Identification and characterization of a new species of Taxus - Taxus qinlingensis by multiple taxonomic methods.

BACKGROUND: The taxonomy of Taxus Linn. remains controversial due to its continuous phenotypic variation and unstable topology, thus adversely affecting the formulation of scientific conservation strategies for this genus. Recently, a new ecotype, known as Qinling type, is mainly distributed in the Qinling Mountains and belongs to a monophyletic group. Here, we employed multiple methods including leaf phenotype comparison (leaf shapes and microstructure), DNA barcoding identification (ITS + trnL-trnF + rbcL), and niche analysis to ascertain the taxonomic status of the Qinling type. RESULTS: Multiple comparisons revealed significant differences in the morphological characters (length, width, and length/width ratio) among the Qinling type and other Taxus species. Leaf anatomical analysis indicated that only the Qinling type and T. cuspidata had no papilla under the midvein or tannins in the epicuticle. Phylogenetic analysis of Taxus indicated that the Qinling type belonged to a monophyletic group. Moreover, the Qinling type had formed a relatively independent niche, it was mainly distributed around the Qinling Mountains, Ta-pa Mountains, and Taihang Mountains, situated at an elevation below 1500 m. CONCLUSIONS: Four characters, namely leaf curvature, margin taper, papillation on midvein, and edges were put forward as primary indexes for distinguishing Taxus species. The ecotype Qingling type represented an independent evolutionary lineage and formed a unique ecological niche. Therefore, we suggested that the Qingling type should be treated as a novel species and named it Taxus qinlingensis Y. F. Wen & X. T. Wu, sp. nov.

Biportal Endoscopic Spinal Cord Stimulation Paddle Lead Implantation: Technical Note and Preliminary Clinical Results.

OBJECTIVE: This study aims to elucidate a novel, minimally invasive surgical technique using a biportal endoscope for the implantation of spinal cord stimulation (SCS) paddle leads and to report the preliminary results of its clinical application. MATERIALS AND METHODS: The perioperative data of patients who underwent the biportal endoscopic SCS paddle lead implantation in our department were collected; the surgical procedure was delineated, and the clinical outcomes were assessed. RESULTS: From February 2022 to December 2023, six patients underwent biportal endoscopic SCS paddle lead implantation. The median follow-up time was nine months (range one to three months). The median intraoperative blood loss was 30 mL (range 25-50 mL), and the median operative time was 87.5 minutes (range 75-110 minutes). One patient experienced severe neck pain during the operation, whereas the other five patients experienced no surgical complications. One patient was found to have a slight lead migration three months after surgery, which did not affect the therapeutic effect. The median visual analogue scale (VAS) of the surgical area was 0.5 (range 0-2), 2.5 (range 1-4), and 0.5 (range 0-1) during the operation and one day and one week after the operation, respectively. The median VAS of the six patients' primary disease was 8 (range 7-9) before surgery and 2.5 (range 1-4) at the last postoperative follow-up (pain reduction ≥50%). CONCLUSION: Paddle lead systems for SCS can be implanted successfully using a biportal endoscopic technique.

Integrated transcriptome and metabolome analysis unveils the mechanism of color-transition in Edgeworthia chrysantha tepals.

