Genome-wide analysis of the SWEET gene family in Hemerocallis citrina and functional characterization of HcSWEET4a in response to salt stress.

Sugars will be eventually effluxed transporters (SWEETs) have been confirmed to play diverse physiological roles in plant growth, development and stress response. However, the characteristics and functions of the SWEET genes in Hemerocallis citrina remain unclear and poorly elucidated. In this study, the whole genome of Hemerocallis citrina was utilized to conduct bioinformatics analysis and a total of 19 HcSWEET genes were successfully identified. Analysis of the physicochemical properties indicated dominant differences among these HcSWEETs. A phylogenetic analysis revealed that HcSWEET proteins can be divided into 4 clades ranging from Clade I to IV, where proteins within the same clade exhibited shared conserved motifs and gene structures. Five to six exons were contained in the majority of HcSWEET genes, which were unevenly distributed across 11 chromosomes. The gene duplication analysis showed the presence of 4 gene pairs. Comparative syntenic maps revealed that the HcSWEET gene family might present more closed homology in monocotyledons than dicotyledons. Cis-acting element analysis of HcSWEET genes indicated key responsiveness to various hormones, light, and stresses. Additionally, transcriptome sequencing analysis suggested that most HcSWEET genes had a relatively higher expression in roots, and HcSWEET4a was significantly up-regulated under salt stress. Overexpression further verified the possibility that HcSWEET4a was involved in response to salt stress, which provides novel insights and facilitates in-depth studies of the functional analysis of HcSWEETs in resistance to abiotic stress.

Associations between earlobe creases and MRI SVD markers in a Chinese cohort of patients with ischemic stroke.

BACKGROUND: The association between earlobe crease (ELC) and cerebral small vessel disease (CSVD), including white matter hyperintensities (WMHs) and brain atrophy, is unclear, especially in the setting of acute ischemic stroke (AIS). Here, we aimed to investigate the association between ELC and WMHs as well as brain atrophy among AIS patients. METHODS: A total of 730 AIS patients from China were enrolled. Patients were divided into groups without and with ELC, unilateral and bilateral ELC according to pictures of bilateral ears. Logistic regression models were employed to assess the impact of ELC, bilateral ELC on WMHs, periventricular hyperintensities (PVH), deep white matter hyperintensities (DWMH), and brain atrophy, as measured by the Fazekas scale and global cortical atrophy scale, in brain magnetic resonance imaging (MRI). RESULTS: There were 520 (71.2%) AIS patients with WMHs, 445 (61.0%) with PVH, 462 (63.3%) with DWMH and 586 (80.3%) with brain atrophy. Compared to those without ELC, patients with ELC were significant associated with an increased risk of PVH (odds ratio [OR] 1.79; 95% confidence interval [CI], 1.15-2.77) and brain atrophy (OR 6.18; 95% CI, 3.60-10.63), but not WMHs and DWMH. The presence of bilateral ELC significantly increased the odds of WMHs (OR 1.60; 95% CI, 1.00-2.56), PVH (OR 1.87; 95% CI, 1.18-2.96), and brain atrophy (OR 8.50; 95% CI, 4.62-15.66) when compared to individuals without ELC. Furthermore, we discovered that the association between bilateral ELC and WMHs, PVH, and DWMH was significant only among individuals aged ≤68 (median age) years (all P trend ≤0.041). However, this association was not observed in patients older than 68 years. CONCLUSIONS: In Chinese AIS patients, the presence of the visible aging sign, ELC, especially bilateral ELC, showed independent associations with both white matter hyperintensities and brain atrophy, particularly among those younger than 68 years old.

Radiation-induced exosomes promote oral squamous cell carcinoma progression via enhancing SLC1A5-glutamine metabolism.

