Boosting Up Electrosynthesis of Urea with Nitrate and Carbon Dioxide via Synergistic Effect of Metallic Iron Cluster and Single-Atom.

Electrocatalytic conversion of nitrates and carbon dioxide to urea under ambient conditions shows promise as a potential substitute for traditional urea synthesis processes characterized by high consumption and pollution. In this study, a straightforward one-pot method is employed to prepare a highly efficient FeNC-Fe1N4 electrocatalyst, consisting of atomically dispersed Fe1N4 sites and metallic Fe clusters (FeNC) with particle size of 4-7 nm. The FeNC-Fe1N4 catalyst exhibits remarkable electrocatalytic activity for urea synthesis from nitrate anion (NO3 -) and carbon dioxide (CO2), achieving a urea production rate of 38.2 mmol gcat -1 h-1 at -0.9 V (vs RHE) and a Faradaic efficiency of 66.5% at -0.6 V (vs RHE). Both experimental and theoretical results conclusively demonstrate that metallic Fe clusters and Fe1N4 species provide active sites for the adsorption and activation of NO3 - and CO2, respectively, and the synergistic effect between Fe1N4 and metallic Fe clusters significantly enhances the electrochemical efficiency of urea synthesis. In all, this work contributes to the rational design and comprehensive synthesis of a dual-active site iron-based electrocatalyst, facilitating efficient and sustainable urea synthesis.

Kinetically matched C-N coupling toward efficient urea electrosynthesis enabled on copper single-atom alloy.

Chemical C-N coupling from CO2 and NO3-, driven by renewable electricity, toward urea synthesis is an appealing alternative for Bosch-Meiser urea production. However, the unmatched kinetics in CO2 and NO3- reduction reactions and the complexity of C- and N-species involved in the co-reduction render the challenge of C-N coupling, leading to the low urea yield rate and Faradaic efficiency. Here, we report a single-atom copper-alloyed Pd catalyst (Pd4Cu1) that can achieve highly efficient C-N coupling toward urea electrosynthesis. The reduction kinetics of CO2 and NO3- is regulated and matched by steering Cu doping level and Pd4Cu1/FeNi(OH)2 interface. Charge-polarized Pdδ--Cuδ+ dual-sites stabilize the key *CO and *NH2 intermediates to promote C-N coupling. The synthesized Pd4Cu1-FeNi(OH)2 composite catalyst achieves a urea yield rate of 436.9 mmol gcat.-1 h-1 and Faradaic efficiency of 66.4%, as well as a long cycling stability of 1000 h. In-situ spectroscopic results and theoretical calculation reveal that atomically dispersed Cu in Pd lattice promotes the deep reduction of NO3- to *NH2, and the Pd-Cu dual-sites lower the energy barrier of the pivotal C-N coupling between *NH2 and *CO.

Multi-layer core-shell metal oxide/nitride/carbon and its high-rate electroreduction of nitrate to ammonia.

The electroreduction of nitrate to ammonia is both an alternative strategy to industrial Haber-Bosch ammonia synthesis and a prospective idea for changing waste (nitrate pollution of groundwater around the world) into valuable chemicals, but still hindered by its in-process strongly competitive hydrogen evolution reaction (HER), low ammonia conversion efficiency, and the absence of stability and sustainability. Considering the unique electronic structure of anti-perovskite structured Fe4N, a tandem disproportionation reaction and nitridation-carbonation route for building a multi-layer core-shell oxide/nitride/C catalyst, such as MoO2/Fe4N/C, is designed and executed, in which abundant Fe-N active sites and rich phase interfaces are in situ formed for both suppressing HER and fast transport of electrons and reaction intermediates. As a result, the sample's NO3RR conversion displays a very high NH3 yield rate of up to 11.10 molNH3 gcat.-1 h-1 (1.67 mmol cm-2 h-1) with a superior 99.3% faradaic efficiency and the highest half-cell energy efficiency of 30%, surpassing that of most previous reports. In addition, it is proved that the NO3RR assisted by the MoO2/Fe4N/C electrocatalyst can be carried out in 0.50-1.00 M KNO3 electrolyte at a pH value of 6-14 for a long time. These results guide the rational design of highly active, selective, and durable electrocatalysts based on anti-perovskite Fe4N for the NO3RR.

