Molecular dynamics investigation of IEPOX chemical behavior at the interface and in the bulk phase of acidic aerosols.

Isoprene epoxydiol (IEPOX) is an important reactive gas-phase intermediate produced by the photooxidation of isoprene under low NOx conditions, playing a key role in the formation of secondary organic aerosols (SOA). Previous studies have mostly focused on the liquid-phase reactions of IEPOX within aerosols; however, interfacial heterogeneous chemical reactions are equally important in SOA formation. This study systematically explores the reaction mechanisms of IEPOX at the acidic aerosol interface and in the bulk phase using classical molecular dynamics (MD) and ab initio molecular dynamics simulations (AIMD). The study found that the free energy of IEPOX at the aerosol interface significantly decreases, indicating that interfacial heterogeneous chemical reactions are indispensable for the formation of IEPOX-derived SOA. The research reveals the formation pathways of 2-methyltetrols (2-MTO) and 1,3,4-trihydroxy-3-methylbutan-2-yl sulfates (2-MTOOS), finding that the protonation of the epoxy O atom and the cleavage of the C-O bond are the rate-controlling steps, while the nucleophilic addition is a spontaneous process. Through multiple sets of simulations, it was observed that the formation frequency of 2-MTO at the acidic aerosol interface and in the bulk phase reached 53.8%, significantly higher than the 30.8% of 2-MTOOS, which is consistent with field observation data. Additionally, through metadynamics (MTD) simulations, it was suggested that IEPOX could undergoes acid-catalyzed ring-opening reactions at the interface, potentially followed by the transfer of H atoms from primary alcohols into the aerosol, leading to the possible formation of the intermediate product 3-methylbut-3-ene-1,2,4-triol (one of the proposed structures of C5-alkene triols). These findings provide new insights into the formation mechanism of IEPOX-derived SOA and offer a scientific basis for future studies on their physicochemical properties and atmospheric fate.

A manganese-doped layered double hydroxide loaded with lactate oxidase and DNA repair inhibitors for synergistically enhanced tumor immunotherapy.

Tumor immunotherapy has gained more and more attention in tumor treatment. However, the accumulation of lactic acid in tumor tissue inhibits the response of immune cells to form an immunosuppressive microenvironment (ISME). To reverse the ISME, an acid-responsive nanoplatform (termed as MLLN@HA) is reported for synergistically enhanced tumor immunotherapy. MLLN@HA is constructed by the co-loading of lactate oxidase (LOX) and DNA repair inhibitor (NU7441) in a manganese-doped layered double hydroxide (Mn-LDH), and then modified with hyaluronic acid (HA) for tumor-targeted delivery. After endocytosis by tumor cells, MLLN@HA decomposes and releases LOX, NU7441 and Mn2+ ions in the acidic tumor microenvironment. The released LOX catalyzes the conversion of lactic acid into hydrogen peroxide (H2O2), which not only alleviates the ISME, but also provides reactants for the Mn2+-mediated Fenton-like reaction to enhance chemodynamic therapy (CDT). Released NU7441 prevents CDT-induced DNA damage from being repaired, thereby increasing double-stranded DNA (dsDNA) fragments within tumor cells. Importantly, the released Mn2+ ions enhance the sensitivity of cyclic GMP-AMP synthase (cGAS) to dsDNA fragments, and activate the stimulator of interferon genes (STING) to induce an anti-tumor immune response. Such an orchestrated immune-boosting strategy ultimately achieves effective tumor growth inhibition and prevents tumor lung metastasis. STATEMENT OF SIGNIFICANCE: To improve the efficacy of tumor immunotherapy, an innovative acid-responsive MLLN@HA nanoplatform was developed for synergistically enhanced tumor immunotherapy. The MLLN@HA actively targets to tumor cells through the interaction of HA with CD44, and then degrades to release LOX, NU7441 and Mn2+ ions in the acidic tumor microenvironment. The released LOX generates H2O2 for the Mn2+-mediated Fenton reaction and reverses the ISME by consuming lactate. NU7441 prevents DNA damage repair, leading to an increased concentration of free DNA fragments, while Mn2+ ions activate the cGAS-STING pathway, enhancing the systemic anti-tumor immune response. The orchestrated immune-boosting nanoplatform effectively inhibits tumor growth and lung metastasis, presenting a promising strategy for cancer treatment.

