Boosting Electrochemical Urea Synthesis via Constructing Ordered Pd-Zn Active Pair.

Electrochemical co-reduction of nitrate (NO3-) and carbon dioxide (CO2) has been widely regarded as a promising route to produce urea under ambient conditions, however the yield rate of urea has remained limited. Here, we report an atomically ordered intermetallic pallium-zinc (PdZn) electrocatalyst comprising a high density of PdZn pairs for boosting urea electrosynthesis. It is found that Pd and Zn are responsible for the adsorption and activation of NO3- and CO2, respectively, and thus the co-adsorption and co-activation NO3- and CO2 are achieved in ordered PdZn pairs. More importantly, the ordered and well-defined PdZn pairs provide a dual-site geometric structure conducive to the key C-N coupling with a low kinetical barrier, as demonstrated on both operando measurements and theoretical calculations. Consequently, the PdZn electrocatalyst displays excellent performance for the co-reduction to generate urea with a maximum urea Faradaic efficiency of 62.78% and a urea yield rate of 1274.42 µg mg-1 h-1, and the latter is 1.5-fold larger than disordered pairs in PdZn alloys. This work paves new pathways to boost urea electrosynthesis via constructing ordered dual-metal pairs.

Eurochevalierines A-I, Sesquiterpene Alkaloid Hybrids with Anti-Triple Negative Breast Cancer Activity from Penicillium sp. HZ-5.

Nine new sesquiterpene alkaloids, eurochevalierines A-I (1-9), were separated from the rice cultures of the endophytic fungus Penicillium sp. HZ-5 originated from the fresh leaf of Hypericum wilsonii N. Robson. The structures' illumination was conducted by single-crystal X-ray diffraction, extensive spectroscopic analysis, alkaline hydrolysis reaction, and Snatzke's method. Importantly, the antitumor activities screen of these isolates indicated that 1 could suppress triple negative breast cancer (TNBC) cell proliferation and induce apoptosis, with an IC50 value of 5.4 µM, which is comparable to the positive control docetaxel (DXT). Flow cytometry experiments mentioned that compound 1 significantly reduced mitochondrial membrane potential (MMP) of TNBC cells. In addition, 1 could activate caspase-3 and elevated the levels of reactive oxygen species (ROS) and expressions of suppressive cytokines and chemokines. Further Western blot analysis showed that 1 could selectively induce mitochondria-dependent apoptosis in TNBC cells via the BAX/BCL-2 pathway. Remarkably, these finding provide a new natural product skeleton for the treatment of TNBC.

Microbial-induced calcium precipitation: Bibliometric analysis, reaction mechanisms, mineralization types, and perspectives.

Microbial-induced calcium precipitation (MICP) refers to the formation of calcium precipitates induced by mineralization during microbial metabolism. MICP has been widely used as an ecologically sustainable method in environmental, geotechnical, and construction fields. This article reviews the removal mechanisms of MICP for different contaminants in the field of water treatment. The nucleation pathway is explained at both extracellular and intracellular levels, with a focus on evaluating the contribution of extracellular polymers to MICP. The types of mineralization and the regulatory role of enzyme genes in the MICP process are innovatively summarized. Based on this, the environmental significance of MICP is illustrated, and the application prospects of calcium precipitation products are discussed. The research hotspots and development trends of MICP are analyzed by bibliometric methods, and the challenges and future directions of MICP technology are identified. This review aims to provide a theoretical basis for further understanding of the MICP phenomenon in water treatment and the effective removal of multiple pollutants, which will help researchers to find the breakthroughs and innovations in the existing technologies, with a view to making significant progress in MICP technology.

Glutamine metabolism improves left ventricular function but not macrophage-mediated inflammation following myocardial infarction.

