The attenuated hepatic clearance of propionate increases cardiac oxidative stress in propionic acidemia.

Propionic acidemia (PA), arising from PCCA or PCCB variants, manifests as life-threatening cardiomyopathy and arrhythmias, with unclear pathophysiology. In this work, propionyl-CoA metabolism in rodent hearts and human pluripotent stem cell-derived cardiomyocytes was investigated with stable isotope tracing analysis. Surprisingly, gut microbiome-derived propionate rather than the propiogenic amino acids (valine, isoleucine, threonine, and methionine) or odd-chain fatty acids was found to be the primary cardiac propionyl-CoA source. In a Pcca-/-(A138T) mouse model and PA patients, accumulated propionyl-CoA and diminished acyl-CoA synthetase short-chain family member 3 impede hepatic propionate disposal, elevating circulating propionate. Prolonged propionate exposure induced significant oxidative stress in PCCA knockdown HL-1 cells and the hearts of Pcca-/-(A138T) mice. Additionally, Pcca-/-(A138T) mice exhibited mild diastolic dysfunction after the propionate challenge. These findings suggest that elevated circulating propionate may cause oxidative damage and functional impairment in the hearts of patients with PA.

Survey of physicians' knowledge about pediatric nonalcoholic fatty liver disease in China.

OBJECTIVES: To evaluate physicians' awareness and knowledge towards pediatric nonalcoholic fatty liver disease (NAFLD) and their attitude toward change in nomenclature from NAFLD to metabolic dysfunction-associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) in China. METHODS: The questionnaire survey contained five parts (characteristics of the participants, epidemiology, diagnosis, management of NAFLD, and attitudes toward the nomenclature of MAFLD/MASLD). The participants included 53 hepatologists, 88 gastroenterologists (GEs), 74 endocrinologists (ENDOs), 61 primary care physicians (PCPs), and 157 pediatricians across 31 municipalities, provinces and autonomous regions of China's mainland. RESULTS: Hepatologists saw the largest number of pediatric NAFLD patients annually (median 9 [range 1-20]), with the lowest number by PCPs (even notwithstanding one patient annually). The primary sources of pediatric NAFLD knowledge were acquired via guidelines. Hepatologists had the highest total knowledge score among all five types of physicians. Approximately one-third of nonspecialists (ENDOs and PCPs) considered liver biopsy necessary for pediatric NAFLD patients, and this percentage increased to half in specialists (hepatologists and GEs). For nonspecialists, the major barriers to the management of pediatric NAFLD were poor patient adherence to lifestyle modifications and lacking confidence in managing NAFLD. Above 90% physicians agreed to change the nomenclature NAFLD to MAFLD; however, they were not sure whether it could reduce the economic burden. CONCLUSIONS: Despite the epidemic of pediatric NAFLD in China, a significant knowledge gap remains in the identification, diagnosis, and treatment of pediatric NAFLD, particularly among frontline workers such as pediatricians and PCPs. More education programs should be carried out in the future.

A comparison of antibiotic resistance genes and mobile genetic elements in wild and captive Himalayan vultures.

As the most widely distributed scavenger birds on the Qinghai-Tibetan Plateau, Himalayan vultures (Gyps himalayensis) feed on the carcasses of various wild and domestic animals, facing the dual selection pressure of pathogens and antibiotics and are suitable biological sentinel species for monitoring antibiotic resistance genes (ARGs). This study used metagenomic sequencing to comparatively investigate the ARGs and mobile genetic elements (MGEs) of wild and captive Himalayan vultures. Overall, the resistome of Himalayan vultures contained 414 ARG subtypes resistant to 20 ARG types, with abundances ranging from 0.01 to 1,493.60 ppm. The most abundant resistance type was beta-lactam (175 subtypes), followed by multidrug resistance genes with 68 subtypes. Decreases in the abundance of macrolide-lincosamide-streptogramin (MLS) resistance genes were observed in the wild group compared with the zoo group. A total of 75 genera (five phyla) of bacteria were predicted to be the hosts of ARGs in Himalayan vultures, and the clinical (102 ARGs) and high-risk ARGs (35 Rank I and 56 Rank II ARGs) were also analyzed. Among these ARGs, twenty-two clinical ARGs, nine Rank I ARG subtypes, sixteen Rank II ARG subtypes were found to differ significantly between the two groups. Five types of MGEs (128 subtypes) were found in Himalayan vultures. Plasmids (62 subtypes) and transposases (44 subtypes) were found to be the main MGE types. Efflux pump and antibiotic deactivation were the main resistance mechanisms of ARGs in Himalayan vultures. Decreases in the abundance of cellular protection were identified in wild Himalayan vultures compared with the captive Himalayan vultures. Procrustes analysis and the co-occurrence networks analysis revealed different patterns of correlations among gut microbes, ARGs, and MGEs in wild and captive Himalayan vultures. This study is the first step in describing the characterization of the ARGs in the gut of Himalayan vultures and highlights the need to pay more attention to scavenging birds.

