Mixed effects of ambient air pollutants on oocyte-related outcomes: A novel insight from women undergoing assisted reproductive technology.

Air pollution is widely acknowledged as a significant risk factor for human health, especially reproductive health. Nevertheless, many studies have disregarded the potentially mixed effects of air pollutants on reproductive outcomes. We performed a retrospective cohort study involving 8048 women with 9445 cycles undergoing In Vitro Fertilization (IVF) and Intracytoplasmic Sperm Injection (ICSI) in China, from 2017 to 2021. A land-use random forest model was applied to estimate daily residential exposure to air pollutants, including sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), ozone (O3), and fine particulate matter (PM2.5). Individual and joint associations between air pollutants and oocyte-related outcomes of ART were evaluated. In 90 days prior to oocyte pick-up to oocyte pick-up (period A), NO2, O3 and CO was negatively associated with total oocyte yield. In the 90 days prior to oocyte pick-up to start of gonadotropin medication (Gn start, period B), there was a negative dose-dependent association of exposure to five air pollutants with total oocyte yield and mature oocyte yield. In Qgcomp analysis, increasing the multiple air pollutants mixtures by one quartile was related to reducing the number of oocyte pick-ups by -2.00 % (95 %CI: -2.78 %, -1.22 %) in period A, -2.62 % (95 %CI: -3.40 %, -1.84 %) in period B, and -0.98 % (95 %CI: -1.75 %, -0.21 %) in period C. During period B, a 1-unit increase in the WQS index of multiple air pollutants exposure was associated with fewer number of total oocyte (-1.27 %, 95 %CI: -2.16 %, -0.36 %) and mature oocyte (-1.42 %, 95 %CI: -2.41 %, -0.43 %). O3 and NO2 were major contributors with adverse effects on the mixed associations. Additionally, period B appears to be the susceptible window. Our study implies that exposure to air pollution adversely affects oocyte-related outcomes, which raises concerns about the potential adverse impact of air pollution on women's reproductive health.

Engineered probiotic cocktail with two cascade metabolic Escherichia coli for the treatment of hyperlysinemia.

Engineering probiotics have emerged as a potential strategy for the treatment of metabolic diseases. However, due to the exceptional complexity of these metabolic disorders and the intricate relationship between gut microbes, it is difficult to achieve an ideal therapeutic effect in a specific metabolic disorder using only a single engineered strain. In this work, we proposed a probiotic cocktail strategy by engineering two cascade metabolic bacteria to treat hyperlysinemia, an inherited lysine metabolic disorder with loss of α-aminoadipate semialdehyde synthase (AASS) activity. A probiotic E. coli Nissle 1917 strain EcNT (pTLS) with a heterologous enzyme pathway in Saccharomyces cerevisiae was engineered to metabolize the excess lysine. Another one EcNT (pK25) was engineered to consume the products of lysine metabolism. The bacterial cocktail enables the maintenance of a metabolic cascade with AASS-like functional activity to maintain the blood lysine concentrations and downstream metabolites. In vitro experimental results showed that the cocktail bacteria had a better metabolic capacity and metabolites balance at a ratio of EcNT (pTLS) and EcNT (pK25) of 1:2. Feeding of the cocktail bacteria to the mouse model effectively reduced the concentration of lysine and balanced saccharopine in the plasma of hyperlysinemia-like mice. These findings not only provide a promising strategy of probiotic stains for the treatment of hyperlysinemia but also highlight the potential of engineered cascade cocktails to intervene and even cure other inherited metabolic diseases.

A Study on the Effect of Lidocaine-Assisted Non-Coring Needle Placement Using Painless Encircling Puncture in Children with Totally Implantable Venous Access Device.

