Design, Synthesis, and Antimicrobial Activity Evaluation of Novel Isocryptolepine Derivatives against Phytopathogenic Fungi and Bacteria.

This research adopted the Fischer indole synthesis method to continue constructing a novel drug-like chemical entity based on the guidance of isocryptolepine and obtained four series of derivatives: Y, Da, Db, and Dc. The antimicrobial activity of these derivatives against plant pathogens was further evaluated. The results showed that Dc-2 had the best antifungal effect against Botrytis cinerea, and its EC50 value was up to 1.29 µg/mL. In addition, an in vivo activity test showed that the protective effect of Dc-2 on apples was 82.2% at 200 µg/mL, which was better than that of Pyrimethanil (45.4%). Meanwhile, it was found by scanning electron microscopy and transmission electron microscopy that the compound Dc-2 affected the morphology of mycelia. The compound Dc-2 was found to damage the cell membrane by PI and ROS staining. Through experiments such as leakage of cell contents, it was found that the compound Dc-2 changed the permeability of the cell membrane and caused the leakage of substances in the cell. According to the above studies, compound Dc-2 can be used as a candidate lead compound for further structural optimization and development.

Identification of hub genes and key pathways in arsenic-treated rice (Oryza sativa L.) based on 9 topological analysis methods of CytoHubba.

BACKGROUND: Arsenic is a toxic metalloid that can cause acute and chronic adverse health problems. Unfortunately, rice, the primary staple food for more than half of the world's population, is generally regarded as a typical arsenic-accumulating crop plant. Evidence indicates that arsenic stress can influence the growth and development of the rice plant, and lead to high concentrations of arsenic in rice grain. But the underlying mechanisms remain unclear. METHODS: In the present research, the possible molecules and pathways involved in rice roots in response to arsenic stress were explored using bioinformatics methods. Datasets that involving arsenic-treated rice root and the "study type" that was restricted to "Expression profiling by array" were selected and downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between the arsenic-treated group and the control group were obtained using the online web tool GEO2R. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to investigate the functions of DEGs. The protein-protein interactions (PPI) network and the molecular complex detection algorithm (MCODE) of DEGs were analyzed using STRING and Cystoscope, respectively. Important nodes and hub genes in the PPI network were predicted and explored using the Cytoscape-cytoHubba plug-in. RESULTS: Two datasets, GSE25206 and GSE71492, were downloaded from Gene Expression Omnibus (GEO) database. Eighty common DEGs from the two datasets, including sixty-three up-regulated and seventeen down-regulated genes, were then selected. After functional enrichment analysis, these common DEGs were enriched mainly in 10 GO items, including glutathione transferase activity, glutathione metabolic process, toxin catabolic process, and 7 KEGG pathways related to metabolism. After PPI network and MCODE analysis, 49 nodes from the DEGs PPI network were identified, filtering two significant modules. Next, the Cytoscape-cytoHubba plug-in was used to predict important nodes and hub genes. Finally, five genes [Os01g0644000, PRDX6 (Os07g0638400), PRX112 (Os07g0677300), ENO1(Os06g0136600), LOGL9 (Os09g0547500)] were verified and could serve as the best candidates associated with rice root in response to arsenic stress. CONCLUSIONS: In summary, we elucidated the potential pathways and genes in rice root in response to arsenic stress through a comprehensive bioinformatics analysis.

A risk prediction model based on machine learning algorithm for parastomal hernia after permanent colostomy.