Exploring the inverse relationship between serum total bilirubin and systemic immune-inflammation index: insights from NHANES data (2009-2018).

BACKGROUND: Bilirubin is known for its multifaceted attributes, including antioxidant, anti-inflammatory, immunomodulatory, and antiapoptotic properties. The systemic immune-inflammation index (SII) is a recent marker that reflects the balance between inflammation and immune response. Despite the wealth of information available on bilirubin's diverse functionalities, the potential correlation between the total bilirubin (TB) levels and SII has not been investigated so far. METHODS: Leveraging data from the National Health and Nutrition Examination Survey spanning 2009-2018, the TB levels were categorized using tertiles. Employing the chi-squared test with Rao and Scott's second-order correction and Spearman's rank correlation analysis, the association between TB and SII was examined. The potential nonlinearities between TB and SII were evaluated using restricted cubic spline (RCS) analysis. Weighted linear regression, adjusted for covariates, was used to explore the correlation between TB and SII, with further subgroup analyses. RESULTS: A total of 16,858 participants were included, and the findings revealed significant SII variations across TB tertiles (p < 0.001). The third tertile (Q3) exhibited the lowest SII level at 495.73 (295.00) 1000 cells/µL. Spearman rank correlation disclosed the negative association between TB and SII. RCS analysis exposed the lack of statistically significant variations in the nonlinear relationship (p > 0.05), thereby providing support for a linear relationship. Weighted linear regression analysis underscored the negative correlation between TB and SII (ß 95% CI - 3.9 [- 5.0 to - 2.9], p < 0.001). The increase in the TB levels is associated with a significant linear trend toward decreasing SII. After controlling for relative covariates, this negative correlation increased (p < 0.001). Subgroup analysis confirmed the significant negative TB-SII association. CONCLUSION: A notable negative correlation between TB and SII implies the potential protective effects of bilirubin in inflammation-related diseases.

Enhanced oxygen anions generation on Bi2S3/Sb2S3 heterostructure by visible light for trace H2S detection at room temperature.

Bismuth sulfide (Bi2S3) possesses unique properties that make it a promising material for effective hydrogen sulfide (H2S) detection at room temperature. However, when exposed to light, the oxygen anions (O2-(ads)) adsorbed on the surface of Bi2S3 can react with photoinduced holes, ultimately reducing the ability to respond to H2S. In this study, Bi2S3/Sb2S3 heterostructures were synthesized, producing photoinduced oxygen anions (O2-(hv)) under visible light conditions, resulting in enhanced H2S sensing capability. The Bi2S3/Sb2S3 heterostructure sensor exhibits a two-fold increase in sensing response to 500 ppb H2S under in door light conditions relative to its performance in darkness. Additionally, the sensing response of the Bi2S3/Sb2S3 sensor (Ra/Rg= 23.3) was approximately five times higher than pure Bi2S3. The improved sensing performance of the Bi2S3/Sb2S3 heterostructures is attributable to the synergistic influence of the heterostructure configuration and light modulation, which enhances the H2S sensing performance by facilitating rapid charge transfer and increasing active sites (O2-(hv)) when exposed to visible light.

