A quantitative study on the terrestrial input to the tropical Northeast Atlantic.

Eolian dust and riverine discharge are identified as two key components of terrestrial input to the oceans. They supply micronutrients to the oceans and modify marine carbon biogeochemistry and global climate through dust-land-ocean interactions. However, it is challenging to accurately constrain regional terrestrial inputs in the past, with currently available models and geochemical proxies. The present study utilizes sedimentary wtCaCO3% records to estimate lithogenic fluxes. The depth-dependance of CaCO3 preservation in the Holocene and Last Glacial Maximum (LGM) sediments in two major basins of the tropical Northeast Atlantic Ocean is described using a carbonate dissolution model. Results show that during the LGM, reduced dust deposition and slight drops of fluvial input are found in the Canary Basin and Cape Verde margins, respectively. To supplement, carbonate deposition during the LGM indicates that the deep subtropical Northeast Atlantic is seized by more sluggish deep waters relative to today.

An antibacterial and anti-oxidant hydrogel containing hyperbranched poly-l-lysine and tea polyphenols accelerates healing of infected wound.

Both bacteria-infection and excessive inflammation delay the wound healing process and even create non-healing wound, thus it is highly desirable to endow the wound dressing with bactericidal and anti-oxidation properties. Herein an antibacterial and antioxidation hydrogel based on Carbomer 940 (CBM) and hydroxypropyl methyl cellulose (HPMC) loaded with tea polyphenols (TP) and hyperbranched poly-l-lysine (HBPL) was designed and fabricated. The hydrogel killed 99.9 % of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli) at 107 CFU mL-1, and showed strong antioxidation against H2O2 and 2,2-di(4-tert-octylphenyl)-1-picryl-hydrazyl (DPPH) radicals without noticeable cytotoxicity in vitro. The CBM/HPMC/HBPL/TP hydrogel significantly shortened the inflammatory period of the MRSA-infected full-thickness skin wound of rats in vivo, with 2 orders of lower MRSA colonies compared with the blank control, and promoted the wound closure especially at the earlier stage. The inflammation was suppressed and the vascularization was promoted significantly as well, resulting in reduced pro-inflammatory factors including interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α), and increased anti-inflammatory factors such as interleukin-4 (IL-4) and interleukin-10 (IL-10).

Antitumor Effect of Poplar Propolis on Human Cutaneous Squamous Cell Carcinoma A431 Cells.

Propolis is a gelatinous substance processed by western worker bees from the resin of plant buds and mixed with the secretions of the maxillary glands and beeswax. Propolis has extensive biological activities and antitumor effects. There have been few reports about the antitumor effect of propolis against human cutaneous squamous cell carcinoma (CSCC) A431 cells and its potential mechanism. CCK-8 assays, label-free proteomics, RT-PCR, and a xenograft tumor model were employed to explore this possibility. The results showed that the inhibition rate of A431 cell proliferation by the ethanol extract of propolis (EEP) was dose-dependent, with an IC50 of 39.17 µg/mL. There were 193 differentially expressed proteins in the EEP group compared with the control group (p < 0.05), of which 103 proteins (53.37%) were upregulated, and 90 proteins (46.63%) were downregulated. The main three activated and suppressed Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were extracellular matrix (ECM)-receptor interaction, amoebiasis, cell adhesion molecules (CAMs), nonalcoholic fatty liver disease (NAFLD), retrograde endocannabinoid signaling, and Alzheimer's disease. The tumor volume of the 100 mg/kg EEP group was significantly different from that of the control group (p < 0.05). These results provide a theoretical basis for the potential treatment of human CSCC A431 cell tumors using propolis.

A diagnostic model for sepsis-induced acute lung injury using a consensus machine learning approach and its therapeutic implications.

