ROS-responsive curcumin-encapsulated nanoparticles for AKI therapy via promoting lipid degradation in renal tubules.

Lipid accumulation is a factor contributing to the pathogenesis of acute kidney injury (AKI), yet there are currently no approved pharmacotherapies aside from adjuvant therapy. A developed reactive oxygen species (ROS)-responsive drug delivery system (NPSBG@Cur) was developed to deliver the autophagy activator curcumin (Cur) in order to alleviate AKI by activating autophagy and promoting lipid droplet degradation. The nanoparticles were shown to be ROS-responsive in the H2O2 medium and demonstrate ROS-responsive uptake in palmitate (PA)-induced oxidative stress-damaged cells. NPSBG@Cur was found to effectively inhibit lipid accumulation by autophagosome transport in kidney tubular cells. Additionally, in a mouse AKI model, NPSBG@Cur was observed to significantly ameliorate renal damage by activating autophagy flux and improving lipid transport. These results suggest that the ROS-responsive drug delivery system augmented the therapeutic effect of Cur on AKI by improving lipid metabolism through autophagy activation. Therefore, targeting lipid metabolism with NPSBG@Cur may be a promising AKI treatment strategy.

The mechanism and experimental verification of Ixeris sonchifolia promoting apoptosis of hepatocellular carcinoma based on network pharmacology: Ixeris sonchifolia Induces Hepatocellular Carcinoma Apoptosis via the PI3K/AKT Pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Ixeris sonchifolia alias Kudiezi, it was named Ixeris sonchifolia (Bunge) Hance, a synonym for Crepidiastrum sonchifolium (Bunge) Pak & Kawano in the https://www.iplant.cn/. And it was first published in J. Linn. Soc., Bot. 13: 108 (1873), which was named Ixeris sonchifolia (Maxim.) Hance in the MPNS (http://mpns.kew.org). As a widely distributed medicinal and edible wild plant, it possesses unique bitter-cold characteristics and constituents with various pharmacological activities. Its main antitumor substances, same as artemisinin and paclitaxel, are classified as terpenoids and have become research foci in recent years. However, its specific biological activity and role in antitumor treatment remain largely unclear. AIM OF THE STUDY: This study aimed to elucidate the molecular targets and potential mechanisms of hepatocellular carcinoma apoptosis induced by Ixeris sonchifolia. MATERIALS AND METHODS: We used network pharmacology methods to analyze and screen the active ingredients and possible underlying mechanisms of Ixeris sonchifolia in treating liver cancer and employed integrative time- and dose-dependent toxicity, transcriptomics, and molecular biology approaches to comprehensively verify the function of Ixeris sonchifolia extract (IsE) in human hepatoblastoma cell (HepG2) apoptosis and its potential mechanism. RESULTS: A total of 169 common targets were screened by network pharmacology, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that IsE inhibited HepG2 cell activity in a time- and dose-dependent manner. Western blot analysis confirmed that IsE promoted HepG2 cell apoptosis by inhibiting the PI3K/AKT signaling pathway and that the PI3K/AKT inhibitor LY294002 also substantially enhanced IsE-induced apoptosis. The PI3K/AKT signaling pathway exhibited significant differences compared to that in the control group. CONCLUSION: Combining network pharmacology with experimental verification, IsE inhibited mitochondrial function and the PI3K/AKT pathway while inducing hepatoma cell apoptosis. IsE may have promising potential for liver cancer treatment and chemoprevention.

Evaluation of the effect of a novel substrate that is composed of landfill-mined-soil-like-fractions on plant growth and heavy metal accumulation.

In the pursuit of a safe, low-cost, and sustainable method for the reuse of landfill-mined-soil-like-fractions (LFMSFs), pot experiments were conducted using seven growth substrates consisting of LFMSFs, tea residue, and peat for the cultivation of Photinia × fraseri. Six of the substrates had 40 %:60 %, 60 %:40 %, and 80 %:20 % volume ratios of LFMSFs to tea residue or peat, and one substrate consisted entirely of LFMSFs. The physicochemical properties of the substrate, growth parameters of the plants, and heavy metal content in the different pots were determined after one year of growth. The results indicated that the physicochemical properties of the substrate, that was composed of a mixture of LFMSFs and tea residue showed a significant improvement in organic matter, nitrogen, phosphorus, and potassium. However, there was also an increase in the salt and heavy metal contents when compared with those of peat. The plant growth in the LFMSF and tea residue substrate was slightly lower than that in the LFMSF and peat mixture. Notably, the best plant growth and environmentally friendly effects were observed when LFMSFs were added at 40 %. Additionally, most of the heavy metals were primarily removed from the substrate through the leaves of the seedlings, with the heavy metal contents being relatively low. In conclusion, LFMSFs as a cultivation substrate, represent a practical approach for reutilization, which could contribute to the reduction of reliance on traditional resources.

