Systems genetics identifies methionine as a high risk factor for Alzheimer's disease.

As a dietary strategy, methionine restriction has been reported to promote longevity and regulate metabolic disorders. However, the role and possible regulatory mechanisms underlying methionine in neurodegenerative diseases such as Alzheimer's disease (AD), remain unexplored. This study utilized the data from BXD recombinant inbred (RI) mice to establish a correlation between the AD phenotype in mice and methionine level. Gene enrichment analysis indicated that the genes associated with the concentration of methionine in the midbrain are involved in the dopaminergic synaptic signaling pathway. Protein interaction network analysis revealed that glycogen synthase kinase 3 beta (GSK-3ß) was a key regulator of the dopaminergic synaptic pathway and its expression level was significantly correlated with the AD phenotype. Finally, in vitro experiments demonstrated that methionine deprivation could reduce the expression of Aß and phosphorylated Tau, suggesting that lowering methionine levels in humans may be a preventive or therapeutic strategy for AD. In conclusion, our findings support that methionine is a high risk factor for AD. These findings predict potential regulatory network, theoretically supporting methionine restriction to prevent AD.

Highly Efficient and Reversible Carbon Dioxide Capture by Carbanion-Functionalized Ionic Liquids.

Due to the active unstable nature of carbon anions, it is challenging to develop carbanion-functionalized ionic liquids (ILs) for efficient and reversible carbon dioxide (CO2) capture. Here, a series of carbanion-based ILs with large conjugated structures were designed and a promising system was achieved through tuning the nucleophilicity of carbanions and screening the cation. The ideal carbanion-functionalized IL trihexyl(tetradecyl)phosphonium N,N-diethycyanoacetoamide ([P66614][DECA]) showed equimolar chemisorption of CO2 (up to 0.98 mol CO2 /mol IL) under ambient pressure and excellent absorption rate. What's more, the combined CO2 can be released easily, leading to excellent reversibility due to high stability of anion conjugated structures. More importantly, the presence of water had negligible effect on the absorption capacity, which makes it potential to be applied to the CO2 capture in industrial flue gas. The chemisorption mechanism of the carbanion and CO2 was confirmed by spectroscopic investigations and DFT calculations, where carboxylic acid product was formed through proton transfer after the carbanions reacted with CO2. Considering that high capacity, quick rate as well as excellent reversibility, these carbanion-functionalized IL should certainly represent competitive candidates for further scale up and practical application in CO2 capture.

Dual-Tuning Azole-Based Ionic Liquids for Reversible CO2 Capture from Ambient Air.

A strategy of tuning azole-based ionic liquids for reversible CO2 capture from ambient air was reported. Through tuning the basicity of anion as well as the type of cation, an ideal azole-based ionic liquid with both high CO2 capacity and excellent stability was synthesized, which exhibited a highest single-component isotherm uptake of 2.17 mmol/g at the atmospheric CO2 concentration of 0.4 mbar at 30 °C, even in the presence of water. The bound CO2 can be released by relatively mild heating of the IL-CO2 at 80 °C, which makes it promising for energy-efficient CO2 desorption and sorbent regeneration, leading to excellent reversibility. To the best of our knowledge, these azole-based ionic liquids are superior to other adsorbent materials for direct air capture due to their dual-tunable properties and high CO2 capture efficiency, offering a new prospect for efficient and reversible direct air capture technologies.

Improved NH3 Uptake of a Macromolecule-Metal Complex Constructed with Dual Polymeric Ligands and M(II).

MOFs are considered as efficient NH3 adsorbents for their high capacity but are accompanied by the collapse of MOFs. In this work, macromolecule-metal complexes (MMCs), which could provide metal sites like MOFs, were developed for reversible NH3 uptake with high capacity with the assistance of the polymeric ligands. Based on the tunable structure of MMCs, the role of the polymeric ligands and metallic center was investigated. Thereinto, MMCs-3 with dual polymeric ligands presented higher NH3 adsorption capacity and reversibility of adsorbents compared with MMCs containing a single polymeric ligand (MMCs-1 and MMCs-2). Combined with the NH3 adsorption test, characterization of FT-IR, UV-vis, EPR spectroscopy, NH3-TPD measurement, and the DFT calculations, it was found that the neutral polymeric ligands PVIm contributed to improve the stability of MMCs-3 under a NH3 atmosphere for the tough networks of PVIm-M(II), while the polymeric ligands with a carboxylate anion together with M(II) enhanced the NH3 capacity for the feasible coordination of a carboxylate anion with M(II). The mechanism of NH3 uptake by PVIm-Co-PVBA was proposed that the NH3 was fixed through the coordination with Co(II) along with the departure of PVBA and the following hydrogen bonding interaction with PVBA, while the coordination between PVIm and Co(II) was not destroyed. Thus, MMCs-3 with dual polymeric ligands presented a higher NH3 uptake capacity and stability. Optimally, PVIm-M-PVBA with the metal center of Co(II), Cu(II), and Ni(II) were obtained with a high capacity of 20.8-23.7 NH3 mmol/g at 25 °C and 1 bar and a high selectivity of NH3 over CO2 (54.9-99.9) and N2 (73.0-187.6) through the breakthrough measurement with a gas mixture of 0.2% NH3, 2% CO2, and 99.6% N2 at 25 °C.

