Comparative physiological and transcriptomic analysis of sono-biochemical control over post-acidification of Lactobacillus delbrueckii subsp. bulgaricus.

Thermosonication (UT) prestress treatments combining with varied fermentation patterns has been revealed as an effective method to regulate post-acidification as exerted by Lactobacillus delbrueckii subsp. bulgaricus (L. delbrueckii), but sono-biochemical controlling mechanisms remain elusive. This study employed physiological and transcriptomic analysis to explore the response mechanism of L. delbrueckii to UT-induced microstress (600 W, 33 kHz, 10 min). UT stress-induced inhibition of acidification of L. delbrueckii during (post)-fermentation was first confirmed, relying on the UT process parameters such as stress exposure duration and UT power. The significantly enhanced membrane permeability in cells treated by 600 W for 10 min than the microbes stressed by 420 W for 20 min suggested the higher dependence of UT-derived stresses on the treatment durations, relative to the ultrasonic powers. In addition, ultrasonication treatment-induced changes in cell membrane integrity enhanced and/or disrupted permeability of L. delbrueckii, resulting in an imbalance in intracellular conditions associated with corresponding alterations in metabolic behaviors and fermentation efficiencies. UT-prestressed inoculum exhibited a 21.46% decrease in the membrane potential during the lag phase compared to untreated samples, with an intracellular pH of 5.68 ± 0.12, attributed to the lower activities of H+-ATPase and lactate dehydrogenase due to UT stress pretreatments. Comparative transcriptomic analysis revealed that UT prestress influenced the genes related to glycolysis, pyruvate metabolism, fatty acid synthesis, and ABC transport. The genes encoding 3-oxoacyl-[acyl-carrier-protein] reductases I, II, and III, CoA carboxylase, lactate dehydrogenase, pyruvate oxidase, glucose-6-phosphate isomerase, and glycerol-3-phosphate dehydrogenase were downregulated, thus identifying the relevance of the UT microstresses-downregulated absorption and utilization of carbohydrates with the attenuated fatty acid production and energy metabolisms. These findings could contribute to provide a better understanding of the inactivated effects on the post-acidification of L. delbrueckii by ultrasonic pretreatments, thus providing theoretical basis for the targeted optimization of acidification inhibition efficiencies for yogurt products during chilled preservation processes.

New insights into the pH-dependent removal of sulfamethoxazole in peracetic acid activation systems: From mechanistic exploration to practical application potentials.

Peracetic acid (PAA) as emerging oxidant in advanced oxidation processes (AOPs) has attracted widespread attention in purifying water pollution. In this research, the removal of target contaminant (sulfamethoxazole, SMX) was investigated through PAA activation by a facile catalyst (Co@C), and the active sites of catalyst were identified as sp3-C, Oads, and Co0 by correlation analysis. Especially, different pH adjustment strategies were designed, including System A (adjusting pH after adding PAA) and System B (adjusting pH before adding PAA), to investigate the impact of oxidant acidity and alkalinity on solution microenvironment as well as effect and mechanism of pollutant removal. The results showed that HO· and CH3C(O)OO· dominated in System A, while Co(IV)O2+ was also observed in System B. Both systems showed optimal SMX degradation (98 %). However, System A exhibited excellent water quality tolerance (efficiency > 78 %), superior sustained catalyst activation (efficiency > 80 % in 40 h), less ion leaching (41 µg L-1), and lower products toxicity. Moreover, the pH of solution after reaction in System B was intensely acidic, requiring costly pH adjustments for discharge. This study unveils the strategy of adjusting pH after adding PAA is preferable for water purification, enriching the emerging research of PAA-based AOPs for the remediation of environments.

Development of a TaqMan polymerase chain reaction detection method for the precise identification and quantification of an attenuated Eimeria maxima vaccine strain in poultry.