Fine-Scale Characterization of Plant Diterpene Glycosides Using Energy-Resolved Untargeted LC-MS/MS Metabolomics Analysis.

Plant diterpene glycosides are essential for diverse physiological processes. Comprehensive structural characterization proved to be a challenge due to variations in glycosylation patterns, diverse aglycone structures, and the absence of comprehensive reference databases. In this study, a method for fine-scale characterization was proposed based on energy-resolved (ER) untargeted LC-MS/MS metabolomics analysis using steviol glycosides as a demonstration. Energy-dependent fragmentation patterns were unveiled by a series of model compounds. Distinct glycosylation sites were discerned by leveraging varying fragmentation energies for the precursor ions. The sugar moiety linkage at C19OOH (R1) exhibited facile and intact cleavage at low collision energies, while the sugar moiety at C13-OH (R2) demonstrated consecutive cleavage with increasing energy. Aglycone ions exhibited a higher relative intensity at NCE 50, with relative intensities ranging from 95% to 100%. Subsequently, aglycone candidates, R1 sugar composition, and R2 sugar sequence were deduced through ER-MS/MS analysis. The developed method was applied to Stevia rebaudiana leaves. A total of 91 diterpene glycosides were unambiguously identified, including 16 steviol glycosides with novel acetylglycosylation patterns. This method offers a rapid alternative for glycan analysis and the structural differentiation of isomers. The developed method enhances the understanding of diterpene glycosides in plants, providing a reliable tool for the in-depth characterization of complex metabolite profiles.

Extraction, rapid preparation and neuroprotective effect of texasin, a main active constituent from Caragana jubata (Pall.) Poir.

Searching for new anti-ischemic stroke (anti-IS) drugs has always been a hot topic in the pharmaceutical industry. Natural products are an important source of discovering anti-IS drugs. The aim of the present study is to extract, rapidly prepare and explore the neuroprotective effect of texasin, a main active constituent from Caragana jubata (Pall.) Poir., which is a kind of Tibetan medicine with a clear anti-IS effect. The results showed that 95% ethanol was the optimal extraction solvent. A three-step rapid preparation method for texasin was successfully established, with a purity of 99.2%. Texasin at the concentration of 25-100 µM had no effect on the viability of normal cultured PC12 cells; 12.5 and 25 µM texasin could enhance the viability of PC12 cells damaged by oxygen and glucose deprivation/reoxygenation (OGD/R), and their effects are comparable to the positive drug edaravone at the concentration of 50 µM. Compared with the normal group, the expression of Bcl-2 protein in OGD/R-injured PC12 cells was downregulated (p < 0.01), and that of PERK, eIF2α, ATF4, CHOP, Bax and Cleaved caspase-3 proteins were upregulated (p < 0.01, p < 0.001). Compared with the OGD/R group, 25 µM texasin could upregulate the expression of Bcl-2 protein (p < 0.01), and downregulate that of PERK, eIF2α, ATF4, CHOP, Bax and Cleaved caspase-3 proteins (p < 0.01, p < 0.001). The 7-OH and 1-O of texasin formed H-bonds with residues Cys891 of the hinge ß-strand of PERK, which is crucial for kinase inhibitors. The above results suggest that the method established in the present study achieved rapid preparation of high-purity texasin. Texasin might inhibit neuronal apoptosis via the regulation of endoplasmic reticulum stress PERK/eIF2α/ATF4/CHOP signalling pathway to exert a protective effect on OGD/R-injured PC12 cells. Aiding by molecular docking, texasin was assumed to be a potential PERK inhibitor.

The protective effects of icariin against testicular dysfunction in type 1 diabetic mice Via AMPK-mediated Nrf2 activation and NF-κB p65 inhibition.