Glutamine is a critical amino acid that serves as an energy source, building block, and signaling molecule for the heart tissue and the immune system. However, the role of glutamine metabolism in regulating cardiac remodeling following myocardial infarction (MI) is unknown. In this study, we show in adult male mice that glutamine metabolism is altered both in the remote (contractile) area and in infiltrating macrophages in the infarct area after permanent left anterior descending artery occlusion. We found that metabolites related to glutamine metabolism were differentially altered in macrophages at days 1, 3, and 7 after MI using untargeted metabolomics. Glutamine metabolism in live cells was increased after MI relative to no MI controls. Gene expression in the remote area of the heart indicated a loss of glutamine metabolism. Glutamine administration improved LV function at days 1, 3, and 7 after MI, which was associated with improved contractile and metabolic gene expression. Conversely, administration of BPTES, a pharmacological inhibitor of glutaminase-1, worsened LV function after MI. Neither glutamine nor BPTES administration impacted gene expression or bioenergetics of macrophages isolated from the infarct area. Our results indicate that glutamine metabolism plays a critical role in maintaining LV contractile function following MI, and that glutamine administration improves LV function. Glutamine metabolism may also play a role in regulating macrophage function, but macrophages are not responsive to exogenous pharmacological manipulation of glutamine metabolism.

Accurately Predicting Spatiotemporal Variations of Near-Surface Nitrous Acid (HONO) Based on a Deep Learning Approach.

Gaseous nitrous acid (HONO) is identified as a critical precursor of hydroxyl radicals (OH), influencing atmospheric oxidation capacity and the formation of secondary pollutants. However, large uncertainties persist regarding its formation and elimination mechanisms, impeding accurate simulation of HONO levels using chemical models. In this study, a deep neural network (DNN) model was established based on routine air quality data (O3, NO2, CO, and PM2.5) and meteorological parameters (temperature, relative humidity, solar zenith angle, and season) collected from four typical megacity clusters in China. The model exhibited robust performance on both the train sets [slope = 1.0, r2 = 0.94, root mean squared error (RMSE) = 0.29 ppbv] and two independent test sets (slope = 1.0, r2 = 0.79, and RMSE = 0.39 ppbv), demonstrated excellent capability in reproducing the spatiotemporal variations of HONO, and outperformed an observation-constrained box model incorporated with newly proposed HONO formation mechanisms. Nitrogen dioxide (NO2) was identified as the most impactful features for HONO prediction using the SHapely Additive exPlanation (SHAP) approach, highlighting the importance of NO2 conversion in HONO formation. The DNN model was further employed to predict the future change of HONO levels in different NOx abatement scenarios, which is expected to decrease 27-44% in summer as the result of 30-50% NOx reduction. These results suggest a dual effect brought by abatement of NOx emissions, leading to not only reduction of O3 and nitrate precursors but also decrease in HONO levels and hence primary radical production rates (PROx). In summary, this study demonstrates the feasibility of using deep learning approach to predict HONO concentrations, offering a promising supplement to traditional chemical models. Additionally, stringent NOx abatement would be beneficial for collaborative alleviation of O3 and secondary PM2.5.

Celiac trunk aortic dissection induced by bevacizumab therapy for rectal cancer: A case report.

RATIONALE: Bevacizumab (Bev) is a humanized monoclonal antibody that targets vascular endothelial growth factor A and is primarily used for the treatment of various solid tumors. Aortic dissection (AD) is a severe vascular disease caused by the tearing of the intimal layer of the aorta or bleeding within the aortic wall, resulting in the separation of different layers of the aortic wall. However, the pathogenesis is not fully understood. Some studies have suggested that Bev treatment is associated with the occurrence of AD. PATIENT CONCERNS: A 67-year-old Chinese male was diagnosed with rectal cancer accompanied by liver and lung metastasis. Three days after starting combined chemotherapy with Bev, the patient developed persistent abdominal pain. Abdominal CT scan revealed celiac trunk AD in the abdominal aorta. DIAGNOSES: The patient was diagnosed with rectal cancer accompanied by liver and lung metastases. Abdominal CT tomography revealed a celiac trunk AD. INTERVENTIONS: Somatostatin combined with valsartan was used to control blood pressure. The patient was subsequently referred for vascular surgery and underwent an abdominal aortic angiography. Conservative treatment was continued. OUTCOMES: Three months after the initiation of treatment, follow-up abdominal CT scans showed stability in the condition of celiac trunk AD, with no abdominal pain or hypertension. There were no signs of worsening dissection, aneurysm formation, or inadequate perfusion of end organs. LESSONS: There may be a connection between Bev and elevated blood pressure as well as celiac trunk AD.