BACKGROUND: Edgeworthia chrysantha, a deciduous shrub endemic to China, is known for its high ornamental value, extensive cultivation history, and wide-ranging applications. However, theoretical research on this plant is severely lacking. While its flowering process displays striking color transitions from green (S1) to yellow (S2) and then to white (S3), the scientific exploration of this phenomenon is limited, and the underlying regulatory mechanisms are yet to be elucidated. RESULTS: Correlation analysis between phenotypic measurements and pigment content revealed that carotenoids and chlorophyll are the key pigments responsible for the color changes. Metabolomic analysis of carotenoids demonstrated that lutein and ß-carotene were present at higher levels in S1, while S2 exhibited increased diversity and quantity of carotenoids compared to other stages. Notably, antheraxanthin, zeaxanthin, lycopene, and α-cryptoxanthin showed significant increases. In S3, apart from the colorless phytoene, other carotenoid metabolites were significantly reduced to extremely low levels. Transcriptomic data indicated that PSY, Z-ISO, crtZ, ZEP, PDS and ZDS are key genes involved in carotenoid biosynthesis and accumulation, while NCED plays a crucial role in carotenoid degradation. SGR was identified as a key gene contributing to the progressive decline in chlorophyll content. Additionally, three transcription factors potentially regulating carotenoid metabolism were also identified. CONCLUSIONS: This study represents the first systematic investigation, spanning from phenotypic to molecular levels, of the color-changing phenomenon in E. chrysantha. The study elucidates the crucial pigments, metabolites, genes, and transcription factors responsible for flower color changes during the flowering process, thereby providing preliminary understanding of the intrinsic regulatory mechanisms. These findings establish a theoretical foundation for the genetic improvement of flower color in E. chrysantha.

Population pharmacokinetics, pharmacodynamics and pharmacogenetics modelling of oxypurinol in Hmong adults with gout and/or hyperuricemia.

AIMS: The aim of this study was to quantify identifiable sources of variability, including key pharmacogenetic variants in oxypurinol pharmacokinetics and their pharmacodynamic effect on serum urate (SU). METHODS: Hmong participants (n = 34) received 100 mg allopurinol twice daily for 7 days followed by 150 mg allopurinol twice daily for 7 days. A sequential population pharmacokinetic pharmacodynamics (PKPD) analysis with non-linear mixed effects modelling was performed. Allopurinol maintenance dose to achieve target SU was simulated based on the final PKPD model. RESULTS: A one-compartment model with first-order absorption and elimination best described the oxypurinol concentration-time data. Inhibition of SU by oxypurinol was described with a direct inhibitory Emax model using steady-state oxypurinol concentrations. Fat-free body mass, estimated creatinine clearance and SLC22A12 rs505802 genotype (0.32 per T allele, 95% CI 0.13, 0.55) were found to predict differences in oxypurinol clearance. Oxypurinol concentration required to inhibit 50% of xanthine dehydrogenase activity was affected by PDZK1 rs12129861 genotype (-0.27 per A allele, 95% CI -0.38, -0.13). Most individuals with both PDZK1 rs12129861 AA and SLC22A12 rs505802 CC genotypes achieve target SU (with at least 75% success rate) with allopurinol below the maximum dose, regardless of renal function and body mass. In contrast, individuals with both PDZK1 rs12129861 GG and SLC22A12 rs505802 TT genotypes would require more than the maximum dose, thus requiring selection of alternative medications. CONCLUSIONS: The proposed allopurinol dosing guide uses individuals' fat-free mass, renal function and SLC22A12 rs505802 and PDZK1 rs12129861 genotypes to achieve target SU.

HO-1 overexpression alleviates senescence by inducing autophagy via the mitochondrial route in human nucleus pulposus cells.

Intervertebral disc degeneration (IDD) is closely associated with aging. Our previous studies have confirmed that heme oxygenase-1 (HO-1) can inhibit nucleus pulposus (NP) cell apoptosis. However, whether or not HO-1 is involved in NP cell senescence and autophagy is unclear. Our results indicated that HO-1 expression was reduced in IDD tissues and replicative senescent NP cells. HO-1 overexpression using a lentiviral vector reduced the NP cell senescence level, protected mitochondrial function, and promoted NP cell autophagy through the mitochondrial pathway. Autophagy inhibitor 3-MA pretreatment reversed the anti-senescent and protective effects on the mitochondrial function of HO-1, which promoted the degradation of the extracellular matrix (ECM) in the intervertebral disc. In vivo, HO-1 overexpression inhibited IDD and enhanced autophagy. In summary, these results suggested that HO-1 overexpression alleviates NP cell senescence by inducing autophagy via the mitochondrial route.

HLA-B*58: 01 carrier status of Hmong in Minnesota: first in Hmong genotyping for prevalence of this biomarker of risk for severe cutaneous adverse reactions caused by allopurinol.