BACKGROUND: Owing to the early suffering age and the rising incidence of type 1 diabetes (T1D), the resulting male reproductive dysfunction and fertility decline have become a disturbing reality worldwide, with no effective strategy being available. Icariin (ICA), a flavonoid extracted from Herba Epimedium, has been proved its promising application in improving diabetes-related complications including diabetic nephropathy, endothelial dysfunction and erectile dysfunction. Ensuring the future reproductive health of children and adolescents with T1D is crucial to improve global fertility. However, its roles in the treatment of T1D-induced testicular dysfunction and the potential mechanisms remain elusive. PURPOSE: The purpose of this present study was to investigate whether ICA ameliorates T1D-induced testicular dysfunction as well as its potential mechanisms. METHODS: T1D murine model was established by intraperitoneal injection of STZ with or without treated with ICA for eleven weeks. Morphological, pathological and serological experiments were used to determine the efficacy of ICA on male reproductive function of T1D mice. Western blotting, Immunohistochemistry analysis, qRT-PCR and kit determination were performed to investigated the underlying mechanisms. RESULTS: We found that replenishment of ICA alleviated testicular damage, promoted testosterone production and spermatogenesis, ameliorated apoptosis and blood testis barrier impairment in streptozotocin-induced T1D mice. Functionally, ICA treatment triggered adenosine monophosphate protein kinase (AMPK) activation, which in turn inhibited the nuclear translocation of nuclear factor kappa B p65 (NF-κB p65) to reduce inflammatory responses in the testis and activated nuclear factor erythroid 2-related factor 2(Nrf2), thereby enhancing testicular antioxidant capacity. Further studies revealed that supplementation with the AMPK antagonist Compound C or depletion of Nrf2 weakened the beneficial effects of ICA on testicular dysfunction of T1D mice. CONCLUSION: Collectively, these results demonstrate the feasibility of ICA in the treatment of T1D-induced testicular dysfunction, and reveal the important role of AMPK-mediated Nrf2 activation and NF-κB p65 inhibition in ICA-associated testicular protection during T1D.

Angucyclinones with IDO and TDO inhibitory activities isolated from the actinomycetes Umezawaea beigongshangensis.

Four previously undescribed angucyclinones umezawaones A-D (1-4) were isolated from the liquid cultures of Umezawaea beigongshangensis. Their structures were determined by spectroscopic analyses, single crystal X-ray diffraction, quantum chemical 13C NMR and electronic circular dichroism calculations. All compounds displayed strong inhibitory activities against indoleamine 2,3-dioxygenase and tryptophan-2,3-dioxygenase in enzymatic assay, especially compound 2.

[Optimization of extraction process for classic prescription Yihuang Decoction based on Box-Behnken design-response surface methodology, standard relation, and analytic hierarchy process combined with entropy weight method].

Based on the concept of quality by design(QbD), the Box-Behnken design-response surface methodology combined with standard relation(SR) and analytic hierarchy process(AHP)-entropy weight method(EWM) was applied to optimize the extraction process of the classic prescription Yihuang Decoction. The content of geniposidic acid, phellodendrine hydrochloride, and berberine hydrochloride in Yihuang Decoction, the extract yield, and fingerprint similarity were used as the critical quality attributes(CQAs) of the extraction process. The extraction time, water addition, and extraction times were used as the critical process parameters(CPPs). After determining the levels of each factor and level through single-factor experiments, response surface experiments were designed according to the Box-Behnken principle, and the experimental results were analyzed. The SR between each sample and the reference sample under various evaluation indicators of different extraction parameters was calculated. The weights of the five evaluation indicators were determined using AHP-EWM, followed by comprehensive evaluation. A function model between CPPs and CQAs characterized by comprehensive scores was established to predict the optimal extraction process parameters. In the final comprehensive weight coefficients, the yield rate accounted for 43.1%, and the content of berberine hydrochloride, phellodendrine hydrochloride, and geniposidic acid accounted for 35.1%, 6.3%, and 15.5%, respectively. After comprehensive score analysis with SR, the established second-order polynomial model was statistically significant(P<0.01, and the lack of fit was not significant). The predicted optimal extraction conditions for Yihuang Decoction were determined as follows: 8-fold volume of water, extraction time of 1.5 h, and extraction once. The mean comprehensive score of the validation experiment was 85.77, with an RSD of 0.99%, and it met the quality control stan-dards for the reference sample of Yihuang Decoction. The results indicate that the optimized extraction process for Yihuang Decoction is stable and reliable, and the water extract is close in quality attributes to the reference sample. This can serve as a foundation for the research and development of granules in the future. Box-Behnken design-response surface methodology combined with SR and AHP-EWM can provide references for the modern extraction process research of other classic prescriptions.