BACKGROUND: Radiotherapy (RT) can drive cancer cells to enter a state of cellular senescence in which cells can secrete senescence-associated secretory phenotype (SASP) and produce small extracellular vesicles (sEVs) to interact with cells in the tumor microenvironment (TME). Tumor-derived sEVs that are taken up by recipient cells contribute to cancer cell metabolic plasticity, resistance to anticancer therapy, and adaptation to the TME. However, how radiation-induced sEVs support oral squamous cell carcinoma (OSCC) progression remains unclear. METHODS: Beta-galactosidase staining and SASP mRNA expression analysis were used to evaluate the senescence-associated activity of OSCC cells after irradiation. Nanoparticle tracking analysis was performed to identify radiation-induced sEVs. Liquid chromatography-tandem mass spectrometry (LC-MS) was used to explore changes in the levels of proteins in radiation-induced sEVs. Cell Counting Kit-8 and colony formation assays were performed to investigate the function of radiation-induced SASP and sEVs in vitro. A xenograft tumor model was established to investigate the functions of radiation-induced sEVs and V-9302 in vivo as well as the underlying mechanisms. Bioinformatics analysis was performed to determine the relationship between glutamine metabolism and OSCC recurrence. RESULTS: We determined that the radiation-induced SASP triggered OSCC cell proliferation. Additionally, radiation-induced sEVs exacerbated OSCC cell malignancy. LC-MS/MS and bioinformatics analyses revealed that SLC1A5, which is a cellular receptor that participates in glutamine uptake, was significantly enriched in radiation-induced sEVs. In vitro and in vivo, inhibiting SLC1A5 could block the oncogenic effects of radiation-induced sEVs in OSCC. CONCLUSION: Radiation-induced sEVs might promote the proliferation of unirradiated cancer cells by enhancing glutamine metabolism; this might be a novel molecular mechanism underlying radiation resistance in OSCC patients.

NMDA receptor antagonists engender neuroprotection against gp120-induced cognitive dysfunction in rats through modulation of PKR activation, oxidative stress, ER stress and IRE1α signal pathway.

It is widely accepted that the surface glycoprotein (gp120) of human immunodeficiency virus-1 (HIV-1) plays an important role in HIV-1-induced nerve damage and pathogenesis of HIV-associated neurocognitive disorders (HAND). Our previous work has demonstrated that gp120 enhanced excitatory postsynaptic currents (EPSCs) mediated by N-methyl-d-aspartate receptors (NMDARs) and caused neural injury. However, the relationship between gp120, NMDARs and HAND is still unclear. Several lines of evidence indicate that double-stranded RNA-activated protein kinase (PKR) is involved in NMDA-induced cerebral ischaemia and retinal damage, but because its role in neuropathology is still debated, we examined whether PKR links oxidative stress and endoplasmic reticulum (ER) stress to exert a deleterious role in the rat model with gp120-induced dementia. In this study, we found that NMDAR antagonist memantine or PKR inhibitor C16 improved gp120-induced learning and memory impairment and inhibited gp120-induced PKR activity. Furthermore, memantine or C16 was found to attenuate gp120-induced neuroinflammation, oxidative stress, ER stress and its downstream IRE1α/JNK pathway. Additionally, memantine or C16 evidently inhibited apoptotic pathways by reducing the Bax and caspase-3, -8, -9 expressions and increasing Bcl-2 expression. So the NMDA receptor antagonists could alleviate HIV/gp120-induced dementia in the rat model by altering PKR level. In conclusion, this study demonstrates that NMDARs play a key role in HIV/gp120-induced hippocampal damage and cognitive dysfunction through PKR-mediated oxidative stress, ER stress, and IRE1α/JNK signalling pathway in rats, and implicating PKR inhibitors could provide a novel neuroprotective strategy for HAND via inhibiting ER stress and its downstream IRE1α signalling pathway.

Double Perovskite Mn4+-Doped La2CaSnO6/La2MgSnO6 Phosphor for Near-Ultraviolet Light Excited W-LEDs and Plant Growth.

