Analysis of Forsythia suspensa fruit and leaf extracts using UHPLC-Q-Exactive-Orbitrap/MS: In vivo antioxidant activity on D-galactose-induced aging mice.

Making health-enhancing tea from Forsythia suspensa leaves has been a tradition of Chinese folk culture for centuries. However, these leaves were not officially recognized as a new food source until 2017 by the Chinese government. In this study, ethyl acetate fractions from Forsythia suspensa fruit and leaves exhibited excellent antioxidant activity in vitro antioxidant assays and in vivo D-galactose-induced aging mice model. The antioxidant activity of the leaves was higher than that of fruit both in vitro and in vivo. The chemical constituents present in these ethyl acetate fractions were comprehensively analyzed using UHPLC-Q-Exactive-Orbitrap/MS. A total of 20 compounds were identified, among which forsythoside E, (+)-epipinoresinol, dihydromyricetin, chlorogenic acid, and ursolic acid were exclusively detected in the ethyl acetate fraction of Forsythia suspensa leaves, but absent in the ethyl acetate fraction derived from its fruit. This study provides theoretical support for the utilization of Forsythia suspensa fruit and leaves.

Induced neural stem cells regulate microglial activation through Akt-mediated upregulation of CXCR4 and Crry in a mouse model of closed head injury.

JOURNAL/nrgr/04.03/01300535-202505000-00025/figure1/v/2024-07-28T173839Z/r/image-tiff Microglial activation that occurs rapidly after closed head injury may play important and complex roles in neuroinflammation-associated neuronal damage and repair. We previously reported that induced neural stem cells can modulate the behavior of activated microglia via CXCL12/CXCR4 signaling, influencing their activation such that they can promote neurological recovery. However, the mechanism of CXCR4 upregulation in induced neural stem cells remains unclear. In this study, we found that nuclear factor-κB activation induced by closed head injury mouse serum in microglia promoted CXCL12 and tumor necrosis factor-α expression but suppressed insulin-like growth factor-1 expression. However, recombinant complement receptor 2-conjugated Crry (CR2-Crry) reduced the effects of closed head injury mouse serum-induced nuclear factor-κB activation in microglia and the levels of activated microglia, CXCL12, and tumor necrosis factor-α. Additionally, we observed that, in response to stimulation (including stimulation by CXCL12 secreted by activated microglia), CXCR4 and Crry levels can be upregulated in induced neural stem cells via the interplay among CXCL12/CXCR4, Crry, and Akt signaling to modulate microglial activation. In agreement with these in vitro experimental results, we found that Akt activation enhanced the immunoregulatory effects of induced neural stem cell grafts on microglial activation, leading to the promotion of neurological recovery via insulin-like growth factor-1 secretion and the neuroprotective effects of induced neural stem cell grafts through CXCR4 and Crry upregulation in the injured cortices of closed head injury mice. Notably, these beneficial effects of Akt activation in induced neural stem cells were positively correlated with the therapeutic effects of induced neural stem cells on neuronal injury, cerebral edema, and neurological disorders post-closed head injury. In conclusion, our findings reveal that Akt activation may enhance the immunoregulatory effects of induced neural stem cells on microglial activation via upregulation of CXCR4 and Crry, thereby promoting induced neural stem cell-mediated improvement of neuronal injury, cerebral edema, and neurological disorders following closed head injury.

Frustrated Lewis Pair Mediated f-p-d Orbital Coupling: Achieving Selective Seawater Oxidation and Breaking *OH and *OOH Scaling Relationship.

The development of materials for hydrogen production via seawater electrolysis at high current densities plays a crucial role in producing renewable hydrogen energy. However, during the seawater electrolysis process, the anode inevitably undergoes chloride oxidation reaction (ClOR) due to Cl- adsorption, making the seawater electrolysis process difficult to sustain. Inspired by the selective permeability of cell membranes, we propose a biomimetic design of frustrated Lewis pairs (FLPs) layers. Combining experimental results and molecular dynamics simulations, it has been demonstrated that cerium dioxide layers with FLPs sites can decompose water molecules, capture hydroxyl anions, and repel chloride ions simultaneously. DFT theoretical analysis indicates that the FLP sites regulate the Ce 4f-O 2p-Ni 3d gradient orbital coupling, providing additional oxygen non-bonding (ONB) to stabilize the Ni-O bond and optimize the adsorption strength of intermediates, thereby breaking the *OH and *OOH scaling relationship. Assembled anion exchange membrane electrolyzers exhibit an efficiency of 95.7% at a current density of 0.1 A cm-2 and can stably operate for 250 hours at a current density of 0.2 A cm-2.