[Electroacupuncture at acupoints of yangming meridians for sarcopenia: a randomized controlled trial].

OBJECTIVE: To observe the clinical effect of electroacupuncture at acupoints of yangming meridians for sarcopenia. METHODS: A total of 60 patients with sarcopenia were randomized into an observation group and a control group, 30 cases in each group. In the control group, conventional nutrition intervention for sarcopenia was adopted. In the observation group, on the basis of the treatment in the control group, acupuncture was applied at bilateral Binao (LI 14), Quchi (LI 11), Zusanli (ST 36), Yanglingquan (GB 34), etc.,ipsilateral Quchi (LI 11) and Zusanli (ST 36) were connected to electroacupuncture, with discontinuous wave, 2 Hz in frequency, 1-10 mA in intensity, 2 times a week, with a interval of 3 days. A total of 12-week treatment was required in the two groups. Before and after treatment, the appendicular skeletal muscle mass index (ASMI), grip strength, 6 m-walking time, body fat percentage and body moisture percentage were observed in the two groups. RESULTS: Compared with those before treatment, after treatment, ASMI and grip strength were increased while 6 m-walking time was shortened in the two groups (P<0.05); body fat percentage was decreased while body moisture percentage was increased in the observation group (P<0.05). After treatment, in the observation group, ASMI, grip strength and body moisture percentage were increased (P<0.05), 6 m-walking time was shortened and body fat percentage was decreased (P<0.05) compared with those in the control group. CONCLUSION: Electroacupuncture at acupoints of yangming meridians can effectively improve the skeletal muscle mass, muscle function, body fat percentage and body moisture percentage in patients with sarcopenia, and make the distribution of muscle and fat more reasonable.

Efficacy and safety of selenium or vitamin E administration alone or in combination in ICU patients: A systematic review and meta-analysis.

BACKGROUND: Micronutrient administration that contributes to antioxidant defense has been extensively studied in critically ill patients, but consensus remains elusive. Selenium and vitamin E are two important micronutrients that have synergistic antioxidant effects. This meta-analysis aimed to assess the effect of selenium or vitamin E administration alone and the combination of both on clinical outcomes in patients hospitalized in the ICU. METHODS: After electronic searches on PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), SinoMed, VIP database and Wanfang data, initially 1767 papers were found, and 30 interventional studies were included in this analysis. We assessed the risk-difference between treatment and control (standard treatment) groups by pooling available data on length of stay (ICU length of stay and hospital length of stay), mortality (ICU mortality, hospital mortality, 28-day mortality, 6-month mortality and all-cause mortality), duration of mechanical ventilation, adverse events and new infections. RESULTS: By analyzing the included studies, we found no significant effect of selenium administration alone on mortality, mechanical ventilation duration, or adverse events in ICU patients. However, after excluding studies with high heterogeneity, the meta-analysis showed that selenium alone reduced the length of hospital stay (MD: -1.38; 95% CI: -2.52, -0.23; I-square: 0%). Vitamin E administration alone had no significant effect on mortality, duration of mechanical ventilation, or adverse events in ICU patients. However, after excluding studies with high heterogeneity, the meta-analysis showed that vitamin E alone could reduce the length of ICU stay (MD: -1.27; 95% CI: -1.86, -0.67; I-square: 16%). Combined administration of selenium and vitamin E had no significant effect on primary outcomes in ICU patients. CONCLUSIONS: Selenium administration alone may shorten the length of hospital stay, while vitamin E alone may reduce the length of ICU stay. The putative synergistic beneficial effect of combined administration of selenium and vitamin E in ICU patients has not been observed, but more clinical studies are pending to confirm it further.

Ultraviolet Light Responsive N-Nitroso Polymers for Antibacterial Nitric Oxide Delivery.