Expression of mitochondrial transcription factor A in granulosa cells: implications for oocyte maturation and in vitro fertilization outcomes.

OBJECTIVE: In vitro fertilization-embryo transfer (IVF-ET) is a widely used treatment for infertility, with oocyte maturation and quality having a significant impact on oocyte fertilization, embryo development, and fetal growth. Mitochondrial transcription factor A (TFAM) is essential for maintaining the mitochondrial oxidative respiratory chain and supplying energy for oocyte development, fertilization, and embryonic development. In this study, we aimed to examine TFAM expression in women undergoing IVF-ET and assess its impact on the IVF outcomes. METHODS: We recruited 85 women who underwent IVF-ET treatment for infertility. On the date of egg collection, granulosa cells were extracted from the clear follicular fluid of the first mature egg using ultrasound-guided needle aspiration. The collected granulosa cells served three purposes: (1) detecting TFAM gene expression in granulosa cells via immunocytochemistry, (2) determining TFAM mRNA expression using reverse transcription-PCR (RT-PCR), and (3) measuring TFAM protein expression through western blotting. RESULT: Based on the results, we found that TFAM was localized and expressed in the cytoplasm of granulosa cells, whereas no expression was detected in the nucleus. Granulosa cells exhibited a linear correlation between TFAM mRNA and TFAM protein expression. The study participants were divided into three groups using the ternary method based on relative TFAM mRNA expression thresholds of 33% and 76%: the low-expression group (n = 30), the moderate-expression group (n = 27), and the high-expression group (n = 28). When compared to the other two groups, the moderate expression group exhibited a significantly higher egg utilization rate, 2 pronucleus rate, fertilization rate, and clinical pregnancy rate (P < 0.05). CONCLUSION: TFAM was detected in the cytoplasm of human ovarian granulosa cells. Women with moderate TFAM expression demonstrate enhanced outcomes in IVF.

Porous acid-base hybrid polymers for enhanced NH3 uptake with assistance from cooperative hydrogen bonds.

Carboxylic acid-modified materials are a common means of achieving efficient NH3 adsorption. In this study, we report that improved NH3 adsorption capacity and easier desorption can be achieved through the introduction of substances containing Lewis basic groups into carboxylic acid-modified materials. Easily synthesized mesoporous acid-base hybrid polymers were constructed with polymers rich in carboxylic acid and Lewis base moieties through cooperative hydrogen bonding interactions (CHBs). The hybrid polymer PAA-P4VP presented higher NH3 capacity (18.2 mmol g-1 at 298 K and 1 bar NH3 pressure) than PAA (6.0 mmol g-1) through the acid-base reaction and the assistance from CHBs with NH3, while the NH3 desorption from PAA-P4VP was easier for the reformation of CHBs. Based on the introduction of CHBs, a series of mesoporous acid-base hybrid polymers was synthesized with NH3 adsorption capacity of 15.8-19.3 mmol g-1 and high selectivity of NH3 over CO2 (SNH3/CO2 = 25.4-56.3) and N2 (SNH3/N2 = 254-1068), and the possible co-existing gases, such as SO2, had a lower effect on NH3 uptake by hybrid polymers. Overall, the hybrid polymers present efficient NH3 adsorption owing to the abundant acidic moieties and CHBs, while the concomitant Lewis bases promote NH3 desorption.

Efficacy of progestin-primed ovarian stimulation (PPOS) versus minimal stimulation in women of advanced maternal age with poor ovarian response under the Patient-Oriented Strategies Encompassing Individualized Oocyte Number (POSEIDON) criteria.

