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Cisplatin (CP) induces acute kidney injury (AKI) whereby proximal tubules undergo regulated necrosis. Repair is almost complete after a single dose. We now demonstrate a role for Apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (Apobec-1) that is prominently expressed at the interface between acute and chronic kidney injury (CKD), in the recovery from AKI. Apobec-1 knockout (KO) mice exhibited greater mortality than in wild type (WT) and more severe AKI in both CP- and unilateral ischemia reperfusion (IR) with nephrectomy. Specifically, plasma creatinine (pCr) 2.6 ± 0.70 mg/dL for KO, n = 10 and 0.16 ± 0.02 for WT, n = 6, p < 0.0001 in CP model and 1.34 ± 0.22 mg/dL vs 0.75 ± 0.06, n = 5, p < 0.05 in IR model. The kidneys of Apobec-1 KO mice showed increased necrosis, increased expression of KIM-1, NGAL, RIPK1, ASCL4 and increased lipid accumulation compared to WT kidneys (p < 0.01). Neutrophils and activated T cells were both increased, while macrophages were reduced in kidneys of Apobec-1 KO animals. Overexpression of Apobec-1 in mouse proximal tubule cells protected against CP-induced cytotoxicity. These findings suggest that Apobec-1 mediates critical pro-survival responses to renal injury and increasing Apobec-1 expression could be an effective strategy to mitigate AKI. [ABSTRACT FROM AUTHOR]

Although programmed cell death protein 1 (PD-1) inhibitors have revolutionised treatment for advanced melanoma, not all patients respond. We previously showed that inhibition of the flavoprotein renalase (RNLS) in preclinical melanoma models decreases tumour growth. We hypothesised that RNLS inhibition promotes tumour rejection by effects on the tumour microenvironment (TME). We used two distinct murine melanoma models, studied in RNLS knockout (KO) or wild-type (WT) mice. WT mice were treated with the anti-RNLS antibody, m28, with or without anti-PD-1. 10X single-cell RNA-sequencing was used to identify transcriptional differences between treatment groups, and tumour cell content was interrogated by flow cytometry. Samples from patients treated with immunotherapy were examined for RNLS expression by quantitative immunofluorescence. RNLS KO mice injected with wild-type melanoma cells reject their tumours, supporting the importance of RNLS in cells in the TME. This effect was blunted by anti-cluster of differentiation 3. However, MØ-specific RNLS ablation was insufficient to abrogate tumour formation. Anti-RNLS antibody treatment of melanoma-bearing mice resulted in enhanced T cell infiltration and activation and resulted in immune memory on rechallenging mice with injection of melanoma cells. At the single-cell level, treatment with anti-RNLS antibodies resulted in increased tumour density of MØ, neutrophils and lymphocytes and increased expression of IFNγ and granzyme B in natural killer cells and T cells. Intratumoural Forkhead Box P3 + CD4 cells were decreased. In two distinct murine melanoma models, we showed that melanoma-bearing mice treated with anti-RNLS antibodies plus anti-PD-1 had superior tumour shrinkage and survival than with either treatment alone. Importantly, in pretreatment samples from patients treated with PD-1 inhibitors, high RNLS expression was associated with decreased survival (log-rank P = 0.006), independent of other prognostic variables. RNLS KO results in melanoma tumour regression in a T-cell-dependent fashion. Anti-RNLS antibodies enhance anti-PD-1 activity in two distinct aggressive murine melanoma models resistant to PD-1 inhibitors, supporting the development of anti-RNLS antibodies with PD-1 inhibitors as a novel approach for melanomas poorly responsive to anti-PD-1. • Renalase (RNLS) knockout in immune cells substantially inhibits tumour growth. • Anti-RNLS antibodies enhance effects of anti-programmed cell death protein 1 (PD-1) in melanoma-bearing mice. • T cells (but not MØ) are required for anti-RNLS effects on tumours. • Immunotherapy-treated patients with melanoma with high tumour RNLS have worse survival. • Anti-RNLS antibodies might have therapeutic value in anti-PD-1–resistant melanomas. [ABSTRACT FROM AUTHOR]

As an important energy base in China, Shanxi Province, in its economic development, has depended heavily on coal resources. However, enormous coal consumption produces a large amount of carbon dioxide and an aggravated ecological problem. In this paper, the super efficiency slack-based measure and data envelopment analysis (SBM-DEA) model and Malmquist index were used to calculate the energy consumption and carbon emission efficiency of 11 prefecture-level cities in Shanxi in the period from 2000 to 2020. The results were as follows: (1) The primary form of energy consumption in Shanxi Province is the burning of coal, and the carbon emission efficiencies of the 11 prefecture-level cities are quite different. The technical efficiency, technological progress, and total factor productivity of Taiyuan and Shuozhou were found to be greater than 1 compared to other cities in Shanxi. (2) On the whole, although the carbon emission rate of Shanxi Province has slowed down, it still faces the problems of a large total emission base, high carbon emission intensity, and low efficiency of the unit carbon emission output. Industrial structure is the key factor restricting improvements in the efficiency of carbon emissions in Shanxi Province. (3) From the spatial and temporal evolution of the carbon emission efficiency in Shanxi Province, we can see that the carbon emission efficiency of the whole province gradually dispersed and improved from the central and northern regions to the southern regions during the period of 2000–2020. In order to achieve a low-carbon economy, Shanxi Province must optimize its industrial structure, accelerate research and development in low-carbon technologies, adjust the energy structure, and promote the construction of an energy supply system with clean low-carbon energy as the main source. [ABSTRACT FROM AUTHOR]