Non-rare earth doped oxide phosphors with far-red emission have become one of the hot spots of current research due to their low price and excellent physicochemical stability as the red component in white light-emitting diodes (W-LEDs) and plant growth. Herein, we report novel Mn4+-doped La2CaSnO6 and La2MgSnO6 phosphors by high-temperature solid-phase synthesis and analyzed their crystal structures by XRD and Rietveld refinement. Their excitation spectra consist of two distinct excitation bands with the dominant excitation range from 250 to 450 nm, indicating that they possess strong absorption of near-ultraviolet light. Their emission is located around 693 and 708 nm, respectively, and can be absorbed by the photosensitive pigments Pr and Pfr, proving their great potential for plant growth. Finally, the prepared samples were coated with 365 nm UV chips to fabricate far-red LEDs and W-LEDs with low correlation color temperature (CCT = 4958 K/5275 K) and high color rendering index (Ra = 96.4/96.6). Our results indicate that La2CaSnO6:Mn4+ and La2MgSnO6:Mn4+ red phosphors could be used as candidate materials for W-LED lighting and plant growth.

Viral communities associated with porcine diarrhoeal disease and genetic characterization of a bufavirus in Tibetan pigs in China.

To investigate the viral communities in diarrhoeal faeces of Tibetan pigs, 146 diarrhoeic samples were collected from 16 pigs farms on the Tibetan plateau. Nineteen viruses belonging to eleven viral taxonomic families were identified in a pooled library. Metagenomics analysis revealed that the viruses were mainly small linear and circular DNA viruses. Furthermore, sequences of 10 NS1 genes and two complete genomes of PBuVs were obtained by PCR amplification. Sequence comparisons and phylogenetic analysis showed that the PBuVs from Tibetan pigs displayed more abundant genetic diversity than those from domestic pigs. This is the first description of the faecal viral community in Tibetan pigs associated with diarrhoea.

Effects of chemerin and homocysteine levels and their associations with occurrence and development of ischemic cerebrovascular disease.

BACKGROUND: The current study was conducted to explore the effects of chemerin and homocysteine (Hcy) levels and their associations with the occurrence and development of ischemic cerebrovascular disease (ICVD). METHODS: There involved a total of 187 patients with ICVD and 190 healthy people for physical examination in Cangzhou Central hospital from January 2020 to April 2021. The participants enrolled were divided into four groups based on the digital subtraction angiography: mild stenosis group (64 cases, stenosis rate 30-49 %), moderate stenosis group (72 cases, stenosis rate 50-69 %), severe stenosis group (51 cases, stenosis rate 70-99 %) and control group (190 cases, in healthy condition). The laboratory indexes of ICVD group and control group were observed and the four groups were further compared. Pearson linear correlation was applied to analyze the link between chemerin and Hcy levels and the degree of cerebral vascular stenosis in ICVD patients, and multivariate logistic regression was used to analyze the influencing factors of ICVD. RESULTS: No significant difference was found in general information including age, gender, body mass index (BMI), heart rate, systolic blood pressure, diastolic blood pressure, smoking and drinking between the two groups (P > 0.05). Moreover, there was no significant difference in fasting blood glucose (FBG), total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) levels between the two groups (P > 0.05). However, the levels of triglyceride (TG), low density lipoprotein cholesterol (LDL-C), chemerin and Hcy in ICVD group were significantly higher than those in control group (P < 0.05). When comparing the four groups, there was no significant difference in FBG and TC levels (P > 0.05). The levels of TG, LDL-C, chemerin and Hcy in mild, moderate and severe stenosis groups were higher than those in control group, the above levels in moderate and severe stenosis group were higher than those in mild stenosis group, and severe stenosis group higher than moderate stenosis group (P < 0.05). Chemerin and Hcy levels were positively correlated with the degree of cerebral vascular stenosis in ICVD patients (r = 0.612, 0.519, P < 0.001). ICVD was regarded as the dependent variable, and the abovementioned general data as well as significant laboratory indicators, including TG, LDL-C, chemerin and Hcy, as independent variables. The results of multivariate logistic regression analysis revealed that TG, LDL-C, chemerin and Hcy were independent influencing factors of ICVD. CONCLUSIONS: Chemerin and Hcy levels exerted a close link to the occurrence and development of ICVD as independent influencing factors.

