Ligand-Controlled Regiodivergent Nickel-Catalyzed Hydroaminoalkylation of Unactivated Alkenes.

Ligand modulation of transition-metal catalysts to achieve optimal reactivity and selectivity in alkene hydrofunctionalization is a fundamental challenge in synthetic organic chemistry. Hydroaminoalkylation, an atom-economical approach for alkylating amines using alkenes, is particularly significant for amine synthesis in the pharmaceutical, agrochemical, and fine chemical industries. However, the existing methods usually require specific substrate combinations to achieve precise regio- and stereoselectivity, which limits their practical utility. Protocols allowing for regiodivergent hydroaminoalkylation from the same starting materials, controlling both regiochemical and stereochemical outcomes, are currently absent. Herein, we report a ligand-controlled, regiodivergent nickel-catalyzed hydroaminoalkylation of unactivated alkenes with N-sulfonyl amines. The reaction initiates with amine dehydrogenation and involves aza-nickelacycle intermediates. Tritert-butylphosphine promotes branched regioselectivity and syn diastereoselectivity, whereas ethyldiphenylphosphine enables linear selectivity, yielding regioisomers with inverse orientation. Systematic evaluation of diverse monodentate phosphine ligands reveals distinct regioselectivity cliffs, and % Vbur (min), a ligand steric descriptor, was established as a predictive parameter correlating ligand structure to regioselectivity. Computational investigations supported experimental findings, offering mechanistic insights into the origins of regioselectivity. Our method provides an efficient and predictable route for amine synthesis, demonstrating broad substrate scope, excellent tolerance toward various functional groups, and practical advantages. These include the use of readily available starting materials and cost-effective nickel(II) salts as precatalysts.

The prediction model of operative link on gastric intestinal metaplasia stage III-IV: A multicenter study.

Purpose: Intestinal metaplasia plays a crucial role in the risk stratification of gastric cancer development. The objective of the study was to develop a prediction model for Operative Link on Gastric Intestinal Metaplasia (OLGIM) Stage III-IV. Methods: We analyzed 7945 high-risk gastric cancer individuals from 115 hospitals who underwent questionnaires and gastroscope. The participants were assigned to either the development or validation cohort randomly. Demographics and clinical characteristics were obtained. The outcome measurement was OLGIM III-IV. Univariate logistic regression was used for feature selection and multivariate logistic analysis was performed to develop the nomogram. Area under the curves, calibration plots, decision curve and clinical impact analysis were used to assess the performance of the nomogram. Results: 4600 individuals and 3345 individuals were included in the development and validation cohort, of which 124 and 86 individuals were diagnosed with OLGIM III-IV, respectively. Parameters in the training validation cohort matched well and there was no significant difference between two cohorts. A nomogram model for predicting OLGIM Stage III-IV consisted of 4 significantly associated variables, including age, gender, PG I and G-17 (AUC 0.723 and 0.700 for the 2 cohorts). The nomogram demonstrated excellent performance in the calibration curve. Decision curve and clinical impact analysis suggested clinical benefit of the prediction model. Conclusions: This reliable individualized nomogram might contribute to more accurate management for patients with OLGIM III-IV. Therefore, we suggest that this study be used as an incentive to promote the application.

Intracellular delivery of nitric oxide enhances the therapeutic efficacy of mesenchymal stem cells for myocardial infarction.

Cell therapy by autologous mesenchymal stem cells (MSCs) is a clinically acceptable strategy for treating various diseases. Unfortunately, the therapeutic efficacy is largely affected by the low quality of MSCs collected from patients. Here, we showed that the gene expression of MSCs from patients with diabetes was differentially regulated compared to that of MSCs from healthy controls. Then, MSCs were genetically engineered to catalyze an NO prodrug to release NO intracellularly. Compared to extracellular NO conversion, intracellular NO delivery effectively prolonged survival and enhanced the paracrine function of MSCs, as demonstrated by in vitro and in vivo assays. The enhanced therapeutic efficacy of engineered MSCs combined with intracellular NO delivery was further confirmed in mouse and rat models of myocardial infarction, and a clinically relevant cell administration paradigm through secondary thoracotomy has been attempted.