A biodegradable calcium sulfite nanoreactor for pH triggered gas therapy in combination with chemotherapy.

As a gasotransmitter, endogenous sulfur dioxide (SO2) plays an important role in cardiovascular regulation. In addition, excessive SO2 can react with overexpressed hydrogen peroxide (H2O2) in tumor cells to generate toxic radicals, which can induce severe oxidative damage to tumor cells and result in cell apoptosis. This highlights the potential of SO2 in oncotherapy. However, the limited availability of endogenous H2O2 and uncontrolled release of SO2 gas significantly impede the effectiveness of SO2 gas therapy. To address this challenge, a biodegradable calcium sulfite (CS) nanocarrier loaded with 10-hydroxycamptothecin (HCPT) was developed for tumor pH-triggered SO2 gas therapy in combination with chemotherapy. This nanoreactor could be degraded in an acidic tumor microenvironment to release SO2 gas and the HCPT drug. The released SO2 gas induced serious oxidative damage to tumor cells by depleting glutathione (GSH) and generating toxic radicals through a reaction with intracellular H2O2. Simultaneously, the HCPT drug promoted tumor cell apoptosis through chemotherapy and boosted SO2 gas therapy by elevating the H2O2 level within the tumor cells. Consequently, the combination of SO2 gas therapy and chemotherapy provided a promising approach for effective tumor treatment.

Stereochemical insights into enantioselective antiplasmodial lignanamides from the twigs and leaves of Solanum erianthum.

Stereochemical investigations on the twigs and leaves of Solanum erianthum afforded five pairs of lignanamide enantiomers and a previously undescribed phenolic amide (3). Particularly, two pairs of previously undescribed lignanamide racemates (1a/1b-2a/2b) represent the first case of natural products that feature an unreported 5/5-fused N/O-biheterocyclic core. Their structures, including the absolute configurations, were determined unambiguously by using spectroscopic analyses and electronic circular dichroism calculations. A speculative biogenetic pathway for 1-3 was proposed. Interestingly, these lignanamides exhibited enantioselective antiplasmodial activities against drug-sensitive Plasmodium falciparum 3D7 strain and chloroquine-resistant Plasmodium falciparum Dd2 strain, pointing out that chirality plays an important role in drug development.

Let-7b-5p promotes triptolide-induced growth-inhibiting effects in glioma by targeting IGF1R.

Glioma is one of the most common malignancies of the central nervous system. The therapeutic effect has not been satisfactory despite advances in comprehensive treatment techniques. Our previous studies have found that triptolide inhibits glioma proliferation through the ROS/JNK pathway, but in-depth mechanisms need to be explored. Recent studies have confirmed that miRNAs may function as tumor suppressor genes or oncogenes and be involved in cancer development and progression. In this study, we found that let-7b-5p expression levels closely correlated with WHO grades and overall survival in patients in tumor glioma-CGGA-mRNAseq-325, and the upregulation of let-7b-5p can inhibit the proliferation and induce apoptosis of glioma cells. Functionally, upregulation of let-7b-5p increased the inhibitory effect on cell viability and colony formation caused by triptolide and promoted the apoptosis rate of triptolide-treated U251 cells. Conversely, downregulation of let-7b-5p had the opposite effect, indicating that let-7b-5p is a tumor suppressor miRNA in glioma cells. Moreover, target prediction, luciferase reporter assays and functional experiments revealed that IGF1R was a direct target of let-7b-5p. In addition, upregulation of IGF1R reversed the triptolide-regulated inhibition of cell viability but promoted glioma cell apoptosis and activated the ROS/JNK signaling pathway induced by triptolide. The results obtained in vivo experiments substantiated those from the in vitro experiments. In summary, the current study provides evidence that triptolide inhibits the growth of glioma cells by regulating the let-7b-5p-IGF1R-ROS/JNK axis in vitro and in vivo. These findings may provide new ideas and potential targets for molecularly targeted therapies for comprehensive glioma treatment.

Sesquiterpenoids and Cytochalasins with Immunosuppressive Activity from Sonchus wightianus.