BACKGROUND: A significant proportion of septic patients with acute lung injury (ALI) are recognized late due to the absence of an efficient diagnostic test, leading to the postponed treatments and consequently higher mortality. Identifying diagnostic biomarkers may improve screening to identify septic patients at high risk of ALI earlier and provide the potential effective therapeutic drugs. Machine learning represents a powerful approach for making sense of complex gene expression data to find robust ALI diagnostic biomarkers. METHODS: The datasets were obtained from GEO and ArrayExpress databases. Following quality control and normalization, the datasets (GSE66890, GSE10474 and GSE32707) were merged as the training set, and four machine learning feature selection methods (Elastic net, SVM, random forest and XGBoost) were applied to construct the diagnostic model. The other datasets were considered as the validation sets. To further evaluate the performance and predictive value of diagnostic model, nomogram, Decision Curve Analysis (DCA) and Clinical Impact Curve (CIC) were constructed. Finally, the potential small molecular compounds interacting with selected features were explored from the CTD database. RESULTS: The results of GSEA showed that immune response and metabolism might play an important role in the pathogenesis of sepsis-induced ALI. Then, 52 genes were identified as putative biomarkers by consensus feature selection from all four methods. Among them, 5 genes (ARHGDIB, ALDH1A1, TACR3, TREM1 and PI3) were selected by all methods and used to predict ALI diagnosis with high accuracy. The external datasets (E-MTAB-5273 and E-MTAB-5274) demonstrated that the diagnostic model had great accuracy with AUC value of 0.725 and 0.833, respectively. In addition, the nomogram, DCA and CIC showed that the diagnostic model had great performance and predictive value. Finally, the small molecular compounds (Curcumin, Tretinoin, Acetaminophen, Estradiol and Dexamethasone) were screened as the potential therapeutic agents for sepsis-induced ALI. CONCLUSION: This consensus of multiple machine learning algorithms identified 5 genes that were able to distinguish ALI from septic patients. The diagnostic model could identify septic patients at high risk of ALI, and provide potential therapeutic targets for sepsis-induced ALI.

Network Pharmacology-Based Identification of Key Targets of Ziyin Mingmu Pills Acting on Age-Related Macular Degeneration.

Objective: This study is designed to find out the molecular targets of effective Chinese medicine Ziyin Mingmu pills (ZMPs) in treating age-related macular degeneration (AMD) based on network pharmacology and experimental data. Methods: A comprehensive network pharmacology strategy that consists of three sequential modules (drug-disease target molecular docking, enrichment analysis, and external verification) was carried out to identify potential targets of ZMPs acting on AMD. Results: The active ingredients of ZMPs targeting 66 genes have effects on the process of AMD. GO and KEGG pathway enrichment analyses suggested that response to oxidative stress, regulation of angiogenesis, and lipid and atherosclerosis might serve as the most important signaling pathways in ZMPs for AMD treatment. Combined with the GSE29801 dataset for further analysis, two key genes, EGFR and VEGFA, were identified. Immune infiltration analysis showed that there was a strong association between EGFR and immune cell content. In addition, images were acquired following 24 h in the scratch experiment showed that ZMPs can reduce the percentage of wound healing distance. The Western blot assay found that ZMPs increased the expression of EGFR and decreased the expression of VEGFA. Conclusion: This study sheds light on some mechanisms of ZMP therapy for AMD, particularly the effect of ZMP on the oxidative stress in RPE and cell survival and angiogenesis in AMD. We propound ZMPs as a promising strategy to intervene in the process of AMD.