OBJECTIVE: To develop a machine learning-based risk prediction model for postoperative parastomal hernia (PSH) in colorectal cancer patients undergoing permanent colostomy, assisting nurses in identifying high-risk groups and devising preventive care strategies. METHODS: A case-control study was conducted on 495 colorectal cancer patients who underwent permanent colostomy at the Second Affiliated Hospital of Anhui Medical University from June 2017 to June 2023, with a 1-year follow-up period. Patients were categorized into PSH and non-PSH groups based on PSH occurrence within 1-year post-operation. Data were split into training (70%) and testing (30%) sets. Variable selection was performed using Least Absolute Shrinkage and Selection Operator (LASSO) regression, and binary classification prediction models were established using Logistic Regression (LR), Support Vector Classification (SVC), K Nearest Neighbor (KNN), Random Forest (RF), Light Gradient Boosting Machine (LGBM), and Extreme Gradient Boosting (XgBoost). The binary classification label denoted 1 for PSH occurrence and 0 for no PSH occurrence. Parameters were optimized via 5-fold cross-validation. Model performance was evaluated using Area Under Curve (AUC), specificity, sensitivity, accuracy, positive predictive value, negative predictive value, and F1-score. Clinical utility was evaluated using decision curve analysis (DCA), model explanation was enhanced using shapley additive explanation (SHAP), and model visualization was achieved using a nomogram. RESULTS: The incidence of PSH within 1 year was 29.1% (144 patients). Among the models tested, the RF model demonstrated the highest discrimination capability with an AUC of 0.888 (95% CI: 0.881-0.935), along with superior specificity, accuracy, sensitivity, and F1 score. It also showed the highest clinical net benefit on the DCA curve. SHAP analysis identified the top 10 influential variables associated with PSH risk: body mass index (BMI), operation duration, history and status of chronic obstructive pulmonary disease (COPD), prealbumin, tumor node metastasis (TNM) staging, stoma site, thickness of rectus abdominis muscle (TRAM), C-reactive protein CRP, american society of anesthesiologists physical status classification (ASA), and stoma diameter. These insights from SHAP plots illustrated how these factors influence individual PSH outcomes. The nomogram was used for model visualization. CONCLUSION: The Random Forest model demonstrated robust predictive performance and clinical relevance in forecasting colonic PSH. This model aids in early identification of high-risk patients and guides preventive care.

Optimizing Skim Milk Yogurt Properties: Combined Impact of Trans-glutaminase and Protein-Glutaminase.

The lack of fat in yogurt can lead to alterations in taste and whey separation, reducing consumer acceptance. In this study, the feasibility of enhancing the quality of skim milk yogurt through a combination of transglutaminase (TG) and protein-glutaminase (PG) was investigated. The combination of TG and PG resulted in simultaneous cross-linking and deamidated of casein micelles, with PG deamidation taking priority over TG cross-linking, leading to higher solubility and lower turbidity of milk proteins compared with TG alone. When 0.06 U/mL TG and 0.03 U/mL PG were added, firmness and viscosity indexes significantly increased by 38.26 and 78.59%, respectively as compared with the control. Microscopic images revealed increased cross-linking with casein and filling of cavities by smaller sub-micelles in the combination of TG and PG treatment. Furthermore, the combination of TG and PG resolved issues of rough taste and whey separation, leading to improved overall liking. This study highlights the benefits of using both enzymes in dairy production and has important implication for future research.

Chlorogenic Acid Alleviates High Glucose-induced HK-2 Cell Oxidative Damage through Activation of KEAP1/NRF2/ARE Signaling Pathway.

OBJECTIVE: To investigate the alleviating effect of chlorogenic acid (CGA) on oxidative damage in high glucose (HG)-induced HK-2 cells and to explore its potential mechanisms. METHODS: We cultured the human proximal tubular cell line HK-2 and divided them into the control group and different concentrations of CGA groups (0, 5, 10, 25, 50, 100, 200 µM). The trypan blue dye test was used to detect CGA's potential cytotoxicity on HK-2 cells. Then, we treated HK-2 with HG and CGA; the Cell Counting Kit-8 (CCK-8) method was used to detect the cell viability of HK-2 cells in each group. Flow cytometry was employed to measure the apoptosis rate of cells. Western blot was performed to detect the expression of apoptosis proteins B-cell lymphoma-2 (BCL-2), BCL-2-associated X protein (BAX), cysteinyl aspartate specific proteinase (CASPASE)-9, and CASPASE-3. In addition, enzymatic activities, including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and lipid peroxide (LPO), were measured with the corresponding detection kits. 2',7'-Dichlorodihydrofluorescein diacetate (DCFH-DA) assay and flow cytometry were performed to detect reactive oxygen species (ROS) production. Western blot analysis and Reverse Transcription-Polymerase Chain Reaction (RT-PCR) were conducted to evaluate protein and mRNA expressions of the Kelch-like ECH-associated protein-1 (KEAP1)/Nuclear factor erythroid 2-related factor 2 (NRF2)/Antioxidant Response Elements (ARE) signaling pathway. RESULTS: The outcomes showed that, in a dose-dependent way, CGA dramatically increased the vitality of HK-2 induced by HG. Furthermore, CGA significantly reduced the HG-stimulated HK-2 cell apoptosis, which may be linked to the promotion of BCL-2 and the suppression of BAX, cleaved-CASPASE-3, and cleaved-CASPASE-9 expression. In HK-2 cells, CGA reduced the formation of ROS generated by HG levels and markedly boosted the activity of the antioxidant enzymes SOD, GSH-Px, and CAT. Furthermore, compared with the HG group, CGA significantly raised NRF2 nuclear expression and downregulated NRF2 cytosolic expression and increased the mRNA expression of NRF2 and its target genes, heme oxygenase-1 (HO-1), KEAP1, and NAD(P)H dehydrogenase quinone 1 (NQO1). CONCLUSION: These results show that CGA might be useful in managing oxidative damage in HG-induced HK-2 cells.

