absorbance, complex refractive index, and energy bandgap were determined between ultraviolet-visible to terahertz (THz) range. These films have a direct allowed transition with the optical energy bandgap of 3.66, 3.64, and 3.54 eV at as-deposited temperatures (RTs) of 400°C and 450°C. The effect of the annealing temperature on the morphology and surface roughness of the films was investigated using atomic force microscopy. The nonlinear optical parameters, which are the refractive index and absorption coefficients, were calculated using THz time domain spectroscopy. The microstructure variation of the T e O 2 films in terms of surface orientation plays an important role in understanding the change in the nonlinear optical properties of the films. Finally, these films were subjected to 800 nm wavelength of 50 fs pulse duration obtained from a Ti:sapphire amplifier at a 1 kHz repetition rate for efficient THz generation. The power of incidence of the laser beam was tuned at a range between 75 and 105 mW; the highest power of the generated THz signal was of the order of 210 nW for 450°C annealed film with respect to the incident power of 105 mW. The conversion efficiency was found to be ∼0.22×10-5 %, which is 2.025 times more than the film annealed at 400°C.