Calcineurin suppresses rat H9c2 cardiomyocyteprotective autophagy under chronic intermittent hypoxia by downregulating the AMPK pathway.

Calcineurin plays a key role in cardiovascular pathogenesis by exerting pro-apoptotic effects in cardiomyocytes. However, whether calcineurin can regulate cardiomyocyte autophagy under conditions of chronic intermittent hypoxia (CIH) remains unclear. Here, we showed that CIH induced calcineurin activity in H9c2 cells, which attenuated adenosine monophosphate-activated protein kinase (AMPK) signaling and inhibited autophagy. In H9c2 cells, autophagy levels, LC3 expression, and AMPK phosphorylation were significantly elevated under conditions of CIH within 3 days. However, after 5 days of CIH, these effects were reversed and calcineurin activity and apoptosis were significantly increased. The calcineurin inhibitor 17-Allyl-1,14-dihydroxy-12-[2-(4-hydroxy-3-methoxycyclohexyl) -1-methylvinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo- [22.3.1.04,9]octacos-18- ene-2,3,10,16-tetrone (FK506) restored AMPK activation and LC3 expression and attenuated CIH-induced H9c2 cell apoptosis. In contrast, calcineurin overexpression significantly attenuated the increase in LC3 expression and enhanced H9c2 cell apoptosis under conditions of CIH. Calcineurin inhibition failed to induce autophagy or alleviate apoptosis in H9c2 cells expressing a kinase-dead K45R AMPK mutant. Autophagy inhibition abrogated the protective effects of FK506-mediated calcineurin inhibition. These results indicate that calcineurin suppresses adaptive autophagy during CIH by downregulating AMPK activation. Our findings reveal the underlying mechanism of calcineurin and autophagy regulation during H9c2 cell survival under conditions of CIH and may provide a new strategy for preventing CIH-induced cardiomyocyte damage.

Genetically engineered mesenchymal stem cells as a nitric oxide reservoir for acute kidney injury therapy.

Nitric oxide (NO), as a gaseous therapeutic agent, shows great potential for the treatment of many kinds of diseases. Although various NO delivery systems have emerged, the immunogenicity and long-term toxicity of artificial carriers hinder the potential clinical translation of these gas therapeutics. Mesenchymal stem cells (MSCs), with the capacities of self-renewal, differentiation, and low immunogenicity, have been used as living carriers. However, MSCs as gaseous signaling molecule (GSM) carriers have not been reported. In this study, human MSCs were genetically modified to produce mutant ß-galactosidase (ß-GALH363A). Furthermore, a new NO prodrug, 6-methyl-galactose-benzyl-oxy NONOate (MGP), was designed. MGP can enter cells and selectively trigger NO release from genetically engineered MSCs (eMSCs) in the presence of ß-GALH363A. Moreover, our results revealed that eMSCs can release NO when MGP is systemically administered in a mouse model of acute kidney injury (AKI), which can achieve NO release in a precise spatiotemporal manner and augment the therapeutic efficiency of MSCs. This eMSC and NO prodrug system provides a unique and tunable platform for GSM delivery and holds promise for regenerative therapy by enhancing the therapeutic efficiency of stem cells.

Animals are made up of cells of different types, with each type of cell specializing on a specific role. But for the body to work properly, the different types of cells must be able to coordinate with each other to respond to internal and external stimuli. This can be achieved through signaling molecules, that is, molecules released by a cell that can elicit a specific response in other cells. There are many types of different molecules, including hormones and signaling proteins. Gases can also be potent signaling molecules, participating in various biological processes. Nitric oxide (NO) is a gas signaling molecule that can freely diffuse through the membranes of cells and has roles in blood vessel constriction and other disease processes, making it a promising therapeutic agent. Unfortunately, using artificial carriers to deliver nitric oxide to the organs and tissues where it is needed can lead to issues, including immune reactions to the carrier and long-term toxicity. One way to avoid these effects is by using cells to deliver nitric oxide to the right place. Huang, Qian, Liu et al. have used mesenchymal stem cells ­ which usually develop to form connective tissues such as bone and muscle ­ to develop a cell-based NO-delivery system. The researchers genetically modified the mesenchymal stem cells to produce a compound called ß-GAL^H363A. On its own ß-GAL^H363A does not do much, but in its presence, a non-toxic, non-reactive compound developed by Huang, Qian, Liu et al., called MGP, can drive the release of NO from cells. To confirm the usefulness of their cells as a delivery system, Huang, Qian, Liu et al. transplanted some of the genetically modified mesenchymal stem cells into the kidneys of mice, and then showed that when these mice were given MGP, the levels of NO increased in the kidneys but not in other organs. This result confirms that the cell-based delivery system provides spatial and temporal control of the production of NO. These findings demonstrate a new delivery system for therapies using gas molecules, which can be controlled spatiotemporally in mice. In the future, these types of systems could be used in the clinic for long-term treatment of conditions where artificial carriers could lead to complications.