Case report: Pediatric floating elbow fracture with monteggia-equivalent lesion, ipsilateral humeral shaft fracture, and radial nerve injury: a unique case and favorable treatment outcomes.

This case report presents a rare and intricate pediatric floating elbow fracture involving a Monteggia-equivalent fracture, ipsilateral humeral shaft fracture, and radial nerve injury. The unique mechanism of injury highlights the importance of increased awareness and parental education for accident prevention. Elastic intramedullary nailing was employed for both humeral shaft and forearm fractures, leading to favorable outcomes. Despite the severity of the fractures and radial nerve injury, the prognosis was positive, with nerve function restoration and satisfactory functional recovery. However, the development of avascular necrosis of the radial head remains a challenge, emphasizing the need for further research to better understand and manage these uncommon and complex injuries.

A tumor microenvironment-stimuli responsive nano-prodrug for overcoming gemcitabine chemoresistance by co-delivered miRNA-21 modulator.

Gemcitabine (Gem) has been recommended as a first-line clinical chemotherapeutics for pancreatic ductal adenocarcinoma (PDAC) treatment. Gem treatment could generate chemoresistance associated with abnormal expressions of multiple miRNAs. In the PDAC setting, miRNA-21 (miR-21) overexpression is an important contributing factor of inducing Gem chemoresistance. Inhibition of miR-21 can significantly increase Gem chemosensitivity, which requires an efficient delivery platform to conduct combinational Gem and miR-21 siRNA (miR-21i) therapy. Herein, we synthesized a tumor microenvironment (TME) stimuli-responsive poly(beta-amino ester)s (PBAE)-based polymer nano-prodrug (miR-21i@HA-Gem-SS-P12) that could co-deliver miR-21 siRNA and Gem. The disulfide linkages conjugating GEM onto PBAE can be triggered by elevated reduction stimulus in TME to release the cargo Gem. The hyaluronic acid (HA) fabrication further improved the drug accumulation at the tumor site. Benefiting from the multiple functional improvements and synergism between Gem and miR-21i, the miR-21i@HA-Gem-SS-P12 nano-prodrugs displayed superior tumor inhibition in PDACin vitroandin vivo. This study established an effective stimuli-responsive nano-prodrug strategy for cooperative treatment with small molecule agents and nucleotide modulators in PDAC.

Risk factors for postoperative avascular necrosis of the femoral head in children with developmental dysplasia of the hip.

Aim: To investigate factors associated with postoperative avascular necrosis of the femoral head (ANFH) in developmental dysplasia of the hip (DDH) patients, and if or how the associations varied among different subpopulations of age, sex and surgical method. Methods: Patients with DDH were enrolled between October 31, 2016 and July 15, 2020 in this retrospective cohort study. The average follow-up time was 21.42 ± 10.02 months. The outcome was postoperative ANFH. The main study variables were the DDH classification, Tonnis grade, International Hip Dysplasia Institute (IHDI) classification, and preoperative traction. Multivariate logistic regression was employed to assess the associations between main study variables and postoperative ANFH. Subgroup analysis was carried out based on age at reduction, sex and surgical method. Odds ratio (ORs) and 95% confidence intervals (CIs) were calculated. Results: A total of 427 children with DDH were included, with 92 (21.55%) in the ANFH group, and 335 (78.45%) in the non-ANFH group. DDH classification was positively correlated with the risk of postoperative ANFH (OR = 4.14, 95% CI, 1.08-15.77, P = 0.038). Children with preoperative traction had a significantly decreased risk of postoperative ANFH in contrast to those without preoperative traction (OR = 0.37, 95% CI, 0.22-0.61, P < 0.001). Children aged 1-3 years who received preoperative traction has a significantly reduced risk of postoperative ANFH than those who did not receive preoperative traction (OR = 0.28, 95% CI, 0.15-0.51, P < 0.001). For children aged >3 years, positive association was found between DDH classification and the risk of postoperative ANFH (OR = 3.75, 95% CI, 1.51-9.31, P = 0.004). Girls with a more severe DDH type had a significantly higher risk of postoperative ANFH (OR = 3.80, 95% CI, 1.80-8.02, P < 0.001). Receiving preoperative traction was associated with a significantly decreased risk of postoperative ANFH in girls (OR = 0.37, 95% CI, 0.22-0.61, P < 0.001). For children undergoing open reduction, DDH classification was positively associated with the risk of postoperative ANFH (OR = 3.01, 95% CI, 1.65-5.50, P < 0.001), and those with preoperative traction had a lower risk of postoperative ANFH compared with those without preoperative traction (OR = 0.35, 95% CI, 0.20-0.61, P < 0.001). Conclusion: DDH classification and preoperative traction were associated with the risk of postoperative ANFH, and these associations varied across DDH patients with different ages, sexes and surgical methods.