The plant species, Sonchus wightianus DC., was historically used in China for both medicinal and dietary uses. In present study, seven new guaiane sesquiterpenoids (1-7) and one cytochalasin (8), along with five known guaianes (9-13) and two known cytochalasins (14 and 15), were isolated from the whole plants of S. wightianus. These guaianes showed structural variations in the substituents at C-8 and/or C-15, and compounds 6 and 7 are two sesquiterpenoid glycoside derivatives. Their structures were determined by extensive analysis of spectroscopic, electronic circular dichroism, and X-ray diffraction data, and chemical method. Biological tests revealed that compounds 5 and 8 are potent and selective immunosuppressive reagents.

Enantioselective synthesis of [4]helicenes by organocatalyzed intermolecular C-H amination.

Catalytic asymmetric synthesis of helically chiral molecules has remained an outstanding challenge and witnessed fairly limited progress in the past decades. Current methods to construct such compounds almost entirely rely on catalytic enantiocontrolled fused-ring system extension. Herein, we report a direct terminal peri-functionalization strategy, which allows for efficient assembling of 1,12-disubstituted [4]carbohelicenes via an organocatalyzed enantioselective amination reaction of 2-hydroxybenzo[c]phenanthrene derivates with diazodicarboxamides. The key feature of this approach is that the stereochemical information of the catalyst could be transferred into not only the helix sense but also the remote C-N axial chirality of the products, thus enabling the synthesis of [4]- and [5]helicenes with both structural diversity and stereochemical complexity in good efficiency and excellent enantiocontrol. Besides, the large-scale preparations and representative transformations of the helical products further demonstrate the practicality of this protocol. Moreover, DFT calculations reveal that both the hydrogen bonds and the C-H---π interactions between the substrates and catalyst contribute to the ideal stereochemical control.

Phthalate metabolites in breast milk from mothers in Southern China: Occurrence, temporal trends, daily intake, and risk assessment.

The extensive production and use of phthalates means that these compounds are now ubiquitous in the environment and various biota, which raises concerns about potential harmful health effects. In this study, phthalate metabolites (mPAEs) were measured in breast milk (n = 100) collected from mothers of southern China between 2014 - 2022. Of the nine target mPAEs, five were detected in all of the samples, including mono-methyl phthalate (MMP), mono-ethyl phthalate (MEP), mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), and mono-(2-ethylhexyl) phthalate (MEHP). The total levels of mPAEs in breast milk ranged from 4.76 to 51.6 ng/mL, with MiBP and MnBP being the predominant isomers (MiBP + MnBP > 48.3%). Increasing trends were observed in MMP (5.7%/year) and MEHP (7.1%/year) levels during the study period, while a decreasing trend were observed in MiBP (-6.6%/year); no clear temporal trends were found for the other metabolites and total mPAE levels. The results indicate that exposure to phthalates is still prevalent in southern China. Breastfeeding was found to contribute to estimated daily phthalate intakes of 0.383-6.95 µg/kg-bw/day, suggesting insignificant health risks to infants based on dietary exposure. However, the increasing exposure to MMP and MEHP calls for more research into the possible sources and potential risks.

Interaction and joint association of gestational diabetes mellitus and subsequent weight gain rate on macrosomia.