This study investigates the incorporation of active secondary amine moieties into the polymer backbone by co-polymerizing 2,4,6-tris(chloromethyl)-mesitylene with three diamines, namely 1,4-diaminobutane, m-phenylenediamine, and p-phenylenediamine. This process results in the stabilization of the amine moieties and the subsequently introduced nitroso groups. Charging bioactive nitric oxide (NO) into the polymers is accomplished by converting the amine moieties into N-nitroso groups. The ability of the polymers to store and release NO depends on their structures, particularly the amount of incorporated active secondary amines. With grafting photosensitive N-nitroso groups into the polymers, the derived NO@polymers exhibit photoresponsivity. NO release is completely regulated by adjusting UV light irradiation. These resulting polymeric NO donors demonstrate remarkable bactericidal and bacteriostatic activity, effectively eradicating E. coli bacteria and inhibiting their growth. The findings from this study hold promising implications for combining NO delivery with phototherapy in various medical applications.

Nanotechnology-based photo-immunotherapy: a new hope for inhibition of melanoma growth and metastasis.

Melanoma is the most aggressive form of skin cancer and there is a need for the development of effective anti-melanoma therapies as it shows high metastatic ability and low response rate. In addition, it has been identified that traditional phototherapy could trigger immunogenic cell death (ICD) to activate antitumor immune response, which could not only effectively arrest primary tumour growth, but also exhibit superior effects in terms of anti-metastasis, anti-recurrence for metastatic melanoma treatment. However, the limited tumour accumulation of photosensitizers/photothermal agents and immunosuppressive tumour microenvironment severely weaken the immune effects. The application of nanotechnology facilitates a higher accumulation of photosensitizers/photothermal agents at the tumour site, which can thus improve the antitumor effects of photo-immunotherapy (PIT). In this review, we summarise the basic principles of nanotechnology-based PIT and highlight novel nanotechnologies that are expected to enhance the antitumor immune response for improved therapeutic efficacy.

Association of lung-intestinal microecology and lung cancer therapy.

In recent years, the incidence of lung cancer is increasing. Lung cancer has become one of the most malignant tumors with the highest incidence in the world, which seriously affects people's health. The most important cause of death of lung cancer is metastasis. Therefore, it is crucial to understand the mechanism of lung cancer progression and metastasis. This review article discusses the physiological functions, pathological states and disorders of the lung and intestine based on the concepts of traditional Chinese medicine (TCM), and analyzes the etiology and mechanisms of lung cancer formation from the perspective of TCM. From the theory of "the exterior and interior of the lung and gastrointestinal tract", the theory of "the lung-intestinal axis" and the progression and metastasis of lung cancer, we proposed e "lung-gut co-treatment" therapy for lung cancer. This study provides ideas for studying the mechanism of lung cancer and the comprehensive alternative treatment for lung cancer patients.

Uncovering the effect of Moringa oleifera Lam. leaf addition to Fuzhuan Brick Tea on sensory properties, volatile profiles and anti-obesity activity.

As a nutritious plant with valuable potential, the Moringa oleifera Lam. leaf addition to Fuzhuan Brick Tea (FBT) for co-fermentation is an industrial innovation and a new route to make full use of Moringa oleifera Lam. leaves. However, the sensory properties, volatile profiles and anti-obesity activity of Fuzhuan Brick (Moringa oleifera Lam.) tea (MFBT) are still unknown. The results demonstrated that MFBT has richer and more complex smell and taste, better color and higher overall acceptance scores. In total, 57 volatile flavor compounds, consisting of 3 acids, 16 hydrocarbons, 5 esters, 8 ketones, 13 aldehydes, 6 alcohols and others, were identified using HS-SPME-GC-MS. The characteristic odor components in MFBT were 3-buten-2-one, 4-(2,6,6-trimethyl-1-cyclohexen-1-yl)- and 1-cyclohexene-1-carboxaldehyde, 2,6,6-trimethyl-, which gave it a floral, woody, sweet, herbal and fruity aroma. 2-Octenal, (E) contributed significantly to the aroma of FBT, which could impart fresh, fatty and green aromas. In addition, MFBT could better regulate lipid accumulation, glucose tolerance, insulin tolerance and inflammation response more effectively than FBT. The mechanism is that MFBT could better regulate the dysbiosis of gut microbiota induced by HFFD, mainly increasing the abundance of beneficial bacteria such as SCFA-producing bacteria (Bacteroidetes, Lactobacillaceae, Bacteroidales_S24-7_group and Clostridiaceae_1) and decreasing the abundance of harmful bacteria such as pro-inflammatory/obesity and metabolic syndrome-related bacteria (Proteobacteria, Deferribacteres, Desulfovibrio, Catenibacterium and Helicobacter), which in turn increased feces short-chain fatty acids and lowered circulating lipopolysaccharides. These results suggested that co-fermentation with Moringa oleifera Lam. leaf could significantly improve the quality and enhance the anti-obesity effect of FBT.