Reversal of ciprofloxacin-induced testosterone reduction by probiotic microbes in mouse testes.

CPFX is a highly effective antibiotic, but it has been reported to significantly impair both testicular function and structure in rats. In this study, we assessed reversal of CPFX-induced variation in mice testicular structure and testosterone synthesis by probiotic microbes in the infected model and normal model. We detected testicular weight, testicular structure and Leydig cell variables in numbers. We detected the levels of serum testosterone and steroidogenic enzymes, as well as DBC1, Sirt1, NF-κB, and related redox state and inflammatory response in the testes. The results showed that probiotic microbes had significantly elevated serum testosterone levels and steroidogenic enzymes, higher Sirt1, anti-oxidative enzymes and anti-inflammatory cytokine expression, and lower NF-κB, DBC1, oxidative damage, pro-inflammatory cytokine expression. The results suggest that the testis-protective, antiinflammatory and antioxidation effects of probiotics largely resulted from its ability to decrease oxidative stress and preserve antioxidant activity by stabilizing antioxidant defense systems, reducing oxidative damage and inflammatory response.

Inhibitory effects of tanshinones towards the catalytic activity of UDP-glucuronosyltransferases (UGTs).

CONTENTS: Danshen is a popular herb employed to treat cardiovascular and cerebrovascular diseases worldwide. Danshen-drug interaction has not been well studied. OBJECTIVE: The inhibitory effects of four major tanshinones (tanshinone I, tanshinone IIA, cryptotanshinone, and dihydrotanshinone I) on UDP-glucuronosyltransferases (UGTs) isoforms were determined to better understand the mechanism of danshen-prescription drugs interaction. MATERIALS AND METHODS: In vitro recombinant UGTs-catalyzed 4-methylumbelliferone (4-MU) glucuronidation reaction was employed. Tanshinones (100 µM) was used to perform the initial screening of inhibition capability. High-performance liquid chromatography (HPLC) was used to separate 4-MU and its glucuronide. In vitro-in vivo extrapolation (IV-IVE) was employed to predict in vivo inhibition situation. RESULTS: Cryptotanshinone inhibited UGT1A7 and UGT1A9 with IC50 values of 1.91 ± 0.27 and 0.27 ± 0.03 µM, respectively. Dihydrotanshinone I inhibited UGT1A9-catalyzed 4-MU glucuronidation reaction with the IC50 value of 0.72 ± 0.04 µM. The inhibition of cryptotanshinone towards UGT1A7 and UGT1A9 was best fit to competitive inhibition type, and UGT1A9 was non-competitively inhibited by dihydrotanshinone I. Using in vitro inhibition kinetic parameters (Ki) and in vivo maximum plasma concentration (Cmax) of cryptotanshinone and dihydrotanshinone I, the change of area-under-the-concentration-time curve (AUC) was predicted to be 0.4-4.2%, 3.7-56.3%, and 0.6-6.4% induced by cryptotanshinone and dihydrotanshinone inhibition towards UGT1A7 and UGT1A9, respectively. DISCUSSION AND CONCLUSION: The inhibitory effects of tanshinones towards important UGT isoforms were evaluated in the present study, which provide helpful information for exploring the mechanism of danshen-clinical drugs interaction.

Rapid and Sensitive Differentiating Ischemic and Hemorrhagic Strokes by Dried Blood Spot Based Direct Injection Mass Spectrometry Metabolomics Analysis.