BACKGROUND & AIMS: Gestational diabetes mellitus (GDM) and gestational weight gain are two crucial modifiable nutritional factors during pregnancy in preventing macrosomia, warranting appropriate management of both glycemic levels and weight gain to prevent macrosomia, particularly in individuals with GDM. Unfortunately, current general weight targets appear not to apply to individuals with GDM, suggesting that weight gain, specifically following an oral glucose tolerance test (OGTT), may affect risk of macrosomia dependent on GDM status. Therefore, this study aims to evaluate the interaction and joint association of GDM and post-OGTT weight gain rate (PWGR) in relation to macrosomia. METHODS: This was a population-based cohort study of 59,421singleton pregnant women in South China during 2017-2020. Among them, 9856 were diagnosed with GDM while 49,565 did not have the condition. All participants underwent an OGTT between 20 and 28 weeks of pregnancy, typically occurring between 24 and 28 weeks. PWGR was defined as the average rate of change in maternal weight with gestational weeks following OGTT, which was estimated using a repeated linear mixed effects model including a random intercept and slope for each individual. The relative risk (RR) of macrosomia associated with GDM and PWGR was estimated using a multivariate generalized linear model. RESULTS: There was a significant interaction between GDM and PWGR in increasing the risk of macrosomia. The combination of GDM and a 1-SD increase in PWGR was associated with a 2.26-fold higher risk of macrosomia (95% CI 1.92 to 2.65), with the interaction of these two factors contributing to 58.0% (95% CI 31.4%-84.7%) of this association. Moreover, we observed a significant heterogeneity in susceptibility to macrosomia due to increased PWGR between GDM and non-GDM populations, with the highest PWGR quartile having respective RRs of 2.27 (95% CI 1.62 to 3.18) and 1.41 (95% CI 1.18 to 1.69) compared to the lowest quartile category, which was corresponded to 55.9% (95% CI 38.3%-68.6%) and 29.1% (95% CI 15.3%-40.8%) preventable proportions of macrosomia cases in these populations. CONCLUSIONS: GDM and PWGR had a synergistic effect in increasing the risk of macrosomia. Furthermore, individuals with GDM exhibited a heightened susceptibility to macrosomia due to elevated PWGR. These findings emphasize the importance of appropriate weight interventions during late pregnancy and suggest the need for different weight targets between these two populations, with a stricter PWGR potentially being more effective for the GDM population.

Construction of iron metabolism-related prognostic features of gastric cancer based on RNA sequencing and TCGA database.

BACKGROUND: Researches have manifested that the disorder of iron metabolism is participated in Gastric cancer (GC), but whether iron metabolism-relevant genes (IMRGs) is related to the survival outcome of GC remain unknown. METHODS: Eleven tumor as well as nine adjacent normal tissues from GC patients were underwent mRNA sequencing, and the The Cancer Genome Atlas Stomach Cancer (TCGA-STAD) datasets were acquired from the TCGA database. Cox analyses and least absolute shrinkage and selection operator (LASSO) regression were applied to build a IMRGs signature. The relationship between signature genes and the infiltration profiling of 24 immune cells were investigated using single-sample GSEA (ssGSEA). Meanwhile, the potential biological significance, genes that act synergistically with signature genes, and the upstream regulatory targets were predicted. Finally, the abundance of the signature genes were measured via the quantitative real-time PCR (qRT-PCR). RESULTS: A IMRGs signature was constructed according to the expression and corresponding coefficient of DOHH, P4HA3 and MMP1 (The Schoenfeld individual test showed risk score was not significant with P values = 0.83). The prognostic outcome of patients in the high-risk group was terrible (p < 0.05). Receiver operating characteristic (ROC) curves confirmed that the IMRGs signature presented good efficiency for predicting GC prognosis (AUC > 0.6). The nomogram was performed well for clinical utilize (C-index = 0.60), and the MMP1 expression significantly increased in the cohorts at age > 60 and Stage II-IV (p < 0.05). The positive correlation of P4HA3 and MMP1 expression as well as the negative correlation of DOHH expression with risk score (p < 0.0001) and worse prognosis (p < 0.05) were detected as well. Furthermore, 11 differential immune cells were associated with these signature genes (most p < 0.01). Finally, qRT-PCR revealed that the abundance of DOHH, P4HA3 and MMP1 were high in tumor cases, indicating the complex mechanism between the high expression of DOHH as a protective factor and the high expression of P4HA3 and MMP1 as the risk factors in the development of GC. CONCLUSION: An iron metabolism-related signature was constructed and has significant values for foretelling the OS of GC.

The composition, pharmacological effects, related mechanisms and drug delivery of alkaloids from Corydalis yanhusuo.