Overlooked Spherical Nanoparticles Exist in Plant Extracts: From Mechanism to Therapeutic Applications.

To date, plant medicine research has focused mainly on the chemical compositions of plant extracts and their medicinal effects. However, the therapeutic or toxic effects of nanoparticles in plant extracts remain unclear. In this study, large numbers of spherical nanoparticles were discovered in some plant extracts. Nanoparticles in Turkish galls extracts were used as an example to examine their pH responsiveness, free radical scavenging, and antibacterial capabilities. By utilizing the underlying formation mechanism of these nanoparticles, a general platform to produce spherical nanoparticles via direct self-assembly of Turkish gall extracts and various functional proteins was developed. The results showed that the nanoparticles retained both the antibacterial ability and intracellular carrier ability of the original protein or catechol. This work introduces a new member of the plant-derived edible nanoparticle (PDEN) family, establishes a simple and versatile platform for mass production nanoparticles, and provides new insight into the formation mechanism of nanoparticles during plant extraction.

Near-infrared light activated photosensitizer with specific imaging of lipid droplets enables two-photon excited photodynamic therapy.

Two-photon excited phototherapy has attracted considerable attention due to its advantages such as deeper penetration depth and higher spatial resolution. The lack of a high-performance photosensitizer with large two-photon absorption cross-sections and specific targeting ability makes the efficacy of phototherapy in the treatment of cancer unsatisfactory. Here, a new BODIPY-derived photosensitizer 6DBF2 is designed with two-photon photosensitization for two-photon excited photodynamic therapy in vivo. 6DBF2 possesses good two-photon absorption and efficient 1O2 generation upon near-infrared laser excitation. Excellent targeting specificities to lipid droplets of 6DBF2 without any encapsulation or modification at a low working concentration of 0.1 µM is in favor of efficient photodynamic therapy. In vitro cancer cell ablation and in vivo tumor ablation inside mice models upon two-photon irradiation in NIR demonstrate the outstanding therapeutic performance of 6DBF2 in two-photon excited photodynamic therapy. This work thus discusses a rare example of lipid droplets targeting two-photon excited photodynamic therapy for deep cancer tissue imaging and treatment under near-infrared light irradiation.

[Vitamins and Immune System Health].

Keeping the immune system healthy forms an effective way to fight infections. Past experience has shown that, in addition to effective interventions including vaccination, drug therapy, and non-pharmaceutical intervention (NPI), dietary nutrition and mental health are also key factors in maintaining immune system health and combating emerging and sudden outbreaks of infections. As the main dietary nutrients, vitamins are active regulators of the immune response and exert a critical impact on the immunity of the human body. Vitamin deficiency causes increased levels of inflammation and decreased immunity, which usually starts in the oral tissues. Appropriate vitamin supplementation can help the body optimize immune function, enhance oral immunity, and reduce the negative impact of pathogen infection on the human body, which makes it a feasible, effective, and universally applicable anti-infection solution. This review focuses on the immunomodulatory effects of vitamin A, B, C, D, and E and proposes that an omics-based new systemic approach will lead to a breakthrough of the limitations in traditional single-factor single-pathway research and provide the direction for the basic and applied research of vitamin immune regulation and anti-infection in all aspects.

Emergence of Antifungal Resistant Subclades in the Global Predominant Phylogenetic Population of Candida albicans.