Controlled release of curcumin by a pH-sensitive carrier provides long-term preservation, which extends the shelf lives of fish. FTIR, XRD, 1H NMR, zeta potential, swelling ratio, and TG analyses indicated that a pH-sensitive starch-based carrier with a narrow pH-sensitivity range (pH 6–7) was fabricated from the carboxymethyl starch grafted with methacrylic acid and then cross-linked with β-cyclodextrin to achieve dual functionality. FTIR, XRD, and fluorescence spectroscopy revealed that the mechanism by which curcumin was encapsulated in the starch-based carriers involved hydrophobic interactions and intermolecular hydrogen bonding. The encapsulated curcumin showed improved stability, higher antioxidant activity, antibacterial activity, and biocompatibility. The pH, TVB-N, TVC, and drip loss tests confirmed that the use of the carrier-curcumin complex at a concentration of 10 mg/mL for the preservation of yellow catfish extended the shelf life for 2–4 days during cold storage and improved the storage quality of the resulting fillets. This work provides a dual functionality strategy for constructing a pH-sensitive starch-based carrier to deliver curcumin and offers a promising choice for fish preservation.Graphical Abstract: Controlled release of curcumin by a pH-sensitive carrier provides long-term preservation, which extends the shelf lives of fish. FTIR, XRD, 1H NMR, zeta potential, swelling ratio, and TG analyses indicated that a pH-sensitive starch-based carrier with a narrow pH-sensitivity range (pH 6–7) was fabricated from the carboxymethyl starch grafted with methacrylic acid and then cross-linked with β-cyclodextrin to achieve dual functionality. FTIR, XRD, and fluorescence spectroscopy revealed that the mechanism by which curcumin was encapsulated in the starch-based carriers involved hydrophobic interactions and intermolecular hydrogen bonding. The encapsulated curcumin showed improved stability, higher antioxidant activity, antibacterial activity, and biocompatibility. The pH, TVB-N, TVC, and drip loss tests confirmed that the use of the carrier-curcumin complex at a concentration of 10 mg/mL for the preservation of yellow catfish extended the shelf life for 2–4 days during cold storage and improved the storage quality of the resulting fillets. This work provides a dual functionality strategy for constructing a pH-sensitive starch-based carrier to deliver curcumin and offers a promising choice for fish preservation. [ABSTRACT FROM AUTHOR]

The outbreak of a novel coronavirus pneumonia (COVID-19), wherein more than 200 million people have been infected and millions have died, poses a great threat to achieving the United Nations 2030 sustainable development goal (SDGs). Based on the Baidu index of 'novel coronavirus', this paper analyses the spatial and temporal characteristics of and factors that influenced the attention network for COVID-19 from January 9, 2020, to April 15, 2020. The study found that (1) Temporally, the attention in the new coronavirus network showed an upward trend from January 9 to January 29, with the largest increase from January 23 to January 29 and a peak on January 29, and then a slow downward trend. The level of attention in the new coronavirus network was basically flat when comparing January 22 and March 4. (2) Spatially, first, from the perspective of regional differences, the network attention in the eastern and central regions decreased in turn. The network users in the eastern region exhibited the highest attention to the new coronavirus, especially in Guangdong, Shandong, Jiangsu and other provinces and cities. The network attention in Tibet, Xinjiang, Qinghai and Ningxia in the western region was the lowest in terms of the national network attention. Second, from the perspective of interprovincial differences, the attention in the new coronavirus network was highly consistent with the Hu Huanyong line of China's population boundary. The east of the Hu Huanyong line is densely populated, and the network showed high concern, mostly ranking at the third to fifth levels. (3) The number of Internet users in the information technology field, the population, and the culture and age characteristics of individuals are important factors that influence the novel coronavirus attention network. [ABSTRACT FROM AUTHOR]

Formate dehydrogenase (FDH) has been widely used for the regeneration of the reduced nicotinamide adenine dinucleotide (NADH). To utilize nicotinamide cytosine dinucleotide (NCD) as a non‐natural redox cofactor, it remains challenging as NCDH, the reduced form of NCD, has to be efficiently regenerated. Here we demonstrate successful engineering of FDH for NCDH regeneration. Guided by the structural information of FDH from Pseudomonas sp. 101 (pseFDH) and the NAD–pseFDH complex, semi‐rational strategies were applied to design mutant libraries and screen for NCD‐linked activity. The most active mutant reached a cofactor preference switch from NAD to NCD by 3700‐fold. Homology modeling analysis showed that these mutants had reduced cofactor binding pockets and dedicated hydrophobic interactions for NCD. Efficient regeneration of NCDH was implemented by powering an NCD‐dependent D‐lactate dehydrogenase for stoichiometric and stereospecific reduction of pyruvate to D‐lactate at the expense of formate. [ABSTRACT FROM AUTHOR]

A non‐natural cofactor and formate driven system for reductive carboxylation of pyruvate is presented. A formate dehydrogenase (FDH) mutant, FDH*, that favors a non‐natural redox cofactor, nicotinamide cytosine dinucleotide (NCD), for generation of a dedicated reducing equivalent at the expense of formate were acquired. By coupling FDH* and NCD‐dependent malic enzyme (ME*), the successful utilization of formate is demonstrated as both CO2 source and electron donor for reductive carboxylation of pyruvate with a perfect stoichiometry between formate and malate. When 13C‐isotope‐labeled formate was used in in vitro trials, up to 53 % of malate had labeled carbon atom. Upon expression of FDH* and ME* in the model host E. coli, the engineered strain produced more malate in the presence of formate and NCD. This work provides an alternative and atom‐economic strategy for CO2 fixation where formate is used in lieu of CO2 and offers dedicated reducing power. [ABSTRACT FROM AUTHOR]

A non‐natural cofactor and formate driven system for reductive carboxylation of pyruvate is presented. A formate dehydrogenase (FDH) mutant, FDH*, that favors a non‐natural redox cofactor, nicotinamide cytosine dinucleotide (NCD), for generation of a dedicated reducing equivalent at the expense of formate were acquired. By coupling FDH* and NCD‐dependent malic enzyme (ME*), the successful utilization of formate is demonstrated as both CO2 source and electron donor for reductive carboxylation of pyruvate with a perfect stoichiometry between formate and malate. When 13C‐isotope‐labeled formate was used in in vitro trials, up to 53 % of malate had labeled carbon atom. Upon expression of FDH* and ME* in the model host E. coli, the engineered strain produced more malate in the presence of formate and NCD. This work provides an alternative and atom‐economic strategy for CO2 fixation where formate is used in lieu of CO2 and offers dedicated reducing power. [ABSTRACT FROM AUTHOR]