Corydalis yanhusuo W. T. Wang, also known as yanhusuo, yuanhu, yanhu and xuanhu, is one of the herb components of many Chinese Traditional Medicine prescriptions such as Jin Ling Zi San and Yuanhu-Zhitong priscription. C. yanhusuo was traditionally used to relieve pain and motivate blood and Qi circulation. Now there has been growing interest in pharmacological effects of alkaloids, the main bioactive components of C. yanhusuo. Eighty-four alkaloids isolated from C. yanhusuo are its important bioactive components and can be characterized into protoberberine alkaloids, aporphine alkaloids, opiate alkaloids and others and proper extraction or co-administration methods modulate their contents and efficacy. Alkaloids from C. yanhusuo have various pharmacological effects on the nervous system, cardiovascular system, cancer and others through multiple molecular mechanisms such as modulating neurotransmitters, ion channels, gut microbiota, HPA axis and signaling pathways and are potential treatments for many diseases. Plenty of novel drug delivery methods such as autologous red blood cells, self-microemulsifying drug delivery systems, nanoparticles and others have also been investigated to better exert the effects of alkaloids from C. yanhusuo. This review summarized the alkaloid components of C. yanhusuo, their pharmacological effects and mechanisms, and methods of drug delivery to lay a foundation for future investigations.

Gut microbiota trajectory in ß-thalassemia major children who underwent allogeneic hematopoietic stem cell transplantation.

BACKGROUND: The gut microbiota of patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) changes, leading to complications such as acute graft-versus-host disease (GVHD). This study aimed to evaluate the human microbiota composition before and after HSCT in ß-thalassemia major (ß-TM) children. METHOD: Twenty-two ß-TM children who received allo-HSCT between December 2018 and March 2020 were enrolled. They were followed up for more than 100 days after HSCT, and their gut microbiota information and disease data were recorded at five-time points. RESULTS: The dominant bacteria were Bacteroidetes and Firmicutes at the phylum level and Lachnospiraceae at the family level before and after HSCT. In the differential analysis, Ruminococcaceae constantly decreased after HSCT. Besides, Rothia mucilaginosa was the most abundant 2 months after HSCT compared to before it. Additionally, GVHD patients presented decreased levels of Bacteroidetes compared to those without GVHD. Moreover, Blautia levels significantly decreased in critically ill GVHD patients. CONCLUSION: The gut microbiota of the 22 ß-TM children showed a clear trend of destruction and reconstruction within 100 days after HSCT. The extra-oral infections and inflammations of Rothia mucilaginosa, a Gram-positive bacterium of the normal oropharyngeal tract microbiota, might play an important role in the recovery process of HSCT. Finally, decreased Bacteroidetes levels were associated with GVHD onset.

Weight progression and adherence to weight gain target in women with vs. without gestational diabetes: a retrospective cohort study.

BACKGROUND: Weight management has been an important component of the service in obstetric care offered to pregnant women. Current gestational weight gain recommendations were primarily for the general obstetric population, raising concern about the applicability to women with gestational diabetes mellitus (GDM). We aimed to assess the difference in weight progression and adherence to the recommended gestational weight gain targets between women with gestational diabetes mellitus (GDM) and women with normal glucose tolerance (NGT). METHODS: This was a hospital-based retrospective study of 56,616 pregnant women (9,430 GDM women and 47,186 NGT women) from Guangzhou between 2017 and 2021. The average change in weight progression was estimated based on serial weight measurements throughout pregnancy, using a mixed effects model with a random intercept to account for repeated measures of the same individual. RESULTS: Women with GDM gained less weight (12.07 [SD 5.20] kg) than women with NGT (14.04 [SD 5.04] kg) throughout pregnancy. Before OGTT, a small difference was observed in the average change in weight progression between the two groups (GDM, 0.44 kg/week vs. NGT, 0.45 kg/week, p < 0.001), however, this gap widened significantly after the test (0.34 vs. 0.50 kg/week, p < 0.001). GDM individuals were identified with an approximately 4-fold increased proportion of insufficient weight gain (41.1% vs. 10.4%) and a 2-fold decreased proportion of excessive weight gain (22.6% vs. 54.2%) compared to NGT individuals. These results were consistently observed across different BMI categories, including underweight (insufficient: 52.7% vs. 19.9%; excessive: 15.6% vs. 35.3%), normal weight (insufficient 38.2% vs. 7.4%; excessive: 22.2% vs. 57.3%), and overweight/obese (insufficient: 43.1% vs. 9.8%; excessive: 30.1% vs. 68.8%). CONCLUSION: Weight progression varied significantly between GDM and NGT individuals, resulting in a substantial difference in identifying insufficient and excessive weight gain between the two groups under current gestational weight gain guidelines.