ß-Hydroxybutyric acid upregulated by Suhuang antitussive capsule ameliorates cough variant asthma through GSK3ß/AMPK-Nrf2 signal axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Cough variant asthma (CVA) is a chronic inflammatory disease characterized by cough as the main symptom. Suhuang antitussive capsule (Suhuang), one of traditional Chinese patent medicines, mainly treats CVA clinically. Previous studies have shown that Suhuang significantly improved CVA, post-infectious cough (PIC), sputum obstruction and airway remodeling. However, the effect of Suhuang on ovalbumin-induced (OVA-induced) metabolic abnormalities in CVA is unknown. AIM OF THE STUDY: This study aimed to identify potential metabolites associated with efficacy of Suhuang in the treatment of CVA, and determined how Suhuang regulates metabolites, and differential metabolites reduce inflammation and oxidative stress. MATERIALS AND METHODS: Rats were given 1 mg OVA/100 mg aluminum hydroxide in the 1st and 7th days by intraperitoneal injection and challenged by atomizing inhalation of 1% OVA saline solution after two weeks to establish the CVA model. Rats were intragastrically (i.g.) administrated with Suhuang at 1.4 g/kg and ß-hydroxybutyric acid (ß-HB) were given with different concentrations (87.5 and 175 mg/kg/day) by intraperitoneal injection for 2 weeks. After 26 days, GC-MS-based metabolomic approach was applied to observe metabolic changes and search differential metabolites. The number of coughs, coughs latencies, enzyme-linked immunosorbent assay (ELISA), histological analysis and quantitative-polymerase chain reaction (Q-PCR) were used to investigate the effects of Suhuang. Then ß-HB on CVA rats, NLRP3 inflammasome and GSK3ß/AMPK/Nrf2 signalling pathway were detected by western blotting. RESULTS: The results showed that Suhuang treatment significantly enhanced the serum level of ß-HB. Interestingly, exposure to exogenous ß-HB was also protective against OVA-induced CVA. ß-HB significantly reduced the number of coughs and lengthened coughs latencies, improved lung injury, reduced the secretion of various cytokines, and directly inhibited the NLRP3 inflammasome. In addition, ß-HB increased the nuclear accumulation of Nrf2 by activating the GSK3ß/AMPK signaling axis, and then inactivating the NF-κB signaling pathway, effectively protecting OVA-induced CVA from oxidative stress and inflammation. CONCLUSIONS: The results of this study shows that ß-HB can reduce inflammation and oxidative stress, the increased production of ß-HB in serum might be the crucial factor for Suhuang to exert its effect in the treatment of CVA.

Metabolomics and transcriptomics provide insights into the flavonoid biosynthesis pathway in the roots of developing Aster tataricus.

Aster tataricus (L.) is an important medicinal plant in China. Its roots are rich in flavonoids, the main medicinal components. However, the molecular basis of flavonoid biosynthesis in the roots of A. tataricus remains unclear. In this study, the content of total flavonoid of A. tataricus roots at different developmental stages was measured first, and the results showed that the content of total flavonoid gradually decreased from September to November, which may be caused by the stagnation of A. tataricus growth due to the decrease in temperature after September. Then, an integrated analysis of transcriptome and metabolome was conducted on five developing stages of A. tataricus roots to identify flavonoid compositions and potential genes involved in flavonoid biosynthesis. A total of 80 flavonoid metabolites, of which 75% were flavonols and flavonoids, were identified in metabolomic analyses, among which isorhamnetin, kaempferol, quercetin, and myricetin were the main skeletons of these flavonoids. Cluster analysis divided these 80 flavonoids into 3 clusters. The compounds in cluster I mainly accumulated in S1, S3, and S5. In cluster II, the relative content of the flavonoid metabolites showed an upward trend from S2 to S4. In cluster III, the flavonoids decreased from S1 to S5. A total of 129 structural genes, including 43 PAL, 23 4CL, 9 C4H, 4 CHS, 18 CHI, 3 F3H, 5 F3'H, 1 F3'5'H, 21 FLS, and 2 FSII, and 65 transcription factors, including 22 AP2/ERF, 7 bHLH, 5 bZIP, 8 MYB, 11 NAC, and 12 WRKY, showed significant correlation with total flavonoid content. Eighteen genes (7 4CL, 5 C4H, 2 CHI, 1 F3H, and 3 FLS) and 30 genes (5 PAL, 9 4CL, 1 C4H, 2 CHI, 1 F3H, 1 DFR, 7 3AT, 1 BZ1, and 3 UGT79B1) were identified as key structural genes for kaempferol and anthocyanins biosynthesis, respectively. Our study provides valuable information for understanding the mechanism of flavonoid biosynthesis in A. tataricus root.