Treatment of Candida albicans liver abscess complicated with COVID-19 after liver metastasis ablation: A case report.

BACKGROUND: Liver interventional surgery is a relatively safe and minimally invasive surgery. However, for patients who have undergone Whipple surgery, the probability of developing a liver abscess after liver interventional surgery is very high. Fungal liver abscess has a high mortality rate, especially when complicated with malignant tumors, diabetes, coronavirus disease 2019 (COVID-19) and other complications. Fungal liver abscess is rare, and there are no guidelines or expert consensus on the course of antifungal therapy. CASE SUMMARY: A 54-year-old woman with pancreatic head cancer received albumin-bound paclitaxel in combination with gemcitabine chemotherapy after laparoscopic pancreaticoduodenectomy. Liver metastasis was found 1 mo after completion of 8 cycles of chemotherapy, followed by ablation of the liver metastasis. After half a month of liver metastasis ablation, the patient experienced fever after chemotherapy and was diagnosed with liver abscess complicated with COVID-19 by contrast-enhanced abdominal computed tomography and real-time polymerase chain reaction detection. The results of pus culture showed Candida albicans, which was sensitive to fluconazole. The patient underwent percutaneous catheter drainage, antifungal therapy with fluconazole, and antiviral therapy with azvudine. During antifungal therapy, the patient showed a significant increase in liver enzyme levels and was discharged after liver protection therapy. Oral fluconazole was continued for 1 wk outside the hospital, and fluconazole was used for a total of 5 wk. The patient recovered well and received 4 cycles of fluorouracil, leucovorin, oxaliplatin, and irinotecan after 2 mo of antifungal therapy. CONCLUSION: Effective treatment of Candida albicans liver abscess requires early detection, percutaneous catheter drainage, and 5 wk of antifungal therapy. Meanwhile, complications such as COVID-19 should be actively managed and nutritional support should be provided.

Structural Modification Endows Small-Molecular SN38 Derivatives with Multifaceted Functions.

As a camptothecin derivative, 7-ethyl-10-hydroxycamptothecin (SN38) combats cancer by inhibiting topoisomerase I. SN38 is one of the most active compounds among camptothecin derivatives. In addition, SN38 is also a theranostic reagent due to its intrinsic fluorescence. However, the poor water solubility, high systemic toxicity and limited action against drug resistance and metastasis of tumor cells of SN38 indicates that there is great space for the structural modification of SN38. From the perspective of chemical modification, this paper summarizes the progress of SN38 in improving solubility, increasing activity, reducing toxicity and possessing multifunction and analyzes the strategies of structure modification to provide a reference for drug development based on SN38.

Helicobacter pylori Infection Combined with OLGA and OLGIM Staging Systems for Risk Assessment of Gastric Cancer: A Retrospective Study in Eastern China.