Purpose: This study aimed to investigate the maintenance effect of two puncture methods using non-coring needles in children with totally implantable venous access device (TIVAD). Methods: The 110 children who received TIVAD implantation for short bowel syndrome and solid tumors in our department from 2021.12 to 2022.12 were selected as the study subjects. Blinded method was used and divided into experimental group and control group according to random number table The experimental group underwent painless surround puncture method to place the needles and compound lidocaine ointment for topical anesthesia, while the control group underwent traditional puncture method to complete this operation. The effects of the two puncture methods on pain, catheter seal fluid volume, and catheter occlusion rate were evaluated using the Facial Pain Scale Revised, Behavioral Assessment Scale, and in vitro digital subtraction angiography test. Results: In the control group, the degree of puncture pain was mild in 5 patients, moderate in 19 patients, and severe in 28 patients; the amount of catheter sealing solution was 9.32 ± 1.32 mL, and the catheter occlusion rate was 25.00%. In the experimental group, the degree of puncture pain was mild in 16 patients, moderate in 22 patients, and severe in 16 patients; the amount of sealing solution was 7.66 ± 1.08 mL, and the blocking rate was 9.26%. The total pain score in the experimental group was lower than that in the control group (5.23±6.17 VS 7.89±2.38). The difference between the two groups had statistical significance (P < 0.05). Conclusion: The use of the painless surround puncture method can effectively reduce the pain experienced by children during puncture, decrease the volume of catheter sealing fluid, reduce the rate of catheter blockage, provide a valuable basis for enhancing the maintenance effect of TIVAD in clinical practice for children.

Nondestructive Detection of Sunflower Seed Vigor and Moisture Content Based on Hyperspectral Imaging and Chemometrics.

Sunflower is an important crop, and the vitality and moisture content of sunflower seeds have an important influence on the sunflower's planting and yield. By employing hyperspectral technology, the spectral characteristics of sunflower seeds within the wavelength range of 384-1034 nm were carefully analyzed with the aim of achieving effective prediction of seed vitality and moisture content. Firstly, the original hyperspectral data were subjected to preprocessing techniques such as Savitzky-Golay smoothing, standard normal variable correction (SNV), and multiplicative scatter correction (MSC) to effectively reduce noise interference, ensuring the accuracy and reliability of the data. Subsequently, principal component analysis (PCA), extreme gradient boosting (XGBoost), and stacked autoencoders (SAE) were utilized to extract key feature bands, enhancing the interpretability and predictive performance of the data. During the modeling phase, random forests (RFs) and LightGBM algorithms were separately employed to construct classification models for seed vitality and prediction models for moisture content. The experimental results demonstrated that the SG-SAE-LightGBM model exhibited outstanding performance in the classification task of sunflower seed vitality, achieving an accuracy rate of 98.65%. Meanwhile, the SNV-XGBoost-LightGBM model showed remarkable achievement in moisture content prediction, with a coefficient of determination (R2) of 0.9715 and root mean square error (RMSE) of 0.8349. In conclusion, this study confirms that the fusion of hyperspectral technology and multivariate data analysis algorithms enables the accurate and rapid assessment of sunflower seed vitality and moisture content, providing robust tools and theoretical support for seed quality evaluation and agricultural production practices. Furthermore, this research not only expands the application of hyperspectral technology in unraveling the intrinsic vitality characteristics of sunflower seeds but also possesses significant theoretical and practical value.

Exploring the neuroprotection of the combination of astragaloside A, chlorogenic acid and scutellarin in treating chronic cerebral ischemia via network analysis and experimental validation.