Efficacy and Safety of Oral Administration of Wine Lees Extract (WLE)-Derived Ceramides and Glucosylceramides in Enhancing Skin Barrier Function: A Randomized, Double-Blind, Placebo-Controlled Study.

BACKGROUND: Our search for plant-derived ceramides from sustainable sources led to the discovery of ceramides and glucosylceramides in wine lees. OBJECTIVE: This study evaluated the efficacy and safety of wine lees extract (WLE)-derived ceramides and glucosylceramides in enhancing skin barrier function. METHODS: A randomized, double-blind, placebo-controlled study was conducted with 30 healthy Japanese subjects aged 20-64. Subjects were allocated to receive either the WLE-derived ceramides and glucosylceramides (test group) or placebo for 12 weeks. The primary outcome was transepidermal water loss (TEWL), and secondary outcomes included skin hydration, visual analog scale (VAS) of itching sensation, and the Japanese Skindex-29. RESULTS: One participant withdrew for personal reasons, resulting in 29 subjects for data analysis (placebo n = 15; test n = 14). The test group showed a tendency of lower TEWL compared to the placebo after 8 weeks (p = 0.07). Furthermore, after 12 weeks of administration, the test group had significantly lower TEWL than the placebo (p = 0.04). On the other hand, no significant differences were observed in the secondary outcome parameters. No adverse events related to the supplements were reported. CONCLUSIONS: Oral supplementation of WLE-derived ceramides and glucosylceramides is a prominent and safe approach to enhancing skin barrier function and health. TRIAL REGISTRATION: (UMIN000050422).

Expanding the targeting scope of CRISPR/Cas9-mediated genome editing by Cas9 variants in Brassica.

CRISPR/Cas9, presently the most widely used genome editing technology, has provided great potential for functional studies and plant breeding. However, the strict requirement for a protospacer adjacent motif (PAM) has hindered the application of the CRISPR/Cas9 system because the number of targetable genomic sites is limited. Recently, the engineered variants Cas9-NG, SpG, and SpRY, which recognize non-canonical PAMs, have been successfully tested in plants (mainly in rice, a monocot). In this study, we evaluated the targeted mutagenesis capabilities of these Cas9 variants in two important Brassica vegetables, Chinese cabbage (Brassica rapa spp. pekinensis) and cabbage (Brassica oleracea var. capitata). Both Cas9-NG and SpG induced efficient mutagenesis at NGN PAMs, while SpG outperformed Cas9-NG at NGC and NGT PAMs. SpRY achieved efficient editing at almost all PAMs (NRN > NYN), albeit with some self-targeting activity at transfer (T)-DNA sequences. And SpRY-induced mutants were detected in cabbage plants in a PAM-less fashion. Moreover, an adenine base editor was developed using SpRY and TadA8e deaminase that induced A-to-G conversions within target sites using non-canonical PAMs. Together, the toolboxes developed here induced successful genome editing in Chinese cabbage and cabbage. Our work further expands the targeting scope of genome editing and paves the way for future basic research and genetic improvement in Brassica. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-024-00155-7.

Composite Hydrogel Sealants for Annulus Fibrosus Repair.

Intervertebral disc (IVD) herniation is a leading cause of disability and lower back pain, causing enormous socioeconomic burdens. The standard of care for disc herniation is nucleotomy, which alleviates pain but does not repair the annulus fibrosus (AF) defect nor recover the biomechanical function of the disc. Existing bioadhesives for AF repair are limited by insufficient adhesion and significant mechanical and geometrical mismatch with the AF tissue, resulting in the recurrence of protrusion or detachment of bioadhesives. Here, we report a composite hydrogel sealant constructed from a composite of a three-dimensional (3D)-printed thermoplastic polyurethane (TPU) mesh and tough hydrogel. We tailored the fiber angle and volume fraction of the TPU mesh design to match the angle-ply structure and mechanical properties of native AF. Also, we proposed and tested three types of geometrical design of the composite hydrogel sealant to match the defect shape and size. Our results show that the sealant could mimic native AF in terms of the elastic modulus, flexural modulus, and fracture toughness and form strong adhesion with the human AF tissue. The bovine IVD tests show the effectiveness of the composite hydrogel sealant for AF repair and biomechanics recovery and for preventing herniation with its heightened stiffness and superior adhesion. By harnessing the combined capabilities of 3D printing and bioadhesives, these composite hydrogel sealants demonstrate promising potential for diverse applications in tissue repair and regeneration.