Mental Health Literacy Among Urban and Rural Residents of Guangdong Province, China.

Purpose: The study aims to understanding the mental health literacy level of urban and rural residents in Guangdong Province, the first major province in China, and its influencing factors is crucial. Methods: A multi-stage stratified equal-volume random sampling method was adopted in October-December 2022 to select permanent residents aged 18 years and above in Guangdong Province for the questionnaire survey, which consisted of a general demographic information questionnaire and a national mental health literacy questionnaire. Rao-Scott χ²-test with correction based on sampling design, independent samples t-test and binary multivariate logistic regression analysis were performed. Results: A total of 51744 individuals completed the questionnaire, including 31822 urban residents and 19200 rural residents. The rate of achievement of mental health literacy was 13.6% among urban residents, which was significantly higher compared to the rate of 8.6% among rural residents. Logistic regression analysis showed that female, higher education, being mental worker, being a retiree, having a higher monthly household income, maintaining a regular diet, and using electronic products for 2-6 hours per day were protective factors for mental health literacy attainment in urban residents, while having chronic diseases, being a smoker and having a history of drinking were identified as risk factors in urban residents. Among in rural residents, married, younger, higher education, being mental worker and using electronic products for 2-6 hours per day, maintaining a regular diet, and engaging in regular exercise were protective factors for achieving mental health literacy, while previous smoking was a risk factor. Conclusion: The study revealed a low level of mental health literacy among urban and rural residents of Guangdong Province, with a significant disparity between the two areas. These findings highlight the need for continuing efforts to increase the dissemination of mental health knowledge in rural communities and improve levels of mental health literacy.

Aged garlic oligosaccharides modulate host metabolism and gut microbiota to alleviate high-fat and high-cholesterol diet-induced atherosclerosis in ApoE-/- mice.

Atherosclerosis (AS) is a cardiovascular disease caused by excessive accumulation of lipids in arterial walls. In this study, we developed an AS model in ApoE-/- mice using a high-fat, high-cholesterol diet and investigated the anti-AS mechanism of aged garlic oligosaccharides (AGOs) by focusing on the gut microbiota. Results revealed that AGOs exhibited significant anti-AS effects, reduced trimethylamine N-oxide levels from 349.9 to 189.2 ng/mL, and reduced aortic lipid deposition from 31.7 % to 9.5 %. AGOs significantly increased the levels of short-chain fatty acids in feces, in which acetic, propionic, and butyric acids were increased from 1.580, 0.364, and 0.469 mg/g to 2.233, 0.774, and 0.881 mg/g, respectively. An analysis of the gut microbiota indicated that AGOs restored alpha and beta diversity, decreased the Firmicutes/Bacteroidetes ratio, and promoted the dominance of the genus Akkermansia. A metagenomic analysis revealed that AGOs alleviated AS through the ABC transporter pathway and the lipopolysaccharide biosynthesis pathway.

Cleft lip and palate transmembrane protein 1-like is a putative regulator of tumorigenesis and sensitization of cervical cancer cells to cisplatin.

Background: Cervical cancer stands as one of the leading causes of cancer-related mortality in women worldwide, yet the precise functions of host genes implicated in its pathogenesis remain elusive. Genome-wide association studies (GWAS) have revealed a significant association between the CLPTM1L locus and cervical cancer risk in European women, and aberrant expression of CLPTM1L has been noted in various malignant tumors. However, the role of CLPTM1L in cervical cancer remains largely unexplored. Methods: The expression of CLPTM1L in cervical cancer cells and tissues was detected by RT-qPCR. Furthermore, the potential biological functions of CLPTM1L in the context of cervical cancer were explored via RNA sequencing. Cell proliferation rates and the responsiveness of cervical cancer cells to cisplatin were evaluated using the CCK-8 assay, while cell apoptosis was quantified through the utilization of flow cytometry. Nude mouse xenograft models were utilized to explore the impact of CLPTM1L on tumor formation in vivo. Results: Our findings demonstrated a significant increase in CLPTM1L mRNA expression levels in HeLa and C33A cells, as well as in cervical carcinoma tissues, compared to ECT1/E6E7 cells and adjacent normal tissues. Genes related to CLPTM1L were found to be enriched in the Hedgehog signaling pathway. In vitro and in vivo studies showed that reducing CLPTM1L expression markedly inhibited cell proliferation via downstream candidate genes BOC and LRP2. Furthermore, the downregulation of CLPTM1L was found to enhance cisplatin-induced cell apoptosis and increase the susceptibility of cervical cancer cells to cisplatin through DAP1. Conclusions: CLPTM1L could impact cervical cancer cell proliferation and cisplatin-induced cell apoptosis, as well as cisplatin susceptibility in cervical cancer cells. This investigation has bestowed upon us novel insights into the pathogenesis of cervical cancer, underscoring the potential of CLPTM1L as a promising target for chemotherapeutic sensitization in the management of this malignancy.