Cerebral infarction (CI) and intracerebral hemorrhage are lethal cerebrovascular diseases, sometimes sharing similar clinical manifestations but with distinct therapeutic strategies. Delayed treatment usually resulted in poor prognosis. A timely diagnosis report is highly warranted especially in emergency. One hundred twenty-nine CI patients, 73 intracerebral hemorrhage (ICH) patients, and 98 controls were enrolled in this study. A direct injection mass spectrometry metabolomics approach was adopted using dried blood spot samples. This targeted metabolomics analysis focused on absolute quantitation of 23 amino acids, 26 carnitine/carnitine esters, and 22 calculated ratios parameters. Compared to the normal control group, CI and ICH showed distinct metabolite changes, respectively. For stroke differentiation, Tyr, C5-OH/C0, Cit, Asn, Pro, Val, Arg/Orn, Leu, and Val/Phe were elevated in the CI group. On the contrary, C5:1, Phe/Tyr, (C0 + C2 + C3 + C16 + C18:1)/Cit, and Met/Leu were of lower levels in the CI group. Using regression model based on some of the above-mentioned parameters, 79.07% of stroke patients from a new set could be definitely confirmed. This study proved the targeted metabolomics analysis was a promising tool for rapid and timely stroke differentiation.

Chirality Influence of Zaltoprofen Towards UDP-Glucuronosyltransferases (UGTs) Inhibition Potential.

Zaltoprofen (ZLT) is a nonsteroidal antiinflammation drug, and has been clinically employed to treat rheumatoid arthritis, osteoarthritis, and other chronic inflammatory pain conditions. The present study aims to investigate the chirality influence of zaltoprofen towards the inhibition potential towards UDP-glucuronosyltransferases (UGTs) isoforms. In vitro a recombinant UGT isoforms-catalyzed 4-methylumbelliferone (4-MU) glucuronidation incubation system was employed to investigate the inhibition of (R)-zaltoprofen and (S)-zaltoprofen towards UGT isoforms. The inhibition difference capability was observed for the inhibition of (R)-zaltoprofen and (S)-zaltoprofen towards UGT1A8 and UGT2B7, but not for other tested UGT isoforms. (R)-zaltoprofen exhibited noncompetitive inhibition towards UGT1A8 and competitive inhibition towards UGT2B7. The inhibition kinetic parameters were calculated to be 35.3 µM and 19.2 µM for UGT1A8 and UGT2B7. (R)-zaltoprofen and (S)-zaltoprofen exhibited a different inhibition type towards UGT1A7. Based on the reported maximum plasma concentration of (R)-zaltoprofen in vivo, a high drug-drug interaction between (R)-zaltoprofen and the drugs mainly undergoing UGT1A7, UGT1A8, and UGT2B7-catalyzed glucuronidation was indicated.

Enantioselective inhibition of carprofen towards UDP-glucuronosyltransferase (UGT) 2B7.

UDP-glucuronosyltransferases (UGTs)-catalyzed glucuronidation conjugation reaction plays an important role in the elimination of many important clinical drugs and endogenous substances. The present study aims to investigate the enantioselective inhibition of carprofen towards UGT isoforms. In vitro a recombinant UGT isoforms-catalyzed 4-methylumbelliferone (4-MU) glucuronidation incubation mixture was used to screen the inhibition potential of (R)-carprofen and (S)-carprofen towards multiple UGT isoforms. The results showed that (S)-carprofen exhibited stronger inhibition potential than (R)-carprofen towards UGT2B7. However, no significant difference was observed for the inhibition of (R)-carprofen and (S)-carprofen towards other UGT isoforms. Furthermore, the inhibition kinetic behavior was compared for the inhibition of (S)-carprofen and (R)-carprofen towards UGT2B7. A Lineweaver-Burk plot showed that both (S)-carprofen and (R)-carprofen exhibited competitive inhibition towards UGT2B7-catalyzed 4-MU glucuronidation. The inhibition kinetic parameter (Ki ) was calculated to be 7.0 µM and 31.1 µM for (S)-carprofen and (R)-carprofen, respectively. Based on the standard for drug-drug interaction, the threshold for (S)-carprofen and (R)-carprofen to induce a drug-drug interaction is 0.7 µM and 3.1 µM, respectively. In conclusion, enantioselective inhibition of carprofen towards UDP-glucuronosyltransferase (UGT) 2B7 was demonstrated in the present study. Using the in vitro inhibition kinetic parameter, the concentration threshold of (S)-carprofen and (R)-carprofen to possibly induce the drug-drug interaction was obtained. Therefore, clinical monitoring of the plasma concentration of (S)-carprofen is more important than (R)-carprofen to avoid a possible drug-drug interaction between carprofen and the drugs mainly undergoing UGT2B7-catalyzed metabolism.