[Display omitted] • Oriented β-chitin nanofiber hydrogel was obtained by electroassembly. • The hydrogel structure and properties can be easily modulated by the process parameters. • Oriented cryogel shows superior properties in cell proliferation and wound healing. • The strategy provides a preferential route to obtain anisotropic natural nanogels. The construction of natural polymeric nanocomponents with tunable hierarchical structure in a simple and controllable process remains a great challenge. Herein, an oriented β-chitin nanofiber hydrogel was fabricated by an electro-assembly process in water phase, during which the internal structure of the hydrogel was facilely tuned by the process parameters. The orientation of the β-chitin nanofibers hydrogel was influenced by the concentration of nanofibers and pH, and strengthened by increased current density and longer deposition time. Cryogels with extraordinary physical and biological properties were subsequently obtained by freeze drying. When used as wound dressing in cell and animal models, the oriented β-chitin nanofiber cryogels could significantly promote cell proliferation and accelerate wound healing, outperforming the healing effect of unoriented structure. [ABSTRACT FROM AUTHOR]

• Substrate scope of GsADH clarified. • Crystal structure of GsADH determined. • GsADH preferring isopropanol over other short chain alcohols. • Insights into substrate preference elucidated. Many alcohol dehydrogenases (ADHs) catalyze oxidation of a broad scope of alcohols. When an NAD-dependent ADH oxidizes methanol, albeit at a poor rate, it may be treated as methanol dehydrogenase (MDH). One ADH from Geobacillus stearothermophilus DSM 2334 (GsADH) has been widely used as MDH, but its actual substrate scope remains less characterized. Here we purified recombinant GsADH from Escherichia coli and determined its crystal structure. We collected kinetics data of this enzyme towards a number of short chain alcohols, and found that isopropanol is by far the most favorable substrate. Moreover, molecular docking analysis suggested that substrate preference is mainly attributed to the conformer energy of the protein-substrate complex. Our data clarified the substrate scope of GsADH and provided structural insights, which may facilitate more efficient cofactor regeneration and rational metabolic engineering. [ABSTRACT FROM AUTHOR]

Abstract Aims We explored the relationship between inflammation, renalase an anti-inflammatory protein, and acute chest pain with coronary microvascular dysfunction (CMD). Methods and results We used cardiac Rb-82 PET/CT imaging to diagnose coronary artery disease (CAD/CALC) (defect or coronary calcification) and CMD (depressed coronary flow reserve without CAD) in patients with chest pain in an emergency department (ED). Blood samples were collected pre-imaging within 24 h of ED presentation and were analyzed for renalase and inflammatory markers including C-reactive protein, interleukins, interferon gamma, tumor necrosis factor, vascular endothelial growth factor, and metalloproteinases. Exclusions were age ≤30 years, myocardial infarction, hemodynamic instability, hypertensive crisis, heart failure or dialysis. Between 6/2014 and 11/2015, 80 patients undergoing PET/CT provided blood and were categorized as normal (18%), CAD/CALC (27%) and CMD (55%). Median renalase values were highest in patients with CMD (5503 ng/ml; IQR 3070) compared to patients with normal flows (4266 ng/ml; IQR 1503; p = 0.02) or CAD/CALC (4069 ng/ml IQR 1850; p = 0.004). CMD patients had similar median values for inflammatory markers as normal patients (p > 0.05). Renalase remained an independent predictor of CMD (OR 1.34; 95% CI = 1.1–1.7, per 1000 ng/ml) after adjustment for smoking, family history, obesity and Framingham risk score. In a model for CMD diagnosis with Framingham risk score, typical angina history and CRP, renalase improved discrimination from C-statistic = 0.60 (95% CI 0.47, 0.73) to 0.70 (95% CI, 0.59–0.82). Conclusion We found elevated renalase in response to ischemia from acute CMD. Its role as a biomarker needs validation in larger trials. [ABSTRACT FROM AUTHOR]

Recycling of rare earth metals is important for their supply risk in the future. In this work, a greener and highly efficient liquid-liquid extraction strategy is presented for rare earth metals from aqueous solution with PEG-functionalized ionic liquids. The factors influencing the solvent extraction process such as phase volume ratio, equilibrium time, pH value of aqueous phase, alkyl chain length of the ionic liquids and temperature of the system were investigated systematically. It was found that under optimal conditions, the single-step extraction efficiency was > 96.8% for the studied 11 kinds of rare earth metal ions Sc(III), La(III), Ce(III), Y(III), Nd(III), Sm(III), Gd(III), Dy(III), Ho(III), Yb(III) and Lu(III). After the extraction, about 100% of the rare earth metals could be stripped from the ionic liquids phases by using dilute aqueous oxalic acid, and the ionic liquids would be recovered and reused in the next extraction process. In addition, the extraction mechanism was investigated in some details, and an ion pair association mechanism was suggested. Since the extraction procedure was performed without saponification, addition of extra extractant, organic diluents or salt, the approach described here has the potential to be used as a sustainable strategy for the separation and enrichment of rare earths from complex matrixes. [ABSTRACT FROM AUTHOR]

Photocatalytic oxidation plays an important role in organic synthesis. This research systematically studied the effect of reactive oxidation species (ROSs) such as surface-bounded hydroxyl radicals ( OH b ), free hydroxyl radicals ( OH f ), and hole (h + ) on the photocatalytic selective oxidation of phenol in the TiO 2 /UV system and its corresponding important chemical intermediates, dihydroxybenzenes. Experimental results showed that (1) the oxidation of phenol by hydroxyl radicals, whether in free ( OH f ) or bounded states ( OH b ), led mainly to the ortho - (catechol) and para -oriented hydroxy derivatives (hydroquinone), whereas the meta -oriented hydroxy derivative (resorcinol) became the main product when holes were used as the active species; (2) in naked TiO 2 suspensions, where OH b was the main ROSs, the selectivity of the catechol detected in the solution was much lower than that on the surface of the fluorinated TiO 2 system (TiO 2 -F), where OH f served as the main ROSs. This finding can be attributed to the very strong catechol adsorption on the surface of naked TiO 2 . However, this adsorption was severely inhibited in the presence of fluorine because of the competitive adsorption between catechol and fluoride ions over TiO 2 photocatalyst; and (3) the hole oxidation of phenol provided a slower oxidation rate but a higher yield of dihydroxybenzenes compared with hydroxyl radical-mediated oxidation. [ABSTRACT FROM AUTHOR]