Dual-Intermetallic Heterostructure on Hierarchical Nanoporous Metal for Highly Efficient Alkaline Hydrogen Electrocatalysis.

Constructing well-defined active multisites is an effective strategy to break linear scaling relationships to develop high-efficiency catalysts toward multiple-intermediate reactions. Here, dual-intermetallic heterostructure composed of tungsten-bridged Co3W and WNi4 intermetallic compounds seamlessly integrated on hierarchical nanoporous nickel skeleton is reported as a high-performance nonprecious electrocatalyst for alkaline hydrogen evolution and oxidation reactions. By virtue of interfacial tungsten atoms configuring contiguous multisites with proper adsorptions of hydrogen and hydroxyl intermediates to accelerate water dissociation/combination and column-nanostructured nickel skeleton facilitating electron and ion/molecule transportations, nanoporous nickel-supported Co3W-WNi4 heterostructure exhibits exceptional hydrogen electrocatalysis in alkaline media, with outstanding durability and impressive catalytic activities for hydrogen oxidation reaction (geometric exchange current density of ≈6.62 mA cm-2) and hydrogen evolution reaction (current density of ≈1.45 A cm-2 at overpotential of 200 mV). Such atom-ordered intermetallic heterostructure alternative to platinum group metals shows genuine potential for hydrogen production and utilization in hydroxide-exchange-membrane water electrolyzers and fuel cells.

In Situ Engineering Multifunctional Active Sites of Ruthenium-Nickel Alloys for pH-Universal Ampere-Level Current-Density Hydrogen Evolution.

Developing robust non-platinum electrocatalysts with multifunctional active sites for pH-universal hydrogen evolution reaction (HER) is crucial for scalable hydrogen production through electrochemical water splitting. Here ultra-small ruthenium-nickel alloy nanoparticles steadily anchored on reduced graphene oxide papers (Ru-Ni/rGOPs) as versatile electrocatalytic materials for acidic and alkaline HER are reported. These Ru-Ni alloy nanoparticles serve as pH self-adaptive electroactive species by making use of in situ surface reconstruction, where surface Ni atoms are hydroxylated to produce bifunctional active sites of Ru-Ni(OH)2 for alkaline HER, and selectively etched to form monometallic Ru active sites for acidic HER, respectively. Owing to the presence of Ru-Ni(OH)2 multi-site surface, which not only accelerates water dissociation to generate reactive hydrogen intermediates but also facilitates their recombination into hydrogen molecules, the self-supported Ru90Ni10/rGOP hybrid electrode only takes overpotential of as low as ≈106 mV to deliver current density of 1000 mA cm-2, and maintains exceptional stability for over 1000 h in 1 m KOH. While in 0.5 m H2SO4, the Ru90Ni10/rGOP hybrid electrode exhibits acidic HER catalytic behavior comparable to commercially available Pt/C catalyst due to the formation of monometallic Ru shell. These electrochemical behaviors outperform some of the best Ru-based catalysts and make it attractive alternative to Pt-based catalysts toward highly efficient HER.