Exploring the Molecular Mechanism of Comorbidity of Type 2 Diabetes Mellitus and Colorectal Cancer: Insights from Bulk Omics and Single-Cell Sequencing Validation.

The relationship between type 2 diabetes mellitus (T2DM) and colorectal cancer (CRC) has long been extensively recognized, but their crosstalk mechanisms based on gene regulation remain elusive. In our study, for the first time, bulk RNA-seq and single-cell RNA-seq data were used to explore the shared molecular mechanisms between T2DM and CRC. Moreover, Connectivity Map and molecular docking were employed to determine potential drugs targeting the candidate targets. Eight genes (EVPL, TACSTD2, SOX4, ETV4, LY6E, MLXIPL, ENTPD3, UGP2) were identified as characteristic comorbidity genes for T2DM and CRC, with EVPL and ENTPD3 further identified as core comorbidity genes. Our results demonstrated that upregulation of EVPL and downregulation of ENTPD3 were intrinsic molecular features throughout T2DM and CRC and were significantly associated with immune responses, immune processes, and abnormal immune landscapes in both diseases. Single-cell analysis highlighted a cancer-associated fibroblast (CAF) subset that specifically expressed ENTPD3 in CRC, which exhibited high heterogeneity and unique tumor-suppressive features that were completely different from classical cancer-promoting CAFs. Furthermore, ENTPD3+ CAFs could notably predict immunotherapy response in CRC, holding promise to be an immunotherapy biomarker at the single-cell level. Finally, we identified that droperidol may be a novel drug simultaneously targeting EVPL and ENTPD3. In conclusion, previous studies have often focused solely on metabolic alterations common to T2DM and CRC. Our study establishes EVPL and ENTPD3 as characteristic molecules and immune biomarkers of comorbidity in T2DM and CRC patients, and emphasizes the importance of considering immunological mechanisms in the co-development of T2DM and CRC.

Evaluating Fluorinated-Aniline Units with Functionalized Spiro[Fluorene-9,9'-Xanthene] as Hole-Transporting Materials in Perovskite Solar Cells and Light-Emitting Diodes.

In the field of perovskite optoelectronics, developing hole-transporting materials (HTMs) on the spiro[fluorene-9,9'-xanthene] (SFX) platform is one of the current research focuses. The SFX inherits the merits of spirobifluorene in terms of the configuration and property, but it is more easily derivatized and regulated by virtue of its binary structure. In this work, we design and synthesize four isomeric SFX-based HTMs, namely m-SFX-mF, p-SFX-mF, m-SFX-oF, and p-SFX-oF, through varying the positions of fluorination on the peripheral aniline units and their substitutions on the SFX core, and the optoelectronic performance of the resulting HTMs is evaluated in both perovskite solar cells (PSCs) and light-emitting diodes (PeLEDs) by the vacuum thermal evaporating hole-transporting layers (HTLs). The HTM p-SFX-oF exhibits an improved power conversion efficiency of 15.21% in an inverted PSC using CH3NH3PbI3 as an absorber, benefiting from the deep HOMO level and good HTL/perovskite interface contact. Meanwhile, the HTM m-SFX-mF provides a maximum external quantum efficiency of 3.15% in CsPb(Br/Cl)3-based PeLEDs, which is attributed to its perched HOMO level and shrunken band-gap for facilitating charge carrier injection and then exciton combination. Through elucidating the synergistic position effect of fluorination on aniline units and their substitutions on the SFX core, this work lays the foundation for developing low-cost and efficient HTMs in the future.

Feature-Based Molecular Network-Assisted Cannabinoid and Flavonoid Profiling of Cannabis sativa Leaves and Their Antioxidant Properties.