Background Bcl-2 has been implicated in the development and progression of a number of cancers including colorectal cancer. Reports of Bcl-2 expression in colorectal cancer and patient outcomes have been inconsistent due to small cohorts and semi-quantitative grading methods. Study Design We used a high throughput tissue microarray system (automated quantitative analysis [AQUA]), analyzing colorectal adenocarcinoma samples from 443 patients resected during the period of 1967 to 1986. This system uses fully quantitative, automated fluorescent microscopy to accurately assess Bcl-2 expression in colorectal cancer samples. Clinicopathologic variables were collected prospectively and were assessed using log-rank tests and Cox proportional hazards models. Results At a median follow-up of 54 months, the 5- and 10-year disease-specific survivals for all patients were 59.2% and 52.1%, respectively. Loss of Bcl-2 expression was seen in 70.4% of tumors and was associated with a decreased 5-year disease-specific survival (55.8% vs 75.6%, p = 0.001 and relative risk [RR] 1.8) and decreased 5-year overall survival (45.8% vs 56.5%, p = 0.046 and RR 1.2). On univariate analysis, T stage, N stage, and loss of Bcl-2 expression predicted poor disease-specific survival. On multivariate analysis, Bcl-2 expression was an independent prognostic factor for disease-specific survival (p = 0.034). Conclusions Our results indicate that loss of Bcl-2 expression in colorectal cancer is associated with decreased disease-specific and overall survival. This finding may help identify a subset of patients with a more aggressive phenotype and guide adjuvant chemotherapy choices. [ABSTRACT FROM AUTHOR]

Hemorrhage control, especially noncompressible wound hemostasis, is a tremendous challenge in military injuries and other traumas worldwide. Here, a cryogelation strategy and subsequent solvent exchange are developed for the hydrogen bond‐induced self‐assembly of chitosan fibers and the production of fast expandable chitosan cryogel. Importantly, the ambient drying process facilitates the repeatable deformation performance of the shape‐memory cryogel with a response time of ≈1.7 s. Due to the capillary‐like structure of the cryogel and high hydrophilicity, rapid shape recovery is accompanied by 41 times water absorption ability. It is further demonstrated that chitosan cryogel is beneficial for in situ tissue regeneration by taking advantage of the biodegradability and biocompatibility of chitosan. Thus, chitosan cryogels prepared by this simple and benign method should have efficient hemostatic effect on noncompressible bleeding and severe fatal high‐pressure hemorrhage. [ABSTRACT FROM AUTHOR]

Public environmental cognition is an important basis for optimizing environmental management and reducing tensions between humans and land. Although the level of environmental cognition is a gradual process under normal conditions, it often changes qualitatively because of major public emergencies. During the 2019 new coronavirus epidemic (COVID-19), the most significant public health event in recent years, 24,188 national samples were obtained based on a network survey. The comprehensive evaluation method was used to assess the impact of major public events on public environmental cognition and the characteristics of spatial and temporal distribution. The findings are as follows. (1) During the epidemic period, sudden public health emergencies effectively promoted the national residents' environmental awareness, whether urban residents or rural; most respondents generally agreed with the concept of "respect nature and cherish life". (2) The environmental cognition of national residents was higher in the northwest and lower in the northeast of China, which is suitable for economic and social development and humanistic tradition. (3) There was a clear positive correlation between environmental awareness and education level. (4) During the epidemic, nervousness of respondents had a negative effect on environmental cognition. This study provides scientific support and a basis for decision making for the government to carry out environmental management optimization and improve the ecological and environmental cognition of the public, as well as devise effective intervention mechanisms with different time and space dimensions for similar future public health emergencies. [ABSTRACT FROM AUTHOR]

Programmable asymmetric hydrogels with tunable structure/shape or physical/chemical properties in response to external stimuli show particular significance in smart systems, but there is lack of simple, rapid, and cheap strategy to design such hydrogel systems. Herein, we report a one-step electrodeposition method to construct chitosan asymmetric hydrogels with tunable thickness and pore size that can be conveniently modulated by the process parameters. Our approach greatly simplifies the process of hydrogel preparation with complex shapes and asymmetric structure organization. The formation mechanism of asymmetric structure has been proposed, based on gelation behavior and entanglement of chitosan chains in the hydrogel-solution system under the electric field. By changing the shape of the electrodes, hydrogels with the morphology of strip, tube, flower, etc. can be obtained precisely and conveniently. They can perform programmable 2D to 3D smart dynamic deformation under pH and metal ions stimulation, indicating the broad application potential in soft robot and biosensor areas. [Display omitted] [ABSTRACT FROM AUTHOR]

Endothelial and smooth muscle cell-derived neuropilin-like protein (ESDN) is up-regulated in the neointima of remodeling arteries and modulates vascular smooth muscle cell (VSMC) growth. Platelet-derived growth factor (PDGF) is the prototypic growth factor for VSMCs and plays a key role in vascular remodeling. Here, we sought to further define ESDN function in primary human VSMCs. ESDN down-regulation by RNA interference significantly enhanced PDGF-induced VSMC DNA synthesis and migration. This was associated with increased ERK1/2, Src, and PDGF receptor (PDGFR)β phosphorylation, without altering total PDGFRβ expression levels. In binding assays, ESDN down-regulation significantly increased 125I-PDGF maximum binding (Bmax) to PDGF receptors on VSMCs without altering the binding constant (Kd), raising the possibility that ESDN regulates PDGFR processing. ESDN down-regulation significantly reduced ligand-induced PDGFRβ ubiquitination. This was associated with a significant reduction in the expression level of c-Cbl, an E3 ubiquitin ligase that ubiquitinylates PDGFRβ. Thus, ESDN modulates PDGF signaling in VSMCs via regulation of PDGFR surface levels. The ESDN effect is mediated, at least in part, through effects on PDGFRβ ubiquitination. ESDN may serve as a target for regulating PDGFRβ signaling in VSMCs. [ABSTRACT FROM AUTHOR]

Enzymes with dedicated cofactor preference are essential for advanced biocatalysis and biomanufacturing, especially when employing nonnatural nicotinamide cofactors in redox reactions. However, directed evolution of an enzyme to switch its cofactor preference is often hindered by the lack of efficient and affordable method for screening as the cofactor per se or the substrate can be prohibitively expensive. Here, we developed a growth-based selection platform to identify nonnatural cofactor-dependent oxidoreductase mutants. The growth of bacteria depended on the nicotinamide cytosine dinucleotide (NCD) mediated conversion of non-metabolizable phosphite into phosphate. The strain BW14329 lacking the ability to oxidize phosphite was suitable as host, and NCD-dependent phosphite dehydrogenase (Pdh*) is essential to the selection platform. Previously confirmed NCD synthetase with NCD synthesis capacity and NCD-dependent malic enzyme were successfully identified by using the platform. The feasibility of this strategy was successfully demonstrated using derived NCD-active malic enzyme as well as for the directed evolution of NCD synthetase in Escherichia coli. A phosphite-based screening platform was built for identification of enzymes favoring nonnatural cofactor NCD. In the future, once Pdh variants favoring other biomimetic or nonnatural cofactors are available this selection platform may be readily redesigned to attain new enzyme variants with anticipated cofactor preference, providing opportunities to further expand the chemical space of redox cofactors in chemical biology and synthetic biology. [ABSTRACT FROM AUTHOR]