Chronic cerebral ischemia (CCI) primarily causes cognitive dysfunction and other neurological impairments, yet there remains a lack of ideal therapeutic medications. The preparation combination of Astragalus membranaceus (Fisch.) Bunge and Erigeron breviscapus (Vant.) Hand.-Mazz have been utilized to ameliorate neurological dysfunction following cerebral ischemia, but material basis of its synergy remains unclear. The principal active ingredients and their optimal proportions in this combination have been identified through the oxygen and glucose deprivation (OGD) cell model, including astragaloside A, chlorogenic acid and scutellarin (ACS), and its efficacy in enhancing the survival of OGD PC12 cells surpasses that of the combination preparation. Nevertheless, mechanism of ACS against CCI remains elusive. In this study, 63 potential targets of ACS against CCI injury were obtained by network pharmacology, among which AKT1, CASP3 and TNF are the core targets. Subsequent analysis utilizing KEGG and GO suggested that PI3K/AKT pathway may play a crucial role for ACS in ameliorating CCI injury. Then, a right unilateral common carotid artery occlusion (rUCCAO) mouse model and an OGD PC12 cell model were established to replicate the pathological processes of CCI in vivo and in vitro. These models were utilized to explore the anti-CCI effects of ACS and its regulatory mechanisms, particularly focusing on PI3K/AKT pathway. The results showed that ACS facilitated the restoration of cerebral blood flow in CCI mice, enhanced the function of the central cholinergic nervous system, protected against ischemic nerve cell and mitochondrial damage, and improved cognitive function and other neurological impairments. Additionally, ACS upregulated the expression of p-PI3K, p-AKT, p-GSK3ß and Bcl-2, and diminished the expression of Cyto-c, cleaved Caspase-3 and Bax significantly. However, the PI3K inhibitor (LY294002) partially reversed the downregulation of Bax, Cyto-c and cleaved Caspase-3 expression as well as the upregulation of p-AKT/AKT, p-GSK3ß/GSK3ß, and Bcl-2/Bax ratios. These findings suggest that ACS against neuronal damage in cerebral ischemia may be closely related to the activation of PI3K/AKT pathway. These results declared first time ACS may become an ideal candidate drug against CCI due to its neuroprotective effects, which are mediated by the activated PI3K/AKT pathway mitigates mitochondrial damage and prevents cell apoptosis.

Development of nanoparticles incorporated with quercetin and ACE2-membrane as a novel therapy for COVID-19.

INTRODUCTION: Angiotensin-converting enzyme 2 (ACE2) and AXL tyrosine kinase receptor are known to be involved in the SARS-CoV-2 entry of the host cell. Therefore, targeting ACE2 and AXL should be an effective strategy to inhibit virus entry into cells. However, developing agents that can simultaneously target ACE2 and AXL remains a formidable task. The natural compound quercetin has been shown to inhibit AXL expression. MATERIALS AND METHODS: In this study, we employed PLGA nanoparticles to prepare nanoparticles encapsulated with quercetin, coated with ACE2-containing cell membranes, or encapsulated with quercetin and then coated with ACE-2-containing cell membranes. These nanoparticles were tested for their abilities to neutralize or inhibit viral infection. RESULTS: Our data showed that nanoparticles encapsulated with quercetin and then coated with ACE2-containing cell membrane inhibited the expression of AXL without causing cytotoxic activity. Nanoparticles incorporated with both quercetin and ACE2-containing cell membrane were found to be able to neutralize pseudo virus infection and were more effective than free quercetin and nanoparticles encapsulated with quercetin at inhibition of pseudo virus and SARS-CoV-2 infection. CONCLUSIONS: We have shown that the biomimetic nanoparticles incorporated with both ACE-2 membrane and quercetin showed the most antiviral activity and may be further explored for clinical application.

[Discussion and analysis the value of supine median³ nystagmus in the diagnosis and treatment of HC-BPPV].

Objective:To explore the clinical value of supine median³ nystagmus in the accurate diagnosis of horizontal semicircular canal benign paroxysmal positional vertigo（HC-BPPV）. Methods:A total of 187 patients with HC-BPPV admitted to the First Affiliated Hospital of Xi'an Jiaotong University from June 2020 to March 2021 were selected. Among them 42 cases of Cupulolithiasis and 145 cases of Canalithiasis. The nystagmus parameters of patients left and right supine position and supine median³ position were recorded in detail by RART. According to the direction of supine median³ nystagmus, patients were divided into three groups: group A（nystagmus to weak side）, group B（nystagmus to strong side）, group C（negative nystagmus）. The canalith repositioning manoeuvres（CRM） was carried out by utility of an automatic vestibular function diagnosis and therapy system（SRM-IV）. The cure rate of CRM in three groups of HC-BPPV patients was compared, Multivariate logistic regression analysis was performed to analyze the influencing factors of CRM for HC-BPPV. Results:The cure rates of group A, group B and group C were 81.58%, 16.13% and 56.25%, respectively. The difference among the three groups was statistically significant. Then a pairwise comparison of group A, B and C, the difference was statistically significant（χ²A-B=40.294,P<0.001,χ²B-C=14.528, P<0.001,χ²A-C=11.606, P=0.001）; the results of multivariate logistic regression analysis showed that the direction of supine median³ nystagmus and BMI were the influencing factors of CRM for HC-BPPV. Conclusion:The direction, intensity and duration of supine median³ nystagmus play an important role in determining the responsibility semicircular canal of HC-BPPV.