Purpose: Helicobacter pylori (H. pylori) infection is a high-risk factor for gastric cancer (GC). The main aim of this study was to evaluate the effect of H. pylori on gastritis staging systems and the value of H. pylori combined with gastritis staging systems in predicting GC risk. Patients and Methods: This study enrolled 609 patients with gastric atrophy (GA) and 527 patients with gastric intestinal metaplasia (GIM), who were graded by the OLGA and OLGIM staging systems, respectively. Each individual underwent serum pepsinogen (PG) test, H. pylori detection and questionnaire investigation. We did a real-world retrospective follow-up survey for them in April 2022. Results: Compared with H. pylori-negative patients, H. pylori-positive patients had higher serum PGs/gastrin-17 (G-17) levels and lower PGR levels, regardless of OLGA/OLGIM stages I-II or III-IV. Furthermore, eight patients with atrophic gastritis who progressed to GC were previously in OLGA stages III-IV and OLGIM stages II-IV. The average duration of this process was 2.19±1.03 years. Logistic regression analysis indicated that PGI and H. pylori infection were independent risk factors of individuals with OLGA stages III-IV. Age and PGR were independent risk factors of patients with OLGIM stages III-IV. PGI and PGR had good clinical diagnostic values for OLGA stages III-IV and OLGIM stages III-IV, respectively. Conclusion: Patients with OLGA/OLGIM stages III-IV should undergo endoscopic surveillance regardless of H. pylori infection. H. pylori-positive patients with OLGIM stage II also have a high risk of GC. H. pylori combined with PGI and PGR is helpful to evaluate the severity of chronic gastritis.

Endoscopic submucosal dissection versus esophagectomy for t1 esophageal squamous cell carcinoma: a propensity score-matched analysis.

Background: Endoscopic submucosal dissection (ESD) has been a preferred treatment option for superficial esophageal squamous cell carcinoma (SESCC). Objectives: To compare the outcomes of ESD and esophagectomy in the treatment of SESCC, especially for lesions invading muscularis mucosa or submucosa (pT1a-MM/T1b). Design: We retrospectively analyzed data from patients with SESCC who underwent ESD or esophagectomy between 2015 and 2021. Methods: After propensity score matching, overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), and treatment-related events were compared between the ESD and esophagectomy groups. Furthermore, we performed a Cox regression analysis to identify factors associated with survival. Results: OS and DSS were significantly higher in the ESD group (n = 508) than that in the esophagectomy group (n = 466). After matching, 404 patients (202 per group) were included in the study. No significant differences were found between the ESD and esophagectomy groups in OS (p = 0.566), RFS (p = 0.586), and DSS (p = 0.912). The ESD group showed less blood loss, shorter procedure duration and hospital stay, lower hospital cost, and fewer adverse events. However, a lower R0 resection rate was observed in the ESD group compared to the esophagectomy group. Subgroup analysis showed comparable survival outcomes between the two groups. In Cox regression analysis, age was the independent factor associated with OS. Conclusion: In the treatment of SESCC, ESD showed sufficient safety and advantages. Even for pT1a-MM/pT1b SESCC, ESD may be an alternative treatment to esophagectomy.

Comparison between Endoscopic Submucosal Dissection and Surgery in Patients with Early Gastric Cancer.

Background: Endoscopic submucosal dissection (ESD) has become a preferred treatment option for early gastric cancer (EGC). This study aimed to compare the clinical outcomes of ESD and surgical resection for EGC. Methods: This was a retrospective case-control study. Patients with a diagnosis of EGC who underwent ESD or surgery in our hospital from 2011 to 2020 were enrolled. We compared the clinical characteristics and treatment outcomes of these two groups according to propensity score-matching. The primary outcome comparison was overall survival (OS). Secondary outcomes were disease-specific survival (DSS), recurrence-free survival (RFS), and treatment-related events. Results: In the matched cohort, the ESD group showed comparable OS, RFS, and DSS with the surgery group. Statistical differences were shown in blood loss and adverse events. Furthermore, the ESD group showed lower hospital cost, as well as a shorter operative time and hospital duration than the surgery group. The R0 resection and recurrence rates were similar between the two groups. In Cox regression analysis, age, tumor size, poor differentiation, and lymphovascular invasion were regarded as independent factors of OS. Conclusions: With sufficient safety and advantages, ESD can be a first-line treatment of EGC. Preoperative evaluation is vital to the appropriate treatment and prognosis.

Ascyrones A-E, type B bicyclic ployprenylated acylphloroglucinol derivatives from Hypericum ascyron.