BACKGROUND: We investigated the efficacy of progestin-primed ovarian stimulation (PPOS) and minimal stimulation using clomiphene citrate (CC) + gonadotropin (Gn) for in-vitro fertilization-embryo transfer (IVF-ET) in advanced maternal age (AMA) women with poor ovarian response (POR) according to the Patient-Oriented Strategies Encompassing Individualized Oocyte Number (POSEIDON) criteria. METHODS: A retrospective analysis was performed using the data of AMA patients who had received IVF-ET due to a low ovarian reserve. The enrolled patients were screened according to the POSEIDON group 4 criteria. 102 patients were included in the study, including 52 in the PPOS group and 50 in the minimal stimulation group (who received CC + Gn). The duration of Gn administration, Gn dose, estradiol (E2), and luteinizing hormone (LH) levels on the day of trigger, the cancellation rate of the oocyte retrieval cycle, the number of oocytes retrieved, the number of metaphase II (MII) oocytes, and IVF laboratory outcomes during ovarian stimulation were compared between the 2 groups. RESULTS: No significant differences were found in terms of age, infertility, body mass index (BMI), and basal follicle-stimulating hormone, LH, E2, AFC, and AMH between the 2 groups (all P>0.05). The duration of ovarian stimulation [(9.43±2.44) vs. (7.48±3.09) days, P<0.05] was significantly longer and the total Gn dose [(2,423.22±738.66) vs. (1,579.68±728.86) IU, P<0.05] were significantly higher in the PPOS group than the minimal stimulation group. The LH value on the day of trigger in the PPOS group (3.28 mIU/mL) was significantly lower than that in the minimal stimulation group (5.57 mIU/mL) (P<0.05). The number of oocytes retrieved, normal fertilization rate, number of good-quality embryos on day 3, number of transferable embryos, and number of frozen blastocysts did not differ significantly between the 2 groups (all P>0.05). The proportion of MII oocytes was significantly higher in the PPOS group than the minimal stimulation group (94.05% vs. 81.40%, P<0.05). CONCLUSIONS: For patients in the POSEIDON group 4, PPOS effectively blocked the premature LH surge and increased the proportion of mature oocytes. Thus, it is a feasible ovulation stimulation protocol for AMA women with POR.

Heterogeneous Catalysis of Ozone Using Iron-Manganese Silicate for Degradation of Acrylic Acid.

Iron-manganese silicate (IMS) was synthesized by chemical coprecipitation and used as a catalyst for ozonating acrylic acid (AA) in semicontinuous flow mode. The Fe-O-Mn bond, Fe-Si, and Mn-Si binary oxide were formed in IMS on the basis of the results of XRD, FTIR, and XPS analysis. The removal efficiency of AA was highest in the IMS catalytic ozonation processes (98.9% in 15 min) compared with ozonation alone (62.7%), iron silicate (IS) catalytic ozonation (95.6%), and manganese silicate catalytic ozonation (94.8%). Meanwhile, the removal efficiencies of total organic carbon (TOC) were also improved in the IMS catalytic ozonation processes. The IMS showed high stability and ozone utilization. Additionally, H2O2 was formed in the process of IMS catalytic ozonation. Electron paramagnetic resonance (EPR) analysis and radical scavenger experiments confirmed that hydroxyl radicals (•OH) were the dominant oxidants. Cl-, HCO3-, PO43-, Ca2+, and Mg2+ in aqueous solution could adversely affect AA degradation. In the IMS catalytic ozonation of AA, the surface hydroxyl groups and Lewis acid sites played an important role.

Growth hormone improved oxidative stress in follicle fluid by influencing Nrf2/Keap1 expression in women of advanced age undergoing IVF.

OBJECTIVES: To investigate whether growth hormone (GH) can improve oxidative stress (OS) by affecting) /nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) in women of advanced age undergoing in vitro fertilization (IVF). METHODS: This retrospective study enrolled 141 patients, including 65 aged C patients (patients not treated with GH) and 76 aged GH patients (patients treated with GH). The outcomes included IVF-ET results, OS markers in follicle fluid (FF) and Nrf2 and Keap1 mRNA and protein expressions in granulosa cells (GCs). RESULTS: The results showed that GH improved the available blastocyst (p=.047) and implantation rate (p=.043) in women of advanced age undergoing IVF. The malondialdehyde (MDA) content of FF was significantly higher in the aged-C group than in the aged-GH group (p=.013). The antioxidant enzyme activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-px) and catalase (CAT) were significantly lower in the aged-C group than in the aged-GH group (p= .000, p= .049, p= .012 respectively). Nrf2 mRNA and protein expression was significantly higher and Keap1 mRNA and protein expression was lower in the aged-GH group than in the aged-C group (p= .000, p= .000 respectively). CONCLUSIONS: The study showed that GH improved embryo quality and implantation rate and alleviated OS in FF, which may be related to Nrf2/Keap1.