Avian coccidiosis, a parasitic disease prevalent in poultry, is caused by Eimeria species and leads to significant economic losses. The use of attenuated live oocyst vaccines has been adopted as an alternative to the use of anticoccidial drugs. However, the accurate detection and differentiation of vaccine strains from virulent ones remain challenging. Therefore, this study presents a novel TaqMan polymerase chain reaction (PCR) detection method that offers enhanced sensitivity, specificity, and reproducibility compared with traditional PCR techniques. Through whole-genome resequencing and bioinformatics analysis, we identified a molecular marker gene, Em_marker6, with a unique 21-base pair deletion specific to the Eimeria maxima attenuated vaccine strain. Optimized primers and probes targeting this marker enabled rapid quantification cycle value achievement and high fluorescence intensity. The standard curve's slope of -3.540 and correlation coefficient of 0.9971 confirmed precise quantification capabilities. The TaqMan PCR method detected as few as 30 plasmid DNA copies and 50 oocysts per reaction, outperforming traditional PCR techniques by an order of magnitude. No cross-reactivity was observed with other E. maxima wide-type strains or common intestinal pathogens, ensuring the exclusive detection of the E. maxima EMPY vaccine strain. Weekly testing over 3 weeks demonstrated minimal variability, indicating robust consistency in the method's application. Testing on 61 clinical samples revealed a 57.38% positivity rate for E. maxima species and 13.11% for the vaccine strain. The Em_marker6 gene exhibited genetic stability across multiple generations, confirming the detection method's robust stability for the attenuated E. maxima vaccine strain. This study significantly advances the field of avian coccidiosis research and control by providing a valuable tool for monitoring vaccine purity and preventing inadvertent infections in vaccinated flocks, aligning with global efforts to curb antibiotic use in animal feed.

Development and anatomy of petals with specialized nectar holder and pollen container in Fumarioideae (Papaveraceae).

MAIN CONCLUSION: Petal developmental characteristics in Fumarioideae were similar at early stages, and the specialized nectar holder/pollen container formed by the outer/inner petals. The micro-morphology of these two structures, however, shows diversity in seven species. Elaborate petals have been modified to form different types, including petal lobes, ridges, protuberances, and spurs, each with specialized functions. Nectar holder and pollen container presumably have a function in plant-pollinator interactions. In Fumarioideae, four elaborate petals of the disymmetric/zygomorphic flower present architecture forming the "nectar holder" and "pollen container" structure at the bottom and top separately. In the present study, the petals of seven species in Fumarioideae were investigated by scanning electron microscopy, light microscope, and transmission electron microscopes. The results show that petal development could divided into six stages: initiation, enlargement, adaxial/abaxial differentiation, elaborate specializations (sacs, spurs, and lobes formed), extension, and maturation, while the specialized "nectar holder" and "pollen container" structures mainly formed in stage 4. "Nectar holder" is developed from the shallow sac/spur differentiated at the base of the outer petal, eventually forming a multi-organized complex structure, together with staminal nectaries (1-2) with individual sizes. A semi-closed ellipsoidal "pollen container" is developed from the apical part of the 3-lobed inner petals fused by middle lobes and attain different sizes. The adaxial epidermis cells are specialized, with more distinct punctate/dense columnar protrusions or wavy cuticles presented on obviously thickening cell walls. In addition, a large and well-developed cavity appears between the inner and outer epidermis of the petals. As an exception, Hypecoum erectum middle lobes present stamen mimicry. Elaborate petal structure is crucial for comprehending the petal diversity in Fumarioideae and provides more evidence for further exploration of the reproductive study in Papaveraceae.

Basiliximab Treatment for Patients With Steroid-Refractory Acute Graft-Versus-Host Disease Following Matched Sibling Donor Hematopoietic Stem Cell Transplantation.

Basiliximab is an important treatment for steroid-refractory acute graft-versus-host disease (SR-aGVHD). We performed this retrospective study to evaluate the efficacy and safety of basiliximab treatment in SR-aGVHD patients following matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) (n = 63). Overall response rate (ORR) was 63.5% and 54% at any time and at day 28 after basiliximab treatment. Grade III-IV aGVHD before basiliximab treatment predicted a poor ORR after basiliximab treatment. The rates of virus, bacteria, and fungi infections were 54%, 23.8%, and 3.1%, respectively. With a median follow-up of 730 (range, 67-3,042) days, the 1-year probability of overall survival and disease-free survival after basiliximab treatment were 58.6% (95% confidence interval [CI] = 47.6%-72.2%) and 55.4% (95% CI = 44.3%-69.2%), respectively. The 3-year cumulative incidence of relapse and non-relapse mortality after basiliximab treatment were 18.9% (95% CI = 8.3%-29.5%) and 33.8% (95% CI = 21.8%-45.7%), respectively. Comorbidities burden before allo-HSCT, severity of aGVHD and liver aGVHD before basiliximab treatment showed negative influences on survival. Thus, basiliximab was safe and effective treatment for SR-aGVHD following MSD-HSCT.