Characterization of anti-CD79b/CD3 bispecific antibody, a potential therapy for B cell malignancies.

High rates of relapse and poor prognosis confer an urgent need for novel therapeutic agents for B cell non-Hodgkin lymphomas (B-NHLs). Herein, we describe a human IgG-like anti-CD79b/CD3 bispecific antibody (IBI38D9-L) that selectively depletes antigen-positive malignant B cells as an alternative treatment option for relapsed or refractory NHL patients. The antitumor activity and mechanism of action of IBI38D9-L were investigated in vitro using B-NHL cell lines and human primary effector cells and in vivo using xenograft models reconstituted with human PBMCs (peripheral blood mononuclear cells). Pharmacokinetic (PK) properties and preclinical toxicology were evaluated in cynomolgus monkeys and HSC-NPG mice. IBI38D9-L exerted potent B cell killing as well as T cell activation and proliferation in a tumor cell-dependent manner in vitro and was active against B-NHL cell lines with various CD79b expression levels. Subcutaneous xenograft tumors in NOG mice engrafted with human PBMCs were eradicated by IBI38D9-L treatment. Moreover, IBI38D9-L-treated mice showed a strong infiltration of activated T cells. In HSC-NPG mice, IBI38D9-L resulted in potent B cell depletion in peripheral blood and induced only slight body weight loss and cytokine release syndrome without significant toxicological findings. In cynomolgus monkeys, IBI38D9-L was well tolerated with good pharmacokinetic profiles. Collectively, these preclinical efficacy and safety data provide strong scientific rationales for using anti-CD79b/CD3 bispecific antibody as a promising therapeutic agent for B cell malignancies.

Efficient interlayer confined nitrate reduction reaction and oxygen generation enabled by interlayer expansion.

Electrochemically converting nitrate ions back to ammonia can not only eliminate water pollution but also obtain valuable ammonia without a serious carbon footprint, and is thus deemed as an efficient supplement to the traditional Haber-Bosch process. Currently reported catalysts can achieve a single electrode reaction in the electrochemical nitrate reduction reaction. However, the bifunctionality of a single catalyst for both cathodic and anodic reactions has not yet been reported. Herein, we report Fe-doped layered α-Ni(OH)2 with expanded interlayer spacing as an efficient bifunctional catalyst for the nitrate reduction reaction and oxygen evolution reaction. The expanded interlayer spacing facilitates in situ electrochemical potassium ion intercalation between layers. In situ Raman spectroscopy characterization confirms that both the nitrate reduction reaction and oxygen evolution reaction are confined between layers and are triggered by the accumulation of potassium ions. The obtained α-Ni0.881Fe0.119(OH)2 nanosheets deliver an ammonia yield rate of 8.1 mol gcat.-1 h-1 with a NO3--to-NH3 faradaic efficiency of 97.5% at the cathode. The overpotential of oxygen generation at 10 mA cm-2 is reduced to 254 mV at the anode. As a bifunctional catalyst in overall electrolysis, the current density of α-Ni0.881Fe0.119(OH)2 reaches 24.8 mA cm-2 at a voltage of 2.0 V and performs continuously for 50 h with a current retention of 80.2%.

Direct Electron Transfer from Upconversion Graphene Quantum Dots to TiO2 Enabling Infrared Light-Driven Overall Water Splitting.