Clinical effect of Chinese herbal medicine for removing blood stasis combined with acupuncture on sequelae of cerebral infarction.

OBJECTIVE: To assess the clinical efficacy of Chinese herbal medicine for removing blood stasis combined with acupuncture in the treatment of sequelae of cerebral infarction. METHODS: Ninety patients with cerebral infarction admitted to our hospital from April 2018 to April 2020 were enrolled and equally allocated to an experimental group and a control group. The control group was treated with aspirin, and the experimental group was treated with Chinese herbal medicine for removing blood stasis combined with acupuncture. The recovery of the ability of daily living (ADL), recovery of hemiplegic limb function, blood viscosity, total cholesterol (TC), triglyceride (TG), and quality of life were evaluated. RESULTS: After treatment, the ADL of patients in the two groups witnessed a remarkable recovery, with superior results in the experimental group than the control group (P < 0.05). The hemiplegic limb recovery of the experimental group was observed to be significantly improved when compared with the control group (P < 0.05). Remarkably lower blood viscosity-related indexes of TC and TG of the experimental group compared to the control group were identified (P < 0.05). As to the total remission rate (TRR), the experimental group demonstrated a higher level than the control group (P < 0.05). The scores of quality of life of patients in the experimental group after treatment were evidently higher than those of the control group (P < 0.05). CONCLUSION: Chinese herbal medicine for removing blood stasis combined with acupuncture treatment can better improve the hemiplegic limb function and the quality of life, and reduce blood viscosity of patients with sequelae of cerebral infarction.

Clinical nephrotoxicity induced by cyclosporin A combined with hormone therapy for nephrotic syndrome.

This study aims to explore the nephrotoxicity due to use of combination of cyclosporine A and hormone in the treatment of nephrotic syndrome. From January 2018 to November 2019, 100 patients with primary nephrotic syndrome were divided into experimental and control groups, with 50 patients per group. The experimental group took oral cyclosporine A and prednisone tablets, while the control group received oral cyclosporine A combined with shock therapy. The contents of white blood cells, triglycerides, urine protein and cholesterol in the experimental group were lower than those in the control group, while their albumin content was significantly higher than the control values. Blood concentrations of cyclosporine A were significantly lower in non-nephrotoxic patients than in nephrotoxic patients. The high blood cyclosporine A level in patients (>200ng/mL) may be a factor for inducement of nephrotoxicity. Basal serum creatinine levels in nephrotoxic patients were significantly higher than those in non-nephrotoxic patients. Therefore, high basal creatinine level may be a contributing factor to nephrotoxicity. The combination of cyclosporine A and hormone is effective in the treatment of nephrotic syndrome. Blood cyclosporine A levels greater than 200ng/ml or elevated basal serum creatinine may be the cause of nephrotoxicity.

Effects of a combination of erythromycin sequential therapy and azithromycin on lung function and inflammatory factors in children with severe mycoplasma pneumonia.

This study aimed to investigate the effect of erythromycin sequential therapy plus azithromycin on lung function and inflammatory factors in children with severe mycoplasma pneumonia (MP). Ninety-three severe MP children were selected and randomized into azithromycin group, erythromycin group, and combination group, 31 cases in each. The disappearance time of cough, fever, lung rale and X-ray shadow in the combination group were shorter than those in the azithromycin group and erythromycin group. The clinical treatment efficiency of the combination group was higher than that of the azithromycin group. After treatment, FVC, FEV1/FVC and PEF in combination group were higher than before treatment; IL-8, IL-6, CRP in combination group were lower than erythromycin group and azithromycin group. IL-8, IL-6, CRP are negatively correlated with disappearance time of cough, fever, pulmonary rale, X-ray shadow and clinical treatment efficiency; FEV1/FVC is positively correlated with disappearance time of cough and fever, pulmonary rales and X-ray shadow, and clinical treatment efficiency. Sequential erythromycin therapy combined with azithromycin in the treatment of MP can effectively inhibit high inflammatory reactions, control the disease in a timely manner, improve lung function and produce fewer adverse reactions.