Inhibition of UDP-Glucuronosyltransferases (UGTs) Activity by constituents of Schisandra chinensis.

Structure-activity relationship for the inhibition of Schisandra chinensis's ingredients toward (Uridine-Diphosphate) UDP-glucuronosyltransferases (UGTs) activity was performed in the present study. In vitro incubation system was employed to screen the inhibition capability of S. chinensis's ingredients, and in silico molecular docking method was carried out to explain possible mechanisms. At 100 µM of compounds, the activity of UGTs was inhibited by less than 90% by schisandrol A, schisandrol B, schisandrin, schisandrin C, schisantherin A, gomisin D, and gomisin G. Schisandrin A exerted strong inhibition toward UGT1A1 and UGT1A3, with the residual activity to be 7.9% and 0% of control activity. Schisanhenol exhibited strong inhibition toward UGT2B7, with the residual activity to be 7.9% of control activity. Gomisin J of 100 µM inhibited 91.8% and 93.1% of activity of UGT1A1 and UGT1A9, respectively. Molecular docking prediction indicated different hydrogen bonds interaction resulted in the different inhibition potential induced by subtle structure alteration among schisandrin A, schisandrin, and schisandrin C toward UGT1A1 and UGT1A3: schisandrin A > schisandrin > schisandrin C. The detailed inhibition kinetic evaluation showed the strong inhibition of gomisin J toward UGT1A9 with the inhibition kinetic parameter (Ki ) to be 0.7 µM. Based on the concentrations of gomisin J in the plasma of the rats given with S. chinensis, high herb-drug interaction existed between S. chinensis and drugs mainly undergoing UGT1A9-mediated metabolism. In conclusion, in silico-in vitro method was used to give the inhibition information and possible inhibition mechanism for S. chinensis's components toward UGTs, which guide the clinical application of S. chinensis.

Revising the American dream: how Asian immigrants adjust after an HIV diagnosis.

AIM: We explored how acculturation and self-actualization affect depression in the HIV-positive Asians and Pacific Islanders immigrant population. BACKGROUND: Asians and Pacific Islanders are among the fastest growing minority groups in the USA. Asians and Pacific Islanders are the only racial/ethnic group to show a significant increase in HIV diagnosis rate. DESIGN: A mixed-methods study was conducted. METHODS: Thirty in-depth interviews were conducted with HIV-positive Asians and Pacific Islanders in San Francisco and New York. Additionally, cross-sectional audio computer-assisted self-interviews were conducted with a sample of 50 HIV-positive Asians and Pacific Islanders. Content analysis was used to analyse the in-depth interviews. Also, descriptive, bivariate statistics and multivariable regression analysis was used to estimate the associations among depression, acculturation and self-actualization. The study took place from January-June 2013. DISCUSSION: Major themes were extracted from the interview data, including self-actualization, acculturation and depression. The participants were then divided into three acculturation levels correlating to their varying levels of self-actualization. For those with low acculturation, there was a large discrepancy in the Center for Epidemiologic Studies Depression Scale scores between those who had totally lost their self-actualization and those who believed they could still achieve their 'American dreams'. Among those who were less acculturated, there was a significant difference in depression scores between those who felt they had totally lost their ability to self-actualize and those who still believed they could 'make their dreams come true.' CONCLUSION: Acculturation levels influence depression and self-actualization in the HIV-positive Asians and Pacific Islanders population. Lower acculturated Asian Americans achieved a lower degree of self-actualization and suffered from depression. Future interventions should focus on enhancing acculturation and reducing depression to achieve self-actualization.

Acculturation and perceived stress in HIV+ immigrants: depression symptomatology in Asian and Pacific Islanders.