Candida albicans remains the most common species causing invasive candidiasis. In this study, we present the population structure of 551 global C. albicans strains. Of these, the antifungal susceptibilities of 370 strains were tested. Specifically, 66.6% of the azole-nonsusceptible (NS)/non-wild-type (NWT) strains that were tested belonged to Clade 1. A phylogenetic analysis, a principal components analysis, the population structure, and a loss of heterozygosity events revealed two nested subclades in Clade 1, namely, Clade 1-R and Clade 1-R-α, that exhibited higher azole-NS/NWT rates (75.0% and 100%, respectively). In contrast, 6.4% (21/326) of the non-Clade 1-R isolates were NS/NWT to at least 1 of 4 azoles. Notably, all of the Clade 1-R-α isolates were pan-azole-NS/NWT that carried unique A114S and Y257H double substitutions in Erg11p and had the overexpression of ABC-type efflux pumps introduced by the substitution A736V in transcript factor Tac1p. It is worth noting that the Clade 1-R and Clade 1-R-α isolates were from different cities that are distributed over a large geographic span. Our study demonstrated the presence of specific phylogenetic subclades that are associated with antifungal resistance among C. albicans Clade 1, which calls for public attention on the monitoring of the future spread of these clones. IMPORTANCE Invasive candidiasis is the most common human fungal disease among hospitalized patients, and Candida albicans is the predominant pathogen. Considering the large number of infected cases and the limited alternative therapies, the azole-resistance of C. albicans brings a huge clinical threat. Here, our study suggested that antifungal resistance in C. albicans could also be associated with phylogenetic lineages. Specifically, it was revealed that more than half of the azole-resistant C. albicans strains belonged to the same clade. Furthermore, two nested subclades of the clade exhibited extremely high azole-resistance. It is worth noting that the isolates of two subclades were from different cities that are distributed over a large geographic span in China. This indicates that the azole-resistant C. albicans subclades may develop into serious public health concerns.

Characterization and comparison of lipids from human and ewe colostrum based on lipidomics analysis.

Colostrum is essential for immune system development and has a protective role for infants in early life. However, the lipid compositions of human and ewe colostra have not been characterized. We hypothesized that lipidomics can be used to compare lipids in two mammalian colostra. Herein, 1004 lipids assigned to 26 subclasses were identified in both human and ewe colostra using a quantitative lipidomics approach. In total, 173 significantly different lipids (SDLs) were investigated (variable importance in projection > 1.1, fold change (FC) ≥ 2 or ≤0.5, and P < 0.0001). Four potential lipid biomarkers, namely, DG (19:0/18:0), TG (10:0/15:0/16:0), FFA (22:0), and TG (18:1/24:1/18:2), were selected from the 173 SDLs based on FC values. These different lipids were involved in 44 metabolic pathways, of which sphingolipid metabolism and glycerophospholipid metabolism were the major pathways. Our results improve the understanding of the differences between human and ewe colostra lipids.

Novel Method for Comprehensive Annotation of Plant Glycosides Based on Untargeted LC-HRMS/MS Metabolomics.

Glycosides are a large family of secondary metabolites in plants, which play a critical role in plant growth and development. Due to the complexity and diversity in structures and the limited availability of authentic standards, comprehensive annotation of the glycosides remains a great challenge. In this study, using maize as an example, a deep annotation method of glycosides was proposed based on untargeted liquid chromatography-high-resolution tandem mass spectrometry metabolomics analysis. First, knowledge-based in silico aglycone and glycosyl/acyl-glycosyl libraries were built. A total of 1240 known and potential aglycones from databases and literature were recorded. Next, the MS parameters beneficial to aglycone ion-rich MS/MS were explored using 1782 high-resolution MS/MS spectra of glycosides from the MassBank of North America (MoNA) and confirmed by 52 authentic glycoside standards. Then, screening rules for aglycon ions in MS/MS were recommended. Glycoside candidates were further filtered by MS/MS-based chemical classification and MS/MS similarity of aglycon-glycoside pairs. Finally, the glycosylation sites of flavonoid mono-O-glycosides were recommended by characteristic fragmentation patterns. The developed method was validated using glycosides and nonglycosides from the MoNA library. The annotation accuracy rates were 96.8, 94.9, and 98.0% in negative ion mode (ESI-), positive ion mode (ESI+), and the combined ESI- & ESI+, respectively. The annotation specificity was 99.6% (ESI-), 99.6% (ESI+), and 99.2% (ESI- & ESI+). A total of 274 glycosides (including 34 acyl-glycosides) were tentatively annotated in maize by the developed method. The method enables effective and reliable annotation for plant glycosides.