Analysis of Chinese Medical Syndrome Features of Ischemic Stroke Based on Similarity of Symptoms Subgroup.

OBJECTIVE: To derive the Chinese medicine (CM) syndrome classification and subgroup syndrome characteristics of ischemic stroke patients. METHODS: By extracting the CM clinical electronic medical records (EMRs) of 7,170 hospitalized patients with ischemic stroke from 2016 to 2018 at Weifang Hospital of Traditional Chinese Medicine, Shandong Province, China, a patient similarity network (PSN) was constructed based on the symptomatic phenotype of the patients. Thereafter the efficient community detection method BGLL was used to identify subgroups of patients. Finally, subgroups with a large number of cases were selected to analyze the specific manifestations of clinical symptoms and CM syndromes in each subgroup. RESULTS: Seven main subgroups of patients with specific symptom characteristics were identified, including M3, M2, M1, M5, M0, M29 and M4. M3 and M0 subgroups had prominent posterior circulatory symptoms, while M3 was associated with autonomic disorders, and M4 manifested as anxiety; M2 and M4 had motor and motor coordination disorders; M1 had sensory disorders; M5 had more obvious lung infections; M29 had a disorder of consciousness. The specificity of CM syndromes of each subgroup was as follows. M3, M2, M1, M0, M29 and M4 all had the same syndrome as wind phlegm pattern; M3 and M0 both showed hyperactivity of Gan (Liver) yang pattern; M2 and M29 had similar syndromes, which corresponded to intertwined phlegm and blood stasis pattern and phlegm-stasis obstructing meridians pattern, respectively. The manifestations of CM syndromes often appeared in a combination of 2 or more syndrome elements. The most common combination of these 7 subgroups was wind-phlegm. The 7 subgroups of CM syndrome elements were specifically manifested as pathogenic wind, pathogenic phlegm, and deficiency pathogens. CONCLUSIONS: There were 7 main symptom similarity-based subgroups in ischemic stroke patients, and their specific characteristics were obvious. The main syndromes were wind phlegm pattern and hyperactivity of Gan yang pattern.

Ultrathin-FeOOH-Coated MnO2 Sonosensitizers with Boosted Reactive Oxygen Species Yield and Remodeled Tumor Microenvironment for Efficient Cancer Therapy.

Sonodynamic therapy (SDT) typically suffers from compromised anticancer efficacy owing to the low reactive oxygen species (ROS) yield and complicated tumor microenvironment (TME) which can consume ROS and support the occurrence and development of tumors. Herein, ultrathin-FeOOH-coated MnO2 nanospheres (denoted as MO@FHO) as sonosensitizers which can not only facilitate ultrasound (US)-triggered ROS but also tune the TME by hypoxia alleviation, H2 O2 consumption as well as glutathione (GSH) depletion are designed. The FeOOH coating will boost the production yield of singlet oxygen (1 O2 ) and hydroxyl radicals (• OH) by inhibiting the recombination of US-initiated electron-hole pairs and Fenton-like reaction, respectively. Additionally, the catalase-like and GSH peroxidase-like activities of MO@FHO nanospheres enable them to break the TME equilibrium via hypoxia alleviation and GSH depletion. The combination of high ROS yield and fundamental destruction of TME equilibrium results in satisfactory antitumor outcomes, as demonstrated by the high tumor suppression efficacy of MO@FHO on MDA-MB-231-tumor-bearing mice. No obvious toxicity is detected to normal tissues at therapeutic doses in vivo. The capability to modulate the ROS production and TME simultaneously can afford new probability for the development of advanced sonosensitizers for synergistic comprehensive cancer therapy.

Study on Synergistic Antioxidant Effect of Typical Functional Components of Hydroethanolic Leaf Extract from Ginkgo Biloba In Vitro.