Asians and Pacific Islanders (API) are among the fastest growing minority groups within the USA, and this growth has been accompanied by an increase in HIV incidence. Between 2000 and 2010, the API HIV infection rate increased from 4.5% to 8.7%; however, there is a paucity of HIV-related research for this group, and even less is known about the prevalence and correlates of antiretroviral therapy adherence behavior, quality of life, impact of stress, and efficacious self-management among HIV+ API Americans. This paper examines how acculturation and perceived stress affect depression symptomatology and treatment seeking in the HIV+ API population. A series of cross-sectional audio computer-assisted self-interviews were conducted with a convenience sample of 50 HIV+ API (29 in San Francisco and 21 in New York City). The relationship between acculturation and perceived stress was analyzed, and the results indicate that for those HIV+ API who reported low or moderate acculturation (as compared to those who reported high acculturation), stress was significantly mediated by depression symptomology. Interventions to address acculturation and reduce perceived stress among API generally and Asians specifically are therefore needed.

Chronic ethanol consumption decreases serum sulfatide levels by suppressing hepatic cerebroside sulfotransferase expression in mice.

Epidemiological studies demonstrate a possible relationship between chronic ethanol drinking and thrombotic diseases, such as myocardial infarction and stroke. However, the precise mechanism for this association remains unclear. Sulfatides are endogenous glycosphingolipids composed of ceramide, galactose, and sulfate, known to have anti-thrombotic properties. Low (0.5 g/kg/day), middle (1.5 g/kg/day), and high (3.0 g/kg/day) doses of ethanol were administered for 21 days intraperitoneally to female wild-type mice, and serum/liver sulfatide levels were measured. No significant changes in cholesterol and triglycerides were seen in serum and liver by ethanol treatment. However, serum/liver sulfatide levels were significantly decreased by middle- and high-dose ethanol treatment, likely due to downregulation of hepatic cerebroside sulfotransferase (CST) levels. Marked decreases in the expression of catalase and superoxide dismutases and ensuing increases in lipid peroxides were also observed in the livers of mice with middle- and high-dose ethanol treatment, suggesting the association between the suppression of hepatic CST expression and enhancement of oxidative stress. Furthermore, serum levels of tissue factor, a typical pro-coagulant molecule, were significantly increased in the mice with middle- and high-dose ethanol treatment showing decreases in serum sulfatide levels. Collectively, these results demonstrate that chronic ethanol consumption reduces serum sulfatide levels by increasing oxidative stress and decreasing the expression of CST in the liver. These findings could provide a mechanism by which chronic ethanol drinking increases thrombotic events.

Study on the role and mechanism of Tan IIA in Alzheimer's disease based on CREB-BDNF-TrkB pathway.

The occurrence and development of Alzheimer's disease (AD) is closely related to neuronal loss, inflammatory response, cholinergic imbalance, and Tau protein hyperphosphorylation. Previous studies have confirmed that Streptozotocin (STZ) can be used to establish a rat model of AD by injecting it into the rat brain via the lateral ventricle. Our previous research showed that Danshentone IIA (Tan IIA) can improve cognitive dysfunction in rats caused by CC chemokine ligand 2, and network pharmacology results show that Tan IIA is very likely to improve AD symptoms through the cyclic adenosine monophosphate response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), and tyrosine kinase receptor protein (TrkB) pathway. The results of the water maze experiment showed that after Tan IIA treatment, the escape latency of AD rats was shortened and the number of platform crossings increased; in the new object recognition experiment, the discrimination index of AD rats significantly increased after treatment; Nissl staining and Tunel staining results showed that Tan IIA increased the number of surviving neurons in the hippocampus of cognitively impaired rats and reduced neuronal apoptosis; Bielschowsky silver staining results showed that Tan IIA reduced neurofibrillary tangles (NFTs) in the AD rats; Tan IIA can reduce the inflammatory response and oxidative stress reaction in the hippocampus of AD rats, and at the same time reduce the activity of acetylcholinesterase. Tan IIA can significantly increase the expression of CREB, BDNF, TrkB in the hippocampal tissue of STZ-injured rats (P < 0.05). These data suggest that Tan IIA may upregulate the expression of the CREB-BDNF-TrkB signaling pathway in the hippocampus of brain tissue, produce anti-neuroinflammatory, antioxidant stress, inhibit neuronal apoptosis effects, and improve cholinergic neurotransmitter disorder induced by STZ, reduce the neuronal damage and learning and memory impairment caused by STZ in rats, and improve the cognitive function of rats.