Lamellar Nanoporous Metal/Intermetallic Compound Heterostructure Regulating Dendrite-Free Zinc Electrodeposition for Wide-Temperature Aqueous Zinc-Ion Battery.

Aqueous zinc-ion batteries are attractive post-lithium battery technologies for grid-scale energy storage because of their inherent safety, low cost and high theoretical capacity. However, their practical implementation in wide-temperature surroundings persistently confronts irregular zinc electrodeposits and parasitic side reactions on metal anode, which leads to poor rechargeability, low Coulombic efficiency and short lifespan. Here, this work reports lamellar nanoporous Cu/Al2Cu heterostructure electrode as a promising anode host material to regulate high-efficiency and dendrite-free zinc electrodeposition and stripping for wide-temperatures aqueous zinc-ion batteries. In this unique electrode, the interconnective Cu/Al2Cu heterostructure ligaments not only facilitate fast electron transfer but work as highly zincophilic sites for zinc nucleation and deposition by virtue of local galvanic couples while the interpenetrative lamellar channels serving as mass transport pathways. As a result, it exhibits exceptional zinc plating/stripping behaviors in aqueous hybrid electrolyte of diethylene glycol dimethyl ether and zinc trifluoromethanesulfonate at wide temperatures ranging from 25 to -30 °C, with ultralow voltage polarizations at various current densities and ultralong lifespan of >4000 h. The outstanding electrochemical properties enlist full cell of zinc-ion batteries constructed with nanoporous Cu/Al2Cu and ZnxV2O5/C to maintain high capacity and excellent stability for >5000 cycles at 25 and -30 °C.

Recent advances in early pregnancy loss diagnosis in dairy cows: New approaches.

Early pregnancy loss is a primary cause of low reproductive rates in dairy cows, posing severe economic losses to dairy farming. The accurate diagnosis of dairy cows with early pregnancy loss allows for oestrus synchronization, shortening day open, and increasing the overall conception rate of the herd. Several techniques are available for detecting early pregnancy loss in dairy cows, including rectal ultrasound, circulating blood progesterone, and pregnancy-associated glycoproteins (PAGs). Yet, there is a need to improve on existing techniques and develop novel strategies to identify cows with early pregnancy loss accurately. This manuscript reviews the applications of rectal ultrasound, circulating blood progesterone concentration, and PAGs in the diagnosis of pregnancy loss in dairy cows. The manuscript also discusses the recent progress of new technologies, including colour Doppler ultrasound (CDUS), interferon tau-induced genes (ISGs), and exosomal miRNA in diagnosing pregnancy loss in dairy cows. This study will provide an option for producers to re-breed cows with pregnancy loss, thereby reducing the calving interval and economic costs. Meanwhile, this manuscript might also act as a reference for exploring more economical and precise diagnostic technologies for early pregnancy loss in dairy cows.

Management of anastomotic biliary stricture through utilizing percutaneous transhepatic cholangioscopy.

AIM: Occurrence of anastomotic biliary stricture (AS) remains an essential issue following hepatobiliary surgeries, and percutaneous transhepatic cholangioscopy (PTCS) has great therapeutic significance in handling refractory AS for patients with altered gastrointestinal anatomy after cholangio-jejunostomy. This present study aimed to investigate feasibility of PTCS procedures in AS patients for therapeutic indications. MATERIALS AND METHODS: This study was a single-center, retrospective cohort study with a total number of 124 consecutive patients who received therapeutic PTCS due to AS. Clinical success rate, required number, and adverse events of therapeutic PTCS procedures as well as patients survival state were reviewed. RESULTS: These 124 patients previously underwent choledochojejunostomy or hepatico-jejunostomy, and there was post-surgical altered gastrointestinal anatomy. Overall, 366 therapeutic PTCS procedures were performed for these patients through applying rigid choledochoscope, and the median time of PTCS procedures was 3 (1-11). Among these patients, there were 34 cases (27.32%) accompanied by biliary strictures and 100 cases (80.65%) were also combined with biliary calculi. After therapeutic PTCS, most patients presented with relieved clinical manifestations and improved liver functions. The median time of follow-up was 26 months (2-86 months), and AS was successfully managed through PTCS procedures in 104 patients (83.87%). During the follow-up period, adverse events occurred in 81 cases (65.32%), most of which were tackled through supportive treatment. CONCLUSION: PTCS was a feasible, safe and effective therapeutic modality for refractory AS, which may be a promising alternative approach in clinical cases where the gastrointestinal anatomy was changed after cholangio-jejunostomy.