The predicted anti-oxidation is related to apoptosis, proliferation, lipid metabolism, cell differentiation, and immune response. There are some differences in the antioxidant capacity of the four typical components of ginkgo biloba extract (EGb) including ginkgo flavone (GF), ginkgolide (G), procyanidins (OPC), and organic acids (OA), and any two members of them can exhibit apparent synergistic effects. The order of DPPH scavenging ability was: OPC > GF > OA > G. The scavenging ability of procyanidins was close to that of VC; the scavenging capacity of ABTS was GF > OPC > OA > G. The GF:OPC (1:9) showed the best synergism in scavenging DPPH and ABTS radicals. The 193 kinds of small molecules reported in EGb were obtained by analyzing the properties of EGb. In order to construct a corresponding biological activity target set, molecular docking and the network pharmacology method were employed to build the molecular action mechanism network of a compound target, and the main biological functions and signaling pathways involved with their antioxidant activities were predicted. The results displayed that the top ten compounds which belonged to the two broad categories, ginkgo flavonoids and proanthocyanidins, could interact closely with several important target proteins (CASP3, SOD2, MAPK1, HSPA4, and NQO1). This would be expected to lay a theoretical foundation for the deep development of Ginkgo biloba extract.

Using the Symptom Patient Similarity Network to Explore the Difference between the Chinese and Western Medicine Pathways of Ischemic Stroke and its Comorbidities.

METHODS: Individualized treatment of traditional Chinese medicine (TCM) provides a theoretical basis for the study of the personalized classification of complex diseases. Utilizing the TCM clinical electronic medical records (EMRs) of 7170 in patients with IS, a patient similarity network (PSN) with shared symptoms was constructed. Next, patient subgroups were identified using community detection methods and enrichment analyses were performed. Finally, genetic data of symptoms, herbs, and drugs were used for pathway and GO analysis to explore the characteristics of pathways of subgroups and to compare the similarities and differences in genetic pathways of herbs and drugs from the perspective of molecular pathways of symptoms. RESULTS: We identified 34 patient modules from the PSN, of which 7 modules include 98.48% of the whole cases. The 7 patient subgroups have their own characteristics of risk factors, complications, and comorbidities and the underlying genetic pathways of symptoms, drugs, and herbs. Each subgroup has the largest number of herb pathways. For specific symptom pathways, the number of herb pathways is more than that of drugs. CONCLUSION: The research of disease classification based on community detection of symptom-shared patient networks is practical; the common molecular pathway of symptoms and herbs reflects the rationality of TCM herbs on symptoms and the wide range of therapeutic targets.

An efficient photochemotherapy nanoplatform based on the endogenous biosynthesis of photosensitizer in macrophage-derived extracellular vesicles.

Extracellular vesicles (EVs) have been emerged as versatile drug delivery vehicles due to their outstanding biocompatibility and long-term circulation, yet are constrained with low targeting property and inefficient loading capacity from post-synthetic passive EVs encapsulation. Herein, we report a simple and feasible in situ biosynthetic approach to encapsulate tumor-targeting folate (FA)-modified EVs with intracellularly produced protoporphyrin X (PpIX) and doxorubicin (DOX). As compared with the traditional directly drug-incubated or drug-electroporated EVs, these biosynthesized EVs revealed high drug-loading efficiency with minimized structural and functional perturbations. Our multifunctional EVs revealed the enhanced accumulation and penetration into deep tumor parenchyma, as well as the strengthened immune response to ablate orthotopic and metastatic tumors, thus realizing the more reliable photochemotherapy. As an intelligent multi-mode therapeutic system, our biosynthetic EVs could be engineered with more therapeutic agents and show great promise for biomedicine applications.

Precision photothermal therapy and photoacoustic imaging by in situ activatable thermoplasmonics.