DNA methylation profiles of ovarian cysts resemble ovarian tissues but not endometrial tissues.

INTRODUCTION: Endometriosis is a heritable, complex chronic inflammatory disease, for which much of the causal pathogenic mechanism remain unknown.Despite the high prevalence of ovarian chocolate cyst, its origin is still under debate. METHODS: Prevailing retrograde menstruation model predicts that ectopic endometrial cells migrate and develop into ovarian chocolate cyst. However, other models were also proposed. Genome-wide association studies (GWASs) have proved successful in identifying common genetic variants of moderate effects for various complex diseases. RESULTS: A growing body of evidence shows that the remodeling of retrograde endometrial tissues to the ectopic endometriotic lesions involves multiple epigenetic alterations, such as DNA methylation, histone modification, and microRNA expression.Because DNA methylation states exhibit a tissue specific pattern, we profiled the DNA methylation for ovarian cysts and paired eutopic endometrial and ovarian tissues from four patients. Surprisingly, DNA methylation profiles showed the ovarian cysts were closely grouped with normal ovarian but not endometrial tissues. CONCLUSIONS: These results suggested alterative origin of ovarian cysts or strong epigenetic reprogramming of infiltrating endometrial cells after seeding the ovarian tissue. The data provide contributing to the pathogenesis and pathophysiology of endometriosis.

CD56bright NK cell expansion correlated with EBV reactivation control post allogeneic hematopoietic stem cell transplantation.

Natural killer (NK) cells are equipped with anti-Epstein-Barr virus (EBV) function, however, whether EBV infection will affect NK cells reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. To identify the characteristics of NK cells, we prospectively enrolled 11 patients who occurred EBV reactivation post allo-HSCT and 11 patients without EBV infection as control. We found that that EBV infection induced the expansion of CD56bright and NKG2A+KIR- NK subsets,and decreased the cytotoxicity function of NK cells. The frequency of NKG2A+KIR- NK cells were higher in patients who progressed into post-transplant lymphoproliferative disorder (PTLD) than EBV viremia patients, which also correlated with decreased proliferation and cytotoxic function. By screening the activation receptors of NK cells, we found the DNAM-1+CD56bright NK cells is significantly increased after EBV stimulation, further we demonstrated that DNAM-1 is essential for EBV induced NK cells activation as the cytokine release against EBV-transformed lymphoblastoid cell lines(EBV-LCLs) of CD56bright NK cells were significantly decreased after DNAM-1 blockade. NK cells infusion suppressed the progression of EBV-related tumor mice model. A prospective cohort indicated that old donor age was an independent risk factor for EBV infection. Rapid CD56bri expansion and high expression of DNAM-1 on CD56bri NK cells in response to EBV reactivation correlated with rapid EBV clearance post allo-HSCT in patients with younger donors. In summary, our data showed that high expression of DNAM-1 receptors on NK cell may participate protective CD56bri NK cells response to EBV infection after allo-HSCT.