Cannabis sativa (C. sativa) leaves are rich in cannabinoids and flavonoids, which play important antioxidant roles. Since the environmental factors may influence the accumulation of antioxidants in herbal medicines, which affects their activity, this study aimed to investigate the correlation between the chemical composition of C. sativa leaves and their geographical origin and antioxidant activity. Firstly, a high-resolution mass spectrometry method assisted by semi-quantitative feature-based molecular networking (SQFBMN) was established for the characterization and quantitative analysis of C. sativa leaves from various regions. Subsequently, antioxidant activity analysis was conducted on 73 batches of C. sativa leaves, and a partial least squares regression (PLS) model was employed to assess the correlation between the content of cannabinoids and flavonoids in the leaves and their antioxidant activity. A total of 16 cannabinoids and 57 flavonoids were annotated from C. sativa, showing a significant regular geographical distribution. The content of flavonoid-C glycosides in Sichuan leaves is relatively high, and their antioxidant activity is also correspondingly high. However, the leaves in Shaanxi and Xinjiang were primarily composed of flavonoid-O glycosides, and exhibited slightly lower antioxidant activity. A significant positive correlation (p < 0.001) was found between the total flavonoids and cannabinoids and the antioxidant activity of the leaves, and two flavonoids and one cannabinoid were identified as significant contributors.

The Association between Discrepancies in Parental Emotional Expressivity, Adolescent Loneliness and Depression: A Multi-Informant Study Using Response Surface Analysis.

Incongruent perceptions of parental emotional expressivity between parents and adolescents may signify relational challenges, potentially impacting adolescents' socioemotional adjustment. Direct evidence is still lacking and father-adolescent discrepancies are overlooked. This study employed a multi-informant design to investigate whether both mother-adolescent and father-adolescent discrepancies in perceptions of parental expressivity are related to adolescents' mental well-being, specifically focusing on loneliness and depression. Analyzing data from 681 families (mean age of adolescents = 15.5 years old, 51.2% girls, 40% only-children) in China revealed that adolescents tended to perceive paternal and maternal emotional expressivity more negatively than their parents, particularly fathers. Polynomial regression and response surface analysis showed significant links between parent-adolescent congruence and incongruence and adolescent loneliness. (In)Congruence between adolescents and mothers or fathers predicted later adolescent depression, mediated by adolescent loneliness and varied by the dimension of emotional expressivity. These findings provide insights into the roles of mothers' and fathers' emotional expressivity in shaping children's mental well-being during adolescence.

Energy strategy alteration, rather than toxicity itself, interferes with the population fluctuation of Brachionus plicatilis exposed to water-accommodated fractions (WAFs) of crude oil.

Oil spills are reported to have conflicting impacts of either injury or resilience on zooplankton communities, and physiological plasticity is speculated to be the possible causative factor. But how? An explanation was sought by exposing the marine rotifer Brachionus plicatilis to a series of water-accommodated fractions (WAFs) of crude oil under controlled laboratory conditions, and population dynamics, which is the core issue for zooplankton facing external stress, were analyzed. The total hydrocarbon concentration of WAFs was quickly degraded from a concentration of 5.0 mg L-1 to half within 24 h and then remained stable. No acute lethality was observed; only motion inhibition was observed in the group treated with 10 %, 50 % and 100 % WAFs, which occurred simultaneously with inhibition of feeding and filtration. However, sublethal exposure to the WAFs concentration series presented stimulation impacts on reproduction and even the population of B. plicatilis. The negative correlation between motion and reproduction seemed to indicate that a shift in the distribution of individual energy toward reproduction rather than motion resulted in increased reproduction after exposure to WAFs. More evidence from transmission electron microscopy (TEM) revealed ultrastructural impairment in both the ovaries and cilia in each treated group, and imbalance in mitochondrial numbers was one of the distinct features of alteration. WAFs stress may alter the energy utilization and storage paradigm, as indicated by the significant elevation in glycogen and the significant decrease in lipid content after WAFs exposure. Further evidence from metabolomics analysis showed that WAFs stress increased the level of lipid metabolism and inhibited some of the pathways in glucose metabolism. Sublethal acute toxicity was observed only in the first 24 h with WAFs exposure, and an energy strategy consisting of changes in the utilization and storage paradigm and reallocation is responsible for the population resilience of B. plicatilis during oil spills.

Epidemiological trends in serotypes distribution and antimicrobial resistance in Salmonella from humans in Taiwan, 2004-2022.