Utilization of infrared light in photocatalytic water splitting is highly important yet challenging given its large proportion in sunlight. Although upconversion material may photogenerate electrons with sufficient energy, the electron transfer between upconversion material and semiconductor is inefficient limiting overall photocatalytic performance. In this work, a TiO2/graphene quantum dot (GQD) hybrid system has been designed with intimate interface, which enables highly efficient transfer of photogenerated electrons from GQDs to TiO2. The designed hybrid material with high photogenerated electron density displays photocatalytic activity under infrared light (20 mW cm-2) for overall water splitting (H2: 60.4 µmol gcat. -1 h-1 and O2: 30.0 µmol gcat. -1 h-1). With infrared light well harnessed, the system offers a solar-to-hydrogen (STH) efficiency of 0.80% in full solar spectrum. This work provides new insight into harnessing charge transfer between upconversion materials and semiconductor photocatalysts and opens a new avenue for designing photocatalysts toward working under infrared light.

Closed Reduction Percutaneous Intramedullary Fixation with Kirschner Wires in 4 Children with Displaced Fractures of the Distal Humerus.

BACKGROUND This study describes the use of closed reduction percutaneous intramedullary fixation with Kirschner wires in 4 children with displaced metaphyseal-diaphyseal junction (MDJ) fractures of the distal humerus. MATERIAL AND METHODS Between August 2016 and August 2019, 4 patients (3 boys and 1 girl), whose mean age was 4 years 5 months (range: 3 years 6 months to 5 years 4 months), with displaced MDJ fractures of the distal humerus were treated using closed reduction percutaneous intramedullary fixation with Kirschner wires. Three of the fractures were oblique and 1 was transverse. The operation time and the frequency of intraoperative fluoroscopy were recorded. All children were followed up for greater than 18 months, taking anteroposterior and lateral radiographs of the elbow joint to evaluate the outcomes. At the last follow-up, the Flynn elbow joint function score was used to evaluate clinical outcomes, and complications were recorded. RESULTS The mean operation time was 37.5 min (range: 35-40 min) and the frequency of intraoperative fluoroscopy was 11.7 times (range: 8-15 times). All of the fractures were confirmed to be healed based on radiographic results at 4 weeks after surgery. At the last follow-up, 4 children had normal elbow joint motion without elbow deformity. The Flynn score showed their outcomes were excellent. CONCLUSIONS Closed reduction percutaneous intramedullary fixation using Kirschner wires was an effective treatment for displaced MDJ fractures of the distal humerus in the 4 children described and was shown to be easy to perform with a short operation time.

Atomically Dispersed Cu Sites on Dual-Mesoporous N-Doped Carbon for Efficient Ammonia Electrosynthesis from Nitrate.

The industrial Haber-Bosch process for ammonia synthesis is extremely important in modern society. However, it is energy intensive and leads to severe pollution, which has motivated eco-friendly NH3 synthesis research. Electroreduction of contaminant nitrate ions back to NH3 is an effective complement but is still limited by low NH3 yields and nitrate-to-NH3 selectivities. In this study, the electrochemical nitrate reduction reaction (NTRR) is carried out over a single-atom Cu catalyst. Atomically dispersed Cu sites anchored on dual-mesoporous N-doped carbon framework display excellent NTRR performance with NH3 production rate of 13.8 mol NH 3 gcat -1 h-1 and NO3 - -to-NH3 faradaic efficiency (FE) of 95.5 % at -1.0 V. Cu-N-C catalyst can sustain continuous 120 h NTRR test in the simulated NH3 synthesis scenarios with large current density (about 200 mA cm-2 ) and amplified volume of NO3 - solution (9 times). Theoretical calculations reveal that atomically dispersed Cu1 -N4 sites reduce the energy barrier of potential-determining step in NTRR and promote the decomposition of primary intermediate in NO3 - -to-N2 process. These findings provide a guideline for the rational design of highly active, selective and durable electrocatalysts for the NTRR.

Ultrapotent neutralizing antibodies against SARS-CoV-2 with a high degree of mutation resistance.