Inhibiting the m6A Reader IGF2BP3 Suppresses Ovarian Cancer Cell Growth via Regulating PLAGL2 mRNA Stabilization.

Background: The oncogene IGF2 mRNA binding protein 3 (IGF2BP3) could function as an m6A reader in stabilizing many tumor-associated genes' mRNAs. However, the relevant oncogenic mechanism by which IGF2BP3 promotes ovarian cancer growth is largely unknown. Methods: The IGF2BP3 expression in ovarian cancer was identified by retrieving the datasets from The Cancer Genome Atlas (TCGA). GEO datasets evaluated the relevant signaling pathways in IGF2BP3 knockdown in ovarian cancer cells. IGF2BP3 positive correlation gene in TCGA was calculated. MTS proliferation assay was identified in IGF2BP3 knockdown and rescued by PLAG1 like zinc finger 2 (PLAGL2) overexpression in ES-2 and SKOV3 cells. Bioinformatic analysis and RIP-qPCR were predicted and identified the IGF2BP3 binding site and PLAGL2 mRNA stability. The animal experiment identified IGF2BP3 proliferation inhibition. Results: IGF2BP3 was upregulated in ovarian cancer tissue and cells. The depletion of IGF2BP3 in ovarian cancer cells leads to an enhancement of the pathway involved in cellular proliferation and mRNA stability. IGF2BP3 positive correlation suppressed pro-proliferation gene PLAGL2. IGF2BP3 knockdown suppressed ovarian cancer cell proliferation and was rescued by PLAGL2 overexpression. Luciferase reporter assay confirmed that IGF2BP3 could bind to 3'-UTR of PLAGL2 to maintain the mRNA stability. Further, in in vivo experiments, IGF2BP3 knockdown suppressed ovarian cancer cell proliferation via inhibiting PLAGL2 expression. Conclusion: All of these indicate that PLAGL2 mediates the main function of IGF2BP3 knockdown on ovarian cancer proliferation inhibition through mRNA stability regulation.

Gram-level NH3 Electrosynthesis via NOx reduction on a Cu Activated Co Electrode.

Ambient electrochemical ammonia (NH3 ) synthesis is one promising alternative to the energy-intensive Haber-Bosch route. However, the industrial requirement for the electrochemical NH3 production with amperes current densities or gram-level NH3 yield remains a grand challenge. Herein, we report the high-rate NH3 production via NO2 - reduction using the Cu activated Co electrode in a bipolar membrane (BPM) assemble electrolyser, wherein BPM maintains the ion balance and the liquid level of electrolyte. Benefited from the abundant Co sites and optimal structure, the target modified Co foam electrode delivers a current density of 2.64 A cm-2 with the Faradaic efficiency of 96.45 % and the high NH3 yield rate of 279.44 mg h-1 cm-2 in H-type cell using alkaline electrolyte. Combined with in situ experiments and theoretical calculations, we found that Cu optimizes the adsorption behavior of NO2 - and facilitates the hydrogenation steps on Co sites toward a rapid NO2 - reduction process. Importantly, this activated Co electrode affords a large NH3 production up to 4.11 g h-1 in a homemade reactor, highlighting its large-scale practical feasibility.

The Predictive Value of NGF, TMAO, SIRT1 and apoA1 in Patients With Ischemic Heart Failure.