Evaluation of forest ecosystem resilience to drought considering lagged effects of drought.

Drought can cause significant disruption to forest ecosystems and may have long-term impacts on the structure and function of ecosystems after the end of drought. This is the key to quantifying the ability of ecosystem to respond to disturbance events by comprehensively analyzing the impact of drought on vegetation, the lagged effect, and ecosystem resilience to drought. This article takes broad-leaved forests and coniferous forests in multiple temperature zones of China as the object of study, using distributed lagged nonlinear model (DLNM) to construct a systematic method. Our results show that the main sensitive lagged time for coniferous forests and broad-leaved forests is the first 3 months in various temperature zones, with the strongest lagged effect in the month when the drought incidents occur. Coping capacity represents ecosystems to remain stable during droughts, and we quantified the indicator by the ratio of the resistance (the difference between NDVI value before the drought and during the drought) to recovery (the difference between NDVI value after the drought and during the drought). When dealing with intensive drought events, the coping capacity of subtropical broad-leaved forests (-0.67) and tropical broad-leaved forests (-0.88) exhibit the strongest coping capacity (value tends to -1). Overall, vegetation growth in subtropical and tropical regions is less affected by drought compared to temperate and cold temperate zones. The research results help us understand the comprehensive impact of drought on vegetation and the strategies for different vegetation to cope with drought.

Unlocking the potential of LHPP: Inhibiting glioma growth and cell cycle via the MDM2/p53 pathway.

The recurrence of glioma after treatment has remained an intractable problem for many years. Recently, numerous studies have explored the pivotal role of the mouse double minute 2 (MDM2)/p53 pathway in cancer treatment. Lysine phosphate phosphohistidine inorganic pyrophosphate phosphatase (LHPP), a newly discovered tumor suppressor, has been confirmed in numerous studies on tumors, but its role in glioma remains poorly understood. Expression matrices in The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases were analyzed using gene set enrichment analysis (GSEA), revealing significant alterations in the p53 pathway among glioma patients with high LHPP expression. The overexpression of LHPP in glioma cells resulted in a reduction in cell proliferation, migration, and invasive ability, as well as an increase in apoptosis and alterations to the cell cycle. The present study has identified a novel inhibitory mechanism of LHPP against glioma, both in vivo and in vitro. The results demonstrate that LHPP exerts anti-glioma effects via the MDM2/p53 pathway. These findings may offer a new perspective for the treatment of glioma in the clinic.

Erratum: Publisher Correction: Removal of the C4-domain preserves the drought tolerance enhanced by CsMYB4a and eliminates the negative impact of this transcription factor on plant growth.

[This corrects the article DOI: 10.1007/s42994-024-00149-5.].

Removal of the C4-domain preserves the drought tolerance enhanced by CsMYB4a and eliminates the negative impact of this transcription factor on plant growth.

The MYB4 transcription factor family regulates plant traits. However, their overexpression often results in undesirable side effects like growth reduction. We have reported a green tea (Camellia sinensis) MYB4 transcription factor (CsMYB4) that represses the phenylpropanoid and shikimate pathways and stunts plant growth and development. In the current study, we observed that in CsMYB4a transgenic tobacco (Nicotiana tabacum) plants, primary metabolism was altered, including sugar and amino acid metabolism, which demonstrated a pleiotropic regulation by CsMYB4a. The CsMYB4a transgenic tobacco plants had improved drought tolerance, which correlated to alterations in carbohydrate metabolism and an increase in proline content, as revealed by metabolic profiling and transcriptomic analysis. To mitigate the undesirable repressive side effects on plant traits, including dwarfism, shrunken leaves, and shorter roots of CsMYB4a transgenic plants, we deleted the C4 domain of CsMYB4a to obtain a CsMYB4a-DC4 variant and then overexpressed it in transgenic plants (CsMYB4a-DC4). These CsMYB4a-DC4 plants displayed a normal growth and had improved drought tolerance. Metabolite analysis demonstrated that the contents of carbohydrates and proline were increased in these transgenic plants. Our findings suggest that  an approriate modification of TFs can generate novel crop traits, thus providing potential agricultural benefits and expanding its application to various crops. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-024-00149-5.