Natural products as inhibitors against pancreatic cancer cell proliferation and invasion: possible mechanisms.

Pancreatic cancer is one of the gastrointestinal tumors with the lowest survival rate and the worst prognosis. At the time of diagnosis, the majority of patients have missed the opportunity for radical surgical resection and opt for chemotherapy as their primary treatment choice. And drug resistance emerges during the application of the most widely used chemotherapeutic regimens such as modified FOLFIRINOX regimen, gemcitabine monotherapy or 5-Fluorouracil combination therapy, which further reduces the therapeutic efficacy. Therefore, it is urgent to explore better treatment strategies for pancreatic cancer. In recent years, more and more studies have found that natural products have significant anti-pancreatic cancer properties. In this paper, we reviewed the possible mechanisms by which natural products inhibit the proliferation and invasion of pancreatic cancer cells, including the possible mechanisms of targeting the inhibition of the growth and proliferation regulatory pathways of pancreatic cancer cells, inducing apoptosis and autophagy of pancreatic cancer cells, inhibiting the EMT process of pancreatic cancer cells, and inhibiting the angiogenesis of pancreatic cancer. Meanwhile, natural products have also hindered the progress of their basic and clinical research due to the complexity of their composition and the limitation of biological extraction technology. Further exploration of the specific molecular mechanisms of natural products to inhibit the proliferation and invasion of pancreatic cancer cells, optimization of purification and preparation techniques, and enrichment of basic and clinical trials to verify their efficacy and safety may be the future direction of natural products in the field of anti-pancreatic cancer research.

Cross-border regulation of the STK39/MAPK14 pathway by Lycium barbarum miR166a to inhibit triple-negative breast cancer.

OBJECTIVE: To investigate the effects of Lycium barbarum miRNA166a (Lb-miR166a) on human gene expression regulation during the therapy for triple-negative breast cancer (TNBC). METHODS: Transcriptome sequencing was used to analyze the distribution and composition of miRNA in Lycium barbarum fruit. Lb-miR166a was introduced into TNBC MB-231 cells by lentiviral transfection to study its effects on cell proliferation, apoptosis, invasion, and metastasis both in vivo and in vitro. Bioinformatic and dual-luciferase assays identified the target gene of Lb-miR166a. The role of STK39 in TNBC progression was elucidated through clinical data analysis combined with cellular studies. The influence of Lb-miR166a on the STK39/MAPK14 pathway was confirmed using a target-specific knockout MB-231 cell line. RESULTS: Lb-miR166a was found to be highly expressed in Lycium barbarum. It inhibited MB-231 cell proliferation, invasion, and metastasis, and promoted apoptosis. STK39 was overexpressed in TNBC and was associated with increased invasiveness and poorer patient prognosis. Gene enrichment analysis and dual-luciferase assays demonstrated that Lb-miR166a regulates STK39 expression cross-border and inhibits MAPK14 phosphorylation, impacting the phosphorylation of downstream target genes. CONCLUSION: The downregulation of STK39 and subsequent inhibition of MAPK14 phosphorylation by Lb-miR166a leads to reduced proliferation, migration, and invasion of TNBC cells. These findings suggest a novel therapeutic strategy for TNBC treatment, highlighting possible clinical applications of Lb-miR166a in managing this aggressive cancer type.

The Characteristics of Coronary Artery Lesions in COVID-19 Infected Patients with Coronary Artery Disease:An Optical Coherence Tomography Study.