Objective: The present study aimed to explore the predictive value and prognosis of SYNTAX score, nerve growth factor (NGF), trimethylamino oxide (TMAO), silent information regulator 1 (SIRT1), and apolipoprotein A1 (apoA1) for ischemic heart failure (IHF) patients. Methods: From January 2020 to January 2021, 87 patients diagnosed with IHF in the Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, and 42 healthy people were included and analyzed retrospectively. The 87 patients were divided into 3 subgroups according to New York Heart Association (NYHA) heart function classification, as group 1 (n=9, classes I-II heart function), group 2 (n = 7, class III heart function), and group 3 (n = 31, class IV heart function). The levels of left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), left atrium diameter (LAD), NGF, TMAO, SIRT1, SYNTAX score, and apoA1 were compared among these groups. Results: The SIRT1 and apoA1 of patients with classes I-II, III, and IV heart function were significantly lower than that of healthy people in the control group, while TMAO and NGF were significantly higher than those of healthy people (all P < .05). The SYNTAX score of grade I-II, grade III, and grade IV groups was significantly lower than that of the healthy group (P < .05). The two groups had no significant difference in the number of coronary artery lesions (P > .05). The SIRT1 and apoA1 of patients with classes III and IV heart function were significantly lower than that of patients with classes I -II heart function, while TMAO and NGF were significantly higher than those of class I-II people (all P < .05). The SIRT1 and apoA1 of patients with class IV heart function were significantly lower than those of patients with class III heart function, while TMAO and NGF were significantly higher than those of patients with class III heart function (all P < .05). After 1 year follow-up of these IHF patients, 22 patients were readmission because of cardiac events, and 6 patients died in hospital or during follow-up. These 28 patients were allocated to the event group, while the rest 59 patients were allocated to the events-free group. The SIRT1 and apoA1 level in event group was significantly lower than those of event-free group, while the TMAO, SYNTAX score, and NGF level were significantly higher than those of the event-free group (all P < .001). Baseline characters and heart function with significant differences (LVEF, LAD and LVEDD) among these groups, and NGF, TMAO, SIRT1, SYNTAX score and apoA1 were enrolled into Logistic regression. SYNTAX score, NGF, TMAO, SIRT1 and apoA1 were independent risk factors for the prognosis of IHF patients (all P < .05). Conclusion: SIRT1, apoA1, TMAO and NGF serum levels in patients with IHF are abnormally expressed and closely related to cardiac function. The levels of SYNTAX score, NGF, TMAO, SIRT1, and apoA can effectively predict adverse events in patients with IHF.

Effect of protein-glutaminase on the texture, rheology, microstructure and sensory properties of skimmed set-type yoghurt.

The effects of enzymatic deamidation by protein-glutaminase (PG) on the texture, rheology, microstructure, and sensory properties of skimmed set-type yoghurt were studied. The proportion of small-particle size milk protein micelles (10-50 nm) increased significantly from 0 to 99.39% after PG deamidation. Cryo-SEM results revealed that PG-treated yoghurt had a denser and less open 3D structure. PG was effective at inhibiting post-acidification during storage at 4 ℃. The water holding capacity of PG-treated yoghurt (0.12 U·mL-1) increased by more than 15%. The fluidity and viscosity of yoghurt were significantly improved with increasing PG dose. Sensory evaluation revealed that PG (0.06 U·mL-1) significantly improved the smoothness and creaminess of skimmed set-type yoghurt, which corresponded to the pastiness in texture. In summary, PG can effectively address the problems of post-acidification, gel fracture, and flavors change in skimmed set-type yoghurt, providing new applications for PG in the food industry.

A Bifunctional Catalyst for Green Ammonia Synthesis from Ubiquitous Air and Water.

Ammonia (NH3 ) is essential for modern agriculture and industry, and, due to its high hydrogen density and no carbon emission, it is also expected to be the next-generation of "clean" energy carrier. Herein, directly from air and water, a plasma-electrocatalytic reaction system for NH3 production, which combines two steps of plasma-air-to-NOx - and electrochemical NOx - reduction reaction (eNOx RR) with a bifunctional catalyst, is successfully established. Especially, the bifunctional catalyst of CuCo2 O4 /Ni can simultaneously promote plasma-air-to-NOx - and eNOx RR processes. The easy adsorption and activation of O2 by CuCo2 O4 /Ni greatly improve the NOx - production rate at the first step. Further, CuCo2 O4 /Ni can also resolve the overbonding of the key intermediate of * NO, and thus reduce the energy barrier of the second step of eNOx RR. Finally, the "green" NH3 production achieves excellent FENH3 (96.8%) and record-high NH3 yield rate of 145.8 mg h-1  cm-2 with large partial current density (1384.7 mA cm-2 ). Moreover, an enlarged self-made H-type electrolyzer improves the NH3 yield to 3.6 g h-1 , and the obtained NH3 is then rapidly converted to a solid of magnesium ammonium phosphate hexahydrate, which favors the easy storage and transportation of NH3 .