Polymorphisms in miRNA Genes Targeting the AMPK Signaling Pathway are Associated with Cervical Cancer Susceptibility in a Han Chinese Population.

Purpose: Cervical cancer (CC) poses a significant threat to women's health worldwide, and multiple signaling pathways have been confirmed to be involved in its development. The AMPK signaling pathway plays a central role in maintaining energy homeostasis, and its dysregulation is closely associated with the occurrence of CC. Changes in microRNA (miRNA) expression levels might be related to the AMPK signaling pathway. Single nucleotide polymorphisms (SNPs) can affect the function of miRNA and result in the development of CC. To investigate the association between the SNPs of AMPK pathway-associated miRNAs and CC in a Han Chinese population, we selected eight miRNA genes located in the AMPK pathway and analyzed nine SNP loci within these genes to explore whether they are associated with genetic susceptibility to cervical intraepithelial neoplasia (CIN) and CC. Methods: A total of 2,220 subjects were included in this study, including 928 healthy controls, 421 CIN patients, and 871 CC patients. Nine candidate SNPs (rs895819 in miR-27a, rs10061133 in miR-449b, rs41291179 in miR-216a, rs76481776 in miR-182, rs10406069 in miR-5196, rs12803915 and rs550894 in miR-612, rs66683138 in miR-3622b, and rs2620381 in miR-627) were genotyped using the TaqMan method. Results: The results showed significant differences in the allele distribution of rs41291179 and rs12803915 between the control group and the CIN group, as well as between the control group and the CC group (all P values < 0.005). The A allele of rs41291179 and the G allele of rs12803915 were associated with decreased risk of CIN (OR = 0.05, 95% CI: 0.01-0.39; OR = 0.61, 95% CI: 0.49-0.76) and CC (OR = 0.08, 95% CI: 0.01-0.66; OR = 0.71, 95% CI: 0.59-0.86), respectively. Conclusion: Our results suggest that polymorphisms in miRNA genes of the AMPK signaling pathway are associated with the development of CC.

Downregulation of RhoB Inhibits Cervical Cancer Progression and Enhances Cisplatin Sensitivity.

RhoB, a member of the Rho GTPase family, has been implicated in the malignant progression of various cancer types. However, its role in cervical cancer (CC) remains unclear. Therefore, this study aims to elucidate the biological function of RhoB in CC and its relationship with cisplatin sensitivity. We analyzed data from the TCGA, GTEx, and GEO databases, revealing that RhoB mRNA expression is downregulated in CC tissues compared to normal cervical tissues. The further analysis of the TCGA database and Tongji samples showed that CC patients with a high RhoB expression had a shorter overall survival (OS). Subsequently, we found that the knockdown of RhoB inhibited the proliferation, migration, and invasion of cancer cells, while increasing apoptosis. Through Western blot (WB) analysis, we found that knocking down RhoB resulted in an increased expression of the epithelial marker E-cadherin, while the levels of N-cadherin, MMP2, MMP9, Vimentin, and Snail1 were reduced. Additionally, RhoB mRNA expression was upregulated in CC tissues after chemotherapy compared to CC tissues before chemotherapy. In CC cells, RhoB expression increased with cisplatin concentration, and the IC50 value decreased following RhoB knockdown. Moreover, the knockdown of RhoB could enhance the cellular apoptosis triggered by cisplatin. This study demonstrated that RhoB plays an oncogenic role in CC and that its knockdown could enhance the sensitivity of CC cells to cisplatin.

Research on the expression of Mir-218-2 in the serum of patients with papillary thyroid cancer and its clinical significance.