RNF114 facilitates the proliferation, stemness, and metastasis of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC), the fourth of the world's major common malignancy, poses a serious threat to the physical and mental health of the population. Nevertheless, the prognosis of CRC patients remains unsatisfactory. Consequently, it is still imperative to continuously discover the CRC mechanisms. METHODS: The expression profiles of mRNAs were recognized by whole transcriptome sequencing to identity differentially expressed mRNA (DE-mRNA). TCGA COAD cohort, PPOGgene and Kaplan-Meier Plotter databases were utilized to validate RNF114 relevance to CRC prognosis. The effect of RNF114 on the malignant biological behavior of CRC was explored in CRC cells and subcutaneous tumor models and lung metastasis model after exogenous regulation of RNF114. RESULTS: A total of 1358 DE-mRNAs were identified, including 617 up-regulated and 741 down-regulated DE-mRNAs, and they were mainly involved in the term of receptor ligand activity, Wnt signaling pathway and pathway in cancer. Notably, RNF114 was hyper-expressed in tissues and cell of CRC, and significantly correlated with tumor invasion depth and TNM stage of CRC patients. RNF114 expression were significantly associated with overall survival, and had superior diagnostic value in CRC. In vitro, knockdown of RNF114 statistically diminished the proliferation, stemness, invasion and wound healing of CRC cells and facilitated their apoptosis, and the opposite result was observed for overexpression of RNF114. In vivo, knockdown of RNF114 effectively diminished the mass and volume of tumors, and lung metastasis in animal model. CONCLUSIONS: In summary, we identified DE-mRNAs in CRC, and elucidated that RNF114 facilitates CRC process. The discovery will contribute to theoretical foundation for RNF114 as a potential therapeutic target and biomarker, and offer new perspectives for CRC research.

Discovery of grey matter lesion-related immune genes for diagnostic prediction in multiple sclerosis.

Background: Multiple sclerosis (MS) is a chronic debilitating disease characterized by inflammatory demyelination of the central nervous system. Grey matter (GM) lesions have been shown to be closely related to MS motor deficits and cognitive impairment. In this study, GM lesion-related genes for diagnosis and immune status in MS were investigated. Methods: Gene Expression Omnibus (GEO) databases were utilized to analyze RNA-seq data for GM lesions in MS. Differentially expressed genes (DEGs) were identified. Weighted gene co-expression network analysis (WGCNA), least absolute shrinkage and selection operator (LASSO) algorithm and protein-protein interaction (PPI) network were used to screen related gene modules and candidate genes. The abundance of immune cell infiltration was analyzed by the CIBERSORT algorithm. Candidate genes with strong correlation with immune cell types were determined to be hub genes. A diagnosis model of nomogram was constructed based on the hub genes. Gene set enrichment analysis (GSEA) was performed to identify the biological functions of hub genes. Finally, an MS mouse model was induced to verify the expression levels of immune hub genes. Results: Nine genes were identified by WGCNA, LASSO regression and PPI network. The infiltration of immune cells was significantly different between the MS and control groups. Four genes were identified as GM lesion-related hub genes. A reliable prediction model was established by nomogram and verified by calibration, decision curve analysis and receiver operating characteristic curves. GSEA indicated that the hub genes were mainly enriched in cell adhesion molecules, cytokine-cytokine receptor interaction and the JAK-STAT signaling pathway, etc. Conclusions: TLR9, CCL5, CXCL8 and PDGFRB were identified as potential biomarkers for GM injury in MS. The effectively predicted diagnosis model will provide guidance for therapeutic intervention of MS.

Multifunctional nanoreactors with nutrient consumption and ROS generation capabilities for antibacterial and skin repair.