Objectives: Salmonella, a zoonotic pathogen, significantly impacts global human health. Understanding its serotype distribution and antimicrobial resistance is crucial for effective control measures and medical interventions. Methods: We collected Salmonella isolates and demographic data from Taiwanese hospitals between 2004 and 2022, analyzing their serotypes and antimicrobial susceptibility. Results: Among 40,595 isolates, salmonellosis predominated in children aged 0-4 (61.2%) years and among males (55.2%). Males also showed higher rates of extraintestinal infections (18.1% vs 16.0%, P <0.001), particularly, in the ≥65 years age group (52.4%). The top five serovars were S. Enteritidis (32.8%), S. Typhimurium (21.7%), S. Newport (6.2%), S. Stanley (4.7%), and S. Anatum (4.0%). Notably, S. Enteritidis prevalence increased from 23.9% (2004-2005) to 43.6% (2021-2022). Antimicrobial resistance was high, with a 51.6% multidrug resistance (MDR) rate. Disturbingly, MDR rates exceeded 90% in serovars Albany, Schwarzengrund, Choleraesuis, and Goldcoast. Resistance to key therapeutic agents, azithromycin, cefotaxime, and ciprofloxacin, exhibited concerning upward trends, and the surge in cefotaxime and ciprofloxacin resistance was closely linked to the emergence and spread of MDR S. Anatum and S. Goldcoast clones. Conclusions: Prioritizing control measures against S. Enteritidis and closely monitoring the prevalence and spread of MDR clones are imperative to mitigate Salmonella infections in Taiwan.

Cardiorespiratory fitness attenuates the association between fatness and cardiometabolic risk in Chinese children.

Background: Childhood obesity tends to persist into adulthood, predisposing individuals to cardiometabolic risk (CMR). This study aims to investigate the mediating role of cardiorespiratory fitness (CRF) in the associations between multiple fatness indicators and individual CMR markers and clustered CMR-score, and explore sex differences. Methods: We recruited 1,557 children (age: 8 to 10, male/female: 52.7%/47.3%) in September 2022 in Ningbo, China. Physical examinations, overnight fasting blood test, and CRF was evaluated. The CMR-score was calculated by summing age- and sex-specific z scores of four CMR markers, including mean arterial blood pressure, triglycerides, the total cholesterol to high-density lipoprotein cholesterol ratio, and homeostatic model assessment for insulin resistance. Generalized linear mixed models were used to identify the associations, mediation analyses were performed to dissect the function of CRF. Results: Partial correlation analyses revealed positive associations between high fatness indicators (including body mass index [BMI], BMI z score, body fat mass index [BFMI] and waist-to-height ratio [WHtR]) and increased CMR markers, whereas high CRF was associated with decreased CMR markers (all P < 0.05). In the mediation analyses, CRF emerged as a partial mediator, attenuating the relationship between four fatness indicators and CMR-score. Specifically, CRF mediated 6.5%, 7.7%, 5.3%, and 12.5% of the association between BMI, BMI z score, BFMI, WHtR and CMR-score (all P < 0.001). And the mediating effects of CRF between WHtR and four individual CMR markers was particularly robust, ranging from 10.4% to 21.1% (all P < 0.05). What's more, CRF mediates the associations between WHtR and CMR-score more pronounced in girls than boys with a mediation effect size of 17.3% (P < 0.001). Conclusion: In Chinese children, CRF partially mitigates the adverse effects of fatness on CMR, underscoring the significance of enhancing CRF in children.

Library Screening, In Vivo Confirmation, and Structural and Bioinformatic Analysis of Pentapeptide Sequences as Substrates for Protein Farnesyltransferase.