• CNF/metal hydrogels are created by electrochemically induced counterion exchange. • The electrochemical counterion exchange is straightforward, mild and quick. • The hydrogel displays enhanced thermal degradation, improved mechanical strength. • The hierarchical nanoporous hydrogel exhibits anti-microbial performance. The fabrication of polymeric composite hydrogel with hierarchical structure in a simple, controllable, and straightforward process poses great importance for manufacturing nanomaterials and subsequent applications. Herein, we report a one-step and template-free counterion exchange method to construct free-standing carboxylated cellulose nanofiber composite hydrogels. Metal ions were electrochemically and locally released from the electrode and chelated with carboxylated cellulose nanofibers, leading to the in-situ formation of composite hydrogels. The properties of composite hydrogels can be easily programmed by the type of electrode, current density, and electrodeposited suspension. Significantly, the composited hydrogels exhibited interconnected nanoporous structure, enhanced thermal degradation, improved mechanical strength and antibacterial activity. The results suggest great potential of anodic electrodeposition to fabricate nanofiber/metal composite hydrogels. [ABSTRACT FROM AUTHOR]

Renalase is a secreted flavoprotein with anti-inflammatory and pro-cell survival properties. COVID-19 is associated with disordered inflammation and apoptosis. We hypothesized that blood renalase levels would correspond to severe COVID-19 and survival. In this retrospective cohort study, clinicopathologic data and blood samples were collected from hospitalized COVID-19 subjects (March—June 2020) at a single institution tertiary hospital. Plasma renalase and cytokine levels were measured and clinical data abstracted from health records. Of 3,450 COVID-19 patients, 458 patients were enrolled. Patients were excluded if <18 years, or opted out of research. The primary composite outcome was intubation or death within 180 days. Secondary outcomes included mortality alone, intensive care unit admission, use of vasopressors, and CPR. Enrolled patients had mean age 64 years (SD±17), were 53% males, and 48% non-whites. Mean renalase levels was 14,108·4 ng/ml (SD±8,137 ng/ml). Compared to patients with high renalase, those with low renalase (< 8,922 ng/ml) were more likely to present with hypoxia, increased ICU admission (54% vs. 33%, p < 0.001), and cardiopulmonary resuscitation (10% vs. 4%, p = 0·023). In Cox proportional hazard model, every 1000 ng/ml increase in renalase decreased the risk of death or intubation by 5% (HR 0·95; 95% CI 0·91–0·98) and increased survival alone by 6% (HR 0·95; CI 0·90–0·98), after adjusting for socio-demographics, initial disease severity, comorbidities and inflammation. Patients with high renalase-low IL-6 levels had the best survival compared to other groups (p = 0·04). Renalase was independently associated with reduced intubation and mortality in hospitalized COVID-19 patients. Future studies should assess the pathophysiological relevance of renalase in COVID-19 disease. [ABSTRACT FROM AUTHOR]

Dysregulated expression of the secretory protein renalase can promote pancreatic ductal adenocarcinoma (PDAC) growth in animal models. We characterized renalase expression in premalignant and malignant PDAC tissue and investigated whether plasma renalase levels corresponded to clinical PDAC characteristics. Renalase immunohistochemistry was used to determine the presence and distribution of renalase in normal pancreas, chronic pancreatitis, PDAC precursor lesions, and PDAC tissues. Associations between pretreatment plasma renalase and PDAC clinical status were assessed in patients with varied clinical stages of PDAC and included tumor characteristics, surgical resection in locally advanced/borderline resectable PDAC, and overall survival. Data were retrospectively obtained and correlated using non-parametric analysis. Little to no renalase was detected by histochemistry in the normal pancreatic head in the absence of abdominal trauma. In chronic pancreatitis, renalase immunoreactivity localized to peri-acinar spindle-shaped cells in some samples. It was also widely present in PDAC precursor lesions and PDAC tissue. Among 240 patients with PDAC, elevated plasma renalase levels were associated with worse tumor characteristics, including greater angiolymphatic invasion (80.0% vs. 58.1%, p = 0.012) and greater node positive disease (76.5% vs. 56.5%, p = 0.024). Overall survival was worse in patients with high plasma renalase levels with median follow-up of 27.70 months vs. 65.03 months (p < 0.001). Renalase levels also predicted whether patients with locally advanced/borderline resectable PDAC underwent resection (AUC 0.674; 95%CI 0.42–0.82, p = 0.04). Overall tissue renalase was increased in both premalignant and malignant PDAC tissues compared to normal pancreas. Elevated plasma renalase levels were associated with advanced tumor characteristics, decreased overall survival, and reduced resectability in patients with locally advanced/borderline resectable PDAC. These studies show that renalase levels are increased in premalignant pancreatic tissues and that its levels in plasma correspond to the clinical behavior of PDAC. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Selective biocarboxylation of substituted phenols. • Whole-cells catalyzed formation of ortho-hydroxybenzoates. • Method potential for synthesis of new lignin-derived compounds. Abstract Selective carboxylation of substituted phenols is realized in the presence of bicarbonate under ambient pressure by engineered Escherichia coli whole-cells expressing various hydroxybenzoate decarboxylases, leading to their corresponding ortho-hydroxybenzoates. This process may be further developed as an efficient route to upgrade lignin-derived phenolic compounds as valuable building blocks. [ABSTRACT FROM AUTHOR]