Clinical manifestations, prognostic factors, and outcomes of adenovirus pneumonia after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Severe pneumonia is one of the most important causes of mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Adenovirus (ADV) is a significant cause of severe viral pneumonia after allo-HSCT, and we aimed to identify the clinical manifestations, prognostic factors, and outcomes of ADV pneumonia after allo-HSCT. METHODS: Twenty-nine patients who underwent allo-HSCT at the Peking University Institute of Hematology and who experienced ADV pneumonia after allo-HSCT were enrolled in this study. The Kaplan-Meier method was used to estimate the probability of overall survival (OS). Potential prognostic factors for 100-day OS after ADV pneumonia were evaluated through univariate and multivariate Cox regression analyses. RESULTS: The incidence rate of ADV pneumonia after allo-HSCT was approximately 0.71%. The median time from allo-HSCT to the occurrence of ADV pneumonia was 99 days (range 17-609 days). The most common clinical manifestations were fever (86.2%), cough (34.5%) and dyspnea (31.0%). The 100-day probabilities of ADV-related mortality and OS were 40.4% (95% CI 21.1%-59.7%) and 40.5% (95% CI 25.2%-64.9%), respectively. Patients with low-level ADV DNAemia had lower ADV-related mortality and better OS than did those with high-level (≥ 106 copies/ml in plasma) ADV DNAemia. According to the multivariate analysis, high-level ADV DNAemia was the only risk factor for intensive care unit admission, invasive mechanical ventilation, ADV-related mortality, and OS after ADV pneumonia. CONCLUSIONS: We first reported the prognostic factors and confirmed the poor outcomes of patients with ADV pneumonia after allo-HSCT. Patients with high-level ADV DNAemia should receive immediate and intensive therapy.

Biochemical risk factors and outcomes of acute promyelocytic leukemia patients with thrombotic events: a matched pair analysis.

Acute promyelocytic leukemia (APL) stands out as a distinctive form of acute leukemia, exhibiting a higher occurrence of thrombotic events when contrasted with other leukemia subtypes. Since thrombosis is a relatively rare but unfavorable condition with poor prognostic implications, it is crucial to determine the risk factors for thrombotic events in APL(thrombosis in large venous or arterial from onset to differentiation therapy in 30d). We performed a retrospective study involving 950 APL patients between January 2000 and October 2022, from which 123 were excluded by younger than 16 years of age, 95 were excluded by incomplete data, and 6 were excluded by thrombosis related to CVC or PICC. A total of 23 APL patients with thrombosis for inclusion in our analysis were performed a 1:5 ratio matching based on sex (perfect match) and age (within 5 years) to patients without thrombosis. These patients were continuously monitored in the outpatient department over a period of 5 years. We meticulously examined clinical and laboratory data to pinpoint the risk factors related to thrombotic events in APL. Our primary clinical endpoints were all-cause mortality and achieving complete remission, while secondary clinical outcomes included APL relapse. Thrombotic events were observed in 2.4% (23/950) of APL patients. Compared to patients without thrombosis, patients with thrombosis had higher lactate dehydrogenase (LDH) [313 (223, 486) vs. 233 (188, 367) U/L, p = 0.020], higher indirect bilirubin [11.2 (7.4, 18.6) vs.8.3 (6.0, 10.7) umol/L, p = 0.004], higher creatinine [72 (62, 85) vs. 63 (54, 74) umol/L, p = 0.026], higher CD2 expression (65.2 vs. 15.2%, p < 0.001), higher CD15 expression (60.9 vs. 24.3%, p = 0.001), and PML/RARαisoforms (p < 0.001). Multivariate-logistic-regression analysis revealed several factors that were markedly related to thrombosis, including LDH (OR≈1.003, CIs≈1.000-1.006, p = 0.021), indirect bilirubin (OR≈1.084, CIs≈1.000-1.188, p = 0.043), CD2 expression positive (OR≈16.629, CIs≈4.001-62.832, p < 0.001), and CD15 expression positive (OR≈7.747, CIs≈2.005-29.941, p = 0.003). The S-type (OR≈0.012, CIs≈0.000-0.310, p = 0.008) and L-type (OR≈0.033, CIs≈0.002-0.609, p = 0.022) PML/RARα isoforms were negatively associated with thrombosis. Kaplan-Meier curves indicated that the survival rates were remarkably varied between APL patients with and without thrombosis (HR:21.34, p < 0.001). LDH and indirect bilirubin are variables significantly associated with thrombosis in APL, S-type and L-type PML/RARαisoforms exhibit a negative association with thrombotic events. The thrombotic events of APL can predict the subsequent survival of thrombosis. The findings of our study have the potential to facilitate early detection of thrombosis and enhance the prognosis for individuals with APL who develop thrombosis. Further validation of our findings will be essential through future prospective or multicenter studies.

COVID-19 was associated with the complications after allogeneic hematopoietic stem cell transplantation.