High LGALS3 expression induced by HCP5/hsa-miR-27b-3p correlates with poor prognosis and tumor immune infiltration in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is widely recognized for its unfavorable prognosis. Increasing evidence has revealed that LGALS3 has an essential function in initiating and developing several malignancies in humans. Nevertheless, thorough analysis of the expression profile, clinical prognosis, pathway prediction, and immune infiltration of LGALS3 has not been fully explored in HCC. METHODS: In this study, an initial pan-cancer analysis was conducted to investigate the expression and prognosis of LGALS3. Following a comprehensive analysis, which included expression analysis and correlation analysis, noncoding RNAs that contribute to the overexpression of LGALS3 were subsequently identified. This identification was further validated using HCC clinical tissue samples. TIMER2 and GEPIA2 were employed to examine the correlation between LGALS3 and HCP5 with immunological checkpoints, cell chemotaxis, and immune infiltration in HCC. The R program was applied to analyze the expression distribution of immune score in in HCC patients with high and low LGALS3 expression. The expression profiles of immune checkpoints were also analyzed. Use R to perform GSVA analysis in order to explore potential signaling pathways. RESULTS: First, we conducted pan-cancer analysis for LGALS3 expression level through an in-depth analysis of public databases and found that HCC has a high LGALS3 gene and protein expression level, which were then verified in clinical HCC specimens. Meanwhile, high LGALS3 gene expression is related to malignant progression and poor prognosis of HCC. Univariate and multivariate analyses confirmed that LGALS3 could serve as an independent prognostic marker for HCC. Next, by combining comprehensive analysis and validation on HCC clinical tissue samples, we hypothesize that the HCP5/hsa-miR-27b-3p axis could serve as the most promising LGALS3 regulation mechanism in HCC. KEGG and GO analyses highlighted that the LGALS3-related genes were involved in tumor immunity. Furthermore, we detected a significant positive association between LGALS3 and HCP5 with immunological checkpoints, cell chemotaxis, and immune infiltration. In addition, high LGALS3 expression groups had significantly higher immune cell scores and immune checkpoint expression levels. Finally, GSVA analysis was performed to predict potential signaling pathways linked to LGALS3 and HCP5 in immune evasion and metabolic reprogramming of HCC. CONCLUSIONS: Our findings indicated that the upregulation of LGALS3 via the HCP5/hsa-miR-27b-3p axis is associated with unfavorable prognosis and increased tumor immune infiltration in HCC.

Comparative analysis of biofilm characterization of probiotic Escherichia coli.

Biofilms are thought to play a vital role in the beneficial effects of probiotic bacteria. However, the structure and function of probiotic biofilms are poorly understood. In this work, biofilms of Escherichia coli (E. coli) Nissle 1917 were investigated and compared with those of pathogenic and opportunistic strains (E. coli MG1655, O157:H7) using crystal violet assay, confocal laser scanning microscopy, scanning electron microscopy and FTIR microspectroscopy. The study revealed significant differences in the morphological structure, chemical composition, and spatial heterogeneity of the biofilm formed by the probiotic E. coli strain. In particular, the probiotic biofilm can secrete unique phospholipid components into the extracellular matrix. These findings provide new information on the morphology, architecture and chemical heterogeneity of probiotic biofilms. This information may help us to understand the beneficial effects of probiotics for various applications.

Case Report: Two cases of advanced primary cardiac angiosarcoma treated with anlotinib and a retrospective analysis of the literature.