Protein farnesylation is a post-translational modification where a 15-carbon farnesyl isoprenoid is appended to the C-terminal end of a protein by farnesyltransferase (FTase). This process often causes proteins to associate with the membrane and participate in signal transduction pathways. The most common substrates of FTase are proteins that have C-terminal tetrapeptide CaaX box sequences where the cysteine is the site of modification. However, recent work has shown that five amino acid sequences can also be recognized, including the pentapeptides CMIIM and CSLMQ. In this work, peptide libraries were initially used to systematically vary the residues in those two parental sequences using an assay based on Matrix Assisted Laser Desorption Ionization-Mass Spectrometry (MALDI-MS). In addition, 192 pentapeptide sequences from the human proteome were screened using that assay to discover additional extended CaaaX-box motifs. Selected hits from that screening effort were rescreened using an in vivo yeast reporter protein assay. The X-ray crystal structure of CMIIM bound to FTase was also solved, showing that the C-terminal tripeptide of that sequence interacted with the enzyme in a similar manner as the C-terminal tripeptide of CVVM, suggesting that the tripeptide comprises a common structural element for substrate recognition in both tetrapeptide and pentapeptide sequences. Molecular dynamics simulation of CMIIM bound to FTase further shed light on the molecular interactions involved, showing that a putative catalytically competent Zn(II)-thiolate species was able to form. Bioinformatic predictions of tetrapeptide (CaaX-box) reactivity correlated well with the reactivity of pentapeptides obtained from in vivo analysis, reinforcing the importance of the C-terminal tripeptide motif. This analysis provides a structural framework for understanding the reactivity of extended CaaaX-box motifs and a method that may be useful for predicting the reactivity of additional FTase substrates bearing CaaaX-box sequences.

Northwestern Pacific Oceanic circulation shaped by ENSO.

The intricate currents of the Northwest Pacific Ocean, with strong manifestations along the westside rim, connect tropical and subtropical gyres and significantly influence East Asian and global climates. The El Niño/Southern Oscillation (ENSO) originates in the tropical Pacific Ocean and disrupts this ocean circulation system. However, the spatiotemporal dependence of the impact of ENSO events has yet to be elucidated because of the complexities of both ENSO events and circulation systems, as well as the increased availability of observational data. We thus combined altimeter and drifter observations to demonstrate the distinct tropical and subtropical influences of the circulation system on ENSO diversity. During El Niño years, the North Equatorial Current, North Equatorial Countercurrent, Mindanao Current, Indonesian Throughflow, and the subtropical Kuroshio Current and its Extension region exhibit strengthening, while the tropical Kuroshio Current weakens. The tropical impact is characterized by sea level changes in the warm pool, whereas the subtropical influence is driven by variations in the wind stress curl. The tropical and subtropical influences are amplified during the Centra Pacific El Niño years compared to the Eastern Pacific El Niño years. As the globe warms, these impacts are anticipated to intensify. Thus, strengthening observation systems and refining climate models are essential for understanding and projecting the enhancing influences of ENSO on the Northwest Pacific Oceanic circulation.

The efficacy of immune checkpoint inhibitors on low PD-L1 cervical cancer: A meta-analysis.

Background and Aims: The effectiveness of immune checkpoint inhibitors (ICIs) in low programmed death ligand 1 (PD-L1) expression in cervical cancer (CC) patients remains unknown. We aimed to evaluate the efficacy of ICIs in low PD-L1 expression CC patients. Methods: The study is an individual patient data (IPD)-based meta-analysis. IPD were compiled through KMSubtraction and IPDfromKM methodologies from high-quality randomized clinical trials and single-arm studies which reported overall survival (OS) or progression-free survival (PFS) stratified by PD-L1 expression. Kaplan-Meier curves and Cox regression analysis were employed to evaluate the survival benefits of ICIs. Results: A total of eight studies and 1110 cases were included in the analysis. Within the low PD-L1 expression subgroup, ICI combination therapy, but not ICI monotherapy, demonstrated significant OS benefits over non-ICI treatment (hazard ratio [HR] = 0.61, 95% confidence interval [CI]: 0.36-1.04, p = 0.06). Concerning PFS, ICI monotherapy was associated with a negative effect compared to non-ICI treatment (HR = 4.59, 95% CI: 2.32-9.07, p < 0.001). Notably, both OS and PFS outcomes were unfavorable for ICI monotherapy compared to both non-ICI and ICI combination therapy in the combined positive score <1 subgroup (OS: HR = 2.60, 95% CI: 1.31-5.16, p = 0.008; PFS: HR = 7.59, 95% CI: 3.53-16.31, p < 0.001). Conclusion: In patients with CC and low PD-L1 expression, ICI monotherapy may not be considered as the optimal treatment strategy when compared to non-ICI treatment or ICI combination therapy. Registration: CRD42023395103.