Papillary thyroid carcinoma is an epithelial malignancy with follicular cell differentiation and sets of defined nuclear features and appearance of an irregular solid mass. The main objective of our study is to research on the expression of miR-218-2 in the serum of patients with papillary thyroid cancer and its clinical significance. Our study involved patients with thyroid nodules were divided into a capitate cancer group (N = 100) and a benign nodule group (N =100). Lastly, 50 cases of healthy individuals were used as controls. The total sample size was 250. All cases were clinically diagnosed and underwent histopathological examinations at the Tonglu County Hospital of Traditional Chinese Medicine between January 2023 and January 2024. Quantitative RT-PCR was used to assess the expression levels of miR-218-2 and its host gene SLIT3 in normal and cancer thyroid tissues. We found that 45% of tumour sizes were less than 1 cm with 90% of tumours did not infiltrate the glandular capsule, implying a favourable prognosis. Lastly, 85% of tumours were well differentiated with about 75% showing no metastasis while 60% of TNM stage were classified as stage I. Also, miR-218-2 and its host gene SLIT3 are significantly down-regulated in papillary thyroid carcinoma. The inhibitory effects of miR-218-2 act in synergy with its host gene SLIT3 to alter the rates of cell invasion, cell migration and cell proliferation. Our findings have clinical significance on the involvement of miR-218-2 and SLIT3. There exists a functional relationship between host genes and intronic miRNAs in the tumorigenesis of thyroid cancers.

Age-related analysis of corneal biomechanical parameters in healthy Chinese individuals.

To report the correlation between corneal biomechanical parameters and age in healthy Chinese individuals. This cross-sectional study was conducted on 864 eyes of 543 healthy participants. A comprehensive ophthalmic examination and corneal biomechanics examination using Corneal Visualization Scheimpflug Technology (Corvis ST) were conducted. Based on age, all participants were further divided into five age groups (n) as follows: group A, 11-20 years (105); group B, 21-30 years (112); group C, 31-40 years (113); group D, 41-50 years (100); and group E, > 50 years (113). Using Corvis ST, we examined 35 corneal biomechanical parameters and compared them across the different age groups. Spearman's correlation coefficients and stepwise multivariate linear regression models were used to investigate whether the corneal biomechanical parameters were related to demographic and ocular characteristics. A correlation analysis between the left and right eyes revealed that 13 parameters were significantly associated with eye differences. Among the 35 corneal biomechanical parameters, 28 exhibited significant differences across the age groups, with stiffness parameter at applanation 1(SPA1) showing an upward trend after the age of 30 and stress-strain index (SSI) demonstrates a statistically significant upward trend when comparing the five age groups in the study. Additionally, Spearman's correlation analysis and stepwise multivariate linear regression analysis revealed that 11 corneal biomechanical parameters were positively correlated with age and 10 were negatively correlated with age. Corvis biomechanical index (CBI) was significantly negatively correlated with intraocular pressure (IOP) and central corneal thickness (CCT), SSI was significantly positively correlated with age and IOP, and SPA1 were positively correlated with IOP and CCT. In conclusion, most corneal biomechanical parameters showed a significant correlation with age, with corneal stiffness progressively increasing alongside advancing age, IOP, or CCT.

Multi-omics analyses reveal the mechanisms underlying the responses of Casuarina equisetifolia ssp. incana to seawater atomization and encroachment stress.

Casuarina equisetifolia trees are used as windbreaks in subtropical and tropical coastal zones, while C. equisetifolia windbreak forests can be degraded by seawater atomization (SA) and seawater encroachment (SE). To investigate the mechanisms underlying the response of C. equisetifolia to SA and SE stress, the transcriptome and metabolome of C. equisetifolia seedlings treated with control, SA, and SE treatments were analyzed. We identified 737, 3232, 3138, and 3899 differentially expressed genes (SA and SE for 2 and 24 h), and 46, 66, 62, and 65 differentially accumulated metabolites (SA and SE for 12 and 24 h). The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that SA and SE stress significantly altered the expression of genes related to plant hormone signal transduction, plant-pathogen interaction, and starch and sucrose metabolism pathways. The accumulation of metabolites associated with the biosynthetic pathways of phenylpropanoid and amino acids, as well as starch and sucrose metabolism, and glycolysis/gluconeogenesis were significantly altered in C. equisetifolia subjected to SA and SE stress. In conclusion, C. equisetifolia responds to SA and SE stress by regulating plant hormone signal transduction, plant-pathogen interaction, biosynthesis of phenylpropanoid and amino acids, starch and sucrose metabolism, and glycolysis/gluconeogenesis pathways. Compared with SA stress, C. equisetifolia had a stronger perception and response to SE stress, which required more genes and metabolites to be regulated. This study enhances our understandings of how C. equisetifolia responds to two types of seawater stresses at transcriptional and metabolic levels. It also offers a theoretical framework for effective coastal vegetation management in tropical and subtropical regions.