Five new polycyclic polyprenylated acylphloroglucinols (1-5), ascyrones A-E, and four known compounds (6-9) were isolated from the aerial parts of Hypericum ascyron. All of the isolates containing a bicyclo[3.3.1]nonane-2,4,9-trione core and a benzoyl group, belonged to type B bicyclic polyprenylated acylphloroglucinols (BPAPs). Their structures and absolute configurations were established based on spectroscopic analyses and calculated electronic circular dichroism (ECD) data. The anti-inflammatory, neuroprotective and cytotoxicity activities of compounds 1-4 and 6-9 were evaluated. Compound 6 exhibited obvious anti-inflammatory activity in lipopolysaccharide (LPS)-induced RAW264.7 cells. Compounds 1 and 9 exhibited slight cytotoxicity against Hep3B cells. Meanwhile, compound 1 showed mild neuroprotective activity against corticosterone (CORT)-induced PC12 cell damage at 10 µmol·L-1.

Nitric oxide improves regeneration and prevents calcification in bio-hybrid vascular grafts via regulation of vascular stem/progenitor cells.

Vascular bypass surgery continues to use autologous grafts and often suffers from a shortage of donor grafts. Decellularized xenografts derived from porcine veins provide a promising candidate because of their abundant availability and low immunogenicity. Unfortunately, transplantation outcomes are far from satisfactory because of insufficient regeneration and adverse pathologic remodeling. Herein, a nitrate-functionalized prosthesis has been incorporated into a decellularized porcine vein graft to fabricate a bio-hybrid vascular graft with local delivery of nitric oxide (NO). Exogenous NO efficiently promotes vascular regeneration and attenuates intimal hyperplasia and vascular calcification in both rabbit and mouse models. The underlying mechanism was investigated using a Sca1 2A-CreER; Rosa-RFP genetic-lineage-tracing mouse model that reveals that Sca1+ stem/progenitor cells (SPCs) are major contributors to vascular regeneration and remodeling, and NO plays a critical role in regulating SPC fate. These results support the translational potential of this off-the-shelf vascular graft.

MSC-derived sEV-loaded hyaluronan hydrogel promotes scarless skin healing by immunomodulation in a large skin wound model.

Designing hydrogel-based constructs capable of adjusting immune cell functions holds promise for skin tissue regeneration. Mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEVs) have attracted increasing attention owing to their anti-inflammatory and proangiogenic effects. Herein, we constructed a biofunctional hydrogel in which MSC-derived sEVs were incorporated into the injectable hyaluronic acid hydrogel, thus endowing the hydrogel with immunomodulatory effects. When implanted onto the wound site in a mouse large skin injury model, this functional hydrogel facilitates wound healing and inhibits scar tissue formation by driving macrophages towards an anti-inflammatory and anti-fibrotic (M2c) phenotype. Further investigation showed that the M2c-like phenotype induced by MSC-derived sEVs markedly inhibited the activation of fibroblasts, which could result in scarless skin wound healing. Taken together, these results suggest that modulation of the immune response is a promising and efficient approach to prevent fibrotic scar formation.

Anti-Sca-1 antibody-functionalized vascular grafts improve vascular regeneration via selective capture of endogenous vascular stem/progenitor cells.

Small-diameter vascular grafts fabricated from synthetic biodegradable polymers exhibit beneficial mechanical properties but often face poor regenerative potential. Different tissue engineering approaches have been employed to improve tissue regeneration in vascular grafts, but there remains a requirement for a new generation of synthetic grafts that can orchestrate the host response to achieve robust vascular regeneration. Vascular stem/progenitor cells (SPCs) are mostly found in quiescent niches but can be activated in response to injury and participate in endothelium and smooth muscle regeneration during neo-artery formation. Here, we developed a functional vascular graft by surface immobilization of stem cell antigen-1 (Sca-1) antibody on an electrospun poly(ε-caprolactone) graft (PCL-Sca-1 Ab). PCL-Sca-1 Ab promoted capture and retainment of Sca-1+ SPCs in vitro. In rat abdominal aorta replacement models, PCL-Sca-1 Ab stimulated in vivo recruitment of Sca-1+ SPCs, and drove SPCs differentiation towards vascular cell lineages. The origin of infiltrated Sca-1+ SPCs was further investigated using a bone marrow transplantation mouse model, which revealed that Sca-1+ SPCs originating from the resident tissues and bone marrow contributed to rapid vascular regeneration of vascular grafts. Our data indicated that PCL-Sca-1 Ab vascular grafts may serve as a useful strategy to develop next generation cell-free vascular grafts.