Transcriptomic and metabolomic analyses reveal CmMYB308 as a key regulator in the pink flower color variation of 'Dante Purple' chrysanthemum.

KEY MESSAGE: CmMYB308 was identified as a key regulator in chrysanthemum flower color variation from purple to pink by conducting transcriptome and metabolome analysis. CmMYB308 can inhibit anthocyanin biosynthesis by suppressing the expression of CmPAL, CmC4H, and Cm4CL. Flower color variation is a widespread natural occurrence that plays a significant role in floral breeding. We discovered a variation in the flower of the chrysanthemum cultivar 'Dante Purple' (abbreviated as 'DP'), where the flower color shifted from purple to pink. We successfully propagated these pink flowers through tissue culture and designated them as DPM. By conducting transcriptome and metabolome analysis, we identified a reduction in the expression of critical genes involved in anthocyanin biosynthesis-CmPAL, CmC4H, and Cm4CL-in the DPM. This downregulation led to an accumulation of phenylalanine and cinnamic acid within the general phenylpropanoid pathway (GPP), which prevented their conversion into cyanidin and cyanidin 3-glucoside. As a result, the flowers turned pink. Additional transformation and biochemical experiments confirmed that the upregulation of CmMYB308 gene expression in the DPM directly suppressed CmPAL-1 and CmC4H genes, which indirectly affected Cm4CL-3 expression and ultimately inhibited anthocyanin biosynthesis in the DPM. This study offers a preliminary insight into the molecular mechanism underlying chrysanthemum flower color mutation, paving the way for genetic improvements in chrysanthemum flower color breeding.

Heterogeneous Oxidase-Type Catalysis for H2 Generation at Low Temperatures.

The long-term objective in the field of heterogeneous catalysis is to develop an enzyme-like catalytic pathway that can achieve exceptional catalytic performance even at low temperatures. Herein, we have demonstrated a heterogeneous oxidase-type catalysis on the ZnO-supported Ru clusters (Ru/ZnO) for efficient H2 generation from an aqueous solution of formaldehyde (HCHO) at low temperatures. Due to its unique reaction pathway, the Ru/ZnO catalysts exhibited a temperature-insensitive activity for H2 generation at the temperature of 15 to 45 °C. Remarkably, even at a low temperature of 5 °C, the Ru/ZnO catalysts still enabled an H2 generation rate of 13.8 mmol gcat-1 h-1 with a turnover frequency (TOF) of 1678 h-1. Additionally, instead of producing a CO2/CO molecule, the HCHO molecule underwent a transformation into formic acid and/or formate as the byproduct. This finding presents a novel class of heterogeneous catalysts to expand the potential application scenarios of liquid hydrogen storage and transportation systems.

Development of erythrina-based PARP-1/FTase dual-target inhibitors against lung cancer epithelial-mesenchymal transition (EMT) in vivo and in vitro.

A novel series of erythrina derivatives as PARP-1/FTase inhibitors were synthesized, and evaluated for their biological activities. Compound T9 had excellent inhibitory effects on cell viability (A549: IC50 = 1.74 µM; A549/5-Fu: IC50 = 1.03 µM) and in vitro enzyme activities (PARP-1: IC50 = 0.40 µM; FTase: IC50 = 0.067 µM). Molecular docking and point mutation assays demonstrated the interaction of compound T9 with key amino acid residues. The compound T9 exhibited potent anti-proliferation and anti-migration capabilities against A549 and A549/5-Fu cells. PCR array and western blot results showed that compound T9 could effectively inhibit EMT-related proteins in A549 and A549/5-Fu cells, thereby inhibiting the development of lung cancer. Importantly, compound T9 could significantly inhibit tumor growth in the A549 xenograft tumor model (TGI = 65.3 %). In conclusion, this study was the first presentation of the concept of dual-target inhibitors of the PARP-1/FTase enzymes. It also provides the basis for further research and development of novel PARP-1/FTase inhibitors.