Predicting Gene Comutation of EGFR and TP53 by Radiomics and Deep Learning in Patients With Lung Adenocarcinomas.

PURPOSE: This study was designed to construct progressive binary classification models based on radiomics and deep learning to predict the presence of epidermal growth factor receptor (EGFR) and TP53 mutations and to assess the models' capacities to identify patients who are suitable for TKI-targeted therapy and those with poor prognoses. MATERIALS AND METHODS: A total of 267 patients with lung adenocarcinomas who underwent genetic testing and noncontrast chest computed tomography from our hospital were retrospectively included. Clinical information and imaging characteristics were gathered, and high-throughput feature acquisition on all defined regions of interest (ROIs) was carried out. We selected features and constructed clinical models, radiomics models, deep learning models, and ensemble models to predict EGFR status with all patients and TP53 status with EGFR-positive patients, respectively. The validity and reliability of each model were expressed as the area under the curve (AUC), sensitivity, specificity, accuracy, precision, and F1 score. RESULTS: We constructed 7 kinds of models for 2 different dichotomies, namely, the clinical model, the radiomics model, the DL model, the rad-clin model, the DL-clin model, the DL-rad model, and the DL-rad-clin model. For EGFR- and EGFR+, the DL-rad-clin model got the highest AUC value of 0.783 (95% CI: 0.677-0.889), followed by the rad-clin model, the DL-clin model, and the DL-rad model. In the group with an EGFR mutation, for TP53- and TP53+, the rad-clin model got the highest AUC value of 0.811 (95% CI: 0.651-0.972), followed by the DL-rad-clin model and the DL-rad model. CONCLUSION: Our progressive binary classification models based on radiomics and deep learning may provide a good reference and complement for the clinical identification of TKI responders and those with poor prognoses.

Diversity of Treatments in Overcoming Morphophysiological Dormancy of Paeonia peregrina Mill. Seeds.

Paeonia peregrina Mill. is a protected, herbaceous species native to Southeastern Europe and Turkey. Due to its vulnerability, it has to be protected both in its natural habitats and through cultivation. Peonies are known to have a low potential for natural regeneration due to their seed dormancy, low germination rate, and long germination period. In this study, treatments with gibberellic acid (GA3 150, 200, 250, 300, and 350 mg L-1 GA3) and warm (at 20/16 °C day/night regime) and cold stratification (at 4 °C) were used to accelerate dormancy release and increase the germination rate. The seeds of P. peregrina from four natural habitats in Serbia and the Institute's collection were collected and analyzed. They showed an underdeveloped embryo that needs to grow inside the seed before it can germinate. The application of GA3 accelerated each stage of germination (seed coat rapturing, hypocotyl dormancy release, and epicotyl dormancy release) for approximately 10 days compared to the control. It was also found that two-day imbibition with 200 mg L-1 GA3 significantly accelerated and equalized germination. Higher GA3 concentrations had a more pronounced impact on each stage but also resulted in greater seed infection after the seed coat rupture, elongated and weak seedlings, while lower concentrations did not result in obtaining uniform seedlings. There were no significant differences observed between localities. Restoring P. peregrina through seeds and nursery-produced plants is crucial for conserving the genetic diversity of the tested species.

Preparation of ceftiofur-encapsulated hen-egg low-density lipoproteins and their antibacterial effects on intracellular Staphylococcus aureus.

Hen egg low-density lipoprotein (heLDL), as alternative of serum-derived LDL, was used as drug delivery system of ceftiofur (CEF). The CEF-loaded hen egg low-density lipoprotein (CEF-heLDL) with complete apolipoprotein structure and high drug loading rate was synthesized, possesses suitable particle size. CEF-heLDL undergoes cellular uptake and colocalizes with lysosomes in vitro. An intracellular infection model of the bovine endometrial epithelial cells and a coeliac-induced inflammation model of mice by Staphylococcus aureus (S. aureus) were established, and significantly lower intracellular S. aureus levels of CEF-heLDL group than CEF-free group (P < 0.001) was observed. The antibacterial efficacy was sustained for 24 h. Up to 400 mg/kg of CEF-heLDL, 20 times the clinical practice, were intraperitoneally administrated, and no significant toxicity signs on mice were observed. HeLDLs is an effective, safe, and cheap drug carrier, and could also be used for transmembrane delivering other antibiotics.