Primary cardiac angiosarcoma is a rare malignant soft-tissue sarcoma derived from vascular endothelial cells or lymphatic endothelial cells, with a high malignancy, poor prognosis, and a lack of effective medical therapy. This article reports on two patients with primary cardiac angiosarcoma who received first-line treatment with multi-targeted anti-angiogenic agent, anlotinib monotherapy. The treatment rapidly controlled pleural and pericardial effusion, significantly reduced the tumor, improved symptoms, and showed satisfactory recent efficacy. This indicates that anlotinib offers a new first-line treatment option for advanced primary cardiac angiosarcoma.

First-principles prediction of one-dimensional conductive metallic organic polymers as ultrahigh energy density anode for lithium-ion batteries.

Metal-Organic Polymers (MOPs) have attracted growing attention for lithium-ion battery (LIB) applications due to their merits in orderly ionic transportation and robust structure stability in electrochemical reactions. However, they suffer from poor electronic conductivity. In this work, we apply first-principles density functional theory to explore the potential of three one-dimensional (1D) electrically conductive C6H2S4TM (TM = Fe, Co, and Ni) MOPs with the π-d conjugated coordination as anode materials for Li+ ions storage. Our theoretical results reveal that these 1D MOPs possess a superior theoretical capacity of over 748 mA h g-1. In particular, the 1D C6H2S4Ni MOP shows an exceptional theoretical specific capacity of 1110 mA h g-1 based on the three-electron transferring reaction, which significantly outperforms the traditional graphite-based anode material in LIBs. Moreover, the resonant charge transfer between Ni metal and ligand within the 1D C6H2S4Ni MOP reduces the diffusion energy barrier of the Li atoms when they migrate on the surface of the MOP. The ultrahigh theoretical specific capacity of the C6H2S4Ni MOP predicts that it can be a promising anode material for LIBs.

Management of neurotoxicity syndrome complicated by autologous hematopoietic stem cell transplantation bridge to chimeric antigen receptor T-Cell therapy: A case report.

Effectively addressing the challenges posed by relapsed and refractory diffuse large B-cell lymphoma, particularly when employing autologous hematopoietic stem cell transplantation and CAR-T therapy, requires a comprehensive approach to treatment and nursing. This case report emphasizes a nursing strategy focused on managing neurotoxicity post-CAR-T therapy. Nursing interventions include the identification of neurotoxicity symptoms, neuropsychiatric management, careful support during lumbar puncture and intrathecal administration, psychological assistance, and adaptive nutritional guidance. The diligent application of treatment and nursing care resulted in a remarkable recovery for the patient, as evidenced by the alleviation of central facial paralysis, improvement in swallowing function (from Grade 4 to Grade 2), and enhanced vocalization. Consistent and specialized nursing care is paramount for effectively managing complications, especially neurotoxicity, in patients undergoing CAR-T therapy. A thorough monitoring of symptoms and personalized care contribute to optimizing treatment outcomes and ensuring patient safety.

Editorial for the Special Issue "Environmental Exposure and Reproductive Health".

In recent decades, the decline in human fertility has emerged as a significant public health concern, garnering global attention [...].

Co-exposure to 55 endocrine-disrupting chemicals linking diminished sperm quality: Mixture effect, and the role of seminal plasma docosapentaenoic acid.