The association between cytokine receptor-like factor 2 (CRLF2) and clinical outcomes in acute lymphoblastic leukemia (ALL) has been a topic of ongoing debate, with divergent findings. This article intended to investigate the influence of CRLF2 alterations on ALL prognosis. Following the PRISMA 2020 guidelines, this meta-analysis was conducted. Hazard ratio (HR) values and confidence intervals (CIs) were the primary statistical measures used. Data heterogeneity was judged using the chi-square test and I2 statistic. Publication bias was appraised with funnel plots, Begg's test, and Egger's test. 16 studies with 6771 patients were finally screened out. CRLF2 over-expression (CRLF2 OE) was associated with poorer event-free survival (EFS) (HR = 1.70, 95% CI = 1.18–2.44, P = 0.004) and relapse-free survival (RFS) (HR = 1.70, 95% CI = 1.28–2.24, P = 0.000) in pediatric ALL. Patients with CRLF2-deregulation (CRLF2-d), also known as CRLF2 rearrangement, exhibited shorter overall survival (OS) (HR = 2.22, 95% CI = 1.49–3.32, P = 0.000), EFS (HR = 1.93, 95% CI = 1.43–2.60, P = 0.000), and RFS (HR = 2.2, 95% CI = 1.53–3.18, P = 0.000) compared to those without CRLF2-d. Subgroup analysis of multivariate HRs and corresponding CIs indicated that childhood with CRLF2 OE had a shorter RFS (HR = 1.70, 95% CI = 1.28–2.24, P = 0.006), and CRLF2-d was identified as an independent prognostic biomarker for OS (HR = 2.22, 95% CI = 1.49–3.32, P = 0.000), EFS (HR = 1.95, 95% CI = 1.44–2.64, P = 0.000), and RFS (HR = 2.2, 95% CI = 1.53–3.18, P = 0.000) in pediatric ALL patients. Both CRLF2 OE and CRLF2-d are associated with poor prognosis in ALL patients. [ABSTRACT FROM AUTHOR]

Aeromonas veronii is associated with food spoilage and some human diseases, such as diarrhea, gastroenteritis, hemorrhagic septicemia or asymptomatic and even death. This research investigated the mechanism of the growth, biofilm formation, virulence, stress resistance, and spoilage potential of Bacillus subtilis lipopeptide against Aeromonas veronii. Lipopeptides suppressed the transmembrane transport of Aeromonas veronii by changing the cell membrane's permeability, the structure of membrane proteins, and Na+/K+-ATPase. Lipopeptide significantly reduced the activities of succinate dehydrogenase (SDH) and malate dehydrogenase (MDH) by 86.03% and 56.12%, respectively, ultimately slowing Aeromonas veronii growth. Lipopeptides also restrained biofilm formation by inhibiting Aeromonas veronii motivation and extracellular polysaccharide secretion. Lipopeptides downregulated gene transcriptional levels related to the virulence and stress tolerance of Aeromonas veronii. Furthermore, lipopeptides treatment resulted in a considerable decrease in the extracellular protease activity of Aeromonas veronii , which restrained the decomposing of channel catfish flesh. This research provides new insights into lipopeptides for controlling Aeromonas veronii and improving food safety. [Display omitted] • Lipopeptides reduced Aeromonas veronii biofilm formation. • Lipopeptides reduce the virulence and resistance of Aeromonas veronii. • Lipopeptides inhibit the spoiling potential of Aeromonas veronii. [ABSTRACT FROM AUTHOR]

Flaviviruses, represented by Zika and dengue virus (ZIKV and DENV), are widely present around the world and cause various diseases with serious consequences. However, no antiviral drugs have been clinically approved for use against them. Azelnidipine (ALP) is a dihydropyridine calcium channel blocker and has been approved for use as an antihypertensive drug. In the present study, ALP was found to show potent anti-flavivirus activities in vitro and in vivo. ALP effectively prevented the cytopathic effect induced by ZIKV and DENV and inhibited the production of viral RNA and viral protein in a dose-dependent manner. Moreover, treatment with 0.3 mg/kg of ALP protected 88.89% of mice from lethal challenge. Furthermore, using the time-of-drug-addition assay, the enzymatic inhibition assay, the molecular docking, and the surface plasmon resonance assay, we revealed that ALP acted at the replication stage of the viral infection cycle by targeting the viral RNA-dependent RNA polymerase. These findings highlight the potential for the use of ALP as an antiviral agent to combat flavivirus infections. [ABSTRACT FROM AUTHOR]

Enterovirus infections can cause hand, foot, and mouth disease (HFDM), aseptic meningitis, encephalitis, myocarditis, and acute flaccid myelitis, leading to death of infants and young children. However, no specific antiviral drug is currently available for the treatment of this type of infection. The Unites States and United Kingdom health authorities recently approved a new antiviral drug, molnupiravir, for the treatment of COVID-19. In this study, we reported that molnupiravir (EIDD-2801) and its active form, EIDD-1931, have broad-spectrum anti-enterovirus potential. Our data showed that EIDD-1931 could significantly reduce the production of EV-A71 progeny virus and the expression of EV-A71 viral protein at non-cytotoxic concentrations. The results of the time-of-addition assay suggest that EIDD-1931 acts at the post-entry step, which is in accordance with its antiviral mechanism. The intraperitoneal administration of EIDD-1931 and EIDD-2801 protected 1-day-old ICR suckling mice from lethal EV-A71 challenge by reducing the viral load in various tissues of the infected mice. The pharmacokinetics analysis indicated that the plasma drug concentration overwhelmed the EC50 for enteroviruses, suggesting the clinical potential of molnupiravir against enteroviruses. Thus, molnupiravir along with its active form, EIDD-1931, may be a promising drug candidate against enterovirus infections. [ABSTRACT FROM AUTHOR]

Hypoxic germination tolerance is an important trait for seedling establishment of direct-seeded rice. Our comparative metabolomics analysis revealed that weedy rice accumulated more sugar and amino acids than cultivated rice accumulated in the embryo and coleoptile tissues under hypoxic stress. At the transcriptional level, oxidative phosphorylation activity in weedy rice was higher than in cultivated rice that likely led to more efficient energy metabolism during hypoxic stress. Based on our comparative proteomics analysis, enriched proteins related to cell wall implied that the advantages in energy metabolism of weedy rice were ultimately reflected in the formation of tissue structures. In this study, we found that most of key hypoxic germination tolerance (HGT) genes shared the same genetic backgrounds with Oryza japonica , however, several of them genetically similar to other Oryza plant also play important roles. Our findings suggest weedy rice can serve as genetic resources for the improvement of direct-seeding rice. • Strong oxidative phosphorylation reactions caused weedy rice to promoting coleoptile elongation under hypoxic stress. • An informative multi-omics data set and genetic resources were provided for the improvement of direct-seeding rice. • Weedy rice genome can serve as an important reference for the discovery of new adaptive genes in rice. [ABSTRACT FROM AUTHOR]