Phototherapy holds great promise for disease treatment; however, traditional "always-on" photoagents have been restricted to clinical translation due to their nonspecific response and side effects on normal tissues. Here, we show a tumor microenvironment activated photothermal and photoacoustic agent as an activatable prodrug and probe that allows precise cancer diagnosis and treatment. Such an in situ revitalized therapeutic and contrast agent is achieved via controllable plasmonic heating for thermoplasmonic activation. This enables monitoring of signal molecule dynamics, real-time photothermal and photoacoustic imaging of tumors and lymph node metastasis, and targeted photothermal therapy without unwanted phototoxicity to normal tissues. Our study provides a practical solution to the non-specificity problem in phototherapy and offers precision cancer therapeutic and theranostic strategies. This work may advance the development of ultrasensitive disease diagnosis and precision medicine.

First-Trimester Maternal Folic Acid Supplementation Modifies the Effects of Risk Factors Exposures on Congenital Heart Disease in Offspring.

This study aimed to examine effect modification of maternal risk factor exposures and congenital heart disease (CHD) by maternal folic acid supplementation (FAS)/non-FAS. We included 8379 CHD cases and 6918 CHD-free controls from 40 clinical centers in Guangdong Province, Southern China, 2004-2016. Controls were randomly chosen from malformation-free fetuses and infants and frequency matched to the echocardiogram-confirmed cases by enrollment hospital and year of birth. We used multiple regression models to evaluate interactions between FAS/non-FAS and risk factors on CHDs and major CHD categories, adjusted for confounding variables. We detected statistically significant additive and multiplicative interactions between maternal FAS/non-FAS and first-trimester fever, viral infection, and threatened abortion on CHDs. An additive interaction on CHDs was also identified between non-FAS and living in a newly renovated home. We observed a statistically significant dose-response relationship between non-FAS and a greater number of maternal risk factors on CHDs. Non-FAS and maternal risk factors interacted additively on multiple critical CHDs, conotruncal defects, and right ventricular outflow tract obstruction. Maternal risk factor exposures may have differential associations with CHD risk in offspring, according to FAS. These findings may inform the design of targeted interventions to prevent CHDs in highly susceptible population groups.

Seed oil of Brucea javanica induces apoptosis through the PI3K/Akt signaling pathway in acute lymphocytic leukemia Jurkat cells.

Brucea javanica oil emulsion (BJOE) has been used to treat tumor in China for more than 40 years. However, its components and effectiveness in the treatment of acute lymphocytic leukemia (ALL) and its mechanism of anti-cancer activity remain unknown. In the current study, high-performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD) was used to analyze the components of BJOE. Then, the anti-leukemia effects of BJOE were examined both in vitro and in vivo using ALL Jurkat cells and the p388 mouse leukemia transplant model, respectively. The primary ALL leukemia cells were also used to confirm the anti-leukemia effects of BJOE. The apoptotic-related results indicated that BJOE induced apoptosis in Jurkat cells and were suggestive of intrinsic apoptotic induction. Moreover, BJOE inhibited Akt (protein kinase B) activation and upregulated its downstream targets p53 and FoxO1 (forkhead box gene, group O-1) to initiate apoptosis. The activation of GSK3ß was also involved. Our findings demonstrate that BJOE has anti-leukemia effects on ALL cells and can induce apoptosis in Jurkat cells through the phosphoinositide3-kinase (PI3K) /Akt signaling pathway.

The n-butanol fraction of the Xiao-Chai-Hu decoction alleviates the endocrine disturbance in the liver of mice exposed to lead.