Allopurinol, a common medication to treat gout, is associated with severe cutaneous adverse reactions, and the occurrence is highly predicted by an individual's HLA-B*58:01 carrier status. Guidelines endorse preemptive testing in select Asian populations before initiating allopurinol. The Hmong, an Asian subpopulation originally from China who now live dispersed around the world, have a 2.5-fold higher risk of gout when compared to non-Hmong in Minnesota. Given the concern for severe cutaneous adverse reactions when prescribing allopurinol, we quantified the carrier status of HLA-B*58:01 in Hmong from two independent cohorts in Minnesota. Using a community-based participatory research approach, HLA-B*58:01 carrier status was determined in 49 US-born Hmong without a history of gout or allopurinol use. Further, 47 Hmong patients undergoing clinical evaluation to receive gout pharmacotherapy were also tested. The frequency of HLA-B*58:01 positive carrier status in these two cohorts were compared to published data from a Han Chinese (n = 2910) and a Korean cohort (n = 485) using a Fisher's exact test with a Bonferroni-corrected P-value <0.025 for significance. With one uninterpretable result, we identified two out of 95 people (2.1%) who carried HLA-B*58:01. This 2.1% incidence in these Hmong adults is notably lower than Han Chinese (19.6%, P < 0.0001) and Korean (12.2%, P = 0.0016) populations. Though commonly understood to be of Chinese descent, the lower prevalence within the Hmong underscores the risk of generalizing genotypic findings from Chinese to Asian subpopulations. We suggest no change to the current guidelines recommending which populations should be tested for HLA-B*58:01 before allopurinol use until further validation.

Propionibacterium acnes induces intervertebral disc degeneration by promoting nucleus pulposus cell pyroptosis via NLRP3-dependent pathway.

Recent evidence suggests that Propionibacterium acnes (P. acnes) is a novel pathogenic factor promoting intervertebral disc degeneration (IVDD), however, whose mechanism remains unclear. A key component of inflammatory responses to P. acnes appears to be interleukin (IL)-1ß, which has been proved to be high expression in degenerative nucleus pulposus cells (NPCs). This study aimed to explore the inflammatory mechanism driving the host response to P. acnes infection in IVDD. Our data demonstrated that the number of nod-like receptor protein 3 (NLRP3)-positive cells was significantly increased in the P. acnes-infected nucleus pulposus (NP) tissue. Meanwhile, the up-regulated expressions of NLRP3, caspase-1, caspase-5, IL-1ß, IL-18, Gasdermin D (GSDMD) were observed in NPCs after co-culturing with P. acnes, which suggested NPCs pyroptosis activation induced by P. acnes. To further investigate the underlying mechanisms, NLRP3 inflammasome inhibitor MCC950 and thioredoxin binding protein (TXNIP)-siRNA were used. With the addition of MCC950 to NPCs co-cultured with P. acnes in vitro, the secretions of mature IL-1ß and IL-18 were reduced. Moreover, these MCC950-mediated effects were repeated by siRNA-transfected TXNIP knockdown. These results implied P. acnes activated inflammatory response by the TXNIP-NLRP3 pathway. To further reveal the anti-degeneration role of MCC950 in vivo, MCC950 was injected into the rabbit IVDD models infected by P. acnes. The MRI and histological detection provided more solid evidence that MCC950 treatment effectively retarded the degenerative process of the intervertebral discs in vivo. In summary, these results suggest that P. acnes-induced NPCs pyroptosis activation via the NLRP3-dependent pathway is likely responsible for the inflammatory pathology of IVDD. MCC950 can alleviate inflammatory injury and NPCs pyroptosis under P. acnes infection and may delay the progression of disc degeneration, which provides a new direction for the treatment of IVDD.

Awareness of state legislation on naloxone accessibility associated with willingness to prescribe naloxone.