Integrative single-cell and bulk transcriptomes analyses reveals heterogeneity of serine-glycine-one-carbon metabolism with distinct prognoses and therapeutic vulnerabilities in HNSCC.

Metabolic heterogeneity plays a central role in sustaining uncontrolled cancer cell proliferation and shaping the tumor microenvironment (TME), which significantly compromises the clinical outcomes and responses to therapy in head and neck squamous cell carcinoma (HNSCC) patients. This highlights the urgent need to delineate the intrinsic heterogeneity and biological roles of metabolic vulnerabilities to advance precision oncology. The metabolic heterogeneity of malignant cells was identified using single-cell RNA sequencing (scRNA-seq) profiles and validated through bulk transcriptomes. Serine-glycine-one-carbon (SGOC) metabolism was screened out to be responsible for the aggressive malignant properties and poor prognosis in HNSCC patients. A 4-SGOC gene prognostic signature, constructed by LASSO-COX regression analysis, demonstrated good predictive performance for overall survival and therapeutic responses. Patients in the low-risk group exhibited greater infiltration of exhausted CD8+ T cells, and demonstrated better clinical outcomes after receiving immunotherapy and chemotherapy. Conversely, high-risk patients exhibited characteristics of cold tumors, with enhanced IMPDH1-mediated purine biosynthesis, resulting in poor responses to current therapies. IMPDH1 emerged as a potential therapeutic metabolic target. Treatment with IMPDH inhibitors effectively suppressed HNSCC cell proliferation and metastasis and induced apoptosis in vitro and in vivo by triggering GTP-exhaustion nucleolar stress. Our findings underscore the metabolic vulnerabilities of HNSCC in facilitating accurate patient stratification and individualized precise metabolic-targeted treatment.

Transcriptomic analysis reveals candidate genes associated with anther development in Lilium Oriental Hybrid 'Siberia'.

Lily (Lilium spp. and hybrids) is an important cut flower crop worldwide. Lily flowers have large anthers, which release a large amount of pollen that stains the tepals or clothing and thus can affect the commercial value of cut flowers. In this study, lily Oriental 'Siberia' was used to investigate the regulatory mechanism of lily anther development, which may provide information to prevent pollen pollution in the future. Based on the flower bud length, anther length and color, and anatomical observations, lily anther development was categorized into five stages: green (G), green-to-yellow 1 (GY1), green-to-yellow 2 (GY2), yellow (Y), and purple (P). Total RNA was extracted from the anthers at each stage for transcriptomic analysis. A total of 268.92-Gb clean reads were generated, and 81,287 unigenes were assembled and annotated. The number of differentially expressed genes (DEGs) and unique genes were largest for the pairwise comparison between the G and GY1 stages. The G and P samples were clustered separately, whereas the GY1, GY2, and Y samples were clustered together in scatter plots from a principal component analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of DEGs detected in the GY1, GY2, and Y stages revealed that the pectin catabolic process, hormone levels, and phenylpropanoid biosynthesis were enriched. The DEGs associated with jasmonic acid biosynthesis and signaling were highly expressed at the early stages (G and GY1), whereas the DEGs associated with phenylpropanoid biosynthesis were mainly expressed in the intermediate stages (GY1, GY2, and Y). The DEGs involved in the pectin catabolic process were expressed at advanced stages (Y and P). Cucumber mosaic virus-induced gene silencing of LoMYB21 and LoAMS caused a strongly inhibited anther dehiscence phenotype, but without affecting the development of other floral organs. These results provide novel insights for understanding the regulatory mechanism of anther development in lily and other plants.