Isolated effects of single endocrine-disrupting chemicals (EDCs) on male reproductive health have been studied extensively, but their mixture effect remains unelucidated. Previous research has suggested that consuming diet enriched in omega-3 polyunsaturated fatty acids (PUFA) might be beneficial for reproductive health, whether omega-3 PUFA could moderate the effect of EDCs mixture on semen quality remains to be explored. In this study of 155 male recruited from a reproductive health center in China, we used targeted-exposomics to simultaneously measure 55 EDCs in the urine for exposure burden. Regression analyses were restricted to highly detected EDCs (≥55%, n = 34), and those with consistently elevated risk were further screened and brought into mixture effect models (Bisphenol A, ethyl paraben, methyl paraben [MeP], benzophenone-1 [BP1], benzophenone-3, mono(3-carboxypropyl) phthalate [MCPP]). Bayesian Kernel Machine Regression (BKMR) and quantile-based g-computation (QGC) models demonstrated that co-exposure to top-ranked EDCs was related to reduced sperm total (ß = -0.18, 95%CI: -0.29 - -0.07, P = 0.002) and progressive motility (ß = -0.27, 95%CI: -0.43 - -0.10, P = 0.002), but not to lower semen volume. BP1, MeP and MCPP were identified as the main effect driver for deteriorated sperm motion parameters using mixture model analyses. Seminal plasma fatty acid profiling showed that high omega-3 PUFA status, notably elevated docosapentaenoic acid (DPA, C22:5n-3) status, moderated the association between MCPP and sperm motion parameters (total motility: ß = 0.26, 95%CI: 0.01 - -0.51, Pinteraction = 0.047; progressive motility: ß = 0.64, 95%CI: 0.23 - 1.05, Pinteraction = 0.003). Co-exposure to a range of EDCs is mainly associated with deteriorated sperm quality, but to a lesser extent on sperm quantity, high seminal plasma DPA status might be protective against the effect. Our work emphasizes the importance of exposomic approach to assess chemical exposures and highlighted a new possible intervention target for mitigating the potential adverse effect of EDCs on semen quality.

Effects of long-term exposure to ambient fine particulate matter and its specific components on blood pressure and hypertension incidence.

BACKGROUND: Epidemiological evidence on the association of PM2.5 (particulate matter with aerodynamic diameter ≤ 2.5 µm) and its specific components with hypertension and blood pressure is limited. METHODS: We applied information of participants from the World Health Organization's (WHO) Study on Global Ageing and Adult Health (SAGE) to estimate the associations of long-term PM2.5 mass and its chemical components exposure with blood pressure (BP) and hypertension incidence in Chinese adults ≥ 50 years during 2007-2018. Generalized linear mixed model and Cox proportional hazard model were applied to investigate the effects of PM2.5 mass and its chemical components on the incidence of hypertension and BP, respectively. RESULTS: Each interquartile range (IQR = 16.80 µg/m3) increase in the one-year average of PM2.5 mass concentration was associated with a 17 % increase in the risk of hypertension (HR = 1.17, 95 % CI: 1.10, 1.24), and the population attributable fraction (PAF) was 23.44 % (95 % CI: 14.69 %, 31.55 %). Each IQR µg/m3 increase in PM2.5 exposure was also related to increases of systolic blood pressure (SBP) by 2.54 mmHg (95 % CI:1.99, 3.10), and of diastolic blood pressure (DBP) by 1.36 mmHg (95 % CI: 1.04, 1.68). Additionally, the chemical components of SO42-, NO3-, NH4+, OM, and BC were also positively associated with an increased risk of hypertension incidence and elevated blood pressure. CONCLUSIONS: These results indicate that long-term exposure to PM2.5 mass and its specific components may be major drivers of escalation in hypertension diseases.

Prenatal phthalate exposure and neurodevelopmental differences in twins at 2 years of age.

BACKGROUND: Previous studies of singletons evaluating prenatal phthalate exposure and early neurodevelopment reported mixed results and the associations could be biased by parental, obstetrical, and genetic factors. METHODS: A co-twin control design was employed to test whether prenatal phthalate exposure was associated with children's neurocognitive development. We collected information from 97 mother-twin pairs enrolled in the Wuhan Twin Birth Cohort between March 2016 and October 2018. Fourteen phthalate metabolites were measured in maternal urine collected at each trimester. Neurodevelopmental differences in twins at the age of two were examined as the outcome of interest. Multiple informant model was used to examine the covariate-adjusted associations of prenatal phthalate exposure with mental development index (MDI) and psychomotor development index (PDI) scores assessed at 2 years of age based on Bayley Scales of Infant Development (Second Edition). This model also helps to identify the exposure window of susceptibility. RESULTS: Maternal urinary levels of mono-2-ethyl-5-oxohexyl phthalate (MEOHP) (ß = 1.91, 95% CI: 0.43, 3.39), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) (ß = 1.56, 95% CI: 0.33, 2.79), and the sum of di-(2-ethylhexyl) phthalate metabolites (∑DEHP) (ß = 1.85, 95% CI: 0.39, 3.31) during the first trimester showed the strongest and significant positive associations with intra-twin MDI difference. When stratified with twin chorionicity, the positive associations of monoethyl phthalate (MEP), monoisobutyl phthalate (MiBP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), individual DEHP metabolites, and ∑DEHP exposure during pregnancy with intra-twin neurodevelopmental differences were more significant in monochorionic diamniotic (MCDA) twins than those in dichorionic diamniotic (DCDA) twins. CONCLUSIONS: Neurodevelopmental differences in MCDA twins were strongly associated with prenatal phthalate exposure. Our findings warrant further confirmation in longitudinal studies with larger sample sizes.