BACKGROUND: Increasing rates of opioid-related deaths, state naloxone legislation changes, and negativity prompted investigation of predictive factors associated with willingness to prescribe naloxone to populations at risk of overdose, including knowledge of risk factors, assessment of persons at risk, awareness of legislative changes, perceptions of professional responsibility, and confidence around naloxone prescribing and distribution. METHODS: Cross-sectional, Web-based, anonymous, voluntary survey to prescribers of 2 regional health care systems serving urban and rural North Dakota, northern Minnesota, and northwestern Wisconsin. Human subject research was approved by university and health care systems' institutional review boards. RESULTS: Overall, 203 of 1586 prescribers responded; however, not all prescribers completed each survey item. A majority (89.4%, n = 127/142) of respondents had never prescribed naloxone for overdose prevention. Willingness to prescribe naloxone for 4 patient care scenarios involving substantial opioid overdose risk ranged from 43.4% to 70.5%. Knowledge mean score was 15.5 (SD = 2.9) out of 22 with median 15 (range: 5-22). Naloxone legislation awareness score was 8.8 (SD = 3.8) out of 15 with median 8 (range: 3-15). There was a statistically significant but modest correlation between willingness to prescribe naloxone and the other variables, including awareness of state naloxone-related legislation (r = 0.43, P < .0001), level of self-confidence about dosing, prescribing, and writing protocols for naloxone (r = 0.37, P < .0001), general knowledge (r = 0.24, P = .0032), and perception of professional responsibility (r = 0.19, P = .03). Multivariate regression analysis indicated willingness to prescribe naloxone was associated with statistically significant predictors, including awareness of the naloxone laws (P = .0016) and self-confidence about dosing, prescribing, and writing protocols (P = .0011). CONCLUSIONS: Prescribers who are more aware of state laws regarding naloxone and confident in their knowledge of dosing, administration, and writing protocols may be more willing to prescribe naloxone.

Medication management in Minnesota schools: The need for school nurse-pharmacist partnerships.

BACKGROUND: Pharmacist participation in school medication management (MM) is minimal. School nurses are responsible for increasingly complex medication administration and management in schools. OBJECTIVES: The purpose of this study was to 1) assess the MM needs of school nurses in Minnesota, and 2) determine if and how interprofessional partnerships between nurses and pharmacists might optimize MM for students. METHODS: Researchers from the University of Minnesota College of Pharmacy, School Nurse Organization of Minnesota, and Minnesota Department of Health conducted a 32-item online survey of school nurses. RESULTS: Nurses administered the majority of medications at their school (69.9%) compared with unlicensed assistive personnel (29%). Stimulants (37.7%), asthma medications (25.7%), over-the-counter analgesics (17.8%), and insulin (6.6%) were the most commonly administered drug therapies. A clear majority of school nurses were interested in partnering with pharmacists: 90.3% thought that a pharmacist could assist with MM, 80% would consult with a pharmacist, and 12.3% reported that they already have informal access to a pharmacist. Topics that nurses would discuss with a pharmacist included new medications (71.6%), drug-drug interactions (67.1%), proper administration (52%), and storage (39.4%). The top MM concerns included 1) availability of students' medications and required documentation, 2) health literacy, 3) pharmacist consultations, 4) lack of time available for nurses to follow up with and evaluate students, 5) family-centered care, 6) delegation, 7) communication, and 8) professional development. CONCLUSION: Although the majority of school nurses surveyed indicated that partnerships with pharmacists would improve school MM, few had a formal relationship. Interprofessional partnerships focused on MM and education are high on the list of services that school nurses would request of a consultant pharmacist. Study results suggest that there are opportunities for pharmacists to collaborate with school nurses; further study is necessary to advance high-quality MM for students in Minnesota schools.

Metabolome integrated with transcriptome reveals the mechanism of three different color formations in Taxus mairei arils.