Many SARS-CoV-2 neutralizing antibodies (nAbs) lose potency against variants of concern. In this study, we developed 2 strategies to produce mutation-resistant antibodies. First, a yeast library expressing mutant receptor binding domains (RBDs) of the spike protein was utilized to screen for potent nAbs that are least susceptible to viral escape. Among the candidate antibodies, P5-22 displayed ultrahigh potency for virus neutralization as well as an outstanding mutation resistance profile. Additionally, P14-44 and P15-16 were recognized as mutation-resistant antibodies with broad betacoronavirus neutralization properties. P15-16 has only 1 binding hotspot, which is K378 in the RBD of SARS-CoV-2. The crystal structure of the P5-22, P14-44, and RBD ternary complex clarified the unique mechanisms that underlie the excellent mutation resistance profiles of these antibodies. Secondly, polymeric IgG enhanced antibody avidity by eliminating P5-22's only hotspot, residue F486 in the RBD, thereby potently blocking cell entry by mutant viruses. Structural and functional analyses of antibodies screened using both potency assays and the yeast RBD library revealed rare, ultrapotent, mutation-resistant nAbs against SARS-CoV-2.

Preparation of combined cross-linked enzyme aggregates containing galactitol dehydrogenase and NADH oxidase for L-tagatose synthesis via in situ cofactor regeneration.

The combined cross-linked enzyme aggregates (combi-CLEAs) containing galactitol dehydrogenase (Gdh) and NADH oxidase (Nox) were prepared for L-tagatose synthesis. To prevent the excess consumption of cofactor, Nox in the combi-CLEAs was used to in situ regenerate NAD+. In the immobilization process, ammonia sulfate and glutaraldehyde were used as the precipitant and cross-linking reagent, respectively. The preparation conditions were optimized as follows: 60% ammonium sulfate, 1:1 (molar ratio) of Gdh to Nox, 20:1 (molar ratio) of protein to glutaraldehyde, and 6 h of cross-linking time at 35 °C. Under these conditions, the activity of the combi-CLEAs was 210 U g-1. The combi-CLEAs exhibited higher thermostability and preserved 51.5% of the original activity after eight cycles of reuses at 45 °C. The combi-CLEAs were utilized for the preparation of L-tagatose without by-products. Therefore, the combi-CLEAs have the industrial potential for the bioconversion of galactitol to L-tagatose.

Heterochronous Metastases of Lung Adenocarcinoma to Pancreas and Liver: A Case Report from Pathological Perspectives.

Immunohistochemistry (IHC) is a vital tool to distinguish tumor metastases from primary lesions in addition to morphologic analysis. In this study, a 64-year-old female with a past surgical history of lung adenocarcinoma 11 years ago was presented with recurrence of liver nodular lesions after multiple surgical procedures, including the Whipple procedure for pancreatic head adenocarcinoma and cytoreductive surgery for liver metastasis. Liver biopsy and review of the previous specimens, based on IHC analyses, suggested heterochronous metastases of lung adenocarcinoma to the digestive systems in a long-time span, instead of primary pancreatic adenocarcinoma. This case demonstrates the potential for misdiagnoses from morphologic analysis alone and suggests the necessity of IHC analyses to avoid misjudgment on tumor phenotypes, when a previous oncologic history is presented.

New Insights into LINC00346 and its Role in Disease.

Accumulating evidence has shown that long intergenic non-protein-coding RNA 346 (LINC00346) functions as an oncogene in the tumorigenesis of several cancers. The expression level of LINC00346 has been shown to be obviously correlated with prognosis, lymphoma metastasis, histological grade, TNM stage, tumor size and pathologic stage. LINC00346 has been found to regulate specific cellular functions by interacting with several molecules and signaling pathways. In this review, we summarize recent evidence concerning the role of LINC00346 in the occurrence and development of diseases. We also discuss the potential clinical utility of LINC00346, thereby providing new insight into the diagnosis and treatment of diseases. In addition, we further discuss the potential clinical utility of LINC00346 in the diagnosis, prognostication, and treatment of diseases.

Integrative genomics analysis identifies promising SNPs and genes implicated in tuberculosis risk based on multiple omics datasets.