Coronavirus disease 2019 (COVID-19) may predispose patients to cardiac injuries but whether COVID-19 infection affects the morphological features of coronary plaques to potentially influence the outcome of patients with coronary artery disease (CAD) remains unknown. By using optical coherence tomography (OCT), this study compared the characteristics of coronary plaque in CAD patients with/without COVID-19 infection. The 206 patients were divided into two groups. The COVID-19 group had 113 patients between December 7, 2022 and March 31, 2023 who received optical coherence tomography (OCT) assessment after China decided to lift the restrict on COVID-19 and had a history of COVID-19 infection. The non-COVID-19 group had 93 patients without COVID-19 infection who underwent OCT before December 7, 2022. The COVID-19 group demonstrated a higher incidence of plaque ruptures (53.1% vs. 38.7%, p=0.039), erosions (28.3% vs. 11.8%, p=0.004), fibrous (96.5% vs. 89.2%, p=0.041) and diffuse lesions (73.5% vs. 50.5%, p<0.001) compared to the non-COVID-19 group, whereas non-COVID-19 group exhibited a higher frequency of cholesterol crystals (83.9% vs. 70.8%, p=0.027), deep calcifications (65.6% vs. 51.3%, p=0.039) and solitary lesions (57.0% vs. 34.5%, p=0.001). Kaplan-Meier survival analysis revealed a significantly lower major adverse cardiac events (MACE)-free probability in COVID-19 group (91.6% vs. 95.5%, P=0.006) than non-COVID-19 group. In conclusion, OCT demonstrated that COVID-19 infection is associated with coronary pathological changes such as more plaque ruptures, erosions, and fibrosis as well as diffuse lesions. Further, COVID-19 infection is associated with the higher propensity for acute coronary events and the higher risk of MACE in CAD patients.

Gastric microbiota transplantation as a potential treatment for immune checkpoint inhibitor-associated gastritis.

Immune-related adverse events (irAEs) are complications of the use of immune checkpoint inhibitors (ICIs). ICI-associated gastritis is one of the main irAEs. The gastric microbiota is often related to the occurrence and development of many gastric diseases. Gastric microbiota adjustment may be used to treat gastric disorders in the future. Faecal microbiota transplantation can alter the gut microbiota of patients and has been used for treating ICI-associated colitis. Therefore, we propose gastric microbiota transplantation as a supplementary treatment for patients with ICI-associated gastritis who do not respond well to conventional therapy.

LncRNA BBOX1-AS1 Contributes to Laryngeal Carcinoma Progression by Recruiting SRSF1 to Maintain EFNB2 mRNA Stability.

Laryngeal cancer is a common malignancy of the larynx with a generally poor prognosis. This study systematically assessed the functional role of lncRNA BBOX1-AS1 in laryngeal carcinoma progression and associated molecular regulatory mechanisms. The proliferation, migration, and invasion of laryngeal carcinoma cells were detected by Cell Counting Kit-8, wound healing, clonal formation, and transwell assays. In addition, the interaction between BBOX1-AS1, Serine/Arginine Splicing Factor 1 (SRSF1), and Ephrin-B2 (EFNB2) mRNA was examined employing RNA immunoprecipitation and RNA pull-down experiments. Furthermore, western blotting, and RT-qPCR assays were adopted to detect the expression levels of BBOX1-AS1, SRSF1, and EFNB2. The impact of BBOX1-AS1 and SRSF1 on EFNB2 mRNA stability was examined using the RNA stability assay. BBOX1-AS1 was highly expressed in human laryngeal carcinoma tissues and cell lines. BBOX1-AS1 knockdown suppressed the growth, proliferation, migration, and invasion of laryngeal carcinoma cells. BBOX1-AS1 maintained the stability of EFNB2 mRNA in laryngeal carcinoma cells by recruiting SRSF1. EFNB2 knockdown inhibited the growth and metastatic function of laryngeal carcinoma cells in vitro. EFNB2 overexpression reversed the influence of BBOX1-AS1 knockdown on laryngeal cancer tumorigenesis. BBOX1-AS1 maintained EFNB2 mRNA stability by recruiting SRSF1, thereby aggravating laryngeal carcinoma malignant phenotypes. BBOX1-AS1 might be a new theoretical target for the treatment of laryngeal carcinoma.

Risk factors for mid- and long-term mortality in lung transplant recipients aged 70 years and older.