We aimed to identify the severity and duration of COVID-19 infection on complications after allo-HSCT. Enrolled 179 hospitalized patients with COVID-19 were categorized into long-term infection (> 18 days, n = 90) or short-term infection group (≤ 18 days, n = 89) according to the median duration of COVID-19. The severity of COVID-19 was categorized as asymptomatic infection, mild, moderate, severe, and critical illness according to guidelines of National Institutes of Health. Particularly, severe illness and critical illness were classified as serious infection. Asymptomatic infection, mild illness and moderate illness were classified as non-serious infection. The 150-day probabilities of poor graft function (PGF), cytomegalovirus (CMV) pneumonia and non-relapse mortality (NRM) were significantly higher in long-term infection group. The 150-day probabilities of CMV pneumonia and NRM after COVID-19 were higher in serious infection group. The 150-day probabilities of overall survival (OS) was significantly lower in long-term and serious infection group. In multivariable analysis, the severity of COVID-19 was associated with NRM and OS, and the duration of COVID-19 was associated with PGF. In summary, our data reported that the severity and duration of COVID-19 were associated with several complications and contribute to poor outcomes after allo-HSCT.

Mechanochemical Backbone Editing for Controlled Degradation of Vinyl Polymers.

The chemically inert nature of fully saturated hydrocarbon backbones endows vinyl polymers with desirable durability, but it also leads to their significant environmental persistence. Enhancing the sustainability of these materials requires a pivotal yet challenging shift: transforming the inert backbone into one that is degradable. Here, we present a versatile platform for mechanochemically editing the fully saturated backbone of vinyl polymers towards degradable polymer chains by integrating cyclobutene-fused succinimide (CBS) units along backbone through photo-iniferter reversible addition-fragmentation chain-transfer (RAFT) copolymerization. Significantly, the evenly insertion of CBS units does not compromise thermal or chemical stability but rather offers a means to adjust the properties of polymethylacrylate (PMA). Meanwhile, reactive acyclic imide units can be selectively introduced to the backbone through mechanochemical activation (pulse ultrasonication or ball-milling grinding) when required. Subsequent hydrolysis of the acyclic imide groups enables efficient degradation, yielding telechelic oligomers. This approach holds promise for inspiring the design and modification of more environmentally friendly vinyl polymers through backbone editing.

Study on the bioactive ingredients and mechanism of Huangqi against diabetic retinopathy based on network pharmacology and experimental verification.

BACKGROUND: Diabetic retinopathy (DR) is one of the most well-known microvascular complications of diabetes mellitus. As a traditional Chinese medicine, Huangqi (HQ), has been used for treating DR for a long time. However, its anti-DR active ingredients and mechanism are still unknown. Therefore, we designed this study to explore the active components and mechanism of HQ against DR via network pharmacology analysis. METHODS: The ingredients of HQ, potential targets of HQ and DR were obtained from public databases. We employed the protein-protein interaction (PPI) network, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and Gene Ontology (GO) analysis to identify core targets and pathways of HQ against DR. Finally, molecular docking and vitro experiments were applied to validate our results. RESULTS: A total of 34 potential targets of HQ against DR were obtained. Based on PPI network, VEGFA, PTGS2, IL6 and CCL2 were considered as core targets. GO analysis involved 692 biological processes, 21 cellular components and 35 molecular functions. KEGG enrichment analysis manifested that the anti-DR effect of HQ was mainly mediated via the AGE-RAGE signaling pathway in diabetic complications. The molecular docking results indicated that kaempferol had higher affinity with CCL2, IL-6, VEGFA and PTGS2. The vitro experiments showed that the mRNA expressions of CCL2, IL-6, VEGFA and PTGS2 in ARPE-19 cell were differentially decreased after kaempferol treatment. CONCLUSION: This study preliminarily unveiled that the therapeutic efficacy of HQ against DR might be attributed to the reduced expression of CCL2, IL-6, VEGFA and PTGS2.

NEK2 promotes the development of ovarian endometriosis and impairs decidualization by phosphorylating FOXO1.