More than 10 GWASs have reported numerous genetic loci associated with tuberculosis (TB). However, the functional effects of genetic variants on TB remains largely unknown. In the present study, by combining a reported GWAS summary dataset (N = 452,264) with 3 independent eQTL datasets (N = 2,242) and other omics datasets downloaded from public databases, we conducted an integrative genomics analysis to highlight SNPs and genes implicated in TB risk. Based on independent biological and technical validations, we prioritized 26 candidate genes with eSNPs significantly associated with gene expression and TB susceptibility simultaneously; such as, CDC16 (rs7987202, rs9590408, and rs948182) and RCN3 (rs2946863, rs2878342, and rs3810194). Based on the network-based enrichment analysis, we found these 26 highlighted genes were jointly connected to exert effects on TB susceptibility. The co-expression patterns among these 26 genes were remarkably changed according to Mycobacterium tuberculosis (MTB) infection status. Based on 4 independent gene expression datasets, 21 of 26 genes (80.77%) showed significantly differential expressions between TB group and control group in mesenchymal stem cells, mice blood and lung tissues, as well as human alveolar macrophages. Together, we provide robust evidence to support 26 highlighted genes as important candidates for TB.

Combined cross-linked enzyme aggregates of glycerol dehydrogenase and NADH oxidase for high efficiency in situ NAD+ regeneration.

Cofactor regeneration is an important method to avoid the consumption of large quantities of oxidized cofactor NAD+ in enzyme-catalyzed reactions. Herein, glycerol dehydrogenase (GDH) and NADH oxidase preparations by aggregating enzymes with ammonium sulphate followed by cross-linking formed aggregates for effective regeneration of NAD+. After optimization, the activity of combi-CLEAs and separate CLEAs mixtures were 950 and 580 U/g, respectively. And the catalytic stability of combi-CLEAs against pH and temperature was superior to the free enzyme mixture. After ten cycles of reuse, the catalytic efficiency could still retain 63.3% of its initial activity, indicating that the constructed combi-CLEAs system had excellent reusability. Also, the conversion of glycerol to 1,3-dihydroxyacetone (DHA) was improved by the constructed NAD+ regeneration system, resulting in 4.6%, which was 2.5 times of the free enzyme system. Thus, wide applications of this co-immobilization method in the production of various chiral chemicals could be expected in the industry for its high efficiency at a low cost.

Food-grade gene transformation system constructed in Lactobacillus plantarum using a GlmS-encoding selection marker.

Food-grade gene expression systems in lactic acid bacteria enable production of functional proteins or product testing without antibiotic requirement. Here, we expanded the available selection markers by developing a novel food-grade genetic transformation system for Lactobacillus plantarum WCFS1 using the glucosamine-6-phosphate synthase gene (glmS1). A glmS-vector pSIPH497 was constructed by replacing the erythromycin resistance gene (erm) with L. plantarum glmS1 under control of the PldhL promoter from WCFS1. The selection efficiency and stability of the glmS-vector were shown to be comparable to those of the erm-based plasmid. Moreover, using mCherry expression as a reporter gene, we showed the feasibility of the system for producing foreign proteins. This food-grade host/vector system will provide an effective and safe technique for the application of lactic acid bacteria in the food and medical industries. Furthermore, this study provides a useful strategy for developing food-grade selection markers in other host/vector systems.

Using concanavalinA as a spacer for immobilization of E. coli onto magnetic nanoparticles.

ConcanavalinA (conA) is a protein extracted from the concanavalin, which has specific recognition through mannose components on bacterial cell surfaces. A magnetic nanocarrier with the structure of a dopamine functionalized magnetic nanoparticles was grafted with conA, and was used for immobilization of recombinant Escherichia coli harboring glycerol dehydrogenase with the specific recognition between glycoconjugates and glycoprotein. The effect of various factors on the immobilization including temperature, pH, cell concentration and immobilization time were investigated. The highest immobilization yield of 91% was obtained under the conditions: enzyme/support 1.28mg/mg, pH 8.0, immobilization time 2h and temperature 4°C. The obtained immobilized cell was characterized and exhibited higher thermal stability compared with the free cell. After ten cycles, the immobilized cell remained 62% initial activity. These results indicate that the cell immobilized onto conA-grafted nanoparticles by specific recognition of glycoconjugates and glycoprotein is a potential method for preparation of stable cell, and the immobilized cell showed perspective applications in the biocatalysis and biosensors.