Antimicrobial resistance and genetic relatedness among Campylobacter coli and Campylobacter jejuni from humans and retail chicken meat in Taiwan.

OBJECTIVES: Campylobacter is a significant zoonotic pathogen primarily transmitted through poultry. Our study aimed to assess antimicrobial resistance and genetic relationships among Campylobacter isolates from retail chicken meat and humans in Taiwan. METHODS: Campylobacter isolates were analysed using whole-genome sequencing to investigate their antimicrobial resistance, genetic determinants of resistance, and genotypes. RESULTS: Campylobacter coli and Campylobacter jejuni accounted for 44.9% and 55.1% of chicken meat isolates, and 11.4% and 88.6% of human isolates, respectively. C. coli displayed significantly higher resistance levels. Furthermore, isolates from chicken meat exhibited higher levels of resistance to most tested antimicrobials compared to isolates from humans. Multidrug resistance was observed in 96.3% of C. coli and 43.3% of C. jejuni isolates from chicken meat and 80.6% of C. coli and 15.8% of C. jejuni isolates from humans. Macrolide resistance was observed in 85.5% of C. coli isolates, primarily attributed to the erm(B) rather than the A2075G mutation in 23S rRNA. Among the 511 genomes, we identified 133 conventional MLST sequence types, indicating significant diversity among Campylobacter strains. Notably, hierarchical Core-genome multilocus sequence typing clustering, including HC0, HC5, and HC10, revealed a significant proportion of closely related isolates from chicken meat and humans. CONCLUSIONS: Our research highlights significant associations in antimicrobial resistance and genetic relatedness between Campylobacter isolates from chicken meat and humans in Taiwan. The genetic analysis data suggest that campylobacteriosis outbreaks may occur more frequently in Taiwan than previously assumed. Our study emphasizes the need for strategies to control multidrug-resistant strains and enhance outbreak prevention.

Metagenomic comparison of gut communities between wild and captive Himalayan griffons.

Introduction: Himalayan griffons (Gyps himalayensis), known as the scavenger of nature, are large scavenging raptors widely distributed on the Qinghai-Tibetan Plateau and play an important role in maintaining the balance of the plateau ecosystem. The gut microbiome is essential for host health, helping to maintain homeostasis, improving digestive efficiency, and promoting the development of the immune system. Changes in environment and diet can affect the composition and function of gut microbiota, ultimately impacting the host health and adaptation. Captive rearing is considered to be a way to protect Himalayan griffons and increase their population size. However, the effects of captivity on the structure and function of the gut microbial communities of Himalayan griffons are poorly understood. Still, availability of sequenced metagenomes and functional information for most griffons gut microbes remains limited. Methods: In this study, metagenome sequencing was used to analyze the composition and functional structures of the gut microbiota of Himalayan griffons under wild and captive conditions. Results: Our results showed no significant differences in the alpha diversity between the two groups, but significant differences in beta diversity. Taxonomic classification revealed that the most abundant phyla in the gut of Himalayan griffons were Fusobacteriota, Proteobacteria, Firmicutes_A, Bacteroidota, Firmicutes, Actinobacteriota, and Campylobacterota. At the functional level, a series of Kyoto Encyclopedia of Genes and Genome (KEGG) functional pathways, carbohydrate-active enzymes (CAZymes) categories, virulence factor genes (VFGs), and pathogen-host interactions (PHI) were annotated and compared between the two groups. In addition, we recovered nearly 130 metagenome-assembled genomes (MAGs). Discussion: In summary, the present study provided a first inventory of the microbial genes and metagenome-assembled genomes related to the Himalayan griffons, marking a crucial first step toward a wider investigation of the scavengers microbiomes with the ultimate goal to contribute to the conservation and management strategies for this near threatened bird.