CSF1 receptor inhibition of tenosynovial giant cell tumor using novel disease-specific MRI measures of tumor burden.

Aim: Monitoring treatment of tenosynovial giant cell tumor (TGCT) is complicated by the irregular shape and asymmetrical growth of the tumor. We compared responses to pexidartinib by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with those by tumor volume score (TVS) and modified RECIST (m-RECIST). Materials & methods: MRIs acquired every two cycles were assessed centrally using RECIST 1.1, m-RECIST and TVS and tissue damage score (TDS). Results: Thirty-one evaluable TGCT patients were treated with pexidartinib. From baseline to last visit, 94% of patients (29/31) showed a decrease in tumor size (median change: -60% [RECIST], -66% [m-RECIST], -79% [TVS]). All methods showed 100% disease control rate. For TDS, improvements were seen in bone erosion (32%), bone marrow edema (58%) and knee effusion (46%). Conclusion: TVS and m-RECIST offer potentially superior alternatives to conventional RECIST for monitoring disease progression and treatment response in TGCT. TDS adds important information about joint damage associated with TGCT.

The root iron transporter 1 governs cadmium uptake in Vicia sativa roots.

Cadmium is a non-essential element for plants and that inhibits plant growth and development. The Zhangye Mawan (ZM) variety of Vicia sativa is more sensitive to Cd toxicity than that Lanjian 3# (L3) variety, but the underlying mechanism is not fully understood. Here, we demonstrated that ZM showed higher Cd accumulation than L3 based on root Cd content and Cd fluorescence intensity in root protoplasts. VsRIT1, a member of the ZIP (ZRT/IRT-like protein) family, showed expression levels in ZM roots 8-fold higher than those in L3 roots under Cd exposure. VsRIT1 expression increased Cd transport and accumulation in Arabidopsis and yeast. These suggests that VsRIT1 participates in Cd uptake by V. sativa roots. Furthermore, ZM root tips have a higher capacity for transient Cd influx than L3 roots when exposed to Cd alone or Cd and iron (Fe) together, owing to the higher VsRIT1 expression in ZM. Our findings also imply that Cd may compete with Fe or/and zinc (Zn) for uptake via VsRIT1 in V. sativa or yeast.

Microgravity versus Microgravity and Irradiation: Investigating the Change of Neuroendocrine-Immune System and the Antagonistic Effect of Traditional Chinese Medicine Formula.

During spaceflight, the homeostasis of the living body is threatened with cosmic environment including microgravity and irradiation. Traditional Chinese medicine could ameliorate the internal imbalance during spaceflight, but its mechanism is still unclear. In this article, we compared the difference of neuroendocrine-immune balance between simulated microgravity (S) and simulated microgravity and irradiation (SAI) environment. We also observed the antagonistic effect of SAI using a traditional Chinese medicine formula (TCMF). Wistar rats were, respectively, exposed under S using tail suspending and SAI using tail suspending and 60Co-gama irradiation exposure. The SAI rats were intervened with TCMF. The changes of hypothalamic-pituitary-adrenal (HPA) axis, splenic T-cell, celiac macrophages, and related cytokines were observed after 21 days. Compared with the normal group, the hyperfunction of HPA axis and celiac macrophages, as well as the hypofunction of splenic T-cells, was observed in both the S and SAI group. Compared with the S group, the levels of plasmatic corticotropin-releasing hormone (CRH), macrophage activity, and serous interleukin-6 (IL-6) in the SAI group were significantly reduced. The dysfunctional targets were mostly reversed in the TCMF group. Both S and SAI could lead to NEI imbalance. Irradiation could aggravate the negative feedback inhibition of HPA axis and macrophages caused by S. TCMF could ameliorate the NEI dysfunction caused by SAI.

Gene-Environment Interaction between the IL1RN Variants and Childhood Environmental Tobacco Smoke Exposure in Asthma Risk.