Pea protein has attracted attentions as an alternative for soy protein, but its weaker gelling properties has limited its applications in food formulations. This research reports a heat-induced strong and elastic gel from pea protein isolate (PPI) pre-treated by a modified pH-shifting method. The scanning electron microscopy (SEM) observation and rheological measurement revealed that the formation of three-dimensional (3D) coagulum for pea protein at pH 12 by extending the alkali holding time (1, 24 and 48 h) and such coagulum maintained their structure when adjusting pH back to neutral. Further heating the pH-shifted PPI suspension at 92 °C led to gels of densely cross-linked polymer-like network with thin connective walls and pore size of 1–2 μm. Such uniform polymer-like gel network microstructure obtained in this work might be related to a high level of pea protein unfolding during pH-shifting treatment, which made the protein chain flexible and created more active sites to promote molecular interactions including hydrogen bonds and hydrophobic interactions when the protein was neutralized and heated. Notably the gel mechanical strength was dramatically increased to 21 kPa, accompanied by excellent elasticity and water holding capacity (>95%). The modified method of pH-shifting process has provided a new approach for preparation of pea protein gels with superior strength, thus may enable wider applications of pea protein applications in food formulations where gelling and texturization functions are required. [Display omitted] • pH shifting method enhanced the gelling capacity of pea protein at neutral pH. • Long-time holding at extreme alkali pH resulted in elastic pea protein hydrogels. • Hydrogen bonds plays more important role in elastic pea protein hydrogels. • Evenly distributed protein network was formed in elastic pea protein hydrogels. • Gel microstructure shows relation to the corresponding mechanical properties. [ABSTRACT FROM AUTHOR]

Polysaccharide-based nanoparticles formed by the polyelectrolyte complexation between chitosan (CS) and flaxseed gum (FG) was developed in this work, and it was further used as a carrier for bighead carp peptide (BCP) delivery. The CS molecular weight (M W) of 50 kDa and CS/FG mass ratio of 1:2 at pH 3.5 were optimal conditions for the NP preparation, with the minimum particle size (∼155.1 nm) and the maximum BCP encapsulation efficiency (60.3 %). The BCP-loaded CS/FG NPs exhibited the smallest particle size (175.8 nm). Both CS/FG NPs and CS/FG-BCP NPs exhibited roughly uniform spherical shape. FT-IR spectra confirmed the existence of hydrogen bonds and electrostatic interactions in the nanoparticles. The BCP-loaded NPs displayed a higher thermal stability than BCP. Moreover, the release of BCP was controllable and dose-dependent, following a first-order kinetics model. These findings suggested that our CS/FG NPs are a promising carrier for bioactive peptide delivery. Schematic diagram of preparation and structure of CS/FG-BCP NPs. [Display omitted] • Polysaccharide-based nanoparticles (NPs) were developed by chitosan (CS)-flaxseed gum (FG) complexation. • Bighead carp peptide (BCP)-loaded CS/FG NPs showed good thermal stability. • CS/FG NPs showed good protective effect on BCP functionalities. • CS/FG NPs are successfully applied for controlled release of BCP. [ABSTRACT FROM AUTHOR]

This study investigated the influence of different explosion puffing pressures (0.6 MPa-1.0 MPa) on the structural characteristics, physicochemical characteristics, and digestibility of surimi-starch blends. With increased explosion puffing pressures, the starch granules attached to the protein network and bound to the protein increasingly tight. The results of X-ray diffraction and Fourier-transform infrared spectroscopy (FTIR) showed that explosion puffing destroyed ordered starch molecule chains resulting in a starch structure chaos. In addition, explosion puffing reduced the secondary structure number of surimi proteins by loosening intramolecular hydrogen bonds. The explosion puffing decreased the digestibility of puffed surimi-starch blends, while increased the resistant starch content. Maillard reaction in the puffing process led to the browning of the surimi-starch blends. the surimi-starch blends exhibited the optimal qualities with homogeneous pore structure, good color (70.11), excellent crispness (25.55 mm), desirable hardness (1967.57 Pa), and high expansion rate (398.85%) at explosion pressure 0.8 MPa. Our findings provide a reference for processing non-fried high-protein puffed food. [Display omitted] • The puffing pressure markedly affected the structure and texture of surimi-starch blends. • The binding of starch and protein became tighter as the puffing pressure increased. • The content of resistant starch in puffed surimi-starch blends increased. [ABSTRACT FROM AUTHOR]

Ge quantum dots (QDs) have been applied to increase the internal quantum efficiency (IQE) of a photodetector up to 1500% at 400 nm and are expected to benefit the performance of solar cells. Ge QDs have been successfully prepared on silicon-based solar cells using plasma enhanced chemical vapor deposition (PECVD) at temperature lower than 300 °C. By adjusting the deposition time, RF power and H 2 -plasma treatment time, the Ge QDs are optimized for obtaining the highest solar cell efficiency. It is found that the quantum efficiency of the solar cells has been significantly improved by the presence of Ge QDs, particularly in the long wavelength range (>600 nm). As a result, the short-circuit current density (Jsc) is increased by 3.3%, and, consequently, the solar cell efficiency is increased. [ABSTRACT FROM AUTHOR]

Polycrystalline silicon (p-Si) thin films are fabricated by plasma enhanced chemical vapor deposition (PECVD) at low substrate temperature (180 °C) with high-hydrogen dilution. Negative DC substrate bias is applied during the deposition process for improving the crystallinity of thin films. It is found that there is a phase transition from nanocrystalline phase to polycrystalline phase at negative bias = 50 V, as identified by scanning electron microscopy (SEM). The optimized p-Si thin film with large grains (~ 480 nm) are obtained at negative bias = 100 V. The deconvoluted Raman spectra reveal that the p-Si thin film is a mixture including amorphous silicon (a-Si), nanocrystalline silicon (nc-Si) and p-Si, and the crystalline volume fraction gradually increases with the substrate negative bias in the range of 0–100 V. The impacts of negative bias on the optical and electrical properties of p-Si thin films have been investigated. The growth mechanism of the p-Si grains has been discussed in detail. A grain-merging model is proposed for explaining the effect of negative bias on the formation of large p-Si grains at low temperature. [ABSTRACT FROM AUTHOR]