Exosomes derived from TGF-ß1-pretreated mesenchymal stem cells alleviate biliary ischemia-reperfusion injury through Jagged1/Notch1/SOX9 pathway.

BACKGROUND: This study aimed to evaluate the efficacy of exosomes (EXO) derived from TGF-ß1-pretreated mesenchymal stem cells (MSCs) on biliary ischemia reperfusion injury (IRI) and further reveal the possible mechanisms. METHODS: Bone marrow-derived MSCs were treated with exogenous TGF-ß1, Jagged1/Notch1/SOX9 pathway inhibitor LY450139, or their combination. Then, EXO were isolated from the culture supernatants and further characterized. After establishing IRI model of biliary epithelial cells (EpiCs), EXO derived from differently-treated MSCs were applied to detect their protective effects on EpiCs, and LY450139 was applied in EpiCs to detect the possible mechanisms after treatment with MSCs-EXO. EXO derived from differently-treated MSCs were further injected into the hepatic artery immediately after establishment of intrahepatic biliary IRI for animal studies. RESULTS: Pretreatment with TGF-ß1 significantly enhanced MSCs-EXO production and elevated the levels of massive miRNAs associated with anti-apoptosis and tissue repair, which were evidently decreased after TGF-ß1 plus LY450139 cotreatment. Notable improvement was observed in EpiCs after MSCs-EXO treatment, evidenced by reduced cellular apoptosis, increased cellular proliferation and declined oxidative stress, which were more evident in EpiCs that were treated with EXO derived from TGF-ß1-pretreated MSCs. However, application of EXO derived from TGF-ß1 plus LY450139-cotreated MSCs reversely enhanced cellular apoptosis, decreased cellular proliferation and anti-oxidants production. Interestingly, LY450139 application in EpiCs after treatment with MSCs-EXO also reversed the declined cellular apoptosis and enhanced oxidative stress induced by TGF-ß1 pretreatment. In animal studies, administration of EXO derived from TGF-ß1-pretreated MSCs more effectively attenuated biliary IRI through reducing oxidative stress, apoptosis, inflammation and enhancing the expression levels of TGF-ß1 and Jagged1/Notch1/SOX9 pathway-related markers, which were reversed after administration of EXO derived from TGF-ß1 plus LY450139-cotreated MSCs. CONCLUSION: Our results provided a vital insight that TGF-ß1 pretreatment endowed MSCs-EXO with stronger protective effects to improve biliary IRI via Jagged1/Notch1/SOX9 pathway.

Achieving volatile potassium promoted ammonia synthesis via mechanochemistry.

Potassium oxide (K2O) is used as a promotor in industrial ammonia synthesis, although metallic potassium (K) is better in theory. The reason K2O is used is because metallic K, which volatilizes around 400 °C, separates from the catalyst in the harsh ammonia synthesis conditions of the Haber-Bosch process. To maximize the efficiency of ammonia synthesis, using metallic K with low temperature reaction below 400 °C is prerequisite. Here, we synthesize ammonia using metallic K and Fe as a catalyst via mechanochemical process near ambient conditions (45 °C, 1 bar). The final ammonia concentration reaches as high as 94.5 vol%, which was extraordinarily higher than that of the Haber-Bosch process (25.0 vol%, 450 °C, 200 bar) and our previous work (82.5 vol%, 45 °C, 1 bar).

Construction and validation of a predictive model for the risk of three-month-postoperative malnutrition in patients with gastric cancer: a retrospective case-control study.