Bacterial wound infection has brought a serious threat to human health and caused huge economic losses. Attempts to develop biomaterials with excellent antibacterial effects are meaningful to promote wound healing. Herein, we report a multifunctional nanoreactor with nutrient consumption and reactive oxygen species (ROS) generation capabilities for antibacterial and skin wound repair. The nanoreactor was constructed by the encapsulation of glucose oxidase (GOx) into a Cu2+-doped zeolite-based imidazole framework (ZIF-8) through a one-pot synthesis method. The nanoreactor not only consumes the nutrients of bacteria by the GOx-driven oxidation reaction, but also generates highly toxic hydroxyl radicals (˙OH) to kill bacteria via a Cu+-mediated Fenton-like reaction. Moreover, Zn2+ released from the nanoreactor is also capable of exhibiting synergistic antibacterial activity. In addition to mediating Fenton-like reactions, Cu2+ promotes angiogenesis to accelerate wound healing. Thus, the multifunctional nanoreactor has the ability to cut off the nutrient supply and starve the bacteria, produce ROS to kill bacteria, and promote angiogenesis to accelerate wound healing, enabling it to be promising for the treatment of wound infection.

Anthropometric parameters of obesity can be alternative biomarkers for the potential cardiac dysfunction in obese children.

Childhood obesity, as one of the potential risk factors of cardiovascular diseases, is closely associated with the incidence of cardiovascular disease at a younger age and has become a public health concern worldwide. However, its potential effects on the cardiovascular system have still remained elusive. In this study, we systematically evaluated the cardiovascular characteristics of 79 obese children and 161 normal weight children in Guangzhou (China) using the potential biomarkers for cardiovascular disease. Compared with normal weight children, obese children not only exhibited significantly higher levels of creatine kinase (CK), lactate dehydrogenase (LHD), soluble fms-like tyrosine kinase-1 (s-Flt-1), high-sensitivity C-reactive protein (hs-CRP), and uric acid (UA) (p = 0.0062, 0.0012, 0.0013, 0.0225, and <0.0001, respectively) but also significantly higher diastolic blood pressure (p = 0.0074) and the heart rate (p = 0.0049) were found in obese children. Of 79 obese children, cardiac functions of 40 cases were further assessed by color Doppler echocardiography. The results showed that there were significant differences between the obesity group and the healthy weight group in terms of interventricular septal wall thickness at end-diastolic (IVSd), the left ventricular posterior wall thickness at end-diastolic (LVPWD), and aortic annulus (AO) (p < 0.0001, 0.0003, and p < 0.0001, respectively). Besides, the left and/or right ventricular functions were declined in 52.4% of obese children. Correlation analysis revealed that the anthropometric parameters of obesity were not only significantly correlated with a blood lipid profile but also exhibited a more significant correlation with most of the parameters of cardiac dysfunction than a blood lipid profile. Therefore, our study indicated that obese children in Guangzhou suffered from functional damages related to cardiovascular events, which were characterized by cardiac dysfunction, and the anthropometric parameters of obesity could be economically alternative biomarkers for monitoring of cardiac dysfunction in obese children.

Fear Stress During Pregnancy Affects Placental m6A-Modifying Enzyme Expression and Epigenetic Modification Levels.

As the hub connecting mother and offspring, the placenta's normal development is vital for fetal growth. Fear stress can cause some structural alterations in the placenta and affect placental development and function. N6-methyladenosine (m6A) is the most common mRNA modification and is involved in regulating the development of the placenta and embryo. There are no reports on the potential role of m6A modification in placental damage caused by fear stress during pregnancy. In this study, we demonstrated that fear stress during pregnancy increases the levels of methylated enzymes (METTL3, METTL14, and WTAP), decreases the levels of demethylase FTO, and increases the overall methylation levels in the placenta of pregnant rats. MeRIP-seq data analysis revealed 22,010 m6A peaks associated with 12,219 genes in the placenta of the model and 21,060 m6A peaks associated with 11,730 genes in the placenta of the control. The peaks were mainly concentrated in the coding region and the 3' untranslated region. In addition, 50 genes with abnormal modification and expression (double aberrant genes) were screened out by combining MeRIP-seq and RNA-seq data. Mefv, Erbb2, and Cgas were selected from 50 double aberrant genes, and MeRIP-qPCR and real-time quantitative polymerase chain reaction were used to verify their modification and expression levels. Our findings suggest that m6A modifications play an important role in placental dysfunction induced by fear stress during pregnancy.