Maire yew (Taxus mairei), an evergreen conifer, has high ornamental and medicinal value. The arils of this species has three different colors. However, the variation mechanisms of arils color formation remains unclear. Here, the gene expression and metabolite concentration were profiled for red (RTM), yellow (YTM), and purple (PTM) arils in different developmental stages. A total of 266 flavonoids and 35 carotenoids were identified. The predominant pigments identified in YTM were epiafzelechin, lutein, and ß-Cryptoxanthin, while malvidin-3,5-di-O-glucoside and apigenin played crucial roles in PTM. And significant differential expression was observed among the HCT, DFR, LAR, ANS, crtB, NCED, and CCoAOMT genes across different color arils. During the maturation of yellow arils, the upregulation of HCT was strongly correlated with the accumulation of epiafzelechin. The diminished expression of DFR, LAR, and ANS seemed to inhibit the production of delphinidin-3-O-rutinoside. The decrease in crtB expression and concurrent increase in NCED expression potentially regulate the heightened accumulation of lutein. Meanwhile, the accumulation of ß-cryptoxanthin appeared seemed to be positively influenced by NCED. As aril turning purple, the decreased expression of CCoAOMT seemed to facilitate the synthesis of apigenin. The substantial upregulation of DFR promoted the production of malvidin-3,5-di-O-glucoside. Additionally, the overexpression of MYBs may plays the important role in regulating the formation of different colored arils. In total, 14 genes were selected for qRT-PCR validation, the results indicated the reliability of the transcriptome sequences data. Our findings could provide valuable insight into the molecular breeding, development, and application of Maire yew resources.

Effect of ginger supplementation on the fecal microbiome in subjects with prior colorectal adenoma.

Ginger has been associated with a decreased incidence of colorectal cancer (CRC) through reduction in inflammatory pathways and inhibition of tumor growth. Recent pre-clinical models have implicated changes in the gut microbiome as a possible mediator of the ginger effect on CRC. We hypothesized that, in adults previously diagnosed with a colorectal adenoma, ginger supplementation would alter the fecal microbiome in the direction consistent with its CRC-inhibitory effect. Sixty-eight adults were randomized to take either ginger or placebo daily for 6 weeks, with a 6-week washout and longitudinal stool collection throughout. We performed 16S rRNA sequencing and evaluated changes in overall microbial diversity and the relative abundances of pre-specified CRC-associated taxa using mixed-effects logistic regression. Ginger supplementation showed no significant effect on microbial community structure through alpha or beta diversity. Of 10 pre-specified CRC-associated taxa, there were significant decreases in the relative abundances of the genera Akkermansia (p < 0.001), Bacteroides (p = 0.018), and Ruminococcus (p = 0.013) after 6-week treatment with ginger compared to placebo. Ginger supplementation led to decreased abundances of Akkermansia and Bacteroides, which suggests that ginger may have an inhibitory effect on CRC-associated taxa. Overall, ginger supplementation appears to have a limited effect on gut microbiome in patients with colorectal adenomas.

Metabolome and transcriptome integration reveals insights into petals coloration mechanism of three species in Sect. Chrysantha chang.

Background: Sect. Chrysantha Chang, belonging to the Camellia genus, is one of the rare and precious ornamental plants distinguished by a distinctive array of yellow-toned petals. However, the variation mechanisms of petal color in Sect. Chrysantha Chang remains largely unclear. Methods: We conducted an integrated analysis of metabolome and transcriptome to reveal petal coloration mechanism in three species, which have different yellow tones petals, including C. chuongtsoensis (CZ, golden yellow), C. achrysantha (ZD, light yellow), and C. parvipetala (XB, milk white). Results: A total of 356 flavonoid metabolites were detected, and 295 differential metabolites were screened. The contents of 74 differential metabolites showed an upward trend and 19 metabolites showed a downward trend, among which 11 metabolites were annotated to the KEGG pathway database. We speculated that 10 metabolites were closely related to the deepening of the yellowness. Transcriptome analysis indicated that there were 2,948, 14,018 and 13,366 differentially expressed genes (DEGs) between CZ vs. ZD, CZ vs. XB and ZD vs. XB, respectively. Six key structural genes (CcCHI, CcFLS, CcDFR1, CcDFR2, CcDFR3, and CcCYP75B1) and five candidate transcription factors (MYB22, MYB28, MYB17, EREBP9, and EREBP13) were involved in the regulation of flavonoid metabolites. The findings indicate that flavonoid compounds influence the color intensity of yellow-toned petals in Sect. Chrysantha Chang. Our results provide a new perspective on the molecular mechanisms underlying flower color variation and present potential candidate genes for Camellia breeding.