Ovarian endometriosis is a common gynecological disease, and one of its most significant symptoms is infertility. In patients with endometriosis, defects in endometrial decidualization lead to impaired endometrial receptivity and embryo implantation, thus affecting early pregnancy and women's desire to have children. However, the mechanisms underlying the development of endometriosis and its associated defective decidualization are unclear. We find that NEK2 expression is increased in the ectopic and eutopic endometrium of patients with endometriosis. Meanwhile, NEK2 interacts with FOXO1 and phosphorylates FOXO1 at Ser184, inhibiting the stability of the FOXO1 protein. Importantly, NEK2-mediated phosphorylation of FOXO1 at Ser184 promotes cell proliferation, migration, invasion and impairs decidualization. Furthermore, INH1, an inhibitor of NEK2, inhibits the growth of ectopic lesions in mouse models of endometriosis and promotes endometrial decidualization in mouse models of artificially induced decidualization. Taken together, these findings indicate that NEK2 regulates the development of endometriosis and associated disorders of decidualization through the phosphorylation of FOXO1, providing a new therapeutic target for its treatment.

Circulating neuropeptide Y as a biomarker in postoperative atrial fibrillation cases administered off-pump coronary bypass Graft surgery.

Background and aims: Postoperative atrial fibrillation (POAF) is considered the most prevalent irregular heart rhythm after heart surgery. The cardiac autonomic nervous system significantly affects POAF, and neuropeptide Y (NPY), an abundant neuropeptide in the cardiovascular system, is involved in this autonomic regulation. The current work aimed to examine the potential association of NPY with POAF in individuals administered isolated off-pump coronary artery bypass grafting. Methods: From January 1 to May 31, 2020, we examined consecutive cases administered successful isolated off-pump coronary artery bypass grafting with no previously diagnosed atrial fibrillation (AF). Clinical characteristics and plasma samples were collected before surgery. NPY was quantified by enzyme-linked immunosorbent assay (ELISA) in peripheral blood, and POAF cases were identified through a 7-day Holter monitoring. Results: Among 120 cases with no previously diagnosed AF, 33 (27.5 %) developed POAF during hospitalization. Median NPY levels were markedly elevated in the POAF group in comparison with the sinus rhythm group (31.72 vs. 27.95, P = 0.014). Multivariable logistic regression analysis revealed age (OR = 1.135, 95%CI 1.054-1.223; P = 0.001), left atrial size (OR = 1.136, 95%CI 1.004-1.285; P = 0.043), and NPY levels in peripheral blood (OR = 1.055, 95%CI 1.002-1.111; p = 0.041) independently predicted POAF. Additionally, NPY levels were positively correlated with high-frequency (HF) (r = 0.2774, P = 0.0022) and low-frequency (LF) (r = 0.2095, P = 0.0217) components of heart rate variability. Conclusion: In summary, this study demonstrates an association between elevated NPY levels in peripheral blood before surgery and POAF occurrence.

Plerixafor-based mobilization and mononuclear cell counts in graft increased the risk of engraftment syndrome after autologous hematopoietic stem cell transplantation.

Engraftment syndrome (ES) is one of the most common complications in the early phase after autologous hematopoietic stem cell transplantation (ASCT), and we aimed to evaluate the incidence and risk factors for ES patients receiving ASCT in the era of plerixafor-based mobilization. A total of 294 were enrolled, and 16.0% (n = 47) experienced ES after ASCT. The main clinical manifestations were fever (100%), diarrhea (78.7%), skin rash (23.4%), and hypoxemia/pulmonary edema (12.8%). Plerixafor-based mobilization was associated with higher counts of CD3+ cells, CD4+ cells, and CD8+ cells in grafts. In univariate analysis of the total cohort, age ≥60 years, receiving ASCT at complete remission (CR), higher number of mononuclear cell (MNC), CD3+ cell counts, CD4+ cells as well as CD8+ cells transfused and plerixafor-based mobilization were associated with ES after ASCT. Multivariate analysis showed that age ≥60 years (P = .0014), receiving ASCT at CR (P = .002), and higher number of MNC transfused (P = .026) were associated with ES in total cohort. In plasma cell disease subgroup, age ≥60 years (P = .013), plerixafor-based mobilization (P = .036), and receiving ASCT at CR (P = .002) were associated with ES. Patients with more risk factors had a higher risk of ES. The 1-year probabilities of relapse, non-relapse mortality, and survival were comparable between patients with and without ES. Thus, plerixafor-based mobilization may influence the composition of T lymphocytes in grafts and increase the risk of ES, particularly in patients with plasma cell disease.