OBJECTIVES: With increased lung transplantation in those aged 70 and older, limited literature addresses risk factors affecting their survival. Our study aims to identify independent factors impacting mid- and long-term mortality in this elderly population. METHODS: This study analyzed lung transplant patients over 70 from May 2005 to December 2022 using United Network for Organ Sharing data. The 3- or 5-year cohort excluded multi-organ, secondary transplantation and loss to follow-up. Univariable Cox analysis was conducted to assess recipient, donor and transplant factors. Factors with a significance level of P < 0.2 were subsequently included in a multivariable Cox model to identify correlations with 3- and 5-year mortality in patients aged over 70. RESULTS: Multivariable analysis has identified key factors affecting 3- and 5-year mortality in elderly lung transplant patients over 70. Common notable factors include recipient total bilirubin, intensive care unit status at the time of transplantation, donor diabetes, Cytomegalovirus (CMV) mismatch and single lung transplantation. Additionally, Hispanic/Latino patients and ischaemia time of the transplant significantly impact the 3-year mortality, while recipient age, diabetes, nitric oxide use before transplantation and creatinine were identified as unique independent risk factors affecting the 5-year morality. CONCLUSIONS: The study identified several independent risk factors that impact the mid- and long-term survival of lung transplantation for individuals over 70 years. These findings can contribute to the optimization of lung transplant treatment strategies and perioperative management in elderly patients, thereby enhancing the survival rate of this age group.

The effects of temperament type on infusion extravasation in newborns.

Infusion extravasation has an increased incidence in newborns, which can result in various adverse outcomes. This study aimed to investigate the effects of different types of temperament on infusion extravasation in newborns. A total of 209 newborns aged 4-7 days who were treated with infusion therapy were assessed for temperament type using the neonatal behavioral assessment scale score (NBAS). The 2009 Infusion Nurses Society clinical grading criteria for extravasation were used, and the clinical data of the newborns, such as gestational age and body weight, were collected. Out of 209 newborns assessed, 107 developed infusion extravasations, with an incidence rate of 51.2%. Newborns with intermediate temperament type were more prone to develop infusion extravasation. Newborns with low body weight, amniotic fluid aspiration syndrome, or meconium aspiration syndrome were prone to develop infusion extravasation. Body weight, temperament type of consolability, temperament type of peak of excitement, diseases, general temperament type, and NBAS total scores of the neonates were independent risk factors for infusion extravasation. Thus, different types of temperament can have an impact on neonatal extravasation.

W-Shaped π-Extended Double Undecabenzo[7]helicene.

A chiral W-shaped fully π-extended double [7]helicene (ED7H) has been synthesized and fully characterized. It displays fluorescence emission (λem = 636 nm) with a quantum yield (Φf) of 0.10. In comparison to its X-shaped and monomict π-extended [7]helicene analogues, enantiopure W-shaped ED7H exhibited superior chiral optical characteristics, including distinct circular dichroism signals from 400 to 650 nm, a good dissymmetric emission factor |glum| of 4 × 10-3, and a circularly polarized luminescence brightness value BCPL of 42 M-1 cm-1.

Fenofibrate-promoted hepatomegaly and liver regeneration are PPARα-dependent and partially related to the YAP pathway.

Fenofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist, is widely prescribed for hyperlipidemia management. Recent studies also showed that it has therapeutic potential in various liver diseases. However, its effects on hepatomegaly and liver regeneration and the involved mechanisms remain unclear. Here, the study showed that fenofibrate significantly promoted liver enlargement and regeneration post-partial hepatectomy in mice, which was dependent on hepatocyte-expressed PPARα. Yes-associated protein (YAP) is pivotal in manipulating liver growth and regeneration. We further identified that fenofibrate activated YAP signaling by suppressing its K48-linked ubiquitination, promoting its K63-linked ubiquitination, and enhancing the interaction and transcriptional activity of the YAP-TEAD complex. Pharmacological inhibition of YAP-TEAD interaction using verteporfin or suppression of YAP using AAV Yap shRNA in mice significantly attenuated fenofibrate-induced hepatomegaly. Other factors, such as MYC, KRT23, RAS, and RHOA, might also participate in fenofibrate-promoted hepatomegaly and liver regeneration. These studies demonstrate that fenofibrate-promoted liver enlargement and regeneration are PPARα-dependent and partially through activating the YAP signaling, with clinical implications of fenofibrate as a novel therapeutic agent for promoting liver regeneration.