Distribution pattern and change prediction of Phellodendron habitat in China under climate change.

Phellodendron has always been of great significance in promoting human health and ecological restoration. However, human activities and climate change have severely affected habitat, population dynamics and sustainable use of Phellodendron. Little is known about the geographical distribution pattern and their responses to climate change of Phellodendron. In order to reveal the impact of climate change on Phellodendron, we conducted a study based on natural distribution data of two species (297 occurrence points), 20 environmental factors, and an optimized MaxEnt model. Our results identified the main environmental factors influencing Phellodendron, predicted their potential geographical distribution, and assessed migration trends under climate change in China. Our analysis showed that Ph. amurense and Ph. chinense have potential suitable habitats of 62.89 × 104 and 70.71 × 104 km2, respectively. Temperature and precipitation were found to play an essential role in shaping the present geographical distribution of Phellodendron populations. Based on two future climate scenarios, we forecasted that the potential suitable habitat of Ph. amurense would decrease by 12.52% (SSP245) and increase by 25.28% (SSP585), while Ph. chinense would decline by 19.61% (SSP245) and 15.78% (SSP585) in the late-21st century. The potential suitable habitats of Ph. amurense and Ph. chinense would shift to northward and westward, respectively. Hydrothermal change was found to be the primary driver of the suitable habitat of Phellodendron populations in the future. We recommend establishing nature reserves for existing Phellodendron populations, especially Ph. chinense. Our study provided a practical framework for the impact of climate change on the suitable habitat of Phellodendron species and guided regional cultivation, long-term conservation, and sustainable use.

Evaluation of Truncated AUC as an Alternative Measure to Assess Pharmacokinetic Comparability in Bridging Biologic-Device Using Prefilled Syringes and Autoinjectors.

Pharmacokinetic (PK) comparisons between therapeutic biologics have largely been based on the total area under the concentration-time curve (AUC) and the maximum concentration (Cmax ). For biologics with a long half-life, a PK comparability study may be long in duration and costly to conduct. The goal of this study was to evaluate whether a truncated AUC (tAUC) can be used to assess PK comparability when bridging prefilled syringe (PFS) and autoinjector (AI) treatment options for biologics with a long half-life. Fifteen biologics license applications (BLAs) were included to determine the concordance and geometric percent coefficient of variation (%CV) between tAUCs evaluated on days 7, 14, 21, and 28 and AUC evaluated to infinity (AUC0-inf ). Concordance is established if the tAUCs are comparable with AUC0-inf . Trial simulation was performed to examine the effect of the absorption rate constant (ka ) and sample size on the concordance of tAUCs. The tAUCs evaluated on day 14, 21, and 28 had 100% concordance with AUC0-inf for all 15 BLAs. The concordance of tAUC evaluated at day 7 was 87.5%. Based on the trial simulation, tAUC evaluated to day 28 post-dose can achieve high concordance (≥85%) for biologics exhibiting linear or nonlinear elimination with a ka of ≥0.1/day and with a sample size of 70 subjects per arm. tAUC appears to be a promising alternative PK measure, relative to AUC0-inf , for PK comparability assessments.

Time-dependent effects of microplastics on soil bacteriome.