ETHNOPHARMACOLOGICAL RELEVANCE: Lead is a toxic heavy metal that causes health risks globally. However, the mechanism of endocrine poisoning and detoxification of lead poisoning, especially in the liver, still needs to be studied. Xiao-Chai-Hu decoction (XCHD) is regarded as an antidote and an anti-hepatotoxic traditional prescription that has been recorded in the pharmacopeia of the People's Republic of China. AIM OF THE STUDY: The study aimed to probe the hepatoprotective activity of XCHD in the regulation of endocrine dysfunction in the liver and its molecular mechanism. MATERIALS AND METHODS: The mice from the Institute of Cancer Research (ICR) were exposed to different concentrations of XCHD and lead. Then, serum biochemical indices and liver pathology were analyzed. The key differential genes were detected by qRT-PCR and Western blot. RESULTS: According to the biochemical and histopathological analysis, XCHD-NBA was the most effective in attenuating lead-induced hepatotoxicity. From the transcriptome, we analyzed the key genes of XCHD-NBA in the regulation of lead toxicity, including Tubb2a, Stip1, Cyp4a12a, Cyp2c50, Ugt1a1, Cyp3a11, Cyp4a12b, Ahsa1, Cyp2c54, Tubb4b, Esr1, Hsp90aa1, Tuba1a, Tuba1c, and Hsph1. We also analyzed the main components of XCHD-NBA by LC-MS. Because of their extensive role in regulating the endocrine function, baicalin and glycyrrhizin were identified as the main active components of XCHD in regulating endocrine disorders caused by lead. CONCLUSIONS: Lead can disturb the endocrine regulatory process of the liver, while XCHD-NBA alleviates lead-induced liver injury by regulating the endocrine regulatory process.

Therapeutic Effect and Cost-Benefit Analysis of Three Different Nutritional Schemes for Esophageal Cancer Patients in the Early Post-operative Period.

Objective: To retrospectively investigate the comparative efficacy, safety and cost-benefits of three nutritional treatment schemes including short peptide jejunal nutrition (SPJN), whole protein jejunal nutrition (WPJN), and partial parenteral nutrition (PPN) in patients underwent esophagectomy for esophageal cancer in our hospital. This study was carried out in accordance with the conceptual framework of nutritional therapy in fast-track rehabilitation surgery. Methods: We retrospectively reviewed 305 patients who were assigned to receive esophagectomy for esophageal cancer. Eligible patients was naturally divided into SPJN group [n = 98 (32.1%)], WPJN group [n = 95 (31.1%)], and PPN group [n = 112 (36.7%)] according to the type of nutritional scheme which was actually prescribed to patients by the attendingphysician in clinical practice. The differences of the serum total protein (TP), albumin (ALB), pre-albumin (PA), hemoglobin (HGB), white blood cells (WBCs), red blood cells (RBCs) and neutrophils were compared among 3 nutritional schemes groups. We also investigated the relationship of the fluid intake, urine output, gastric juice drainage volume and thoracic drainage volume among 3 nutritional groups at 3 days after surgery. Moreover, the differences of cost-benefit indexes, complications, length of hospitalization and hospital expenditure were also compared. Results: The serum TP, ALB, and PA in the SPJN group were all higher than those in the WPJN and PPN groups (p < 0.05). The gastric juice volume of gastrointestinal decompression drainage and fluid volume of thoracic drainage in the SPJN group were all less than that in the WPJN group (p < 0.05). The overall hospital stay and post-operative hospital stay in the SPJN group were all shorter than that in WPJN group (p < 0.05). Moreover, the incidence of post-operative complications including anastomotic leakage, infection, and gastrointestinal reaction was remarkably lower in the SPJN group compared to the WPJN group (p < 0.05). Interesting, hospital expenditure in the PPN group was less than that in the SPJN and the WPJN groups (p < 0.001). Conclusion: Patients may obtain benefits in improving protein level after receiving SPJN scheme at the early stage after esophagectomy. Meanwhile, patients may obtain benefits in improving post-operative complications and hospital stay after receiving SPJN or PPN compared to WPJN protocol. However, the difference between SPJN and PPN requires further study because no difference was detected in terms of clinical outcomes including complications and the length of hospitalization although PPN may achieve a possible decrease of medical expenditure.

Cascaded Amplifier Nanoreactor for Efficient Photodynamic Therapy.