Lily (Lilium spp.) LhERF4 negatively affects anthocyanin biosynthesis by suppressing LhMYBSPLATTER transcription.

Anthocyanins are among the main pigments involved in the colouration of Asiatic hybrid lily (Lilium spp.). Ethylene, a plant ripening hormone, plays an important role in promoting plant maturation and anthocyanin biosynthesis. However, whether and how ethylene regulates anthocyanin biosynthesis in lily tepals have not been characterized. Using yeast one-hybrid screening, we previously identified an APETALA2 (AP2)/ETHYLENE RESPONSE FACTOR (ERF) named LhERF4 as a potential inhibitor of LhMYBSPLATTER-mediated negative regulation of anthocyanin biosynthesis in lily. Here, transcript and protein analysis of LhERF4, a transcriptional repressor, revealed that LhERF4 directly binds to the promoter of LhMYBSPLATTER. In addition, overexpression of LhERF4 in lily tepals negatively regulates the expression of key structural genes and the total anthocyanin content by suppressing the LhMYBSPLATTER gene. Moreover, the LhERF4 gene inhibits anthocyanin biosynthesis in response to ethylene, affecting anthocyanin accumulation and pigmentation in lily tepals. Collectively, our findings will advance and elucidate a novel regulatory network of anthocyanin biosynthesis in lily, and this research provides new insight into colouration regulation.

Nano-modified viruses prime the tumor microenvironment and promote the photodynamic virotherapy in liver cancer.

BACKGROUND: As of 2020, hepatocellular carcinoma (HCC), a form of liver cancer, stood as the third most prominent contributor to global cancer-related mortality. Combining immune checkpoint inhibitors (ICI) with other therapies has shown promising results for treating unresectable HCC, offering new opportunities. Recombinant adeno-associated viral type 2 (AAV2) virotherapy has been approved for clinical use but it efficacy is stifled through systemic administration. On the other hand, iron oxide nanoparticles (ION) can be cleared via the liver and enhance macrophage polarization, promoting infiltration of CD8+ T cells and creating a more favorable tumor microenvironment for immunotherapy. METHODS: To enhance the efficacy of virotherapy and promote macrophage polarization towards the M1-type in the liver, ION-AAV2 were prepared through the coupling of ION-carboxyl and AAV2-amine using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC)/N-hydroxysulfosuccinimide (Sulfo-NHS). Efficacy after systemic delivery of ION-AAV2 in an orthotopic HCC model was evaluated. RESULTS: After 28 days, the tumor weight in mice treated with ION-AAV2 was significantly reduced by 0.56-fold compared to the control group. The ION-AAV2 treatment led to an approximate 1.80-fold increase in the level of tumor associated M1-type macrophages, while the number of M2-type macrophages was reduced by 0.88-fold. Moreover, a proinflammatory response increased the population of tumor-infiltrating CD8+ T cells in the ION-AAV2 group. This transformation converted cold tumors into hot tumors. CONCLUSIONS: Our findings suggest that the conjugation of ION with AAV2 could be utilized in virotherapy while simultaneously exploiting macrophage-modulating cancer immunotherapies to effectively suppress HCC growth.