(1) Background: Variants of the interleukin-1 receptor antagonist (IL1RN) gene, encoding an anti-inflammatory cytokine, are associated with asthma. Asthma is a chronic inflammatory disease of the airway influenced by interactions between genetic variants and environmental factors. We discovered a gene-environment interaction (GEI) of IL1RN polymorphisms with childhood environmental tobacco smoke (ETS) exposure on asthma susceptibility in an urban adult population. (2) Methods: DNA samples from the NYU/Bellevue Asthma Registry were genotyped for tag SNPs in IL1RN in asthma cases and unrelated healthy controls. Logistic regressions were used to study the GEI between IL1RN variants and childhood ETS exposures on asthma and early onset asthma, respectively, adjusting for population admixture and other covariates. (3) Results: Whereas the rare genotypes of IL1RN SNPs (e.g., GG in SNP rs2234678) were associated with decreased risk for asthma among those without ETS exposure (odds ratio OR = 0.215, p = 0.021), they are associated with increased risk for early onset asthma among those with childhood ETS (OR = 4.467, p = 0.021). (4) Conclusions: We identified a GEI between polymorphisms of IL1RN and childhood ETS exposure in asthma. Analysis of GEI indicated that childhood ETS exposure disrupted the protective effect of some haplotypes/genotypes of IL1RN for asthma and turned them into high-risk polymorphisms for early onset asthma.

Chitiniphilus eburneus sp. nov., a novel chitinolytic bacterium isolated from sludge.

A novel Gram-stain-negative, curved rod-shaped, motile and non-endospore-forming strain, designated HX-2-15T, was isolated from activated sludge of agricultural chemical plant in Nanjing, Jiangsu province, PR China (32° 03' N, 118° 46' E) . Growth was observed at 15-37 °C (optimum between 25 and 30 °C), at pH 6.0-8.0 (optimum at pH 7.0) and with 0-3.0 % (w/v) NaCl (optimum at 0.5 %). Phylogenetic analysis based on 16S rRNA gene sequences revealed that the strain showed closest affiliation to Chitiniphilus shinanonensis SAY3T, with a sequence similarity of 99.0 %. The predominant cellular fatty acids were C16:0, C17:0 cyclo and summed feature 3 (C16:1 ω7c and/or C16:1 ω6c). The major quinone was ubiquinone Q-8 . The polar lipid profile was composed of phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, three unidentified phospholipids, one unidentified lipid and one unidentified aminophosphoglycolipid . The genomic DNA G+C content of the strain was 63.6 mol%. The ANI and dDDH values obtained between the genomes of HX-2-15T and C. shinanonensis SAY3T were 85.3 and 29.3 % respectively. On the basis of data from phenotypic, chemotaxonomic and genotypic analysis, strain HX-2-15T represents a novel species of the genus Chitiniphilus, for which the name Chitiniphilus eburneus sp. nov. is proposed. The type strain is HX-2-15T (=KCTC 72286T=CCTCC AB 2019178T).

Polyaspartate and liquid amino acid fertilizer are appropriate alternatives for promoting the phytoextraction of cadmium and lead in Solanum nigrum L.

Traditional metal chelators, such as ethylenediaminetetraacetic acid (EDTA), have been gradually replaced due to their poor biodegradability in soil and high risk of heavy metal leaching into groundwater, which pose high environmental risks to the health of humans and animals. In this study, a liquid amino acid fertilizer (LAAF, waste proteins from hydrolysates of animal carcasses) and polyaspartate (PASP) were used as additives to enhance the phytoextraction of cadmium (Cd) and lead (Pb) from contaminated soil. We conducted pot experiments to investigate the phytoextraction capacity of Solanum nigrum, a Cd accumulator, grown on soil highly contaminated with Cd and Pb in the absence (as controls) or presence of PASP and LAAF. Both PASP and LAAF significantly improved plant growth, Cd accumulation, and total Cd and Pb content in S. nigrum shoots and roots. PASP and LAAF application promoted Cd translocation from roots to shoots in S. nigrum and Cd bio-accessibility in rhizosphere soils, but this was not the case for Pb. Both PASP and LAAF increased Cd and Pb phytoextraction by S. nigrum plants, and Cd phytoextraction was more effective in LAAF-assisted S. nigrum than in PASP-assisted S. nigrum. These findings demonstrate that the low cost and ecofriendly features of recycled waste proteins make them good candidates for chelant-enhanced phytoextraction from heavy metal-contaminated soils.