Photodynamic therapy (PDT) utilizes reactive oxygen species (ROS) to treat established diseases and has attracted growing attention in the field of cancer therapy. However, in a tumor microenvironment (TME), the inherent hypoxia and high level of antioxidants severely hamper the efficacy of ROS generation. Here, we describe a cascaded amplifier nanoreactor based on self-assembled nanofusiforms for persistent oxygenation to amplify ROS levels. The nanofusiform assembly is capable of photothermal and photodynamic treatment and regulation of redox oxidation stress by antioxidant depletion to prevent ROS tolerance. The Pt nanozyme decoration of the nanofusiform enables efficient oxygen supplements via Pt nanozyme-catalyzed decomposition of H2O2 overexpressed in TME and generation of O2. Furthermore, the temperature elevation resulted from the photothermal effect of the nanofusiform increases the catalase-like catalytic activity of the Pt nanozyme for boosted oxygen generation. Thus, such a triple cascade strategy using nanozyme-based nanofusiforms amplifies the ROS level by continuous oxygenation, enhancing the efficacy of PDT in vitro and in vivo. Meanwhile, an in vivo multi-modal imaging including near-infrared fluorescence imaging, photothermal imaging, and magnetic resonance imaging achieves precise tumor diagnosis. The rationally designed nanofusiform acts as an efficient ROS amplifier through multidimension strengthening of continuous oxygenation, providing a potential smart nanodrug for cancer therapy.

Dracomolphin A-E, new lignans from Dracocephalum moldavica.

Eight new lignans, dracomolphin A-E (1-8), together with eight known lignans (9-16) were isolated from the aerial part of Dracocephalum moldavica. The structures of the isolated compounds were established based on NMR and HRESIMS data. Dracomolphin A (1-4) was elucidated as a lignan possessed a 5-membered ketal ring formed between C-8' and C-3, C-4. The two stereogenic centers rendered dracomolphin A as a mixture of two diastereomeric pairs of enantiomers (1-4). All of the four isomers were separated successfully by using chiral HPLC and their stereochemical features were determined by CD spectra. Bioactivity screening revealed that compounds 1-4, 6, 7, 12, 15 and 16 were potential Nrf2 transcriptional activators. Dracomolphin E (8) reduced cell viability of lung cancer NCI-H292 cells associated with apoptosis.

Maternal folic acid supplementation mediates the associations between maternal socioeconomic status and congenital heart diseases in offspring.

Low maternal socioeconomic status (SES) is considered as a risk factor of congenital heart diseases (CHDs) in offspring. However, the pathways underpinning the SES-CHDs associations are unclear. We assessed if first trimester maternal folic acid supplementation (FAS) is a mediator of the SES-CHDs associations. This case-control study included 8379 CHD cases and 6918 CHD-free controls from 40 participating centers in Guangdong, Southern China, 2004-2016. All fetuses were screened for CHDs using ultrasound and cases were confirmed by echocardiogram. We collected SES and FAS information during face-to-face interview by obstetricians using a structured questionnaire. Low SES was defined as education attainment <12 years, household individual income <3000 Chinese Yuan/person/month or unemployment. FAS referred to at least 0.4 mg of daily folic acid intake over 5 days/week continuously. We used causal mediation analysis to estimate the direct, indirect and proportion mediated by FAS on the SES-CHDs associations adjusted for confounders. Both low maternal income and education were significantly associated with increased risks of CHDs and lower prevalence of FAS. Low maternal FAS prevalence mediated 10% [95%CI:5%,13%] and 3% [95%CI:1%,5%] of the maternal low income-CHDs and the maternal low education-CHDs associations, respectively. In addition, FAS mediated the highest proportion of the associations between income and multiple critical CHDs [46.9%, 95%CI:24.7%,77%] and conotruncal defects [31.5%, 95%CI:17.1%,52.0%], respectively. Maternal FAS partially mediated the SES-CHDs associations, especially among the most critical and common CHDs. Promoting FAS in low SES women of childbearing age may be a feasible intervention to help prevent CHDs.