Evolution of PIN gene family between monocotyledons and dicotyledons and VvPIN1 negatively regulates freezing tolerance in transgenic Arabidopsis.

The PIN-FORMED (PIN) proteins mediate the auxin flow throughout the plant and have been identified in many species. However, evolution differences in the PIN gene families have not been systematically analyzed, and their functions under abiotic stresses in grape are largely unexplored. In this study, 373 PIN genes were identified from 25 species and divided into 3 subgroups. Physicochemical properties analysis indicated that most of the PIN proteins were unstable alkaline hydrophobic proteins in nature. The synteny analysis showed that the PINs contained strong gene duplication. Motif composition revealed that PIN gene sequence differences between monocotyledons and dicotyledons were due to evolutionary-induced base loss, and the loss was more common in dicotyledonous. Meanwhile, the codon usage bias showed that the PINs showed stronger codon preference in monocotyledons, monocotyledons biased towards C3s and G3s, and dicotyledons biased towards A3s and T3s. In addition, the VvPIN1 can interact with VvCSN5. Significantly, under freezing treatment, the ion leakage, O 2 · - $$ \left({O}_2^{\cdotp -}\right) $$ , H2O2, and malondialdehyde (MDA) were obviously increased, while the proline (Pro) content, peroxidase (POD) activity, and glutathione (GSH) content were decreased in VvPIN1-overexpressing Arabidopsis compared to the wild type (WT). And quantitative real-time PCR (qRT-PCR) showed that AtICE1, AtICE2, AtCBF1, AtCBF2, and AtCBF3 were down-regulated in overexpression lines. These results demonstrated that VvPIN1 negatively regulated the freezing tolerance in transgenic Arabidopsis. Collectively, this study provides a novel insight into the evolution and a basis for further studies on the biological functions of PIN genes in monocotyledons and dicotyledons.

Targeted metabolomics study of fatty-acid metabolism in lean metabolic-associated fatty liver disease patients.

BACKGROUND: The annual incidence of metabolic-associated fatty liver disease (MAFLD) in China has been increasing and is often overlooked owing to its insidious characteristics. Approximately 50% of the patients have a normal weight or are not obese. They are said to have lean-type MAFLD, and few studies of such patients are available. Because MAFLD is associated with abnormal lipid metabolism, lipid-targeted metabolomics was used in this study to provide experimental evidence for early diagnosis and pathogenesis. AIM: To investigate the serum fatty-acid metabolic characteristics in lean-type MAFLD patients using targeted serum metabolomic technology. METHODS: Between January and June 2022, serum samples were collected from MAFLD patients and healthy individuals who were treated at Shanghai Putuo District Central Hospital for serum metabolomics analysis. Principal component analysis and orthogonal partial least squares-discriminant analysis models were developed, and univariate analysis was used to screen for biomarkers of lean-type MAFLD and analyze metabolic pathways. UPLC-Q-Orbitrap/MS content determination was used to determine serum palmitic acid (PA), oleic acid (OA), linoleic acid (LA), and arachidonic acid (AA) levels in lean-type MAFLD patients. RESULTS: Urea nitrogen and uric acid levels were higher in lean-type MAFLD patients than in healthy individuals (P < 0.05). Alanine transaminase and cholinesterase levels were higher in lean-type MAFLD patients than in healthy individuals (P < 0.01). The expression of high-density lipoprotein and apolipoprotein A-1 were lower in lean-type MAFLD patients than in healthy individuals (P < 0.05) and the expression of triglycerides and fasting blood glucose were increased (P < 0.01). A total of 65 biomarkers that affected the synthesis and metabolism of fatty acids were found with P < 0.05 and variable importance in projection > 1". The levels of PA, OA, LA, and AA were significantly increased compared with healthy individuals. CONCLUSION: The metabolic profiles of lean-type MAFLD patients and healthy participants differed significantly, yielding 65 identified biomarkers. PA, OA, LA, and AA exhibited the most significant changes, offering valuable clinical guidance for prevention and treatment of lean-type MAFLD.