Dietary Montmorillonite Improves the Intestinal Mucosal Barrier and Optimizes the Intestinal Microbial Community of Weaned Piglets.

The study investigated the impact of dietary montmorillonite on the growth performance, intestinal mucosal barrier, and microbial community in weaned piglets with control group (CON) and dietary supplementation of 0.2% montmorillonite (0.2% M). Compared with the CON group, 0.2% M feed in the diet increased the average daily gain (ADG) on days 15-35 and day 1-35 and the average daily feed intake on days 1-35 (ADFI) (0.05 < P < 0.1). Besides, higher villus height of the duodenum and jejunum and lower crypt depth of duodenum and colon were revealed in the 0.2% M group than in the CON group (P < 0.05). Moreover, the V/C (ratio of the villus height and crypt depth) in the 0.2% M group was increased compared to that in the CON group both from the duodenum and ileum (P < 0.05). The relative mRNA expression of mucin-1, ITGB1 (ß1-integrins), and PKC (protein kinase C) of ileum in the 0.2% M group were upregulated (P < 0.05) compared to that in the CON group. The digesta sample of ileum from piglets in the 0.2% M group contained greater (P < 0.05) intestinal bacterial diversity and abundances of probiotics, such as Streptococcus, Eubacterium_rectale_group, and Lactobacillus, which could promote the synthesis of carbon-containing biomolecules. Overall, dietary supplementation of 0.2% M was shown to have a tendency to improve the growth performance of weaned piglets and may enhance their intestinal mucosal barrier function via altering the gut microbiota.

Design and tuning of ionic liquid-based HNO donor through intramolecular hydrogen bond for efficient inhibition of tumor growth.

Developing ionic liquid (IL) drugs broaden new horizons in pharmaceuticals. The tunable nature endows ILs with capacity to delivery active ingredients. However, the tunability is limited to screen ionic components, and none realizes the kinetic tuning of drug release, which is a key challenge in the design of IL drugs. Here, a series of ILs are developed using biocompatible ionic components, which realizes absorption of gaseous NO to yield IL-NONOates. These IL-NONOates serve as HNO donors to release active ingredient. The release kinetics can be tuned through configuring the geometric construction of ILs (release half-lives, 4.2 to 1061 min). Mechanism research indicates that the tunability depends on the strength of intramolecular hydrogen bond. Furthermore, the IL-based HNO donors exert pharmacological potential to inhibit tumor progression by regulating intratumoral redox state. Coupled with biosafety, these IL-based HNO donors with facile preparation and tunable functionalization can be promising candidates for pharmaceutical application.

Epidemiological study of Trichosporon asahii infections over the past 23 years.

Trichosporon is a yeast-like basidiomycete, a conditional pathogenic fungus that is rare in the clinic but often causes fatal infections in immunocompromised individuals. Trichosporon asahii is the most common pathogenic fungus in this genus and the occurrence of infections has dramatically increased in recent years. Here, we report a systematic literature review detailing 140 cases of T. asahii infection reported during the past 23 years. Statistical analysis shows that T. asahii infections were most frequently reported within immunodeficient or immunocompromised patients commonly with blood diseases. Antibiotic use, invasive medical equipment and chemotherapy were the leading risk factors for acquiring infection. In vitro susceptibility, clinical information and prognosis analysis showed that voriconazole is the primary drug of choice in the treatment of T. asahii infection. Combination treatment with voriconazole and amphotericin B did not show superiority over either drug alone. Finally, we found that the types of infections prevalent in China are significantly different from those in other countries. These results provide detailed information and relevant clinical treatment strategies for the diagnosis and treatment of T. asahii infection.

Bipyridinium-Based Ionic Covalent Triazine Frameworks for CO2, SO2, and NO Capture.

The exploitation of novel porous materials for capturing/adsorption of harmful gases is considered a very promising approach to deal with air pollution. Herein, bipyridinium-based ionic covalent triazine frameworks (ICTFs) were synthesized via ZnCl2-catalyzed ionothermal polymerization. The as-prepared ICTFs had a satisfactory total pore volume and specific surface of approximately 0.4582 cm3 g-1 and 1000 m2 g-1, respectively. Moreover, the specific surface area, pore size and distribution, and total pore volumes of ICTFs could be adjusted via ion-exchange of the anion. The obtained ICTFs were explored as the adsorbent for the separation/adsorption of the mixed gases (SO2, CO2, NO, and N2), and they showed the strong adsorption ability for CO2 (2.75 mmol g-1), SO2 (9.22 mmol g-1), and NO (4.05 mmol g-1) at 1 bar and 298 K. This unique design provides a new insight to prepare high-efficiency porous materials for CO2, SO2, and NO capture.