Microplastic threats to biodiversity, health and ecological safety are adding to concern worldwide, but the real impacts on the functioning of organisms and ecosystems are obscure owing to their inert characteristics. Here we investigated the long-lasting ecological effects of six prevalent microplastic types: polyethylene (PE), polypropylene (PP), polyamide (PA), polystyrene (PS), polyethylene terephthalate (PET), and polyvinyl chloride (PVC) on soil bacteria at a 2 % (w/w) level. Due to the inertia and lack of available nitrogen of these microplastics, their effects on bacteriome tended to converge after one year and were strongly different from their short-term effects. The soil volumes around microplastics were very specific, in which the microplastic-adapted bacteria (e.g., some genera in Actinobacteria) were enriched but the phyla Bacteroidetes and Gemmatimonadetes declined, resulting in higher microbial nitrogen requirements and reduced organic carbon mineralization. The reshaped bacteriome was specialized in the genetic potential of xenobiotic and lipid metabolism as well as related oxidation, esterification, and hydrolysis processes, but excessive oxidative damage resulted in severe weakness in community genetic information processing. According to model predictions, microplastic effects are indirectly derived from nutrients and oxidative stress, and the effects on bacterial functions are stronger than on structure, posing a heavy risk to soil ecosystems.

Hmong microbiome ANd Gout, Obesity, Vitamin C (HMANGO-C): A phase II clinical study protocol.

BACKGROUND: Hmong men in Minnesota exhibit a high prevalence of gout and hyperuricemia. Although evidence of vitamin C's effectiveness as a treatment for gout is mixed, analysis of therapeutic benefit based on an individual's multiomic signature may identify predictive markers of treatment success. OBJECTIVES: The primary objective of the Hmong Microbiome ANd Gout, Obesity, Vitamin C (HMANGO-C) study was to assess the effectiveness of vitamin C on serum urate in Hmong adults with and without gout/hyperuricemia. The secondary objectives were to assess if 1) vitamin C impacts the taxonomic and functional patterns of microbiota; 2) taxonomic and functional patterns of microbiota impact vitamin C's urate-lowering effects; 3) genetic variations impact vitamin C's urate-lowering effects; 4) differential microbial biomarkers exist for patients with or without gout; and 5) there is an association between obesity, gut microbiota and gout/hyperuricemia. METHODS: This prospective open-labelled clinical trial was guided by community-based participatory research principles and conducted under research safety restrictions for SARS-CoV-2. We aimed to enroll a convenient sample of 180 Hmong adults (120 with gout/hyperuricemia and 60 without gout/hyperuricemia) who provided medical, demographic, dietary and anthropometric information. Participants took vitamin C 500mg twice daily for 8 weeks and provided pre-and post- samples of blood and urine for urate measurements as well as stool samples for gut microbiome. Salivary DNA was also collected for genetic markers relevant to uric acid disposition. EXPECTED RESULTS: We expected to quantify the impact of vitamin C on serum urate in Hmong adults with and without gout/hyperuricemia. The outcome will enhance our understanding of how gut microbiome and genomic variants impact the urate-lowering of vitamin C and associations between obesity, gut microbiota and gout/hyperuricemia. Ultimately, findings may improve our understanding of the causes and potential interventions that could be used to address health disparities in the prevalence and management of gout in this underserved population. TRIAL REGISTRATION: ClinicalTrials.gov NCT04938024 (first posted: 06/24/2021).

An integrated metabolome and transcriptome analysis of the Hibiscus syriacus L. petals reveal the molecular mechanisms of anthocyanin accumulation.

Hibiscus syriacus L. var. Shigyoku is a new double-flowered bluish-purple variety in China that changes color during flower development from bluish-purple to light purple. There is limited information on the anthocyanin accumulation patterns and associated transcriptome signatures in Shigyoku from D1 (bud) to open flower (D3). Here, we employed a combined transcriptome and metabolome approach to understanding the mechanism of this color change. Our results demonstrate that cyanidins, pelargonidins, delphinidins, petunidins, peonidins, and malvidins were differentially accumulated in Shigyoku petals. The anthocyanin biosynthesis started in D1, was significantly upregulated in D2 (semi-open flower), and reduced in D3. However, malvidins, pelargonidins, and peonidins could be associated with the bluish-purple coloration on D2. Their reduced accumulation in D3 imparted the light purple coloration to Shigyoku petals on D3. Significant contributions in the color change could be associated with the expression changes in anthocyanin biosynthesis genes i.e., LARs, ANSs, DFRs, UGT79B1, C3'Hs, 3ATs, and BZ1s. The UFGTs were associated with the higher accumulation of glycosylated anthocyanins in D2 and D3. Furthermore, the changes in the expressions of the MYB and bHLH transcription factors were consistent with the anthocyanin accumulation. Finally, we discussed the possible roles of Jasmonic acid, auxin, and gibberellic acid signaling in regulating the MBW complex. Taken together, we conclude that H. syriacus petal coloration is associated with anthocyanin biosynthesis genes, the MBW complex, and phytohormone signaling.