Epidemics caused by flaviviruses occur globally; however, no antiviral drugs treating flaviviruses infections have yet been developed. Nafamostat (NM) is a protease inhibitor approved for pancreatitis and anti-coagulation. The anti-flavivirus potential of NM has yet to be determined. Here, utilizing in vitro and in vivo infection assays, we present that NM effectively inhibits Zika virus (ZIKV) and other flaviviruses in vitro. NM inhibited the production of ZIKV viral RNA and proteins originating from Asia and African lineage in human-, mouse- and monkey-derived cell lines and the in vivo anti-ZIKV efficacy of NM was verified. Mode-of-action analysis using time-of-drug-addition assay, infectivity inhibition assay, surface plasmon resonance assay, and molecular docking revealed that NM interacted with viral particles and blocked the early stage of infection by targeting the domain III of ZIKV envelope protein. Analysing the anti-flavivirus effects of NM-related compounds suggested that the antiviral effect depended on the unique structure of NM. These findings suggest the potential use of NM as an anti-flavivirus candidate, and a novel drug design approach targeting the flavivirus envelope protein. • Nafamostat exhibits antiviral effect against ZIKV infection in vitro and in vivo. • Nafamostat blocks the early stage of ZIKV infection by targeting the domain III of envelope protein. • Nafamostat has potential as broad-spectrum antiviral drug candidate. [ABSTRACT FROM AUTHOR]

Many viruses use the host cell division cycle to facilitate replication. Cyclin-dependent kinases (CDKs) are a group of serine/threonine kinases that play a central role in regulating cell cycle progression. However, the prospect of using CDKs for anti-influenza virus treatment remains to be elucidated. We conducted this study to investigate the potential of the CDK1 inhibitor Ro-3306 in preventing influenza virus infection and to elucidate the underlying mechanism. We showed that Ro-3306, a CDK1 inhibitor, exerts anti-influenza activity both in vitro and in vivo. Proof-of-concept studies revealed that knockdown of host CDK1 might affect the splicing of M2 viral mRNA, leading to the restriction of viral replication. Moreover, Ro-3306 directly bound to viral PB2 protein and inhibited viral RNA replication. Transcriptome analysis further revealed that Ro-3306 treatment inhibited the expression of MAPK-regulated genes, which might also contribute to the antiviral activity of Ro-3306. This study highlighted the multifunctional role of Ro-3306 as a novel anti-influenza virus agent. [ABSTRACT FROM AUTHOR]

Zanthoxylum myriacanthum var. pubescens (Maqian) is an economically important plant that is widely consumed as a flavoring agent or indigenous medicine by local ethnic groups in Southwest China. The pharmacological activities, such as the anti-inflammatory activity of Maqian essential oil, have been highlighted in recent years. In this study, the in vitro and in vivo anti-influenza activities of Maqian essential oil and its major ingredient, d / L -limonene, were assessed. The Maqian essential oil and d / L -limonene were effective against the influenza A and influenza B viruses in vitro. Notably, the Maqian essential oil was highly inhibitive against the drug-resistant influenza virus strain with an EC 50 of 1.87 ± 1.04 μg/ml and a selective index of 85.13. Mode-of-action analysis revealed that Maqian essential oil and d / L -limonene inhibited the influenza virus at the stage of intracellular replication. For in vivo therapeutic efficacy, both intragastric and intranasal administration of d / L -limonene protected over 50% of mice from lethal influenza virus challenge. Both infectious viral particles and viral genome RNA were decreased approximately 2-fold in the d / L -limonene-treated mice compared with the virus group. Treatment with d / L -limonene potently improved the pathological features of the influenza virus-infected mice. Analysis of the gene expression level revealed that the major proinflammatory cytokines, including IL-1β, IL-6 and TNF-α, were significantly decreased in the d / L -limonene treated mouse lung tissues. Interestingly, we found that D -limonene was more potent than L -limonene in inhibiting proinflammatory cytokines. Transcriptome analysis revealed 32 host genes that participated in the antiviral process, most of which were related to the immune system and signal transduction. Combined with the antiviral and immunoregulatory effects of limonene, we believe that this multi-functional monoterpene has potential to become a novel candidate against influenza virus infections. • Maqian essential oil (MQEO) and d / L -limonene possessed anti-influenza activities in vitro. • MQEO and d / L -limonene inhibited influenza virus at the stage of intracellular replication. • d / L -limonene protected mice from lethal influenza virus challenge. • d / L -limonene could alleviate influenza infection-induced lung damage. • MQEO and d / L -limonene inhibited influenza virus by regulating host innate immunity. [ABSTRACT FROM AUTHOR]

To discover novel inhibitors that target the influenza polymerase basic protein 2 (PB2) cap-binding domain (CBD), commercial ChemBridge compound libraries containing 384,796 compounds were screened using a cascade docking of LibDock–LigandFit–GOLD, and 60 compounds were selected for testing with cytopathic effect (CPE) inhibition assays and surface plasmon resonance (SPR) assay. Ten compounds were identified to rescue cells from H1N1 virus-mediated death at non-cytotoxic concentrations with EC50 values ranging from 0.30 to 67.65 μM and could bind to the PB2 CBD of H1N1 with Kd values ranging from 0.21 to 6.77 μM. Among these, four compounds (11D4, 12C5, 21A5, and 21B1) showed inhibition of a broad spectrum of influenza virus strains, including oseltamivir-resistant ones, the PR/8-R292K mutant (H1N1, recombinant oseltamivir-resistant strain), the PR/8-I38T mutant (H1N1, recombinant baloxavir-resistant strain), and the influenza B/Lee/40 virus strain. These compounds have novel chemical scaffolds and relatively small molecular weights and are suitable for optimization as lead compounds. Based on sequence and structure comparisons of PB2 CBDs of various influenza virus subtypes, we propose that the Phe323/Gln325, Asn429/Ser431, and Arg355/Gly357 mutations, particularly the Arg355/Gly357 mutation, have a marked impact on the selectivities of PB2 CBD-targeted inhibitors of influenza A and influenza B. [ABSTRACT FROM AUTHOR]