Genomic and transcriptome identification of fluconazole-resistant genes for Trichosporon asahii.

Trichosporon asahii infection is difficult to control clinically. This study identified a case with over 15 years of T. asahii infection-related systemic dissemination disease and conducted genome and transcriptome sequencing to identify fluconazole-resistant genes in fluconazole-resistant versus susceptible strains isolated from this patient's facial skin lesions. The data revealed mutations of the ergosterol biosynthetic pathway-related genes in the T. asahii genome of the fluconazole-resistant strain, that is, there were 36 novel mutations of the ERG11 gene, three point mutations (V458L, D457V, and D334S) in the ERG3, and a missense mutation (E349D) in ERG5 in the fluconazole-resistant strain of the T. asahii genome. To ensure that ERG11 is responsible for the fluconazole resistance, we thus simultaneously cultured the strains in vitro and cloned the ERG11 CDS sequences of both fluconazole-susceptible and -resistant strains into the Saccharomyces cerevisiae. These experiments confirmed that these mutations of ERG11 gene affected fluconazole resistance (> 64 µg/ml vs. <8 µg/ml of the MIC value between fluconazole-resistant and -susceptible strains) in Saccharomyces cerevisiae. In addition, expression of ergosterol biosynthesis pathway genes and drug transporter was upregulated in the fluconazole-resistant strain of T. asahii. Collectively, the fluconazole resistance in this female patient was associated with mutations of ERG11, ERG3, and ERG5 and the differential expression of drug transporter and fatty acid metabolic genes.

A succinct strategy for construction of nanoporous ionic organic networks from a pyrylium intermediate.

Hydroxyl group and pyridinium salt-bifunctionalized nanoporous ionic organic networks prepared via a simple two-step strategy under metal- and template-free conditions are presented. The structural features of the resultant polymer (e.g. high surface area, abundant hydroxyl groups and ionic functionalities) made it a promising candidate as an efficient scavenger of toxic oxo-anions from water.

Tuning the Capture of CO2 through Entropic Effect Induced by Reversible Trans-Cis Isomerization of Light-Responsive Ionic Liquids.

Despite a great deal of gas capture strategies based on ionic liquids, reversible tuning of gas absorption by pure ionic liquids using light irradiation has never been reported. Herein, we demonstrate a novel strategy for tuning the capture of CO2 by light-responsive ionic liquids through reversible trans-cis isomerization. These light-responsive ionic liquids were constructed by tailoring the azobenzene group to the cationic moiety, which exhibited different CO2 absorption ability before and after ultraviolet (UV) irradiation. Through a combination of absorption experiments, NMR spectroscopy, differential scanning calorimetry analysis, viscosity measurement, and quantum chemical calculations, the results indicated that the significant difference in CO2 absorption capacity originated from the entropic effect, which was induced by the change in the aggregation state during trans-cis isomerization. This reversible isomerization of ionic liquids upon alternating irradiation of UV light and blue light shows the potential to control the capture and release of CO2 in an energy-saving way.

Integrated transcriptomic analysis of Trichosporon Asahii uncovers the core genes and pathways of fluconazole resistance.

Trichosporon asahii (T. asahii) has emerged as a dangerous pathogen that causes rare but life-threatening infections. Its resistance to certain antifungal agents makes it difficult to treat, especially for patients undergoing long-term antibiotic therapy. In this study, we performed a series of fluconazole (FLC) perturbation experiments for two T. asahii strains, a clinical isolate stain CBS 2479 (T2) and an environmental isolate strain CBS 8904 (T8), to uncover potential genes and pathways involved in FLC resistance. We achieved 10 transcriptomes of T2 and T8 that were based on dose and time series of FLC perturbations. Systematic comparisons of the transcriptomes revealed 32 T2 genes and 25 T8 genes that are highly sensitive to different FLC perturbations. In both T2 and T8 strains with the phenotype of FLC resistance, the processes of oxidation-reduction and transmembrane transport were detected to be significantly changed. The antifungal susceptibility testing of FLC and penicillin revealed their resistance pathways are merged. Accumulated mutations were found in 564 T2 and 225 T8 genes, including four highly mutated genes that are functionally related to the target of rapamycin complex (TOR). Our study provides abundant data towards genome-wide understanding of the molecular basis of FLC resistance in T. asahii.