Comparison of the Warfarin Dosing and Outcomes in Hmong Versus East Asians Patients: Real-World Data From an Integrated Healthcare System.

Background Previous research predicted that Hmong, an understudied East Asian subpopulation, might require significantly lower warfarin doses than East Asian patients partially due to their unique genetic and clinical factors. However, such findings have not been corroborated using real-world data. Methods This was a retrospective cohort study of Hmong and East Asian patients receiving warfarin. Warfarin stable doses (WSD) and time to the composite outcome, including international normalized ratio (INR) greater than four incidences or major bleeding within six months of warfarin initiation, were compared. Results This cohort study included 55 Hmong and 100 East Asian patients. Compared to East Asian patients, Hmong had a lower mean WSD (14.5 vs. 20.4 mg/week, p<0.05). In addition, Hmong had a 3.1-fold (95% CI: 1.1-9.3, p<0.05) higher hazard of the composite outcome. Conclusion Using real-world data, significant differences in warfarin dosing and hazard for the composite outcome of INR>4 and major bleeding were observed between Hmong and East Asian patients. These observations further underscore the importance of recognizing subpopulation-based differences in warfarin dosing and outcomes.

Pharmacogenomic variabilities in geo-ancestral subpopulations and their clinical implications: Results of collaborations with Hmong in the United States.

Underrepresentation of subpopulations within geo-ancestral groups engaged in research can exacerbate health disparities and impair progress toward personalized medicine. This is particularly important when implementing pharmacogenomics which uses genomic-based sources of variability to guide medication selection and dosing. This mini-review focuses on pharmacogenomic findings with Hmong in the United States and their potential clinical implications. By actively engaging Hmong community in pharmacogenomic-based research, several clinically relevant differences in allele frequencies were observed within key pharmacogenes such as CYP2C9 and CYP2C19 in Hmong compared to those in either East Asians or Europeans. Additionally, using state-of-the-art genome sequencing approaches, Hmong appear to possess novel genetic variants within CYP2D6, a critical pharmacogene affecting pharmacokinetics of a broad range of medications. The allele frequency differences and novel alleles in Hmong have translational impact and real-world clinical consequences. For example, Hmong patients exhibited a lower warfarin stable dose requirement compared to East Asian patients. This was predicted based on Hmong's unique genetic and non-genetic factors and confirmed using real-world data from clinical practice settings. By presenting evidence of the genetic uniqueness and its translational impact within subpopulations, such as the Hmong, we hope to inspire greater inclusion of other geo-ancestrally underrepresented subpopulations in pharmacogenomic-based research.

Knowledge and attitudes of incoming pharmacy students toward pharmacogenomics and survey reliability.

Aims: To assess knowledge and attitudes toward pharmacogenomics (PGx) of incoming doctoral pharmacy students, to evaluate the internal structure and reliability of the PGx survey and to identify variables associated with the different responses. Methods: A PGx survey based on the core pharmacist competencies in PGx was created. Results: Of 83.2% analyzable responses, 91% believed PGx is a useful tool and relevant to future practice but over 70% stated they lack confidence in clinical PGx knowledge. This 38-item PGx survey included three factors showing high reliability. Prior genetic/PGx testing and unsatisfactory medication experiences were associated with a more positive attitude toward PGx. Conclusion: The majority of students have positive attitudes toward PGx, but lack knowledge in genetic concepts and clinical PGx.

A pharmacogenomics (PGx) survey with high reliability showed that incoming doctoral pharmacy students have positive attitudes toward PGx, but lack knowledge of genetic concepts and clinical PGx.