Expression and Mutation of SLC45A2 Affects Iris Color in Quail.

Iris color is a prominent phenotypic feature of quail. To understand the mechanism of melanin deposition related to quail iris color, iris tissues were selected from Beijing white and Chinese yellow quail for transcriptome analysis. Differentially expressed genes (DEGs) associated with pigmentation were identified using RNA sequencing and validated by quantitative real-time polymerase chain reaction (RT-qPCR). The identified single nucleotide polymorphisms were studied using bioinformatics and iris color correlation analyses. A total of 485 DEGs were obtained, with 223 upregulated and 262 downregulated. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed. Thirty-two genes were annotated using the GO database. Three important pigment synthesis pathways (Notch signaling, melanogenesis, and tyrosine metabolism) were identified in quail iris tissue (P < 0.05). The expression levels of solute carrier family 45 member 2 (SLC45A2), tyrosinase-related protein 1, vitamin D receptor, opsin 5, and docking protein 5 were significantly different between Beijing white and Chinese yellow quail, as verified by RT-qPCR. The c.1061C>T mutation in SLC45A2, which caused a single amino acid change at position 354 (threonine to methionine), was significantly associated with iris color in Beijing white and Chinese yellow quail, and might be the main reason for the different iris colors between these two quail species.

Activation of PPARδ in bone marrow endothelial progenitor cells improves their hematopoiesis-supporting ability after myelosuppressive injury.

Dysfunctional bone marrow (BM) endothelial progenitor cells (EPCs) with high levels of reactive oxygen species (ROS) are responsible for defective hematopoiesis in poor graft function (PGF) patients with acute leukemia or myelodysplastic neoplasms post-allotransplant. However, the underlying mechanism by which BM EPCs regulate their intracellular ROS levels and the capacity to support hematopoiesis have not been well clarified. Herein, we demonstrated decreased levels of peroxisome proliferator-activated receptor delta (PPARδ), a lipid-activated nuclear receptor, in BM EPCs of PGF patients compared with those with good graft function (GGF). In vitro assays further identified that PPARδ knockdown contributed to reduced and dysfunctional BM EPCs, characterized by the impaired ability to support hematopoiesis, which were restored by PPARδ overexpression. Moreover, GW501516, an agonist of PPARδ, repaired the damaged BM EPCs triggered by 5-fluorouracil (5FU) in vitro and in vivo. Clinically, activation of PPARδ by GW501516 benefited the damaged BM EPCs from PGF patients or acute leukemia patients in complete remission (CR) post-chemotherapy. Mechanistically, we found that increased expression of NADPH oxidases (NOXs), the main ROS-generating enzymes, may lead to elevated ROS level in BM EPCs, and insufficient PPARδ may trigger BM EPC damage via ROS/p53 pathway. Collectively, we found that defective PPARδ contributes to BM EPC dysfunction, whereas activation of PPARδ in BM EPCs improves their hematopoiesis-supporting ability after myelosuppressive therapy, which may provide a potential therapeutic target not only for patients with leukemia but also for those with other cancers.

Coherent beam combining of femtosecond third-harmonic generators: towards high-power, high-beam-quality UV light generation.

Coherent beam combining (CBC) of two femtosecond third-harmonic (TH) generators is proposed and demonstrated. By applying phase modulation to one of the fundamental laser pulses, the feedback loop effectively eliminates both phase and pointing errors between the two TH femtosecond laser beams. The system delivers 345-nm femtosecond laser pulses with 22-W average power at 1-MHz repetition rate. The average combining efficiency is 91.5% over approximately 1 h of testing. The beam quality of the combined ultraviolet (UV) laser beam is near-diffraction-limited with M2 factors of M X2=1.36, M Y2=1.24, which are similar to those of the individual channels. This scheme exhibits promising potential for increasing high-beam-quality UV laser power.