Background: This study analyzed both the influencing factors of malnutrition in patients with gastric cancer and established a multi-dimensional risk model to predict postoperative malnutrition three months after surgery. Methods: The clinical data of gastric cancer patients hospitalized for the first time and receiving laparoscopic surgery in the general surgery department of our hospital were retrospectively analyzed through the hospital information system and divided into a training set and a validation set in the ratio of 7:3. Nutritional status was assessed using the Patient Generated Subjective Global Assessment scale and follow-up records three months after surgery. Patients were divided into a non-malnutrition group and a malnutrition group, and a risk prediction model was established and displayed in the form of a nomogram. Results: A total of 344 patients were included, with 242 in the training and 102 in the validation set. Tumor node metastasis stage (TNM Stage, P=0.020), cardiac function grading (CFG, P=0.013), prealbumin (PAB, P<0.001), neutrophil-to-lymphocyte ratio (NLR, P=0.027), and enteral nutrition within 48 hours post-operation (EN 48 h post-op, P=0.025) were independent risk factors. We established a prediction model with the above variables and displayed it via a nomogram, then verified its effectiveness through internal and external verification. This revealed a C-index of 0.84 (95% CI: 0.79-0.89), and the area under curve (AUC) areas of 0.840 (training set) and 0.854 (validation set), which was better than the nutritional risk screening 2002 (NRS2002) scale. The calibration curve brier scores were 0.159 and 0.195, and the Hosmer-Lemeshow test chi-square values were 14.070 and 1.989 (P>0.05). The decision curve analysis (DCA) of the training set model indicated the clinical applicability was good and within the threshold probability range of 10%-85%, which was also better than NRS2002. Conclusions: A clinical prediction model including multi-dimensional variables was established based on independent risk factors of malnutrition three months after gastrectomy in patients with gastric cancer. The model yields greater prediction accuracy of the risk of three-month-postoperative malnutrition in patients with gastric cancer, helps screen high-risk patients, formulates targeted nutritional prescriptions early, and improves the overall prognosis of patients.

Exosomes: The role in mammalian reproductive regulation and pregnancy-related diseases.

Exosomes are a kind of extracellular vesicles that are produced and secreted by different mammalian cells. They serve as cargo proteins and can transfer different kinds of biomolecules, including proteins, lipids, and nucleic acids, which consequently act on target cells to exert different biological effects. Recent years have witnessed a significant increase in the number of studies on exosomes due to the potential effects of exosomes in the diagnosis and treatment of cancers, neurodegenerative diseases, and immune disorders. Previous studies have demonstrated that exosomal contents, especially miRNAs, are implicated in numerous physiological processes such as reproduction, and are crucial regulators of mammalian reproduction and pregnancy-related diseases. Here, we describe the origin, composition, and intercellular communication of exosomes, and discuss their functions in follicular development, early embryonic development, embryonic implantation, male reproduction and development of pregnancy-related diseases in humans and animals. We believe this study will provide a foundation for revealing the mechanism of exosomes in regulating mammalian reproduction, and providing new approaches and ideas for the diagnosis and treatment of pregnancy-related diseases.

Lamella-heterostructured nanoporous bimetallic iron-cobalt alloy/oxyhydroxide and cerium oxynitride electrodes as stable catalysts for oxygen evolution.

Developing robust nonprecious-metal electrocatalysts with high activity towards sluggish oxygen-evolution reaction is paramount for large-scale hydrogen production via electrochemical water splitting. Here we report that self-supported laminate composite electrodes composed of alternating nanoporous bimetallic iron-cobalt alloy/oxyhydroxide and cerium oxynitride (FeCo/CeO2-xNx) heterolamellas hold great promise as highly efficient electrocatalysts for alkaline oxygen-evolution reaction. By virtue of three-dimensional nanoporous architecture to offer abundant and accessible electroactive CoFeOOH/CeO2-xNx heterostructure interfaces through facilitating electron transfer and mass transport, nanoporous FeCo/CeO2-xNx composite electrodes exhibit superior oxygen-evolution electrocatalysis in 1 M KOH, with ultralow Tafel slope of ~33 mV dec-1. At overpotential of as low as 360 mV, they reach >3900 mA cm-2 and retain exceptional stability at ~1900 mA cm-2 for >1000 h, outperforming commercial RuO2 and some representative oxygen-evolution-reaction catalysts recently reported. These electrochemical properties make them attractive candidates as oxygen-evolution-reaction electrocatalysts in electrolysis of water for large-scale hydrogen generation.